Quasi-solid composited electrolytes were produced by LiFSI initiated polymerized poly-(Dioxolane) (PDOL) with garnet-LLZO (Li7La2Zr3O12) nanofibers and used in lithium-metal batteries. Linear sweep voltammetry shows that the initial oxidation voltage of 4.6 V for Gel-10% (G10, 10% wt. LLZO in PDOL) vs Li/Li+. EIS test of stainless steel// stainless steel symmetric cells for Gel-1% (G1), Gel-5% (G5) and Gel-10% (G10) show ion conductivity (5*10-5 S/cm). Li/G10/Li symmetric cells have stable stripping-plating cycling performance over 1300 hours continuously with the current density of 0.1 mA/cm2 at 25 oC, indicating a good interface contact and stable lithium-ion transport pathway through the composite electrolytes. LFP/G10/Li batteries have stable charge-discharge plateau, low polarization voltage of 0.07-volt, energy efficiency of 95% and coulombic efficiency of ~99% at current density of 26.3 mA/g at 25 oC for over 100 cycles.

Taiwan’s auditors have suffered from processing excessive audit data, including drawing audit evidence. This study advances sampling techniques by integrating machine learning with sampling. This machine learning integration helps avoid sampling bias, keep randomness and variability, and target the risker samples. We first apply a Naive Bayes classifier to classify data into some classes. Next, a user-based, item-based, or hybrid approach is employed to draw audit evidence. The representativeness index is the primary metric for measuring the representativeness of audit evidence. The user-based approach denotes the selection of samples between two percentiles in a class as audit evidence. It may be equivalent to a combination of monetary and variable sampling methods. The item-based approach represents the choice of risky samples as audit evidence. It may be identical to a combination of non-statistical and monetary sampling methods. Auditors can hybridize those user-based and item-based approaches to balance representativeness and riskiness in selecting audit evidence. Three experiments show that sampling using machine learning integration has the benefits of drawing unbiased samples, handling complex patterns, correlations, and unstructured data, and improving efficiency in sampling big data. However, the limitations are the classification accuracy output by machine learning algorithms and the range of prior probabilities.

We prove an analog of the removable singularity theorem for bounded harmonic functions on stratified sets. The harmonic functions are understood in the sense of the soft Laplacian. The result can become one of the main technical components for extending the well-known Poincaré–Perron’s method of proving the solvability of the Dirichlet problem for the soft Laplacian.

Early weaning management followed by energy supplementation can lead to metabolic alterations in the calf that exert long-term effects on the animal’s health and performance. It is believed that the main molecular basis underlying these metabolic adaptations are epigenetic mechanisms that regulate, activate, or silence genes at different stages of development and/or in response to different environmental stimuli. However, little is known about postnatal metabolic programming in Bos indicus. Therefore, this study aimed to compare the DNA methylation profile of Nellore animals submitted to conventional and early weaning and to correlate the findings with genes differentially expressed in Longissimus thoracis skeletal muscle of Bos indicus cattle. A total of 481 differentially methylated regions were identified, with 52% (250) being hypermethylated and 48% (231) hypomethylated. Functional enrichment analysis of 53 differentially methylated and differentially expressed genes was performed. The main enriched terms and pathways were associated with 3’-5’-cyclic adenosine monophosphate (cAMP) signaling which present the upregulated adenylate cyclase 3 (ADCY3) gene and significatively hypomethylated in promoter region. Alterations in cAMP signaling are involved in numerous processes, many of them related to lipid metabolism. The relative differential expression of key genes of this pathway demonstrates the relationship between cAMP signaling and de novo lipogenesis. These findings suggest an important role of postnatal metabolic programming through DNA methylation mechanisms in determining fat deposition in beef.

The production of a ton of steel in an integrated steel plant generates of approximately 1 ton of ferrous slag. A great part of ferrous slags is recycled in civil and road construction etc., but a huge amount is still dumped. Recycling ferrous slag as cement precursor was considered the upcycling route. Regulation (EU) 2024/1252 requires the Member States to provide information, until November 2026, on the critical raw materials (CRM) amount in their secondary resources and on quantification methods used for. This study addresses two synergic objectives: ensuring the reliability of XRFS results and screening for CRM in ferrous slags based on XRFS outcomes. The main novelty of the paper is the way of ensuring the reliability of the XRFS results based on weighted arithmetic mean and on the maximum likelihood approach. Secondly, the XRFS measurements carried on ferrous slags demonstrate that they contain significant amounts of CRM like Ba, Sr, Y, etc. XRFS cannot detect light CRM. Our preliminary LIBS measurements on ferrous slags disclosed the presence of Li and Be. The drawbacks of the XRFS technique impose further research to develop an integrated XRFS, LIBS and XRD procedure for comprehensive and trustworthy CRM screening in extractive waste piles.

Extracting entities from large volumes of chicken epidemic texts is crucial for knowledge sharing, integration, and application. However, Named Entity Recognition (NER) encounters significant challenges in this domain, particularly due to the prevalence of nested entities and domain-specific named entities, coupled with a scarcity of labeled data. To address these challenges, we compiled a corpus from 50 books on chicken diseases, covering 28 different disease types. Utilizing this corpus, we developed a nested NER model, MFGFF-BiLSTM-EGP. This model integrates the Multiple Fine-Grained Feature Fusion (MFGFF) module with a BiLSTM neural network and employs an Efficient Global Pointer (EGP) for predicts the entity location encoding. In MFGFF module we designed three encoders, character encoder, word encoder and sentence encoder, this design effectively captures fine-grained features and improves the recognition accuracy of nested entities. Experimental results show that the model performs robustly, with F1 scores of 91.98%, 73.32%, and 82.54% on the CDNER, CMeEE V2, and CLUENER datasets, respectively, outperforming other commonly used NER models. Specifically, on the CDNER dataset, the model achieved an F1 score of 79.68% for nested entity recognition. This research not only advances the development of knowledge graph and intelligent question-answering system for chicken diseases but also provides a viable solution for extracting disease information that can be applied to other livestock species.

Effectively mapping and monitoring rubber plantation is still changing. Previous studies have explored the potential of phenology features for rubber plantation mapping through a pixel-based approach (pixel-based phenology approach). However, in fragmented mountainous Xishuangbanna, it could lead to noises and low accuracy of resultant maps. In this study, we investigated the capability of an integrated approach by combining phenology information with an object-based approach (object-based phenology approach) to map rubber plantations in Xishuangbanna. Moderate Resolution Imaging Spectroradiometer (MODIS) data were firstly used to acquire the temporal profile and phenological features of rubber plantations and natural forests, which delineates the time windows of defoliation and foliation phases. Landsat images were then used to extract a phenology algorithm comparing three different approaches: pixel-based phenology, object-based phenology, and extended object-based phenology to separate rubber plantations and natural forests. The results showed that the two object-based approaches achieved higher accuracy than the pixel-based approach, having overall accuracies of 96.4%, 97.4%, and 95.5%, respectively. This study proved the reliability of a phenology-based rubber mapping in fragmented landscapes with a distinct dry/cool season using Landsat images. This study indicated that the object-based phenology approaches can effectively improve the accuracy of the resultant maps in fragmented landscapes.

The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydoxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by significant decrease in non enzymatic antioxidants and TAS concentrations. 8-OHdG and cell proliferation level were negatively correlated with non enzymatic antioxidants viz., Vitamin A, Vitamin C, vitamin E level and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity amongst the malignant, benign and controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. Among the oxidative stress markers and cell proliferation index, decreased level of vitamin A, vitamin C, vitamin E, TAS and increased level of 8-OHdG, cell proliferation index emerged as best predicted biomarkers for subjects with malignancy and benign breast disease.

Crawling robots are the focus of intelligent inspection research, and the main feature of this type of robot is the flexibility of in-plane attitude adjustment. The crawling robot HIT_Spibot is a new type of steam generator heat transfer tube inspection robot with a unique mobility capability different from traditional quadrupedal robots. This paper introduces a hierachical motion planning approach for HIT_Spibot, aiming to achieve efficient and agile maneuverability. The proposed method integrates three distinct planners to handle complex motion tasks: a nonlinear optimization-based base motion planner, a TOPSIS-based base orientation planner, and a Mask-D3QN (MD3QN) algorithm-based gait motion planner. Initially, the robot's base and foot workspace are delineated through envelope analysis, followed by trajectory computation using Larangian methods. Subsequently, the TOPSIS algorithm is employed to establish an evaluation framework conducive to foundational turning planning. Finally, the MD3QN algorithm trains foot points to facilitate robot movement along predefined paths. Experimental results demonstrate the method's adaptability across diverse tube structures, showcasing robust performance even in environments with random obstacles. Compared to the D3QN algorithm, MD3QN achieves a 100% success rate, enhances average overall scores by 6.27%, reduces average stride lengths by 39.04%, and attains a stability rate of 58.02%. These results not only validate the effectiveness and practicality of the method but also showcase the significant potential of HIT_Spibot in the field of industrial inspection.

1) Background: Several studies have shown the benefit of drawing when learning anatomy. Virtual Reality (VR) also appears to be useful to increase the understanding of the location of anatomical structures. This study aims to describe how students in an Operating Room Nursing (OR nursing) master study program perceive the benefit of active learning methods, including drawing and the use of VR. 2) Methods: We combined these two methods in a class of 29 students. 38 half-finished drawings of anatomical structures were made. The students were to complete these during lectures with guidance from the teacher. The students also attended a two-hour VR session where they were to find various anatomical structures. A paper questionnaire was applied to evaluate the teaching program. Data were analyzed statistically. 3) Results: The students highly appreciated these learning methods. They reported that drawing made them work more actively during lectures and increased their learning outcome. They also perceived that the use of VR technology increased their understanding of the location of anatomical structures. 4) Conclusion: The combination of drawing and VR technology may be of benefit to OR Nursing students when learning anatomy by both increasing student activity and learning outcomes.

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

Underwater visual detection technology plays a pivotal role in fields such as marine exploration. With the increasing demand for underwater monitoring, the quest for efficient and reliable methods for underwater target recognition has become particularly significant. To address this requirement, this study developed an innovative underwater object detection architecture based on YOLOv8, named YOLOv8-MU, aimed at significantly enhancing detection accuracy.By integrating the LarK module proposed in UniRepLKNet to optimize the backbone network, YOLOv8-MU aims to achieve a larger receptive field without increasing the model’s depth. Further, this research introduces C2fSTR, an innovative method that combines Swin Transformer with the C2f module. Additionally, we have incorporated the SPPFCSPC_EMA module, which combines Cross-Stage Partial Fast Spatial Pyramid Pooling (SPPFCSPC) with attention mechanisms, significantly improving the detection accuracy and robustness of various biological targets. Moreover, by introducing a fusion block based on DAMO-YOLO into the neck of the model, we further enhanced the model’s capability in multi-scale feature extraction. Finally, the adoption of the MPDIoU loss function, designed around vertex distance, effectively tackles the challenges of localization accuracy and boundary clarity in underwater organism detection. Experimental results on the URPC2019 dataset demonstrate that the YOLOv8-MU model achieved an mAP@0.5 of 78.4%, marking improvements of 5.6%, 1.1%, and 4.0% over YOLOv5s, YOLOv7, and YOLOv8n respectively, indicating the leading performance (SOTA) of this method. On the other hand, further evaluation on the URPC2020 dataset confirmed the generalization capability of the YOLOv8-MU architecture, with its mAP@0.5 reaching 80.4%, surpassing various models including YOLOv5x and YOLOv8n, showcasing the wide applicability of our proposed improved model architecture.

The extensive collection of paper documents and books stored in the archives of universities worldwide is a hidden cultural heritage that is frequently inaccessible. To overcome this problem, the University of Genoa, Italy, seeks to collect, store, and digitize a wide variety of items, encompassing books, manuscripts, archival materials, and documents related to museum artifacts, which together form a cultural heritage of great importance and historical significance. To make such a cultural heritage accessible to both humans and machines, images and videos must be provided with alternate descriptions, metadata, and speech-to-text transcriptions while ancient texts, for which OCR techniques are often not effective, must be accompanied by word-for-word transcripts. This work presents the design of a transcription system for the “University Museum System” at the University of Genoa, Italy (SMA-UniGe), including user interface elements and users’ engagement techniques. The goal is to create an accessible digital heritage that can be enjoyed by all, facilitated by a community of digital volunteers who are eager to dedicate their time, have a great experience, socialize, and interact on the proposed transcription system. The system exploits gamification theory to transform the typically monotonous task of transcription into a captivating experience. This activity is in line with the so-called University third mission, i.e., the activity of public engagement that aims at generating knowledge outside the academic environment to the benefit of the social, cultural, and economic development.

Antioxidant, anti-inflammatory and chemo-preventive features have been reported for the carotenoid diatoxanthin. Diatoxanthin is only produced by a few groups of microalgae where it functions in photoprotection. Its large-scale production in microalgae is currently not feasible. In fact, rapid conversion into the inactive pigment diadinoxanthin is triggered when the cells are removed from the high-intensity light source, which will be the case during large-scale harvesting of microalgae biomass. Zeaxanthin epoxidase (ZEP) 2 and/or ZEP3 have been suggested to be responsible for the back-conversion of high-light accumulated diatoxanthin to diadinoxanthin in low light in diatoms. Using the CRISPR/Cas9 gene editing technology we knocked out the ZEP2 and ZEP3 genes in the already commercially used marine diatom Phaeodactylum tricornutum to investigate their role in the diadinoxanthin-diatoxanthin cycle, and to determine if one of the mutant strains could function as a diatoxanthin production line. Light shift experiments proved that ZEP3 encodes the enzyme converting diatoxanthin to diadinoxanthin in low light. Loss of ZEP3 caused the high-light accumulated diatoxanthin to be stable for several hours after the cultures had been returned to low light, suggesting that zep3 mutant strains could be suitable as commercial production lines of diatoxanthin.

In this paper, a continuous power management for a decentralized DC microgrid (DCMG) is proposed to achieve voltage regulation and power balance even under system uncertainty and voltage sensor failure. The DCMG system achieves a continuous power management through only the primary controller to reduce the computational burden of each power agent. To enhance the reliability and resilience of the DCMG system under voltage sensor failure, a DC bus voltage (DCV) sensor fault detection algorithm is proposed. In this algorithm, the DCV sensor failure is detected by comparing the measured DCV with the estimated DCV. When the power agent identifies the DCV sensor failure, it changes the operation properly according to the proposed control mode decision algorithm to maintain the stability of the DCMG system. When uncertain conditions such as the power variation of the distributed generations, sudden grid disconnection, DCV sensor failure, electricity price change, and critical battery status occur, the DCMG system is changed to transitional operation modes. These transitional operation modes are employed to transmit the power agent information to other agents without digital communication links (DCLs) and to accomplish power sharing even under such uncertain conditions. In the transitional operation modes of the DCMG system, the DCV levels are temporarily shifted to an appropriate level, enabling each power agent to detect the uncertainty conditions, and subsequently to determine its operation modes based on the DCV levels. Simulation and experimental results under different test conditions confirm the reliability and effectiveness of the proposed control scheme.

This study aimed to identify miRNA editing sites during adipose tissue development in Ningxiang pigs and analyze their characteristics and functions. Based on the small RNA-seq data from subcutaneous adipose tissue samples of Ningxiang pigs at four stages (30, 90, 150 and 210 days), we constructed a developmental atlas of the miRNA editome in adipose tissue of Ningxiang pigs. The characteristics and functions of this editome were further explored through bioinformatics analysis. The findings revealed that a total of 505 miRNA editing sites were identified with C-to-U editing types being the most prevalent, followed by U-to-C, A-to-G and G-to-U. Importantly, these four types of miRNA editing exhibited a base preference. The number of editing sites showed obvious differences among age groups, with the highest occurrence of miRNA editing events observed at 90 days of age and the lowest at 150 days of age. In the miRNA seed region, a total of 9 miRNA editing sites were identified with significant differences in editing levels (P < 0.05), and located in ssc-miR-23a, ssc-miR-27a, ssc-miR-30b-5p, ssc-miR-15a, ssc-miR-497, ssc-miR-15b, and ssc-miR-425-5p, respectively. Target gene prediction and enrichment analysis revealed that the editing of miR-497 may potentially regulate fat deposition by inhibiting adipose synthesis via influencing target binding. These results provide new insights into the regulatory mechanism of pig fat deposition.

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

The advancement in science and technology has led to luffa sponge (LS) being widely used as a natural material in industrial application as its polyporous structure and light texture. In order to enhance the utility of LS fibers as the reinforcement of lightweight composite materials, this study investigate its water absorption, mechanical properties, anatomical characteristic and thermal performance. Hence, moisture regain, tensile properties of LS fiber bundles were measured in accordance with standards and the structural characteristics were investigated via microscopic observation. Scanning electron microscopy (SEM) was used to observe the surface morphology and fracture surface of fiber bundles. Test results shows that the special structure where the phloem tissues degenerate to cavities had a significant influence on the mechanical properties of LS fiber bundles. Additionally, the transverse sectional area occupied by fibers in a fiber bundle (SF), wall thickness and ratio of wall to lumen of fiber cell, and crystallinity of cellulose had an impact on the mechanical properties of LS fiber bundles. Furthermore, the fiber bundles density of LS varies range of 385.46-468.70 kg/m³, much less than that of jute (1360.40 kg/m³) and Arenga engleri (950.20 kg/m³) while LS fiber bundles has superior specific modulus.

The aim of this study was to examine the oxidation of human serum albumin (HSA) caused by oxidative stress after an exhaustive exercise such as ultra-marathon race. Thus, blood samples from 12 adult runners who underwent a 103 km mountain ultra-marathon race were collected pre- and 24, 48 and 72 h post race. HSA was partially purified using affinity chromatography and then was subjected to Western blot analysis for disulfide dimers determination, indicating oxidation. The results were correlated with those from a previous study in which the same samples were analyzed using different oxidative stress markers and a good correlation with protein carbonyls (PC) at all time points was observed. Moreover there was a significant correlation with static oxidation-reduction potential (sORP) at 24 h, and a negative correlation with capacity oxidation-reduction potential (cORP) at 24 and 48 h. In addition, an individual analysis of albumin dimers exhibited great inter-individual differences. This inter-individual variability in the oxidation of HSA may suggest different interventions (e.g. through diet) in order to confront the effects on athletes’ organism after a strenuous exercise. In conclusion, this study supported the importance of the assessment of albumin dimers as a predictive marker for exercise-induced oxidative stress.

The supply chain has incorporated products by putting them into hair scarfs. This study introduces the use of mini chips in health and beauty products and can reduce fatigue through enhanced sleep patterns. The mini chip could be placed in the scarf and used as a prototype. RFID technology provides the supply chain with specific information that is used to identify products and make communication easier. (Muhammad, et. al. 2013) This paper presents a new tool herein referred to as a scarf prototype which is developed to analyse EMG (electromyogram), ECG (electrocardiography), EEG (electroencephalogram), and EOG (electro-oculogram) signals that focuses in the area of sleep disorders. The mini chips used can be used to determine a solution for sleep disruption by using automated analytics. This could lead to improvement in our understanding of sleep disruption and overall sleep physiology. Automated technology allows repeated measurements, evaluation of sleep patterns, and provide suggestions to improve a person’s quality of sleep. This analysis compares the use of polysomnography and the scarf prototype. The analytics provide models and shows correlation between variables, such as EMG, ECG, EEG, and EOG. This study shows that the results from the scarf prototype is just as reliable as the original method, polysomnography.

It is documented that maternal diseases or treatments influence a newborn’s clinical status at birth; autoimmune diseases with circulating antibodies are often clinically expressed transiently in newborns due to the crossover of the specific IgG through the placenta during pregnancy. The offspring can inherit maternal genetic anomalies, but clinical expression usually becomes patent later in life. If prenatal medical history is not available or if signs or symptoms of a mother’s disease are revealed for the first time during pregnancy or postpartum, their effects on the newborn may be misattributed. In this article, we present three cases of pregnant women, without any known pathology before or during pregnancy, who gave birth to very sick preterm newborns that required admission to the Neonatal Intensive Care Unit (NICU). The neonates’ complications were considered initially as consequences of prematurity or infection, but later investigations revealed transient autoimmune disease in two of the cases (myasthenia gravis and hyperthyroidism) and a severe form of thrombophilia in the third case. In all cases, mothers were asymptomatic and unaware of their subclinical disease. Preemies’ diagnosis has contributed to the identification of their mothers’ pathology and adequate treatment was prescribed with favourable short- and long-term outcomes. In one of the cases (myasthenia gravis) both mother and child had associated infectious diseases in the perinatal period that complicated the clinical picture and created problems of diagnosis. This article intends to emphasize the paramount importance of prenatal care, for both mother and newborn. Repeated medical visits and investigations throughout the pregnancy are a good opportunity to detect subclinical diseases or predispositions. As newborns usually develop non-specific signs, one should have experience and pay attention to differentiate among etiologies. Our paper takes a reversed approach to the usual medical diagnosis pathway: from infant to mother instead of mother towards the infant, proving that inter-speciality collaboration can work bi-directionally.

The Mining Industry has changed significantly in recent decades with the introduction of advanced technologies such as Artificial Intelligence (AI) and Machine Learning (ML). These innovations contribute to the creation of expert systems that help in optimizing processes, increasing the safety and sustainability of operations. This article is a literature review of modern AI and ML methods and technologies used in the Mining Industry. Discusses various intelligent and expert systems used to improve productivity, reduce operating costs, improve occupational safety, environmental sustainability, machine automation, predictive analytics, quality monitoring and control, and inventory and logistics management. The advantages and disadvantages of different approaches are analyzed, as well as their potential impact on the future of the Mining Industry. The review highlights the importance of integrating AI and ML into mining processes to achieve more efficient and safer solutions.

Rock materials failures are accompanied by the co-existence of various failure mechanisms, in-cluding rock fracturing, shearing, and compaction yield. These mechanisms manifest macro-scopically as multiple failure modes and nonlinear strength characteristics related to stress levels. Considering the limitations of current rock mechanics strength theories, which are primarily derived from single failure mechanisms, this study evaluates the applicability of alternative strength theories. Based on the extensional-strain criterion and the PMC (Paul-Mohr-Coulomb) model, a piecewise linear strength model was proposed that is suitable for analyzing multiple failure mechanisms in rocks and revealing the intrinsic mechanisms of multi-mechanism rock material failure. A multiple failure mechanism strength model in the form of inequalities was proposed, using the generalized shear stress, mean stress, and stress Lode angle as parameters. Strength tests conducted on sandstone and granite rock material samples under different stress conditions revealed distinct piecewise linear strength characteristics for both rock types, vali-dating the rationality and applicability of the multiple failure mechanism model. The findings construct a multi-mechanism failure model for rocks, providing enhanced predictive capabilities and aiding in the prevention of rock structural failures.

A new heterocyclic compound, 2-(2,6-diisopropylphenyl)-1-methylimidazo[1,5-a]quinolin-2-ium tetrafluoroborate 1 was obtained from its precursor, N-(2,6-diisopropylphenyl)-N-(quinolin-2-ylmethyl)acetamide 2, by POCl3-mediated cyclization. For the first time – the tertiary acetamide 2, precursor of 1, was synthesized by using commercially available starting materials. The structure of 1 was unquestionably confirmed by 1H-, 13C-, 2D-NMR-, IR- spectroscopy and mass-spectrometry. Its optical properties were also studied.

(1) Background: Youths with multiple risks and severe disadvantages experience poorer health and educational outcomes than less disadvantaged peers. To address problems with coping and self-regulation in this group, mental skills training (MST) approaches more commonly used in sport are an emerging intervention approach. (2) Methods and Results: This narrative review synthesizes literature to explain the need for MST, how it works, and evidence to support it works by focusing on two well evaluated programmes: LifeMatters and My Strengths Training for Life™. (3) Conclusions: To support positive youth development, MST is a strengths-based, flexible and adaptable approach to help fill the shortage of available evidence-based programs for those youths facing multiple disadvantages. The findings of this review may facilitate policy makers, commissioners, program planners, and researchers in the uptake of MST or similar psychoeducational approaches in future.

This paper presents a methodology based on deep learning models and metaheuristic algorithms for the optimization of airfoils for the design of aircraft wings with large endurance. The use of AZTLI-NN (a neural network with an architecture composed of a multilayer perceptron and a variational autoencoder) is implemented for the prediction of graphs of the aerodynamic coefficients of the airfoil as a function of the angle of attack. This neural network presents good predictions of the aerodynamic coefficients, similar to the coefficients obtained with computational fluid dynamics simulations. AZTLI-NN in combination of metaheuristic algorithms and the CST profile parameterization method show excellent performance in single-objective and multi-objective profile optimization tasks.

As the demand of heating and air conditioning is increasing day by day due to getting a comfortable life, for that reason, the market for heat pump and air conditioning systems or both, is seeing a steady increase in low global warming potential. All researchers on heat pump and air conditioning systems are searching for environmentally friendly refrigerants. However, a significant number of contemporary refrigerants (HCFCs) have the potential to cause global warming and ozone depletion, such as those found in heat pump air conditioning systems. Using more environmentally friendly refrigerants, including hydrocarbon and blend refrigerant mixtures, is one way to lower GWP and Ozone depletion potential. This study examines the performance of several alternative refrigerants, including R32, R134A, R410A, R22, and R290. In order to examine the performance of R290, theoretical and simulation results are compared on various refrigerants while taking into account a number of performance parameters, including the refrigerant energy efficiency ratio, mass flow rate, coefficient of performance, cooling capacity, and compressor work for one ton of refrigeration (1TR) air conditioners. One player with a very low GWP is R290. However, the only drawback is that it can catch fire and is hazardous to use in split-type commercial heat pump air conditioning applications. The environmental and thermo physical properties of HC-290 are significantly better than those of other materials, according to theoretical and simulation studies utilizing Cool Pack software, hence it is a viable replacement.

Carboxymethyl cellulose (CMC) can act as a nonpermeating cryoprotectant, reducing the toxici-ty of glycerol. The dog spermatozoa were diluted and frozen in freezing extender supplemented with 0 (control), 0.1, 0.25, 0.5, or 0.75 % (w/v) CMC. Post-thaw, the sperm kinematic parameters (CASA), viability (SYBR-14/PI), and acrosome integrity (FITC-PSA) were evaluated. The expres-sion of genes related to apoptosis (BCL2, BAX, and ANAXA), motility (BACTIN), cold shock proteins (YBX3), and ROS (CAT, ROMO1, and SMOX) was evaluated using qPCR. The total mo-tility was higher in the 0.1 % CMC group compared to the other groups (p

Wear-resistant steel/carbon steel composite plate not only has the double performance advantage of high strength and wear-resistance, but also can reduce energy consumption and production cost. Based on 50% reduction rate, the wear resistance of BTW1/Q345 composite was studied at different annealing temperatures, and the dry friction and wear tests of BTW1/Q345 composite at different annealing temperatures were carried out by using RETC MFT-5000. The macro-micro morphology and wear mechanism of wear marks at different annealing temperatures were analyzed by using white light interference three-dimensional surface profiler, Scanning electron microscope scanning electron microscope (SEM) and backscatter electron diffraction (EBSD) . The results show that with the increase of annealing temperature, the grain size near the scratch of BTW1 in the wear-resistant layer of the composite plate is refined, and the wear-resistant property is higher than that of the original sample.When the annealing temperature is 860℃,the wear resistance is the best.

As the number of end-of-life vehicles continues to grow, the field of separation technology for broken copper and aluminium parts of end-of-life vehicles has emerged as a significant area of research. As a key technology for the separation of non-magnetic non-ferrous metals, such as copper and aluminium, eddy current separation can achieve efficient separation of non-magnetic non-ferrous metals according to their differing conductivity and density. Nevertheless, further research is required in the separation of large-scale broken copper and aluminium parts of end-of-life vehicles. This paper presents a novel magnetic roller model comprising circumferential and axial periodic arrangements of permanent magnets. A single permanent magnet was constructed as an equivalent current model, and the magnetic scalar potential equations were solved using simulation tools. This allowed the distribution of the magnetic field outside the magnetic roller to be studied. The results demonstrate that the novel permanent magnet array magnetic roller can enhance the magnetic field intensity and action distance of the external magnetic field, which is more conducive to the separation of large-scale broken copper and aluminium parts of scrap cars. The findings of this research provide a theoretical foundation for the separation of scrap car broken copper and aluminium parts.

Background: Our previous study highlighted important healthcare access and utilization concerns among new immigrants. Hence, in this study, we aimed to explore the role of public and patient involvement (PPI) may have in enhancing the accessibility and their contribution to migration health studies. Method: An open and in-depth interactive consecutive virtual discussion was conducted among volunteer asylum seekers and refugees from Eritrea and Syria in Switzerland. The novel PPI establishment had three phases; inception, training phase, and contribution phase. Result: At the beginning, the concept of PPI was apprehensive to grasp, as it was a new approach. After training and consecutive discussions, volunteers were ardent to engage actively. Hence, among the prime findings were the PPI's role and effect in raising awareness, PPI's role in exploring and communicating the healthcare system accessibilities and utilization among their community, the impact of PPI in echoing the healthcare needs of their fellow migrants, and PPI's contribution in enhancing and strengthening migration health researches. Conclusion: The PPI volunteers in the study were keen to raise their community's awareness through their networks, and bridge the research gap between researchers and the public.

Sinojackia Hu. comprises five to eight Chinese endemic species with high ornamental and medicinal value. However, the generic limits, interspecific relationships and evolutionary history of the genus remain unresolved. In this study, we newly sequenced and assembled three plastomes of S. oblongicarpa and compared them with those of the other congeneric species to explore the taxonomic delimitation of the species and the evolutionary history of the genus. Plastomes structure of Sinojackia species were extremely conserved in terms of number of genes, sequence length and GC content. Codon usage patterns revealed that natural selection may be the main factor shaping codon usage bias. Our phylogenetic tree shows that Sinojackia is monophyletic and can be divided into two clades. Sinojackia oblongicarpa as a distinct species is supported for it is distantly related to S. sarcocarpa. The evolutionary analysis of morphological features indicates that woody mesocarp is an ancestral feature, while mesocarp undeveloped, spongy and fleshy are the later derived. Sinojackia originated in Central-Southeast China during the early Miocene. In this period, it experienced elevated diversification and migrated from the Central-Southeast China to Hunan Province and Sichuan Province with the development of the Asian monsoon and East Asian flora. Sinojackia experienced elevated diversification at intraspecies levels that mainly occurred in the Quaternary. Glacial-interglacial interactions with the monsoon climate may provide favorable expansion conditions for Sinojackia on a small-scale.

Electrochemical methods are used for the treatment of both municipal and industrial wastewater, either independently or in conjunction with biological methods. This conjunction is used for pretreatment or posttreatment of biologically treated wastewater. In our work, we focused on the combination of these processes, where pre-electrolysis was used to produce dissolved iron before the activation process. Electrolysis was also directly introduced into the activation using either iron or carbon electrodes. The surface of one iron electrode was 32.2 cm2, the applied voltage was 21 V, and the supplied current was 270 mA. The surface of one carbon electrode was 7.54 cm2, the supplied current was 82.5 mA, and the applied voltage was 21 V. From laboratory research on the treatment of synthetic municipal wastewater using a combination of electrolysis and activation processes, it resulted that the use of iron electrodes increased the efficiency of phosphorus removal compared to its precipitation with iron salts. The electrolysis had a positive effect on the sedimentation properties of sludge and the destruction of filamentous microorganisms. Electrolysis negatively affected the respiration rates of activated sludge and the efficiency of denitrification. However, it did not have a negative impact on the nitrification activity of the sludge.

Attribute reduction is a core technique in the rough set domain and an important step in data preprocessing. Researchers have proposed numerous innovative methods to enhance the capability of attribute reduction, such as the emergence of multi-granularity rough set models, which can effectively process distributed and multi-granularity data. However, these innovative methods still have many shortcomings, such as how to deal with complex constraints and how to perform multi-angle effectiveness evaluations. Based on the multi-granularity model, this study proposes a new method of attribute reduction, namely using multi-granularity neighborhood information gain ratio as the measurement criterion. This method combines both supervised and unsupervised perspectives, and by integrating multi-granularity technology with neighborhood rough set theory, constructs a model that can adapt to multi-level data features. This model can select the optimal granularity level or attribute set according to the requirements. Finally, the proposed method is experimented with on 15 UCI datasets against six other attribute reduction algorithms. The experimental outcomes, upon analysis and comparative review, substantiate the reliability and consistency of the attribute reduction approach introduced in this study.

Computer vision is a rapidly developing field that focuses on highly sophisticated picture analysis, manipulation, and comprehension. Its objective is to analyze what is happening in front of a camera and utilize that understanding to control a computer or robotic system or to present users with fresh visuals that are more enlightening or appealing than the original camera images. Computer vision technologies make it feasible for new user interfaces, augmented reality gaming, biometrics, automobile, photography, movie creation, Web search, and many more applications. This essay seeks to explain how computer vision can be utilized to play blackjack successfully.

The influence and importance of research and development (R&D) for business sustainability have gained increasing interests, especially in the high-tech sector. However, the efforts of R&D might cause complex and mixed impacts on the financial results considering the associated expenses. Thus, this study aims to examine how R&D efforts may influence business to improve its financial performance considering the dual objectives: the gross and the net profitability. This research integrated a rough-set-based soft computing technique and multiple criteria decision-making (MCDM) methods to explore this complex and yet valuable issue. A group of public listed companies from Taiwan, all in the semiconductor sector, was analyzed as a case study. Initially, more than 30 variables were considered, and the adopted soft computing technique retrieved 14 core attributes—for the dual profitability objectives—to form the evaluation model. The importance of R&D for pursuing superior financial prospects is confirmed, and the empirical case demonstrates how to guide an individual company to plan for improvements to achieve its long-term sustainability by this hybrid approach.

Background In 2016, Global Polio Eradication Initiative (GPEI) recommended cessation of type 2 oral poliovirus vaccine (OPV) and OPV using countries switched from trivalent to bivalent OPV (bOPV) with addition of inactivated poliovirus vaccine (IPV) in the routine immunization schedule. The current GPEI strategy 2022-2026 includes bOPV cessation plan and switching to IPV standalone or the combination vaccine schedules in future. The focus of our study was to evaluate immunogenicity of monovalent OPV type 1 (mOPV1) with IPV and IPV only schedules. Methods This was a three-arm, multi-center randomized controlled trial conducted in 2016-2017 in India. Participants, at birth, were randomly assigned to bOPV-IPV (Arm A) or mOPV1-IPV (Arm B) or IPV (Arm C) schedules. Serum specimens collected at birth, 14-, 18- and 22- weeks age were analyzed with standard microneutralization assay for all three poliovirus serotypes. Results Results of 598 participants were analyzed. The type 1 cumulative seroconversion rates four weeks after completion of the schedule at 18 weeks were 99.5% (97.0-99.9), 100.0% (97.9-100.0) 96.0% (92.0-98.1) in Arms A (4bOPV+IPV), B (4mOPV1+IPV) and C (3IPV) respectively. Type 2 and type 3 seroconversion at 18 weeks were 80.0% (73.7-85.1), 76.9% (70.3-82.4), 93.2% (88.5-96.1) and 100.0% (98.0-100.0), 81.9% (75.6-86.8), 99.4% (96.9-99.9) respectively in the three arms. Conclusions This study shows high efficacy of different polio vaccines for serotype 1 in all three schedules. Type 1 seroconversion rate of mOPV1 is non-inferior to bOPV. All the vaccines provide high type specific immunogenicity. The program can adopt the use of different vaccines or schedules depending on epidemiology from time-to-time.

The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden of disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels in diabetes can cause structural and functional changes in proteins throughout the body, and the accumulation of protein aggregates in the brain is associated with the progression of Alzheimer's Disease (AD).To address this burden of type 2 diabetes mellitus (T2DM), a combined aerobic and resistance exercise program was developed based on the recommendations of the American College of Sports Medicine. The prospectively registered clinical trials (https://www.clinicaltrials.gov/ct2/show/NCT04626453, https://www.clinicaltrials.gov/ct2/show/NCT04812288) involved two groups: an Intervention group of older sedentary adults with T2DM and a Control group of healthy older adults who could be either active or sedentary. The completion rate for the 2-month exercise program was high, with participants completing on an average of 89.14% of the exercise sessions. This indicated that the program was practical, feasible, and well-tolerated, even during the COVID pandemic. It was also safe, requiring minimal equipment and no supervision. The exercise instructions were easy to understand, making them suitable for older adults with cognitive decline.The near-infrared spectroscopy (NIRS) based brain and muscle oxygenation study provided evidence on brain overactivation among older adults with T2DM, supporting the compensatory theory. It also demonstrated that the 2-month combined exercise intervention effectively reduced brain overactivation and contributed to improved cognitive function. Operational modal analysis showed an exercise-related effect on the very low-frequency hemodynamic oscillations cluster, which may be associated with better vascular muscle and/or perivascular neurogenic regulation. Furthermore, we personalized the exercise duration and interval based on muscle oxygenation during physical tasks, leading to improvements in muscle oxidative capacity within just two months. This finding has practical implications for physical therapists, as they can target muscle oxygenation changes during physical tests to prescribe appropriate exercise doses for enhancing physical performance.

COVID-19 is characterized by an unprecedented abrupt increase in the viral transmission rate (SARS-CoV-2) relative to its pandemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through its receptor binding domain (RBD_Spike). One potential therapeutic strategy to combat COVID-19 could thus be limiting the infection by blocking this key interaction. In this current study, we adopt a protein design approach to predict and propose non-virulent structural mimics of the RBD_Spike which can potentially serve as its competitive inhibitors in binding to ACE2. The RBD_Spike is an independently foldable protein domain, resilient to conformational changes upon mutations and therefore an attractive target for strategic re-design. Interestingly, in spite of displaying an optimal shape fit between their interacting surfaces (attributed to a consequently high mutual affinity), the RBD_Spike–ACE2 interaction appears to have a quasi-stable character due to a poor electrostatic match at their interface. Structural analyses of homologous protein complexes reveal that the ACE2 binding site of RBD_Spike has an unusually high degree of solvent-exposed hydrophobic residues, attributed to key evolutionary changes, making it inherently ‘reaction-prone’. The designed mimics aimed to block the viral entry by occupying the available binding sites on ACE2, are tested to have signatures of stable high-affinity binding with ACE2 (cross-validated by appropriate free energy estimates), overriding the native quasi-stable feature. The results show the apt of directly adapting natural examples in rational protein design, wherein, homology-based threading coupled with strategic ‘hydrophobic ↔ polar’ mutations serve as a potential breakthrough.

EUS–TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS–TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS–TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS–TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity ≥ 20% and tissue area ≥ 4 mm2), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.

The particulars of stimulus-response experiments done on dynamic biosystems clearly limit what one can learn and validate about their structural interconnectivity (topology), even when collected kinetic output data are perfect (noise-free). As always, available access ports and other data limitations rule. For linear systems, exponential modes, visible and hidden, play an important role in understanding data limitations, embodied in what we call dynamical signatures in the data. We show here how to circumscribe and analyze modal response data in compartmentalizing model structures – so that modal analysis can be used constructively in systems biology model building – for nonlinear (NL) as well as linear biosystems. We do this by developing and exploiting the modal basis for dynamical signatures in hypothetical (perfect) input-output data associated with a structural model – one that includes inputs and outputs explicitly – and for NL as well as linear biosystems. The methodology establishes model dimensionality (size, complexity) from particular data sets; helps select among multiple candidate models (model distinguishability); helps in designing new experiments to extract “hidden” structure; and helps to simplify (reduce) models to their essentials. For NL biosystems, results are not as comprehensive, similarly informative about their dominant dynamical properties, and unified with linear models on invariant 2-dimensional manifolds in phase space. Some automation of these highly technical aspects of biomodeling is also introduced.

Advances in nanomedicine bring the attention of researchers to the molecular targets which can play a major role in the development of novel therapeutic and diagnostic modalities for cancer management. The choice of a proper molecular target can decide on the efficacy of the treatment and endorse the personalized medicine approach. Gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled membrane receptor, well known to be overexpressed in numerous malignancies including pancreatic, prostate, breast, lung, colon, cervical and gastrointestinal cancers. Therefore, many research groups express a deep interest in targeting GRPR with their nanoformulations. A broad spectrum of the GRPR ligands has been described in the literature, which allows tuning of the properties of the final formulation, particularly in the field of the ligand affinity to the receptor and internalization possibilities. Hereby the recent advances in the field of applications of various nanoplatforms which are able to reach the GRPR expressing cells are reviewed.

The incidence of diabetes mellitus (DM) continues to rise worldwide and one of the most serious microvascular complications is diabetic kidney disease (DKD), which is the leading cause of end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection of DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques to quantify previously analyzed metabolites, such as tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. We performed the targeted analy-sis of metabolites from urine and serum samples, collected from 110 subjects. Of these, 90 patients with type 2 DM (T2DM) were divided according to the urinary albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects were rep-resented by healthy controls. Through various validation methods, we identified several metabolites as potential biomarkers, such as kynurenic acid, glycine, and l-tryptophan in serum and l-acetylcarnitine, tiglylglycine, and tau-rine in urine.

Background: Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as immunological carrier protein. PreS includes the binding site of HBV to its receptor on hepatocytes. We investigated if immunological non-responsiveness to HBV after repeated HBsAg-based vaccinations can be overcome by immunization with VVX001 (i.e., Alum-adsorbed BM325, a component of BM32). Methods: A subject failing to develop protective HBV-specific immunity after HBsAg-based vaccination received five monthly injections of 20 µg VVX001. PreS-specific antibody responses were measured by ELISA and micro-array technology. Serum reactivity to subviral particles of different HBV genotypes was determined by sandwich ELISA. PreS-specific T cell responses were monitored by CFSE staining and subsequent FACS analysis. HBV neutralization was assessed using cultured HBV-infected HepG2 cells. Results: Vaccination with VVX001 induced a strong and sustained preS-specific antibody response composed mainly of the IgG1 subclass. PreS-specific IgG antibodies were primarily directed to the N-terminal part of preS containing the NTCP attachment site. IgG reactivity to sub-viral particles as well as to the N-terminal preS-derived peptides was comparable for HBV genotypes A-H. A pronounced reactivity of CD3+CD4+ lymphocytes specific for preS after the complete injection course remaining up to one year after the last injection was found. Maximal HBV neutralization (98.4%) in vitro was achieved 1 month after the last injection which correlated with the maximal IgG reactivity to the N-terminal part of preS. Conclusion: Our data suggest that VVX001 may be used as a preventive vaccination against HBV even in non-responders to HBsAg-based HBV vaccines.

Adjunctive treatment of periodontitis lacks solutions allowing enough time for wound healing in the periodontal pockets by avoiding a fast re-colonization. Such a solution might be an antibiotic containing formulation with a controlled release over weeks. Here, a recently described minocycline containing approach is qualified for further clinical development by focusing on proof-of-concept, systemic burden, resistance development and degradation studies. Animal studies were done in two different (mouse-chamber, rat Porphyromonas gingivalis challenging) models, including effects on inflammation markers, bone loss and bone structure. Also, serum concentrations of minocycline after local application were determined by HPLC-MS/MS. The resistance status of bacterial clinical isolates against minocycline was investigated and the degradation of the formulation was characterized by laser scanning- and scanning electron microscopy. Animal studies clearly demonstrated the applicability of the new formulation in the investigated models. Inflammation markers decreased dosage dependent and reduced bone loss compared to non-treated group was observed. Thereby, the systemic burden of the antibiotic was neglectable. Minocycline is still effective against oral pathogens; resistance development was not seen. The biodegradable thread was first swollen and subsequently degraded over weeks. The results support the continued clinical development of this new formulation. A phase I clinical trial is planned to further evaluate its safety and efficacy.

(1) Background: In a society with an advancing aging rate, medical systems are coming under pressure due to an increasing flow of elderly patients with multiple somatic diseases, exacerbated by their fragile psychological and sociological backgrounds. We aimed to investigate the relationship be-tween frailty and loneliness in elderly people. Our research question was “Is there a link between the loneliness and frailty in elderly people?” (2) Methods: To assess the link between loneliness and frailty, we conducted a search accessing Index Medicus and PubMed; the timeframe of our research was from 2013 till 2023. Data regarding the study population, as well as loneliness and fragility assessments and approaches, were extracted. (3) Results: A positive relationship between loneliness and the appearance and progression of frailty in elderly people is argued for. (4) Conclusions: Maintaining a balance in the body’s functionality for as long as possible requires the diagnosis and periodic assessment of health status at any age and, due to the various socio-financial and emotional implications, is particularly imperative for elderly patients. Frailty can be prevented, and it appears that it could even be reversed if early diagnosis and appropriate interventions are made. Therefore, knowledge of relevant risk factors—most likely including loneliness—is an absolute necessity to slow down, stop, and even reverse the frailty process.

In this paper, we investigate a class of hierarchical variational inequalities (HVIPs, i.e., strongly monotone variational inequality problems defined on the solution set of multiple-set split common fixed point problems) with quasi-pseudocontractive mappings in real Hilbert spaces, which special cases can be found in many important engineering practical applications such as image recognizing, signal processing and machine learning. In order to solve HVIPs of potential application value, inspired by the primal-dual algorithm, we propose a novel accelerated cyclic iterative algorithm that combines the inertial method with a correction term and a self-adaptive step-size technique. Our approach eliminates the need for prior knowledge of the bounded linear operator norm. Under appropriate assumptions, we establish strong convergence of the algorithm. Finally, we apply our novel iterative approximation to solve multiple-set split feasibility problems and verify the effectiveness of the proposed iterative algorithm through numerical results.

Background: Bacterial resistance to several antibiotic classes is seen as a grave threat worldwide. Bacterial resistance to antibiotics was mostly caused by the abuse and overuse of antibiotics, particularly penicillins and first-generation cephalosporins, in Egypt's primary healthcare facilities. Aim of the study: To investigate the main resistant bacteria to a few chosen penicillins and first-generation cephalosporins, as well as the characterization of these antibiotics' resistant genes and their detrimental effects in Egypt's main medical facilities. Methodology: Two hundred respiratory and urinary tract infection (RTI and UTI) specimens were gathered from Egyptian primary medical center patients. The turbidimetric assay at 630 nm wavelength, the broth dilution technique, and the nanopore sequencing homology approach were used to characterize the major resistant pathogenic bacteria and their resistant genes to cefadroxil (first generation cephalosporins) and nafcillin (antipseudomonal penicillin). Moreover, adverse outcomes resulting from antibiotic resistance were noted. Results: Out of 200 specimens with RTI and UTI, 186 samples showed the proliferation of resistant bacteria isolates. Enterococcus faecium strain NFC and Staphylococcus aureus strain CDX were among them. Nanopore sequencing confirmed that the antibiotic-resistant gene in Enterococcus faecium was the NFC gene, whereas the antibiotic-resistant gene in Staphylococcus aureus was the CDX gene. Penicillin-binding proteins with modest affinity were encoded by both genes. These bacterial resistance patterns were linked to a low death rate of 5% and a high morbidity rate of 47%. Conclusion: By expressing low-affinity penicillin-binding proteins through resistant NFC and CDX genes, Enterococcus faecium strain NFC and Staphylococcus aureus strain CDX were found to be the predominant bacterial isolates that cause antibiotic resistance to first-generation cephalosporins and penicillins.

The digital transformation of the global economy presents new challenges and opportunities for businesses and nations. With the growing role of digital technologies and the dynamic changes in the structure of the economy, there is a need for a better understanding of the processes shaping contemporary enterprises. This article analyzes the impact of digital transformation on businesses and the global economy, identifying key areas where these changes are most evident. As part of this discussion, a modification of the “9 Pillars of Industry 4.0” concept is proposed, incorporating solutions that have emerged since its inception. The resulting model, “11 Pillars of Industry 4.0,” enabled the analysis of the “born digital” and “born global” concepts, highlighting their numerous common features in the context of the digital transformation of economies. This became the basis for proposing a new concept: “born digibal” — enterprises that from the outset operate in multiple markets, with their main sphere of activity based on digital solutions.The conclusions of the article provide an assessment of the changes occurring in businesses and the global economy in the digital age. They suggest that the dynamics of globalization in the 21st century will be shaped by complex interactions between digital transformation and the actions of businesses and nations, requiring flexibility and innovation in adapting to new economic realities.

The demand for improved service in mobile networks is always increasing. That means signal transmission with higher capacity is required. To achieve that goal a combined optical and wireless link using double polarization multiplexing has been developed. A high quality signal transmission is achieved by applying high polarization extinction ratio. The new concept is validated by experiments varying the bit rate and fiber length. A signal with 12 Gbit/s bit rate was transmitted over a 25 km long combined link with about 1.10-8 bit error rate. That result is much better than the already published data which were measured on links transmitting information with 2.5 Gbit/s bit rate. The polarization multiplexing technique is very practical for capacity enhancement in a specific section of an existing optical fiber by inserting a new link into it without deploying a new fiber.

Determining the general-name-derived semantic relationships between geographic names often requires consulting many geographic name documents for verification. In geographic name translation and geographic name knowledge graphs, this method cannot meet the needs of large-scale extraction of general-name-derived semantic relationships between geographic entities. To solve this problem, this paper proposes a general-name derivation relation recognition method based on Prompt learning and Semantic Spatiotemporal Distribution Attention Feature Fusion (SSD-AFF). This method adopts a pipe-based relationship recognition strategy. First, the Prompt learning method is adopted to form a general-name derivation pattern with the general-name-derived geographical name category and the original geographical name category as the prompt word, and then the derivation pattern is combined with the geographical name as the input of the model so that the recognition problem of the general-name derivation of the geographical name can be transformed into a classification problem using the bidirectional language model. Then, by analyzing the characteristics of the semantic association and geographical spatio-temporal distribution between the general-name-derived geographical name and the original geographical name, the semantic spatio-temporal distribution characteristics of the general-name-derived geographical name are constructed. Finally, the network model based on the semantic spatio-temporal distribution Attention Feature Fusion (SSD-AFF) is used to distinguish the general-name-derived semantic relationships. The experimental results show that the proposed method has good performance. It can effectively mine the general-name-derived semantic relations between the vector data of geographical entities and has important application value in geographical name translation and geographical name knowledge maps.

This article aims to identify the relationship between sustainability and strategic management to determine whether sustainability can be considered a strategic management research fashion. This involves a bibliometric analysis of recent academic literature from 2021 to 2023 to identify the latest academic research, key trends, collaboration and keyword networks within this relationship. The analysis was conducted using two datasets from the Scopus database. These datasets focus on English-language journal articles on business, management and accounting. The first covers academic research on strategic management, while the second expands to sustainability and sustainable development. The results show that strategic management research focusing on sustainability has recently grown faster (24.70%) than the whole strategic management research area (14.30%). Furthermore, the geographical analysis of co-authorship identified articles from 88 countries, suggesting a broad interest in this relationship. Notably, the strategic management network mapping revealed a unique, sustainable development, corporate social responsibility and sustainability cluster. Moreover, extended mapping revealed four clusters covering crisis management, strategic and creative sustainable development, operational and regulatory sustainability, sustainable supply chains, and resource management. The results thus confirm the rapid growth and widespread coverage of research on sustainability and strategic management, highlighting sustainability as a strategic management research fashion.

In order to make full use of the complementarity of existing navigation systems to improve the navigation and positioning accuracy, this paper investigates the visual/INS integrated navigation system based on the factor graph optimization (FGO) algorithm. In the traditional visual/INS integrated navigation system, there is often the problem of image blurring due to the rapid change of light and shadow captured by the vision sensor and the attitude change of the carrier, which leads to the decrease of the positioning accuracy of the combined navigation system. Therefore, this paper firstly introduces Retinex algorithm and BID algorithm to carry out the design of image de-blurring method; then implements the visual/INS integrated navigation algorithm based on the factor graph optimization method; finally, the experimental scheme is designed, comparative experiments are carried out, and the researched method is verified by using the public dataset. The experimental results show that the combined navigation algorithm realized in this paper has high accuracy, and its positioning accuracy is improved by 40% compared with visual positioning.

Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as the Broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml. In contrast, it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. The maximum concentration was 7-8 mcg/ ml at a maximum time of 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the bactericidal antibiotic Myxopyronin A production from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

The Active Distribution Networks (ADNs) are Multi-Input Multi-Output (MIMO) systems with coupled dynamics which cause interactions among the control loops of the Distributed Energy Resources (DERs). This undesired effect lead to performance degradation in the voltage control. To mitigate the effects of these unavoidable coupling, the present paper proposes a systematic design procedure based on the analysis of the interaction's sources. In details, each DER is equipped with a double loop PI to control the active and reactive powers output by the Voltage Source Converter (VSC) which connects the DER to the network's node. Furthermore, to guarantee Ancillary Services (ASs), the two loops are coupled by a simple mechanism of cooperation of the active power to voltage regulation realized by a filtered droop law. To achieve voltage regulation with reduced loop interactions, the PI parameters and the filter's pulse are designed according to a two sequential steps procedure based on the (Internal Model Control) IMC technique. Simulation studies are finally presented to demonstrate that the proposed design method achieves both reduction of the loop interaction and robust voltage control in presence of model parameter uncertainty in the MIMO model.

In this paper, we studied the problem of early detection of natural phenomena associated with the formation of severe floods and the possibility of constant monitoring of their occurrence. The test object for the study was severe floods on the Crimean Peninsula, which occurred due to heavy rainfall in the summer of 2021. Based on the selected satellite and other data related to this period, an analysis carried out and key atmospheric objects identified, according to the proposed algorithm for their identification and grouping. Based on the results of the work, a positive conclusion made on the issue of their use to identify the likelihood of natural disasters that could lead to floods. In addition, the authors proposed to develop a portal for collecting and processing a large amount of satellite data related to flood prevention and monitoring the development of such processes, and stressed the need to create it.

As argued by ‘Declaration of Concrete Environment (2010)’ of Korea and ‘Declaration of Asian Concrete Environment (2011)’ of six Asian countries, concrete as a single material has lately shown extremely large impact on environmental issues such as climate change. Assessment of environmental impact from concrete material and production has considerable importance. Concrete is a major material used in the construction industry that emits a large amount of substances with environmental impacts during its life cycle. Accordingly, technologies for the reduction in and assessment of the environmental impact of concrete from the perspective of Life Cycle Assessment must be developed. At present, the studies in relation to greenhouse gas emission from concrete are being carried out globally as a countermeasure against climate change. In this study, a sustainable concrete mix design algorithm was designed using correlation analyses, and its carbon emission and cost reduction performances were assessed. Using correlation analyses, the concrete strength, w/b and s/a ratios, and CO₂ emissions were identified as major variables of concrete mix design that influenced other variables. Also, this study aims to evaluate the CO₂ emission reduction performance of the algorithm-deduced sustainable concrete mix design, and therefore, the CO₂ emissions of the sustainable concrete mix design are compared with those of the actual concrete mix design applied to the construction of the office building A in South Korea.

The craft guilds have been at the core of important historiographical debates on the economic, social and political history of medieval cities for twenty years. The aim of this article is to examine the seamen’s guilds in the town ports of Northern Peninsula in the late Middle Ages. This study analyzes fundamental aspects of the social assistance, labour organization and social identity of the town ports, located on the maritime border of the Kingdom of Castile. In contrast to the more classical view of the craft guilds as protectionist institutions, which only served the interests of a privileged group of masters, this analysis highlights the contribution of the seamen craft guilds to the organization of labor at sea, the training of sea workers, the ability to negotiate with merchants and avoid labor exploitation, the provision of social assistance to the most vulnerable population, and the ability to lead the social protest for the guilders’ representation in the urban government. In summary, it is concluded that the seafarers’ guilds were constituted as networks of mutual help between individuals in the labor, welfare and political spheres of the population of the town ports of Northern Iberia in the late Middle Ages.

Contradictory reports are available on vaccine-associated hyperstimulation of the immune system, provoking the formation of pathological autoantibodies. Despite being interconnected within the same network, the role of the quieter, yet important non-pathological; natural autoantibodies (nAAbs) is less defined. We hypothesize that upon a prompt immunological trigger, also physiological nAAbs exhibit a moderate plasticity. We investigated their inducibility through aged and recent antigenic triggers. Anti-viral antibodies (anti-MMR; n=1739 and anti-SARS-CoV-2 IgG; n=330) and nAAbs (anti-citrate synthase IgG, IgM; n=1739) were measured by in-house and commercial ELISAs, using Croatian (Osijek) anonymous samples with documented vaccination background. Results were subsequently compared for statistical evaluation. Interestingly, IgM isotype nAAb showed a statistically significant connection with anti-MMR IgG seropositivity (p< 0.001 in all cases), while IgG isotype nAAb levels were elevated in association with anti-SARS CoV-2 specific seropositivity (p= 0.019) and in heterogeneous vaccine regimen recipients (unvaccinated controls; vector/mRNA vaccines p= 0.002). Increasing evidence supports the interplay between immune activation and the dynamic expansion of nAAbs. Consequently, further questions may emerge regarding the ability of nAAbs silently shaping the effectiveness of immunization. We suggest re-evaluating the impact of nAAbs on the complex functioning of the immunological network.

Background & Aims: Gut microbial imbalances are linked to colorectal cancer (CRC), but archae-‎a's role remains underexplored. Here, we performed bioinformatic and statistical analysis looking ‎for archaeal taxonomic and functional signatures related to CRC. Methods: We analyzed pub-‎lished fecal metagenomic data from 390 subjects, comparing the archaeomes of CRC and healthy ‎individuals. We conducted a biostatistical analysis to investigate the relationship between Candi-‎datus Mancarchaeum acidiphilum (DPANN superphylum) and other archaeal species associated ‎with CRC. Using the Prokka tool, we annotated the data focusing on archaeal genes, subsequently ‎linking them to CRC and mapping them against UniprotKB and GO databases for specific ar-‎chaeal gene functions. Results: Our analysis identified enrichment of methanogenic archaea in ‎healthy subjects, with an exception for Methanobrevibacter smithii, which correlated with CRC. ‎Notably, CRC showed a strong association with archaeal species, particularly Natrinema sp. J7-2, ‎Ferroglobus placidus, and Candidatus Mancarchaeum acidiphilum. Furthermore, the DPANN ar-‎chaeon exhibited a significant correlation with other CRC-associated archaea (p < 0.001). Func-‎tionally, we found a marked association between MvhB-type polyferredoxin and colorectal can-‎cer. We also highlighted the association of archaeal proteins involved in the biosynthesis of leucine ‎and the galactose metabolism process with the healthy phenotype. Conclusion: The archaeomes ‎of CRC patients show identifiable alterations, including a decline in methanogens and an increase ‎in Halobacteria species. MvhB-type polyferredoxin, linked with CRC and species like Candidatus ‎Mancarchaeum acidiphilum, Natrinema sp. J7-2 and Ferroglobus placidus emerge as potential archaeal ‎biomarkers. Archaeal proteins may also offer gut protection, underscoring archaea’s role in CRC ‎dynamics.

At least six small alternate-frame open reading frames (ORFs) overlapping well-characterized SARS-CoV-2 genes have been hypothesized to encode accessory proteins. Researchers have used different names for the same ORF or the same name for different ORFs, resulting in erroneous homological and functional inferences. We propose standard names for these ORFs and their shorter isoforms, developed in consultation with the Coronaviridae Study Group of the ICTV. We recommend calling the 39 codon Spike-overlapping ORF ORF2b; the 41, 57, and 22 codon ORF3a-overlapping ORFs ORF3c, ORF3d, and ORF3b; the 33 codon ORF3d isoform ORF3d-2; and the 97 and 73 codon Nucleocapsid-overlapping ORFs ORF9b and ORF9c. Finally, we document conflicting usage of the name ORF3b in 32 studies, and consequent erroneous inferences, stressing the importance of reserving identical names for homologs. We recommend that authors referring to these ORFs provide lengths and coordinates to minimize ambiguity due to prior usage of alternative names.

Well-annotated gene and genomic sequences serve as a foundation for making inferences in molecular biology and evolution, and can directly impact public health. The first SARS-CoV-2 genome was submitted to GenBank and used to develop the two successful vaccines. Conserved protein domains are often chosen as targets for developing antiviral medicines or vaccines. Mutation and substitution patterns provide crucial information not only on functional motifs and genome/protein interactions but also for characterizing phylogenetic relationships among viral strains. These patterns, together with the collection time of viral samples, serve as the basis for addressing the question of when and where the host-switching event occurred. Unfortunately, viral genomic sequences submitted to GenBank undergo little quality control, and critical information in the annotation is frequently changed without being recorded. Researchers often have no choice but to hold blind faith in the accuracy of the sequences. There have been reports of incorrect genome annotation but no report that casts doubt on the genomic sequences themselves because it seems theoretically impossible to identify genomic sequences that may not be authentic. This paper takes an innovative approach to show that some SARS-CoV-2 genomes submitted to GenBank cannot be possibly authentic. Specifically, some SARS-CoV-2 genomic sequences deposited in GenBank with collection time in 2023 and 2024, isolated from saliva, nasopharyngeal, sewage, and stool are identical to the reference genome of SARS-CoV-2 (NC_045512). The probability for such occurrence is effectively 0. I also compile SARS-CoV-2 genomes with changed sample collection time. One may led astray in bioinformatic analysis without being aware of errors in sequences and sequence annotation.

The presence of clays in copper minerals has a significant negative impact during their processing, leading to low recoveries during the flotation process. In saline environments such as seawater, the presence of clays contribute to an increase in operational problems caused by salinity, a decrease in the grade of the copper concentrate, alteration of the rheology of the mineral pulp, a decrease in the selectivity of copper during the flotation process, a reduction in the quality of clarified water, and excessive corrosion of metallic components. This study explores the electroflotation of kaolinite and montmorillonite clays in NaCl solutions using a modified Hallimond tube coupled with Ti Gr. 2 electrodes for bubble generation via water electrolysis, and the corrosion analysis of these electrodes applying the superposition model. The electroflotation results show recovery of clays close to 72.68% for kaolinite, 88.44% for montmorillonite, and 67.36% for a mixtures of both clays. The presence of clays helps reduce the corrosive effects of Ti Gr. 2 from 0.069 A/m2 in NaCl to 0.0073 A/m2 in NaCl with montmorillonite clay.

Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case-control study aimed to investigate the association between the rs9896052 polymorphism (A>C) upstream of GRB2 and proliferative diabetic retinopathy (PDR) in patients with T2DM from Southern Brazil, taking into consideration self-reported skin color (white or non-white) and the known duration of diabetes (< 10 years or ≥ 10 years). Genotypes were determined using real-time PCR in 838 patients with T2DM (284 cases with PDR and 554 controls without DR). In the total study group and in the analysis stratified by skin color, the genotype and allele frequencies were similar between the cases and controls. However, among patients with less than 10 years of diabetes, the C allele was more frequent in cases than in controls (63.3% versus 51.8%, p = 0.032), and the CC genotype was independently associated with an increased risk of PDR (adjusted OR = 2.82, 95% CI 1.17-6.75). In conclusion, our findings support the hypothesis that the rs9896052 polymorphism near GRB2 is associated with PDR in Brazilian patients with T2DM.

Introduction: This population-based retrospective cohort study assesses rates of adverse events (AEs) involving cerebral thromboembolism (CTE) after COVID-19 vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) database from January 1, 1990 to December 31, 2023. CTE AEs after COVID-19 vaccines were compared to those after influenza vaccines and after all other vaccines using proportional reporting ratio (PRR) analysis by time. Results: There are 5137 cerebral thromboembolism AEs reported in the 3 years (36 months) after COVID-19 vaccines compared to 52 AEs for the influenza vaccines over the past 34 years (408 months) and 282 AEs for all other vaccines (excluding COVID-19) over the past 34 years (408 months). The PRR’s are significant when comparing AEs by time from COVID-19 vaccines to that of the influenza vaccines (p < 0.0001) or to that of all other vaccines (p < 0.0001). The CTE AEs PRR by time (95% confidence intervals) for the COVID-19 vaccine AEs vs influenza AEs is 1120 (95% confidence interval (723-1730), p < 0.0001) and for COVID-19 vaccines vs all others is 207 (95% confidence interval (144-296), p < 0.0001). Cerebral venous thromboembolism AEs are female predominant with a female/male odds ratio of 1.63 (95% confidence interval (1.52-1.74), p < 0.0001). Conversely, cerebral arterial thromboembolism has a nonsignificant male preponderance. Cerebral venous thromboembolism is far more common than cerebral arterial thromboembolism over 36 months with an odds ratio (OR) of 14.8 (95% confidence interval 14.0-15.5, p < 0.0001). Atrial fibrillation, the most common identifiable cause of cerebral arterial thromboembolism, occurs far more commonly after the COVID-19 as compared to all other vaccines with a PRR of 123 (95% CI 88.3-172, p < 0.0001) Conclusions: There is an alarming breach in the safety signal threshold concerning cerebral thrombosis AEs after COVID-19 vaccines compared to that of the influenza vaccines and even when compared to that of all other vaccines. An immediate global moratorium on the use of COVID-19 vaccines is necessary with an absolute contraindication in women of reproductive age.

SARS-CoV-2 is an obligatory intracellular pathogen that requires of a lipid bilayer membrane for its transport, to build its nucleocapsid envelope and to fuse with the host cell. The biological membranes are constituted by phospholipids (PLs) and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if the treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFA), fatty acid of the phospholipids (FAPL), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6) and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HS). COVID-19 patients showed a decrease in Vit E, TPLs, FAPL and TFA in serum in comparison to HS (p≤0.01) and Vit E treatment restored their levels (p≤0.04). Likewise, there was an increase IL-6 and CRP in COVID-19 patients in comparison with HS (p≤0.001) and the treatment with Vit E decreased their levels (p≤0.001). Treatment with Vit E contributes to restore the modified profile of the PLs in the SARS-CoV-2 infection and this leads to a decrease of OS and of the inflammatory process.

The objective of this study is to investigate how different therapies modulating insulin resistance, either causally or consequently, affect metabolic parameters in treatment-naive subjects with T2DM. A total of 212 subjects were assigned to receive either a tight Japanese diet (n=65), pioglitazone at doses ranging from 15-30 mg/day (n=70), or canagliflozin at doses ranging from 50-100 mg/day (n=77) for a duration of three months. Correlations and changes (Δ) in metabolic parameters relative to insulin resistance were investigated. Across these distinct therapeutic interventions, ΔHOMA-R exhibited significant correlations with ΔFBG and ΔHOMA-B, while demonstrating a negative correlation with baseline HOMA-R. However, other parameters such as ΔHbA1c, ΔBMI, ΔTC, ΔTG, Δnon-HDL-C, or ΔUA displayed varying patterns depending on the treatment regimens. Participants were stratified into two groups based on the median value of ΔHOMA-R: the lower half (X) and upper half (Y). Group X consistently demonstrated more pronounced reductions in FBG compared to Group Y across all treatments, while other parameters including HbA1c, HOMA-B, TC, TG, HDL-C, non-HDL-C, TG/HDL-C ratio, or UA exhibited distinct regulatory responses depending on the treatment administered These findings suggest that 1) regression to the mean is observed in the changes of insulin resistance across these therapies. 2) modulation of insulin resistance with these therapies, either causally or consequentially, results in differential effects on glycemic parameters, beta-cell function, specific lipids, body weight or UA.

Network centrality analyses have proven successful in identifying important nodes in diverse host-pathogen interactomes. The current study presents a comprehensive investigation of the human interactome and SARS-CoV-2 host targets. We first constructed a comprehensive human interactome by compiling experimentally validated protein-protein interactions (PPIs) from eight distinct sources. Additionally, we compiled a comprehensive list of 1,449 SARS-CoV-2 host proteins and analyzed their interactions within the human interactome, which identified enriched biological processes and pathways. Seven diverse topological features were employed to reveal the enrichment of SARS-CoV-2 targets in the human interactome, with Load centrality emerging as the most effective metric. Furthermore, a novel approach called CentralityCosDist was employed to predict SARS-CoV-2 targets, which proved effective in expanding the pool of predicted targets. Pathway enrichment analyses further elucidated the functional roles and potential mechanisms associated with predicted targets. Overall, this study provides valuable insights into the complex interplay between SARS-CoV-2 and the host cellular machinery, contributing to a deeper understanding of viral infection and immune response modulation.

In Tropical Monsoon climates, precipitation exceeds evapotranspiration, leading to increased surface runoff, especially in floodplain regions. The Bhagirathi-Hooghly River in India is the focus of the study, which analyses hydrology, sediment yield, and water balance in this floodplain area. This investigation employs the Soil and Water Assessment Tool (SWAT) model within the ArcGIS environment, using remote sensing data. The study area is divided into 4 sub-basins and 40 Hydrological Response Units (HRUs), with a focus on Land Use/Land Cover (LULC) parameters, soil attributes, and slope characteristics. Calibration (1998-2010) and validation (2011-2018) of river discharge and sediment yield are performed using the SUFI-2 algorithm within SWAT-CUP. The calibration process shows a strong correlation between observed and simulated data points, indicating the model's accuracy. The study reveals a pattern of early-year evapotranspiration followed by increasing rainfall during the monsoon season, leading to heightened surface runoff and sediment yield. Excessive rainfall, therefore, emerges as a pivotal driver of flood incidences within the floodplain. The insights derived from the SWAT model's floodplain data have the potential to inform flood control and sedimentation mitigation strategies. The assimilation of this data can empower local stakeholders and contribute to sustainable livelihoods and improved living conditions, offering guidance for future governmental policies.

Lifestyle interventions halt the progression of prediabetes to frank type 2 diabetes (T2D). However, the feasibility of a diabetes prevention program promoting tailored interventions on a national scale and conducted by primary care physicians is unclear. To explore this issue, general practitioners dislocated in ten different regions throughout Italy enrolled random subjects without known metabolic diseases to identify individuals with prediabetes and prescribe them an intervention based on physical activity. Using a simple stepwise approach, people referring to their primary care physician for any reason were screened for their diabetes risk with a web-based app of the Findrisc questionnaire. Those at risk for T2D, i.e. with a Findrisc score > 9, were invited to come back after overnight fasting to measure fasting glycaemia (FG). Those with 100 ≤ FG < 126 mg/dL were considered as people with prediabetes and compiled the Physical Activity Readiness Questionnaire (PAR-Q) to then receive a personalized prescription of physical activity. Overall, 5928 people were enrolled and compiled the questionnaire. Of these, 2895 (48.8 %) were at risk for T2D. Among these, FG was measured in 2168 subjects (participation rate 75%). The numbers of individuals with undetected prediabetes and T2D according to FG were 755 and 79 (34.8% and 3.6% of those assessing FG), respectively. Of the 755 subjects in the prediabetes range, 739 compiled the PAR-Q and started a personalized program of physical activity (participation rate 97%). Physicians involved in the study reported a mean of 6 minutes to perform the screening. Overall, these data suggest the feasibility of a national diabetes prevention program developed by general practitioners using a simple stepwise approach starting from a web-app to intercept individuals with prediabetes.

Background: So far, vaccination has been considered the most crucial defense against viral infection, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncology patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. Objective: This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. Material and methods: 1,668 people were observed. Over two years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in three groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. Results: The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, and colon cancer, although the response varies significantly depending on the type of cancer. Summary: The size of the humoral response and the presence of specific antibodies directed against the SARS-CoV-2, IgM, and IgG, in response to the supply of the vaccine antigen or assessed after COVID-19, is an indicator of adequate immune protection against reinfection. This study highlights for the first time the phenomenon of increased humoral response in response to a viral infection in patients with certain types of cancer that are assumed to be sensitive to oncological therapy, the initiation of which, according to generally accepted principles, was blocked by infection with the SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also seems to explain the asymptomatic course of SARS-CoV-2 infection in some of the above patients. It remains an open question to what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients.

Achieving glycemic control and sustaining functional pancreatic β-cell activity remains an unmet medical need in the treatment of type 2 diabetes mellitus (T2DM). Glucokinase activators (GKAs) constitute a class of anti-diabetic drugs designed to regulate blood sugar levels and enhance β-cell function in patients with diabetes. A significant progression in GKA development is underway to address the limitations of earlier generations. Dorzagliatin, a dual-acting GKA, targets both the liver and pancreas and has successfully completed two Phase III trials, demonstrating favorable results in diabetes treatment. The hepato-selective GKA—TTP399— emerges as a strong contender, displaying clinically noteworthy outcomes with minimal adverse effects. This paper seeks to review the current literature, delve into the mechanisms of action of these new-generation GKAs, and assess their efficacy and safety in treating T2DM based on published pre-clinical studies and clinical trials.

During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral thera-pies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants, which strongly challenged the containment measures and some therapeutic treatments. To assess whether an impaired immunity could lead to an increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimize the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients expe-rienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low frequency mutations. This study suggests that a compro-mised immune system alone does not affect SARS-CoV-2 within-host genomic variability.

This study is to explore the feasibility using neural network (NN) and deep learning to diagnose three common respiratory diseases with only few symptom words. These three diseases are nasopharyngitis, upper respiratory infection, and bronchitis/bronchiolitis. Through natural language processing, the symptom word vectors are encoded by GPT-2 and classified by the last linear layer of the NN. The experimental results are promising, showing that this model achieves a high performance in predicting all these three diseases. They reach 90% in accuracy, which suggests the implications of the developed model, highlighting its potential use in assisting patients understanding their conditions via a remote diagnosis. Unlike previous studies that focus on extracting various categories of information from medical records, this study directly extracts sequential features from unstructured text data, reducing the effort required for data pre-process.

To study the fermentation process of biocatalyzing decanoic acid to synthesize trans-2-decenoic acid, this study was based on the engineering E.coli constructed in the laboratory in the early stage and studied the effect of seed liquid culture time, culture temperature, inoculum amount, induction temperature, dissolution effects of substrate solvent, metal ions, and substrate loading on the yield of trans-2-decenoic acid. Based on single-factor experimental optimization, the Box–Behnken design was used to conduct response surface testing using the substrate feeding concentration, inducer concentration, and MnCl2 concentration as response variables and trans-2-decenoic acid production as the response value. The optimal fermentation process was determined through experiments: seed culture time 20 h, culture temperature 37°C, inoculation amount 1%, induction temperature 30°C, substrate flow amount 0.15 g/L, inducer concentration 5.60 g/L, MnCl2 concentration was 0.10 mM. Under these conditions, the average production of trans-2-decenoic acid was 1.982 ± 0.110 g/L. Compared with the basic LB medium, the production of trans-2-decenoic acid increased by 1.042 g/L; compared with the previous period, the yield of trans-2-decenoic acid studied increased by 1.501 ± 0.110 g/L, which provides a reliable basis for further research on the fermentation process of biocatalytic decanoic acid synthesis of trans-2-decenoic acid.

In this paper, we give all non splitting bi-unitary superperfect polynomials divisible by one or two irreducible polynomials over the prime field of two elements. We prove the nonexistence of odd bi-unitary superperfect polynomials over F2.

The liver is not only a digestive gland, but also an immune tissue that receives a double infusion from the hepatic artery and the hepatic portal vein. Receiving 80% of its blood supply from the intestine through the hepatic portal vein system, the liver is enriched with a large number of innate immune cells, which carry out the process of immune response by detecting pathogens entering the organism through the intestine. The intestine and liver communicate extensively through the bile ducts, portal vein and the somatic circulation, a bidirectional communication known as the intestinal-liver axis. The mammalian gut is considered an important microbial ecosystem. The interplay between the natural immune system and microbes coordinates the physiology of the whole organism, and in specific mammalian lineages, there is a dependency between the host and its associated microbes. To this end, we explored the regulatory mechanisms of natural immunity genes at the genome-wide level. Based on comparative genomics, 1473 bovine natural immunity genes were obtained by collecting the latest reports of human natural immunity genes and updated bovine genomic data for comparison, and a bovine natural immunity gene database was initially constructed to screen and match calf liver natural immunity differential genes mainly affected by the phylum Mimosoidea and the phylum Thick-walled Bacteria, and 16 differentially expressed natural immunity genes were obtained. In addition, the results of IPA analysis indicated that the upstream factor IL-2 initiated the PI3K/AKt/mTOR, mitogen-activated protein kinase (MAPK) pathway and JAK/STAT5 pathway, leading to the liver's involvement in gut microbial immune regulation.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

Preterm birth (PB) is a leading cause of perinatal morbidity and mortality. PB prediction is per-formed by measuring cervical length, with a detection rate of around 70%. Although it is known that a cytokine-mediated inflammatory process is involved in the pathophysiology of PB, no screening method implemented in clinical practice includes cytokine levels as a predictor varia-ble. Here, we quantified cytokines in cervical-vaginal mucus of pregnant women (18-23.6 weeks of gestation) with high- or low-risk for PB determined by cervical length, collecting relevant obstetric information. IL-2, IL-6, IFN-γ, IL-4, and IL-10 were significantly higher in the high-risk group, while IL-1ra was lower. Two different models for PB prediction were created using the Random Forest machine-learning algorithm: the full model with 12 clinical variables and cyto-kine values, and the adjusted model, including the most significant variables -maternal age, IL-2, and cervical length- (detection rate 66 vs 87%, false positive rate 12 vs 3.33%, false negative rate 28 vs 6.66%, and area under the curve 0.722 vs 0.875, respectively). The adjusted model integrat-ing cytokines showed a detection rate 8 points higher than the gold standard calculator, which may allow us to identify PB risk more accurately and implement strategies for preventive in-terventions

Kidney transplant recipients (KTR) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTR. Between February 1, 2020 and July 1, 2022, 578 KTR were infected with SARS-CoV-2, with 25 (4%) recurrent infections. 208 KTR (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU-admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed, being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both, virological changes in the Omicron variant and vaccination, reduce the risk for morbidity and mortality from COVID-19 in KTR. Our data extend the knowledge from the general population to KTR and provide important insights into outcome during the Omicron era.

The COVID-19 pandemic has posed a significant threat to society in recent times, endangering human health, life, and economic well-being. The disease spreads quickly due to the highly infectious SARS-CoV-2 virus, which has undergone numerous mutations. Despite intense research efforts by the scientific community since its emergence in 2019, no effective therapeutics have been discovered yet. While some repurposed drugs have been used to control the global outbreak and save lives, none have proven universally effective, particularly for severely infected patients. Although the spread of the disease is generally under control, anti-SARS-CoV-2 agents are still needed to combat current and future infections. This study reviews some of the most promising repurposed drugs containing indolyl heterocycle, which is an essential scaffold of many alkaloids with diverse bio-properties in various biological fields. The study also discusses natural and synthetic indole-containing compounds with anti-SARS-CoV-2 properties, as well as computer-aided drug design (in-silico studies) for optimizing anti-SARS-CoV-2 hits/leads.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 enters the host by infecting nasal ciliated cells. Then, the virus can spread towards the oropharyngeal cavity and the pulmonary tissues. The antiviral adaptive immunity is promptly induced in response to virus detection, with virus-specific T lymphocytes appearing before antiviral antibodies. Both breadth and potency of the antiviral CD8+ T cell immunity have a key role in containing viral spread and disease severity. Current anti-SARS-CoV-2 vaccines do not impede the virus replication in the upper respiratory tract, and there is consensus on the fact that the best potency of the antiviral immune response in both blood and upper respiratory tract can be reached upon infection in vaccinees (i.e., breakthrough infection). However, whether the antiviral CD8+ T cells developing in response to the breakthrough infection in the upper respiratory tract diffuse to the lungs also is still largely unknown. To fill the gap, we checked the CD8+ T cell immunity elicited after infection of K18-hACE2 transgenic mice both 3 weeks and 3 months after anti-Spike vaccination. The virus-specific CD8+ T cell immunity was monitored in both blood and the lungs before and after infection. By investigating the de novo generation of CD8+ T cells specific for SARS-CoV-2 viral proteins, we found that both membrane (M) and/or nucleocapsid (N)-specific CD8+ T cells were induced at comparable levels in blood of both unvaccinated and vaccinated mice. Conversely, N-specific CD8+ T cells were readily found in the lungs of control mice, but were either rare or absent in those of vaccinated mice. These results support the idea that the hybrid cell immunity developing after asymptomatic/mild breakthrough infection strengthens the antiviral cell immunity at lungs only marginally, implying that the direct exposition of the viral antigens is required for the induction of an efficient antiviral cell immunity in the lungs.

The COVID-19 pandemic cost 7-8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the SARS-CoV2 virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in ARDS and lung injury. Anti-inflammatory intervention with anti-IL6 (anti-IL-6 receptor monoclonal antibodies (mAbs) (e.g., sarilumab, tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and /or steroid-based approach lead to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this short review, we summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus–host immune cross talks and presenting the possibilities of therapeutic intervention.

During one of the worst global health crises, millions of people were vaccinated against SARS-CoV-2. In rare cases, new onset systemic inflammatory diseases were reported with temporal coincidence to the vaccination. We describe a case of severe Eosinophilic Granulomatosis with Polyangiitis (EGPA) in a young asthmatic woman, occurring after a 2nd dose of mRNA-1273 vaccine. She presented with multisystem EGPA with cardiac and central nervous system involve-ment, complicated by secondary immune thrombocytopenia (ITP). We review the reported cases of EGPA coinciding with SARS-CoV-2 mRNA vaccination. All potentially vaccine-related EGPA cases reported so far occurred within 14 days from immunization. EGPA is very rare with an incidence of 1:1’000’000 inhabitants and the number of reported post-vaccination EGPA cases lies within the expected incidence rate for the period. While we cannot prove a causal relationship between the vaccine and EGPA onset, the temporal relationship with the vaccine immune stimulation is intriguing, in a disease occurring almost always in adults with asthma and/or chronic rhinosinusitis and driven by an aberrant Th2 lym-phocyte activation with hypereosinophilia. Nevertheless, cases of inflammatory diseases emerging in the context of vaccination remain rare and the benefits of preventing severe Covid presentations with SARS-CoV-2 mRNA vaccines remains unquestionable.

A land cover map of two arctic catchments, nearby the Abisko Scientific Research Station, was obtained from a classification of a Sentinel-2 satellite image and a ground survey performed in July 2022. The two contiguous catchments, Miellajokka and Stordalen, are covered by various ecotypes, from boreal forest to alpine tundra and peatland. The random forests algorithm correctly identified 88% of polygon pixels reserved for testing. The developed workflow relied solely on open source software and acquired ground observations. Space organization was directed by the altitude as demonstrated by the intersection of the land cover with the topography. Comparison between this new land cover map and previous ones based on data acquired between 2008 and 2011 shows some trends of vegetation cover evolution in response to climate change in the considered area.

Polymorphism in cytochrome P450 (CYP) 2C9 enzyme is known to cause significant inter-individual differences in drug response and occurrence of adverse drug reactions. Different alleles of the CYP2C9 gene have been identified but the notable alleles responsible for reduced enzyme activity are CYP2C9*2 and CYP2C9*3. No pharmacogenetic data is available on CYP2C9*2 and CYP2C9*3 alleles in Pakistani population. In Pakistan pharmacogenetics which examines the relationship between genetic factors and drug response, are in the early stages of development. We for the first time investigated the association between the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 and the incidence of hypoglycemia in diabetic patients who were receiving the sulfonylurea medications. A total of n=400 individuals of Pashtun ethnicity were recruited from ten different districts of Khyber Pakhtunkhwa, Pakistan to participate in the study. The study participants were divided into two distinct groups: the case group (n=200) and the control group (n=200). The case group consisted of individuals with Type 2 Diabetes Mellitus (T2DM) who were receiving sulfonylurea medications and experience hypoglycaemia with it whereas the control group included individuals with T2DM who were receiving sulfonylurea medication but did not experience sulfonylurea-induced hypoglycaemia (SIH). Blood samples were obtained from study participants following informed consent. DNA was isolated from whole blood samples using Wiz-Prep DNA extraction kit. Following DNA isolation, CYP2C9 alleles were genotyped using MassARRAY sequencing platform at centre of genomics Rehman Medical Institute (RMI). The frequency of CYP2C9*2 (low activity allele) was more frequent in the diabetic patients with sulphonylurea-induced hypoglycaemia (SIH) compared to the control group (17.5% vs. 6.0%, p=0.021). The frequency of its corresponding genotype CYP2C9*1/*2 was higher in cases compared to control group (10% vs. 6% with P=0.036), same was true for genotype CYP2C9*2/*2 (7% vs. 3.5 % with P=0.028). Logistic regression analysis evident potential association of CYP2C9*2 allele and its genotypes with SIH. When adjusted for confounding factors such age, weight, sex, daily dose of sulphonylurea and triglyceride level the association between the CYP2C9*2 allele and hypoglycemia remains consistent. Confounding factors played no role in SIH because both groups (cases and controls) were closely matched in term of age, weight, sex, mean daily dose of sulphonylurea and trigyleride levels. Our study suggests that genetic information about a patient's CYP2C9 gene/enzyme can potentially assist physicians in prescribing the most suitable and safest drug based on their genetic make-up.

Background: The therapeutic benefits of fermented foods in the treatment and prevention of Type 2 diabetes mellitus have been reported. Aim: Inhibitory effect of fermented rice beverages on α-amylase, α-glucosidase and pancreatic lipase was evaluated. Method: Two fermented rice beverages-fermented rice alone (FKR) and fermented rice plus roasted peanuts (FKRG) were produced using spontaneous fermentation. Capacity of the beverages to inhibit al-pha-glucosidase, alpha-amylase and pancreatic lipase in vitro was evaluated and compared with standards (positive controls). Results: FKR exerted inhibition of α-glucosidase between 9.23-21.11% and FKRG 1.11-17.36% at the various concentrations respectively, with both samples showing the most significant inhibition (about 20%) at 125 μg/mL. FKRG exhibited greater alpha-amylase inhibition activity than FKR, but for both samples, the most significant (P < 0.05) inhibition occurred at 500 μg/mL. With pancreatic lipase, no significant inhibition was observed for both FKR and FKRG at the tested concentrations compared to Orlistat used as control; how-ever, at 31.25 μg /mL FKRG showed an inhibitory effect of approximately 15%, which was not evident at higher concentrations. Conclusion: Low to moderate inhibition of α-amylase, α-glucosidase and pancreatic lipase by both FKR and FKRG, showed that the fermented rice beverages have potential to modulate hyperglycemia in type 2 diabetes in vitro. This is an indi-cation that fermented rice beverage could prevent postprandial hyperglycemia in vivo.

The Shisa family is a type of single-transmembrane adaptor proteins containing an N-terminal cysteine-rich domain and a proline-rich C-terminal region. Nine Shisa subfamily genes have been proposed in most vertebrates; however, some of them might be species-specific. The number of Shisa genes present in zebrafish remains unclear. The purpose of this study was to investigate the evolutionary relationships among Shisa family genes in zebrafish (TU strain) using phylogenetic and syntenic analyses. The function of shisa-2 was preliminarily examined via CRISPR/Cas13d-mediated knockdown. Following identification in zebrafish,10 Shisa family genes, namely shisa-1, 2, 3, 4, 5, 6, 7, 8, 9a, and 9b, were classified into three main clades and six subclades. Their encoding proteins contained a cysteine-rich N-terminal domain and a proline-rich C-terminal region containing different motifs. A specific syntenic block containing atp8a2 and shisa-2 was observed to be conserved across all species. Furthermore, all these genes were found to be expressed during embryogenesis. shisa-2 was expressed in the presomitic mesoderm, somites, and so on. shisa-2 was identified as a regulator of the expression of the somite formation marker mesp-ab. Overall, our study provides new insights into the evolution of Shisa family genes and the control of shisa-2 over the convergent extension cells of somatic precursors in zebrafish.

Periodontitis is a widely spread chronic inflammatory disease caused by a changed oral microbiome. Although multiple species and risk factors have been associated with periodontitis, Porphyromonas gingivalis undoubtedly stands in the center as a keystone pathogen. The immune-modulatory function of P. gingivalis has been well characterized, but the mechanism by which peptidyl arginine deiminase (PPAD), a citrullinating enzyme, contributes to the infinite loop of inflammation is not fully understood. To determine the functional role of hypercitrullination in the context of periodontitis, we performed a comparative analysis on neutrophils stimulated by the wild type and the PPAD mutant strain that lacks an active enzyme. Our flow cytometric analysis revealed that PPAD contributes to the prolonged neutrophil survival upon bacteria stimulation, which was accompanied by aberrant IL-6 and TNF-α secretion in the experimental environment. To further elaborate on the complex mechanism by which citrullination sustains the chronic inflammatory state, we assessed the ROS production and phagocytic activity of neutrophils. Flow cytometry and colony formation assay demonstrated that PPAD obstructs the resolution of inflammation by promoting neutrophil survival and the release of pro-inflammatory cytokines while making the bacteria itself more resilient to phagocytosis.

Following the well-known pandemic, declared on 30 January 2020 by the World Health Organi-zation, the request for new global strategies for the prevention and mitigation of the spread of the infection has come to the attention of the scientific community. Nanotechnology has often managed to provide solutions, effective responses, and valid strategies to support the fight against SARS-CoV-2. This work reports a collection of information on nanomaterials that have been used to counter the spread of the SARS-CoV-2 virus. In particular, the objective of this work is to illustrate the strategies that have made it possible to use the particular properties of nanomaterials, for the production of personal protective equipment (DIP) for the defense against the SARS-CoV-2 virus.

Evaluating the performance of water indices and mapping the spatial distribution of water-related ecosystems are important for monitoring surface water resources. This is particularly the case for Ethiopia since there is limited information available on water resources development over time despite its relevance for the people and ecosystems. To address this problem, this paper evaluates the performance of seven water indices for country-scale surface water detection based on high spatial and multi-temporal resolution Sentinel-2 data, processed using the Google Earth Engine cloud computing system. Results show that the water index (WI) and automatic water extraction index with shadow (AWEIsh) are the most accurate ones to extract surface water. Comparisons are based on qualitative visual inspections and quantitative accuracy indicators. For the latter, WI and AWEIsh obtained kappa coefficients of 0.96 and 0.95, respectively, and an overall accuracy of 0.98 each. Both indices accounted for similar spatial coverages of surface waters with 82,650 km2 (WI) and 86,530 km2 (AWEIsh) for the whole of Ethiopia.

The main problem in creating anti-coronavirus vaccines that target mainly proteins of the outer membrane of the virus remains the rapid variability of the RNA genome of the pathogen that encodes these proteins. In addition, the introduction of technologies that can provide affordable and fast production of flexible vaccine formulas that easily adapt to the emergence of new subtypes of SARS-CoV-2 is required. Universal oligonucleotide vaccine can take into account the dynamics of rapid changes in the virus genome, as well as be synthesized on automatic DNA synthesizers in large quantities in a short time. In this brief report, the effectiveness of four phosphorothioate constructs of the La-S-so type oligonucleotide vaccine will be evaluated for the first time on transgenic mice [B6.Cg-Tg (K18-ACE2)2]. In our primary trials, the oligonucleotide vaccine increased the survival rate of animals infected with SARS-CoV-2 and also reduced the destructive effects of the virus on the lung tissue of mice. The obtained results show the perspective of the development of vaccine constructs of the La-S-so type for the prevention of coronavirus infections, including those caused by SARS-СoV-2.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2’-fucosyllactose (2’-FL), a human milk oligosaccharide, has anti-inflammatory effects and plays a protective role in arterial thrombosis, but its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2’-FL and its potential mechanisms in a mouse model of ischemic stroke. The administration of 2’-FL led to a reduction in the size of cerebral infarct and reactive oxygen species (ROS)-related products in the brain of MCAO mice. Further, 2’-FL promotes the recovery of neurological deficits and motor function in neurological scores and behavior tests. Biochemical studies showed that 2’-FL reduced upregulated IL-10 and downregu-lated TNF-α. Additionally,2’-FL enhanced M2-type microglial polar2’-FL upregulated IL-10 and downregulated TNF-α ization at 7 days after MCAO, with an increase in IL-4 levels and STAT6 activation at 3 days after MCAO. Our data showed that 2’-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type mi-croglial polarization in MCAO mice. These results demonstrate that 2’-FL is a potentially effective therapeutic agent for ischemic stroke.

This study assesses the durability of severe acute respiratory coronavirus-2 (SARS-CoV-2) anti-nucleocapsid (anti-N) immunoglobulin G (IgG) after infection, and examines its association with established risk factors among South African healthcare workers (HCWs). Blood samples were obtained from 390 HCWs with diagnosis of coronavirus disease 2019 (COVID-19) for assay of the SARS-CoV-2 anti-N IgG at two time points (Phase 1 &amp; 2) between November 2020 and February 2021. Out of 390 HCWs with COVID-19 diagnosis, 267 (68.5%) had detectable SARS-CoV-2 anti-N IgG antibodies at the end of phase I. These antibodies persisted for 4-5 and 6-7 months in 76.4% and 16.1%, respectively. In the multivariate logistic regression model analysis, black participants were more likely to sustain SARS-CoV-2 anti-N IgG for 4-5 months. However, participants who were HIV positive were less likely to sustain SARS-CoV-2 anti-N IgG antibodies for 4-5 months. In addition, individuals who were &lt;45 years of age were more likely to sustain SARS-CoV-2 anti-N IgG for 6-7 months. Of the 202 HCWs selected for phase 2, 116 participants (57.4%) had persistent SARS-CoV-2 anti-N IgG for an extended mean period of 223 days (7.5 months). Findings support the longevity of vaccine responses against SARS CoV-2 in black Africans.

Due to species barriers and poor adaptability to new host environments, few pathogens cause global pandemics. But, SARS-CoV-2 is one exception with its high transmissivity and delayed onset of symptoms. Fortunately, the world was able to tap on the technologies especially the maturing RT-qPCR designed to combat SARS to launch an initial offensive on SARS-CoV-2. These initial efforts may have bought time for scientists to develop more refined diagnostic tests that specifically target SARS-CoV-2. This article describes the effort put forth by the biotech industry and academia in Singapore to develop diagnostic tests that aid the early detection of positive cases, and thereby help contain the virus. Direct tests such as RT-qPCR and antigen rapid test profile the virus nucleic acid and surface proteins, respectively. But, of equal importance in case detection and treatment is serological tests that measure the relative abundance of IgM and IgG which is indicative of infection phase and quality of immune response in positive cases. Other tests such as isothermal amplification, CRISPR-based diagnostics and breath tests are also in development or at initial field deployment, and would undoubtedly provide valuable use experience useful for the development of molecular assays to detect and combat the next pathogen of global concern.

In spite of its incidence on pistachio trees, the chemical ecology of Labidostomis lusitanica (Germar) (Coleoptera: Chrysomelidae) has been neglected so far. In this work we provide the first evidence of a biologically active male-specific compound that may be promoting field aggregation. Headspace collections by solid-phase microextraction from feral males and females reported the presence of 2-isobutyl-3-methoxypyrazine exclusively on males. Electroantennographic recordings revealed that males and females responded in a dose-dependent manner to increasing stimuli of 2-isobutyl-3-methoxypyrazine, with females overall displaying a higher response than males. In dual-choice tests, both males and females showed a significant preference for the compound in comparison to a pure air stimulus. In the light of these results, the possible role of 2-isobutyl-3-methoxypyrazine as an aggregation cue in L. lusitanica is discussed.

In 2018, the author identified a previously unknown/unreported association between dexrazoxane and poly(ADP-ribose) (PAR). Interestingly, PAR is a close structural analogue of the polyadenine nucleotide polymer, polyadenosine monophosphate (poly(A)). In this report, subsequent in silico modelling of the interaction between dexrazoxane and poly(A) reveals some notable differences from the previously reported interaction between dexrazoxane and PAR. Significantly, the supramolecular self-assembly of dexrazoxane and poly(A) is distinguished by vertically-orientated nonelectrostatic forces comparable to the stabilizing interactions between stacked bases within DNA. Notably, the vertical separation of 3.4 Å between each stack is consistent with solvent entropy as a dominant driving force in stabilising the interaction. Additionally, concomitant conformational analysis by the author reveals the existence of low energy planar conformers of dexrazoxane. This analysis enables an explanation for the considerable discrepancies and conflicts that exist within the reported pharmacokinetic data for dexrazoxane. Exploring the significance of the interaction between dexrazoxane and poly(A), the author illustrates that survival, translation and replication of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) is absolutely dependent upon the mature and unhindered poly(A) tail of the SARS-CoV-2 genome. The proposition herein, that dexrazoxane, as a chameleonic agent sequesters the poly(A) tail of the SARS-CoV-2 genome by the catalysis of a supramolecular hybrid assembly establishes SARS-CoV-2 infected cells as deep compartments for the accumulation of dexrazoxane. Taken together, dexrazoxane or its demethylated analogue, represent a novel treatment to kill the SARS-CoV-2 virus by irreversible destabilization of the SARS-CoV-2 poly(A) tail.

Background: The duration of the vaccine's protective efficacy against SARS-CoV-2 is unknown. Evaluation of the clinical performance of available tests is required. Objectives: To evaluate the clinical performance of three immunoassays for the detection of IgG antibodies generated by mRNA vaccines against SARS-CoV-2. Methods: Two automated immunoassays (Euroimmun Anti-SARS-CoV-2 ELISA IgG and Abbott SARS-CoV-2 CLIA IgG) and one lateral flow immunoassay (LFIA Test Livzon IgG) were tested. 300 samples distributed in 3 groups were analyzed: 100 subjects over 18 years old and under 45 years old, 100 subjects between 45-65 years old and another 100 over 65 years old. collected before vaccination, at 21 days, 1, 2, 3 and 6 months post-vaccination. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and agreement (I. Kappa) were calculated for each serological test. Results: Maximum sensitivity for IgG was 98.7%, 98.1%, and 97.8% for the ELISA Euroimmun, CLIA Abbott, and Livzon LFIA assays and maximum specificity for IgG was 99.4%, 99.9%. % and 98.4% ELISA, CLIA and LFIA respectively at 3 months after vaccination with a decrease in antibody levels from the sixth month. The best agreement was observed between ELISA and CLIA 100%; (k = 1.00). The agreement between ELIA, CLIA and LIFIA was 99% (k = 0964) at the second and third month after vaccination. Seroconversion was faster and longer lasting in the younger age groups. Conclusion: Our study showed an equivalent and homogeneous clinical performance for IgG of three immunoassays after vaccination and that the LIFIA assay is the most cost-effective, reliable and accurate for routine use in population studies of seroconversion and seroprevalence.

The unprecedented growth of publicly available SARS-CoV-2 genome sequence data has increased demand for effective and accessible SARS-CoV-2 data analysis and visualization tools. A majority of the currently available tools either require computational expertise to deploy or limit user input to pre-selected subsets of SARS-CoV-2 genomes. To address these limitations, we developed ViralVar, a publicly available, point-and-click webtool that gives users the freedom to investigate and visualize user-selected subsets of SARS-CoV-2 genomes obtained from the GISAID public database. ViralVar has two primary features that enable: 1) visualization of spatiotemporal dynamics of SARS-CoV-2 lineages, and 2) structural/functional analysis of genomic mutations. As proof-of-principle, ViralVar was used to explore the evolution of the SARS-CoV-2 pandemic in the USA in the pediatric, adult, and elderly population (n > 1.7 million genomes). While the spatiotemporal dynamics of variants did not differ between these age groups, several USA-specific sublineages arose relative to the rest of the world. Our development and utilization of ViralVar to provide insights on the evolution of SARS-CoV-2 in the USA demonstrates the importance of developing accessible tools to facilitate and accelerate large-scale surveillance of circulating pathogens. The ViralVar webserver is freely available at http://viralvar.org/.