Triticale is recognized worldwide due to its high protein and lysine content, high production capacity and adaptability to biotic and abiotic stress conditions, these qualities being taken over from wheat and rye. Triticale is widely used in various fields such as animal feed in various forms, in medicine, the bakery, beer, alcohol, cellulose, bioethanol industry and many others. Thus, the demand for triticale grains is increasing, and this has led to the research and improvement of culture technology to obtain superior products, both quantitatively and qualitatively. The purpose of this study was to identify the best varieties of triticale cultivated in the north-west of Romania, sown in different plots and fertilized on the ground or additionally, the study being carried out over a period of two years at the Livada Agricultural Research and Development Station, Satu Mare county. The study was located on an acidic soil with a pH between 5.19 and 6.65 and a humus content of 2.82%. The climatic conditions in the reference period were extremely variable, in the first year a deficit of more than 90 mm/m2 of precipitation was registered, and in the second year of the study, an increase of more than 34 mm/m2. The effects of additional fertilization were influenced by the level of precipitation, so in the experimental variants additionally fertilized, lower productions were obtained compared to the variants fertilized only on the soil. Compared to the Negoiu control, the Utrifun variety proved to be the most productive, but this will be proven in the following years of study, under different climatic conditions.

Background: This study provides a comprehensive analysis of Acinetobacter baumannii in aquatic environments and fish microbiota by integrating culture-dependent methods, 16S metagenomics, and antibiotic resistance profiling. Methods: A total of 83 A. baumannii isolates were recovered using culture-dependent methods from intra-hospital infections (IHI), wastewater (WW) and surface water (SW) samples from two southern Romanian cities in august 2022. The antibiotic susceptibility was screened using disc diffusion, microdilution, PCR and Whole Genome Sequencing assays. Results: The highest microbial load in the analyzed samples was found in Glina, Bucharest for both WW and SW samples across all investigated phenotypes. For Bucharest isolates, the resistance levels corresponded to fluoroquinolones > aminoglycosides > β-lactam antibiotics. In contrast, A. baumannii from upstream SW samples in Targoviste showed the highest resistance to aminoglycosides. The blaOXA-23 gene was frequently detected in IHI, WW, and SW isolates in Bucharest but was absent in Targoviste. Molecular phylogeny revealed presence of ST10 in Târgoviște isolates and ST2 in Bucharest isolates, while other minor STs were not specifically correlated with a sampling point. Using 16S rRNA sequencing, significant differences in microbial populations between the two locations was identified. The low abundance of Alphaproteobacteria and Actinobacteria in both locations suggests environmental pressures or contamination events. Conclusions: These findings indicate significant fecal contamination and potential public health risks, emphasizing the need for improved water quality monitoring and management.

This research work deals hybrid control system based integrated Cuk converter fed brushless DC motor (BLDCM) for power factor correction. In this work, moth-flame optimization (MFO) and fuzzy logic controller (FLC) has been combined and moth –flame fuzzy logic controller (MFOFLC) has been proposed. Firstly, the BLDC motor modelling is composed with power factor correction (PFC) based integrated Cuk converter and BLDC speed is regulated using variable DC-Link inverter voltage which makes low switching operation with less switched losses. Here, with the use of switched inductor, the task and execution of proposed converter is redesigned. The DBR (diode bridge rectifier) trailed by proposed PFC based integrated Cuk converter operates in discontinuous inductor conduction mode(DICM) for achievement of better power factor.MFO is exhibited for gathering of dataset from the input voltage signal. At that point separated datasets is send to FLC to improve the updating function and minimization of torque ripple. However, our main objective is to assess adequacy of proposed method, the power factor is broke down. The execution of the proposed control methodology is executed in MATLAB/Simulink working platform and the display is assessed with the existing techniques.

:Peat substrate is made from peat from drained peatlands, which is a limited resource. A realistic estimate is that 50% of the world’s wetlands have been lost. Peat is used in horticulture, especially for the cultivation of vegetables in greenhouses. The consequences of peatland exploitation are an in-crease in the greenhouse effect and a decrease in carbon stocks. Wood fiber can be used as an al-ternative to peat. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the growing container. This study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) variety “Dirigent H” developed in the Netherlands, were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) con-ventional fertilization (CF); (2) N13; (3) N23; (4) N30. The experiment was carried out in three repli-cations. As the amount of wood fiber increased, the humidity and pH of the growing medium in-creased. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in 50/50 and 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat sub-strate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

: Greenhouse plants are usually grown in containers filled with growing media. Peat is the main component of the growing media used in greenhouses. However, peat substrate is made from peat from drained peatlands, which is a limited resource. Wood fiber can be an alternative to use as a growing media for controlled-climate crops. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the vegetative container. Therefore, this study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) conventional fertilization (CF); (2) N13; (3) N23; (4) N30. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in WF/PS 50/50 and WF/PS 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat substrate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

Microbe bioengineering has the potential to improve the nutritional value and health benefits of food products. Modifying microbial cells to produce specific proteins or compounds that can improve human health is one approach. Penicillin and recombinant insulin are two examples of this. The production of recombinant insulin by genetically modified E. coli bacteria has transformed diabetes treatment by providing a consistent and cost-effective source of insulin. Previously, insulin was extracted from the pancreas of animals, which was an expensive process that frequently resulted in impurities that could cause adverse reactions. Bioengineered insulin is now the standard diabetes treatment, providing a safe and effective method of controlling blood glucose levels. Bacteria, for example, can be genetically modified to produce vitamins like B12, which are difficult to obtain from plant sources. Likewise, yeasts can be genetically modified to produce β-carotene, a precursor to vitamin A that is required for vision, immune function, and skin health. Overall, bioengineered microorganisms have the potential to provide significant health benefits by producing essential compounds and proteins. Because of ongoing advances in genetic engineering techniques and understanding microbial metabolism, the possibilities for improving human health through bioengineering are limitless.

Global emerge of zoonotic novel corona virus (COVID-19) became a pandemic and its effect to mankind is talk of the town now a days. This tiny, invisible enemy has affected every country in the world and almost every living directly or indirectly and nationwide complete lockdown has triggered a short-term environmental impact. Since 2003, corona virus came into existence in the form of Severe Acute Respiratory Syndrome (SARS) and more evolved Middle East Respiratory Syndrome (MERS) in 2012. This time, at the end of December 2019, outbreak of novel corona virus COVID-19 (also known as SARS-CoV₂, nCoV-2019) draw attention as global health emergency. World Health Organization (WHO) report says that the outbreak of this virus is so immense, it has already affected 35,57,235 people and caused death to 2,45,150 people worldwide and 46,433 Indians got affected with 1568 death as on 5^th May 2020 (2:00 am) and these numbers are increasing exponentially day by day. Virologist, micro-biologist and science community are hammering their head very hard to find out cure and vaccine against this powerful virus and to prevent mass demise of mankind. In order to curb the spread of COVID-19, Janta curfew on 22.03.2020 and nationwide complete lockdown was implemented in India for 21 days (phase-I, from 25.03.2020 to 14.04.2020) to stop community transmission of third stage, for 19 days (phase-II, 15.04.2020 to 03.05.2020) and 14 days (phase-III, 04.05.2020 to 17.05.2020) complete lockdown to minimize the community transmission effect. During complete lockdown and quarantine period a drastic change in Earth’s atmosphere, including reduction in emission of greenhouse gases, air pollution (~50% fall in air quality index), noise pollution, water pollution and solid waste pollution, have been recorded by government agencies as well as private agencies. In this paper we considered data of Janta curfew, phase-I and phase-II lockdown to link between geological and environmental aspect related to environmental impact due to emerge of COVID-19 and massive reduction in pollution level during complete lockdown in India. We propose future lockdown strategies to minimize the emission of greenhouse gas by ~100 Mt to ~200Mt (3.33% to 6.66%) of GHG_total per year by 2-4 days per month nationwide lockdown or ~70 Mt to ~140 Mt (2.33% to 4.66%) of GHG_total per year by 2-4 days per month complete lockdown of energy sectors only.

A simple protocol for preparation of O-acylated enol form - (R/S)-ethyl-2-acetoxy-4-phenyl-4H-chromene-3-carboxylate 5 was presented. The compound was characterized by 1H-, 13C-and DEPT135 NMR spectra, including {1H,1H} COSY, {1H,13C} HSQC, {1H,13C} HMBC and 2D-NOESY spectra. The preferred regioselectivity for O-acylation of 3,4-dihydrocoumarin 5 in the presence of substituent in 4-th position in the chroman ring and accounting the steric hindrance of the ester group in 3-th place was confirmed.

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a β-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.

This paper investigates the constructability of angles multiples of 3 within the framework of Euclidean geometry. It makes a significant contribution by presenting the first geometric construction for all such angles, offering a rigorous solution to a longstanding geometric problem. The paper reaffirms the efficacy of Euclidean geometry in providing precise constructions and robust proofs for these angles, demonstrating the enduring strength of Euclidean principles from classical to modern times. The presented workflow goes beyond Euclidean geometry to examine non-Euclidean methods, particularly analytical approaches, revealing misconceptions that compromise the genetic and geometric rigor of Euclidean principles. The paper exposes incongruities when algebraic proofs related to angle constructability are applied to the Euclidean system, emphasizing the misalignment of fundamental geometric concepts. A notable result in the paper is the construction of a angle, introducing the “ angle chord” as a novel geometric property. This property challenges assumptions made by non-Euclidean methods and highlights the nuanced geometric properties crucial for rigorous constructions. The paper refutes the fallacy of relying solely on algebra for solutions to angles multiples of , emphasizing the necessity of embracing Euclidean geometry for geometric discoveries. The paper underscores the merits and resilience of Euclidean geometry, showcasing its independence and depth across historical and modern perspectives. The newly presented geometric construction not only resolves a longstanding question but also emphasizes the intrinsic strength and uniqueness of Euclidean principles in contrast to alternative methodologies.

This study delves into the Southern Aegean region where the subduction of the oceanic Mediterranean lithosphere under the Aegean continental one takes place. This region is considered one of the most active ones in the Eastern Mediterranean Sea due to intense tectonic movements in the Late Quaternary. More than 1200 manually revised events from 2018 to 2023 have been used in order to obtain the 3-D structure of body-wave velocity and VP/VS ratio to 80 km depth, through Earthquake Tomography. A series of resolution tests have been performed and demonstrated fair resolution of the derived velocity structures in area of interest. The derived anomalies of body waves (dVP, dVS), and VP/VS ratio provided important information about the Southern Aegean regional tectonics, and secondarily active faults of smaller scale (>20 km). The region is marked by significant low-velocity anomalies in the crust and uppermost mantle, beneath the active arc volcanoes. The seismicity related to the Hellenic Subduction Zone (HSZ) is connected to a low-angle positive anomaly of VP and VS, correlated to the observed intermediate-depth seismicity (H≥40 km) in this part of the study area. This result could be related to the diving HSZ slab.

Background: Cell-free plasma DNA (cfDNA) is composed of circulating extracellular DNA originating from apoptosis or cell necrosis. It is generally present in healthy individuals, but its levels increase in different clinical conditions, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. Caspase-3 plays a central role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis of chronic kidney disease (CKD). Methods: We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating the modification of their concentrations according to CKD stage. We also analyzed the correlation between cfDNA and caspase-3 levels in CKD patients and the correlation between cfDNA and caspase-3 levels and creatinine and urea. Results: CfDNA and caspase-3 levels were higher in CKD patients compared to healthy subjects, in particular in patients with advanced renal disease. A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea was also observed. Conclusion: Patients with chronic kidney disease present higher levels of cfDNA and caspase-3 levels compared with healthy subjects. The worsening of renal damage and the increase in uremic toxin concentration are associated to higher levels of cfDNA and caspase-3 levels, thus reflecting a central role of apoptosis in the pathogenesis of CKD.

2-(5,6-diphenyl-1,2,4-triazin-3-yl)pyridinium dichloroiodate (I) (1) was synthesized by reacting 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine with ICl in dichloromethane solution. The structural characterization of 1 by SC-XRD analysis was accompanied by elemental analysis, FT-IR, and FT-Raman spectroscopy measurements.

This paper examines the potential of Artificial Intelligence (AI) to address societal megatrends, with a specific focus on OpenAI’s Generative Pre-Trained Transformer 3 (GPT-3). To do this, we con-ducted an analysis using GPT-3 in order to explore the benefits of AI for digitalization, urbanization, globalization, climate change, automation and mobility, global health issues and aging population. We also looked at emerging markets as well as sustainability in this study. Interaction with GPT-3 was done solely through prompt questions and generated responses were analyzed. Our results indicate that AI can significantly improve our understanding of these trends by providing insights into how they develop over time and what solutions could be implemented. Further research is needed to determine how effective AI will be in addressing them successfully but initial findings are encouraging. Our discussion focuses on the implications of our findings for society going forward and suggests that further investigation should be done into how best to utilize new technologies like GPT-3 when tackling these challenges. Lastly, we conclude that while there is still much work left to do before any tangible effects can be seen from utilizing AI tools such as GPT-3 on societal mega-trends; early indications suggest it may have a positive impact if used correctly.

Many years and $$$ spent for research did not yet produced a universally effective gene therapy of prostate cancer (PCa). Our studies indicated that not only each human, but even each cancer nodule in the same tumor has unique and dynamic gene expression profile, control and coordination. The tumor heterogeneity of the transcriptome topology is a strong argument in favor of personalized gene therapies, tailored on patients’ primary tumor unique characteristics. Here, we propose a bioinformatics procedure by which to identify the Gene Master Regulators (GMR) of cancer cells from transcriptomic data and predict consequences of their experimental manipulation. The procedure, based on our Genomic Fabric Paradigm (GFP), can determine the most important gene in each cancer nodule whose controlled alteration would selectively kill the cancer cells. In this report, the method is applied to our microarray data on two men PCs (each with three distinct cancer nodules) and two standard human PCa cell lines (DU145 and LNCaP). We expect the industry to produce ready-to-use CRISPR constructs for all genes allowing the clinical oncologist to prescribe the adequate personalized CRISPR cocktail for his/her patient. Thus, the GMR approach may provide the most effective, yet affordable solution in fighting cancer.

A two-link model of exoskeleton with variable-length links for supporting the lower limbs of the human musculoskeletal system is proposed in the article. The researched model differs from the existing ones by the variable-length links, and by the angle calculation method. While in the existing models, the angles are calculated from the regular direction – from vertical, or from horizontal, - in the proposed research they are calculated between the links. As for practical exoskeleton implementation, the proposed method of angle calculation is appropriate to the actual working conditions of the electrical motors with the reduction gears installed in the hinges, which change the angles between the links. The mathematical model in the form of the system of Lagrange differential equations of the second kind is obtained. The obtained mathematical model is examined for existence and uniqueness of the Cauchy solution. The kinematic trajectory of the link motion has been synthesized. The controlling actions required for its implementation have been found.

We present a cost- and time-efficient method for the controlled preparation of single phase La(IO3)3 nanoparticles via a simple soft-chemical route which takes a matter of hours, thereby providing an alternative to the common hydrothermal method which takes days. Nanoparticles of pure α-La(IO3)3 and pure δ-La(IO3)3 were synthesised via the new method depending on the source of iodate ions, thereby demonstrating the versatility of the synthesis route. The crystal structure, nanoparticle size-dispersal and chemical composition were characterised via angle- and energy-dispersive powder X-ray diffraction, scanning electron microscopy and Fourier-transform infrared spectroscopy.

Powders with phase composition including syngenite K2Ca(SO4)2·H2O and/or calcium sulfate di-hydrate (gypsum) CaSO4·2H2O were synthesized from powder of calcium carbonate CaCO3 and water solutions of potassium hydrosulfate KHSO4 of various (0.5M, 1M and 2M) concentrations. Molar ratio of starting salt KHSO4/CaCO3=2 were used to provide formation of syngenite K2Ca(SO4)2·H2O. But when using 0.5M water solution of potassium hydrosulfate KHSO4 the phase composition of synthesized powder was presented by calcium sulfate dihydrate (gypsum) CaSO4·2H2O. When using 1M and 2M water solution of potassium hydrosulfate KHSO4 the syn-genite K2Ca(SO4)2·H2O was found as predominant phase in synthesized powders. According es-timations made from thermal analysis data when 1.0M and 2.0M water solutions of potassium hydrosulfate KHSO4 were used the content of calcium sulfate dihydrate (gypsum) CaSO4·2H2O in these powders were not higher then as 7.9 and 1.9 % respectively. Phase composition of products isolated from mother liquors via water evaporation consisted of syngenite K2Ca(SO4)2·H2O and potassium sulfate (arcanite) K2SO4. Synthesized powders can be used in preparation of biocom-patible bioresorbable materials with phase composition in the K2O‑CaO‑SO3‑H2O system; as matrix of thermo- or photo-luminescent materials; as components reducing the setting time and increasing strength of sulfate cements; in the fertilizing industry and also as a components of Martian regolith simulant.

The growing requirements regarding the safety of using polymers and their composites are related to the emergence of more effective, sustainable, and hazardous-limited fire retardants (FR). Significant amounts of FR are usually required to effectively affect the polymer burning behavior, while the knowledge of their recycling potential is still insufficient. At the same time, concerns are related not only to the reduced effectiveness of flame retardancy but, above all, to the potential deterioration of mechanical properties caused by the degradation of temperature-affected additives under processing conditions. This study describes the impact of four-time reprocessing of bio-based polyamide 11 (PA11) modified with an intumescent flame retardant (IFR) system composed of ammonium polyphosphate (APP), melamine cyanurate (MC) and pentaerythritol (PER) and its composites containing additionally short basalt fibers (BF). Composites manufactured by twin-screw extrusion were subjected to four reprocessing cycles by injection molding, comprehensively analyzing structural, mechanical, and fire behavior changes in each cycle. The obtained results confirmed the safety of using the proposed flame-retardant system for polyamide, processed under the recommended process parameters, without the risk of significant changes in the structure despite the partial increase in flammability caused mainly by the degradation of the polymer.

The genus Fritillaria belongs to the widely distributed family Liliaceae. The bulbs of Fritillaria ussuriensis and Fritillaria cirrhosa are valuable herbaceous medicinal ingredients. However, they are still used indiscriminately in herbal medicine. Identification and molecular phylogenic analysis of Fritillaria species is therefore required. Here, we report the complete chloroplast (cp) genome sequences of F. ussuriensis and F. cirrhosa. The two Fritillaria cp genomes were 151,524 and 151,083 bp in length, respectively, including a pair of inverted repeat regions (52,678 and 52,156 bp) separated by a large single copy region (81,732 and 81,390 bp) and small single copy region (17,114 and 17,537 bp). A total of 111 genes in F. ussuriensis and 112 in F. cirrhosa comprised 77 protein-coding genes in F. ussuriensis and 78 in F. cirrhosa, 30 tRNA genes, and four rRNA genes. The gene order, content, and orientation of the two Fritillaria cp genomes exhibited the general structure of flowering plants, and were similar to those of other Fritillaria species. Comparison of the six Fritillaria species’ cp genomes indicated seven highly divergent regions in intergenic spacers and in the matK, rpoC1, rpoC2, ycf1, ycf2, ndhD, and ndhF coding regions. We established the position of the six species through phylogenic analysis. The complete chloroplast genome sequences of two Fritillaria species will be useful genomics resources for identification of Fritillaria species and for studying the phylogenetic relationship among Fritillaria species within the Liliaceae family.

The relationships between the relative abundances of chemical elements and their second ionization potentials, as well as their condensation temperatures, were analyzed using four published homogeneous abundance surveys of halo and thin disk stars. We selected 932 stars with effective temperatures ranging from 4900 K to 5900 K and used the abundances of 10 chemical elements common across all surveys: Mg, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, and Ni. The correlation coefficients between the relative abundances of these elements and their second ionization potentials and condensation temperatures were investigated in relation to metallicity and the stars' location in the Galaxy. The observed correlations may result from certain physical processes, such as the accretion of interstellar gas onto stellar atmospheres. We also analyzed the dependencies of relative abundances on second ionization potentials based on published abundance patterns in five halo stars. Evidence of charge-exchange reactions in the atmospheres of these stars was found. For more accurate determination of stellar ages from the abundance ratios of radioactive and stable chemical elements in stellar atmospheres, processes such as charge-exchange reactions and dust-gas separation should be considered in future detailed investigations. Additionally, changes in the chemical abundances in the atmospheres of halo stars after crossing the Galactic plane were found to be possible.

Background and objectives: Chronic Kidney Disease and Mineral Bone Disorders (CKD-MBD) are frequently associated with an increased risk of both Vascular Calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and osteocalcin (BGP), have pivotal roles both for VCs and BFs. The Vitamin K Italian (VIKI) dialysis study, highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP as compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs, beyond the beneficial effect to reduce PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age and sex-matched patients treated with Calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusion: The study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. Keywords: bone fractures; etecalcetide; hemodialysis; vascular calcification; vitamin K

(1) Background: The rapid evolution of the internet and technological infrastructure has led to a surge in data generation across various contexts, increasing the use of machine learning tools to extract valuable information. Clustering, particularly using the K-means algorithm, is a common technique. However, determining the optimal number of clusters in K-means is challenging, as traditional methods like the elbow method can be imprecise and subjective. This study proposes a more accurate and objective method to identify the optimal number of clusters. (2) Methods: The proposed method utilizes the numerical derivative of cluster inertias and the maximum value of the ratio between contiguous derivatives. Implemented in Python using sklearn, numpy, and matplotlib, the method was validated with synthetic datasets generated by artificial intelligence, where cluster numbers are clearly distinguishable. (3) Results: The method proved to be more precise and less subjective than the traditional elbow method, accurately identifying the optimal number of clusters in all tested synthetic datasets. Additionally, it demonstrated computational efficiency with minimal RAM usage and execution time, making it suitable for practical data analysis applications. (4) Conclusions: This new mathematical and computational method significantly improves the determination of the optimal number of clusters in K-means, offering a more accurate and objective alternative to traditional techniques. Future work will extend this method to hierarchical clustering and develop a cloud service for wider accessibility.

Non-Vitamin K Oral Anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—Apixaban, Rivaroxaban, Edoxaban, and Dabigatran—not only as anticoagulants but also as modulators of inflammation via Protease-Activated Receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as FXa and Thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles but also paves the way for future research and clinical applications in inflammation and cardiovascular health

The interaction between O2 and reduced ceria nanocubes was mainly investigated by FTIR spectroscopy. Nanorods and nanoparticles were also studied for comparison. Adsorption of O2 at 100 K on unreduced ceria produces only O2 molecularly adsorbed on Ce4+ sites. The Ce3+ cations in H2-reduced ceria were monitored by the 2F5/2 → 2F7/2 electronic transition band at 2133-2095 cm-1. This band possesses a fine structure well resolved at 100 K. The positions of the individual components depend on the Ce3+ environment, including the presence of nearby species such as OH groups. Even at 100 K, the interaction of O2 with reduced ceria leads to fast oxidation of about half of the Ce3+ cations, including all Ce3+ sites bound to OH groups and carbonates, and the simultaneous formation of superoxo (O2) and peroxo (O22) species. The remaining fraction of Ce3+ sites disappears upon heating up to 348 K. At higher temperatures, the peroxo species decompose directly, yielding lattice oxygen. Superoxides are converted to hydroperoxides, which then decompose to terminal OH groups. Reduced samples evacuated at T < 773 K contain sorbed H2. Part of this hydrogen is also fast oxidized to H2O even at 100 K.

Following legalization, cannabis has quickly become an important horticultural crop in Canada and increasingly so in other parts of the world. However, due to previous legal restrictions on cannabis research there are limited scientific data on the relationship between nitrogen (N), phosphorus (P), and potassium (K) supply (collectively: NPK) and the crop yield and quality. This study examined the response of a high delta-9-tetrahydrocannabinol (THC) Cannabis sativa cultivar grown in deep-water culture with different nutrient solution treatments varying in their concentrations (mg L^-1) of N (70, 120, 180, 250, 290), P (20, 40, 60, 80, 100) and K (60, 120, 200, 280, 340) according to a central composite design. Results demonstrated that inflorescence yield responded quadratically to N and P, with the optimal concentrations predicted to be 194 and 59 mg L^-1, respectively. Inflorescence yield did not respond to K in the tested range. These results can provide guidance to cultivators when formulating nutrient solutions for soilless cannabis production and demonstrates the utility of surface response design for efficient multi-nutrient optimization.

Blockchains such as the bitcoin blockchain depend on reaching a global consensus on the distributed ledger; therefore, they suffer from well know scalability problems. This paper proposes an algorithm that avoids double-spending in the short term with just O(√n) messages; each node receiving money off-chain performs the due diligence of consulting k√n random nodes to check if any of them is aware of double-spending. Two nodes receiving double-spent money will in this way consult at least one common node with very high probability, due to the ‘birthday paradox’, and any common honest node consulted will detect the fraud. Since the velocity of money in the real world has coins circulating through at most a few wallets per day, the size of the due diligence communication is small in the short term. This `k-root-n’ algorithm is suitable for an environment with synchronous or asynchronous (but with fairly low latency) communication and with Byzantine faults. The presented k-root-n algorithm should be practical to avoid double-spending with arbitrarily high probability, while feasibly coping with the throughput of all world commerce. It is resistant to Sybil attacks even beyond 50% of nodes. In the long term, the k-root-n algorithm is less efficient. Therefore, it should preferably be used as a complement and not a replacement to a global distributed ledger technology.

Flashes of superoxide anion (SA) in mitochondria are generated spontaneously or during the opening of the permeability transition pore (PTP) and a sudden change in the metabolic state of a cell. Under certain conditions, SA can leave the mitochondrial matrix and perform signaling functions beyond mitochondria. In this work, we studied the kinetics of the release of SA and H2O2 from isolated mitochondria upon PTP opening and the modulation of the metabolic state of mitochondria by the substrates of respiration and oxidative phosphorylation. It was found that PTP opening leads to suppression of H2O2 emission and activation of SA burst. When the induction of PTP was blocked by its antagonists (cyclosporine A, ruthenium red, EGTA), the level of substrates of respiration and oxidative phosphorylation and the selective inhibitors of complexes I and V determined the type of ROS emitted by mitochondria. It was concluded that upon complete and partial reduction and complete oxidation of redox centers of the respiratory chain, mitochondria emit H2O2, SA, and nothing, respectively. The results indicate that the PTP- and substrate-dependent switching of the type of ROS leaving mitochondria may be the basis for SA- and H2O2-selective redox signaling in a cell.

Ash dieback (ADB), caused by the invasive fungal pathogen Hymenoscyphus fraxineus, poses a significant ecological and economic challenge across Europe. Fraxinus excelsior (European ash), a key component of forest ecosystems, has experienced mortality rates reaching up to 85% in affected regions, severely threatening its ecological role and economic value. This study examines the relationship between the phenological traits of ash clones, particularly the timing of spring bud burst, and their susceptibility to H. fraxineus infection. The study was conducted in a clonal seed orchard located in northeastern Poland, encompassing 31 ash clones from different bioclimatic regions. Phenological observations of bud burst were carried out from early April to late May during the years 2018-2020, and crown damage and de-foliation levels were assessed multiple times throughout the growing season. The results confirm that clones with earlier bud burst exhibit significantly higher survival rates and reduced crown damage. It was found that the timing of bud burst is strongly correlated with susceptibility to ash dieback, suggesting that phenological timing is a crucial factor in the selection of genotypes resistant to ash dieback. Statistical analyses, including ANOVA and mixed models, revealed significant differences in susceptibility to infection among clones from different bioclimatic regions. Furthermore, the study high-lights the potential of breeding strategies focused on these traits to enhance the resilience of ash popula-tions. These findings are critical for the development of effective forest management practices aimed at conserving ash resources and maintaining biodiversity in the face of climate change and the ongoing spread of the pathogen.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

Therapeutic hypothermia (TH) has emerged as a promising approach with neuroprotective effects that can mitigate secondary brain damage and intracranial pressure in the acute phase after successful mechanical thrombectomy. However, the effect of TH on cognitive impairment has yet fully elucidated. In the present study, we demonstrated whether TH can improve cognitive impairment in a transient middle cerebral artery occlusion (tMCAO) mouse model Nine-week-old C57BL/6N mice (male) were randomized to three groups: sham, tMCAO, and tMCAO with TH. One month after model induction, cognitive function test and regional cerebral glucose metabolism were evaluated using the Y-maze test and positron emission tomography with fluorine-18 fluorodeoxyglucose, respectively. tMCAO led to cognitive impairment, which was improved by TH. The cerebral glucose metabolism of the thalamus was significantly recovered in the TH group compared to that in the tMCAO group. These results suggest that TH might have potential as a therapeutic strategy for improving the ischemia/reperfusion-induced cognitive impairment.

Prenatal diagnosis of clubfoot traditionally relied on two-dimensional ultrasonography. To enhance diagnosis and predict postnatal outcomes, we examined the parameters that differentiate pathological clubfoot using three-dimensional ultrasonography. In our retrospective study, we examined the findings of prenatal ultrasound and the postnatal outcomes of pregnancies with suspected congenital clubfoot between 2018 and 2021. Based on the three-dimensional perspective, we measured the angles of varus, equinus, calcaneopedal block and forefoot adduction and compared the sonographic variables between the postnatal treated and non-treated groups. We evaluated 31 pregnancies (47 feet) with suspected clubfoot using three-dimensional ultrasonography. After delivery, a total of 37 feet (78.7%) underwent treatment involving serial casting only or additional Achilles tenotomy. The treated group showed significantly greater hindfoot varus deviation (60.5° vs. 46.6°, p=0.026) and calcaneopedal block deviation (65.6° vs. 26.6°, p <0.05) compared to the non-treated group. The calcaneopedal block had an area under the curve of 0.98 with a diagnostic threshold of 46.2 degrees (sensitivity of 97%, specificity of 90%, positive predictive value of 97%, and negative predictive value of 90%). During prenatal evaluation of clubfoot using three-dimensional ultrasonography, the calcaneopedal block deviation has the potential to predict postnatal treatment.

As renewable energy generation prediction systems have been introduced into the energy trading market, accurate prediction of solar photovoltaic (PV) energy generation has become a crucial challenge for ensuring stable trade of variable energy. Therefore, it is essential to quantitatively investigate and analyze current prediction technology and develop more advanced prediction systems. In this study, three models for predicting PV energy generation were investigated. Multiple regression, random forest, and gradient boosting machine (GBM) models were con-structed for 15 utility-scale power plants throughout South Korea. Model performance was evaluated in terms of root mean square error (RMSE) and mean absolute error (MAE). The multiple regression-based model had an RMSE of 12.00% and MAE of 9.06%. The random forest model had an RMSE of 11.69% and MAE of 8.61%. The GBM model had an RMSE of 11.34% and MAE of 8.18%, indicating its superior accuracy among the three models in predicting PV energy generation. These findings provide valuable insights that may contribute to the development of advanced PV energy generation models and their application in grid operations.

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

The inter-subspecific crossing between indica and japonica subspecies in rice have been utilized to improve the yield potential of temperate rice. In this study, a comparative study of the genomic regions in the eight high-yielding varieties (HYVs) was conducted with those of the four non-HYVs. The Next-Generation Sequencing (NGS) mapping on the Nipponbare reference genome identified a total of 14 common genomic regions of japonica-originated alleles. Interestingly, the HYVs shared japonica-originated genomic regions on nine chromosomes, although they were developed through different breeding programs. A panel of 94 varieties was classified into four varietal groups with 38 single nucleotide polymorphism (SNP) markers from 38 genes residing in the japonica-originated genomic regions and 16 additional trait-specific SNPs. As expected, the japonica-originated genomic regions were only present in the japonica (JAP) and HYV groups, except for Chr4-1 and Chr4-2. The Wx gene, located within Chr6-1, was present in the HYV and JAP variety groups, while the yield-related genes were conserved as indica alleles in HYVs. The japonica-originated genomic regions and alleles shared by HYVs can be employed in molecular breeding programs to further develop the HYVs in temperate rice.

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC-MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.

Background: Animal-assisted therapy has positive effects on cognitive function, depression, performance ability, and social functioning in elderly patients. The aim of this study was to evaluate the effects of rearing pet insects on the cognitive function of healthy elderly participants, with fMRI (functional magnetic resonance imaging) being used for this purpose. Methods: Community-dwelling elderly women (≥60 years) with normal cognitive function were enrolled during April 2015. They were randomized at a 1:1 ratio into two groups: insect-rearing and control (n=16) groups, with the insect-rearing group being further classified into two groups for analysis according to the subjects’ scores in the Wisconsin Card Sorting Test, WCST) at the first fMRI: insect-rearing group I with a relatively high score (n=13), and insect-rearing group II with a relatively low score (n=6). All subjects were educated on a healthy lifestyle for better cognitive function at every visit, and the insect-rearing groups received and reared crickets as pet insects. The fMRI was performed at baseline and after 8 weeks using the WCST as a stimulus. The WCST consisted of two variations, a high level baseline (HLB) and semi-WCST version. Results: There were no significant differences in the baseline characteristics among the three groups. There was a significant difference accuracy of the HLB–semi-WCST (p<0.05) in insect-rearing group II after 8 weeks from the baseline test. In the fMRI analysis involving the WCST reaction test, increased activation was observed in the right dorsal lateral prefrontal cortex and parietal cortex in insect-rearing group II when the semi-WCST, rather than the HLB, was performed. There were no significant differences in the other groups. Conclusion: The rearing of pet insects as an animal-assisted therapy is cost-effective, easy, and occupies little space. In this study, it showed positive effects on executive functions and performance improvement in elderly women. Further larger studies on the effects of pet insects on cognitive function are warranted.

"Redesigning Education: A Transformative Approach" outlines comprehensive strategies for re-forming educational systems from primary to secondary levels to promote holistic student de-velopment. Traditional educational models fail to address diverse learning needs and cultivate critical thinking, creativity, and emotional intelligence. This study introduces innovative approaches such as personalized education through AI, wellness schools, professional skill development programs, and social and emotional learning (SEL) integration. The methodology includes an extensive literature review of contemporary educational books, peer-reviewed articles, and case studies from highly developed European countries, ensuring that the proposed strategies are grounded in credible and current research. Key reforms include continuous professional development for teachers, enhanced teacher training and support, comprehensive counseling services, and robust support systems for students. Strengthening school-family collaboration and promoting multiculturalism through inclusive policies and cultural events are emphasized. Additionally, upgrading school infrastructure to create safe and welcoming learning environments is essential for student prosperity. The proposed educational reforms aim to create an inclusive, innovative, and supportive learning environment, ensuring students thrive academically, emotionally, and socially. By integrating these comprehensive reforms, the study seeks to develop effective educational systems that foster student well-being and excellence, equipping future generations for success in a rapidly evolving world.

Let $(\{f_n\}_{n=1}^\infty, \{\tau_n\}_{n=1}^\infty)$ and $(\{g_n\}_{n=1}^\infty, \{\omega_n\}_{n=1}^\infty)$ be unbounded continuous p-Schauder frames ($0<p<1$) for a disc Banach space $\mathcal{X}$. Then for every $x \in ( \mathcal{D}(\theta_f) \cap\mathcal{D}(\theta_g))\setminus\{0\}$, we show that \begin{align}\label{UB} \|\theta_f x\|_0\|\theta_g x\|_0 \geq \frac{1}{\left(\displaystyle\sup_{n,m \in \mathbb{N} }|f_n(\omega_m)|\right)^p\left(\displaystyle\sup_{n, m \in \mathbb{N}}|g_m(\tau_n)|\right)^p}, \end{align} where \begin{align*} & \theta_f: \mathcal{D}(\theta_f) \ni x \mapsto \theta_fx \coloneqq \{f_n(x)\}_{n=1}^\infty\in \ell^p(\mathbb{N}), \quad \theta_g: \mathcal{D}(\theta_g) \ni x \mapsto \theta_gx \coloneqq \{g_n(x)\}_{n=1}^\infty\in \ell^p(\mathbb{N}). \end{align*} Inequality (1) is unexpectedly different from both bounded uncertainty principle \textit{[arXiv:2308.00312v1]} and unbounded uncertainty principle \textit{[arXiv:2312.00366v1]} for Banach spaces.

We derive an uncertainty principle for Lipschitz maps acting on subsets of Banach spaces. We show that this nonlinear uncertainty principle reduces to the Heisenberg-Robertson-Schrodinger uncertainty principle for linear operators acting on Hilbert spaces.

FACTS devices provide significance to enhance the functioning of both static and dynamic power systems. The type, size, and location of FACTS devices determine how well they achieve the goals of enhancing voltage stability, loadability, and loss minimization simultaneously. The aim of the function in this study includes voltage stability, line loadings, and loss minimization, which are expected to obtain the most benefits from their installation and other weights allocated to them. It has been determined how installing TCSC, and SVC will improve loadability under situations of continuously increasing load. In this study, a novel optimization technique known as differential evolution invasive weed optimization (DEIWO) is utilized to locate the optimal location for FACTS devices within the IEEE 14 bus system by considering valve point effects. DEIWO was a recently developed, dominant, and simple metaheuristic algorithm for genuine parameter optimization. DEIWO was inspired by the natural process of weed colonization and dissemination, and it is highly effective at addressing broad multi-dimensional, linear and nonlinear optimization problems. The proposed method was implemented in the IEEE 14 bus testing system. Different methods from the research papers have been used to compare and analyze the results. The results demonstrate the DEIWO algorithm's capability and show how it may be used in practice to locate FACTS devices in deregulated electricity networks in the most advantageous place. A comparison of the proposed process to existing algorithms found in the literature and implemented using traditional techniques reveals that it performs better in terms of precision and convergence

We investigate, whereas the SU(4)/SU(2) model, is viable for describing strong interactions. The existing problems of confinement and asymptotic freedom, two phenomena that can not be described by the SU(3) model, might indicate that we need something "larger" than the SU(3) model. The considered coset SU(4)/SU(2) or the Stiefel manifold V^2(C_4) contains an su(3) algebra, plus additional degrees of freedom that resembes the Feddev-Poppov concept. The richer structure of this coset, give us enough room, to seek for new phenomena, as its dimensionality is 12. The consideration of the SU(4)/SU(2) model flavors firstly the unification of nuclear fields (strong and weak) in an SU(4) model.

We explore the possibility to form a physical theory in $C^4$. We argue that the expansion of our usual 4-d real space-time to a 4-d complex space-time, can serve us to describe geometrically electromagnetism and nuclear fields and unify it with gravity, in a different way that Kaluza-Klein theories do. Specifically, the electromagnetic field $A_\mu$, is included in the free geodesic equation of $C^4$. By embedding our usual 4-d real space-time in the symplectic 8-d real space-time (symplectic $R^8$ is algebraically isomorphic to $C^4$), we derive the usual geodesic equation of a charged particle in gravitational field, plus new information which is interpreted. Afterwards, we formulate and explore the extended special relativity and extended general relativity an $C^4$ or$R^8$. After embedding our usual 4-d space-time in $R^8$, two new phenomena rise naturally, that are interpreted as "dark matter" and "dark energy". A new cosmological model is presented, while the geometrical terms associated with "dark matter" and "dark energy" are investigated. Similarities, patterns and differences between "dark matter", "dark energy", ordinary matter and radiation are presented, where "dark energy" is a dynamic entity and "dark matter" reveal itself as a "mediator" betwen ordinary matter and "dark energy". Moreover, "dark matter" is deeply connected with "dark energy". Furthermore, the extended Hamilton-Jacobi equation of the extended space-time, is transformed naturally as an extended Klein-Gordon equation, in order to get in contact with quantum theories. By solving the Klein-Gordon equation analytically, we derive an eigenvalue for Higg's boson mass value at 125,173945 $Gev/c^{2}$. The extended Klein-Gordon equation, also connects Higg's boson (or vacuum) with Cosmology, due to the existence of our second "time" T (cosmological time), which serve us to connect quantum theories with Cosmology. Afterwards, in the general case, we explore the symmetries of the curved Hamilton-Jacobi equation locally, in order to investigate the consequences of a $C^4$ space-time in Standard Model. An extension to Standard Model is revealed, especially in the sector of strong nuclear field. The Stiefel manifold $SU(4)/SU(2)$ seems capable not only to describe the strong nuclear field but give us,as well, enough room to explore in the future, the possibility to explain quark confinment. Our extension, flavors firstly the unification of nuclear fields and afterwards the unification of nuclear fields with electromagnetic field. The desired grand unification, is achieved locally, through the symmetry group $GL(4,C)\simeq SO(4,4)\cap U(4)$ and we present a potential mechanism to reduce the existing particle numbers to just six. Afterwards,23 present the extended Dirac equation in $C^4$ space-time (Majorana-Weyl representation) plus a preliminary attempt to introduce a pure geometric structure for fermions. Finally, we consider a new geometric structure through n-linear forms in order to give geometric explanation for quantisation

We explore several ways, in order to include fermionic structures naturally in a physical theory in C⁴. We begin with the standard Dirac formalism and we proceed by using Cartan's property of triality as a second option. Afterwards, we suggest a new approach (in a preliminary basis), by introducing an 1-linear form, as the "square root of the geometry" derived by the usual 2-linear forms (quadratic forms). Keeping this way, we introduce n-linear forms, in order to formulate a new geometric structure, which could be suitable for the formulation of a pure geometric unied theory.

After developed the formulation of a "general relativity" in C⁴ [2], we proceed with the formulation of a Hamilton-Jacobi equation in C⁴. We argue that in this consideration, the usual problems of the ADM formalism, do not exist, due to the complex time as it exists in our consideration. Specically, we can derive a suitable dispersion relation in order to work with and nd a generalised super Hamiltonian

We explore the possibility to nd the usual quantum theories, within the formulation of a classic theory of mechanics in C⁴. Specically, by releasing the end-point of the integral of the action derived in C⁴, we derive the dynamic path length of the geodesic equation in C⁴. In the at case, the derived Hamilton-Jacobi equations, were identied as the usual Klein-Gordon equation, where the complex functional action S(z_i), is identied as the usual complex scalar field φ. Afterwards, we study the energy-momentum 4-d complex vector, in order to re-establish the usual covariant derivative of gauge theories.

We explore the field equations in a 4-d complex space-time, in the same way, that general relativity does for our usual 4-d real space-time, forming this way, a new "general relativity" in C⁴ space-time, free of sources. Afterwards, by embedding our usual 4-d real space-time in C⁴ space-time, we describe geometrically the energy-momentum tensor T_μν as the lost geometric information of this embedding. We further give possible explanation of dark eld and dark energy.

The arrival of new developments in the field of power electronics circuit’s applications in power systems builds new control strategy to improve voltage quality for power grid by overcome interruptions. Wind energy resources are unconventional resources and get advanced problems to power grid when it is connected. Uncertainty of load sharing, peak energy management, climatic conditions, wind velocity and wind energy injected into power grid leads many of power quality problems on power grid based on the existing guidelines specified in IEC-61400 standard. This system plans efficient operation of DFIG to eliminate the voltage collapse and mismatch frequency to power grid. The DFIG connected diode rectifier and rotor side converter wind generator works as an Efficient Static Synchronous Compensator (E-SATCOM) for supplying the demand of reactive power for power grid to mitigate PQ problems. The benefit of using a combined controller was verified by simulink/Matlab and its simulated results used Doubly Fed Induction Generator (DFIG), wind Turbine. This simulation results gives good quality transient and stable state response to manage and support reactive power for both symmetrical and unsymmetrical faults in connection of grid codes to provide continuous quality of power supply, multiple wind generators are required for 140 bus power grid.

The Wind Energy Conversion System (WECS) plays an inevitable role across the world. In particular, the attention for Permanent Magnet Synchronous Generators (PMSGs) connected with wind farm is popular. This paper deals with the literature review that describes the recent advances, progresses and innovatory trends on PMSGs for WECS. Comparison between geared and direct-driven conversion systems and the classification of electrical machines used in WECS are discussed. A detailed analysis on the design aspects considering various topologies of PMSGs are encompassed in the literature. The PMSG design and optimization problems are solved by field computation techniques and optimized by using Soft Computing (SC) techniques .The three-dimensional, finite element software platform for the analysis and design of PMSGs is discussed. This paper also deals with the interdisciplinary modeling, analysis, and optimization of PMSG using Finite Element Analysis (FEM) and SC techniques. Finally, PMSGs are reviewed and compared for further exploration.

Atypical Polypoid Adenomyoma (APA) is a benign uterine lesion that occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Our work consists of a systematic review of the literature, including the description and analysis of a case study, and assesses the main immunohistochemical and molecular markers that contribute to making a differential diagnosis against endometrial adenocarcinoma. This allows offering patients conservative treatment compared to the radical management required for endometrial cancer, due to the significant physical and psychological consequences that one procedure or another can have on women's health. The goal of this research is to carry out an adequate diagnosis of APA by providing the necessary information to guide clinical management, establish patient prognosis, and minimize the emotional impact associated with the disease, all in combination with clinical and histopathological findings and complementary imaging tests. In conclusion, an appropriate immunohistochemical and molecular approach, along with the presumptive histological diagnosis, determine the correct classification of the lesion as APA and not as other malignant pathologies, which allows establishing a treatment protocol adjusted to the biological reality of this pathology.

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs, and able to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials: they exhibit good features in terms of impermeability, deformability and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration: however, this kind of materials lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these mate-rials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields: in the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance and patency will be herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance will be been disclosed.

Three different populations of sulfated polysaccharides can be found in the cell wall of the red alga Botryocladia occidentalis. In a previous work, the structures of the two more sulfated polysaccharides were revised. In this work, NMR-based structural analysis was performed on the least sulfated polysaccharide and its chemically modified derivatives. Results have revealed the presence of both 4-linked α- and 3-linked β-galactose units having the following chemical features: more than half of the total galactose units are not sulfated, the α-units occur primarily as 3,6-anhydro-galactose units either 2-O-methylated or 2-O-sulfated, and the β-galactose units can be 4-O-sulfated or 2,4-O-disulfated. SPR-based results indicated weaker binding of the least sulfated galactan to thrombin, factor Xa, and antithrombin, but stronger binding to heparin cofactor II than unfractionated heparin. This report together with our previous publication completes the structural characterization of the three polysaccharides found in the cell wall of the red alga B. occidentalis and correlates the impact of their composing chemical groups with the levels of interaction with the blood co-factors.

Abiotic stresses, including drought, salinity, cold, heat, and heavy metals, extensively reduce global agricultural production. Approaches such as conventional breeding and transgenic breeding have been widely used to cope with these environmental stresses. The clustered regularly interspaced short palindromic repeat- Cas (CRISPR/Cas) based gene-editing tool has revolutionized due to its simplicity, accessibility, adaptability, flexibility, and wide applicability. This system has a great potential to build up crop varieties with enhanced tolerance against abiotic stresses. In this review, we summarize the most recent findings on understanding the mechanism of abiotic stress response in plants and the application of CRISPR/Cas mediated gene-editing system towards enhanced tolerance to drought, salinity, cold, heat, and heavy metals stresses. Furthermore, in this review, we highlighted the recent advancements in prime editing and base editing tools for crop improvement.

A robust hydrological assessment is challenging in regions where human interference, within all aspects of the hydrological system, significantly alters the flow regime of rivers. The challenge was to extend a large-scale water resources model, GWAVA, to better represent water resources without increasing the model complexity. A groundwater and a regulated reservoir routine were incorporated into GWAVA using modifications of the existing AMBHAS-1D and Hanasaki methodologies, respectively. The groundwater routine can be varied in complexity when sufficient input data is available but fundamentally is driven by three input parameters. The reservoir routine was extended to account for the presence of large, regulated reservoirs using two calibratable parameters. The additional groundwater processes and reservoir regulation was tested in two highly anthropogenically influenced basins in India: the Cauvery and Narmada. The inclusion of the revised groundwater routine improved the simulation of streamflow in the headwater catchments and was successful in improving the representation of the baseflow component. In addition, the model was able to produce a time series of daily groundwater levels, recharge to groundwater and groundwater abstraction. The regulated reservoir routine improved the simulation of streamflow in catchments downstream of major reservoirs, where the streamflow was largely reflective of reservoir releases, when calibrated using downstream observed streamflow records. The model was able to provide a more robust representation of the annual volume and daily outflow released from the major reservoirs and simulate the major reservoir storages adequately. The addition of one-dimensional groundwater processes and a regulated reservoir routine proved successful in improving the model performance and traceability of water balance components, without excessively increasing the model complexity and input data requirements.

Diseases such as diabetes are known to reduce blood circulation in the capillaries and arterioles; however, there are no devices that can easily measure this on a daily basis. In this study, we developed a tool for measuring finger photoplethysmograms using green-light and near-infrared LEDs. We then conducted photoplethysmography on 25 diabetic inpatients/outpatients as well as 21 adult males and females who had not been diagnosed or treated for diabetes, hypertension, or cardiovascular disease (as a control group). In the diabetic patients, the inverse full width at half maximum velocity plethysmogram (1/FWHMVPG) tended to be smaller compared to the control group, and the delay in the green light a-wave peak relative to the near-infrared light a-wave peak in the acceleration plethysmogram was significantly increased. The results suggest that peripheral hemodynamics could be easily estimated at home using a photoplethysmography device mounted on a ring-wearable device.

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

Endolysin of bacteriophage T5 (EndoT5) is a Zn2+-dependent and Ca2+-activated L-alanyl-D-glutamate peptidase that hydrolyses peptidoglycans during the destruction of the cell wall of the phage host bacterium Escherichia coli. To elucidate the mechanism of calcium activation, the spatial solution structure of EndoT5 in a complex with two ions - catalytic Zn2+ and regulatory Ca2+ (EndoT5-Zn2+Ca2+, PDB ID: 8P3A) was determined by high-resolution NMR and deposited in the Protein Data Bank. We show that coordination of the Ca2+ ion fix the spatial position of polar amino acid residues D113, N115 and S117. As a result, the intramolecular mobility of extended protein loops (residues 40-70 and 111-132) is significantly reduced compared to the mobility of these loops in the structure of an enzyme containing only a catalytic a Zn2+ ion (EndoT5-Zn2+, PDB ID: 2MXZ). In the stabilized EF-like calcium-binding loop (residues 111-132), the number of van der Waals interactions with amino acid residues of the globular core of the protein increases. The binding of the Ca2+ ion is accompanied by the selection of the functional states of both extended loops of the enzyme (residues 40-70 and 111-132), because of which EndoT5-Zn2+Ca2+ acquires the structural integrity necessary for catalysis. Therefore, the mechanism of activation of L-alanyl-D-glutamate peptidase of bacteriophage T5 by Ca2+ ions involves stabilization of the enzyme molecule in a catalytically active “open” conformation. This work sheds light on the structural grounds of the ion-dependent functional proteoforms of this interesting protein.

The literature shows that both in laboratory and in industrial conditions, photocatalytic oxidation method copes quite well with the degradation of the most organic substances, including environmental toxins and molecular components of pathogenic microorganisms. However, the effective utilization of photocatalytic processes for environmental decontamination and disinfection require significant technological advancement both in the area of semiconductor material synthesis and its application. Here we focused on the presence and ‘photocatalytic capability‘ of photocatalysts among soil minerals, and their potential contribution to the environmental decontamination in vitro and in vivo. (The issue is sketched from the perspective of chemists and environmental scientist.) Reactions caused by sunlight on the soil surface are involved in its normal redox activity. It appears that some of them may take part in the soil decontamination. However, their importance for decontamination in vivo cannot be overstated due to diversity of soils on the Earth caused by the environmental conditions, such as climate, parent material, relief, vegetation etc. The solar-light induced reactions are just a part of extremely complicated processes dependent on a plethora of environmental determinates. Such multiplicity of affecting factors, which we tried to sketch from the perspective of chemists and environmental scientist, makes us rather sceptical about the effectiveness of the photocatalytic processes in vivo. On the other hand, there is a huge potential of the soils as the alternative source of useful photocatalytic materials of unique properties

Through the use of Smart Sensor Networks (SSN), Marine Observatories (MO) provide continuous ocean monitoring. Deployed sensors may not perform as intended due to the heterogeneity of SSN devices’ hardware and software when combined with the Internet. Hence, SSN are regarded as complex distributed systems. As such, SSN designers will encounter challenges throughout the design phase related to time, complexity, sharing diverse domain experiences (viewpoints), and ensuring optimal performance for the deployed SSN. To this end, we describe in this article how we extended our previously proposed ArchiMO meta-model and design tool by extending an Enterprise Architecture Framework based on the ArchiMate Modeling Language. This extension proposes the incorporation of new Underwater Environmental Constraints (UEC) for SSN in ArchiMO which is coupled with the fusion of sensors with Artificial Intelligence. This serves as the basis for generating a new version of our ArchiMO design tool, which incorporates the new added constraints and invokes the AI created Database. To illustrate our proposal, we use the newly generated ArchiMO to create a model in the MO domain. Furthermore, we use our self-developed domain-specific model compiler to produce the relevant simulation code. Throughout the design phase, our approach contributes to handle and control the uncertainties and variances of the provided quality of service that may occur during the performance of the SSN, hence reducing the design activity’s complexity and time. It provides a way to share the different viewpoints of the designers in the domain of SSN.

Levels of trace element pollution in surface soil can be estimated using soil analyses and leaching tests. These methods may reveal different results due to the effect of soil properties, such as grain size and mineral composition, on elemental availability. Therefore, this study advocates an alternative method for monitoring and assessment of trace element pollution in surface soil using terricolous fruticose lichens. Lichens growing at abandoned mine sites and unpolluted areas in southwest Japan and their substrata were analyzed using inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry to clarify the relationships between Cu, Zn, As, and Pb concentrations in lichens and soils, including their absorption properties. Concentrations of these elements in the lichens were positively correlated with those in the soils regardless of lichen species, location, habitat, or conditions of soils. The analyzed lichens had neither competitive nor antagonistic properties in their elemental absorption, which made them good biomonitors of trace element pollution in surface soil. The distribution maps of average Cu, Zn, As, and Pb concentrations at each sampling region detected almost all of the Cu, Zn, and As pollution of the soils. Therefore, lichens could be used in practical applications to monitor Cu, Zn, and As pollution in surface soils.

Sudden cardiac arrest (SAC) is a leading cause of mortality. In recent years, though, many lives have been saved through the use of defibrillators by random bystanders. As a result, defibrillators have been popping up in various locations. In this work we propose a state mandate demanding the presence of a defibrillator at every pharmacy store and argue that it could greatly enhance and augment the impact of the defibrillator network. We support our claim via detailed calculations of the immediate (a defibrillator readily available) and partial (a defibrillator available at a reasonable distance) population coverage achievable by the implementation of our proposal, taking the Argolis area in Peloponnese Greece as a case study. Our findings indicate that, in addition to other benefits, the use of pharmacies to establish a defibrillator network could bring an eight-fold increase in the immediate population coverage of defibrillators and would provide immediate / partial access to a defibrillator to 18 / 24 incidents of SCA per year that would otherwise lead to death, potentially leading to the saving of numerous lives. Alternative scenaria are also discussed.

The 14-3-3 protein in dimorphic fungi from the Ajellomycetaceae family, including Blastomyces spp., Histoplasma spp., Paracoccidioides spp., Emergomyces spp., and Emmonsia spp., play a crucial role in host-pathogen interactions. Thus, we performed a comparative genomic analysis across 21 fungal species which revealed the presence of two 14-3-3 gene copies in most fungi, with exceptions in Histoplasma ohiense and Emergomyces africanus which revealed one and three gene copies, respectively. Moreover, in this study it was found a high degree of similarity (over 70%) between fungal 14-3-3 proteins and the human 14-3-3ɛ isoform, particularly in conserved Ser/Thr phosphorylation sites. However, distinct differences were noted in the C- and N-terminal regions, where fungal 14-3-3 proteins have additional amino acids. Though not directly linked to pathogenicity, these structural differences may offer insights into new therapeutic strategies. The conserved regions and 3D similarities identified could serve as potential targets for broad-spectrum antifungal drug development and vaccine production. Further research is necessary to validate these in silico findings and explore the functional roles of these phosphorylation sites, which could contribute to understanding fungal pathogenicity and developing specific antifungal interventions.

Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.

The increased cultivation of high THC-containing Cannabis sativa L. (cannabis), particularly in greenhouses, has resulted in a greater incidence of diseases and molds that can negatively affect the growth and quality of the crop. Among them, the most important diseases are root rots (Fusarium and Pythium spp.), Botrytis bud rot (Botrytis cinerea), powdery mildew (Golovinomyces ambrosiae), cannabis stunt disease (caused by Hop latent viroid), and a range of microbes that reduce post-harvest quality. An integrated management approach to reduce the impact of these diseases/microbes requires combining different approaches that target the reproduction, spread and survival of the associated pathogens, many of which can occur on the same plant simultaneously. These approaches will be discussed in the context of developing an integrated plan to manage the important pathogens of greenhouse-grown cannabis at different stages of plant development. These stages include maintenance of stock plants, propagation through cuttings, vegetative growth of plants, and flowering. The cultivation of cannabis genotypes with tolerance or resistance to various pathogens is a very important approach, followed by the maintenance of pathogen-free stock plants. When combined with cultural approaches (sanitation, management of irrigation, and monitoring for diseases) and environmental approaches (greenhouse climate modification), a significant reduction in pathogen development and spread can be achieved. The use of preventive applications of microbial biological control agents and reduced risk biorational products can also reduce disease development at all stages of production in jurisdictions where they are registered for use. The combined use of promising strategies for integrated disease management on cannabis plants during greenhouse production will be reviewed. Future areas for research are identified.

The growing importance of sustainability in organizational success, particularly in the pharma-ceutical industry, underscores the need for leveraging technologies like blockchain to enhance sustainability indicators across environmental, social, and economic pillars. This study aims to identify and understand the challenges hindering the adoption of blockchain in the pharmaceuti-cal sector for improving sustainability performance, addressing two research questions: the spe-cific challenges faced by blockchain adoption in this context and the interdependencies among these challenges. Employing a two-step approach, the study compiles challenges through a litera-ture review, refines them via expert opinions, and establishes their interrelationships using methodologies like Fuzzy Interpretive Structural Modeling (FISM) and Cross-Impact Matrix Multiplication Applied to Classification (MICMAC). The research contributes to unraveling the complex relationships and dependencies within the system, providing a structured framework for improved decision-making and strategic planning. It fills a literature gap by being the first attempt to outline driving and dependent factors related to the challenges of adopting blockchain technology for sustainability enhancement in the pharmaceutical sector, offering insights that can significantly impact brand image, company perception, and consumer value.

In the dynamic landscape of drug discovery, Computer-rAided Drug Design (CADD) emerges as a transformative force, bridging the realms of biology and technology. This paper overviews CADD's historical evolution, categorization into structure-based and ligand-based approaches, and its crucial role in rationalizing and expediting drug discovery. As CADD advances, incorporating diverse biological data and ensuring data privacy become paramount. Challenges persist, demanding the optimization of algorithms and robust ethical frameworks. Integrating Machine Learning and Artificial Intelligence amplifies CADD's predictive capabilities, yet ethical considerations and scalability challenges linger. Collaborative efforts and global initiatives, exemplified by platforms like Open Source Malaria, underscore the democratization of drug discovery. The convergence of CADD with personalized medicine offers tailored therapeutic solutions, though ethical dilemmas and accessibility concerns must be navigated. Emerging technologies like quantum computing, immersive technologies, and green chemistry promise to redefine the future of CADD. The trajectory of CADD, marked by rapid advancements, anticipates challenges in ensuring accuracy, addressing biases in AI, and incorporating sustainability metrics. The paper concludes by highlighting the need for proactive measures in navigating the ethical, technological, and educational frontiers of CADD to shape a healthier, brighter future in drug discovery.

Microbial foodborne pathogens can cause major risks to public health and the food industry. Rapid and accurate detection of these pathogens is crucial to prevent outbreaks and ensure food safety. Traditional single-mode biosensing approaches have their limitations in terms of specificity, sensitivity, and speed. Over the years, there has been an increasing research interest in developing multimodal biosensing strategies that integrate multiple sensing techniques to achieve enhanced accuracy, efficacy, and precision in foodborne pathogen detection. This article review paper explores the current state of multimodal biosensing technologies and their promising applications in the food industry. We discuss various integrated biosensing platforms, including optical, electrochemical, and nanomaterial-based systems, among others. The advantages, challenges, and future prospects of multimodal biosensing for foodborne pathogens are thoroughly examined, highlighting the potential impact of these advanced technologies on food safety and public health.

Salmonella is the intracellular pathogen and etiological known for the cause of asymptomatic carriage, gastroenteritis, systemic disease (typhoid fever), in severe cases death may also occur. Altered function of mitochondria due to Salmonella infection impacts the immune response. Mitochondria which are recognized as the “powerhouse” of the cells are also know to play central role in the immune metabolism. Mitochondrial dynamics such as fusion, fission, signaling, transport and mitophagy influences the immune system and also maintains the cellular integrity. Mitochondrial DNA and Reactive oxygen species formation also elicits the inflammatory responses. This review discusses the immune metabolism and effect of altered mitochondrial dynamics in case of Salmonella infection.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

Current stock market forecasting methods encompass fundamental, technical, emotional, and bargaining factors. Predominantly, price prediction hinges on order volume and price, although correlating these two within existing models proves challenging. This study employs Cycle Generative Adversarial Network (Cycle GAN) to unravel the intricate price-volume relationship, combining it with Bollinger Bands for trading signal analysis, overcoming hurdles in short-term forecasting prevalent in numerical analysis and AI. Focusing on TSMC (2330.TW) stock price, the research leverages Cycle GAN in deep learning to master the price-volume nexus, juxtaposed with LSTM and RNN. Historical TSMC closing prices and transaction counts are model inputs, scrutinizing their interconnectedness for predictions. This innovative approach aligns stock price, volume, market value, taxes, and prior changes via system engineering. By intertwining Bollinger Bands with stock price forecasts, trading signals are distilled, factoring in extended index %b for a comprehensive market picture.

IQGAP1 is a multi-functional scaffold protein. However, its role in B cell development and function is not known. Here, we demonstrate Iqgap1mice contained significantly increased numbers of B220+ B, B220+IgM pro/pre-B, and B220+IgM+ immature-B cells in the bone marrow. Here, we show IQGAP1 as the essential scaffold that regulates early B cell development and function. Iqgap1mice contained significantly increased numbers of B220+ B, B220+IgM pro/pre-B, and B220+IgM+ immature-B cells in the bone marrow. New-forming and follicular B cell numbers were increased, while the marginal zone B cell numbers were significantly reduced in the spleen of the Iqgap1mice. Lack of IQGAP1 reduced T-dependent and T-independent humoral responses. Mechanistically, the lack of IQGAP1 considerably decreased the phosphorylation of Mek1/2, Erk1/2, and Jnk1/2. B cells from Iqgap1mice failed to suppress IL-7R-mediated activation of Stat5a/b, an essential step for cell-cycle exit and initiate light-chain recombination, leading to a reduction in RS rearrangement frequency. Lack of IQGAP1 resulted in a significant reduction of IRF4 and IRF8 in BM B cells. Our study provides the first evidence that IQGAP1-based signalosome is essential for the development and functions of B cells.

In the realm of modern drug discovery, the integration of chemoinformatics and quantitative structure-activity relationship (QSAR) modeling has emerged as a formidable alliance, enabling researchers to harness the vast potential of machine learning (ML) techniques for predictive molecular design and analysis. This review delves into the fundamental aspects of chemoinformatics, elucidating the intricate nature of chemical data and the crucial role of molecular descriptors in unveiling the underlying molecular properties. Molecular descriptors, including 2D fingerprints and topological indices, in conjunction with the structural-activity relationships (SARs), play a pivotal role in unlocking the pathway to small-molecule drug discovery. Technical intricacies of developing robust ML-QSAR models, including feature selection, model validation, and performance evaluation, are discussed herewith. Various ML algorithms, such as regression analysis and support vector machines, are showcased in the text for their ability to predict and comprehend the relationships between molecular structures and biological activities. This review serves as a comprehensive guide for researchers, providing an understanding of the synergy between chemoinformatics, QSAR, and ML. By embracing these cutting-edge technologies, predictive molecular analysis holds promise for expediting the discovery of novel therapeutic agents in the pharmaceutical sciences.

Reinventing approved therapeutic proteins for a new dose, a new formulation, a new route of administration, an improved safety profile, a new indication, or a new conjugate with a drug or a radioactive source is a creative approach to benefit from the billions spent on developing new therapeutic proteins. These new opportunities were created only recently with the arrival of AI/ML tools and high throughput screening technologies. Furthermore, the complex nature of proteins offers mining opportunities that are not possible with chemical drugs; bringing in newer therapies without spending billions makes this path highly lucrative financially while serving the dire needs of humanity. This paper analyses several practical reinventing approaches and suggests regulatory strategies to reduce development costs significantly. This should enable the entry of hundreds of new therapies at affordable costs.

The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). Newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. Regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

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.

Neurological / neurovascular disorders constitute the leading cause of disability and second leading cause of deaths in the world. Some of the major neurological / neurovascular disorders or diseases include stroke, Alzheimer’s disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, etc. Their pathophysiology is considered as highly complex and has been blamed as the main obstacle in the development of any drugs for these diseases. In this review, we have described the endothelin system, their involvement in neurovascular disorders, importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN - sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders / diseases. We have highlighted the results of our pre-clinical and clinical studies related to these diseases. The phase I, safety and tolerability study of sovateltide has shown it as a highly safe and well tolerable compound at tested dosages, while pre-clinical and clinical phase II studies have demonstrated its efficacy in treating acute ischemic stroke, where it is currently being developed as a “First in Class” drug. Its testing in Alzheimer’s disease (AD), acute spinal cord injury and neonatal hypoxic-ischemic encephalopathy (HIE) is currently being carried out and are at different stages of drug development. Successful completion of these studies will prove the involvement of ETBRs signaling in neurological / neurovascular diseases and help in development of novel neurological drugs in future.

Visceral Leishmaniasis is a neglected tropical disease affecting 12 million people annually. Even in the second decade of the 21st century, it has remained without an effective vaccine for human use. In the current study, we have designed three multiepitope vaccine candidates by the selection of multiple IFN-γ inducing MHC-I and MHC-II binder T-cell specific epitopes from 3 previously identified antigen genes of Leishmania donovani from our lab, by immune-informatic approach using IFNepiotpe, NET-MHC-1 and NET MHC-2 webservers. We have tested the protective potential of these three multiepitope proteins as vaccine in a hamster model of visceral leishmaniasis. The immunization data revealed that the vaccine candidates induced a very high level of Th-1 biased protective immune response in-vivo in a hamster model of experimental visceral Leishmaniasis, with one of the candidates inducing a sterile immunity. The vaccinated animals displayed highly activated monocyte macrophages with the capability of clearing intracellular parasites due to increased respiratory burst. Additionally, these proteins induced activation of polyfunctional T cells secreting INF-γ, TNF-α, and IL-2 in ex-vivo stimulation of human peripheral blood mononuclear cells, further supporting the protective nature of designed candidates.

Dirofilaria immitis infection is one of the most severe parasitic diseases of dogs. Prevention is achieved by the administration of drugs containing macrocyclic lactones (MLs). These products are very safe and highly effective, targeting the third and fourth larval stages (L3, L4) of the parasite. Until 2011, claims of ineffectiveness of MLs, reported as “Lack of Efficacy” (LOE), were generally attributed to owners’ non-compliance, or other reason for inadequate preventative coverage. There was solid argumentation that a resistance problem is not likely to occur because of i) the great extent of refugia, ii) the complexity of resistance development to MLs, and iii) the possible big number of genes involved in resistance selection. Nevertheless, today it is unequivocally proven that ML resistant D. immitis strains exist, at least in the Lower Mississippi region, USA. Accordingly, tools have been developed, to evaluate and confirm the susceptibility status of D. immitis strains. A simple, in-clinic, microfilariae suppression test, 14-28 days after ML administration, and a “decision tree” (algorithm), including compliance and preventatives’ purchase history, and testing gaps, may be applied for assessing any resistant nature of the parasite. On the molecular level, specific SNPs may be used as markers of ML resistance, offering a basis for validation of clinically suspected resistant strains. In Europe, no LOE/resistance claims have been reported so far, and the existing conditions (stray dogs, rich wildlife, majority of owned dogs not on preventive MLs treatment) do not favor selection pressure on the parasites. Considering the genetic basis of resistance and the epizootiological characteristics of D. immitis, ML resistance neither establishes easily nor spreads quickly, a fact confirmed by the current known dispersion of the problem, which is limited. Nevertheless, ML resistance may propagate from an initial geographical point, via animal and vector mobility, to other regions, while it can also emerge as an independent evolutionary process in a new area. For these reasons and considering the current chemoprophylaxis recommendations and increasing use of ML endectoparasiticides as a potential selection pressure, it is important to remain vigilant for timely detection of any ML LOE/resistance, in all continents where D. immitis is enzootic.

Many corporations and governments aspire to become Net Zero Carbon Dioxide by 2030-2050. Achieving this goal requires understanding where energy is produced and consumed, the magnitude of CO₂ generation, and the Carbon Cycle. Many prior proposed solutions focus on reducing future CO₂ emissions from continued use of fossil fuels. Examination of these technologies exposes their limitations and shows that none offer a complete solution. For example, bioethanol is shown to be both carbon and energy inefficient. Direct Air Capture technologies are needed to reduce CO₂ already in the air. The most natural form of Direct Air Capture involves letting nature do the work of creating biomass via photosynthesis. However, it is necessary to break the Carbon Cycle by permanently sequestering that biomass carbon in “landfills” modified to discourage decomposition to CO₂ and methane. Tree leaves and biomass grown on-purpose, such as high yield switchgrass, are proposed as good biomass sources for this purpose. Left unsequestered, leaves decompose with a short Carbon Cycle time constant releasing CO₂ back to the atmosphere. While in any given year, leaves represent a small fraction of a tree’s above ground biomass, leaves can represent a substantial fraction of the total biomass generated by a tree when integrated over a tree’s lifetime. Understanding the chemistry of the distinct phases landfills undergo is the key to minimizing or eliminating decomposition. First, the compact cross-linked structure of cellulose and keeping water out will make it difficult for initial depolymerization to release sugars. Air ingress should be minimized to minimize Phase I aerobic decomposition. pH manipulation can discourage acid formation during Phase II. Lignocellulose is low in nutrients needed for anaerobic decomposition. Inhibitors can be added if needed. The goal is to move quickly to the dormant phase where decomposition stops. The cost for Carbon Capture and Storage (CCS) for growing and sequestering high yield switchgrass is estimated to be lower than CCS for steam reforming of methane hydrogen plants (SRM) and supercritical or combined cycle coal power plants. Thus, sequestration of biomass is a natural, carbon efficient, and low-cost method of Direct Capture. Biomass sequestration can provide CO₂ removal on giga tonnes per year scale and can be implemented in the needed timeframe (2030-2050).

A The present investigation was undertaken in foothill regions of Uttarakhand from July-2016 up to December-2018. A total of thirty four different sites ranging from the roadside areas, grasslands to forests were studied and Mushroom fruiting bodies were collected. A total of One Hundred sixty six fruiting counts were obtained and 68 mushroom genera belonging to 15 orders and 43 families were identified. During collection visits mushroom were apparent from organic debris of diversified habitats ranging from humid soil; grassland; leaf litter; living tree trunk; dead wood log of forest zone. Maximum fruiting bodies (75%) were obtained between July to September and minimum i.e. 6% between November – February. Among the collected mushroom Stereum rugosum, Crepidotus variabilis, Laccaria laccata, Schizophyllum commune, Ganoderma applantum, Cantharellus cibarius were more prevalent. Out of all collected mushroom sample the frequency of Mushroom belonging to order Agaricales was 45.18% followed by Polyporales i.e., 27.7%. The collected mushroom were cultured on PDA medium and their mycelial forms were preserved for further studies.

Background: General Practitioners (GP) have an important role in the prevention of suicidal behavior. The purpose of this study was to explore their views and experiences of identifying and assessing suicidal ideation. Methods: Ten GPs were recruited through convenience sampling, based on accessibility, interest and willingness to participate. In-depth interviews were carried out and results transcribed ver-batim. Aspects of experiences with suicidal patients emerged through the thematic analyses process. Results: The GPs described the varied clinical picture when patients presented in their office. How they identified depressive symptoms apart from originally somatic complaints, formed a trusting relationship and addressed suicide ideation. They described customized interventions as well as obstacles and factors that facilitated communication: time, own personal traits, pa-tient’s disclosure and organizational barriers. Conclusions: The levels of the suicidal process among patients in general practice vary greatly. GPs adjust their appraisals to profundity understand and intervene in order to prevent a crisis to escalate into subsequent suicidal behavior.

There is a crucial need for advancement in the online educational system due to the unexpected, forced migration of classroom activities to a fully remote format, due to the coronavirus pandemic. Not only this, but online education is the future, and its infrastructure needs to be improved for an effective teaching-learning process. One of the major concerns with the current video call-based online classroom system is student engagement analysis. Teachers are often concerned about whether the students can perceive the teachings in a novel format. Such analysis was involuntarily done in the offline mode, however, is difficult in an online environment. This research presents an autonomous system for analyzing the students' engagement in the class by detecting the emotions exhibited by the students. This is done by capturing the video feed of the students and passing the detected faces to an emotion detection mode. The emotion detection model in the proposed architecture was designed by finetuning VGG16 pre-trained image classifier model. Lastly, the average student engagement index is calculated. We received considerable performance setting reliability of the use of the proposed system in real-time giving a future scope to this research.

Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds, are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.

Amorphous chalcogenide (ChGs) glasses are intrinsically metastable, highly photosensitive, and therefore exhibit numerous lightinduced effects upon bandgap and sub-bandgap illumination. Depending on the pulse duration of the excitation laser, ChGs exhibit a series of lightinduced effects spanning over femtosecond to seconds time domain. For continuous wave illumination, the effects are dominantly metastable in terms of photodarkening (PD) and photobleaching (PB) that takes place via homopolar to heteropolar bond conversion. On the other hand, under nanosecond and ultrafast pulsed illumination, ChGs exhibit transient absorption (TA) that is instigated from the transient bonding rearrangements through self-trapped exciton recombination. In the first part of the review, we pay special attention to continuous wave lightinduced PD and PB, while in the second part we will focus on the TA and controlling such effects via internal and external parameters e.g., chemical composition, temperature, sample history etc.

Emerging paradigms in interferon (IFN) biology suggest a dynamic INF induced interactome that extends through broader Interferon Stimulated Gene (ISG)- induction, which implicates interferon- ISG coordinated cross-talk with mRNA processing, post-translational modification and metabolic processes that underlie pathological (viral, autoimmune and tumor biology) and physiological (stem cell regenerative pathways) processes. INF immune responses can also be triggered by endogenous host-derived molecules that are generated in response to cellular stress or hemostasis imbalance to establish tissue repair and regeneration in first place, however, overactivation or lack of countermeasures can result in host tissue damage. The proteases are integral to viral and tumor pathology, and importantly serine proteases TMPRSS2 and trypsin have been identified as important molecular determinants underlying COVID-19 pathology, and emergence of coronaviruses cultured in vitro, respectively. We propose that pathogen associated proteases can act as novel stress-inducers to facilitate viral- competent immunomodulation. We term it as Protease Induced Transcriptomic/ epi-Transcriptomic Reshaping (PITTR) of host cells to counter cellular stress. We present a novel experimental model and our preliminary findings of trypsin- primed Caco-2 cells (CPT) that result in translational halt comparable to cells grown under serum-starvation conditions (CSS). CPT at escalating trypsin concentration (CPT- EC) induce upregulation of selective proteins that majorly map to ribosomal, RNA transport, and spliceosome ribonucleoproteins (RNPs). The inclusion of proinflammatory IL1-b to CPT (CPT- IL) resulted in global overexpression of proteins comparable to Caco-2 cells cultured in growth-factor rich serum conditions (CFBS), indicating a likely de-repression of trypsin- induced translational halt. Caco-2 cells display abortive interferon proteome under differential trypsin conditions (CPT, CPT-EC and CPT-IL), which is marked by complete lack of INF generation despite induction of intermediate ISGs, suggestive of protease (trypsin)- dependent regulation of INF response. Viruses regulate the proteome of stress granules (SGs) that are induced to cope transient translational halt as a central adaptive response to pathogen induced cellular stress. The integral components of SGs include non-translating mRNA, ribonucleoproteins (RNPs) and RNA binding proteins (RBPs), which together form biological condensates through a biophysical process involving weak electrostatic interactions through intrinsically disordered regions in RBPs resulting in liquid- liquid phase separation. We compared the CPT- EC proteome to the Mammalian Stress Granules Proteome (MSGP) database to explore potential RBPs that could possibly regulate INF response (and could act as potential anti-viral targets). Notably, differentially upregulated RNPs and potential RBPs from ISG family including ADAR and PRKRA, and RNA helicases implicated in viral pathogenesis were found to be upregulated in the CPT- EC proteome further strengthening the role of proteases (trypsin) in regulating INF pathways independent of the pathogen. We propose that the supplementation of viable SARS-CoV-2 viral loads to trypsin- primed host cells could recapitulate an infectious disease model, which may closely phenocopy pathogen- driven inflammation and signaling events. Based on the global downregulation of seven SERPINS (serine protease inhibitors) linked to thromboinflammation in our LCMS profiling data, we support the candidature of serine protease inhibitors for protease mediated viral pathologies. COVID-19 is increasingly linked to coagulopathy and resemblance to Neutrophil Extracellular Trap (NET) related thromboinflammatory features; SERPIN A1AT (alpha 1 antitrypsin) being a potent neutrophil- elastase inhibitor and a negative regulator of coagulation complement pathway may be a promising candidate for establishing hemostasis rebalancing in COVID-19 pathology.

Understanding the physical properties of ultramafic rocks is important for evaluating awide variety of petrologic models of the oceanic lithosphere, particularly upper mantle and lower crust. Hydration of oceanic peridotites results in increasing serpentine content, which affects lithospheric physical properties and the global bio/geochemical cycles of various elements. In understanding tectonic, magmatic and metamorphic history of the oceanic crust, interpreting seismic velocities, rock composition and elastic moduli are of fundamental importance. In this study we show that as serpentine content increases, density decreases linearly with a slope of 7.85. We also correlate increase in serpentine content with a linear decline in shear, bulk and Young’s moduli with slopes of 0.48, 0.77, 0.45 respectively. Our results show that increase in serpentine content of lower crust and forearc mantle could decrease elasticity of lithospehere and result in break-offs. Therefore tectonic processes at peridotite rich slow spreading ridges may be strongly affected by serpentine content, particularly serpentinization may be responsible for discontinuities in thin crust, and formation of weak fault zones.

In this paper, we introduce a new class of Hermite-Fubini numbers and polynomials and investigate some properties of these polynomials. We establish summation formulas of these polynomials by summation techniques series. Furthermore, we derive symmetric identities of Hermite-Fubini numbers and polynomials by using generating functions.

The aim of this article is to extend the local as well as the semi-local convergence analysis of multi-point iterative methods using center Lipschitz conditions in combination with our idea, of the restricted convergence region. It turns out that this way a finer convergence analysis for these methods is obtained than in earlier works and without additional hypotheses. Numerical examples favoring our technique over earlier ones completes this article.

This paper presents a configuration of dual output single phase current source inverter with 6 switches for microgrid applications. The inverter is capable of delivering power to two independent set of loads of equal voltages or different voltages at the load end. The control strategy is based on Integral Sliding Mode Control (ISMC). The remote monitoring of the inverter is performed with cyber infrastructure. The cyber physical test bench is developed based on Reconfigurable I/O processor (NI MyRIO-1900) for control and monitoring of the inverter. The inverter prototype is tested in cyber physical test bench in laboratory conditions. The performance of the inverter is analyzed and monitored through the remote system. Also, the inverter is analyzed with different voltage conditions.

Background/Objectives: RAS is associated with coronary artery disease (CAD), exacerbation of arterial hypertension and progression to heart failure, but remains frequently unrecognised in clinical practice. Methods: We conducted a systematic review and meta-analysis of studies by pooling data of patients undergoing CAG due to suspected or stable CAD that received a bilateral renal artery angiography; Results: A total of 31 studies with 31,689 patients were included (mean age 63.2±8.7 years, 20.9% were female). Overall, 13.4% (95%CI 10.5-16.7%) of patients undergoing coronary angiography had significant RAS, with 6.5% (95% CI 4.5-8.9%) and 3.7% (95%CI 2.5-5.2%) having severe and bilateral RAS. The mean weighted proportion of patients with 3-vessel coronary disease (3VD) was 25.1 (95%CI 19.6-30.9%) while 4.2% (95%CI 2.6-6.2%) had leftmain (LM) coronary disease. Patients with RAS compared to those without RAS were significantly older (mean difference - MD 4.2 years, (95%CI 3.8-4.6). The relative risk of RAS was greater for the female sex (risk ratio, 95%CI; RR 1.3, 1.03-1.57), presence of diabetes (RR 1.2, 1.10-1.36), arterial hypertension (RR 1.3, 1.21-1.46), dyslipidemia (RR 1.1, 1.06-1.14), peripheral artery disease-PAD (RR 2.1, 1.40-3.16), chronic kidney disease-CKD (RR 2.6, 2.04-3.37), 3VD (RR 1.6, 1.30-1.87), and LM disease (RR 1.8, 1.28-2.47). Smoking had a neutral effect on the risk of RAS occurrence (RR 1.0, 0.94-1.06); Conclusions: RAS is common in patients undergoing coronary angiography. CKD, PAD, older age, and severe CAD were among the strongest predictors for the presence of significant RAS.

Objective: To report time-loss match injuries in Portugal’s “Divisão de Honra” (Portuguese First Tier) 2022/23 season focusing on injury incidence, injury burden, anatomical region and type of injury. Methods: A cohort prospective observational study was conducted. Data was collected through an online form sent for every team medical department categorizing player position, injury type, location and severity. Injury incidence and burden were calculated per 1000-player-match-hours. Results: The overall injury incidence was 54.4 injuries per 1000 player-match-hours (CI95% 30.3-96.2). Forwards had a higher incidence comparing to backs. Lower limbs were the most affected location (52% of the injuries). Sprain/ligaments injuries were the most common type of injury followed by muscle injuries. Discussion: The injury incidence was higher than what is reported in amateur competitions and lower than professional ones. Injury severity was similar to other studies. Our study suggests a lower injury burden compared to other semi-professional and elite leagues. Further research with broader participation and training injury data is needed.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

On February 28th, 2023, Spanish Royal Decree 150/2023 as published, approving the plans for the management of the maritime space of the five Spanish marine demarcations. This Royal Decree Law inaugurates the Planning of the Maritime Space in Spain. Terrestrial Space Planning is very advanced, both in the legislation and in the instruments that are enabled to organize this space, from the national scale to the municipal scale, passing through the regional, provincial, and supra-municipal scales. Naturally, both Planning must converge and thus speak of an Integrated Space Planning. In some of the countries that we can take as global references, this convergence in the form of integration is taking place. On the other hand, and within the context of climate change, coastal cities will be the most affected, both by the potential rise in sea level and by the increasingly continuous and greater extreme events. Integrated Space Planning is postulated as the most effective tool to carry out adequate territorial and urban planning of our coastal cities, as well as to analyse the influence and possible corrective measures to apply against the effects produced by climate change.

Background: During the stay in the neonatal intensive care unit, parents play a crucial role in the care of their infants. Recent studies reported a decrease in parental participation due to Coronavirus Disease (COVID-19) pandemic that determined restricted access policies in hospitals. The aim of this study is to describe the barriers to a good parents’ participation during the stay in the neonatal intensive care unit in the COVID-19 era. Methods: A quantitative observational study was carried out. Results: 270 parents participated in this study. Mothers’ participation in care seems to be higher as compared to fathers (p = 0.017). Parents who lived the birth of their first child reported a better level of participation in care when compared to those who lived the birth of their second born (p = 0.005). Parents of extremely preterm neonates reported a lower interaction with their infant if compared to parents of term newborns (p &lt; 0.001). Conclusions: Some more disadvantaged categories have reported lower scores: cultural and linguistic minorities, parents of multiple children and fathers. COVID-19 pandemic made several Family Centred Care activities not possible with a higher impact on those who benefited the most of these facilities. This study was prospectively registered by the IRB-CRRM of the University “G. d’Annunzio” Chieti-Pescara on the 23/01/2024 with registration number CRRM;2023_12_07_01.

The decline in global pollinator populations has raised serious concerns about the sustainability of ecosystems and agricultural productivity. Urban environments, often characterized by habitat loss and environmental stressors, are considered challenging habitats for pollinators. However, urban green spaces, including street and ornamental trees, can play a crucial role in supporting pollinators by providing essential food resources. This study aimed to evaluate the sugar and amino acid production of eight urban tree species to determine their potential contributions to pollinator nutrition. Our findings revealed significant variability among species regarding nectar volume, sugar content, and amino acid composition, emphasizing the importance of considering multiple factors when assessing the utility of floral resources. Consequently, Tilia amurensis, Heptacodium miconioides, Aesculus turbinata, and Wisteria floribunda demonstrated superior potential in supporting urban pollinator communities. Contrastingly, Sorbus commixta, Styrax japonicus, and Cornus kousa, often favored for their aesthetic appeal, showed less potential. This study underscores the need for urban tree selection that prioritizes species that provide diverse and abundant nutritional resources for pollinators while balancing aesthetic and ecological values. Our results offer a foundation for better-informed urban biodiversity management and contribute to creating pollinator-friendly urban environments.

We develop an action principle for producing a single fluid, two-constituent system with dissipation in general relativity. The two constituents in the model are particles and entropy. The particle flux creation rate is taken to be zero, while the entropy creation rate is non-zero. Building on previous work, it is demonstrated that a new term (the proper time derivative of the matter space ``metric'') is required in the Lagrangian in order to produce terms typically associated with bulk and shear viscosity. Equations of motion, entropy creation rate, and energy-momentum-stress tensor are derived. Using an Onsager approach of identifying thermodynamic ``forces'' and ``fluxes'' a model is produced which delivers the same entropy creation rate as the standard, relativistic Navier-Stokes equations. This result is then contrasted with a model generated in the spirit of the action principle, which takes as its starting point a specific Lagrangian and then produces the equations of motion, entropy creation rate, and energy-momentum-stress tensor. Unlike the equations derived from Onsager reasoning, where the analogs of the bulk and shear viscosity coefficients are prescribed ``externally'', we find that the form of the coefficients in the second example are a direct result of the specified Lagrangian. Furthermore, the coefficients are shown to satisfy evolution equations along the fluid worldline; also a product of the specific Lagrangian.

To the best of the author’s knowledge, studies of mature plasmacytoid dendritic cell proliferation associated with T lymphoblastic lymphoma were extremely rare in the literature. Here, we report a patient who underwent both mature plasmacytoid dendritic cell proliferation and T lymphoblastic lymphoma. With the findings of lymph node biopsy taken from the right cervical and inguinal regions, we identified eye-catching mature plasmacytoid dendritic cells that were considered to be responsible for this lesion at the beginning, until the immunostaining of Ki67 and TDT showed a small group of positive cells hiding in these plasmacytoid dendritic cells. Bone marrow biopsy was also performed in this patient. Microscopically, the hematopoietic tissue was almost completely replaced by lymphoblastoid cells with condensed chromatin, inconspicuous nucleoli and scanty cytoplasm, which were basically the same as those seen in the lymph nodes in morphology. However, there was no sign of plasmacytoid dendritic cells or Langerhans cells in the bone marrow biopsy. With the help of bone marrow biopsy, our final diagnosis of the lymph node was T lymphoblastic lymphoma coexisting with mature plasmacytoid dendritic cell proliferation . Although accumulations of plasmacytoid dendritic cells may occur in some infections or reactive lymphadenopathy, the presence of extensive nodules or infiltration of plasmacytoid dendritic cells strongly reminds the pathologist to carefully evaluate the bone marrow or peripheral blood status of the patient to exclude a hidden myeloid or other neoplasm.

in order to enhance the separation performance and to reduce the heat loss of the transmembrane for membrane distillation, the thermal efficiency and hydrophobicity of the membrane distillation should be simultaneously enhanced. In this work, a PVDF/PET hydrophobic/hydrophilic membrane is prepared by non-solvent phase inducing method. Nanosized silica aerogel (SiAG) with high porosity is added to the composite membranes. The modifying effects and operating conditions on permeate flux and thermal efficiency in direct contact membrane distillation (DCMD) are investigated. Furthermore, the latent heat of vaporization and the heat transfer across the membranes are compared for SiAG addition, which indicates that the composite PVDF@SiAG/PET membranes display a great potential for distillation-separation application with high heat efficiency.

The key enzyme, 1-hydroxy-2-methyl-2-(E)-butenyl-4-pyrophosphate reductase HDR, responsible for the final step in the MEP pathway, was successfully cloned from the petals of Narcissus tazetta var. chinensis, herein referred to as NtHDR (accession number OQ739816). NtHDR exhibits a full-length coding sequence spanning 1380 base pairs, encoding a total of 460 amino acids. Through phylogenetic tree analysis, it has been determined that NtHDR shared the closest evolutionary relationship with monocotyledons, specifically Asparagus officinalis and Zingiber officinale. Utilizing quantitative real-time PCR analysis, it was observed that NtHDR exhibited significant expression in both petals and corona, with expression levels varying throughout the flowering process of Narcissus. Specifically, in petals, NtHDR expression demonstrated a pattern of initial increase followed by subsequent decrease, while in corona, it consistently increased. Subsequent subcellular localization experiments indicated that NtHDR was localized within the chloroplasts. To investigate the functional impact of NtHDR, stable transformation was performed, where NtHDR was introduced into Nicotiana benthamiana. The resulting transgenic N. benthamiana flowers were analyzed using solid-phase microextraction coupled with gas chromatography–mass spectrometry (SPME-GC-MS) to characterize their volatile components. The analysis revealed the presence of the monoterpene compound linalool, as well as the phenylpropanoids benzyl alcohol and phenylethanol, within the floral fragrance components of the transgenic N.benthamiana plants. However, these compounds were absent in the floral fragrance components of wild-type tobacco plants, thus highlighting the impact of NtHDR transformation on the floral scent profile.