In recent years, the consumption of over-the-counter probiotics used to promote health has grown rapidly worldwide and become an industry. In medicine, various studies have proven that probiotics can help improve the immune system and intestinal health. They are usually safe, but in some rare cases, they may cause concerning adverse reactions. Although the use of probiotics has been widely popularized in the public, the results of many probiotics clinical trials are contradictory. Especially for the cancer patients, the feasibility of probiotics management to provide benefits by targeting cancer and lessening anti-cancer side effects requires further investigations. And this review summarizes the interactions between probiotics and the host and current pros and cons of applying probiotics in the cancer patients.

Background: Measuring vital signs has always been a central task for Critical Care Nurse´s (CCNs) and Registered Nurse Anesthetist`s (RNAs) providing care in the post-anesthesia care unit (PACU) and a prerequisite for their decision-making. Properly measuring and understanding pediatric vital signs is a challenge in younger pediatric patients up to 36 months old. Purpose: gain a greater understanding of CCNs' and RNAs' perceptions of decision-making regarding the level of vital sign monitoring children require in the PACU. Method: A qualitative study design involving the critical-incident technique was used. Interviews were carried out with a purposeful sample of CCNs and RNAs (n=17) from two different hospitals. Findings: According to the nurses' experience, grounds for decisions concerning children’s need of vital-sign monitoring were both adequate and inadequate. They used actions to adjust the monitoring of vital signs to optimise conditions for assessment and the prospects of a safe recovery for the child. Conclusions: Evidence-based care and safety are compromised when the technology has limitations and is not adapted for children. Its use means that experience and clinical assessment are relied on to a greater extent. This not only makes experience important for reliable assessment, but also means that greater risks are accepted.

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.

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.

Inducer of C-Repeat Binding Factor (CBF) expression (ICE), a well-known MYC-type bHLH transcription factor, plays a crucial role in the ICE-CBF-cold regulated (COR) cold signaling pathway. Brassica rapa (B. rapa), an important oilseed and vegetable crop, exhibits strong chilling and freezing tolerance. However, the exact molecular mechanisms by which ICE1 functions in B. rapa remain unclear. Here, 41 ICE1 homologous genes were identified from six widely cultivated Brassica species using a bioinformatics approach. These genes exhibit high conservation but reveal evolutionary complexity between diploid and allotetraploid species. Low-temperature stress induced ICE1 homolog expression, with patterns differing between strong and weak cold-tolerant varieties. Two novel ICE1 paralogs, BrICE1 and BrICE2, were cloned from Longyou 6. They positively regulate cold tolerance in B. rapa via a CBF-dependent pathway, contributing to reactive oxygen species (ROS) scavenfging and osmotic adjustment. Immunoblot analysis revealed that low temperatures induce BrICE1 and BrICE2 degradation via the 26S-proteasome pathway. In summary, ICE1 exhibits complex evolutionary relationships in Brassica species. BrICE1 and BrICE2 positively regulate cold tolerance via the CBF-dependent pathway and ROS scavenging mechanism and are also responsible for balancing the development and cold defense of B. rapa.

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.

Infrared thermography is a contactless imaging technique, useful to measure surface temperature at distance which has been widely applied in animal production. The possible applications within the pig husbandry include sow heat detection, reduction of the incidence of neonatal mortality, recognition of febrile state caused by pathogens, study of metabolic efficiency, evaluation of stress caused by heat, by constraints, or by aggressive interaction and meat quality prediction. Even if this technique could be easily influenced by environmental factors, the continuous improvement in the procedures and the decrease in the cost of the equipment will allow in the next future new and more applications in swine farming.

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 cross-sectional study investigates the impact of Virtual Private Networks (VPNs) on Nigerians during the 2021 Twitter ban, prompted by the Nigerian government's suspension of Twitter operations following the deletion of a tweet by the President. The study aims to analyze the frequency and awareness of VPN and Twitter usage among Nigerians during the ban, addressing specific objectives. Employing a survey research method, data was collected from 400 respondents through online and offline questionnaires. Descriptive statistical tools were used for data analysis, revealing significant findings. Results indicate a substantial decrease in Twitter usage during the ban, with IPVanish emerging as the preferred VPN brand. The study also highlights an increase in VPN awareness post-ban, emphasizing the need for educational initiatives. The demographic analysis reveals a dominant age group of 21 to 25 among social media users. Overall, the research underscores the complex interplay between social media dynamics, VPN adoption, and demographic factors, emphasizing the importance of nuanced regulatory approaches and ongoing user education in Nigeria's online landscape.

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.

Lung cancer is the leading cause of global cancer-related mortality resulting in ~1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or biobanked sections/biopsy of lung tumors, PDXs, and pleural affusion. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and immune therapy agents. PDOs mainly recapitulated the genomic alterations, transcriptomic landscape and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remained, PDOs showed promise to screen novel therapy drugs. With the technical advance of high throughput, tumor-on-chip, combined microenvironment, and air-liquid interface (ALI), the drug screening using PDOs would serve better for precision care of lung cancer patients.

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.

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.

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain per-iodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tis-sue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL-cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotions of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as il-lustrated by the production of the antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the perio-dontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.

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.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

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.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

Comparing to males, females require much more morphine to produce comparable levels of analgesia, suggesting a difference in the endogenous hyperalgesia and analgesia modulation between sexes. Aside from hormones, emerging evidence suggests sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and American College of Gastroenterology (ACG), up to 25 % of the population having visceral pain at any one time, and in the United States 10-15 percent of adults suffering from irritable bowel syndrome (IBS). Here we analyzed literatures on clinical reports of sex differences in visceral pain focusing on IBS, other form of bowel dysfunction and comorbidities, and summarized animal models that provided means to investigate the underlying molecular mechanisms in sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems all contribute to sex-dependent nociception and nociplasticity in the painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.

Ketamine as an old - new drug has variety of clinical implications. In the last 30 years, ketamine has become popular for acute use in humans. Ketamine at standard doses is principally utilized for the induction and maintenance in surgical procedures. Beside its use in anesthesia and analgesia, recently studies had shown that ketamine find the place in the treatment of asthma, epilepsy, depression, bipolar affective disorders, alcohol and heroin addiction. Its mechanism of action is complex, but it mostly acts as a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. Ketamine is generally considered relatively secure and does not result in serious adverse effects when used at low doses and for short periods- Also, ketamine is known as a powerful psychostimulant. During the past decade, ketamine has been one of the commonly abused drug.

Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancers, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development [1]. Therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options [1-4]. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection [5-7]. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy and targeted agents are occurring.

Background: Transient Hypogammaglobulinemia of Infancy (THI) is a primary immunodeficiency caused by a temporary decline of serum levels of immunoglobulin G (IgG) greater than 2 standard deviations below the mean age-specific reference values in an infant between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as, in the third trimester of pregnancy, IgG is transferred across the placenta from mother to infant.Objective: To systematically review the diagnostic criteria of Transient Hypogammaglobulinemia of infants.Design & Methods: Systematic Review. Manual searching of 3 electronic databases (PubMed, Medline, & Google Scholar) from September 2021 – April 2022. Abstracts were screened to assess fit to the inclusion criteria. Data was extracted from the selected studies by using an adapted extraction tool from Cochrane.org. Studies were then assessed for bias by using an assessment tool also adapted from Cochrane.org.Results: Of the 215 articles identified, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in 6 domains. 5 studies (31%) had a low risk of bias, while 4 studies (25%) had a high risk of bias, & 7 studies (44%) were unclear for bias.Conclusion: We can conclude that THI is only definitively diagnosed after the abnormal IgG levels have normalized, hence THI is mostly a benign condition, but must be monitored for subsequent recurrent infections. The diagnostic criterion also includes vaccine & isohaemagglutinin responses to differentiate against other immunological disorders in infants.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

Background: Mucormycosis is a worldwide angio-invasive fungal infection that is associated with high morbidity and mortality. A few European studies have focused on the epidemiology. Methodology: A retrospective longitudinal descriptive study was performed with inpatients diagnosed with mucormycosis (ICD-9-CM, code 117.7, cases 1997-2015; and ICD-10, code B46, cases 2016-2018; along with length of hospital stay) in Spanish public hospitals between 1 January 1997 and 31 December 2018. Data were obtained from the Minimum Basic Data Set (CMBD in Spanish). Principal findings: A total of 962 patients were recorded; 665 were men. The mean age (±SD) was 55±18.8 years. The annual incidence rate increased from 0.74 to 1.24 cases per million person-years. The lethality rate was 31.3%. Renal failure (41.6%) and hematological malignancy (36.3%) were the main factors involved. Conclusions: Mucormycosis is a rare infectious disease in Spain, but it has had a significantly increased incidence in the last two decades. Being an adult male and having diabetes, neoplasm or renal failure are the main factors associated. High mortality is usually associated mainly with hematological malignancy and renal failure. CMBD studies could be an efficient tool for assessing changes in the epidemiology of mucormycosis.

The treatment of peptides has played an important role in clinical practice since the discovery of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States (US and other regional mar-kets, and peptides continue to undergo drug discovery steadily. Peptide research and development has lev-eraged a wider range of structures known from other plant sources, via pharmacology and medicinal molecular biology, beyond its conventional focus on individual endogenous peptides. We build a comprehensive database of peptides that have met scientific studies with more than 150 constantly evolving peptides. Here we provide a simple overview of the peptide-based drug therapy environment, comprising evolutionary points of view, structural properties, operational thresholds, and explanation of the therapeutic area.

Background: Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed diagnosis when initial clinical symptoms do not fulfill the traditional criteria. We aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD. Method: We retrospectively enrolled a total of 83 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data. Results: In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A patient with a neutrophil to lymphocyte ratio greater than 1.33 combined with a C-reactive protein more than 33 mg/L was more likely to have KD. Conclusion: Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

Clinical training in medical schools in Spain is performed by rotations in university hospitals. During these internships, students are expected to acquire and master basic procedural skills. However, the assessment tools available rarely check whether these skills are completely acquired by the students. We have used an e-portfolio to determine the optimal number of times the students need to repeat a procedure to be able to perform it independently. The results were compared with the actual performance during the internships. An e-portfolio collected qualitative information about the internships. Quantitative information was also requested about the number of times each clinical skill was performed. Later, a survey asked these students and their teachers the optimal number of times each skill should be repeated before it could be considered fully acquired. The questionnaire was answered by 98.6% of the students and 70.3% of their teachers. Out of the 21 clinical skills and procedures selected, both students and their tutors agreed in a similar optimal value in 16 of them; only in five of them, teachers thought that students needed a greater number of times than that selected by the students. When these optimal values were compared with the actual values recorded in the portfolio during the internships, it was found that about half of the clinical skills were carried out less frequently than expected, thus providing an important feedback about the internships. Quantitative information collected in portfolios reveals a moderate mismatch between students and tutors perceptions of their training needs.

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.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Current drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and CSF biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of the Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are currently assessed in clinical trials. The abovementioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are consequential to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

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.

Instagram is a popular social media platform among youth, with over a billion active users worldwide. The platform allows users to share photos, videos, and stories and connect with friends and followers. Instagram has become a significant part of youth culture, with many young people spending a considerable amount of time on the app. According to Enterprise (2012:02), Instagram is a community shared among one member with other members from all over the world. This study examines the impact of Instagram on the physical and mental well-being of Indian youth. With the rapid proliferation of social media platforms in India, Instagram has emerged as a prominent influence on the lives and perceptions of young individuals. Studies have shown that using Instagram among youth can have positive and negative effects. On the positive side, Instagram can be a way for young people to express themselves, connect with others, and discover new interests. However, excessive use of the platform can also lead to negative outcomes, such as social comparison, anxiety, and low self-esteem. Instagram addiction among youth is a growing concern. Some young people may feel compelled to check their accounts frequently and may experience negative emotions if they are unable to do so. In extreme cases, excessive use of the platform can interfere with daily activities and relationships, leading to a negative impact on mental health. Parents and educators can play a role in helping young people manage their Instagram use. This can include setting limits on screen time, encouraging healthy online habits, and promoting offline activities and social interaction. Additionally, mental health professionals can offer support to young people who are struggling with addiction or other negative effects of Instagram use. This study explores the prevalence of Instagram dependency among Indian youth.

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.

Flavin-dependent monooxygenases (FMOs) have made substantial influence as catalysts for monooxygenation reactions, impacting diverse field such as drug metabolism, environmental studies, and natural product synthesis. Their application in biocatalysis boasts several advantages over conventional chemical catalysis, such as heightened selectivity, safety, sustainability, and eco-friendliness. In the realm of biomedicine, FMOs are pivotal in antibiotic research, modulating natural products, antimicrobial agents, and pathways involved in drug synthesis. They're also underscored as potential pharmaceutical targets, pivotal in disease progression and viable for therapeutic intervention. Additionally, FMOs play a substantial role in environmental science, especially in pesticide processing and plant vitality. Their involvement in biosynthesizing compounds like polyethers, tropolones, and ω-hydroxy fatty acids, with remarkable regio- and stereoselectivity, renders them indispensable in drug discovery and development. As our comprehension of FMOs' catalytic mechanisms and structures advances, coupled with cutting-edge biotechnologies like computational design and directed evolution, FMOs are poised to occupy an increasingly significant role in both scientific exploration and industrial applications.

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.

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

Although working memory (WM) is crucial for intellectual abilities, not much is known about its brain underpinnings, especially the structural connectivity. We used diffusion tensor imaging (DTI) to look across the whole brain for the white matter integrity correlates of the individual differences in the reading span (verbal WM capacity during reading) in healthy adults. Right-handed healthy native Russian speakers (N = 67) underwent DTI on a 3T Philips Ingenia scanner. Verbal WM was assessed with the Daneman-Carpenter reading span test (Russian version). Fractional anisotropy maps from each participant were entered into the group tract-based spatial statistics analysis with the reading span as a covariate; the results were TFCE-corrected. After taking into account effects of age, sex, education and handedness, reading span positively correlated with the white matter integrity in multiple sites: the body, the genu and the splenium of corpus callosum; bilateral corona radiata (anterior, posterior, and superior); bilateral superior longitudinal fasciculus; several tracts in the right hemisphere only, including the internal and external capsule; bilateral superior parietal and frontal white matter. Although the left hemisphere is central for verbal processing, we revealed the important role of the right hemisphere white matter for the verbal WM capacity. Our finding indicates that larger verbal working memory span may originate from additional processing resources of the right hemisphere.

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.

Suppose for n∈ ℕ, set A⊆ℝⁿ and function f∶A→ℝⁿ. If set A, using the Hausdorff outer measure, is measurable in the sense of Carathèodory; we want to find an extension of the expected value, w.r.t the Hausdorff measure, that's unique, finite and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. The issue is current extensions of the expected value are finite for all functions in only a shy subset of ℝᴬ. The reason this issue wasn't resolved is mathematicians have not thought of the problem, focusing on application rather than generalization. Despite the lack of potential use, we'll attempt to solve the problem by defining a choice function---this shall choose a unique set of equivalent sequences of sets (Fₖ***) , where the set-theoretic limit of Fₖ*** is the graph of f; the measure Hʰ is the ℎ-Hausdorff measure, such for each k∈ℕ, 0 < Hʰ(Fₖ***) < +∞; and (fₖ*) is a sequence of functions where {(x,fₖ*(x))∶x∈ dom(Fₖ***)}=Fₖ***. Thus, the extended expected value of or E**[f,Fₖ***] is: ∀(ε>0)∃(N∈ℕ)∀(k∈N)(k≥N⇒1/Hʰ(dom(Fₖ***))∫dom(Fₖ*** )fₖ* dHʰ - E**[f,Fₖ***]<ε ) which should be unique, finite, and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. Note we guessed the choice function using computer programming but we don’t use mathematical proofs due to the lack of expertise in the subject matter. Despite this, the biggest use of this research is the extension of the expected value is finite for "almost all" functions: this is easier to use in application when finding the "average" of functions covering an infinite expanse of space.

Cucurbitacin phytonematicides consistently suppress population densities of plant nematodes, but have no effect against bacteria, fungi and insects. This study investigates the mechanism through which cucurbitacin phytonematicides consistently exert nematicidal properties on nematodes. Post 72-h exposure of second-stage juveniles (J2) of Meloidogyne enterolobii to geometric concentration of Nemafric-BL phytonematicide, J2 total proteins were measured using TruspecCHNS Macro. Total proteins versus phytonematicide exhibited a negative quadratic relation (R² = 0.97), with the minimum total proteins achieved at x = 4.9% phytonematicide. Beyond the minimum, total proteins increased gradually, depicting the existence of both isoprenylation (breakdown) and farnesylation (biosynthesis) of total proteins. In conclusion, cucurbitacins and nematode cuticles are both chemically structured, which provides the mechanism through which the test chemicals consistently decrease population densities of plant nematodes.

The objectives of this paper are to investigate the tradeoffs between a physically constrained neural network and a deep, convolutional neural network and to design a combined ML approach ("VarioCNN"). Our solution is provided in the framework of a cyberinfrastructure that includes a newly designed ML software, GEOCLASS-image, modern high-resolution satellite image data sets (Maxar WorldView data) and instructions/descriptions that may facilitate solving similar spatial classification problems. Combining the advantages of the physically-driven connectionist-geostatistical classification method with those of an efficient CNN, VarioCNN provides a means for rapid and efficient extraction of complex geophysical information from submeter resolution satellite imagery. A retraining loop overcomes the difficulties of creating a labeled training data set. Computational analyses and developments are centered on a specific, but generalizable, geophysical problem: The classification of crevasse types that form during the surge of a glacier system. A surge is a glacial catastrophe, an acceleration of a glacier to typically 100-200 times its normal velocity. GEOCLASS-image is applied to study the current (2016-2024) surge in the Negribreen Glacier System, Svalbard. The geophysical result is a description of the structural evolution and expansion of the surge, based on crevasse types that capture ice deformation in six simplified classes.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

The purpose of this study is to analyze how global research cooperation patterns in the secondary battery industry have changed over recent years and to identify the evolution in the focus of research. To this end, network analysis was performed using the nationality information of the authors of a 10-year multinational joint research paper related to lithium-ion batteries. Furthermore, keyword analysis and topic modeling were performed using the abstract data from the study. The results of this study confirm that some countries that are not well-known in the field, such as Australia, Spain, and France, showed high centrality, compared with the level of cooperation scale. Additionally, six research topics were identified. According to a comparison over the first half of the decade, no difference was observed in the appearance of keywords indicating high energy density and conductivity with lithium, a key mineral. Keyword distribution was high for topics like battery charging and discharging in the first half of the decade, and for next-generation battery materials, such as solid electrolytes, lithium metal anodes, and lithium-sulfur batteries in the second. These results provide insights into the establishment of R&D cooperation strategies by countries and pre-planning by companies in the battery industry.

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

Astronauts in space are subject to a continuous bombardment of ionizing radiation. The Earth's magnetic field and the ISS shield some biologically damaging particles traveling through. Still, travel beyond low-Earth orbit and extravehicular activities are exceedingly more dangerous and there is a concern for the acute and late-occurring adverse health effects befalling astronauts. So, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models may improve. This article reviews the historical development and current state of knowledge of radiation effects impacting astronauts in orbit. We explain the space radiation environment, cellular microenvironment, and how these may be incorporated in radiobiological models to aid in our understanding of the influence space travel may have on astronaut health. The topics discussed in this paper include a review of DNA damage and repair mechanisms and the numerical models that aim to explain the biological effects resulting from ionizing radiation damage. Historically, radiobiological models focused on how radiation damages nuclear DNA, built upon the hypotheses of Crowther and Lea in the 1940s and 1960s, and neglected other sub-cellular targets outside of nuclear DNA.

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798, had shown the highest level of evidence about their association with FPs response. The EMA and FDA-approved drug labels for FPs, recommend genotyping these variants before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still find patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the association with the response to FPs of DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595; as explanatory candidates of the interindividual differences for the FP-related toxicities. We also studied the impact of DPYD*2A, *13, *HapB3, and rs67376798 genotype for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found that FP dose lowering based on DPYD genotype does not affect the treatment efficacy. Also, the DPYD*4 (defined by rs1801158) allele was associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R.= 5.66; 95% C.I.= 1.35 – 23.67; p= 0.014) and multivariate analyses (O.R.= 5.73; 95% C.I.= 1.41 – 28.77; p= 0.019). This makes it a candidate variant for implementation in clinical practice.

Elevated immunoglobulin E (IgE) levels are commonly associated with allergies. However, high IgE levels are also found in several other infectious and non-infectious disorders. Elevated IgE levels typically suggest allergies, eczema, or recurrent skin infections. Very high IgE levels are uncommon in patients with active eczema but typically reflect a monogenic atopic condition or inborn immune defects with an atopic phenotype. The aim of our research is to identify if the possible cause of high IgE levels is also dependent on external factors, age, or associated recurrent pathologies such as infections. To answer this question, we performed a one-year retrospective study that included 200 hospitalized children who had at least two viral or bacterial infections in the six months preceding hospitalization. Measurements of IgE and allergen panels (respiratory and digestive) using blood samples revealed that individuals who tested positive for the body’s synthesis of hyperimmunoglobulin E were not observably allergic to any potential allergens despite having higher total serum IgE. According to the results, there was a strong correlation between elevated IgE serum levels and a history of infectious diseases among the patients.

Background/Objectives:The first attempts of posterior lumbar interbody fusion can be traced back to the 1940s, where their performance was marked by animosity due to high rates of failure. Nowadays, the use of interbody fusion involves a much more complicated consideration of factors such as global alignment, disc height, fusion rates, and operative risk, all combined at once.Our study aims to examine all these effects using Flarehawk 9 as a means of interbody fusion.Materials and methods: A total of 58 patients underwent open posterior lumbar surgery using Flarehawk 9 between September 2021 and February 2023 with a mean follow up of 1 year.The mean age was 59.8 years old ( range between 33 and 79 years old), 36 of them are males while 22 of them are females. The diagnostic groups included spinal canal stenosis (n=40), failed back surgery syndrome-revision surgery (n=5),spondylolisthesis with slip percentage 25% (n=4),recurrent herniated disc (n=7) and adjacent segment disease (n=2). Results: The majority of patients demonstrated remarkable improvement based on ODI scores.The rate of union varied based on the fused levels and whether the patients had previous surgery or not.The amount of lordosis postoperatively is increased by 2±0.4 degrees.Conclusions: Even though anterior approaches become more and more popular and advanced nowadays, posterior fusion with interbody cage still remains a safe and effective method to treat various spine surgical pathologies with optimal results.

This study investigates the pivotal areas where Artificial Intelligence (AI) integration in healthcare warrants further exploration, leveraging insights from Boston Specialists, a forefront healthcare provider in AI adoption. Employing a qualitative case study approach, enriched by in-depth interviews and comprehensive literature reviews, we identify three main domains for potential AI expansion: scheduling efficiency, clinical documentation, and AI-driven medical research. Our results underscore the substantial enhancements AI brings to operational workflows and patient care, notably through improved scheduling systems, accuracy in medical documentation, and the facilitation of data-driven research methodologies. These findings suggest a critical need for healthcare institutions to further invest in AI technologies, focusing on these key areas to harness AI's full potential in personalizing care, optimizing efficiency, and advancing medical knowledge. The study concludes with a call for continued investigation into AI's integration within healthcare settings, emphasizing the importance of a supportive organizational infrastructure, ethical considerations, and data security in realizing AI's transformative impact on healthcare delivery and patient outcomes.

Cacipacoré virus (CPCV) was discovered in 1977 deep in the Amazon rainforest, from the blood of a black-faced ant thrush (Formicarius analis). As a member of the family Flaviviridae, genus orthoflavivirus, CPCV's intricate ecological association with vectors and hosts raises profound questions. CPCV’s transmission cycle may involve birds, rodents, equids, bovines, marsupials, non-human primates and bats as potential vertebrate hosts, whereas Culex and Aedes spp mosquitoes, have been implicated as potential vectors of transmission. The virus' isolation across diverse biomes, including urban settings suggests its adaptability as well as presents challenges for its accurate diagnosis and thus its impact on veterinary and human health. With no specific treatment or vaccine, prevention hinges on traditional arbovirus control measures. Here we provide an overview of the ecology, transmission cycles, epidemiology, pathogenesis and prevention, aiming in improving our ability to better understand this neglected arbovirus.

Blood-based biomarkers for early detection of recurrence have a significant clinical impact on the improved management of breast cancer patients, as cancer recurrence results in poor prognosis. This study aimed to investigate if the measurement of blood endocan in breast cancer patients with high ESM1 expression could be an effective tool to detect postoperative recurrence compared with existing tumor markers. Blood was collected before and after the tumor resection from the mouse models of breast cancer, and endocan levels were measured while visualizing metastatic recurrence with noninvasive luminescence imaging. In clinical settings, blood was withdrawn from 16 breast cancer patients before and after the tumor resection, and the effect of lumpectomy on blood endocan level was evaluated. Additionally, the blood endocan from 20 patients diagnosed with postoperative recurrence was measured, and their positivity rate for endocan was compared with that for serum carcinoembryonic antigen (CEA) or cancer antigen 15-3 (CA15-3). Our preclinical and clinical experiments revealed that blood endocan levels reflected tumor burden. Furthermore, over 60% of patients suffering from postoperative recurrence who tested negative for CEA or CA15-3 were positive for endocan. Our results support the clinical significance of endocan in breast cancer patients for detecting breast cancer recurrence.

Dietzia natronolimnaea C79793-74 has emerged as a potential probiotic strain with implications for managing Crohn's disease. This study evaluates the safety profile of D. natronolimnaea C79793-74 as a probiotic sup-plement. Genotypic characterization involved a 16S rRNA gene and genomic sequencing and genome an-notation. The safety assessment included interrogation of the assembled genome for antibiotic resistance genes and virulence factors, utilizing the CARD and VFDB databases. Notably, the analysis revealed an ab-sence of antibiotic resistance or virulence factors in Dietzia natronolimnaea C79793-74. The safety and tol-erability of D. natronolimnaea C79793-74 were further investigated in an 8-week double-blind, place-bo-controlled clinical trial involving healthy adult participants. A daily dose of 5 x 109 CFU of the probiotic strain was administered. This clinical trial represents the first assessment of the safety of D. natronolimnaea C79793-74 in human subjects. Results demonstrated that participants in both the Dietzia and Placebo groups maintained clinical and hematologic markers within the normal range throughout the study. More-over, the probiotic strain was well-tolerated, with nearly all participants experiencing no severe or medium adverse events. Collectively, the comprehensive data obtained in this study support the inference that Dietzia natronolimnaea C79793-74 is safe and well-tolerated as a nutritional supplement for human con-sumption

This review explores the complex interrelationships between emotion, attention, and behavior, drawing upon empirical evidence from psychological, neuroscientific, and clinical studies. It delves into the neural mechanisms that underlie these interactions, with a focus on key brain regions such as the prefrontal cortex and amygdala. Clinical cases involving stroke and attention-deficit/hyperactivity disorder (ADHD) are examined to illustrate the real-world implications of these cognitive interactions. The review also discusses the impact of effective emotion regulation strategies and the role of attention as a cognitive mechanism that influences both emotion and behavior. Neuroimaging studies, particularly functional MRI, are highlighted for their role in providing a deeper understanding of these intricate relationships. The review concludes by emphasizing the importance of this triadic relationship in adaptive functioning and its broader implications for mental health, interpersonal relationships, and quality of life.

Post operative recurrence (POR) is the rule in patients with Crohn’s disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single center randomized open label clinical study, in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 post-operatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score≥i2. We enrolled 35 patients (25 males, mean age 35±1.4 years, median disease duration 5±6.1 years) following ileocecectomy. Of these, 7(20%) were current smokers and 9(26%) biologics experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs 69%, p=0.004) and 58 (47% vs 75%), (p=0.03, HR=0.39, 95% CI=0.16-0.93). POR was associated with increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin and serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab is more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower post-operative BMI were associated with ePOR. Eighteen weeks serum hemoglobin and ALT, and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB therapy is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a serious medical and epidemic problem all over the world. We present here a series of clinical cases consist of two patients diagnosed with isoniazid resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. And the pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis1,2 via the following mutation c.947G&gt;A; p.Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons, as well as mutations in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the katG315 mutation worldwide. The second most common mutation is inhA-15, and it has been reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and katG 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.

BACKGROUND: Retinoblastoma is a malignant tumour that develops from the immature cells of the retina. It is the most frequent type of paediatric intraocular cancer and is curable. Clinical and histological findings after enucleation of the affected eye dictate not only the patient's secondary care but also their prognosis. We assessed the clinical and histopathologic predictors of survival among children with retinoblastoma from two tertiary health facilities in Uganda. METHODS: This retrospective research utilized archived formalin fixed & paraffin embedded blocks of eye specimens enucleated between 2014 to 2016 at Mbarara University, pathology department and Ruharo Eye Centre. The specimens were then processed and stained with haematoxylin and eosin. The confirmation of retinoblastoma was made to include histologic stage and features of the tumor. Biographic data of the patients and the clinical features such as leukocoria, proptosis, phthisis, staphyloma, buphthalmos were retrieved from the records.RESULTS: Males (55.1%) dominated the study population (N=78). The median age was 31 months. The commonest clinical sign was leukocoria (69.2%) and the most abundant histopathological stage was stage 1 (41%). Optic nerve invasion 39.5%, choroidal invasion 29.5%, scleral invasion 7.7% and orbital extension 16.7% were seen. Flexner-Wintersteiner rosettes were seen in 24.6%. Necrosis was a prominent feature (71.2%). The two-year survival was estimated to be 62%. Leukocoria (RR 1.1), female gender (RR 1.4), intralaminar optic nerve invasion (RR 7.6) and a lack of orbital extension (RR- 7) were significant predictors of survival.CONCLUSION: Leukocoria and proptosis are noticeable clinical signs of retinoblastoma. Most patients present while in stage one although stage four presentation is also common. Leukocoria, optic nerve invasion, orbital extension, and gender are significant factors predictive of survival in patients with retinoblastoma.

Purpose: The goal of this article was to introduce a new technique for root coverage (RC), the Mixed-Thickness Tunnel access (MiTT), approaching a full-split design, showing the results obtained in a case series and demonstrating it step-by-step. Methods: Healthy individuals, non-smokers, and non-diabetics, who were diagnosed with gingival recession (GR) type 1 or 2 (RT1 or RT2). After all necessary evaluations, prophylaxis was performed 14 days before the surgical procedure. Then, after the basics clinical conduct and anesthesia, one or two vertical incision(s) on the mucosa (around 1-2 mm apical to the MGJ), lateral to the papilla base, were done. Initial detachment of the mucosa from the muscles (split design); it was permitted (but not mandatory) to do intrasulcular incisions; from the MGJ to coronal, subperiosteal access was done to raise the full-thickness tunnel. It must communicate up to the gingival sulcus area and the papilla’s base, keeping the papilla’s tip intact. A connective tissue graft was harvested, which was inserted through the linear incision or intrasulcularly. Interrupted sutures were done and may be used as adjunctive material. Results: Nine healthy individuals (7 females and 2 males) aged 19 and 43 years were enrolled. They were treated following the MiTT steps. There were four cases with a single GR, 2 patients with 2 teeth involved, and three with 3 or 4 GR. Seven cases were RT1 and two RT2. All RT1 cases achieved 100% RC, while the mean RC obtained for RT2 was around 80%. Conclusion: MiTT can be considered a more straightforward approach for minimally invasive surgical technique, which is a feasible option to treat RC with a high success rate, predictability, and esthetic preservation. There is a technical sensitivity to performing the full-split design procedure.

Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 among healthy children to those of VarivaxTM (control). Children aged 12 months to 12 years were randomized 1:1 to receive either NBP608 or control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. A total of 499 participants (NBP608, n = 251; control, n = 248) was enrolled. The seroconversion rate (SCR) measured using FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for SCR difference (NBP608 minus control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of –15%. In assessment by gpELISA, the SCR was 99.53% in the NBP608 group; and the 95% LCL for SCR difference was 6.5%, which was higher than the specified non-inferiority margin of –15%. There were no significant differences between the NBP608 and control group with respect to proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to VarivaxTM.

ChatGPT is gaining widespread acceptance for its ability to generate natural language sentences in response to various inputs and is expected to become a supplementary tool for diagnosing and determining treatment policies in clinical settings. ChatGPT was used to evaluate its ability to perform clinical inference and accuracy in answering questions on the 117th Japanese National Medical Licensing Examination held in February 2023. The exam questions were manually inputted into ChatGPT's window, and the accuracy of ChatGPT's responses was determined based on answers provided by a preparatory school. ChatGPT provided answers for 389 out of 400 questions, and its overall correct answer rate was 55.0%. The correct answer rate for 5-choice-1, 5-choice-2, and 5-choice-3 were 57.8%, 42.9%, and 41.2%, respectively. The highest correct answer rate was for the compulsory exam (67.0%), followed by the specific knowledge exam (54.1%) and the cross category exam (47.9%). The correct answer rate for non-image questions was 56.2% and for image questions, it was 51.5%. The study suggests that ChatGPT has potential to support healthcare professionals in clinical decision-making in Japanese clinical settings, but caution should be exercised in interpreting and using the answers generated by ChatGPT due to room for improvement in performance.

Introduction: Leprosy, caused by Mycobacterium leprae is one of the oldest infectious diseases in human history and its eradication is linked to poverty control, lack of basic sanitation, the fragility of health, and education services. Objective: To evaluate the frequency of blood groups (ABO/Rh) and the sociodemographic and clinical profile of Angolan patients with Leprosy treated at the Anti-Tuberculosis and Leprosy Dispensary in Luanda, the capital city of Angola. Methodology: A descriptive, introspective, cross-sectional study with a quantitative approach was carried out with 102 patients of Luanda, in the second half of 2021. Results: Of the 102 patients included in the study, the majority belonged to the ORh+ group (51.9%), followed by the BRh+ group (27.4%) and ARh+ (18.6%), most were under 51 years of age ( 87.3%), with low education (54.9%), coming from urban areas (44.1%). As for clinical conditions, most had a multibacillary infection (93.1%), diagnosed mainly by smear microscopy (75.5%) without other infection (79.4%), some of them with complications (28.4%) and individuals with non-O blood group showed changes in the blood count. Conclusion: Leprosy seems to be common in ORh+ individuals, it continues to affect especially those residing in areas of population agglomerations and with low education, presenting itself as a multibacillary infection, where changes in the blood count are greater in non-O individuals.

Laboratory medicine is a digital science. Every large hospital produces a wealth of data each day - from simple numerical results from e.g. sodium measurements to highly complex output of “-omics” analyses, as well as quality control results and meta-data. Processing, connecting, storing, and ordering extensive parts of these individual data requires Big Data techniques. Whereas novel technologies such as artificial intelligence and machine learning have exciting application for the augmentation of laboratory medicine, the Big Data concept remains fundamental for any sophisticated data analysis in large databases. To make laboratory medicine data optimally usable for clinical and research purposes, they need to be FAIR: findable, accessible, interoperable, and reusable. This can be achieved for example by automated recording, connection of devices, efficient ETL (Extract, Transform, Load) processes, careful data governance, and modern data security solutions. Enriched with clinical data, laboratory medicine data allow a gain in pathophysiological insights, can improve patient care, or they can be used to develop reference intervals for diagnostic purposes. Nevertheless, Big Data in laboratory medicine do not come without challenges: The growing number of analyses and data derived from them is a demanding task to be taken care of. Laboratory medicine experts are and will be needed to drive this development, take an active role in the ongoing digitalization, and provide guidance for their clinical colleagues engaging with the laboratory data in research.

The World Health Organization has identified antimicrobial resistance as a public health emergency and developed a global priority pathogens list of antibiotic-resistant bacteria that can be summarized in the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales species), reminding us of their ability to escape the effect of antibacterial drugs. We previously tested new heteroaryl-ethylene compounds in order to define their spectrum of activity and antibacterial capability. Now, we focus our attention on PB4, a compound with promising MIC and MBC values in all conditions tested. In the present study, we evaluate the activity of PB4 on selected samples of ESKAPE isolates from nosocomial infections: 14 S. aureus, 6 E. faecalis, 7 E. faecium, 12 E. coli and 14 A. baumanii. Furthermore, an ATCC control strain was selected for all species tested. MICs were performed according to the standard method, with some modifications. PB4 MIC values were within very low ranges regardless of bacterial species and resistance profiles: from 0,12 to 2 mg/L for S. aureus, E. faecalis, E. faecium and A. baumannii. For E. coli, the MIC values obtained were slightly higher (4-64 mg/L), butstill promising. The PB4 heteroaryl-ethylenic compound was able to counteract the bacterial growth of both high-priority Gram-positive and Gram-negative clinical strains. In the future, it would be interesting to evaluate the activity of PB4 in animal models to test for its toxicity.

All the available botulinum type A neurotoxins for clinical uses are of A1 subtype. We developed a subtype A2 low molecular weight (150kD) neurotoxin (A2NTX), with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed its efficacy superior to A1 toxins. We conducted an open study exploring its safety and tolerability profile in comparison with A1LL (onabotulinumtoxinA) and low molecular weight (150kD) A1 neurotoxin (A1NTX). Those who had been using A1LL (n=90; 50-360 mouse LD50 units) or A1NTX (n=30; 50-580 units) were switched to A2NTX (n=120; 25-600 units) from 2010 till 2018 (number of sessions ~ 27, cumulative doses ~11,640 units per patient). Adverse events for A2NTX included weakness (n=1, ascribed to alcoholic polyneuropathy), dysphagia (1), local weakness (4), spread to other muscles (1), whereas those for A1LL or A1NTX comprised weakness (n=2, A1NTX), dysphagia (8), ptosis (6), local weakness (7) and spread to other muscles (15). After injections, 89 out of 120 patients preferred A2NTX to A1 for the successive sessions. The present study demonstrated that A2NTX had the clinical safety up to the dose of 500 units, and was well tolerated compared to A1 toxins.

This post-hoc analysis of an Italian active pharmacovigilance study describes pharmacological differences of ADEs leading to emergency department (ED) visit and hospitalization in women and men. During the study period (January 2007 – December 2018), 61,855 reports of ADE leading to ED visit were collected. Overall, 30.6% of ADEs resulted in hospitalization (30% in women and 31% in men). Multivariate logistic regression showed that, among women, drug classes significantly associated with an increased risk of hospitalization were heparins (ROR 1.41, CI 1.13-176), antidepressants (ROR 1.12, CI 1.03-1.23) and antidiabetics (ROR 1.13, CI 1.02-1.24). Among men only vitamin K antagonists (ROR 1.28, CI 1.09-1.50), opioids (ROR 1.30, CI 1.06-1.60) and digitalis glycosides (ROR 1.32, CI 1.09-1.59) were associated with a higher risk of hospitalization. Overall, older age, multiple suspected drugs and the presence of comorbidi-ties were significantly associated with a higher risk of hospitalization. A significantly reduced risk of hospitalization was observed in both women and men experiencing and adverse event following immunization (ROR 0.36, CI 0.27-0.48 and 0.83, 0.42-0.74, respectively) compared to drugs. Results obtained from this real-world analysis highlight important aspects of drug safety between sexes.

Chikungunya is a mosquito-borne viral disease caused by Chikungunya virus (CHIKV. We conducted this study determine the seroprevalence and clinical presentation of Chikungunya infection among outpatients seeking healthcare in Mzuzu City, Malawi. Blood samples were collected from malaria negative and non-septic febrile outpatients with fevers ≥38 °C, for not more than 5 days. The enzyme- linked immunosorbent assay (ELISA) test was used to detect anti-CHIKV IgM antibodies and its results were used to determine seroprevalence of Chikungunya. A total of 119 serum samples were tested, of these, 73 (61.3%) tested positive for anti-CHIKV IgM antibodies by ELISA. Laboratory requisition forms were used to capture demographic information such as age, sex, clinical signs and symptoms presented by the enrolled patients. Age groups of 1-9, 10- 19, 20- 29, 30- 39, 40- 49, and ≥50 years had 17.8% (n= 13), 12.3 %,( n=9), 15.1%) (n=11), 19.2%; (n=14), 17.8% (n=13) and 17.8% (n=13) proportion of seroprevalence respectively. Most of the CHIKV infected individuals presented with fever (52.05%), joint pain (45.21%) and abdominal pain (42.67%). The presence of anti- CHIKV IgM antibodies suggest the presence of recent CHIKV infection and therefore accurate laboratory assays are highly recommended for CHIKV diagnosis and appropriate management of febrile patients.

Delirium occurs in 50-80% of end-of-life patients but it is often misdiagnosed. Identification of clinical factors potentially associated with delirium onset can lead to a correct early diagnosis. To this aim, we conducted an observational prospective study on patients from an Italian Palliative Care Unit (PCU) in 2018-2019 and evaluated the presence of clinical factors at patients’ admission. We then compared their presence in patients who developed delirium and in those who did not during follow-up. On 503 enrolled patients, 95 (18.9%) developed delirium. In univariate analyses, factors significantly more frequent in patients with delirium were advanced age, care in hospice, very compromised performance status, hypoxia, high number of simultaneous clinical factors, presence of breathlessness, poor well-being, severe drowsiness, and background therapy with haloperidol and drugs acting on CNS. In multivariate analyses, setting of care (odds ratio, OR, 1.68 for hospice versus home care, 95% confidence interval, CI 1.02-2.75; p=0.040), and administration of psychiatric drugs (OR 1.74 for administration versus no administration, 95% CI 1.08-2.81; p=0.023) were significantly associated with the risk of developing delirium, while the associations with age (OR 1.82 for > 80 years versus ≤ 70 years, 95% CI=0.98-3.36; p=0.046) and presence of breathlessness (OR 1.70, 95%, CI 0.99-2.89, p=0.053) were of borderline significance. The study indicates that some clinical factors are associated with the probability of delirium onset. Their evaluation in PC patients could help the healthcare professionals to timely identify the development of delirium in those patients.

Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. The aim of this study was to identify immune-related biomarkers that more effectively predict outcome of glioblastoma. Since heat shock protein 70 (Hsp70) and IL-2 are known to increase the expression of activatory NK cell receptors, recognizing aggressive human tumor cells that present Hsp70 on their cell surface, extracellular Hsp70 levels were determined in glioma patients together with activatory NK cell receptors. All gliomas are membrane Hsp70-positive (mHsp70+) and high grade gliomas more frequently show an overexpression of Hsp70 in the nucleus and cytosol. Significantly increased extracellular Hsp70 levels are detected predominantly in glioblastomas with large necrotic areas. Overall survival (OS) is more favorable in patients with low Hsp70 serum levels indicating that a high Hsp70 expression is associated with an unfavorable prognosis. Elevated frequencies of NK cells are associated with a more favorable outcome. Of caution, a glucocorticoid therapy reduces the prevalence of NK cells. In summary, elevated frequencies of Hsp70-reactive NK cells at diagnosis and lower Hsp70 levels predict a more favorable prognosis in glioblastoma patients.

COVID-19 was identified in Wuhan, China in in December 2019, and rapidly spread worldwide, being declared global pandemic one month later on 30 January 2020. Since its emergence, COVID-19 has raised global concerns associated with drastic measures that were never adopted in any previous outbreak, to contain the situation as early as possible. The 2019 novel corona virus (2019-nCoV) or SARS-CoV-2 is the causative agent of COVID-19. 2019-nCoV genetic sequence was rapidly identified within few days since the first reported cases and RT-PCR kits became available for COVID-19 diagnosis. However, RT-PCR diagnosis carries a risk of false-negative results, therefore additional serologic test are needed. The most important approach in the battle against COVID-19 is rapid diagnosis of suspicious cases, timely therapeutic intervention and isolation to avoid community spread. In this review, we summarize the clinical scenario that raises suspicion of COVID-19 and available laboratory diagnostics.

Abstract: This review addresses the complexities of type 1 diabetes (T1D)and its associated complications, with a par-ticular focus on diabetic retinopathy (DR). This review outlines the progression from non-proliferative to proliferative diabetic retinopathy and diabetic macular edema, highlighting the role of dysglycemia in the pathogenesis of these conditions. A significant portion of the review is devoted to technological advances in diabetes management, particu-larly the use of Hybrid Closed Loop systems (HCLS) and to the potential of open-source HCLS systems, which could be easily adapted to different patiens’needs using big data analytics and machine learning. Personalized HCLS algorithms that integrate factors such as patient lifestyle, dietary habits, and hormonal variations are highlighted as critical to reducing the incidence of diabetes-related complications and improving patient outcomes.

Clinical trials often involve new substances characterized or developed for a specific pathology or class of pathologies. At other times, a clinical trial is observational; in other words, a known sub-stance has a range of effects on a given cohort of subjects. The types of trials are different and complex, and often, young clinical novice and the inexperienced researchers may struggle to evaluate how to proceed correctly. In this paper, we aim to create a mini-guide for beginners in clinical trials and provide elements for designing a clinical trial. Our intention is to highlight where to find the materials and how to adapt, even in the absence of sponsors, so that even the most inexperienced and under-resourced researcher can gain an understqanding of the complexi-ty of the process andaddress it appropriately. We do not claim to be exhaustive or cover all ele-ments, but rather, we aim to create a checklist. With this approach, starting discussioms about the experimental phases of the drug and concluding with the clinical trial, we aim to assist those facing this challenging "world."

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

Homeostasis and its interaction with gene expression in the development and maintenance of living systems is discussed in order to formulate a new method to diagnose and treat diseases on this causative level. This includes an inquiry into the unsolved homeostasis problems of: location (where in the cell are calculations performed?), communication (what language used?), identity (set of plans/hierarchy of set points?) and computational (mechanisms used to make necessary adjustments?). As these functions require the processing of vast amounts of information which is communicated at every level of organization including the mechanisms of epigenetics, different computer models are discussed, with examples for each; analog, digital and the possibility of quantum biological. Each one allows certain properties and cell functions to emerge. The difference between functional homeostasis and dysfunctional homeostasis is discussed with strategies to indirectly study them in terms of epigenetic signatures. Hormesis is discussed as a mechanism to reverse the epimutations, leading to a method of treatment to almost any chronic disease. These topics are discussed as being a whole interconnected system.

This study investigates the role of sustainable inventory management within supply chains, exploring strategies, benefits, challenges, and implications for organizations. Through qualitative research involving semi-structured interviews with supply chain professionals from diverse industries, key themes emerged. Sustainable practices such as green logistics, waste minimization, and ethical sourcing were identified as critical strategies to reduce environmental impact and enhance operational efficiency. Technological advancements, including AI, IoT, and blockchain, facilitate real-time monitoring, predictive analytics, and transparency, supporting data-driven decision-making in inventory management. Benefits include cost reduction, improved brand reputation, regulatory compliance, and risk mitigation, positioning organizations favorably in a competitive landscape shaped by environmental regulations and consumer expectations. Challenges such as cost constraints, regulatory complexities, and organizational inertia necessitate strategic investments, collaborative efforts, and leadership commitment to overcome. The study underscores the importance of integrating environmental, social, and economic considerations into supply chain practices to foster sustainability and resilience. Looking forward, the study advocates for a holistic approach to sustainable supply chain management, emphasizing innovation, stakeholder engagement, and capacity building. By aligning organizational values with societal expectations and regulatory frameworks, businesses can navigate complexities, drive positive environmental and social impacts, and achieve sustainable growth. This research contributes insights into current practices and future directions for sustainable inventory management, informing strategies that balance profitability with environmental stewardship and societal responsibility.

Color change is the most obvious characteristic of tomato ripening stage and an important indicator of tomato ripening condition, which directly affects the commodity value of tomato. To visualize the color change of tomato fruit in mature stage, a gated recurrent unit network with an encoder-decoder structure that dynamically simulates tomato growth and development with time-dependent lines using tomato color and shape as real-time data was proposed in this paper. Firstly, the .json file was converted into a mask.png file, the tomato mask was extracted, and the tomato was separated from the complex background environment, and the tomato growth and development data set was successfully constructed. Then, a network of gated recurrent units with encoder-decoder structure was constructed to predict the future growth trend of tomato under different greenhouse temperatures. The experimental results showed that for the gated recurrent unit network of encoder-decoder structure proposed, when the hidden layer number was 1 and hidden layer number was 512, a high consistency and similarity between the model predicted image sequence and the actual growth and development image sequence would be realized, and the structural similarity index measure was 0.746. It was proved that when the average temperature was 24.93℃, the average soil temperature was 24.06℃, and the average light intensity was 11.26 Klux, the environment was the most suitable for tomato growth. The environmental data-driven tomato growth model was constructed to explore the growth status of tomato under different environmental conditions, thus to understand the growth status of tomato in time. The statement provided a theoretical foundation for determining the optimal greenhouse environmental conditions to achieve tomato maturity. And it offered recommendations for investigating the growth cycle of tomatoes, as well as technical assistance for standardized cultivation in solar greenhouses.

Major depressive disorder (MDD) and substance use disorder (SUD) are of immense medical and social concerns. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, only relatively recently the role of glia in these disorders have attracted attention. Detail understanding of the glial function in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, specific contribution of the neurotrophic factors, neuroinflammation and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes and synantocytes) on phenotypic manifestation of MDD or SUD are emphasized. In addition, potential use of this knowledge in developing novel therapeutics is touched upon.

Telecoupling, interactions between social-ecological systems across large, often global, distances, drives negative impacts from the forest-based carbon market. Yet, these negative impacts have been underreported; and therefore, likely vastly underestimated. We identify how these unintended negative impacts may occur and provide recommendations for the forest-based carbon market to better account for externalities by prioritising positive social impact, expanding comprehensive ecological outcomes and improving transparency of investments. We call for a carbon market that is designed to account for its global interconnectedness.