Varicella (chickenpox) is one of the most common infectious diseases in preschool children and can be prevented by immunization. While immunization program promotes higher vaccine coverage, there are still challenges with implementing vaccination programs particularly in low-income countries. Economic barriers can increase inequality in vaccination, which highlights the importance of distributing cost-effective varicella vaccines. Varicella vaccines have been developed with two main Varicella-Zoster Virus (VZV) strains globally: MAV/06 and Oka strains. Most of the vaccines are based on the Oka strain, while MAV/06 strain vaccines were exclusively developed by GC Biopharma. Although more than 30 million doses of MAV/06 vaccines as cost-effective vaccines have been distributed internationally, there is no comprehensive review on safety, immunogenicity, and effectiveness of MAV/06 vaccines in the literature. This paper aims to summarize and present more than 30 years of accumulated evidence from research on safety, immunogenicity, and effectiveness of MAV/06 vaccines. We expect that MAV/06 vaccines as cost-effective varicella vaccines make a significant contribution to improving global public health and health equality in children.

Insulin therapy is a cornerstone in the management of diabetes, yet the pursuit of optimizing its pharmacokinetic profile remains a focal point in diabetes research. For instance, insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising once-weekly treatment option for diabetic patients. However, designing insulin analogues with lower receptor affinity than that of insulin icodec could still produce a further extended duration of action than that of insulin icodec through the suppression of receptor-mediated internalization of insulin analogues. In this study, therefore, I present the design of a novel series of insulin analogues engineered towards lower binding affinity to the insulin receptor compared to that of insulin icodec. Through computational structural biophysics-based rational design strategies, this article aims to further extend the duration of action while maintaining therapeutic efficacy of insulin analogues. Utilizing homology molecular modeling and structural biophysics-based binding affinity calculations, this article puts forward a set of insulin analogues with lower binding affinity to insulin receptor than that of insulin icodec from a structural and biophysical point of view. Overall, this article calls for subsequent in vitro and in vivo evaluations of the efficacy and prolonged action of the engineered insulin analogues to pharmacokinetically test whether these analogues acutally surpass that of insulin icodec as hopeful candidates for next-generation insulin analogue therapies with improved duration of action and enhanced control of blood glucose levels for diabetic patients in future.

Wireless Sensor networks (WSNs) are gaining more and more research interest due to their ability to monitor large areas more or less independent. However, their reliability is an important issue, since their system reliability is influenced from a hardware, a data and an energetic point of view due to different factors like loading conditions, signal attenuation and battery lifetime. Regarding these issues, the positions of sensor nodes have to be chosen correctly to maximize the system reliability, which has to be considered during the development of new products equipped with WSNs. In this paper, an approach to estimate a WSNs system reliability during the development phase based on the analysis of the measurements on the example of strain measurements in finite elements (FE) models is presented. For that, the part under consideration is divided into regions with similar strains by the use of a Region Growing Algorithm (RGA). Afterwards, the WSN’s configuration is analyzed regarding its reliability in accordance to the data paths and measurement redundancy due to the sensor positions in the found measuring regions. This methodology is tested on an exemplary WSN configuration at an aircraft wing box under bending load and was found to work very well regarding the estimation of the hardware perspective on the system reliability. Therefore, the methodology and the developed algorithm show potentials for optimizations in sensor node positions for better reliability results.

Thorough and precise gene structure annotations are essential for maximizing the benefits of genomic data and unveiling valuable genetic insights. The cucumber genome was first released in 2009 and updated in 2019. To increase the accuracy of predicted gene models, 64 published RNA-seq data and 9 new strand-specific RNA-seq data from multiple tissues were used for manual comparison with the gene models. The updated annotation file (version 2.0) contains increased 24,145 predicted genes from previous version (24317 genes) with a higher BUSCO value of 96.9%. 6231 and 1490 transcripts were adjusted and newly added, respectively, accounting for 31.99% of the overall gene tally. These newly added and adjust genes were renamed (CsaV3.1_XGXXXXX), while genes remaining unaltered preserve their original des ignations. A random selection of 21 modified/added genes were validated using RT-PCR analyses. Additionally, tissue-specific patterns of gene expression were examined using newly obtained transcriptome data with the revised gene prediction model. This improved annotation of cucumber genome will provide essential and accurate resources for studies in cucumber.

This article explores the emerging concept of atrial myopathy (AM) and its potential role as a risk factor for stroke and dementia, both independently and in association with atrial fibrillation (AF). AM refers to structural and functional abnormalities of the atria, potentially causing blood clots formation and their subsequent embolization even in patients without AF. Echocardiography, particularly Left Atrial (LA) strain analysis, is a promising non-invasive tool for AM evaluation and might offer additional risk stratification beyond the established CHADS2-VASc score, potentially impacting anticoagulation decisions. By understanding AM and utilizing advanced imaging techniques like LA strain, clinicians can achieve a more comprehensive understanding of thromboembolic risk in specific patient groups. Integrating LA strain analysis into routine clinical practice holds promise for improved patient management and targeted therapies, allowing for better risk stratification in AF patients. However, standardized definitions and diagnostic criteria for AM are essential for consistent evaluation and research. Further studies are needed to explore the efficacy and safety of anticoagulation in AM patients without AF.

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both hereditary and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variations that can be transmitted from one generation to another can be a significant contributor to causing family or isolated DCM. Genetic variation also plays a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a diverse range of phenotypic expressions. It is crucial to select the most probable patients to have advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the crucial relationships between genotype and phenotype, and the usefulness of genetic testing in the therapeutic care of both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.

Tailings generated by mining account for the largest proportion of global waste from industrial activities. Copper is relatively uncommon world-wide, with low concentrations in sediments and waters, yet is very elevated around mining sites. On the Keweenaw Peninsula of Michigan, USA, jutting out into Lake Superior, 140 mines extracted native copper from the Portage Lake Volcanic Series, part of an intercontinental rift system. Between 1901-1932, two mills at Gay (Mohawk, Wolverine) sluiced 22.7 million metric tonnes (MMT) of copper-rich tailings (stamp sands) into Grand (Big) Traverse Bay. Here we examine: 1) 3D coastal elevation and reef bathymetry, 2) particle dispersal, 3) copper concentrations and leaching, plus 4) shoreline toxicity. About 10 MMT of tailings created a migrating coastal beach that stretches 7 km from the Gay pile to the Traverse River Seawall. Another 10 MMT are moving underwater on the coastal shelf, threatening Buffalo Reef, an important lake trout and whitefish breeding ground. Aerial photos, ALS (plane) LiDAR, and relatively inexpensive UAS (drone) surveys characterize shoreline structure and aid initial remediation. Because sands (natural beach quartz, stamp sand basalt) are silicates of similar density, particle dispersal is similar and challenging. However, stamp sand beaches contrast greatly with natural sand beaches in both physical profile and chemistry. Dispersing particles retain copper, and release toxic concentrations. Leaching is elevated by exposure to high DOC and low pH waters. Field experiments, shoreline seining, and benthic sampling confirm serious impacts on aquatic biota, supporting tailings removal.

Abstract: Dispersal strategies of a species can affect its invasion success. Investigation into the dispersal strategies of invasive species in relation to different factors helps our understanding of the invasion mechanisms and provides knowledge for population management and invasion evaluation. Tetranychus ludeni Zacher (Acari: Tetranychidae) is an invasive species, which is native to Europe but now cosmopolitan. Here, we examined the effects of age and density on dispersal in mated females. Our results show that older females with more eggs were more likely to disperse and moved longer distances than younger ones with fewer eggs. Older females spread most of their eggs out of the natal habitats and over longer distances, which reduced competition and increased offspring fitness. Females significantly increased dispersal probability and distance with the increase of population density to avoid crowding. The synchronization of dispersal and reproduction, along with the positive density-dependent dispersal strategy, may facilitate habitat colonization and invasion speed of T. ludeni.

This review delves into the growing field of flexible and stretchable strain sensors utilized in human gait analysis, focusing on determining knee bending angle and muscle activities when a human subject walks. Recent advancements have enabled these sensors to accurately capture biomechanical parameters while accommodating the body's natural movements. We examine the principles underlying these sensors' design and fabrication techniques, emphasizing their flexibility, stretchability, and biocompatibility for seamless integration into wearable systems. Through critical evaluation of existing methodologies, we assess the reliability and validity of these sensors in quantifying gait parameters. Furthermore, we discuss this technology's clinical and research implications, highlighting its potential in personalized rehabilitation and sports performance optimization. We provide an overview of flexible strain sensors and their application for analyzing human walking gait, especially for observing walking gait in rehabilitation programs. First, we present the basic working principles of various flexible strain sensors. Second, by the application of flexible strain sensors as walking gait monitoring. Finally, current challenges and future opportunities in this research area are discussed. By synthesizing current knowledge and outlining future directions, this review aims to provide insights for researchers and practitioners seeking to leverage flexible and stretchable strain sensors for comprehensive human gait analysis.

This study uses a mass-spring-damping system to simulate the repeated strain of liquefaction cyclic triaxial tests. The two results are compared in this paper to understand the feasibility of the mass-spring-damping system developed in this paper and the feasibility of future research on this related topic and development potential. The main factors affecting this mode's repeated strain are the spring coefficient k and the external force Q0. The spring coefficient has an inverse relationship but does not increase in multiples. The external force has a direct proportional relationship but does not increase the result- a non-multiple increase. When the pore water pressure of the liquefied cyclic triaxial test specimen rises, it will cause the specimen to liquefy, decreasing effective stress, shear modulus G, and damping ratio D, causing an increase in strain. The shear modulus and damping ratio are related to the spring coefficients k and c. Both are variables that change with time. This article takes an original thin-tube specimen at point A in the Yunlin area in Taiwan as a testing example. Through Mathematica software, it can be obtained that the mass m=1kg, the spring coefficient k=244e-0.1t kgf/cm, and the damping coefficient c=0.739e-0.257t kgf-s/cm and external force Q0=10.1sin2πt kg; Finally, this study selected the original thin-tube specimens from four locations in the Yunlin area, and simulated the repeated strain amount of the cyclic triaxial test specimens through a spring-damping system. The results show that the spring-damping system is feasible for simulated cyclic triaxial tests because the model is simple and the parameters are easy to understand and obtain, which also shows the extensibility of this model. Preliminary results of the research show that this model can further simulate the repeated strain obtained by cyclic triaxial tests without considering the increased trend in pore water pressure and the decrease in effective stress during cyclic loading.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

Tanning, crucial for leather production, relies heavily on chromium yet poses risks due to chromium's oxidative conversion, leading to significant wastewater and solid waste generation. Physico-chemical methods are typically used for heavy metal removal, but they have drawbacks, prompting interest in eco-friendly biological remediation techniques like biosorption, bioaccumulation, and biotransformation. The EU Directive (2018/850) mandates alternatives to landfilling or incineration for industrial textile waste management, highlighting the importance of environmentally conscious practices for leather products' end-of-life management, with com-posting being the most researched and viable option. This study aimed to isolate microorganisms from tannery wastewater and identify those responsible for different types of tanned leather biodegradation. Using a leather biodegradation assay (ISO 20136) with tannery and municipal wastewaters as inoculum, bacterial shifts during leather biodegradation were observed. Over 10,000 bacterial species were identified in all analyzed samples, with 8 bacterial strains isolated from tannery wastewater. Identification of bacterial genera like Acinetobacter, Brevundimo-nas, and Mycolicibacterium provides insights into potential microbial candidates for enhancing leather biodegradability, wastewater treatment, and heavy metal bioremediation in industrial applications.

This paper comprehensively reviews sensors and sensing devices developed or/and proposed so far utilizing two smart materials: electrorheological fluids (ERFs) and magnetorheological materials (MRMs) whose rheological characteristics such as stiffness and damping can be controlled by external stimuli, an electrical voltage for ERFs and a magnetic field for MRMs, respectively. In this review article, the MRMs are classified into magnetorheological fluid (MRF), magnetorheological elastomer (MRE) and magnetorheological plastomer (MRP). To easily understand the history of sensing research using the two smart materials, the order of this review article is organized in a chronological manner of ERF sensors, MRF sensors, MRE sensors and MRP sensors. Among many sensors fabricated from each smart material, one or two sensors or sensing devices are adopted to discuss on the sensing configuration, working principle and specifications such as accuracy and sensitivity. Some sensors adopted in this article include force sensor, tactile device, strain sensor, wearable bending sensor, magnetometer, display device and flux measurement sensor. After briefly describing what have been reviewed in a conclusion, several challenging future works, which should be done for practical applications as sensors or sensing devices, are remarked in terms of new technologies such as artificial intelligence neural network in which several parameters affecting the sensor signals can be precisely tuned or controlled. It is sure that this review article is very helpful to make creative sensors using not only the proposed smart materials but also several different types of smart materials including shape memory alloys and active polymers.

Dielectric elastomers, such as thermoplastic polyurethanes (TPU), are widely used as dielectric layer, emulation layer and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become an urgent need to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This article reports a device for in-situ measuring the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.47 to 2.94. In addition, combined Fourier-transform infrared spectroscopy, X-ray scattering technique, and atomic force microscopy have been utilized to characterize the evolution of microstructure under strain. The investigation under tensile strain reveals that a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction of the dielectric constant parallel to the electric field in TPU. Our work provides valuable experimental reference for improving the stability of flexible sensors and actuators based on dielectric elastomers.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

The rehabilitation of the road embankments alongside the irrigation canal, which is constructed on a Bangkok soft clay foundation, has resulted from land use growth for several decades. As a result, the embankment is always confronted with the problem of instability. Numerous articles have demonstrated that rapid drawdown of the water level in the canal could be one of the most significant reasons, whereas vehicle cyclic loading may potentially contribute to some effect of the embankment failure. To explore and assess the effects of the influence factors, the finite element method (FEM) and conventional and dynamic triaxial approaches were employed. The study also investigated the consequences of varying thicknesses of soft clay and cyclic loading with different magnitudes and frequencies. Consequently, cyclic loading can lead to an augmentation in strain distribution and excess pore water pressure. Likewise, more significant deformation and excess pore water pressure were induced by a lower frequency and deeper thickness of soft clay compared to a higher frequency and thinner thickness. In brief, vehicle repetitive loading is one of the primary factors contributing to embankment failure, with the threshold stress being approximately three-fourths of the undrained shear strength. In contrast, threshold strain is approximately one to two-fold of the monotonic strain condition.

This study investigates the impacts of climate change policies on businesses across various sectors, aiming to understand how these regulations affect operational, financial, and strategic aspects of business management. Utilizing a mixed-methods approach, data was collected from 500 businesses through surveys and interviews, encompassing a wide range of industries, sizes, and geographic locations. The findings reveal a complex landscape where 30% of businesses report positive impacts, primarily in the renewable energy and technology sectors, citing increased demand for green products and improvements in energy efficiency. Conversely, 45% of businesses, especially from manufacturing and agriculture, experience negative impacts, including increased operational costs and regulatory compliance challenges. Notwithstanding, a significant majority of businesses are committed to enhancing their sustainability practices, viewing climate change policies as an opportunity for innovation and long-term growth. The study highlights the nuanced effects of climate change policies, emphasizing the need for sector-specific support measures to alleviate financial and operational burdens on negatively impacted businesses. Moreover, it points to a broader shift towards sustainability within the business community, suggesting that climate policies, despite their varied impacts, are driving significant changes in business strategies towards environmental stewardship.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

(1) Background: The proportion of fully mechanized harvesting systems in Austria is constantly increasing especially because of the technological development of the machines, which allows them to drive on increasingly steep terrain. This leads to additional challenges and potential hazards for the operators, which may also cause higher stress levels. The purpose of this study is to develop and debate a new set of methodologies for determining time and space resolved psychophysiology data to analyze stressful and non-stressful work situations for harvester and forwarder operators; (2) Methods: we suggest a study protocol to analyze a) tasks performed by the driver, b) environmental factors, like slope gradient, c) the psychophysiological response of experts during these tasks, and d) evaluate the worker´s subjective stress and fatigue before and after a harvest operation. (3) Results: Within this manuscript we present a study protocol based on quantitative and qualitative methods, like time and space resolved psychophysiology, questionnaires, qualitative interviews, as well as video and sensor-based analysis of environmental and machine data. The first results from real measurements of a forwarder driver are presented; (4) Conclusions: This multimodal research protocol serves to explore the relationship between stress, fatigue, and performed tasks. Through our quantitative and qualitative methodology, researchers can improve the health and safety of forest workers at work, improve their productivity and reduce damage to remaining trees.

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

Balsam fir trees are a specialty agricultural species that are largely used as Christmas trees. Soil or tissue sampling is seldom performed to assess balsam fir nutrition needs, which can contribute to over or under fertilization and subsequent environmental challenges. Remote sensing to determine the normalized difference vegetation index (NDVI) has had strong relationships with nutrition in other plants. This research aimed to determine whether there is a relationship between NDVI and nutrition in balsam fir. A random sample of 45 trees was selected in autumn of 2021 and then another 70 trees selected in spring of 2022. Soil and needle tissue samples were analyzed for N, P, K, Ca, Mg, S, Fe, Zn, Mn, B, and Cu. An uncrewed aerial vehicle equipped with a multispectral camera was flown over the orchard to determine the NDVI for each tree. Nutrition and NDVI were analyzed for correlations through all sampled trees. Separate correlation analyses were repeated for mature trees (greater than 5 years old) and young trees (less than 5 years old). Soil nutrients N, P, K had a significant relationship with NDVI in autumn sampling. Only N was correlated consistently in both autumn and spring, with R2 of 37% and 33% respectively. Relationships were much stronger when only mature trees were considered, increasing to 60% and 51% respectively. NDVI was found to offer predictive power for tissue N that can be useful to producers to help optimize fertilizer input. However, further work is needed to refine these relationships.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A>G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

In patients with heart failure, the evaluation of left ventricular (LV) diastolic function is vital, offering crucial insights into hemodynamic impact and prognostic accuracy. Echocardiography stands as the primary imaging modality for diastolic function assessment, and using it effectively requires a profound understanding of the underlying pathology. This review covers four main topics: first, the fundamental driving forces behind each phase of normal diastolic dynamics, along with the physiological basis of two widely used echocardiographic assessment parameters, E/e' and mitral annulus early diastolic velocity (e'); second, the intricate functional relationship between the left atrium and LV in patients with varying degrees of LV diastolic dysfunction (LVDD); third, the role of stress echocardiography in diagnosing LVDD and the significance of parameter changes in this context; and fourth, the clinical utility of evaluating diastolic function from echocardiography images across diverse cardiovascular care areas.

Background: Penile squamous cell carcinoma (PSCC) is classified into two prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. Conversely, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with prognosis in a large series of PSCC patients. p53 was analysed according to a recently described immunohistochemical (IHC) pattern-based framework that includes two normal (scattered, mid-epithelial) and four abnormal patterns (diffuse, basal overexpression, cytoplasmic and null) and closely correlates with TP53 mutational status. Methods: A total of 122 patients with surgically treated PSCC in three hospitals in Barcelona, Spain, were included. Based on HPV in situ hybridization and p16 and p53 IHC expression, the tumors were classified into three molecular types: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed for at least 22 months (median 56.9 months), and disease-specific survival (DSS) was analysed. Results: Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (p<0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 patterns not recognized in the classical p53 IHC interpretation (basal, null, cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired DSS (hazard ratio=23.4, 95% confidence interval [CI]= 2.7-3095.3; p=0.001 and 16.3, 95% CI=1.8-2151.5; p=0.008, respectively). CONCLUSION: Compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define two prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

The mixing of terrestrial groundwater and seawater creates dynamic reaction zones in intertidal areas, where land-derived Fe(II) is oxidized to Fe(III) and then precipitates as Fe hydroxides at groundwater-seawater interface. These hydrogeochemical processes contribute to the formation of iron curtains beneath soil surface, which in turn influences the evolution of coastal aquifers. This paper provides a comprehensive review of physical and geochemical processes at field scale in coastal areas, explores the impact of mineral precipitation on pore structure at pore scale, and synthesizes reactive transport modeling (RTM) approaches for illustrating continuum-scale soil physio-chemical parameters during the evolution of porous media. Upon this review, knowledge gaps and research needs are identified. Additionally, challenges and opportunities are presented. Therefore, the incorporation of observational data into a comprehensive physico-mathematical model becomes imperative for capturing the pore-scale processes in porous media and their influence on groundwater flow and solute transport at large scales. Furthermore, a synergistic approach integrating pore-scale modeling and non-invasive imaging can provide detailed insights into intricate fluid-pore-solid interactions for future studies, as well as facilitate the development of regional engineering-scale models and physio-chemical coupled models with diverse applications in submarine science and engineering.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

This study introduces a specialized Automatic Speech Recognition (ASR) system, leveraging the Whisper Large-v2 model, specifically adapted for radiological applications in French language. Our methodology focused on adapting the model to accurately transcribe medical terminology and diverse accents within the French language context, achieving a notable Word Error Rate (WER) of 17.121%. The research involved extensive data collection and preprocessing, utilizing a wide range of French medical audio content. The results demonstrate the system's effectiveness in transcribing complex radiological data, underscoring its potential to enhance medical documentation efficiency in French-speaking clinical settings. The discussion extends to the broader implications of this technology in healthcare, including its potential integration with Electronic Health Records (EHRs) and its utility in medical education. The study also explores future research directions, such as tailoring ASR systems to specific medical specialties and languages. Overall, this research contributes significantly to the field of medical ASR systems, presenting a robust tool for radiological transcription in the French language and paving the way for advanced technology-enhanced healthcare solutions.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

This study examines the capacity of a Site-Specific Fodder Management Decision Support System (SSFM-DSS) model to assist in successful cultivation of sericea lespedeza [SL; Lespedeza cuneata (Dum.-Cours.) G. Don.], with a specific focus on small-scale agricultural systems in the southeastern United States (U.S.). The study emphasizes incorporating advanced geospatial technologies, such as Geographic Information Systems (GIS), remote sensing, and Global Navigation Satellite Systems (GNSS), to improve fodder production. The research showcases the versatility of SL under varying environmental conditions, underscoring its significance in promoting sustainable livestock production. The methodology integrates empirical field data, geospatial analysis, and predictive modeling to formulate an SSFM strategy customized to address the distinct difficulties climate change presents, such as sudden and severe drought conditions. The study introduces an automated geospatial model for assessing the appropriateness of SL production throughout Alabama, Georgia, and South Carolina. The model uses many environmental criteria, including soil properties, climate fluctuations, and terrain. Furthermore, the research was instrumental in development of a WebGIS Dashboard, which offers farmers a decision assistance system to enhance the sustainable production of SL. The results highlight the significant impact that a SSFM-DSS can have on promoting sustainable agricultural practices, providing a solution to address the issues of food security and environmental concerns in agriculture.

Developing sustainability competences is an important endeavor for education, as competence development can be complex and requires appropriate approaches. In the case of preparing future educators, this becomes even more important, because of their multiplier role. The current study presents how a project, based on living-lab methodology, helped preservice preschool teachers, attending a course on sustainability issues, develop sustainability-specific professional action competence. Students collaborated with an organization and a school and were trained to deliver to 6-year-old pupils, activities concerning the protection of sea turtles. The process included reflection, based on a given template. After the intervention, the preservice preschool teachers reflected upon their role and professional performance and discussed how they, benefited from this project. They further analyzed through a group interview, how the Living Lab methodology raised their professional confidence and self-efficacy, and helped them develop content knowledge, pedagogical content knowledge, and a sense of purpose and motivation for teaching about sustainability. Outcomes indicate that participants felt confident and efficacious to teach about sustainability, and developed their content knowledge, pedagogy content knowledge, motivation, and volition due to a strong sense of purpose and responsibility. The overall process facilitated the development of critical thinking, systemic thinking, reflection, and collaboration..

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

This research work has been based on a previous study by the authors that characterized the behavior of a polyimide-coated FBG sensor in a structural monitoring system. Sensors applied to structural health monitoring are affected in the presence of a state of multidirectional strains simultaneously. The previous study observed the influence of transverse strain (ε_y) while keeping longitudinal strain constant (ε_x), where the direction x is the direction of the optical fiber. The present study developed an experimental methodology which has consisted of carrying out a campaign of biaxial tests on cruciform specimens with three embedded FBG sensors coated with polyimide, acrylate and ORMOCER®. Applying the Strain–Optic Theory as reference, a comparison of the results obtained with the different coatings has been studied. This experimental work has done it possible to study the influence of transverse strain (ε_y) in the longitudinal measurement of each of the FBG sensor and the influence of the coating material. Finally, the calibration procedure as well as the strain sensitivity factor K for each sensor has been defined.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Bridges enable communications and transportation of goods nationally and internationally, underpinning economic and social activities, thus they are pylons of our prosperity and mobility. Bridges worldwide are constantly subjected to physical wear, ageing, deterioration, hazards, environmental influences, and increased loading. Loss of performance and functionality of bridge structures would have a crucial impact on overall infrastructural resilience and would cause significant negative economic and social consequences. Monitoring their behaviour for different loading conditions relies on accurate estimations of the stress-strain state of various critical components and remaining capacities. These activities are of high importance for better planning lifespan prolongation, that is the extension of their service life and prevention of unforeseen collapses, in line with sustainability principles of well-informed maintenance. In many cases, access to the structure is limited or even impossible, which causes the need for the deployment of remote and contactless methods. One such innovative technique, which has recently attracted attention in scientific and practical applications is the digital image correlation (DIC). DIC is a contactless approach applicable for long-term measurements, which enables obtaining the full field of strains and deformations. Although the DIC approach has been widely used in world engineering practice for monitoring bridges and has proved to be a reliable and accurate method, there is a lack of systematic integral review on previous practical applications, revealing limitations and perspectives. This is the main motivation and novelty of this study, which will describe selected case studies, in which DIC was used on real full-scale bridge structures and propose improvements for the method.

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3-D structure which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC, about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK’s clinical performance was also studied in HCC patients with viral and non-viral cirrhosis including cirrhosis caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84 while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK has significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71%-91% of HCC patients with false-negative AFP test results in viral associated HCC and non-viral associated HCC.

The purpose of the study is to establish compliance of the design of the modernized car with the requirements for safe operation. An option has been proposed for upgrading a passenger wagon to a Mobile Diagnostic Complex for transporting a combined vehicle equipped with appropriate flaw detection equipment intended for rail diagnostics. The authors have established the most optimal option for locating the diagnostic vehicle on board the Mobile Diagnostic Complex (MDC) wagon, taking into account the additional load from the vehicle. To achieve this goal, the article developed a three-dimensional model of the supporting structure of the wagon body, proposed a methodology and presented the results of a study of the stress-strain state of the wagon body, taking into account the additional weight of the wagon. The article develops a methodology for studying the natural frequencies of vibrations of the wagon body and develops a three-dimensional model of the wagon for calculating dynamic indicators in the Universal Mechanism software package. Taking into account the previously carried out strength calculations, as well as in order to maintain the factory life cycle indicators of the supporting structure of the wagon body, it is recommended to use the model in the first version.

Livestock management is challenging for resource-poor (R-P) farmers due to unavailability of quality feed, limited professional advice and rumor-spreading about animal health condition in a herd. This research seeks to improve animal health in southern Africa by promoting sericea lespedeza (Lespedeza cuneata), a nutraceutical fodder legume. An automated geospatial model for precision agriculture (PA) can identify suitable locations for its cultivation. Additionally, a novel approach of radio frequency identifier (RFID) supported telemetry technology can track animal movement, and the analyses of data using artificial intelligence can determine sickness of small ruminants. This RFID-based system is being connected to a smartphone app (under construction) to alert farmers of potential livestock health issues in real-time so they can take immediate corrective measures. An accompanying Decision Support System (DSS) site is being developed for R-P farmers to obtain all possible support on livestock production, including the designed PA and RFID-based DSS.

Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells by pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx). The flavin mononucleotide dependent PNPOx enzyme converts pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B6 vitamers. However, for those depending on vitamin B6 as nutrient, PNPOx participates only in the salvage pathway. Transferring PLP produced by PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting to specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx enzymes from different organisms maintain PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding influencing substrate transformation at the active site. Despite shared features, species-specific regulations are evident among PNPOx enzymes.

Oak woodlands are a keystone ecosystem that may not be sustainable under ongoing fire management regimes and climate change. For example, in 2014, sassafras saplings started to emerge in degraded woodlands at the 1200 ha Drury Conservation Area as part of research at the Bull Shoals Field Station in Taney County, Missouri where burning was initiated in 1999. After Spring (March) 2021 burnt, we examined trend in the potential community and ecosystem effects, we assessed sapling density, height, and specific leave weigh (SLW) of white oak and sassafras (<1.0 m) from fall 2021 through fall 2022. In fall 2021, sassafras density was 560/0.1ha with mean height of 25.42cm and SLW of 0.00436g/cm² while white Oak density was 171/0.1ha with mean height of 10.2cm and SLW of 0.00680g/cm. However, in fall 2022, Sassafras density was 582/0.1ha with mean height of 71.689cm and SLW of 0.00366 g/cm² meanwhile, white Oak density was 213/0.1ha with mean height of 50.544cm and SLW of 0.00563 g/cm². We analyzed mass loss for sassafras and white oak after buried for 198 days. The weight loss for sassafras was 0.857g while oak was 0.790g for 61 days of buried. Subsequent sassafras weight loss was 1.942g, 3.343g, 4.222g and 4.82g while that of white Oak was 1.877g, 2.862g, 3.344g and 4.28g for day 105, 153 and 198 respectively. The nutrients composition and carbon sequestration of sassafras and white oak species need to be determined to better understand the effect of their dominance in fire management regime of degraded oak woodland in Southwest Missouri Ozarks.

An eight-sided prism sample, obtained from a hot-rolled AZ31 magnesium alloy sheet, was compressed at room temperature along the transverse direction to investigate the influence of local strain on twinning behavior using electron backscatter diffraction (EBSD) measurements. The octagonal surface of the sample was divided into distinct regions based on hardness distribution and metallographic observations. The EBSD maps of different areas show significant variations, suggesting that these areas experienced different local strain conditions. The EBSD measurements provided detailed data from three distinct regions, with the strain state known in two regions and uncertain in the third. The combined analysis of the Schmid factor (SF) and the strain compatibility factor (m') was employed to study twin variant selection. The comparison of twinning behavior in different regions showed that the strain compatibility factor offered a more comprehensive explanation for the observed twinning pattern in the region with local shear strain.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary &amp; safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem-cell derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue specific EVs or cell type specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in signaling for physiological function and maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis, but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

This study employs molecular docking simulations using Autodock Vina with the Pyrx program to investigate the binding interactions between Human prostate-specific antigen (PSA) and natural compounds, namely Amentoflavone, Ginketin, Rutin, and Hypericin. The evaluation reveals excellent binding energy values, averaging around -10 kcal/mol, suggesting robust and favorable interactions between the selected compounds and PSA. The results provide valuable insights into the potential therapeutic applications of these natural compounds in the context of prostate cancer treatment or management. Further experimental validation is warranted to confirm these findings and explore the viability of these compounds as promising candidates for innovative therapeutic strategies. This research contributes to the growing body of knowledge in the field of molecular docking and its applications in drug discovery and bioinformatics.

To better understand how immunity develops against SARS-CoV-2 during the pandemic period of 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined 8 months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after 6 months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred even among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN- or CD107a were detected early. In saliva, SARS-CoV-2-specific IgG but not IgA was detected. Interestingly, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Thus, SARS-CoV-2 infection triggers typical immune responses in humans against acute viral infections, but mucosal immune responses, which are temporarily induced early during infection, may be more important for protection than current intramuscular vaccines.

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were col-lected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial respondseproteins. 16S rRNA sequencing assessed mi-crobiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial inva-sion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

The 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Buenos Aires, Brazil, Northern California, Colombia, Nigeria, Europe, Vietnam, Spain, Switzerland, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam linked to a new Mpox sublineage in women emphasizes the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of the disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

Background: Evaluation of left ventricular(LV) functions in patients with idiopathic premature ventricular contraction(PVC) with preserved LV Ejection Fraction(LVEF), especially in the subclinical stage, may be of great importance in terms of directing early treatment. Methods: A total of 122 patients, retrospectively recruited, were divided into three groups according to PVC burden: Group 1; 5%PVC<10%, Group 2; 10%PVC<15%, and Group 3; 15% PVC. Transthoracic echocardiography(TTE) was performed to evaluate LV parameters. Results: LV-GLS was found to be significantly lower in groups 2 and 3 with high PVC burden (18.89 ± 1.4, 17.55 ± 2.1, 16.26 ± 1.3; p<0.001 respectively). Correlation analysis revealed a positive and significant correlation between PVC burden with deterioration in LV-GLS (r:0.536; p<0.001). In addition, PVC burden was found to be an independent predictor of LV-GLS deterioration in multiple linear regression analysis(:0.525, p<0.001). The ROC curve analysis demonstrated that a PVC burden cut-off value of 8.4% was associated with a LV-GLS deterioration greater than -18, with a specificity of 75.4% and a sensitivity of 75.4% (AUC: 0.81 [0.73-0.88] 95% CI; p<0.001). Conclusions: PVC burden was an independent predictor of deterioration in LV-GLS. In the presence of subclinical LV injury associated with PVC burden, early catheter ablation strategies may be therapeutically beneficial.

Repurposing previously approved drugs may fast track the route to clinic for potential senotherapeutics and improves the inefficiency of the clinical drug development pipeline. We carried out a repurposing screen of 240 clinically approved molecules in human primary dermal fibroblasts for effects on CDKN2A expression. Molecules demonstrating effects on CDKN2A expression underwent secondary screening for senescence-associated beta galactosidase (SAB) activity, based on effect size, direction and/or molecule identity. Selected molecules then underwent a more detailed assessment of senescence phenotypes including proliferation, apoptosis, DNA damage, senescence-associated secretory phenotype (SASP) expression and regulators of alternative splicing. A selection of the molecules demonstrating effects on senescence were then used in a new bioinformatic structure-function screen to identify common structural motifs. 90 molecules displayed altered CDKN2A expression at one or other dose, of which 15 also displayed effects on SAB positivity in primary human dermal fibroblasts. Of these, three were associated with increased SAB activity, and 11 with reduced activity. The female synthetic sex hormones; diethylstilboestrol, ethynyl estradiol and levonorgestrel; were all associated with a reduction in aspects of the senescence phenotype in male cells, with no effects visible in female cells. Finally, we identified that the 30 compounds that decreased CDKN2A activity the most had a common substructure linked to this function. Our results suggest that several drugs licenced for other indications may warrant exploration as future senotherapies, but that different donors and potentially different sexes may respond differently to senotherapeutic compounds. This underlines the importance of consideration of donor-related characteristics when designing drug screening platforms.

This experimental study probes the dynamic behaviour of a 3mm ABS sheet during positive mould vacuum-assisted thermoforming. In this process, the sheet undergoes large and fast deformations, caused by the applied vacuum and mechanical stretching by the mould. The objective is to elucidate the complexities of these large, rapid and non-isothermal deformations. The non-isothermal conditions are caused by the radiative heating of the sheet, convective heat loss to the surrounding air and conductive heat transfer from the sheet to the mould. Utilizing stereo Digital Image Correlation (DIC) in tandem with thermal imaging, the present study accurately maps the occurring displacement, strain and strain rate field in relation to real-time temperature variation of the material. The study progresses to observe the ABS material from the moment it contacts the mould until it conforms to a positive 250mm diameter semi-sphere cast aluminium mould. The DIC methods are validated by comparing thickness values derived from DIC’s principal strain directions to ultrasonic thickness gauge readings. This knowledge not only broadens the understanding of the thermo-mechanical behaviour of the material but also aids in optimizing process parameters for improved thickness uniformity in thermoformed products.

The metrological performance of FBG strain sensing systems is a critical premise for the precision of plastics water support pipeline structural deformation measurement, but the strain transfer loss of FBG attached on the plastics pipe subjected by dynamic force is unclear. This paper presents the first study on the effects of strain transfer between FBG, and acrylate polymer blended with poly resin (ABR)pipe sheets loaded by static and dynamic force. Theoretical methods of dynamic strain transfer theory combine with the exponentially decaying sinusoidal shock force time course is deduced and various dynamic parameters sensitivities studies are carried out, as well as that of the geometric parameters. The result of the dynamic theory is compared with the calibration test outcomes, while the ASTR of FBG attached on ABR sheet is compared with distributed optical fiber sensors (DOFS) and other pipe materials such as PVC, concrete, and steel. Results show that the ASTR of FBG is more accurate than that of the DOFS, and the grows of ASTR depending on the paste length of FBG, the Young's modulus of the middle materials, the thickness of the middle materials and attenuation coefficient. Paste length produced the largest increase, yet the magnitude and loading speed of the external force has unexpectedly little effect on ASTR. FBG seem low error, insensitive with dynamic force and independent with the material of matrix, and this demonstrates benefits that are stronger across the board than DOFS. This is not currently recognized by standards or by most reported studies.

This work presents noble composites of AAILs@MCM-48 by functionalizing ordered mesopo-rous silicon MCM-48 with two amino acid-based ionic liquids (AAILs) ([Emim][Gly] and [Em-im][Ala]) to improve carbon capture and selectivity of CO2 over nitrogen. Thermogravimetric and XRD analyses of the composites show that the MCM-48 support's thermal and structural in-tegrity was preserved after the AAILs were encapsulated. An N2 adsorption-desorption study at 77 K also confirms AAIL encapsulation in the porous support. Under post-combustion flue gas conditions, both [Emim][Gly]@MCM-48 and [Emim][Ala]@MCM-48 demonstrated improved CO2 adsorption in comparison to unmodified MCM-48, with a CO2 partial pressure of around 0.15 bar. In terms of maximal CO₂ uptake, the 40wt%-[Emim][Gly] composite outperformed the others at 303K, with values of 0.74 and 0.82 mmol g-1, respectively, at 0.1 and 0.2 bar. These numbers show a 10x and 5x increase, respectively, as compared to the pure MCM-48 under iden-tical conditions. In addition, the selectivity of the composites was improved significantly, at 0.1 bar, the selectivity of composites containing 40wt% [Emim][Ala] increased to 17, compared to 2 for pristine MCM-48.

The rapid development of electric vehicles, unmanned aerial vehicles, and wearable electronic devices has led to a high interest in research related to the synthesis of graphene with a high specific surface area for energy applications. However, the problem of graphene synthesis scalability, as well as the lengthy duration and high energy intensity of the activation processes of carbon materials, are significant disadvantages. In this study, a reactor was developed for the green, simple, and scalable electrochemical synthesis of graphene oxide with a low oxygen content of 14.1 %. The resulting material was activated using a fast joule heating method. The processing of mildly oxidized graphene with a high–energy short electrical pulse (32 ms) made it possible to obtain a graphene–based porous carbon material with a specific surface area of up to 1984.5 m2/g. The low energy intensity, simplicity, and use of environmentally friendly chemicals render the proposed method scalable.

The loads generated inside agricultural silos under static and dynamic conditions depend on the mechanical properties of the materials stored inside them. The silo calculation methodologies are based on these mechanical properties. Although it is known that moisture content greatly influences the values reached by these mechanical properties, just few studies have been conducted to determine them. The present work determines the angle of internal friction, the apparent cohesion, the dilatancy angle and the apparent specific weight of wheat when subjected to different moisture contents. Direct shear and oedometer assay devices were used. In addition, a climatic chamber was used to moisten the wheat samples used in this work. The moisture content applied to the samples ranged from 7.5% to 15.5%. From the different assays carried out it could be observed that the values of the angle of internal friction and apparent cohesion obtained from direct shear assays, as well as those related to the apparent specific weight obtained from oedometer assays were like those found in the literature. The apparent specific weight increased as moisture content increased, reaching a peak value at a moisture content of 13.4%, followed by a drop at a moisture content of 15.5%. The values here provided can be used in silo load calculations involving numerical methods.

Salt stress is one of the most severe environmental stresses limiting the productivity of crops, including rice. However, there is a lack of information on how salt-stress sensitivity varies across different developmental stages in rice. In view of this, a comparative evaluation of contrasting rice varieties CSR36 (salt tolerant) and Jaya (salt sensitive) was conducted, wherein NaCl stress (50 mM) was independently given either at seedling (S-stage), tillering (T-stage), flowering (F-stage), seed-setting (SS-stage) or throughout the plant growth, from seedling till maturity. Except for S-stage, CSR36 exhibited improved NaCl stress tolerance than Jaya, at all other tested stages. Principal component analysis (PCA) revealed that the improved NaCl stress tolerance in CSR36 coincided with enhanced activities/levels of enzymatic/non-enzymatic antioxidants (root ascorbate peroxidase for T- and S+T stages and root catalase for F-, S+T and S+T+F-stages) and higher accumulation of osmolytes (shoot proline for F-stage and S+T+F-stage), indicating better antioxidant capacitance and osmotic adjustment, respectively. In contrast, higher shoot accumulation of Na+ and consequent increase in Na+/K+, Na+/Ca+2 and Na+/Mg+2 ratio in root and shoot, were identified as major variables associated with NaCl stress induced growth reduction in Jaya. In addition, CSR36 exhibited higher levels of Fe3+, Mn2+ and Co3+ and lower Cl- and SO42-, suggesting its potential to discriminate essential and non-essential nutrients, which might contribute to NaCl stress tolerance. Taken together, the findings provided the frame-work for stage-specific salinity responses in rice, which will facilitate crop-improvement programs for specific ecological niches including the coastal regions. Rice, salt stress, stage-specific salinity, antioxidant defense, ionic homeostasis, salt tolerance

This study investigated whether reciprocal collaborative pedagogy significantly impacts Indonesian electrical engineering polytechnic students in reducing reading anxiety and improving self-efficacy in ESP reading comprehension skills. Fifty Polytechnic students were equally assigned to two groups. Control groups learned in the traditional reciprocal teaching method individually. Experimental group engaged in reciprocal collaborative pedagogy. Each group received a 6-week reading strategy training. E-learning platforms were used in this study as a complementary tool to distribute ESP reading materials, announcements, and the experiment details being taught. The quantitative and qualitative results demonstrated that the tasks in reciprocal collaborative pedagogy positively affects Indonesian electrical engineering polytechnic students' learning experience and outcomes. This pedagogy promotes a productive learning environment through peer interaction, active engagement, and peer group discussions of the whole learning activities, reducing feelings of anxiety and building confidence in ESP-specialized text.

Sexual selection involving female choice or female preference (‘inter-sexual’ selection) or male-male competition (‘intra-sexual’ selection) is one of the key mechanisms for evolutionary diversification and speciation. In particular, sexual selection is recently suggested to be an important mode to drive the evolution of “novel” phenotype (i. e. “evolutionary novelty”). Despite extensive studies performed on sexually selected traits or male-specific ornaments (or weapon-like structures) with respect to their evolutionary origin and history and fitness benefits, relatively little is known about the molecular genetic mechanisms underlying their developmental process. However, with advances of genomic technologies (including whole transcriptome analysis using Next Generation Sequencing [NGS] techniques; RNA-Seq), progresses have been made to unveil the genetic background underpinning diverse sexually selected traits in different animal taxa. In the present review, we compile empirical data on the genes, genetic mechanisms or regulatory pathways underlying various sexually selected traits to explore whether the “common” genetic architectures shape the development and evolution of those traits across evolutionarily distant animal lineages. We show that the recruitment of pre-existing genetic network for a new purpose (i.e. gene network “co-option”) is rather widespread in the development and evolution of sexually selected traits, indicating that particular genes or gene-sets are repeatedly involved in different sexually selected traits. Information of genes or genetic mechanisms regulating the development of sexually selected traits would be an essential piece to complete a whole picture of the origin and evolution of sexually selected traits.

In this paper, a novel nonlocal strain gradient anisotropic elastic shell model is developed to analyse the vibrations of simply supported single‒walled carbon nanotubes (SWCNTs). Sanders‒Koiter shell theory is used to obtain the strain‒displacement relationships. Eringen nonlocal elasticity theory and Mindlin strain gradient theory are adopted to derive the constitutive equations, where the anisotropic elastic constants are expressed via Chang molecular mechanics model. The complex variable method is used to analytically solve the equations of motion and to obtain the natural frequencies of SWCNTs. First, the anisotropic elastic shell model is validated via comparisons with the results of molecular dynamics simulations reported in the literature. Then, the effect of nonlocal and material parameters on the natural frequencies of SWCNTs with different geometries and wavenumbers is analysed. From the numerical simulations it is obtained that the natural frequencies decrease with increasing nonlocal parameter, while they increase with increasing material parameter. Moreover, the decrease of natural frequencies with increasing SWCNT radius is exponential as the material parameter increases, while it is linear as the nonlocal parameter increases. Finally, as the number of waves increases, the natural frequencies linearly vary with increasing nonlocal parameter, while they exponentially increase with increasing material parameter.

Numerous experimental and theoretical studies undertaken to determine the effective-stress coefficient for seismic velocities in rocks stem from the importance of this geomechanical parameter both for monitoring changes in rock saturation and pore pressure distribution in connection with reservoir production, and for overpressure prediction in reservoirs and formations from seismic data. The present work pursues a task to determine, in the framework of a low-frequency laboratory study, the dependence of the elastic moduli of n-decane saturated sandstone on the relationship between pore and confining pressures. The study was conducted on a sandstone sample with high quartz and notable clay content in the quasi-static regime, when the 100 ml tank filled with n-decane was directly connected to the pore space of the sample. The measurements were carried out at a seismic frequency of 2 Hz and strains, controlled by semiconductor strain gauges, not exceeding 10-6. The study was performed using a forced-oscillation laboratory apparatus utilizing stress-strain relationship. The dynamic elastic moduli have been measured in two sets of experiments: at constant pore pressures of 0, 1 and 5 MPa and differential pressure (defined as a difference between confining and pore pressures) varied from 3 to 19 MPa; and at а constant confining pressure of 20 MPa and pore pressure varied from 1 to 17 MP. It was shown that the elastic moduli obtained in the measurements are in good agreement with the Gassmann moduli calculated for the range of differential pressures used in our experiments, which corresponds to the effective-stress coefficient equal to unity.

According to the guidelines of the European Association of Urology (EAU), it is recommended to exclude PSA testing when the expected remaining lifespan is less than 10 years. In this study, we provide a comprehensive analysis of the impact of prostate-specific antigen (PSA) testing on the quality of life of elderly men who are frail. We conducted a comprehensive literature review to identify publications that examine the use of PSA as a screening and prognostic tool for prostatic illnesses in frail men. Our search included the following keywords: Prostate-specific antigen, Frailty, Prostate cancer screening, Hypogonadism, and Benign Prostatic Obstruction (BPO). Prostate-specific antigen (PSA) testing can be used to identify prostate cancer in its early and treatable stages in fragile men with a life expectancy of over 15 years. Additionally, PSA testing allows for the evaluation of the effectiveness of various prostate cancer treatments and the monitoring of testosterone replacement therapy for hypogonadism. PSA is also indicative of the clinical development of patients with benign prostatic obstruction (BPO). Nevertheless, PSA is being extensively provided without individualised patient assessment, contributing to the economic strain on healthcare systems. Conducting a frailty evaluation on men to determine the potential advantages of PSA tests on their quality of life will help minimise avoidable expenses.

This article describes a novel electrochemical on-chip biosensor that utilizes anti-PSA antibody (Ab) and silver nanoparticles (AgNPs) to enhance the sensing and detection capability of prostate specific antigen (PSA) in the blood. The AgNPs are prepared, characterized, and applied onto a silicon photonic on-chip biosensing receptor platform designed to enhance the accurate detection of PSA. The AgNPs were synthesized by a chemical reduction method using silver nitrate (AgNO₃) as the precursor. Transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersion X-ray spectroscopy (EDS), small angle X-ray scattering (SAXS), X-ray diffraction (XRD), and light microscopy were among the methods used in the characterization and analysis of the AgNPs. Each stage of the immunosensor fabrication was characterized using cyclic voltammetry. The proposed immunosensor was applied in the detection of PSA, a prostate cancer biomarker, with a high sensitivity and a limit of detection of 0.17 ng/mL over a linear concentration range of 2.5 to 11.0 ng/mL. The immunosensor displayed good stability and was selective in the presence of interfering species like immunoglobulin (Ig) in human serum, ascorbic acid (AA), and diclofenac (Dic). The detectivity and sensitivity are significantly higher than previous reports on similar or related technologies.

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is an important target for monoclonal antibody (mAb) therapy. All therapeutic mAbs, including anti-HER2 mAbs, exhibit adverse effects probably due to the recognition of antigens expressed in normal cells. Therefore, tumor-selective or specific mAbs can be beneficial in reducing the adverse effects. In this study, we established a novel cancer-specific anti-HER2 antibody, named H₂Mab-250/H₂CasMab-2 (IgG₁, kappa). H₂Mab-250 reacted with HER2-positive breast cancer BT-474 and SK-BR-3 cells. Importantly, H₂Mab-250 did not react with non-transformed normal epithelial cells (HaCaT and MCF 10A) and immortalized normal epithelial cells in flow cytometry. In contrast, most anti-HER2 mAbs including H₂Mab-119 (IgG₁, kappa) reacted with both cancer and normal epithelial cells. Furthermore, a core-fucose deleted IgG_2a-type H₂Mab-250 (H₂Mab-250-mG_2a-f) could trigger the antibody-dependent cellular cytotoxicity activity to BT-474, but not to HaCaT cells. Furthermore, H₂Mab-250-mG_2a-f exhibited an in vivo antitumor effect against BT-474 xenograft. Immunohistochemical analysis demonstrated that H₂Mab-250 possesses much higher reactivity to the HER2-positive breast cancer tissues compared to H₂Mab-119, and did not react with normal tissues, including heart, breast, stomach, lung, colon, kidney, and esophagus. The epitope mapping demonstrated that the Trp614 of HER2 domain IV mainly contributes to the recognition by H₂Mab-250. H₂Mab-250 could contribute to the development of chimeric antigen receptor-T or antibody-drug conjugates without adverse effects for breast cancer therapy.

Prostate cancer (PC) is the second most diagnosed cancer among men. It was observed that early diagnosis of disease is highly beneficial for survival of cancer patients. Therefore, extension and increasing quality of life of PC patients can be achieved by broadening the Cancer Screening programs that are aimed at the identification of cancer manifestation in patients at earlier stages before they demonstrate well-understood signs of the disease. Therefore, there is an urgent need in standard, sensitive, robust, and commonly available screening and diagnosis tools for identification of early signs of cancer pathologies. In this respect, “Holy Grail” of cancer researchers and bioengineers for decades have been molecular sensing probes that would allow diagnosis, prognosis, and monitoring of cancer diseases by their interaction with cell-secreted and cellassociated PC biomarkers, e.g. PSA and PSMA correspondinly. At present, most PSA tests are performed at centralized laboratories using high throughput Total PSA immune analyzers which are suitable for dedicated laboratories and are not readily available for the broad health screening. Therefore, the current trend in detection of PC is developments of the portable biosensors for mobile laboratories and individual use. Phage display since its conception by George Smith in 1985 has emerged as a premier tool in molecular biology with widespread applications. This review describes how the paradigm of molecular evolution and phage display revolutionized the methods of early diagnosis and monitoring of PC.

Increasingly, firms are expected to implement ESG (Environment, Social, and Governance) mandates to appeal to the global market. However, this requires overcoming practical challenges and capitalizing on emerging opportunities. This paper conducts an in-depth analysis of the ESG practices of leading Korean global firms. The study selects five firms for case studies representing industries such as electronics, automotive, steelmaking, and chemicals. It examines ESG reports, performance indicators, and corporate disclosures of these firms. The analysis reveals the adoption of industry-specific ESG strategies, highlighting how these firms tailor their approaches to address unique industry challenges while aligning with global sustainability trends. Key findings include a strong emphasis on innovative solutions to ESG challenges, the integration of ESG into core business operations, and a balanced approach to economic, social, and environmental responsibilities. This study contributes to a broader understanding of how ESG practices are implemented in various industrial contexts, particularly in the dynamic and evolving landscape of Korean global businesses. It offers valuable insights and benchmarks for global companies, underlining the importance of contextualized and industry-specific ESG strategies in achieving sustainable and ethical business practices

Cellular therapies have started an important new therapeutic direction for Autistic Spectrum Disease (ASD), and the ample diversity of ASD pathophysiology and the different types of cell therapies need an equally ample effort for studying the applicable ASD causes and the specific benefits of cell therapies via clinical studies.CORDUS Clinical Study is a crossover study in which autologous cord blood was administered intravenously to 56 patients between January 2019 and July 2023, and has compared its efficacy versus an individualized combination of supplements; both treatments were administered in a different sequence to all participants. Treatment efficacy was evaluated pre- and post- treatments by an independent psychotherapist with ATEC, Q-CHAT and a 16-item comparative table score, after interviews with the children’s parents and therapists.Cord blood was beneficial in the group of 3–7-year-old children (n=28; 3 out of 4 children – 78.57% - improved scores), but was much less effective in kids older than 8 years or with body weight of more than 35 kg (n=28; 1 out of 10 children improved scores). Individualized supplements were more efficacious than cord blood in 5 cases out of 28, while in 23 kids cord blood brought more improvement than supplements; 6 kids registered minor or no improvement. Statistically significant improvements were seen after cord blood infusion on areas such as verbalization and social interaction, but not on irritability or aggressive behavior; also ample individual differences were noted. No serious adverse reactions were noted during and after cord blood or supplement administration.

There is a growing concern about climate change being a serious threat to insurance business sustainability. Knowing if climate warming is a cause for claims and losses increase, and how this cause-effect relationship will develop in the future are two open major questions. In this article, we answer both questions by particularizing the geographical area of Spain, and a precise risk, hailstorm in crop insurance in the line of business of wine grapes. We measure climate change thanks to the Spanish Actuarial Climate Index (SACI). We use a database containing all the claims caused by hail risk in Spain from 1990 to 2022. With homogenized data, we consider as dependent variables the monthly number of claims, monthly number of loss costs equal to one, and monthly total losses. The independent variable is the monthly Spanish Actuarial Climate Index (SACI). We try to explain the former through the latter using regression and quantile regression models. Our main finding is that climate change as measured by SACI explains these three dependent variables. We also give an estimation of the increase of the monthly total losses Value at Risk, corresponding to a future increase in climate change measured in units of SACI. Spanish crop insurance managers should carefully incorporate these conclusions into their decision-making process to keep this line of business sustainable in the future.

This study aims at the sustainable valorization of eggshells (ES) from different countries of origin in cement concrete as a cement replacement for Hong Kong. For this purpose, sixteen different eggs from different regions across the world were selected from the local market. Firstly, the extent of uniformity in the weight and mineral content of sampled eggshells were assessed by a specific gravity test and thermogravimetric analysis (TGA), respectively. It was found that specific gravity varies between 2.02 and 2.39, with an average value of 2.20 ± 0.01, whereas CaCO₃ varies between 94.65% and 97.23%, with an average value of 96.33%. These values were a bit lower than those of extra-pure limestone (LS) because of the organic part and the porous structure of eggshells. Secondly, three different eggshells were selected for cement replacement in cement concrete, both in the uncalcined and calcined states, based on having the highest, medium, and lowest CaCO₃ content, respectively. To get the calcined eggshells, the eggshells were calcined at 800^oC for three hours. It was found that the strength of eggshells varies with CaCO₃, but the variation was acceptable. The calcined eggshells showed comparatively more compressive strength and were close to the LS because of the free CaO and the absence of an organic part. In general, the variation in the basic properties of eggshells from different regions across the world is negligible and suitable to use as a cement replacement with acceptable variation in strength in Hong Kong.

The assessment of Health-Related Quality of Life (HRQoL) in Thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of Transfusion-Dependent Thalassemia (TDT) patients in Greece. This was a multicentre, cross-sectional study conducted in 2017, involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower, compared to the general population in Greece. The mean summary score of TranQol was relatively high (71±14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment in a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

Background: We aimed to evaluate whether baseline GLS and NT-proBNP and their changes after cardiac resynchronization therapy (CRT) can predict the long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). Methods: We enrolled 143 patients with stable, ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiogram were obtained before and 6 months after. The patients were followed-up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint) Results: 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered as CRT-responders and 39 as non-responders. At baseline, event-free patients had higher absolute GLS values (p&lt;0.001) and lower NT-proBNP serum levels (p&lt;0001) than those achieving primary endpoint. A similar pattern was observed in favor of CRT-responders vs non-responders. In Cox regression analysis, lower baseline absolute GLS value (HR=0.77;95%CI, 0.51-1.91; p=0.002), higher baseline NT-proBNP levels (HR=1.55;95%CI, 1.43-2.01;p=0.002) and diabetes (HR=1.27;95%CI, 1.12-1.98;p=0.003) were associated with lower incidence of primary endpoint. Conclusions: In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

Premature failure and degradation of layers are the main problems for transportation infrastruc-ture. Addressing these issues necessitates implementing structural health monitoring (SHM) for transportation layers. This strategic approach is instrumental in mitigating maintenance expenses, prolonging the operational lifespan, and preventing accidents resulting from abrupt layer col-lapse. To this end, this research investigated the stress/strain and damage detection capabilities of a self-sensing cementitious composite developed for potential utilization in the construction of an intelligent subgrade layer. The prepared self-sensing cementitious composite consisted of 10% cement and hybrid conductive fillers, including multiwalled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) in sand. Initial findings reveal that the electrical resistivity of the composite is significantly affected by the concentration of MWCNTs/GNPs, with a minimum concentration of more than 0.5% needed to achieve a responsive cementitious composite. More-over, the piezoresistive analysis indicates that an increase in the concentration of MWCNTs/GNPs and stress levels leads to an improvement in the stress/strain sensing perfor-mance. When the self-sensing cementitious composite is subjected to equivalent stress levels, variations in the FCR exhibit an increasing trend with decreasing resilient modulus, stemming from a decrease in stiffness due to the increased concentration of MWCNTs/GNPs. Additionally, the EIS analysis demonstrates a contraction for the Nyquist curves under compressive ramp loading prior to failure, followed by the expansion of these curves postfailure. Scanning electron microscopy (SEM) images visually showcase the bridging effects of MWCNTs and the filling ef-fects of GNPs within the composite structure.

Fiber-based flexible sensors have promising applications potential in human motion and healthcare monitoring, owing to their merits of lightweight, flexibility, and easy processing. Now, high-performance elastic fiber-based strain sensors with high sensitivity, large working range and excellent durability are in great demand. Herein, we have easily and quickly prepared a highly-sensitive, durable fiber-based strain sensor by dip-coating of highly-stretchable polyurethane (PU) elastic fiber in MXene/ waterborne polyurethane (WPU) dispersion solution. Benefiting from the electrostatic repulsion force between the negatively charged WPU and MXene sheets in the mixed solution, very homogeneous and stable MXene/WPU dispersion was successfully obtained and the interconnected conducting networks were correspondingly formed in coated MXene/WPU shell layer, which makes as-prepared strain sensor exhibit a gauge factor of over 960, a large sensing range of over 90% and detection limit as low as 0.5% strain. As elastic fiber and mixed solution have the same polymer constitute, tight bonding of MXene/WPU conductive composite on PU fibers was achieved, enabling the as-prepared strain sensor endure over 2500 stretching-releasing cycles and thus show good durability. Full-scale human motion detection was also performed by the strain sensor, and a body posture monitoring, analysis, and correction prototype system was developed via embedding the fiber-based strain sensors into sweater, strongly indicating the great application prospect in exercise, sports and healthcare.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

This study focuses on the modification of ion-exchange membranes by incorporating phosphorylated dendrimer into sulfonated polytetrafluoroethylene membranes to enhance specific selectivity between mono-/divalent ions, using the Ca2+/Na+ pair as an example. The research employs mechanical, physico-chemical, and electrochemical analyses to explore the effects of P-H20 incorporation on membrane properties. Bulk modification significantly increases membrane selectivity towards calcium ions (specific permselectivity coefficient rises from 1.5 to 7.2), while maintaining the same level of the limiting current density. Other findings indicate that bulk modification significantly changes the transport-channel structure of the membrane and alters the mechanism of over-limiting mass transfer. The over-limiting current for the pristine membrane is mainly due to non-equilibrium electroconvection, while modified membranes actively participate in the water-splitting reaction, leading to the suppression of the electroconvection. Despite this drawback, the decrease of the over-limiting potential drop results in a decrease in specific energy consumption from 0.11 to 0.07 kWh/mol. In the under-limiting current mode, the specific energy consumption for all studied membranes remains within the same limits of 0.02-0.03 kWh/mol.

We report a simple and high-performance flexible strain sensor based on liquid metal nanoparticles (LMNPs) on polyimide substrate by laser induced deposition. The LMNPs were prepared by ultrasonic method, and then the femtosecond laser direct writing technology was used to induce the assembly and deposition of the LMNPs to form liquid metal microwires. Laser local sintering enhances the connection between particles, and a wearable strain sensor was fabricated with the high sensitivity as high as 76.18, the good linearity (a correlation coefficient of 0.999) in a wide sensing rage, the fast response/recovery time of 159 ms/120 ms. Attributed to these extraordinary strain sensing performances, the sensor can sense various dynamic strains in real time, monitor both subtle physiological activities and large human motions. It can be adhered to human skin, and well reflect the change of facial expression and realize real-time monitoring of facial expression. And the vocal cord vibration can be detected for speech recognition while the sensor attached to the outside of the throat.

The stability of deep soft rock tunnels is of particular concern under seepage conditions. Aiming at thoroughly discussing the seepage actions and their consequences on the support scheme of such structures, the host rocks of the Weilai Tunnel situated in Guangxi province of China are taken as the research substance. Emphasizing on seepage conditions, stresses, displacements and plastic zone radii along the surrounding rocks of such tunnel are adequately examined taking into consideration the Mogi-Coulomb strain criterion and the elastic-plastic theory. Subsequently, based on strain-softening model, the coupled actions of seepage and softening on the rocks surrounding the tunnel are studied. According to the results, it is revealed that the support scheme of deep soft rock tunnels must be of highest resistance possible to better decrease the plastic zone and the tangential stress along the host rocks. Moreover, throughout the surrounding rocks, the dissemination of pore water pressure is strongly affected by the uneven permeability coefficient under anisotropic seepage states. Combined effects of softening and seepage are very dangerous for the surrounding rocks of deep-buried tunnels. To better guarantee reasonable longevity of such tunnels, long-term monitoring of their support structures with reliable remote sensors is strongly recommended.

This paper constitutes an original and new methodology for the determination of the surface properties of carbon fibers in the two oxidized and untreated forms by inverse gas chromatography technique at infinite dilution based on the effect of the temperature on the surface area of the various organic molecules adsorbed on the carbon fibers. The studied thermal effect proved a large deviation of the classical methods or models relative to the new determination of the surface properties of carbon fibers, such as the dispersive component of their surface energy, the free surface energy, the free specific energy, the enthalpy and entropy of adsorption of molecules on the carbon fibers. The obtained specific enthalpy and entropy of adsorption for the polar solvents led to the determination of the Lewis’s acid-base constants of carbon fibers. Different molecular models and chromatographic methods were used to quantify the surface thermodynamic properties of carbon fibers and compared to the thermal model. The obtained results proved that the oxidized carbon fibers gave more specific interaction energy and greater acid-base constants than that of the untreated carbon fibers and thus highlighting the important role of the oxidization on the acid-base of fibers. The determination of the specific acid-base surface energy of the two carbon fibers showed greater values of the oxidized carbon fibers relative to the untreated carbon fibers. An important basic character was highlighted for the two studied carbon fibers, larger than the acidic character. It was observed that the Lewis’s acid-base constants of the oxidized carbon fibers are larger than that of the untreated fibers with more accentuated basic charterer. This result was confirmed by all molecular models and chromatographic methods.

The initiation of micro-cracks in concrete is primarily due to its brittleness, which causes severe impacts on the overall behavior of the concrete. However, incorporating fibers in concrete could significantly improve its mechanical properties. The current study demonstrates the influence of two types of fibers on the mechanical properties of concrete. Nylon Fiber Threads (NFT) and Nylon Fiber Strands (NFS) at a fiber content of 2.5 kg/m³ were incorporated in the concrete mix. Concrete with a compressive strength of 30 MPa and a water-cement ratio of 0.4 was produced to investigate the fresh and mechanical properties of conventional and nylon-fiber reinforced concrete (NFRC). The concrete prims and cylinders were tested for compressive, splitting, and flexural strength using ASTM standards (ASTM C-39, C-496, and D-790, respectively). It was found that NFT-reinforced samples achieved higher mechanical properties of concrete (13.05%) compared to NFS-reinforced samples. Test results showed that incorporation of nylon fibers (NF) in concrete decreased the compressive strength of cylindrical and cubical specimens by 0–10% and 5–15%, respectively. However, it increased the splitting tensile and flexural strengths by 0-15%, and 5-15% respectively. Furthermore, the incorporation of NF in concrete significantly improved the ductility and delayed the crack initiation in concrete.

This study explores the application of numerical analysis and material models to predict ice impact loads on ships and offshore structures operating in polar regions. An explicit finite element analysis (FEA) approach was employed to simulate an ice and steel plate collision experiment conducted in a cold chamber. The pressure and strain history during the ice collision were calculated and compared with the experimental results. Various material model configurations were applied to the FEA to account for the versatile behavior of ice—whether ductile or brittle—its elastic-plastic yield criteria, and its dynamic strain rate dependency. In addition to the standard linear elastic perfectly plastic and linear elastic-plastic relationships, this study incorporated the crushable foam and Drucker-Prager models, based on the specific ice yield criteria. Considering the ice’s strain rate dependency, collision simulations were conducted for each yield criteria model to compute the strain and reaction force of the plate specimens. By comparing the predicted pressures for each material model combination with the pressures from ice collision experiments, our study proposes material models that consider the yielding, damage, and behavioral characteristics of ice. Lastly, our study proposes a combination of ice material properties that can accurately predict collision force.

African Swine Fever (ASF) poses a significant threat to domestic pig populations worldwide. This study investigates the histopathological alterations in confirmed ASF-positive domestic pigs, focusing on over 100 cases from 2018 to 2021. Biological material from 118 pigs, confirmed ASF-positive via PCR examination, was histopathologically examined. Tissue samples from various organs were processed, embedded, and analyzed using hematoxylin and eosin staining. Immunohistochemistry (IHC) was employed to detect the major capsid protein (p72) of the ASF virus.Histological examination revealed characteristic ASF lesions, including severe hemorrhages, lymphoid depletion, and inflammatory infiltrates. Vascular anomalies leading to hemorrhagic events were widespread. Microthromboses were prevalent in lymph nodes and kidneys. IHC detected p72 in various organs, with tonsils consistently showing the highest viral presence.This comprehensive study underscores the pivotal role of lymph nodes, spleen, and kidneys in ASF pathogenesis, highlighting prominent vascular involvement and hemorrhagic manifestations. The study establishes the efficacy of IHC in detecting ASF virus, even in autolyzed tissue samples. Tonsils emerge as a consistent epicenter of viral presence, shedding light on the intricate pathogenesis of ASFV.

Study design: Creating and psychometric testing of a new QoL Questionnaire about Physiotherapeutic Specific Exercises of Scoliosis (Questionnaire of Physiotherapeutic Specific Exercises of Scoliosis -QPSSE). Purpose: The purpose of this study is to create a reliable and valid questionnaire for patients suffering mild and moderate adolescent idiopathic scoliosis (AIS) who have been treated with Physiotherapeutic Specific Exercises of Scoliosis (PSSE) in order to evaluate their quality of life. Materials and Methods: The developed questionnaire was based on a thorough literature review as well as on authors experience. It consists of 53 questions, of which 37 have a positive meaning, 15 have a negative meaning, and one is multiple choice question, additionally there are six “open” questions. Except for the multiple choice question, all other questions are answered on a Likert scale ranging from 1 to 5 scores. 5 represents a positive meaning or very much, whereas 1 stands for a negative meaning or not at all. Questions were developed by the authors who subsequently categorized the 53 questions into the following 8 domains: physical functioning, self-image, Physiotherapeutic Scoliosis-Specific Exercises (PSSEs), psychosocial functioning, cognitive functioning, compliance, motivation and pain. A pilot study was conducted so that we could calculate Cronbach’s Alpha based on the outcome. Due to the COVID-19 pandemic, the authors worked through the Zoom online platform to structure the questionnaire. Results: Pearson's correlation coefficient was used for all correlations evaluated. P values of less than 0.05 were considered to be significant. Internal consistency was evaluated with Cronbach's alpha. Although there were very few missing values, accounting for 0.78% of the total values of the questionnaire, expectation maximization likelihood algorithm was used to impute data. IBM® SPSS® Statistics Software v.25 was used for the analysis. Cronbach's alpha coefficients for the overall score was 0.84. Conclusion: This original QPSSE was found to be a reliable and valid tool for AIS treated conservatively with PSSE and for their clinicians.

In recent years, strain sensors have penetrated various fields. The capability of sensors to convert physical signals into electrical signals is of great importance in healthcare. However, it is still challenging to obtain sensors with high sensitivity, large operating range and low cost. In this paper, a stretchable strain sensor made of a double-layer conductive network, including a biomimetic multilayer graphene-Ecoflex (MLG-Ecoflex) substrate and a multilayer graphene-carbon nanotubes (MLG-CNTs) composite up-layer was developed. The combined action of the two layers led to an excellent performance with an operating range of up to 580% as well as a high sensitivity (gauge factor (GFmax) of 1517.94). In addition, a pressure sensor was further designed using the bionic vein-like structure with a multi-layer stacking of MLG-Ecoflex/MLG-CNTs/MLG-Ecoflex to obtain a relatively high deformation along the direction of thickness. The device presented a high sensing performance (up to sensitivity of 0.433 kPa-1), capable of monitoring small movements of the human body such as vocalisations and gestures. The good performance of the sensors together with a simple fabrication procedure (flip-molding) make it potential for some applications, for example, human health monitoring and other areas of human interaction.

Cathinone is a natural stimulant found in Catha edulis and commonly used in new psychoactive substances. The objective of this study was to examine the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats. Cathine and cathinone concentrations were identified and quantified using ion trap liquid chromatography (LC-IT/MS), while the metabolic profile was determined using the quadrupole time of flight UPLC-QTOF/MS method in the serum, brain, lung, liver, kidney, and heart over a period of 0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours. The findings revealed a dynamic interplay between the pharmacokinetics of cathinone and its impact on organ-specific biomarkers. The distribution of cathinone and cathine was determined in serum, brain, heart, lung, kidney, and liver. The highest concentration of cathinone was found in the kidney at 1438.6 ug/L. It gradually decreased to 1.97 within 48 hours and disappeared after 72 hours. Within half an hour, cathinone levels in the lungs, liver, and heart were found to be 859, 798.9, and 385.8 ug/L, respectively. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 ug/L and kept decreasing until they became undetectable after 24 hours. The concentration of cathinone in the rat brain reduces quickly, dropping to undetectable levels within six hours, with levels decreasing from 712.7 ug/L after just 30 minutes. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours. This indicates that the conversion of cathinone to cathine is slower in the brain and serum. The study found that cathinone's pharmacokinetics have a significant impact on organ-specific biomarkers. After administering the cathinone, there was a sharp change in biomarker levels, particularly in the liver and brain, during the initial hours. It is essential to investigate the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine. The results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. In conclusion, this comprehensive analysis of cathinone's impact on organ-specific biomarkers provides a basis for informed decision-making in medical practices and further research into the cathinone's pharmacological properties.

Abstract: Extensive research shows nurses’ work environment to be particularly stressful. This study develops, explores, and psychometrically tests a new profession specific ques-tionnaire identifying generalized and specific resistance resources, that make it possible to measure resources to manage work-related stress. An exploratory study design was em-ployed. The questionnaire was developed inspired by the MEASURE approach and the salutogenic theory of health. Building on the results from a literature review of nursing re-search and salutogenesis, supplemented by twelve interviews with hospital nurses, an item pool was generated. A first version was pilot tested in a group of nurses who were studying to become specialist nurses. A second version of the questionnaire was psycho-metrically tested on nurses in close patient care (n = 475), analysed using Principal Com-ponent Analysis as the extracting technique to identify the underlying structure of the questionnaire. The Principal Component Analysis revealed a four-component model of 19 items. “Manageability as a resource for handling the workload” was the strongest compo-nent, accounting for 21 % of the explained variance. “Contacts with patients as resources for nurses’ job satisfaction” (17.8 %). “Professional attitudes are labelled as resources to nursing” (15 %). “Colleagues are important resources for remaining in the nursing profes-sion” (11 %). The structure of the questionnaire indicates its usefulness in clinical practice for measuring resistance resources.

Insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising treatment option for individuals with diabetes. It has been reported that the incorporation of fatty acid moieties into insulin icodec plays a crucial role in its prolonged action, as these fatty acid chains facilitate the formation of stable hexameric structures, thereby delaying insulin absorption and promoting sustained release. Yet, the underlying biophysics still is elusive of the roles of the three site-specific mutations (Y14A\_E, Y37B\_H, F46B\_H) of insulin icodec in its prolonged activity. Thus, through a comprehensive structural and biophysical analysis of the insulin (both native and icodec) structures bound to its receptor, this article delves deep into the biophysics underlying the molecular design of insulin icodec, and identified a delicate biophysical mechanism through which two missense mutations of insulin icodec (Y37B\_H and F46B\_H) contribute to its prolonged duration of action. Overall, this structural and biophysical investigation provides valuable insights into the mechanisms underlying the relationship between three site-specific mutations and prolonged duration of action of insulin icodec, while understanding these modifications at a structural and biophysical level can aid in the rational design of future long-acting insulin analogues, offering further enhanced therapeutic options for diabetic patients.

A new utilization of entropy in the context of buckling is presented. The novel concept connecting strain energy and entropy for a pin-ended strut is derived. This concept rationalizes the ranking of buckling modes based on strain energy under the assumption of given entropy. By assigning identical entropy to all buckling modes, they can be ranked according to their deformation energy. Conversely, with identical strain energy assigned to all modes, ranking according to entropy is possible. Decreasing entropy was found to represent the scaling factors of buckling modes that coincide with the measurement of initial out-of-straightness imperfections in IPE160 beams. Applied to steel plane frames, scaled buckling modes can be used to model initial imperfections. It is demonstrated that the entropy (scale factor) for given energy roughly decreases with the inverse square of the mode index. For practical engineering, the study presents the possibility of using scaled buckling modes of steel plane frames to model initial geometric imperfections. Entropy proves to be a valuable complement to strain energy in structural mechanics.

Influenza virus strain A/South Africa/3626/2013 (H1N1)pdm09 (SA-WT) is a non-mouse-adapted model strain, which has naturally high pathogenic properties for mice. It has been suggested that the high pathogenicity of this strain for mice could be due to the three strain-specific substitutions in the polymerase complex (Q687R in PB1, N102T in PB2, and E358E/K heterogeneity also in PB2). To evaluate the role of these replacements, SA-WT was passaged five times in mouse lungs, and the genome of the mouse-adapted version of the SA-WT strain (SA-M5) was sequenced. SA-M5 lost E358E/K heterogeneity and retained E358, which is the prevalent amino acid at this position among H1N1pdm09 strains. Besides, in the hemagglutinin of SA-M5, two heterogeneous substitutions (G155G/E and S190S/R) were identified. Both viruses, SA-M5 and SA-WT, were compared for their toxicity, ability to replicate, pathogenicity, and immunogenicity for mice. In mice infected with SA-M5 or SA-WT strains, toxicity, virus titer in pulmonary homogenates, and mouse survival did not differ significantly. Contrarily, an increase in the immunogenicity of SA-M5 compared to SA-WT was observed. This increase could be due to the substitutions G155G/E and S190S/R in the HA of SA-M5. The prospects for using SA-M5 in studying the immunogenicity mechanisms were also discussed.

Background: We aimed to evaluate the impact of two different phytotherapeutic agents on the decision making regarding prostate biopsy in patients with higher-than-normal prostate-specific antigen (PSA) levels. Methods: From June 2022 to May 2023, all patients attending two urological institutions due to higher-than-normal PSA levels were randomized to receive either oral capsules of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica (Group A) or Serenoa Repens 320 mg (Group B), for 3 months. At the follow-up visit after 3 months all patients underwent PSA test and multiparametric magnetic resonance imaging (mpMRI). Results: In the per-protocol analysis, data from 66 patients in Group A and 76 in Group B were analyzed. Fifty patients in Group A (75.7%) showed a significant reduction of total PSA compared to 49 in Group B (64.4%) (p<0.001). Twenty-eight patients had PI-RADS III or higher at mpMRI: 12 in Group A and 14 in Group B. Twenty-three patients (34.8%) in Group A underwent prostate biopsy based on mpMRI findings and PSA values and 59 (77.6%) in Group B (p<0.001). Three patients in Group A showed a significant reduction of total PSA value while having positive findings at mpMRI (6%) compared with 9 in Group B (19.5%) (p<0.001). On the contrary, 7 patients in Group A did not show a significant reduction of total PSA value and had negative findings at mpMRI (43%) compared to 22 in Group B (81.4%) (p&lt;0.001). Conclusions: In conclusion, a three-month course of a combination of Curcuma Longa, Boswellia, Pinus pinaster, and Urtica dioica seems an interesting tool to avoid unnecessary prostate biopsies in men with higher-than-normal PSA levels.

Defects in low-density lipoprotein receptor (LDLR) are associated with familial hypercholesterolemia (FH), manifested by atherosclerosis and cardiovascular disease. Defective LDLR in hepatocytes leads to increased blood cholesterol level that damage vascular cells, especially endothelial cells, through oxidative stress and inflammation. However, the distinctions between endothelial cells from individuals with normal and defective LDLR are not yet fully comprehended. In this study, we obtained and examined endothelial derivatives of induced pluripotent stem cells (iPSC) generated previously from conditionally healthy donors and compound heterozygous FH patients carrying pathogenic LDLR alleles. In normal iPSC-derived endothelial cells (iPSC-EC), we detected the LDLR protein predominantly in its mature form, while iPSC-EC from patients with FH display reduced level of mature LDLR and show abolished low-density lipoprotein uptake. RNA-seq of iPSC-EC with mutant LDLR revealed a unique transcriptome profile comprising downregulated genes related to monocarboxylic acid transport, exocytosis and cell adhesion, as well as upregulated signaling pathways of cell secretion and leukocyte activation. Overall, these findings suggest that LDLR defects increases susceptibility of endothelial cells to inflammation and oxidative stress. This, combined with elevated extrinsic cholesterol levels, may result in accelerated endothelial dysfunction, contributing to early progression of atherosclerosis and other cardiovascular pathologies related to FH.

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using the fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33–60 years in the first study) were scanned twice, 7 years apart. An age-related decrease in MPF was found in global WM, GM, and mixed WM-GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2-5%), genu of the corpus callosum (CC) (4.0%) and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM-GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

Road-embedded inductive power transfer (IPT) systems have the potential to accelerate the electrification of the transportation sector. For these systems to be economically viable however, they need to have a similar durability and lifespan compared to that of asphalt roads. One area that has lacked investigation is thermally induced stresses in a primary IPT pad, which is caused by the increase in temperature of the pad when it is energized and the differing thermal expansion of the materials within. This paper presents an experimental and a finite-element based methodology for investigating the thermal-mechanical behaviour of a ¼-scale double-D pad, which was energized while suspended in air, as well as energized when embedded in pavement. A focus was placed on the measurement and prediction of strains in the magnetic ferrite cores because of their brittleness. Ferrite strains were measured using a combination of resistive strain gauges and non-metallic Fibre Bragg Grating (FBG) sensors. Coupled electromagnetic-thermal-structural simulations were conducted to predict temperature and strains in the system, with temperature-dependent properties obtained through physical testing. At an ambient temperature of 50°C, the temperature in the middle of the copper litz wire coil was predicted to be 100°C in both the suspended and embedded case. There was excellent correlation to experimental results, with a difference of less than 10% for most temperature measurements. When energized, the pad was predicted to experience an upward bow due to its temperature rise, resulting bending strains in the ferrite cores. At an ambient temperature of 50°C, maximum tensile strain in the ferrites of the embedded pad was measured to be 62 microstrain (με), with a root-mean square error that was 18 με across three sensors. The experimental and validated numerical methodology can be applied to full-scale operational IPT pads to analyse and improve their thermal-mechanical performance.

Intracranial compliance (ICC) plays a pivotal role in understanding the underlying mechanisms of various brain disorders and is of great clinical importance. Therefore, addressing the challenges in practical application of ICC is crucial for neurosurgeons. This study explored the significance of ICC assessment considering the time-dependency of specific brain disorders through two distinct approaches: short and large time elapsed (TE) in measuring volume or intracranial pressure (ICP) changes in the ICC equation (∆Volume/∆ICP). Variations in ICC values were observed across various ICC assessment methods and different TE values. Notably, the compensatory response of the brain exhibited non-monotonic and variable changes in a large TE for certain brain disorders, diverging from patterns observed in short TE assessments. Furthermore, the recovery behavior of the brain changed under different brain disorders when exposed to short and long TE conditions. These findings emphasized the dynamic nature of ICC and provided valuable insights into the correct practical assessment of ICC by selecting the appropriate TE, as well as considering the differences in strain rates and loading durations on the brain in different brain disorders. These insights also shed light on the reasons why, despite its clinical significance, ICC monitoring has not yet become a standard component of clinical care, unlike ICP monitoring.

This study focused on the precise detection and concordant analysis of circulating tumor cells (CTCs) to verify the usefulness of CTCs as promising clinical markers. CTCs are traditionally achieved using immune-fluorescence and morphological techniques. By combining two prostate cancer-specific genes (PSA and PSMA) and two epithelial-specific genes (EpCAM and KRT19), the CTC detection efficiency can be enhanced. The detection rates of localized prostate cancer (LPC), locally advanced prostate cancer (LAPC), metastatic hormone-sensitive prostate cancer (mHSPC), and metastatic castration-resistive prostate cancer (mCRPC) were 63.04 % (29/46), 70.59% (34/51), 94.34% (50/53), and 90% (126/140), respectively. Subsequent correlation analysis between the four genes, baseline PSA, and CTC count revealed that only the CTC count correlated with baseline PSA in the localized stages of prostate cancer, whereas all four genes were correlated with baseline PSA and CTC count in the metastatic stages of prostate cancer. The precise detection of CTCs using both numerical and transcriptomic analyses can improve the accuracy of biomarker investigations. This study provides valuable insights into the limitations of serum PSA testing and offers a promising alternative to diagnose and manage prostate cancer via the CTC number and specific genes for prostate cancer.

In Geo Polymer bricks (GPB), fly ash content which is a waste from power plants is converted into bricks by chemical treatment. GPB can be dried by using appropriate curing methods. Conven-tionally electric oven curing is one of the prominent methods. Using solar dryer instead of elec-trical oven gives added advantage of saving high grade electrical energy. So in this work solar dryer with PCM (Phase Change materials) Paraffin Wax and without PCM is used for curing ap-plication. GPB are gaining added advantage when compared to conventional bricks like cement and sand bricks in terms of strength. GPB has been taken as specimen for comparing the com-pressive, tensile split strength and flexural strength by electrical energy based curing and solar energy based curing. It is experimentally observed that solar energy based curing with PCM and without PCM exhibits higher compressive strength, higher tensile split strength and flexural strength when compared to electrical energy based curing. Solar curing with PCM shows higher compressive strength, higher tensile split strength and flexural strength when compared to Solar curing without PCM. Open solar curing is a traditional technique but nowadays aggressive cli-matic conditions can lead to severe damage of Geo polymers. The novelty of this work is to suggest to study the effect of PCM like paraffin wax in solar drying on curing time, mechanical properties of GPB.

This study is based on the fatty acid and amino acid profile of 7 edible insect species: Acheta domesticus, Alphitobius diaperinus, Blaptica dubia, Galleria mellonella, Locusta migratoria, Tenebrio molitor and Zophobas morio. The fatty acid distribution within lipid classes (neutral lipids, glycolipids and phospholipids) was studied, while the amino acid profile was used to calculate the species-specific nitrogen-protein conversion factor (Kp). The profiles were used to evaluate the nutritional quality of the lipids and proteins. Oleic acid was the predominant fatty acid in all insects except for A. domesticus, in which a larger percentage of linoleic acid was found. The majority of the lipids were neutral lipids. L. migratoria showed a remarkably high content of α-linolenic acid in its phospholipid fraction, while T. molitor phospholipids were the only fraction in which a measurable amount of docosahexaenoic acid was found. Overall, in most insects, the phospholipid fraction had the highest polyunsaturated fatty acid content compared to the other classes, which may be protective in terms of autoxidative stability. Kp values in the range of 4.17 to 6.43 were obtained. Within the nutritional quality indices, all insects showed healthy fatty acid and high quality amino acid profiles.

Myocardial involvement among critical patients with coronavirus disease 2019 (COVID-19) has a worse outcome. The occurrence of an imbalance in oxygen supply results in the release of pro-inflammatory cytokines which leads to increased ventilation support requirement and increase risk of mortality. Our aim was to evaluate the association between hs-Troponin I level and global longitudinal strain as evidence of myocardial involvement among critical COVID-19 patients. Methods. We performed prospective cohort study from February 1st – July 31st, 2021 at Dr. Soetomo General Hospital, Surabaya as referral center for COVID-19 care. Of the 65 critical COVID-19 included, 41 (63.1%) were men, with a median (interquartile range) age of 51.0 years (20.0-75.0).Subjects were recruited according to WHO criteria for severe COVID-19 and CDC criteria for myocarditis. All subjects recruited were examined using echocardiography to measure global longitudinal strain (GLS) and blood samples were taken to measure hs-Troponin. Subjects were then followed to assess their needs for mechanical ventilation and in-hospital mortality. Severe COVID-19 subjects with cardiac injury were associated with an increased need for intubation (78.5%) and an increased incidence of myocarditis (50.8%). There was an association between the use of intubation and the risk of mortality in patients (66.7% vs. 33.3%, p-value &lt;0.001). Both reduced GLS and increased hs-troponin are associated with increased myocarditis (p-value &lt;0.001 and 0.004 respectively). Reduced GLS is associated with higher mechanical ventilation needs (12.17 + 4.79 vs.15.65 + 4.90, p-value 0.02) and a higher mortality rate (11.36 + 4.64 vs. 14.74 + 4.82; p-value 0.005). Increased hs-troponin is associated with higher mechanical ventilation needs (25.33% vs. 3.56%, p-value 0.002) and a higher mortality rate (34.57% vs. 5.76%, p-value 0.002). Compared with contemporary controls, critical COVID-19 patients with myocardial involvement and elevated cardiac troponin level are associated with higher mechanical ventilation needs and a higher mortality rate.

Podocalyxin (PODXL) overexpression is associated with poor clinical outcomes in various tumors. PODXL is involved in tumor malignant progression through the promotion of invasiveness and metastasis. Therefore, PODXL has been considered as a promising target of monoclonal antibody (mAb)-based therapy. However, PODXL also plays an essential role in normal cells such as vascular and lymphatic endothelial cells.Therefore, cancer-specificity or selectivity is required for the reduction of adverse effects on normal cells. Here, we developed an anti-PODXL cancer-specific mAb (CasMab), PcMab-6 (IgG₁, kappa), by immunizing mice with soluble PODXL ectodomain derived from a glioblastoma LN229 cell.PcMab-6 reacted with the PODXL-positive LN229 cells, but not with PODXL-knockout LN229 cells in flow cytometry. Importantly, PcMab-6 recognized pancreatic ductal adenocarcinoma (PDAC) cell lines (MIA PaCa-2, Capan-2, and PK-45H), but did not react with normal lymphatic endothelial cells (LECs). In contrast, one of the non-CasMabs, PcMab-47 showed high reactivity to both the PDAC cell lines and LECs. Next, we engineered PcMab-6 into a mouse IgG_2a type (PcMab-6-mG_2a) and a humanized IgG₁-type (humPcMab-6) mAbs, and further produced the core fucose-deficient types (PcMab-6-mG_2a-f and humPcMab-6-f, respectively) to potentiate the antibody-dependent cellular cytotoxicity (ADCC). Both PcMab-6-mG_2a-f and humPcMab-6-f exerted ADCC and complement-dependent cellular cytotoxicity in the presence of effector cells and complements, respectively. In the PDAC xenograft model, both PcMab-6-mG_2a-f and humPcMab-6-f exhibited potent antitumor effects. These results indicated that humPcMab-6-f could apply to antibody-based therapy against PODXL-expressing pancreatic cancers.

The mechanical behavior, microstructures as well as the crystallographic textures of the Ti57-Nb43 alloy were investigated on cylindrical specimens compressed at high temperatures, in the range of 700-1000 °C, and strain rates between 0.001 and 1.0 s-1. Hardening, followed by softening behaviours were observed as a function of strain, due to the occurrence of dynamic recrystallization/recovery in hot deformation. The modified five-parameter Voce type equation described well the stress-strain curves, but for the present alloy, it was also possible with only four parameters. A new two-variables polynomial function was employed on the four parameters that described well the flow curves as a direct function of temperature and strain rate. It permitted to reduce the number of parameters and had the predictive capacity for the flow stress at any temperature, strain, and strain rate in the investigated range. The crystallographic textures were similar at all temperatures with an increase of intensity from 900 °C. The textures could be characterized by a double &lt;100&gt; and &lt;111&gt; fiber and a unique component of (001)&lt;110&gt;, the latter inherited from the initial hot rolling texture. Viscoplastic polycrystal self-consistent deformation modeling reproduced the measured textures showing that dynamic recrystallization did not alter the development of the deformation texture, only increased it intensity.

The COVID-19 pandemic was declared in March 2020 and is still ongoing. The course of the epidemic remains uncertain, and mutations in the coronavirus, as well as the emergence of new variants of concern, make it possible that there will be periodic surges in the number of cases. Moreover, it is not clear how quickly and to what extent the effectiveness of vaccination will decline as the virus continues to mutate. One possible solution to combat the rapidly mutating coronavirus is the development of pan-coronavirus vaccines that stimulate the production of antibodies against conserved elements of the virus. Another approach could be the creation of safe vaccine platforms that can be rapidly adapted to deliver new, specific antigens in response to viral mutations. Recombinant probiotic microorganisms that can produce viral antigens by inserting specific viral DNA fragments into their genome show promise as a platform and vector for mucosal vaccine antigen delivery. With a well-established safety profile and the ability to transform into vaccine candidates, probiotic bacteria have significant research potential. The authors of this study have developed a convenient and universal technique for inserting the DNA sequences of pathogenic bacteria and viruses into the gene that encodes the pili protein of the probiotic strain E. faecium L3. The paper presents data on the immunogenic properties of two E. faecium L3 vaccine strains, which produce two different fragments of the coronavirus S1 protein, and provides an assessment of the protective efficacy of these oral vaccines against coronavirus infection in Syrian hamsters.

The Suter curves for Wh and Wm characteristics of collected and the first time presented Four-quadrant (4Q) diagrams of 11 radial pump-turbine models with different specific speeds (nq=24.34, nq=24.8, nq=27, nq=28.6, nq=38, nq=41.6, nq=41.9, nq=43.83, nq=50, nq=56, and nq=64.04) are given in the paper, as well as the Suter curves for 2 pump models (nq=25, and nq=41.8) which were already published in the literature. These 11+2 curves were analyzed to establish a certain universal law of behavior in dependence on the specific speed. For the determination of existing laws in behavior, the fitting procedure using the Regression and Spline methods was used. The paper presents a research plan and structures that include: data collection of four-quadrant diagrams for models of pump-turbines and pumps with different specific speeds (nq), the procedure of recalculation of Four-quadrant diagrams of the models into Suter curves for Wh and Wm characteristics, the definition of the optimal point for the pump and turbine operating mode in pump-turbine models for different specific speeds, and developing numerical models in the MATLAB program to obtain the Universal Equation for the Wh and Wm characteristics. The scientific contribution of this paper is the firstly published original mathematical curve named Universal Equation for the Wh and Wm characteristics for radial pumps and pump-turbines. Application of the equation has been demonstrated at the pumping station where two radial pumps are installed. The calculation of transient processes was performed using the numerical model developed by the authors in the mathematical program MATLAB. Comparison of the transition process results has been made for the two cases - when input data in the numerical model have been firstly used with the values of Suter curves for Wh and Wm characteristics obtained by recalculation from the Four-quadrant operating characteristics (Q11, n11, M11) of model’s specific speed, and then secondly with the values of the Suter curves for Wh and Wm characteristics obtained from the Universal Equation.

This study investigates the microstructures and deformation mechanism of hetero-structured pure titanium under different high strain rates (500 s-1，1000 s-1，2000 s-1). The influence of strain rate on the deformation mechanism is examined. As the strain rate increases, the dominance of dislocation slip decreases while deformation twinning becomes more prominent. Notably, at a strain rate of 2000s-1, nanoscale twin lamellae are activated within grain with a size of 500nm, which is a rarely observed phenomenon in pure Ti. Additionally, martensitic phase transformation is also identified. These findings can greatly enhance our understanding of the mechanical responses of Ti and broaden the potential applications of Ti in dynamic deformation scenarios.