We introduce the notion of p-adic equiangular lines and derive the first fundamental relation between common angle, dimension of the space and the number of lines. More precisely, we show that if {τj} n j=1 is p-adic γ-equiangular lines in Qd p , then (1) |n| 2 ≤ |d| max{|n|, γ2 }. We call Inequality (1) as the p-adic van Lint-Seidel relative bound. We believe that this complements fundamental van Lint-Seidel [Indag. Math., 1966] relative bound for equiangular lines in the p-adic case. Keywords: Equiangular lines, p-adic Hilbert space.

This article presents a proposed system that enables energy transfer from the dc grid to a single-phase onboard grid, operating at an hi frequency. In addition to the energy transfer function, it additionally enables compensation of reactive power in the ac grid when the converter operates at less than rated power. To operate in compensator mode, it is necessary to decouple the current from the grid into active and reactive components and control them independently. To achieve good dynamics, synchronizers that operate in the dq system are used. In the case of a single-phase grid, it requires such a synchronizer to generate virtual quadrature signals. The used systems based on second-order generalized integrator are good, but to improve dynamics in the work a quadrature generator based on trigonometric calculations was proposed. The developed system was implemented in a proportional resonant current control system. Tests performed in steady state and in dynamic states related to typical grid disturbances showed better dynamic properties than the standard integrator-based system.Keywords: power transfer; compensator; P+R controller

Arc sensors have been used in seam tracking and widely studied since the 80s; commercial arc sensing products for T and V shaped grooves have been developed. However, it is difficult to use these arc sensors in narrow gap welding because arc stability and sensing accuracy are not satisfactory. Pulse gas melting arc welding (P-GMAW) has been successfully applied in narrow gap welding and all position welding processes, so it is worthwhile to research P-GMAW arc sensing technology. In this paper, we derived a linear mathematical P-GMAW model for arc sensing, and the assumptions for the model are verified through experiments and finite element methods. Finally, the linear characteristics of the mathematical model were investigated. In torch height changing experiments, uphill experiments, and groove angle changing experiments the P-GMAW arc signals all satisfied the linear rules. In addition, the faster the welding speed, the higher the arc signal sensitivities; the smaller the groove angle, the greater the arc sensitivities. The arc signal variation rate needs to be modified according to the welding power, groove angles, and swing or rotate speed.

Pardosa pseudoannulata is one of the most common wandering spiders in agricultural fields and a potentially good bioindicator for heavy metal contamination. However, little is known about the mechanism by which spiders respond to heavy metals at the molecular level. In this study, high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and to identify differentially expressed genes (DEGs) after cadmium exposure. We obtained 60,489 assembled unigenes, 18,773 of which were annotated in the public databases. Ultimately, 3450 cDNA simple sequence repeats were identified and validated as potential molecular markers in the unigenes. A total of 2939, 2491 and 3759 DEGs were detected among the three libraries of two Cd-treated groups and the control. Functional enrichment analysis revealed that metabolism processes and digestive system function were predominately enriched in response to Cd stress. At the cellular and molecular levels, significantly enriched pathways in lysosomes and phagosomes as well as replication, recombination and repair demonstrated that oxidative damage resulted from Cd exposure. Based on the selected DEGs, certain critical genes involved in defence and detoxification were analysed. These results may elucidate the molecular mechanism underlying spiders' responses to heavy metal stress.

The emergence of mRNA vaccines represents a significant advancement in public health by conferring protection against a variety of infectious diseases. However, concerns regarding the potential risk of inducing or exacerbating autoimmune disorders, particularly connective tissue diseases (CTDs), have arisen. This paper explores the mechanisms by which mRNA vaccines may lead to the onset or worsening of CTDs, focusing on the immune responses induced by Pathogen-Associated Molecular Patterns (PAMPs), the interactions between Toll-like receptors 7/8 and 9 (TLR7/8 and TLR9), and the activation of self-reactive B cells. Furthermore, guidelines are suggested for administering vaccines to individuals at elevated risk, such as those with a positive antinuclear antibody (ANA) test or specific rheumatic disease genes. Our findings underscore the necessity for targeted vaccination strategies that mitigate risks while maintaining public health efficacy.

Tick-borne encephalitis (TBE) is the most significant arboviral infection in Croatia. The aim of the study was to analyse and correlate 17-year TBE seroprevalence data with winter temperature, precipitation and wildlife abundance to identify possible patterns that can be predictive of TBE incidence. TBE diagnosis was based on IgM/IgG anti-TBE antibodies and individual clinical interpretation of the results. Of the 19,094 analysed patients, 4.2% had acute TBE, significantly more often in older age (p<0.001) and in men (p<0.001). Overall seroprevalence of TBE among the tested population was 5.8%, and varied annually from 2.8% to 10.7%. The mean acute TBE incidence rate was 1.1 per 100.000 population with significant regional differences: 1.7 in the continental vs. 0.2 and 0.5 in the Mediterranean and Alpine regions, respectively. Particularly high incidence of 3.1 was recorded in northern Croatia. TBE displayed a seasonal pattern, peaking in June and July. Moderate negative correlations were observed between TBE acute cases and winter temperatures from December to February (r=-0.461; p=0.062), relative rodent abundance (r=-0.414; p=0.098) and yearly precipitation from one year before (r=-0.401; p=0.123). Considerable efforts are needed to understand the impact on TBE incidence to improve disease prevention.

Understanding the factors that contribute to slope failures, such as soil saturation, is essential for mitigating rainfall-induced landslides. Cost-effective capacitive soil moisture sensors have the po-tential to be widely implemented across multiple sites for landslide early warning systems. How-ever, these sensors need to be calibrated for specific applications to ensure high accuracy in readings. In this study, a soil-specific calibration was performed in a laboratory setting to integrate the soil moisture sensor with an automatic monitoring system using the Internet of Things (IoT). This re-search aims to evaluate a low-cost soil moisture sensor (SKU:SEN0193) and develop calibration equations for the purpose of slope model experiment under artificial rainfall condition using silica sand. The results indicate that a polynomial function is the best fit, with a coefficient of determi-nation (R²) ranging from 0.92 to 0.98 and a root mean square error (RMSE) ranging from 1.17 to 2.67. The calibration equation was validated through slope model experiments, with soil samples taken from the model after the experiment finished. Overall, the moisture content readings from the sensors showed approximately a 10% deviation from the actual moisture content. The findings suggest that the cost-effective capacitive soil moisture sensors has the potential to be used for the development of landslide early warning system.

In the present study, we introduce the two dimensional Chlodovsky type Bernstein operators based on (p,q)−integer. We examine approximation properties of our new operator by the help of Korovkin-type theorem. Further, we present the local approximation properties and establish the rates of convergence by means of the modulus of continuity and the Lipschitz type maximal function. Also, we give a Voronovskaja type theorem for this operators. And, we investigate weighted approximation properties of these operators and estimate rate of convergence in the same space. Finally, with the help of Maple, illustrative graphics show the rate of convergence of these operators to certain functions . The optimization of approximation speeds by operators during system control provides significant improvements in stability and performance. As a result, the control and modeling of dynamic systems become more efficient and effective through innovative methods. These advancements in the fields of modeling fractional differential equations and control theory offer substantial benefits to both modeling and optimization processes, expanding the range of applications in these areas.

This article advances the discourse on sustainable and energy-efficient software by examining the performance and energy efficiency of intelligent algorithms within the framework of green and sustainable computing. Building on previous research, it explores the theoretical implications of Bremermann's Limit on efforts to enhance computer performance through more extensive methods. The study presents an empirical investigation into heuristic methods for search and optimisation, demonstrating the energy efficiency of various algorithms in both simple and complex tasks. It also identifies key factors influencing the energy consumption of algorithms and their potential impact on computational processes. Furthermore, the article discusses cognitive concepts and their interplay with computational intelligence, highlighting the role of cognition in the evolution of intelligent algorithms. The conclusion offers insights into the future directions of research in this area, emphasising the need for continued exploration of energy-efficient computing methodologies.

Glutamate transporter-1 (GLT-1) dynamics are implicated in excitotoxicity and Alzheimer's disease (AD) progression. Early stages of AD are often marked by hyperactivity and increased epileptiform activity preceding cognitive decline. Previously, we identified a direct interaction between GLT-1 and Presenilin 1 (PS1) in the brain, highlighting GLT-1 as a promising target in AD research. This study reports the significance of this interaction and uncovers a novel role of GLT-1 in modulating amyloid-beta (Aβ) production. Overexpression of GLT-1 in cells reduces the levels of Aβ40 and Aβ42 by decreasing γ-secretase activity pertinent to APP processing and induces a more "open" PS1 conformation, resulting in decreased Aβ42/40 ratio. Inhibition of the GLT-1/PS1 interaction using cell-permeable peptides produced an opposing effect on Aβ, highlighting the pivotal role of this interaction in regulating Aβ levels. These findings emphasize the potential of targeting GLT-1/PS1 interaction as a novel therapeutic strategy for AD.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

The study aimed to explore the correlation among Angiopoietin-1, (Ang-1) and Angiopoietin-2, (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio, (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 COVID-19 adult patients, with 30 hospitalized in intensive care and 30 in ward units and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured, and statistical analysis was performed using IBM SPSS Statistics software, version 29. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU -ICU groups) for the Ang-1 and Ang-2 indexes. The Ang-2/Ang-1 ratio has differed significantly among all individual patient groups. A ROC analysis was conducted to find an optimal threshold for distinguishing (outpatients – non-ICU) and (non-ICU –ICU) groups. It was based on Youden's Index and was 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analysed as indicators for severity in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated more excellent prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies for improved outcomes.

This article explores how Artificial Intelligence (AI) is drastically changing the logistics industry by transforming operations and significantly improving customer satisfaction. Through meticulous analysis of real-life cases and extensive examination of numerical data, this comprehensive research thoroughly investigates the profound impact of AI on supply chain management. The findings clearly reveal the multifaceted role of AI in significantly reducing costs, greatly improving delivery accuracy, and significantly enhancing inventory control. AI is not just an incremental advancement, but rather a revolutionary leap forward for the future logistics industry, firmly paving the way for unparalleled automation, digital transformation, and operational effectiveness.

Pancreatic cancer, one of the deadliest cancers worldwide, necessitates improved therapeutics due to its low survival rate (12% in 5 years) and typically late-stage diagnosis [1]. This malignancy tends to present asymptomatically until advanced stages, leading to high rates of metastasis and limiting surgical options [2]. Genetic mutations in key genes like KRAS, CDKN2A, TP53, and SMAD4 are central to pancreatic cancer pathogenesis, driving uncontrolled cell proliferation and making treatment difficult [3]. Current treatment modalities include surgery, chemotherapy, radiation, and emerging immunotherapies. Surgery, particularly the Whipple procedure, offers the only potential cure but is applicable in just 15-20% of cases due to the late diagnosis [4]. Chemotherapy, though commonly used, offers limited long-term survival benefits [5]. Radiation therapy has seen advancements with techniques like stereotactic body radiation therapy (SBRT), which shows promise in reducing toxicity and improving outcomes [6] . Immunotherapy, particularly mRNA vaccines, has demonstrated potential in prolonging recurrence-free survival (>18 months), especially when combined with traditional therapies (13.4 months with surgical resection alone) [7] . Combinations of different treatments have been found to be effective. The challenge of early pancreatic cancer diagnosis mirrors the difficulty of disease management. Prophylactic immunotherapies, like vaccines, could offer a crucial breakthrough for prevention and recurrence reduction. As pancreatic cancer remains difficult to treat effectively, continued research and development in preventative and therapeutic strategies are essential to improving outcomes.

In an outstanding article published in 2008, Suzuki obtained a nice generalization of the Banach contraction principle from which derived a characterization of metric completeness. Although Suzuki’s theorem has been successfully generalized and extended in several directions and contexts, we here show by means of a simple example that the problem of achieving, in an obvious way, its full extension to the framework of w-distances does not have an emphatic response. Motivated by this fact we introduce the concept of presymmetric w-distance on metric spaces, we give some properties and examples of this new structure and show that it provides a reasonable setting to obtain a real and hardly forced w-distance generalization of Suzuki’s theorem. This is realized in our main result, which is a fixed point theorem that involves presymmetric w-distances and certain contractions of Suzuki-type. We also discuss the relationship between our main result and the well-known w-distance full generalization of the Banach contraction principle, due to Suzuki and Takahashi. Connected to this approach we prove another fixed point result that compare with our main result through some examples. Finally, we state a characterization of metric completeness by using our fixed point results.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) are environmental pollutants with a great persistence, capacity of bioaccumulation, and well known important toxic effects in humans and animals. Incinerators of hazardous, municipal and medical waste, chlorine bleaching of paper pulp, cement plants, and the traffic of motor vehicles are the most frequent emission sources of these compounds. The diet, followed at a great distance by inhalation, is generally the main way of human exposure to PCDD/Fs. Human biomonitoring is of a great importance to prevent potential adverse effects derived from exposure to chemicals such as PCDD/Fs. In relation to this, blood is among the most used biological monitors. In the current review, we have summarized the recent information (2000-2009) published in the scientific literature (databases: Scopus and PubMed) on the concentrations of PCDD/Fs in blood samples of non-occupationally exposed populations, as well as in some groups of occupationally exposed individuals. We have revised a number of studies conducted in various African American, Asian and European countries, and Australia. Unfortunately, the information is quite limited. No data are available for most countries over the world. Based on the results here reviewed –where available- the current health risks for the general populations do not seem to be of concern. Moreover, taking into account the important reductions observed in the levels of PCDD/Fs in foodstuffs, new decreases in the concentrations of PCDD/Fs in blood -and other biological tissues- are very probable in the immediate years.

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of short anthranilamide-based peptidomimetic compounds 1-17 against two viruses: Murine Hepatitis Virus 1 (MHV-1-single stranded RNA virus) which is a surrogate of human coronaviruses and Herpes Simplex Virus 1 (HSV-1-double stranded DNA virus). The half-maximal inhibitory concentration (IC50) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds 11 and 14 displayed the most potent inhibitory effect with IC50 values of 2.38μM, and 6.3μM against MHV-1 while compounds 9 and 14 showed IC50 values of 14.8μM and 13μM, against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

The earthquake alert of the early warning systems is based on the delay that the S waves have in reference to the P waves and on the interpretation of the P waves’ specific parameters. One of the most used parameters for estimating the moment magnitude of an earthquake is the characteristic period measured in the first 3 seconds of the appearance of the P wave. The typical method determines the characteristic period in the time domain, based on the velocity wave and the displacement wave. In the present work, we present a method for estimating the frequency of the characteristic period. This method includes zero padding of the P wave sequence, conversion of the extended sequence from the time domain to the frequency domain, the identification of local frequency maxima and the calculation of the weighted average of the frequency based on the identified maxima. Tests conducted on synthetic signals, as well as standard deviation evaluation tests for simultaneous recordings on several stations, reveal better performance to the usual method.

Cell migration crucial contributor to metastasis, a critical process associated with the mortality of cancer patients. The initiation of metastasis is triggered by epithelial-mesenchymal transition (EMT), along with the changes of the expression of EMT marker proteins. Inflammation plays a significant role in carcinogenesis and metastasis. Lipopolysaccharide (LPS), a typical inflammatory agent, promoted the generation of superoxide through the activation of p-Tyr42 RhoA, Rho-dependent kinase 2 (ROCK2) and the phosphorylation of p47phox. In addition, p-Tyr42 RhoA activated phospholipase D1 (PLD1), with PLD1 and phosphatidic acid (PA) being involved in superoxide production. PA also regulated the expression of EMT maker proteins. Consequently, we have identified MHY9 (Miosin IIA, NMIIA) as a PA-binding protein in response to LPS. MYH9 also contributed cell migration and the alteration of the expression of EMT marker proteins. P-Tyr42 RhoA, PLD1 and MYH9 associated to form a complex, which was distributed in both the cytosol and nucleus. In addition, we have found that p-Tyr42 RhoA and PLD1 associated with the ZEB1 promoter. Taken together, we propose that p-Tyr42 RhoA and PLD1, responsible for producing PA, and PA-bound MYH9 are involved in the regulation of ZEB1 expression, thereby promoting cell migration.

Abstract: (1) Background: Surgery is the best curative option for Gastric Cancer (GC). However, morbimortality associated with surgery still a significant problem. Thus, it is essential to determine the preoperative surgical risk, to optimize outcomes in higher risk patients. (2) Methods: Patients who underwent curative gastrectomy between January 2010 and December 2013 were included, obtaining a sample of 131 patients, and the acuity of the scales understudy was evaluated. The predictive power of the scales was evaluated through calibration and discrimination. (3) Results and Conclusions: Regarding mortality, the scales demonstrated good calibration, with POSSUM and P-POSSUM obtaining the best O:E ratio. The scales presented good discrimination, with POSSUM showing the best result. Considering morbidity, the scales showed good calibration and discrimination. POSSUM and P-POSSUM seem to have potential in predicting morbidity and mortality when applied to the studied population, but there is a need for further studies in this area.

Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. In order to facilitate the early management of poorly healing wounds, we developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis in a timely manner. We isolated and then quantitatively examined exosomal miR-21 in wound fluids from normal tissues, acute and chronic wounds. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status.

If an algebra of type $A$ contains a subalgebra which is also an algebra of type $B$, then it is a Smarandache $B$-type $A$-algebra provided the subalgebra of type $B$ contains at least two elements. This generalizes the notion of Smarandache group, where the group of order $\geq 2$ is a subsemigroup of a semigroup. In this paper we investigate a number of such pairings and we deduce a number of conclusions as a consequence.

This study explores the impact and significance of implementing a comprehensive education system for children with special needs. The research aims to understand how inclusive practices influence the academic, social, and emotional development of these students. Using a mixed-methods approach that includes case study analysis, reviews of global education models, and theoretical frameworks, the study identifies key strategies for fostering inclusivity. The findings reveal that inclusive education not only enhances academic performance but also promotes social integration and emotional well-being. The analysis compares inclusive practices with traditional special education models and highlights the advantages of equity-driven, accessible learning environments. The study also addresses the challenges faced, such as inadequate resources and the need for continuous teacher training. Recommendations include policy reforms, increased funding, and the adoption of assistive technologies to support diverse learning needs. The research underscores the importance of a collaborative approach involving educators, parents, policymakers, and the community in creating an education system where every child has the opportunity to thrive.

The Median Based Unit Weibull is a new 2 parameter unit Weibull distribution defined on the unit interval (0,1). Estimation of the parameters using MLE encountered some problems like large variance. Using generalized method of moments (GMMs) and percentile method may ameliorate this condition. This paper introduces GMMs and the percentile methods for estimating the parameters of the new distribution with illustrative real data analysis.

Interspecific competition between mosquito larvae may affects adult vectorial capacity, potentially reducing disease transmission. It also influences population dynamics, cannibalistic and predatory behaviors. However, knowledge of interspecific competition between Ae. aegypti and Anopheles species is limited. The study examined interspecific competition between Ae. aegypti larvae and either An. arabiensis, An. gambiae, or An. funestus on individual fitness in semi-field settings. The experiments involved density combinations of 100:100, 200:0, and 0:200 (Ae. aegypti: Anopheles), reared with and without food, in small habitat (8.5 cm height × 15 cm diameter) with 0.5 litre and medium habitats (15 cm height × 35 cm diameter) with 1 litre of water. The first group received Tetramin® fish food (0.02 g), while the second group was unfed to assess cannibalism and predation. While, interspecific competition affected both genera, Anopheles species experienced greater effect, with reduced survival and delayed development, compared to Ae. aegypti. The mean wing lengths of all species were significantly small in small habitats in mixed population (p &lt; 0.001). The presence of food reduced cannibalism and predation compared to its absence. These interactions have implications for diseases transmission dynamics and can serve as biological indicators to signal the impacts of vector control interventions.

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (DChol.) from consumption of saturated fat (DS), polyunsaturated fat (DP), and cholesterol (DZ): ΔChol. = 1.2(2ΔS − ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.

In this paper, we define and investigate modified p-Leonardo, p-Leonardo-Lucas and p-Leonardo sequences as special cases of the generalized Leonardo sequence. We present Binet's formulas, generating functions, Simson formulas, and the summation formulas for these sequences. Moreover, we give some identities and matrices related with these sequences. Furthermore, we show that there are close relations between modified p-Leonardo, p-Leonardo-Lucas, p-Leonardo numbers and Fibonacci, Lucas numbers.

For evaluating probabilities of arbitrary random events with respect to a given multivariate probability distribution, specific techniques are of great interest. An important two-dimensional high risk limit law is the Gauss-exponential distribution whose probabilities can be dealt with based upon the Gauss-Laplace law. The latter will be considered here as an element of the newly introduced family of (p,q)-spherical distributions. Based upon a suitably defined non-Euclidean arc-length measure on (p,q)-circles we prove geometric and stochastic representations of these distributions and correspondingly distributed random vectors, respectively. These representations allow dealing with the new probability measures similarly like with elliptically contoured distributions and more general homogeneous star-shaped ones. This is demonstrated at hand of a generalization of the Box-Muller simulation method. En passant, we prove an extension of the sector and circle number functions.

Let an odd integer be represented as $\sum \limits_{n > m} 2^n + 2^m - 1$ for $m \geq 1$. To transform $2^m - 1$ according to the Collatz rules, the $3x + 1$ step is applied, resulting in the even integer $2^{m + 1} + 2^m - 2$. This even integer, being exactly once divisible by 2, becomes the next odd integer $2^m + 2^{m - 1} - 1$. This represents the growth phase, as exactly one even step follows an odd step. However, while the overall value of the integer increases, terms with decreasing indices are generated after each odd-even cycle. After $m$ such cycles, a term $2^{m - m}$ (which equals 1) is generated, canceling the negative 1. Additional even steps are then performed until the integer becomes odd again, which occurs when the next smallest index becomes zero. The positive 1 thus obtained is written as $2^1 - 1$. If uninterrupted, the term $2^1 - 1$ has the trivial cycle $2^1 - 1 \rightarrow 2^2 \rightarrow 2^1 \rightarrow 2^1 - 1$. This represents the shrinkage phase, as two even steps follow an odd step. To interrupt the trivial cycle, a sequence such as $2^1 + 2^2 + \cdots$ must be available to combine with $2^1 - 1$ and produce $2^{\mathcal{M}} - 1$. This starts another growth phase that lasts for $\mathcal{M}$ odd-even cycles. Finally, there is an attempt to craft an integer that can escape the shrinkage phase in the Collatz dynamics.

It has been discovered that representing odd integers as modified binary expressions of the form $\sum \limits_{n > m}2^n + 2^m - 1$ for $m \geq 1$ helps in understanding the dynamics of Collatz-type sequences. Starting with the original Collatz sequence $3x + 1$, it is found that when the odd step is applied to an odd integer $\sum \limits_{n > m}2^n + 2^m - 1$, an even integer $3\left(\sum \limits_{n > m}2^{n}\right) + 2^{m + 1} + 2^m - 2$ is obtained, which is exactly once divisible by 2, unless the lowest index reduces to zero. This implies that the sequence alternates between odd and even steps $m$ times. This governs the dynamics of the Collatz-type sequences because the value of $m$ determines the number of times the integer can be divided by 2 in each even step. A shortcut method is developed based on this dynamics that states that the even integer after $m$ odd-even steps are completed is $\left(\left(\frac{3}{2}\right)^m \sum \limits_{n > m}2^n\right) + 3^m - 1$. A shortcut method of this magnitude has never been utilized anywhere. The shortcut method for the modified Collatz sequence $5x + 1$ is also presented.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on the structure similarity. TDP1 is a key enzyme involved in repairing stalled topoisomerase 1 (TOP1)-DNA complexes. Previously we obtained with the CRISPR/Cas9 method HEK293A cells with the homozygous knockout of the Tdp1 gene and used knockout cells as a cellular model for studying the mechanisms of anticancer therapy. In this work we studied for the first time by transcriptomic analysis the effect of Tdp1 gene knockout on genes expression changes in human HEK293A cell line. We received original data that may indicate a role of TDP1 in other process besides repair of DNA-TOP1 complex. The differentially expressed genes (DEGs) analysis revealed that TDP1 could be involved in different processes such as cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, cytokine response, and MAPK pathway signaling.

In this research paper, we implement the theory of the primorial function, to develop the Supremum and Infimum bounds for the sum of (log(p))². There are, however, considerable computational difficulties related to these bounds. Therefore, from a pragmatic point of view, a set of Upper and Lower bounds had been developed to bypass this issue. Despite the increased estimation error, the Upper and Lower bounds are still considered sufficiently accurate, while facilitating an easy and fast computation of the estimate of the sum.

Polyhedral cages (p-cages) describe the geometry of some families of artificial protein cages. We identify the p-cages made out of families of equivalent polygonal faces such that the faces of 1 family has 5 neighbours and P_1 edges, while those of the other family have 6 neighbours and P_2 edges. We restrict ourselves to polyhedral cages where the holes are adjacent to at most 4 faces. We characterise all the p-cages with a deformation of the faces, compared to regular polygons, not exceeding 10%.

Mevcut çalışmada, (p, q)−tam sayıya dayalı iki boyutlu Chlodovsky tipi Bernstein operatörlerini tanıtıyoruz. Yeni operatörümüzün yaklaşıklık özelliklerini Korovkin tipi teorem yardımıyla inceliyoruz. Ayrıca, yerel yaklaşıklık özelliklerini sunuyoruz ve süreklilik modülü ve Lipschitz tipi maksimal fonksiyon vasıtasıyla yakınsama oranlarını belirliyoruz. Ayrıca, bu operatörler için bir Voronovskaja tipi teorem veriyoruz. Ve, bu operatörlerin ağırlıklı yaklaşıklık özelliklerini inceliyoruz ve aynı uzayda yakınsama oranını tahmin ediyoruz. Son olarak, Maple'ın yardımıyla, açıklayıcı grafikler bu operatörlerin belirli fonksiyonlara yakınsama oranlarını göstermektedir. Sistem kontrolü sırasında operatörler tarafından yaklaşıklık hızlarının optimizasyonu, kararlılık ve performansta önemli iyileştirmeler sağlar. Sonuç olarak, dinamik sistemlerin kontrolü ve modellenmesi yenilikçi yöntemlerle daha verimli ve etkili hale gelir. Kesirli diferansiyel denklemlerin modellenmesi ve kontrol teorisi alanındaki bu gelişmeler, hem modelleme hem de optimizasyon süreçlerine önemli faydalar sunarak bu alanlardaki uygulama yelpazesini genişletmektedir.

In our previous study of 291 cancer patients, we showed that 20% did not respond to two doses of COVID-19 vaccine administered six weeks apart. Here we investigated if psychological factors (distress, anxiety and depressive symptoms) affected antibody response and markers of vaccine activation (D-dimer) after 6 months from initial vaccination. Overall, 31 subjects (14.2%) had no antibody response at 6 months. Our analysis revealed significant predictors of vaccine failure, including stage of metastatic disease and high stress levels (OR=2.46, 95% CI, 1.05-5.77, p=0.04). Notably, nonresponders showed twice the prevalence of distress than responders (21% vs. 10%, p=0.04). Longitudinal measurements of IgG levels indicated that participants with high depressive symptoms at baseline maintained lower antibody levels over six months (p=0.003). In addition, women with high anxiety showed reduced levels of D-dimer at 6 month time (p=0.03). The data also showed that smokers and former smokers had significantly lower antibody levels than their nonsmoking counterparts (p=0.0004). At baseline, the high discomfort rate (≥5) was 34.4% in women and 23.8% in men; only men experienced an increase in median discomfort during the observation period. Moreover, higher educational level was related to increased distress among women (p=0.046). These findings underscore a critical association between elevated psychological distress and reduced immune responses to the COVID-19 vaccine, emphasizing the urgent need for targeted psychological and behavioral support within this vulnerable population.

CO₂-soluble surfactant foam systems have garnered significant attention in the fields of enhanced oil and gas recovery, environmental protection, and greenhouse gas emission reduction. This review provides a comprehensive explanation of the basic theory of CO₂-soluble surfactant foam, the mechanism of enhanced oil recovery, and the classification and application of various CO₂-soluble surfactants.The mechanism of enhanced oil recovery by CO₂-soluble surfactant foam involves the effective reduction of CO₂ fluidity, the decrease in oil-air flow ratio, and the stabilization of the displacement front. Foam plays a vital role in mitigating the issues of channeling and gravity separation often caused by simple CO₂ injection. The reduction in gas fluidity can be attributed to the increase in apparent viscosity and trapped gas fraction.Future research should prioritize the development of more efficient and environmentally-friendly CO₂-soluble surfactants. It is essential to further explore the advantages and challenges associated with their practical applications in order to maximize their potential impact.

Objectives: Cardiogenic shock [CS] is associated with a high-mortality. Suitable patients maybe successfully bridged using newer intravascular micro-axial left-ventricular assist devices [M-LVAD] for recovery or determination of definitive therapy. Methods: Between January-2020 and July-2024, 107 patients underwent placement of M-LVAD for CS. The cohort was divided into 4 groups based on their destination; group-1: 34 patients [32%] receiving transplant; group-2: 25 patients [23%] receiving durable LVAD; group-3: 42 patients [39%] bridging from post-cardiotomy CS [PCCS]; and group-4: 6 patients [5.6%] bridging decision/recovery [these were excluded from analysis]. Multivariable logistic-regression [MLR] and Cox-regression [MCR] models identified predictors of early-hospital and late mortality, with data reported as odds ratios [ORs], and hazard ratios [HRs], respectively. P<0.05 was statistically significant. Results: Complications included device-malfunction [n=6, 6%], gastrointestinal bleed [n=9, 9%], stroke [n=11, 11%]; long-term hemodialysis [n=21, 21%]. Early-hospital mortality included 13 patients [13%]: 2 in group-1, 1 in group-2 and 10 in group-3 [p=0.02]. In the MLR model, the category of cardiogenic shock requiring M-LVAD placement was statistically significant [OR=4.7 (0.9-24), P=0.05]. Patients were followed for up to 4.5-years, and 23 deaths occurred; group-1: 3 patients, group-2: 5 patients, and group-3: 15 patients [p=0.019]. At 4.5-years, actuarial survival was 90.7±5.1% in group-1, 79.2±8.3% in group-2, and 62.8%±7.7% in group-3 [P=0.01]. In the MCR model, M-LVAD category [HR=3.63 (1.03-12.9) P=0.04], and long-term postoperative dialysis [HR=3.9 (1.6-9) P=0.002], emerged as statistically significant predictors of long-term mortality. Conclusions: In cardiogenic shock, our mid-term outcomes demonstrate good survival with M-LVADs as bridge to transplant and durable LVAD, and reasonable survival as bridge to recovery following cardiotomy, reduced ECMO usage and early ambulation/rehabilitation.

Antimalarial drug resistance has become a real public health problem despite WHO measures. New sequencing technologies make it possible to investigate genomic variations associated with resistant phenotypes at the genome-wide scale. Based on the use of hemisynthetic nanopores, the PromethION technology from Oxford Nanopore Technologies can produce long-read sequences, in contrast to previous short-read technologies used as gold-standard to sequence Plasmodium. Two clones of P.falciparum (Pf3D7 and PfW2) were sequenced in long-read using the PromethION sequencer from Oxford Nanopore Technologies without genomic amplification. This made it possible to create a processing analysis pipeline for human Plasmodium with ONT Fastq only. De novo assembly revealed N50 lengths of 18,488 kb and 17,502 kb for the Pf3D7 and PfW2, respectively. The genome size was estimated at 23,235,407 base pairs for the Pf3D7 clone and 21,712,038 base pairs for the PfW2 clone. The average genome coverage depth was estimated at 787X and 653X for the Pf3D7 and PfW2 clones, respectively. This study proposes an assembly processing pipeline for the human Plasmodium genome using software’s adapted to large ONT data and the high AT percentage of Plasmodium. This search provides all the parameters, which have been optimized, for use with the software selected in the pipeline.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Brazil, Russia, China, India, and the Republic of South Africa (BRICS) represent developing economies facing different energy and economic development challenges. The current study aims to forecast energy consumption in BRICS at aggregate and disaggregate levels using the annual time series data set from 1992 to 2019 and to compare results obtained from a set of models. The time-series data are from the British Petroleum (BP-2019) Statistical Review of World Energy. The forecasting methodology bases on a novel Fractional-order Grey Model (FGM) with different order parameters. This study contributes to the literature by comparing the forecasting accuracy and the forecasting ability of the FGM(1,1) with traditional ones, like standard GM(1,1) and ARIMA(1,1,1) models. Also, it illustrates the view of BRICS's nexus of energy consumption at aggregate and disaggregates levels using the latest available data set, which will provide a reliable and broader perspective. The Diebold-Mariano test results confirmed the equal predictive ability of FGM(1,1) for a specific range of order parameters and the ARIMA(1,1,1) model and the usefulness of both approaches for energy consumption efficient forecasting.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

This study aims to explore methods for automating the replication of correlated portfolios across shares using various algorithms. The goal is to select one algorithm for implementation in a visualization tool that will facilitate portfolio building. The dynamics of the stock market provide a comprehensive view of the global economy, acting as a catalyst for stakeholders to participate and benefit various sectors financially, primarily through investments in companies that yield returns and contribute to the economy. The evaluation and comparison of these algorithms are crucial for making well-informed decisions regarding the core objectives of the study. Ultimately, a determination will be made as to whether the program can effectively analyse data from Yahoo finance to provide a quick overview of the financial market state of companies in the S&P 500 US stock prices.

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, leading to neuroinflammation. The bacteria destroy periodontal tissue through its virulence factors which are retained in the bacteria’s outer membrane vesicles (OMV). The purpose of this study was to determine the real time effect of intraperitoneal in-jection of P. gingivalis OMV on the production and expression of inflammatory markers as well as histopathological changes in the central nervous system (CNS) of adult zebrafish. Fol-lowing the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMV and control group with normal saline at 7 different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 minutes while IL-1β and IL-6 were expressed at subsequent 12- and 24-hours. respectively. Histopatho-logical changes such as blood coagulation, astrocytosis, oedema, spongiosis, and necrosis were also observed between 6- and 24-hours. The two apoptotic enzymes, caspases 3 and 9 were not expressed at any time point. In summary, the OMV induced neuroinflammatory responses and histopathological changes in adult zebrafish were time point dependent

Aluminum (Al) toxicity and low phosphorus availability (LP) are the top two co-existing edaphic constraints limiting agriculture productivity in acid soils. Plants have evolved versatile mechanisms to cope with the two stresses alone or simultaneously. However, the specific and common molecular mechanisms, especially those on flavonoids and carbohydrate metabolism, are still unclear. Laboratory studies were conducted on two wheat genotypes, Fielder (Al-tolerant and P-efficient) and Ardito (Al-sensitive and P-inefficient), exposed to 50 μM Al and 2 μM Pi (LP) in hydroponic solutions. After 4 days of stress, wheat roots were analyzed via transcriptomic and targeted metabolomic techniques. A total of 2296 differentially expressed genes (DEGs, 1535 up and 761 down) under Al and 3029 DEGs (1591 up and 1438 down) under LP were identified in Fielder. Similarly, 4404 DEGs (3191 up and 1213 down) under Al and 1430 DEGs (1176 up and 254 down) under LP were identified in Ardito. The GO annotation analysis results that 4079 DEGs annotated to the metabolic processes term. These DEGs were significantly enriched in the phenylpropanoid, flavonoid, flavone and flavonol biosynthesis, and carbohydrate metabolism pathways by performing the KEGG enrichment analysis. The targeted metabolome analysis detected 19 flavonoids and 15 carbohydrate components in Fielder and Ardito under Al and LP. More responsive genes and metabolites were involved in flavonoid metabolism under LP than Al in the Fielder, while an opposite trend in the Ardito. In the carbohydrate metabolism pathway, the genes and metabolites were higher in Fielder than in Ardito. The combined transcriptome and metabolome analysis revealed that the flavonoid and carbohydrate genes and metabolites differed between Fielder and Ardito under Al and LP, which may be an important reason for Fielder’s high Al and LP resistance. The results of this study lay a foundation for pyramiding genes and breeding multi-resistance varieties.

Flexible capacity applications demands to large energy storage density and high breakdown electric field strength of flexible films. Here, P(VDF-HFP) with ultra-thin Al2O3 nanosheets composite films were designed and fabricated through an electrospinning process followed by hot-pressing in sandwich structured. The results show that the insulating ultra-thin Al2O3 nanosheets and the sandwich structure can enhance the composites' breakdown field (by 24.8%) and energy density (by 30.6%) remarkedly to P(VDF-HFP) polymer matrix. An energy density of 23.5 J/cm3 at the ultrahigh breakdown field of 740kV/mm can be therefore realized. Insulating test and phase-field simulation results reveal that ultra-thin nanosheets insulating buffer layers can reduce the leakage current in composites, thus it effects the electric field spatial distribution to enhance breakdown strength. Our research provides a feasible method to increase the breakdown strength of ferroelectric polymers, which is comparable to those of non-ferroelectric polymers.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of some cellular tissues, and is expressed through the VDR gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of single nucleotide polymorphism (SNP) BsmI of the vitamin D receptor (VDR) gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. Individuals were invited to participate and, after signing the informed consent form, answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p&lt;0.05. Results: 98 individuals with vitamin D ≤20 ng/dL were evaluated, and the SNP BsmI of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: SNP Bsm I of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

The multidrug efflux transporter ABCB1 is clinically important for drug absorption and distribution and can be a determinant of chemotherapy failure. Recent structure data shows that three glutamines donate hydrogen bonds to co-ordinate taxol in the drug binding pocket. This is consistent with earlier drug structure-activity relationships that implicated the importance of hydrogen bonds in drug recognition by ABCB1. By replacing the glutamines with alanines we have tested whether any or all of Q347, Q725 and Q990 are important for the transport of three different drug classes. Flow cytometric transport assays show that Q347A and Q990A act synergistically to reduce transport of Calcein-AM, BODIPY-verapamil and OREGON GREEN-taxol bisacetate but the magnitude of the effect was dependent on the test drug and no combination of mutations completely abrogated function. Surprisingly, Q725A mutants generally improved transport of Calcein-AM and BODIPY-verapamil, suggesting that engagement of the wild-type Q725 in a hydrogen bond is inhibitory for the transport mechanism. To test transport of unmodified taxol, stable expression of Q347/725A and the triple mutant was engineered and shown to confer equivalent resistance to the drug as the wild-type transporter, further indicating that none of these potential hydrogen bonds between transporter and transport substrate are critical for function of ABCB1. The implications of the data for plasticity of the drug binding pocket are discussed.

During their complex life cycles, the Apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii employ several genetic switches to regulate their gene expression. One such switch is mediated at the level of translation through upstream Open Reading Frames (uORFs). As uORFs are found in the upstream regions of a majority of genes in both the parasites, it is essential that their roles in translational regulation be appreciated to a greater extent. This review provides a comprehensive summary of studies that show uORF-mediated gene regulation in these parasites and highlights examples of clinically and physiologically relevant proteins that exhibit uORF-mediated regulation. In addition to these examples, several studies that use bioinformatics, transcriptomics, proteomics, and ribosome profiling also indicate the possibility of widespread translational regulation by uORFs. Further analysis of genome-wide datasets will reveal novel genes involved in key biological pathways such as cell-cycle progression, stress-response, and pathogenicity. The cumulative evidence from studies presented in this review suggests that uORFs will play crucial roles in regulating gene expression during clinical disease caused by these important human pathogens.

It was once thought that high QoS (Quality of Service) performance solves recurrent problems of low-quality multimedia services. Since then, solutions have been proposed to ensure a high level of QoE (Quality of Experience). In this document, the authors attempt to outline their understanding of an accurate meaning of quality of multimedia services. Starting from QoS and passing through generalised QoE, the authors focus on aspects of subjective and objective quality modelling and optimisation of visual performance for TRV (Target Recognition Video) applications (such as video surveillance), outlining the path of ITU-T standardisation in this area. The authors revised the ITU-T Recommendation P.912 to reflect improved subjective test techniques developed since this Recommendation was approved. The authors also attempt to predict at least some existing errors of reasoning, which are likely to become evident for the industry in the next decade.

Prediction and early detection of atrial fibrillation (AF) remain a permanent challenge in everyday practice. Timely identification of an increased risk for AF episodes (which are frequently asymptomatic) is essential in the primary and secondary prevention of cardioembolic events. One of the noninvasive modalities of AF prediction is represented by the electrocardiographic P-wave analysis. This includes the study and diagnosis of interatrial conduction block (Bachmann`s bundle block). Bayés’ Syndrome (named after its first descriptor) denotes the association between interatrial conduction defect and supraventricular arrhythmias (mainly AF) predisposing to cardioembolic events. Our short review presents an update of the most important data concerning this syndrome: brief history, main ECG features, pathophysiological background and clinical implications.

SARS-CoV-2 infections underlie the current Coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium (Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. Mortality risk from severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples (n=166) from COVID-19 patients (n=33) were collected consecutively and analysed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (r=0.7758, p<0.001), pointing to an insufficient Se status for optimal selenoprotein expression. In comparison to reference data from a European cross sectional analysis (EPIC, n=1915), the patients showed a pronounced deficit in total serum Se (mean±SD, 50.8±15.7 vs. 84.4±23.4 µg/L) and SELENOP (3.0±1.4 vs. 4.3±1.0 mg/L). A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared to non-survivors (Se; 53.3±16.2 vs. 40.8±8.1 µg/L, SELENOP; 3.3±1.3 vs. 2.1±0.9 mg/L). We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion on a relevant role of Se for COVID convalescence, and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Possibilities of utilization of two frequencies synthetic aperture radar (SAR) operating simultaneously in P-band and S or L-band are considered. Advantages of such system are shown. They are caused by improvement of data interpretation and by decrease of ionosphere influence. Tasks of surface and subsurface sensing by the complex SAR were under investigation for vegetation, soil covers are given. As an example, the investigation results of coniferous forest areas backscattering by the spaceborne P-band SAR together with L-band SAR in the September-February period are presented. Studies have shown that the joint use of the results in L and P bands offer unique opportunities to explore the effects of changes in the backscattering properties of forest surfaces.

In winter 2008-2009, Lake Occhito, a strategic multiple-uses reservoir in South Italy, was affected by an extraordinary Planktothrix rubescens bloom. P. rubescens is a filamentous potentially toxic cyanobacterium which has recently colonized many environments in Europe. A number of studies is currently available on the use of remote sensing techniques to monitor different fresh water cyanobacteria species. By contrast no specific applications are available on the remote sensing monitoring of P. rubescens. In this paper we present a specific algorithm, based on Water Leaving Reflectances (WLR) from MERIS data, atmospherically corrected using the Aerosol Optical Thickness (AOT) retrieved by MODIS data, to detect P. rubescens blooms. The high accuracy in AOT data, provided by MOD09 surface reflectance product, at 1km spatial resolution, allowed obtaining a good correlation between the WLR and the P. rubescens chlorophyll-a concentrations measured in the field, through multiple stations fluorometric profiles. A modified Normalized Difference Chlorophyll index (NDCI) algorithm is presented. The performance of the proposed algorithm has been successfully compared with other specific algorithms for turbid productive waters. We demonstrated how important is to verify the spectral behaviour of bio-optical parameters in order to develop an ad hoc algorithm that better performs with respect to standard algorithms.

In this paper, we establish some inequalities bounding the ratio Г_p,k(x)/Г_p,k(y), where Г_p,k(.) is the (p,k)-analogue of the Gamma function. Consequently, some previous results are recovered from the obtained results.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Backround: Thoracic trauma causes life-threatening organ injuries, ranging from simple abrasions to contusions of intrathoracic organs. In this study, we aimed to investigate the effects of bosentan on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB) and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Methods: Thirty-seven animals male Sprague-Dawley rats were divided into 5 groups. All 4 groups, except for the control group, were performed to PC. In the first group, C: control group (n=6) consisted of unprocessed and untreated. The second group, PC3 (n=8) underwent of 3 days PC performed. The third group, PC-B3 (n=8) received 100 mg/kg bosentan was given orally once a day for 3 days. The fourth group, PC7 group (n=7) underwent of 7 days PC performed, and the fifth group PC-B7 (n=8) received 100 mg/kg bosentan was given orally once a day for 7 days. While ET-1, NF-B, TNF-, and HIF-1 was measured by ELISA method, TAC and PAB by spectrophotometric in lung tissue samples. Results: ET-1, NF-B, TNF-, HIF-1, and PAB levels were higher, while TAC activities were lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-- levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05) while NF-B, HIF-1, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan treatment causes decreased ET-1, NF-B, TNF-, HIF-1, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: We found that the use of bosentan decreased the severity of oxidative stress in the lung and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, oxidative stress in some diseases that may be accompanied by ischemia.

Transcriptome assembly and functional annotation are essential for understanding gene expression and biological function. Nevertheless, many existing tools lack the flexibility to integrate both short- and long-read sequencing data or fail to provide a complete, customizable workflow for transcriptome analysis. Here, we present TrAnnoScope, a comprehensive transcriptome analysis pipeline that provides a complete, customizable workflow capable of efficiently processing and integrating short- and long-read sequencing data to generate high-quality, full-length transcripts with detailed functional annotation. The pipeline encompasses steps from quality control to functional annotation, employing a range of tools and established databases, such as SwissProt, Pfam, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes. As a case study, TrAnnoScope was applied to RNA-Seq data from zebra finch brain, ovary, and testis tissues. TrAnnoScope produced comprehensive transcriptome, demonstrating strong alignment with the reference genome (99.63%) and capturing a significant proportion of nearly complete protein sequences (92.7%). The functional annotation process yielded extensive matches to known protein databases and successfully assigned relevant functional terms to majority of the transcripts. As such, TrAnnoScope successfully integrates multiple sequencing technologies to generate comprehensive transcriptomes with minimal user input. Its modular design, flexibility, and ease of use make it a valuable tool for researchers working with complex datasets, particularly for non-model organisms.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

We prove the continuous non-Archimedean (resp. p-adic) Banach space and Hilbert space versions of non-Archimedean (resp. p-adic) Welch bounds proved by M. Krishna. We formulate continuous non-Archimedean and p-adic functional Zauner conjectures.

We prove the non-Archimedean (resp. p-adic) Banach space version of non-Archimedean (resp. p-adic) Welch bounds recently obtained by M. Krishna. More precisely, we prove following results. \begin{enumerate}[\upshape(i)] \item Let $\mathbb{K}$ be a non-Archimedean (complete) valued field satisfying $\left|\sum_{j=1}^{n}\lambda_j^2\right|=\max_{1\leq j \leq n}|\lambda_j|^2$ for all $ \lambda_j \in \mathbb{K}, 1\leq j \leq n$, for all $n \in \mathbb{N}.$ Let $\mathcal{X}$ be a $d$-dimensional non-Archimedean Banach space over $\mathbb{K}$. If $\{\tau_j\}_{j=1}^n$ is any collection in $\mathcal{X}$ and $\{f_j\}_{j=1}^n$ is any collection in $\mathcal{X}^*$ (dual of $\mathcal{X}$) satisfying $f_j(\tau_j) =1$ for all $1\leq j \leq n$ and the operator $S_{f, \tau} : \text{Sym}^m(\mathcal{X})\ni x \mapsto \sum_{j=1}^nf_j^{\otimes m}(x)\tau_j^{\otimes m} \in \text{Sym}^m(\mathcal{X})$, is diagonalizable, then \begin{align}\label{NONFUNCTIONALWELCH} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |f_j(\tau_k)f_k(\tau_j)|^{m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{NONFUNCTIONALWELCH}) as non-Archimedean functional Welch bounds. \item For a prime $p$, let $\mathbb{Q}_p$ be the p-adic number field. Let $\mathcal{X}$ be a $d$-dimensional p-adic Banach space over $\mathbb{Q}_p$. If $\{\tau_j\}_{j=1}^n$ is any collection in $\mathcal{X}$ and $\{f_j\}_{j=1}^n$ is any collection in $\mathcal{X}^*$ (dual of $\mathcal{X}$) satisfying $f_j(\tau_j) =1$ for all $1\leq j \leq n$ and there exists $b \in \mathbb{Q}_p$ such that $ \sum_{j=1}^{n}f_j^{\otimes m}(x) \tau_j^{\otimes m} =bx$ for all $ x \in \text{Sym}^m(\mathcal{X}),$ then \begin{align}\label{PADICFUNCTIONALWELCH} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |f_j(\tau_k)f_k(\tau_j)|^{m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{PADICFUNCTIONALWELCH}) as p-adic functional Welch bounds. \end{enumerate} We formulate non-Archimedean functional and p-adic functional Zauner conjectures.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

Since cART was introduced to treat AIDS, the mortality rate due to AIDS has markedly decreased and the convalescence of HIV-infected individuals has improved drastically. However, HIV-1 sexual transmission has made HIV become a global epidemic. Sacran is a megamolecular poly-saccharide extracted from cyanobacterium Aphanothece sacrum that exhibits numerous desirable characteristics for transdermic applications, such as safety as a biomaterial, a high moisture re-tention effect, the ability to form a film and hydrogel, and an anti-inflammatory effect. In this study, we evaluated the anti-HIV-1 effects of Sacran as a barrier to HIV transmission. Sacran inhibited HIV-1 infection and envelope-dependent cell-to-cell fusion. Moreover, we used a Transwell assay to confirm that sacran inhibited viral diffusion and captured viruses. The synergistic effects of sacran and other anti-HIV infection drugs were also evaluated.HIV-1 infections can be reduced through the synergistic effects of sacran and anti-HIV-1 drugs. Our study suggests the use of sacran gel to protect against HIV-1 transmission.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

The main objective of the present study is to demonstrate the possibility of actively influencing the position of the bow shock wave and the main parameters of supersonic flow over a blunt body by organizing a gas discharge near the front surface, in the region between the body and the bow shock wave. The research is carried out using both experimental and numerical methods. The working gas was xenon. It is shown that the steady bow shock wave stand-off distance along with the current and power of the discharge, is associated with the change in the adiabatic index of the plasma created by the discharge, which, in turn, is determined by the plasma parameters, such as the degrees of nonequilibrium and the degree of ionization. It is shown that the adiabatic index with the power supplied to the impact zone in the range of 30-120 kW can both increase and de-crease in the range of 1.25-1.288. The study of the discharge created plasma zone was conducted and the correspondence between the discharge current and power, and the average parameters in the plasma zone created by the discharge is presented. A good agreement between the numerical and experimental data was shown. The results may be useful in developing control systems for high-speed civil aircrafts.

The introduction provides an overview of beginning the development of a plastic design of metal thin-walled cross-sections. This large study investigates in detail together 14 steel and four extruded aluminium cross-sections. Six groups of various shaped cross-sections that consist of: four I-shaped doubly symmetric sections (two I-sections, one I-section with lips, one H-section); three monosymmetric sections with axis of symmetry z (monosymmetric I-section, T-section, diamond section); four monosymmetric sections with axis of symmetry y (two channels, channel with inside lips, channel with outside lips); two point symmetric sections (Z-section with and without lips); four asymmetric sections (L-profile, sigma section, two closed sections: oblique and irregular sections; non-warping sections along midline, but with negligible warping along the element's thicknesses: Tsection and L-profile are included in the above groups. Four extruded aluminium cross-sections are: I 200a section, diamond section and closed oblique and irregular sections. For all 18 cross-sections, the plastic section moduli of three kinds were calculated: Wpl,y,nB, Wpl,z,nB for bimoment not considered to be constraint; Wpl,y, Wpl,z, Wpl,wfor bimoment considered to be restraint; maximum values Wpl,y,max, Wpl,z,max, Wpl,w,max. The values of cross-section plastic resistances Npl, Mpl,y,Rd, Mpl,z,Rd and Bpl are also calculated in numerical examples. The values of cross-section properties are calculated in different ways to verify the correctness of the results. The following ways of calculations are used: the rules in Eurocode EN 1993-1-1: 2022; own MathCad programmes; own software. Recommendations for educational institutes and designers in practice are provided, including simple formulae for all the cross-sectional properties for the doubly and monosymmetric I-shaped sections, channels and Z-sections. Formulae are presented in six tables containing formulae in the dimensionless form, which are useful for parametrical studies and formulae for direct designs. The background of the Eurocode rules in EN 1993-1-1: 2022 is explained together with recommendations about how to avoid problems with using them.

Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Here, we used the rhesus macaque (RM) model to characterize the immunopathogenic impact of Plasmodium fragile co-infection during antiretroviral therapy (ART)-treated simian immunodeficiency virus (SIV)-infection. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VL) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines linked with neutrophil function, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in neutrophil functionality during co-infection. Finally, we characterized levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these data indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.

Opuntia ficus-indica has always interacted with many phytophagous insects at its center of origin; two of them are Dactylopius coccus and D. opuntiae. D. coccus, or true cochineal, is produced to extract carminic acid, and D. opuntiae or wild cochineal is a key invasive pest of O. ficus-indica in more than 20 countries around the world. Despite the economic and environmental relevance of this cactus and, D. opuntiae and D. coccus, there are few studies that have explored volatile organic compounds (VOCs) derived from the plant-insect interaction. The aim of this work was to determine VOCs of D. coccus and D. opuntiae feeding on cultivars suitable for their development and to identify different VOCs in cladodes infested by each Dactylopius species. Volatiles were identified through their essential oils, which were obtained by hydrodistillation. A total of 66 VOCs from both Dactylopius species were identified, and 125 from the Esmeralda and Rojo Pelón cultivars infested by D. coccus and D. opuntiae, respectively, were determined. Differential VOCs production due to infestation by each Dactylopius species was also found. Some changes in methyl salicylate, terpenes such as linalool or the alcohol p-vinylguaiacol were related to Dactylopius feeding on cladodes of their respective cultivars. Changes in these VOCs and their probable role in plant defense mechanisms should receive more attention because this knowledge could improve D. coccus rearing, or to its inclusion in breeding programs for D. opuntiae control in regions where it is a key pest of O. ficus-indica.

In the recent past, the number of invasive species around the world has increased significantly due to increased globalization and climate change. Understanding biological invasions under climate change is crucial for sustainable conservation of biodiversity. The insect pest Pseudococcus viburni (Signoret) can cause damages to plants, resulting in leaf yellowing, leaf defoliation, and reduced plant growth. A serious attack by this insect post can even lead to the entire plant withering and dying, bringing huge economic and ecological losses. Despite these damages, the potential distribution range and management strategies for this insect pest are poorly understood. Based on historical distribution data and environmental factors, the present study predicted the potentially suitable areas for P. viburni spread under different climate change scenarios using MaxEnt (maximum entropy). The results showed that precipitation of the coldest quarter (Bio19), precipitation seasonality (Bio15), and mean temperature of the wettest quarter (Bio8) were the most important environmental factors determining the distribution of P. viburni. Under the current climate conditions, its potential suitable areas are southern China, the whole of Japan, North America (especially the eastern part of the United States), the southwestern part of South America, the Mediterranean coast and most of Europe, the central part of Africa i.e., the south of the Sahara Desert and most of the southern coast of Australia. The total area of habitats suitable for this insect pest is predicted to be increased in the future. In order to prevent P. viburni transmission and spread, there is a need to strengthen the monitoring and quarantine measures against this pest at the Southern ports.

Lignin, and its by-products in the effluent of most agrochemical-based industries like pulp and paper, increase environmental pollution. There is, therefore, an increasing demand to degrade lignin and its derivatives using bacteria-produced ligninolytic enzymes. This study focused on optimizing growth and lignin peroxidase production of ligninolytic potential bacterial strains (E. coli accession no: LR0250096.1 and P. aeruginosa accession no: CP031449.2) for the first time. A submerged fermentation process was used to simultaneously optimize growth and crude lignin peroxidase production using kraft lignin as the substrate. The E. coli and P. aeruginosa were separately cultured under different pH, temperature, lignin (substrate) concentration and incubation periods. It was observed that the enzyme production was growth dependent. The optimum conditions for E. coli were pH 7.5, temperature 30 °C and lignin concentration 1 g/L. For P. aeruginosa the best conditions were pH 6.5, temperature 40 °C and lignin concentration 1 g/L. The enzyme production peaked after 7 days of incubation for both organisms were 21.53 ± 3.11 mg/ml and 18.13 ± 2.1 mg/ml respectively. It is apparent that both E. coli (LR0250096.1) and P. aeruginosa (CP031449.2) are mesophiles bacteria. E. coli function best in alkaline pH while P. aeruginosa prefers a slightly acidic environment. Hence, they are promising candidates in the reduction of lignocellulosic wastes.

The development of good conductivity p-type β-Ga2O3 is critical to realize its devices and applications. The nitrogen-doped p-type β-Ga2O3 films with enhanced conductivity characteristics were prepared through the thermal oxidation of GaN in the N2O atmosphere. Further measurements were performed on the oxidized films at 1000, 1050, and 1100 °C to have insight into the underlying mechanism of the thermally activated transformation process. The room temperature photoluminescence (PL) spectra demonstrated a moderate ultraviolet emission peak at 246 nm, confirming the generation of gallium oxide with a band gap of ~5.0 eV. The normalized X-ray diffraction (XRD), the high-resolution transmission electron microscopy (HRTEM), and the selected area electron diffraction (SAED) patterns were used to confirm the characteristic of polycrystalline and anisotropic growth. Then, the effects of the oxidation temperature on the amount of incorporated nitrogen were analyzed using secondary ion mass spectrometry (SIMS). Moreover, the ionization energy of the acceptor of films oxidized at 1000, 1050, and 1100 °C was calculated and analyzed using the temperature-dependent Hall test results. The results showed that nitrogen doping was the main contributor to p-type electrical properties. The activation energy of the polycrystalline β-Ga2O3 prepared through thermal oxidation of GaN in the N2O atmosphere was estimated to be 147.175 kJ·mol-1 using the Arrhenius plot, which was considerably lower than that of both dry and wet oxidations of GaN in O2 ambient, thus confirming the efficiency of thermal oxidation of GaN in N2O.

The Mediterranean region offers good weather conditions for outdoor pig production (OPP), which is considered more environmentally friendly than intensive indoor production. However, the continuous input of food and pigs' excreta increases the soil organic matter (SOM) and phosphorus (P), increasing the risk of waterbodies eutrophication. This work aimed at evaluating in OPP areas soil P dynamics and the role of SOM on P sorption and P release. The experiment was done for two years, at an area of 2.8 ha with an animal charge of 9 adults ha-1. Georeferenced soil samples were taken at 0.20 m depth, and a soil P sorption experiment was carried out. At the end of the experiment, for the background value, the levels of SOM increased between 85–376%, and Olsen P values ranged between -82–884%. SOM levels above 2% caused a decrease in the binding energy of P sorption according to the linear model b=-15.541SOM+115.20 (p <0.01) as well as a decrease of the soil P sorption capacity Qmax=-41.272SOM+298.37 (p <0.01). To avoid the accumulation of SOM and P preventing hotspots for waterbodies eutrophication, an adequate animal charge together with soil cultivation for pig grazing can be a cost-effective practice.

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeted resistance to β-lactams including carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones.

Adsorption is an effective strategy for the removal of pollutants from the wastewater. Herein, a 2-hydroxyterephthalic acid (HTC) modified hypercrosslinked polymer (HTC-HCP) is successfully synthesized via Friedel-Crafts reactions, and used as an adsorbent for the different types of pollutants including organic contaminants and heavy metal ions from wastewater. Excellent adsorption capacities are observed for amines (aniline, p-methylaniline (p-MA), p-chloroaniline (p-CA), and p-aminobenzoic acid (p-ABA)), phenols (phenol, p-chlorophenol (4-CP) Bisphenol A (BPA), 1-Naphthol (1-NP)), dyes (rhodamine B (RhB) and methyl orange (MO)), and metal ions (Pb2+, Hg2+, and Cd2+). The resulting polymers exhibited excellent adsorption performance towards these pollutants. Especially, the removal rate of aniline is above 95% in the concentration of 2.5 mg/L in 40 min at 25 °C. The interaction mechanism has been investigated, and confirmed by FTIR and the theoretical calculation results. It is due to surface complexation and chemisorption between adsorbent and adsorbate. The polymer exhibits good performance such as high adsorption capacity, high separation efficiency, biodegradable properties, and easy regeneration, suggesting that its potential technological applications for the removal of organic compounds and heavy metal ions from actual industrial effluent.

In these times electricity is big trouble of problem facing by the world. Therefore, there is necessitating for the property basis of energy that is employed for as bio-electricity. Many of the scientists and researchers are trying to find out the sustainable energy generates with the help of plant microbial fuel cell. Plant microbial fuel cell (P-MFCs) could be feasibility technology approach of bio-electricity generation which is mutualism interaction of the plants along with their rhizospheric bacteria. In the present study, Plant-microbial fuel cell was observed in grass e-table evaluated in term of bioelectricity generation from Cynodon dactylon (Dooba Ghas). This e-table was connected with electrode and different condition (physical and chemical) to detect the change in bioelectric potential. It was found that maximum voltage generated among all the conditions was 4.24 ±2V at 15 days by using Cynodon dactylon through P-MFCs. The potential difference generated through P-MFCs was measured using a multimeter. The generation of bioelectricity was observed under different conditions like exposure to light and shade condition measured for voltage was found to be significantly different parameters. The maximum recorded under light and shade conditions were 3.82 ±2 V and 4.25 ±2 V respectively at 15 days of incubation.

Alterations in root morphology and physiology are important strategies in plants to adapt to low-phosphorus (P) environments. Maize genotypes differed in nitrogen (N) efficiency may also respond differently to low P stress. This study aimed to investigate the responses of root morphological and physiological traits of these two maize cultivars to P deficit and how these traits were linked with the acquisition of soil P. Two maize cultivars, XY335 (N efficient) and ZD958 (N inefficient), were cultivated for 40 days in a calcareous loamy soil amended with (high P) or without (low P) P. Functional root traits were used to evaluate the morphological and physiological responses to low P supply. Two separate short-term experiments determined the correlation between P uptake rate and P supply intensity (hydroponic) or root hair length under two P treatments (rhizobox). Low P status significantly simulated biomass allocation to roots, specific root length and exudations of carboxylates, while decreased root diameter and rhizosphere pH in both maize cultivars. Two cultivars had different total root length and root surface area under low P stress: increased in ZD958 and decreased in XY335. Both genotypes developed longer root hair under P deficit. ZD958 (greater biomass and shoot P content) has a greater capability at accessing soil P than XY335. Rhizosphere exudation of citric acid was significantly higher in ZD958 than in XY335, while there was not significant genotypic difference in rhizosphere pH and exudation of malic acid and acid phosphatase activity. ZD958 had higher P uptake rate than XY335 when solution P was between 12.5 and 250 µM. This study identified ZD958 as a P-efficient genotype, which better adapted to low P stress by altering root physiological traits (exudation of citric acid and P uptake rate), rather than root morphological traits (total root length, root surface area, root hair length). Our results highlight the importance of analyzing root morphological and physiological traits to enhance our understanding of the physiological mechanisms of P acquisition.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Cisplatin-based chemotherapy has long been the standard first-line treatment for metastatic urothelial carcinoma (mUC). However, owing to comorbidities, up to 50% of patients are ineligible for cisplatin, necessitating alternative primary treatment options. Immune checkpoint inhibitors (ICIs) have emerged as a vital alternative for those unable to receive cisplatin. However, the prognosis for advanced urothelial carcinoma remains grim, with challenges persisting in optimizing first-line therapy. Recent advancements have redirected attention towards innovative combinations in primary treatment. The combination of enfortumab vedotin (EV) and pembrolizumab has significantly improved overall and progression-free survival compared to chemotherapy alone. This marks a critical shift in first-line treatment options for patients who are cisplatin-ineligible or require alternatives to standard chemotherapy. While platinum-based chemotherapy continues to be essential for many patients, the approval of EV and pembrolizumab as first-line treatments for cisplatin-ineligible patients signifies a significant breakthrough in primary care. These therapies offer new options and enhance outcomes in terms of survival and response rates, highlighting the increasing relevance of ICI-containing regimens in frontline care. This review provides an exhaustive overview of the current frontline treatment landscape for mUC, incorporating clinical trial evidence and exploring investigational agents to aid in clinical decision-making and guide future therapeutic strategies.

The general-purpose Compact Muon Solenoid (CMS) detector at the Large Hadron Collider (LHC) at CERN studies a production of new particles in the proton-proton collisions at the LHC center of mass energy 13.6 TeV. The detector includes the magnet based on the 6 m diameter superconducting solenoid coil operating with the current of 18.164 kA. This current creates a central magnetic flux density of 3.8 T that allows to measure momenta of the produced in collisions charged particles with tracking and muon subdetectors at a high precision. The CMS magnet contains a 10,000 ton flux-return yoke made of construction steel that bends muons in steel blocks magnetized with the solenoid returned magnetic flux. To reconstruct the muon trajectories, and thus, to measure the muon momenta, the drift tube and cathode strip chambers are located between the layers of the steel blocks and serve for this purpose. To describe the distribution of the magnetic flux in the magnet yoke layers, a three-dimensional computer model of the CMS magnet is used. To prove the calculations, the special measurements are performed with the flux loops wound in 22 cross-sections of the flux-return yoke blocks. The measured voltages induced in the flux loops during the CMS magnet ramp ups and downs, as well as during the superconducting coil fast discharges with the 190 s time constant, are integrated over time to obtain the initial magnetic flux densities in the flux loop cross-sections. The measurements obtained during the seven standard ramp downs of the magnet have been analyzed in 2018. From that time three fast discharges are occurred during the standard ramp downs of the magnet. This allows to single out the contributions of the eddy currents, induced in steel, to the flux loop voltages registered during the fast discharges of the coil. Accounting for these contributions to the flux loop measurements during manually triggered fast discharges in 2006 allows to perform the validation of the CMS magnet computer model with a better precision. The technique of the flux loop measurements, and the obtained results are presented and discussed.

This paper examines the fundamental distinctions and complementary relationships between generative and descriptive methods in research and analysis. Through a systematic review of their applications across various fields, we explore how descriptive methods excel in capturing and characterizing existing phenomena, while generative methods enable the creation of new instances based on learned patterns. The analysis reveals that while these approaches serve different primary purposes, their integration often leads to more robust and comprehensive research outcomes. Our findings suggest that understanding the strengths and limitations of both methodologies is crucial for researchers and practitioners in choosing appropriate approaches for their specific contexts.

Background/Objectives: Post traumatic growth (PTG) has the potential to draw positive consequences from trauma. Hence, the interest of finding ways to promote PTG. Research has identified an attentional bias towards positive resilience-related words (e.g., “persistence”, “purpose”) in university students who report high PTG after experiencing adversities. Although people can respond to these experiences by showing low PTG, this bias seems to help with their struggle by making purposeful contents more accessible. Therefore, boosting attentional bias towards positive resilience-related words could help people with low PTG. Methods: In this study, the participants were thirty-six university students who had experienced bullying before entering university. Using a Stroop emotional task, they identified the color of resilience and neutral words, either positive or negative, before and after being submitted to transcranial direct current stimulation. Stimulation was targeted at the right temporal area involved in intentionality processing. Results: In the anodal condition, the results support a stimulation effect on the resilience attentional bias that could benefit participants with low PTG. A significant moderation of approach motivation for this effect was also found. Specifically, only when participants had medium or high approach motivation, did stimulation boost the attentional bias in students with low PTG. Conclusions: These results support that tDCS stimulation in this brain area is effective in enhancing resilience attentional bias in low PTG students. However, for this effect to occur it is necessary to have approach motivation, which is motivation related to goals.

This paper presents a comprehensive review of the transformative impact of 3D printing technology on smart cities. As cities face rapid urbanization, resource shortages, and environmental degradation, innovative solutions such as additive manufacturing (AM) offer potential pathways for sustainable urban development. By synthesizing 66 publications from 2015 to 2024, the study examines how 3D printing improves urban infrastructure, enhances sustainability, and fosters community engagement in city planning. Key benefits of 3D printing include reducing construction time and material waste, lowering costs, and enabling the creation of scalable, affordable housing solutions. The paper also addresses emerging areas such as the integration of 3D printing with digital twins (DT), machine learning (ML), and AI to optimize urban infrastructure and predictive maintenance. It highlights the use of smart materials and soft robotics for structural health monitoring (SHM), and repairs. Despite the promising advancements, challenges remain in terms of cost, scalability, and the need for interdisciplinary collaboration among engineers, urban planners, and policymakers. The findings suggest a roadmap for future research and practical applications of 3D printing in smart cities, contributing to the ongoing discourse on sustainable and technologically advanced urban development.

This article explores the use of vegetation indices (VIs) in remote sensing for estimating standing wood volume and volume increments in forest ecosystems. The study investigates the correlations between various VIs and wood volume across different forest stand age classes, focusing on the effectiveness of commonly used indices such as Squared Ratio Simple Red Edge (SQSR) and Red-Edge Ratio Vegetation Index (RERVI), as well as other typical indicators including Enhanced Vegetation Index (EVI), Red-Edge EVI (RE-EVI), and Green Normalized Difference Vegetation Index (GNDVI). Additionally, the analysis considers a pair of indicators based on blue and near-infrared channels, resembling the Blue-normalized Difference Vegetation Index (BNDVI). The research reveals that quadratic and power-law models of SQSR and RERVI demonstrate higher correlations (>0.40) with wood volume, especially in younger forest stands (>0.80). Furthermore, the study highlights the potential of NDII and NDWI indices for estimating volume increments in certain classes of forest stands (0.70). However, correlations vary across different forest stand classes, suggesting the need for further investigation into the reliability of VIs for monitoring wood volume and volume increments in forest ecosystems. Overall, this research contributes to the understanding of the applicability of VIs in remote sensing for forest management and ecosystem monitoring.

This communication is to summarize our single center experience on applications of anti-IL-1 biologic response modifiers on autoimmune and autoinflammatory conditions in children. We present our rationale for off-label utilization of Anakinra and discuss evolving treatment paradigms that warrants further research and validation. Based on our observations and successful treatment outcomes, we advocate future multilateral efforts to liberate access to anti-IL-1 medications to control inordinate and detrimental inflammation in children.

Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of WS1 results in death by the age of 30. Severe brain atrophy leads to central respiratory failure, which is the main cause of death in WS1 patients. Mutations in the WFS1 gene, located on chromosome 4p16, account for approximately 90% of WS1 cases. The gene produces wolframin, a transmembrane glycoprotein widely distributed and highly expressed in retinal, neural, and muscular tissues. Wolframin plays a crucial role in the regulation of apoptosis, insulin signaling, and ER calcium homeostasis, as well as the ER stress response. WS1 has been designated as a neurodegenerative and neurodevelopmental disorder due to the numerous abnormalities in the ER stress-mediated system. WS1 is a devastating neurodegenerative disease that affects patients and their families. Early diagnosis and recognition of the initial clinical signs may slow the disease's progression and improve symptomatology. Moreover, it is critical to provide genetic counseling to the patient's relatives in order to reduce the risk of transmitting WS1. Regrettably, there are currently no specific drugs for the therapy of this fatal disease. A better understanding of the etiology of WS1 will make possible the development of new therapeutic approaches that may enhance the life expectancy of patients. This review will examine the pathogenetic mechanisms, development, and progression of neuropsychiatric diseases commonly associated with WS1. A thorough understanding of WS1's neurophysiopathology is critical for achieving the goal of improving patients' quality of life and life expectancy.

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+ BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

The United Nations Global Sustainability Agenda 2030 introduces a transformative framework through its Sustainable Development Goals (SDGs), which are designed to achieve equitable, prosperous, and sustainable development globally. Unlike the incremental Millennium Development Goals (MDGs), the SDGs aim for systemic changes across economic, social, and environmental dimensions, ensuring that no one is left behind. This research paper provides a comprehensive examination of Pakistan's progress towards achieving the SDGs under the UN Global Sustainability Agenda 2030. Specifically, it includes an analysis of the prioritization of SDGs in Pakistan, highlights federal and institutional initiatives aimed at promoting sustainable development, and explores the role of the China-Pakistan Economic Corridor (CPEC) in advancing these goals. Additionally, the paper critically analyzes the SDGs in Pakistan’s annual status report, identifies the key challenges faced by the nation in implementing these goals, and offers recommendations for enhancing the effectiveness of SDG implementation. Overall, the focus is primarily on the detailed analysis of the annual status report, the challenges encountered, and strategic recommendations for achieving excellence in SDGs in Pakistan. Purpose: The objectives of this research are to assess how effectively Pakistan has prioritized the Sustainable Development Goals (SDGs) within its national framework, identifying the key areas of focus. This includes exploring the role of key federal institutions and initiatives, such as the China-Pakistan Economic Corridor (CPEC), in advancing the country’s SDGs. Additionally, the study aims to analyze the development and framework of the 17 SDGs in Pakistan by evaluating the country's status report on SDGs implementation. Furthermore, the research will examine the challenges Pakistan faces in achieving significant outcomes on the SDGs and provide actionable recommendations for enhancing the effectiveness and success of these initiatives.

Bayesian networks have emerged as a powerful tool for modelling complex probabilistic relationships in uncertain environments. The process of inducing Bayesian networks involves learning both the structure of the network and the parameters of the associated probability distributions. This paper provides a detailed examination of the two main approaches to Bayesian network induction: structure learning and parameter estimation, highlighting the use of both constraint-based and score-based techniques. Furthermore, the role of distribution-based methods in the estimation and inference of probabilistic models is explored. These methods, including Maximum Likelihood Estimation, Bayesian Estimation, and Monte Carlo techniques, offer robust ways to handle parameter uncertainty and facilitate efficient inference in large, complex models. This comprehensive view aims to bridge the gap between the theoretical foundations and practical applications of these methods, providing insights for researchers and practitioners in the field of machine learning and probabilistic reasoning.

This study presents an advanced integration of Multi-modal Raman Light Sheet Microscopy with zero-shot learning-based computational methods to significantly enhance the resolution and analysis of complex three-dimensional biological structures, such as 3D cell cultures and spheroids. The Multi-modal Raman Light Sheet Microscopy system incorporates Rayleigh scattering, Raman scattering, and fluorescence detection, enabling comprehensive, marker-free imaging of cellular architecture. These diverse modalities offer detailed spatial and molecular insights into cellular organization and interactions, critical for applications in biomedical research, drug discovery, and histological studies. To improve image quality without altering or introducing new biological information, we apply Zero-Shot Deconvolution Networks (ZS-DeconvNet), a deep learning-based method that enhances resolution in an unsupervised manner. ZS-DeconvNet significantly refines image clarity and sharpness across multiple microscopy modalities without requiring large, labeled datasets, or introducing artifacts. By combining the strengths of multi-modal light sheet microscopy and ZS-DeconvNet, we achieve improved visualization of subcellular structures, offering clearer and more detailed representations of existing data. This approach holds significant potential for advancing high-resolution imaging in biomedical research and other related fields.

Aim: To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. Methods: A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from 6 hospitals across Catalonia, Spain, from April 2020 to April 2022. The primary outcome was large for gestational age rate at birth. Secondary outcomes were composite adverse outcomes including pregnancy complications, delivery complications, and neonatal complications. Cost differences between screening methods were also evaluated. A similar analysis was performed in the subgroup diagnosed with GDM. Results: Data were collected from 1,543 pregnant individuals in the standard screening group and 2,197 in the alternative screening group. The standard screening group had a higher GDM diagnostic rate than the alternative screening group (10.8% vs 6.9%, respectively; p<0.0001). The primary outcome (large for gestational age rate) was similar between groups: 200/1543 (13.0%) vs 303/2197 (13.8%). The adjusted OR for this outcome was 1.74 (95% CI: 0.74-4.10). An adjusted analysis showed no differences between groups in composite adverse outcomes for pregnancy complications (OR: 1.11; 95% CI: 0.91-1.36), delivery complications (OR: 0.95; 95% CI: 0.75-1.19), and neonatal complications (OR: 1.28; 95% CI: 0.94-1.75). Among individuals diagnosed with GDM, the large for gestational age rate was similar between groups: 13/166 (7.8 %) vs 15/151 (9.9 %). The OR adjusted for this outcome was 1.24 (95% CI: 0.51-3.09). An adjusted analysis showed no differences in composite adverse outcomes for pregnancy complications (OR: 1.57; 95% CI: 0.84-2.98), delivery complications (OR: 1.21; 95% CI: 0.63-2.35), and neonatal complications (OR: 1.35; 95% CI: 0.61-3.04). The mean cost (which included expenses for consumables, equipment and personnel) of the alternative screening method was 46.0 euros (22.3 SD), as compared to 85.6 euros (67.5 SD) for the standard screening method. Conclusions: In this Spanish population during the COVID-19 pandemic, GDM prevalence was lower in the alternative screening group than in the standard screening group. After adjusting for GDM risk factors, outcomes related to obstetrics, delivery, and neonatal complications were comparable between both groups. Finally, the alternative screening method was cheaper than the standard screening method.

Equine herpesvirus type 1 (EHV-1) causes rhinopneumonitis, abortion and neurological outbreaks (equine herpesvirus myeloencephalopathy, EHM) in horses. EHV-1 also causes lethal encephalitis in laboratory small animals such as mice and hamsters experimentally. EHV-1 ORF76 is a homologue of HSV-1 US9, which is a herpesvirus kinase. Starting with an EHV-1 bacterial artificial chromosome clone of neuropathogenic strain Ab4p (pAb4p BAC), we constructed an ORF76 deletion mutant (Ab4p∆ORF76) by replacing ORF76 with the rpsLneo gene. Deletion of ORF76 had no influence on replication, cell-to-cell spread in cultured cells or replication in primary neuronal cells. In western blots of EHV-1-infected cell lysates, an EHV-1 Us9-specific polyclonal antibody detected multiple bands ranging from 35 to 42-kDa. In a CBA/N1 mouse infection model following intranasal inoculation, the parent and Ab4p∆ORF76 revertant caused the same histopathology in the brain and olfactory bulbs. The parent, Ab4p∆ORF76 and revertant mutant replicated similarly in the olfactory mucosa, although Ab4p∆ORF76 was not transported to the olfactory bulbs and was unable to infect the CNS. These results indicated that the ORF76 (US9) plays an essential role in the anterograde spread EHV-1.

Several studies have shown promising treatments for type 1 diabetes mellitus (T1DM) using developing gene therapy methods. This review article focuses on summarizing possible new treatment options and outlining their pros and cons, since there is no cure for T1DM as of yet. New treatments involve islet and stem cell transplantation, genetic vaccination, and immunological precursor cell-mediated therapy. Since most of these methods are still in their early stages, efficacy in human trials of this type of treatment is still largely unknown, however, researchers are hopeful after numerous successes in trials with non-obese diabetic (NOD) mice.