Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), may increase LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed de-identified electronic health records of 1,040,341 T2DM patients treated between 2005-2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

This study investigates the impact of Government Consumption (GC) on Saudi Arabia’s GDP during major economic crises from 1969 to 2022, with a focus on periods marked by fluctuations in oil and non-oil revenues. By integrating these revenue streams, the research provides a more comprehensive analysis of fiscal policy effectiveness during economic downturns. Using an Autoregressive Distributed Lag (ARDL) model, the study reveals the complex role of Government Consumption (GC) in stabilizing and stimulating the Saudi economy amidst revenue volatility.Key findings indicate that while GC does not significantly influence GDP in the short term, its long-term effectiveness varies across different crises. Specifically, GC has acted as a buffer against immediate economic shocks during certain crises while providing a stimulus for economic recovery in others. For instance, during the 2020 COVID-19 pandemic, timely fiscal measures significantly boosted GDP, underscoring the importance of adaptive and proactive fiscal policies. Conversely, the 2014-2016 oil price collapse demonstrated that GC alone was insufficient to counteract economic downturns, emphasizing the need for diversified revenue strategies.These findings underscore the dual role of GC in economic stabilization and recovery. During the COVID-19 pandemic, GC played a crucial role in both mitigating negative economic impacts and supporting recovery efforts, showcasing its effectiveness in times of global disruptions. This demonstrates GC's capability as an immediate buffer against economic shocks and a stimulus for economic recovery. In contrast, during the 2014-2016 oil price collapse, GC was less effective, indicating the limitations of relying solely on government spending without broader economic diversification. This highlights the necessity of diversified revenue strategies to complement fiscal measures for long-term economic resilience.The robustness of the findings was ensured through various diagnostic tests, including checks for autocorrelation, heteroskedasticity, and stationarity of residuals. The absence of significant autocorrelation and heteroskedasticity, along with the stationarity of differenced variables, confirms the validity of the econometric models used.The study contributes to the discourse on fiscal policy in oil-dependent economies by illustrating the critical role of diversified revenue strategies and adaptive fiscal measures in enhancing economic resilience. Recommendations are offered for policymakers to optimize fiscal strategies, ensuring robust economic recovery and long-term stability in volatile markets. This research highlights the necessity for Saudi Arabia to refine its fiscal policies towards greater economic diversification and stability.

We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS>50%; n=10) or low (TPS<1%; n=10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array. Both hypermethylation and hypomethylation play significant roles in tumor development, progression, and metastasis. They also impact the formation of the tumor microenvironment, which plays a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. The gained methylation patterns were correlated with PD-L1 expression. Our analysis has identified distinct methylation patterns in lung adenocarcinomas with high and low PD-L1 expression. After analyzing the correlation between methylation results of genes and promoters with their pathobiology, we found that tumors with high expression of PD-L1 tend to exhibit oncogenic effects through hypermethylation. On the other hand, tumors with low PD-L1 expression show loss of their suppressor functions through hypomethylation. The suppressor functions of hypermethylated genes and promoters are ineffective compared to simultaneously activated dominant oncogenic mechanisms. The tumor microenvironment supports tumor growth in both groups.

The method for quantitative analysis is based on the direct measurement of the analyte using differential pulse voltammetry (DPV), exploiting its oxidation peak. Calibration curves are set up to evaluate the figures of merit of the analytical method (LOD, LOQ, linear range). The application of the sensor for the dosing of GA in real matrices is carried out by analyzing non-alcoholic and alcoholic beverages and comparing the results with those reported in the literature and with the content of total polyphenols determined by the Folin-Ciocalteu method. In all cases, concentrations of GA align with those previously found in the literature for the beverages examined. Moreover, the values are always lower than the total polyphenols content; this demonstrates the good selectivity of the sensor that can discriminate the target molecule from other polyphenols present.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) are currently available for the management of type 2 diabetes mellitus. SGLT2i act by inhibiting renal SGLT2, thereby increasing glucosuria and lowering serum glucose. Recent trials are emerging supporting a role for SGLT2i irrespective of the diabetic status pointing towards that SGLT2i have other mechanisms of actions beyond blood sugar control. In this review, we will shed light on the role of this group of medications that act as SGLT2i in non-diabetics focusing on pre-clinical and clinical data highlighting the mechanism of renoprotection and effects of SGLT2i in the non-diabetic kidneys.

Objectives: Non-adhesive gel-like embolic materials (NAGLEMs) are becoming increasingly dominant in the endovascular treatment of hypervascularised formations in the head and neck due to a combination of their key properties. The main advantages include their lack of adhesion, effective distribution and penetration through pathological vessels, and crucially, their controlla-bility during the process. Our assigned duty was to scrutinise the literature and assess the efficacy and outcomes of administering NAGLEMs, in comparison to other embolizing substances (name-ly, coils, glue, and particles), among patients treated at our clinic. The procedures involved ana-lyzing the technical aspects, efficiency, and safety of endovascular therapy applied to two catego-ries of hypervascular pathological anomalies, surgically managed from 2015 to 2023. Arteriove-nous malformations (AVMs) located in the head, neck, and paragangliomas with jugular/carotid body localization are combined by intense shunting blood flow and shared requirements for em-bolizates used in endovascular treatment (such as penetration, distribution, delayed polymeriza-tion and controllability). An analysis of the literature was also conducted. Results showed 18 pa-tients diagnosed with neck paragangliomas of the carotid body and jugular type. Five patients with arteriovenous malformation (AVM) of the face and neck were included, consisting of 16 fe-males and 7 males with an average age of 55 ± 13 years. Endovascular procedures were conduct-ed using NAGLEMs (ONYX (Medtronic), SQUID (Balt), and PHIL (Microvention)) and dimethyl sulfoxide (DMSO)-compatible balloon catheters. All patients achieved complete or partial embo-lization of hypervascularized formations using one or more stages of endovascular treatment. Additionally, three AVMs of the face and two paragangliomas of the neck were surgically ex-cised following embolization. In other instances, formations were not deemed necessary to be re-moved. The patients' condition upon discharge was assessed by the modified Rankin Scale (mRs) and rated between 0 and 2. Conclusion: Currently, NAGLEMs are predominantly used to treat hypervascularized formations in the neck and head due to their fundamental properties. These properties include a lack of adhesion and a delay in predictable polymerization (after 30-40 minutes). NAGLEMs also exhibit excellent distribution and penetration throughout the vascular bed of the formation. Adequate controllability of the process is largely achieved through the pres-ence of embolism forms of different viscosity, as well as excellent X-ray visualization.

Background: The prognostic impact of non-cardiac comorbidities can vary in relation to the left ventricular ejection fraction (EF) in patients with ST-elevation myocardial infarction (STEMI). The aim was to analyze prevalence and long-term prognostic impact of non-cardiac co-morbidities in patients with reduced and preserved EF following STEMI. Method: 3115 STEMI patients undergoing primary PCI were divided in two groups: reduced EF <50% and preserved EF≥50%. Follow-up period was 8 years. Results: Preserved EF was present in 1726 (55.4%) patients and reduced EF was present in 1389 (44.5%) patients. Non-cardiac comorbidities were more frequent in patients with reduced EF as compared with patients with preserved EF (38.9% vs 27.4%, respectively, p<0.001). Lethal outcome was registered in 240 (17.2%) patients with reduced EF and in 40 (2.3%) patients with preserved EF, p<0.001. Diabetes and CKD were independent predictors for 8-year mortality in patients with preserved EF while in patients with reduced EF only CKD was independently associated with 8-year mortality. Conclusion: In the present study the prevalence of non-cardiac comorbidities is similar in patients with reduced and preserved EF after STEMI, but only DM and CKD are independently associated with long-term mortality.

This work aims to investigate the expression levels of four preselected miRNAs previously linked to Cancer and/or Obesity, with the purpose of finding potential biomarkers in the clinical management of Colorectal Cancer (CRC) developed by obese and non-obese patients. We analyzed samples from a total of 65 subjects, 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were analyzed, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2-∆∆Ct) levels of 4 miRNAs (miR-181a-5p, miR-143-3p, miR-132-3p and miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC serum levels of miR-181a-5p, miR-143-3p and miR-23a-3p correlated with their levels in both SAT and OAT. Moreover, in the case of miR-181a-5p, these correlations were significantly influenced by the body mass index (BMI). From these data, we can conclude that both adiposity and CRC induce changes in the expression of the miRNAs investigated, demonstrating the potential utility of this panel of miRNAs in the diagnosis and prognosis of CRC patients.

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

The presence of a non-structural protein 1 (NS1) in tick-borne encephalitis (TBE) vaccines and the possible induction of an NS1-specific immune response in vaccinated individuals remains a somewhat controversial topic. Previously, we detected the presence of NS1 in Encepur TBE vaccine by mass spectrometry and found the induction of NS1-specific IgG antibodies in mice vaccinated with FSME-Immun TBE vaccine. Here, in this follow-up study, we examined the dynamics and extent of the NS1-specific IgG response in mice vaccinated with these two vaccines in more detail and compared it with the IgG response to the whole virus (WV). Mice were vaccinated at two-week intervals with a total of six doses of each vaccine, and levels of IgG antibodies to TBE virus WV and NS1 were measured by ELISA after each dose. Both vaccines elicited a robust anti-WV IgG response after two doses. The Encepur vaccine did not elicit NS1-specific IgG even after all six doses. In contrast, FSME-Immun vaccine triggered production of NS1-specific IgG after four doses. The results indicate that FSME-Immun is the only vaccine that elicits an NS1-specific antibody response in mice. However, compared to WV-specific IgG, the NS1-specific response is weaker, and a higher number of doses is required to induce detectable levels of NS1-specific IgG antibodies.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

The imipramine ONC201 exerts a novel anti-proliferative activity over a wide spectrum of cancer cell types. ONC201 activates integrated stress response pathway that is associated with induction of Damage Inducible Transcript 3 (DDIT3, also known as C/EBP homologous protein or CHOP). We questioned whether the ONC201/CHOP crosstalk is regulated by diverse signaling pathways in non-metastatic versus metastatic cancer cell lines. Therefore, the Dukes' type B colorectal adenocarcinoma non-metastatic (SW480) and metastatic (LS-174T) cell lines were treated with ONC201. Cell proliferation and apoptosis were evaluated by MTT assay, flow cytometry analysis, gene expression was assessed by Affymetrix microarray, and key regulatory proteins were validated by Western blot assays. Unlike LS-174T cells, SW480 cells were resistant to ONC201 treatment. Gene ontology pathway enrichment analysis of differentially expressed genes revealed substantial differences between LS-174T and SW480 responsiveness to ONC201 treatment. In both cell lines, CHOP expression was upregulated in response to ONC201 treatment, however, its upstream regulatory mechanisms were not identical. Although, PERK, ATF6 and IRE1 ER-stress pathways were found to upregulated CHOP in both cell types, the BAK/BAX pathway was a notable regulator of CHOP in the metastatic LS-174T cells alone. In addition, CHOP RNA splicing profiles were varied between the two cell lines, which was further modified in response to ONC201 treatments. In conclusion, we delineated the signaling mechanisms regulating the expression of CHOP in non-metastatic versus metastatic colorectal cells in response to ONC201 treatment. The observed differences were related to cellular plasticity and metabolic reprogramming.

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific western blot analysis detected anti-NS1 antibodies also in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

Brand trust holds significant importance in the Mongolian cashmere industry. This study examines the primary predictors of customer brand trust among Mongolian cashmere users. Our research includes a survey with 800 participants and 20 individual interviews conducted among both Mongolian cashmere users and non-users. We utilized an online platform to reach participants, employing convenience sampling. The study investigates the relationship between various factors and brand trust within the context of Mongolian cashmere brands. Through a combination of in-dividual interviews and statistical analysis, we test six hypotheses. The findings indicate that higher brand quality, a strong reputation, greater transparency, effective issue resolution, commitment to environmental and social responsibility, and pre-purchase research on such commitments positively impact brand trust. Key insights gleaned from the interviews emphasize the importance of quality, reputation, transparency, customer service, and environmental responsibility in shaping consumer trust. These results offer valuable implications for cashmere brands aiming to bolster consumer trust and foster loyalty.

In this paper, we study the asymptotic behavior of the sequential empirical process and the sequential empirical copula process, both constructed from residuals of multivariate stochastic volatility models. Applications for the detection of structural changes and specification tests of the distribution of innovations are discussed. It is also shown that if the stochastic volatility matrices are diagonal, which is the case if the univariate time series are estimated separately instead of being jointly estimated, then the empirical copula process behaves as if the innovations were observed; a remarkable property. As a by-product, one also obtains the asymptotic behavior of rank-based measures of dependence applied to residuals of these time series models.

From their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses [1]. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3 to 10% of reported cases [2-5]. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches have been taken for the treatment of BRAF mutant cancers. In this review we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.

A case of low level windshear at Beijing Daxing International Airport is studied in the present pa-per. It is related to the synoptic scale/mesoscale changes of the airflow pattern over northern China. The shear was captured well by the Doppler LIDAR at the airport and timely alerts had been issued. This study considers the technical feasibility of forecasting the shear feature using a high resolution numerical weather prediction model with a lead time of several hours. It turns out that the shear feature could be forecast well, and is generally consistent with the actual observations. However, there are still discrepancies between reality and the simulation, such as the strength of the shear and persistency of the feature. More cases of windshear at Daxing airport would be studied in the fu-ture in order to understand the nature of windshear over there.

Smart cities, leveraging advanced data analytics, predictive models, and digital twin techniques, offer a transformative model for sustainable urban development. Predictive analytics plays a crucial role in proactive planning, enabling cities to adapt to evolving challenges. Concurrently, digital twin techniques provide a virtual replica of the urban environment, fostering real-time monitoring, simulation, and analysis of urban systems. This research underscores the significance of real-time monitoring, simulation, and analysis of urban systems to support test scenarios that identify bottlenecks and enhance smart city efficiency. The paper delves into the crucial roles of citizen report analytics, prediction, and digital twin technologies at the neighborhood level. The study integrates ETL/ELT processes, AI techniques, and a digital twin methodology to process and interpret urban data streams derived from citizen interactions with the city's coordinate-based problem mapping platform. By employing an interactive GeoDataFrame within the digital twin methodology, dynamic entities facilitate simulations based on various scenarios. This approach enables users to visualize, analyze, and predict the response of the urban system at the neighborhood level. Consequently, antecedent and predictive patterns, trends, and correlations are visualized at the physical level of each city area, leading to improvements in urban functionality, resilience, and resident quality of life.

MicroRNAs are small ribonucleotides which act as key gene regulators. Their altered expression is often associated with onset and progression of several human diseases, including cancer. Given their potential use as biomarkers, there is a need to find detection methods of microRNAs suitable for use in clinical setting. Field Effect Transistor based biosensors (bioFETs) appear to be valid tools to detect microRNAs, since they may reliably quantitate the specific binding between the immobilized probe and free target in solution through an easily detectable electrical signal. We have investigated the detection of human microRNA 155 (miR-155) using an innovative cap-turing probe constituted by a synthetic peptide nucleic acid (PNA), which has the advantage to form a duplex even at ionic strengths approaching the physiological conditions. With the aim to develop an optimized BioFET setup, the interaction kinetics between miR-155 and the chosen PNA was preliminary investigated by Surface Plasmon Resonance (SPR). By exploiting both these results and our custom-made bioFET system, we were able to attain a low-cost, real-time, label-free, highly specific detection of miR-155 in the nano-molar range.

Background:. Knowledge and positive perception of climate change are crucial for public participation in activities that contain climate change. Limited studies, particularly in South Africa have reported on the knowledge and perceptions of climate change by university students. Study Aim: This study aimed to assess the level of knowledge and perceptions of climate change by the science students at the University of South Africa (UNISA). Methods: This was a quantitative cross sectional survey, undertaken among science students using questionnaire emailed to 500 students in the School of Science through Unisa email system. Bivariate logistic regression was used to test the association between socio-demographics, level of knowledge and perceptions of climate change. Results: A total of 420 students participated in the study. They were predominantly male (70.3%), mostly younger than 35 years of age. Most of the respondents were in the 2nd (34.7%) and 3rd (33.8%) year of study. Majority of respondents (97.9%) knew and perceived (93.6%) that climate change was happening. Overall, 93.8% of respondents had an excellent knowledge and basic concepts of climate change. Conclusion: The majority of students were knowledgeable and had positive perceptions about the basic concepts of climate change. However, the year of study was not significantly associated with positive perceptions of climate change. There is need to include climate change modules in South African university curriculum.

Aim at a better understanding of the flow field around a fully appended Joubert BB2 submarine model and complementing the experimental investigations of the wake of the hydroplanes and sail, the Large eddy simulation (LES) with the dynamic Smagorinsky model is conducted. Three sets of grids with a maximum grid number of up to 228 million are designed, to perform the LES simulation for the Joubert BB2 at 10° yaw conditions, with a freestream Reynolds (Re) number based on the local freestream velocity and the hull length of ReL=2.2×107. And comparison of the wake of the cruciform appendage is made with experiments, to verify the computational accuracy and examine the influence of the spatial resolution. A satisfactory result shows more favorable agreement with experimental measurements as the improvement of spatial resolution, with the relative error of the vortice centers well within 7.2% in the most refined grid arrangement. And under this grid arrangement, the evolution characteristics of three co-rotating vortices originating from the cruciform appendage are further described in detail at straight ahead and 10° yaw conditions.

ABSTRACT: Waterlogging is a common abiotic stress in global maize production. Maize flowering stage (from tasseling to silking) is more fragile to environmental stresses among different growth stages. The effects of waterlogging at flowering stage on the grain yield and starch quality of waxy maize were studied using Suyunuo5 (SYN5) and Yunuo7 (YN7). The grain yield and starch concentration of both hybrids were reduced by waterlogging. The size of starch granules and proportion of small-molecule amylopectin increased in SYN5 and decreased in YN7 when plants suffered waterlogging at flowering, in contrast to the change trend of relative crystallinity. The pasting viscosities and gelatinization temperatures were reduced, whereas the gelatinization enthalpy was unaffected by waterlogging in both hybrids. Our study indicated that waterlogging at flowering reduced the grain yield, restricted starch deposition, and deteriorated the pasting property of waxy maize. Between the two hybrids, YN7 and high pasting viscosities and low retrogradation percentage than SYN5, indicated its advantages on produce starch for viscous and less retrograde food. Results provide information for utilization of waxy maize grain in food production.

The paper discusses the experience of implementing an efficient economic management system at the University of Vigo in Spain. This system, which focuses on managing secondments, aims to minimize bureaucracy and standardize economic procedures for various staff groups. By adopting a qualitative methodology and utilizing content analysis, the study compares the University of Vigo's fully digital administrative procedure with other universities in the CRUE network. The results show significant time and cost savings due to this implementation. The improved traceability and information for users support the administrative change, and the positive environmental impacts highlight the commitment to a more sustainable approach. The paper's originality lies in demonstrating how this approach enhances efficiency, reduces costs, and improves sustainability within a Spanish public administration setting.

This study examined the effect of colleagues uncivil behavior on extra-role performance of teachers. The study further explored the mediating role of emotional exhaustion to intensify the effect. In parallel, moderation of psychological hardiness to absorb the negative shocks was also determined. For examining the direct, mediating, and moderating effects, primary data were collected through mailed questionnaires. To overcome the issues of common method biases, dyadic and time lagged approaches were used for collection of data. Responses were collected in three phases, with appropriate time intervals. Data of independent, mediating, and moderating variables were collected from teachers while of dependent variable form their immediate supervisors, i.e. HoDs. The study found a significant effect of colleagues’ discourteous behavior on extra-role performance of victims at job. Significant mediation of emotional exhaustion in the effect was also observed. In the meantime, hardiness of targets absolutely moderated the effect to minimize the associated consequences. Based on results, several policy implication and interventions were suggested.

Several coastal barriers experienced significant erosion and change in shape throughout the Mediterranean coasts over the past decades, and the issue has become of increasing concern for scientists and policymakers. With reference to a case study and by meteorological and geomorphological investigations, this note aims to infer recent shoreline dynamics and define coastal phenomena shaping the beach-dune barrier of Cesine Lagoon (South Italy), to finally point out the weather-driven processes. A challenge for this research was to obtain significant results from publicly available sources and simple and inexpensive methods. The retreat of the dune toe, the accretion of washover fans, and the formation of gravel beaches have been related to the analyzed wind-wave conditions. Net longshore transport was found in accordance with the direction of the more intense winds. The role of extreme events in the shaping of coastal landforms is yet to be established even if they greatly increase the vulnerability to flooding of the study area. The results achieved so far are starting points for further data collection and analysis in the perspective of assessing the impact of climate changes on the lagoon barrier.

Aaron Copland’s only full-length opera, The Tender Land has had a difficult production history. Critics of the 1954 New York City Opera Premiere bemoaned the atypical storyline, the music declared too dry, and the singing too sparse. The opera’s failure to dazzle initial audiences is likely because it was originally written for television. Copland was commissioned to write this opera for television in 1952, but was rejected by NBC in 1953, with no official explanation given as to why. The New York City Opera premiere, therefore, was not an accurate representation of Aaron Copland's vision. The opera eventually did find receptive audiences, each success marked by a smaller, more intimate venue, not unlike the intimacy afforded on a sound stage. Perhaps most notable of these was the touring 1993 University of Minnesota production that performed in barns and farmhouses throughout the Midwest. Through this tour, the opera reached a rural community mirrored in the story, providing much more opportunity for the audience to connect to the characters. However, the question remains what caused NBC to initially reject the opera. This paper exposes the likely political obstacles that prevented Copland’s opera from premiering in its intended medium, and the subsequent consequences of displacing The Tender Land from its television premiere.

Purpose: While resultant maximal voluntary contraction (MVC) is commonly used to assess muscular performance, the simultaneous activation of antagonist muscles could dramatically underestimate the strength of the agonist muscles. While quantification of antagonist torque has been performed in plantar- (PF) and dorsi-flexion (DF) joint in isometric conditions, it has yet to be determined in anisometric (concentric and eccentric) conditions. Methods: The experiment was performed in 9 participants through 2 sessions (reliability). The MVCs in DF and PF were measured in isometric, concentric and eccentric conditions (10°.s^-1). Electromyographic (EMG) activities from the soleus, gastrocnemius medialis and lateralis, and tibialis anterior muscles were simultaneously recorded. The EMG biofeedback method was used to quantify antagonist torque, where participants were asked to maintain a level of EMG activity, corresponding to antagonist EMG activity and related to the muscle contraction type, according to a visual EMG bio-feedback displayed on a screen. Results: Resultant torque significantly underestimated agonist torque in DF MVC (30-65%) and to a lesser extent in PF MVC (3%). Triceps surae antagonist torque was significantly modified with muscle contraction type, showing higher antagonist torque in isometric (29 Nm) than eccentric (23 Nm, p < 0.001) and concentric (14 Nm, p < 0.001) conditions and resulting in modification of the DF MVC torque-velocity shape. The difference between DF eccentric and concentric MVC was attenuated when considered agonist torque (12%) rather than resultant torque (45%). Conclusion: Estimation of the antagonist torque in isometric or anisometric condition brings new insights to assessment of muscular performance and could result in costly misinterpretation in strength training and/or rehabilitation programs.

In this study, we discuss the properties of absolute void space or the universe at zero seconds, and how these properties play a vital role in creating a mechanism in which the very first particle gets created simultaneously everywhere and we find the limit in which when the absolute void volume reaches will lead to the collapse that leads to the creation of the first particle. This discussion is made following the elementary dimensions theory study that was peer-reviewed at the end of 2020, everything in the universe is made from four elementary dimensions, these dimensions are the three spatial dimensions (X, Y, and Z) and the Void resistant as the factor of change among the four, time itself wasn’t considered as the fourth dimension, rather time corresponds to a factor of change, and during the research, it was found out that the Void resistant is the factor of change in the Absolute Void space, where time is a hypothetical concept, that represents changes during certain events compared to a constant change rate event. Therefore, time does exist, but as a factor of change, and as the Void resistant in the absolute void space, Time= factor of change= Void resistant. In the study, the internal and external void resistant volume equivalent is found, External Void resistant=3.2857602*10^15 *mass. This equation is used to identify to amount of Free external void resistant created during nuclear fission and fusion: The initial mass of the excited nucleuses → mass of the created new nucleuses+ 3.2857602*10^15 * the lost Mass. In elementary dimensions, the energy created during nuclear reactions is equivalent to the free External void resistant created through nuclear reactions, and mass is equivalent to the internal Void resistant.

Background: We aimed to study the frequency, management, and outcomes of patients with blunt pancreatic trauma. Methods: We reviewed the medical records for all patients admitted with pancreatic injuries between 2011 and 2017 at the only level 1 trauma center in the country. Results: There were 71 patients admitted with pancreatic trauma (0.6% of trauma admissions and 3.4% of abdominal injury admissions) with a mean age of 31 years. Sixty-two patients had pancreatic injury grade I-II and 9 had grade III-IV. Thirty-eight percent had GCS <9 and 73% had ISS >16. The level of pancreatic enzymes was significantly proportional to the grade of injury. Over half of patients required a laparotomy, of them 12 patients had an intervention on the pancreas. Eight patients developed complications related to pancreatic injuries ranging from pancreatitis to pancreatico-cutaneous fistula while 35% developed hemorrhagic shock. Mortality was 31% and regardless of the grade of injury, the mortality was associated with high ISS, low GCS and presence of hemorrhagic shock. Conclusion: Pancreatic injuries following blunt trauma are rare and the injured subjects are usually young male. However, most injuries are of low-grade severity. This study shows that shock, higher ISS and lower GCS are associated with worse in-hospital out-comes. Non-operative management may suffice in patients with lower grade injuries, which may not be the case in patients with higher grade injuries unless carefully selected

Background: To investigate any associations between new clinical policies implemented because of the COVID-19 pandemic and harm to patients. Methods: Retrospective data collection of incidents and complaints reported through Datix®, and the Patient Liaison Service respectively. The setting was the Family Health division in a University teaching hospital in the UK. Primary and secondary outcome measures included; Proportion of incidents reported on Datix from 23/3/20 to 25/5/20, compared to the period from 23/3/19 to 29/5/19. COVID-19 related incidents and complaints and association with newly published guidelines or pathways from 23/3/20 to 29/5/20. Results: There was no significant difference in the proportion of overall patient activity resulting in incidents reported on Datix in 2020 (2.08%) compared to 2019 (2.09%), with 98% resulting in no/low harm in 2020. Three incident categories had increases in relative proportions of incidents including terms “COVID” or “Corona” compared to incidents that did not; “Child death”, “delay/failure to treatment and procedure” and “information governance”. One of the child deaths was a miscarriage and we were unable to link the second child death to a change in clinical policy at this stage. We were only able to link 2 COVID-19 associated incidents with a pathway or procedural change (one to the Children's Emergency Department admission pathway and the second to the introduction of virtual antenatal clinics). Eighteen complaints related to COVID-19 were logged. However, at this stage, we are unable to link any of these to a published change in clinical policy. Conclusions: Practice in the division was overall deemed to be safe in the designated period, with only 2 COVID-19 related incidents clearly related to a change in pathways and procedures. Continued surveillance and improved metrics for monitoring the impact of changes to pathways and procedures should be sought with the sustained presence of COVID-19 in clinical areas.

COVID19 is a current pandemic disease due to the novel coronavirus SARS-CoV-2. The scientific community mounted a strong response by accelerating research and innovation, and rapidly setting the basis to the understanding of molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key step of SARS-CoV2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of structural and functional data on key actors of the replicatory machinery of SARS-CoV-2, filling the gaps in the current availability of structural data using homology modelling. Moreover, learning from similar viruses, we collect literature data to reconstruct the pattern of interactions among protein actors of the SARS-CoV-2 RNA polymerase machinery. In this pattern, an important role is played by co-factors, like Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors holding the entire machinery together to enhance the efficiency of RNA replication.

The novel coronavirus SARS-CoV2 (CoV2) emerged in December 2019. This virus has 88% genomic similarity with SARS-CoV (CoV), and both viruses largely depend on their main protease (M^pro) to regulate infection. M^pro thus represents an attractive target for anti-SARS drug design. The CoV and CoV2 M^pro are 97% identical at the sequence level, with 12 variable residues, and their X-ray structures appear similar. We thus structurally analysed how these variable residues affect the intra-molecular interactions between key residues in the CoV2 M^pro active-site. Compared to CoV M^pro, the 12 divergent residues in CoV2 M^pro exhibit modified intra-molecular interaction networks that ultimately restructure the molecular micro-environment. These altered networks also indirectly affect the networks of other active-site residues at the entrance (T26, M49 and Q192) and near the catalytic region (F140, H163, H164, M165 and H172) of the M^pro. This suggest CoV2 indirectly (via neighbours) reshape key molecular networks around the M^pro active-site. It seems that the CoV2 M^pro deceives us with its apparent structurally identical to the CoV M^pro while this viral system accumulates mass mutations (12 variable residues) at key positions. Some of these identified CoV2 M^pro networks at the active-site might guide design of efficient CoV2 M^pro inhibitors.

Sexual Issues played a significant role in Judaism’s engagement with its Greco-Roman world. This paper will examine that engagement in the Hellenistic Greco-Roman era to the end of the first century CE. In part sexual issues were a key element of demarcation between Jews and the wider community, alongside such matters as circumcision, food laws, sabbath keeping and idolatry. Jewish writers, such as Philo of Alexandria, make much of the alleged sexual profligacy of their Gentile contemporaries, not least in association with wild drunken parties, same-sex relations and pederasty. Jews, including the emerging Christian movement, claimed the moral high ground. In part, however, matters of sexuality were also areas where intercultural influence is evident, such as in the shift in Jewish tradition from polygyny to monogyny, but also in the way Jewish and Christian writers adapted the suspicion and sometimes rejection of passions characteristic of some popular philosophies of their day, seeing them as allies in their moral crusade.

Over the years, the Egyptian temples at Luxor city have been intensely investigated, but most of these studies just focused on the classical sides of the archaeological and historical descriptions. Many of the environmental problems are inevitable results of the unplanned urban crawling around the monuments temples. This paper aims at assessing the environmental changes around some temples of Luxor City using Remote sensing and GIS techniques. In particular, a historical database made up of Corona and Landsat TM data have been investigated along with the new acquisitions of Quickbird2 and Sentinel2. Results from our investigation highlighted rapid changes in urban and agricultural areas, which adversely affected the Egyptian monumental temples causing serious degradation phenomena. Using the information obtained from our RS&GIS based analysis, mitigation strategies have been also identified for supporting the preservation of the archaeological area.

The study, conducted at the Department of Medicine, Maulana Azad Medical College and associated Lok Nayak Hospital, aimed to investigate the prevalence of iron deficiency anaemia among anaemic overweight and obese individuals. Fifty participants were included after screening and consent, undergoing socio-demographic assessment, clinical evaluation, and laboratory investigations. Middle to old-aged individuals predominated (Mean ± SD: 54.54 ± 11.32 years), with females comprising 62%. All subjects were obese (mean BMI: 37.27 ± 5.71 kg/m²), with common comorbidities including hypertension (68%), diabetes (36%), and obstructive sleep apnea-hypopnea syndrome (32%). Nutritional deficiencies, particularly iron deficiency, were prevalent, affecting 62% of subjects, with 48% having iron deficiency alone. Anemia of chronic illness was observed in 38%. Laboratory parameters showed low hemoglobin (8.53 ± 1.23 g/dL), MCV (78.75 ± 10.13 fL), and elevated ESR (20.56 ± 21.47 mm/hour) and CRP levels (4.71 ± 3.32 mg/dL), indicating inflammation. Correlation analyses revealed negative associations between BMI and serum iron/ferritin and positive associations with serum hepcidin. The study underscores the significance of addressing nutritional deficiencies and monitoring iron status in obese populations, suggesting potential associations between obesity and iron metabolism. Further research is needed to explore these relationships for clinical management implications.

The study explores how different dimensions of perfectionism influence psychological well-being (PWB) in emerging adults. Literature has deepened the relationships between maladaptive perfectionism (e.g., excessive self-criticism, perceived discrepancy from the standards) and low PWB. Less is known about whether and how adaptive perfectionism (e.g., pursuing personal standards) relates to PWB. Secondly, the study has investigated whether self-compassion (i.e., self-benevolence, seeing personal imperfections as a common condition) may mediate the relationships between adaptive/maladaptive perfectionism and PWB. Participants (N=217, 18-35 y. o.) completed self-report questionnaires measuring: adaptive/maladaptive perfectionism (Almost Perfect Scale-Revised, APS-R: high standards and order/discrepancy, respectively), PWB, and self-compassion (SCS). Adaptive perfectionism resulted associated with PWB, particularly higher presence of purpose in life, environmental mastery, self-acceptance, and personal growth. Conversely, discrepancy resulted the most robust predictor of low PWB (β=-.68), followed by high standards with a positive direction (β=.23; Rc²=.514, p&lt;.001). A strong negative association emerged between discrepancy and SCS (r=-.67, p&lt;.001). A mediation analysis shows that self-compassion has an indirect effect reducing the strength of the relationship between discrepancy and low PWB. Results suggest focusing on self-compassion as a buffer factor that reduces the negative impact of maladaptive perfectionism on psychological well-being. Implications for education and health psychology are discussed.

Knowledge is not merely the characteristic of certain pieces of information being deemed true and justifiable, but rather a process. Within an axiomatic system, the set of information that reaches the status of knowledge forms a universe that provides an interpretation of the reality one aims to describe. Language exchanges information through communication and the process of justification (exchange of information), if it consistently justifies a particular piece of information, it elevates it to knowledge. In this paper, we provide a framework for knowledge within an axiomatic model where we define the fundamental elements of communication and grammar. As a result, the structure dictates that knowledge, to be considered as such, must be investigateable by anyone who utilizes it in its entirety, both in form and content. Ultimately, the development of knowledge processing, referred to as \emph{knowmatics}, represents a clear evolution of the computer science that processes information (subset of knowledge).

In current transportation hubs, it is a common phenomenon that passengers travel with necessary wheeled-luggage or suitcases. Due to the fact that most luggage occupies certain space within dense passenger crowds with giant mass inertia, its abnormal motions, such as drifting, frequently trig unavoidable local disturbances and turbulence in surrounding pedestrian flows, further increasing security risk. While, current researches primarily concentrate on examining the impact of luggage on crowd evacuation efficiency through scenario-based experiments and analyzing the spatial characteristics of crowd distribution in surveillance videos. There still lacks of the dynamic disturbance mechanisms and crowd stability associated with the combined motion of passengers and luggage. Therefore, this study considers the luggage-laden passenger as a deformable particle, the resulting disturbance on surrounding non-luggage passengers is analyzed and quantified into a nonlinear pressure term. Subsequently, the disturbance propagation model of passenger-luggage is developed by adapting the classical Aw-Rascle traffic flow model with incorporation of the pressure term. Simulation experiments of disturbances caused by luggage drifting and retrograding validate that the proposed propagation model aligns with real-world situations in transportation hubs. Quantitively, when luggage-laden passenger drifted left, the disturbing force of left side crowd can reach a peak of 238N in the passenger density of 3.0 p/m2, and the maximum difference between the left and right sides disturbing force can reach 153N. Furthermore, it is recommended that the proposed model can be applied to crowd flow analysis and risk assessment.

This paper applied the space-time generalized finite difference scheme for solving the nonlinear dispersive shallow water waves as the modified Camassa−Holm equation, modified Degasperis-Procesi equation, Fornberg-Whitham equation, and its modified form. The proposed meshless numerical scheme was composed of the space-time generalized finite difference method, the two-step Newton-Raphson method, and the time-marching method. The space-time approach can treat the temporal derivative as one of the spatial derivatives. This numerical technique enables all the partial derivatives in the governing equation can be discretized by a spatial discretization method, and the mixed derivative can efficiently deal with using the proposed meshless numerical scheme. The space-time generalized finite difference method is advanced from the Taylor series expansion and the moving-least square method. The numerical discretization process is only related to functional data and weighting coefficients on the central node and its nearby nodes. Thus, the matrix system composed of nonlinear algebraic equations will be a sparse matrix and can be efficiently solved by the two-step Newton-Raphson method. Furthermore, the time-marching method was utilized to proceed with the space-time domain along the time axis. In this paper, several numerical examples were tested to verify the capability of the proposed space-time generalized finite difference scheme.

Barrett’s esophagus (BE) is a known precursor to Esophageal Adenocarcinoma (EAC). Guidelines recommend BE screening in populations with multiple risk factors, for which non-endoscopic esophageal cell collection with biomarker testing is considered an acceptable alternative to esophagogastroduodenoscopy (EGD). This study presents analytical validation of EsoGuard® (EG), a two gene DNA methylation biomarker assay, in esophageal cell samples collected with the 510(k)-cleared, swallowable EsoCheck® (EC) device. EG is a Next Generation Sequencing (NGS) assay that evaluates methylated Vimentin (VIM) and Cyclin A1 (CCNA1) genes, clinically validated biomarkers for detection of BE and EAC. The studies were conducted according to standards of College of American Pathology (CAP), Clinical Laboratory Improvement Amendments (CLIA), and New York (NY) state requirements for analytical validation of molecular assays. Comparison to Sanger sequencing showed EG was 100% accurate at all 31 CpG sites evaluated by the assay. Analytical sensitivity, specificity and accuracy of the assay was 89%, 100% and 96% respectively. Intra- and inter-assay precision was 100%. Limit of detection (LOD) was 1 in 400 methylated cells and reference range was 84%. In summary, EsoGuard is a robust DNA methylation test to detect BE with high accuracy, repeatability, and reproducibility in samples collected using the EsoCheck device.

Rebar cages form the skeletal framework of reinforced concrete structural members. They comprise longitudinal and transverse reinforcing bars, usually connected by tie wires. Past studies have identified tie-wire connections as the "weak links" in large, prefabricated rebar cages, leading to their failure during site handling and construction stages. Recent research has explored the use of mechanical U-bolt connectors to bolster stability and safety of rebar cages while reducing their vulnerability and risk of failure. This paper presents a comprehensive experimental and numerical investigation of a new type of mechanical connector, referred to as "Cage Clamp", to enhance rebar cage stability and safety. Component-level experimental tests are conducted to determine the force-displacement response of Cage Clamp connectors for crossbar connections in different degrees of freedom. The results highlight the remarkable strength and stiffness of Cage Clamp connectors, significantly outperforming traditional tie-wire connections. Furthermore, full-scale experimental tests are performed on a circular underground pile-shaft rebar cage with Cage Clamp connectors to assess its behavior under various site handling conditions. The data obtained from these experiments are used to construct and refine detailed 3D finite element models of the rebar cages, capable of capturing the complex behavior of rebar cages with Cage Clamp connectors. Using the numerical model, a sensitivity analysis is performed to assess the effect of the number of Cage Clamps on the deflection and stability of the rebar cage. The findings show that using cage clamps to connect pick-up rebar with lateral reinforcement at every 8 to 10 feet is sufficient to ensure the stability of the cage during typical site handling conditions. The results of this study serve as a basis for establishing analysis, design, fabrication, and handling guidelines for rebar cages, contributing to safe and efficient construction practices.

Background: Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation, intraperitoneal chemotherapy), secondary to medications ( beta-blockers); however, PS or EPS typically occur in patients undergoing peritoneal dialysis as a form of renal function substitution. Medical or surgical treatments can be applied, but morbidity and mortality have high rates . This condition typically presents clinically as an intestinal obstruction caused by the inclusion of the intestinal loops in the peritoneal fibrous membrane. Methods: Herein we present data from a single tertiary surgery center that has dedicated teams for patients receiving dialysis. In 12 years we analyzed a group of 63 patients admitted for catheter replacement/removal or for acute surgical pathology. In 5 cases (7,9%) we diagnosed EPS . Two patients with EPS presented with atypical abdominal pathologies requiring emergency surgery: one case of hemoperitoneum caused by a ruptured ovarian cyst and one case of uterine fibroids and metrorrhagia. Results: The definitive diagnoses were established intraoperatively and by analyzing the morpho-pathological changes of the peritoneum. The possible intraoperative challenges included laborious dissection, difficulties in restoring the correct anatomical landmarks, increased duration of the surgical intervention and a high rate of incidents and accidents Conclusions: The aim of the present study was to emphasize the possibility of other surgical pathologies overlapping with EPS, increasing the complexity of the surgical intervention. Also, we sought to determine whether there is a correlation between the morpho-pathological results of these patients who underwent emergency surgery and the common EPS morpho-pathological changes.

The regulation of cell death is a fundamental issue in cell biology and continues to be intensely investigated worldwide. The significance of research in this field persists because understanding the determinants of cell lifespan directly impacts the maintenance of multicellular organism homeostasis and, consequently, is crucial for addressing biomedical challenges associated with various diseases. It is recognized that the initiation of cell death can be prompted by both specific signals (such as cytokines or hormones) and nonspecific stimuli, including radiation, temperature increase, or oxidants. When these factors affect a cell, numerous signaling pathways are triggered in the cell, leading to neutralization of the effects of their negative effects or, in case of irreparable damage, to cell elimination. This removal of damaged cells occurs through apoptosis or programmed cell death, a highly regulated process. Numerous signaling molecules participate in orchestrating the apoptotic process, many of which also govern other essential functions within the organism. Physiological factors capable of triggering the apoptotic program in cells include nitric oxide (NO), which serves as one of the key signaling molecules regulating the functions of the cardiovascular, nervous, and immune systems of the organism. The unique chemical nature of NO, along with its numerous intracellular targets and physiologically active redox forms, raises questions about the specific mechanisms through which NO exerts its damaging effects on cells. Utilizing pharmacological preparations- such as sources (donors) of exogenous nitric oxide- represents an approach to investigating the initiation and execution of the apoptotic program in sensitive target cells. Furthermore, this approach holds promise as a direction for discovering new selective drugs.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

Electromagnetic cloaking approach is employed with the intention to curb the destructive effects of mutual interference for rectangular and circularly shaped patch antennas situated in a tight spacing (sub-wavelength separation is employed). Primarily, we show that by coating the top surface of each patch with an appropriately designed metasurface, it is possible to considerably reduce the mutual coupling between the said antennas. We also demonstrate that, despite the close proximity of these patches, the individual radiation characteristic of each antenna is reinstated to emulate their performance in an isolated scenario. Furthermore, the cloak construct is extended to a tightly spaced, interleaved linear patch antenna array configuration and it is shown that the coated metasurfaces successfully enhance the performance of each array in terms of their matching characteristics, total efficiencies as well as their far-field realized gain patterns for a broad range of beam-scan angles. The decoupling and cloaking action of these metasurfaces are demonstrated by various full-wave numerical simulation results. We believe that the simple planar structure of our metasurface design (according to simulation models) makes it feasible for fabrication and the fact that it is used to accomplish cloaking of an electrically large antenna surface, makes it unique in itself.

We study theoretically the Josephson diode effect (JDE) realized in a system composed of parallel-coupled double quantum dots (DQDs) sandwiched between two semiconductor nanowires deposited on an s-wave superconductor surface. Due to the combined effects of the proximity-caused superconductivity, strong Rashba spin-orbit interaction and Zeeman splitting inside the nanowires, a pair of Majorana bound states (MBSs) may possibly emerge at opposite ends of each nanowire. Different phase factors arisen from the superconductor substrate can be generated in the coupling amplitudes between the DQDs and MBSs prepared at the left and right nanowires, and will result in the Josephson current. We find that the critical Josephson currents in positive and negative directions are different from each other in amplitude within an oscillation period with respective to the magnetic flux penetrating through the system, a phenomenon known as the JDE. It arises from the quantum interference effect in this double-path device, and can hardly occur in system of one QD coupled to MBSs. Our results also show that the diode efficiency can reach up to 50%, and depends on the overlap amplitude between the MBSs and the energy levels of the DQDs adjustable by gate voltages. The present model is realizable within current nanofabitication technologies and may find practical use in interdisciplinary field of Majorana and Josephson physics.

With buildings accounting for a significant portion of global energy consumption and greenhouse gas emissions, the application of artificial intelligence (AI) holds promise for enhancing sustainability in the building lifecycle. This systematic literature review addresses the current understanding of AI's potential to optimize energy efficiency and minimize environmental impact in building design, construction, and operation. A comprehensive literature review and synthesis were conducted to identify AI technologies applicable to sustainable building practices, examine their influence, and analyze the challenges of implementation. The review was guided by a meticulous search strategy utilizing keywords related to AI application in sustainable building design, construction, and operation. The findings reveal AI's capabilities in optimizing energy efficiency through intelligent control systems, enabling predictive maintenance, and aiding design simulation. Advanced machine learning algorithms facilitate data-driven analysis and prediction, while digital twins provide real-time insights for informed decision-making. Furthermore, the review identifies barriers to AI adoption, including cost concerns, data security risks, and challenges in implementation. AI presents a transformative opportunity to enhance sustainability in the built environment, offering innovative solutions for energy optimization and environmentally conscious practices. However, addressing technical and practical challenges will be crucial for the successful integration of AI in sustainable building practices.

Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. This plaque accumulation obstructs blood flow to the heart, resulting in a heart attack. While distinct features of CAD have been identified, its causes remain largely unclear, with the exception of environmental and nutritional factors. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase (TS) gene, a gene involved in one-carbon metabolism. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact TS gene expression and lead to dysfunction. Our findings strongly associate the TS 1100T&gt;C and 1170A&gt;G genotypes with CAD susceptibility. We observed that TS 1100T&gt;C polymorphisms increased disease susceptibility in several groups, while the TS 1170A&gt;G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the TS 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the 3'-UTR miRNA binding site of the TS gene could serve as clinically useful biomarkers for the prevention, prognosis, and management of CAD.

As large language models (LLMs) continue to advance, evaluating their comprehensive capabilities becomes significant for their application in various fields. This research study comprehensively evaluates the language, vision, speech, and multimodal capabilities of GPT-4o. The study employs standardized exam questions, reasoning tasks, and translation assessments to assess the model's language capability. Additionally, GPT-4o's vision and speech capabilities are tested through image classification and object recognition tasks, as well as accent classification. The multimodal evaluation assesses the model's performance in integrating visual and linguistic data. Our findings reveal that GPT-4o demonstrates high accuracy and efficiency across multiple domains in language and reasoning capabilities, excelling in tasks that require few-shot learning. GPT-4o also provides notable improvements in multimodal tasks compared to its predecessors. However, the model shows variability and faces limitations in handling complex and ambiguous inputs, particularly in audio and vision capabilities. This paper highlights the need for more comprehensive benchmarks and robust evaluation frameworks, encompassing qualitative assessments involving human judgment as well as error analysis. Future work should focus on expanding datasets, investigating prompt-based assessment, and enhancing few-shot learning techniques to test the model's practical applicability and performance in real-world scenarios.

Although vitamin D deficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH) D) and atherogenic indices predictive of CVD. This study aimed to investigate the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred healthy women, aged 18 to 50 years, from Meknes were included. Fasting 25(OH) D and lipid concentrations were determined using a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (Atherogenic index of plasma (AIP), non-HDL cholesterol (Non-HDL-C), Atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH) D levels associated with high atherogenic indices. 25(OH) D below 20 ng/ml was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, Non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959); 3.637(2.149-6.158); 3.589(1.673-7.700); 2.074(1.215-3.540), and 2.481(1.481-4.123), respectively. According to ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, Non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/ml, ≤ 17.5 ng/ml, ≤ 19.8 ng/ml, ≤ 20.1 ng/ml and ≤ 19.5 ng/ml, respectively, all p &lt; 0.01. Based on atherogenic indices, this study indicates that vitamin D below 20 ng/ml may increase the risk of cardiovascular disease in adult women. Additional health efforts are needed to raise awareness among women and healthcare providers in preventing and controlling cardiovascular risk factors.

Gas sensing is crucial for detecting hazardous gases in industrial environments, ensuring safety and preventing accidents. Additionally, it plays a vital role in environmental monitoring and control, helping to mitigate pollution and protect public health. Integrated photonic gas sensors are important due to their high sensitivity, rapid response time, and compact size, enabling precise recognition of gas concentrations in real-time. These sensors leverage photonic technologies, such as waveguides and resonators, to enhance performance over traditional gas sensors. Advancements in materials and fabrication techniques could further improve their efficiency, making them invaluable for environmental monitoring, industrial safety, and healthcare diagnostics. In this review, we delved into photonic gas sensors that operate based on the principles of evanescent field absorption (EFA) and wavelength interrogation methods. These advanced sensing mechanisms allow for highly sensitive and selective gas detection, leveraging the interplay of light with gas molecules to produce precise measurements.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

In this paper, we prove the existence of three solutions for a $p$-Kirchhoff problem with $\psi$-Hilfer fractional derivative. To be more precise, we use the variational method and we prove that the associated functional energy admits a critical point in each of the three constructed sets, these critical points are weak solutions for a studied problem. Moreover, by definition of these sets, one of these solutions is positive, the second is negative, and the third one change sign. At the end of this work, we present an example to validate our main results.

In bone tissue engineering, ceramics have been the choice due to their excellent biological properties. But the paradigm changed with the discovery of bioactive glasses (BGs) in 1969 by Larry Hench and co-workers, due to their ability to bond to living tissues through the formation of an interfacial bone-like hydroxyapatite layer when the bioglass was put in contact with biological fluids in vivo. Among a number of tested compositions, the one exhibiting the highest bioactivity index is the well-known trademarked 45S5 Bioglass®. The topic received increasing attention particularly after 1985 when this material entered in the market of biomedical devices, inspiring many other investigations aiming at further exploring the in vitro and in vivo performances of this BG, or developing other related BG compositions. The research efforts gradually revealed a number of shortcomings of 45S5 Bioglass®, mostly derived from its high sodium content, initially intended to decrease the melting temperature and accelerating the degradation of the silicate network over time. But the extensive release of sodium from 45S5 Bioglass® in the biological fluids creates a high pH cytotoxic environment. Other serious drawbacks include a fast degradation rate, and a poor sintering ability, which hinders the reliable fabrication of porous scaffolds. Therefore, sol-gel was regarded as an attractive alternative to prepare alkali-free BG compositions. The process uses inorganic and/or organic precursors, which undergo hydrolysis and condensation at room-temperature, being less costly. When properly conducted, the sol-gel process might result in amorphous structures with all the components intimately mixed at the atomic scale. Moreover, developing new better performing materials for bone tissue engineering is a growing concern, as the ageing of the world’s population leads to lower bone density and osteoporosis. This work describes the sol-gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO2 – 34 CaO – 4 MgO – 2 P2O5 (mol%) was prepared using acidified distilled water as single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The results of XRD of samples calcined within the temperature range from 600-900 ºC demonstrated that amorphous nature was maintained until 800 ºC, followed by partial crystallization at 900 ºC. The specific surface area, an important factor in osteoconduction, was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m2/g at 600 ºC down to 2.2 ± 0.1 m2/g at 900 ºC, being accompanied consistent changes in average pore size and agreeing pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering.

Most of the mid-high permeability sandstone oilfields in China have entered the ultra-high water cut stage, accompanied with the highly-dispersed residual oil, and the control effect of mi-cro-heterogeneity on the residual oil is increasingly prominent. Understanding the microscopic characteristics of pore structural and its evolution during the long-term waterflooding is critical for enhancing the accuracy and efficiency of oil field exploitation. While the previous insights paid more attention to the geometrical and morphological features of pore structure and ignores the relation of pore structure with the fluid flow capacity. In this study, we propose a microscopic pore structure classification method considering pore size and local permeable capacity, which realizes the physical classification and quantitative evaluation of pore structure characteristics for different permeability rocks. The micro-pore structure is classified into 6 types based on the key evaluation parameters of pore diameter and flow flux area. By taking six mid-high permea-bility sandstone core samples from Daqing oilfield in China, a series of long-term waterflooding experiments are carried out and the interior pore structure was captured using high precision CT scanning technique. The results reveals that high-permeability reservoirs exhibit concentrated pores diameters and finer throats, whereas mid-permeability reservoirs exhibit smaller pores and throats in greater quantity. With the increase of water injection volumes, the permeable ca-pacity and connectivity of the high-connectivity pore space in ultra-high- and high-permeability reservoirs are enhanced, and in mid-permeability reservoirs, the micro-heterogeneity intensifies the increase in low-connectivity small pores. These findings provide new insights for the micro-scopic heterogeneity and a solid theoretical basis for investigating the occurrence of microscopic residual oil and optimising enhanced oil recovery strategies at the late stage of ultra-high water cut.

Biometric fingerprint identification hinges on the reliability of its sensors, however, calibrating and standardizing these sensors poses significant challenges, particularly in regard to repeatability and data diversity. To tackle these issues, we propose methodologies for fabricating synthetic 3D fingerprint targets, or phantoms, that closely emulate real human fingerprints. These phantoms enable the precise evaluation and validation of fingerprint sensors under controlled and repeatable conditions. Our research employs laser engraving, 3D printing, and CNC machining techniques, utilizing different materials. We assess the phantoms' fidelity to synthetic fingerprint patterns, intra-class variability, and interoperability across different manufacturing methods. The findings demonstrate that a combination of laser engraving or CNC machining with silicone casting produces finger-like shaped phantoms with high accuracy and consistency for rolled fingerprint recordings. For slap recordings, direct laser engraving of flat silicone targets excels and in the contactless fingerprint sensor setting, 3D printing and silicone filling provides the most favorable attributes. Our work enables a comprehensive, method-independent comparison of various fabrication methodologies, offering a unique perspective on the strengths and weaknesses of each approach. This facilitates a broader understanding of fingerprint recognition system validation and performance assessment.

Enteroaggregative Escherichia coli (EAEC) are highly heterogeneous in virulence; we wanted to understand the pathogenic potential of EAEC isolated various clinical and non-clinical sources in an animal model. We infected male BALB/c mice in six mice/group with 50 EAEC isolates, isolated from clinical and non-clinical sources. We studied colonization, weight loss, stool shedding, inflammatory markers and its relationship with 21 virulence genes and phylogroups, EAEC organ burden and histopathological changes. We detected significantly more inflammatory changes and fecal lactoferrin and calprotectin levels in mice infected with EAEC isolated from symptomatic cases. In clinical EAEC isolates, the presence of chromosomal genes {(aap (46%), aaiC (23.3%), and SPATEs (pet (13.3%), sat (20%), sigA and pic (6.6%)}, adhesive variants {(agg4A (53.3%), aggA (53.3%), aafA (36.6%), agg3A (40%)} of EAEC, and master regulator gene aggR (66.6%) were associated with higher levels of lactoferrin and calprotectin. Also, 70% (9/13) of EAEC isolated from acute diarrheal cases bearing chuA (70%) in our study were assigned to group B2 (4 isolates) and D (5 isolates). Real-time PCR analysis revealed that colonization by EAEC strains from different clinical and non-clinical sources occurs up to 10-15 days of life. Even from non-diarrhoeal stools and non-clinical sources, had the potential to cause prolonged colonization, weight loss, and inflammation in the intestine though the degree varied. Moreover, better understanding of EAEC pathogenic pathways is desperately needed in different clinical scenarios.

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

A case-crossover study examined how PM_2.5 from Asian Dust Storms (ADS) affects the number of emergency room (ER) admissions for cardiovascular diseases (CVDs) and respiratory diseases (RDs). Our data indicated that PM_2.5 concentration from ADS was highly correlated with ER visits for CVDs and RDs. The odds ratios (OR) increased by 2.92 (95% CI: 1.22-5.08) and 1.86 (95% CI: 1.30-2.91) per increase 10 µg/m³ in PM_2.5 levels, for CVDs and RDs, respectively. A 10 µg/m³ increase in PM_2.5 from ADSs was significantly associated with increase in ER visits for CVDs among those 65 years of age and older (an increase of 2.77 in OR) and for females (an increase of 3.09 in OR). In contrast, PM_2.5 levels had a significant impact on RD ER visits among those under 65 years of age (OR=1.77). The risk of ER visits for CVDs increased on the day when the ADS occurred in Taiwan and the day after (lag 0 and lag 1); the corresponding risk increase for RDs only increased on the fifth day after the ADS (lag 5). In Taiwan’s late winter and spring, the severity of ER visits for CVDs and RDs increases. Environmental protection agencies should employ an early warning system for ADS to reduce high-risk groups’ exposure to PM_2.5.

In recent years, bioengineered and biotechnological products have gained tremendous attention to identify unique biologic features associated with oncology. To overwhelm the complexity of tumor personalized medicines (PM) or vaccines could be a promising way-out to be considered. Cancer is a heterogeneous disease. This characteristic variability of cancer provides itself to the emergent era of PM i.e., precision oncology. The prime objective of PM is merely to deliver the right treatment to the right patient at the right time. For instance, imatinib was effectively targeted chronic myeloid leukemia. To date, attainment in using PM approaches to cancer treatment have been mixed. The next-generation sequencing (NGS), and the use of several biomarkers (e.g., HER2, BRAF, ALK, etc.), to drive precise cancer treatment through a timely and cost-effective manner. In current review, author summarizes the advancement in the field of PM such as CRISPR-Cas9, NGS, pharmacogenomics, and the benefits of machine learning techniques. The precise communication between healthcare professionals, regulatory bodies, and patients is essential to translate advances in PM into immense benefits for patients with cancer globally.

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

Background: Annual influenza epidemics are a serious public health problem, causing particularly severe morbidity and mortality in high-risk groups. The study aimed to understand Poles' attitudes and beliefs towards influenza vaccinations in the flu season of 2022–2023, analyze preferences and unmet needs regarding influenza vaccinations, and examine the perception and acceptance of the influenza vaccine among individuals at risk of flu complications. Methods: A cross-sectional survey-based study was carried out on a sample of 1446 respondents. The Google Forms questionnaire was created and disseminated electronically using social media and e-mail. The pre-test was performed at the beginning of the project. Results: The majority of respondents (71%) could identify "high-risk groups" recommended for influenza vaccination. Furthermore, it was observed that individuals aged 21 to 59 demonstrated a higher level of knowledge in this regard compared to those below 20 and above 65 years old, and individuals with higher and medium education levels were much better at identifying risk groups for influenza virus infection. The majority of respondents (52.01%) reported receiving influenza vaccination at some point in the past, with 32.12% receiving it in the 2022–2023 flu season and 41.09% in the 2021–2022 season. The majority of respondents declaring acceptance of the vaccine for the 2022-2023 season were in the high-risk group. Only 17.28% of respondents declared receiving both influenza and SARS-CoV-2 vaccines in the 2022-2023 season, with the vast majority being respondents from the "high-risk group" (p

Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic antiinflamatory and antioxidant activity. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with a potential anti-inflammatory and antioxidant action for topical treatment of inflammatory skin disorders. The micro-emulsion system was obtained from a 20% CBD oil as hydrophobic phase, Labrasol/Plurol Oleique (1:1) as surfactant and cosurfactant (S/CoS) respectively and an aqueous vegetal extract obtained from S. ebulus L. ripe fruits, with a potential anti-oxidant and anti-inflammatory activity, as water phase. A pseudo-ternary phase diagram was elaborated, selecting an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after testing its reproducibility, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size by laser scattering, compatibility of components by differential scanning calorimetry and rheological properties using a rotational rheometer. The designed microemulsion showed good stability and a slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the water phase of the microemulsion were studied by in vitro diffusion experiments using flow-through diffusion cells in comparison to a CBD oil and a microemulsion only with CBD as active substance. It was evidenced that the inclusion of the original oil in microemulsions did not provoke a significant modification of the release of CBD, incorporating the possibility of including hydrophilic active compounds in the formulation, stablishing an interesting strategy for the development of future formulations.

In our study, we assessed the effects of verbenone, the most widely studied bark beetle aggregation inhibitor, on saproxylic beetles of a Mediterranean pine forest in Tuscany. Verbenone pouches were devised in the laboratory and then applied to Ips sexdentatus pheromone traps so that catches could be compared to those of traps with just the bait. The trial was carried out in spring-summer 2023, collecting insect catches every two weeks. A total of 9440 beetles were collected, belonging to 32 different families and 57 species. About 80% of captures were bark beetles, mainly Orthotomicus erosus. Beetle predators accounted for about 17% of the captures, with a total of 12 species. Some of these predator species had never been studied yet in relation to verbenone effects, like other saproxylic beetles recorded in this study. A significant reduction of captures was recorded for some beetles (e.g. I. sexdentatus and O. erosus), for other species no differences emerged, and in some cases captures increased significantly when verbenone was present in the traps (i.e.. Hylurgus ligniperda, Corticeus pini, Aulonium ruficorne). The diversity of caught saproxylic beetles increased significantly in verbenone traps, highlighting possible implications of the use of verbenone when managing bark beetle outbreaks.

MATERIAL AND METHOD: This is an observational analytical cohort study carried out on a total of 160 patients, divided into 4 groups: healthy, with myopia, with primary open-angle glaucoma (POAG), and with POAG and myopia together. The study variables were Bruch's membrane opening area (BMO), the thickness of the RNFL and the RGC layer using the Glaucoma Premium program of the OCT Spectralis of Heidelberg. RESULTS: Regarding the analysis between age and the thickness of the RNFL, significant results were found in the healthy and glaucoma groups with myopia, for the rest of the groups, although there are no significant results, the correlation is negative, the older the younger is the thickness. Regarding intraocular pressure (IOP), significant results have been found in the nasal sector in the glaucoma group. In the glaucoma with myopia group, statistically significant results have been obtained when analyzing the thickness of the RNFL with refraction. In the analysis between the thickness of the RNFL and the RGC layer, significant results were obtained in the myopia and glaucoma groups; in the group of glaucoma with myopia, it occurs in the superior temporal sector. CONCLUSION: In the case of myopic patients with glaucoma, damage at the functional, both the thickness of the RNFL, the RCG and the BMO-MRW are greater than other groups. All these alterations can be evaluated and monitored with the OCT Spectralis thanks to the programs it includes, making this instrument one of the best for an early diagnosis of glaucoma and the damage produced in myopic patients.

People experiencing homelessness are at risk from a number of co-morbidities including traumatic brain injury, mental health disorders and various infections. Little is known about the rehabilitation needs of this population. This study took advantage of unique access to a specialist ‘Access’ GP practice for people experiencing homelessness and a local inclusion health initiative to explore the five year period prevalence of these conditions in a population of people experiencing homelessness, through electronic case record searches; and identify barriers and facilitators to healthcare provision for this population in the context of an interdisciplinary and multi specialist inclusion health team, through semi structured interviews with 12 staff working in primary and secondary care who interact with this population. The five year period prevalence of TBI, infections and mental health disorders was 9.5%, 4% and 22.8% respectively. Of those who had suffered a brain injury only 3, had accessed rehabilitation services. Themes from thematic analysis of interviews included: lack of resource, stigmatisation, under recognised multi-morbidity (including from brain injury) as barriers, trauma-informed, person-centred, adaptable, &amp; integrated and collaborative models of care as facilitators. The combination of quantitative and qualitative data suggests a potential role for rehabilitation medicine in inclusion health initiatives.

The Badenian/Sarmatian boundary in the Central Paratethyan basins is characterized by a change from open marine conditions during the late Badenian to the assumed brackish conditions during the early Sarmatian. Foraminiferal and palynological results of the Badenian/Sarmatian boundary interval in the Babczyn 2 borehole (SE Poland) showed that the studied interval accumulated under variable, unstable sedimentary conditions. The Badenian/Sarmatian boundary as correlated with a sudden extinction of stenohaline foraminifera is interpreted as due to the shallowing of the basin. The lack of foraminifera and palynomorphs just above the Badenian/Sarmatian boundary can reflect short-term anoxia. The composition of euryhaline assemblages characteristic for the lower Sarmatian part of the studied succession indicates marine to hypersaline conditions.

Satellite-based broad-scale (i.e., global and continental) human settlement data offer foundational information for diverse applications spanning climate hazard mitigation, sustainable development monitoring, spatial epidemiology, and demographic modeling. While many human settlement products report exceptional detection accuracies above 85%, there is a substantial blind spot in that product validation is typically centered on large urban areas rather than rural, small-scale settlements that are home to 3.4 billion people. In this study, we make use of a data-rich collection of 30 refugee settlements in Uganda to produce a targeted assessment of small-scale settlement detection by four broad-scale human settlement products: Global Human Settlements Built-Up Sentinel-2 (GHS-BUILT-S2), World Settlement Footprint (WSF), High Resolution Settlement Layer (HRSL), and Geo-Referenced Infrastructure and Demographic Data for Development (GRID3). We measured each product’s areal coverage within refugee settlements, assessed product detection accuracies in comparison to an independent dataset of 317,416 refugee settlement building footprints, and examined agreement between products. For refugee settlements established before 2016, the human settlement products had a low median F1-Score (F1) of 0.24, a high median false alarm rate of 0.59, and tended to only agree at locations of highest building density. Individually, WSF entirely overlooked 8 of the 30 study refugee settlements (median F1=0.17); GHS-BUILT-S2 underestimated the building footprint area by a median 50% (F1=0.15); GRID3 overestimated the building footprint area by a median 280% (F1=0.38); and HRSL underestimated the median area by 7% (F1=0.34). All products suffer from low detection accuracy and high false alarm rates, but GRID3 and HRSL, based on 0.5 meter resolution imagery, offer better detection accuracy than GHS-BUILT S2 and WSF, which are based on 10-30 meter resolution imagery. These results show that human settlement products have far to go in providing an accurate depiction of small-scale refugee settlements and would benefit from incorporating refugee settlements in training and validation of broad-scale human settlement detection.

This article presents a quantitative assessment of pedagogical support aimed at improving collaborative education at a modern technical university. The article analyzes the structural composition of the universal communicative competence in a foreign language to identify the advantages of the proposed content detailization. An algorithm for constructing educational and speech actions of students with the use of collaborative digital technology, regarding the monitoring and control of tools, is developed and theoretically justified. Microsoft Teams is offered as a platform for implementing digital collaborative learning technology. The didactic possibilities and methodological functions of Microsoft Teams in foreign language teaching are revealed. The digital technology of the collaborative learning algorithm is relevant for building collaborative actions is relevant, since it contributes to the development of the ability to solve common professional tasks. The algorithm of the dialogic communication, including problem, contradiction, conflict, intellectual difficulty, having general professional context as a stimulus to enhance the interaction in pair work is proposed as pedagogical support. The analysis and quantitative assessment of students' oral responses showed that the dialogue in a foreign language, based on the algorithmic component, is more structured and stimulates students' communication on relevant professional-oriented topics.

Very little is known about laboratory confirmed blood stream infections (LCBIs) in neonatal intensive care units (NICUs) in resource-limited settings. The aim of this cohort study was to determine the incidence, risk factors, and causative agents of LCBIs in a level-2 NICU in India. The diagnosis of LCBIs was established using the Centre for Disease Control, USA criteria. A predesigned questionnaire containing risk factors associated with LCBIs was filled-in. A total of 150 neonates (43% preterm) were included in the study. The overall incidence of LCBIs was 31%. The independent risk factors for LCBIs were: preterm neonates (relative risk (RR) 2.23), duration of NICU stay more than 14 days (RR 1.75), chorioamnionitis in the mother (RR 3.18), premature rupture of membrane in mothers (RR 2.32), neonate born through meconium-stained amniotic fluid (RR 2.32), malpresentation (RR 3.05), endotracheal intubation (RR 3.41), umbilical catheterization (RR 4.18), and ventilator-associated pneumonia (RR 3.17). The initiation of minimal enteral nutrition was protective from LCBIs (RR 0.22). The predominant causative organisms were gram-negative pathogens (58%). The results of the present study can be used to design antibiotic interventions to reduce LCBIs in resource-limited settings.

The present work consisted of an exploratory study aiming to evaluate in vitro the potential of AuNPs during Radiation Therapy (RT) in human pancreatic adenocarcinoma cells. AuNPs coated with hyaluronic and oleic acids (HAOA-AuNPs) or with bombesin peptides (BBN-AuNPs) were used. AuNPs were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering. BxPC-3 tumour cells were irradiated with a 6 MV X-rays beam, in the absence or presence of AuNPs. AFM showed that HAOA-AuNPs and BBN-AuNPs are spherical with a mean size of 83+-20 nm and 49+-12 nm, respectively. For RT alone, a reduction in cell viability of up to 33+-12% was obtained compared to the control (p ≤ 0.0001). HAOA-AuNPs alone at 200 and 400 μM showed a reduction in cell viability of 20+-4% and 35+-4%, respectively, while for BBN-AuNPs, at 50 and 200 μM, a reduction in cell viability of 25+-3% and 37+-3% was obtained, respectively, compared to the control (p < 0.0001). At 72 h post-irradiation, a decrease in cell viability of 26+-3% and 22+-2% between RT+HAOA-AuNPs at 400 μM and RT+BBN-AuNPs at 50 μM, compared to RT alone, was obtained (p < 0.004). The combination of RT with AuNPs led to a significant decrease in cell viability compared to the control, or RT alone, thus representing an improved effect.

The Leguminosae (legume family) is divided into three sub-families, the Caesalpiniodeae, Mimosoideae and Papilionoideae. Here, the literature on legume-rhizobia symbioses was reviewed, and genotypically characterised rhizobia related to the taxonomy of the legumes they were isolated from. Only data from field soils were considered. The objective of the work was to assess to what extent legume specificity for rhizobial symbiont is related to legume taxonomy. Bradyrhizobium spp. were the exclusive rhizobial symbionts of species in the Caesalpinioideae but data are limited. Where tested, species within the two Mimosoideae tribes, Ingeae and Mimoseae were nodulated by different rhizobial genera. Generally, Papilionoideae species with indeterminate nodules were promiscuous in relation to rhizobial symbionts but high specificity for rhizobial partners appears to hold at tribe level for the Fabeae (Rhizobium spp.), genus level for Medicago (Ensifer spp.), Cytisus (Bradyrhizobium spp.) and Lupinus (Bradyrhizobium spp.), and species level for Galega spp. (Neorhizobium galegeae), Hedysarum coronarium (Rhizobium sullae), Cicer arietinum (Mesorhizobium spp.) and New Zealand native Sophora spp. (Mesorhizobium spp.). High legume specificity for rhizobial symbionts was linked to specific rhizobial symbiosis genes. For Papilionoideae species with determinate nodules, the Dalbergieae were primarily nodulated by Bradyrhizobium but were promiscuous with respect to Bradyrhizobium spp. while those in the Desmodieae, Phaseoleae, Psoraleae and Loteae were promiscuous across different rhizobial genera. Possible advantages and disadvantages of high specificity or promiscuity are discussed.

Singapore, being a land-scarce country, is heavily dependent on imported food, which poses a challenge in ensuring food security. In addition, the substantial amount of food waste generated in Singapore further deepens food insecurity challenges, imposing enormous pressure on the country's food and land resources. In the recent years, valorising food waste streams into higher value products has been an increasing trend in tackling food wastage due to its economical and environmental benefits. This paper provides a thorough review on food waste valorisation in Singapore and summarizes critical information from the current food landscape to the food waste management strategies adopted. The review highlights the prototypes developed from food waste streams by the local research and development capabilities and the technological processing and techniques used for versatile applications ranging from food and nutraceuticals to urban agriculture. The challenges associated with the valorisation of food waste are also addressed. Two ambitious Initiatives by the Singapore government Zero Waste Plan and the 30-by-30 food security goal to encourage food waste valorisation are explored and presented. The review serves as a reference for other countries in ensuring food security and achieving sustainable development goals.

The Shimensi super-large tungsten polymetallic deposit is located in Late Jurassic- Early Cretaceous Porphyry-Skarn tungsten ore belt in the south Yangtze metallogenic belt. There are 3 types of mineralization: veinlet-disseminated type, thick quartze vein type and hydrothermal crypto-explosive breccia type. Based on geological studies, this paper presents new petrographic, microthermometric, laser Raman spectroscopic and hydrogen and oxygen isotope research of the fluid inclusions from the deposit. The results show that there are five different types of fluid inclusions: liquid-rich inclusions, vapor-rich inclusions, pure liquid inclusions, pure vapor inclusions, and fluid inclusions containing a solid crystal. The homogenization temperatures of the fluid inclusion range from 140℃-270℃, the salinities are 3%-5% NaCleq and the densities of ore-forming fluid range from 0.64 g/cm3 to 0.99 g/cm3. For the analyses of Laser Raman spectroscopic, the ore-forming fluids can be approximated by a Ca2+-Na+-SO42--Cl- fluid system with small amount of CO2, CH4 and N2. Otherwise, the datas of the pressure, pH and Eh show a fluid metallogenic environment of low pressure, weak acid and weak reduction. The values of the homogenization temperature in 3 types of orebodies suggest that the mineralization is characterized by the decrease of the temperature under the condition of the fluid immiscibility. The H-O isotope values are interpreted to indicate that the ore-forming fluids are mainly composed of magmatic water, and also the meteoric water was added with the process of the magma rising.

Accurately estimating shrub biomass in arid and semi-arid regions is critical for understanding ecosystem productivity and carbon stocks at both local and global scales. However, capturing the shrub biomass accurately by satellite observations is challenging due to the short and sparse features of shrubs. In this study, we presented a framework to estimate shrub biomass at a 10m spatial resolution by integrating ground in-situ data, unmanned aerial vehicle (UAV), Sentinel-2, and Sentinel-1 observations. The pilot study was conducted in the Helan mountains of Ningxia province, China. First, the spatial distribution map of shrubland and other land cover types was generated in 2023. Then, a prediction model of shrub biomass was developed in a Random Forest Regression (RFR) approach driven by different predicted variable datasets based on in-situ measurements, UAV, and satellite images. Finally, the developed model was used to produce the biomass map of shrubland in 2023. The uncertainty was characterized by creating a standard deviation (SD) map using the Leave-One-Out Cross-Validation (LOOCV) method in the shrub biomass estimates. The resultant shrubland distribution map in 2023 has an F1 score of 0.92. The shrub biomass model driven by spectral bands and vegetation indices (R2= 0.62) demonstrated superior performance than that only driven by spectral bands (R2=0.33) or vegetation indices (R2=0.55). The uncertainty of the estimated biomass was lower than 4%, with the lowest values (<2%) happening in the high shrub coverage (>30%) and biomass production (>30kg/m2) regions. Furthermore, the findings show that the magnitude of shrub biomass was affected by the aridity and precipitation significantly in the study region. This study provides a workflow to accurately monitor the biomass of shrublands in a complicated environment based on remote sensing images from multi-platform observations.

A testable hypothesis with quantitative predictions is put forward, proposing that strong acids produced on land are a major cause of increasing atmospheric pCO2. Our modelling analysis of reactions by dissolved inorganic carbon shows that increasing atmospheric CO2 could be caused thermodynamically by falling land surface pH values. This hypothesis challenges the imbalance assumed between the global uptake of CO2 by photosynthesis and emissions of CO2 from all sources, including the combustion of fossil fuels. Strong acids generated by oxygen from reduced nitrogen and sulphur emits CO2 almost stoichiometrically from dissolved bicarbonate in the pH range of most global soils from pH 6.5 to above 8. Each general decrease of aqueous pH value of 0.01 units from acidification of surface water potentially increases the pCO2 in the atmosphere by about 7 ppmv. Contrary to prevailing assumptions that CO2 emissions from combusting fossil fuels can remain in the atmosphere for more than a millennium, such emissions may be partly nullified by global greening from enhanced rates of photosynthesis as well as oceanic absorption. The surface pH value of the ocean has been shown to decrease as atmospheric pCO2 rises. Therefore, our qualitative estimates of increasing atmospheric CO2 driven by irreversible acidification on land are critical and need broad scale validation. To the extent that significant acidification of the land is occurring, through export of alkaline produce, the use of artificial nitrogen fertilisation and possible other causes, the prevailing methods of reducing CO2 emissions will fail. However, these acidifying processes on land have not been considered by previous biogeochemical reviews. Despite counter measures, including carbon capture and geological storage, the increasing Keeling curve for pCO2 may continue to rise because zero carbon policies do not address such a major cause. This hypothesis can be tested by in situ experiments in neutral soils and water, designed to compare CO2 emissions under the acidifying conditions described in this article with those when corrective counter measures are applied.

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

As previous study in many countries shown that stroke patient onsets are not distributed randomly, but associate with meteorological factors. However, the relationship between stroke occurence and meteorological factors remain unknown in mountain area in Guizhou China. This paper firstly introduces multi-source fusion data which is integrated by the mountain meteorological factor, geographic mapping elevation information data and stroke population monitoring of Guizhou province. Mainly elaborates from a few aspects, which concludes data collection, data sorting, data extraction, data cleaning and data production in detail. A completed and detailed meteorological stroke data set was successfully established and multi-source data fusion was realized by the use of Gbase and unified data service interface of Guizhou meteorological big data cloud platform. And we report the impact of meteorological variables in Guizhou mountain area climate on stroke. In this study, we performed a statistical fusion data between January 2017 and December 2020 about stroke incidence rate and meteorological factors respectively, for instance, concerning the mean (Mean), maximum (Max), minimum (Min), median (Median), standard deviation (Std) . We calculated stroke rates (date stroke occurence)/(year stroke occurence) and we investigated the distribution of days included in the label. Results: the distribution of the incidence rate basically conforms to the normal distribution with the label Max 0.007399, label Min 0.000204, label Mean 0.002738, label Median 0.002643, label Std 0.00076. We observed a positive significant correlation of stroke incidence rate directly proportional to the daily temperature difference (between 0 and 20 degrees Celsius), as the value of this factor exhibits variation larger, the incidence rate is gradually increasing. And we investigated from the Pearson correlation coefficients that stroke incidence increasing when meteorological factors at low humidity (less than 40% (RH 80%), temperature higher than 31℃); the 24-hour daily temperature difference varies between 6 and 10℃ (6

Primary congenital hypothyroidism is readily diagnosed based on elevated plasma TSH levels. In contrast, in the rare disorders of thyroid hormone resistance, TSH and often also thyroid hormone levels are within the normal range. Thyroid hormone resistance is caused by defects in hormone metabolism, transport, or receptor activation and has the same severe consequences for childhood development as congenital hypothyroidism. A total of 23,522 data points from a large cohort of children and young adults were used to generate normal values and sex-specific percentiles for the ratio of free T3 to free T4 (fT3/fT4 ratio). The aim was to determine whether cases with genetically confirmed thyroid hormone resistance (MCT8, THRα, and SECSIBP2 defects) had an abnormal fT3/fT4 ratio. Indeed, we were able to demonstrate a clear separation of patient values for the fT3/fT4 ratio from normal and pathological controls (e.g., children with severe cerebral palsy). We therefore recommend the use of the fT3/fT4 ratio as a readily available screening parameter in children with developmental delay for the identification of thyroid hormone resistance syndromes. The fT3/fT4 ratio can be plotted on centile charts using our free online tool at http://www.thyroid-hormone-ratio.org that accepts various SI and non-SI units.

Rabies is a viral zoonotic disease caused by the lyssavirus and endemic to most tropical and sub-tropical areas of the world. This study reports on the occurrence of rabies in dogs and relates the results to the vaccination status of the dogs. A total of each of the 50 brain and 50 saliva samples from 100 dogs were tested for Lyssavirus using RT-PCR and visualized using gel electrophoresis. Additionally, a histopathological diagnosis of rabies was made on the brain samples. A lyssavirus positivity of 34 % was realized with 29/50 from brain and 5/50 from saliva being positive for rabies. Statistical significance was associated with vaccination (p=0.011) and health (p=0.0) statuses and attack by a stray dog prior to exhibition of signs of rabies (p=0.002). The rabid positive dogs had bitten at least 15 humans and a dog before their demise. This study confirms vaccination as an effective tool for the prevention of rabies. However, elimination of the disease is possible if there is an established and effective collaboration between veterinary and human medicine through one health.

This paper presents geometric analyses of welded frames after free relaxing and vibratory stress relief (VSR). Respected frames were tested components of a prototype packaging machine. Two types of relaxation were carried out to remove stresses introduced as a result of welding process. One of the frame was subjected to free relaxing, while the other one to accelerated vibration relaxing. Detection of the frame geometry changes was performed using a photogrammetric system. In addition, an evaluation of the geometry change was conducted for fifteen variants of steel frame support. A comparative analysis of the geometric deviations of the frames after free and vibratory stress relief confirmed the assumption that the frame after vibration stress relief better reproduces the nominal dimensions. Nevertheless, it should be emphasized that after vibratory stress relief the frame is not subject to further deformation, which is a desirable effect. In the case of free relaxing, the frame undergoes dimensional changes in a random manner. In summary, carrying out accelerated vibratory stress relief allows control of spontaneous dimensional changes in the designed frame of a packaging machine resulting from spontaneous relaxation of stresses arising from the welding process. The shortening of the relaxation process of the welded frame is also an unquestionable advantage.

Bigeye grunt Brachydeuterus auritus is an important economic species in the waters off Sierra Leone in West Africa, with great ecological value. Based on the survey data of bottom trawl nets from 6 voyages from 2019 to 2021, the body weight-length relationship (WLR), as well as their relative fatness, were studied in depth using the method of body length and its corresponding mean body weight. This study fitted the WLR of bigeye grunt by gender, calculated its fullness, and analyzed the influence of environmental factors. The results showed that month and gender had a significant impact on body length and weight distribution (P&lt;0.01). There was a highly significant negative correlation (P&lt;0.01) between the condition factor (a) and the allometric factor (b) in the WLR, and salinity significantly affects b (P&lt;0.05). The (lga)/b ratio was less affected by environmental factors which may be related to the body size and density of the fish. The difference in b between male and female populations was extremely significant (P&lt;0.01). The relative fatness had significant seasonal variation characteristics, with highly significant effects of sex and body length (P&lt;0.01). With increasing body length, the relative fatness showed two types of changes, continuously increasing and first increasing then decreasing, with salinity and b significantly affecting the type of change (P&lt;0.05) and depth having a highly significant effect (P&lt;0.01). The bigeye grunt off the coast Sierra Leone exhibited significant seasonal growth characteristics, with significant differences in growth characteristics between male and female individuals. This study suggested that salinity may be the main factor affecting its growth and development. In addition, this study hypothesised that the peak breeding season may occur during the dry season, beginning in December and ending before April of the following year. The study provides updated and more comprehensive insights into the biology and ecology of the bigeye grunt offshore Sierra Leone, West Africa, which can provide scientific basis for its resource assessment, development and utilization, and resource management.

Hydrogels have gained significant attention as vehicles for transdermal delivery systems. These polymeric-structured substances have been implemented in pharmaceutical and cosmetic applications. Many factors are employed in their preparation. Light, pH, temperature and specific molecules ligands are commonly used in the production of hydrogels. The Transdermal delivery system (TDD) is a widely used route, used to deliver actives/drugs via the skin. Hydrogels as a TDD have been shown to be efficient in enhancing the efficacy in delivering the actives and drugs. The aim of this review is to discuss the hydrogels application in both dermatological therapeutic and cosmetic applications, covering the types, and properties of hydrogel polymer networks. Furthermore, this review presents one of the most extensively used polymers (Hyaluronic acid HA) in this field and discusses the properties, preparation methods and applications of HA hydrogel patches as a delivery system, including methods of loading the actives and the releasing of these actives from them.

Directed energy deposition (DED) parameters were determined for near-β alloy Ti-55511 by employing statistical design of experiments (DOE) methods. Parameters resulting in fully dense freeform deposits were identified using two sequential DOEs. Single laser tracks were printed with several laser power, traverse rate, and powder feed rate settings in an initial DOE to identify promising build parameters. Capture efficiency and effective deposition rate were used to characterize and rank the single track deposits. The best parameters were then used to print solid cube with various X-Y and Z-overlaps (different hatch spacing, HS, and layer thickness, ZS) in a second DOE. Suitable deposition parameters were selected based on cube density and microstructure and were used to fabricate larger tensile samples for mechanical testing. Multiple parameter sets were found to provide dense Ti-55511 deposits with acceptable mechanical properties and parametric models showed statistical significance.

Consumption of refined foods and beverages high in sugar make the teeth susceptible to the formation of biofilm, and lead to dental caries and diseases of the oral cavity such as periodontitis and periodontal disease. The aim of the present study was to determine the ability of selected probiotics to inhibit growth and biofilm formation by the cariogenic bacterium Streptococcus mutans in vitro. We screened strains of latic acid bacteria (LAB) (n=120) from the Bioresources Collection and Research Center (BCRC), saliva of healthy adults and infant stool. The antimicrobial activity of LAB in vitro was evaluated by agar spot culture and co-culture of the S. mutans strains. We determined the effect of heating and dilution factors (2- and 4-fold) on the antagonistic activity of LAB. Antagonistic substances in the spent culture suspensions (SCS) of LAB were precipitated by extraction with ammonium sulphate and chloroform to characterise the protein and lipophilic fractions. Results of co-culturing show that the SCS of the three LAB strains (Lactobacillus pentosus 13-1, 13-4 and Lactobacillus crispatus BCRC 14618) subjected to heat treatment showed significantly high antimicrobial activity. We found that substances produced by L. pentosus 13-4 which have the potential to exhibit antimicrobial properties might be lipophilic proteins. Additionally, we infer that the mechanism of reducing biofilm formation by Lactobacillus strains is associated with sucrose-dependent cell–cell adhesion and the gtfC level of glucosyltransferases (Gtfs) in the biofilm. Native LAB strains screened in our study may be used in chewing gums and other processed foods for preventing tooth decay.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

Objective: This research was aimed to estimate the anti-fatigue effects of arecoline and elucidate its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Methods: Seventy-two male C57BL/6 mice were randomly allocated into six groups: a control group, a SD-induced fatigue model group, a group receiving Rhodiola Rosea capsules (2.5 mg/kg), and arecoline groups administered low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on the mouse fatigue-related behaviors was assessed by the behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. Enzyme-linked immunosorbent assays (ELISAs) were utilized to measure the levels of the relevant biochemical markers. Western blotting was employed to quantify the expression of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Results: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline significantly reduced both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased serum levels of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol, while elevated total testosterone, lactate dehydrogenase, and immunoglobulin G levels. Furthermore, it significantly increased superoxide dismutase(SOD), catalase(CAT), and glutathione peroxidase activity in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels were significantly increased, cytokine levels were markedly reduced, and the expression of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissue was significantly upregulated. Conclusion: The current study for the first time demonstrated that arecoline has significant anti-fatigue activity, and its mechanism of action is related to elevate the levels of glucose and lipid metabolism, relieve oxidative stress damage, inhibit neuroinflammatory response, regulate neurotransmitter levels and Keap1/Nrf2/HO-1 signaling pathway. The current study provides a new insight into the potential of arecoline in prevention and improvement of fatigue.

There is no doubt that seagrass beds constitute one of the most productive ecosystems in shallow coastal waters. Despite this, picoplankton in seagrass ecosystems has received relatively little attention. The purpose of this study was to compare picoplankton growth and mortality rates between seagrass and unvegetated habitats using chamber incubations. We tested two main hypotheses: (i) incubation with seagrass would result in higher bacterial growth rates due to increased DOM release from seagrass photosynthesis, and (ii) Synechococcus spp. would be lower in the presence of seagrass due to competition for inorganic nutrients. Our results showed bacterial growth rates of 2.31 and 2.44 d–1 without and with seagrass, respectively. In seagrass chambers, bacterial growth was higher than that in non-seagrass chambers, suggesting that organic carbon coming from the seagrass community may support bacterial production. Furthermore, we observed a negative Synechococcus spp. growth rate (-0.9 d–1) in the seagrass treatment, likely reflecting nutrient competition with the seagrass. Small-scale chambers proved to be a useful tool for studying the factors controlling spatial and temporal patterns of picoplankton across different habitats. Furthermore, future studies should examine picoplankton growth over a wider range of spatial scales in seagrass beds and adjacent unvegetated sediment.

Rapid urbanization has profoundly impacted regional ecosystem services. However, few studies have comprehensively examined the spatiotemporal relationship between multi-dimensional urbanization processes and ecosystem services. This study investigated the spatiotemporal dynamics of urbanization and ecosystem services value (ESV) in the Yangtze River Delta (YRD) region, China, from 2010 to 2020. We measured urbanization levels from two dimensions: Urbanization I (demographic, economic, and land urbanization) and Urbanization II (social and cultural urbanization). The ESV was quantified using the equivalent factor method. The results showed that: (1) The level of Urbanization I increased steadily, while Urbanization II, despite a lower level, exhibited a faster growth rate, especially after 2017; (2) The total ESV declined, with regulating services decreasing the most. The spatial distribution of ESV showed significant heterogeneity; (3) Urbanization had a significant negative correlation with ESV, with Urbanization I exerting a greater negative impact than Urbanization II; (4) The eastern region was dominated by high urbanization-low ESV clusters, while the western region was characterized by low urbanization-high ESV clusters. The findings provide important implications for regional sustainable development and can serve as a reference for related studies in other rapidly urbanizing areas around the world.

Background: Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, which is shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of anti-inflammatory and pro-inflammatory signatures using microarray-based gene ex-pression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, CD20) and immune checkpoints (PD-1) were also evaluated. Materials and Methods: The study investigated the prognostic significance of an an-ti-inflammatory interleukin signature (IL-12, IL-21, IFN-γ) and a pro-inflammatory inter-leukin signature (IL-4, IL-5, IL-10, IL-13, IL-17, CXCL1) for metastasis-free survival (MFS) using Kaplan-Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman-Rho correlation coef-ficient. Results: Kaplan-Meier curves revealed that the prognostic significance of the an-ti-inflammatory signature was specifically pronounced in the basal-like subtype (p=0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290-0.741; p=0.001). Higher expression of the anti-inflammatory interleukin signature was associated with longer MFS. The pro-inflammatory interleukin signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p=0.034). Strong cor-relations were found between the anti-inflammatory signature and CD8 expression (ρ=0.391; p

The objective of the present contribution was to design and characterize resveratrol (RSV) and tocopherol (TOC) loaded 11S quinoa seed protein nanocomplexes. Firstly, molecular docking was performed to describe the probable binding sites between protein and ligands. Isothermal titration calorimetry allowed to obtain the thermodynamic parameters that described the molecular interactions between RSV or TOC with the protein. 11S globulin intrinsic fluorescence spectra showed a quenching effect exerted by RSV and TOC, demonstrating protein-bioactive compounds interactions. Stern-Volmer, Scatchard and Förster resonance energy transfer models application confirmed static quenching and allowed to obtain parameters that described the 11S-RSV or 11S-TOC complexation process. Secondly, protein aggregation induced by bioactive compounds interactions was confirmed by dynamic light scattering and atomic force microscopy with diameters <150 nm, detected by both techniques. Finally, it was found that antioxidant capacity of single 11S globulin did not decrease, meanwhile was additive for 11S-RSV. These nanocomplexes could constitute a real platform for the design of nutraceutical products.

Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolism and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

Neuronal cells are believed to rely on autophagy to maintain cellular homeostasis. Nevertheless, autophagy may be a therapeutic target for neurodegenerative diseases because of the role it plays in neuronal cell death. Despite Beclin 1 association with autophagy and apoptosis, the molecular mechanisms that underlie Tau-induced vesicular pathology and Tau protein aggregates in humans remain poorly understood. Here, we set out to examine the role of three genes-ATG14L, Beclin 1 and VPS34- in autophagy nucleation failure-associated Tau disorders in fruit fly models. We found that either reduced ATG14L levels improve neuronal outcomes, or transgenic expression of ATG6/Beclin 1 greatly reduced age-dependent neurodegeneration and Tau pathology; whereas, the loss of Beclin 1 exacerbated these effects. Prior to p-Tau accumulation, the neuronal Beclin 1 network is critical for reducing p-Tau accumulation, indicating that the loss of Beclin 1 causes Tau pathology and neurodegeneration. As neurodegeneration progressed, glial cells showed an upregulation of vesicular Beclin 1 immunoreactivities. The reduced VPS34 also resulted in p-Tau accumulation, suggesting that neurons require both Beclin 1 and VPS34 to reduce p-Tau accumulation. Our results provide mechanistic insight into the molecular pathways that cause age-dependent Tau pathology and neurodegeneration due to an excess of autophagy nucleation processes and autophagy activity, and we derive novel inferences on the therapeutic possibilities of rebalanced Beclin 1 network by reducing autophagic specific nucleation component of ATG14L.

In the study of relativistic jets one of the key open questions is their interaction with the environment on the microscopic level. Here, we study the initial evolution of both electron–proton (e^- - p⁺) and electron–positron (e^±) relativistic jets containing helical magnetic fields, focusing on their interaction with an ambient plasma. We have performed simulations of "global" jets containing helical magnetic fields in order to examine how helical magnetic fields affect kinetic instabilities such as the Weibel instability, the kinetic Kelvin-Helmholtz instability (kKHI) and the Mushroom instability (MI). In our initial simulation study these kinetic instabilities are suppressed and new types of instabilities can grow. In the e^- - p⁺ jet simulation recollimation-like instability occurs and jet electrons are strongly perturbed. In the e^± jet simulation a recollimation-like instability occurs at early times followed by a kinetic instability and the general structure is similar to a simulation without helical magnetic field. Simulations using much larger systems are required in order to thoroughly follow the evolution of global jets containing helical magnetic fields.

Biopolymer gels have gained tremendous potential for therapeutic applications due to their biocompatibility, biodegradability, and ability to adsorb and bind biological fluids, making them attractive for drug delivery and therapy. The versatility of biopolymer gels in theranostic backgrounds, with a focus on integrating imaging features and facilitating real-time monitoring of drug delivery. Different methods of delivery are explored imaging agents into biopolymer gels, including encapsulation, surface functionalization, nanoparticle encapsulation and layer-by-layer assembly techniques. Integration of Agents and Real-Time Monitoring Drug Delivery We summarize the synthesis methods, general properties, and mechanisms of biopolymer gels functionality, demonstrating their broad applications as multimodal systems for imaging-based therapeutics. These techniques not only enable multiple imaging but also provide signal enhancement and imaging a targeted facilitates, increasing the diagnostic accuracy and therapeutic efficacy. In addition, current techniques for incorporating imaging agents into biopolymer gels are discussed, and their role in precise drug delivery and monitoring.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

The feeling of beauty is one of the positive human feelings. In architecture and design, it is associated with forms appropriate to their purpose. The usefulness of products to meet needs is also important. They are well received by users. The task of designers is to achieve perfection in their work. The rational design and use of artificial living environments are expressions of concern for natural resources (sustainable environment). These issues are addressed, i.e., by an interdisciplinary initiative of the New European Bauhaus. The aim of the paper is to expand knowledge about beauty and utility. They are important when choosing mass-produced goods. The article uses research methods: interpretive research, analyses, comparisons, logical argumentation, etc. Experimental qualitative research using a checklist was used. The results expand the knowledge on the selected topic and research scope of the research of the paper. The survey can be used to rationally evaluate architecture, interiors, and design facilities. It can be helpful for various aesthetic and functional strategies dedicated to different users. The paper demonstrates the role of beauty and functionality in the built environment. They are analyzed in the context of social and technical conditions, as well as contemporary sustainable design

The paper presents a new type of hydraulic clutch operating with magnetorheological (MR) fluids and the results achieved from both theoretical analysis and experimental measurement. The hy-draulic clutch system of its own design with MR working fluid and a rotating magnetic field lo-cated is designed. The principle of this clutch is to use a rotating magnetic field created by an al-ternating current electromagnet to set the MR fluid in motion. In the tests of the hydraulic clutch with a rotating magnetic field, MR fluid produced on their own, consisting of solid iron particles of various diameters mixed with a silicone oil, are used as working fluids. The rheological properties of MR fluids are assessed on the basis of tests carried out with a Brookfield DV2T rheometer equipped with a magnetic device for generating the magnetic field of its own design. The char-acteristics of the hydraulic clutch with MR working fluid and the rotating magnetic field are tested on a specially built test stand. As a result of the research, it has been found that the torque transmitted by the clutch is the greater, the higher the rotational speed of the magnetic field and the lower the rotational speed of the beaker in which the working fluid is placed, and that the greatest torque occurs for the working fluid with the highest iron content. Based on the analysis of the structure and characteristics of the clutch in which the magnetic field is used, it has been shown that the design of the developed clutch is similar to that of an induction clutch, and its characteristics correspond to the characteristics of the eddy current clutch. Therefore, the proposed new clutch working with MR fluid and the rotating magnetic field can be applied to stationary power transmission system similarly to an eddy current clutch.

Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have an elevated resistance to exogenous antimicrobial peptides (AMPs) – both, with regard to peptide bulk concentration in the medium, and the numbers of peptide molecules per cell. By monitoring integration of the AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy-coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.