Oral cancer is the 16th most common malignant tumor worldwide. The risk of recurrence and mortality is high, and the survival rate is low over the following five years. Recent studies have shown that curcumin causes apoptosis in tumor cells by affecting F_oF₁-ATP synthase (ATP synthase) activity, which, in turn, hinders cell energy production, leading to a loss of cell viability. Additionally, irradiation of curcumin within cells can intensify its detrimental effects on cancer cell viability and proliferation (photodynamic therapy). We treated the OHSU-974 cell line, a model for human head and neck squamous cell carcinoma (HNSCC), and primary human fibroblasts. The treatment involved a 1 h exposure of cells to 0.1, 1.0, and 10 μM curcumin, followed or not by irradiation or the addition of the same concentration of pre-irradiated curcumin. Both instances involved a diode laser with a wavelength of 450 nm (0.25 W, 15 J, 60 s, 1 cm², continuous wave mode). The treatment with non-irradiated 1 and 10 µM curcumin caused ATP synthase inhibition and a consequent reduction in the oxygen consumption rate (OCR) and the ATP/AMP ratio, which was associated with a decrement in lipid peroxidation accumulation and a slight increase in glutathione reductase and catalase activity. By contrast, 60 s curcumin irradiation with 0.25 W—450 nm caused a further oxidative phosphorylation (OxPhos) metabolism impairment that induced an uncoupling between respiration and energy production, leading to increased oxidative damage, a cellular growth and viability reduction, and a cell cycle block in the G1 phase. These effects appeared to be more evident when the curcumin was irradiated after cell incubation. Since cells belonging to the HNSCC microenvironment support tumor development, curcumin’s effects have been analyzed on primary human fibroblasts, and a decrease in cell energy status has been observed with both irradiated and non-irradiated curcumin and an increase in oxidative lipid damage and a slowing of cell growth were observed when the curcumin was irradiated before or after cellular administration. Thus, although curcumin displays an anti-cancer role on OHSU-974 in its native form, photoactivation seems to enhance its effects, making it effective even at low dosages. Full article

Non-Intrusive Load Monitoring (NILM), which provides sufficient load for the energy consumption of an entire building, has become crucial in improving the operation of energy systems. Although NILM can decompose overall energy consumption into individual electrical sub-loads, it struggles to estimate thermal-driven sub-loads such as occupants. Previous studies proposed Non-Intrusive Thermal Load Monitoring (NITLM), which disaggregates the overall thermal load into sub-loads; however, these studies evaluated only a single building. The results change for other buildings due to individual building factors, such as floor area, location, and occupancy patterns; thus, it is necessary to analyze how these factors affect the accuracy of disaggregation for accurate monitoring. In this paper, we conduct a fundamental evaluation of NITLM in various realistic office buildings to accurately disaggregate the overall thermal load into sub-loads, focusing on occupant thermal load. Through experiments, we introduce NITLM with deep learning models and evaluate these models using thermal load datasets. These thermal load datasets are generated by a building energy simulation, and its inputs for the simulation were derived from realistic data like HVAC on/off data. Such fundamental evaluation has not been done before, but insights obtained from the comparison of learning models are necessary and useful for improving learning models. Our experimental results shed light on the deep learning-based NITLM models for building-level efficient energy management systems. Full article

The well-known inspection paradox or waiting time paradox states that, in a renewal process, the inspection interval is stochastically larger than a common interarrival time having a distribution function F, where the inspection interval is given by the particular interarrival time containing the specified time point of process inspection. The inspection paradox may also be expressed in terms of expectations, where the order is strict, in general. A renewal process can be utilized to describe the arrivals of vehicles, customers, or claims, for example. As the inspection time may also be considered a random variable T with a left-continuous distribution function G independent of the renewal process, the question arises as to whether the inspection paradox inevitably occurs in this general situation, apart from in some marginal cases with respect to F and G. For a random inspection time T, it is seen that non-trivial choices lead to non-occurrence of the paradox. In this paper, a complete characterization of the non-occurrence of the inspection paradox is given with respect to G. Several examples and related assertions are shown, including the deterministic time situation. Full article

The safety and sustainability of urban underground spaces have become crucial considerations in development projects. Seepage and cyclic loads are the principal reasons for the instability and failure of old underground space structures. This study investigates the variations in physical fields of underground spaces in cities under the coupling disturbance of seepage and cyclic loads, focusing on underground civil air defense engineering in Beijing as a case study. Different seepage conditions and the effects of seepage–cyclic load coupling were simulated using the numerical calculation software Plaxis 3D V20. The results show that change in groundwater can affect the deformation of underground space, and the severity is related to the quantity and intersection state of tunnels, the location of rivers above, and the strength of materials. The coupling effect of seepage–cyclic load on urban underground space structures is more serious than that of a single percolation. Decrease in material strength and high traffic loads are the principal reasons for the failure of underground structures. A 30% decrease in material strength causes the displacement to increase almost 1.5 times, and maximum displacement under different traffic loads can vary by 3 times. This study holds significant implications for the design, maintenance, and engineering management of underground spaces, emphasizing the importance of sustainable practices in urban development and infrastructure. Full article

This study advances the understanding of the Preferred Habitat Model’s capacity to shed light on the inter-market transfer of mean returns and the diffusion of price volatility in Pakistani investment markets. It examines the extent to which returns in one market exert a systematic influence on returns across others under the potential sway of interest rate policy shifts, USD exchange rate volatility, and domestic inflation trends. Employing a methodological arsenal that includes the GARCH process, enhanced by Dynamic Conditional Correlations (DCC), as well as the Markov Switching Model, this research assesses the propagation of mean returns and volatility across markets. The analysis uncovers significant linkages between monetary policy and stock market indices, underscoring the profound impact of monetary policy on cross-market performance transmission. These insights are pivotal for regulators overseeing the nuanced interaction between monetary policy and market performance. They are crucial for local and international investors interested in developing economies, especially in Pakistan’s markets. Full article

Rapid methods for assessing the fatigue properties of materials have been developed, among which the self-heating method stands out as particularly promising. This approach analyzes the thermal signal of the specimen when subjected to cyclic loading. In this research, the self-heating method was utilized for the first time with laser powder bed fusion (LPBF) of NiTi alloys, examining two specific loading conditions: loading ratios of 0.1 and 10. A thorough examination of the material self-heating behavior was conducted. For comparative purposes, conventional fatigue tests were also conducted, alongside interrupted fatigue tests designed to highlight the underlying mechanisms involved in high cycle fatigue and potentially self-heating behavior. The investigation revealed several key mechanisms at play, including intra-grain misorientation, the emergence and growth of persistent slip bands, and the formation of stress-induced martensite. These findings not only deepen our understanding of the fatigue behavior of LPBF NiTi alloys but also highlight the self-heating method potential as a tool for studying material fatigue. Full article

Congestion not only represents a cardinal sign of heart failure (HF) but is also now recognized as the primary cause of hospital admissions, rehospitalization, and mortality among patients with acute heart failure (AHF). Congestion can manifest through various HF phenotypes in acute settings: volume overload, volume redistribution, or both. Recognizing the congestion phenotype is paramount, as it implies different therapeutic strategies for decongestion. Among patients with AHF, achieving complete decongestion is challenging, as more than half still experience residual congestion at discharge. Residual congestion is one of the strongest predictors of future cardiovascular events and poor outcomes. Through this review, we try to provide a better understanding of the congestion phenomenon among patients with AHF by highlighting insights into the pathophysiological mechanisms behind congestion and new diagnostic and management tools to achieve and maintain efficient decongestion. Full article

In the United States, patients with chronic conditions experience disparities in health outcomes across the care continuum. Among patients with multiple sclerosis, diabetic retinopathy, and lung cancer, there is a lack of evidence summarizing interventions to improve care and decrease these disparities. The aim of this rapid literature review was to identify interventions among patients with these chronic conditions to improve health and reduce disparities in screening, diagnosis, access to treatment and specialists, adherence, and retention in care. Using structured search terms in PubMed and Web of Science, we completed a rapid review of studies published in the prior five years conducted in the United States on our subject of focus. We screened the retrieved articles for inclusion and extracted data using a standard spreadsheet. The data were synthesized across clinical conditions and summarized. Screening was the most common point in the care continuum with documented interventions. Most studies we identified addressed interventions for patients with lung cancer, with half as many studies identified for patients with diabetic retinopathy, and few studies identified for patients with multiple sclerosis. Almost two-thirds of the studies focused on patients who identify as Black, Indigenous, or people of color. Interventions with evidence evaluating implementation in multiple conditions included telemedicine, mobile clinics, and insurance subsidies, or expansion. Despite documented disparities and a focus on health equity, a paucity of evidence exists on interventions that improve health outcomes among patients who are medically underserved with multiple sclerosis, diabetic retinopathy, and lung cancer. Full article

Streptococcus suis (S. suis) is a zoonotic pathogen with a global distribution, which causes serious diseases in both humans and animals and economic losses in the swine industry. As antibiotic resistance increases, there is an urgent imperative to explore novel antibacterial alternatives. In the present study, we selected the anticancer drug 5-fluorouracil (5-FU) approved by the Food and Drug Administration (FDA) as a candidate drug to treat S. suis infections. The results showed that various pathogens, especially S. suis, are more sensitive to 5-FU. Moreover, the cytotoxicity of 5-FU is relatively low. Extensive in vitro assays demonstrated the pronounced bacteriostatic and bactericidal efficacy of 5-FU against susceptible and multidrug-resistant S. suis strains. Its mechanisms of action include damage to the bacterial cell walls and membranes, resulting in the leakage of intracellular components, and the inhibition of thymidylate synthase (TS), leading to a depletion of deoxythymidine triphosphate (dTTP) pools, ultimately causing thymine-less death and lethal DNA damage in bacteria. Gene-knockout experiments further showed that 5-FU played a role by inhibiting the thyA gene-encoding thymidine synthase. Finally, we determined that S. suis infections can be alleviated by 5-FU in the mouse infection model. This study emphasizes the antibacterial potential of 5-FU against S. suis and provides evidence for its targeting of bacterial membrane damage and DNA damage. In summary, 5-FU can control S. suis infection and is expected to become a new alternative to antibiotics. Full article

Background: Extracorporeal shock wave lithotripsy (ESWL) is a common treatment for pancreatic stones in chronic pancreatitis. In contrast, peroral pancreatoscopy-guided lithotripsy (POPS-L) remains underexplored, with limited comparative studies to ESWL. This study compared the treatment outcomes of disposable POPS-L tools and ESWL for pancreatic stones. Methods: A retrospective analysis was conducted on 66 patients who had undergone pancreatic stone treatment at three institutions between 2006 and 2022. The treatment outcomes of POPS-L and ESWL were compared. Results: This study included 19 and 47 patients who had undergone POPS-L and ESWL, respectively. In a comparison between POPS-L and ESWL, the stone clearance rates were 78.9% vs. 70.2% (p = 0.55), while the procedure-related complication rates were 21% vs. 6.3% (p = 0.09). The median total session counts were 1 vs. 5 (p < 0.01). The cumulative stone recurrence rates were comparable in both groups. Multivariate analysis revealed no significant factors influencing the stone clearance rates, and the choice between POPS-L and ESWL did not affect the stone clearance rates. Conclusions: POPS-L and ESWL exhibited comparable treatment outcomes in terms of stone clearance, complications, and recurrence rates. Furthermore, POPS-L is advantageous due to the need for fewer sessions to achieve pancreatic stone clearance. Full article

In 3D microsphere tracking, unlike in-plane motion that can be measured directly by a microscope, axial displacements are resolved by optical interference or a diffraction model. As a result, the axial results are affected by the environmental noise. The immunity to environmental noise increases with measurement accuracy and the signal-to-noise ratio (SNR). In compound digital holography microscopy (CDHM)-based measurements, precise identification of the tracking marker is critical to ensuring measurement precision. The reconstruction centering method (RCM) was proposed to suppress the drawbacks caused by installation errors and, at the same time, improve the correct identification of the tracking marker. The reconstructed center is considered to be the center of the microsphere, rather than the center of imaging in conventional digital holographic microscopy. This method was verified by simulation of rays tracing through microspheres and axial moving experiments. The axial displacements of silica microspheres with diameters of 5 μm and 10 μm were tested by CDHM in combination with the RCM. As a result, the SNR of the proposed method was improved by around 30%. In addition, the method was successfully applied to axial displacement measurements of overlapped microspheres with a resolution of 2 nm. Full article

Research into innovative techniques in food technology is developing dynamically. This is indicated by the significant increase in the number of scientific studies in this field. The aim of this work was to provide a comprehensive, in-depth analysis of the available scientific evidence on new techniques used in food that not only increase efficiency but also enable the creation of products with desirable sensory and nutritional characteristics. Research on techniques including cold plasma, high-pressure processing, ultrasound, pulsed electric fields, sous vide, and microwave heating aims to provide innovative methods of food processing, in the context of meeting growing consumer expectations and optimizing production processes in the food industry. Compared to traditional food processing methods, innovative techniques can provide more efficient solutions in the processing of products. Research on alternative non-thermal methods in food technology suggests their possible benefits, including enhancing sensory and nutritional quality, minimizing environmental impact, and increasing production efficiency, which are a significant challenge in the modern food industry. Despite the many benefits, it is worthwhile to continue research to further improve modern food technologies. Full article

The modalities of schooling and the educational measures for students with special educational needs (SENs) are postulated as important aspects within the field of study of inclusive education. The general objective of this research is to analyse the processes, through the voice of their peers, for the inclusion of students with SENs enrolled in specialised classrooms (SCs) in mainstream centres in Spain when they attend mainstream classrooms (MCs). The design of the research is mixed (QUAN-Qual), non-experimental, and descriptive. The participants in the quantitative phase were 2649 peers from MCs that have students enrolled in the SCs, and the participants in the qualitative phase were 57 students from MCs. A questionnaire designed ad hoc was used for collecting the quantitative information and discussion groups for the qualitative information. This study shows the barriers and facilitators towards the inclusion of students in the SU within mainstream centres or classrooms. Among the facilitators which stand out is the wish of classmates from mainstream classrooms to share times, spaces, and activities with their classmates with SENs from the SU. Among the barriers highlighted by a large number of students in the MCs are the fact that they do not participate in group activities with their peers with SENs and that the latter do not usually participate in common activities developed at the centre (like celebrations or excursions). Full article

A new Cu(II) complex, [CuL₁L₂(CH₃COO)₂(H₂O)]·H₂O, was synthesized by the reaction of Cu(CH₃COO)₂·H₂O, 6-phenylpyridine-2-carboxylic acid (HL₁), and 4-[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]pyridine (L₂) in ethanol-water (v:v = 1:1) solution. The Cu(II) complex was characterized using elemental analysis, IR, UV-vis, TG–DTA, and single-crystal X-ray analysis. The fluorescence properties of the copper complex were also evaluated. The structural analysis results show that the Cu(II) complex crystallizes in the triclinic system with space group P-1. The Cu(II) ion in the complex is five-coordinated with one O atom (O2) and one N atom (N1) from one 6-phenylpyridine-2-carboxylate ligand (L₁), one N atom (N2) from 4-[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]pyridine ligand (L₂), one O atom (O4) from acetate, and one O atom (O5) from a coordinated water molecule, and it adopts a distorted trigonal bipyramidal geometry. Cu(II) complex molecules form a two-dimensional layer structure through intramolecular and intermolecular O-H^…O hydrogen bonding. The two-dimensional layer structures further form a three-dimensional network structure by π-π stacking interactions of aromatic rings. The analysis of the Hirschfeld surface of the Cu(II) complex shows that the H^…H contacts made the most significant contribution (46.6%) to the Hirschfeld surface, followed by O^…H/H^…O, N^…H/H^…N and C^…H/H^…C contacts with contributions of 14.2%, 13.8%, and 10.2%, respectively. In addition, the photocatalytic CO₂ reduction using Cu(II) complex as a catalyst is investigated under UV-vis light irradiation. The findings reveal that the main product is CO, with a yield of 10.34 μmol/g and a selectivity of 89.4% after three hours. Full article

The question of how we measure, categorise, and represent ethnicity poses a growing challenge for identifying and addressing ethnic inequalities. Conceptual critiques and qualitative studies highlight the complexities and challenges of measuring ethnicity, yet there remains a lack of quantitative studies investigating the implications of these complexities for inequalities research. This paper addresses this gap by scrutinizing methodological processes and analysing the implications of measurement and categorisation in the Crime Survey for England and Wales (CSEW), critiquing the UK’s standardised measurement of ethnicity in national survey data and government statistics. Based on our comparative quantitative analysis of standardised ethnicity categories and regional origins and our evaluation of the CSEW and census’ methodologies, we propose an alternative categorisation of ethnicity, focusing on the ‘Mixed’, ‘Asian’, and ‘Latinx/Hispanic’ ethnic groups. Using adjusted crosstabulations and logistic regression models, we found variations in ethnic patterns of violence based on standardised measures and our alternative recategorisation, particularly relating to the distinction between ‘Asian’ sub-groups, the recategorisation of ‘Mixed’ ethnicities, and the inclusion of ‘Latinx/Hispanic’ as a distinctive ethnic group. Our findings reveal valuable insights into the implications of ethnic categorisation for understanding violence inequalities, with significant implications for further policy and research areas. Full article

Regenerative medicine harnesses stem cells’ capacity to restore damaged tissues and organs. In vitro methods employing specific bioactive molecules, such as growth factors, bio-inductive scaffolds, 3D cultures, co-cultures, and mechanical stimuli, steer stem cells toward the desired differentiation pathways, mimicking their natural development. Chondrogenesis presents a challenge for regenerative medicine. This intricate process involves precise modulation of chondro-related transcription factors and pathways, critical for generating cartilage. Cartilage damage disrupts this process, impeding proper tissue healing due to its unique mechanical and anatomical characteristics. Consequently, the resultant tissue often forms fibrocartilage, which lacks adequate mechanical properties, posing a significant hurdle for effective regeneration. This review comprehensively explores studies showcasing the potential of amniotic mesenchymal stem cells (AMSCs) and amniotic epithelial cells (AECs) in chondrogenic differentiation. These cells exhibit innate characteristics that position them as promising candidates for regenerative medicine. Their capacity to differentiate toward chondrocytes offers a pathway for developing effective regenerative protocols. Understanding and leveraging the innate properties of AMSCs and AECs hold promise in addressing the challenges associated with cartilage repair, potentially offering superior outcomes in tissue regeneration. Full article

Trochoidal milling is one of the solutions for increasing the efficiency of machining processes. A decreased cutting tool’s arc of contact leads to a reduction in the generated cutting forces, thus improving process stability. Vibration is an inherent part of any machining process, affecting the accuracy and quality of the manufactured components, but it can also pose a danger to machine operators. Chatter is particularly detrimental, leaving characteristic marks on shaped surfaces and potentially leading to catastrophic tool damage. Therefore, it is important to ensure the stability of machining and also reduce vibration. The primary purpose of the conducted research is to evaluate the stability of the milling process of the AZ91D magnesium alloy performed through a trochoidal strategy. An additional objective is to establish the effect of the variation in machining parameters and toolholder types on milling stability. Three types of toolholders most commonly used in industry are used in the study. The basis of the investigation is the measurement of vibration displacement and acceleration analysed in the time domain. A spectral analysis of the signals is also performed based on Fast Fourier Transform, to identify signal components and detect the susceptibility to chatter occurrence. An important part of the study is also an attempt to use the Composite Multiscale Entropy as an indicator to determine the stability of the machining processes. Entropy does not exceed the values of 1.5 for cutting speed and 2.5 for feed per tooth, respectively. Vibration acceleration does not exceed (in most cases) the value of 20 m/s² for the peak-to-peak parameter and the shrinkfit toolholder. For vibration displacement (peak-to-peak parameter), there are oscillations around the value of 0.9 mm for all kinds of toolholders. Full article

Polarization states define a fundamental property in optics. Consequently, polarization state characterization is essential in many areas of both field industrial applications and scientific research. However, a full identification of space-variant Stokes parameters faces great challenges, like multiple power measurements. In this contribution, we present a spatially resolved polarization measurement using artificial birefringent metallic elements, the so-called hollow waveguides. Differently oriented and space-variant hollow waveguide arrays, a stationary analyzer and a CMOS camera form the basis of the experimental setup for one single spatially resolved power measurement. From this power measurement, the Stokes parameters can be calculated in quasi-real-time, with a spatial resolution down to 50 $\mathsf{\mu }$m in square. The dimensions of the individual hollow waveguides, which are less than or equal to the employed wavelength, determine the spectral range, here in the near infrared around $\mathsf{\lambda }$ = 1550 nm. This method allows for the rapid and compact determination of spatially resolved Stokes parameters, which is experimentally confirmed using defined wave plates, as well as an undefined injection-molded polymer substrate. Full article

(1) Background: Since the advent of zidovudine in 1987, antiretroviral therapy has undergone significant evolution, marked by the introduction of 34 antiretroviral drugs and 24 fixed-dose combinations. Despite these advances, hepatotoxicity remains a formidable challenge, influencing morbidity, mortality, and treatment adherence in HIV-infected patients. This study aims to compare the hepatotoxic effects of latest-generation antiretroviral medications with those of older-generation therapies, assessing their long-term impact on liver health in HIV patients. (2) Methods: This retrospective study analyzed data from 304 HIV patients treated with either latest-generation or older-generation antiretroviral drugs over four years. Patients were monitored for hepatotoxicity through liver function tests at diagnosis, six months, and one-year post-treatment initiation. (3) Results: Initial and six-month liver function tests showed no significant differences between the two groups. However, at one-year post-treatment, patients on latest-generation antiretrovirals exhibited significant improvements in ALT, AST, and ALP levels, suggesting a better safety profile regarding hepatotoxicity. Additionally, a significantly lower incidence of splenomegaly was observed in patients treated with newer medications. (4) Conclusions: The findings suggest that the latest-generation antiretroviral medications may offer a safer profile in terms of hepatotoxicity compared to older therapies, with potential benefits for long-term liver health. This study underscores the importance of continuous monitoring and further research to optimize ART strategies, ensuring improved patient outcomes and quality of life for individuals living with HIV. Full article

Salt stress poses a significant threat to crop yields worldwide. Melatonin (MT), an endogenous hormone synthesized in plants, has emerged as a crucial player in plant responses to various abiotic stresses, including drought, salinity, heat, and cold. However, the precise molecular mechanisms underlying MT-mediated abiotic stress responses remain incompletely understood. To elucidate the key genes and pathways involved in MT-mediated alleviation of salt stress, we conducted physiological, biochemical, and transcriptomic analyses on alfalfa seedlings. Our results demonstrated that alfalfa seedlings treated with melatonin exhibited higher germination rates, longer bud lengths, and greater fresh weights compared to those subjected to salt stress alone. Furthermore, the levels of malondialdehyde (MDA) and superoxide anion (O²⁻) were reduced, while the activities and contents of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), and glutathione (GSH) increased in response to melatonin treatment. Transcriptome analysis revealed 2181 differentially expressed genes (DEGs) in the salt-treated group, with 780 upregulated and 1401 downregulated genes. In contrast, the MT-treated group exhibited 4422 DEGs, including 1438 upregulated and 2984 downregulated genes. Functional annotation and pathway enrichment analysis indicated that DEGs were primarily involved in the biosynthesis of flavonoids, isoflavones, plant hormones, glutathione (GSH), soluble sugars, and other substances, as well as in ABC transporter and MAPK signaling pathways. Notably, the MT-treated group showed greater enrichment of DEGs in these pathways, suggesting that MT mitigates salt stress by modulating the expression of genes related to phytohormones and antioxidant capacity. Overall, our findings provide valuable insights into the molecular mechanisms underlying MT-mediated salt tolerance in alfalfa, with important implications for breeding salt-tolerant alfalfa and other crops. Full article

The identification of heterogeneous and homogeneous groups of students using clustering analysis in learning analytics is still rare. The paper describes a study in which the students’ performance data stored in the micro-learning platform Priscilla are analyzed using learning analytics methods. This study aims to identify the groups of students with similar performances in micro-learning courses focused on learning programming and uncover possible changes in the number and composition of the identified groups of students. The CRISP-DM methodology was used to navigate through the complexity of the knowledge discovery process. Six different datasets representing different types of graded activities or term periods were prepared and analyzed for that purpose. The clustering analysis using the K-Means method found two clusters in all cases. Subsequently, performance metrics, the internal composition, and transfers of the students between clusters identified in different datasets were analyzed. As a result, this study confirms that analyzing student performance data from a micro-learning platform using learning analytics methods can reveal distinct groups of students with different academic performances, and these groups change over time. These findings align with teachers’ assumptions that the micro-learning platform with automated evaluation of programming assignments highlights how the students perceive the role of learning tools during learning programming in different term periods. Simultaneously, this study acknowledges that clustering, as an exploratory method, provides a solid basis for further research and can identify distinct groups of students with similar characteristics. Full article

Numerous studies suggest the involvement of adenosine-5′-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5′-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y₂ and P2Y₄ receptors and K⁺ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K⁺ (K_V) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K⁺ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K⁺ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). K_V channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y₂), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K⁺ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y₄ receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of K_V1.2 and K_V1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y₄ signaling and K_V channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males. Full article