According to the World Health Organization, cardiovascular disease (CVD) is the leading cause of death among women worldwide, yet its magnitude is often underestimated. Biological and gender differences affect health, diagnosis, and healthcare in numerous ways. The lack of sex and gender awareness in health research and healthcare is an ongoing issue and affects not only research, but also treatment and outcomes. The importance of recognising the impact of both sex and gender on health and of knowing the differences between the two in healthcare is beginning to gain ground. There is more appreciation of the role that biological differences (sex) and sociocultural power structures (gender) have, and both sex and gender affect health behaviour, the development of diseases, their diagnosis, management, and long-term effects of an illness. An important issue is the knowledge and awareness of women about vascular diseases. The risk of cardiovascular events is drastically underestimated by women themselves, as well as by those around them. The purpose of this review is to draw attention to improving the medical care and treatment of women with vascular diseases.

When integrating data from different sources, there are problems of synonymy, different languages, concepts of different granularity. This paper proposes a simple but effective approach to evaluate the semantic similarity of short texts, especially keywords. The method is capable of matching keywords from different sources and languages by exploiting transformers and WordNet-based methods. Key features of the approach include its unsupervised pipeline, mitigation of the lack of context in keywords, scalability for large archives, support for multiple languages and real-world scenarios adaptation capabilities. The work aims to provide a versatile tool for different cultural heritage archives without requiring complex customization. The objectives of the paper are to explore different approaches to identifying similarities in 1- or n-gram tags, to evaluate and compare different pre-trained language models, and to define integrated methods to overcome limitations. Tests to validate the approach have been conducted using the QueryLab portal, a search engine for cultural heritage archives, to evaluate the proposed pipeline.

This paper presents a discrete compartmental Susceptible-Exposed-Infected-Recovered/Dead (SEIR/D) model to address the expansion of Covid-19 pandemic. When time passes, the status of the cells is determined by binary rules that update following both a neighbourhood and a delay pattern. The model assumes the environmental parameters have a crucial impact on the expansion of the disease so a grid is assigned to each parameter to model the single effect caused by this parameter. The expansion is then the weighted sum of all the grids. This proposal shows how the grid architecture, along with an update rule and a neighbourhood pattern is a valuable tool to model the pandemic expansion. This model has already been analyzed in previous works and compared with the corresponding continuous models solved by ordinary differential equations (ODE), coming to find the homologous parameters between both approaches. Thus, it has been possible to prove that the combination neighborhood-update rule is responsible for the rate of expansion and recovering/death of the illness. The delays (between Susceptible and Asymptomatic, Asymptomatic and Infected, Infected and Recovered/Dead) may have a crucial impact on both the peak of Infected and the Recovery/Death rate. This theoretical model has been successfully tested in the case of the dissemination of information through mobile social networks and in the case of plant pests.

Oral mucositis is most frequently a toxic effect of chemotherapeutic and/or radiotherapeutic treatment, resulting from complex multifaceted biological events involving DNA damage. The clinical manifestations have a negative impact on the life quality of cancer patients. Preventive measures and curative treatment of mucositis are still not well established. The glycine has anti-inflammatory, immunomodulatory and cytoprotective actions, being a potential therapeutic in mucositis. The objective was to evaluate the effects of glycine on the expression of collagen and growth factors, platelet and epidermal in oral mucositis. The mucositis of which was induced by the protocol of Sonis. 40 hamsters were used, divided into two groups: Group I- control; Group II- supplemented with 5% intraperitoneal glycine, 2,0 mg/g diluted in hepes. Histopathological sections were used to perform the immune-histochemical method, the evaluation collagen expression and the growth factors: EGF and PDGF. It was observed that the group supplemented with glycine higher amounts of collagen expression and predominance type of collagen I. The glycine group presented lower immunoexpression of the growth factors, EGF and PDGF. The group supplemented with glycine showed a marked healing process of the oral mucosite, demonstrated by the predominance of collagen type I and reduction of growth factors, EGF and PDGF.

We have studied the very large amount of literary works written by the Italian mystic Maria Valtorta to assess similarities and differences in her writings because she claims that most of them are due to mystical visions. We have used mathematical and statistical tools developed for specifically studying deep linguistic aspects of texts. The general trend indicates that the literary works explicitly attributable to Maria Valtorta differ significantly from her other literary works, that she claims are attributable to the alleged characters Jesus and Mary. Mathematically, they seem to have been written by different authors. The comparison with the Italian literature is very striking. A single author, namely Maria Valtorta, seems to be able to write texts so diverse to cover the entire mathematical range (suitable defined) of the Italian literature of seven centuries.

Extensive evidence indicates that activation of P2X7 receptor (P2X7R), an ATP-gated ion channel highly expressed in immune and brain cells, is strictly associated with the release of extracellular vesicles. Through this process, P2X7R-expressing cells regulate non-classical protein secretion and transfer bioactive components to other cells, including misfolded proteins, participating in inflammatory and neurodegenerative diseases. In this review, we summarize and discuss the studies addressing the impact of P2X7R activation on extracellular vesicle release and their activities.

A transport process was studied from an aqueous solution containing oxalic acid and 100 mg/L Ge using a flat sheet supported liquid membrane (FSSLM) system. Cyanex 923 immobilized in a polytetrafluoroethylene membrane was employed as a carrier. The solution chemistry and related diagrams were applied to study the transport of germanium. The effectual parameters such as oxalic acid, carrier concentration, and strip reagent composition were evaluated in this study. Based on the results, the oxalic acid concentration of 0.075 mol/L and the carrier concentration of 20 %v/v were the condition in which the efficient germanium transport occurred. Among strip reagents, NaOH (0.04-0.1 mol/L) had the best efficiency to transport germanium through the SLM system. Furthermore, the permeation model was obtained to calculate the mass transfer resistances of the membrane (Δ_m) and feed (Δ_f) phases. According to the results, the values of 1 and 1345 s/cm were evaluated for Δ_m and Δ_f, respectively.

The intensive variables, geochemical, mineralogical and petrogenetic constraints of the Iberian rare metal granites, many of them unknown, are presented. It allows to distinguish two main granitic types with contrasting characteristics: Nb-Ta-rich granites and Nb-Ta-poor granites. The former have lower emplacement temperatures, higher water contents and probably lower emplacement pressures than Nb-Ta-poor granites. Nb-Ta-rich granites also have higher fluoride contents, strong fractionation into twin pairs such as Zr-Hf, Y-Ho and Nb-Ta, and an abundant, probably exsolved, fluid phase, which is not or not as evident in Nb-Ta-poor granites, probably in part because the Nb-Ta-rich granites reach their solidus later (about 550 ºC). The geochemical signature of the Iberian rare metal granites follows the trends of mainly two-mica granites and P-rich cordierite granites, but also of granodiorites and even type I granites, suggesting that the rare metal granites may have different parental magmas. Thermodynamic modeling shows that many of the geochemical characteristics of the RMGs can be explained by a process of extreme differentiation, while others cannot, e.g. Na evolution. In terms of ore deposition, white mica plays a very important role in explaining the variation of the Ta/Nb ratio, although the latter could also be controlled by late Nb-Ta oxides crystallization and even by acidic fluids that remove Nb relative to Ta from earlier Nb-Ta oxides.

This study investigates the diversity and evolution of research topics within the dental sciences from 1994 to 2023 using topic modeling and Shannon's entropy as a measure of research diversity. We analyzed a dataset of 412036 scientific articles across six dental disciplines: Orthodontics, Pros-thodontics, Periodontics, Implant Dentistry, Oral Surgery, and Restorative Dentistry. This research relies on BERTopic to identify distinct topics within each field. The study revealed significant shifts in research focus over time, with some disciplines exhibiting robust growth in article numbers such as Periodontics and Prosthodontics. The application of Shannon's entropy revealed an increasing diversification of research efforts in disciplines such as Restorative Dentistry, while others, like Prosthodontics, in spite of their size and their high number of research topics, maintain a more specialized research focus. Taken together, our findings describe the dynamic nature of dental re-search and highlight the balance shifts in research focus across several key areas of Dentistry.

Background: Coronavirus disease (COVID-19) has caused more than 745,000 deaths worldwide. Vitamin D has been identified as a potential strategy to prevent or treat this disease. The purpose of the study was to measure vitamin D at hospital admission of COVID-19; Methods: We included critically ill patients with the polymerase chain reaction positive test for COVID-19, from March to April, 2020. Statistical significance was defined as P < .05. All tests were 2-tailed; Results: A total of 35 patients (median age, 60 years; 26 [74.3%] male) were included. Vitamin D levels were categorized as deficient for 14 participants (40%). Vitamin D deficiency was associated with vitamin A (P= 0.003) and Zinc (P= 0.019) deficiency and lower levels of albumin (P= 0.026) and prealbumin (P= 0.009). Overall, none of the studied variables were associated with vitamin D status: mortality, intensive care unit (ICU) or hospital stay, necessity of vasoactive agents, intubation, prone position, C reactive protein (CRP), Dimer-D, Interleukin 6 levels (IL-6), ferritin levels, or bacterial superinfection; Conclusions: In this single-center, retrospective cohort study, deficient vitamin D status was found in 40% in COVID-19 critically ill patients. However, deficient vitamin D status was not associated with inflammation or outcome.

With the increase in life expectancy and consequent aging of the world’s population, the prevalence of many neurodegenerative diseases is increasing, without concomitant improvement in diagnostics and therapeutics. These diseases share neuropathological hallmarks, including mitochondrial dysfunction. In fact, as mitochondrial alterations appear prior to neuronal cell death at an early phase of the disease onset, the study and modulation of mitochondrial alterations rise as promising strategies to predict and prevent neurotoxicity and neuronal cell death before the onset of cell viability alterations. In this work, differentiated SH-SY5Y cells were treated with the mitochondrial-targeted neurotoxicants 6-hydroxydopamine and rotenone. These compounds were used at different concentrations and for different time points to understand the similarities and differences in their mechanisms of action. To accomplishing this, data on mitochondrial parameters was acquired and analyzed using unsupervised (hierarchical clustering) and supervised (decision tree) machine learning methods. Both biochemical and computational analyses resulted in an evident distinction between the neurotoxic effects of 6-hydroxydopamine and rotenone, specifically for the highest concentrations of both compounds.

The continued exploration of the diversity of lactic acid bacteria in little-studied ecological niches represents a fundamental activity to understand the diffusion and biotechnological significance of this heterogeneous class of prokaryotes. In this study, Lactiplantibacillus plantarum (Lpb. plantarum) strains have been isolated from Tunisian vegetable sources, including fermented olive, fermented pepper and from dead locust intestines, subsequently evaluated for their antimicrobial activity against foodborne pathogenic bacteria, including Escherichia coli O157:H7 CECT 4267 and Listeria monocytogenes CECT 4031, as well as against some fungi, including Penicillium expansum, Aspergilus niger and Botrytis cinerea. In addition, their resistance to the oro-gastro-intestinal transit, aggregation capabilities, biofilm production capacity, adhesion to human enterocyte-like cells and cytotoxicity to colorectal adenocarcinoma cell line were determined. Further, the adhesion to tomatoes and the biocontrol potential on this model food matrix were analyzed. It has been found that all the strains were able to inhibit the indicator growth, mostly through organic acids production. Besides, these strains showed promising probiotic traits, including in vitro tolerance to oro-gastrointestinal conditions, adhesion to abiotic surface and to Caco-2 cells. Moreover, all tested Lpb. plantarum strains were able to adhere to tomatoes with similar rate (4.0-6.0 LogCFU/g tomato). The co-culture of LAB strains with pathogens on tomatoes showed that Lpb. plantarum could be a good candidate to control pathogen growth. Nonetheless, further studies are needed to guarantee their use as probiotic strains for biocontrol on food matrices.

Estimating age at death is essential to establish a biological profile from human skeletal remains in both forensic and archeological settings. Imaging studies of skeletal age changes in adults have described metamorphosis of trabecular bone structure and bone loss in the proximal femur , as well as changes in morphology during different stages of life. This study aims to assess the utility of a digital representation of conventional X-ray films of the proximal femur for the estimation of age at death in a sample of 91 adult individuals (47 females and 44 males) of the Coimbra Identified Skeletal Collection. The proposed approach showed a root mean squared error (RMSE) of 17.32 years (and mean absolute error of 13.47 years) for females and an RMSE of 14.06 years (mean absolute error of 11.08 years) for males. The main advantage of this approach is the consistency in the feature detection and extraction, as X-ray images projected on the femora space will always produce the same set features to be analyzed for age estimation while more traditional methods rely heavily on operator experience which can lead to inconsistent age estimates among experts.

We have previously reported on the diachronical changes in the narrative structure of research articles (RAs) and review manuscripts, using corpora of abstracts from MEDLINE. The present study investigates 5 linguistic dimensions (D1-5) of the text, following Biber’s well established Multimensional Analysis, on the same corpora, to assess how writing practices have changed in these two biomedical literature sub-genres over the years. Our analysis encompassed a sample of more than 1.2 million subtracts from manuscripts that were published over the course of more than 30 years. Both RAs and reviews have reinforced their informational, emotionally detached tone (D1), and have progressively refrained from the use of narrative devices (D2), while increasing their context-independent content (D3). Both RAs and reviews have displayed low levels of overt persuasion (D4), while steering away from abstract content to focus on a more marked author agency and identity adfirmation. When the linguistic features that underly these 5 dimensions are compared, it becomes apparent that RAs and review papers have often changed quite independently, both usually converging to standardized stylistic canons.

Polysaccharides such as alginate and gellan gum are biocompatible and easily accessible biopolymers with excellent properties to produce microparticles as drug delivery systems. However, the production methods often fail in reproducibility, compromising the translational potential of such systems. In this work, microparticles made from gellan gum and alginate were optimized using the coaxial air flow method, and an inexpensive and reproducible production method. A Design of Experiments was used to identify the main parameters that affect the microparticle’s production and optimization, focusing on the diameter and dispersibility. Airflow was the most significant factor for both parameters. Pump flow affected the diameter, whilst the gellan gum/alginate ratio affected dispersibility. After optimization, microparticle swelling, drug entrapment and release profile were analyzed at two pH, 7.4 and 6.5. Using methylene blue as a model drug, higher encapsulation and swelling indexes were obtained at pH 7.4, whilst a more pronounced release occurred at pH 6.5. The microparticle release profiles were studied by resorting to well-known models, showing a Fickian type release. The developed microparticles show promising results as drug-delivery vehicles for biomedical applications.

Our investigation focused on the degradation of perfluorooctanoic acid (PFOA) and 6:2 fluorotelomer sulfonamide alkyl betaine (6:2 FTAB, Capstone B), using UV photolysis under various pH conditions. Initially, we used PFOA as a reference, finding a 90% decomposition after 360 minutes at the original (unadjusted) pH 5.6, with a decomposition rate constant of (1.08 ± 0.30) × 10-4 sec-1 and a half-life of 107 ± 2 minutes. At pH 4 and 7, degradation averaged 85% and 80%, respectively, while at pH 10, it reduced to 57%. For 6:2 FTAB at its natural pH 6.5, almost complete decomposition occurred. The primary UV transformation product was identified as 6:2 fluorotelomer sulfonic acid (6:2 FTSA), occasionally accompanied by shorter-chain perfluoroalkyl acids (PFAA). Interestingly, the overall decomposition percentages were unaffected by pH for 6:2 FTAB, though pH influenced rate constants and half-lives. In PFOA degradation, direct photolysis and reaction with hydrated electrons were presumed mechanisms, excluding the involvement of hydroxyl radicals. The role of superoxide radicals remains uncertain. For 6:2 FTAB, both direct and indirect photolysis were observed, with potential involvement of hydroxyl, superoxide radicals, and/or other reactive oxygen species (ROS). Clarification is needed regarding the role of eaq- in the degradation of 6:2 FTAB.

The current manuscript presents a review on existing kiln burner technologies for the cement production process, in the context of the current climate of energy transition and environmental remediation. Environmental legislation has become ever stricter in response to global climate change, and cement plants need to adapt to this new reality in order to remain competitive in the market and ensure their longevity. The cement production process is a well-established technology with more than a century of existence. There are several plants in operation whose process is outdated by modern standards, particularly considering the current industry decarbonization needs. The cement process requires tremendous amounts of energy, mainly recovered from the combustion of solid, liquid or gaseous fuels, which yields massive emissions of greenhouse gases. Thus, an important onus is placed upon the minimization of pollutant emission in the combustion system, as well as a substitution of fossil fuels with more sustainable alternatives. One of the sus-tainable alternative fuels comes in the form of refuse derived fuels (RDF). These high caloric frac-tions of municipal solid waste present a double advantage by reducing the amount of fossil fuels used and reducing the landfilling fraction of waste. However, their use in rotary kiln burners comes with important limitations for burner operation, namely that a high degree of control over primary air supply is needed to ensure complete combustion with minimal pollutant emission.

Mineral extraction is one of the most important for the economies of different countries, and Brazil is one of the world's primary iron ore producers. Unfortunately, the dams are still the main problem, mainly in Minas Gerais, especially after the Fundão Dam rupture happened in 2015. Additionally, there is still a massive presence of buildings produced on earth throughout the Minas Gerais mining region, built from the 18th century to today. Investigating the potential of IOT to be incorporated into traditional earthen construction techniques in regions affected by dam ruptures presents a relevant and innovative research approach. In addition, the local reuse of these sediments should be the priority. Thus, the main objective of this work was to collect, characterize, and analyze the possibilities of application of these tailings to produce RE. XRD, XRF, granulometry, porosity, specific density, toxicity, and MEV/EDS were performed on the samples collected at three points. To analyze the soil-IOT compatibility, representative mixtures of RE were produced, and the specific mass, compaction, and compressive strength were performed. It was observed that the IoT samples have a high silica content and that the mixtures of IOT-soil, even without cement, reached compressive strength values above the current international standards.

The need to develop novel lightweight materials and their manufacturing processes is sets out to meet the new aerospace, automotive and construction requirements. Within this context, this research work is proposed to develop a novel thermoplastic composite material with high mechanical properties. These composites will be based on thermoplastic matrixes made from polyamide and 35% short glass fiber filled-polyamide reinforced with different types of fabrics. As reinforcement, glass fiber fabrics will be used as the base. They will be treated with different processes, both chemical and physical, to promote adherence to the matrix. Textile overmoulding technology was selected for manufacturing these composites. This technology was primarily developed to manufacture aesthetic lined components and has achieved a great implantation. Once these new composites are manufactured, they will be submitted to different tests to evaluate their behavior regarding adhesion, impact strength and stiffness. It is expected an improvement on stiffness and impact absorption.

Taiwan's bed and breakfast (B&B) development has been more than 25 years ago, from the first generation of retirement to the B&B industry, serving tourists from all over the world accom-modation, providing breakfast and accommodation mode to the present, after the change of employees from the second generation, more and more attention is paid to the cultivation and cultivation of business ability. With the advent of the era of AI technology networking, the ca-pabilities required for B&B operation are more focused on all aspects of service, and the good marketing ability of B&B can promote a green chimney-free tourism economy, which is also a favorite industry of various governments and the public. This study explores the basic vocational competency indicators required for running a B&B, with (1)EQ emotion management skills, (2)Financial management ability, (3)(SK) technical skills, and (4)Marketing and promotion management capabilities. Through the study method, the K-S Z test was determined by the con-sensus conclusion of expert reliability and validity p value

Cathode materials based on SrCoO3- perovskite-type oxides hold great potential, given the huge oxygen permeability exhibited by the cubic phase of this oxide, which must be stabilized though suitable cationic substitutions. We present here two novel materials of the series Sr1-xYxCoO3- (x= 0.1, 0.2), prepared by solid state reactions. The crystalline structure was explored by neutron powder diffraction. At RT, we identified a subtle tetragonal superstructure, yet preserving the wanted framework of vertex-sharing CoO6 octahedra. A noteworthy result of the neutron analysis is the presence of conspicuous amounts of oxygen vacancies, ordered in layers and responsible for the formation of the mentioned superstructure. The stability was investigated by thermal analysis, using thermogravimetry (TGA). The electrical conductivity gave a maximum value of 800 °C of 122 S·cm–1. To determine the resistance associated with the oxygen reduction reaction (ORR), electrochemical impedance spectroscopy as a function of temperature was carried out, finding a value for the activation energy of Ea= 0.82 eV. This is a much lower value than that usually obtained for cathodes with a high catalytic activity for the oxygen reduction reaction. In single-cell tests, the materials generated a power density up to 0.25 Wcm−2 at 800ºC, using pure H2 as fuel. All these features make this perovskite a suitable candidate as cathode material in intermediate-temperature SOFCs

Maria Valtorta (MV) (1897–1961) – an Italian mystic who claimed to have visions of Jesus’s life – describes Jesus’ crucifixion with many details from which significant data can be retrieved. My investigation based on these data and the topography of northwest Jerusalem in the I century AD, shows that Jesus’ crucifixion place, Golgotha (the “skull”), is neither at the Holy Sepulchre nor in the Garden Tomb area. The paved road to Golgotha she accurately describes arrives at its top with the minimum mean route gradient; its half way defines two distinct tracts with same height and same walking time but different mean route gradient; at half way Jesus is allowed to walk to the top in a spiral country road less steep than the second tract. The paved road leads to a place where few years after Jesus’ crucifixion the Psephinus Tower, described by Flavius Josephus, was erected, in the area known today as the Russian Compound. In conclusion, the Golgotha reveiled by MV’s writings was located at the same site of the Psephinus Tower.

Quantification of erythrocytes and leukocytes is an essential aspect of hemogram diagno- 23 sis in Veterinary Medicine. Flow cytometry analysis, laser scattering, and impedance detection are 24 standard laboratory techniques, verified by manual microscopy counting. Although single-cell scat- 25 tering is already used as a standard technology for differentiating cell counts in flow cytometry, it 26 requires capillary cell separation. The current study investigates the scattering characteristics of 27 whole blood to identify correlations with erythrocytes and leukocytes counts. The scattering infor- 28 mation present in blood samples can be classified into three types: i) geometrical scattering, which 29 occurs when non-absorbed light is reflected and scattered, ii) Mie scattering, which happens when 30 light is scattered by particles of a similar size to the wavelength, and iii) Rayleigh scattering, which occurs when light is scattered by particles that are smaller than the incident light wavelength. In 32 this study, we investigate the scattering correction coefficients of dog blood absorption spectra in 33 the visible-near infrared range, to establish direct correlations with erythrocytes and leukocytes 34 counts, using multivariate linear regression. Our findings demonstrate the possibility of using the 35 scattering properties of dog blood, which is a step towards the existence of a portable and miniatur- 36 ized hemogram diagnosis in Veterinary Clinics worldwide.

Onion skin waste (OSW), the primary non-edible byproduct from onion processing, offers a renewable source of bioactive compounds. This study aims to valorize OSW through subcritical water extraction (SWE), aligning with circular economy and biorefinery principles. SWE was carried out at 145 °C, 50 bar and 50 min in a discontinuous reactor, producing a phenolic-rich extract (32 ± 3 mg/g), dominated by protocatechuic acid (20 ± 3 mg/g), quercetin-4´-O-glucoside (7.5 ± 0.2 mg/g), and quercetin (3.2 ± 0.6 mg/g). Additionally, it contains sugars (207 ± 20 mg sucrose-Eq/g), proteins (22.8 ± 1.6 mg BSA-Eq/g) and free amino acids (20.4 ± 1.2 mg arginine-Eq/g). Its phenolic richness determines its scavenging activity against ●NO and O2●- radicals, and its α-glucosidase and aldose-reductase inhibition without affecting α-amylase. Notably, the extract demonstrates significant α-glucosidase inhibition (IC50 = 76 ± 4 µg/mL), surpassing acarbose (IC50 = 129.5 ± 1.0 µg/mL), in both pure enzyme and cell culture tests without showing cytotoxicity on AGS, HepG2 and Caco-2 human cell lines. The extract’s bioactivity and nutritional content make it suitable for developing antioxidant and antidiabetic nutraceutical/food components, highlighting the SWE potential for OSW valorization without using organic solvents.

Exosomes, nanoscale extracellular vesicles, are a hot area of investigation in the biomedical field, as they have been shown to play a crucial role in the physiology of numerous tissues, including bone. This study explores the landscape of exosome-based bone regeneration research using infometric techniques. By relying on BERTopic, an advanced topic modeling algorithm, we analyzed a comprehensive corpus of scientific literature to identify key themes and trends in exosome research in the bone regeneration field. We then extracted significant concepts from the abstracts of the corpus and we used them to create knowledge graphs using GPT 3.5 turbo Large Language Model, to map the distribution of information within this domain. The resulting ide-oscape highlights the key ideas that aggregate most of the recent research in the area, from mesenchymal stem cell-derived exosomes to engineered exosome-integrated biomaterials. This exploration provides a holistic view of the field and uncovers its emerging trends, providing useful insight to guide future research directions.

Sensors and actuators are fundamental units in Cyber-Physical and Internet of Things systems. Because they are included in a variety of systems, using many technologies, it is very useful to characterize their functions abstractly by describing them as Abstract Entity Patterns (AEPs), that are patterns that describe abstract conceptual entities. For concreteness, we study them here in the context of autonomous cars. An autonomous car is a complex system because, in ad-dition to its own complex design, it interacts with other vehicles and with the surrounding in-frastructure. To handle these functions, it must incorporate various technologies from different sources. An autonomous car is an example of a Cyber-Physical System, where some of its func-tions are performed by Internet of Things units. Sensors are extensively used in autonomous cars to measure physical quantities; actuators are commanded by controllers to perform appro-priate physical actions. From AEPs we can derive concrete patterns, a structure combining re-lated AEPs is an Entity Solution Frame (ESF). Both sensors and actuators are susceptible to mali-cious attacks due to the large attack surface of the system where they are used. Our work is in-tended to make autonomous cars more secure, which also increases their safety. Our final objec-tive is to build a Security Solution Frame for sensors and actuators of autonomous cars that will facilitate their secure design. A Security Solution Frame is a solution structure that groups to-gether and organizes related security patterns. This article is the first stage of a secure unit that can be used to design not only secure autonomous cars but also any system where sensors and actuators are used. This paper concentrates on AEPs and ESFs for sensors and actuators; that is, on the functional aspects of these devices.

The current emergency due to the worldwide spread of the COVID-19 caused by the new SARS-CoV-2 is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness was not yet assessed. The main protease (Mpro) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent Mpro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed to highlight some crucial aspects. Seventeen potential SARS-CoV-2 Mpro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

Training has a significative effect on physiology of blood coagulation both in humans and in horses. Several hemostatic changes have been reported after exercise in the horse but data available are inconclusive. The aim of this study was to investigate the platelet activation and primary platelet-related hemostasis modifications in young untrained Thoroughbred racehorses in the first 4-month timeframe incremental training period in order to improve knowledge on this topic. Twenty-nine clinically healthy, untrained, 2-year-old Thoroughbred racehorses. Never trained Thoroughbreds were followed during their incremental 4-month sprint exercise schedule. Blood collection was performed once a month (T-30, T0, T30, T60, and T90). Platelet aggregation was measured by light transmission aggregometer in response to various agonists: adenosine diphosphate (ADP), collagen and calcium ionophore A23187. Platelet function was evaluated using the Platelet Function Analyzer (PFA-100®) using collagen/ADP and collagen/adrenaline cartridges. Nitrite-nitrate (NOx) plasma concentrations were measured by a colorimetric assay to assess in vivo nitric oxide bioavailability. Platelet activation was investigated also through gene expression analyses (selectin P-SELP, ectonucleotidase CD39-ENTPD1, prostaglandin I2 synthase-PTGIS, endothelial nitric oxide synthase 3-NOS3). Differences among the time points were analyzed and mean±SEM were calculated. Significant modifications were identified compared with T-30 with increase of platelet aggregation (collagen:32.6±4.8 vs 21.6±4.9%; ADP: 35.5±2.0 vs 24.5±3.1%; A23187: 30±4.7 vs 23.8±4%) and a shorter closure time of C-ADP cartridges (75.6±4.4 vs 87.7±3.4 sec) that tended to return to baseline value at T90. NOx concentrations in plasma significantly increased after 30 days of training program compared with baseline. The first long-term training period induce platelet hyperactivity already after 30 days in untrained Thoroughbreds. Regular physical training blunts the negative effects of acute efforts on platelets activation.

Iberian holm oak meadows are savannah-like ecosystems that result from traditional silvo pastoral practices. However, such traditional uses are declining, driving changes in the typical tree – open grassland structure of these systems. Yet, there are no studies integrating the whole ecosystem — including the arboreal and the herbaceous layer — as drivers of greenhouse gas (GHG: CO2, CH4 and N2O) dynamics. Here we aim at integrating the influence of tree canopies and interactions among plant functional types (PFT: grasses, forbs, and legumes) of the herbaceous layer as GHG exchange drivers. For that purpose, we performed chamber based GHG surveys in plots dominated by representative canopy types of Iberian holm oak meadows, including Quercus species and Pinus pinea stands, the last a common tree plantation replacing traditional stands; and unravelled GHG drivers through a diversity interaction model approach. Our results show that the tree – open grassland structure especially drove CO2 and N2O fluxes, with higher emissions under the canopy than in the open grassland. Emissions under P. pinea canopies being higher than those under Quercus species. In addition, the inclusion of diversity and compositional terms of the herbaceous layer improve the explained variability, legumes enhancing CO2 uptake and N2O emissions. Changes in the tree cover and tree species composition, in combination with changes in the structure and composition of the herbaceous layer, will imply deep changes in the GHG exchange of Iberian holm oak meadows. These results may provide some guidelines to perform better management strategies of this vast but vulnerable ecosystem.

Resumo: Este estudo teve como objetivo avaliar a Saúde Mental Positiva (SPM) e a sua relação com características sociodemográficas, literacia em saúde mental e escala de vulnerabilidade psicológica (PVS) em estudantes universitários portugueses com idades compreendidas entre os 17 e os 62 anos. Foi realizado um estudo descritivo-correlacional. Uma pesquisa online foi realizada para avaliar variáveis ​​demográficas, e vários questionários foram aplicados para avaliar saúde mental positiva, vulnerabilidade psicológica e alfabetização em saúde mental. Os dados foram coletados de 1º de novembro de 2019 a 1º de setembro de 2020. No geral, 3.405 alunos participaram do estudo. Os resultados mostram que 67,8% dos alunos revelaram um alto nível de PMH, 31,6% apresentaram um nível médio de PMH e 0,6% apresentaram um nível baixo de PMH. Os estudantes do sexo masculino relataram maior satisfação pessoal (t (3170) = -2,39, p=0,017) e autonomia (t (3170) = -3,33, p=0,001), no PMH em relação ao sexo feminino. Alunos sem bolsa pontuaram mais alto (t (3.127) = -2,04, p=0,42) no PMH do que alunos com bolsa. Estudantes que não foram deslocados de casa relataram maior (t (3170) = -1,99, p=0,047) Autocontrole em PMH do que aqueles deslocados de sua casa. Estudantes universitários com resultados de PMH mais altos têm resultados de PVS mais baixos e resultados de Alfabetização mais altos. Os achados deste estudo contribuirão para identificar as necessidades de intervenção dos alunos na PMH. Estudantes universitários com resultados de PMH mais altos têm resultados de PVS mais baixos e resultados de Alfabetização mais altos. Os achados deste estudo contribuirão para identificar as necessidades de intervenção dos alunos na PMH. Estudantes universitários com resultados de PMH mais altos têm resultados de PVS mais baixos e resultados de Alfabetização mais altos. Os achados deste estudo contribuirão para identificar as necessidades de intervenção dos alunos na PMH.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Ryegrass is one such cereal that has been underutilized in human nutrition despite its high nutritional and functional value due to the presence of phytochemicals and dietary fibers It is a viable option, especially for countries that do not produce wheat, as it is easily adaptable and overgrows, making it economically viable. This study evaluated the nutritional impact, bioactive compounds, and physicochemical and technological properties of partially substituting maize flour (MF) with sprouted whole ryegrass flour (SR) in developing extrusion-cooked breakfast cereals. A completely randomized design with substitutions ranging from 0 to 20 % of MF with SR was employed as the experimental strategy (P < 0.05). Partial incorporation of SR increased the bioavailability of γ-aminobutyric acid and total soluble phenolic compounds. Using sprouted grains can adversely affect the technological quality of extruded foods, but ryegrass, with its high dietary fiber and low lipid content, mitigates these negative effects. Consequently, breakfast cereals containing 4 and 8 % SR exhibited better physicochemical properties, such as reduced hardness and increased crispness. These results are promising for ryegrass and suggest combining the age-old germination process with extrusion can enhance cereal-based breakfast products' nutritional quality and bioactive compound content.

Tissue programmed death ligand-1 (PD-L1) protein expression is predictive of immune checkpoint inhibitor (ICI) benefit. However, tissue PD-L1 can be fraught with tissue acquisition and heterogeneity limitations. Plasma testing can overcome these limitations. However, the overall survival (OS) predictive benefit of plasma PD-L1 assays have not been well characterized. Patients with stage IV non-small cell lung cancer (NSCLC) and plasma cfRNA PD-L1 by PCR expression were identified and assessed for OS. 16 patients treated with front-line ICI-based regimens were assessed and represented a real-world patient population with over half with a performance status of 2 or greater. 10 contemporaneous patients at the same institution treated with chemotherapy alone were also identified and assessed. With a median follow-up of 33 months, median OS was 13 months with a 30% 3-year OS for the ICI treated patients compared to a median OS of 3 months and a 10% 3-year OS for those treated with chemotherapy alone. Comparative log-rank test p-value = 0.014 and a hazard ratio 0.376 (95%-CI 0.134-1.057). Plasma cfRNA PD-L1 was associated with a statistically significant survival benefit from ICI-based treatment compared to chemotherapy in the first line treatment of a real-world patient population of advanced NSCLC.

: Background: The aim of this study was to evaluate Phenylketonuria (PKU) patients’ oral health habits and the efficiency of tailored recommendations for PKU patients in Latvia on the correct management of oral hygiene. The-free amino acid formula can negatively impact PKU patient’s oral health as it contains a high amount of complex carbohydrates. Materials and methods: In this study with a one-month interval pre and post implementation of oral hygiene recommendations, two questionnaires regarding oral hygiene habits and knowledge were prepared and provided by trained medical personnel to be filled in for all diagnosed PKU patients in Latvia who were not lost to follow-up. Results: Based on the questionnaires among the PKU patients under 18 years of age, 27% cleaned their teeth once a day. However, 6% of patients did not engage in regular teeth brushing at all. Among PKU patients over and 18 years of age, 26% brushed their teeth only once a day. Additionally, a mere 39% of PKU patients ≥18 years of age and 17% &lt; 18 years of age incorporated flossing into their oral hygiene routine. In total, 45% of PKU patients ≥18 years of age and 44% &lt; 18 years of age visited a dentist once a year, but 40% ≥18 years of age and 39% &lt;18 years of age visited a dentist less often than once per year. After reading the recommendations, a remarkable number of PKU patients &lt; 18 years of age had improved their daily oral hygiene routine, including toothbrushing (25%) and flossing (23%). Conclusion: Given the unique dietary requirements and the implementation of these daily at-home oral health practices, motivation and regular reminders should result in better oral health of PKU patients and cooperation with clinicians.

Despite the recent approval of novel immunotherapies, as immunomodulatory drug, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable and the acquisition of triple-refractoriness leads to really dismal outcomes, in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody drug conjugates, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

The move towards a new Circular Economy (CE) economic model has been advocated and supported in Portugal, however, there is limited research on this topic. To address this gap, a quantitative research based on an online survey was carried out among 99 Portuguese organizations, encompassing a wide range of sectors and sizes. The results show that CE is regarded as a strategic and relevant issue for profitability and value creation. Furthermore, the perception that it requires the adoption of new business models in addition to the classical “reduce, reuse, and recycle” approach is growing. Moreover, based on the hypotheses raised, results suggest that the level of CE adoption is positively impacted by the status of the EMS (Environmental Management System) certification and the willingness to improve the environmental performance and achieve a sustainable business model. However, CE activities are still relatively modest and a friendlier context (fiscal, legal, organizational, etc.) and the stronger support from supply chain agents and consumers are required. Future research should focus on how to design and shape the transition from a linear to a CE economy, and to ascertain if the positive attitude towards CE is materialized in changing the way business is done.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

Patients with COPD have a higher prevalence of coronary ischemia and other factors that put them at risk for COVID-19-related complications. We aimed to explore the impact of COVID-19 in a large population-based sample of patients with COPD in Castilla-La Mancha, Spain. We analyzed clinical data in electronic health records from January 1st to May 10th, 2020 by using Natural Language Processing through the SAVANA Manager® clinical platform. Out of 31,633 COPD patients, 793 had a diagnosis of COVID-19. The proportion of patients with COVID-19 in the COPD population (2,51%; CI95% 2,33 – 2,68) was significantly higher than in the general population aged > 40 years (1,16%; 95%CI 1,14 – 1,18); P < .001. Compared with COPD-free individuals, COPD patients with COVID-19 showed significantly poorer disease prognosis, as evaluated by hospitalizations (31,1 % vs 39,8%: OR 1,57; 95%CI 1,14 – 1,18) and mortality (3,4% vs 9,3%: OR 2,93; 95%CI 2,27 – 3,79). Patients with COPD and COVID-19 were significantly older (75 vs. 66 years), predominantly male (83% vs 17%), smoked more frequently, and had more comorbidities than their non-COPD counterparts. Pneumonia was the most common diagnosis among COPD patients hospitalized due to COVID-19 (59%); 19% of patients showed pulmonary infiltrates suggestive of pneumonia and heart failure. Mortality in COPD patients with COVID-19 was associated with older age and prevalence of heart failure (P<0.05). COPD patients with COVID-19 showed higher rates of hospitalization and mortality, mainly associated with pneumonia. This clinical profile is different from exacerbations caused by other respiratory viruses in the winter season.

We present a model that incorporates the effect of two-body currents in quasielastic electron-nucleus scattering within the framework of a consistent superscaling formalism. This is achieved by defining an averaged single-nucleon hadronic tensor based on the 1p1h matrix element of the one-body current plus meson-exchange currents (MEC). The consistent treatment of one- and two-body currents in our model enables the calculation of exchange current effects in the kinematical region where the Fermi gas response is zero, but not the scaling function. The effect of MEC is consistently taken into account when extracting the phenomenological scaling function from electron scattering data. With this model, we investigate the effect of MEC on the response functions taking into account the effective mass of the nucleon, and examine the consequences it has on the inclusive (e,e′) cross section. We find that 1p1h MEC deplete the quasielastic transverse response, while they not alter significantly the scaling behavior of (e,e′) data.

Protein-DNA interactions are critical for the successful functioning of all natural systems. The key role in these interactions is played by processes of protein search for specific sites on DNA. Although it has been studied for many years, only recently microscopic aspects of these processes became more clear. In this work, we present a review on current theoretical understanding of the molecular mechanisms of the protein target search. A comprehensive discrete-state stochastic method to explain the dynamics of the protein search phenomena is introduced and explained. Our theoretical approach utilizes a first-passage analysis and it takes into account the most relevant physical-chemical processes. It is able to describe many fascinating features of the protein search, including unusually high effective association rates, high selectivity and specificity, and the robustness in the presence of crowders and sequence heterogeneity.

Background: Parkinson's disease (PD) is a neurodegenerative disorder that affects both patients and their caregivers, particularly parents who often become informal caregivers. Caring for someone with PD is linked to increased psychiatric morbidity and persistent anxiety-depressive distress. Methods: This study investigates the burden on caregivers of PD patients using multi-dimensional scales and identifies the personological and environmental factors contributing to this burden. Results: 20.6% of participants reported a severe burden according to the Caregiver Burden Inventory (CBI), while 13.8% had a moderate to severe burden according to the Zarit Caregiver Burden Inventory (ZBI). The Family Strain Questionnaire Short Form (FSQ-SF) high-lighted a minority of caregivers needing psychological support, with some cases requiring ur-gent attention, particularly in stress-related symptoms (SR) and urgent support (U). The Depres-sion Anxiety Stress Scales Short Version (DASS-21) results showed a higher prevalence of stress-related symptoms compared to anxiety and depression. Retired caregivers reported higher ZBI scores and lower life satisfaction levels compared to working caregivers. Additionally, years of schooling negatively correlated with the ZBI score. T-test analysis indicated that caregivers of patients with cognitive impairment were at greater risk compared to caregivers of patients with-out cognitive impairment. Conclusions: The results underscore the need for early recognition of risky situations and adequate support for caregivers.

Rising raw material prices can have a significant impact on the financial performance of the food and beverage (F&B) business. The purpose of this study was to determine the impact of rising prices of staples onfinancial resilience F&B business in Indonesia. This study uses a quantitative approach with bivariate correlation analysis and secondary data from the financial reports of F&B companies listed on the Indonesia Stock Exchange for the 2020-2022 period. The results showed that the increase in the price of basic commodities had a significant positive impact onfinancial resilience F&B company. This can be seen from the decline in the profitability and liquidity of F&B companies as a result of the increase in the price of basic commodities. Therefore, F&B companies must pay attention to and manage the risk of rising prices of basic commodities to maintainfinancial resilience and sustainable business continuity.

In this paper, we introduce a computational procedure that enables autonomous LEO laser trackers endowed with INSs to increase the current accuracy when shooting at middle distant medium-size LEO debris targets. The code is designed for the trackers to throw the targets into the Atmosphere by means of ablations. In case that the targets are eclipsed to the trackers by the Earth, the motions of the trackers and targets are modeled by equations that contain post-Newtonian terms accounting for the curvature of space. Otherwise, when the approaching targets become visible for the trackers, we additionally use more accurate equations, which allow to account for the local bending of the laser beams aimed at the targets. We observe that under certain circumstances the correct shooting configurations that allow to safely and efficiently shoot down the targets, differ from the current estimations by distances that may be larger than the size of many targets. In short, this procedure enables to estimate the optimal shooting instants for any middle distant medium-size LEO debris target.

Percutaneous aortic valve replacement (TAVI) has become the treatment of choice for elderly patients with severe aortic valve stenosis because of its less invasiveness compared to surgery. However, it introduces new complications, such as vascular lesions, access site problems, paravalvular leaks, and aortic dissection. Aortic dissection after TAVI is rare but serious, occurring in 0.2% to 0.3% of cases, with both intraprocedural and late cases reported. This case study concerns a 68-year-old woman who developed Stanford B aortic dissection, external iliac artery dissection, and right common femoral artery occlusion after TAVI. Treatment included stenting of the iliac and common femoral arteries, followed by a staged procedure: debranching, thoracic endovascular aortic repair (TEVAR) and endovascular aneurysm repair (EVAR), with satisfactory results. This case, underscores the importance of vigilance in the management of TAVI-related complications to optimize patient care and outcomes.

In this paper, a distinction is first made between environmental, sustainable and green chemistry; the last two are then examined in relation to the more general problem of the environmental education. A brief historical digression on the STS (Science, Technology and Society) movement tries to dissect the reasons why chemistry is seen by the general public as a problem, not as a decisive resource for the realization of the ecological transition. Although sustainable and green chemistry can be decisive in overcoming the insularity of chemical disciplines in the high school, it fails to effectively embed itself in educational practices. Specific operational goals, supporting a real scientifical and technological literacy in sustainable and green chemistry, can help chemical educators. They are provided at the end of an examination of the founding axes of sustainable and green chemistry, according to the criteria of scientific and technological literacy.

Is there a qualitative difference between apes’ and human Theory-of-Mind (or ability to estimate others’ mental states)? After opting for the idea that expectations are empty profiles that recognize a particular content when it arrives, I apply the same description to ‘vicarious expectations’ –very probably present in apes. Thus, (empty) vicarious expectations and one’s own (full) contents are distinguished without need of meta-representation. Then, three proposals are made. First, vicarious expectations are enough to support apes’ Theory-of-Mind (including ‘spontaneous altruism’). Second, since vicarious expectations require a profile previously built in the subject that activates them, this subject cannot activate any vicarious expectation of mental states that are intrinsically impossible for him. Third, your mental states that think of me as a distal individual are intrinsically impossible states for me, and therefore, to estimate them, I must estimate your mental contents. This ability (the original nucleus of human Theory-of-Mind) is essential in human lifestyle. It is involved in unpleasant and pleasant self-conscious emotions, which respectively contribute to ‘social order’ and to cultural innovations. More basically, it makes possible the human (prelinguistic or linguistic) communication, since it originally made possible the understanding of others’ mental states as states that are addressed to me, and that are therefore impossible for me.

Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia and anemia. Moreover, it is associ-ated with SRSF2 mutations and rarely with CSF3R variants. The presented case is an 84-year-old patient with persistent anemia and monocytosis. Due to the presence of dysmorphic granulocytes, monocyte atypia and myeloid precursors in peripheral blood, the patient was submitted to bone marrow examination. The diagnosis was consistent with CMML type 2. Hemocoagulative test showed an increase of fibrinolysis markers. Next generation targeted sequencing showed TET2 and SRSF2 mutations, along with an unexpected CSF3R germline missense variant, rarely encountered in CMML. The pa-tient started Azacitidine treatment reaching normal hemostatic process values. In con-clusion, we identified a heterozygous germline mutation that, cooperating with TET2 and SRSF2 variants, have been responsible for the hemorrhagic manifestation.

Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the WHO Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting in dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. This increasing detection of resistant gonococcal strains may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics, (2) development of new antibiotics and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this Superbug. This has lead the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

During the last few years, the world witnessed one of the worst calamities to humankind- the COVID-19 pandemic. We also witnessed the development of vaccines at an unprecedented pace against the SARS-CoV-2- the causative agent. India was among the hard-hit countries by COVID-19, developed its indigenous vaccine and implemented vaccines developed in other countries as well. Initially, the antibody level and the neutralizing antibody titer against the pathogen were considered as the correlates of immune protection from the disease. However, the long-term protection from the pathogen was provided by the immune memory cells viz. T and B memory cells and their ability to efficiently make recall responses. In this regard, globally the research studies focused mainly on the mRNA-based vaccines. The studies on immune memory response, particularly- the B cell memory response bestowed by the vaccines given to Indians is relatively obscure. We studied the level of RBD specific memory B cells in the peripheral circulation of the study participants and the ability of B cells to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D) and Sputnik Light (Gam-COVID-Vac) as well as unvaccinated individuals. Our study revealed that Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses.

Abstract: Five patients with standard medical treatment-resistant symptoms of skin lesions, ear infections, allergic rhinitis, nasal congestion, asthma, heartburn, and failure to thrive were success- fully treated with an integrative medicine assessment and integrative medicine treatment approach. The integrative medicine assessment method of autonomic response testing enabled the identifica- tion of nickel sensitivity as a common element in these patients. It guided the use of the integrative medicine therapies of low dose immunotherapy, gamma linoleic acid supplementation, chelation, dietary nickel restriction, and removal of nickel containing dental and cosmetic appliances. A chart review of 151 patients indicated a strong association of nickel and the simultaneous presence of skin lesions.

Lophomonas are flagellated protozoa which have been increasingly associated with upper and lower airway infection in humans. The prevalence and characterization of this disease in the critically ill remains poorly understood. We present a series of eleven ICU patients with confirmed Lophomonas spp. identification in respiratory samples.

As global life expectancy continues to rise, we are challenged with maintaining health into old age, and research has thus concentrated on various strategies aimed at mitigating the effects of skin aging. Aromatic plants stand out as potential sources of anti-aging compounds due to their secondary metabolites, particularly essential oils (EO). The aim of this study was to ascribe to Ferulago lutea EO several biological activities that could be useful in the context of skin aging. The EO was obtained using hydrodistillation and characterized by gas chromatography-mass spectrometry (GC/MS). The anti-inflammatory potential was assessed using lipopolysaccharide (LPS)-stimulated macrophages. The effect on cell migration was disclosed using scratch wound assay. Lipogenesis was induced using T0901317, hyperpigmentation with 3-isobutyl-1-methylxantine (IBMX) and senescence with Etoposide. Our results show that the EO was characterized mainly by α-pinene and limonene. The EO was able to decrease nitric oxide (NO) release as well as iNOS and pro-IL-1β protein levels. The EO promoted wound healing while decreasing lipogenesis and having depigmenting effects. The EO also reduced senescence associated β-galactosidase and p21/p53 protein levels and nuclear accumulation of γH2AX. Overall, our study highlights the properties of F. lutea EO that make it a compelling candidate for dermocosmetics applications.

This study reports rapid hydrolysis, acylation, and lipolysis with lipase B from Candida antarctica (CalB) and nanofructosome encapsulated CalB (CalB@NF) enzymes immobilized on silica-coated magnetic nanoparticles (Si-MNPs). Enzymatic hydrolysis was confirmed for conversion to p-nitrophenol (p-NP, λex=400 nm) from p-nitrophenyl butyrate (p-NPB, λex=270 nm), and various catalytic parameters such as Km, Vmax, and Kcat were calculated from Michaelis-Menten and Lineweaver-Burk plot. Efficiency of enzymatic hydrolysis was in the order of CalB > Si-MNPs@CalB > CalB@NF > Si-MNPs@CalB@NF, and reusability was much better with the enzyme immobilized on Si-MNPs than with the native enzyme. Enzymatic acylation was confirmed by the formation of benzyl benzoate (λex=229 nm) from benzoic anhydride (λex=240 nm), and efficiency exceeded 99% in all samples. Finally, enzymatic lipolysis was confirmed by the decomposition of olive oil to fatty acid such as oleic acid (λex=230 nm) using thin-layer chromatography (TLC), column chromatography, and proton nuclear magnetic resonance (1H -NMR). The lipases immobilized on Si-MNPs have the advantage of good thermal stability and reusability and are thus applicable to a wide range of industries.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N’, N’-tetrakis(2-pyridylmethyl)-ethylenediamine).is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cells. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), in vitro. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n=3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

The immune system is central in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, developing a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyses the critical variables related to the safety, efficacy, and effectiveness of CHB treatments. HeberNasvac's experience is revisited to address the challenges and potentialities of therapeutic vaccines, as well as the current roadblocks in research and development, registration, and large-scale implementation.

Despite laws and directives for the regulation and restriction of pesticide in farming, the large use of Plant Protection Products (PPPs) in paddy fields is a relevant worldwide cause of contamination of the environment. The aim of this work is to evaluate the environmental impact due to the use of PPPs by using an integrated approach based on chemical analyses and ecotoxicological hazard assessment, supported by statistical tools, in order to overcome the issues related to the traditional tabular evaluation. Samples of soil and water of seven conventional and organic paddies located in Northern Italy have been examined for two years by extensive chemical and ecotoxicological analyses. The results evidenced a direct relationship between the presence of Oxadiazon in water and bioassays responses as the main cause of the toxicity measured. This phenomenon affected both biological and conventional rice fields, due to the free circulation of water through irrigation canals. Therefore, the implementation of organic districts with a water circulation isolated from conventional fields represents a simple and effective countermeasure to safeguard the agricultural practices of organic crops.

Background: The nutritional status of women during pregnancy can have a considerable effect on maternal and fetal health, and on perinatal outcome. The aim was to assess the changes occurring in dietary iodine intake, KI supplementation, and smoking habit, and the impact of these changes on the urinary iodine concentration (UIC) during pregnancy in a population of women in Catalonia (Spain). Methods: Between 2009-2011 an observational study including a cohort of women whose pregnancy was monitored in the publically-funded health system in a central region of Catalonia. Women received individual educational counseling imparted, a dietary questionnaire was completed, and a urine sample collected for iodine determination at each trimester visit. Results: 633 (67.9%) women answered the questionnaire at all 3 visits. The percentage of women with a desirable UIC (≥150μg/L) increased from the first to the second trimester and remained stable in the third (p<0.001). Analysis of the relationship between UIC≥150 μg/L and the women’s dietary habits showed that the percentage with UIC≥150 μg/L increased with greater consumption of milk, fresh vegetables, and fruit in the first trimester, and the same was true for iodized salt use in all three trimesters and iodine supplementation in all three. Conclusion: During pregnancy increased intake of milk, iodized salt, and iodine supplements was associated with an increase in the UIC.

The aim of this paper is to obtain Karush-Kuhn-Tucker optimality conditions for weakly efficient solutions to vector equilibrium problems with the addition of constraints in the novel context of Hadamard manifolds as opposed to the classical examples of Banach, normed or Hausdorff spaces. More specifically, classical necessary and sufficient conditions for weakly efficient solutions to the constrained vector optimization problem are presented. As well as some examples. The results presented in this paper generalize results obtained by Gong (2008) and Wei and Gong (2010) and Feng and Qiu (2014) from Hausdorff topological vector spaces, real normed spaces and real Banach spaces to Hadamard manifolds, respectively.

Margarine exhibits significant variations in composition, allowing it to cater to diverse consumer segments. This study aimed to characterize the physical and sensory attributes of margarine samples available in the Brazilian market. Twelve commercial samples from six different brands, encompassing 30% to 80% of lipid contents, were subjected to instrumental texture analysis, sensory profiling, and hedonic assessment. A total of 112 consumers participated in acceptance tests and Check-All-That-Apply (CATA) evaluations, while another group of 62 subjects performed Projective Mapping. Samples with lipid percentages exceeding 70% achieved the highest average acceptance scores for taste and overall impression. The brand with the lowest lipid content (30%) exhibited a stronger association with negative attributes, including rancid flavor and aroma, bitterness, and metallic flavor, resulting in lower average scores for aroma, flavor, texture, and overall impression. However, these scores were not statistically different from those of samples with 50% and 60% lipid content. Reducing lipid levels in fat-based products such as margarine poses a challenge to food manufacturers, as consumers generally perceive higher lipid percentages as indicative of superior flavor quality.

This lack of information is due to the primary role of HSTs in fungal pathogenesis, which often masks the functions of NSTs and CWDEs. So, the toxic effects of A. alternata metabolites due to NSTs and CWDEs have received minor attention than those reported for HSTs mycotoxins [11]. A wider study of the activity of isolated fungal metabolites can allow the identification of compounds directly related to the pathogenic activity of the fungus, making it possible to create chemo libraries that facilitate the linking of the structure of the compounds with the species that produce it and its effect on host and non-host crops, as well as with biosynthetic features [12]. In this context, our work reports a study focused on NSTs and CWDEs used by an A. alternata strain isolated from infected pears in Italy. To this aim, the characterization of hydrolytic enzyme activities of A. alternata and the identification of the metabolites produced in vitro were performed. Furthermore, the phytotoxic activity of the isolated compounds was evaluated on pear (host and non-host varieties) and lemon fruits [13]. Finally, the competition of A. alternata with other pathogens was evaluated to investigate the role of NSTs on co-infections.

The production of recombinant enzymes, mainly used for obtaining pure and functional target molecules, holds significant importance in modern biotechnology. This study aimed to produce recombinant α-amylases (Amy3500 and Amy1974), derived from B. amyloliquefaciens MDC1974 and B. subtilis MDC3500 respectively, using the pBE-S shuttle vector, and to characterize them. Both α-amylase genes were molecularly cloned into the E. coli/B. subtilis pBE-S shuttle vector, both with (Amy1974sig and Amy3500sig) and without their own signal peptides (Amy1974 and Amy3500), along with a signal peptide originating from the plasmid, and tested in flask fermentations. For recombinant Amy3500, the amylase variants resulted in similar levels of volumetric activity (700-750 U/mL). In contrast, the expression of Amy1974 nearly doubled compared to Amy1974sig with double signal peptides, reaching 2000 U/mL. The SDS-PAGE estimated the molecular weight of Amy1974 α-amylase to be 54.6 kDa, which was in accordance with the theoretical molecular mass calculations. However, the estimated molecular weight of Amy3500 amylase was significantly reduced when exiting the producer cells. Ca2+ had no significant activating effect on the activities of Amy1974 amylase and Amy3500 amylase, likely due to its tight binding to the protein scaffold. Both enzymes exhibited broad activity peaks between 45-70°C, with a maximum at 65°C. The Amy1974 and Amy3500 α-amylases demonstrated broad pH optima and pH-dependent thermostability, with optimum pH values at 6.5 and 5.8, and thermal stability peaks at pH 7.6 and 5.9, respectively. Both α-amylases displayed high relative activity against various starches, including corn amylopectin and potato amylose, while showing comparatively lower activity towards cyclodextrins. The Amy1974 amylase converts starch to dextrins of varying lengths, whereas Amy3500 almost entirely converts starch into glucose.

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed an HBV screening in all Romanian adults hospitalized in 4 COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment or immunosuppressive conditions, whom we followed virologically at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed in 13 patients with positive hepatitis B surface antigen (HbsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) in all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish an appropriate and cost-effective management in these patients.

Indoleamine 2,3-dioxygenase 2 (IDO2) is a paralogue of IDO1, a tryptophan-degrading enzyme producing immunomodulatory molecules. However, the two proteins are unlikely to carry out the same functions. IDO2 shows little or no tryptophan catabolic activity and exerts contrasting immunomodulatory roles in a context-dependent manner, in both cancer and autoimmune diseases. The recently described potential non-enzymatic activity of IDO2 has suggested its possible involvement in alternative pathways resulting in either pro- or anti-inflammatory effects in different models. In a previous study on non-small cell lung cancer (NSCLC) tissues, we found that IDO2 expression, revealed at the plasma membrane level of tumor cells, was significantly associated with poor prognosis. In this study, the A549 human cell line, basally expressing IDO2, was used as an in vitro model of human lung adenocarcinoma to gain more insights on a possible alternative function of IDO2, different from the catalytic one. In these cells, immunocytochemistry and isopycnic sucrose gradient analyses confirmed the IDO2 protein localization in the cell membrane compartment, and immunoprecipitation of tyrosine-phosphorylated proteins revealed that IDO2 can be targeted by kinase activities. The different localization than the cytosolic one and the phosphorylation state are the first indications for the signaling function of IDO2, suggesting that the IDO2 non-enzymatic role in cancer cells is worthy of deeper understanding.

In this review, we highlight new findings that have deepened our understanding of the mechanisms of leukemogenesis, therapy and resistance in APL. PML-RARa sets the cellular landscape of Acute promyelocytic leukemia (APL) by repressing transcription of RARa target genes and disrupting PML-NBs. RAR receptors control the homeostasis of tissue growth, modeling and regeneration, PML NBs are involved in self-renewal of normal and cancer stem cells, DNA damage response, senescence and stress response. Additional somatic mutations in APL mainly involve FLT3, WT1, NRAS, KRAS, ARID1B and ARID1A genes. Treatment outcomes in patients with newly diagnosed APL improved dramatically since the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). ATRA activates the transcription of blocked genes and degrades PML-RARα, while ATO degrades PML-RARa by promoting apoptosis and has a pro-oxidant effect. Resistance to ATRA and ATO may derive from mutations in the RARa ligand binding domain (LBD) and in the PML-B2 domain of PML-RARa, but such mutations cannot explain the majority of resistances experienced in the clinic, globally accounting for 5-10% of cases. Several studies are ongoing to unravel clonal evolution and resistance, suggesting the therapeutic potential of new retinoid molecules and combinatorial treatments of ATRA or ATO with different drugs acting through alternative mechanisms of action, which may lead to synergistic effects on growth control or induction of apoptosis in APL cells.

LASER cladding is a technique which has as main purpose to improve mechanical properties of materials surface with the addition of thin layers of other materials. Cladding/coating/addition material can be transferred to the substrate by powder injection, wire feeding or paste feeding and by the method of pre-placing the powders on the substrate. LASER cladding as a technique has only about 40 years. Is not yet a current technology and more work is needed, namely in the characterization of mechanical properties of new alloys used as base or cladding materials in this process. In this paper will be done initially an historical approach, followed by a description of the principles of the LASER cladding, a description of the applicability of the process and its advantages and limitations and the paper will end with a state of the art about the advances in new metallic alloys. So, this paper presents a review and the state of the art of the technological process and will be a contribution for the divulgation of this recent technique.

This paper presents a study about the integration of Piezoelectric Energy Harvesting Systems (PE-EHS) in building envelopes for powering Fiber Bragg Grating (FBG) sensors, enabling efficient and low-consumption monitoring with the objective to leverage Structural Health Monitoring (SHM). The research includes preliminary tests conducted in a real environment to validate the PE-EHS when fully integrated into the façade, capturing mechanical vibrations generated mainly by wind loads. Based on these activities, the final configuration of PE-EHS is defined to provide a complete system for façade monitoring. This integrated system includes the Piezoelectric Generator (PEG), Supercapacitor (SC), Power Conditioner Circuit (PCC), Fibre Optic Sensing (FOS) Interrogator, and the IoT Gateway trans-mitting measurement data within an Internet of Things (IoT) monitoring platform. This configuration is tailored to address the challenges related to the structural integrity of building envelopes. Results demonstrate a potential for a stand-alone solution in the façade sector, but, raising issues for certain limitations, requiring further investigation. In particular, the study emphasizes constraints related to the energy production of PE-EHS for façade integration. It highlights the necessity to carefully consider these limitations within the broader context of their applicability, providing insights for the informed deployment of Piezoelectric Energy Harvesting technology in building envelope monitoring.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Our concern was to obtain a biocomposite material with improved properties of the constituent materials (poly(lactic- co-glycolic acid) (PLGA) and zinc–boron (Zn–B) complex) in accordance with the novelties in the field of delivery systems for therapeutic agents which lately redefine the importance of biopolymer nanocomposites with PLGA (biodegradable composites). The advantages of such a biomaterial target the health system, being easy to obtain, through a cost-effective method. The water/oil/water double emulsion method also allows the adjustment of the synthesis parameters, to maximize the degree of Zn–B complex encapsulation. The morphological aspects of the samples (size, shape, porosity) were established by scanning electron microscopy (SEM). Particle size distribution (by volume and by number) was determined by direct light scattering (DLS). For all the synthesized materials, the observed morphology was typical for PLGA, spherical one. The particle size distribution showed that depending on the synthesis conditions, the particles can be obtained with diameters between 10–450 nm range and the value of the zeta potential (ZP) shows that the particles have electronegative surface charge, which offers a favorable perspective on the phenomena of aggregation, flocculation, dispersion. It was observed, applying the design of experiments (DoE), that the size of the particles increased with increasing amounts of PLGA and polyvinyl alcohol (PVA) in the formulation, while ZP increased with higher PLGA and smaller PVA. The encapsulation efficiency was determined by ultra-high performance liquid chromatography/mass spectrometry (UHPLC/MS).

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

The aim of this paper is to present a comprehensive overview of the main aims and scopes in screening of botanicals, a task which thin-layer chromatography (TLC) is on an everyday basis confronted with and engaged in. Stunning omnipresence of this modest analytical technique (both in its standard format (TLC) and the high-performance one (HPTLC), either hyphenated or not) for many analysts might at a first glance appear chaotic and random, with an auxiliary rather than leading role in research, and not capable of issuing meaningful final statements. Based on these reflections, our purpose is not to present a general review paper on TLC in screening of botanicals, but a blueprint rather (illustrated with a selection of practical examples), which highlights a sovereign and important role of TLC in accomplishing the following analytical tasks: (i) solving puzzles related to chemotaxonomy of plants, (ii) screening a wide spectrum of biological properties of plants, (iii) providing quality control of herbal medicines and alimentary and cosmetic products of biological origin, and (iv) tracing psychoactive plants under forensic surveillance.

PET imaging of bacterial infection could potentially provide added benefit for patient care by non-invasive means. [68Ga]Ga-desferrioxamine B – a radiolabelled siderophore – shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa as well as sufficient serum stability for clinical application. Here, we provide data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette based synthesis modules (Modular-Lab PharmTracer and GRP 3V) using commercially available cassettes together with an approved 68Ge/68Ga radionuclide generator. Quality control including determination of radiochemical purity as well as a system suitability test was set up via RP-HPLC on a C18 column. The two described production processes, using an acetic acid/acetate buffer system with ascorbic acid as a radiation scavenger for radiolabelling, yield ready-to-use formulations with sufficient activity yield. Batch data showed radiochemical purity of &gt;95 % as determined by RP-HPLC and ITLC as well as excellent stability over 2 hours post production. Specifications for routine production were set up and validated with four master batches for each synthesis module. Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable reproducible, automated in-house production of [68Ga]Ga-desferrioxamine B for clinical application.

The aim is to evaluate a program for direct oral anticoagulants (DOACs) management in nonvalvular atrial fibrillation (NVAF) patients, according to patient profiles, appropriateness of dosing, patterns of crossover, effectiveness and safety. This is an observational and longitudinal retrospective study in a cohort of patients attended in daily clinical practice in a single regional hospital in Spain with a systematic follow-up plan for up to 3 years for patients initiating dabigatran, rivaroxaban or apixaban between JAN/2012-DEC/2016. We analyzed 490 episodes of treatment (apixaban 2.5 mg: 9.4%, apixaban 5 mg: 21.4%, dabigatran 75 mg: 0.6%, dabigatran 110 mg: 12,4%, dabigatran 150 mg: 19.8%, rivaroxaban 15 mg: 17.8% and rivaroxaban 20 mg: 18.6%) in 445 patients. 13.6% of patients on dabigatran, 9.7% on rivaroxaban, and 3.9% on apixaban, switched to other DOACs or changed dosing. Apixaban was the most frequent DOAC switched to. The most frequent reasons for switching were toxicity (23.8%), bleeding (21.4%) and renal deterioration (16.7%). Inappropriateness of dose was found in 23.8% of episodes. Patients taking apixaban 2.5 mg were older, had higher CHA2DS2VASc score and lower creatinine clearance. Patients taking dabigatran 150 mg and rivaroxaban 20 mg were younger, had lower CHA2DS2VASc and higher creatinine clearance. Rates of stroke/transient ischemic attack (TIA) were 1.64/0.54 events/100 patients-years, while rates of major, clinically relevant non-major (CRNM) bleeding and intracranial bleeding where 2.4, 5, and 0.5 events/100 patients-years. Gastrointestinal and genitourinary bleeding were the most common type of bleeding events (BE). On multivariable analysis, prior stroke (RR: 4.2; CI: 1.5-11.8; p=0.006) and age (RR: 1.2; CI: 1.1-1.4; p=0.006) were independent predictors of stroke/TIA. Concurrent platelet inhibitors (RR: 7.1; CI: 2.3-21.8; p=0.001), male gender (RR: 2.1; CI: 1.2-3.7; p=0.0012) and age (RR: 1.1; CI: 1.02-1.13; p=0.005) were independent predictors of BE. This study complements the scant data available on the use of DOACs in NVAF patients in Spain, confirming a good safety and effectiveness profile

Background: The effect of the COVID-19 pandemic has transformed medical education and is likely to have long-lasting effects on student learning, mental well-being, and eating behaviour. This study aimed to examine the learning behaviors of medical students at the American University of Integrative Sciences (AUIS), Barbados, during the COVID-19 pandemic. Methods: A cross-sectional web-based online survey was administered to medical students at AUIS from July until November 2021. The data collecting instrument recorded students’ demographic and learning behaviour information (Meo et al. 2020), and eating disorders (SCOFF questionnaire). Results: The overall response rate was 55% (n=120). In relation to learning behaviour, students agreed with the following statements: ‘deterioration in work performance and studying’ (48.4%), ‘remember subject’s contents appropriately’ (40.4%), ‘concentration on the studies’ (40.3%), ‘difficulty in performing two tasks simultaneously’ (38.7%), ‘difficulty in performing mental calculations’ (33.9%), ‘difficulty in recalling recent information’ (32.3%), and ‘difficulty in recalling old information’ (38.7%). Among the 8 dimensions of learning behaviors, deterioration in work performance or studying, and difficulties in recalling recent information were found to be significantly associated with the gender of the students. For SCOFF questionnaire, approximately 24.2% screened positive for eating disorders. Screening with the SCOFF test demonstrated that female, older (>25 years), overweight + obese, Clinical Sciences + PreMed, and non-USA-based students were at more risk of eating disorders. Conclusions: The results indicate that during the COVID-19 pandemic AUIS students have developed learning difficulties, and are likely to have eating disorders. University policymakers should take appropriate measures to support a healthy learning environment and improve students' mental well-being and eating behaviours.

The search for molecular biosignatures at the surface of Mars is complicated by an intense irradiation in the mid- and near- ultraviolet (UV) spectral range for several reasons: (i) many astrobiologically relevant molecules are electronically excited by efficient absorption of UV radiation and rapidly undergo photochemical reactions; (ii) even though the penetration depth of UV radiation is limited, aeolian erosion continually exposes fresh material to radiation; and (iii) UV irradiation generates strong oxidants such as perchlorates that can penetrate deep into soils and cause subsurface oxidative degradation of organics.As a consequence, it is crucial to investigate the effects of UV radiation on organic molecules embedded in mineral matrices mimicking the martian soil, in order to validate hypotheses about the nature of the organic compounds detected so far at the surface of Mars by the Curiosity rover, as well as organics that will be possibly found by the next rover missions Mars 2020 and ExoMars 2020. In addition, studying the alteration of possible molecular biosignatures in the martian environment will help to redefine the molecular targets for life detection missions and devise suitable detection methods.Here we report the results of mid-UV irradiation experiments of Mars soil analog samples obtained adsorbing relevant organic molecules on a clay mineral that is quite common on Mars, i.e. montmorillonite, doped with 1 wt% of magnesium perchlorate. Specifically, we chose to investigate the photostability of a plausible precursor of the chlorohydrocarbons detected on Mars by the Curiosity rover, namely phthalic acid, along with the biomarkers of extant life L-phenylalanine and L-glutamic acid, which are proteomic amino acids, and adenosine 5’-monophosphate, which is a nucleic acid component.We monitored the degradation of these molecules adsorbed on montmorillonite through in situ spectroscopic analysis, investigating the reflectance properties of the samples in the Near InfraRed (NIR) spectral region. Such spectroscopic characterization of molecular alteration products provides support for two upcoming robotic missions to Mars that will employ NIR spectroscopy to look for molecular biosignatures, through the instruments SuperCam on board Mars 2020, ISEM, Ma_Miss and MicrOmega on board ExoMars 2020.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Objectives Listeria monocytogenes (LM), the etiological agent of Listeriosis, can cause foodborne zoonosis. In this study, we characterized 23 strains that caused human listeriosis in Palermo (Sicily, Italy) during the period 2018-2020. In addition, we assessed the phenotypic susceptibility of clinical isolates to antibiotics in accordance with EUCAST guidelines. Methods The serogroup was determined by PCR. While MLST and MVLST were identified through the sequencing of housekeeping genes. Finally, susceptibility to antibiotics was assessed by means of the Phoenix automatic system. Results Patients hospitalized with listeriosis were predominantly males (56% vs. 44% of females). The cases were not associated with pregnancy included patients >65 years of age (60%), two of whom were affected by cancer, while cases associated with pregnancy included two pregnant women and three preterm infants. Data collected found that the main pathologies shown by patients were meningitis (60,9%) and bacteremia (39,1%). The LM strains were isolated from blood (52%), cerebrospinal fluid (26%), cerebrospinal fluid + blood (13%), blood + nasal swab (4%), and ascitic fluid (4%). The predominant serogroup was IVb (96%), whereas only one strain belonged to serogroup IIa (4%). Among the strains with serotype 4b, 4d, 4e, ST 2/VT 21 (92%) and ST6/VT19 (4%) were determined, while only isolates with serotype 1/2a, 3a show ST155/VT45 (CC155). Conclusion This study revealed the widespread circulation of a single clinical strain (ST2/VT21) associated with suspected food contamination, demonstrating the importance of carrying out molecular epidemiological surveillance. Our clinical isolates were susceptible to the assayed beta-lactams, in agreement with the literature data.

This paper compares the Medieval (ca. 400–1500 CE) dynamics of forests from low-mountain (Montcortès; ca. 1000 m a.s.l.) and high-mountain (Sant Maurici; 1900 m a.s.l.) areas of the Iberian Pyrenees, both of which experienced similar climatic forcing but different anthropogenic pressures. The main aim is to identify forest changes over time and associate them with the corresponding climatic and anthropogenic drivers (or synergies among them) to test how different forests at different elevations respond to external forcings. This could be useful to evaluate the hypothesis of general Pyrenean deforestation during the Middle Ages leading to present-day landscapes and to improve the background for forest conservation. The study uses palynological analysis of lake sediments, historical documents and paleoecological reconstructions based on pollen-independent proxies. The two sites studied showed different forest trajectories. The Montcortès area was subjected to intense human pressure during regional deforestation up to a maximum of ca. 1000 CE. Further forest recovery took place until the end of the Middle Ages due to a change in forest management, including the abandonment of slash-and-burn practices. Climatic shifts indirectly influenced forest trends by regulating human migrations and the resulting shifts in the type and intensity of forest exploitation. The highland Sant Maurici forests exhibited a remarkably long-standing constancy and an exceptional resilience to climatic shifts, which were unable to affect forest extension and composition, and to local human pressure, from which they rapidly recovered. The Montcortès and Sant Maurici records did not follow the rule of an irreversible forest clearing during the Middle Ages leading to present-day landscapes. The present Montcortès landscape was shaped after a Medieval forest recovery, a new Modern-Age deforestation and a further forest recovery during the last centuries. The Sant Maurici forests remained apparently untouched since the Bronze Age and were never cleared during the Middle Ages. The relevance of these findings for forest conservation is briefly addressed, and the need for the development of more high-resolution studies on Pyrenean forest dynamics is highlighted.

Direct intercellular communication, mediated by gap junctions formed by the connexin transmembrane protein family, is frequently dysregulated in cancer. Connexins have been described as tumour suppressors, but emerging evidence suggests that they can also act as tumour promoters. This feature is connexin- and tissue-specific and may be mediated by complex signalling pathways through gap junctions or hemichannels or by completely junction-independent events. Lung cancer is the number one cancer in terms of mortality worldwide, and novel biomarkers and therapeutic targets are urgently needed. Our objective was to gain a better understanding of connexins in this setting. We used several in silico tools to analyse TCGA data in order to compare connexin mRNA expression between healthy lung tissue and lung tumours and correlated these results with gene methylation patterns. Using Kaplan-Meier plotter tools, we analysed a microarray dataset and an RNA-seq dataset of non-small cell lung tumours in order to correlate connexin expression with patient prognosis. We found that connexin mRNA expression is frequently either upregulated or downregulated in lung tumours. This correlated with both good and poor prognosis (overall survival) in a clear connexin isoform-dependent manner. These associations were strongly influenced by the histological subtype (adenocarcinoma versus squamous cell carcinoma). We present an overview of all connexins but particularly focus on four isoforms implicated in lung cancer: Cx26, Cx30.3, Cx32 and Cx43. We further analysed the protein expression and localization of Cx43 in a series of 72 human lung tumours. We identified a subset of tumours that exhibited a unique strong nuclear Cx43 expression pattern that predicted worse overall survival (p=0.014). Upon sub-stratification, the prognostic value remained highly significant in the adenocarcinoma subtype (p=0.002) but not in the squamous carcinoma subtype (p=0.578). This finding highlights the importance of analysis of connexin expression at the protein level, particularly the subcellular localization. Elucidation of the underlying pathways regulating Cx43 localization may provide for novel therapeutic opportunities.

Buildings are subject to intrinsic and extrinsic failures at all stages of the construction process, i.e., design to occupancy (i.e., use) as several failure types can affect them. There are three basic steps for researching building failures: listing, cataloging, and solving/deciding whether highlighting the least invasive and lowest cost intervention. Therefore, this research presents some methods used in construction for the intervention prioritization and seeks to illustrate the most suitable methodology for different settings failure x diagnosis x intervention. Therefore, the most traditional tools are shown: BASICO, SWIFT, FEMEA, AAF, and GUT matrix, where a critical assessment of the strengths and weaknesses is carried out. After that, a case study on maintenance services for the moisture on the building facades was performed. Finally, the GUT matrix and the FMEA method are the best results

Cell identity is determined by chromatin structure and the profiles of gene expression, which are dependent on chromatin accessibility and DNA methylation of regions critical for gene expression, such as enhancers and promoters. These epigenetic modifications are required for mammalian development and are essential for the establishment and the maintenance of the cellular identity. DNA methylation was once thought to be a permanent repressive epigenetic mark, but systematic analysis in various genomic contexts reveals a more dynamic regulation than previously thought. In fact, both active DNA methylation and demethylation occur during cell fate commitment and terminal differentiation. To link methylation signatures of specific genes to their expression profiles, we have determined the methyl-CpG configurations of the promoters of five genes switched on and off during murine postnatal brain differentiation by bisulfite-targeted sequencing. We report here the structure of significant, dynamic and stable methyl-CpG profiles associated with silencing or activation of expression of genes during neural stem cell and brain postnatal differentiation. Strikingly, these methylation cores mark different mouse brain areas and cell types derived from the same areas during differentiation.

Anticipating future successional forest trends in the face of ongoing global change is an essential conservation target. Mountain forests are especially sensitive to environmental shifts, and their past responses to climatic and anthropogenic (external) drivers may provide a basis for improving predictions of future developments. This paper uses independent high-resolution palynological and paleoclimatic reconstructions to statistically analyze the long-term effects of external drivers on regional forest succession in the central Iberian Pyrenees during the last 500 years. The dominant taxa of these forests (Quercus, Betula, Pinus) showed significant relationships with summer temperature, summer drought and autumn precipitation. Immediate and delayed (by two or more decades) responses of these trees to climatic drivers were identified. Regional succession showed a closed path, starting at the end points around the attraction domain of pine-dominated forests. This trajectory was determined by a trend toward anthropogenic forest clearing (16th to 18th centuries) and a reverse trend of natural forest recovery (18th to 20th centuries). Forest clearing was due to burning, facilitated by drought, and was followed by the expansion of cropping and grazing lands. Forest recovery was fostered by reduced human pressure and rising temperatures. The statistical approach used in this work has unraveled ecological relationships that remained unnoticed in previous works and would be important for predicting future successional trends under changing climates. The reported response lags of individual taxa to climatic drivers may complicate the establishment of reliable ecological relationships and should be addressed in future studies.

Long-term safety of a nutraceutical combination based on agnus castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli, and effectiveness on vasomotor symptoms and sleep disorders in postmenopausal women, were assessed. A controlled study was carried-out in menopausal women comparing this nutraceutical combination (ESP group) with formulation containing isoflavones alone (C group), at the dosage recommended. Kuppermann index, PSQI, and SF-36 were determined at baseline, 3, 6 and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. 180 women (100 in ESP group and 80 in C group, mean age 55.5 years, in menopause for about 36 months) were enrolled in the study. At the treatment end, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. Kuppermann index, and particularly hot flushes, were progressively and significantly decreased in frequency and severity during ESP versus C treatment. No adverse events were observed. Agnus castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. Endometrium, mammary glands and liver function, were unaffected after 12 months treatment.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

Systemic Lupus Erythematosus (lupus) and B-cell lymphoma (lymphoma) are serious diseases. Lupus and lymphoma co-occur at higher-than-expected rates and primarily depend on B-cells for their pathology, implicating shared inflammation-related B-cell molecular mechanisms as a potential cause of co-occurrence. We consequently implemented a novel Immune Imbalance Transcriptomics (IIT) algorithm and applied IIT to lupus, lymphoma, and healthy B-cell RNA-seq data to find shared- and contrasting mechanisms potentially targetable for treatment. We observed 8,562 genes significantly dysregulated in both lupus and lymphoma. Of those genes, we found 5,335 to have a significant immune imbalance, defined as significant dysregulation by both diseases, as determined by IIT. Gene Ontology (GO) term and pathway enrichment of IIT genes yielded immune-related “Neutrophil Degranulation” and “Adaptive Immune System”, validating that the IIT algorithm isolates biologically relevant genes in immunity and inflammation. We found that 389 IIT gene products are drug-targetable with established or repurposed drugs. Among our results, we found 40 known and 349 novel lupus targets, along with 151 known and 238 novel lymphoma targets. Known disease drug targets in our IIT results further validate that IIT isolates genes with disease-relevant mechanisms. We anticipate the IIT algorithm and shared and contrasting gene mechanisms uncovered here will contribute to the development of immune-related therapeutic options for lupus and lymphoma patients.

This study was conducted to propose the Green Economic Development Plan for Manufacturing S.M.E.s based on financial performance and operations thru Green Initiatives. The descriptive survey method used to gather data to determine the green initiative's implementation of small and medium (S.M.E.s) manufacturing enterprises. Green initiatives use as a basis for crafting a green economic development plan. Document analysis was also employed to obtain data from any available printed materials and records provided by the respondents. Such methods of gathering information used to validate data gathered from local and foreign-related literature. The observation also employed to survey the assets owned and validate any green initiatives practiced, including their implementation. The study's findings show that among the green initiatives implemented by SMMEs, which resulted in the reduction of total costs and expenses, were the proper disposal and segregation of waste materials, water management by recycling wastewater and using water-efficient equipment, natural resources, and raw materials management. SMMEs should encourage active participation and support of suppliers and customers in achieving G.E.D.'s objectives by developing incentive schemes.Furthermore, SMMEs should continue to benchmark with G.E.D. Practitioners are operating locally and abroad to adopt best greening strategies and regularly network with concerned government agencies for continuous updating on G.E.D. Initiatives that may benefit the firm. Further research may be conducted on green initiatives implemented by small and medium enterprises in other industry sectors.

Plant diseases not only cause economic losses, but they also pose a health risk. In this regard, aflatoxins are linked to the development of some type of liver cancer, especially the hepatocellular carcinoma. Aflatoxins are usually produced by the fungi Aspergillus flavus and Parsiticus in figs, and their identification is usually carried out using invasive and complex methods or by visual inspection at an advanced stage. Given that Spain is one of the main producers of figs and Extremadura is the leading region in the country, it is necessary to explore alternative ways of detecting the presence of aflatoxins in figs and preventing them from entering the food chain. The aim of this research is to address the early detection of Aspergillus flavus fungus using non-invasive techniques with the aid of hyperspectral imaging and the application of artificial intelligence techniques, in particular deep learning. The images were taken after inoculation of the microtoxin using 3 different concentrations, related to three different classes and healthy figs (healthy controls). The analysis of the hyperspectral images was performed at the pixel level. Firstly, a full connected neural network was used to analyse the spectral signature associated with each pixel; second, the wavelet transform was applied to each spectral signature. The resulting images are fed to a convolutional neural network. The hyperparameters of the proposed models were adjusted based on the parameter tuning process also performed. The results are promising, with 83% accuracy, 82.75% recall and 83.25% F1-measure for the single neural network, and 77.25% accuracy, recall and F1 for the convolution neural network.

This paper presents and demonstrates the development of a new lightweight coating for aluminium alloy using a novel multicomponent alloy based on the AlSiMgCu system. This coating was applied using a newly designed approach that combined High-Velocity Oxy-Fuel (HVOF) and Plasma Spraying processes. This hybrid technique enables the deposition of coatings with enhanced performance characteristics. The microstructure was studied using optical microscopy (OM) and scanning electron with energy dispersive X-ray spectroscopy (SEM+EDS) microscopy, revealing good adhesion and compaction between the multicomponent coating and the A6061 substrate with 50 to 150 µm thickness. Vickers indentations were performed on the substrate and the new coating material, revealing a 50% improvement in the material's hardness compared to the casted alloy. Additionally, electrical conductivity measurements showed approximative x3.3 times values compared to the alloy in as-cast condition due to high solidification rates altering the morphology of the phases. Corrosion tests demonstrated a lower corrosion rate compared to other multicomponent aluminium alloys and similar to thermal treated A6061 alloy. Finally, tribological results obtained using ball on disc (BOD) test and laser scanning confocal microscopy, confirmed that the new multicomponent coating exhibited reductions in both friction coefficient and wear rate by more than 20% and 50%, respectively. This study demonstrates that using multi-component aluminium coatings could lead to developing of new automotive parts with enhanced properties for corrosion resistance, electrical conductivity, and wear conditions. Optimizing the thermal spraying parameters could further enhance the coating, achieving greater and more homogeneous thicknesses and yielding even higher performance properties.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

This paper details the comprehensive activities conducted in a laboratory setting to assess the Structural Health Monitoring (SHM) of prefabricated building envelopes. Aimed at enhancing the structural evaluation of buildings, the focus of this research lies in employing nondestructive sensors for SHM with the objective to advance in the understanding and assessment of facade conditions. The paper outlines the methodologies employed, starting with a modal analysis to define the structural vibration's modal frequency. Subsequently, tests were defined and executed to validate building envelope compliance in case of stress typical of high-rise building. Throughout these tests, continuous monitoring of the façade was conducted using both conventional (accelerometers, extensimeter washers) and non-conventional sensors (Fiber Optic Sensing) The gathered data underwent thorough processing and analysis to provide an overall perspective on the structure's behavior during the stress test. The investigation aimed to identify whether specific physical phenomena correlate with distinct signals and to evaluate if continuous façade monitoring over the building's lifespan aids in preventing potential structural damage. Moreover, two modal analyses were conducted to compare final data and frequencies with earlier data, enabling the detection of any structural alterations. The results from compliance testing and structural analysis yielded noteworthy insights contributing to the evolving field of structural health monitoring, offering valuable findings that advance our ability to proactively manage and maintain the integrity of building structures.

Chronic Hepatitis B (CHB) Virus infection is major etiological factor for liver cirrhosis and/ or liver cancer. The viral protein, major contributor in predisposition of chronicity and Hepatocellular Carcinoma (HCC) is Hepatitis B x (HBx) protein. Its dynamic subcellular distribution to an extent determines its multifactorial role. It is a regulatory protein which modulates viral as well as host machinery in favours to HBV persistence. An insight on HBx stabilising factors is critical for therapeutic purpose. The precise role of HBx in the pathogenesis of Chronicity of HBV is not known. Summary: This review comprehensively summarizing different mechanisms and their regulation by HBx protein with respect to chronicity and HCC emphasising viral persistence. Key Messages 1. HBx is a key protein for viral persistence. 2. Dynamic subcellular distribution of HBx determines its function. 3. HBx modulates cellular machinery to favours HBV survival. 4. HBx affects various intermediary mechanisms contributing to disease progression. 5. HBx may be a potent target to prevent the disease progression towards HCC.

The COVID-19 pandemic crisis has brought about unprecedented economic and social consequences worldwide. The implementation of isolation measures, including national and international travel restrictions, significantly affected contact-intensive sectors such as tourism. During this lockdown period, Information and Communication Technology (ICT) was crucial in maintaining connectivity and enabling remote activities. Governments across the world implemented discretionary measures to mitigate the crisis's adverse effects on economic activity. This paper aims to analyze whether the level of ICT adoption and the importance of tourism influence the fiscal policy efforts pursued by governments. Based on the results of a linear regression analysis for 154 countries, the findings suggest that in countries with higher international tourism receipts, the governments had to promote higher fiscal stimulus. At the same time, ICT development diminished the efforts of the fiscal policy response to the crisis since it facilitated economic resilience. The findings of this study can contribute to understanding how governments responded to the pandemic crisis and the factors that influenced their fiscal policy decisions.

Alkali-containing submicron particles were measured continuously during three months, including late winter and spring seasons in Gothenburg, Sweden. The overall aims were to characterize the ambient concentrations of combustion-related aerosol particles and to address the importance of local emissions and long-range transport for the atmospheric concentrations in the urban background environment. K and Na concentrations in the PM1 size range were measured by an alkali aerosol mass spectrometer (Alkali-AMS) and a cluster analysis was conducted. Local meteorological conditions and some other data sets were obtained, and back trajectory analyses and chemical transport model (CTM) simulations were included for the evaluation. The Alkali-AMS cluster analysis indicated three major clusters: 1) biomass burning origin, 2) mixture of other combustion sources, and 3) marine origin. Low temperatures and low wind speed conditions correlated with high concentrations of K-containing particles, mainly due to regional emissions from residential biomass combustion; transport of air masses from continental Europe also contribute to cluster 1. The CTM results indicate that open biomass burning in the eastern parts of Europe may have contributed substantially to high PM2.5 concentrations (and to cluster 1) during an episode in late March. According to the CTM results the mixed cluster (2) is likely to include particles emitted from different source types and no single geographical source region seems to dominate for this cluster. The back trajectory analysis and meteorological conditions indicated that the marine origin cluster was correlated with westerly winds and high wind speed; this cluster had high concentrations of Na-containing particles, as expected for sea salt particles.