Verification of inclusivity of molecular detection methods gives indications on the reliability of viral infections diagnosis because of the tendency of viral pathogens to undergo sequence variation. This study was aimed to select inclusive probe based reverse transcription quantitative PCR (RT-qPCR) assays for the diagnosis of the most widespread and detrimental viruses infecting honeybees, namely the acute bee paralysis virus (ABPV), the black queen cell virus (BQCV), the chronic paralysis bee virus (CBPV), the deformed wing virus variants A (DWVA) and B (DWVB), and the sacbrood virus (SBV). Therefore, detection methods previously described were re-evaluated in silico for specificity and inclusivity. Based on this evaluation, selected methods were modified or new ones were designed and tested in duplex RT-qPCR reactions. The limits of detection (LODs), effect of multiplexing on sensitivity and viral RNA quantification potential in bees and hive debris were assessed. This study made available diagnostic assays able to detect an increased number of virus variants compared to previously described tests and two viral pathogens in a single PCR reaction.

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

Given the increased provision of international exchange programmes in higher education, this paper examines students’ perceptions of their learning process in one Erasmus+ programme in Food Innovation and Product Design. Using evaluation model of international exchange programme and triple helix model as the analytical framework, students’ testimonials from 2015–2021 were analysed using a critical discourse analysis. EU and non-EU students had similar perceptions of learning outcomes related to knowledge of the food innovation industry, but non-EU students had a stronger sense of awareness of both the international context and multicultural interaction.

In this report we describe the case of a healthy, young, athletic woman who developed acute lymphoblastic leukaemia (ALL)/lymphoblastic lymphoma (LBL) after receiving the second dose of the Pfizer/BioNTech modified mRNA (modRNA) COVID-19 genetic vaccine (marketed as Comirnaty^®). The first dose of the genetic vaccine did not appear to illicit any noticeable side effects, but within 24 hours of the second dose the patient suffered widespread and intensifying bone pain, fever, vomiting, and general malaise. Due to the persistence of the symptoms, the patient underwent a series of tests and examinations including a full laboratory workup, a consult with a clinical immunologist and rheumatologist, a Positron Emission Tomography (PET) imaging, as well as an osteomedullary biopsy. These together led to a definitive diagnosis of ALL. A time interval of 16 weeks from the second vaccination to the diagnosis of cancer was noted. Several similar cases with identical pathology which developed after the modRNA COVID-19 vaccination, are described in case reports in the scientific literature. The massive and indiscriminate use of genetic vaccines to fight COVID-19 is raising serious concerns about their safety and about the technology platform as a whole for this purpose. Growing evidence is accumulating regarding the biodistribution and persistence of the modRNA which can reach, thanks to the lipid nanoparticles, a multitude of tissues and organs of the body, including the bone marrow and other blood-forming organs and tissues. Moreover, there is evidence that the modRNA vaccines display a particular tropism for the bone marrow, influencing the immune system at multiple levels and being able to trigger not only autoimmune-based pathologies, but also neoplastic mechanisms. The aim of this article is to assess, on the basis of the available scientific literature, the risk of developing haematopoietic cancers after modRNA vaccination, and to investigate the potential genetic mechanisms involved in the pathogenesis of disease.

Efficient triaging and referral assessment are critical in ensuring prompt medical intervention in the Community Health Care (CHC) system. However, the existing triaging systems in many Community Health Services are an intensive, time-consuming process and often lack accuracy, particularly for various symptoms that might represent heart failure or other health-threatening conditions. There is a noticeable limit of research papers describing AI technologies for triaging patients. This paper proposes a novel quantitative data-driven approach using machine learning (ML) modelling to improve the community clinical triaging process. Furthermore, this study aims to employ the feature selection process and machine learning power to reduce the triaging process’s waiting time and increase accuracy in clinical decision-making. The model was trained on medical records of “Heart Failure” patients’ dataset, which included demographics, past medical history, vital signs, medications, and clinical symptoms. A comparative study was conducted using the list of machine learning algorithms where XGBoost demonstrated the best performance among other ML models. The triage levels of 2,35,982 patients achieved an accuracy of 99.94%, precision of 0.9986, recall of 0.9958, and f1-score of 0.9972 within 0.059 seconds. The proposed diagnostic model can be implemented for the CHC decision system and be developed further for other medical conditions.

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell culture due to various limitations of in vivo testing. Unfortunately, in vitro cell culture fails to provide an accurate microenvironment, and in vivo cell culture is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The key component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

We demonstrate that multiple well-known metrics, such as the Schwarzschild metric and the extremal solution of the Reissner-Nordstr ̈om metric, can be expressed in what we will call thermodynamic form. These formulations appear to be valid for all Rs = ct growing black holes and, therefore, also within the framework of Rh = ct growing black hole cosmology. However, the metrics can also be applied to non-black hole gravitational objects as long as one calculates the CMB and Hawking temperature of the hypothetical black hole from the gravitational mass.

This study delves into the realm of potential therapeutics for breast cancer by conducting a comprehensive docking simulation and virtual screening analysis using Autodock Vina Algorithm. The focus based on the human epidermal growth factor receptor 2 (HER2), a key protein associated with various cancers, particularly in the context of breast cancer.The results reveal compelling insights into the binding interactions of several natural compounds and drugs with HER2. Notably, Acebilustat, Bemcentinib, and Amentoflavone exhibit outstanding binding energies, averaging around -10 kcal/mol, suggesting strong and favorable interactions with the HER2 target.These encouraging findings not only emphasize the potential biological significance of these compounds but also hint at their potential usefulness in fighting breast cancer.Their promising binding affinities with HER2 position them as potential candidates for further investigation and development as therapeutic agents against breast cancer.

This study investigates the potential antimicrobial utility of the natural substance Amentoflavone against four dangerous bacterial strains—Mycobacterium tuberculosis, Helicobacter pylori, Haemophilus influenzae, and Pseudomonas aeruginosa. Utilizing molecular docking studies, are assessed the binding interactions between Amentoflavone and key protein targets crucial for the viability of these bacteria. The findings suggest promising binding affinities, particularly in the active sites of Aminoglycoside 2'-N-acetyltransferase, Thioredoxin Reductase, N-acetylneuraminate Lyase, and Glucose-1-phosphate Thymidylyltransferase in the respective bacterial strains. While these in silico results provide initial insights, further in vitro and in vivo experiments are essential to validate the biological relevance and efficacy of Amentoflavone as a potential antimicrobial agent against these bacterial pathogens.

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception. p38 mitogen-activated protein kinase (p38) is downstream of several signaling pathways specific to treatment resistance and progression. Therefore, in recent years, developing therapeutic alternatives directed at p38 MAPK has been of great interest, in order to reverse chemotherapy resistance and prevent progression. In this review, we discuss recent findings on the role of p38, including recent advances in our understanding of its expression and activity as well as its isoforms, and its possible clinical role based on the mechanisms of resistance and progression in multiple myeloma.

This paper explores the interactions of dynamic dark energy with other components of the cosmos, such as dark matter and baryonic matter, and its wide-ranging implications in cosmology. By investigating the interplay between dynamic dark energy and the universe's large-scale structure, we aim to provide a deeper understanding of cosmic evolution and the behavior of dark energy in different cosmological epochs. We also examine the potential of dynamic dark energy to offer novel insights into long-standing cosmological puzzles and their impact on the formation and evolution of cosmic structures.

Chinese calligraphy, revered globally for its therapeutic and mindfulness benefits, encompasses styles such as Regular (Kai Shu), Running (Xing Shu), Official (Li Shu), and Cursive (Cao Shu) scripts. Beginners often start with Regular script, advancing to more intricate styles like Cursive. Each style, marked by unique historical calligraphers' contributions, requires learners to discern distinct nuances. The integration of AI in calligraphy analysis, collection, recognition, and classification are pivotal. This study introduces an innovative Convolutional Neural Network (CNN) architecture, pioneering the application of CNN in the classification of Chinese calligraphy. Focusing on the four principal calligraphers' styles from the Tang dynasty (690-907 A.D), this research spotlights the era when the traditional regular script font (Kai Shu) was refined. A comprehensive dataset of 8282 samples from these calligraphers, representing the zenith of regular style, was compiled for CNN training and testing. The model distinguishes personal styles for classification, showing superior performance over existing networks. Achieving 89.5-96.2% accuracy in calligraphy classification, our approach underscores the significance of CNN in both font and artistic style categorization. This research paves the way for advanced studies in Chinese calligraphy and its cultural implications.

Chronological frameworks based on artefact typologies are essential for interpreting the archaeological record, but they inadvertently treat transitions between phases as abrupt events and disregard the temporality of transformation processes within and between individual phases. This study presents an absolute chronological investigation of a dynamic material culture from Early Iron Age urnfields in Denmark. The chronological framework of Early Iron Age in Southern Scandinavia is largely unconstrained by absolute dating, primarily due to it coinciding with the so-called ‘Hallstatt calibration plateau’ (c.750 to 400 cal BC), and it is difficult to correlate it with Central European chronologies due to a lack of imported artefacts. This study applies recent methodological advances in radiocarbon dating and Bayesian chronological modelling, specifically a statistical model for wood-age offsets in cremated bone and presents the first large-scale radiocarbon investigation of regional material culture from Early Iron Age in Southern Jutland, Denmark. Dated material is primarily cremated bone from 111 cremation burials from three urnfields. The study presents absolute date ranges for 16 types of pottery and 15 types of metalwork, which include most of the recognised metalwork types from the period. This provides new insights into gradual change in material culture, when certain artefact types were in production and primary use, how quickly types were taken up and later abandoned, and distinguishing periods of faster and slower change. The study also provides the first absolute chronology for the period, enabling correlation with chronologies from other regions. Urnfields were introduced at the Bronze-Iron Age transformation, which is often assumed to have occurred c.530-500 BC. We demonstrate that this transformation took place in the 7^th century BC, however, which revives the discussion of whether the final Bronze Age period VI should be interpreted as a transitional phase to the Iron Age.

Real-Time Kinematic (RTK) is currently the most widely used method for positioning using Global Navigation Satellite Systems (GNSS) due to its accuracy, efficiency and ease of use. In forestry, position is a critical factor for numerous applications, with GNSS nowadays the preferred solution for obtaining such data. However, the decreased performance of GNSS observations in challenging environments, such as under the forest canopy, must be considered. This paper analyzes the performance of a survey-grade GNSS receiver under coniferous/deciduous tree cover, with short observation times of 30 seconds and corrections received in the field from a Continuously Operating Reference Station (CORS) of the national RTK network in Romania. 84 test points were determined, randomly distributed under the canopy, with reference data collected by topographical surveys using total station equipment. Relatively good accuracies were obtained, especially for horizontal position (RMSEs of 1.47 – 2.07 meters). The variation of GNSS performance under the different forest compositions was found to be statistically significant, while GNSS-specific factors such as DOP values only influenced the precision and not the accuracy of observations. We established that this methodology offers sufficient accuracy, application-dependent, even if the majority of GNSS solutions were code-based, rather than carrier phase-based, due to strong interference from the vegetation.

The autonomous displacement and displacement measurement functions of the maglev ruler are performed by the mover core. The stability of the four magnetic field in air gaps and the levitation position of the maglev ruler is one of the key factors for the stability of the thrust force on the power core, and it is also one of the key factors for ensuring the precision of the maglev ruler. There is cross-coupling between the two ends of the mover core of the maglev ruler, resulting in a strongly coupled, nonlinear, multi-input and multi-output system for the levitating system of the maglev ruler. This paper establishes a mathematical model for the levitating system of the maglev ruler, and designs a levitating control system for the maglev ruler based on ADRC control algorithm to achieve decoupling and disturbance suppression. Through simulation analysis and experimental testing of the levitating system with starting and disturbance, it is proved that the levitating control system of the maglev ruler has good dynamic characteristics, static characteristics, and robustness.

Constructing a globally consistent high-precision map is essential for the application of mobile robots. Existing optimization-based mapping methods typically constrain robot states in pose space during the graph optimization process, without directly optimizing the structure of the scene, thereby causing the map to be inconsistent. To address the above issues, this paper presents a three-dimensional (3D) LiDAR mapping framework (i.e., BA-CLM) based on LiDAR bundle adjustment (LBA) cost factors. We propose a multivariate LBA cost factor, which is built from a multi-resolution voxel map, to uniformly constrain the robot poses within a submap. The framework proposed in this paper applies the LBA cost factors for both local and global map optimization. Experimental results on several public 3D LiDAR datasets and a self-collected 32-line LiDAR dataset demonstrated that the proposed method achieves accurate trajectory estimation and consistent mapping.

Vitronectin is a glycoprotein, present in plasma and extracellular matrix, implicated in cell migration. The high amount of vitronectin found in neuroblastoma biopsies was associated with poor prognosis. However, there are almost no studies of vitronectin levels in neuroblastoma cell culture media nor in plasma of neuroblastoma patients. Vitronectin concentration in culture media of four neuroblastoma cell lines grown in monolayer and in 3D-models, and in plasma of 114 neuroblastoma patients, was quantified using ELISA. Three of the neuroblastoma cell lines secreted vitronectin to culture media when cultured in monolayer and 3D-models. Vitronectin release was higher by neuroblastoma cells cultured in 3D-models than in monolayer, and was still great when cells grown in 3D-scaffolds with cross-linked vitronectin. Vitronectin secretion occurred independently of cell numbers in cultures. Its concentration in plasma of neuroblastoma patients ranged between 52.4 and 870µg/mL (median, 218µg/mL). A ROC curve was used to establish a cutoff of 361µg/mL, above which patients over 18-months-old had worse prognosis (p=0.0018). Vitronectin could be considered a new plasma prognostic biomarker in neuroblastoma, and warrants confirmation in collaborative studies. Drugs inhibiting vitronectin interaction with cells and/or extracellular matrix could represent a significant improvement in survival for neuroblastoma patients.

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

Biliary tract cancers, including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer, are a heterogeneous group of cancers with distinct molecular characteristics in each anatomic and pathological subtype. The pathological classification of BTC includes grossly classifiable growth patterns, such as mass-forming, periductal infiltrating, and intraductal growing. The small duct and large duct types of intrahepatic cholangiocarcinoma have been recently introduced in the WHO classification. Typical clinical presentations and various radiological, endoscopic, and molecular modalities for diagnosis are described in detail. To overcome the limitations of traditional tissue acquisition, new diagnostic modalities are being investigated. In fact, the treatment landscape is evolving rapidly owing to the emergence of distinct subgroups harboring unique molecular alterations with corresponding targeted therapies. In addition, we highlight the key points in the diagnostic process in real-world clinical practice for biliary tract cancer.

Myelodysplastic neoplasm (MDS) is a heterogenous clonal disorder of hemopoietic stem cells charac-terized by cytomorphologic dysplasia, ineffective hematopoiesis, peripheral cytopenias and risk of pro-gression to Acute Myeloid Leukemia (AML). Our understanding of this disease has continued to evolve over the last century. More recently prognostication and treatment are determined by cytogenetic and molecular data. Specific genetic abnormalities such as 5q deletion (del 5q), TP53 inactivation and SF3B1 mutation, are increasingly associated with disease phenotype and outcomes, as reflected in the recently updated 5th edition of the World Health Organization Classification of Hematolymphoid Tumors (WHO5) and International Consensus Classification 2022 (ICC 2022) classifications. Treatments are in-creasingly being tailored for patient specific phenotypes, and trials exploring the efficacy of targeted treatments are ongoing in this era of precision medicine.

Neurocutaneous disorders, also known as phakomatoses, are congenital and acquired syndromes resulting in simultaneous neurologic and cutaneous involvement. In several of these conditions, the genetic phenomenon is understood, providing a pivotal role in the development of therapeutic options. This review encompasses the discussion of the genetic and clinical involvement of neurocutaneous disorders and examines clinical management and treatment options. With the current advances in genetics, the role of precision medicine and targeted therapy plays a substantial role in addressing management of these conditions. The interconnectedness between therapeutic options highlights the importance of precision medicine in treating each disorder’s unique molecular pathway. This review provides an extensive synthesis of ongoing and current therapeutics in the management of such clinically unique and challenging conditions.

The current review comprehensively explores the multifaceted landscape of anaplastic lymphoma kinase (ALK) and its pivotal role, specifically within non-small cell lung cancer (NSCLC). It traces the trajectory of ALK's discovery, notably its fusion with nucleolar phosphoprotein (NPM)-1 in anaplastic large cell non-Hodgkin's lymphoma (ALCL) in 1994. It unfolds the subsequent impact of ALK gene alterations across various malignancies, including inflammatory myofibroblastoma (IMT) and NSCLC. The prevalence of intricate ALK rearrangements affecting roughly 3–5% of NSCLC patients prompted the approval of six ALK-tyrosine kinase inhibitors (TKIs) by 2022, revolutionizing the treatment landscape for advanced metastatic ALK+ NSCLC. Second-generation TKIs like alectinib, ceritinib, and brigatinib have notably emerged to combat resistance issues initially associated with crizotinib, the pioneer ALK-TKI approval. Moreover, this review delves into the intersection of ALK and immunotherapy, exploring the potential of immune checkpoint inhibitors in ALK-altered NSCLC tumors. Despite promising preclinical data, challenges encountered in trials evaluating combinations like nivolumab-crizotinib, primarily due to severe hepatic toxicity, underscore the need for cautious exploration of these novel approaches. Additionally, the review delves into innovative avenues such as ALK vaccines and biosensors, shedding light on their promising potential within ALK-driven cancers. This comprehensive analysis encompasses molecular mechanisms, therapeutic strategies, and immune interactions associated with ALK-rearranged NSCLC. Ultimately, the review is a pivotal resource guiding future research and therapeutic interventions in ALK-targeted therapy for NSCLC.

Precision agriculture including camera-guided row detection and hydraulic steering are often used as an alternative because crop damage can be decreased and driving speed can be increased comparable to herbicide applications.The effects of different approaches as uncontrolled (UC), mechanical weed control (MWC), herbicide weed control (HWC) and mechanical + herbicide control (MWC+HWC) on weed density and yield of sugar beet were tested and evaluated in two trials (2021 and 2022) in South Transylvania at the tested intervals BBCH 19 and 31. Weed control efficacy (WCE) depends on the emergence of the weeds and a good timing of weed controls in all the trials and methods, though the highest yield of sugar beet roots was recorded in the treatment MWC+HWC, with an increase up to 12-15% (56.48 t ha-1) yield from HWC (50.22 t ha-1) and a yield increase of more than 35- 40% than MWC (42.34 t ha-1). Our trials show that is possible to increase yield and have less chemical applications with the introduction of the new precision technologies in agriculture included here the sensor-guided mechanical controls.

Leaf area estimation is a critical component in the study of plant growth and productivity within agricultural systems. This research introduces the LeafArea package, a specialized tool designed to calculate the leaf area of six distinct Andean fruit species: S. quitoense, S. betaceum, P. peruviana, R. fruticosus, P. ligularis and P. edulis. Leveraging response variables such as species type, leaf length and width, the package employs advanced machine learning algorithms to estimate leaf area accurately. The primary focus of the study is to identify the most effective model for describing the relationship between leaf width, length, and area for each plant species. Currently, the LeafArea package utilizes four different machine learning algorithms, namely generalized linear model (GLM), generalized linear mixed model (GLMM), Random Forest and XGBoost. Among these, XGBoost stands out as a top-performing algorithm, exhibiting exceptional predictive accuracy. The evaluation metrics employed in the program provide valuable insights for researchers, aiding in informed decision-making. Specifically, XGBoost demonstrates significantly lower prediction errors and approaches a near-perfect R2 value, emphasizing its potential to enhance predictive accuracy. These results underscore the efficacy of machine learning techniques, as a compelling choice for researchers seeking precise and robust predictions in leaf area estimation. The LeafArea package thus represents a valuable tool for advancing our understanding of plant growth dynamics, resource allocation, and overall productivity within agricultural ecosystems.

The advancement of precision medicine in medical care has led behind the conventional symptom-driven treatment process by allowing early risk prediction of disease through improved diagnostics and customization of more effective treatments. It is necessary to scrutinize overall patient data alongside broad factors to observe and differentiate between ill and relatively healthy people to take the most appropriate path toward precision medicine, resulting in an improved vision of biological indicators that can signal health changes. Precision and genomic medicine combined with artificial intelligence have the potential to improve patient healthcare. Patients with less common therapeutic responses or unique healthcare demands are using genomic medicine technologies. AI provides insights through advanced computation and inference, enabling the system to reason and learn while enhancing physician decision-making. Many cell characteristics, including gene up-regulation, proteins binding to nucleic acids, and splicing, can be measured at high throughput and used as training objectives for predictive models. Researchers can create a new era of effective genomic medicine with the improved availability of a broad range of data sets and modern computer techniques such as machine learning. This review article has elucidated the contributions of ML algorithms in precision and genome medicine.

The emergence of three-dimensional human organoids has opened the door for development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. Mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource- and time-intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell-cell and cell-stromal interactions, tumor microenvironment, and therapeutic responsiveness. PDO models and drug screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant timeframes and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.

Optical sensor data can be used to determine changes in anthocyanins, chlorophyll and soluble solids content (SSC) in apple production. In this study, visible and near-infrared spectra (729 to 975 nm) were transformed to SSC values by advanced multivariate calibration models i.e. partial least square regression (PLSR) in order to test the substitution of destructive chemical analyses through non-destructive optical measurements. Spectral field scans were carried out from 2016 to 2018 on marked ’Braeburn’ apples in Southwest Germany. The study combines an in-depth statistical analyses of longitudinal SSC values with horticultural knowledge to set guidelines for further applied use of SSC predictions in the orchard to gain insights into apple carbohydrate physiology. The PLSR models were investigated with respect to sample size, seasonal variation, laboratory errors and the explanatory power of PLSR models when applied to independent samples. As a result of Monte Carlo simulations, PLSR modelled SSC only depended to a minor extent on the absolute number and accuracy of the wet chemistry laboratory calibration measurements. The comparison between non-destructive SSC determinations in the orchard with standard destructive lab testing at harvest on an independent sample showed mean differences of 0.5 % SSC over all study years. SSC modelling with longitudinal linear mixed-effect (LME) models linked high crop loads to lower SSC values at harvest and higher SSC values for fruit from the top part of a tree.

Despite recent scientific advancements, there is a gap in the use of technology to measure signals, behaviors, and processes of adaptation physiology of farm animals. Sensors present exciting opportunities for sustained, real-time, non-intrusive measurement of farm animal behavioral, mental, and physiological parameters with the integration of nanotechnology and instrumentation. This paper critically reviews the sensing technology and sensor data-based models used to explore biological systems such as animal behavior, energy metabolism, epidemiology, immunity, health, and animal reproduction. The use of sensor technology to assess physiological parameters can provide tremendous benefits and tools to overcome and minimize production losses while making positive contributions to animal welfare. Of course, sensor technology is not free from challenges; these devices are at times highly sensitive and prone to damage from dirt, dust, sunlight, colour, fur, feathers, and environmental forces. Rural farmers unfamiliar with the technologies must be convinced and taught to use sensor-based technologies in farming and livestock management. While there is no doubt that demand will grow for non-invasive sensor-based technologies that require minimum contact with animals and can provide remote access to data, their true success lies in the acceptance of these technologies by the livestock industry.

Background: As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: i) determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large case-control studies, are applicable to blood pressure control in subjects from a rural population; ii) measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and iii) identify other SNPs that may help understand patient-specific responses to an intervention. Methods and Results: We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) or Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. Conclusions: Identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine.

In this work, we explore Conjecture 1 proposed in the newly released pioneering paper “Volatility transformers: an optimal transport-inspired approach to arbitrage-free shaping of implied volatility surfaces” by Zetocha Valer, which posits that the “One-X” property is both a necessary and sufficient condition for convex order between non-negative continuous strictly increasing distributions with the same mean. We provide a counterexample demonstrating that the conjecture, as originally stated, does not hold. By examining stochastic orders, particularly the increasing convex order, and the “One-X” property, we propose an enhanced version of the conjecture which is shown to be valid. Furthermore, we discuss the implications of these findings in the context of equity implied volatility fitting and the construction of implied volatility surfaces, highlighting the challenges posed by real-market conditions. In the end, we propose several applications in implied volatility surface construction or simulation.

Heat exchangers play a vital role in numerous sectors like power generation and automotive manufacturing. Enhancing the energy efficiency of these exchangers stands as a significant hurdle. Utilizing nanofluids emerges as an optimal solution to augment heat transfer rates, leveraging their superior thermal conductivity while addressing economic constraints linked with traditional heat exchanger technologies. The motivation for this study is to consider the comprehensive synergistic features of MWCNTs, SiO₂, and hybrid MWCNTs–SiO₂ EG-based nanofluids in plate heat exchangers. This was achieved by simulating a plate heat exchanger using CFD (Fluent and Gambit softwares) considering the comparison of two SiO₂, MWCNTs, and their hybrid forms at different mass concentrations. The Reynolds-Averaged Navier-Stokes (RANS) method was employed to model turbulent flows, and the nanoparticles were compared in both single-phase and two-phase states, with their properties derived from experimental studies. Moreover, Nusselt number, convective heat transfer coefficient, and pressure drop variations were computed at different Reynolds numbers. The findings indicated an increase in the Nusselt number with the incorporation of the hybrid nanofluid, achieving a maximum enhancement of 11.19% in comparison to EG at a Reynolds number of 240 and a concentration of 0.86 wt.%. Noticeably, the pressure drop remained negligible at lower Reynolds numbers, exhibiting marginal variations up to 0.3% at higher Reynolds numbers. At a concentration of 0.86 wt.% and a Reynolds number of 480, the introduction of MWCNTs, hybrid, and SiO₂ nano-additives resulted in respective increases in the heat transfer coefficient by 21.02%, 10.76%, and 2.16% and corresponding alterations in pressure drop of 0.11%, 0.04%, and 0.02%.

Artificial intelligence (AI) driven language models have seen a rapid rise in development, deployment, and adoption over the last few years. This surge has sparked many discussions about their societal and political impact, including political bias. Bias is a crucial topic in the context of large models due to its far-reaching consequences on technology, politics, and society. It significantly influences public perception, decision-making, political discourse, and AI policy governance and ethics. This study investigates political bias through a comparative analysis of four prominent AI models: ChatGPT-4, Perplexity, Google Gemini, and Claude.Through a comprehensive analysis by systematically and categorically evaluating their responses to politically and ideologically charged tests and prompts, utilizing the Pew Research Center’s Political Typology Quiz, the Political Compass assessment, and ISideWith political party quiz, this study identifies significant ideological leanings and the nature of political bias within these models. The findings revealed that ChatGPT-4 and Claude exhibit a liberal bias, Perplexity is more conservative, while Google Gemini adopts more centrist stances. The presence of such biases underscores the critical need for transparency in AI development and the incorporation of diverse training datasets, regular audits, and user education to mitigate these biases. This analysis also advocates for more robust practices and comprehensive frameworks to assess and reduce political bias in AI, ensuring these technologies contribute positively to society and support informed, balanced, and inclusive public discourse, which will point towards neutrality.The results of this study add to the ongoing discourse about the ethical implications and development of AI models, highlighting the critical need to build trust and integrity in AI models. Additionally, future research directions have been outlined to explore and address the complex issue of bias in AI.

Grass pea (Lathyrus sativus L.) is a protein-rich crop that is resilient to various abiotic stresses, including drought. However, it is not cultivated widely for human consumption due to the neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid (β-ODAP), and its association with neurolathyrism. Though some varieties with low β-ODAP have been developed through classical breeding, the β-ODAP content is increasing due to genotype x environment interactions. This review covers grass pea nutritional quality, β-ODAP biosynthesis, mechanism of paralysis, traditional ways to reduce β-ODAP, candidate genes for boosting sulfur-containing amino acids, and the potential and targets of gene editing to reduce β-ODAP content. Recently, two key enzymes (β-ODAP synthase and β-cyanoalanine synthase) have been identified in the biosynthetic pathway of β-ODAP. We proposed four strategies through which the genes encoding these enzymes can be targeted and suppressed using CRISPR/Cas9 gene editing. Compared to its homology in Medicago truncatula, the grass pea β-ODAP synthase gene sequence and β-cyanoalanine synthase showed 62.9% and 95% similarity, respectively. The β-ODAP synthase converts the final intermediate L-DAPA into toxic β-ODAP whist β-cyanoalanine synthase converts O-Acetylserine into β-isoxazolin-5-on-2-yl-alanine. Since grass pea is low in methionine and cysteine amino acids, improvement of these amino acids is also needed to boost its protein content.

Present experimental study assesses the mechanical properties of glass/carbon/glass hybrid composite laminates after exposure to moisture and elevated temperatures for extended periods. The top and bottom layers of the hybrid laminates are glass fiber reinforced and the middle layer is carbon fiber reinforced with the matrix specified as a polymer material. The hybrid laminates were manufactured using the resin transfer molding method and their compressive and tensile properties were determined using a tensile testing machine. The material parameters such as the storage modulus, the loss modulus, and the damping factors of the laminates were identified using dynamic mechanical analysis as a function of the temperature and the vibration frequency. The experimental results on compressive and tensile properties revealed slight variations when the hybrid laminates were kept at low temperatures for extended periods. This might occur due to the increasing molecular cross-linking of the polymer network. As the temperature increased, compressive, tensile, storage modules, loss modulus, and damping factors decreased. This might occur due to the increasing mobility of the binder material. Particularly, the highest stiffness parameters were obtained on -80°C/GCG (Glass/Carbon/Glass) laminates due to the presence of beta transition on the glassy region. The relationships between the glass transitions and the targeted frequencies were characterized. The values of the glass transition shift towards higher temperatures as the frequency increases. This might occur due to a reduction in the gaps between the crosslinking of the epoxy network when the frequency increases. The accuracy of the storage modulus results was compared with the empirical models. The model based on the Arrhenius law provided the closest correlation. Meanwhile, another model was observed that was not accurate enough to predict when gamma and beta relaxations occur under a glassy state.

This paper presents a comparative study of fundamental similarity functions for Siamese networks in semantic textual similarity (STS) tasks. We evaluate various similarity functions using the STS Benchmark dataset, analyzing their performance and stability. Additionally, we introduce a multi-objective approach for optimal threshold selection. Our findings provide insights into the effectiveness of different similarity functions and offer a straightforward method for threshold selection optimization, contributing to the advancement of Siamese network architectures in STS applications.

Human papillomavirus (HPV), a DNA virus, causes one the most common sexually transmitted infections (STI), spreading through direct sexual contact to the anogenital and oropharyngeal regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals HPV causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). More than 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. The HPV driven OPCs present some unique infection driven cellular and molecular features, constituting distinct preventive, therapeutic and prognostic strategies, in contrast to HPV negative (HPV-) OPC. In this manuscript, we drive through the role of HPV, from a sexually transmitted infection to malignancy transformation landscape, while parsing through the significant immune response environment. In this comprehensive review we collate key literature around transmission and epidemiology of HPV, while addressing the current state of clinical management, diagnosis, prevention and screening strategies, that can help shed light on this critical area.

Dark pigmentation can be observed in various parts of the plant, ranging from foliage to petals to berries. The molecular basis of black pigmentation appears to vary among species, with anthocyanins playing a significant role, although specific anthocyanin types and their mechanisms differ. These findings suggest that the development of phenotypes is species-specific or varies between larger taxonomic groups; this is further supported by the polyphyletic nature of dark pigmentation. Additionally, several different regulatory mechanisms have been described for the occurrence of dark pigmentation. Firstly, the repression or knockout of the competing flavone biosynthesis has been shown to lead to darker pigmentation while another mechanism is based on the activation and upregulation of the anthocyanin biosynthesis genes in the presence of MYB transcription factors. Potential ecological functions of dark pigmentation were identified as the protection of the photosynthesis apparatus, camouflage against herbivores, and the attraction of pollinators. Promising industrial applications include microbial factories for the production of natural food colourants, induction of novel phenotypes for the ornamental plant industry and lastly the increase of anthocyanins within agriculturally relevant crops.

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

The energy transition is a challenge that affects all sectors, from transport to civil structures and industry. With reference to the industrial sector, the greatest need is the decarbonisation of industries energy-intensive, such as producers of iron and steel, aluminium, cement, petrochemicals, paper, etc. In particular, the steel industry is a hard to abate high-emissivity industry which due to chemical processes and high thermal demands (often above 500 °C) contributed to 7.4% of global CO₂ in the year 2021. This paper has explored the potential applications of hydrogen in the hard-to-abate sectors, highlighting its versatility and significance in decarbonization efforts. It provides an overview of hydrogen production methods, emphasizing the importance of sustainable and green hydrogen production. It reviews hydrogen production methods, storage, and potential in blended combustion. In the final part of the article, some considerations are introduced on the possible role of hydrogen in the steel sector (both as a supplementary fuel and as a reducing agent in innovative processes), showing how although there is potential for its inclusion as an element for the decarbonization, it is necessary to evaluate the energy balances of the various processes and the methods of hydrogen production very carefully, in order not to risk obtaining a marginal effect.

This paper examines the transformative journey of Artificial Intelligence (AI) agents from copilots to integral coworkers within diverse sectors. Beginning with a foundational overview, we delve into the historical evolution of AI agents, highlighting key technological milestones and the shift from simple automated tools to sophisticated decision-making systems capable of learning and adapting over time. We explore the capabilities of AI agents, including problem-solving, predictive analytics, and automation, and their applications across healthcare, business, and education, showcasing their role in diagnostics, customer service, and personalized learning, among other areas. We also address the integration of AI agents in the workplace, presenting strategies for collaboration between humans and AI, and outline the challenges and ethical considerations that accompany the development and deployment of AI technologies. A comprehensive tutorial provides insight into the development process of AI agents, emphasizing goal definition, data handling, algorithm selection, and ethical guidelines. We also consider the pathway towards Artificial General Intelligence (AGI) and the societal and ethical implications of widespread AI integration, proposing strategies for equitable and ethical AI use.

Based on our recent thermodynamic formulation of the Friedmann equation, we demon- strate how the age of the universe must be approximately 14.6 billion years. This is about 800 million years older than predicted by the Λ-CDM model and therefore greatly alleviates the early galaxy formation problem.

The importance of detecting and diagnosing the imminence of aneurysm rupture before it occurs cannot be overstated. However, this process is often time-consuming and challenging, with variability in conclusions not uncommon among experts. Furthermore, current state-of-the-art models in medical image segmentation suffer from limited availability of large annotated datasets for training, exacerbated by an immense data imbalance. In most segmentation tasks, 3D segmentation is preferred due to its capacity to leverage more contextual information. However, these models require more data, which is constrained by the aforementioned issues. In the realm of current diagnosis models, those lacking geographic context are notably ineffective. To address these issues, the aim is to develop a model pipeline to accurately detect cerebral intracranial aneurysms and diagnose rupture imminence through 3D magnetic resonance angiography (MRA) and tabular input, augmented with the implementation of neuro-symbolic ai. The utilization of data fusion to tackle the lack of context in tabular models is proposed, leveraging extracted geographical features from a segmentation model. To enhance segmentation results and tackle the data imbalance in aneurysm segmentation, a two-stage model pipeline that extracts contextual geographic features before aneurysm segmentation is suggested. Segmentation results are additionally improved through ensemble techniques and novel preprocessing techniques. Finally, a neuro-symbolic aspect is introduced to enhance model diagnosis, interpretability and performance. The multi-step Integrated Neuro-Symbolic Analysis Pipeline for Cerebral Aneurysm Rupture Diagnosis is introduced.

Friction stir welding (FSW) is a solid state welding process for joining metallic alloys and dissimilar metals. It has emerged as an alternative technology for welding high strength alloys that are difficult to join with conventional techniques. FSW is used to produce products with better mechanical properties. Now a days aluminum alloys have been widely used in several industrial applications such as aerospace, marine, automobile and commercial applications due to their light weight structure, better mechanical properties and high corrosion resistance.In this work, three welding parameters such as spindle speed, welding speed and plunge depth were considered for friction stir welding. FSW was carried out between dissimilar aluminum alloy plates (AA6061 and AA 8011) to produce butt joint.A Box-Behnken design with three factors and three levels was chosen to minimize the number of experimental conditions .The tensile strength and hardness of the welded regions were evaluated. The optimum level settings and the major parameters that influence the joint strength were obtained by Box-Behnken design.

This study explores the potential of natural compounds, including Daidzin, Luteolin, and Silibinin, as inhibitors of human monoamine oxidase B (MAO-B) for the treatment of Parkinson's disease. Docking simulations were performed using Autodock Vina with Pyrx program to evaluate the binding affinities of these compounds with MAO-B. Results indicate that Daidzin, Luteolin, and Silibinin exhibit promising binding affinities with MAO-B, with Daidzin demonstrating the highest affinity. Toxicity parameters were further predicted using the PkCSM Server, confirming the low toxicity of these compounds. Overall, the findings suggest that Daidzin, Luteolin, and Silibinin have the potential to be effective and safe treatments for Parkinson's disease through their inhibition of MAO-B. Further experimental validation is warranted to support their therapeutic efficacy in clinical settings.

“All diseases originate in the gut.” Hippocrates (400 BC) A healthy gut microbiome via the gut-brain-axis (GBA) elevates heart rate variability (HRV), a general measure of health and well-being. A dysbiotic gut microbiome, low in biodiversity and butyrate producers, alters tryptophan metabolism with release of proinflammatory cytokines, predominantly TNF-α, IL-6, and IL-1β. These also characterize chronic inflammation, oxidative stress, and a multitude of diseases, all exhibiting low HRV. Gut dysbiosis upregulates IFN-γ and with it IDO (indoleamine 2,3 dioxygenase). Tryptophan pivots from serotonin synthesis to that of IDO induced kynurenine, increasing the kynurenine to tryptophan ratio (KTR). An elevated KTR is positively linked to neurodegenerative and autoimmune diseases and negatively linked to HRV. Elevated IDO activity is not only enzymatic but also an intracellular signal transducer potentiated by TGF-β. This cytokine is the primary determinant of the TME. Also proposed is the gut-lung dysbiosis concept and consequent degradation of ACE2 (richest in lungs and gut). Leaky gut induced autoantibodies related to G-protein coupled receptors (GPCRs) in combination with increased Ang II further potentiate oxidative stress. Aldosterone and paroxysmal orthostatic tachycardia syndrome (POTS) paradoxes are highlighted in the context of GPCR and gut dysbiosis, and the role of Candida is explored. The triple play of a prebiotic (d-mannose), probiotic (bifidobacteria and lactobacilli), and postbiotic (butyrate) might improve intestinal barrier integrity, oppose entry of GPCR antigens, suppress the inflammatory cytokine triad, balance IFN-γ and TGF-β, suppress oxidative stress, depress KTR, elevate HRV, and extend lifespan and its quality.

With continued scaling of semiconductor devices , the value of predictive analysis through 1 accurate quantum transport modeling is exponentially increasing. Quantum transmitting Boundary 2 method (QTBM) has been a well-known method of choice to model quantum transport in simple 1-D 3 devices. Here, we present an extension of the QTBM to the 2-D domain and apply it for more realistic 4 devices for accurate performance analysis.

The necessity for effective intrusion detection systems (IDS) in big data environments has grown critical due to the rising prevalence of big data systems and the rising amount of security threats. Applying conventional intrusion detection methods to the enormous and intricate data produced by big data ecosystems presents difficulties. Deep learning, has proven to be exceptionally adept at deciphering complex, large-scale data. This study proposes a Deep Learning-based Intrusion Detection System (IDS) created specifically for the Big Data environment. Traditional intrusion detection systems struggle to efficiently identify and prevent cyber threats due to the ever-increasing volume and complexity of data in current networks. We suggest an IDS that makes use of Deep Learning (CNN, LSTM, GAN, etc.), to address this problem. These cutting-edge neural network topologies give the system the ability to process and analyze massive amounts of data for precise intrusion detection. Data collection, data preprocessing, feature engineering, DL model training, intrusion detection, warning generation, and reaction are some of the crucial parts of the suggested IDS. The data collection module mines the Big Data environment for network traffic, system logs, and security event information. To make sure the data is suitable for analysis, it is preprocessed. To improve the detection abilities of the DL models, important features are extracted from the data using feature engineering approaches.

There is a great need to develop research-based models for supporting collaboration between educational institutions. Collaboration models are needed, for example, to assist the transition from lower educational level to higher education or from higher education to work life. In this research, collaboration was conducted through a joint upper-secondary school and university course that addressed global challenges by using a project-based learning approach. There is a shortage of research exploring students’ perceptions of collaboration. Therefore, the main purpose of this qualitative case study is to explore the relevance of the joint course for students and university students. The research was guided by the following research question: What kind of relevance did the students experience in the joint project-based learning course? The data was gathered using questionnaires, interviews, and reflective study reports. The data was analyzed via theory-based content analysis where research-oriented relevance model was used as the analysis framework. The analysis framework enabled categorizing experienced relevance on individual, vocational and societal dimensions. Altogether, the analysis produced 7 relevance categories for upper-secondary students and 9 for university students. According to the analysis, upper-secondary school students felt that the course offered the most on an individual relevance dimension whereas university students experienced the vocational relevance dimension most diverse. As the main conclusion, this research produced new insights on the experienced relevance of upper-secondary level and higher education cooperation from the students’ point of view. The acquired knowledge can be useful for everyone developing new cross-institutional cooperation models.

This study employs molecular docking experiments to investigate the binding interactions of Hypericin with key proteins implicated in Alzheimer's disease (AD). Hypericin demonstrated a significant binding energy of -10.1 kcal/mol with ABAD (3-hydroxyacyl-CoA dehydrogenase type II). The analysis revealed multiple binding interactions, including hydrogen bonds with arginine 6, serine 7, and glutamic acid 140, as well as hydrophobic bonds involving leucine 11, aspartic acid 142, and aspartic acid 86. These findings illuminate the intricate molecular interactions between Hypericin and ABAD, suggesting its potential as a lead compound for further therapeutic development in the context of Alzheimer's disease. Additionally, a parallel docking investigation was conducted for Beta-secretase 1 (BACE1), a protein pivotal in the generation of beta-amyloid peptides—a hallmark of Alzheimer's disease. Inhibiting BACE1 activity is considered a promising therapeutic strategy for AD. Computational analyses suggest that Hypericin may serve as a potential inhibitor of BACE1. Molecular Docking results reveal a robust binding affinity between Hypericin and BACE1, supported by a significant binding energy score of -10.3 kcal/mol. Notably, both ABAD and BACE1 exhibit high binding affinity with Hypericin. This theoretical exploration provides an initial understanding of the intricate molecular pathways involved in Alzheimer's disease and proposes Hypericin as a potential therapeutic compound for mitigating its progression.

This study aimed to overcome the difficulty of conducting the horizontal-well cavity leaching test in the field and to investigate the long-term stability of the horizontal-well salt-cavity natural gas storage. The simulation test design is combined with the similarity theory to study the cavity expansion characteristics and the influence law of cavity leaching parameters. Through the design of a rubber hose connection, an integrated closed test system for multi-stage horizontal-well cavity leaching and brine drainage was built. The test system also realises the repeatable backward movement of the injection well during the test. A similarity simulation of the test design was carried out, and the test platform was constructed to carry out multi-stage horizontal-well leaching tests with a nitrogen cushion. In the horizontal-well leaching tests with a nitrogen cushion, the influence laws of the well spacing, flow rate and liquid level position on cavity expansion were investigated. Based on the morphological characteristics of the horizontal-well cavity, a numerical model of the horizontal-well salt cavity was developed, which reflects the real cavity morphology leached in the test. The long-term stability of the horizontal-well salt-cavity natural gas storage under different internal pressures was investigated through numerical simulation.

Energy communities are key actors in the energy transition since they optimally interconnect renewable energy capacities with the consumers. Despite versatile objectives, they usually aim at improving the self-consumption of renewable electricity within low voltage grids to maximize revenues. In addition, energy communities are an excellent opportunity to supply renewable electricity to regional and national energy systems. However, effective price signals have to be designed to coordinate the needs of the energy infrastructure with the interests of these local stakeholders. The aim of this paper is to demonstrate the integration of energy communities at the national level with a bottom-up approach. District energy systems with a building scale resolution are modelled in a mixed integer linear programming problem. The Dantzig-Wolfe decomposition is applied to reduce the computational time. The methodology lies within the framework of renewable energy hub, characterized by a high share of photovoltaic capacities. Both investments into equipment and its operation are considered. The model is applied on a set of five typical districts and weather locations representative of the Swiss building stock. The extrapolation to the national scale revealed a heterogeneous photovoltaic potential throughout the country. Present electricity tariffs promote a maximal investment into photovoltaic panels in every region, reaching an installed capacity of 67.2 GW and generating 80 TWh per year. Since the national PV capacity needed is forecast at 15.4 GW peak, coordinated investments between local and national actors are needed to prevent dispensable expenses. An uncoordinated design is expected to increase the total costs for residential energy systems by 43.2% and curtails 48.2% of local renewable electricity.

Physical properties like shape, volume and size affect the dynamics of biological systems. Along these lines, we focus on the topological properties of biological fluids and their biochemical and physiological outcomes. We take as a paradigmatic example the salivary fluid and describe how its topological features may affect the physiopathology of the oral cavity. Topological approaches assess the general properties of saliva, ignoring small-scale physical details such as density, flow rate, stiffness, viscosity. Specifically, the mucin aggregates scattered in the salivary fluid can be tackled in terms of topological holes, i.e., vortical clusters that modify the direction, flow, impulse, local rate-of-change and velocity of saliva. While the current methodological approaches are inclined to remove the effects of impurities assessing systems as homogeneous structures, we argue that the occurrence of mucins breaks up the salivary fluid’s homogeneity, leading to unexpected biophysical modifications. We suggest that every collected salivary sample is not reliable for accurate clinical and experimental investigation, since it displays highly local as well as variable chemical, physical and biological features, not reflecting the current physiological state of the oral cavity. Therefore, the assessment of a single salivary sample is not fully reproducible and cannot provide information about the biophysical, enzymatic and microbiological content of the whole saliva. In sum, the very topological features of the saliva - such as volume, shape, antipodal cells, vortex area, whirling fluid mass, segmentation, discretization, triangulation, node numbering - produce unnoticed biological consequences and network connectivity features with intriguing operational implications.

A paddle wheel aerator is developed in this research, which includes a wireless sensor network for measuring the water quality in the aquaculture of marine shrimp ponds. It can also move to the desired position to fill oxygen and measure water quality. A basic requirement is good standard water quality to prevent shrimp from epidemics and improve production. The water quality paddle wheel aerator applies a microcontroller and sensors to measure eight parameters of water quality. These water quality parameters are observed on the web application via an IoT module. The movement system of the water-quality paddle wheel aerator consists of a LiDAR, GPS, and remote RF signal. Each item of data is recorded immediately on the cloud server while the water-quality paddle wheel moves in the marine shrimp farm. The controlled paddle wheel aerator is harnessed automatically to enhance precisely the spatial monitoring resolution of the measurement system installed, which is needless for a multiple measurement system with high cost of investment. Also, farmers can access real data through the Line application. Hence, they are able to plan and control a good environment for aquaculture, preventing the occurrence of various epidemics and decomposing organic matter in the pond.

There are many features of homeostasis worth investigating such as how it works (information pathways, set point processing), where its command and control processors are located in the cell, the language used and how homeostasis interacts with all effectors (all aspects of an organism's functional maintenance and development such as cell differentiation). All are necessary and valid inquiries, but this paper examines the implications of ignoring it as a factor of disease causation. Alternatively when properly understood the homeostasis profile becomes a rational explanation for any individual’s range of health; where some areas are very resistant to disease (resilient) and other areas of homeostasis are dysfunctional leading to minor, moderate or very susceptible tendencies to disease (a lack of resilience in homeostasis). An understanding of this phenomenon, its interactions with gene expression (epigenetics) is necessary in order to evaluate the solutions for acute and chronic diseases. By this method diseases can be defined more precisely as specific susceptibilities in homeostasis, leading to a method to restore specific homeostasis functions.

The rapid acceleration of artificial intelligence (AI) has sparked extensive debate about its impact on the safety and security of society. While AI has shown trans- formative potential, particularly in areas such as healthcare and independent structures where it complements productivity and minimizes human error, accu- racy and protection. However, the misuse of artificial intelligence poses real risks, along with threats such as deep counterfeiting, computer cyber-attacks and the manipulation of social behavior through disinformation. These risks vary from privacy and cyber security breaches to moral dilemmas around liability. The unchecked improvement of AI is expected to threaten the social order, so the relationship between innovation and governance is essential so that AI-related threats do not overshadow its benefits. This article offers a detailed assessment and review of the literature that studies the potential dangers that AI poses to society. The cumulative effects underscore the urgent need for comprehensive regulatory frameworks to mitigate these threats.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

Traditional urban design often overlooks the synchronisation of human and ecological connectivities, typically favouring corridors for ecological continuity. Our study challenges this convention by introducing a computational design approach, Meta-Connectivity, leveraging the deep generative models performing cross-domain translation to integrate human-wildlife landscape connectivity in urban morphology amidst the planetary urbanisation. Utilising chained Pix2Pix models, our research illustrates a novel meta-connectivity design reasoning framework, combining landscape connectivity modelling with conditional reasoning based on deep generative models. This framework enables the adjustment of both human and wildlife landscape connectivities based on their correlative patterns in one single design process, guiding the re-materialisation of urban landscapes without the need for explicit prior ecological or urban data. Our empirical study in East London demonstrated the framework's efficacy in suggesting wildlife connectivity adjustments based on human connectivity metrics. The results demonstrate the feasibility of creating an innovative urban form in which the land cover guided by the connectivity gradients replaces the corridors based on simple geometries. This research thus presents a methodology shift in urban design, proposing a symbiotic approach to integrating disparate yet interrelated landscape connectivities within urban contexts.

This paper deals with the design and kinematic analysis of a novel mechanism for the elbow joint of an upper-limb exoskeleton, with the aim of helping operators, in terms of effort and physical resistance, in carrying out heavy operations. In particular, the proposed eight-bar el-bow joint exoskeleton mechanism consists of a motorized Watt I six-bar linkage and a suitable RP dyad, which connects mechanically the external parts of the human arm with the corre-sponding forearm by hook and loop velcro and thus, helping their closing relative motion for lifting objects during repetitive and heavy operations. This relative motion is not a pure rotation and thus, the upper part of the exoskeleton is fastened to the arm, while the lower part is not rigidly connected to the forearm, but through a prismatic pair which allows both rotation and sliding along the forearm axis. Instead, the human arm is sketched by means of a crossed four-bar linkage, which coupler link is considered as attached to the glyph of the prismatic pair, that is fastened to the forearm. Therefore, the kinematic analysis of the whole ten-bar mecha-nism, which is obtained by joining the Watt I six-bar linkage and the RP dyad to the crossed four-bar linkage, is formulated to investigate the main kinematic performance and for design purposes. The proposed algorithm has given several numerical and graphical results. Finally, a double-parallelogram linkage, as particular case of the Watt I six-bar linkage, was considered in combination with the RP dyad and the crossed four-bar linkage, by giving a first mechanical de-sign and a 3D printed prototype.

This article examines the integration of artificial intelligence (AI) and robotic process automation (RPA) in financial accounting and management, underscoring their role in driving the digital transformation of corporate finance. It discusses the shortcomings of traditional financial processes and highlights the potential of AI and RPA technologies to enhance efficiency, accuracy, and cost-effectiveness. The paper also explores the limitations of RPA, such as its challenges in processing unstructured data and handling complex decision-making scenarios. Looking forward, it considers the future trends in AI and RPA, emphasizing the benefits of cloud technology in scaling automated systems and addressing associated challenges.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

Avian influenza viruses (AIVs) are highly contagious respiratory viruses of birds, lead-ing to significant morbidity and mortality globally and causing substantial economic losses to the poultry industry. Since their first isolation in 2013, the Asian-origin H5N1 highly pathogenic avian influenza viruses (HPAI) of clade 2.3.4.4b have undergone unprecedented evolution and re-assortment of internal gene segments and have spread to Asia, Europe, Africa, and America, caus-ing outbreaks in all the poultry categories. Novel epidemiological and pathobiological character-istics, distinct from other clades, are specific of clade 2.3.4.4b viruses. Wild waterfowl, the natu-ral reservoir of AIVs, are frequently found infected with clade 2.3.4.4b viruses, which can also cause high morbidity and mortality in these birds. The sustained clade 2.3.4.4b virus circulation in waterfowl has also led to virus infection in other wild bird species, with implications for the conservation of endangered species. Furthermore, clade 2.3.4.4b viruses have been isolated in var-ious wild and domestic mammals worldwide, and critical mutations related to virus adaptation to mammalian species have been identified, raising concerns about virus spillover to humans. The main clinical signs, and anatomopathological findings associated to clade 2.3.4.4b virus infection in birds and non-human mammals are hereby summarized.

This paper is dedicated to examining dynamic dark energy models in the context of observational constraints and their implications for the universe's future. By integrating theoretical models with various observational data, we aim to provide a comprehensive view of how dynamic dark energy influences cosmic evolution and the universe's fate. This study tests these models against the latest observational evidence, including the Cosmic Microwave Background, supernovae, and large-scale structure surveys, to refine our understanding of the universe's accelerating expansion and the mysterious nature of dark energy.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

A typical halogen-free flame-retardant (HFFR) formulation for electric cables may contain polymers, various additives, and fire-retardant fillers. In this study, composites are prepared by mixing natural magnesium hydroxide (n-MDH) with linear low-density polyethylene (LLDPE) and a few types of ethylene-octene copolymers (C₈-POE). Depending on the content of LLDPE and C₈-POE, we obtained composites with different crystallinity that affected the final mechanical properties. The nucleation effect of the n-MDH and the variations in crystallinity caused by the blending of C₈-POE/LLDPE/n-MDH were investigated. In the C₈-POE/LLDPE blend, we found a decrease in the crystallization temperature of LLPDE compared to pure LLDPE and an increase in the crystallization temperature of C₈-POE compared to pure C₈-POE. On the contrary, the addition of n-MDH led to an increase in the crystallization temperature of LLDPE. As expected, the increase in the crystallinity of the polyolefin matrix of composites led to higher elastic modulus, higher tensile strength, and lower elongation at break. Overall, these results show how to obtain the required mechanical features for halogen-free flame-retardant compounds for electric cable applications depending on the quantities of the two miscible components in the final blend.

Plant diseases not only cause economic losses, but they also pose a health risk. In this regard, aflatoxins are linked to the development of some type of liver cancer, especially the hepatocellular carcinoma. Aflatoxins are usually produced by the fungi Aspergillus flavus and Parsiticus in figs, and their identification is usually carried out using invasive and complex methods or by visual inspection at an advanced stage. Given that Spain is one of the main producers of figs and Extremadura is the leading region in the country, it is necessary to explore alternative ways of detecting the presence of aflatoxins in figs and preventing them from entering the food chain. The aim of this research is to address the early detection of Aspergillus flavus fungus using non-invasive techniques with the aid of hyperspectral imaging and the application of artificial intelligence techniques, in particular deep learning. The images were taken after inoculation of the microtoxin using 3 different concentrations, related to three different classes and healthy figs (healthy controls). The analysis of the hyperspectral images was performed at the pixel level. Firstly, a full connected neural network was used to analyse the spectral signature associated with each pixel; second, the wavelet transform was applied to each spectral signature. The resulting images are fed to a convolutional neural network. The hyperparameters of the proposed models were adjusted based on the parameter tuning process also performed. The results are promising, with 83% accuracy, 82.75% recall and 83.25% F1-measure for the single neural network, and 77.25% accuracy, recall and F1 for the convolution neural network.

Electronic skin is widely employed in multiple applications such as health monitoring, robot tactile perception, and bionic prosthetics. In this study, we fabricated millimeter-scale electronic skin featuring compact sensing units using Boston Micro Fabrication S130 (a high-precision additive manufacturing device) and the template removal method. We used a gallium-based liquid metal and achieved an inner channel diameter of 0.1 mm. The size of the sensing unit was 3 × 3 mm². This unit exhibited a wide linear sensing range (10–22000 Pa) and high pressure resolution (10 Pa) even on an ultracurved surface (radius of curvature was 6 mm). Sliding was successfully detected at speeds of 8–54 mm/s. An artificial nose with nine sensing units was fabricated, and it exhibited excellent multitouch and sliding trajectory recognition capabilities. This confirmed that the electronic skin functioned normally even on an ultracurved surface.

Ranked Set Sampling (RSS) is a useful technique for improving the estimator of population mean when the sampling units in a study can be easily ranked than the actual measurement. RSS performs better than simple random sampling (SRS) when the mean of units corresponding to each rank is used. The performance of RSS can be increased further by assigning weights to the ranked observations. In this paper, we propose weighted RSS procedures to estimate the population mean of positively skew distributions. It is shown that the gain in the relative precisions of the population mean for chosen distributions are uniformly higher than those based on RSS. The gains in relative precisions are substantially high. Further, the relative precisions of our estimator are slightly higher than the ones based on Neyman’s optimal allocation model for small sample sizes. Moreover, it is shown that, the performance of the proposed estimator increases as the skewness increases by using the example of lognormal family of distributions.

Mutations in epidermal growth factor receptor (EGFR) occur in about 48% of Asian and 19% of Western patients with lung adenocarcinoma (LUAD), leading to its constitutive activation and subsequent uncontrolled cell proliferation. To counteract this, tyrosine kinase inhibitors (TKIs) have been developed, targeting EGFR activity. However, the emergence of metastases and resistance mutations often undermines the durability of the treatment response. Knowledge-based mechanistic models that replicate existing clinical trial outcomes, tailored to specific population characteristics, provide invaluable assistance in designing future clinical trials. These models are particularly effective in identifying optimal responders to specific treatments, thereby enhancing therapeutic efficacy. We have developed physiologically based pharmacokinetic (PBPK) models for gefitinib and osimertinib, representing two distinct generations of EGFR TKIs, to accurately simulate the drugs’ distribution within the primary tumor and metastatic sites following oral administration. These models were integrated with a pathophysiological mechanistic model of EGFR-mutant LUAD, enabling the representation of the effects of both gefitinib and osimertinib on EGFR activation-induced signaling pathways. This comprehensive model outputs detailed evolutions of the primary tumor and each metastatic site, facilitating the evaluation of patient progression in alignment with RECIST guidelines (version 1.1). Notably, the model encapsulates the heterogeneity within the tumor, through the representation of various subclones, each characterized by unique mutation profiles, thereby reflecting differential responses to treatment. Calibration of the model was achieved using publicly available data from the NEJ002 and FLAURA clinical trials. Rigorous visual predictive checks and statistical tests were employed to ensure the proper behavior of the model. The model adeptly replicated the time to progression observed in real clinical trials in EGFR-mutant LUAD patients receiving gefitinib or osimertinib as first-line therapy. In addition, the model was able to reproduce the results from a retrospective study comparing gefitinib and osimertinib, a study that was not used to inform the model. With a consistent virtual population as a reference, the combined model facilitated a comparative analysis of the efficacy of both treatments, thereby underscoring its utility in evaluating therapeutic strategies. The faithful replication of real-world data significantly enhances the credibility of our model, rendering it a vital investigational tool for deriving pertinent insights and informing treatment strategies, particularly in identifying optimal responders to various generations of EGFR TKIs. Following its consecutive prospective validations in the FLAURA2 and MARIPOSA trials, the model is poised to facilitate the generation of synthetic control arms in future clinical trials. This advancement promises a more nuanced analysis of covariate relationships, especially when comparing investigational treatments to established standards of care. Additionally, it potentially reduces the required patient cohort size in such trials, optimizing resource utilization.

Using nanoparticles (NPs) in drug delivery has exhibited promising therapeutic potential 13 in various cancer types. Nevertheless, several challenges must be addressed, including the 14 formation of the protein corona, reduced targeting efficiency and specificity, potential immune 15 responses, and issues related to NP penetration and distribution within 3-dimensional tissues. 16 To tackle these challenges, we have successfully integrated iron oxide nanoparticles into 17 neuroblastoma-derived extracellular vesicles (EVs) using the parental labeling method. We first de- 18 veloped a tissue-engineered (TE) neuroblastoma model, confirming the viability and proliferation 19 of neuroblastoma cells for at least 12 days, supporting its utility for EV isolation. Importantly, EVs 20 from long-term cultures exhibited no differences compared to short-term cultures. Concurrently, 21 we designed Rhodamine (Rh), Polyacrylic acid (PAA)-functionalized magnetite nanoparticles 22 (Fe3O4@PAA-Rh) with high crystallinity, purity, and superparamagnetic properties (average size: 23 9.2 ± 2.5 nm). We then investigated the internalization of Fe3O4@PAA-Rh nanoparticles within 24 neuroblastoma cells within the TE model. Maximum accumulation was observed overnight while 25 ensuring robust cell viability. However, nanoparticle internalization was low. Taking advantage of 26 the enhanced glucose metabolism exhibited by cancer cells, glucose (Glc)-functionalized nanoparti- 27 cles (Fe3O4@PAA-Rh-Glc) were synthesized, showing superior cell uptake within the 3D model 28 without inducing toxicity. These glucose-modified nanoparticles were selected for parental labeling 29 of the TE models, showing effective NPs encapsulation into EVs. 30 Our research introduces innovative approaches to advance NPs delivery. By partially addressing 31 the challenges associated with 3D systems, optimizing internalization, and enhancing NPs stability 32 and specificity through EV-based carriers. Also, our findings hold the promise of more precise and 33 effective cancer therapies while minimizing potential side effects.

Road traffic transportation has flourished in the process of urbanization by its advantages, but it also produces harmful environmental vibrations. The vibration problem is especially significant for production workshops with precision instruments. A field measurement was conducted to analyze the source characteristics and propagation laws of traffic-induced vibrations. Off the northern side of an urban highway lies a microelectronics workshop. When a large truck passes by, both the vibration responses on the ground and in the workshop considerably increase. Greater vibration is produced in the vertical direction than in the X and Y axes. The predominant frequency band of the vibration response caused by road traffic vehicles is lower than 20 Hz. The vertical vibration responses of the first and second floors in the workshop greatly exceed the VC-C limit because of the high daily traffic flow. Attribute to the excitation of the operation of the manufacturing equipment on the second floor, the vertical vibration level of the second floor is essentially higher than that of the first floor. Therefore, it is impossible to disregard the micro-vibration in the workplace produced by the manufacturing machinery as well as the ex-citement of the road traffic. The measured data can be used to test potential numerical models for forecasting vibrations caused by traffic on roads as well as to guide vibration assessment work throughout the planning and design stages of roads.

Anemia is a well-developed discipline where the concepts of precision medicine have, in part and being studied extensively. This review discusses the treatment of EPO-deficient anemia and resistance in Chronic Kidney Disease (CKD). Traditionally, erythropoietin-stimulating agents (ESA) and iron supplementation have been used to manage anemia in CKD. However, these treatments have potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron, and erythropoietin-iron combination therapy. Another novel approach is using hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). This review highlights the need for precision medicine targeting genetic components of EPO-deficient anemia in CKD and discusses individual variability of genes such as the erythropoietin gene (EPO), Interleukin-β gene (IL-β), and hypoxia-inducible factor gene (HIF). Pharmacogenomics testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, optimizing treatment outcomes and minimizing resistance and adverse effects. The article concludes by suggesting the potential of receptor modification to revolutionize treatment outcome of erythropoietin deficiency anemia through integration of the mentioned approach.

Knowing the spatial variability of factors that influence crop yield is essential to carry out a localized treatment. The present study aimed to map the spatial variability of apparent soil electrical conductivity (ECa) in two cultivation areas, delimit management zones (MZ), characterize the soil density (Sd) at two depths, in each MZ, and assess whether the delimitation of MZ, based on the spatial variability of ECa, was able to identify regions of the productive field with different Sd. Spatial variability of ECa was detected. MZ with the highest mean value of ECa also presented the highest mean values of Sd. The highest Sd values were observed for the 0.1 – 0.2 m layer, regardless of the studied area. Regardless of granulometry, the proposed method was able to detect density differences from ECa. The delimitation of MZ, based on the spatial variability of ECa mapping, was able to differentiate the mean values of Sd between MZ 1 (1.53 g cm-3) and MZ 2 (1.67 g cm-3) in the Area A, in the 0.1 – 0.2 m layer. A statistical difference was observed for the mean values of Sd, in MZ 1, layer 0.1 - 0.2 m, when comparing the two study areas: A (1.53 g cm-3) and B (1.64 g cm-3). We suggest that further studies should be carried out, as the mapping of the spatial variability of the apparent soil electrical conductivity showed potential in the differentiation of soil bulk density at different depths.

Rheumatoid arthritis (RA) is a chronic, systemic, abnormal inflammatory immune response. It is characterized by the involvement of the synovium and multiple organs and the destruction of joints and articular cartilage. Over the past 30 years, several promising novel compounds and antibodies have been developed for the treatment of RA. The introduction of new drugs and precision medicine for all forms of RA raises several issues related to access to novel treatments by patients, optimal regimen selection, cost-effectiveness, prognosis monitoring and outcome surveillance, particularly with regarding to the development of low drug response rates, drug resistance and adverse side effects. Tremendous attention has been given to the identification of optimized drug combinations for the treatment of RA, particularly in early high-risk vulnerable and early individuals. Addressing these issues requires novel therapeutic approaches with new mechanisms and the establishment of accurate guidelines for drug selection, drug recombination, and non-chemical therapeutic efforts. In this study, we reviewed the most exciting recently established or ongoing novel drugs and methods according to the clinical trial database maintained by the United States National Library of Medicine and discussed the trends in RA drug development and challenges in the treatment, providing a reference significant for the accurate treatment of RA and the research direction in the future.

Multiple sclerosis (MS) is a debilitating disease of the brain and spinal cord (central nervous system). In MS, the immune system attacks the protective sheath (myelin) that covers the nerve fibers, causing communication problems between the brain and the rest of the body. Eventually the disease can cause permanent damage or nerve damage. The signs and symptoms of MS are very different and depend on the extent of the nerve damage and which nerves are affected. Some people with severe MS may lose the ability to walk independently or completely, while others may experience a long recovery period without any new symptoms. Most people with MS have a relapsing-remitting illness. They experience periods of new symptoms or recurrences that occur over days or weeks and usually improve somewhat or completely. Following these recurrences, there are periods of recovery that can last for months or even years. In this Project, we used some methods of machine learning in order to evaluate the precision and accuracy of Methods to Predict and classification of Multiple Sclerosis with different stages. In order to calculate accuracy, precision, recall Fscore we used some different method such as Art Fuzzy, SVM, Decision tree to compare the classes two by two. To improve the results we used the method of Adaptive fuzzy optimization. we used two options Genetic algorithm and particle swarm optimization.

Introduction: The current generation of 3D printers are lighter, cheaper, and smaller, making them more accessible to the chairside digital dentist than ever before. 3D printers in general in the industrial and chairside setting can work with various types of materials including, metals, ceramics, and polymers. Evidence presented in many studies show that an ideal material used for dental restorations is characterised by several properties related to durability, cost-effectiveness, and high performance. This review is the second part in a 3D Printing series that looks at the literature on material science and applications for these materials in 3D printing as well as a discussion on the potential further development and future evolution in 3D printing materials. Conclusions: Current materials in 3D printing provide a wide range of possibilities for providing more predictable workflows as well as improving efficiency through less wasteful additive manufacturing in CAD/CAM procedures. Incorporating a 3D printer and a digital workflow into a dental practice is challenging but the wide range of manufacturing options and materials available mean that the dentist should be well prepared to treat patients with a more predictable and cost effective treatment pathway. As 3D printing continues to become a commonplace addition to chair side dental clinics, the evolution of these materials, in particular reinforced PMMA, resin incorporating zirconia and glass reinforced polymers offer increased speed and improved aesthetics that will likely replace subtractive manufacturing milling machines for most procedures.

Introduction: The term 3D printing is commonly used to depict an assembling method whereby the final form of an object is the result of the addition of different layers to build the frame of an object. This procedure is more accurately portrayed as additive manufacturing and is likewise alluded to as fast prototyping. The term 3D printing, in any case, is generally new and has been an active part of current developments in Dentistry. Much publicity encompasses the evolution of 3D printing, which is hailed as an innovation that will perpetually change CAM manufacturing, including in the dental sector. This review is the first part in a 3D Printing series that looks at the history of 3D Printing, the technologies available and reviews the literature relating to the accuracy of these technologies. Conclusions: The recent advancement in digital dentistry to incorporate these tools has modernised dental practices by paving the way for computer-aided design (CAD) technology and rapid prototyping. The use of 3D printing has led to 3D digital models produced with intraoral scanners (IOS), which can be manipulated easily for diagnosis, treatment planning, mockups, and a multitude of other uses. Combining 3D Printing with a 3D intraoral scan eliminates the need for physical storage but makes it to retrieve a 3D models for use within all dental modalities.

Gwosch et al. (2020) and Balzarotti et al. (2017) purport MINFLUX as the next revolutionary fluorescence microscopy technique claiming a spatial resolution in the range of 1-3 nm in fixed and living cells. Though the claim of molecular resolution is attractive, I am concerned whether true 1 nm resolution has been attained. Here, I compare the performance with other super-resolution methods focussing particularly on spatial resolution claims, atypical image rendering, visualisation enhancement, subjective filtering of localizations, detection vs labelling efficiency and the possible limitations when imaging biological samples containing densely labelled structures. I hope the analysis and evaluation parameters presented here are not only useful for future research directions but also microscope users, developers and core facility managers when deciding on an investment for the next 'state-of-the-art' instrument.

Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are able to begin treatment within 3 months after surgery. Since the recent publication of the PRODIGE 24 trial results, modified FOLFIRINOX has become the standard-of-care in the non-Asian population with localized pancreatic adenocarcinoma following surgery. Nevertheless, there is still a risk of toxicity, and feasibility may be limited in heavily pre-treated patients. In more frail patients, gemcitabine-based chemotherapy remains a suitable option, for example gemcitabine or 5FU in monotherapy. In Asia, although S1-based chemotherapy is the standard of care it is not readily available outside Asia and data are lacking in non-Asiatic patients. In patients in whom resection is not initially possible, intensified schemes such as FOLFIRINOX or Gemcitabine-Nabpaclitaxel have been confirmed as options to enhance the response rate and resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant treatment after a long sequence of chemotherapy +/- chemoradiotherapy and surgery? Should oncologists consider the response rate, the R0 resection rate alone, or the initial chemotherapy regimen? And finally, should they take into consideration the duration of the entire sequence, or the presence of limited toxicities of induction treatment? The aim of this review is to summarize adjuvant management of resected pancreatic cancer and to raise current and future concerns, especially the need for biomarkers and the best holistic care for patients.

The aim of the instant study was to evaluate relative inline progesterone dynamic changes according to parity and status of reproduction and to estimate the relationship with productivity in dairy cows by inline milk analysis system (IMAS) Herd Navigator. According to a progesterone assay, cows were divided into three periods: postpartum, after insemination, and pregnancy. In the first stage of the postpartum period (0-29 days), the progesterone level in milk was monitored every 6 days. The second stage of the postpartum period (30-65 days) lasted until cows were inseminated. In the third period (0-45 days) after cows were inseminated, progesterone scores were distributed according to whether or not cows became pregnant. The stability of progesterone dynamics was monitored in the last study period (45-90 days). For milk progesterone detection, the fully automated real-time progesterone analyzer Herd Navigator (Lattec I/S. Hillerød. Denmark) was used in combination with a DeLaval milking robot (DeLaval Inc., Tumba, Sweden). The highest progesterone concentration in multiparous cows ranged from 1.08% (11-17 days postpartum) to 34.89% higher than that in cows of the first parity. The lowest progesterone concentrations in the milk of all cows were estimated during the first 5 postpartum days and between 18 and 23 days after calving. Peak milk progesterone concentrations were evaluated in the first stage of the experiment on days 24-29 after calving. In the 30-65-day period after calving, the level of milk progesterone was 2.02-2.08 times higher than that in the 24-29-day postpartum period. After insemination, the level of progesterone in milk increased by 10.77-22.54% compared with the level from cows on days 30-65 after calving. A higher (12.88%) concentration of progesterone in milk was evaluated in multiparous cows compared with that from cows of the first parity. In pregnant cows, milk progesterone within 0-45 days after insemination was 23.88% (in multiparous cows) and 32.54% (in primiparous cows) higher than that in non-pregnant cows. On days 31–35 after insemination, pregnant cows had higher milk progesterone levels, which can predict pregnancy success. According to our study results, we can suggest that an inline progesterone concentration determined by inline milk analysis system Herd Navigator and changes in its dynamics correlate with different reproductive statuses and milk yield of cows. Pregnant cows 11–15 days after insemination have higher milk progesterone levels, what positively, associated with a successful pregnancy.

Previous studies have reported certain sex differences in motor performance precision. The aim of the present study was to analyse sex differences in fine motor precision performance for both hands in different tests conditions. 220 Spanish participants (ages: 12-95) performed fine motor tasks - tracing over the provided models – lines of 40 mm for both hands, two sensory conditions (PV – proprioceptive-visual; P – proprioceptive only) and three movement types (F – frontal, T – transversal and S - Sagittal). Differences in line length (the task focused on precision) were observed through MANOVA analysis for all test conditions, both sexes and different age groups. Sex differences in precision were observed in F and T movement types (statistically significance level and higher Cohens’ d was observed in condition with vision). No any statistically significant differences were observed in both hands and sensory conditions in sagittal type. Sex differences in fine motor precision were more frequently observed in the PV sensory condition in the frontal movement type and less in the sagittal one.

Manufacturing of grinding wheels is continuously adapting to new industrial requirements. New abrasives and new wheel configurations, together with wheel wear control allow for grinding process optimization. However, the wear behavior of the new abrasive materials is not usually studied from a scientific point of view due to the difficulty to control and monitor all the variables affecting the tribochemical wear mechanisms. In this work an original design of pin on disk tribometer is developed in a CNC grinding machine. An Alumina grinding wheel with special characteristics is employed and two types of abrasive are compared: White Fused Alumina (WFA) and Sol-Gel Alumina (SG). The implemented tribometer reaches sliding speeds of between 20 and 30 m/s and real contact pressures up to 190 MPa. The results show that the wear behavior of the abrasive grains is strongly influenced by their crystallographic structure and the tribometer appears to be a very good tool for characterizing the wear mechanisms of grinding wheels, depending on the abrasive grains.

A novel method based on a hybrid incremental modeling approach has been designed and applied to imbalance detection in ultra-high precision rotating machines. The model is obtained by a two-step iterative process that combines an overall model (least-squares fitting) with a local model (fuzzy k-nearest-neighbour) to take advantage of their complementary capacities. Three normalization strategies of evaluating the effect on accuracy are analyzed. A comparative study demonstrates that the hybrid incremental model provides better error-based performance indices for detecting imbalance than a nonlinear regression model and an adaptive neural-fuzzy inference system model. The suitability of Mahanolobis normalization for hybrid incremental modeling is also demonstrated in this case study. The proposed strategy for imbalance detection is simple, fast, and non-intrusive, reducing the deterioration in the performance of ultra-high precision rotating machines due to vibrations.

Valles Marineris (VM), the most prominent example of a Martian Valley Network, has been extensively studied for over 50 years, yet no detailed examination of the principal azimuths of the system exists. To address this, two methods are presented to precisely calculate the principal azimuths, a Bezier Spline analysis, and a GIS technique. The medial axis of the main canyon of VM was determined analytically from cubic polynomial splines fitted to 93 coordinate points along both north and south edges of the canyon. These splines were optimized, and medial axis points were calculated through numerical techniques that ensured orthogonality between the tangents of each spline and their connecting normal lines. 1,000 Medial Axis points were extracted, and various regression models constructed, including fitting to sinusoidal and cubic polynomial curves, achieving accuracies with R² values of 0.98 and 0.99, respectively. Principal azimuths were obtained using the sinusoidal equation with the slope of the tangent at any point x simply determined by the derivative of the curve’s equation. This analytic approach was cross-validated by a GIS method (using QGIS software), where a vector medial axis was obtained which produced principal azimuths that agreed with values from the analytic study with a correlation coefficient of 1.00, and a p value of 6.43e-65. The findings suggest that a deterministic process plays a significant role in the structural geometry of VM, highlighting its potential importance in the canyon’s formation.

This report provides a comprehensive analysis of portfolio risk management using Value at Risk (VaR) for a banking sector investment portfolio. We evaluate a portfolio composed of SBI, HDFC, Axis Bank, and ICICI Bank, using historical data from July 1, 2023, to June 30, 2024. The report covers the calculation of VaR, portfolio variance, and standard deviation, highlighting the impact of different weightage adjustments on the portfolio’s risk profile. Two scenarios—one with increased weightage in SBI and another with increased weightage in HDFC—demonstrate how changes in asset allocation affect potential losses. The findings emphasize the importance of strategic asset allocation for both speculators and hedgers. Speculators are advised to focus on high volatility and market trends, while hedgers should prioritize stability and risk management. This analysis aids investors in making informed decisions to balance risk and return in their banking sector investments.

Costa Rica, widely acknowledged for its environmental leadership, is now facing a significant challenge in managing waste, a situation that could potentially compromise both its environmental and public health achievements. This analysis delves into the waste management issues in Costa Rica, particularly in urban areas such as San José, responsible for nearly half of the country's waste. The study identifies several pressing concerns, including the heavy burden on landfill capacities, a recycling rate of just 9.6%, and substantial regional differences in waste management practices.To address these challenges, the research employs a combined methodology, utilizing Linear Regression (LR) and AutoRegressive Integrated Moving Average (ARIMA) models to project future trends in CO2e emissions and waste minimization from 2024 to 2050. This method underscores the vital need for public involvement and the introduction of innovative strategies in waste management. The research also introduces a Waste Management Innovation Index to compare Costa Rica’s practices with those of leading nations like Germany and South Korea, identifying key areas for improvement.Furthermore, the study incorporates insights from stakeholders, revealing the intricate balance of cultural, economic, and regulatory factors that shape waste management policies. Despite efforts by the government, such as the Environmental Health Route and the National Circular Economy Strategy, results show limited progress, particularly in rural regions. The study highlights the urgent need for better infrastructure, targeted public awareness campaigns, and the use of advanced technologies like Artificial Intelligence (AI) and blockchain to enhance sustainable waste management practices. The research provides strategic recommendations to help Costa Rica improve its waste management systems in line with international standards, ensuring long-term environmental sustainability and protection of public health.

This paper discusses the application of artificial intelligence in imaging omics, especially in cancer research. Imaging omics enables detailed analysis of spatial and temporal heterogeneity of tumours through high-throughput extraction of quantitative features from medical images such as MRI, PET, and CT. This paper focuses on applying PARKS systems to automate the recognition, segmentation, and extraction of image features, significantly enhancing the capabilities of clinical decision support systems (CDSS). The future direction is to establish a robust network infrastructure for radiology Medication-led Health care (RLHC) to facilitate the development and application of personalised treatment protocols, and to improve diagnostic accuracy, prognosis assessment, and treatment recommendations by uploading quantitative image features to a shared database and comparing them with historical images.

The analysis of aggregate data has received increasing attention in the statistical discipline over the past 20 years. Much of this attention has been focused on estimating the cells frequencies of a 2×2 contingency table given only the marginal totals; the analyses proposed have been received with missed reviews. More recently, the focus has shifted toward analysing the overall association structure rather than on the estimation of the cell frequencies. This article provides some insight int how informative the aggregate data of a single 2×2 contingency table is for assessing the association. The information contained in the margins of the table is quantified using the squared deviation of the expected cell frequencies over the possible range of values, where the row and column totals are known and fixed. The new measure we discuss to quantify this association is referred to as the aggregate informative index (AII) and is shown to be the standardized area under the squared deviation curve.

Complexity science studies physical phenomena that cannot be explained by the mere analysis of the single units of a system but requires to account for their interactions. A feature of complexity in connected systems is the emergence of mesoscale patterns in a geometric space, such as groupings in bird flocks. These patterns are formed by groups of points that tend to separate from each other, creating mesoscale structures. When multidimensional data or complex networks are embedded in a geometric space, some mesoscale patterns can appear respectively as clusters or communities, and their geometric separability is a feature according to which the performance of an algorithm for network embedding can be evaluated. Here, we introduce a framework for the definition and measure of the geometric separability (linear and nonlinear) of mesoscale patterns by solving the travelling salesman problem (TSP), and we offer experimental evidence on embedding and visualization of multidimensional data or complex networks, which are generated artificially or are derived from real complex systems. For the first time in literature the TSP’s solution is used to define a criterion of nonlinear separability of points in a geometric space, hence redefining the separability problem in terms of the travelling salesman problem is an innovation which impacts both computer science and complexity theory.

Product attribute extraction is an growing field in e- commerce business, with several applications including product ranking, product recommendation, future assortment planning and improving online shopping customer experiences. Under- standing the customer needs is critical part of online business, specifically fashion products. Retailers uses assortment planning to determine the mix of products to offer in each store and channel, stay responsive to market dynamics and to manage inventory and catalogs. The goal is to offer the right styles, in the right sizes and colors, through the right channels. When shoppers find products that meet their needs and desires, they are more likely to return for future purchases, fostering customer loyalty. Product attributes are a key factor in assortment planning. In this paper we present PAE, a product attribute extraction algorithm for future trend reports consisting text and images in PDF format. Most existing methods focus on attribute extraction from titles or product descriptions or utilize visual information from existing product images. Compared to the prior works, our work focuses on attribute extraction from PDF files where upcoming fashion trends are explained. This work proposes a more comprehensive framework that fully utilizes the different modalities for attribute extraction and help retailers to plan the assortment in advance. Our contributions are three-fold: (a) We develop PAE, an efficient framework to extract attributes from unstructured data (text and images); (b) We provide catalog matching methodology based on BERT representations to discover the existing attributes using upcoming attribute values; (c) We conduct extensive experiments with several baselines and show that PAE is an effective, flexible and on par or superior (avg 92.5% F1-Score) framework to existing state-of-the-art for attribute value extraction task.

Strong-aroma Baijiu is a traditional Chinese spirit distilled from grains that undergo solid-state fermentation. At the end of each fermentation cycle, a significant quantity of Huangshui accumulates at the bottom of the fermentation pit, constituting one of the primary by-products in the brewing process of strong-flavor liquor. In this report, the chemical component analysis of Huangshui obtained from a strong-flavor liquor factory revealed a diverse array of organic acids, alcohols, esters, starch, reducing sugars, amino acids, and other compounds present in Huangshui. Additionally, two specialized solid-state fermentation models were developed to investigate the formation process of Huangshui. Our findings demonstrate a positive correlation between the yield of Huangshui and the initial moisture content of fermented grains. It is concluded that Huangshui is the percolate produced during the solid-state brewing process of strong-flavor liquor, with its water content originating from the initial moisture of fermented grains.

Background/Objectives: Although the role of F-18 FDG PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, we retrospectively studied 134 CRC patients referred for FDG PET/CT imaging on the suspicion of recurrence based on elevated CEA and/or CA 19-9, and/or equivocal radiological findings. According to the Institutional Tumor Board CRC protocol, after initial treatment which was dependent on TNM stage (neoadjuvant therapy, primary resection or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy every 6 months. The statistics including univariate and multivariable analyses were conducted using the IBM SPSS 20.0 statistical software. P-values <0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. FDG PET/CT shows high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA shows a high sensitivity of 98.1%, but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy, for CA 19-9 and CIM for the correct diagnosis in CRC patients were: 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for FDG PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p<0.001), 0.844 (95% CI: 0.772-0.916; p<0.001), 0.753 (95% CI: 0.612-0.844; p<0.001); and 0.547 (95% CI: 0.442-0.652; p=0.358). Univariate analysis shows that both FDG PET/CT- and CIM-positive results were highly associated with CRC recurrence (p<0.001 and p<0.001, respectively), while gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) have no significance (p=0.211, p=0.158, p=0.583, and p=0.201, respectively). Our multivariate analysis shows that independent predictors for CRC recurrence are: positive FDG PET/CT scans (p<0.001), positive CIM results (p=0.001) and elevated CA19-9 levels (p=0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p=0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting CRC recurrence (p=0.023). Conclusions: FDG PET/CT shows a high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the postoperative follow-op in patients with elevated tumor markers.

A recent study revealed a persistent presence of the PP-Spike recombinant protein in 50% of individuals who received ModRNA injections, contrasting with unvaccinated controls, whether SARSCoV-2 infected or not, up to 187 days post-injection. The implications of these findings are discussed in the context of PP-Spike recombinant protein-induced hyperimmune/inflammatory reactions and thrombotic vasculitis as mechanisms to elucidate the serious side effects, long-term organ complications, and excess deaths observed after administering Covid ModRNA products. These results underscore the urgent need for a comprehensive reassessment of the risk-benefit profile of ModRNA injections, including an immediate halt in their use for any person, and a renewed emphasis on understanding and addressing their long-term effects on human health

Aim: the main aim of this study is to compare the onset of effectiveness of mental nerve block with lingual infiltration and inferior alveolar nerve block on patients visiting dental hospital for extraction of mandibular anterior teeth. Materials and methods: The study was set in a clinical setting. This was a randomized controlled double-blind cross study, where 25 subjects received two treatments at an interval of at least 1 week in a within a dental hospital.Inferior alveolar nerve block and lingual nerve block injection is given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered for the right side. Mental nerve block along with lingual infiltration of the corresponding tooth was given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered on the left side.Visual analogue scale (VAS) was used in this study, which consists of a scale with range of 0-10 pain severity on which 0 indicated absence of pain and 10 the worst pain possible. The patients were asked to give scores corresponding to his/her pain, after IANB, mental nerve block and lingual infiltration and these scores were recorde.Results: From the results we can see that patients gave scores between 3-4, stating that they had moderate pain during extraction after administration of IANB (54%) (graph 2) and VAS scores of 0-1 were given by patients, which is suggestive of no pain during extraction after administration of Mental nerve block and lingual nerve infiltration (62%)Conclusion: Within the limits of the study we can conclude that mental nerve block along with lingual infiltration is an effective way to completely and quickly anaesthetise the central incisor to the 1st premolar region.

Hund's rule of maximum multiplicity is a powerful empirical tool for determining the electron population of electronic shells. It was recently discovered that it is also the rule of minimum Shannon entropy. This study extends these findings to the Aufbau rule and discusses them from the perspective of emergent dimensionality, providing a monotonically increasing entropy function. We observed that some elements that violate the Aufbau rule have the same entropies in the actual and Aufbau electron configurations. On the other hand, lower entropies of all actual elements' configurations are associated with higher or equal numbers of unpaired electrons in these configurations compared to the Aufbau configurations. The only exception to this rule is palladium.

Various dietary supplements have been shown to extend the life span of Drosophila melanogaster, including several that promote autophagy, such as rapamycin and spermidine. The goal of the study presented here was to test numerous additional potential anti-aging supplements, primarily inhibitors of the target of rapamycin (TOR) and/or phosphatidylinositol 3-kinase (PI3K). Using a single, comparatively long-lived y w test strain, screening was performed in male flies supplemented either throughout adulthood or in a few cases beginning in middle or late adult life, with concentrations spanning 4-6 orders of magnitude in most cases. Supplementation with PP242 and deferiprone, an iron chelator, beginning in late adult life had no positive effect on life span. Lifelong supplementation with Ku-0063794, LY294002, PX-866-17OH, Torin2 and WYE-28 had no effect at any dose. Rapamycin, spermidine and wortmannin all had significant life-shortening effects at the highest doses tested. AZD8055, PI-103 hydrochloride and WYE-132 yielded slight beneficial effects at 1-2 doses, but only 100 nM AZD8055 was confirmed to have a minor (1.3%) effect in a replicate experiment, which was encompassed by other control groups within the same study. These compounds had no effect on fly fecundity (egg-laying) or fertility (development of progeny to adulthood), but equivalent doses of rapamycin abolished fertility. The solvent DMSO had no significant effect on life span at the concentrations used to solubilize most compounds in the fly medium, but it drastically curtailed both survival and fertility at higher concentrations. 2-hydroxypropyl-β-cyclodextrin also failed to extend the life span when provided throughout adulthood or beginning in mid-adult life. Collectively, the results suggest that inhibition of the TOR/PI3K pathway and autophagy through dietary intervention is not a straightforward anti-aging strategy in Drosophila, and that further extension of life is difficult in comparatively long-lived flies.

The visual span refers to the number of letters readers can identify in a single fixation without using linguistic skills. Proponents of the visual span hypothesis postulate an influence of early visual processing on reading speed. Given the slowness of reading Arabic texts, the present work aims to study the development of the visual span and its effects on reading speed in the Arabic-speaking context. Thirty-four subjects participated in the study. The trigram task and the rapid serial visual presentation (RSVP) paradigm were used to estimate visual span size and reading speed. In line with our initial assumptions, the results showed a significant effect of grade level on reading speed (F(2,31) = 30.93, p<0.001), visual span size (F(2,31) = 20.57, p<0.001). In good alignment with previous work, our results show that visual span size could explain around 40% of the reading speed variability. Interestingly, our analyses revealed a narrowing of visual span size in our Arabic sample. The results of study 2, suggest that the poor performance in the trigram task is due to poor visual attention capacities in our Arabic readers

Introduction:Lumbar radiculopathy, frequently triggered by disc herniation, affects around one in 50 young adults (30-55 ages), leading to significant impacts on quality of life. When conservative treatments fail to alleviate symptoms, surgical intervention such as discectomy is often pursued. Technological advancements have led to various minimally invasive techniques, promising improved outcomes. Our aim was to compare clinical outcomes of different techniques.Methods:We conducted a systematic search in PubMed using "lumbar disc hernia" and the meta-analysis filter. Inclusion criteria comprised meta-analyses focusing on lumbar disc herniation treatments, published in English. A rigorous selection process adhering to PRISMA guidelines ensured high-quality evidence extraction.Results:From 28,171 initial records, 31 meta-analyses involving 87,852 patients were included. Heterogeneity across the literature presented challenges, notably in study populations, surgical techniques, and research designs. Among the techniques evaluated, full-endoscopic lumbar discectomy (FELD) emerged as superior in various perioperative parameters, including Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI), operation time, and complications. Conversely, automated percutaneous discectomy (AUTD) consistently exhibited poorer outcomes, suggesting limited effectiveness compared to other techniques. Conclusion:Despite advancements, the heterogeneity observed in the literature underscores the need for standardized approaches in minimally invasive spinal surgery research. FELD stands out as a preferred technique, offering favorable outcomes across multiple parameters. Conversely, techniques like AUTD raise concerns regarding efficacy. Future research should aim for uniformity in methodologies to facilitate accurate comparisons and guide clinical decision-making.

The integration of deep learning models into financial risk prediction and analysis has significantly transformed traditional approaches. While conventional quantitative methods often rely on simplistic metrics like maximum drawdown, the advent of deep learning necessitates a more nuanced evaluation, emphasizing the model's generalization ability, especially during market crises such as stock market crashes. This paper explores the critical aspects of evaluating deep learning models' risk control capabilities in finance, underscoring the importance of understanding both statistical metrics and generalization abilities, particularly in adverse market conditions. By examining deep learning models' performance in scenarios like stock market crashes and highlighting the significance of cross-validation techniques, this study aims to offer practitioners insights into constructing robust risk management systems. It advocates for a comprehensive approach integrating quantitative analysis with macroeconomic factors to enhance financial risk prediction and analysis in volatile markets. The experimentation reveals that different deep generative models excel in various aspects of financial time series analysis, with generative adversarial networks (GANs) demonstrating superior performance in predicting Value at Risk (VaR) and variational autoencoders (VAEs) excelling in return rate prediction. Moreover, integrating multiple models further enhances predictive performance, leveraging the strengths of each model to compensate for individual weaknesses. Overall, this paper underscores the potential and significance of deep generative models in financial time series analysis, offering a roadmap for improved risk management and decision-making in financial markets.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.