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The collaboration between designers and digital humanists has indeed gained increasing significance in crafting effective projects, with design serving as a centralizing force in the realm of digital humanities by establishing interfaces for individuals to engage with technological resources. Therefore, design's methodological practices, encompassing various research and experiential facets, play a pivotal role in enhancing the usability and accessibility of digital resources within the social sphere. This study aims to expand the discourse on the characteristics and potential of the interplay between inclusive design and digital humanities practices, with a specific focus on the development of bilingual digital narratives (utilizing Brazilian Sign Language and Portuguese). The research adopts a collaborative, qualitative approach, encompassing processes of evaluation, validation, and enhancement. Digital visual narratives are presented as a facilitating tool for integrating LIBRAS and Portuguese, thereby aiding in language acquisition for deaf children. The article contributes to the discussion of the humanistic approach to design, emphasizing the values of empathy, ethics, and social responsibility in the creation of inclusive and accessible projects.

Iconographic themes alluding to salvific parousia created in the mosaic floors depicting divinities and heroes of the Villa del Casale in Piazza Armerina, dating back to the 4th century AD, and attributable to the new forms of philosophies and mystery religions known and professed within the Roman elite classes for whom the large monumental villas were intended during the Late Empire.

Background: In 2018, the authors surveyed the clinical practices among Portuguese gastroenterologists (PGEs) regarding treatment targets in Crohn’s disease (CD) and ulcerative colitis (UC). Since then, new evidence has emerged supporting additional targets, such as transmural remission and histological remission. This study provides an updated assessment of treatment practices among PGE with special emphasis on these new targets. Methods: Using the Portuguese Inflammatory bowel disease Study Group (GEDII) physician database, we invited PGE to participate in an anonymous online survey. Results: Fifty-six physicians agreed to participate in the study. Deep remission, steroid-free clinical remission, endoscopic remission, and biomarker remission were ranked among the most important treatment targets in CD (89%, 80%, 89%, and 84%, respectively) and UC (82%, 84%, 79%, and 84%, respectively). In CD, transmural remission was considered a target by 70% of participants, with 48% agreeing to intensify treatment to achieve it. In UC, histological remission was aimed by only 45% of PGE with most (88%) being unwilling to intensify treatment to achieve this goal. Physicians were more likely to seek endoscopic remission in CD and UC in younger and healthier patients, compared to older patients with comorbidities. Conclusion: PGEs are increasingly pursuing tougher treatment targets such as transmural remission in CD and, to a lesser extent, histological remission in UC. Physicians are more willing to escalate treatment to achieve endoscopic remission in younger patients.

Abstract Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.

Mitoribosome biogenesis is a complex process involving RNA elements encoded in the mitochondrial genome and mitoribosomal proteins typically encoded in the nuclear genome. This process is orchestrated by extra‐ribosomal proteins, nucleus‐encoded assembly factors, which play roles across all assembly stages to coordinate ribosomal RNA processing and maturation with the sequential association of ribosomal proteins. Both biochemical studies and recent cryo‐EM structures of mammalian mitoribosomes have provided insights into their assembly process. In this article, we will briefly outline the current understanding of mammalian mitoribosome biogenesis pathways and the factors involved. Special attention is devoted to the recent identification of iron–sulfur clusters as structural components of the mitoribosome and a small subunit assembly factor, the existence of redox‐sensitive cysteines in mitoribosome proteins and assembly factors, and the role they may play as redox sensor units to regulate mitochondrial translation under stress.

According to developmental psychologists, more supportive and less conflictual relationships with teachers play a positive role in children's social behavior with peers both concurrently and in the future. This meta-analysis examined the association between teacher-student relationship quality, as measured by the Student-Teacher Relationship Scale (STRS), and social competence from early childhood through high school. Based on nearly 30,000 students from 87 studies, the weighted average association between teacher-student relationship quality and social competence with peers was r = 0.31 (z = 0.32; 95% CI: 0.28, 37). Neither age nor length of time between assessments were associated with effect size, suggesting that teacher-student relationships continue to be associated with children's social competence beyond the early years. Additionally, the STRS total score was the best predictor of social competence, whereas dependency was more weakly associated with social competence. The findings of this study suggest that teacher-student relationship quality as measured by the STRS is an important correlate of both concurrent and future social competence from early childhood to adolescence.

Abstract Glioblastoma (GBM) represents an aggressive brain tumor, characterized by intra- and inter-tumoral heterogeneity and therapy resistance, leading to unfavourable prognosis. An increasing number of studies pays attention on the regulation of ferroptosis, an iron-dependent cell death, as a strategy to reverse drug resistance in cancer. However, the debate on whether this strategy may have important implications for the treatment of GBM is still ongoing. In the present study, we used ferric ammonium citrate and erastin to evaluate ferroptosis induction effects on two human GBM cell lines, U-251 MG, with proneural characteristics, and T98-G, with a mesenchymal profile. The response to ferroptosis induction was markedly different between cell lines, indeed T98-G cells showed an enhanced antioxidant defence, with increased glutathione levels, as compared to U-251 MG cells. Moreover, using bioinformatic approaches and analysing publicly available datasets from patients’ biopsies, we found that GBM with a mesenchymal phenotype showed an up-regulation of several genes involved in antioxidant mechanisms as compared to proneural subtype. Thus, our results suggest that GBM subtypes differently respond to ferroptosis induction, emphasizing the significance of further molecular studies on GBM to better discriminate between various tumor subtypes and progressively move towards personalized therapy.

As pesquisas teóricas e práxis educacionais envolvendo sujeitos surdos vêm gradativamente ganhando espaço no cenário educacional. A disciplina Química, quando apresentada de forma descontextualizada, geralmente traz dificuldades na aquisição de saberes pelos discentes e, dentro do cenário surdo, a questão torna-se mais complexa, devido à restrição linguística a que esses sujeitos se encontram em uma sociedade prioritariamente ouvinte. Este artigo tem como objetivo apresentar a ferramenta digital Sinalizando Química – SinQui, destacar suas potencialidades e como ela é utilizada pela equipe de professores de Química do Instituto Nacional de Educação de Surdos – INES. Essa ferramenta foi pensada e desenvolvida no Instituto por professores ouvintes e surdos. O SinQui apresenta conceitos da terminologia química em Língua Brasileira de Sinais - Libras através de vídeos, não apenas apresentando os sinais, mas também as explicações de cada conceito, além disso, o material é ilustrado e apresenta legendas em Língua Portuguesa.

Abstract To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia. Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

Introduction. Platinum-based chemotherapy represents the standard of care (SoC) for the first-line treatment of advanced urothelial carcinoma (mUC). The benefit of adding immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy was recently investigated. We performed an individual patient data (IPD) meta-analysis of phase 3 clinical trials comparing ICI-based treatments. Methods. A systematic literature search was conducted on the MEDLINE and CENTRAL databases. The results were filtered by including only reports on clinical trials or randomized clinical trials from 2018 to 2023, including 3047 patients from four clinical trials (EV302, CHECKMATE-901, IMVIGOR130, KEYNOTE-361). An IPD meta-analysis was performed by reconstructing IPD from Kaplan–Meier curves. The primary endpoints were overall survival (OS) and progression-free survival (PFS) of Pembrolizumab + EV compared to experimental arms of the other trials of immunotherapy + chemotherapy. Results. The OS analysis showed an advantage of IPD from EV302 vs. all the other trials. For EV302 vs. KEYNOTE-361, the HR was 0.51; for EV302 vs. IMVIGOR130, the HR was 0.47; and for EV302 vs. CHECKMATE-901, the HR was 0.66 (CI 95% 0.51–0.85). In the PFS analysis, the EV302 arm showed a statistically significant advantage compared to CHECKMATE-901 (HR 0.66) and versus IMVIGOR130 (HR 0.51). Limitations: By using reconstructed IPD curves, it was not possible to adjust patient-level covariates, and the heterogeneity of the included population may have affected the pooled results. Conclusions: The EV302 experimental arm showed better OS and PFS when compared to the other immunochemotherapy combinations. An immunochemotherapy combination strategy at the beginning of treatment in mUC seems to be superior in terms of OS and PFS compared to platinum-based chemotherapy alone. EV–Pembrolizumab resulted to have better outcomes compared to avelumab, rather than other immunochemotherapy combinations. However, given the heterogeneity of these studies, a longer follow up and prospective trials are needed to confirm these data.

Abstract Background The prevalence of cardiovascular disease is burgeoning in low- and middle-income countries (LMICs). In sub-Saharan Africa, the prevalence of cardiovascular risk factors is increasing, though rates of CVD diagnosis and management remain low. Awareness of the influence of social determinants of health (SDOH) on cardiovascular outcomes is growing, however, most work focuses on high-income countries. Material needs security is a measure of SDOH that may be particularly relevant for LMICs. This study investigated the relationship between material needs security and cardiovascular risk in older adults living in South Africa. Methods The analysis included 5059 respondents age ≥ 40 in the Health and Aging in Africa survey, an observational cohort study administered in 2014 in Mpumalanga Province, South Africa. Linear regression models tested the association between material needs and eight cardiovascular risk factors (waist-to-hip ratio, body mass index, blood pressure, glucose, cholesterol, LDL, and triglycerides). Adjusted linear regression models controlled for sociodemographic confounders. Results There were significant adjusted associations found between increased material needs security and four cardiovascular risk factors, including waist-to-hip ratio (β = 0.001; 95% CI [0.00002,0.002]), BMI (β = 0.19; 95%CI=[0.14,0.24]), glucose (β = 0.46; 95%CI=[0.02,0.90]), and triglycerides (β = 0.26; 95%CI=[0.02,0.49]). Conclusion Increased material needs security was associated with significantly increased cardiovascular risk in older adults in rural South Africa. These findings can inform the approach to treatment and management of cardiovascular disease in South Africa and similar LMICs. Future investigations should evaluate the implementation and efficacy of interventions that recognize the role of material needs security in cardiovascular risk.

Antimicrobial resistance presents a substantial threat to global public health, demanding urgent attention and action. This study focuses on lanthipeptides, ribosomally encoded peptides that display significant structural diversity and hold promising potential as antibiotics. Genome mining was employed to locate biosynthetic gene clusters (BGCs) containing class II lanthipeptide synthetases encoded by lanM genes. A phylogenetic study analyzing homologous sequences of functional LanM sequences revealed a unique evolutionary clade of 17 LanM proteins associated with 12 Clostridium bacterial genomes. In silico exploration identified nine complete BGCs, including one super-cluster containing two co-localized operons from Clostridium cellulovorans 743B, that encode for two new peptides named clostrisin and cellulosin. Each operon was heterologously expressed in Escherichia coli. Molecular weights associated with the expected post-translational modifications of the purified lanthipeptide were confirmed by MS–MS/MS analysis for cellulosin, while clostrisin was not post-translationally modified. Both peptides demonstrated antimicrobial activity against multidrug-resistant bacteria, such as a clinical strain of Staphylococcus epidermidis MIQ43 and Pseudomonas aeruginosa PA14. This is the first report of lanthipeptides from the Clostridium genus produced with its native biosynthetic machinery, as well as chemically and biologically characterized. This study showcases the immense potential of genome mining in identifying new RiPP synthetases and associated bioactive peptides.

IntroductionThe incidence of metabolic diseases tends to be highest during the transition period (±3 weeks around parturition) in dairy cows due to physiological changes and the onset of lactation. Although blood profile testing allows for the monitoring of nutritional and metabolic status, conducting extensive analyses in the herd is costly and stressful for cows due to invasive procedures. Therefore, mid-infrared spectroscopy (MIR) could be seen as a valid alternative.MethodsIn the present study, we used laboratory-determined reference blood data and milk spectra of 349 Holstein cows to (i) identify the non-genetic factors affecting the variability of major blood traits in healthy cows and, subsequently, (ii) test the predictive ability of milk MIR. Cows belonged to 14 Italian commercial farms and were sampled once between 5 and 38 days in milk. For β-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), cholesterol, glucose, urea, total protein, albumin, globulin, minerals, aspartate aminotransferase, gamma-glutamyl transferase, creatine kinase, total bilirubin, and cortisol, the effects of parity, days in milk, and season were investigated using a linear model.Results and discussionThe results indicate that all fixed effects significantly affected the hematic concentration of most of the traits. Regarding MIR, the most predictable traits were BHB, NEFA, and urea, with coefficients of determination equal to 0.57, 0.62, and 0.89, respectively. These values suggest that MIR predictions of BHB and NEFA are not sufficiently accurate for precise and punctual determination of the hematic concentration, however, still the spectrum of the milk can be exploited to identify cows at risk of negative energy balance and subclinical ketosis. Finally, the predictions can be useful for herd screening, decision-making, and genetic evaluation.

Background: Kidney transplant recipients face complex perioperative challenges due to comorbidities from chronic kidney disease. This study aimed to assess perioperative complications in kidney transplant recipients and evaluate the association between the Charlson Comorbidity Index (CCI) and complication severity using the Clavien-Dindo (CD) classification. Methods: A prospective cohort study conducted at a tertiary hospital in South Brazil from September 2020 to March 2022, including 230 adult kidney transplant recipients. Data on demographics, comorbidities, and complications were collected. Complications were categorized using the CD scale, and their relationship with CCI was analyzed using univariate and multivariate Cox regression. Results: Mean age was 49.2 ± 12.7 years, with 58.7% male recipients. The mean CCI score was 3.65 ± 1.5 points. Intraoperative complications occurred in 10.9% of patients, with notable issues including bleeding and airway difficulties. In the immediate postoperative period, 9.1% required urgent dialysis. In the 30-day follow-up, 57.8% had delayed graft function, 21.7% infections, 11.3% had vascular complications, and the mortality was 1.7%. CCI was not a significant predictor of severe complications; however, congestive heart failure was strongly associated with severe complications (HR = 6.6 95% CI 2.6–6.7, p < 0.001). Conclusions: Despite a low overall comorbidity profile, kidney transplant recipients faced significant perioperative challenges. The lack of a significant association between the CCI score and severe complications suggests that traditional risk assessment tools may not fully capture the risks specific to the early postoperative period in kidney transplantation, and future research should focus on developing more refined risk assessment models for chronic kidney disease patients.

Background and purpose: In carbon ion radiotherapy (CIRT), different relative biological effectiveness (RBE) models have been used for calculating RBE-weighted dose (DRBE). Conversion between current RBE predictions and introduction of novel approaches remains a challenging task. Our aim is to introduce a framework considering multiple RBE models simultaneously during CIRT plan optimization, easing the translation between DRBE prescriptions. Materials and methods: An in-house developed Monte Carlo treatment planning system was extended to incorporate the local effect model version I (LEM-I), the modified microdosimetric kinetic model (mMKM) and the MKM-derived Japanese biological model (NIRS-MKM). Four clinical cases (two head-and-neck and two prostate patients), initially optimized with LEM-I for both targets and organs at risk (OARs), underwent two further optimizations: to fulfill mMKM/NIRS-MKM-based target prescriptions (mixed-RBE approach) or to simultaneously consider two biological models within the target regions (multi-RBE approach). Both approaches retained LEM-I-derived dose constraints for OARs. Results: The developed optimization strategies have been successfully applied, fulfilling all the clinical criteria for the applied RBE models. One of the RBE models showed unfavorable dose distribution when not explicitly considered in the optimization, while multi-RBE model optimization allowed meeting dose objectives for the selected OARs for both models simultaneously. Conclusions: The introduced optimization approaches allow for mixed- or multi-RBE optimization in CIRT through the selection of RBE models independently for each region of interest. This capability addresses challenges of adhering to multiple RBE frameworks and proposes an advanced solution for tailored patient treatment plans.

Abstract Background Intramammary infection is the result of invasion and multiplication of microorganisms in the mammary gland and commonly leads to mastitis in dairy animals. Although much has been done to improve cows’ udder health, mastitis remains a significant and costly health issue for dairy farmers, especially if subclinical. In this study, quarter milk samples from clinically healthy cows were harvested to detect pathogens via quantitative PCR (qPCR) and evaluate changes in individual milk traits according to the number of quarters infected and the type of microorganism(s). A commercial qPCR kit was used for detection of Mycoplasma bovis, Mycoplasma spp., Staphylococcus aureus, coagulase-negative staphylococci (CNS), Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis, Prototheca spp., Escherichia coli, Klebsiella spp., Enterococcus spp. and Lactococcus lactis ssp. lactis. Quarter and pooled milk information of 383 Holstein, 132 Simmental, 129 Rendena, and 112 Jersey cows in 9 Italian single-breed herds was available. Results Among the cows with pathogen(s) present in at least 1 quarter, CNS was the most commonly detected DNA, followed by Streptococcus uberis, Mycoplasma bovis, and Streptococcus agalactiae. Cows negative to qPCR were 206 and had the lowest milk somatic cell count. Viceversa, cows with DNA isolated in ≥ 3 quarters were those with the highest somatic cell count. Moreover, when major pathogens were isolated in ≥ 3 quarters, milk had the lowest casein index and lactose content. In animals with pathogen(s) DNA isolated, the extent with whom milk yield and major solids were impaired did not significantly differ between major and minor pathogens. Conclusions The effect of the number of affected quarters on the pool milk quality traits was investigated in clinically healthy cows using a commercial kit. Results remark the important negative effect of subclinical udder inflammations on milk yield and quality, but more efforts should be made to investigate the presence of untargeted microorganisms, as they may be potentially dangerous for cows. For a smarter use of antimicrobials, analysis of milk via qPCR is advisable – especially in cows at dry off - to identify quarters at high risk of inflammation and thus apply a targeted/tailored treatment.