Introduction: Pharmaceutical tablets are solid forms administrated orally and they constitute 80% of the market because of its best stability and ease of large-scale production, adherence and treatment. The Brazilian Legislation establishes that for a drug to be registered as a similar or generic drug is necessary to verify the pharmaceutical equivalence in relation to the reference drug, indicated by ANVISA, through quality control tests, ensuring that the drug is approved with satisfactory quality. Objective: to evaluate the reference, generic and similar glibenclamide tablets through quality control tests, comparing the results with each other and relate clinical impacts on the patient in the face of changes in the quality control of medicines. Methodology: tests of average weight, friability and disintegration were done, according to the Brazilian Pharmacopoeia VI Edition, in uncoated tablets of Glibenclamide 5mg Reference (Daonil), Generic (Glibenclamide) and Similar (Glionil), and the results obtained were compared with the that advocates the scientific literature. Results: Data referring to the average weight: Reference 0.1591g, Generic 0.1002g and Similar 0.0996g; For friability: Reference value 0.54%, Generic value 0.49% and Similar value 0.28%. The disintegration tests showed the following times: Reference 35 seconds, Generic 29 seconds and Similar 33 seconds. Conclusion: the tests to which the glibenclamide tablets were submitted showed results within the parameters established by the Brazilian Pharmacopoeia.

The pandemic crisis of Covid-19 disturbed the social and the economic systems in which some changes happened during the pandemic and other changes extended subsequently. This paper is reflecting on the Sudan case, a country of a moderate population and large area with poor socioeconomic standard and infrastructure. The paper is based on the analysis of primary data and policy recommendations of an original research undertaken in five States in Sudan during the period Sept.2021-Sept.2022. The sample of the study selected from most five States that were affected by the Corona pandemic, namely: Khartoum State, Gezira State in the Central Region, Kassala State and Gadarif State from the Eastern Region, and Nyala State in the South Darfur Region in the west of the country. The research built on a quantitative research method, used the questionnaire as a tool for data collection from a sample size of 723 family head-households. The study is gaining a better understanding of the social, economic and health challenges that faced Sudanese households during the COVID-19 lock down and within the pandemic period. The study showed crucial results that the education of children was disturbed due to unavailability of the distance education in schools. In contrast some families maintained the education of the children as enrolled in private schools. In addition, the paper shows how the families used different approaches to educate their children and involve them into traditional informal and formal education ways. Additionally, the results explained the coping strategies with available resources that families used to manage economic crises and how this interferes with children education. Furthermore, the study proposing appropriate social policies and interventions that address the needs of the family in the current and future pandemic crisis.

In response to the increasing complexity and sophistication of cyber threats, particularly those enhanced by advancements in artificial intelligence, traditional security methods are proving insufficient. This paper explores the zero-trust cybersecurity framework, which operates on the principle of "never trust, always verify" to mitigate vulnerabilities within organizations. Specifically, it examines the applicability of zero-trust principles in environments where large volumes of information are exchanged, such as schools and libraries, highlighting the importance of continuous authentication, least privilege access, and breach assumption. The findings highlight avenues for future research that may help preserve the security of vulnerable organizations.

The article presents the issues related to the operation and modelling of the ship main propulsion steam boiler. Such objects are used widely in seagoing ships especially the very large crude oil carriers as a main propulsion turbine feed. The advantages of such along with simple construction thus great reliability make oil feed boilers an excellent source of power for chosen type of the large ships. It must be pointed out that a lot of research work was done in the previous years regarding automatic control of boiler automation but since then this technology was not in the focus of the researchers. In the future the fossil fuels will become less important than they are now, but the control techniques of boilers would eventually change due to different fuel parameters therefore, development of such is necessary. The article presents the results of research collected in real ship boilers during their operation and then, based on the results, a digital model of such an object was created. This model was implemented into Hardware-In-Loop which is the initial step for preparing the full model (including sensors etc.) of a steam heated boiler. Theoretical background along with chosen simulation and experimental results of control implemented into HIL were presented to validate assumptions...

Ondol, a heating system unique to Korean homes, raises indoor temperatures by supplying hot water through pipes embedded in the floor slab. Known for its comfort and sustained heat advantages, Ondol has garnered international interest in countries requiring efficient heating solutions. Given the inherent challenges during installation and operation, timely inspection is crucial due to difficulties in detecting and pinpointing defects in the buried concrete pipes, often leading to costly rework and removal. Yet, specialized inspection systems tailored for Ondol pipes remain underexplored. Therefore, this study proposes a robotic inspection system capable of assessing the condition of Ondol pipelines. We analyzed the characteristics of Ondol piping to establish the system requirements and developed a prototype of a compact capsule-shaped inspection robot tailored for Ondol pipe inspection. Subsequent laboratory testing validated its performance and usability, confirming its capability for field application through tests on curvature maneuverability and image reception quality. This research aims to motivate advancements in Ondol-specific system implementation and performance validation, potentially contributing to the smartification of Ondol maintenance practices.

The term "sustainable urbanism" has been criticized over its inconsistent and imprecise definition, leading to challenges in implementing actionable reforms and achieving urban sustainability goals. A clearer approach may be to identify its opposite: specifically, forms of urbanism that cause an unacceptable buildup of toxic or climate-altering emissions, deplete resources beyond sustainable levels, progressively destroy critical ecologies, and cause other identifiable sources of potentially catastrophic harm to human and urban welfare. Here we present a model of such an “unsustainable urbanism,” and we observe further that it is in fact the dominant model of urban structure to this day. Its features include an over-reliance on low-occupancy vehicular transport; inefficient envelope, size, orientation and adaptability of buildings; ecologically destructive infrastructure systems for handling water, energy and other resources; and – under-appreciated but fundamentally important, as we will explore – decline of a well-connected, walkable, functionally and aesthetically appealing public realm. This model remains dominant in spite of the many goals, agenda and declarations on sustainable urbanism at the highest policy level. We observe that the lack of progress is in large part the result of system “lock-in” – economic and professional incentives and disincentives, standards, laws, codes, and other forms of feedback that reinforce “business as usual,” and create barriers to reform. Therefore, the agenda ahead must address the specific levers of change to overcome this systemic lock-in, drawing insights from economics, technology and the social sciences to do so. We present the outlines of this agenda, and make conclusions for needed steps ahead.

A typical orchard's mechanical operation consists of three or four stages: lining, digging for plantation, moving the seedling from nurseries to the farm, moving the seedling to the planting hole, and planting the seedling in the hole. However, the digging the planting hole is the most time-consuming operation. In fruit orchards, robots' usage is increasingly becoming more prevalent to increase operational efficiency. They offer practical and effective services to both industry and people, whether they are assigned to plant trees, reduce the use of chemical fertilizers, or carry heavy loads to relieve staff. Robots can operate for extended periods of time and can highly adept at repetitive tasks like planting many trees. The present study aims to identify the locations for planting trees in orchards using geographic information systems (GIS), to develop an autonomous drilling machine and use the developed robot to open planting holes. There isn't a comparable study on autonomous hole planting in the literature in this regard. The agricultural mobile robot is a four wheeled nonholonomic robot with differential steering and forwarding capability to stable target positions. The designed mobile robot can be used in fully autonomous, partially autonomous, or fully manual modes. The drilling system, which is a y-axis shifter driven by a DC motor with reducer includes an auger with a 2.1 HP gasoline engine. SOLIDWORKS software was used for designing and drawing of the mobile robot and drilling system. The Microsoft Visual Basic.NET programming language was used to create the robot navigation system and drilling mechanism software. The cross-track error (XTE), which determines the distances between the actual and desired holes positions, was utilized to analyze the steering accuracy of the mobile robot to the drilling spots. Consequently, the average of the arithmetic means was determined to be 4.35 cm, and the standard deviation was 1.73 cm. This figure indicates that the suggested system is effective for drilling plant holes in orchards.

Abstract: To obtain bovine oocytes in high quality, effects of vitamin C (VC) on in vitro maturation (IVM) of bovine oocytes and early embryo development were investigated. The results showed that: 1) The IVM medium containing 50 µg/mL VC improved the oocyte maturation rate, while no effects on the development of parthenogenetic embryos; 2) The in vitro culture (IVC) medium containing 20 µg/mL VC increased the cleavage rate of the in vitro fertilized (IVF) embryos, enhanced the mRNA levels of pluripotency gene Oct4, Sox2, Cdx2 and Nanog in the blastocysts, but no effect on the blastocyst rate; 3) Combing supplemention of 50 µg/mL in IVM medium + 20 µg/ml VC in IVC medium (VC 50/20) increased the cleavage rate of IVF embryos and enhanced the mRNA levels of Oct4, Sox2, Cdx2 and Nanog in the blastocysts; 4) Combination of VC 0/20 and VC 50/20 enhanced the expression of anti-apoptotic gene Bcl-2 and VC 50/0 weakened the expression of pro-apoptotic gene Bax, while VC 0/40 and VC 0/60 increased Bax expression and decreased the Bcl-2/Bax ratio in blastocysts. Together, VC supplementation at tuned concentration as well its combination in IVM and IVC media improves the developmental rates of bovine oocytes and embryos.

Using two independent speckle imaging systems based on the recently published LSOCI method operating in contact mode on the skin, we assess the reproducibility of in vivo measurements and conduct an inter-instrument comparison. To this aim, we propose a calibration method to handle each imaging system as a comprehensive unit, which includes the laser source, optics, and camera. Our experimental results demonstrate that the microcirculation images produced by both instruments exhibit high accuracy and stability, with microcirculation activity values in excellent agreement, thereby paving the way for clinical applications.

Background: Electrical Impedance Tomography (EIT), combined with variable ventilation strate-gies and Artificial Intelligence (AI), is poised to revolutionize critical care by transitioning from reactive to predictive approaches. This integration aims to enhance patient outcomes through personalized interventions and real-time monitoring. Methods: This narrative review explores the principles and applications of EIT, variable ventilation, and AI in critical care. EIT’s impedance sensing creates dynamic images of internal physiology, aiding in the management of conditions like Acute Respiratory Distress Syndrome (ARDS). Variable ventilation mimics natural breathing variability to improve lung function and minimize ventilator-induced lung injury. AI enhances EIT through advanced image reconstruction techniques, neural networks, and digital twin technology, offering more accurate diagnostics and tailored therapeutic interventions. Conclu-sions: The confluence of EIT, variable ventilation, and AI represents a significant advancement in critical care, enabling a predictive, personalized approach. EIT provides real-time insights into lung function, guiding precise ventilation adjustments and therapeutic interventions. AI inte-gration enhances EIT's diagnostic capabilities, facilitating the development of personalized treatment plans. This synergy fosters interdisciplinary collaborations and sets the stage for in-novative research, ultimately improving patient outcomes and advancing the future of critical care.

The principal function of science education is to introduce students to core scientific concepts and practices; nevertheless, it is now impossible, in such a complex world, to neglect the ethical issues involved. Placing school science in a broader context motivates students and equips them with valuable critical skills. A meaningful example was from palm oil production and pervasive use worldwide: plantations result in major deforestation occurring in species-rich tropical regions, making the palm oil issue global in scope and highly critical for several aspects related to sustainability. This paper reports a sequence of didactic activities starting from palm oil chemistry, gradually extended initially by a multidisciplinary approach, then by interdisciplinary-systemic maps and, ultimately, through a holistic vision - involving anthropological and cultural considerations about indigenous people of deforested territories. This progressive broadening corresponds to an ever-greater penetration into the personal sphere, a condition for a real ethical consciousness. The increased students’ awareness was tested by qualitative considerations, supporting the teaching dimension more than the learning one. Contrary to disciplinary contents, the emergence of moral feelings cannot be measured but only perceived. Therefore, chemistry provides key concepts essential for global competences development in order to deal with sustainability issues with an increased ethical awareness.

The use of antibiotics in neonatal units worldwide varies significantly. We included data from 2015-2022 from the EpicLatino database, which comprises a network of 32 units in Latin America and the Caribbean with gestational age at birth (GA) of ≤ 32 weeks. A questionnaire was sent to the EpicLatino units, to correlate practice with outcomes. Negative binomial regression with standard errors and confidence intervals computed for incidence-rate ratios (IRRs) was used for comparative statistics on antibiotic days per 1000 patient-days between units. All units that responded had 1-6 differences with the reference unit (Unit 2) with the best results, but there was no clear association with the IRR. Each EpicLatino unit should review its statistics to explore possibilities for reducing antibiotic usage.

Museums are called to respond to contemporary challenges and contribute to the formation of more progressive societies. One of the major challenges of our time is climate change and museums could construct cocreated narratives around climate and implement targeted actions for the audiences through their sensorial and affective experiences. More specifically, Geology and Palaeontology museums are repositories of knowledge on geoheritage and geoconservation, recognized for their scientific, pedagogical, cultural and recreational values. The educational potential of geological and paleontological exhibits could be used in informal education activities regarding the climate emergency. Taking the above into consideration, this study focuses on both the creation and evaluation of an educational program for the Natural History Museum of Arsakeio Campus at Psychicko.

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-vivo tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract.

Laser in situ keratomileusis (LASIK) is the gold standard in the surgical correction of refractive errors on the cornea. It entails the creation of a superficial hinged corneal flap by a femtosecond laser, ablation of the underlying stromal bed by an excimer laser, and reposition of the flap. The corneal flap can be build in a 2-dimension (2D) fashion with tapered edges, or in a 3-dimension (3D) fashion, with angled sidecut. The latter reduces the risk of flap dislocation and infiltration of epithelial cells. This retrospective study compares with optical coherence tomography 3D and 2D flaps, and respective intra- and early post-operative complications. Four hundred consecutive eyes were included, 200 for each group. In the 3D group, the mean edge angle was 92°. The procedure was in average 5.2 seconds slower in the 3D group (p=0). Non visually significant flap folds were found in 13 eyes of the 2D group and in 7 eyes of the 3D group (p= 0.17). An intracorneal opaque bubble layer induced by laser photodisruption was more commonly observed in the 3D group (9 eyes vs. 2; p=0.03). In conclusion, the creation of a LASIK flap by a 3D-femtosecond laser cut was safe and effective.

A sedentary lifestyle associated with unregulated diets rich in high-calorie foods have contributed to the great prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) latterly, with up to 60% in high-risk population and 25% in the general population. The absence of specific pharmacological strategies for this syndrome represents one of the major problems in the management of MASLD patients. Lifestyle interventions and adherence to a healthy diet are the main cornerstones of current therapies. The identification of nutraceuticals useful in the treatment of MASLD appears to be one of the most promising strategies for the development of new effective and safe treatments for this disease. The onion, one of the most widely studied foods in the field of nutraceuticals, serves as an inexhaustible reservoir of potent compounds with various beneficial effects. The following preliminary study analyses, mediating in silico studies, the iteration of a library of typical onion compounds with 3-hydroxy-3-methylglutaryl-coenzyme A reductase, Liver receptors X α and β as well as Peroxisome proliferator-activated receptors α and γ. In this study fort the first time promising smart molecules from the onion that could have a beneficial action in MASLD patients were identified.

Vitamin D3 deficiency is a global phenomenon, which can be coped with supplementation and food fortification. However, vitamin D3 bioaccessibility may depend on factors, such as matrix composition and interactions throughout the gastrointestinal tract. This research focused on the effect of different matrices on vitamin D3 content during digestion, and the effect of pH on its bioaccessibility. The INFOGEST protocol was employed to simulate digestion. Three different types of commercial supplements, two foods naturally rich in vitamin D3, and three fortified foods were investigated. High-Performance Liquid Chromatography was used to determine the vitamin D3 initial content in supplements and foods, as well as after each digestion stage. Results indicated that foods exhibited higher bioaccessibility indices compared to supplements, and a higher percentage retention at the end of the gastric phase. The pH study revealed a positive correlation between increased gastric pH and the corresponding content of vitamin D3. Interestingly, exposing the matrix to low pH during the gastric phase resulted in an increased intestinal content of D3. Vitamin D3 is more bioaccessible from foods than supplements, and its bioaccessibility is susceptible to changes in gastric pH. Fasting conditions (i.e. gastric pH=1) enhances vitamin’s bioaccessibility.

With the development of organizational biology and forced from the EU Cosmetic Regulation (EU/1223/2009) with the complete ban of animal testing for cosmetic purposes, 3D skin models have been widely developed due to their similar physiological structure and metabolic function to native human tissue. 3D skin models for in vitro cosmetic evaluation are still promising alternative methods for evaluating phototoxicity, corrosivity and irritation. These models have been used for early screening and later validation of toxicity and efficacy evaluation by many well-known cosmetic companies. 3D skin models have become an important tool in cosmetic evaluation research. This article reviews the development of 3D skin models and their application in cosmetic evaluation. An outlook on the current application and future technological development directions in the cosmetic field is also presented.

The analysis presented is based on actual GHU energy demand. The special feature of this load is the existence of strong daily fluctuations in energy consumption, especially during the summer months. This study presents a methodology for managing such loads with the main objective of maximizing the operating efficiency of MG.

The present state of research in Computational Fluid Dynamics (CFD) is marked by an ongoing process of refining numerical methods and algorithms with the goal of achieving accurate modeling and analysis of fluid flow and heat transfer phenomena. Remarkable progress has been achieved in the domains of turbulence modeling, parallel computing, and mesh generation, resulting in heightened simulation precision when it comes to capturing complex flow behaviors. Nevertheless CFD faces a significant challenge due to the time and expertise needed for meticulous simulation setup and intricate numerical techniques. To surmount this challenge, we introduce paint2sim—an innovative mobile application designed to enable on-the-fly 2D fluid simulations using a device’s camera. Seamlessly integrated with OpenLB, a high-performance Lattice Boltzmann-based library, paint2sim offers accurate simulations. The application leverages the capabilities of the Lattice Boltzmann Method (LBM) to model fluid behaviors accurately. Through a symbiotic interaction with the open-source OpenCV library, paint2sim can scan and extract hand-drawn simulation domains, affording the capability for instant simulation and visualization. Notably, paint2sim can also be regarded as a digital twin, facilitating just-in-time representation and analysis of 2D fluid systems. The implications of this technology extend significantly to both fluid dynamics education and industrial applications, effectively lowering barriers and rendering fluid simulations more accessible. Encouragingly, the outcomes of simulations conducted with paint2sim showcase promising qualitative and quantitative results. Overall, paint2sim offers a groundbreaking approach to mobile 2D fluid simulations, providing users with just-in-time visualization and accurate results, while simultaneously serving as a digital twin for fluid systems.

This study analyzes tree diversity and its ecological importance value in silvopastoral systems in the Sumaco Biosphere Reserve (SBR), Ecuador, along an altitudinal gradient of 400-2000 masl. Twenty-six plots distributed in low (400-700 masl), medium (701-1600 masl) and high (1601-2000 masl) zones were used. The Shannon index and the Importance Value Index (IVI), based on abundance, dominance and relative frequency, were estimated. The results show variations in the diameter structure of the trees, influenced by factors such as settlement history and pasture management. The lower and middle zones showed higher tree density and diversity, linked to regeneration and the presence of nearby forests. Species of high commercial value, such as Cedrela odorata and Jacaranda copaia, were common, reflecting knowledge of the local timber market. In the lower and middle zones, the 10 most important species accounted for more than 70% of the trees, and up to 96% in the upper zone, indicating the need for further research on abundance factors and promotion of diversification in pastures. A total of 51 tree species were identified, mostly native, 64.7% are classified by the IUCN as "Least Concern", 31.4% as "Not Evaluated", and 3.9% as "Vulnerable", specifically highlighting Cedrela odorata and Cedrela Montana. The study concludes with policy recommendations related to the importance of trees in silvopastoral systems for the conservation of species and the livelihoods of local communities, highlighting the need for responsible management of Amazonian pasturelands.

In this communication, we present a new simulated in situ lab/on-deck incubator, light spectrum replicator (LSR), and method to simulate the measured in situ HOCR light spectrum curves in incubation chambers. Carbon flux studies require detailed knowledge of primary and secondary production, including an understanding of temporal and spatial scales of variation. Interpretation of the processes involved during measurements continues to be difficult [1] since the incubation of the samples does not permit the study of rapid variations in carbon assimilation. Further, the significance of Dissolved Organic Matter of DOM in primary production is gaining attention as many autotrophic species are known for using organic substrates for growth, even in the dark [2–4] and since a significant portion of DOM can be accounted for from active release of intracellular metabolites by microbial consortia [5]. On the other hand, the major uncertainties in bacterial production measurements lie with the conversion factors used to calculate bacterial production (BP). For a given thymidine incorporation rate, estimates of BP can range by a factor of more than 20 [6,7]. Even though various new analytical tools have emerged [8], understanding of complex patterns of interactions within the microbial loop remains an open question.

Gamification is the use of game mechanics in non-game situations. It is a solution to which businesses are turning more and more, since, among other things, it also responds to the individual's need for fun. What are the prevailing trends and to what extent can it be exploited in the period we are going through? This paper tries to contribute to a better understanding of gamification with main aim to help employees in their work, and businesses to achieve goals and be more competitive.

Fall detection systems play a crucial role in addressing the significant health concern of elderly falls, a leading cause of health deterioration and mortality. As the aging population grows and life expectancy increases, the development of accessible tools becomes vital for predicting and preventing falls, offering a practical and widely applicable solution in contrast to costly and expertise-dependent assessment tools. In contrast, due to the formidable challenges encountered, a comprehensive investigation into the comparative performance of standard ML models within this field still needs to be explored. This paper proposes a standard pipeline for pre-processing, training, and evaluating ML models for fall detection on the SisFall dataset. We conducted extensive experiments to evaluate the performance of various ML models for fall detection. The results validate the efficiency of the deep model in identifying the time windows in which a fall occurred. Among the deep models, the architecture, including a combination of convolutional neural networks and fully connected layers, outperforms the others by macro-averaged Precision, macro-averaged Recall, and macro-averaged F1-Score of 87.03\%, 86.83\%, and 86.93\%, respectively.

The (Ti, Nb)(C, B)/IN625 composite coating with both homogeneous and defect-free microstructure were successfully prepared by in situ on the surface of 42CrMo steel using the coupling of the ultra-high-speed laser cladding (EHLA in German) technology with the direct reaction synthesis (DRS) technology, and were comparatively analyzed with the IN625 coating prepared by the EHLA. The microstructure of the fused cladding layer was investigated by selected scanning electron microscopy (SEM), energy dispersive spectrometer (EDS) and double spherical aberration transmission electron microscopy (DSA-TEM). The residual stress distribution on both sides of the fused cladding interface was characterised by nanoindentation stress test based on the modified O&P method and the G&S energy method. The results show that the interface of (Ti, Nb)(C, B)/IN625 composite coatings is affected by about 670 kJ Joule heat released from the in-situ reaction, and the interfacial width reaches 24 μm, so that it is 6 times higher than that of IN625 coating prepared by EHLA, which effectively reduces the stress gradient in the interfacial region and alleviates the stress mismatch on both sides of the interface. However, the surface hardness of (Ti, Nb)(C, B)/IN625 composite coating is lower than that of the IN625 coating, with a value of about 240 HV0.2, and the average wear weight loss was only 10% of that of the IN625 coating, which is on the one hand attributed to the in-situ authigenic TiCB, TiC, NbMo3B4, and NbMo2B2 phases supporting the (Ti, Nb)(C, B)/IN625 composite coating substrate to achieve the abrasion reduction and wear resistance. On the other hand, it is attributed to the formation of nano-equiaxial ultrafine grains in the depth range of 250 nm below the wear surface area by the coupling of the three fields of plastic rheology-heat-force, which dynamically strengthens the wear surface.

Encouraged by the administration the gentrification process has been useful in economic terms for the reactivation of socio-cultural fabrics of historic urban spaces in decline. What was initially considered an advantage has led to the touristification of historic centres, and in turn to the alter-ation of their original use. In these settings, the demographic void caused by increasingly shunning local identity has combined with pressure from excessive tourism and the obsolescence of heritage protection bodies in charge of conservation. Given the crisis affecting the definitions of the current system, this study aims to review the envi-ronmental agents of heritage value in relation to the processes of touristification and gentrification. Data obtained from different methodologies are analysed using a multidisciplinary database, a model which enables the analysis of the relevant information from the different interacting fields. The case study focuses on the historic town centre of Seville specifically between 2015 and 2020. Elements are defined as indicators for these processes and the analysis of the case study will com-prise the main results of this research.

This paper exposes the initial part of a research consisting in a need analysis carried out by the Romanian partner in the Erasmus+ "Media Education for Aware Adults" project, regarding digital competences and media education of adult educators or trainers. After a short introduction on the subject, in the paper are presented the main findings of the desk research, and two focus group sessions, first one for identifying the necessary digital competences of adult educators, and second one for identifying the elements that educators need in order to adequately support adults in their learning process, especially in relation to the digital environment. The results of the initial research will lead to the development of the main intellectual outputs, namely the digital competences framework, handbook, online platform and training material on digital and media education. In their development will be taken into account, on the one hand, the needs identified in the initial research, and, on the other hand, the need for a sustainable approach to all activities, resources and outputs produced, as well as education itself, this goal being assumed through the project.

Salmonella infection is one of major challenges to the poultry industry because of its pressing effects on health of poultry, food safety and human well-being that later may devastate economic losses to the poultry sector. The paper reviews public health implications and the use of antibiotics together with the risk of drug resistance. In recent years, the usage of probiotics in poultry industry has been growing to mitigate an increasing pressure to adopt sustainable farming practices. The mechanisms which probiotics may control Salmonella and important criteria for selecting effective probiotics in poultry are reported. Various studies highlighting the additional benefits of probiotics in poultry production in addition to Salmonella controls are also included. While probiotics offer promise in enhancing poultry health, challenges and limitations in their utilization must also be carefully considered.

Immunotherapy with stereotactic body radiotherapy (SBRT), low-dose antiangiogenics, immune adjuvants, nanomedicine, or other combinations will likely play a lead role in managing malignancies soon. Presently, its benefit extends to about 12% to 20% of patients, in the background of possible recurrence eventually and the toxicities, including in non-responders. Stereotactic body radiotherapy (SBRT) not only eliminates the indexed lesions, but recently, the evidence is accumulating about its systemic abscopal effects. It needs to be evolved to a dependable in situ therapeutic vaccine production and to activate short- and long-term memory immune lymphocytes. The in-situ immune cascade happens with the ability of SBRT to generate Tumor-specific neoantigens and neoepitopes, which enhance the activation of antigen-presenting cells, invoke and restore the competence of Tumor-infiltrating lymphocytes, resulting in cancer cell lysis. This cell lysis, in turn, can generate further neoantigens and epitopes, imparting a virtuous cycle that is the hallmark of effective vaccines. Additionally, SBRT can synergistically enhance the other in situ vaccination strategies, concurrent in vitro vaccines or nanomedicines, making it a primary tool for sensitizing even the “cold” tumors for immunotherapy. The present proposed hypotheses, primarily based on a preclinical literature review, focus on the critical aspects of the in-situ vaccination generation capability of SBRT when used in pulsed, cyclical, or intermittent endothelial-sparing single dose schedules along with immunotherapy and other supportive measures. This schedule is categorized as in situ vaccine dose (ISVD) radiotherapy (RT) (distinguishable from the standard therapeutic SBRT schedule) in metastatic cancer settings after standard /first-line therapies.

Castration of stallions is traditionally performed after puberty around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we sought to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses. Testosterone and estradiol levels were monitored from birth to 33 months in these two groups. We quantified the levels of biomarkers of cartilage and bone anabolism (CPII and N-MID) and catabolism (CTX-I and CTX-II), of osteoarthritis (HA and COMP) and inflammation (IL-6 and PGE2). We revealed a lack of parallelism between testosterone and estradiol syntheses after birth and during puberty in both groups. An extra-gonadal synthesis of steroids was observed around the 28 month-mark, regardless of the castration age. We found the expression of estrogen receptor (ESR1) in cartilage and bone, whereas androgen receptor (AR) expression appeared to be restricted to bone. Nevertheless, with regards to osteoarticular metabolism, steroid hormone deprivation resulting from early castration showed no discernable impact on the levels of biomarkers related to bone and cartilage metabolism, nor on those associated with OA and inflammation. Consequently, our research demonstrated that early castration does not disrupt bone and cartilage homeostasis.

The type of implant at the fracture site has effects not only from biological perspective but also from mechanical perspective in fracture healing. Biodegradable implants such as magnesium (Mg) based alloys have shown faster secondary bone healing properties as compared to bioinert implants such as titanium (Ti). The general reasoning behind this is the benefit of Mg from biocompatibility perspectives. We study the effect of Ti and Mg as base materials for implants with their different mechanical properties. The focus of our work is on the displacements at the fracture site of the tibia and their influence on the stimulus for bone healing. We have found that in comparison to Ti, Mg implants have minimal stress shielding problem, only which led to better mechanical stimulus at the fracture site.

This study investigates the stochastic dynamics of hepatitis B virus (HBV) infection using a newly proposed stochastic model. Contrary to deterministic models that fail to encapsulate the inherent randomness and fluctuations in biological processes, our stochastic model provides a more realistic representation of HBV infection dynamics. It incorporates random variability, thereby acknowledging the changes in viral and cellular populations and uncertainties in parameters such as infection rates and immune responses. We examine the solution's existence, uniqueness, and positivity for the proposed model, followed by a comprehensive stability analysis. We provide the necessary and sufficient conditions for local and global stability, offering deep insight into the infection dynamics. Furthermore, we utilize numerical simulations to corroborate our theoretical results. This research provides a robust tool for understanding the complex behavior of HBV dynamics, contributing significantly to the ongoing quest for more effective HBV control and prevention strategies.

Crohn's disease (CD) is a chronic, immune-mediated inflammatory bowel disease characterized by transmural damage of various parts of the gastrointestinal tract. The aim of the study is to present our experience in pre-surgical diagnosis, selection of surgical tactics and volume of intervention in different variants of gastrointestinal tract lesions and disease activity. We undertook cross-sectional, retrospective-prospective study of 64 children who underwent surgery due to complicated CD. We analyzed CD activity via PCDAI, medications used, inflam-mation localization, and changes in mass-growth parameters at pre-surgery stage. Three patients from the group of 44 children with two-stage surgical treatment later showed inefficacy of GEBD in post-operative period. The disease progression was revealed and, therefore, subtotal colectomy was required. Three children had secondary adhesion of surgical wounds by means of active immunosuppressive therapy at preoperative period, and five patients developed suture sinuses at post-operative period. Early adhesive intestinal obstruction was revealed in 3 (4.7%) cases, and they required re-surgery. Personalized approach to the surgical treatment of children with complicated CD has shown its efficacy due to the small percentage of postoperative complications with re-surgery. There was significant improvement in mass-growth parameters, recovery of albumin levels, and anemia decrease in 96.9% of cases in the long-term postoperative period (6 months or more). Two children (3.1%) had the narrowing of anastomotic zone lumen, thus, without any obstruction. These cases were associated with violations in drug treatment

As the human-body controls depend on the brain neuro current, here assay is related to thinking nerve detection. For this purpose, the brain current was analyzed by electrochemical three-electrode systems using 0.1-mm micro wire in vivo probe, which probe was made by using carbon nanotube paste coated needle type. Here working electrode was inserted in the rat brain’s muscle core with a 0.3-mm-diameter needle type Ag/AgCl Cl-coated Ag wire reference, and counter electrode of 0.1-mm-diameter Pt micro needle was inserted 5 mm deep into the in vivo muscle skin, under anesthesia with 2.0 ~ -2.0 V potential windows, 50 mv/s cyclic scan and 1.0x10-5A chrono amperometric sensitivity on the body systems. Under the optimum conditions, diagnostic application was performed to such as smell signal, muscular strength, five sense assay and thinking neuro current.

Soy isoflavones are considered important sources of bioactive compounds, but they are poorly absorbable, due to their large hydrophilic structures. Some biotransformation strategies have been used to convert the glycosidic form into aglycones, making them available for absorption. This study evaluated the potential of enzymatic and/or microbial fermentation bioprocesses in soymilk extract before and after gastrointestinal in vitro digestion. Commercial β-glucosidase and mix of commercial probiotics containing Lactobacillus acidophilus, L. casei, Lactococcus lactis, Bifidobacterium bifidum e B. lactis were used to biotransform soymilk extract. Isoflavone profile was quantified by HPLC-DAD, total phenolic content by Folin–Ciocalteu test, and antioxidant capacity by ORAC and FRAP. Soymilk enzymatically treated (ET) followed by microbial fermentation (ET+F) resulted in the conversion of glycosylated isoflavones (6-fold lower than control for daidzin and 2-fold for genistin) to aglycones (18-fold greater than control for dadzein and genistein), besides to increase the total phenolic content (3.48 for control and 4.48 mg/ml ET+F) and to improve antioxidant capacity represented by the ORAC (120 for control and 151 mg/ml ET+F) and by the FRAP (285 for control and 317 µl/ml for ET+F) before in vitro digestion. Further, the digested ET+F samples resulted a higher content of genistein (2-fold higher than control) also an increase in the total phenolic content (2.81 for control and 4.03 mg/ml for ET+F) and antioxidant capacity by ORAC were greater compared to undigested samples. In addition, the microbial fermentation process isolated also resulted in the positive effects, but de combination of ET followed by F presented a synergistic effect, suggesting the greater potential for both bioprocesses to contribute to functional and nutritional properties on fermented soy-based products.

Blended learning, the integration of online and face-to-face instruction, has garnered attention in education. This paper aims to explore challenges in blended learning faced by students, teachers, and parents and propose mitigating strategies. The study employed qualitative research methods and involved 30 participants from St. Michael's College. Findings revealed primary challenges, including technical difficulties, time management, lack of interaction, and varying digital literacy levels. These challenges influenced engagement, communication, and student achievement. The study utilized a theoretical framework encompassing Technological Pedagogical Content Knowledge, Social Presence Theory, and Activity Theory. Strategies recommended comprise providing technical support, promoting communication and collaboration, offering professional development, and leveraging learning analytics. The study contributes to the existing literature by identifying specific challenges and proposing practical recommendations for enhancing blended learning effectiveness. Limitations include a small sample size and context-specific findings. Future research should investigate these challenges in broader settings and examine the long-term effects of the recommended strategies. Addressing blended learning challenges can empower educators, administrators, and policymakers to create supportive and effective learning environments for all stakeholders involved.

Alphaherpesviruses cause genital lesions and reproductive failure in both humans and animals. Their control is mainly based on prevention by hygienic prophylactic measures, due to the ab-sence of vaccines and limitations of antiviral drug therapy. Ozone is an oxidating gas showing a strong microbicidal activity on bacteria, fungi, viruses, and protozoa. The present study assessed the in vitro virucidal and antiviral activity of ozone against Caprine herpesvirus type 1. Virucidal activity of a gaseous mixture containing O3 at 20 and 50 μg /mL was assessed against the virus for different contact times (30 s, 60s, 90s, 120s, 180s and 300s). Antiviral activity of a gaseous mix-ture containing O3 at 20 and 50 μg /mL was evaluated against the virus to for 30s and 60s. Ozone displayed significant virucidal activity when used at all the tested concentrations whilst signifi-cant antiviral activity was observed using ozone at 50 μg/ml. The gaseous mixture, tested in the present study, showed virucidal and antiviral activity against CpHV-1 with a dose- and a time-contact -dependent fashion. Ozone therapy could be evaluated in vivo for the treatment of CpHV-1-induced genital lesions in goats, through topical applications.

This study describes a comparative in vitro study of the toxicity behavior of zinc oxide (ZnO) nanoparticles and micro-sized particles. The study aimed to understand the impact of particle size on ZnO toxicity by characterizing the particles in different media, including cell culture media, human plasma, and protein solutions (bovine serum albumin and fibrinogen). The study used various techniques such as atomic force microscopy (AFM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) to characterize the particles and their interactions with proteins. Hemolytic activity, coagulation time, and cell viability assays were used to assess ZnO toxicity. The results highlight the complex interactions between ZnO NPs and biological systems, including their aggregation behavior, hemolytic activity, protein corona formation, coagulation effects, and cytotoxicity. Moreover, the study indicates that ZnO nanoparticles are not more toxic than micro-sized particles, and the 50 nm particles resulted in general the least toxic. Furthermore, the study found that at low concentrations, no acute toxicity was observed. Overall, this study provides important insights into the toxicity behavior of ZnO particles and highlights that no direct relationship between nanometer size and toxicity can be directly attributed.

This study aimed to extract bioactive compounds from apple (Malus domestica) peel waste using supercritical CO2 extraction. The bioactive fractions from apple peels from the three Italian cultivars were extracted applying a temperature of 60 °C and a pressure of 250 bar for 15 min. 20% ethanol was used as a co-solvent. The extraction process was carried out at a flow rate of 2 mL/min and their total polyphenol (TP), anthocyanin (TA), ascorbic acid (AA), and antioxidant activity contents (TAC) were measured. The extracts from the Stark cultivar had the highest levels of polyphenols, anthocyanins, and ascorbic acid, while the Royal Gala cultivar had the highest total antioxidant activity. Chromatographic analyses were also performed to characterize polyphenols. The extracts were then tested for their effect on the mitochondrial NADH-ubiquinone oxidoreductase (Complex I) activity on mitochondria isolated from human embryonic kidney cells (HEK239) cells, with the Stark extracts showing the most positive response in terms of NADH oxidation. These findings highlight the potential of apple peel waste as a source of functional phytocompounds and suggest the Stark cultivar extracts may have pharmacological applications. This study supports the circular bioeconomy by promoting the use of waste products as a valuable resource.

Regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new hints on microglia heterogeneity across central nervous system (CNS) regions are still being unraveled by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on in vitro behavior by applying the same experimental protocol and culture conditions. We analyzed microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in spinal cord-derived glial cultures, presenting different expression of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-. Morphologically, cortical microglial cells are more complex and present longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired in the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvation of leukemic cells. The ASNase formulations of E. coli and E. chrysanthemi present notorious adverse effects, especially the immunogenicity they generate, which undermines both their effectiveness as drugs and patient safety. In this study, we developed a humanized chimeric enzyme from E. coli L-asparaginase, which would reduce the immunological problems associated with current L-asparaginase therapy. For these, the immunogenic epitopes of E. coli L-asparaginase (PDB: 3ECA) were determined and replaced with those of the less immunogenic Homo sapiens asparaginase (PDB:4O0H). The structures were modeled using the Pymol software and the chimeric enzyme was modeled using the SWISS MODEL service. A humanized chimeric enzyme with four subunits similar to the template structure was obtained, and the presence of asparaginase enzymatic activity was predicted by protein-ligand docking.

Peatlands in Indonesia are one of the world's largest carbon sinks, helping to regulate greenhouse gas emissions and global climate change. Lophostemon suaveolens is a plant found in Papua's endemic peat ecosystem that grows well in wet areas with low fertility. It is geographically dispersed and has the potential for peatland re-habilitation. We present an efficient and reproducible protocol for in vitro multiplication of plantlets using nodal segments and shoot apices collected from plantlets. The Murashige and Skoog (MS) medium was sup-plemented with single and double kinds of PGRs (BAP and NAA). The concentration used in this study is based on the best findings of earlier preliminary research on single PGR treatment (0.5 ml/l BAP and 0.1 ml/l NAA) for the initiation stage. After 3 months of in vitro axillary shoot initiation, elongated shoots from plant-lets were separated from the clumps and multiplied. Until 6 months incubation, the potential multiplication of axillary shoots was determined by counting the number of nodule multiplication coefficients (NMC), shoot length, root length, and number of leaves (6 successive subculture). The highest average per plantlet of NMC (8.4 0.13) was observed in MS medium with a combination of 0.5 ml/l BAP and 0.1 ml/l NAA (double PGRs), with the longest shoots (5.91 0.17 cm), the longest root length (8.83 0.69 cm), and the most leaves (32 0.69). They were cultured in a pH 5 environment with a light photoperiod (40 mol/m2/s intensity) for 16 hours. When BAP and NAA were used together after acclimatization, seedling survival was highest. This is the first report of L. suaveolens in vitro multiplication, and the protocol could be used to propagate this peatland species on a large scale.

This study aims to develop an in-situ field repair approach, special for aircraft composite structures, to enhance the interlaminar toughness of plain woven composites (PWCs) by adding multi-walled carbon nanotubes (MWCNTs). MWCNTs are dispersed at each interface between prepreg layers by means of solvent spraying with the density is 1.58 g/m2. And then, the layers are stacked with the predefined sequence and cured at 120℃ and 1 bar pressure using the heat repairing instrument. Moreover, double cantilever beam (DCB) standard test is used to investigate the interlaminar toughening effect due to the MWCNTs. For comparison, original samples are also prepared, the results indicate that the introduction of MWCNTs can favorably enhance the interlaminar toughness of PWCs at field repair approach and the Mode I fracture energy release rate GIC increases by 102.92%. Based on finite element method (FEM) of continuum damage mechanics, the original and MWCNTs toughening specimen under DCB Mode I fracture are modeled and analyzed. The simulation and experiment are in good agreement. Finally, the toughening mechanism of MWCNTs is explored by scanning electron microscope (SEM), it is founded that a large amount of Fiber-matrix (F-M) interface debonding and matrix cracking of mountain shape are the major modes of fracture accompanied with few fiber breakage and matrix peeling off for the MWCNTs toughening specimens.

The case of a virtual bosonic scalar field phi(x) gravitationally coupled in a conformally flat spacetime is investigated. The action S is known to be Weyl invariant only for specific expressions of the potential V(phi). In the conformally flat FLRW case the harmonic angular frequency omega_k(eta) becomes uniquely temporally independent. Therefore any inertial observers embedded in a conformally flat FLRW spacetime all agree on the choice of virtual vacuum states. We postulate that the wavenumber k must be quantized in order to be able to regulate the vev by zeta regularization. Some fundamental implications of this result is derived, and likely conclusions drawn.

In this review paper, the occurrence in the plant kingdom and the biological activities associated to two specific phenyl-ethanoid glycosides i.e., leucosceptoside A and leucosceptoside B, were shown and discussed. This is the first work ever done on such subject. Analysis of the literature data clearly indicates that leucosceptoside A is much more common in plants and exerts many more biological activities than leucosceptoside B even if this also presents some important elements. All of this was widely discussed in this paper.

This study aimed to exploring the intra-species distribution of genetic characters that favor the persistence in the gastrointestinal tract (GIT) and host interaction of bacteria belonging to the species Lacticaseibacillus genus. These bacterial species comprise commercial probiotics with the widest use among consumers and strains naturally occurring in GIT and in fermented food. Since little is known on the distribution of genetic traits for adhesion capacity, polysaccharide production, biofilm formation, utilization of substrates critically important for survival in GIT, that influence probiotic characteristics, a list of genetic determinants involved in such functions was created by a search for specific genes involved in the above aspects in the genome the extensively characterized probiotic L. rhamnosus GG. The presence/absence and variability of each gene in other Lacticaseibacillus spp. genomes was assessed by alignment with the publicly available fully annotated genome sequences. Eighty-two gene loci were compared, and 49 of these were found to be absent in some genomes in a species or strain-specific mode. A set of genes was found to be conserved, indicating that all strains of the genus may exert some probiotic effects. Among the variable loci a taurine utilization operon and a α-L-fucosidase were examined for presence/absence in 26 strains isolated from infant feces by PCR based tests. Results were variable among the isolates, though their common origin indicated the capacity to survive in the intestinal niche. This study indicated that the capacity to exert probiotic actions of Lacticaseibacillus spp. depends on a conserved set of genes and is enhanced by variable genetic factors whose role is only in part elucidated. The selection of strains of the most promising probiotic candidates to be used in food is feasible by analyzing presence/absence of a set of variable traits.

Every country has some specific heraldry. In this paper, we will consider heraldry in the Republic of Macedonia, understood by the multitude of coats of arms, and armorial knowledge and art. The paper covers the period from independence until the name change (1991-2019). It covers the state coat of arms of the Republic of Macedonia especially the 2009 change. Special attention is given to the development of the municipal heraldry, including the legal system covering the subject. Also personal heraldry developed in 21 century is considered. The paper covers the development of heraldry and the heraldic thought in the given period, including the role of the Macedonian Heraldic Society and its journal Macedonian Herald in development of theoretic and practical heraldry, as well as its Register of arms and the Macedonian Civic Heraldic System.

The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform the status of both hepatic and systemic metabolic diseases as well as the disposition of medications. As a tool to better understand liver metabolism in these settings, in vivo magnetic resonance spectroscopy (MRS) offers a non-invasive means of monitoring hepatic metabolic activity in real time both by direct observation of concentrations and dynamics of specific metabolites as well as by observation of their enrichment by stable isotope tracers. This review summarizes the applications and advances in human liver metabolic studies by in vivo MRS over the past 35 years and discusses future directions and opportunities that will be opened by the development of ultra-high field MR systems and by hyperpolarized stable isotope tracers.

In silico prediction of the in vivo efficacy of siRNA ionizable-lipid nanoparticles is desirable yet never achieved before. This study aims to computationally predict siRNA nanoparticles in vivo efficacy, which saves time and resources. A data set containing 120 entries was prepared by combining molecular descriptors of the ionizable lipids together with two nanoparticles formulation characteristics. Input descriptor combinations were selected by an evolutionary algorithm. Artificial neural networks, support vector machines and partial least squares regression were used for QSAR modeling. Depending on how the data set is split, two training sets and two external validation sets were prepared. Training and validation sets contained 90 and 30 entries respectively. The results showed the successful predictions of validation set log(dose) with R2val = 0.86 – 0.89 and 0.75 – 80 for validation sets one and two respectively. Artificial neural networks resulted in the best R2val for both validation sets. For predictions that have high bias, improvement of R2val from 0.47 to 0.96 was achieved by selecting the training set lipids lying within the applicability domain. In conclusion, in vivo performance of siRNA nanoparticles was successfully predicted by combining cheminformatics with machine learning techniques.

Background: Zebrafish (Danio rerio) is a model organism emerged for the study of human cancer. Compared with the murine model, the zebrafish model has several properties ideal for personalized therapies. The transparency of the zebrafish embryos and the development of the pigment-deficient “casper” zebrafish line give the capacity to directly observe cancer formation and progression in the living animal. Automatic quantification of cellular proliferation in vivo is critical to the development of personalized medicine. Methods: A new methodology was defined to automatically quantify the cancer cellular evolution. ZFTool was developed to establish a base threshold that eliminates the embryo auto-fluorescence and automatically measures the area and intensity of GFP (green-fluorescent protein) marked cells and define a proliferation index. Results: Proliferation index automatically computed on different targets demonstrates the efficiency of ZFTool to provide a good automatic quantification of cancer cell evolution and dissemination. Conclusion: Our results demonstrate that ZFTool is a reliable tool for the automatic quantification of the proliferation index, being a measure of cancer mass evolution in zebrafish eliminating the influence of its autofluorescence.

In this study, we have first studied the trend in meteorological data from the Harmaleh, Vanai and Farsesh stations in the 50-year period in the Dez catchment area. The meteorological data will be then forecasted using SWAT and Mann-Kendall. Forecasting the results in the Mann-Kendall and SWAT model has been done using the code written in MATLAB software and RCP (4.5, 8.5) scenarios, respectively. Studying the results of the trend in the data of meteorological stations in this catchment area indicated that these two parametric and non-parametric methods have been used to determine trends in meteorological data. The results of the parametric method are positive in all meteorological parameters. Non-parametric method over a period of 50 years shows the presence of trends in the data. The comparison on the forecasting results at maximum temperature suggested that during summer, we will see an increase in temperature compared to the ground state in all three forecasts. The results of the minimum temperature forecast show a decrease in the minimum increase during the winter and the precipitation forecast indicates that at the end of autumn (Nov) precipitation decreased by 20 mm in the Mann-Kendall and 4.5 RCP while RCP8.5 suggests the increase in precipitation compared to the ground state. Studying the runoff forecast results using SWOT show that at the end of winter (Feb) and almost all spring (Mar, Apr) a decrease of about 40%, 15% and 14% will be seen, respectively

Cyanobacteria are prokaryotes whose taxonomy follows the same rules of a code (the International Botanical Nomenclature Code, IBNC) built for eukaryotic photosynthetic organisms. Hence, names of cyanobacteria follow the same rules and are assigned to biological entities (species) that should correspond to eukaryotic species. The main difficulty in the current situation is that the species concept in eukaryotes is based theoretically mainly on the biological species concept, that is centered on genetic exchange through sexual reproduction or lack of them. However, as shown, this difference is important from a theoretical point of view, but also in eukaryotes, the boundaries between different species are very rarely checked experimentally by direct observation of sexual barriers and hybridization events. The main concept for species delimitation is hence that related to morphology and, more recently and always in relation to morphology, DNA sequences. The introduction of distances obtained from matrixes of aligned sequences in the framework of a barcoding project provides a quantitative interpretation of species delimitation in relation to genetic distance that can be used both in eukaryotes and prokaryotes. However, the introduction of quantitative criteria needs the definition of distance thresholds to identify the boundaries between different species and, for doing that, it is necessary to test the distance thresholds in models of traditionally defined and recognized species. An alternative approach may be the comparison of the molecular distance (quantitative approach) to data about the capability of strains/species to exchange genetic information. Unfortunately data about this last question is still scarce. The adoption of molecular criteria to check species boundaries based on morphological characters has proved particularly challenging in cyanobacteria: a known example is provided. In conclusion, the only possible approach appears to be the association of molecular data to the increase of available data about the cell structure and the variation thereof in different physiological situations, particularly at the ultrastructural level. A further necessity is the check of the typus for a large number of cyanobacteria species, often based on old basionyms. In many of these cases the typus is often a drawing and more rarely a herbarium specimen or a microscope slide. In many cases an epitypification or a neotypification appears to be necessary.

Keeping in mind the increasing trend and need for serious games in science education, we have done a systematic literature review. These papers show the trends and patterns of research carried out in this field from the year 2011 to 2020. Specifically, we investigated country-wise concentration and the most common evaluation methods. Literature is reviewed from IEEEexplore, Springer, and Scopus. Moreover, we discussed the role of Augmented Reality(AR) games in teaching physics. Lastly, we have discussed the positive and negative aspects of serious games in science education in particular, and the trend of using serious games in the past decade in education in general.

Segmentation of Magnetic Resonance Images (MRI) of abdominal organs is useful for analysis prior to surgical procedures and for further processing. Deep Learning (DL) has become the standard, researchers have proposed improvements that include multiple views, ensembles and voting. Loss function alternatives, while being crucial to guide automated learning, have not been compared in detail. In this work we analyze limitations of popular metrics and their use as loss, study alternative loss variations based on those and other modifications and search for the best approach. An experimental setup was necessary to assess the alternatives. Results for the top scoring network and top scoring loss show improvements between 2 and 11 percentage points (pp) in Jaccard Index (JI), depending on organ and patient (sequence), for a total of 22 pp over 4 organs, all this being obtained just by choosing the best performing loss function instead of cross-entropy or dice. Our results apply directly to MRI of abdominal organs, with important practical implications for other architectures, as they can be applied easily to any of them. They also show the worth of variants of loss function and loss tuning, with future work needed to generalize and test in other contexts.

This paper investigates the effect of the Internet on tax revenue instability, notably through the international trade channel. It has used a sample of 142 countries over the period 1995-2017, and relied primarily on the two-step system Generalized Methods of Moments (GMM) estimators (but also incidentally on the Error Component Two-Stage Least Squares estimator). Tax revenue instability is primarily measured by the instability of non-resource tax revenue, but also by the instability of total tax revenue (for robustness check). The findings indicate that the Internet exerts a negative effect on tax revenue instability. Interestingly, this effect genuinely translates through the international trade channel, regardless of the measure of tax revenue instability considered. Countries enjoy a higher negative effect of the Internet on tax revenue instability as they enjoy a greater participation in international trade. These findings, therefore, add to the potential benefits of the Internet adoption (e.g., strengthening countries' participation in international trade, enhance their tax revenue performance and promote tax reform, including in developing countries) by showing that it could also help to stabilize tax revenue, particularly through the degree of countries' participation in international trade.

The absorption of medium-chain fatty acids (MCFA) depends on the solubility of these components in the gastric fluid. Parameters such as the total MCFA concentration, carboxyl ionization level, and carbon chain length affect the solubility of these molecules. Moreover, the enzymatic lipolysis of solubilized triacylglycerol (TAG) molecules may depend on the carbon chain length of the fatty acids (FAs) components and their positions on the glycerol backbone. This present study aimed at investigating the effect of electrolyte usually formed during the gastric digestion phase on the solubility of MCFA, and evaluating the influence of the FA carbon chain length on the lipolysis rate during the in vitro digestion simulation. The results obtained here showed that the increasing of electrolyte concentrations tend to decrease the mutual solubility of systems composed by the caproic and caprylic fatty acids + sodium chloride, sodium bicarbonate, and potassium chloride solutions. We also observed that a conventional version of the thermodynamic UNIQUAC model was able to correlate the liquid-liquid phase behavior of the electrolyte solutions. Regarding the in vitro digestion simulation, the experimental data indicated that the action of the pancreatic enzyme occurred preferentially in TAG molecules comprised of short and medium-chain fatty acids.

In-plane electro-optical switching (IPS) is a natural feature of a conventional planar aligned display cell based on deformed helix ferroelectric liquid crystal effect (DHFLC-effect) with sub-wavelength helix pitch if the tilt angle close to 40 degrees.

Groundwater contamination is an ever-growing environmental issue that has attracted much and undiminished attention for the past half century. Groundwater contamination may originate from both anthropogenic (e.g., hydrocarbons) and natural compounds (e.g., nitrate and arsenic); to tackle the removal of these contaminants, different technologies have been developed and implemented. Recently, bioelectrochemical systems (BES) have emerged as a potential treatment for groundwater contamination, with reported in situ applications that showed promising results. Nitrate and hydrocarbons (toluene, phenanthrene, benzene, BTEX and light PAHs) have been successfully removed, due to the interaction of microbial metabolism with poised electrodes, in addition to physical migration due to the electric field generated in a BES. The selection of proper BESs relies on several factors and problems, such as the complexity of groundwater and subsoil environment, scale-up issues, and energy requirements that need to be accounted for. Modeling efforts could help predict case scenarios and select a proper design and approach, while BES-based biosensing could help monitoring remediation processes. In this review, we critically analyze in situ BES applications for groundwater remediation, focusing in particular on different proposed setups, and we identify and discuss the existing research gaps in the field.

Introduction: studies in the last two decades have found declining snake populations in both temperate and tropical sites, including informal reports from Drake Bay, Costa Rica. Objective: to investigate if reports of decreasing snake populations in Drake Bay had a real basis, and if environmental factors, particularly temperature, rain and light, have played a role in that decrease. Methods: we worked at Drake Bay from 2012 through 2017 and made over 4000 h of transect counts. Using head flashlights we surveyed a transect covered by lowland tropical rainforest at an altitude of 12–38 m above sea level, near the Agujas River, mostly at 1930–2200 hours. We counted all the snakes that we could see along the transect. Results: snake counts increase from August to September and then decline rapidly. The May snakes/rainfall peaks coincide, but the second snake peak occurs one month before the rain peak; we counted more snakes in dry nights, with the exception of Imantodes cenchoa which was equally common despite rain conditions. We saw less Leptodeira septentrionalis on bright nights, but all other species were unaffected. Along the six years, the number of species with each diet type remained relatively constant, but the number of individuals declined sharply for those that feed on amphibians and reptiles. We report Rhadinella godmani, a highland species, at 12–38 m of altitude. Conclusion: night field counts of snakes in Drake Bay, Costa Rica, show a strong decline from 2012 through 2017.

Soups show diverse health functions, which should be related with their nutrient profiles. NMR spectroscopy is a robust, sensitive and rapid method to unveil or identify the chemical composition of food or food-derived metabolites. In the current study, 1H-NMR spectroscopy approach was applied to identify the metabolic profiling of two kinds of home-cooked freshwater fish soups (crucian carp and snakehead fish) before and after in vitro gastrointestinal digestion. The nutritional profiles of these two kinds of soups were identified at first. With the help of OPLS-DA method (Orthogonal Partial Least Squares Discriminant Analysis), these two different kinds freshwater fish under different states were completely discriminated. The metabolites changes in digested fish soups could reveal the information of chemical compounds which play important roles in the body. Furthermore, the metabolic patterns of different kinds of fish soups could reflect the various nutrition profiling characteristics for dietary therapy.

In this study, lithium reaction distributions, dependent on charge-discharge rate, were nondestructively visualized for a commercial lithium-ion battery, using the Compton scattering imaging technique. By comparing lithium reaction distributions obtained from two different charge-discharge speeds, residual lithium ions were detected at the center of the negative electrode on a fully discharged state, by relatively high-speed discharge rate. Moreover, we confirmed that inhomogeneous reactions were facilitated on a relatively high-speed charge-discharge rate, in both the negative and positive electrodes. A feature of our technique is that it can be applied to commercially used lithium-ion batteries, because it uses high-energy X-rays with a high penetration power. Our technique thus opens a novel analyzing pathway for developing advanced batteries.

In plants and animals, endogenous biological molecules, termed damage-associated molecular patterns (DAMPs) or alarmins, are released by damaged, stressed or dying cells following abiotic stress such as radiation and drought stress. In turn, a cascade of downstream signaling events is initiated leading to the up-regulation of defense-related genes. In the present study, in an effort to investigate the conservation status of the molecular mechanisms implicated in the danger signaling, thorough in silico phylogenetic and structural analyses of the effector biomolecules were performed in taxonomically diverse plant species. On the basis of our results, the defense mechanisms appear to be largely conserved within the plant kingdom. Of note is our finding that the sequence and/or function of several components of these mechanisms were found to be conserved in animals, as well.

Ferroelectric materials are crucial for today’s technological society, and nanostructured ferroelectric materials are important for downscaling of devices. Controlled and reproducible synthesis of these materials are therefore of immense importance. Hydrothermal synthesis is a well-established synthesis route, with a large parameter space for optimization, but a better understanding of nucleation and growth mechanisms is needed for full utilization and control. Here we use in situ X-ray diffraction to follow the nucleation and growth of BaTiO₃ formed by hydrothermal synthesis using two different titanium precursors, an amorphous titania precipitate slurry and a Ti-citric acid complex solution. Sequential Rietveld refinement was used to extract the time dependency of lattice parameters, crystallite size, strain and atomic displacement parameters. Phase pure BaTiO₃ nanoparticles 10 - 15 nm in size were successfully synthesized at different temperatures (100, 125, and 150 °C) from both precursors after reaction times ranging from a few seconds, to several hours. The two precursors resulted in phase pure BaTiO₃ with similar final crystallite size. Finally, two different growth mechanisms were revealed, where the effect of surfactants present during hydrothermal synthesis is discussed as one of the key parameters.

Cocaine addiction is a global health problem that causes substantial damage to the health of addicted individuals around the world. Dopamine synthesizing neurons in the brain play a vital role in the addiction to cocaine. But the underlying molecular mechanisms that help cocaine exert its addictive effect have not been very well understood. Bioinformatics can be a useful tool in the attempt to broaden our understanding in this area. In the present study, Gene Set Enrichment Analysis (GSEA) was carried out on the upregulated genes from a dataset of Dopamine synthesizing neurons of post-mortem human brain of cocaine addicts. As a result of this analysis, 3 miRNAs have been identified as having significant influence on transcription of the upregulated genes. These 3 miRNAs hold therapeutic potential for the treatment of cocaine addiction.

The financial inclusion, including all the people with the finance, is very concerned issue all over the world where Bangladesh is also trying to include all the people with the finance. Bangladesh lies in such a group of countries where only 17.6% - 38.6% adults are presently under the reach of the formal financial services. This is because the present banks and other formal financial modes consider the outcome and profitability in a way that, the rural and non-developed areas are always out of the consideration. But these areas consist of the most population of Bangladesh. And only then financial inclusiveness will be successful in Bangladesh when people from these regions will be under formal financial consideration. The paper seeks for a solution to the issue and presents the Unit Banking System as a probable way towards financial inclusion. For implementing the system in Bangladesh, the system needs a slight modification to cope in Bangladeshi economic condition and address the specific needs without hampering the surroundings. Considering all these, the paper shows the status, problems and key points of financial scenario of inclusion in Bangladesh and shows policy for a Modified Unit banking System.

The aim of this study is to explore the extent of English language teaching in Higher Institutions of Malaysia and investigate the current changes, trends and challenges in this niche. A sample of 100 English learners from public and private institutions participated in this study. Analysis of the responses indicated that English language is remaining to be difficult to master, due to speaking environment, proficiency of the teachers and other factors. However, the Government is on the right direction to improve this situation by following Common European Framework of Reference of Languages. As any other system, it takes time to put into realization and start up the mechanism. This observation carries a pedagogical perspective and includes the overview of the general picture based on Private, Public and Stand Alone English educational institutions. This study has highlighted the practical importance of British Framework of English learning and suggests to focus on emphasis of the learning process instead of a result.

The static formation temperature (SFT) is required to determine the thermophysical properties and production parameters in geothermal and oil reservoirs. However, the SFT is not easy to be obtained by both experimental and physical methods. In this paper, a mathematical approach to predicting SFT based on a new model describing the relationship between bottom hole temperature (BHT) and shut-in time was proposed. The unknown coefficients of the model were derived from least squares fit by Particle Swarm Optimization (PSO) algorithm. Besides, the ability to predict SFT based on a few BHT data (such as first 3, 4, or 5 ones of a data set) was evaluated. The accuracy of the proposed method to predict SFT was testified with a deviation percentage less than ±4% and high values of regression coefficient R² (>0.98). The proposed method could be used as a practical tool to predict SFT in both geothermal and oil wells.

The FDA has concluded that a biosimilar candidate capable of demonstrating pharmacodynamic biomarkers in a healthy subject need not be tested for clinical efficacy in patients, regardless of if the biomarker correlates with clinical response. Since monoclonal antibodies (mAbs) do not trig-ger pharmacodynamic response, they can be substituted with robust functional disqualifying them for this waiver that can be overcome by allowing comparison of functional properties that eventually result in clinical response. This suggestion is based on the FDA's preference for more sensitive testing methods. However, clinical efficacy testing in patients is the least sensitive method, as confirmed by statistical modeling, a fact that regulatory agencies need to admit. In this paper, I present a logical and rational argument to establish the biosimilarity of products that do not have pharmacodynamic biomarkers based on their orthogonally proven functional bio-similarity. This understanding will significantly lower the development cost of biosimilars, a goal that the FDA outlined in all its guidance. Keywords: biosimilarity 1; biosimilars 2; pharmacodynamic biomarkers 3; monoclonal antibodies 4; FDA 5; clinical efficacy testing in healthy subjects 6; clinical efficacy testing in patients 7; functional assays 8; receptor binding 9.

Although, Artificial intelligence (AI) helps experts with crime analysis, research, and understanding, it has a favourable influence on cyber security. It strengthens the tools that businesses use to safeguard their networks, clients, and workers against dangerous online behaviour. However, artificial intelligence is infamous for requiring a lot of resources. It may not, however, always be relevant. Additionally, it can provide hackers a new tool and advance their abilities. Actually, the VPN industry benefits from AI in the same way. The threat posed by machine learning in AI to user data privacy may be lessened by using a VPN on all of your devices. Because they use machine learning algorithms, VPNs are better equipped to shield their users from internet-based threats. Artificial intelligence (AI) has reportedly being investigated as a means of enhancing internet security for a considerable amount of time, according to Smart Data Collective. We anticipated that AI and machine learning will have a substantial impact on the future of cyber security around two years ago.

Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Of particular interest in this regard are bioactive peptides and peptide-rich protein hydrolyzates, which represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant in rats. The anti-arthritic effect of CETH was studied on the 28th day of the experiment after two weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X-ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non-steroidal anti-inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose-dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammatory edema, inhibition of osteolysis, prevention of osteophitosis, reduction of the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents a potential theoretical strategy for the safe correction of this pathological process and, for the first time, shows that CETH may be a powerful potential nutraceutical agent or bioactive component of functional products in the treatment of rheumatoid arthritis.

Background: This study addresses the burgeoning impact of Large Language Models (LLMs) such as ChatGPT on the integrity of online examinations and seeks to demonstrate latent and advanced LLM reasoning capabilities. The research devises an iterative self-reflective strategy for invoking critical thinking and higher-order reasoning in LLMs based on multimodal exam questions using visuals and text. Methods: The proposed strategy was demonstrated and evaluated on real exam questions by subject experts and the performance of ChatGPT (GPT-4) with vision was estimated on an additional dataset of 600 text descriptions of multimodal exam questions, focusing on its response to complex, visual, and textual prompts. Results: The results indicate that latent multi-hop reasoning capabilities can be invoked using the proposed self-reflective strategy, which can effectively steer ChatGPT towards correct answers by integrating critical thinking from each modality into the final response. Meanwhile, ChatGPT demonstrated considerable proficiency in being able to answer multimodal exam questions across 12 subjects. Conclusions: This work challenges findings from recent studies which claim that existing LLMs are unable to reason on complex multimodal tasks, and therefore this study underscores the need for enhanced online exam security measures like proctoring software, that can mitigate the potential misuse of AI technologies in educational settings.

The paper presents a proposal for an in-house mathematical model of a liquid flat-plate solar collector. The proposed model is a one-dimensional distributed parameter model enabling simulations of the collector operation under arbitrarily variable boundary conditions. The model is based on the solution of energy balance equations for all components of the collector. The formulated differential equations are solved iteratively using an implicit difference scheme. In order to obtain a stable numerical solution, it is necessary to use appropriate steps of the time and spatial division. These were found by comparing the results obtained from the model with the results of the analytical solution available in the literature for the transient state, which constitutes the novelty of the present study. The accuracy of the results obtained from the model was verified experimentally by comparing the measured and the calculated history of the fluid temperature at the outlet of the collector. The calculation of the collector time constant is proposed in the paper as an example of the model practical application. The results of the time constant calculation were compared with the values obtained experimentally on the test stand. This is another novelty of the presented research. The analysed collector instantaneous efficiency was then calculated for selected outdoor conditions. The presented mathematical model can also be used to verify the correctness of the collector operation. Comparing, on an ongoing basis, the measured and the calculated values of the fluid temperature at the collector outlet, conclusions can be drawn about the process of solar glass fouling or glycol gelling. The model's simplicity and the low computational demands enable such comparisons in an online mode.

The complex progression, specialized care, and comorbidities of chronic diseases place a financial and health burden on society. In some instances, the high hospital readmission rate is also a result of chronic diseases. The readmission rates can be decreased if the quality of life for patients is increased and healthcare costs are reduced through effective management and preventive measures. As a result, healthcare professionals, service providers, and policy-makers are looking for innovative approaches to reduce healthcare costs while enhancing the quality of care. There is an emerging trend in deploying technological advancements like artificial intelligence (AI), the Internet of Things (IoT), sensors, wearables, social media, mobile apps, and genomics to decrease hospital readmissions. In some instances, predictive analytics, early warning systems, personal-ized care management, remote monitoring and Telehealth, decision support systems, patient education and engagement, and other areas of artificial intelligence and machine learning have outperformed traditional approaches in lowering hospital readmissions. Although AI effectively reduces readmission, there are potential risks if it is not combined with efficient interventions. Therefore, real-time monitoring and intervention are required for AI systems to increase patient safety and decrease hospital readmissions. To achieve autonomy, prevent harm, achieve fairness, and achieve explicability, the ethical principles relating to AI systems should be taken into ac-count. This study examines the significant impact on health and the economy of hospital read-missions for chronic diseases and the role of AI in reducing readmissions.

Drones, as mobile media of the present day, increase the operational and narrative capabilities of television and accelerate the logistics of shooting. Unmanned aerial vehicles with a camera properly steered by a pilot are able, to some extent, to replace a jimmy jib/crane and a dolly; basic technical devices, used in the studios, enabling the creation of narrative systems of pictures in film and television. Television is more and more often using drone footage to report events, broadcast live, as well as create coverage and television documentaries. In many productions the pilot of the drone simultaneously acts as the drone camera operator, which can improve the effectiveness of shooting, but also carries some risk related to flight safety. The article describes and presents in the form of processed footage the real conditional ties of a Visual Line of Sight (VLOS) flight faced by pilots filming with a drone. VLOS is a type of air operation, which requires maintaining eye contact with the drone. In many countries a drone visibility flight is legally sanctioned as VLOS Operation. An experiment was conducted to investigate the interactions between a human and a machine in airspace steered using a controller with a touchscreen. The drone pilot was considered an integral part of the drone’s flight system control Experimental data was collected with the use of a mobile eye-tracker, video cameras, surveys and pilot declarations. During the experiment, eight television drone pilot operators recaptured a model shot under the regime of VLOS flight at low altitude. They all show that both advanced and beginner pilots did not look at the UAV for over half the time of shot execution. The experiment allowed establishing two coefficients related to the effectiveness of a VLOS flight aiming at filming from the drone. The results point to clear differences in screen perception styles used by drone television pilots.. The coefficients were described in the form of mathematical formulas and their limit values were determined. The research also determines the limits of pilots’ perception, within which they are able to film with a drone. The outcomes may help to optimize the process of aerial filming with the use of a drone, carried out for television, film and other media, as well as in a simulation of such a flight for research and training. From the perspective of media science and social communication, the presented study included a technological component that can be accessed through information science, using statistical models and variable distributions. Media scholars can study the impact of the media without having to look into the metaphorical black box. Computer science opens up this possibility.

This paper provides a review of an emerging field in the food processing sector, referring to efficient and safe food supply chains, ’from farm to fork’, as enabled by Artificial Intelligence (AI). Recent advances in machine and deep learning are used for effective food production, energy management and food labeling. Appropriate deep neural architectures are adopted and used for this purpose, including Fully Convolutional Networks, Long Short-Term Memories and Recurrent Neural Networks, Auto-Encoders and Attention mechanisms, Latent Variable extraction and clustering, as well as Domain Adaptation. Three experimental studies are presented, illustrating the ability of these AI methodologies to produce state-of-the-art performance in the whole food supply chain. In particular, these concern: (i) predicting plant growth and tomato yield in greenhouses, thus matching food production to market needs and reducing food waste or food unavailability; (ii) optimizing energy consumption across large networks of food retail refrigeration systems, through optimal selection of systems that can get shut-down and through prediction of the respective food de-freezing times, during peaks of power demand load; (iii) optical recognition and verification of food consumption expiry date in automatic inspection of retail packaged food, thus ensuring safety of food and people’s health.

Objective: Ensuring bone health is crucial for preventing conditions such as osteoporosis and fractures. Zingerone, a phytochemical compound, has gained attention for its potential benefits in bone health. This study evaluated the osteoprotective potential of zingerone and its effects on differentiation and signalling pathways in vitro using SAOS-2 osteosarcoma and RAW264.7 macrophage cell lines, aiming to elucidate its mechanism of action in bone metabolism. Methods: SAOS-2 osteosarcoma and RAW264.7 macrophage cells were treated with zingerone at concentrations of 0.1-200µM. Osteoblast differentiation was assessed by alkaline phosphatase (ALP) activity, bone mineralisation via alizarin red S stain and gene expression markers (ALP, runt-related transcription factor 2 (Runx2) and osteocalcin) via quantitative polymerase chain reaction. Osteoclast differentiation was evaluated by tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity and mitogen-activated protein kinase (MAPK) pathways. Results: Zingerone at 200µM, did not significantly enhance mineralization in SAOS-2 cells, but upregulated ALP and Runx2 gene expression (p<0.05). Moreover, zingerone significantly inhibited osteoclast differentiation in RAW264.7 cells as evidenced by reduced TRAP staining and activity (p<0.05). Conclusion: The moderate anti-osteoclastic effects of zingerone suggest its potential role in preserving bone mass by reducing bone resorption. This study provides new insights into how zingerone modulates bone cell activity, highlighting its potential as a dietary supplement for bone health. Further research, including its underlying mechanisms for bone-related disorders and in vivo and clinical studies, is needed to fully understand its clinical relevance in bone-related disorders.

In this article, the diversity of mangrove and associate species with anticancer properties are reviewed. Information included their scientific names, synonyms, common names, families and life-forms. Their anticancer properties are documented with description on cancer cell types, effects and mechanisms. Mangroves are exclusive species confined to the mangrove habitat. Plants that occur in the coastal environment and also in mangroves are associates or non-exclusive species. In this article, species with anticancer properties are 20 mangrove species belonging to 13 genera and 11 families, and 26 associate species belonging to 24 genera and 17 families possess. Most reported mangrove species are Avicennia marina and Ceriops tagal with five and four studies, respectively. Associate species most reported are Talipariti tiliaceum or Hibiscus tiliaceus with five studies, followed by Anacardium occidentale, Artocarpus altilis, Ceriops manghas, Pluchea indica and Pongamia pinnata with four studies each. In the conservation of mangrove and associate species with anticancer properties, in in-situ conservation, species are protected in their natural surroundings as ecosystems (e.g., virgin jungle reserves and Ramsar sites) while in ex-situ conservation, species are protected outside their natural habitats (e.g., arboreta and botanical gardens).

Imipramine hydrochloride (IMP), a tricyclic antidepressant used for major depression, enuresis, and neuropathic pain, is limited by gastrointestinal complications, low oral bioavailability (44%), and complex dosing requirements. This study aimed to explore a novel non-invasive nasal delivery system using chitosan nanoparticles (Cs NPs) embedded in an in situ gel to address the limitations of oral IMP administration. Cs NPs loaded with IMP were synthesized via ionic gelation and assessed for precision in drug concentration using a validated HPLC method. The particles were integrated into a thermoresponsive polymer, Pluronic F127, to form an in situ gel suitable for nasal administration. The formulation was characterized for gelation temperature, duration, viscosity, mucoadhesive strength, and overall gel robustness. Drug release kinetics and the controlled release mechanism were studied using ex vivo permeation tests with Franz diffusion cells and nasal sheep mucosa. The optimized nanoparticle formulation (F4-50) exhibited a consistent PS of 141.7±2.2 nm, a ZP of 16.79±2.1 mV, and a high encapsulation efficiency of 67.71±1.9%. The selected in situ gel formulation, F4-50-P1, demonstrated a gelation temperature of 33.6±0.94°C and a rapid gelation time of 48.1±0.7 seconds. Transform-attenuated total reflectance infrared spectroscopy (ATR-IR) confirmed the compatibility and effective encapsulation of IMP within the formulation. The release profile of F4-50 included an initial burst release followed by a sustained release phase, with F4-50-P1 showing improved control over the burst release. The flux rates were 0.50±0.01 mg/cm²/h for F4-50 and 0.33±0.06 mg/cm²/h for F4-50-P1, indicating effective permeation. The developed chitosan nanoparticle-based in situ gel formulation provides a promising approach for the controlled release of IMP, enhancing therapeutic efficacy and patient compliance while mitigating the disadvantages associated with oral delivery.

Our article AI, cultural heritage and bias examines the challenges and potential solutions for using machine learning to interpret and classify human memory and cultural heritage artifacts. We argue that bias is inherent in cultural heritage collections (CHCs) and their digital versions, and that AI pipelines may amplify this bias. We hypothesise that effective AI methods require vast, well-annotated datasets with structured metadata, which CHCs often lack due to diverse digitisation practices and limited interconnectivity. The paper discusses the definition of bias in CHCs and other datasets, exploring how it stems from training data and insufficient humanities expertise in generative platforms. We conclude that scholarship, guidelines, and policies on AI and CHCs should address bias as both inherent and augmented by AI technologies. We recommend implementing bias mitigation techniques throughout the process, from collection to curation, to support meaningful curation, embrace diversity, and cater to future heritage audiences.

Objectives: This study aimed to compare the similarities and differences between the Kawasaki disease (KD) during the SARS-CoV-2 pandemic and multisystem inflammatory syndrome in children (MIS-C). Methods: The medical records of patients diagnosed with KD and MIS-C at a single center between July 2020 and November 2021 were retrospectively reviewed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. Compared with the KD patients, MIS-C patients were older (p<0.001), had longer hospital stays (p=0.023), elevated neutrophil count (p<0.001), C-reactive protein (p<0.001), procalcitonin (p<0.001), interleukin-6 (p<0.014), ferritin (p<0.001), fibrinogen (p<0.001), troponin I (p=0.001), NT-proBNP (p<0.001), and, D-dimer levels (p<0.001). They had more hypotension (p=0.024), decreased left ventricular function (p=0.023), and a greater need for corticosteroids (p<0.001), enoxaparin (p=0.045), and therapeutic plasma exchange (p<0.001). Patients with KD displayed a higher frequency of rash (p<0.001), oral mucosal changes (p<0.001), conjunctival injection (p<0.001), extremity changes (p<0.001), and cervical lymphadenopathy (p<0.001). They had a longer duration of fever (p<0.001), elevated white blood cell count (p<0.001), platelet count (p<0.001), and alanine aminotransferase level (p<0.001). The two groups were similar in terms of hemoglobin levels, erythrocyte sedimentation rate, albumin levels, or the frequency of coronary dilation/aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Older patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas a longer duration of fever and classical clinical features of KD favor KD.

Undernutrition is a significant public health issue in Colombia and globally, influenced by multiple factors. The relationship between food insecurity and acute undernutrition in children has been insufficiently explored. To address this, a descriptive, observational, cross-sectional study was conducted involving 70 children under the age of 5, who presented with moderate to severe acute malnutrition. The study assessed family and child food security using the Latin American and Caribbean Food Security Scale (ELCSA). Analysis of the data revealed that when households face challenges in meeting their basic needs, children are generally the least affected. Caregivers tend to prioritize children's diets, opting to reduce food intake among adults over 18 years of age instead. The causes of malnutrition were explored through the perceptions of guardians, who reported that in 30.2% of cases, malnutrition is linked to inadequate feeding and parenting practices. Specific issues noted by parents included children being too lazy to chew, preferring ultra-processed foods, or refusing to eat altogether. The study found that not all children with acute malnutrition experience food insecurity; in fact, the proportion of children suffering from hunger was very low. The findings suggest that malnutrition in children under 5 years of age is not solely determined by food insecurity but also by other factors such as parenting practices and poor feeding habits. Further research is needed to evaluate food access and quality, particularly in terms of dietary diversity, to better understand the needs of each population. Such studies will be essential in guiding public health interventions aimed at preventing, managing, and addressing malnutrition in children.

It is still unclear why the pineal gland is not able to start its own pulsatile synthesis and secretion of melatonin in the first months of a human's life, so that infants during this time are dependent on the external supply of melatonin via breast milk, unpooled donor milk from breast milk collection centres or industrially produced chrononutrition with melatonin-poor day milk and melatonin-rich night milk. According to current knowledge, the pineal gland and melatonin receptors are already present at birth, the suprachiasmatic nucleus is largely functional and noradrenaline, the key pineal transmitter, can be detected in the early foetal period. However, the development and differentiation of the pineal gland, the pinealocytes as the site of melatonin synthesis and the associated Lhx4 homebox only occurs during the first year of a person's life. The resulting "physiological" melatonin deficiency is associated with sleep disorders, infant colic and increased crying in babies. Intervention studies indicate that this deficiency should be compensated for – through breastfeeding, the administration of unpooled donor milk or through industrially produced chrononutrition made from unpooled cow's milk with melatonin-poor day milk and melatonin-rich night milk [1-3], see also Video [4].

The collection of forty-nine 8-hydroxyquinoline derivatives, substituted at C5, C6 or C7, was designed and studied by computational methods of modified POM analysis, using SwissADME, Osiris and Molinspiration tool. POM analysis (Petra/Osiris/Molinspiration) and its modified version using SwissADME instead of Petra software are indisputably tools of modern chemoinformatics, often published in the professional literature as well as in the field of research of new antibacterial active compounds, developed to replace existing antibiotics that fail due to increased resistance of bacteria. NitroxolineTM and the group of 8-hydroxyquinoline derivatives with their broad antibacterial effect and the possibility of extensive derivatization of the skeleton, represent a promising direction in the research of new antibacterial active substances. Twenty 8-hydroxyquinoline derivatives were also evaluated on their antibacterial activity against eight selected G+ and G- bacterial strains with a defined resistance mechanism. All structures were in accordance with Lipinski's criteria, twenty-one structures were interesting from the point of view of individual or average value of the bioactivity prediction score and fourteen structures showed one or more mechanisms of toxicity prediction. Furthermore, eleven structures showed a low rate of GI absorption or the inability to cross the BBB barrier, fourteen substances showed a BRENK or PAIN warning, eleven substances are an undesirable substrate of P-glycoprotein and all structures predicted the same level of bioavailability and a relatively low rate of metabolism in the liver. Five structures were selected by the intersection of the POM criteria. The virtual structures 17, 25, 35 and 43 can be favored for the continuity of next study. The resulting scores of bioactivity can indicate the potential of studied structures to be used for the design and development of new active antibacterial agents.

On return to campus after the pandemic, students were subjected to receiving lectures online, in class, or by the emerging hybrid approach. This study reports students' preference over the three approaches based on the experience gained during the 2022/23 academic session. One hundred and twenty-seven (127) on-campus Education students in one public university in Malaysia participated in the study. Data was collected through an online forum and interviews with the participants. The data collected was analyzed using content and thematic analysis. Preference for the hybrid approach emerged as a finding with three themes describing what makes the wholly online class unpopular (themes one and two); and, the popularity of the hybrid approach (theme three): 1. On-campus learner-environment challenges; 2. Perceived lack of Faculty engagement and support in the online learning environment; and, 3. Student engagement through faculty presence and technology innovation. What the students valued most in the hybrid approach is the face-to-face technology-enhanced classroom interaction that is retained, believing that learning is more effective and interesting in class than online. They considered the additional online learning activities as complementing the classroom learning. The approach provides an opportunity for fundamental learning in class and supplementary learning online. These findings imply that institutions should prioritize technology integration into face-to-face instruction, leveraging innovative approaches to enhance student engagement and learning outcomes. Lecturers should consider adopting hybrid teaching models that combine the benefits of in-person interaction with the flexibility of online learning, catering to diverse student preferences and optimizing the educational experience.

The purpose of this work is to analyze heat-treated ash wood at temperature of 185 ºC, in order to analyze its dimensional stability. For comparison, native ash/ not thermally treated wood, was be used. In order to analyze heat-treated ash wood, some main properties such as water absorption, swelling in thickness, roughness, Brinell hardness, modulus of rupture and elasticity, color change toward black with CIELab space, and many others properties were determined and processed. The results obtained after processing the experimental data have showed that heat-treated ash wood had good physical properties as absorption and swelling in thickness, and the slight increase in elasticity offers new fields of use. As a general conclusion of the work, it was established that the ash wood can be properly thermally treated, the dimensional stability characteristics being very good, and the decrease in bending resistance being almost imperceptible.

The existing methods of oil palm Fresh Fruit Bunch (FFB) evacuation from in-field to temporary collection point which typically apply medium to large tractors, often result in unexpected soil compaction. Meanwhile, smaller size equipment indicates low working capacity and unable to perform direct unloading to collection bin. This paper addresses the challenge of FFB evacuation by focusing on preventing soil compaction, increasing working capacity and enabling direct unloading to collection bin. For this purpose, a 6x6WD transporter prototype with a scissor lift mechanism was developed. With the design, the transporter could evacuate FFB in both steep mineral terrain and low ground pressure peatland, able to carry FFB with capacity of 750 kg and provide direct unloading into collection bin. The average field working capacity of the transporter was found to be 15 tons day-1. This research offers insights for future designs of medium-sized FFB transporters with advanced unloading mechanisms.

Eliminating anxiety in higher education is essential to creating a positive learning atmosphere and improving students' general well-being. University students frequently struggle with anxiety, which is frequently made worse by social expectations, academic demands, and the adjustment to living on one's own. This article review aims to give collective ideas from relevant research articles to solidify such solutions in eradicating anxiety among students at the tertiary level. Eliminating anxiety in higher education necessitates a multifaceted strategy that includes identifying the problem, offering extensive support networks, encouraging a balanced lifestyle, fostering inclusivity, reducing financial stress, fostering a sense of community, fostering open communication, routinely evaluating tactics, and working with outside organizations. By implementing these measures, universities and colleges may foster a more positive, healthy environment where students can succeed academically and personally.

The aim of this experiment was to investigate the effects of moisture content, additives and their interactions on the fermentation quality, aerobic stability and in vitro digestibility of mixed silage of amaranth and corn meal. Amaranths and corn meal were mixed in mass ratios of 69:31, 76:24 and 84:16, and the silage water content was adjusted to 60% (W1), 65% (W2) and 70% (W3), respectively. Silage treatments included no additives (U), the addition of Lactobacillus plantarum (L), the addition of cellulase (E), and the addition of Lactobacillus plantarum + cellulase (M) mixed reagents. The results showed that pH and ammonia nitrogen (NH3-N/TN) levels were significantly lower (p < 0.05) in W1 compared to W2 and W3. At the same time, dry matter (DM), organic matter (OM), in vitro dry matter digestibility (ivDMD), in vitro dry matter digestibility (ivDMD), in vitro organic matter digestibility (ivOMD), and in vitro crude protein digestibility (ivCPD) were significantly increased (p < 0.05). Meanwhile, the aerobic stability of mixed silage of seed amaranth and corn meal decreased with increasing water content. The aerobic stability of the L, E, and M treatment groups was improved by 15, 105, and 111 hours, respectively, compared to the control group at W1. pH and NH3-N/TN levels were lower in the addition of E (E and M) than in the absence of E (U and L) (3.73, 20.1 g kg−1DM vs. 3.64, 22.9 g kg−1 DM, p < 0.05).NDF and ADF were significantly lower with the addition of E than without the addition of E (598 g kg−1 DM, 145 g kg−1 DM vs. 632 g kg−1 DM, 160 g kg−1 DM, p < 0.05). However, CP, ivDMD, ivOMD, and ivCPD were significantly higher (p < 0.05). AA and NH3-N/TN were significantly reduced (p < 0.05) with the addition of L (L and M) compared to without the addition of (U and E). In conclusion, the best fermentation quality, in vitro digestibility and aerobic stability of amaranth and cornmeal mixed silage treated with Lactobacillus plantarum + cellulase (M) were achieved at 60% water content.

Delta 9 tetrahydrocannabinol (Δ-9-THC or THC), the primary psychoactive constituent of marijuana, has been found to affect the human body in a variety of ways. According to the Substance Abuse and Mental Health Services Administration (SAMHSA) of the U.S. Department of Health and Human Services, the amount of THC in marijuana has steadily climbed over the past few decades, with today's marijuana having three times the concentration of THC compared to 25 years ago. Inhalation is a major route of exposure, allowing substances to enter the body via the respiratory tract. Therefore, it is imperative to understand the molecular underpinning of THC exposure in the lung epithelium, as lung cells receive significant amounts of THC during marijuana smoking. In this study, the transcriptional alterations caused by various concentrations of THC in non-cancerous human bronchial epithelial cell line (BEAS-2B) were studied. THC exposure (0, 800, 1000, 1200, and 1500 ng/mL) caused a significant dose-dependent decrease in cell viability after 24-hour exposure. Transcriptome analysis showed a distinct dose-dependent response. HIF-1 signaling, ferroptosis, AMPK signaling, and immunogenic pathways were activated by upregulated genes associated with dosing concentration of THC. Glutathione and fatty acid metabolic pathways were significantly altered by THC-dependent downregulated genes. and downregulated genes and their associated pathways in BEAS-2B cells. Ingenuity Pathway Analysis revealed several top canonical pathways altered by THC exposure, among which ferroptosis, NRF-2 mediated oxidative stress response, caveolar mediated endocytosis (loss of cell adhesion to the substrate), tumor microenvironment, HIF1alpha signaling, and the unfolded protein response pathways were the major pathways affected. The top genes that were significantly altered as a result of THC exposure were HMOX1, CDK7, HLA-C, and SLC39A4. Present results suggested that THC exposure can induce a variety of effects, including cell death, which may involve ferroptosis and the NRF-2 signaling pathway. Moreover, the Δ-9-THC-induced cell death was ameliorated by inhibiting the ferroptosis pathway. In contrast, the ferroptosis agonist exacerbated the cell death process, suggesting that Δ-9-THC utilizes the ferroptosis pathway to induce cell death in bronchial epithelial cells.

Background Endometrial cancer is the fourth most common type of cancer in the world. Due to the prevalence and high morbidity, it is of key importance to make a quick and accurate diagnosis and effective therapy. The use of photodynamic therapy (PDT) in the treatment of endometrial cancer is a significant challenge in conducting clinical trials. PDT is non-invasive, with few side effects, damaging only neoplastic tissue, leaving healthy adjacent structures intact. Thanks to numerous experiments (also in vitro), PDT is gaining more and more recognition as a potential tool in endometrium cancer treatment. Objective The aim of the study was to analyze the effectiveness of photodynamic therapy on endometrial cancer tissue samples Methods In the in vitro experiment of PDT, sections of endometrial cancer tissue taken from female patients were subjected to. Rose Bengal was used as a photosensitizer in order to assess the usefulness of the applied PDT and to introduce these solutions into the in vivo test procedure. Results Changes on the cellular substrate, such as: chromatin condensation, disturbed structure and shape of cell nuclei were observed in all tissues subjected to PDT. Conclusions The PDT experiment in vitro offers opportunities and hopes for using the chosen procedure also in vivo. Keywords endometrial cancer; photodynamic therapy; in vitro; treatment; rose bengal

Traditional asexual propagation of hops limits its phytosanitary quality and the concomitant plant availability. This scenario worsens with the global climate change. In this study we develop protocols for in vitro propagation of Humulus lupulus var. mapuche. Two explant types were evaluated: shoot tips, from field material collected in Río Negro province (Argentina), and nodal segments, from vitroplants. Different growth regulator, such as 6-Benzylaminopurine, gibberellic acid, indole-3-butyric acid and indole-3-acetic acid, was used to induce desired morphogenic responses. Additionally, the impact of abscisic acid application on acclimatization was assessed, and resulted in robust growth and reduced plant stress symptoms during ex vitro adaptation. Also, the study develops a protocol for synthetic seeds production, with storage at 4°C to enhance conservation and plant material transport, ensuring a constant supply of female plants. This comprehensive approach addresses current producer demands and emerging climate challenges. The findings highlight the fundamental role of in vitro multiplication of hops in improving plant material availability and quality, with significant implications for the brewing industry and related sectors.

Viral pathogens pose a substantial threat to public health and necessitate the development of effective remediation and antiviral strategies. This short communication aimed to investigate the antiviral efficacy of disinfectants on the surface proteins of human pathogenic viruses. Using in silico modeling, ligand binding energies (LBEs) of selected disinfectants were predicted and combined with their environmental impacts and costs through eco-pharmaco-economic analysis (EPEA). Results revealed the binding affinities of chemical disinfectants to viral proteins varied significantly (p

The main focus of the in vitro toxicity assessment methods is on the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division or remaining viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells and liver sinusoidal endothelial cells to rifampicin, ibuprofen and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds as it considers the different cellular responses induced by toxic agents.

Acute and chronic respiratory diseases impose a significant economic and health burden. Distal small airway assessment requires invasive procedures such as a bronchoscopy and bronchoalveolar lavage. The Particles in Exhaled Air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles sized around 0.5-7m and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening. The PExA device can measure particle count and mass according to particle size. Subsequent capture of particles in a thin membrane enables application of various analytical methods to assess a broad range of biomolecules including phospholipids, proteins, inflammatory profile, and other metabolites to characterise inflammation and diseases processes such as asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, lung cancer, and more recently acute infections such as COVID-19. PExA analysis provides a promising alternative to traditional investigative methods in the assessment, diagnosis, and management of respiratory conditions. By evaluating specific biomarkers in the RTLF associated with airway inflammation, PExA may offer a more accurate and comprehensive understanding of the molecular-level changes in the small airways of patients with acute and chronic lung diseases.

In this paper, a proof similar to the Pusey-Barrett-Rudolph (PBR) theorem is given to prove that time in quantum theory is not epistemic but has ontological reality. For this, we first discuss how time can be encoded as an intrinsic property of a quantum system. We prepare a quantum state containing time as an intrinsic property and show by a PBR-type proof that time cannot be an epistemic notion. In fact, the PBR theorem implies an ontic notion of time. Indeed, if the quantum state is a physical property, then quantum state reduction is a physical process involving information destruction. In this case, quantum probabilities are intrinsic probabilities without epistemic origin, and they generate a genuinely new sequence of events. This novelty introduced by quantum probabilities can be interpreted as time.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

Abstract: This article aims to better understand the mechanisms that connect climate change perceptions and general willingness to engage in pro-environmental behavior using Spanish cross-sectional data (N = 403). To do this, we first developed and validated the General Willingness for Environmental Behavior Scale (GWEBS), which includes the classical approach of voluntarily doing new actions but also actions implying not doing things (degrowth) and actions forced by social constraints. The exploratory and confirmatory factor analysis showed a good fit for the one-factor structure, which had adequate validity based on their relationship with other variables. Additionally, the GWEBS distinguished between women and men, left- and right-oriented people, and people who belonged to pro-environmental groups and people who did not. In the second place, we tested the parallel mediator role of eco-anxiety and trust in science in the relationship between climate change perceptions and the GWEBS. The results showed that eco-anxiety, fully, and trust in science partially mediated such a relationship, making them crucial to mobilize the intention to act following the perception. This study contributes to our understanding of the psychological mechanisms that eventually drive pro-environmental behaviors and provides a clear direction for future research.

In this study, we investigated the role of Giardia EVs in cellular communication and their potential as vaccine candidates. Our findings revealed that Giardia EVs activate pro-inflammatory signalling cascades, including SAPK/JNK and ERK1/ERK2, as well as the NF-kB pathway, resulting in IκB-α degradation and p65 translocation to the nucleus, in mouse macrophages. Moreover, Giardia EVs increased the expression of genes encoding pro-inflammatory molecules, such as Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf. Interestingly, Giardia EVs enhanced the maturation status of human Mo-DCs and significantly increased T-cell proliferation with a Th1 profile. Immunization studies demonstrated that Giardia EVs elicited antigen-specific antibodies, with IgG subclasses indicating a balance Th1/ Th2 response. Mass spectrometry analysis identified EV proteins (22 KDa and 50 KDa) that bind to serum antibodies of immunized mice including elongation factor 1-alpha, Alpha-7.3 giardin, tubulin, and Variant Surface Proteins (VSP), known antigenic proteins in Giardia infections. Overall, our results indicated that Giardia EVs modulate innate immune cells in vitro, induce antibody-based immune response in vivo, and contain conserved immunogenic proteins. Consequently, Giardia EVs hold promise as a cell-free vaccine candidate for giardiasis.

Low efficiency of in vivo transfection of a few fibers revealed a novel tissue network which temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibers began to grow after complete fiber degradation, synchronous inflammation, myoblast and myotube formation. The first detection of neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) has been made in this system. The neonatal, fast and slow SERCA isoforms displayed consequent change with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that the expression of the slow myosin heavy chain and the slow muscle type SERCA2a are dif-ferently regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SER-CA1b shRNA stimulated fiber size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished in co-transfection with Cain or in case of perimuscular injection with IL4 antibody. This revealed a novel signalling network resembling to scale-free networks which, starting from transfected fiber myonuclei as “hubs”, can amplify growth stimula-tion uniformly in the entire regenerating muscle.

Mutations in epidermal growth factor receptor (EGFR) occur in about 48% of Asian and 19% of Western patients with lung adenocarcinoma (LUAD), leading to its constitutive activation and subsequent uncontrolled cell proliferation. To counteract this, tyrosine kinase inhibitors (TKIs) have been developed, targeting EGFR activity. However, the emergence of metastases and resistance mutations often undermines the durability of the treatment response. Knowledge-based mechanistic models that replicate existing clinical trial outcomes, tailored to specific population characteristics, provide invaluable assistance in designing future clinical trials. These models are particularly effective in identifying optimal responders to specific treatments, thereby enhancing therapeutic efficacy. We have developed physiologically based pharmacokinetic (PBPK) models for gefitinib and osimertinib, representing two distinct generations of EGFR TKIs, to accurately simulate the drugs’ distribution within the primary tumor and metastatic sites following oral administration. These models were integrated with a pathophysiological mechanistic model of EGFR-mutant LUAD, enabling the representation of the effects of both gefitinib and osimertinib on EGFR activation-induced signaling pathways. This comprehensive model outputs detailed evolutions of the primary tumor and each metastatic site, facilitating the evaluation of patient progression in alignment with RECIST guidelines (version 1.1). Notably, the model encapsulates the heterogeneity within the tumor, through the representation of various subclones, each characterized by unique mutation profiles, thereby reflecting differential responses to treatment. Calibration of the model was achieved using publicly available data from the NEJ002 and FLAURA clinical trials. Rigorous visual predictive checks and statistical tests were employed to ensure the proper behavior of the model. The model adeptly replicated the time to progression observed in real clinical trials in EGFR-mutant LUAD patients receiving gefitinib or osimertinib as first-line therapy. In addition, the model was able to reproduce the results from a retrospective study comparing gefitinib and osimertinib, a study that was not used to inform the model. With a consistent virtual population as a reference, the combined model facilitated a comparative analysis of the efficacy of both treatments, thereby underscoring its utility in evaluating therapeutic strategies. The faithful replication of real-world data significantly enhances the credibility of our model, rendering it a vital investigational tool for deriving pertinent insights and informing treatment strategies, particularly in identifying optimal responders to various generations of EGFR TKIs. Following its consecutive prospective validations in the FLAURA2 and MARIPOSA trials, the model is poised to facilitate the generation of synthetic control arms in future clinical trials. This advancement promises a more nuanced analysis of covariate relationships, especially when comparing investigational treatments to established standards of care. Additionally, it potentially reduces the required patient cohort size in such trials, optimizing resource utilization.