Zika virus (ZIKV) is transmitted to humans by the infectious bite of mosquitoes like Aedes aegypti. After a viremic blood meal, the virus must infect the midgut, disseminate to tissues, and reach the salivary gland to be transmitted to a vertebrate host. Many factors influence the mosquito’s ability to become infected and transmit viruses, such as the mosquito’s genetic diversity, intrinsic antiviral barriers, and midgut microbiota. This study evaluated the patterns of ZIKV infection in Ae. aegypti field populations of a city. The infection rate, disseminated infection rate, viral transmission rate, and transmission efficiency were measured by quantitative PCR at 14 days post-infection. The results showed that all Ae. aegypti populations had individuals susceptible to ZIKV infection and able to transmit the virus. The infection parameters showed the city’s geographical area of origin of the Ae. aegypti influences their vector competence for ZIKV transmission.

Multiple Sclerosis (MS) has a well established link with Epstein-Barr virus (EBV) and a growing association with human endogenous retroviruses (HERVs). In this review, we described how these two pieces may interact in MS pathogenesis

The emergence of SARS-CoV-2 is a challenge in the actual medical scenario. Besides the classical lung and respiratory disease, patients infected with the virus can present with cardiac injury, and pathogenic mechanisms point to a direct infection of the heart.

The time-resolved CIDNP method can provide information about degenerate exchange reactions (DEE) involving short-lived radicals. In the temperature range from 8 to 65°C, the DEE reactions of the guanosine-5’-monophosphate anion GMP(-H)- with the neutral radical GMP(-H)•, of the N-acetyl tyrosine anion NacTyrO- with a neutral radical NacTyrO• and of the tyrosine anion TyrO- with a neutral radical TyrO• were studied. In all the studied cases, the radicals were formed in the reaction of quenching triplet 2,2’-dipyridyl. The reorganization energies were obtained from Arrhenius plots. The rate constant of the reductive electron-transfer reaction in pair GMP(-H)•/TyrO- was determined at T = 25°C. Rate constants of GMP(-H)• radical reduction reactions with TyrO- and NacTyrO- anions calculated by the Marcus cross relation differ from the experimental ones by two orders of magnitude. The rate constants of several other electron transfer reactions involving GMP(-H)-/•, NacTyrO-/•, and TyrO-/• pairs calculated by cross relation agree well with the experimental values. The rate of nuclear paramagnetic relaxation was found for the 3,5 and β-protons TyrO• and NacTyrO•, the 8-proton GMP(-H)• the 3,4-protons DPH• at each temperature. In all cases, the dependences of the rate of nuclear paramagnetic relaxation on temperature are described by the Arrhenius dependence.

The recently emerged coronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) is the newest threat to human health. It has already infected more than half a million people worldwide, leading to a lot of deaths. Although it causes mild flu-like disease in most patients, lethality may increase to more than 20% in elderly subjects, especially those with comorbidities, like hypertension, diabetes or lung and cardiac disease, and the mechanisms are still elusive. Common symptoms at the onset of illness are fever, cough, myalgia or fatigue, headache, and diarrhea or constipation. Interestingly, respiratory viruses have also placed themselves as relevant agents for CNS pathologies. Here we discuss several CNS related features, referred by several patients, especially at the beginning of the disease. Thus, we also discuss the possibility by which SARS-CoV-2 may affect the olfactive system of patients, either directly or indirectly.

In this study a material based on Polyethylene (PE) and Microcrystalline Cellulose (MC) was developed as a breathable packaging film. Surface functionalization of MC with 3 aminopropyltriethoxysilane (APTES) shows to be an efficient alternative to tailor their properties and increase opportunities for the application of MC on the reinforcement of polymers such polyethylene (PE). Functionalization of MC with mentioned silane derivative was achieved using a green method and later used on the development of composites with PE in three percentages (1, 3 and 5%). All the materials were prepared by melt blending and characterized, in terms of structural properties (ATR-FTIR and FTIR in transmittance, EDX, SEM), thermal properties (DSC and TGA), thermomechanical properties (DMA), contact angle measurements and permeability to oxygen and water vapor. The materials demonstrated to have potential to be used as breathable film packaging of fresh products.

Phα1β a spider peptide, purified from the venom of Phoneutria nigriventer inhibits high voltage calcium channels and is antagonist of TRPA1 receptor two important pain transduction path-ways. In the last 15 years, we have showed, in preclinical tests with Phα1β native and recombi-nant in rodent models of pain the potential of Phα1β to become a new analgesic drug. Evaluation of new drug on human ERG channel is requirement of the regulatory agencies. For the hERG channel inhibition assay it was used the commercial kit FLIPR® Potassium Assay. It was tested the effect of Phα1β and as positive control dofetilide, a well characterized hERG block-er. Phα1β 56, 225, 450 and 900 pMol caused at a higher concentration a very weak inhibition of the hERG channel activity of about 13.47 % with channel inhibition at 50%, IC50 > 900 pMol. Dofetilide (0.0001 - 10 µM), a known hERG inhibitor, caused a well-known, concentra-tion-dependent inhibition of the hERG channel with a mean IC50 of 0.1642 µM (0.1189 – 0.2282 µM. For the cytotoxicity assay, Phα1β concentrations of 56, 225, 450 and 900 pMol incubated for 24 h with HEK293-hERG cells did not alter the viability of the HEK293-hERG cells. It is con-cluded that Phα1β even at high concentrations does not interfere with hERG channels.

Mutation in the ethionamide (ETH) activating enzyme, EthA, is the main factor determining resistance to this drug, used to treat TB patients infected with MDR and XDR Mycobacterium tuberculosis isolates. Many mutations in EthA of ETH resistant (ETH-R) isolates have been described but their roles in resistance remain uncharacterized, partly because structural studies on the enzyme are lacking. Thus, we took a two-tier approach to evaluate two mutations (Y50C and T453I) found in ETH-R clinical isolates. First, we used a combination of comparative modeling, molecular docking, and molecular dynamics to build an EthA model in complex with ETH that has hallmark features of structurally characterized homologs. Second, we used free energy computational calculations for the reliable prediction of relative free energies between the wild type and mutant enzymes. The ΔΔG values for Y50C and T453I mutant enzymes in complex with FADH₂-NADP-ETH were 3.34 (+/−0.55) and 8.11 (+/−0.51) kcal/mol, respectively, compared to the wild type complex. The positive ΔΔG values indicate that the wild type complex is more stable than the mutants, with the T453I complex being the least stable. These are the first results shedding light on the molecular basis of ETH resistance, namely reduced complex stability of mutant EthA.

Nowadays, the growing concern about improving thermal comfort in textiles, asphalt pavements and buildings has stimulated research into phase change materials (PCMs). However, the incorporation of PCMs directly causes mechanical impacts. Therefore, this study herein reported focuses on designing coaxial phase change fibres using commercial cellulose acetate (CA) or recycled CA obtained from cotton fabrics (CAt) as a coating and polyethylene glycol (PEG) 2000 as a core. The phase change fibres (PCF) were produced by wet spinning, varying the parameters: (i) CA concentration, molecular weight and source (virgin versus recycled); and (ii) PEG concentration and ejection. For phase change recycled fibres (PCFt), PEG concentration and ejection were varied. The fibres were assessed for their optical, chemical, thermal and mechanical properties. Bright-field microscopy images and Scanning Electron Microscopy (SEM) micrographs proved the coaxial structure. Fourier Transform Infrared spectroscopy (FTIR) confirmed the presence of PEG in the core. Thermogravimetric Analysis (TGA) proved the ability of PCFs to tolerate high temperatures. Differential Scanning Calorimetry (DSC) attested to the presence of PEG2000 peaks, since their melting points were close to those of virgin PEG2000, with a slight change in the PCFs and PCFts caused by the protective sheath of CA and CAt.

An especially important species in southern Brazil, yerba mate (Ilex paraguariensis) is traditionally consumed as tea, chimarrão and tererê. Yerba mate consumption has been stimulated by scientific discoveries that have identified high concentrations of bioactive compounds and their health benefits. There are no studies or scientific evidence to certify or guarantee stability of these compounds’ concentrations during different years in the same plants. We were interested in quantifying caffeine, theobromine, total phenolic compounds and proteins concentrations in leaves of yerba mate genotypes and their stability in the same plants over four consecutive years. Mature leaves from yerba mate genotypes selected on a provenance and progenies trial were collected in August of 2015, 2016, 2017 and 2018. Methylxanthines (caffeine and theobromine), total phenolic compounds and total protein contents were quantified. Our results indicate large variations between genotypes regarding caffeine (0.035 to 2.385 g 100 g^-1), theobromine (0.0004 to 1.772 g 100 g^-1), total phenolic compounds (7.028 to 9.424 g 100 g^-1) and proteins (10.39 to 16.58 g 100 g^-1) contents, and also high stability of those compounds over the four evaluated years. A great variation of the studied bioactive compounds in different Ilex paraguariensis genotypes was found and its stability over four consecutive years was showed.

Starch is a widespread natural polymer used in healthcare applications due to its low cost and antibacterial properties. The use of starch in its many forms and its sometimes combination with metallic nanoparticles have all contributed to the advancement of biomaterials. However, few studies have been conducted on biocomposites composed of jackfruit starch and silver nanopar-ticles (AgNPs). As a result, this research aims to study the physicochemical, morphological, and cytotoxic features of a Brazilian jackfruit (Artocarpus heterophyllus) starch-based scaffold loaded with AgNPs. Gelatinization and chemical reduction were used to synthesize the scaffold and AgNPs, respectively. X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS), and Fourier transform infrared spectroscopy (FTIR) were utilized to explore the properties. The findings supported the development of anisotropic, stable, monodispersed AgNPs. The presence of AgNPs in the scaffold matrix was revealed by XRD and SEM-EDS. AgNPs were found to modify the crystallinity, roughness, and thermal stability of the scaffold while leaving its chemical and physical characteristics unchanged. Finally, the scaffolds did not show adverse effects on the L929 cells.

Tuberculosis (TB) is an infectious-contagious disease caused by M. tuberculosis (Koch’s bacillus). About one-quarter of the world’s population is infected with that bacillus and at risk of developing TB disease. Latent tuberculosis corresponds to people who have been infected by TB bacteria but are not (yet) ill. The most vulnerable population to TB activation includes HIV infected, drug abuse and autoimmune disease patients. Multiple Sclerosis (MS) is a chronic and autoimmune neurological disease caused by lymphocytic infiltration. Its prevalence worldwide is 22.2 million cases of MS. There is a relation between TB and MS: due to immunomodulation or immunosuppression treatment of MS (reactivation of latent infection), or due to the intense inflammatory response before the infection of the bacillus (increased susceptibility to the development of autoimmune diseases). Screening for TB includes complete patient history, physical exam, chest radiography, and Tuberculin Skin Test or IGRA (Interferon Gamma Release Assay). This investigation is suggested when MS drugs (immunomodulatory and immunosuppressant medications) are prescribed. If a patient has positive results, the treatment for MS should not be delayed for the finishing TB treatment. In this paper, considering the high prevalence of tuberculosis, we recommend that TB screening should be also done at the moment of Multiple Sclerosis diagnosis.

Introduction: Unlike cigarette smoking, secondhand smoke (SHS) has not been as well described as an environmental risk for Multiple sclerosis (MS) nor as a risk factor for disease progression. We systematically reviewed the association between SHS and the risk of onset and/or progression of MS.Methods: We systematically screened MEDLINE/PUBMED, Science Direct, LILACs, and SCIELO searching for publications between January 1st , 2010, and July 5, 2021 with the following keywords: “multiple sclerosis and smoking”; “multiple sclerosis and passive smoking”; “multiple sclerosis and secondhand smoking”. An 11-year filter was applied from 2010 to 2021. Results: Fifteen articles were included in this review, which consisted of systematic reviews with meta-analysis (N = 2), systematic reviews (N = 2), and observational studies (N = 11). Both meta-analyses reported an impact of SHS on MS onset among secondhand smokers. One of the systematic reviews selected two observational studies showing the association between SHS and MS development, and one study that did not find a significant association between SHS and the risk of MS development. The other systematic review identified selected eight articles showing a relationship between SHS and MS. Seven observational studies reported higher odds of MS onset when associated with SHS. Four observational studies did not show a relationship between SHS and MS onset or progression.Discussion: Most articles showed a positive association between SHS exposure and the risk of developing MS. On the other hand, an association between SHS and a higher risk for MS progression could not be established.

The Doig Phosphate Zone (DPZ) is a phosphate-bearing marine unit located at the base of the Doig Formation, in the Triassic section of the Western Canada Sedimentary Basin. The DPZ has a maximum thickness of 90 m and extends across northeastern British Columbia and western central Alberta. In this study we characterize the significance and interpret the origin of apatite in the DPZ, through mineralogical and geochemical analyses, thin section study and field emission-scanning electron microscopy. The occurrence of apatite in the DPZ is not evenly distributed, but restricted to discrete 10 to 20 cm thick beds, located near the base of the DPZ. Phosphorites are of two types: grainstones composed primarily of unconformity-bounded coated grains, and intraclastic phosphorites composed of detrital silt-sized grains and apatite coated grains in a cryptocrystalline phosphatic matrix. The phosphorite beds are records of stratigraphic condensation due to low detrital input during transgression. The erosionally-truncated phosphatic coated grains and intraclasts are interpreted to be a result of various phases of phosphatization, exhumation, erosion reworking, winnowing and redeposition in alternating quiescence and storms or bottom currents. The abundance of pyrite and chalcophile trace elements, as well as the low concentration of proxy elements for organic matter productivity and preservation, are further evidences of stratigraphic condensation, with sulfidic pore water development and extensive organic recycling promoted by biological activity during the long exposure times. The phosphorites were formed under oxygenated water conditions, as suggested by the depletion in Ce and presence of a diverse benthic fauna.

Glycerol is a subproduct of biodiesel production and represents an important problem when generated in large scale. Alternatives that can utilize this unrefined byproduct is of potential interest. It is herein described the synthesis of a series of 1,2,3-triazoles using glycerol as starting material. The key step involved in the preparation of triazolic derivatives corresponded to the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes. The eight prepared derivatives were evaluated with regard to their fungicide, phytotoxic and cytotoxic activities. The fungicide activity was assessed in vitro against Colletotrichum gloeosporioides, the causing agent of papaya anthracnose. It was found that the compounds 1-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)cyclohexanol (4g) and 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol (4h) demonstrated high efficiency on controlling C. gloeosporioides when compared to the commercial fungicide tebuconazole. The triazoles did not present any phytotoxic effect when evaluated against Lactuca sativa. However, five derivatives were mitodepressive, inducing cell death detected by the presence of condensed nuclei and acted as aneugenic agents in the cell cycle of L. sativa. It is believed that glycerol derivatives bearing 1,2,3-triazole functionalities may represent a scaffold to be explored toward the development of new agents to control C. gloeosporioides.

Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.

Introduction: Multiple sclerosis (MS) is a demyelinating, chronic, inflammatory and autoimmune disease of the central nervous system (CNS) with axonal degeneration, presenting a progressive and variable course. MS patients usually have complications, such as bladder dysfunction, presence of urinary symptoms and Urinary Tract infection (UTI), which is one of the three most common non-neurological complications in MS patients. Objective: Analyze the most diverse aspects of UTI in MS patients, focusing on risk factors, prevalence, hospitalization and mortality rates of UTIs in this group. Methods: A non-systematic review of articles published on PubMed in the last 10 years with the search terms "Urinary Tract Infection" AND "Multiple Sclerosis". Discussion: MS patients have a high UTI prevalence, mainly due to the occurrence of urinary disorders in these patients. The most common symptoms of UTI in MS patients are urinary urgency, polyuria, nocturia, urinary retention, and incontinence. Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the most found organisms and treatment is based on antibiotic therapy. Moreover, UTIs can precipitate outbreaks, worsen the disease, causing more damage and a severe neurological condition deterioration. Therefore, UTIs in this group are associated with a high hospitalizations rate and a high mortality rate. Conclusion: UTI represents a great risk and concern in MS patients. The high prevalence, hospitalization rate and mortality rate of UTI in MS is worrying, such as the cause-consequence relationship between UTIs and the use of corticosteroids in outbreaks. Therefore, it is important to be aware of a UTI in this group to make early diagnoses, adequate management, and new infections prevention. Thus, further studies are needed to thoroughly analyze each nuance of this important comorbidity for MS patients.

This brief report presents a comparative analysis to examine differences in the mean dose of nitrate supplementation between studies with positive and negative results on exercise performance. Protocols of at least six days that had positive results used lower nitrate doses (~7.7 mmol), whereas those with negative results used higher doses (~10.2 mmol), showing a statistically significant difference (p < 0.05). These findings suggest long-term supplementation with higher doses (~10.2 mmol) may not improve exercise performance. Further research is essential to understand the underlying mechanisms.

This paper presents a case study on using Emacs and Org-mode for literate programming in undergraduate data science courses. Over three academic terms, the author mandated these tools across courses in R, Python, C++, SQL, and more. Onboarding relied on simplified Emacs tutorials and starter configurations. Students gained proficiency after initial practice. Live coding sessions demonstrated the flexible instruction enabled by literate notebooks. Assignments and projects required documentation alongside functional code. Student feedback showed enthusiasm for learning a versatile IDE, despite some frustration with the learning curve. Skilled students highlighted efficiency gains in a unified environment. However, uneven adoption of documentation practices pointed to a need for better incorporation into grading. Additionally, some students found Emacs unintuitive, desiring more accessible options. This highlights a need to match tools to skills levels, potentially starting novices with graphical IDEs before introducing Emacs. Key takeaways include literate programming aids comprehension but requires rigorous onboarding and reinforcement; Emacs excels for advanced workflows but has a steep initial curve. With proper support, these tools show promise for data science education.

Este artigo apresenta o processo de implementação da Hiperautomação no setor público brasileiro, especialmente no âmbito da Procuradoria Geral do Estado de Pernambuco. Devido à atual economia competitiva, a demanda por soluções inteligentes e confiáveis está aumentando. Para atender a essa necessidade, tecnologias inovadoras que abordem a complexidade inerente à transformação digital são desejáveis. Assim, as organizações públicas têm buscado aplicar a automação de processos para atender às necessidades dos cidadãos por um serviço mais eficiente e eficaz. No entanto, podemos observar que a automação pura e direta é apenas parte do processo de transformação. Algumas das razões que explicam a necessidade de ir além da automação de processos e alcançar a hiperautomação é a abundância de dados de várias fontes e tipos. Tudo deve estar dentro dos padrões legais, ressaltando que toda tecnologia deve estar alinhada com transparência e auditabilidade para ser incorporada com segurança. Para a experimentação, foi utilizado o método de pesquisa-ação com a aplicação da Hiperautomação, visando aumentar a arrecadação e a economia do Estado na Procuradoria Geral do Estado de Pernambuco.

Bringing toghether mathematical and philosophical ideas related to transcendental numbers, this paper begins with a survey on transcendence and transcendental numbers, it then presents several properties of the transcendental numbers e and π, and then it gives the proof of a new inequality for transcendental numbers. Also, in relationship with these topics, we study solutions to the Yang-Baxter equation from hyperbolic functions and from logical implication.

Coupled Delft3D-object model has been developed to predict object’s mobility and burial on sandy seafloor. The Delft3D model is used to predict seabed environment such as currents, waves (peak period, significant wave height, wave direction), water level, sediment transport, and seabed change, which are taken as the forcing term to the object model consisting of three components: (a) object‘s physical parameters such as diameter, length, mass, and rolling moment, (b) dynamics of rolling cylinder around its major axis, and (c) empirical sediment scour model with re-exposure parameterization. The model is compared with the observational data collected from a field experiment from 21 April to 23 May 2013 off the coast of Panama City, Florida funded by the Department of Defense Strategic Environmental Research and Development Program. The experimental data contain both objects’ mobility using sector scanning and pencil beam sonars and simultaneous environmental time series data of the boundary layer hydrodynamics and sediment transport conditions. Comparison between modeled and observed data clearly show the model capability.

Cement production contributes to about 7% of CO2 emissions into the atmosphere. Despite our best efforts, we cannot find a competitive substitute that is both reliable and environmentally friendly. The simplest way to solve the problem is to rationalize the resources and try to minimize its use by substitute them with other materials. A concrete that contains a substantial amount of fly ash is already available, but its use is limited by the current shortage in the market and reduced initial resistance. In this context, ternary mixtures have been used to conduct an experiment. A significant volume of cement has been replaced with fly ash and metakaolin, which serves as a correction factor for the performance. In this work the main advantages and disadvantages of the simultaneous use of these two additions, which may reveal to be very interesting with high volumes of substitution will be presented. The performance of this ternary mixture is very promising. Provide a wide range of possibilities for replacing cement, maintaining or even improving its mechanical and durability properties. A solution for an ecological concrete with enhanced performance for general use in construction as an alternative to conventional concrete.

Dye-containing effluent generated in textile industries is polluting and complex wastewater. It should be managed adequately before the final destination. The up-flow anaerobic blanket (UASB) reactor application is an eco-friendly and cost-competitive treatment. The present study briefly reviews the UASB application for dye wastewater valorization. Bioenergy and clean water production potential during dye-containing wastewater treatment are emphasized to promote resource recovery in textile industries. Efficiencies of color and chemical oxygen demand of 50–97% and 60–90% are reported in bench-scale UASB studies. A biogas yield of 0.36–36.04 L d-1 in UASB, which treats dye-containing effluents, is documented. Bioenergy production and water reuse allow environmental and economic benefits. However, data on full-scale UASB treating dye wastewater are missing. Besides, studies on combined systems integrating membrane processes, such as ultrafiltration and nanofiltration, and pretreatment of wastewater and sludge for improvements in biogas production might realize the complete potential for resource recovery of UASB technology.

Vagueira Beach on the Central Portuguese coast, is known as one of the places in Europe most affected by coastal erosion. The area has suffered more than 156 meters of coastline retreat over the period 1958 to 2001. With the aim to evaluate the influence of local factors on coastal erosion, this paper assesses the anthropogenic and natural factors that are related with the retreat of the coastline, by adopting statistical correlation and regression analyses. Through the Pearson's correlation coefficient (r) it was observed that local factors such as annual dredging at the Aveiro Port entrance (r = 0.93), the total length of groins in the Espinho-Vagueira section (r = 0.89), and storm events (r = 0.52) are directly related to coastline retreat in the area. A multiple linear regression model was developed in which coastline retreat is explained by these same factors over the period 1980 to 2006. With a coefficient of determination of R² = 0.91, it was observed that length of groins (significant at the 1% level), dredging of the port entrance (significant at the 5% level) and precipitation (as a proxy for storm events; significant at the 10% level) are significantly correlated with coastline retreat. Hence, it is shown that anthropogenic factors are the main drivers of coastline retreat in Vagueira Beach. This study provides an innovative approach for the assessment of coastal erosion, resulting in important information that can be used for decision-making related to coastal zone management as it allows to understand in greater detail the main drivers of coastal erosion.

Additive Manufacturing (AM) has been proving suitable to support or even replace traditional manufacturing in several industries, offering many advantages such as delivery time and reduction in terms of material waste, energy consumption and greenhouse gas (GHG) emissions. This study aimed to carry out a comparative assessment of the life cycle, from gate to gate, in the production of a low alloy carbon steel flange part using ER-90 wire. The methods utilized were Wire and Arc Additive Manufacturing (WAAM) and conventional manufacturing (CM) by forging, and comparative factors were energy demands, GHG emissions and generated solid waste. The total energy consumption in WAAM was 10,239.40 MJ, total carbon footprint in CO2 equivalent (CO2e) was 714.1 kgCO2e kg-1, and generated solid waste was 68.6 kg, respectively, 90%, 95% and 76% lower than consumption calculated in conventional manufacturing.

Like other organisms, fungi produce extracellular vesicles (EVs) that are involved in various biological processes, including intercellular communication and the transport of molecules between cells. These EVs can be applied in fungal pathogenesis, virulence, and interactions with other organisms, including host cells, in the case of fungal infections. While some types of mycoses are relatively common and easily treatable, certain neglected mycoses pose significant public health challenges, such as sporotrichosis, chromoblastomycosis, and paracoccidioidomycosis. These infectious diseases can cause significant morbidity and disability, leading to a reduced quality of life for the patients. So, research about the virulence factor is essential to understand how fungi escape the immune system. In this context, this manuscript reviews the study of fungi EVs, their cargo, their obtaining, and their role during the infectious process, which is extremely important for understanding this neglected mycosis.

This study analyzes the evolution of Corporate and Social Responsibility (CSR) and Environmental, Social, and Governance (ESG) concepts in social media, specifically on Twitter, from 2007 to 2022. The research aims to understand how society perceives organizational practices related to these aspects. Twitter provides an authentic environment for capturing user perceptions. The methodology involved collecting Tweets using Python and analyzing them in English, Spanish, and Portuguese with RStudio. The study's main findings highlight significant contributions and concerns within the CSR and ESG debates. While CSR's popularity showed a downward trend from 2010 to 2019, ESG grew exponentially during the pandemic and post-pandemic periods. Word analysis revealed the impact of specific hashtags: RSC in Spanish, #CSR in English, and #ESG in Portuguese. Society's increasing concerns concern environmental issues for combating global warming and ensuring a better quality of life, alongside financial transparency and ethical practices in companies. However, the social aspect of ESG, represented by the letter "S," didn't garner the same attention as environmental and governance matters. This discrepancy might stem from a lack of awareness or lower priority in public discussions on social media, overshadowing the social dimension in the ESG framework.

Lower limb exoskeletons have the potential to reduce the prevalence of work-related musculoskeletal disorders; however, they often lack user-oriented control strategies. Human-in-the-loop (HITL) controls can adapt an exoskeleton’s assistance in real-time, to optimize the user-exoskeleton interaction. This study presents a HITL control for a knee exoskeleton to minimize the users’ physical effort, a parameter innovatively evaluated by their interaction torque with the exoskeleton (a muscular effort indicator) and metabolic cost. This work innovates by estimating the user’s metabolic cost within the HITL control through a machine-learning model. The regression model was able to estimate the metabolic cost, in real-time, with a root-mean-squared error of 0.66 W/kg and a mean absolute percentage error of 26%, making faster (10s) and less noisy estimations than a respirometer (K5, Cosmed) device. The HITL reduced the user’s metabolic cost and interaction torque by 7.3% and 32.3%, respectively, when compared to a zero-torque control. The developed HITL control surpassed both a non-exoskeleton and a zero-torque condition regarding the user’s physical effort, even for a simple task such as slow walking. Furthermore, the user-specific control enabled a lower metabolic cost than the non-user-specific assistance. This proof-of-concept demonstrated the potential for HITL controls in assisted working.

In this tutorial review, we compare and contrast the chemical mechanisms of electrophile/oxidant sensing, and the molecular mechanisms of signal propagation. We critically analyze biological systems in which these different pathways are believed to be manifest and what the data really mean. Finally, we discuss applications of this knowledge to disease treatment and drug development.

For several years, drugs bearing reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving drug-protein target spectrum. Studies on natural electrophilic molecules have indicated that in many instances natural electrophiles use similar mechanisms to alter signaling pathways. However, natural reactive species are also endowed with other important mechanisms to hone signaling properties that are uncommon in drug design. These include ability to be active at low occupancy and elevated inhibitor kinetics. Here we discuss how we have begun to harness these properties in inhibitor design.

In these days of information overload and high-throughput analysis, it is easy to lose focus on the study of individual proteins. It is our conjecture that such investigations are still crucially important and offer uniquely penetrative insights. We thus present a discussion of biophysical methods to allow readers to get to know their protein of interest better. Although this perspective is not written with the expert in mind, we hope that for interdisciplinary scientists, or researchers who do not routinely perform biophysical analyses, the content will be helpful and inspiring.

Here we draw insights from the latest serendipitous findings made on the opposing roles of a validated drug-target protein Keap1. We weigh up how natural reactive electrophiles and electrophilic small-molecule drugs in clinical use directly impinge on seemingly conflicting, yet both Keap1-electrophile-modification-dependent, cell-survival- vs. cell-death-promoting behaviors. In the process, we convey how understanding reactive chemical-signal regulation at a single-protein-specific level is an enabling necessity in deconstructing otherwise intricate reactive-small-molecule-responsive cellular pathways. We hope this opinion piece further spurs the broader interests of basic and pharmaceutical research communities toward better understanding of molecular mechanisms underpinning reactive small-molecule-regulated signaling subsystems.

The beer industry is a major producer of solid waste globally, primarily in the form of brewer’s spent grains (BSG), which due to its low value has historically been diverted to livestock as feed or to landfills as waste. Its high moisture content and chemical composition positions BSG as an ideal candidate for further processing with microbial fermentation, and recent research has focused on filamentous fungi and the ability of some species therein to degrade the predominant recalcitrant cellulolignin components of BSG to produce valuable compounds. Many species have been investigated to biovalorize this waste stream, including those in the genuses Aspergillus, Pennicillium, Rhyzopus, and Trichoderma, which have been used to produce a wide array of highly valuable enzymes and other functional compounds, and to increase the nutritional value of BSG as an animal feed. This review of recent developments in the application of filamentous fungi for the valorization of BSG will discuss the biochemical makeup of BSG, the biological mechanisms underlying fungi’s primacy to this application, and the current applications of fungi in this realm. As the majority of these studies are at lab-scale, the challenges to scale-up and more widespread application and will be discussed as well.

CoVID-19 is a multi-symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we will not discuss, the response of scientists and clinicians to this complex problem has reflected the need to detect CoVID-19 rapidly, to diagnose patients likely to show adverse symptoms, and to treat severe and critical CoVID-19. Here we aim to encapsulate these varied and sometimes conflicting approaches and the resulting data in terms of chemistry and biology. In the process we highlight emerging concepts, and potential future applications that may arise out of this immense effort.

Climate change in the coming decades could intensify extreme events such as severe droughts. Combined with the possible increase of water demands, these changes exert a large pressure on the water systems. In order to confirm this assumption, a set of scenarios was proposed in this study to consider the combined impact of climate changes and the increase in water demand on the main multiple-use reservoirs of São Francisco River, Brazil. For this purpose, five CMIP6 climate models were used considering two greenhouse gas emissions scenarios: the SSP2-4.5 and SSP5-8.5. The naturalized and withdraw streamflows were estimated to the adopted reser-voirs considering all existing, new and projected demands. The conjunction of scenarios indicat-ed an increase in Potential Evapotranspiration, a possible significant reduction in water availa-bility, a growth in water demand mainly for irrigation and a substantial reduction in the perfor-mance of the evaluated reservoirs.

Introduction: In an era of increasing public awareness regarding the pivotal role of nutrition in the onset and progression of chronic degenerative diseases, there is a growing demand for information and assistance pertaining to the intricate relationship between diet and disease. Nutritional practices, therefore, emerge as a fundamental element in the prevention and management of these maladies, necessitating a proactive response from healthcare professionals (HCP). This study sought to evaluate the impact of participation in a Culinary Medicine (CM) program on Mediterranean diet adherence, food management skills, culinary proficiency, and counseling confidence among HCP. Methods: A mixed-methods pilot implementation program (PIP) was meticulously designed and executed, engaging a cohort of 20 HCP recruited from Hospital Clinic Barcelona. The program unfolded at the Alícia Foundation kitchen-lab and encompassed a series of interactive, hands-on sessions that delved into the realms of gastronomy, food management, culinary skills, and culinary diet therapy, with a specific focus on prevalent diseases and their prevention, treatment, and care. Tailored questionnaires were administered to all participants both before and after the PIP. Results: Of the 20 participants, 14 successfully completed the study, comprising 86% women, 86% aged above 40, 71% nurses, and 7% medical doctors. Interestingly, 86% of the participants had previously received nutrition training, whereas only 14% had received culinary training. Following the completion of the program, there was a remarkable improvement in adherence to the Mediterranean diet (p < 0.01). However, no statistically significant improvements were observed in food management and culinary skills or counseling confidence (p > 0.5). Despite the absence of statistical significance, there was a noteworthy trend towards greater advocacy for dietary changes before resorting to medication, along with enhanced confidence in providing nutritional and culinary guidance to patients. Conclusion: The findings from this study underscore the potential of hands-on CM training as a vital component of nutrition education for HCP. While statistically significant improvements in certain domains were not observed, the program did demonstrate its ability to influence attitudes, knowledge, and behaviors related to healthy cooking and eating for both HCP themselves and their patients. Given these promising trends, future studies with a larger sample size must be performed to further elucidate the impact of CM training on HCP and its potential benefits for public health.

Life Cycle Assessment (LCA) is a technique developed to measure possible environmental impacts during the manufacture and use of a given product or service. Additive Manufacturing (AM) has proven to be suitable in several industries, especially wire and arc additive manufacturing (WAAM), offering many advantages such as delivery time and reduction in terms of material waste, energy consumption and equivalent CO₂ emissions (CO₂e). This study aimed to develop a methodology to evaluate environmental indicators during the life cycle assessment, from gate-to-gate, in the production of two low-alloy carbon steel metal parts (flanges) using ER-90 wire and allowed identifying the main stages that most influence environmental indicators. The total energy consumption in the production of flanges 1 and 2 were, respectively, 10,239.0 MJ, 12,754.0 MJ and the total carbon footprint, respectively, 714.1 kgCO₂e kg^-1 and 749.3 kgCO₂e kg^-1.

Music perception in foetuses has been explored under different theoretical paradigms such as habituation, categorical perception, sound preferences and recall. This study investigated the temporal dimension of music perception through the habituation and sensitization paradigm. Foetuses of 41 pregnant women, mean gestational age of 34.7 weeks (±2.4), were observed during ultrasound exams. Foetuses’ reaction to two different tempos (Allegro vs Adagio) and sources (internal vs external) of music stimuli was registered by heart rate variability (HR) and motor response according to the Assessment of Preterm Infants Behaviour scale (APIB) by its factors of movement (MOV) and organization (ORG). A folkloric lullaby, sung and played live with a stringed instrument by a musician, was presented in three stages that were compared to baseline: 1) slow tempo (Adagio), 2) fast tempo (Allegro); and 3) now sung by mother at slow tempo (Adagio). Exploratory analyses showed that all factors increased from baseline to first stage. HR and ORG varied significantly among stages, with HR being the strongest factor. MOV merely detected change from baseline to first stage. ORG decreased for Allegro but increased for maternal Adagio, while HR decreased to near baseline values. ANOVA-repeated measures with gestational age as covariate showed that all measures were sensitive to first music presentation (Adagio), although only HR and ORG differed among stages. Considering estimated marginal means, adjusted for gestational age, HR presented a sensitization pattern throughout stages, but ORG kept habituating to external source and increased to maternal Adagio, suggesting foetal discrimination by sound source. We conclude that foetuses showed different behavioural and physiological responses to external versus internal sound source and musical tempo. The combined use of a behavioural scale (APIB) and HR in foetuses proved to be a valid multidimensional instrument.

The Covid‐19 pandemic, evolving needs of students & mentors, and the drive for global educational equality are collectively shifting how courses are packaged/distributed, ushering a more holistic approach and blending of fields. We recently created interdisciplinary courses in chemical biology aimed at massive open online and small private levels. These courses cover biology, chemistry, & physics, and concepts underlying modern chemical‐biology tools. We discuss what we learned while creating/overseeing these courses: content optimization and maintaining material freshness while fostering a stimulating learning environment. We outline mechanisms that help sustain student attention throughout rapidly‐moving courses, how to integrate adaptability to students’ needs in the short & long term, and speculate how we could have improved. We believe this will be an important guide for anyone wanting to develop online learning formats ideal for nurturing interdisciplinary scientists of tomorrow.

(1) Background: Learning and training in variable conditions favors adapting to unstable or changing environments. The aim of the study was to test the effect of variable practice on the accuracy of the forehand net approach shot in tennis.; (2) Methods: Thirty (n=30) first-class national players (12.9 ± 1.1 years old) participated, divided into three groups: i) induced variability training (n=10) (varying court surfaces and balls), ii) specific training (n=10) and iii) usual training -control group- (n=10). All groups trained for a month: 12 sessions of 20 minutes -3 per week-. The accuracy of the shots were analyzed through a 2D capture and digitization process of the ball bounce on the court; (3) Results: The variability group presented better accuracy values after the period without practice than the stable training group (p = 0.041; ES= 0.51).; (4) Conclusions: the application of variability in the game conditions during tennis training seems to have a favorable effect on the retention of accuracy in the forehand down the line approach to the net.

The efficacy of the product development process is measured by the ability to launch a project with product and production process specifications that could guarantee that the manufacturing can produce it with the least impact. If a problem is detected late, they bring consequences beyond the high cost of the solution, if related to physical ergonomics, which will influence the well-being of operators, productivity, and quality. Virtual Reality (VR) and Digital Human Modeling (DHM) are ones of the enabling technologies of Industry 4.0 and has already been applied on a large scale in industries such as automotive, construction, and aeronautics. However, even though the huge applications, these technologies are not yet applied by these industries for the analysis of physical ergonomics during product development phases. This study aims to characterize the state of the art and technology about the application of Virtual Reality and Digital Human Modeling for the physical ergonomics analysis in the during product development phases in the industry through a systematic review of the literature and patents. In patent documents recovery, we used Derwent Innovation database. The research is based on searching the selected terms in the title, summary, and claims of the documents through a search strategy containing IPC code and keywords. In articles recovery, we searched ScienceDirect, Springer, and IEEExplore databases for scientific publications. The search resulted in 311 patents documents and 16 articles in the scientific database. This study analyzed the patents to map out the technological progress in this area, where we found in the charts and data an increasing number of publications per year and a spread application with a considerable number of new technologies presented in these recent patents. The literature review indicated that Virtual Reality technology complements the Digital Human Modeling during physical ergonomics analysis for manufacturing process already designed. The majority of research on the use of VR and DHM technologies for physical ergonomics analysis focus on the automotive industry and the ergonomic assessment of workstations and current processes. Further research is needed to investigate how Virtual Reality and Digital Human Modeling might assist in the understanding of physical ergonomics in certain tasks throughout the product development process, such as the simulation of worker posture or effort when assembling parts.

COVID-19 had a significant impact on construction projects due to labor shortages and COVID-19 restrictions, yet little is known about the impact it had on construction safety. To address this gap, an Australian construction project was selected to study the impact of COVID-19 on safety performance, safety climate and safety leadership. The study collected data from safety climate surveys, leading and lagging safety indicators and used linear regression to compare safety performance pre and post the onset of COVID-19. Our results showed after the onset of COVID-19 there was a significant reduction (Pr&gt;F at 0.05%) in incident rate, an improvement in supervisor safety leadership and safety climate, and satisfaction with organisational communication. The study identified the increase level of safety awareness due to COVID-19 did not result in an increase in the level of engagement in safety leadership. Interestingly, participation in the safety leadership activities did not improve until a change of Project Manager occurred. The study determined leaders who establish a positive safety climate within a project could negate the safety performance impact of COVID-19. The study confirms the importance of site safety leadership in maintaining engagement in risk management and the value of focused safety communication.

Angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are recognized as entry proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and recently their Single Nucleotide Polymorphisms (SNP) have been studied in different populations to elucidate the impact on disease. The aim of this study was to evaluate the genetic SNP of ACE2 (rs35803318) and TMPRSS2 (rs2070788) genes in COVID-19 patients from Northeast Brazil compared with global populations, as well as the expression quantitative trait locus (eQTL). For ACE2 (rs35803318), we found 92.6% CC, 3.4% CT, and 4.0% TT genotype carriers in SARS-CoV-2-positive patients. Surprisingly, only the genotype frequencies of ACE2 SNP were not in Hardy-Weinberg equilibrium. For TMPRSS2 rs2070788, we found 22.3% GG, 50.7% AG, and 27% AA genotype carriers in SARS-CoV-2-positive patients. The expression quantitative trait loci (eQTLs) revealed that rs35803318 was associated with an altered PIR gene expression, and rs2070788 was found eQTLs association only with lung tissue. No significant association was identified between the genotype distribution of SNPs and the 'patient's outcome. In conclusion, our results suggest that ACE2 and TMPRSS2 may not be protective factors for global populations, including the Brazilian population, since the presence of SNPs does not affect the 'patient's outcome as described by other studies.

Mass customization, small batch sizes, high variability of product types and a changing product portfolio during the life cycle of an industrial plant are current trends in the industry. Due to an increasing decoupling of the development of software and hardware components in an industrial context, compatibility problems within industrial control systems arise more and more frequently. In this publication, a strategy concept for compatibility testing is derived and discussed by means of literature review and applied research. This 4-phased strategy concept identifies incompatibilities between software and hardware components in the industrial control environment and enables test engineers to detect problems at an early stage. By automating the compatibility test on an external I-PC, the test can be run both when new software is installed on the industrial controller and when the controller is restarted. Thus, changes to the components are constantly detected and incompatibilities are avoided. Furthermore, early incompatibility detection can ensure that a system remains permanently operational. Based on a discussion, additionally strategies are identified to consolidate the robustness and applicability of the presented concept.

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

This manuscript presents the result of utilizing cellulose as a template to prepare na-nosized WO3-NiWO4 and its application as co-catalysts in Pt/WO3-C and Pt/WO3-NiWO4-C for ethanol and glycerol electro-oxidation. Microcrystalline cellulose was hydrolyzed with phosphotungstic acid (H3PW12O40) to prepare the nanosized template of crystalline cellulose. Next, the template was impregnated with Ni(NO3)2, rendering a precursor mate-rial that is subsequently air-calcinated, removing the carbon-template material to obtain the nanometric WO3 and NiWO4. Elemental analysis confirmed the coexistence of nickel and tungsten, whereas the thermal analysis evidenced the high thermal stability of these materials. The X-ray diffractograms displayed crystal facets of WO3 and, when added Ni, of NiWO4. The transmission electron micrographs corroborated the formation of na-nosized particles with average particle sizes close to 50 nm. Finally, to apply this material, Pt/WO3-C and Pt/WO3-NiWO4-C were prepared and used in ethanol and glycerol electro-oxidation in alkaline medium, observing a promotional effect of the oxide and tungstate by reducing the onset potential and increasing the current density. These materials show great potential to produce clean electricity or green hydrogen contributing to energetic transition.

Arbutus unedo L. is a resilient tree with a circum-Mediterranean distribution. Besides its ecological relevance, it is vital for local economies as a fruit tree. Several microorganisms are responsible for strawberry tree diseases leading to production constrictions. Thus, the development of alternative plant protection strategies is necessary and bacteria endophytes may increase their host overall fitness and productivity. As agricultural practices are a driving factor of microbiota, this paper aimed to isolate, identify and characterize endophytic bacteria from strawberry tree leaves from plants growing spontaneously in a natural environment as well as from plants growing on orchards. 62 endophytes were isolated from leaves and identified as Bacillus, Paenibacillus, Pseudomonas, Sphingomonas and Staphylococcus. Although a slightly higher number of species was found in wild plants, no differences in terms of diversity indexes were found. Sixteen isolates were tested in vitro for their antagonistic effect against A. unedo mycopathogens. B. cereus was the most effective antagonist causing a growth reduction of 20% in Glomerella cingulata and 40% in Phytophthora cinnamomi and Mycosphaerella aurantia. Also, several endophytic isolates exhibited plant growth-promoting potential. This study provides insights into the diversity of endophytic bacteria in A. unedo leaves and their potential role as growth-promoters and pathogen antagonists.

Cacipacoré virus (CPCV) was discovered in 1977 deep in the Amazon rainforest, from the blood of a black-faced ant thrush (Formicarius analis). As a member of the family Flaviviridae, genus orthoflavivirus, CPCV's intricate ecological association with vectors and hosts raises profound questions. CPCV’s transmission cycle may involve birds, rodents, equids, bovines, marsupials, non-human primates and bats as potential vertebrate hosts, whereas Culex and Aedes spp mosquitoes, have been implicated as potential vectors of transmission. The virus' isolation across diverse biomes, including urban settings suggests its adaptability as well as presents challenges for its accurate diagnosis and thus its impact on veterinary and human health. With no specific treatment or vaccine, prevention hinges on traditional arbovirus control measures. Here we provide an overview of the ecology, transmission cycles, epidemiology, pathogenesis and prevention, aiming in improving our ability to better understand this neglected arbovirus.

In Brazil, the production of corn and soybeans has been growing significantly in recent years. Considering that the strategies for investing in the production of these crops are conditioned by production costs and risk, the objective of this article is to propose a simulation model that indicates the trend of production costs for these commodities, considering the dispersion and correlation of selected key variable prices and corn and soybean production costs practiced between the years of 2018 and 2022. Fifty specialized companies in the state of Sao Paulo, Brazil, provided data for this study, and Monte Carlo simulations showed that the total cost of corn production/ha is between USD 600.00 and USD 1150.00, with a level of certainty of 84.7%, and soybeans are in the range of USD 260.00 to USD 420.00, with a level of certainty of 86.4%. The model evidenced a trend of decreasing production costs for the crops for the 2023/24 and 2024/25 harvests, as the input with the greatest impact (fertilizer) is showing a downward trend. On the other hand, costs related to labor, soybean seed, and fungicides are showing an upward trend, while dolomitic limestone corrective remains stable.

(1) Background: Although manual therapy for pain relief has been used as an adjunct in treatments for chronic low back pain (CLBP), there is still the belief that a single session of myofascial release would be effective. This study aimed to investigate whether a single session of a specific technique reduces pain and disability. (2) Methods: This was a crossover clinical trial in which 41 participants over 18 years old with CLBP were randomly enrolled into 3 situations - experimental, placebo, control, in a balanced and cross-over manner. The subjects underwent a single session of myofascial release on thoracolumbar fascia and compare it with the control and placebo. Outcome were pain and functionality, evaluated using the numerical pain rating scale (NPRS), pressure pain threshold (PPT) and Oswestry (ODI). (3) Results: There was no effects between-, within-tests, and interaction for all the outcomes, i.e., NPRS (η 2 = 0.32, F = 0.48, p = 0.61), PPT (η2 = 0.73, F = 2.80, p = 0.06), ODI (η 2 = 0.02, F = 0.02, p = 0.97). (4) Conclusion: A single trial of thoracolumbar myofascial release technique was not enough to reduce pain and disability in subjects with CLBP.

This paper proposes a method based on genetic algorithm (GA) for the security-constrained optimal dispatch of integrated natural gas and electricity networks, considering operating scenarios in both energy systems. The mathematical formulation of the optimization problem consists of a multi-objective function which aims to minimize both cost of thermal generation (diesel and natural gas) as well as the production and transportation of natural gas. The joint gas-electricity system is modeled by two separate groups of nonlinear equation, which are solved by the combination of Newton's method with the GA. The applicability of the proposed method is tested in the Belgian gas network integrated with the IEEE 14-bus test system and a 15-node natural gas network integrated with the IEEE 118-bus test system. The results demonstrate that the proposed method provides efficient and secure solutions for different operating scenarios in both energy systems.

This paper provides a comparative study between microwave tomography and synthetic time-reversal imaging techniques as applied to ground penetrating radar (GPR) surveys. The comparison is carried out by processing experimental data collected at a controlled test site, with various types of buried targets at given subsurface depths and representative soil conditions. It is shown that the two techniques allow us to obtain complementary information about position, depth and size of the targets from a single GPR survey.

The production of fuels and other industrial products from renewable sources has intensified the search for new substrates or for the expansion of the use of substrates already in use, as well as the search for microorganisms with different metabolic capacities. In the present work, we isolated and tested a yeast from the soil of sugarcane irrigated with vinasse, that is, with high mineral content and acidic pH. The strain of Meyerozyma caribbica URM 8365 was able to ferment glucose, but the use of xylose occurred when some oxygenation was provided. However, some fermentation of xylose to ethanol in oxygen limitation also occurs if glucose is present. This strain was able to produce ethanol from molasses substrate with 76% efficiency, showing its tolerance to possible inhibitors. High ethanol production efficiencies were also observed in acidic hydrolysates of each bagasse, sorghum, and cactus pear biomass. Mixtures of these substrates were tested and the best composition was found for the use of excess plant biomass in supplementation of primary substrates. It was also possible to verify the production of xylitol from xylose when the acetic acid concentration is reduced. Finally, the proposed metabolic model allowed calculating how much of the xylose carbon can be directed to the production of ethanol and/or xylitol in the presence of glucose. With this, it is possible to design an industrial plant that combines the production of ethanol and/or xylitol using combinations of primary substrates with hydrolysates of their biomass.

Astrocytes have been implicated in a wide range of neurodegenerative diseases, with the literature indicating harmful or beneficial roles on a case-by-case basis. On such conditions, these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including metabotropic glutamate receptor (mGluR5). However, mGluR5 activation in astrocytes under neuroinflammatory conditions can be neuroprotective or have the opposite effect. In this work, we investigated the role of mGluR5 in hiPSC-derived astrocytes subjected to pro-inflammatory stimulation by recombinant TNF-α (rTNF-α). Our results show that mGluR5 blockade by CTEP is capable of reducing pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) release in rTNF-α-stimulated astrocytes, but, in contrast, leads to an augmented expression of the pan-reactive marker SERPINA3. Additionally, CTEP enhances synaptoneurosomes phagocytosis by astrocytes in both non-stimulated and TNF-α-stimulated conditions, indicating that mGluR5 blockade alone is enough to drive synaptic material engulfment. Finally, mGluR5 antagonism as well as rTNF-α stimulation leads to a reduction in the expression of synaptogenic molecules. Altogether, these data suggest a complex role for mGluR5 in human astrocytes, since its blockage may have beneficial and detrimental effects under inflammatory conditions.

Corneal ulcer (CU) is an ophthalmopathy characterized by depression of the corneal surface with at least one stromal loss. CU is common in canine and feline species and is usually caused, among others, by trauma, infections, toxic contamination and endocrine disorders. They usually result from an increased inflammatory response and are associated with some clinical signs such as blepharospasm, photophobia, epiphora, pain and loss of corneal transparency. Despite advances in conventional and pharmacological therapy, in many cases indolent and recurrent ulcer treatments still lead to loss of visual acuity of the animal. This paper aims to report the effect of topical application of canine adipose tissue-derived mesenchymal stem cell (cATMSCs) as treatment of recurrent CU in a Poodle dog breed that showed clear difficulty in the healing process associated with diabetes. The animal was submitted to two applications of cATMSCs and showed improvement in the blepharospasm, conjunctival hyperemia, mucopurulent ocular secretion, photophobia, corneal opacity, chemosis, pigmentation, neovascularization, and pain parameters. Besides, Fluorescein test, Schirmer test and ocular fundus exam also showed improvement in their values concomitantly with lesion resolution. Due this, we showed that cATMSC therapy contribute to the regeneration of corneal tissue in CU and may contribute to the treatment to others ophthalmopathies.

The uptake of buildings employing cross-laminated timber (CLT) assemblies and designed to Passivhaus standard has accelerated internationally over the past two decades due to several factors including design responses to the climate crisis by decarbonising the building stock. Structural CLT technology and the voluntary Passivhaus certification both show measurable benefits in reducing energy consumption, while contributing to durability and indoor comfort. However, there is a general lack of evidence to support a fast uptake of these technologies in Australia. This paper responds to the compelling need of providing quantitative data and adoption strategies, it explores their combined application as a potential pathway for climate-appropriate design of energy-efficient and durable mass timber envelope solutions for subtropical and tropical Australian climates. Hygrothermal risk assessments of interstitial condensation and mould growth of CLT wall assemblies inform best-practice design of mass timber buildings in hot and humid climates. This research found that the durability of mass timber buildings located in hot and humid climates may benefit from implementing the Passivhaus standard to manage interior conditions. The findings also suggested that climate-specific design of the wall assembly is critical for mass timber buildings, in conjunction with excellent stormwater management practices during construction and corrosion protection for metallic fasteners.

This paper investigates experiences of how local cultural norms and social capital influenced the disaster relief process following the 2011 GEJET disaster. To underline social capital’s multiple‐influence aspects, this paper draws from field research that focuses on collective and individual social capital in disaster relief to systematise the findings according to the social capital framework. The paper uncovers new effects of individual social capital and collective capital in a mega-disaster context, thus contributing to pushing the research agenda toward a more critical appraisal of individual social capital and collective capital. We contribute to the nascent but growing literature that clarifies the relationship between social capital and disaster resilience. A qualitative study was conducted to capture the essence of their shared experiences. Findings revealed three main themes capturing the essence of the research participants’ disaster experiences. First, disaster response relied mostly on locally driven relief due to a clear understanding of the local culture. Second, there was an urgency to establish a sense of normalcy by providing quality supplies that would help survivors. Third, Japanese gender roles and expectations were reflected in the disaster relief process. The themes establish a wide array of lived experiences that are important to reflect on the role social capital plays in the policy-making and needs assessment processes in post-disaster relief and response efforts. The findings provide insights for integrating social dimensions into a humanitarian aid culture as citizens work towards a sense of normalcy.

Barry Turner’s 1978 Man-made Disasters and Charles Perrow’s 1984 Normal Accidents were seminal books but a detailed comparison has yet to be undertaken. Doing so is important to establish content and priority of key ideas underpinning contemporary safety science. Turner’s research found socio-technical and systemic patterns that meant that major organisational disasters could be foreseen and were preventable. Perrow’s macro-structuralist industry focus was on technologically deterministic but unpredictable and unpreventable ‘system’ accidents, particularly rare catastrophes. Andrew Hopkins and Nick Pidgeon respectively suggested that some prominent writers who wrote after Turner may not have been aware of, or didn’t properly acknowledge, Turner’s work. Normal Accidents didn’t cite Turner in 1984 or 1999. Using a methodology involving systematic reading and historical, biographical and thematic theory analysis, a detailed review of Turner’s and Perrow’s backgrounds and publications sheds new light on Turner’s priority and accomplishment, highlighting substantial similarities as well as clear differences. In a previously unpublished letter, Perrow confirmed reading Man-made Disasters while writing Normal Accidents. Turner became better known after a 1997 second edition but under-acknowledgment issues continued. Ethical citation and potential reasons for under-acknowledgment are discussed. It is concluded that Turner’s foundational importance for safety science should be better recognised.

We survey SoTA open-domain conversational AI models with the purpose of presenting the prevailing challenges that still exist to spur future research. In addition, we provide statistics on the gender of conversational AI in order to guide the ethics discussion surrounding the issue. Open-domain conversational AI are known to have several challenges, including bland responses and performance degradation when prompted with figurative language, among others. First, we provide some background by discussing some topics of interest in conversational AI. We then discuss the method applied to the two investigations carried out that make up this study. The first investigation involves a search for recent SoTA open-domain conversational AI models while the second involves the search for 100 conversational AI to assess their gender. Results of the survey show that progress has been made with recent SoTA conversational AI, but there are still persistent challenges that need to be solved, and the female gender is more common than the male for conversational AI. One main take-away is that hybrid models of conversational AI offer more advantages than any single architecture. The key contributions of this survey are 1) the identification of prevailing challenges in SoTA open-domain conversational AI, 2) the unusual discussion about open-domain conversational AI for low-resource languages, and 3) the discussion about the ethics surrounding the gender of conversational AI.

Of the manifold concepts in drug discovery and design, covalent drugs have re-emerged as one of the most promising over the past 20-or so years. All such drugs harness the ability of a covalent bond to drive an interaction between a target biomolecule, typically a protein, and a small molecule. Formation of a covalent bond necessarily prolongs target engagement, opening avenues to targeting shallower binding sites, protein complexes, and other difficult to drug manifolds, amongst other virtues. This opinion piece discusses frameworks around which to develop covalent drugs. Our argument, based on results from our research program on natural electrophile signaling, is that targeting specific residues innately involved in native signaling programs are ideally poised to be targeted by covalent drugs. We outline ways to identify electrophile-sensing residues, and discuss how studying ramifications of innate signaling by endogenous molecules can provide a means to predict drug mechanism and function and assess on- versus off-target behaviors.

Consumer demands for new sensory experiences have driven the research of unconventional yeasts in beer. While much research exists on the use of various common Saccharomyces cerevisiae strains as well as non-Saccharomyces yeasts, there exists a gap in knowledge regarding other non-cerevisiae Saccharomyces species in the fermentation of beer, outside that of S. pastorianus. Here, five distinct species of Saccharomyces from the UC Davis Phaff Yeast Culture Collection, as well as one interspecies hybrid from Fermentis, were chosen to ferment 40 L pilot scale beers. S. kudriavzevii, S. mikatae, S. paradoxus, S. bayanus, and S. uvarum yeasts were fermented in duplicate, with one fermenter in each pair receiving 10 g/L dry-hop during fermentation. Analytical measurements were made each day of fermentation and compared to controls of SafAle US-05 and SafLager W 34/70 for commercial brewing parameters of interest. Finished beers were also analyzed for aroma, taste, and mouthfeel to determine the flavor of each yeast as it pertains to brewing potential. All beers exhibited spicy characteristics, likely from the presence of phenols; dry-hopping increased fruit notes while also increasing perceived bitterness and astringency. All of the species in this study displayed great brewing potential, and might be an ideal addition to beer depending on a brewery’s desire to experiment with flavor and willingness to bring a new yeast into their production environment

Across the global construction industry, fatalities continue to occur from high-risk activities where the risk controls have been defined, however were unreliable. In the mining industry, Critical Control Risk Management has provided positive results in reducing major accidents, which raises the question, could the Critical Control approach reduce the fatality rate in the construction industry? This study analysed 10 years of serious and fatal incident investigation reports from four international construction companies to i) assess the reliability of their Critical Controls (CCs) and ii) assess the factors which affect the reliability of CCs. The results show the reliability of CCs, measured by implementation and effectiveness, averaged just 42%. Human performance factors including risk identification, decision-making and competency together with supervision, job planning, communication organisational factors were identified as affecting the reliability of CCs. The study used bow-tie diagrams with real event data to find the actual CC effectiveness. This gave actionable findings directly related to individual CCs enabling the participating organization to focus resources on improving specific verification processes. The results confirm the applicability of CCs for the Major Accident Event hazards analyzed and highlights further review is required of the factors which need to be considered when implementing a CC program. This paper details our methodology and results, to assist others apply CCs as a risk management tool.

The theory of one-photon ionization and two-photon above-threshold ionization is formulated for applications to heavy atoms in attosecond science using the Dirac-Fock formalism. A direct comparison of the Wigner-Smith-Eisenbud delays for photoionization is made with delays from the Reconstruction of Attosecond Beating By Interference of Two-photon Transitions (RABBIT) method. Photoionization by an attosecond pulse train, consisting of monochromatic fields in the extreme ultraviolet range, is computed with many-body effects at the level of the Relativistic Random Phase Approximation (RRPA). Subsequent absorption and emission processes of infrared laser photons in RABBIT are evaluated using static ionic potentials as well as asymptotic properties of relativistic Coulomb functions. As expected, light elements, such as Argon, show negligible relativistic effects, while heavier elements, such a Krypton and Xenon, exhibit delays that depend on the fine-structure of the ionic target. The relativistic effects are notable close to ionization thresholds and Cooper minima with differences in fine-structure delays predicted to be as large as tens of attoseconds. The separability of relativistic RABBIT delays into a Wigner-Smith-Eisenbud delay and a universal continuum--continuum delay is studied with reasonable separability found for photoelectrons emitted along the laser polarization axis in agreement with prior non-relativistic results.

The reliability analysis allows to estimate the system's probability of detecting and identifying outlier. Failure to identify an outlier can jeopardise the reliability level of a system. Due to its importance, outliers must be appropriately treated to ensure the normal operation of a system. The system models are usually developed from certain constraints. Constraints play a central role in model precision and validity. In this work, we present a detailed optical investigation of the effects of the hard and soft constraints on the reliability of a measurement system model. Hard constraints represent a case in which there exist known functional relations between the unknown model parameters, whereas the soft constraints are employed for the case where such functional relations can slightly be violated depending on their uncertainty. The results highlighted that the success rate of identifying an outlier for the case of hard constraints is larger than soft constraints. This suggested that hard constraints should be used in the stage of pre-processing data for the purpose of identifying and removing possible outlying measurements. After identifying and removing possible outliers, one should set up the soft constraints to propagate the uncertainties of the constraints during the data processing. This recommendation is valid for outlier detection and identification purpose.

The Brazilian livestock is predominantly extensive, with approximately 90% of the production being sustained on pasture, which occupies around 20% of the territory. In the current climate change scenario and where cropland is becoming a limited resource, there is a growing need for a more efficient land use and occupation. It is estimated that more than half of the Brazilian pastures have some level of degradation; however there is still no mapping of the quality of pastures on a national scale. In this study, we mapped and evaluated the spatio-temporal dynamics of pasture quality in Brazil, between 2010 and 2018, considering three classes of degradation: Absent (D0), Intermediate (D1), and Severe (D2). There was no variation in the total area occupied by pastures in the evaluated period, in spite of the accentuated spatial dynamics, with a retraction in the center-south and expansion to the north, over areas of ​​native vegetation. The percentage of non-degraded pastures increased ~12%, due to the recovery of degraded areas and the emergence of new pasture areas as a result of the prevailing spatial dynamics. However, about 44 Mha of the pasture area is currently severely degraded. The dynamics in pasture quality were not homogeneous in property size classes. We observed that in the approximately 2.68 million properties with livestock activity, the proportion with quality gains was twice as low in small properties compared to large ones, and the proportion with losses was three times greater, showing an increase in inequality between properties with more and less resources (large and small, respectively). The areas occupied by pastures in Brazil present an unique opportunity to increase livestock production and make available areas for agriculture, without the need for new deforestation in the coming decades.

Significance: Electrophile signaling is coming into focus as a bona fide cell signaling mechanism. The electrophilic regulation occurs typically through a sensing event (i.e., labeling of a protein) and a signaling event (the labeling event having an effect of the proteins activity, association, etc.). Recent advances: Herein, we focus on the first step of this process, electrophile sensing. Electrophile sensing is typically a deceptively simple reaction between the thiol of a protein-cysteine, of which there are around 200,000 in the human proteome, and a Michael acceptor, of which there are numerous flavors, including enals and enones. Recent data overall paint a picture that despite being a simple chemical reaction, electrophile sensing is a discerning process, showing labeling preferences that are often not in line with reactivity of the electrophile. Critical issues: With a view to trying to decide what brings about highly electrophile-reactive protein-cysteines, and how reactive these sensors may be, we discuss aspects of the thermodynamics and kinetics of covalent/non-covalent binding. Data made available by several laboratories indicate that it is likely that specific proteins exhibit highly stereo- and chemoselective electrophile sensing, which we take as good evidence for recognition between the electrophile and the protein prior to forming a covalent bond. Future directions: We propose experiments that could help us gain a better and more quantitative understanding of the mechanisms through which sensing comes about. We further extoll the importance of performing more detailed experiments on labeling and trying to standardize the way we assess protein-specific electrophile sensing.We propose experiments that could help us gain a better and more quantitative understanding of the mechanisms through which sensing comes about. We further extoll the importance of performing more detailed experiments on labeling and trying to standardize the way we assess protein-specific electrophile sensing.

Performance of the overhead squat may affect golf swing mechanics associated with golf-related low back pain. This study investigates the difference in lumbar kinematics and joint loads during the golf downswing between golfers with different overhead squat abilities. Based on the per-formance of the overhead squat test, 21 golfers aged 18 to 30 years were divided into the highest-scoring group (HS, N=10, 1.61 ± 0.05 cm, and 68.06 ± 13.67 kg) and lowest-scoring group (LS, N=11, 1.68 ± 0.10 cm, and 75.00 ± 14.37 kg). Data collection used a motion analysis system, two force plates, and TrackMan. OpenSim software was used to simulate the joint loads for each lum-bar joint. An independent t-test was used for statistical analysis. Compared to golfers demonstrat-ing limitations in the overhead squat test, golfers with better performance in the overhead squat test demonstrated significantly greater angular extension displacement on the sagittal plane, smaller lumbar extension angular velocity, and smaller L4-S1 joint shear force. Consequently, the overhead squat test is found to be a useful index to reflect lumbar kinematics and joint loading patterns during the downswing, and provides a good training guide reference for reducing the risk of a golf-related low back injury

In this paper we evaluate the effects of hard and soft constraints on the Iterative Data Snooping (IDS), an iterative outlier elimination procedure. Here, the measurements of a levelling geodetic network were classified according to the local redundancy and maximum absolute correlation between the outlier test statistics, referred to as clusters. We highlight that the larger the relaxation of the constraints, the higher the sensitivity indicators MDB (Minimal Detectable Bias) and MIB (Minimal Identifiable Bias) for both the clustering of measurements and the clustering of constraints. There are circumstances that increase the family-wise error rate (FWE) of the test statistics, increase the performance of the IDS. Under a scenario of soft constraints, one should set out at least three soft constraints in order to identify an outlier in the constraints. In general, hard constraints should be used in the stage of pre-processing data for the purpose of identifying and removing possible outlying measurements. In that process, one should opt to set out the redundant hard constraints. After identifying and removing possible outliers, the soft constraints should be employed to propagate their uncertainties to the model parameters during the process of least-squares estimation.

Our bodies produce a host of electrophilic species that can label specific endogenous proteins in cells. The signaling roles of these molecules are underactive debate. However, in our opinion it is becoming increasingly likely that electrophiles can rewire cellular signaling processes at endogenous levels. Attention is turning more to understanding how nuanced electrophile signaling in cells is. In this perspective, we describe recent work from our laboratory that has started to inform on different levels of context-specific regulation of proteins by electrophiles. We discuss the relevance of these data to the field, and to the broader application of electrophile signaling to precision medicine development, beyond the traditional views of their pleiotropic cytotoxic roles.

Objective: Elucidate the main clinical aspects of the CANOMAD spectrum. Methods: Bibliographical review trough databases (PubMed, Google Scholar, Orphanet, Oxford Academic) of articles from 1985 (1) to 2019 and later selection of the most applicable of the above, in order to construct a non-systematic review. Conclusion: CANOMAD is a chronic-ataxic autoimmune neuropathy associated with IgM monoclonal gammopathy. The correct diagnosis of this rare and multi-faceted disease will help optimal treatment.

The COVID-19 pandemic has been challenging for society, especially for those residing in long-term care facilities (LTCF). This study aimed to describe rates of infection, hospitalization, and death due to COVID-19 among older people and staff of LTCF in a state of Southeastern Brazil and identify strategies to prevent and control the disease spread. This cross-sectional study was conducted with 164 LTCF (6,017 older people). Among the studied LTCF, 48.7% confirmed COVID-19 infection in older people, resulting in 39.6% hospitalization and 32.3% death among infected. Moreover, 68.9% of LTCF confirmed COVID-19 infection in the staff, with 7.3% hospitalization and 1.2% death. Preventive measures were identified and classified as organizational, infrastructure, hygiene items and personal protective equipment, and staff training against COVID-19. These measures showed strategies and barriers experienced in the daily routine of LTCF during the pandemic. LTCF in Brazil experienced challenges similar to observed worldwide.

The present study aimed to evaluate the technical feasibility of using a calcined aggregate with mining residue in different pavement layers, including base, sub-base, and wearing course. For this purpose, the physical characterization of the residue and clay was performed, as well as the production of calcined aggregates at temperatures ranging from 800ºC to 1100ºC. Additionally, the suitability of these aggregates in pavement layers was assessed, considering the current standards. The physical results characterization indicated that the studied clay is suitable for manufacturing calcined clay aggregates since the particle size distribution showed ceramic potential - according to the Winkler diagram - and presented a plasticity index (PI) higher than 15%. In the tests of boiling-induced mass loss and unit mass, the values obtained were within the limits established by the standards, being lower than 10% and 0.88 g/cm3, respectively. Regarding the abrasion loss test, the M1100 aggregate showed "Los Angeles" abrasion values lower than the limit established by the standard, demonstrating its potential as an artificial aggregate in pavement applications.

In this paper, we present the idea of Self Supervised learning on the Shape Completion and Classification of point clouds. Most 3D shape completion pipelines utilize autoencoders to extract features from point clouds used in downstream tasks such as Classification, Segmentation, Detection, and other related applications. Our idea is to add Contrastive Learning into Auto-Encoders to learn both global and local feature representations of point clouds. We use a combination of Triplet Loss and Chamfer distance to learn global and local feature representations. To evaluate the performance of embeddings for Classification, we utilize the PointNet classifier. We also extend the number of classes to evaluate our model from 4 to 10 to show the generalization ability of learned features. Based on our results, embedding generated from the Contrastive autoencoder enhances Shape Completion and Classification performance from 84.2% to 84.9% of point clouds achieving the state-of-the-art results with 10 classes.

Meta-analysis has increasingly been used to synthesize the ecosystem services literature, with some testing of the use of such analyses to transfer benefits. These are typically based on local primary studies. However, meta-analyses associated with ecosystem services are a potentially powerful tool for transferring benefits, especially for environmental assets for which no primary studies are available. In this study we use the Ecosystem Service Valuation Database (ESVD), which brings together 1350 value estimates from more than 320 studies around the world, to estimate meta-regression functions for provisioning, regulating &amp; maintenance and cultural ecosystem services across 12 biomes. We tested the reliability of these meta-regression functions and found that even using variables with high explanatory power, transfer errors could still be large. We show that meta-analytic transfer performs better than simple value transfer and, in addition, that local meta-analytical transfer (i.e. based on local explanatory variable values) provides more reliable estimates than global meta-analytical transfer (i.e. based on mean global explanatory variable values). Thus, we conclude that when taking into account the characteristics of the study area under analysis, including explanatory variables such as income, population density and protection status, we can determine the value of ecosystem services with greater accuracy.

Shafts with a stepped shoulder are particularly well known in the field of drive technology. In combination with a form-fit shaft–hub connection, the shaft shoulder fixes the hub on the shaft as well as the absorption of the axial forces. With profiled shafts, there is a notch overlay in the shaft shoulder, involving the shaft shoulder and profile. If the hub is also connected with the profiled shaft, the hub edge acts as an additional notch in the shaft shoulder area. The multiple resulting notches have not previously been part of research activities in the field of innovative trochoidal profile connections. Compared to conventional positive-locking connections, such as the keyway connection or the involute splined shaft profile, the favourable features of trochoidal profiles have only been based on connections with smooth shafts without a shoulder in previous studies. Accordingly, this article addresses the numerical and experimental investigations of trochoidal profile connections with offset shafts for pure torsional loading. Focusing on a hybrid trochoid with four eccentricities and six drivers, a well-founded numerical and experimental investigation was carried out with numerous fatigue tests. In addition, the influence of a shaft shoulder was also demonstrated on simple epi- and hypotrochoidal profiles.

Keap1 is associated with cytoprotective signaling. These roles of Keap1 typically focus on its role as a degrader of the antioxidant response (AR) transcription factor, Nrf2, and the inhibition of this process upon Keap1 labeling by electrophiles. However, work from several laboratories has reemphasized both the important role of Nrf2 binding in negatively regulating AR, and the fact that electrophile Keap1 modification dissociates Nrf2 from Keap1. This model appears to be applicable to other signaling modes regulated by Keap1. Here we use recent data we have derived using experiments in zebrafish and cultured cells to discuss different models of Keap1 regulation.

This study develops a structure for mapping native vegetation in a transition area between Brazilian Cerrado and Atlantic Forest from integrated spatial information from the Sentinel-1 and Sentinel-2 satellites. Most studies use this data separately, however, the integrated use of optical sensors with Synthetic Aperture Radar (SAR) sensors can improve the methodology for classifying land use and land cover (LULC). The fusion of Sentinel-1 and Sentinel-2, for example, can increase the accuracy of mapping algorithms, using complementary information, such as spectral, backscattering, polarimetry, and interferometry. The study area comprises the Lobo Reservoir Hydrographic Basin, which is part of an environmental conservation unit protected by Brazilian law and with significant human development. LULC were classified, using the random forest deep learning algorithm. The classifying attributes were backscatter coefficients, polarimetric decomposition, and interferometric coherence for radar data (Sentinel-1), and optical spectral data, comprising bands in the red edge, near infrared, and shortwave infrared (Sentinel-2). The attributes were evaluated in three settings in which the SAR and optical data were evaluated separately (C1 and C2, respectively) and in an integrated manner (C3). The study found greater accuracy for C3 (96.54%), an improvement of nearly 2% compared to C2 (94.78%) and more than 40% in relation to C1 (55.73%). The classification algorithm encountered significant challenges in identifying wetlandsin C1, but performance improved in C3, enhancing differentiation by stratifying a greater number of classes during training and facilitating visual interpretation during sampling. Accordingly, the use of SAR and optical data becomes an alternative to optimize LULC mapping in tropical regions, due to the limited influence of atmosphere on images in the microwave range.

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.

Objectives: The impact of COVID-19 in metropolitan areas has been extensively studied. The geographic spread to smaller cities is of great concern and may follow hierarchical influence of urban centers. With that in mind, we investigated factors that affect vulnerability of inner municipalities in São Paulo State, Brazil, an area with 24 million inhabitants. Methods: Surveillance data for confirmed COVID-19 cases and admissions for severe acute respiratory disease (SARD) up to April 18^th were recorded for each of 604 municipalities that lay outside São Paulo metropolitan area. Vulnerability was assessed in Multivariable models, including sociodemographic indexes, road distance to the State Capital and the municipalities classification proposed by the Brazilian Institute of Geography and Statistics. Municipalities of great regional relevance were used as reference category for that classification. The outcome of interest for Cox regression was having COVID-cases, with time counting from the first report in São Paulo State. For binomial negative regression models, the outcomes of interest were rates of confirmed COVID-19 cases and admissions for SARD.Results: A total of 198 (32.8%) municipalities had autochthonous COVID-19 cases. In Cox models, affected municipalities were likely to have greater population density (Hazard Ratio[HR] for each 100 inhabitants per square kilometer, 1.07; 95% Confidence Interval [CI], (1.05-1.10)), proportion of inhabitants in urban area (HR, 1.02; 95%CI, 1.00-1.04), higher human development index (HDI, HR for 1%, 1.06; 95%CI, 1.00-1.13) and Gini Index for Inequality of income (HR for 1%, 1.04, 95% CI, 1.00-1.07). On the other hand, distance from the Capital was protective (HR for each 100Km, 0.82; 95%CI, 0.74-0.90). The HR95%[95%CI] also varied negatively according to the categories of influence of major centers (0.41 [0.22-0.77], 0.16 [0.09-0.32], 0.07 [0.03-0.15]). The binomial negative regression models for COVID-19 incidence also detected positive association with population density (Incidence Rate Ratio[IRR], 1.13; 95%CI, 1.07-1.18) and proportion of urban population (IRR, 1.04; 95%CI, 1.01-1.05), protection for cities distant to the Capital (IRR=0.73; 95%CI, 0.68-0.81) and increasing negative association for categories of influence (0.19 [0.09-0.42], 0.07 [0.03-0.15] and 0.03 [0.02-0.08]). Similar findings were detected when we used SARD incidence as outcome.Conclusion: Municipalities with greater population, density and regional influence were more likely to be affected earlier and more intensely by COVID-19. Non-pharmacological measures should be strengthened in those areas of greater risk.

Plant loss in experimental plots occurs occasionally in field experiments with coffee crops. In breeding programmes, such loss can be extremely harmful, especially when the statistical analysis methods used are not consistent with the data generated in the experiments. In this study, we analysed a set of productivity data to determine whether the compensatory effect occurs in coffee crops, analyse the need for correcting the number of failures in experiments, and identify the best stand correction method to use. Productivity data from six harvests of 11 experiments with Coffea arabica plants were used. The experiments were implemented in a randomised block design, with four replications and six plants per plot. The following stand correction methods were evaluated: rule of three, Zuber [1], Vencovsky and Cruz [2]covariance of the average or ideal stands, and Cruz [3] and compared to data without correction adjustments. The most adequate correction methods were chosen based on the existence of genetic variance, selective accuracy, and progeny ordering. The compensatory effect was evident from the analysed data, with stand correction shown to be beneficial in progeny competition experiments. The covariance methods using average or ideal stands presented the best results, followed by the method proposed by Cruz [3]. The rule of three and Zuber [1] methods showed unsatisfactory results and are not recommended for stand correction in progeny competition experiments with coffee crops

Table detection is a preliminary step in extracting reliable information from tables in scanned document images. We present CasTabDetectoRS, a novel end-to-end trainable table detection framework that operates on Cascade Mask R-CNN, including Recursive Feature Pyramid network and Switchable Atrous Convolution in the existing backbone architecture. By utilizing a comparatively lightweight backbone of ResNet-50, this paper demonstrates that superior results are attainable without relying on pre and post-processing methods, heavier backbone networks (ResNet-101, ResNeXt-152), and memory-intensive deformable convolutions. We evaluate the proposed approach on five different publicly available table detection datasets. Our CasTabDetectoRS outperforms the previous state-of-the-art results on four datasets (ICDAR-19, TableBank, UNLV, and Marmot) and accomplishes comparable results on ICDAR-17 POD. Upon comparing with previous state-of-the-art results, we obtain a significant relative error reduction of 56.36%, 20%, 4.5%, and 3.5% on the datasets of ICDAR-19, TableBank, UNLV, and Marmot, respectively. Furthermore, this paper sets a new benchmark by performing exhaustive cross-datasets evaluations to exhibit the generalization capabilities of the proposed method.

3D printing is commonly used to create complex objects at a low cost. It has also been applied in the fabrication of metamaterials and metasurfaces, which alter the propagation path of electromagnetic waves. These structures have diverse applications, including enhancing beam direction, improving antenna gain and signal-to-noise ratio, and creating filters and reflectors. Metasurfaces are cheap to fabricate and their use is expected to boost antenna efficiency in 5G telecommunications and beyond. However, accurately characterizing their profile remains a significant challenge. This paper presents a low-cost fully automated 4-axis instrument for microwave metasurface charac-terization, overcoming limitations of manual methods and offering an efficient and accurate approach. This research represents a significant advancement in microwave metasurface characterization, enabling sophisticated techniques to advance wireless communication technolo-gies, as it is the case of the future 5G and millimeter-wave communication systems. The equipment has an approximate cost of $1550 USD and was able to characterize a metalens with a focal distance of 20 cm designed for signals at 30 GHz. It was possible to create 2D and 3D profiles of the intensity distribution focused by the metalens and extract parameters such as the gain (8.05 dB), 3dB depth of focus (11 cm) and full width at half maximum (2.17 cm). The comparison of the measurements with the diffraction calculations of the metalens showed a very good agreement between the in-tensity distributions and the parameters of the metalens.

Despite a global push in the development and implementation of widespread alternative energy use, significant disparities exist across given nation-states. These disparities, frequently referred to as the local-national gap, reflect both technical and economic factors, as well as the social, political, and ecological gaps between how communities see energy development and national/global policy goals. This dataset is an attempt to bridge the local-national gap regarding solar PV adoption in the state of Georgia (U.S.A.). This dataset is an aggregation of variables from seven different publicly-available sources that was designed to help researchers interested in the context underlying solar adoption on the local scale of governance (e.g. the county level). The SolarView database includes information necessary for informing policymaking activities such as solar installation information, a historical county zip code directory, county-level census data, housing value indexes, renewable energy incentive totals, PV rooftop suitability percentages, and utility rates. As this is a database from multiple sources, incomplete data entries are noted.

Iron-containing nickel sulfides, selenides, and sulfoselenides were synthesized via a simple two-step hydrothermal reaction (temperature 160 °C) for their application as electrocatalysts in the oxygen evolution reaction (OER) in an alkaline solution (1 mol L–1 KOH). The study demonstrated that iron-containing nickel cobalt sulfides and selenides exhibit superior OER performance with lower overpotentials compared to iron-free nickel cobalt sulfide and selenide, which highlights the significant role of iron in enhancing OER nickel cobalt electrocatalysts: Fe0.1Ni1.4Co2.9(S0.87O0.13)4, η50 = 318 mV; Fe0.2Ni1.5Co2.8(S0.9O0.1)4, η50 = 310 mV; Fe0.3Ni1.2Co2.5(S0.9O0.1)4, η50 = 294 mV; Fe0.6Ni1.2Co2.5(S0.83O0.17)4, η50 = 294 mV, Fe0.4Ni0.7Co1.6(Se0.81O0.19)4, η50 = 306 mV compared to Ni1.0Co2.1(S0.9O0.1)4, η50 = 346 mV and Ni0.7Co1.4(Se0.85O0.15)4, η50 = 355 mV (all values at current densities η50 of 50 mA cm–2). Furthermore, the iron-containing nickel cobalt sulfoselenide Fe0.5Ni1.0Co2.0(S0.57Se0.25O0.18)4 displayed exceptional OER performance with η50 = 277 mV, surpassing the benchmark RuO2 electrode with η50 = 299 mV. The superior performance of the sulfoselenide was attributed to its low charge transfer resistance (Rct) of 0.8 Ω at 1.5 V vs. the reversible hydrogen electrode (RHE). Moreover, the sulfoselenide demonstrated remarkable stability, with only a minimal increase in overpotential (η50) from 277 mV to 279 mV after a 20 h chronopotentiometry test. These findings suggest that trimetallic iron, nickel and cobalt sulfide, selenide and especially sulfoselenide materials hold promise as high-performance, cost-effective, and durable electrocatalysts for sustainable OER reactions. This study provides a valuable approach for the development of efficient electrocatalytic materials, contributing to the advancement of renewable energy technologies.

The proposal that the genetic code was formed on the basis of protein synthesis directed by tRNA dimers is reviewed and updated. The tRNAs paired through the anticodon loops are an indication on the process. Dimers are considered mimics of the ribosomes – structures that hold tRNAs together and facilitate the transferase reaction, and of the translation process – anticodons are at the same time codons for each other. The primitive protein synthesis system gets stabilized when the product peptides are able to bind the producers therewith establishing a self-stimulating production cycle. The chronology of amino acid encoding starts with Glycine and Serine, indicating the metabolic support of the Glycine-Serine C1-assimilation pathway, which is also consistent with evidence on origins of bioenergetics mechanisms. Since it is not possible to reach for substrates simpler than C1 and compounds in the identified pathway are apt for generating the other central metabolic routes, it is considered that protein synthesis is the beginning and center of a succession of sink-effective mechanisms that drive the formation and evolution of the metabolic flow system. Plasticity and diversification of proteins construct the cellular system following the orientation given by the flow and implementing it. Nucleic acid monomers participate in bioenergetics and the polymers are conservative memory systems for the synthesis of proteins. Protoplasmic fission is the final sink-effective mechanism, part of cell reproduction, guaranteeing that proteins don’t accumulate to saturation, which would trigger inhibition.

The present research intents to study the evolution of the skin fatty acids and physiological disorders through cold storage in ‘Golden Delicious’ apples treated with 1-MCP and calcium. Harvested fruit were treated with calcium chloride (Ca), 1-MCP (MCP), Ca+MCP or no treatment (control) then subjected to cold storage at 0.5 ºC for 6 months. Fatty acids composition, Malondialdehyde (MDA) and the physiological disorders bitter pit (BP), superficial scald and diffuse skin browning (DSB) were measured at harvest and after storage plus 7 days shelf-life at room temperature ≈22 ºC. Palmitic acid decreased and linoleic acid increased through time, while oleic and stearic acids had few changes. Unsaturated/saturated fatty acids and MDA increased through time, despite Ca and Ca+MCP were related to lower MDA and lower BP and rotten fruit, after cold storage and shelf-life. In those treatments, the unsaturated/saturated fatty acids were higher, mainly due to higher linoleic acid and lower palmitic acids. Further research is needed to clarify the changes in membrane properties and the effect of some treatments in response to chilling injury through storage.

The accurate prediction of molecular properties such as lipophilicity and aqueous solubility are of great importance and pose challenges in several stages of the drug discovery pipeline. Machine learning methods like graph-based neural networks (GNNs) have shown exceptionally good performance in predicting these properties. In this work, we introduce a novel GNN architecture, called directed edge graph isomorphism network (D-GIN). It is composed of two distinct sub-architectures (D-MPNN, GIN) and achieves an improvement in accuracy over its sub-architectures employing various learning, and featurization strategies. We argue that combining models with different key aspects help make graph neural networks deeper and simultaneously increase their predictive power. Furthermore, we address current limitations in assessment of deep-learning models, namely, comparison of single training run performance metrics, and offer a more robust solution.

Lambert-Eaton myasthenic syndrome is a primary autoimmune or paraneoplastic neuromuscular disorder, which causes muscle weakness, areflexia and autonomic disorders through the production of antibodies to voltage-gated calcium channels. Diagnosis may be challenging, yet at the same time extremely important, allowing the detection of a possible underlying malignancy, in cases of paraneoplastic presentation. Some antibodies have good sensitivity and specificity for malignancy and are also discussed. Although most of times being correlated to small cell lung cancer, other types of tumors may be also found in the paraneoplastic syndrome. Misdiagnosis with Myasthenia Gravis may occur and differences between these two disorders are discussed. Therapy choice may vary from each patient depending on drug response and the situation in which the patient is encounter. Overall, the present paper brings a review of Lambert-Eaton, involving the diagnosis, as well as, the pathophysiology, differential diagnosis, tumor investigation and treatment. Also, a brief overview through guidance on therapy during the Corona Virus Disease 2019 pandemic is analyzed.

The aim was to assess the precision and accuracy of cephalometric analyses performed by artificial intelligence (AI) with and without human augmentation. Four dental professionals with varying experience levels and AI identified 31 landmarks on 30 cephalometric radiographs twice. These landmarks were re-identified by all examiners with the aid of AI. Precision and accuracy were assessed by using intraclass correlation coefficients (ICCs) and mean absolute errors (MAEs). AI revealed the highest precision with a mean ICC of 0.97, while the dental student had the lowest (mean ICC: 0.77). AI/human augmentation method significantly improved precision of the orthodontist, resident, dentist, and dental student by 3.26%, 2.17%, 19.75%, and 23.38%, respectively. The orthodontist demonstrated the highest accuracy with a MAE of 1.57 mm/˚. AI/human augmentation method improved the accuracy of the orthodontist, resident, dentist, and dental student by 12.74%, 19.10%, 35.69%, and 33.96%, respectively. AI demonstrated excellent precision and good accuracy in automated cephalometric analysis. The precision and accuracy of the examiners with the aid of AI improved by 10.47% and 27.27%, respectively. The AI/human augmentation method significantly improved the precision and accuracy of less experienced dental professionals to that of an experienced orthodontist.

Recent progress in deep learning has led to accurate and efficient generic object detection networks. Training of highly reliable models depends on large datasets with highly textured and rich images. However, in real-world scenarios, the performance of the generic object detection system decreases when (i) occlusions hide the objects, (ii) objects are present in low-light images, or (iii) they are merged with background information. In this paper, we refer to all these situations as challenging environments. With the recent rapid development in generic object detection algorithms, notable progress has been observed in the field of object detection in challenging environments. However, there is no consolidated reference to cover state-of-the-art in this domain. To the best of our knowledge, this paper presents the first comprehensive overview, covering recent approaches that have tackled the problem of object detection in challenging environments. Furthermore, we present the quantitative and qualitative performance analysis of these approaches and discuss the currently available challenging datasets. Moreover, this paper investigates the performance of current state-of-the-art generic object detection algorithms by benchmarking results on the three well-known challenging datasets. Finally, we highlight several current shortcomings and outline future directions.

This paper introduces a new adaptation of the enthalpic lattice Boltzmann method (LBM) tailored to simulate the intricate dynamics of conjugate heat transfer in non-homogeneous media, showcasing considerable potential for enhancing heat exchanger designs. This approach expands upon the conventional enthalpic LBM framework by seamlessly incorporating tailored source terms, enabling precise representation of local and transient variations in the medium’s thermophysical properties. The resulting LBM model comprehensively captures the energy conservation equation, with exceptions made only for flow compressibility and viscous dissipation, thereby significantly augmenting its versatility in analyzing heat exchanger configurations. Verification tests, comprising assessments of both transient and steady-state solutions, unequivocally validate the accuracy of the proposed model, further bolstering its reliability for analyzing heat exchange processes within intricate heat exchanger geometries. To demonstrate its efficacy, simulations of conjugate heat transfer processes involving fluid natural convection within structured cavities were performed, imposing both Dirichlet and Neumann boundary conditions to emulate scenarios encountered in practical heat exchanger operations. The findings yield compelling insights, particularly in the transient regime, revealing the beneficial impact of structured cavities on enhancing heat transfer processes. These insights inform potential design optimizations for heat exchangers. The results emphasize the potential of the modified enthalpic LBM approach to elucidate complex heat transfer phenomena in non-homogeneous media and structured geometries, offering valuable implications for heat exchanger engineering and optimization.

One of the main challenges in geodetic deformation analysis is to infer whether the geometry of some engineering structures or zones of natural hazards has changed from their initial state or not. The pillar that supports such an analysis is tightly based on the fundamentals of statistical hypothesis testing. The null hypothesis model indicates that no displacement has occurred. It is tested against a class of alternative models, which stipulate different displacement patterns. In this contribution, we present an innovative geodetic displacement detection which integrates combinatorial analysis and likelihood ratio tests into a sequential procedure for the case where the differences between observations of two epochs are in play. This framework is applied and investigated to two test scenarios: a synthetic and a real simulated trilateration network. From a statistical point of view, our approach is rigorous, because the alternative model can identify simultaneously more than one unstable point. In addition, the relationship between the unknown parameters and the observations is always linear, even if the problem manifests itself as non-linear. Consequently, we avoid a potential loss of statistical test power due to the model linearization. In addition, the proposed method controls the false positive rate efficiently. One of the problems that arise here is also related to the selection of the maximum number of points to be considered in the test procedure ( ). Here, we provide an innovative methodology based on rank computation of the design matrices to define , which can even be extended to the problem of outlier detection. Determining avoids the problem of having non-separable models in identifying unstable points. The algorithms and data are available in the repository.

The calibration of three-dimensional (3D) coordinates in augmented reality (AR) systems is a complex activity. It involves the recognition of environmental characteristics and technology that models the 3D space of the device, determining its position and orientation. In the industrial environment, it is common for AR applications to cover large spaces, making it difficult to maintain attributes such as precision and accuracy. The set of sensors and mapping algorithms available in HoloLens stimulate the development of virtual reality (VR) applications, in particular localization techniques. This study proposes calibration models of the 3D coordinates of the HoloLens for indoor industrial environments. The performance of tests in a relevant environment provides data necessary to evaluate the performance of the proposed models in terms of precision and accuracy in determining point coordinates in the study environment. The results show improvements in determining the axes that define the 3D space, with a direct influence on the position of the points observed in the experiment

An iterative outlier elimination procedure based on hypothesis testing, commonly known as Iterative Data Snooping (IDS) among geodesists, is often used for the quality control of the modern measurement systems in geodesy and surveying. The test statistic associated with IDS is the extreme normalised least-squares residual. It is well-known in the literature that critical values (quantile values) of such a test statistic cannot be derived from well-known test distributions, but must be computed numerically by means of Monte Carlo. This paper provides the first results about Monte Carlo-based critical value inserted to different scenarios of correlation between the outlier statistics. From the Monte Carlo evaluation, we compute the probabilities of correct identification, missed detection, wrong exclusion, overidentifications and statistical overlap associated with IDS in the presence of a single outlier. Based on such probability levels we obtain the Minimal Detectable Bias (MDB) and Minimal Identifiable Bias (MIB) for the case where IDS is in play. MDB and MIB are sensitivity indicators for outlier detection and identification, respectively. The results show that there are circumstances that the larger the Type I decision error (smaller critical value), the higher the rates of outlier detection, but the lower the rates of outlier identification. For that case, the larger the Type I Error, the larger the ratio between MIB and MDB. We also highlight that an outlier becomes identifiable when the contribution of the measures to the wrong exclusion rate decline simultaneously. In that case, we verify that the effect of the correlation between the outlier statistics on the wrong exclusion rates becomes insignificant from a certain outlier magnitude, which increases the probability of identification.

Photoacoustic spectroscopy allows the identification of specific molecules in gases. We evaluate the spectral resolution and detection limits for a PAS system in the broadband infrared wavelength region 3270 nm ≲ λ ≲ 3530 nm driven by a continuous wave optical parametric oscillator with P ≈ 1.26 W by measuring the absorption of diluted propane, ethane and methane test gases at low concentrations c ~ 100 ppm for ~1350 discrete wavelengths λ_i. The resulting spectra I_PAS(λ_i) were compared to the high resolution cross section data σ_FTIR obtained by Fourier Transform Infrared Spectroscopy from the HITRAN database. Deviations as little as 7.1(6)% for propane, 8.7(11)% for ethane and 15.0(14)% for methane with regard to the average uncertainty between I_PAS(λ_i) and the expected reference values based on σ_FTIR were recorded. The wavelengths λ_res of the characteristic absorption lines can be pinpointed with a high relative accuracy <5 × 10⁻⁵ corresponding to a resolution of λ_res ~ 0.16 nm. Detection limits range between 7.1 ppb (ethane) to 13.6 ppb (methane) coinciding with high experimental signal-to-noise ratios. Moreover, using EUREQA, an artificial intelligence program, simulated mixed gas samples at low limits of detection could be deconvoluted. These results justify a further development of PAS technology to support, e.g., biomedical research.

In a wide range of lymphoid neoplasms, the process of malignant transformation is associated to somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in non-Hodgkin B-cell lymphoma. Furthermore, we aim to present in close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have greatest potential to improve the prognosis of lymphoma patients.

Self-assembling peptide P11-4 is amphiphilic and pH-triggered with demonstrated effectivity repairing early carious lesions in enamel. However, P11-4 effects on dentin biomineralization and repair remain unexplored. Thus, cytocompatibility and effectiveness of P11-4 inducing mineralization and migration of odontoblast-like cells (MDPC-23) were investigated. MDPC-23 were seeded in contact with P11-4(0.5µg/ml and 1µg/ml), Dentin Matrix Protein 1 (DMP1 0.5µg/ml and 1 µg/ml) or Calcium hydroxide (Ca(OH)2 100µg/ml) solutions. Cytotoxicity was verified using MTT (n=6/group). Mineralization was tested using Alizarin Red (n=4/group). Cell migration was assessed by light microscopy (n=2/group). MTT and Alizarin Red data were compared using Krus-kal-Wallis and Mann-Whitney (α=0.05). P11-4 (0.5µg/ml and 1µg/ml) and DMP1 (0.5µg/ml and 1µg/ml) presented the highest cytocompatibility; Ca(OH)2 presented the lowest. DMP1 1µg/ml exhibited the highest mineralization ability, with no difference to P11-4 1µg/ml. Ca(OH)2 presented lower values than DMP1 1µg/ml (p<0.05), but similar to P11-4 1µg/ml. P11-4 and DMP1 at 0.5 µg/ml showed induced less mineralization than P11-4 and DMP1 at 1µg/ml (p<0.05), with no difference to Ca(OH)2. All materials stimulated cell migration, however, lower concentrations of DMP1 and P11-4 provided better results. P11-4 is cytocompatible, induces mineralization and MDPC-23 migration like DMP1. P11-4 could be an alternative for dentin mineralization and tooth repair.

A 35-year-old man with a late-onset combined immunodeficiency (LOCID) variant of common variable immunodeficiency, severe plaque psoriasis, psoriatic arthritis, and Crohn's disease attended Regional Hospital of Presidente Prudente and HC-FMUSP, São Paulo, Brazil. Anti-IL-12/IL-23 (ustekinumab) monoclonal antibody was prescribed due to failure of other treatments (phototherapy, oral acitretin) for psoriasis and Psoriasis Area Severity Index &lt;10. We evaluated the impact of ustekinumab, a potent immunosuppressor, on the risk of infectious diseases in this patient followed for 8 years. Four quarterly doses of ustekinumab 90 mg and human immunoglobulin replacement (10,000 mg at 28-day intervals) were administered. Immunophenotyping, culture of lymphocytes, genetic sequencing, and whole exome sequencing were performed to investigate the primary immunodeficiency. Normal lymphocyte proliferation, absence of pathogenic variants in the genes analyzed and no clinically significant variants were detected in the whole exome. The main infections included chronic sinusitis, tonsillitis, fungal and bacterial otitis, gastroenteritis, and community-acquired pneumonia. The patient was infected with COVID-19, dengue (twice), and influenza and was hospitalized three times for intravenous antibiotic therapy. Ustekinumab did not influence susceptibility to severe infections and significantly improved psoriasis, psoriatic arthritis, and Crohn's disease in a patient with LOCID.

Background: The association of age at onset of CRC and prevalence of KRAS G12C mutation is unclear; Methods: Retrospective multicenter study evaluating metastatic CRC patients from January 2019 to July 2023 treated at Oncoclinicas units, tested for tissue-based KRAS/NRAS and BRAF mutations in a centralized genomics lab. Mismatch repair (MMR) status was retrieved from different labs and electronic medical records, as were patient demographics (age, gender) and tumor sidedness. Chi-square test was used to examine the association between clinical and molecular variables, with p value <0.05 being statistically significant; Results: A total of 858 cases were included. The median age was 63.7 years (range 22-95) and 17.4% were less than 50 years old at diagnosis of metastatic CRC. Male patients represented 50.3% of the population. Sidedness distribution was left-side 59.2%, right-side 36.8% and not specified 4%. Prevalence of KRAS mutation was 49.4% and NRAS mutation 3.9%. Among KRAS mutated tumors, the most common variants were G12V (27.6%) and G12D (23.5%), while KRAS G12C was less frequent (6.4%), which represented 3.1% of the overall population. BRAF mutant cases were 7.3%, most commonly V600E. Only 5 (<1%) non-V600E mutations were detected. MSI-high or dMMR was present in 14 cases (1.6%). In the age-stratified analysis, left-sidedness (p<0.001) and KRAS G12C mutation (p=0.046) were associated with younger age (<50 years). In the sidedness-stratified analysis, BRAF mutation (p=0.001) and MSI-high/dMMR status (p=0.009), were more common in right-sided tumors; Conclusions: Our data suggest that KRAS G12C mutations are more frequent in early-onset metastatic CRC. To the best of our knowledge, this is the largest cohort in the Latin American population with mCRC reporting RAS, BRAF and MSI/dMMR status.