Abstract: An efficient and environmentally Pumice as a new catalyst for designing of 3,4- dihydropyrimidin-2(1H) ones / thiones via one-pot multi component condensation of aromatic aldehydes, urea/ thiourea and ethyl acetoacetate or acetyl acetone in excellent yields (96-99 %). The advantages using of this new catalyst is very cheap, available, non-toxic, stable under thermal conditions, easy work-up, improved yields, the product of reaction is very pure without using chromatographic methods and solvent free conditions.

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS) and Long COVID are characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and Long COVID, suggesting that use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation, as well as neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and Long COVID.

In this multicenter, retrospective study we evaluated the added value of magnetic resonance dispersion imaging (MRDI) to standard multiparametric MRI (mpMRI) for PCa detection. The study included 76 patients - 51 with clinically significant prostate cancer (csPCa), who underwent radical prostatectomy and had an mpMRI including dynamic contrast enhanced-MRI. Two radiologists performed three separate randomized scorings based on mpMRI, MRDI and mpMRI+MRDI. Radical prostatectomy histopathology was used as the reference standard. Imaging and histopathology were both scored according to the Prostate Imaging-Reporting and Data System V2.0 sector map. Sensitivity and specificity for PCa detection were evaluated for mpMRI, MRDI and mpMRI+MRDI. Inter- and intra-observer variability for both radiologists were evaluated using Cohen’s Kappa. On a per patient level, sensitivity for csPCa for radiologist 1 (R1) for mpMRI, MRDI and mpMRI+MRDI were 0.94, 0.82 and 0.94, respectively. For the second radiologist (R2) these were 0.78, 0.94 and 0.96. R1 detected 4% additional csPCa cases using MRDI compared to mpMRI and R2 detected 20% extra csPCa cases using MRDI. Inter-observer agreement was significant only for MRDI (Cohen’s kappa = 0.4250, p=0.004). The results of this study show the potential of MRDI to improve interobserver variability and the detection of csPCa.

In this research we are reporting gas sensing properties of TiO_2-x/TiO₂-based hetero-structure, which was ‘self-heated’ by current that at constant potential passed through the structure. Amperometric measurements were applied for the evaluation of sensor response towards ethanol, methanol, n-propanol and acetone gases/vapors. The sensitivity towards these gases was based on electrical resistance changes, which were determined by amperometric measurements of current at fixed voltage applied between Pt-based contacts/electrodes deposited on TiO_2-x/TiO₂-based layer. XRD analysis revealed the formation of TiO_2-x/TiO₂-based hetero-structure, which is mainly based on Ti₃O₅/TiO₂ formed during hydro-thermal oxidation based sensing layer preparation process. Additionally, photoluminescence and time-resolved photoluminescence decay kinetics based signals of this sensing structure revealed the presence of TiO₂ mainly in the anatase phase in the TiO_2-x/TiO₂-based hetero-structure, which was formed at 400°C annealing temperature. The evaluation of TiO_2-x/TiO₂-based gas sensing layer was performed at several different temperatures (25°C, 72°C, 150°C, 180°C) and at these temperatures different sensitivity to aforementioned gaseous materials was determined.

Aimed to obtain purple garlic varieties, 360 bolting bulbs from the Protected Geographical Indication (PGI) “Las Pedroñeras” were selected for their size, and the presence of abundant external scales. After a further selection, 243 out of the 360 bulbs were discarded due to undesired characteristics, as light purple color, high number of small cloves, cloves affected by Fusarium spp. and mites, among other. It was stablished that each bulb would give rise to a family. Thus, 117 families were planted under a random design during season 2021-2022. Either physiological, morphological and phenological traits were assessed for each family, and the affectations by pest and pathogens were also controlled. After the assessment of this trial, 103 out 117 families remained in the program, and were used for the establishment of a second trial the next season. Unlike the first trial, after the evaluations only 23 families remained in the program. There was observed a high variability for most of traits, with a great influence of families. The phenotypic behavior of families was significative influenced by environment, highlighting the need of their assessment under different environmental conditions. The high variability registered for the target sample, opens the possibility to select new garlic varieties from this PGI.

Magnesium oxide is typically white and can be colorized with transition metal insertion by doping or by adsorption. We present the preparation of green colored hydroxide by the adsorption of nickel ions by porous MgO. MgO was prepared by the colloidal starch suspension method and used to remove nickel ions from the aqueous solution. The oxides and hydroxides, before and after adsorption, were characterized by X-ray diffraction technical, and show that a phase change occurs, a transition from periclase (MgO) to brucite (Mg(OH)2) due to the interaction with nickel salts (acetate, chloride, and nitrate). The FTIR spectrum corroborates with the DRX data on the formation of brucite like crystal lattices. The new samples present a green color, indicative of the incor-po-ration of the Ni2+ ions. Mixed oxides in the form of brucite were used in microbiological tests and showed action against fungi and bacteria, with bactericidal, bacteriostatic, or fungistatic function. Green brucite (NixMg1-x(OH)2) can be used as an inorganic pigment in white or colorless paints with a special biocidal property.

Studies show that although female soccer players often have shorter change of direction (COD) deficits than males, indicating different biomechanical profiles, there is lack of research on the impact of physical metrics on COD performance in females. The aim of this study was to analyze whether performance metrics based on speed, and jumping could explain the variation in %CODD in young female soccer players. Thirty-three highly trained adolescent female soccer players (age: 16. ± 0.95 years; height: 160.4 ± 5.22 cm; body mass: 55.7 ± 7.22 kg) performed COD180 tests, 10-m and 30-m sprint test and single leg countermovement and horizontal jumps. Acceleration in the first 10 meters of a sprint was identified as a significant predictor of COD180 performance (R2 = 28%), (R2 = 50%), (p

Reproductive disorders are a common event in modern reproductive medicine, occurring both in spontaneous and assisted pregnancies. Studies of the molecular mechanisms of implantation disorders in thin endometrium, including the study of gene transcriptional activity, have shed light on the identification of potential biological markers of endometrial receptivity. Background/Objectives: to reveal significantly dysregulated selected genes expression between RIF and RPL patients with thin endometrium. Methods: Endometrial samples were collected in the implantation window days (LH+7 – LH+10) of the natural menstrual cycle from RIF patients (n=20) and RPL patients (n=19). Ten genes were chosen as target genes regarding their possible relations with the implantation process. Total RNA was purified, reverse-transcribed; gene expression was quantified by RT-PCR. Results: The expression of the IL-15, INFG and HPRT1 genes were significantly decreased in RIF with thin endometrium patients compared to the RPL patients (log2 fold change=0.92, p=0.023 for IL-15, log2 fold change=1.24, p=0.046 for INFG, and log2 fold change=0.579, p=0.046 for HPRT1). There were not significant differences in expression of CXCL8, CXCL1, MMP10, C4BPA, TNC, VEGFB and HAND2 genes between groups. Conclusions: decreased expression of IL-15, INFG and HPRT1 genes was found in patients with RIF with thin endometrium compared to the endometrium of women with RPL. This has practical significance for clinicians for differentiated prescription of immunomodulatory therapy in patients undergoing ART programs.

Cannabidiol (CBD), a non-psychotropic main component of the Cannabis plant, is approved as a drug in the European Union (EU) under the name “Epidyolex”. However, the approval process as a food ingredient under the Novel Food Regulation was paused by the European Food Safety Authority (EFSA) due to a lack of safety data. Nevertheless, there is a growing, unregulated market in which CBD is advertised with various health claims and different dosage instructions. Of particular concern is its toxic effect on the liver and possible reproductive toxicity in humans. Studies suitable for calculating a benchmark dose were identified from the available data. Animal studies yielded a Benchmark Dose Lower Confidence Limit (BMDL) of 43 mg/kg bw/day, which translates into a safe human dose of approximately 15 mg/day. Only a Lowest Observed Adverse Effect Level (LOAEL) of 4.3 mg/kg bw/day could be identified from the human data. This updated risk assessment confirmed the Health-based Guidance Value (HBGV) of 10 mg/day based on human LOAEL. Despite existing data gaps, preliminary regulation appears advisable as the current form of the gray CBD market is unacceptable from the standpoint of consumer safety and protection.

A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such activities were discussed in terms of molecular descriptors like half-wave potentials, hydrophobicity and molar refractivity. Compounds 4 and 11 display the highest antiproliferative activity against the three cancer cells, therefore, they were subject to further studies. The in silico prediction of drug likeness, using pkCSM and SwissADME explorer online, shows that compound 11 is a suitable lead molecule to be developed. Furthermore, the expression of some key genes was studied in DU-145 cancer cells. They include genes involved in apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle regulation (CDC25A), cell cycle progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) and inflammatory pathways (TNF). Compound 11 displays an interesting profile because among these genes, mTOR was significantly less expressed as compared to control conditions. Molecular docking show that compound 11 has good affinity with mTOR, unraveling a potential inhibitory effect on this protein. Due to the key role of mTOR on tumor metabolism, we suggest that impaired DU-145 cells proliferation by compound 11 is caused by a reduced mTOR expression (less mTOR protein) and inhibitory activity on mTOR protein.

Arthroplasty is commonly performed to treat advanced osteoarthritis or other degenerative joint conditions, but it can also be considered for young patients with severe joint damage that significantly limits their functionality and quality of life. Young patients are still at risk of aseptic mobilization and bone resorption due to the phenomenon of stress-shielding that causes an uneven distribution of tensions along the femoral contact surface prosthesis. This phenomenon can be limited by appropriately choosing the material of the prosthesis or by varying its stiffness, making sure that its mechanical behavior simulates that of the femur as much as possible. The aim of this study is to evaluate the mechanical behavior of a prosthesis optimized both in shape and material and in comparing the results with a standard titanium prosthesis. Methods: Through three-dimensional modeling and the use of software finite element method (FEM) such as ANSYS we simulate the mechanical behavior of traditional prosthesis and prosthesis optimized topologically respecting the ASTM F2996-13 standard Results: With topological optimization there is a stress reduction from 987 Mpa to 810 Mpa with a mass reduction of 30%. With the use of carbon fiber, it is possible to further reduce stress to 509 Mpa. Conclusions: The reduction of stress on the femoral stem allows an optimal distribution of the load on the cortical bone thus decreasing the problem of stress-shielding.

The aim of this work is a comprehensive study of the effect of variable atomic composition and structural-phase state of (CoFeZr)x(MgF2)100-x nanocomposites (NCs) on their nonlinear electronic and magnetic/magneto-optical properties. Micrometer-thick nanocomposites layers on the glass substrates were obtained by ion-beam sputtering of a composite target in the argon atmosphere in a wide range of compositions x=9-51at.% The value of the resistive percolation threshold xper=34 at.%, determined from the concentration dependences of the electrical resistance of NCs, coincides with the beginning of nucleation of metallic nanocrystals CoFeZr in MgF2 dielectric matrix. The absolute value of maximum magnetoresistance of NCs is 2.4 % in a magnetic field of 5.5 kOe at x=25 at.%, up to the percolation threshold. Two maxima appear in the concentration dependences of magneto-optical transversal Kerr effect, one of which at x = 34 at.% corresponds to the formation of CoFeZr alloy nanocrystals of a hexagonal structure, and the second one at x=45 at.% corresponds to the phase transition of nanocrystals from a hexagonal to a cubic body-centered structure. The magnetic percolation threshold in (CoFeZr)x(MgF2)100-x system at xfm=34 at.% with the appearance of a hysteresis loop and a coercive force of Hc≈ 8 Oe, coincides with the resistive percolation threshold xper=34 at.%. Concentration dependence of the coercive force showed that at low contents of metallic alloy x<30 at.% NCs are superparamagnetic (Hc=0). With an increase of the alloy content, in the region of magnetic and resistive percolation thresholds NCs exhibit a magnetically soft ferromagnetic character and do not change it far beyond the percolation threshold with the maximum value of the coercive force Hc< 30 Oe. Decrease in magnetic order and soft ferromagnetic are influenced by the diamagnetic phase FeF2 that we discovered at the interface of magnetic nanocrystals CoFeZr with a dielectric matrix MgF2 by the Mössbauer spectroscopy.

Diffuse large B-cell lymphoma (DLBCL) requires a complete staging at diagnosis that may have prognostic and therapeutic implications. The role of bone marrow (BM) biopsy (BMB) is contro-versial in the era of nuclear-imaging techniques. We performed a comparative review of 25 studies focused on BM evaluation at DLBCL diagnosis, including at least two of the following techniques: BMB, flow cytometry, and positron emission tomography (PET-FDG). The report about BM involvement (BMi), diagnostic accuracy and prognostic significance was collected and compared among techniques. A concordance analysis between BMB, FCM and PET was also per-formed, and we deeply evaluated the implications of the different types of BMi: concordant by LBCL or discordant by low-grade B-cell lymphoma for both BMB and FCM, and focal or diffuse uptake pattern for PET. As main conclusion, BMB, FCM and PET are complementary tools which provide different and clinically relevant information in the assessment of BMi in newly DLBCL.

Rigid-hulled inflatable boats are extremely practical and popular nowadays. They offer a effective conciliation among usability and costs. Their stable and seaworthy behaviour is guaranteed by performing hydroplaning hulls coupled with unsinkable inflated tubes. At the same time, their design is often based on tradition and preconceptions. Rarely, the design assumptions are validated by the reality or, even, by deeper investigations. In this article, both numerical methods and experimental mechanics techniques are proposed as an essential way for supporting the designers in their decisive tasks. Three different situations are detailed where a numerical or an experimental approach shows its benefit inside the engineering design process: firstly permitting to investigate the behaviour of materials driving the fiberglass selection; then measuring the levels of stress and strain in the hull during sailing; finally, using all available information as a base for developing numerical models of the hull slamming in waves. Even if the discussion is focused on a rigid inflatable boat, large part of its considerations is relevant beyond this special case.

Background: This study aimed to estimate the prevalence of sexualized drug use (SDU) in gay, bisexual, and other men who have sex with men living with HIV (HIV+GBMSM) in Madrid during 2019/2020 and compare it with data from 2016/2017. Methods: We analysed the frequency of SDU in a sample of HIV+GBMSM attending HIV clinics, who participated in an anonymous online survey regarding sexual behaviour and recreational drug use. The association between SDU, sexual risk behaviours, and STIs was evaluated. The methodology employed in the present study(U-SEX-2) in 2019/2020 was consistent with that of a previous study(U-SEX-1) in 2016/2017. Results: The study included 424 HIV+GBMSM, with a mean age of 40(10.43) years. Overall, 94% (396) reported being sexually active. Additionally, 33% (140) had been diagnosed with an STI within the previous year. Moreover, 54% (229) had used drugs in the last year, 25% (107) engaged in SDU, and 15% (17) reported engagement in slamsex. After adjusting for confounding factors, SDU was associated with STIs, fisting, unprotected anal intercourse, and having &gt; 24 sexual partners in the last year. According to the DUDIT test scores, 76% (81) probably had problematic drug use (≥6 points), and 5% (8) probable drug dependence (≥25 points). When comparing the U-SEX-1(2016/2017) data with the U-SEX-2(2019/2020) data, no significant differences were found in the proportion of participants practicing SDU or slamsex. Conclusion: The prevalence of SDU among HIV+GBMSM has remained high in recent years and without significant changes. We observed a clear association between SDU, high-risk sexual behaviors, STIs, and the risk of drug related problems.

Starfish are keystone species as predators in benthic ecosystems, but when population outbreaks occur this can have devastating consequences ecologically. Furthermore, starfish outbreaks and invasions can have adverse impact economically by impacting shellfish aquaculture. Addressing the imperative need to proactively mitigate starfish invasions requires comprehensive research on their behavior and the underlying mechanisms of outbreaks. This review scrutinizes the historical patterns of outbreaks among diverse starfish species across various regions, delineates the factors contributing to the proliferation of Asterias amurensis in Chinese waters, articulates preventive and remedial strategies, and outlines the potential for sustainable utilization of starfish.

A typhoon-induced storm surge is considered one of the most severe coastal disasters in Taiwan. However, the combination of the storm surge and the astronomical tide called the storm tide can actually cause extreme flooding in coastal areas. This study implemented a two-dimensional hydrodynamic model to account for the interaction between tides and storm surges on the coast of Taiwan. The model was validated with observed water levels at Sauo Fish Port, Hualien Port, and Chenggong Fish Port under different historical typhoon events. The model results are in reasonable agreement with the measured data. The validated model was then used to evaluate the effects of the typhoon's intensity, bathymetric change, and the combination of the typhoon’s intensity and bathymetric change on the maximum storm tide and its distribution along the east coast of Taiwan. The results indicated that the maximum storm tide rises to 1.92 m under a typhoon with an intensity of a 100-year return period. The maximum storm tide increased from a baseline of 1.26 m to 2.63 m for a 90% bathymetric rise at Sauo Fish Port under the conditions of Typhoon Jangmi (2008). The combination of the intensity of a typhoon with a 100-year return period and a 90% bathymetric rise will result in a maximum storm tide exceeding 4 m, 2 m, and 3 m at Sauo Fish Port, Hualien Port, and Chenggong Fish Port, respectively. We also found that the distribution of the maximum storm tide on the east coast of Taiwan can expand significantly subject to the bathymetric rise.

The understanding of the ‘I-Thou’ relationship is the recognition that there is a relation between one and another in the world of human being. Each individual is an entity that carries a great deal of dignity and the good appropriation of this dignity fosters a great interpersonal relationship. For there to be any peace-relation among beings, a way to human enquiry and understanding of common good and advancement, there is a need for unbiasness. In Robert Kane’s view, it is through a positive I-Thou peace-relation which is achievable through ‘openness’ that human beings sustain the moral sphere, and avoid breaking it. It will help them to arrive at truth and a way forward to any debatable issue among human beings. Openness is a form of respect for another even in the face of divided or different opinions. Hence, in any deliberation of any sort, one has to take the part of Openness by limiting narrowness of vision and choose to respect every other point of view and way of life. This will help to foster the ideal I-Thou or inter-human beings’ peace-relation in the face of obstacles and conflicts. However, he seems to take for granted the uniqueness or difference in human thinking patterns and so he creates back the problem which he sets out to resolve by not giving a stand on what truth is and how human beings can get to it when openness fails. Adopting expository and analytic methods, the research argues that Kane’s idea of Openness appears to be a solution to sustain harmony among human beings.

Neuronal timing is critical for many brain functions such as perception and learning. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). Depolarization-induced analogue-digital facilitation (d-ADF) is a form of context-dependent synaptic facilitation that is induced by constant depolarization of the presynaptic neuron and is mediated by voltage inactivation of presynaptic Kv1 channels. Whether synaptic delay is modulated during d-ADF remains unclear. We show here that despite Pr is elevated during d-ADF at L5-L5 synapses, the synaptic delay is surprisingly unchanged, suggesting that both Pr- and AP-dependent changes in synaptic delay compensate for each other. We conclude that in contrast with other short- or long-term modulation of presynaptic release, timing is not affected during d-ADF because of the opposite interaction of Pr- and AP-dependent modulations of synaptic delay.

Small and Medium Enterprises (SMEs) play a crucial role in the European economy, representing the vast majority of businesses and a significant portion of employment. As the global business environment increasingly embraces digital supply chains, coopetition—collaborative competition—has emerged as a vital strategy for sustaining business growth and competitiveness. Despite its recognized importance, the potential of coopetition to enhance firm performance, particularly within SMEs, remains underexplored. This study aims to address this gap by developing and validating a reference model for coopetition networks specifically tailored for SMEs, utilizing the Service-Dominant framework. The research introduces a comprehensive model that guides the formation, management, and dissolution of coopetition networks throughout their lifecycle. The model is empirically validated within the Portuguese ornamental stone sector, providing insights into its practical applicability. Key findings demonstrate that the implementation of coopetition networks can significantly enhance production efficiency and operational effectiveness within SMEs. The study also highlights the critical role of technology as an enabler of service exchange and institutionalization within coopetition networks, facilitating collaborative interactions and value co-creation. While the study makes substantial contributions to the literature, it also identifies areas for further research, including the exploration of human dynamics within coopetition networks and the long-term sustainability of such networks. The findings offer valuable guidance for SMEs seeking to enhance their competitiveness and operational efficiency in an increasingly digital and interconnected business landscape.

The research showsThis paperstudy presents a theoretical model of sustainable tourism in protected areas based on the experiences obtained in fromthrough field work carried out in the Machalilla national park. The units of analysis that compose it and their theoretical–-methodological foundation, and as well as the indications for their practical implementation in the face of the changes imposed by future tourism are exposed. Using the deductive method, the an analysis of the problem and the general theories linked to sustainable tourism in protected areas was carried out., the This involved establishingment of the premises and the developingment of the objectives to reach conclusions on the topic studied. A qualitative investigation is presented that allowed for the integration of contributions from the analyszes carried out for the treatment and processing of information. Among the results, the systematization of theoretical models linked to tourism in protected areas and, from a practical point of view, the application of a sustainable tourism model was were achieved. The results show the relevance of the proposed theoretical model that is proposed as a contribution to the scientific development of tourism. This model highlights, the systemic nature of its components from a new perspective of analysis, which considerings the need for changes as a development factor.

A new clothing resistance model is described and applied to characterize the human thermal and moisture climates. The climate was described by the thermal (rcl,t) and evap-orative (rcl,e) resistances of comfortable, imaginary clothing. The key input variable of the model is the rate of sweating (λEsw). Since sweating is an individual-specific process, the model applies to the individual. The observations were carried out by a single individual in Martonvásár (Hungarian lowland, Central Europe) in the summer of 2023 and the winter of 2024. During the observations, the observer walked at a speed of 1.1-1.7 ms-1 in weather-appropriate clothing. Among the results, we would highlight the following: Dur-ing large environmental heat surpluses, the rcl,t values were found to be between 0.1-0.5 clo-t (clo-t = 0.155 m2·℃·W-1), while the rcl,e values fell between 0.4-0.8 clo-e (clo-e = 0.155 m2·hPa·W-1). The values of the parameters close to 0 were caused by intense sweating (λEsw > 200 Wm-2). The applicability of the model is limited and largely depends on the rela-tionship between λEsw and the metabolic heat flux density.

This paper delves into the concept of information within the context of conscious systems, emphasizing the pivotal role of entropy as a fundamental aspect in comprehending consciousness. Drawing on insights from Integrated Information Theory (IIT) and information theory, the argument posits that consciousness entails dynamic information processing, distinct from the static storage and retrieval model employed by modern computers. The intrinsic dynamics of neural systems are explored, illuminating how they integrate incoming stimuli into a unified state of subjective experience, thereby shaping conscious awareness. By considering entropy as a temporal and qualitative value, its significance in reducing uncertainty and facilitating adaptability in conscious systems is underscored. Through a series of principles, the intricate relationship between entropy, neural dynamics, and consciousness is elucidated. This analysis suggests the necessity of rethinking traditional notions of information when applied to conscious systems, highlighting the dynamic nature of consciousness and its interaction with the environment.

: Schizophrenia and schizoaffective disorder are generally treated with second-generation antipsychotic drugs. These drugs are mostly D2 and 5-HT2A antagonists. They improve positive schizophrenia symptoms sufficiently well; however, they ameliorate negative schizophrenia symptoms and cognitive functions to a small extent. We review novel antipsychotic drugs exerting a partial agonism at dopaminergic and serotonergic receptors such as cariprazine, brexipiprazole and lumateperone. Besides, the mechanisms of actions of non-anti-dopaminergic antipsychotic drugs are pointed out. Updated neural networks are used to explain the mechanism of action of M4 and M1 receptor agonists, for example xanomeline combined with trospium or emraclidine, and trace-amine-associated receptor 1 agonists (TAAR1), for example ulataront. Phase 3 clinical trials of new third generation antipsychotic drugs are presented. Novel antipsychotic drugs with a partial agonism at D2 and D3 receptors improve positive and negative schizophrenia symptoms as well as cognitive symptoms better than second generation antipsychotic drugs. Besides, they are well tolerated. M4 and M1 receptor agonists, i.e. xanomeline combined with trospium or emraclidine, and TAAR1 agonists, i.e. ulataront, have promising results in clinical trials; they well improve negative schizophrenia symptoms and cognitive functions. Phase 3 clinical trials offer promising results for anti-dopaminergic and non-anti-dopaminergic novel antipsychotic drugs. These new non-anti-dopaminergic antipsychotic drugs better emend negative schizophrenia symptoms, and they better improve cognitive functions than second-generation antipsychotic drugs. Promising new antipsychotic drugs are cariprazine, brexipiprazole, lumateperone, ulataront, and xanomeline combined with trospium. Although phase 3 clinical studies are not yet completed, they showed a therapeutic effect superior to those achieved by second-generation antipsychotic drugs. They are tolerated very well, and they better treat negative schizophrenia symptoms and improve cognitive functions.

The rapid growth in scientific article publications allows us to access articles as soon as possible. Therefore, automatic summarization systems (ATSs) are widely preferred. In most studies, the en-tire source document is expected to be summarized, just as it would be summarized by a human. Summarizing long articles, such as scientific articles, is quite difficult due to token restraint and extraction of scientific words. To address this problem, a novel Graph-Based Abstractive Summa-rization (GBAS) model is proposed, which is a novel scientific text summarization model based on SciBERT and the graph transformer network (GTN). The document's integrity is maintained since the SciIE system uses the graph structure to create a terminology-based document structure. Therefore, long documents are also summarized. The proposed model is compared with baseline models and human evaluation. Human evaluation results show that the results of the proposed model are informative, fluent, and consistent with the ground-truth summary. The experimental results indicate that the proposed model outperforms baseline models with a 37.10 and 34.96 ROUGE-L score.

Opportunistic networks, an evolution of mobile Ad Hoc networks (MANETs), offer decentralized communication without relying on preinstalled infrastructure, enabling nodes to route packets through different mobile nodes dynamically. However, due to the absence of complete paths and rapidly changing connectivity, routing in opportunistic networks presents unique challenges. This paper proposes a novel probabilistic routing model for opportunistic networks, leveraging nodes' meeting probabilities to route packets towards their destinations. The model dynamically builds routes based on the likelihood of encountering the destination node, considering factors such as last meeting time and acknowledgment tables to manage network overload. Additionally, an efficient message detection scheme is introduced to alleviate high overhead by selectively deleting messages from buffers during congestion. Furthermore, the proposed model incorporates cross-layer optimization techniques, integrating optimization strategies across multiple protocol layers to maximize energy efficiency, adaptability, and message delivery reliability. Through extensive simulations, the effectiveness of the proposed model is demonstrated, showing improved message delivery probability while maintaining reasonable overhead and latency. This research contributes to the advancement of opportunistic networks, particularly in enhancing connectivity and efficiency for Internet of Things (IoT) applications deployed in challenging environments.

Validation and verification are the critical requirements in the knowledge acquisition method for the clinical decision support system (CDSS). After acquiring the medical knowledge from diverse sources, the rigorous validation and formal verification process are required before creating the final knowledge model. Previously, we have proposed a hybrid knowledge acquisition method for acquiring medical knowledge from clinical practice guidelines (CPGs) and patient data in the Smart CDSS for treatment of oral cavity cancer. The final knowledge model was created by combining knowledge models obtained from CPGs and patient data after passing through a rigorous validation process. However, detailed analysis shows that due to lack of formal verification process, it involves various inconsistencies in knowledge relevant to the formalism of knowledge, conformance to CPGs, quality of knowledge, and complexities of knowledge acquisition artifacts. Therefore, it is required to enhance a hybrid knowledge acquisition method that thwarts the inconsistencies using formal verification. This paper presents the verification process using the Z formal method and its outcome as an enhanced acquisition method – known as the refined knowledge acquisition (ReKA) method. The ReKA method adopted verification method and explored the mechanism of theorem proving using the Z notation. It enables to identify inconsistencies in the validation process used for hybrid knowledge acquisition. Additionally, it refines the hybrid knowledge acquisition method by discovering the missing steps in the current validation process at the acquisition stage. Consequently, ReKA adds a set of nine additional criteria to be used to have a final valid refined clinical knowledge model. The criteria ensure the validity of final knowledge model concerning formalism of knowledge, conformance to GPGs, quality of the knowledge, usage of stringent conditions and treatment plans, and inconsistencies possibly resulting from the complexities. Evaluation, using four medical knowledge acquisition scenarios, shows that newly added knowledge in CDSS due to the addition of criteria by ReKA method always produces a valid knowledge model. The final knowledge model was also evaluated with 1229 oral cavity patient cases, which outperformed with an accuracy of 72.57\% compared to a similar approach with an accuracy of 69.7\%. Furthermore, ReKA method identified a set of decision paths (about 47.8%) in the existing approach, which results in a final knowledge model with low quality, non-conformed from standard CPGs. In conclusion, ReKA is formally proved method which always yields valid knowledge model having high quality, supporting local practices, and influenced from standard guidelines.

Chromosomal instability (CIN), defined by variations in the number or structure of chromosomes from cell to cell, is recognized as a distinctive characteristic of cancer, associated with the ability of tumors to adapt to challenging environments. CIN has been recognized as a source of genetic variation that leads to clonal heterogeneity (CH). Recent findings suggest a potential association between CIN and CH with the prognosis of BC patients, particularly in tumors expressing the epidermal growth factor receptor 2 (HER2+). In fact, information on the role of CIN in other BC subtypes, including luminal B BC, is limited. Additionally, it remains unknown whether CIN in luminal B BC tumors, above a specific threshold, could have a detrimental effect on the growth of human tumors, or if low or intermediate CIN levels could be linked to a more favorable BC patient prognosis when contrasted with elevated levels. Clarifying these relationships could have a substantial impact on risk stratification and the development of future therapeutic strategies aimed at targeting CIN in BC. This study aimed to assess CIN and CH in tumor tissue samples from ten patients with luminal B BC, and compared them with established clinicopathological parameters. The results of our study show that luminal B BC patients exhibit intermediate CIN and stable aneuploidy, both of which correlated with lymphovascular invasion. These findings suggest that evaluating CIN, CH and aneuploidy could improve risk stratification, the prediction of clinical outcomes and future therapeutic approaches in luminal B BC patients.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in Wuhan, Hubei province, China being its epicenter in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11, 2020). COVID-19 has presently spread to more than 195 countries/territories while killing nearly 19,600 humans out of cumulative confirmed cases accounting to more than 430,000 within a short period of just a few weeks. The majority of deaths have been reported in Italy and China. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter COVID-19. The present review presents an overview of COVID-19 and the causative virus SARS-CoV-2, with particular emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread., highlighting in very brief the preventive and control measures along with a few of the recent research developments to counter this pandemic virus/disease.

The development and application of marine current energy are attracting more and more attention around the world. Due to the hardness of its working environment, it is important and difficult to study the fault diagnosis of a marine current generation system. In this paper, an underwater image is chosen as the fault-diagnosing signal, after different sensors are compared. This paper proposes a diagnosis method based on the sparse autoencoder (SA) and softmax regression (SR). The SA is used to extract the features and SR is used to classify them. Images are used to monitor whether the blade is attached by benthos and to determine its corresponding degree of attachment. Compared with other methods, the experiment results show that the proposed method can diagnose the blade attachment with higher accuracy.

In this paper, new types of M-fractional wave solutions of mathematical physics model named as truncated M-fractional (1+1)-dimensional non-linear simplified Modified Camassa-Holm model are achieved by applying the modified simplest equation (MSE), Sardar sub-equation and generalized Kudryashov techniques. The gained solutions containing dark, bright, periodic and mixed wave solitons. Effect of fractional order derivative is also discussed. Achieved wave solitons are verified by Mathematica tool. Few of the gained wave solitons are also described through 2-dimensional, 3-dimensional and contour graphs through Mathematica tool. The gained solutions are helpful for the further development of concerned model. Finally, these techniques are simple, fruitful and effective to deal with non-linear FPDEs.

Present study offers mathematical calculations of the roll-coating procedure lubricated with upper Convected Maxwell Fluid. An incompressible isothermal viscoelastic fluid is considered with roll and the porous web having uniform velocities. By employing Lubrication Approximation Theory, the desired equations of motion for the fluid concerned over porous web are modelled and analyzed. The suction rate on the web and injection rate at the roll surface are anticipated proportionate. Results for velocity profile and pressure gradient are obtained analytically. Fluid parameters of industrial significance i.e. detachment point, pressure, sheet /roll separating force, power contribution and coating thickness are also calculated numerically. Substantial and monotonic increase is witnessed in these quantities with the increase of flow parameters.

The manuscript studies the release kinetic of fluorescein from colloidal liquid crystals made up from monoglyceride and different non-ionic surfactants. The release experiments were carried out under sink conditions, and mathematical models were described as extrapolations from solutions of diffusion equation in different initial and boundary conditions imposed by pharmaceutical formulations. The diffusion equation was solved, using Laplace and Fourier transformed functions for the release kinetic from infinite reservoirs in a semi-infinite medium. Solutions represents a general square root law and can be applied for the release kinetic of fluorescein from monoglyceride colloidal liquid crystals. Akaike, Schwartz and Imbimbo criteria were used to establish the appropriate mathematical model and the hierarchy of performances of different models applied to the release experiments. The Fisher statistic test was applied to perform significance of differences among mathematical models. Differences evaluated by mathematical criteria demonstrated that small or no significant statistic differences were carried out between various applied models and colloidal formulations. Phenomenological models were preferred over to empirical and semi-empirical ones. The general square root model shows that the diffusion-controlled release of fluorescein is the mathematical models extrapolated for monoglyceride colloidal liquids, in the first part of the process.

This article explores the relationship between Wang Yangming's philosophy and the new quality productivity, revealing how the new quality productivity, while inheriting the core ideas of Yangming's philosophy, achieves a higher level through innovation and development. The new quality productivity emphasizes the integration and innovation of knowledge, technology, and information, characterized by knowledge-driven innovation, information technology support, sustainable green development, and global collaborative development. The fusion of Yangming's philosophy and the new quality productivity holds significant theoretical and practical implications.

Stroke is a global leading cause of death and disability. Knowledge of related guidelines is crucial for Emergency Department (ED) staff, influencing early diagnosis and timely treatment. We investigated Greek-Cypriot ED healthcare professionals' (nurses and physicians) knowledge in recognizing and managing stroke. A descriptive cross-sectional study spanned November 2019 to April 2020, encompassing four private and seven public EDs in the Republic of Cyprus. The data were collected through a self-reported questionnaire developed by the research team, consisting of 37 questions. Eight questions focused on sociodemographic and employment characteristics, 28 assessed knowledge in stroke recognition and management (each item was equally weighted without deliberate prioritization), and one question addressed self-assessment of knowledge in stroke care. 255 nurses [Response Rate (RR): 74.1%] and 26 physicians (RR: 47.3%) completed the questionnaire. The average correct response rate was 12.9 out of 28 statements (SD: 4.2), with nurses and physicians scoring 12.6 (SD: 4.1) and 15.7 (SD: 4), respectively. Work experience significantly influenced stroke knowledge, with all groups demonstrating superiority over those with less than one year of experience. Participants with previous training scored an average of 1.45 additional correct answers while educational attainment did not significantly influence stroke knowledge. Investigating stroke knowledge among Emergency Department nurses and physicians in the Republic of Cyprus revealed significant deficits. The study stresses targeted interventions, including, education, yearly examinations, workshops with hands-on training, and repeated training, to address these gaps and enhance the overall stroke care capabilities of the healthcare professionals.

Cervical cancer is mostly diagnosed cancer of women worldwide and the second most common cancer among middle-aged women in Bangladesh. Knowledge and perception of women are considered one of the major components of prevention strategy. We carried out this survey to assess the existing knowledge level of students and their perception to the role of vaccination in preventing cervical cancer. The participants were female undergraduate students studying Public Health in a university in Chattogram city of Bangladesh. A total of 275 female students were interviewed through prescribed questionnaire possessing questions on basic information of cervical cancer, its causal agent, risk factors, prevention methods, and vaccination. We marked the responses of participants with zero for wrong answer and one for every correct answer and ranked the knowledge level of students. The mean age of study participants was 20.68 years. In total, 69.1% students possessed poor knowledge whereas, 30.9% had good knowledge. The country of students has significant association with their level of knowledge. Most of the students got information on cervical cancer from traditional media (49.8%) and doctor (30.9%) and the effect of these two sources was statistically significant on the knowledge level of students. Students mostly identified vaccination (21.1%) and Gynecological examination (14.39%) as preventing methods. However, 65.5% of them acknowledge that vaccines cannot prevent this cancer and 33.4% believe in different risks of vaccine. Although students have heard of cervical cancer the overall knowledge was insufficient and perceived negative concepts about cancer vaccine. Therefore, we recommend the initiation of educational programs on basic reproductive health and health seeking behaviour targeting young women to successfully control and prevention of this life-threatening health problem.

Horizontal transfer of transposons (HTT) is an important source of genomic evolution in eukaryotes. The HTT dynamics is well characterized in eukaryotes including insects however, but there is a huge gap of knowledge about HTT regarding many eukaryotes’ species. In this study we analyzed the events of the HTT between Rhus gall aphids (Hemiptera) and other insects. We analyzed the Mariner-like transposable elements (MLEs) belongs to Rhus gall aphids for the possible HT events. The MLEs have patchy distribution and have high similarity over the entire length of element with insects MLEs from different orders. We selected representative sequences from the Rhus gall MLEs and identified five events of HT between MLEs of Rhus gall aphids and other insects from five different orders. We also found multiple HTT events among the MLEs of insects from the five orders which demonstrate that these Mariner elements have been involved in recurrent HT between these six order of insects. Our current study closed the knowledge gap of HTT and reported the events between Rhus gall aphids and other insects for the first time. We believe that this study about HTT events will help to understand the evolution and spread of transposable elements in the genomes of Rhus gall aphids.

Stunting in children is a serious problem of nutritional disorders and is strictly monitored by the Indonesian government, it is not only cause physical but also cognitive abnormalities in the form of less intelligence in children so that when they grow up, their productivity will decrease. The incidence of stunting in 2018 in Indonesia was 30.8 %, while in West Java was 29.92%, still at a moderate to high level, consequently, prevention and early detection efforts need to be carried out by various parties, including health professionals and health cadres. Therefore, the aim of this study was to examine the association between the socio demographic characteristics factors as well as the knowledge and motivation of health cadres in the stunting prevention in West Java. A correlational study with a cross-sectional approach was employed with the samples of health cadres from 8 districts/cities in West Java Province: Karawang, Tasikmalaya, Garut, Bandung, Subang, Sukabumi, Cianjur, and West Bandung. A total of 363 health cadres participated and the sampling technique used is the stratified method. The data were collected using a questionnaire developed specifically for this study and were analyzed using a correlation with Chi-Square test and presented in the form of a frequency distribution. The study findings found that majority of the health cadres have good knowledge of 81.27%, which was significantly influenced by education level and marital status with p &lt;0.05. Meanwhile, approximately half of the respondents had moderate motivation with 47.66%, while one-third or 39.12% had high motivation. This motivation was significantly influenced by education level, marital status, and age with p &lt;0.05. It was concluded that health cadres need to further enhance the roles and functions in the prevention and early detection of stunting in West Java by providing continuous guidance, stunting training prevention and award presentations.

Sub-Saharan social-ecological systems are undergoing changes in environmental conditions, including modifications in rainfall pattern and biodiversity loss. Consequences of such changes depend on complex causal chains which call for integrated management strategies whose efficiency could benefit from ecosystem dynamic modelling. However, ecosystem models often require lots of quantitative information for estimating parameters, which is often unavailable. Alternatively, qualitative modelling frameworks have proved useful for explaining ecosystem response to perturbations, while requiring fewer information and providing more general predictions. However, current qualitative methods have some shortcomings which may limit their utility for specific issues. In this paper, we propose the Ecological Discrete-Event Network (EDEN), an innovative qualitative dynamic modelling framework based on "if-then" rules which generates many alternative event sequences (trajectories). Based on expert knowledge, observations and literature, we use this framework to assess the effect of permanent changes in surface water and herbivores diversity on vegetation and socio-economic transitions in an East African savanna. Results show that water availability drives changes in vegetation and socio-economic transitions, while herbivore functional groups had highly contrasted effects depending on the group. This first use of EDEN in a savanna context is promising for bridging expert knowledge and ecosystem modelling.

The article presents a new approach to the analysis of the stability of automatic systems with discrete links.In almost all modern automatic control systems, there are links that break signals in time. These are power controlled switches - transistors or thyristors operating in a pulsed mode and digital links in regulators.Time discretization significantly affects the stability of processes in the automatic control system. The theoretical analysis of such systems is rather complicated and requires a significant change in engineering approaches to analysis. In connection with the improvement of digital controllers and a significant increase in their performance, in recent years this problem has practically not been remembered. However, its mathematical "content" has not changed since the 80s of the 20th century, when discreteness began to play a major role among the problems hindering progress in automatic control systems, in terms of the transition to digital systems.In this paper, a new approach is proposed, which consists in interpreting the sampling operation by a link with the proposed frequency characteristic, which determines the suppression of input high-frequency signals. This link greatly simplifies engineering calculations and demonstrates the new capabilities of sampling systems. These possibilities include the rational distribution of digitalization resources - the number of bits and the sampling interval between the regulator channels, depending on the frequency range of the efficiency of these channels. Theoretical statements have been verified and confirmed by simulation. It is shown how this approach makes it possible to formulate new principles of construction of seemingly well-known controllers - PID controllers and variable structure systems (VSS).

The main purpose of this paper is to introduce a new class of $q$-Hermite-Fubini numbers and polynomials by combining the $q$-Hermite polynomials and $q$-Fubini polynomials. By using generating functions for these numbers and polynomials, we derive some alternative summation formulas including powers of consecutive $q$-integers. Also, we establish some relationships for $q$-Hermite-Fubini polynomials associated with $q$-Bernoulli polynomials, $q$-Euler polynomials and $q$-Genocchi polynomials and $q$-Stirling numbers of the second kind.

Urinary infections are very prevalent in pregnant women and are a cause for great concern con-sidering the negative impacts they can have on both, the mother and the baby. The objectives were characterize urinary infections associated with pregnant women, study the most prevalent strains in urinary infections in pregnant women and analyze the antibiogram of the most prevalent strains in infections in pregnant women. A retrospective observational study was carried out on all posi-tive urine cultures from pregnant women between January 2018 and December 2022 at a Hospital Center in the Center of Portugal, totaling 201 samples. Data were collected with computer support, including age, origin, previous antibiotic therapy, catheterization, isolated bacteria and tested an-tibiotic therapy. The majority of pregnant women were in the third trimester of pregnancy and came from the External Consultation. The most identified bacteria was Escherichia coli, followed by Streptococcus agalactiae. Regarding the interaction with antibiotics, Escherichia coli showed total sensitivity to one antibiotic, while Streptococcus agalactiae showed sensitivity to four anti-biotics in 2022. This work contributes to the knowledge of urinary infections in pregnant women in the center of the country, being a contribution to the continued improvement of the care provided

Background: Worldwide, microbes are becoming more dangerous by acquiring virulent skills to adapt and develop antimicrobial resistance (AMR). This is a concern as this increases morbidity, mortality, and costs. Consequently, physicians need to be trained inappropriate prescribing, starting with medical students. Objective: Evaluate medical students' confidence in antimicrobial agent prescribing and drug resistance Methods: Cross-sectional study assessing medical students' knowledge, perception, and confidence in prescribing antimicrobial agents and drug resistance in a Malaysian University. A universal sampling method was used. Results: Most respondents believe that educational input regarding overall prescribing was sufficient. Regarding the principle of appropriate and accurate prescriptions, female medical students had less knowledge [Odds Ratio (OR)=0.51; 95% Confidence Interval (CI) 0.25-0.99; p=0.050]. Year-IV and Year-V students had more excellent knowledge than Year-III students regarding confidence in antibiotic prescribing. Year-V students also showed appreciably higher confidence in the broad principles of prescribing, including infectious diseases, compared to those in other years. Conclusion: Overall, medical students, gain more excellent knowledge and confidence regarding prescribing, including antimicrobials, as their academic careers progress.

The modification of land use is a crucial factor in the dysfunction of ecosystems. It considerably influences the hydrological cycle of basins. This study focuses on the Oueme basin, which represents almost half of the total area of Benin, and describes the current and future evolution of its land cover using the maps of the Land Use Land Cover Dynamics project (1975, 2000 and 2013). A temporal analysis of the surface states was performed with QGIS and the potential land cover in 2025, 2050 and 2085 was estimated using the Markov chain algorithm in the IDRISI software. The results show that the Oueme basin is predominantly savanna (77.70% in 1975, 66.29% in 2000 and 57.10% in 2013). Forest areas, which represented the second class in 1975 with a total proportion of 13.34%, have gradually decreased to 8.66% and 6.89% respectively in 2000 and 2013. Conversely, cultivated areas more than tripled in 2000 and quadrupled in 2013. Residential areas are increasing very strongly in the southern part of the basin with an amplification in the recent period (6% between 2000-2013 against 2% between 1975-2000). The recent period is more exposed to changes in surface condition and these changes are likely to be amplified in the future (probable total disappearance of forested areas in 2085). We recommend clarifying the impacts that each land use category generates/will generate on the hydrological cycle of this basin.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

Some bispecific radiotracers have been developed to overcome the limitations of monospecific tracers and improve detection sensitivity for heterogeneous tumor lesions. Here we aim to synthesize two bispecific tracers targeting prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are key markers expressed in prostate cancer. A pyridine-based FAP-targeted ligand was synthesized through multi-step organic synthesis, and then connected to the 2-Nal-containing PSMA-targeted motif. Ki(PSMA) values of Ga-complexed bispecific ligands, Ga-AV01084 and Ga-AV01088, were 11.6 ± 3.25 and 28.7 ± 6.05 nM, respectively, and the IC50(FAP) values of Ga-AV01084 and Ga-AV01088 were 10.9 ± 0.67 and 16.7 ± 1.53 nM, respectively. The uptake values for PSMA-expressing LNCaP tumor xenografts were 9.05 ± 1.54 and 8.85 ± 1.25 %ID/g for [68Ga]Ga-AV010184 and [68Ga]Ga-AV01088, respectively, which were lower than the monospecific PSMA-targeted tracer [68Ga]Ga-PSMA-617 (16.7 ± 2.30 %ID/g). The uptake values for FAP-expressing HEK293T:hFAP tumor xenografts were 1.90 ± 0.41 and 1.20 ± 0.25 %ID/g for [68Ga]Ga-AV01084 and [68Ga]Ga-AV01088, respectively, which were also lower than the monospecific FAP-targeted tracer, [68Ga]Ga-AV02070 (7.93 ± 1.88 %ID/g). Further investigations are needed to optimize the selection of linkers and targeted pharmacophores to improve the tumor uptake of PSMA/FAP bispecific tracers for prostate cancer imaging.

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.

Alectinib hydrochloride is an anticancer medication used for the first-line treatment of non-small cell lung cancer. Although it has been approved for medical use ten years ago, and three polymorphs of this substance were proposed based on X-ray diffraction patterns, their crystal structures remained unknown to date. The main problem was preparation of high quality single crystals due to very low solubility of the salt. Herein we report on molecular and crystal structure of form I of alectinib hydrochloride as obtained by powder X-ray diffraction data from laboratory source. The refinement revealed that the nitrogen atom of the morpholinyl ring is protonated. The chloride anion interacts with the H(N) atoms of the morpholine and benzo[b]carbazole rings to form infinite H-bonded chains.

Machine learning (ML) techniques can help predict survival among cancer patients and might help with a timely integration in palliative care. We aim to explore the importance of subjective variables self-reported and collected via electronic patient reported outcome measure (ePROM) for survival prediction. A total of 256 advanced cancer patients met the eligible criteria. We analyzed objective variables collected from electronic health records, subjective variables collected via ePROM and all clinical variables combined. We used logistic regression (LR), decision trees, and random forests to predict 1-year mortality. Receiver operating characteristic (ROC) curve - area under the curve (AUC) and the ML models feature importance were analyzed. The performance of all variables for predictions (LR reaches 0.80 [ROC AUC] and 0.72 [F1 Score]) does not improve over the performance of only clinical non-patient reported outcome (non-PRO) variables (LR reaches 0.81 [ROC AUC] and 0.72 [F1 Score]). Our study indicates that patient-reported outcome (PRO) variables, which measure subjective burden, cannot be reliably used to predict survival. Further research in this area is needed to clarify the role of self-reported patient's burden and mortality prediction via ML.

Purpose: To compare the efficacy and safety of graft-free short tunnel small flap (STSF) technique with that of scleral patch graft (SPG) in Ahmed glaucoma valve (AGV) implantation. Design: Randomized clinical trial. Participants: Eighty-eyes of eighty patients with medically uncontrolled glaucoma including 41 in STSF and 39 eyes in SPG. Methods: Patients were enrolled and assigned randomly to STSF or SPG. Main Outcome Measures: tube exposure, Intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), surgical complications, and success rate ( defined as intraocular pressure (IOP) >5 mmHg, ≤21 mmHg, and IOP reduction ≥20% from baseline at two consecutive visits after three months, no reoperation for glaucoma). Results: only one case in SPG developed tube exposure at 1-year follow-up. The cumulative probability of success during the first year of follow-up was 70% in the STSF and 65% in SPG (P = 0.36). IOP decreased significantly from 29.6 ± 8.6 mmHg at baseline to 16.4 ± 3.6 mmHg at the final follow-up in STSF (p = 0.001). The corresponding numbers for SPG were 30.9 ± 11.2 and 15.8 ± 4.7, respectively (p = 0.001). The final IOP was comparable between both groups (p = 0.65). Mean ± standard deviation of the number of glaucoma medications was 1.8 ± 0.9 in STSF and 1.6 ± 0.9 in SPG at final follow-up (P = 0.32). Postoperative complications developed in 8 patients (19%) in STSF and 9 patients (23%) in SPG (P = 0.81). Conclusions: STSF and SPG techniques had comparable complication rate at one-year follow-up. Both techniques were comparable in terms of success rate, postoperative IOP, and glaucoma medications.

The proliferation of SARS-COV-2 through enhanced viral replication and its subsequent triggering of cytokine storm, are some of the hallmark phenotypes in severe COVID-19 patient cases. Cyclosporine, an immunosuppressant drug and Selinexor, an inhibitor of nuclear transporter protein, both have been successfully demonstrated to be effective against SARS-COV-2 infection by targeting those functions individually. However, the highly multifactorial pathology of SARS-COV-2 infection hinders any mono-therapeutic strategy to become an optimal option. In this study, we assess the potential efficacy of the Cyclosporine-Selinexor combination on an integrated interactome by adopting a network-medicine-based repositioning technique, where disease proximity, functional proximity and their topological separation are evaluated, followed by a robust statistical significance test. Results have shown that both drug target modules are highly proximal to the SARS-COV-2 disease modules in terms of network topology and functional associations, in a statistically significant manner, individually. Functional enrichment of both drug modules and SARS-COV-2 infected modules has shown that two drugs target the functions related to viral replication and cytokine storm during infection. Moreover, a high degree of network separation been those two drug target modules has been observed, revealing ``complementary exposure`` patterns, rendering this drug combination as an effective one against SARS-COV-2 infection. We hope that our results will encourage researchers to further investigate the potency of Cyclosporine and Selinexor combination in vivo or in vitro, and ultimately lead that up to clinical trials to treat SARS-COV-2 patients.

Vaccination has proven highly effective against severe acute res-piratory syndrome coronavirus 2 (SARS-CoV-2), but the long-term immunogenicity and the functional preserved im-mune responses of vaccines are needed to inform evolving evi-dence-based guidelines for boosting schedules. We enrolled 205 healthcare workers into a cohort study; all had received three doses of BBIBP-CorV (China Sinopharm Bio-Beijing Company) inactivated vaccine. We assessed SARS-CoV-2 specific binding antibodies, neutralizing antibody, and peripheral T and B cell responses. We demonstrated that more robust antibody re-sponses to SARS-CoV-2 were elicited by booster immunization compared to primary vaccination. Neutralizing antibody titers to SARS-CoV-2 Omicron variant were also efficiently elevated post homologous vaccine booster despite in a lower titer compared to the prototype stain. In addition to S specific humoral and cellular immunity, BBIBP-CorV also induced N-specific antibody and ef-fector T cell responses. The third-dose vaccination led to further expansion of critical polyfunctional T cell responses, likely an essential element for vaccine protection. In particular, a func-tional role for Tfh cell subsets in immunity was suggested by the correlation between both CD4+Tfh and CD8+Tfh with total anti-body, IgG, B cell responses and neutralizing antibodies. Our study details the humoral and cellular responses generated by the BBIBP-CorV booster vaccination in a seven-month follow up study. There is a clear immunologic boosting value of homolo-gous inactivated SARS-CoV-2 vaccine boosters, a consideration for future vaccine strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to the cell receptor angiotensin-converting enzyme-2 (ACE2) as the first step in viral cell entry. SARS-CoV-2 spike protein expression in ACE2-expressing cell surface induces cell–cell membrane fusion, thus forming syncytia. To exert its fusiogenic activity, the spike protein is typically processed at a specific site (S1/S2 site) by cellular proteases such as furin. The C488 residue, located at the spike–ACE2 interacting surface, is critical for the fusiogenic and infectious roles of the SARS-CoV-2 spike protein. We further demonstrated that the C488 residue of spike protein is involved in subcellular targeting and S1/S2 processing. C488 mutant spike localization to the Golgi apparatus and cell surface were impaired. Consequently, the S1/S2 processing of the spike protein, probed by anti-Ser-686-cleaved spike antibody, markedly decreased in C488 mutant spike proteins. Moreover, brefeldin A-mediated endoplasmic reticulum-to-Golgi traffic suppression also suppressed spike protein S1/S2 processing. As brefeldin A treatment and C488 mutation inhibited S1/S2 processing and syncytia formation, the C488 residue of spike protein is required for functional spike protein processing.

The Severe acute respiratory syndrome-Corona virus-2 (SARS-CoV-2) which is responsible for recurring pandemics takes advantage of host-cell processes including the glycosylation pathway. The heavily glycosylated spike protein assists viruses in attachment and penetration. The N-glycans of N-terminal domain N165 and N234 play a significant role in conformational dynamics of the receptor-binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2). In addition, the deletion of N-glycan sites N331 and N334 have been associated with reduced infectivity. This signifies the importance of targeting the N-glycans making them unavailable for interacting with the ACE2 receptor, ultimately leading to reduced infectivity. These glycans can be specifically targeted and can be used for designing SARS specific drugs or neutralizing molecules. In the current study, lectins Griffithsin, Cyanovirin-N, Cyanovirin homolog, and BanLec H84T were used to target the spike protein's N-glycans. Molecular docking programs AutoDock Vina and HADDOCK were used to study lectin-glycan interactions. The interactions look convincible in accordance with the lowest interaction energies best-fit approach but the characteristic feature (scoring functions) of the docking programs are questionable concerning Lectin-Glycan interactions exist in nature. There is a high need of the hour for developing specific algorithms for docking glycans with a preferential selection of terminal residues.

Fusarium culmorum is a major pathogen of grain crops. Infected plants accumulate deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), or nivalenol (NIV), which are mycotoxins of the trichothecene B group. These toxins are also produced by F. graminearum species complex. New trichothecenes structurally similar to trichothecenes B but lacking the carbonyl group on C-8, designated NX toxins, were recently discovered in atypical isolates of F. graminearum from North America. Only these isolates and a few strains of a yet to be characterized Fusarium species from South Africa are known to produce NX-2 and other NX toxins. Here we report that among 20 F. culmorum strains isolated from maize, wheat, and oat in Europe and Asia over a period of 70 years, 18 strains produced NX-2 simultaneously with 3-ADON and DON or NIV. Rice cultures of strains producing 3-ADON accumulated NX-2 in amounts corresponding to 2-8% of 3-ADON (1.2 - 36 mg/kg). A strain producing NIV accumulated NX-2 and NIV at comparable amounts (13.6 and 10.3 mg/kg, respectively). In F. graminearum, producers of NX-2 possess a special variant of cytochrome P450 monooxygenase encoded by TRI1 that is unable to oxidize C-8. In F. culmorum, producers and nonproducers of NX-2 possess identical TRI1; the reason for the production of NX-2 is unknown. Our results indicate that production of NX-2 simultaneously with trichothecenes B is a common feature of F. culmorum.

We report on the design, characterization and validation of a spherical irradiation system for inactivating SARS-CoV-2, based on UV-C 275 nm LEDs. The system is designed to maximize ir-radiation intensity and uniformity, and can be used for irradiating a volume of 18 liters. To this aim: (i) several commercially available LEDs have been acquired and analyzed; (ii) a complete optical study has been carried out in order to optimize the efficacy of the system. (iii) The re-sulting prototype has been characterized optically, and tested for the inactivation of SARS-CoV-2 for different exposure times, doses and surface types. Results indicate that a 99.9% inactivation can be reached after 1 minute of treatment with a dose of 83.1 J/m2.

SARS-CoV-2, the novel coronavirus behind COVID-19 pandemic is acquiring new mutations in its genome. Although some mutations provide benefits to the virus against human immune response, a number of them may result in their reduced pathogenicity and virulence. By analyzing more than 3000 high-coverage, complete genome sequences deposited in the GISAID database, here I report a unique 28881-28883:GGG>AAC trinucleotide-bloc mutation in the SARS-CoV-2 genome that results in two sub-strains, described here as SARS-CoV-2g (28881-28883:GGG genotype) and SARS-CoV-2a (28881-28883:AAC genotype). Computational analysis and literature review suggest that this bloc mutation would bring 203-204:RG(arginine-glycine)>KR(lysine-arginine) amino acid changes in the nucleocapsid (N) protein affecting the SR (serine-arginine)-rich motif of the protein, a critical region for the transcription of viral RNA and replication of the virus. Thus, 28881-28883:GGG>AAC bloc-mutation is expected to modulate the pathogenicity of the SARS-CoV-2. Remarkably, SARS-CoV-2g and SARS-CoV-2a strains can be linked with the heterogeneity of COVID-19 cases across different regions within and between countries by analyzing existing data. Sequence analysis suggests that severely affected cities, such as Milan, Lombardy, New York, Paris have the predominant presence of SARS-CoV-2g strains, whereas less affected places like Abruzzo, Lyon, Valencia have a relatively higher presence of SARS-CoV-2a, an indication that the latter strain may contribute to the reduced cases of COVID-19. A similar relationship is observed when Netherlands, Portugal are compared with Spain, France and Germany. These analyses suggest that the SARS-CoV-2 has already evolved into a less infective SARS-CoV-2a affecting COVID-19 cases in different regions. The time a country or region needs to acquire SARS-CoV-2a strains may be indicative to the time it would need to overcome the peak of the COVID-19 cases. To confirm these assumptions, prompt retrospective and prospective epidemiological studies should be conducted in different countries to understand the course of pathogenicity of the SARS-CoV-2a and SARS-CoV-2g. Potential drugs can be designed targeting 28881-28883 region of the N protein to modulate virus pathogenicity.

Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.

Crystalline β-cobalt hydroxide (β-Co(OH)₂) of different morphologies have been successfully synthesized with the addition of sodium hydroxide to cobalt nitrate solution and aging in the mother liquor. The rate of NaOH addition, ranging from 0.1 mL/min to 10 mL/min, influences the surface morphology with the obtained storage capability of the respective electrode. Characterization of the β-Co(OH)₂ was fully developed, including X-ray diffraction, scanning and transmission electron microscopy, and BET analyses. At a lower rate of NaOH addition, particles are like platelets, while for a higher rate (≥2 mL/min) grains are fused together forming a larger crystallite size. This result is supported by the X-ray diffraction structural analysis, where the phase evolution of (002) plane becomes distinct for the higher rate of NaOH addition. Lithium cobalt oxide (LiCoO₂) was synthesized through oxidation from the as-prepared β-Co(OH)₂ and LiOH. The electrochemical performance of as obtained LiCoO₂ is investigated using charge-discharge and cyclic voltammetric studies. The precursor β-Co(OH)₂ prepared at a lower rate of 0.1 mL/min in LiCoO₂ demonstrated the best electrochemical performance of 155 mAh/g. After 50 cycles, the capacity retention rate was 67% compared with the first cycle. Finally, we have attempted to correlate the amount of the available OH^- ions with the formation of platelets and the discharge capacity. This work has developed a methodology for the synthesis of LiCoO₂ using β-Co(OH)₂ in a facile chemical solution process.

The Hindu Kush Himalaya (HKH) is one of the most flood-prone regions in the world, yet heavy cloud cover and limited in-situ observations have hampered efforts to monitor the impact of heavy rainfall, flooding, and inundation during severe weather events. This paper introduces HydroSAR, a Sentinel-1 SAR-based hazard monitoring service that was co-developed with in-region partners to provide year-round, low-latency weather-hazards information across the HKH. The paper describes the end-user focused concept and overall design of the HydroSAR service. It introduces the main processing algorithms behind HydroSAR’s broad product portfolio, which includes qualitative visual layers as well as quantitative products measuring surface water extent and water depth. We summarize the cloud-based implementation of the developed service, which is providing capability to scale automatically with event size. A performance assessment of our quantitative algorithms is described, demonstrating capabilities to map flood extent and water depth at an accuracy of >90% and

Text annotation is an essential element of the natural language processing approaches. The manual annotation process performed by humans has several drawbacks, such as subjectivity, slowness, fatigue, and possibly carelessness. In addition, annotators may annotate ambiguous data. So, we developed the concept of automated annotation to get the best annotations using several machine-learning approaches. The proposed approach is based on an ensemble algorithm of meta-learners and meta-vectorizer techniques. The approach employs a semi-supervised learning technique for automated annotation, aimed at detecting hate speech. This involves leveraging various machine learning algorithms, including Support Vector Machine (SVM), Decision Tree (DT), K-Nearest Neighbors (KNN), and Naive Bayes (NB), in conjunction with Word2Vec and TF-IDF text extraction methods. The annotation process is performed using 13,169 Indonesian YouTube comments data. The proposed model used a Stemming approach using data from Sastrawi and also new data of 2,245 words. Semi-supervised learning uses 5%, 10%, and 20% of labeled data as compared to performing labeling based on 80% of the datasets. In semi-supervised learning, the model learns from the labeled data, which provides explicit information, and the unlabeled data, which offers implicit insights. This hybrid approach enables the model to generalize and make informed predictions even when limited labeled data is available, ultimately enhancing its ability to handle real-world scenarios with scarce annotated information. In addition, the proposed method uses a variety of thresholds for matching words labeled with hate speech ranging from 0.6, 0.7, 0.8, and 0.9. The experiment showed that the KNN-Word2ec model has the best accuracy value of 96.9% with a scenario of 5%:80%:0.9. However, several other methods have also accuracy above 90%, such as SVM and DT based on both text extraction methods in several test scenarios.

Considering the significant advancements in autonomous vehicle technology, research in this field is of interest to researchers. To automatic parking, controlling steer angle, gas hatch, and brakes need to be learned. Due to the increase in the number of cars and road traffic, car parking space has decreased. Its main reason is information error. Because the driver does not receive the necessary information or receives it too late, he cannot take appropriate action against it. This paper uses two phases: the first phase, for goal coordination, was used genetic algorithms and the Cuckoo search algorithm was used to increase driver information from the surroundings. Using the Cuckoo search algorithm and considering the limitations, it increases the driver’s level of information from the environment. Also, by exchanging information through the application, it enables the information to reach the driver much more quickly and the driver reacts appropriately at the right time. The suggested protocol is called the MODM-based solution. Here, the technique is assessed through extensive simulations performed in the NS-3 environment. Based on the simulation outcomes, it is indicated that the parking system performance metrics are enhanced based on the detection rate, false-negative rate, and false-positive rate.

Background: Research articles are essential for describing new ideas, techniques, and procedures and consolidating concepts. It creates an opportunity to expose studies and publicly assimilate published knowledge. Therefore, one of them is the most used and accepted index to verify the author’s scientific impact is the H-index or Hirsch index. It provides a robust single metric that combines quality and quantity. Therefore, it presents disadvantages, (1) researchers with shorter scientific carriers may have fewer articles and citations than those with longer scientific life; (2) it allows scientists to receive citations even if no new papers are published; (3) it is only useful for comparing the better scientists in a field; (4) this indicator can never decrease; (5) it is only weakly sensitive to the number of citations received; (6) the major and minor (or no) contributor in the research gained equal h-index. Then, the H-index ignores the total of citations and the time of a researcher's experience (“scientific age” [sa]). Objective: Thus, the goal of this study was to present a new index system (GFsa index ©) based on the two variables completely forgotten (total of citations and “scientific age”), introducing a new terminology “scientific age”, to evaluate the best-ranked researchers in Dentistry. Methods: The AD Scientific Index was used, and all researchers included in this study were cited in the AD Scientific Index (2024) in the Dentistry field and had the Google Scholar page accessible for a consultation to manually obtain the total of citations and calculate the “scientific age”. The information was retrieved by two authors (G.V.O.F. and J.C.H.F.), who assessed the data twice to avoid errors or mistakes. For inclusion: a minimum H-index value of 30; for exclusion: (i) the author did not have a Google Scholar page; (ii) duplicated author; or (iii) presented any suspicious activities about manipulation of articles. Then, a dataset of all researchers who were reported in Dentistry was prepared (name, H-index, i10 index, and publications). The formula developed and applied was GFsa=(total number of citations)/(“scientific age)². The Pearson correlation statistically evaluated the data obtained; the confidence interval was 95%. Results: A total of 9,093 researchers in Dentistry were recorded, of whom 1,020 were included. Then, we collected all 1,020 researchers' Google Scholar data (publications, citations, and indexes), and each researcher's total citations and “scientific age” were registered and calculated. The mean “scientific age” registered was 34.18 ± 13.34 (standard error of mean = 0.4181). With this information and data collected, GFsa index © was calculated, presenting a minimum value of 0.2186 and a maximum of 154.8 (mean = 10.33 ± 11.82; standard error of mean = 0.3706). Then, the data was organized and sorted following the ranking obtained in the GFsa index ©. The Pearson correlation showed that the H-index had a weakly positive association with the researcher’s “scientific age”; this fact means that the H-index will increase according to the “scientific age” increase. Otherwise, a moderately negative correlation between GFsa and “scientific age” was demonstrated, whereby a higher GFsa © had a lower “Scientific age”. This assessment shows that the variables introduced were fairly used. Moreover, a positive correlation was observed between both indexes (H-index and GFsa). Conclusion: It is possible to conclude that the new variable reported (“Scientific age”) and using the total citations brought a fairer and more feasible evaluation among the researchers. Thus, we are launching the new GFsa index © and the new information named “Scientific age” for the first time in the literature. The future perspective of the GFsa © application will be (1) the evaluation of the 9,093 researchers in Dentistry (total initially registered), including more authors/researchers in the Dentistry field, (2) expanding the exposition of this new index for other areas of the knowledge, and (3) provide free access of all data through the website (http://gfindex.us.to).

Repetitive elements are a major component of DNA sequences due to their ability to propagate through the genome. Characterization of Metazoan repetitive profiles is picking up, however, current pipelines are failing to identify a significant proportion of divergent repeats in non-model organisms. The order Decapoda, for which repeat content analyses are largely lacking, is characterized by extremely variable genome sizes that suggest an important presence of repetitive elements. Here we developed a new standardized pipeline to annotate repetitive elements in non-model organisms, which we applied on 20 Decapoda and 6 other crustacean genomes. With our new tool we identify 10% more repetitive elements than standard pipelines. Repetitive elements were more abundant in Decapoda species than in other crustaceans, with an incredibly large number of highly repeated satDNA families. Moreover, we demonstrated a high correlation between assembly size and transposable elements and a different repeat dynamics between Dendrobranchiata and Reptantia. The patterns of repetitive elements largely reflect the phylogenetic relationships of Decapoda and the distinct evolutionary trajectories within Crustacea. In summary, our results highlight the impact of repetitive elements on genome evolution in Decapoda and the value of our novel annotation pipeline, which will provide a baseline for future comparative analyses.

There is a need to assess the knowledge of healthcare providers on the use of maternal analgesics during lactation, while a valid instrument is not yet available. This study aimed to develop a valid and reliable questionnaire on the knowledge of analgesics (acetaminophen, ibuprofen, aspirin, tramadol, codeine, oxycodone) during lactation, using a prospective, stepwise approach. To generate a pool of item subgroups, literature was assessed as first step. This preliminary version was subsequently reviewed in two focus groups [midwives (n=4), pediatric nurses (n=6)], followed by an expert panel (n=7, 2 rounds) to confirm content validity [item-level and scale content validity]. This resulted in a instrument consisting of 33 questions, and 5 clincial case descriptions specific for both disciplines. Based on known-groups validity between midwives and pediatric nurses (assuming an a priori difference related to their curricula), high construct validity was subsequently demonstrated in a pilot e-survey (86 midwives, 73 pediatric nurses). We therefore conclude that an instrument to assess knowledge on lactation-related exposure to analgesics was generated, that can be further developed and validated. Furthermore, pilot findings suggest suboptimal knowledge for both professions, so that adaptations in their curricula and postgraduate training are warranted.

The ceramic sherds from approximately 20 samples of lead-glazed tableware, recovered from diverse archaeological sites, including three repurposed storage pits transformed into dumpsters within the medieval city of Santarém (13th-14th century), underwent a meticulous examination. This investigation utilized techniques such as micro-Raman, ground state diffuse reflectance absorption, and X-ray fluorescence spectroscopies, in addition to X-ray diffraction and stereomicroscopy. A parallel study was conducted on contemporaneous European ceramics (glazed sherds) sourced from archaeological sites dating back to the 13th-15th centuries in Saintonge (France), Ardenne, Zomergem, and Bruges (Belgium), as well as Surrey-Hampshire, Kingston, and Cheam (England). The colour of the ceramic bodies is predominantly white or whitish, with a few exhibiting a vivid red hue. Ceramic sherds with a light paste composition were likely crafted using kaolin clays as raw materials. Analyses of fabric, mineralogical, and elemental composition of the sherds suggest that the majority of Santarém's glazed ceramics were locally or regionally produced, potentially derived from a Pliocene kaolin-rich sand formation. However, this conclusion is not supported by the absence of discovered lead glaze kilns or workshops in Santarém for the late Middle Ages. A distinctive feature from the European workshop ceramics lies in the quartz temper content and fabric.

The present grievous situation of the tuberculosis disease can be improved by efficient case management and timely follow-up evaluations. With the advent of digital technology this can be achieved by quick summarization of the patient-centric data. The aim of our study was to assess the effectiveness of the ODK Scan paper-to-digital system during testing period of three months. A sequential, explanatory mixed-method research approach was employed to elucidate technology use. Training, smartphones, application and 3G enabled SIMs were provided to the four field workers. At the beginning, baseline measures of the data management aspects were recorded and compared with endline measures to see the impact of ODK Scan. Additionally, at the end, users’ feedback was collected regarding app usability, user interface design and workflow changes. 122 patients’ records were retrieved from the server and analysed for quality. It was found that ODK Scan recognized 99.2% of multiple choice bubble responses and 79.4% of numerical digit responses correctly. However, the overall quality of the digital data was decreased in comparison to manually entered data. Using ODK Scan, a significant time reduction is observed in data aggregation and data transfer activities, however, data verification and form filling activities took more time. Interviews revealed that field workers saw value in using ODK Scan, however, they were more concerned about the time consuming aspects of the use of ODK Scan. Therefore, it is concluded that minimal disturbance in the existing workflow, continuous feedback and value additions are the important considerations for the implementing organization to ensure technology adoption and workflow improvements.

This paper discusses the application and advantages of artificial intelligence technology in digital media interactive product design. Firstly, the development background of artificial intelligence technology and its promoting effect on design innovation is introduced, and the application of new technologies, such as generative adversarial networks in art creation and design personalization, is definitely analyzed. It then explores in detail the ability of AI to break traditional constraints in interactive design, innovate design, and optimize user experience, especially in digital media. Finally, the case study of Microsoft Cortana shows the method of classifying and processing user queries by machine learning system and its experimental results. The research of this paper provides the theoretical basis and empirical support for the application of artificial intelligence technology in the future interactive design of digital media and has important academic and practical significance.

In this study, we aimed to explore the oral bacteria and fungi that can help discern oral squamous cell carcinoma (OSCC) and investigate the correlations between multiple key pathogens. Methods: Twelve participants (8 females and 4 males; mean age, 54.33 ± 20.65 years) were prospectively recruited into three groups: Group 1: healthy control, Group 2: patients with stomatitis, and Group 3: patients with OSCC, with 4 individuals in each group. Unstimulated whole saliva samples from these participants were analyzed using real-time PCR to assess the presence and abundance of 14 major oral bacterial species and Candida albicans. Results: The analysis revealed significant differences for certain microorganisms, namely Treponema denticola (T. denticola), Lactobacillus casei (L. casei), and Candida albicans. T. denticola was most abundant in the OSCC group (5,358,692.95 ± 3,540,767.33), compared to the stomatitis (123,355.54 ± 197,490.86) and healthy control (9,999.21 ± 11,998.40) groups. L. casei was undetectable in the healthy control group, but was significantly more abundant in the stomatitis group (1,653.94 ± 2,981.98) and even higher in the OSCC group (21,336.95 ± 9,258.79) (p = 0.001). A similar trend was observed for C. albicans, with DNA copy numbers rising from the healthy control (464.29 ± 716.76) to the stomatitis (1,861.30 ± 1,206.15) to the OSCC group (9,347.98 ± 5,128.54) (p = 0.006). The amount of T. denticola was positively correlated with L. casei (r=0.890, p<0.001) and C. albicans (r=0.724, p=0.008). L. casei's DNA copy number was strongly correlated with C. albicans (r=0.931, p<0.001). These three oral microbes exhibited strong positive correlations with each other and had various direct or indirect relationships with other species. Conclusions: In the OSCC group, T. denticola, L. casei, and C. albicans exhibited strong positive correlations with one another, further emphasizing the need for a deeper understanding of the complex microbial interactions in the OSCC environment.

In recent decades, reports of deforestation, mass extinctions, biodiversity loss, and emergencies like floods and droughts have clearly highlighted the impact of human activities on these outcomes. This underscores the need for significant lifestyle changes to mitigate this impact. Pro-environmental behavior (PEB) change involves adopting actions that protect the environment and reducing environmentally harmful activities. While qualitative research may provide unique insights into PEB barriers that are challenging to capture through quantitative methods, reports of qualitative studies are scattered across different literatures with little integration. With the present review, we bring together insights from qualitative studies on PEB barriers and examine whether those studies reveal barriers compatible with existing barrier frameworks from environmental psychology. We identified 38 qualitative studies on barriers to PEB change. Our analysis revealed that most of the barriers to individual pro-environmental action identified in qualitative studies align with environmental psychology frameworks. These barriers were experienced not only by individuals in their role as consumer or citizen, but also by community-level actors (e.g., seeking to implement pro-environmental policies) and industrial decision-makers (e.g., aiming to reduce the ecological footprint of their business activities). Our findings underscore the multifaceted nature of barriers to PEB change and emphasize the importance of addressing structural and institutional factors alongside individual-level interventions.

Background: The accelerated ageing of the world's population will lead to an increase in the number of older persons in the workforce. Computerized Cognitive Training (CCT) is effective in improving cognitive outcomes, but its benefits for older workers remain controversial. We investigate the real-world efficacy of CCT in the workplace, focusing on employees aged 50+ years from a public sector agency. Methods: Case managers (N = 82) were randomized to either Intervention group (24 40-minute CCT sessions two times per week) or waiting list passive Control group. Cognitive ability, wellbeing, job satisfaction, and productivity outcome measures were collected assessed before and after CCT or comparable Control wait time. Results: Participants undergoing CCT improved on a task of executive functioning (p = 0.04). There was a trend toward change in work productivity after CCT (p = 0.09) with the Control group showing a significant decrease (p = 0.02), while the Intervention group remained stable. Conclusions: CCT during office hours has a positive effect on cognition and well-being without affecting the productivity among white-collar office workers. CCT could be considered as an intervention to support the older workforce in managing the cognitive and behavioral challenges of changing workplace demands.

The radiative heat transfer in arc plasma models is considered from the point of view of its description in terms of a net emission coefficient, the method of spherical harmonics in its lowest order, and the discrete ordinate method. Net emission coefficients are computed applying approximate and numerical approaches, the multi-band representation of the spectral absorption coefficient with three kinds of its averaging and two datasets. The self-consistent access to the radiative heat transfer is applied to a two-dimensional axisymmetric model of free-burning arc in argon at atmospheric pressure. The results obtained from the models employing the net emission coefficient, the method of spherical harmonics, and the discrete ordinate method are compared.

Asthma is a significant public health concern. This study identified the provinces with the highest morbidity and mortality rates due to asthma among the working-age population (15-69 years) in the Republic of Ecuador. The secondary objective was to explain the possible differences attribut-able to occupational exposure. This nationwide ecological and exploratory study was conducted in 24 provinces between 2016 and 2019. Government databases were used as sources of infor-mation. Standardized rates were calculated for codes the J45 and J46. The hospitalization mor-bidity rate for asthma decreased from 6.51 to 5.76 cases per 100,000 working-age population, and the mortality rate has consistently been low and stable from 0.14 to 0.15 deaths per 100,000 working-age population. Geographic differences between the provinces were evident. The risk of hospitalization and death due to asthma was higher in the Pacific coast (five provinces) and the Andean region (two provinces). The high rates observed in provinces with greater agricultural and industrial development could be the main determinants of national heterogeneity and could act as occupational risk factors. The contribution of occupational hazards in each province should be examined in depth through ad hoc studies. These findings provide valuable information for creating public policies aimed at promoting and safeguarding the respiratory health of the popu-lation, particularly that of workers.

Preschoolers with disabilities and their family caregivers are missed out in many public health initiatives especially in low-income countries. Yet they can benefit from early intervention to promote their development from soon after birth and to provide a better quality of life for their families. In this paper, we describe how a community-based approach has been implemented with minimal funding in two areas in Zimbabwe: a township in Harare and in rural areas of Manicaland Province. Our aim in sharing this information – allied with references to research studies recently undertaken in Africa – is that it will enable similar supports to be replicated in other communities by local personnel. A logic model is used to describe the situation in which the two projects work, the various inputs they have provided to their community and the different forms of support they have offered to the children and their caregivers. The project outputs are listed in terms of the number of beneficiaries helped and activities undertaken. The outcomes achieved for the children, the family and communities are reported. The sustainability and extensions of community-based projects to address unmet needs are discussed. The main conclusion is that disadvantaged communities can be energized to address the needs of their most marginalized residents.

In this paper we describe a method which combines sentiment analysis with machine learning techniques and/or multivariate statistical analysis. By applying this methodology it is possible to classify a collection of texts into two or more groups or clusters. On the basis of a number of previously defined clusters, the novelty of the outlined approach is the use of the sentiment analysis results as input to the machine learning model or multivariate statistical analysis. Once the classifier has been obtained, we can assign a given text into one of the pre-established clusters. The groups or clusters can represent different time periods, classes of texts transcribed from different conversations, etc. The method is illustrated through an example taken from one of the two studies in which we have applied this methodology. In one of the studies, the method was used to classify press news of a volcanic eruption, while in the other study it was used to classify the conversations recorded between a chatbot with different kinds of speakers (humans or chatbots). This last study was the seminal work in which we introduced this methodology.

We interviewed 48 people including local communities, ex hunters and protected area management professionals. The purpose of the interviews was to understand the motivations for, and the nature of, illegal hunting of prey species of iconic predators - tigers and leopards - in the northern section of Bardia National Park. Participants reported that hunting of prey species occurs mostly in spring and autumn and is less common during the summer. In the past, hunting was primarily for the purposes of obtaining meat for household consumption. Since the introduction of a road network in the region, opportunities to sell wild meat at ad-hoc ‘highway markets’ have developed. The purported medicinal properties of wild meat was also cited as a driver for illegal hunting. Mostly, locally hand-made guns are used for hunting and the use of dogs in hunting was often reported. Protected area managers informed that illegal hunting problems in the study area are associated with a lack of presence of park authorities, remoteness and underdevelopment and poverty of the community. Our study suggested that skills development training for local community members might reduce dependency on wild meat for household consumption and earning thereby reducing illegal hunting.

Iturbide is located in the Northeast of Mexico, it has a rich native and exotic flora, however, there are no ethnobotanical records, therefore, it requires attention in the documentation of traditional practices and uses of its botanical resources. In 2021, twelve field trips were carried out, applying 110 semi-structured interviews. Plant samples were collected, identified and deposited in an herbarium. We used the Chi-square test to compare ethnobotanical uses with respect to others reported in Mexico. To determine the cultural importance, three ethnobotanical indices were applied (UVI, ICF and FL). We recorded 250 species with ethnobotanical uses associated with 121 genera and 83 families, including 140 native and 110 exotic species. The most common plant families were Asteraceae, Lamiaceae, and Fabaceae. The main uses were ornamental, medicinal and food. The species with the highest UVI values ​​were Lepidium peruvianum, Ocimum basilicum and Rosmarinus officinale. The multifunctionality of the native and exotic flora demonstrates the extensive knowledge associated with botanical resources. Examples, the role of ornamental plants, with a direct impact on human well-being, the resilience of healers and traditional inhabitants by using different species for the treatment of various ailments. or indigenous edible plants in the daily diet.

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects (n=207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with “cholesterol absorption”. Statin usage also had a positive correlation with “cholesterol synthesis” Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.

In this work, effects of 20 transition element additives on the interfacial adhesion energy and electronic structure of Al (111)/6H-SiC (0001) interfaces have been studied by first principles method. For clean Al (111)/6H–SiC (0001) interfaces, both Si-terminated and C-terminated interfaces have covalent bond characteristics. The C-terminated interface has stronger binding energy, which is mainly due to the stronger covalent bond formed by the larger charge transfer between C and Al. The results show that the introduction of many transition elements, such as 3d transitional group Mn, Fe, Co, Ni, Cu, Zn and 4d transitional group Tc, Ru, Rh, Pd, Ag, can improve the interfacial adhesion energy of the Si-terminated Al (111)/6H-SiC (0001) interface. However, for the C-terminated Al (111)/6H-SiC (0001) interface, only the addition of Co element can improve the interfacial adhesion energy. Bader charge analysis shows that the increase of interfacial binding energy is mainly attributed to more charge transfer.

Seagrasses are considered as efficient bioindicators of coastal trace element contamination. This chapter provides an overview on the trace element accumulation, tolerance and biomonitoring capacity of the various seagrass species distributed along the coast of India. A total of 10 trace elements are reported in seagrasses, 11 in sediment and nine in the water column from India. From the 11 seagrass species studied, 60% of research have focused on Syringodium isoetifolium, Cymodocea serrulata, Cymodocea rotundata and Halophila ovalis. 78% of seagrass trace element research in India is from Palk bay and Gulf of Mannar (GOM), Tamil Nadu and 16% from Lakshadweep Islands. Out of the 10 trace elements, Cd, Cu, Pb and Zn are the most studied in seagrass, Fe, Mn, Ni and Pb in sediment and Cu, Fe, Mg, Ni and Zn in the water column. Accumulation capacity of various trace elements in seagrass were species-specific. S. isoetifolium have the highest concentration of Cd and Mg at Palk bay and Lakshadweep Islands respectively. The concentration of Cu was higher in C. serrulata at GOM. Halodule uninervis and Halophila decipens have the highest concentration of Co, and Cr, Ni, Pb and Zn from Lakshadweep Islands. The highest concentration of Fe and Mn were highest in Halophila beccarii and H. ovalis from the coast of Goa and Palk bay respectively. Threshold levels (>10 mg L^-1) of Cd, Cu, Pb and Zn were observed for C. serrulata, H. ovalis, H. uninervis and T. hemprichii, that can affect the Photo System -II of these seagrasses and exert cellular stress leading to seagrass loss and die-off. High concentration of these elements can exert negative impacts on seagrass associated trophic assemblages and ecosystem functioning. Seagrasses of India can be utilized as bioindicators of coastal trace element contamination but the associated toxicity and human health risks needs further investigation.

Artificial Intelligence (AI) is increasingly becoming integral to medical practice, potentially enhancing outcomes in thoracic surgery. AI-driven models have shown significant accuracy in diagnosing non-small cell lung cancer (NSCLC), predicting lymph node metastasis, and aiding in the efficient extraction of electronic medical records (EMR) data. Moreover, AI applications in robotic-assisted thoracic surgery (RATS) and perioperative management reveal potential in improving surgical precision, patient safety, and overall care efficiency. Despite these advancements, challenges such as data privacy, biases, and ethical concerns remain. This manuscript explores AI applications, particularly machine learning (ML) and natural language processing (NLP), in thoracic surgery, emphasizing their role in diagnosis and peri-operative management. It also provides a comprehensive overview of the current state, benefits, and limitations of AI in thoracic surgery, highlighting future directions in the field.

The switch from intermittently scanned continuous glucose monitoring (isCGM) to real-time (rt) CGM could improve glycemic management in suboptimal controlled type 1 diabetes patients, but long-term study is lacking. We evaluated retrospectively the ambulatory glucose profile (AGP) in such patients after switching from Free Style libre 1 (FSL1) to Dexcom G4 (DG4) over 1 year. Patients (n=21, 43±15 years, BMI 25±5, HbA1c 8.1±1.0%) had severe hypoglycemia and/or HbA1c≥8%. AGP metrics (time-in-range (TIR) 70-180 mg/dL, time-below-range (TBR)<70 mg/dL or <54 mg/dL, glucose coefficient of variation (%CV), time-above-range (TAR) >180 mg/dL or >250 mg/dL, glucose management indicator (GMI), average glucose) were collected the last 3 months of FSL1 use (M0) and of DG4 for 3, 6 (M6) and 12 (M12) months of use. Values were means ± standard deviation or medians [Q1;Q3]. At M12 versus M0, the higher TIR (50±17 vs. 45±16, P=0.036), and lower TBR<70 mg/dL (2.5 [1.6;5.5] vs. 7.0 [4.5;12.5], P=0.0007), TBR<54 mg/dL (0.7 [0.4;0.8] vs. 2.3 [0.8;7.0], P=0.007) and %CV (39±5 vs. 45±8, P=0.0009), evidenced a long-term effectiveness of the switch. Compared to M6, TBR<70mg/dL decreased, %CV remained stable, while the improvement on hyperglycemia exposure decreased (higher GMI, TAR and average glucose). This switch was a relevant therapeutic option, though a loss of benefit on hyperglycemia stressed the need for optimized management of threshold alarms. Nevertheless, few patients attained the recommended values for AGP metrics, and the reasons why some patients are “responders” vs “non-responders” warrant to be investigated.

(1) E-governance is defined as the application of electronic means in the interaction between government and citizens and government and business, as well as in internal government operations to simplify and improve democratic, governmental, and business aspects of governance. Thus, e-governance is built from a paradigmatic dimension such as e-democracy (relationship between government and citizens) and an operational one such as e-government. The objective was to design and validate an instrument to measure e-governance based on three factors: a) e-administration, b) e-services, and c) e-democracy; (2) Methods: Based on the level of importance given to each factor (sample of 2042 Latin American citizens), as well as the relationships between them, an analysis of the importance of each factor is carried out; (3) Results: After the confirmatory analysis, the definitive instrument with which e-governance can be measured by other researchers and future research is obtained, considering the three selection factors, namely: e-administration, e-services and e-democracy; (4) Conclusions: This research contributes to political science through the design and validation of an instrument consisting of 39 items that can be used to measure e-governance according to the dimensions proposed by the United Nations Educational, Scientific and Cultural Organization.

This study aimed to determine clinical instructors’ perceptions of the assessments used to evaluate the clinical knowledge of undergraduate nursing students. This study uses a descriptive phenomenological approach. Purposive sampling was used to recruit sixteen clinical instructors for semi-structured interviews between August to December 2019. All interviews were audio-recorded and transcribed verbatim. Data were analyzed using Colaizzi’s seven-step method. Four criteria were used to ensure the study’s validity: credibility, transferability, dependability, and confirmability. Three themes were identified in the clinical instructors’ views on evaluating the clinical performance of student nurses: familiarity with students, patchwork clinical learning, and differing perceptions of the same scoring system. Study results suggest the need for a reliable, valid, and consistent approach to evaluating students’ clinical knowledge. If the use of patchwork clinical internships for student nurses is unavoidable, a method for assessing student nurses’ clinical performance that requires instructor consensus is necessary.

Location-specific weather and climate information together with related advisory services are one of the crucial drivers of development in the 21^st century particularly in Sub-Saharan Africa. However, there still exist significant gaps in provision of weather and climate information at scales that effectively address the needs of local people for instance; local farmers and pastoralists. This therefore force local people to rely on indigenous knowledge (IK), to observe and forecast weather conditions. This situation does not exclude Uganda, and thus the current study assessed the efficacy of integrating indigenous knowledge systems into modern weather observational instruments in order to boost and act as a backup mechanism for modern weather observational instruments to increase accuracy and wide coverage of weather observations within Uganda. Results indicated that, respondents across the two pilot sites use a combination of plants, animals, insects, and human behaviours, meteorological and astrological indicators to observe and predict local prevailing weather conditions. Majority of the respondents particularly in Masaka district, believed that the use of indigenous knowledge to observe weather and climatic events is very reliable compared to their counterparts in Entebbe Municipality. Therefore, the integration of indigenous knowledge system in scientific weather observations is very vital.

The COVID-19 pandemic has significantly altered how people work, with an increasing number transitioning to working-from-home (WFH). This paradigm shift has raised various challenges in adapting living spaces to meet the needs of remote work. Dedicated workspaces or home offices need to be customised for creativity and productivity. Thus, this systematic literature review explores the potential challenges and limitations of implementing modern office design features in residential environments. The study synthesises findings from 108 peer-reviewed articles published within the last decade, focusing on ergonomics, productivity, work-life balance, and spatial constraints. The study found several challenges in translating office design features to home settings. Firstly, spatial limitations in residential areas often restrict the implementation of open-plan layouts and collaborative zones, which are hallmarks of modern office designs. Secondly, the integration of ergonomic furniture and adjustable workstations are limited by budget constraints and the dual-purpose nature of many home spaces. Furthermore, the review highlights the psychological challenges of maintaining work-life boundaries when professional and personal spaces overlap. Noise pollution and distractions emerge as significant factors impacting productivity in home offices, which contrasts controlled modern office environments. The review suggests that the complete replication of modern office design in homes may be impractical, a hybrid approach that adapts key features to residential constraints could enhance home office productivity. Potential solutions could include modular furniture designs, the simulation of collaborative spaces, and the development of noise-cancelling technologies specifically for home environments. This study contributes to the growing body of knowledge on remote work environments and provides valuable insights for enhancing work-life balance, environmental sustainability, and economic growth.

In the course of SARS-CoV-2 infection, the 3CL or nsp5 protease plays a pivotal role as the most important viral protease required for the maturation of viral proteins during host infection. Herein, we simulated for 500 ns 3CLproWT, 3CLproH41A, , 3CLproBeta, and 3CLproOmicron, in complex with the substrates nsp 4|5 and nsp 5|6. Our results show that mutations in the 3CLpro present in the SARS-CoV-2 variant of concerns (VOCs) did not lead to significant conformational changes or changes in substrate binding affinities. However, significantly high cleavage rates for the boundary between nsp4 and nsp5 were obtained for 3CLproBeta and 3CLproOmicron and may play a key role in the viral replication and virus fitness gain. Our molecular dynamics data suggest that the cleavage rate of nsp4|5 may be related to the increased amount of viral load observed for these VOCs, releasing more nsp4 than other non-structural proteins. Based on our hydrogen bonding analyses, we also discovered that Gly143 and Glu166 are key residues in substrate recognition, suggesting that these residues may be incorporated as pharmacophoric centers for Beta and Omicron variants in drug design. Our results suggest that Gly143 and Glu166 are essential residues to interact with Gln6 of the different substrates and, therefore, are potential broad-spectrum pharmacophoric centers of SARS-CoV-2 3CLpro.

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

Molecular hydrogen (H2) has been shown to have antioxidant and anti-inflammatory activities that may reduce the development and progression of many diseases. In this study, Hydrogen-rich water (HRW) was obtained by reacting hybrid magnesium-carbon hydrogen storage materials with water. Then the effects of intake of HRW on the activities of xenobiotic-metabolizing enzymes, membrane transporters, and oxidative stress in rats were investigated. Rats were given HRW ad libitum for 4 weeks. Results showed that intake of HRW had no significant effect on the activities of various cytochrome P450 (CYP) enzymes (CYP1A1, 1A2, 2B, 2C, 2D, 2E1, 3A, 4A), glutathione-S-transferase and UDP-glucuronosyltransferase. Except for a slight lower plasma glucose concentration, intake of HRW had no effect on other plasma biochemical parameters in rats. P-Glycoprotein and multidrug resistance-associated protein (Mrp)2 protein expressions in liver were elevated after intake of HRW. However, HRW had no significant effects on glutathione, glutathione peroxidase, or lipid peroxidation in liver. Results from this study suggest that consumption of HRW may not affect xenobiotic metabolism or oxidative stress in liver. However, intake of HRW may increase the efflux of xenobiotics or toxic substances from the liver into bile by enhancing the expression of p-glycoprotein and Mrp2 protein.

Industry 4.0 is an industrial paradigm that is causing changes in form and substance in factories, companies and businesses around the world, and is impacting work and education in general. In fact, the disruptive technologies that frame the fourth industrial revolution have the potential to improve and optimize manufacturing processes and the entire value chain, which can lead to an exponential evolution in the production and distribution of goods and services. All these changes imply that the fields of engineering knowledge must be oriented towards the concept of Industry 4.0, for example Mechanical Engineering. The development of various physical assets that are used by cyber-physical systems and digital twins is based on Mechanics. However, the specialized literature on Industry 4.0 says little about the importance of Mechanics in the new industrial era and more importance is given to the evolution of Information and Communication Technologies and Artificial Intelligence. This article presents a frame of reference about the importance of Mechanical Engineering in Industry 4.0 and proposes an extension to the concept of Mechanics 4.0, recently defined as the relationship between Mechanics and Artificial Intelligence. For the analysis of Mechanical Engineering in Industry 4.0, the criteria of the four driving forces that defined Mechanics in the third industrial revolution was used. An analysis of Mechanical Engineering Education in Industry 4.0 is presented, and the concept of Mechanical Engineering 4.0 Education is improved. Finally, the importance of making changes in the educational models of engineering education is described.

Sharing activity is getting higher attention due to increasing popularity in recent years. In the paper, the authors investigated the main elements affecting the sharing activity. (1) Literature review: The theoretical part starts from the revision of definitions of sharing activity; description of the links between sharing and sustainable development, policy recommendations and relevant regulation in the field; later on, the study emphasises the key elements important for sharing. Finally, the authors investigated how the Covid-19 pandemic affected sharing activity; (2) Methods: During empirical research, the authors revised the list of 37 variables. The study uses data for each of the 27 EU countries from 2011 to 2020. The authors investigated correlation between macroeconomics variables to determine key variables for the regression model; (3) Results: The authors constructed a dynamic regression model that can be applied to predict the number of participants visiting sharing platforms in the European Union (EU); (4) Conclusions: The study shows that seeking to forecast the number of visits to sharing platforms it is necessary to use values of main macroeconomic variables such as consumer price index, productivity index, total unemployment rate, the number of users and households connected to the Internet, etc.

In this paper, the authors identified key elements important for circularity: (1) Background: The primary goal of circularity is to eliminate waste and to prove the constant use of resources. In the paper, we classify studies according to circular approaches. The authors identified main elements and classified them into categories important for circularity, starting with the managing and reducing waste and the recovery of resources; and ending with the circularity of material, and general circularity-related topics and presented scientific works dedicated to each of the above-mentioned categories. The authors analyzed several core elements from the first category aiming to investigate and connect different waste streams and provided a regression model; (2) Methods: The authors used a dynamic regression model to identify relationships among variables and selected the ones, which has an impact on the increase of biowaste. The research was delivered for the 27 European Union countries during the period between 2020 and 2019; (3) Conclusions: The authors indicated that the recycling rate of wasted electrical equipment in the previous year has an impact on the increase of recycling biowaste next year. This is explained as non-metallic spare parts of electronic equipment are used as biowaste for fuel production. And the separation process of the composites of electric equipment takes some time, on average the effect is evident in one year period.

The German wine sector has encountered new challenges in water management recently. To manage water resources responsibly, it is necessary to understand the relationship between the input of water and the output of wine, in terms of quantity and quality. The objectives of this study are to examine water use at the farm scale at three German wineries, and to develop and apply, for the first time, a quality-based indicator. Water use is analyzed in terms of wine production and wine-making over three years. After the spatial and temporal boundaries of the wineries and the water flows are defined, the farm water productivity indicator is calculated to assess water use at the winery scale. Farm water productivity is calculated using the AgroHyd Farmmodel modeling software. Average productivity on a quantity basis is 3.91 L wine per m3 of water. Productivity on a quality basis is 329.24 °Oechsle per m3 of water. Water input from transpiration for wine production accounts for 99.4–99.7% of total water input in the wineries, and, because irrigation is not used, precipitation is the sole source of transpired water. Future studies should use both quality-based and mass-based indicators of productivity.

In the following article I take into consideration the role of knowledge workers in the Italian regions. The analysed data refers to the ISTAT-BES database. The metric analysis consists of an in-depth analysis of the trends of the regions and macro-regions, followed by clustering with the k-Means algorithm, the application of machine learning algorithms for prediction, and the presentation of an econometric model with panel methods date. The results are also critically discussed in light of the North-South divide and the economic policy implications.

This work promotes new methods in Mathematical Modeling, consisting in the use of the methods of Non-standard Analysis in Topoi, having as its main purpose, the mathematical definitions of the pseudoparticles from the title, with arguments from Biology/Physiology (Mathematical Neuroscience), Physics (String Theory and Emergent Quantum Mechanics), and Cybernetics (Global Brain, including Natural and Artificial Intelligence). The connections between brain and mind will be scketched via the genetic/epigenetic interplay. The topoi model the intuitionistic logic (multi-valued) and have been used in Quantum Physics while Non-Standard Analysis in SET (= the Category of sets) has been applied in Mathematical Economics; topics from Theory of Categories were also used in the study of Consciousness; however, the combination topoi - non-standard analysis was never used until now in Applied Mathematics. Another important objective is to produce progress in this aria of Pure Mathematics also - the build of non-standard analysis in classes of topoi, already used in Physics. We propose the logic of non-standard extensions in topoi as a model of the human thinking (based on infons/receptons), these theories representing new top and very difficult results in Abstract Mathematics either.

The Chikungunya virus (CHIKV) poses a significant global public health concern, especially in Africa. Since its first isolation in Tanzania in 1953, CHIKV has caused recurrent outbreaks, challenging healthcare systems in low-resource settings. Recent outbreaks in Africa highlight the dynamic nature of CHIKV transmission and the challenges of underreporting and underdiagnosis. Here, we review literature and analyze publicly available cases, outbreaks, and genomic data providing insights into the epidemiology, genetic diversity, and transmission dynamics of CHIKV in Africa. Our analyses reveal the circulation of geographically distinct CHIKV genotypes, with certain regions experiencing a disproportionate burden of disease. Phylogenetic analysis of sporadic outbreaks in West Africa suggests repeated emergence of the virus through enzootic spillover, which is markedly different from inferred transmission dynamics in East Africa, where the virus is often introduced from Asian outbreaks, including the recent reintroduction of the Indian Ocean lineage from the Indian subcontinent to east Africa. Furthermore, there is limited evidence of viral movement between these two regions. Understanding the history and transmission dynamics of outbreaks is crucial for public health planning. Despite advances in surveillance and research, diagnostic and surveillance challenges persist. This review and secondary analysis highlight the importance of ongoing surveillance, research, and collaboration to mitigate the burden of CHIKV in Africa and improve public health outcomes.

The Mediterranean Diet, characterized by high intake of plant foods and unsaturated fats, has been suggested to improve assisted reproductive technology (ART) outcomes. This literature review aimed to summarize the evidence from observational studies on the associations between preconception Mediterranean Diet and ART outcomes. PubMed/MEDLINE, Embase, ScienceDirect, and Google Scholar databases were searched to identify relevant studies. Seven observational studies (n=2,321 women on ART) were included. Adherence to the Mediterranean Diet was assessed by food frequency questionnaires with 6-195 items. Three studies found that higher Mediterranean Diet scores improved Clinical Pregnancy or Live Birth rates, while two studies showed a positive effect on ART eggs and embryos. However, two studies reported no significant associations with ultimate ART success, and four studies found no effects on oocyte and embryo number or quality. Evidence for the effects of greater adherence to the Mediterranean Diet on ART outcomes is limited but promising. Additional rigorous research is needed to clarify and weigh the degree of association between the Mediterranean Diet and ART success.

Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress, and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect the tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation, including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and 5-AZA group. MiR-18a, miR-21, miR-34a and miR-146a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRNs profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRNs expression levels. Relating to prognostic risk factors, high risk MDS groups (high IPSS-R, high cytogenetic risk, high molecular risk (HMR) mutations tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRNs expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRNs deregulation involved in the MDS development, that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRNs expression levels in MDS patients.

Hepatic Encephalopaty (HE) is a common complications of advanced liver disease and acute liver failure. It is a condition that features both neurological and psychiatric symptoms, that affects mortality, morbidity and quality of patients and caregivers’ life. HE diagnosis is generally an exclusion diagnosis. Once the patient is admitted to hospital, clinical examination, blood tests and eventually neuroimaging should be performed in order to rule out other causes of acute brain dysfunction. Moreover, HE recognizes various precipitants that can potentially promote its onset, alone or in combination, that must be identified. Once the diagnostic process is complete, a correct treatment should be started. The anti-HE treatment is based on a combination of correction of precipitants and non-absorbable disaccharides and non-absorbable antibiotic, such as rifaximin. Once the patient is discharged from the hospital, specific anti-HE therapy should be maintained in order to prevent other HE episodes.

Polymeric wet-strength agents are important additives used in the paper industry to improve the mechanical properties of paper products, especially when they come in contact with water. These agents play a crucial role in enhancing the durability, strength, and dimensional stability of paper products. The aim of this review is to provide an overview of the different types of wet-strength agents available and their mechanisms of action. We will also discuss the challenges associated with the use of wet-strength agents and the recent advances in the development of more sustainable and environmentally friendly agents. As the demand for more sustainable and durable paper products continues to grow, the use of wet strength agents is expected to increase in the coming years.