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.

The assessment of Histone deacetylases in conjunction with Curcumin, conducted through the Mcule Database employing the Autodock Vina algorithm, involves an examination of molecular interactions. This analysis includes the calculation of binding energies, revealing the strength and stability of the interactions between Curcumin and various Histone deacetylase targets. The comparison encompasses diverse aspects such as binding energies, specific binding sites, interactions across different targets, structural details, and potential implications for biological activity. The results imply that Curcumin shows heightened affinity for Histone deacetylase 4 in comparison to other investigated histone deacetylases.

This study centered on examining 60 different antibiotics by assessing their primary toxicity parameters through the pkCSM database. The parameters included Max. Tolerated Dose (Human) (log mg/kg/day), Oral Rat Acute Toxicity (LD50) (mol/kg), Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day), and Minnow Toxicity (LC50) (log mM). The results highlight four potential antibiotics—cefotaxime, ceftriaxone, imipenem, and meropenem—that exhibited lower toxicity effects compared to other compounds. These findings imply a relatively favorable safety profile for these antibiotics concerning the specified toxicity parameters. However, it is crucial to interpret these outcomes within the context of the specific clinical application and to consider additional factors for a comprehensive safety assessment. It's essential to acknowledge that evaluating toxicity is intricate, and the determination of what is considered "less toxic" can rely on specific criteria and the context of use. Furthermore, individual responses to antibiotics may vary, and the selection of an antibiotic should be based on diverse factors, including the specific infection being treated, the patient's health, and potential side effects.

BACE1 is involved in the production of beta-amyloid peptides, and inhibiting its activity is a potential therapeutic strategy for managing Alzheimer's disease, as excessive beta-amyloid accumulation is a characteristic feature of the disease.Computational results suggest that hypericin has the potential to act as an inhibitor of BACE1. The Molecular Docking results indicate a high binding affinity between hypericin and BACE1, with a notable binding energy score of -10.3 kcal/mol. Additionally, the formation of various chemical bonds, including hydrogen bonds and hydrophobic bonds, further supports the idea that hypericin may effectively interact with the active site of BACE1. It's important to note that while the in silico Molecular Docking results are promising, further in vitro and in vivo studies would be necessary to validate and better understand the inhibitory potential of hypericin against BACE1. Additionally, the practical application of hypericin as a BACE1 inhibitor in a therapeutic context would require careful consideration of factors such as bioavailability, safety, and efficacy.

For the first time, this study identified seven potential ligands with high binding energies through the docking approach against the Crystal Structure of human Melanoma-associated antigen B1 (MAGEB1). The ligands—Imatinib, Bafatinib, Diosmin, Ginkgetin, Bilobetin, Amentoflavone, and Hypericin—showing strong binding energies around -10 kcal/mol, indicate a potentially robust interaction with the target protein. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of these ligands. From these results, the parameters for Diosmin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile, making it a potential candidate for further consideration against Melanoma. Moving forward, it's advisable to conduct further experimental validations, including in vitro and in vivo studies, to confirm the efficacy and safety of Diosmin and other potential ligands. Consideration of pharmacokinetics, metabolism, and specific mechanisms of action will contribute to a comprehensive understanding of these compounds' potential as therapeutic agents.

Molecular docking, a computational method predicting how molecules bind to target proteins, is employed in this study to explore Polydatin's interactions with Ras-related protein Rab (Rab) proteins using the Mcule Database. This database validates the docking results and offers insights into the pharmacological properties of Polydatin. Notably, specific Rab proteins like Rab-5A, HRas, and Rab-18 exhibit robust interactions with Polydatin, indicated by favorable binding energies.These findings illuminate the potential roles of Polydatin in therapeutic and biological contexts, emphasizing its interaction with Rab proteins. The Mcule Database enhances the credibility of the study, providing additional perspectives on Polydatin's applications. The observed interactions, particularly with key proteins like HRas, present a promising avenue for modulating cellular signaling pathways. This modulation holds therapeutic potential, potentially addressing conditions associated with pathway overactivity, including specific cancer types.

Background: Thyroid nodules are common, affecting nearly 65% of the general population. While they are widespread, it's crucial to recognize that the majority of these nodules are not cancerous and can be effectively managed through careful monitoring. Thyroid ultrasound is commonly used to evaluate thyroid nodules owing to its low cost, wide availability and technical ease of application. In sonography, it's crucial to assess characteristics and vascular flow. Yet, conventional color and power Doppler ultrasound may not always effectively capture small vessels and low velocities due to their limitations. Superior Microvascular Imaging can display the blood flow of small vessels and low-velocity blood flow, which is difficult to visualize with conventional Doppler ultrasound. Meanwhile other thyroid scans, that utilize either [99mTc] pertechnetate or (18)F-fluorodeoxyglucose, can categorize nodules as hyperactive ('hot'), exhibiting normal activity ('warm'), or having reduced/no activity ('cold'). Thus, the main goal of screening and tracking thyroid nodules is to improve the management of potentially worrisome thyroid malignancies. Methodology: The study was conducted within the structural framework of a network meta-analysis, with the index tests being - SMI, Radionuclide Scanning and Color Doppler, and the general link between them being the reference gold standard. The data collection involved searching for all pertinent literature using PubMed, Google Scholar, and the Cochrane Library databases. The essential data was extracted following the application of specific inclusion and exclusion criteria.This meta-analysis included 7 RCTs with 1,152 patients for Radionuclide Scanning, 10 RCTs with 1,847 patients for SMI and 8 RCTs with 4,480 patients for Color Doppler. They were analyzed using the QualSyst tool and the risk of bias was evaluated by using QUADAS-2 analysis.The statistical software packages MetaDiSc 1.4, RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20) and Excel in Stata 14 were used to perform the statistical analyses. Result: According to the findings, the sensitivity for Radionuclide Scanning is calculated as 0.79 (range: 0.76 to 0.81) and specificity as 0.55 (range: 0.50 to 0.60) with a 95% confidence interval. The overall diagnostic odds ratio (DOR) for Radionuclide Scanning Is 10.54.Additionally, with a 95% confidence interval, SMI exhibits a sensitivity of 0.82 (with a range of 0.79 to 0.84) and a specificity of 0.86 (with a range of 0.84 to 0.88), while the overall DOR is approximately 25.73. Color Doppler demonstrates a calculated sensitivity of 0.71 (ranging from 0.69 to 0.74) and specificity of 0.81 (ranging from 0.79 to 0.83) with a 95% confidence interval, while its DOR is 13.48.Conclusion: As evidenced by this meta-analysis, blood flow dependent imaging techniques are superior in their abilities to be used as diagnostic tests, especially in conjunction with their use in detecting thyroid nodules. This study offers a starting point for delving deeper into the utilization of Radionuclide Imaging, Superior Microvascular Imaging and Color Doppler in diagnosing thyroid nodules in a clinical setting. Key Words: - Thyroid Nodule, Radionuclide Scanning, Superior Microvascular Imaging, Color Doppler Diagnosis, Sensitivity, Specificity, Diagnostic imaging

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

For a number of reasons, a curative treatment for most chronic diseases is still unrealized [2–4] and the incidence of many chronic diseases is rapidly increasing [5–9]. A new model is offered as a solution; that being the individualized diagnosis of homeostasis, leading to the correction of epimutations. Individuals with chronic diseases are increasingly being defined by their epigenetic signatures [10,11]. Modern innovations in toxicogenomic studies are also becoming more accurate in their ability to identify the unique epigenetic signature of each toxin [12–14]. Hormesis studies (over 5,000) [15] suggest a universal principle, that a small dose is always a stimulant [16–18].These three facts present an opportunity; a method to diagnose and reverse chronic disease tendencies. This new model requires a paradigm shift in our understanding of disease origins: that dysfunctions in homeostasis [19,20] are the primary and deepest level of chronic disease causation. This is the level where the diagnosis needs to be made and where the corrections need to take place [21].

This study investigates the potential of natural compounds against HIV-1 protease, a critical enzyme in the replication cycle of human immunodeficiency virus type 1 (HIV-1). HIV-1 protease is essential for cleaving large precursor proteins into smaller functional proteins necessary for viral maturation and infectivity. Protease inhibitors, specifically targeting HIV-1 protease, effectively suppress viral replication, aiding in the management of HIV infection. Using the SWISS DOCK Server, several natural compounds were investigated for their potential as inhibitors of HIV-1 protease. Docking results revealed that Amentoflavone showed excellent binding affinity with high Estimated ΔG values, suggesting its potential as an inhibitor of HIV-1 protease. Additionally, Amentoflavone exhibited similar promising results when tested against Roussarcoma virus protease. These findings indicate the potential of Amentoflavone as a natural compound against HIV and warrant further investigation into its therapeutic applications.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

AbstractBackground: Empowering Communities, Combating HIV/AIDS: The Indispensable Role of Community-Based Strategies in Awareness and PreventionObjective: Highlight the significance of community-based approaches in addressing the ongoing HIV/AIDS pandemic through enhanced awareness, reduced stigma, and effective prevention measures.Method: This article provides a theoretical analysis of community-based HIV/AIDS interventions, drawing upon key strategies and successful examples from diverse settings.Results: Community-based initiatives emerge as critical factors in empowering individuals and communities to take ownership of their health. Through culturally-sensitive education, accessible testing, and comprehensive support services, these initiatives effectively diminish the social stigma surrounding HIV/AIDS and promote preventative behaviors. Examples of successful programs illustrate the potential of community-driven approaches to achieve measurable reductions in transmission rates and improved health outcomes.Conclusion: The fight against HIV/AIDS necessitates robust community engagement. Community-based interventions, grounded in local knowledge and addressing specific needs, offer a promising pathway towards fostering health equity, reducing stigma, and ultimately curtailing the spread of the virus. Further research and investment in these initiatives are crucial to ensuring their scalability and sustained impact on global HIV/AIDS prevention efforts.

Summary— Introduction: HIV (human immunodeficiency virus) is a virus that attacks and destroys one type of white blood cell, in particular, the CD4 lymphocytes, which are responsible for the body's immune response. This weakens the immune system to such an extent that it can no longer fight other viruses, bacteria, protozoa, fungi, and tumors. Methods: We investigated the potential biological role of the natural compound Polydatin (or piceid) using SwissDock, a web service to predict the molecular interactions that can occur between a target protein and a small molecule. Discussion: For the first time, we have investigated the role of polydatin against HIV-1 protease and HIV-2 protease through a computational approach by comparing their estimated ΔG values (kcal/mol) and the nature of the interactions between the residues in the catalytic center of the HIV proteases.Conclusion: From these simulations, Polydatin has excellent physical properties and an excellent estimated ΔG value (kcal/mol) of about -9.9 kcal/mol against HIV-2 protease and ΔG value (kcal/mol) of about -9.5 kcal/mol against HIV-1 protease. In addition, Polydatin was able to bind to two key amino acids of the catalytic triad sequence common to asparagine proteases (Asp25 and Gly27)

The effective treatment of human immunodeficiency virus (HIV), also known as acquired immunodeficiency syndrome (AIDS), has transformed a highly lethal disease into a chronic and manageable condition. However, better methods need to be developed for eliminating the virus from reservoirs, enhancing patient access and adherence to therapy, and improving treatment in the long term to reduce adverse effects. From the perspective of drug discovery, one promising strategy is the development of anti-HIV prodrugs. This approach aims to enhance the efficacy and safety of treatment, promoting the development of more appropriate and convenient systems for patients. In this review, we discussed the use of the prodrug approach for HIV antiviral agents and emphasized nucleoside reverse transcriptase inhibitors. We comprehensively described various strategies that are used to enhance factors such as water solubility, bioavailability, pharmacokinetic parameters, permeability across biological membranes, chemical stability, drug delivery to specific sites/organs, and tolerability. These strategies might help researchers conduct better studies in this field. We also reported successful examples from the primary therapeutic classes while discussing the advantages and limitations. In this review, we highlighted the key trends in the application of the prodrug approach for treating HIV/AIDS..

High incidence of epithelial malignancies in HIV-1 infection is associated with co-infection with oncogenic viruses, such as high-risk human papillomaviruses (HR HPVs), most often HPV16. A collaboration between HIV-1 and HR HPVs in the malignant transformation of epithelial cells exposed to both viruses have long been anticipated. Here, we delineated the effects on in vitro and in vivo properties of HPV16-infected cervical cancer cells of HIV-1 reverse transcriptase. Epidermoid carcinoma Ca Ski cells were made to express RT of HIV-1 clade A (RT_A) or Green Fluorescence Protein (GFP) by lentiviral transduction, subclones with one or six copies of RT_A and six copies of GFP DNA were generated. Expression by subclones of GFP was assessed by flow cytometry, and of RT_A, by Western blotting. Cells were assessed for the levels of mRNA of the RT_A, E6 and its isoforms, and cellular factors characterizing oxidative stress, and EMT by the real-time PCR. Parameters of glycolysis and mitochondrial respiration were assessed by Seahorse technology. Subclones were surveyed for the changes in cell cycle, doubling time, migration capacity, clonogenic activity and for the capacity to form tumors in nude mice. Ca Ski RT_A produced 20-55 fg of RT_A per cell. Expression of RT_A caused a proportional increase in the expression of E6*I isoform. In Ca Ski, RT_A suppressed mitochondrial respiration and oxygen consumption, and increased glycolysis. Compared to parental cells and GFP control, transcription in Ca Ski RT_A of epithelial (E-CADHERIN) state marker was increased, and of mesenchymal (VIMENTIN) decreased, indicating acquisition by cells of the hybrid epithelial/mesenchymal (E/M) phenotype. While Ca Ski GFP and Ca Ski RT_A with one gene insert had reduced migration rate, decreased clonogenic activity in vitro, and diminished capacity to form tumors in nude mice, increase in RT_A copicity/expression mitigated these effects. Altogether, expression of HIV-1 RT_A gave Ca Ski cells the plasticity required to overcome negative effects of lentiviral transduction and potentially increased their tumorigenicity.

The brain being arguably the most complex organ in the human body, its detailed functioning is yet to be fully deciphered, let alone accurately modeled. Nonetheless, the medical community has gathered quite a remarkable amount of studies about the consequences of illnesses and injuries on its development and functioning. This bibliographic review aims to cover mostly the findings related to the changes in the physical distribution of neurons and their connections - the connectome -, both structural and functional, as well as their modelling. It does not intend to offer an extensive medical description of all injuries and diseases affecting the brain, rather presenting the most common ones succinctly so the need for accurate brain modelling can be fully understood and pondered, offering propositions to this aim.

Abstract This study focuses on the toxicity assessment of various flavonoids, with particular emphasis on Hesperidin. Among the investigated compounds, Hesperidin exhibits notable potential and low toxicity in both short and long-term evaluations. The toxicity parameters for Hesperidin include a low Max. Tolerated Dose (Human) (0.525 log mg/kg/day), indicative of its minimal potential harm to humans. Additionally, its Oral Rat Acute Toxicity (LD50) (2.506 mol/kg) suggests a relatively low acute toxicity level. The Oral Rat Chronic Toxicity (LOAEL) (3.167 log mg/kg_bw/day) signifies a higher dose threshold for observing adverse effects over the long term. Furthermore, Hesperidin demonstrates low Minnow Toxicity (7.131 log mM), suggesting minimal impact on aquatic organisms. Overall, this comprehensive assessment positions Hesperidin as a promising flavonoid with favorable properties and minimal toxicity.

Background: Autonomic balance measurement (ABM) is a valuable tool in clinical practice for assessing the functioning of the autonomic nervous system (ANS), which controls involuntary bodily functions. Here we summarize the current understanding of the utility of autonomic balance measurement in clinical practice. Methods: A narrative review of relevant literature was conducted, focusing on studies investigating the use of autonomic balance measures in various clinical settings. Results: ABM holds potential benefits in clinical practice, including aiding in diagnosing autonomic dysfunction, monitoring treatment efficacy, and predicting potential health complications. ABM can be crucial for diagnosing various conditions, including cardiovascular diseases (Heart failure, arrhythmias, and hypertension), neurological disorders (Parkinson's disease, Alzheimer's disease, and diabetic neuropathy), in sports medicine athletes can undergo ABM to optimize training regimens, enhance performance, assessing the impact of training stress, preventing overtraining, and promoting overall well-being and probably to assess potential health risks, in metabolic syndromes ABM can aid in the early detection of autonomic neuropathy, a diabetes-related complication, allowing for timely intervention and better management of the disease, and psychiatric disorders (Anxiety, depression, and post-traumatic stress disorder). In addition, ABM can be helpful in monitoring of treatment efficacy, by tracking changes in autonomic balance, clinicians can assess if treatments for conditions impacting the autonomic nervous system are effective. ABM can also be helpful in predicting outcomes by facilitating early recognition of future health complications in certain populations. However, limitations exist, including non-specificity, variability in measurements, and limited evidence for routine use in specific clinical settings. Conclusion: Incorporating autonomic balance measurement into routine clinical assessments provides a more comprehensive understanding of a patient's health. It complements traditional diagnostic methods, offering additional insights into the body's regulatory mechanisms. While autonomic balance measurement offers potential benefits, careful interpretation and consideration of its limitations are crucial for its effective use in clinical practice. ABM remains a valuable and versatile tool in clinical practice for a deeper understanding of the autonomic nervous system, enabling early detection, targeted interventions, and improved management of various medical conditions across different specialties.

The theory of Ismail's non-extensive maximum entropy solution (NME) is described in detail. It is used as an inductive inference technique for heavy-tailed queues with a non-robust mean queue length and a non-extensive "long-range" interaction. In our novel method, we substitute the non-robust mean queue length for the conventional Pollaczeck-Khinchin mean queue length. In other words, the new non-extensivity parameter q will be included in the resulting state probability function. Numerical portraits are provided to capture the influential effect of the derived formalism, , on the stable M//1 queue with heavy tails. More potentially, some applications of Hurst Exponent to social computing and connected health are provided. Conclusion with some challenging open problems and possible future research pathways are given.

Electromobility has gained significant attention in the auto- motive industry, with car manufacturers striving to improve the charging experience for their users. In this study, we compare multiple realistic charging strategies in order to quantify the benefits arising from better planning of charging sessions. We base our evaluation on electricity price data from three regions: Sweden (SE3 region), Germany (DE region), and Denmark (DK2 region). This data is obtained from the ENTSO-E Transparency Platform, covering the two full years 2021 and 2022. We enhance this dataset with commercial price forecasts from the company StormGeo and benchmark it against a naive forecasting method. The primary aim of our work is to compare how the strategies of varying levels of complexity perform across the three different countries in terms of minimizing energy costs for electric car users.

In this work, several random Boolean networks (RBN) are generated and analyzed from two characteristics: their time evolution diagram and their transition diagram. To do this, its randomness is estimated using three metrics, of which algorithmic complexity is the only one capable of revealing both transitions towards the chaotic regime and the algorithmic contribution of certain states to the transition diagram and their relationship with the order they occupy in the temporal evolution of the respective RBN.

We prove through path integral Monte Carlo computer experiments that the affine quantization of the $\varphi_4^4$ scaled Euclidean covariant relativistic scalar field theory is a valid quantum field theory with a well defined continuum limit of the one- and two-point-function. Affine quantization leads to a completely satisfactory quantization of field theories using situations that involve scaled behavior leading to an unexpected, $\hbar^2/\varphi^2$ which arises only in the quantum aspects.

The Semantic-Enhanced Tree-LSTM (SeT-LSTM) network, a novel advancement in the realm of linguistic modeling, marks a significant step forward from traditional Tree-based Long Short Term Memory (LSTM) networks. By intricately weaving in the nuances of typed grammatical dependencies, SeT-LSTMs offer a more nuanced understanding of language semantics. Traditional models often overlook the semantic shift caused by variations in word or phrase roles, a gap this paper aims to fill by focusing on the types of grammatical connections, or typed dependencies, within sentences. Our proposed architecture, dubbed the Semantic Relationship-Guided LSTM (SRG-LSTM), leverages a control mechanism to model the interplay between sequence elements. Additionally, we present a novel Tree-LSTM variant, the Semantic Dependency Tree-LSTM (SDT-LSTM), which integrates dependency parse structures with dependency types for more robust sentence embedding. The SDT-LSTM demonstrates superior performance in Semantic Relatedness Scoring and Sentiment Analysis compared to its predecessors. Qualitatively, it shows resilience to changes in sentence voice and heightened sensitivity to nominal alterations, aligning well with human intuition. This research underlines the pivotal role of grammatical relationships in sentence understanding and paves the way for further exploration in this domain.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

Well-exposed fluvio-deltaic Surma Group successions of the northeastern Surma Basin provide a direct analogue to its equivalent subsurface successions—the main hydrocarbon reservoirs in Bangladesh. The various levels of lateral and vertical heterogeneities lead to changes in the subsurface sandbody distributions and their reservoir qualities across fields. The present study aims to identify the heterogeneities in the fluvio-deltaic Surma Group successions by detailed sedimentological analysis of the Mio-Pliocene-aged Surma Group successions. Eleven lithofacies have been identified and based on the recurring pattern of these facies within the Surma Group, five facies associations have been identified. The facies associations indicate that these deposits originated from diverse depositional settings, ranging from the prodelta to the alluvial to delta plain. As a whole, they represent a progressive shallowing upward succession with two transgressive events in the upper and lower parts of the Surma Group. Five levels of heterogeneities such as prodelta mud (HL-I), tidal heterolithic deposits (HL-II & III), interbedded mud units in delta front (HL-IV), and intercalated mud laminae, drapes (HL-V) have been identified in the fluvio-deltaic Surma Group. The study suggests that the various levels of reservoir heterogeneities are controlled by the occurrence and distribution of various facies associations.

In small animal models of severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) infection, ferrets (Mustela putorius furo) have been used to investigate the pathogenesis. Podoplanin (PDPN) is an essential marker in lung type I alveolar epithelial cells, kidney podocytes, and lymphatic endothelial cells. Monoclonal antibodies (mAbs) against ferret PDPN (ferPDPN) are useful for the pathological analyses of those tissues. We previously established an anti-ferPDPN mAb, PMab-292 using the Cell-Based Immunization and Screening (CBIS) method. In this study, we determined the critical epitope of PMab-292 using flow cytometry. The N-terminal ferPDPN deletion mutants analysis revealed that the Val34 is located at the N-terminus of the PMab-292 epitope. Furthermore, the PA tag-substituted analysis (PA scanning) showed that Asp39 is located at the C-terminus of PMab-292 epitope. The epitope sequence (₃₄-VRPEDD-₃₉) also exists between Val26 and Asp31 of ferPDPN, indicating that PMab-292recognizes the tandem repeat of the VRPEDD sequence of ferPDPN.

This study focuses on examining various approaches for Tensor Decompositions (TDs) and their potential applications in satellite imaging (SI) and deep learning (DL). The research highlights how these decompositions can contribute to the advancement of SI and DL, providing valuable insights for future utilization of TDs in research. It explores how these techniques contribute to the advancement of SI and DL methods, providing insights into their potential applications and suggesting future research directions. The study aims to enhance the use of TDs techniques to further advance research efforts in these fields. More importantly, the current investigation offers a thorough analysis of the potential advantages and reasons for employing TDs techniques in different domains, including satellite imaging and deep learning. The aim is to enhance research outcomes by utilizing TDs. The review also identifies unresolved issues and proposes future directions for further investigation in this field. Fundamentally, these proposed open problems will open new grounds to the research community to articulate, innovate, and provide more real-life applications to improve the current state of the art by delving into a wider vision for a higher-level performance of both satellite imaging (SI) and deep learning (DL). Looking at the bigger scenario, this also suggests that TDs could be potentially employed to revolutionize existing machine learning technologies as well as the current space AI industry.

Actually, the study aimed to manage and to analyse the results of the laboratory methods, using liver samples, preparing and analizing in pathology service. This mentioned, are known as routinally practice for hepatitis C diagnosis, which conduct to hepatic cirrhosis. In this study direction, chronic liver diseases stimulate a degree of hepatocyte injury. So previously mentioned modifications, alters thet affect the liver architecture and finally ends in cirrhosis are well analyse on microscopic preparates. Folowing morphological steps, it is possible to analyse normal and alterate liver structure, on colored preparates.

This article seeks to strengthen efforts in technological developments based on the classification of PET plastic that positively impacts sustainable development and contributes to suitable solutions in collection centers in Mexico. Three experiment designs and machine learning tools for data processing were developed. For the experimentation, three factors were considered: the bottle's size, the amount of liquids inside the bottle, and the label on the bottle. The first experiment was to identify the distance of the sensor from post-consumer PET bottles. The second experiment was to determine the detection ability of the sensor with different levels of liquids inside the bottles, and the third was to determine the detection ability on the bottle labels. A digital lux meter on a microcontroller was developed to monitor illuminance on post-consumer PET plastic when it contains liquid as it passes through a conveyor belt for processing at an average rate of three bottles per second. With the implemented methodology, liquids were satisfactorily detected inside the transparent PET bottles when they had beverages between 25% and 100% of their capacity. Finally, this paper highlights that it is possible to implement an affordable design to identify bottles with liquids for collection centers.

The ordinary 3D wave equation for nondissipative, homogeneous, isotropic media admits solutions where the point sources are permitted to move, but it does not admit solutions where the receiver is allowed to move. To overcome this limitation, the new wave equation is derived, permitting both the receiver and the source to move. This new wave equation is a generalization of the standard wave equation, and it reduces to the standard wave equation when the receiver is at rest. To derive this new wave equation, we first mathematically define a diverging spherical wave caused by the stationary point source. From this purely mathematical definition, the wave equation for the stationary source and the moving receiver is derived together with the corresponding free-space Green's function. Utilizing the derived Green's function, it was shown that this new wave equation also permits the solutions where both the receiver and the source are permitted to move. In conclusion, this paper demonstrates that, instead of an ordinary wave equation, the wave equation for the moving source and the moving receiver governs the waves emitted by the moving point sources and received by the moving receivers.

The future index prices are viewed as a critical issue for any trader and investor. For this craving, various models have shown up in the literature. The Geometric Brownian motion (GBM) is one of the popular models. This work examines four types of GBM as per the presence of memory or kind of volatility. These models include classical GBM with memoryless and constant volatility assumptions, SVGBM with memoryless and stochastic volatility assumption, GFBM with memory and constant volatility assumption, and SVGFBM with memory and stochastic volatility assumption. These models are utilized in an empirical study to forecast the future index price of Energy Sector in the Saudi Stock Exchange Market. The assessment was led by utilizing two error standards, mean square error (MSE) and mean absolute percentage error (MAPE). The outcomes showed that the SVGFBM occupies the highest level of accuracy according to smallest values of MSE and MAPE. While the accuracy of GBM come in the tail of the list models under study. These results have affirmed the positive affection of combining memory and stochastic volatility assumption into the GBM model, which agreed findings of numerous earlier works. Furthermore, the findings showed the GFBM models are more accurate than GBM models regardless of the type of volatility. While, under the same type of memory, the models with stochastic volatility assumption are more accurate than the corresponding models of constant volatility assumption. In general, all models considered in this work uncovered high accuracy through the value of MAPE ≤ 10%. This indicates of the ability of applying these models in a real financial environment. Through this empirical study, we can say that the Energy Sector in Saudi Arabia is predictable and stable and afterward we urge financial investors and stockholder to trade and invest in this sector.

Polydatin, a polyphenolic compound sourced from various natural origins, has garnered attention due to its potential anti-tumor properties and low toxicity. This research utilized Molecular Docking methods to investigate the molecular interactions between Polydatin and the Crystal Structure of Human UDP-glucuronic acid decarboxylase (UXS1), aiming to uncover the mechanisms contributing to its anti-tumor effects. The study revealed a substantial binding energy value of approximately -10 kcal/mol for the Polydatin-UXS1 interaction, indicating a robust and favorable binding. This suggests that Polydatin holds significant promise in cancer research, offering insights into its ability to interact with and potentially modulate the activity of UXS1. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of polydatin ( or piceid). From these results, the parameters for polydatin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile.These findings position Polydatin as a compelling candidate for further exploration in cancer research, highlighting both its efficacy and safety considerations.

This study employs molecular docking techniques to investigate a spectrum of targets within Escherichia coli (E. coli), with a specific focus on four key proteins: Beta-lactamase, MccE protein, Penicillin G acylase, and DNA polymerase II. The research explores the binding interactions of various natural compounds, emphasizing Hypericin. Through computational analyses, the study aims to unveil the potential interactions between these compounds and essential proteins in E. coli. Notably, Hypericin demonstrates remarkable binding energy scores of approximately -10.5 kcal/mol within the Ligand Binding Site of the specified proteins. This observation suggests Hypericin's potential as a potent modulator of E. coli targets, prompting further investigation into its antimicrobial properties and therapeutic applications.

Cities are complex systems requiring urban design models that balance order and disorder. Collective creativity initiatives engage citizens in these processes, empowering bottom-up approaches that prioritize people and social well-being within urban development. This paper investigates an 'Urban Laboratory' as a case study, examining the potential of collective creativity to address urban complexity. The successful and ongoing project 'El Campo de Cebada' in Madrid, Spain, demonstrates how a community transformed a vacant lot into a vibrant social hub. The phases of this study include case selection, data collection, data analysis, and presentation of the results. This study identifies key enabling factors, including agents, management, social dynamics, infrastructure, and actions. These insights offer a methodological framework for designing future collaborative, resilient, and inclusive urban spaces, addressing the complex needs of communities within our cities.

Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. Previously, we developed a sublingual vaccine formulated with the SARS-CoV-2 receptor binding domain antigen and Poly(I:C) adjuvant in nonhuman primates, cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvant and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccineproduced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines—IFN-alpha, IFN-gamma, and IL-17—in the blood, nor upregulated the gene expression of proinflammatory cytokines—IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B—in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with Poly(I:C) adjuvant is safe and creates a balanced state of enhancing and suppressing the immune-related response.

The work contains a detailed analysis of the electromagnetic field originating from a point source placed above the layered structure.The surface impedance of the multilayer dielectric structure was determined. Based on the boundary conditions, a method for determining the surface impedance of a layered structure with a perfectly conductive screen and or a magnetic screen is presented. The resonance conditions and the conditions for the excitation of surface waves are derived. The integral expression defining the generalized impedance was analyzed with a view to adapting it to numerical implementation. This allowed the development of a computer program based on which calculations were made of the effect of excitation of waves on multilayer dielectric substrates.

Conventional text style transfer (TST) methodologies primarily utilize style classifiers to segregate the content and stylistic elements of text for effective style transformation. Despite the pivotal role of these classifiers, their influence on TST techniques remains largely unexplored. This study embarks on a detailed exploration of the limitations inherent in style classifiers within current TST frameworks. We reveal that these classifiers often inadequately comprehend sentence syntax, leading to diminished performance in TST models. In response, we introduce the Syntax-Enhanced Style Transfer (SEST) model, a groundbreaking approach incorporating a syntax-sensitive style classifier. This classifier ensures that the extracted style representations robustly encapsulate syntax nuances, enhancing TST effectiveness. Rigorous evaluations across diverse TST benchmarks demonstrate that SEST significantly surpasses contemporary models in performance. Additionally, our case studies highlight SEST's proficiency in producing syntactically coherent sentences that aptly retain original content.

The global textile sector, pivotal to economic development, significantly contributes to environmental degradation, prompting a shift towards sustainable raw material sources. Embracing circular economy principles, this industry is exploring the valorization of agricultural by-products. This study introduces an innovative approach to repurposing mango waste into valuable textile fibers, a byproduct of the fruit processing industry, predominantly generated during juice and jam production. The focus is on the lignocellulosic constituents of mango waste, specifically the peel, seed, and fibrous material, traditionally considered as refuse. Previous research has predominantly utilized mango peel in pectin extraction for food applications, whereas the potential of seed and fibrous content remains underexplored. This investigation endeavors to transform these fibrous by-products into high-value materials suitable for textile manufacturing. The process involved washing, drying, and comprehensive physicochemical characterization of mango fibers, emphasizing lignin quantification, revealing a composition of 12.2% lignin. An experimental design was employed to elucidate the impact of variables such as liquid-to-solid ratio, reaction duration, and sodium hydroxide concentration on lignin dissolution through alkaline hydrolysis. Optimal conditions—10% NaOH concentration, 30 mL/g liquid-to-solid ratio over six hours—achieved an 83% reduction in lignin content. The resulting fibers exhibited properties akin to conventional natural fibers, including a favorable aspect ratio indicative of their suitability for textile applications. A subsequent softening process using propylene glycol enhanced the fibers' spinability, producing a durable, textured fabric ideal for eco-conscious fashion applications, including bags, footwear, and accessories. This research demonstrates the feasibility of converting mango waste into a textile-worthy material and underscores the importance of waste revalorization in promoting sustainability within the circular economy framework.

Neisseria gonorrhoeae is a bacterium that causes the sexually transmitted infection gonorrhea. This study employed molecular docking simulations to investigate potential interactions between natural molecules and the Fe(3+) ions import ATP-binding protein fbpC in Neisseria gonorrhoeae FA 1090. Among the screened molecules, Hypericin exhibited a remarkable binding energy of approximately -13.2 kcal/mol, indicating a robust and favorable binding affinity with the target protein. This promising outcome suggests that Hypericin could serve as a potential candidate for further exploration as a therapeutic agent against Neisseria gonorrhoeae infections. However, it is imperative to emphasize that these in silico findings necessitate experimental validation through in vitro and in vivo studies to ascertain the actual efficacy and safety of Hypericin as a treatment option.

The study focused on Molecular Docking simulations using Autodock Vina in conjunction with the Pyrx program to investigate potential drugs and natural compounds against the Bcr-Abl oncoprotein. From initial virtual screening of 200 compounds, 11 potential candidates were selected for further evaluation. Additional investigations included toxicity prediction using the pKCSM server. Among the compounds, Diosmin and Hesperidin showed high maximum tolerated doses in humans and low toxicity. Conversely, only Eltrombopag among the selected drugs exhibited excellent parameters, albeit with a potential risk of liver damage at high dosages. These findings underscore the need for comprehensive evaluation of efficacy and safety in the development of potential treatments targeting the Bcr-Abl oncoprotein.

This study explored what motivates university counselors. By analyzing various factors like personal values and work environment, they found counselors experience greater career satisfaction when their work aligns with their own values and societal impact, and when they receive recognition and opportunities for growth. Universities can utilize these findings to create a more supportive environment for counselors by highlighting their impact, offering development opportunities, and fostering a positive work culture. This can ultimately lead to a more motivated and effective counseling team, benefiting both the counselors and the students they serve.

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

My innovative entropy measure, Ismail entropy, namely, (IE) is an ultimate generalization to numerous generalized entropies within the literature. The fractal dimension of IE is identified in this paper. On another applicative note, this paper offers some potential applications of fractal dimension to smart cities. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

This work is concerned with studying the change of some Optical and Electrical Properties of Ba_xFe_(1-x)TiO₄ thin films due to the change of the nano crystal size. Simple theoretical explanation based on the string theory was developed. The empirical results obtained indicated that the absorption coefficient, electrical conductivity, and the magnetic permeability increase upon decreasing the nano crystal size. However, the transmission coefficient, and the refractive index increase upon increasing the nano crystal size. All these changes are explained using a simple string model with the aid of Newton's laws. The capability of the string theory to explain this nano quantum behavior comes from the fact that the string theory recognize both the particle and the wave nature of the nano system. This is similar of course to the quantum approach which is based mainly on the dual wave particle nature of atomic systems and entities.

ABSTRACTIntroduction and Purpose: Nurses are expected to be competent in practice based on the domain of standards and interpersonal soft skills (ISS). Nurses are faced with inadequate physical assessment 28%, formulating diagnoses 56%, plans 34%, implementation 31%, evaluation 37,5%, and communication skills 41%. Aims to develop an ISS learning model based on transformative learning theory and digitalization (TLTD) to improve nurses’ competencies. Method: Used Explanatory cross-sectional involved 190 practitioner nurses. Variables of individual characters (X1), facilities (X2), Social environment support/SES (X3), TLTD (X4), ISS (X5), and nursing competencies (Y) were measured. Data was collected using a checklist questionnaire, conducted on 6 June to 10 August 2022 at Dili, Baucau, and Maliana hospitals. Used descriptive and inferential analysis with SEM-PLS. Result: Five of the 11 hypotheses of statistical p-value < 0,05 and T-Test > 1,96, including X2>X4, X3>X5, X4>X5, and X5>y, to form ISS learning model. The characteristic of respondents were 81,8% young adults, 67,9% women, 57,8% undergraduates, judging the previous training 35% was unsuccessful, and 45,8% did not meet expectations. Learning facilities that are still lacking include policies 23,7%, curriculum 23,4%, guideline 22,7%, modules 27,9%, infrastructure 20,3%, social environment support 24,2% low, organizational support, 30,0% low peer support and 26,3% low family support. The average TLTD is 25,3% to 34,2%, ISS 22,1% to 30,5%, and nurse competence 25,3% to 30,5%.Suggestion: Result of the study become base to improve nurse’s competencies. Conclusion: Learning model was formed by facilities, SES, TLTD, ISS, and nurses’ competencies.

Due to the advancement and availability of internet in present age, device tend to become wireless as well. Mobile ad-hoc network is a wireless environment that consist of advanced agility of nodes and does not contain on any central administrative authority. As it does not contain any central administrative authority so being wireless environment, the network is vulnerable to security threats and suffers in performance as well. Security of MANET is the core issue in this era, meanwhile the data is sent over untrustworthy network. Several techniques were proposed to secure data over Mobile Adhoc Network though cryptography that is one of the most reliable techniques to protect data. In our proposed methodology a Secure Cryptographic technique for Mobile Adhoc Networks (SCTMA) we proposed A Collusion attack prevention (CAP) scheme with ElGamal key generator along with DNA encryption Algorithm is used to make it more secure. The proposed scheme protects the network against collusion attacks and improves the performance as well. Performance analysis will be measured on the basis of key generation time, response time, encryption time and decryption time. The proposed scheme also protects the network against collusion attacks.

This paper is a brief review of our own work on the Planck quantized version of general relativity theory. It demonstrates several other straightforward methods to simply rewrite the same equations that we have already presented.

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (T_H2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8⁺Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C₈Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C₈Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10^-8 M and 2.0×10^-8 M, respectively. C₈Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

Studies have established the crucial role of sleep among the students which plays a significant role in their mood. This study aimed to examine the mood disorders and sleep quality among undergraduate students at the University of Georgia (UG) and comparison between students’ nationality.This cross-sectional study was a self-reported questionnaire comprised of demographics including age, gender, year of study, current location, lifestyle data (Exercise and smoking), the Depression, Anxiety, and Stress Scale (DAS21) and the Pittsburgh Sleep Quality Index (PSQI). We performed a descriptive analysis, and the Chi-square was statistically significant at p<0.05. The prevalence was at a 95% confidence interval (95% CI) as multivariate analysis examined the multicollinearity. The female students were most of the respondents, below the age of 20 years. The student's mean age was 20.20 (SD± 3.0). DAS report presented 72.7% of students with depressive symptoms, 77.8% with anxiety symptoms, and 62.2% had stress. Georgian students were more at risk of having depressive complaints (95% Cl[1.567-3.788]), anxiety (95% Cl[1.612-4.285]), and stress symptoms (95% Cl[1.743-3.831]). There was a strong relationship between the students who experienced poor sleeping patterns and depressive complaints (aOR 0.10). The students who were smokers (aOR 0.39) were more likely to report anxiety symptoms than the students that do not exercise (aOR 1.68). It was observed that students with depressive symptoms, anxiety, and complaints of stress had a significantly high risk of poor sleep quality. Further studies are recommended to curb psychological symptoms of mood changes in association with sleep disorders among students.

Therapies targeting amyloid, such as monoclonal antibodies like Lecanemab, Aducanumab, and Donanemab, have garnered FDA approval but remain controversial due to limited clinical benefits and significant side effects against Alzheimer. The present theorical work utilized Virtual Screening and Docking techniques to explore potential small natural molecules' interactions with the KIBRA protein, a promising target for drug development. Kibra protein is considered a biomarker for synaptic dysfunction and cognitive decline. Employing Autodock Vina and Pyrx software, on several natural compounds and found Hypericin to exhibit the lowest binding energy of approximately -9 kcal/mol. Previous studies have highlighted Hypericin's strong affinity for Alzheimer's Disease-associated targets like ABAD and BACE1. These findings suggest Hypericin could be as a potential therapeutic agent for Alzheimer's Disease. Further research is warranted to validate its efficacy and safety for clinical use.

Security in the Internet of Things (IoT) is a critical concern due to the growing number of connected devices and the limited resources to implement robust security mechanisms in most of them. Adopting standard assessment frameworks, such as CVSS (Common Vulnerability Score System), allows for systematic vulnerability assessment. At the same time, CVE (Common Vulnerabilities and Exposures) records provide unique identifiers for known security issues, making it easier to share information. However, comparing security solutions is still challenging due to the diverse nature of IoT devices and the ever-evolving threat landscape, requiring continual innovation and collaboration between stakeholders. Furthermore, there still needs to be a simple way to compare technologies and solutions, taking into account the security provided by them. In this sense, in this article, we propose a tool for calculating a security score based on the CVSS index of each existing vulnerability in a given technology. We explain how the tool performs the calculation, discuss some challenges, and propose improvements for future work.

Coastal resources in Lian, Batangas, have undergone significant degradation due to a combination of human activities and natural factors, including sea-level rise, changes in sea-surface temperature, fluctuations in rainfall, increased storm frequency, and sedimentation. This has led to adverse effects on key ecosystems such as corals, mangroves, and seagrasses. To assess the extent of climate change hazards on these coastal resources, a Vulnerability Assessment was conducted in the municipality of Lian, Batangas. The assessment employed a combination of the Coastal Integrity Vulnerability Assessment Toolkit (CIVAT) and Integrated Coastal Sensitivity, Exposure, and Adaptive Capacity to Climate Change (ICSEA-C) guidelines. Additionally, the analysis incorporated detailed mapping using Light Detection and Ranging (LiDAR) data for mangroves and LandSat 8 imagery for corals and seagrasses. The findings at the municipal scale revealed that a staggering 90% of mangroves in Lian, Batangas, were highly vulnerable. This vulnerability was attributed to a high score in intrinsic characteristics and a low adaptive capacity. Similarly, a majority of seagrasses in the area were classified as medium and highly vulnerable at the municipal level. Only 10–20% of seagrasses received low to medium vulnerability scores. Shockingly, almost 100% of the coral reefs in Lian, Batangas, were deemed highly vulnerable, indicating a critical threat to this crucial marine ecosystem.

This study provides a comprehensive comparison of the Peter Chew Sum method and Newton's Sum in Quadratic Root Function Computations. Both methods offer significant advancements by alleviating the need for memorization of multiple formulas. However, when confronted with higher-order quadratic root functions such as the calculation of power 33. Newton's Sum method proves cumbersome due to its requirement of all previous answers for final computation, leading to increased steps and error risks. In contrast, the Peter Chew Sum method simplifies the computational process by requiring only a few previous answers, resulting in a more straightforward series of operations. We contextualize our analysis within the historical progression of mathematical techniques, highlighting the transformative leap represented by the Peter Chew Sum method in quadratic root function computations. Peter Chew Sum addressing the limitations of Newton's Sum , especially concerning higher-order functions such as the calculation of power 256. Furthermore, study demonstrates that the innovative approach of the Peter Chew Sum method not only simplifies complex computations but also fosters enhanced conceptual understanding among students. In conclusion, study findings underscore the profound impact of the Peter Chew Sum method on quadratic root function computations.

Docking results suggest that Amentoflavone has a higher affinity for investigated Serine/threonine-protein kinases, indicating potential interactions that may influence the activities of these kinases. The negative values of the binding energies signify strong and stable interactions, suggesting that Amentoflavone could be a key molecule in modulating the functions of these kinases, which play crucial roles in cellular processes such as cell cycle regulation and apoptosis.

Thyroid hormones are essential for regulating the metabolic rate, growth, development, and maintenance of many physiological processes in vertebrates. They are synthesized by the thyroid gland, which is an ancient organ that evolved early in vertebrate evolution. This study aims to characterize the evolutionary path of polymorphic variants associated with the hypothalamus-pituitary-thyroid (HPT) axis by comparing ancient DNA (aDNA) sequences of Late Pleistocene-Holocene hominin populations with those of modern humans. We evaluated the genetic sequences of several populations, including Neanderthals, Denisovans, Palaeolithic hunter-gatherers from European Russia and Sunghir, and Neolithic hunter-gatherers/farmers from Anatolia focusing on genes involved in the development of the thyroid gland and thyroid hormone (TH) biosynthesis, secretion, and transport. Results showed interesting variants in the DIO2 (rs225014), TPO (rs4927611), and TG (rs2069556 and rs1133076) genes. All SNPs seemed to confirm that Neanderthals, and in part Denisovas, were physiologically hypothyroidic. Probably they had lower T3 levels due to defective production or peripheral conversion. From the moment that the most favourable alleles in terms of T3 production appear during the Paleolithic, we are inclined to assume that their selection was linked to environmental pressure.Our study supports insight into the evolutionary history of the endocrine system and can help in providing understanding into the evolution of physiological systems and their adaptation to changing environments. Understanding the evolution of thyroid hormones can also shed light on the mechanisms underlying thyroid disorders in humans.

Background: As the most invasive breast cancer (BrCa), triple-negative BrCa (TNBC) has the worst survival. The use of dexmedetomidine potentially affected BrCa surgery and dexmedetomidine was reported to have direct effects on TNBC cells. The objective of this study is to explore the mechanisms underlying the effect of dexmedetomidine on TNBC. Methods: Dexmedetomidine targets were predicted using The Cancer Genome Atlas data SwissTargetPrediction. Cell lines MDA-MB-231, MCF7, and MCF10A were used to validate the targets in TNBC with both clinical samples and cell lines. Cancer cell lines and normal breast cell lines were grouped in cancer and normal groups respectively. Both groups were exposed to dexmedetomidine treatment. Cell Counting Kit-8 was used to determine the effect of dexmedetomidine on cells with target silencing. The binding model of the candidate targets was docked and critical amino acids were mutated to validate the binding model. Results: Dexmedetomidine selectively inhibits cancer cells. Catalytic subunit of the DNA-dependent protein kinase (PRKDC), indoleamine 2,3-dioxygenase 1 (IDO1), opioid receptor kappa 1 (OPRK1), glutaminyl-peptide cyclotransferase (QPCT), macrophage migration inhibitory factor (MIF), potassium voltage-gated channel, subfamily H (Eag-related), member 2 (KCNH2), cholinergic receptor, muscarinic 3 (CHRM3), and potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 (KCNN4) were identified as dexmedetomidine targets in TNBC. The expression levels of PRKDC, IDO1, MIF, KCNH2, CHRM3, and KCNN4 were found to be upregulated in TNBC tissues compared to non-TNBC tissues(p<0.05). Silencing of these genes was found to reduce the sensitivity of TNBC cells to dexmedetomidine(p<0.05). This effect was counteracted when the silenced genes were overexpressed, resulting in an increase in the sensitivity of cells to dexmedetomidine (p<0.05). Furthermore, a direct interaction between dexmedetomidine and IDO1 and CHRM3 was observed, which regulated the sensitivity of cells to dexmedetomidine(p<0.05).Conclusion: IDO1 and CHRM3 are direct targets of dexmedetomidine in TNBC.

We review the basics of nuclear binding energy scheme assumed to be associated with the existence of a new strong elementary charge associated with square root of reciprocal of the strong coupling constant.

Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.

Scholars and policymakers see sustainability as depending on the interrelationships between the three pillars of the environment, society and the economy. However, it remains less clear how key stakeholders with a responsibility for educating the next generation perceive the concept of sustainability and act accordingly. In order to gain new insights, this research scrutinises participant perceptions on sustainability and climate change in two eco-schools in England for primary children (aged 5-11 years). Our case study involved individual interviews with classroom teachers and headteachers, group interviews with fourth- and fifth-year students (ages 10-12 years), and in-class observations. We also analysed data from student exercise books and photographs of school grounds to understand participants’ self-reported knowledge and perceptions of sustainability and climate change. Within a framework drawing on theories of science communication and transformative learning (a learning approach based on having challenging experiences), the results show that the integration of sustainability into the curriculum was limited and problematic. That is despite the fact that all students and teachers were aware of the environmental dimensions of sustainability, like climate change and the overuse of natural sources. These findings suggest that schools are no different to other institutional settings when it comes to dealing with the challenges of integrating sustainability into daily practice. We conclude that there is a need for in-service teacher education programmes to enable and motivate teachers to provide richer teaching-learning environments so as to enable effective learning in schools about sustainability and climate change.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

Background: Atopic dermatitis (AD), a common dermatological condition, is often associated with significant economic and social burdens. Despite extensive studies globally, there is a gap in understanding the comprehensive impact of this condition in Romania. Objectives:This study evaluated the economic burden and quality of life impact of AD in Romania, considering both direct and indirect costs. Materials & Methods: A mixed methods cost of illness study was conducted from April to October 2023. A patient survey, expert reviews, and national health data analysis were used to assess direct medical costs (treatments, medical services), direct non-medical costs (transportation, accommodation), and indirect costs (productivity losses). Quality of life was evaluated using the EuroQol EQ-5D-5L instrument. Results: In 2022, the total cost of atopic dermatitis in Romania was 32.983.498 EUR for adults and 31.573.968 EUR for children. Adult costs included 24.534.603 EUR in direct and 8.429.884 EUR in indirect medical costs, with an average annual cost per patient of 447 EUR. Pediatric costs involved 15.026.781 EUR in direct and 16.516.410 EUR in indirect costs, averaging 290 EUR per patient annually. Conclusion: Care expenditure with AD management in Romania is substantially lower than in other countries, posing a significant economic burden, primarily driven by indirect costs. This study provides a foundation for future policy interventions and highlights the need for targeted management strategies for AD.

Background : Probiotics are composed of microorganisms that have positive effects on health when consumed in prescribed quantities. Lately, studies have attempted to establish this role of probiotics in enhancing health. Aim : The aim of this study was to compare the antifungal activity of 3 different probiotics against Candida albicans.Methodology :This was an in-vitro study. 3 types of commercially available probiotics - Bifilac, Pre pro HS and VSL-3 were cultured separately with Candida albicans and were placed under incubation. The maximum zone of inhibition was recorded for each of the probiotic solutions.Results : In this study, it was found that among the three probiotic products, Bifilac exhibited a maximum zone of inhibition of 13mm at concentration of 100µL against C. albicans, while Pre pro HS and VSL-3 showed zone of inhibition of 11mm at concentrations of 50µL and 100µL, respectively.Conclusion : Within the limits of the present study, This study could prove that probiotics can be considered as an alternative and safe treatment option for treatment of Oral candidiasis infections.

In order to search possible residual minor phases in Y-Ba-Cu-O family, powdered mixtures of Y₂O₃ + BaCO₃ + CuO and, independently, superconducting compound YBa₂Cu₃O_7-x have been treated in evacuated cells and elevated temperatures.YBa₂Cu₃O_7-x was reduced to YBa₂Cu₃O₅ by use of the special home designed Taconis-Knudsen vacuum device. A subsequent doping by oxygen converts produced insulator YBa₂Cu₃O₅ to semiconductor or metal YBa₂Cu₃O_5+x (0<x<0.3). In addition to YBa₂Cu₃O₅, 0.05 volume percent of the minor delafossite phase Y₂Cu₂O₄ was being spotted in the powder mixture 1/2 Y₂O₃ + 2BaCO₃+6Cu₂O, heated up to 818 °C in an inert gas atmosphere. An attempt to prepare the insulating bulk delafossite samples was successful, and subsequent doping by oxygen produces novel metallic phases.

A cell-surface ectonucleotidase CD39 mediates the conversion of extracellular ATP into immunosuppressive adenosine with another ectonucleotidase CD73. The elevated adenosine in the tumor microenvironment (TME) attenuates antitumor immunity, which promotes tumor cell immunologic escape and progression. Anti-CD39 monoclonal antibodies (mAbs), which suppress the enzymatic activity, can be applied to antitumor therapy. Therefore, an understanding of the relationship between the inhibitory activity and epitope of mAbs is important. We previously established an anti-mouse CD39 (mCD39) mAb, C₃₉Mab-1 using the Cell-Based Immunization and Screening (CBIS) method. In this study, we determined the critical epitope of C₃₉Mab-1 using flow cytometry. We performed the PA tag (12 amino acids)-substituted analysis (named PA scanning) and RIEDL tag (5 amino acids)-substituted analysis (named RIEDL scanning) to determine the critical epitope of C₃₉Mab-1 using flow cytometry. By the combination of PA scanning and RIEDL scanning, we identified the conformational epitope, spanning three segments of 275^th to 279^th, 282^nd to 291^st, and 306^th to 323^rd amino acids of mCD39. These analyses would contribute to the identification of the conformational epitope of membrane proteins.

Multilingual classrooms are becoming more common worldwide due to increasing mobility. Teaching foreign languages using the mother tongue in multilingual classrooms has become problematic; some of the significant concerns in Japanese language acquisition – such as the high contextuality of the language, vocabulary and kanji learning – make the direct teaching method confusing for many students, especially at the beginner and elementary levels. This article provides the preliminary results of a study carried out as a component of a more extensive empirical research project on instructional languages in classrooms teaching Japanese as a foreign language. It aims to gather, analyse and synthesise data from a survey conducted at a supranational level. The results of the first two sections of a questionnaire containing closed and open-ended questions were used for a quantitative analysis of the profile of Japanese language instructors with a focus on finding possible connections. The wide geographic distribution of the respondents (274 teachers from fifty-seven countries and regions) made it possible to collect data from a more representative sample and draw meaningful conclusions about the spread of multilingual classrooms that would be impossible in smaller-scale research. The study’s primary results show the proportion of multilingual classrooms among countries in different regions and across different educational stages, the distribution of Japanese language instructors in various educational stages depending on the highest level of formal education attained, and the proportion of part-time instructors working in different academic institutions.

We demonstrate how a rigorous mathematical approach can be used to extract a current CMB temperature of 2.7276 ±0.0723 K from the 580 type Ia supernova data points in the Union2 database. Using redshift formula: z = Sqrt(Rh/R_t) − 1, incorporated into our new CMB redshift prediction redshift formula, we find that the above current CMB temperature value is a remarkably good match for this particular data set. In addition, we can alternatively start out with the measured current CMB temperature and extract the Hubble constant from all 580 supernovae. We then get an estimated Hubble constant of H0 = 66.8711+0.0019 km/s/Mpc when using the CMB temperature from the recent Dhal et al study [1] in combination with redshifts from all 580 supernovae. Furthermore, we get an estimated Hubble constant value of H_0 = 66.8943+0.0287 km/s/Mpc when using the CMB temperature measured by Fixsen [2]. In summary, our simple model essentially perfectly matches all 580 type Ia supernova redshifts while extracting H_0 or T_0 values. The Hubble constant we extract by this method fits very well with the Hubble constant extracted from the CMB by other studies. We believe that our new approach likely solves the Hubble tension problem, at least inside R_h = ct cosmology.

The Jakarta LARP community, established in March 2020 and primarily active in Gelora Bung Karno, fosters inclusivity, diversity, and physical role-playing activities. It adheres to a policy of excluding ultra-nationalist ideologies and integrates new members despite language barriers. Bruhn (2011) defines this kind of community sharing the same goals, values, and lifestyles, while McMillan & Chavis (1986) outline four aspects of the sense of community.The research discovered that communities endure by utilizing solidarity built on the basis of their peculiarities. This study employed ethnographic methods alongside grounded research to identify the community's culture and their efforts to sustain and utilize it as community solidarity.

The C-C motif chemokine receptor 8 (CCR8) is highly and selectively expressed in regulatory T (Treg) cells and is associated with tumor progression. The massive accumulation of Treg cells into tumors suppresses the effector function of CD8⁺ cells against tumor cells. Therefore, selective depletion of Treg cells using anti-CCR8 monoclonal antibodies (mAbs) reinvigorates antitumor immune responses and improves responses to cancer immunotherapy. Previously, we developed an anti-mouse CCR8 (mCCR8) mAb, C₈Mab-2, using the Cell-Based Immunization and Screening (CBIS) method. In this study, the binding epitope of C₈Mab-2 was investigated using flow cytometry. The mCCR8 extracellular domain-substituted mutant analysis showed that C₈Mab-2 recognizes the N-terminal region (1–33 amino acids) of mCCR8. Next, 1×alanine (or glycine) scanning and 2×alanine (or glycine) scanning were conducted in the N-terminal region. The results revealed that the _17-DFFTAP_-22 sequence is important for the recognition by C₈Mab-2, and Thr20 is a central amino acid of the epitope. These results revealed the involvement of the N-terminus of mCCR8 in the recognition by C₈Mab-2.

In the wake of increasing digital fraud, this paper introduces an innovative application of Artificial Intelligence (AI) in detecting fraudulent activities across finance, healthcare, and e-commerce sectors. It presents a detailed analysis of machine learning methodologies, specifically focusing on the advantages of supervised, unsupervised, and deep learning techniques. The paper addresses the challenges such as data imbalance, model interpretability, and ethical implications in AI-based fraud detection. It also discusses the necessity of high-quality datasets and advocates for the integration of traditional and advanced machine learning methods to enhance accuracy and adaptability in fraud identification. However, it acknowledges the limitations including computational demands and overfitting risks. The study underscores the importance of collaborative efforts between AI experts and industry professionals to develop ethical, efficient, and reliable AI solutions for fraud detection.

Gradual disability worsening in Multiple Sclerosis (MS) is indicative of confirmed progression that mostly involves progression independent of relapse activity (PIRA) and is associated with neurodegeneration. Insights from pathology reveal grey matter involvement (neocortex, hippocampus, spinal cord, and deep grey matter structures) and microglia activation in early stages of MS. Cortical lesions result in thinning and atrophy and are considered accurate predictors of disability progression and cognitive decline.Neuroimaging biomarkers, such as high-resolution 7T MR images and TSPO-PET, have been examined for the detection of cortical pathology linked to cognitive deficits and thus progression, but are limited in clinical practice due to availability, time constraints, and cost.Electroencephalography (EEG) emerges as a non-invasive, cost-effective tool that reflects cortical activity in MS. Its potential in monitoring cognitive impairment is explored by focusing on nonlinear EEG analysis. The MuST PREDICT^TM project aims to extract linear and nonlinear EEG features, investigating their role in predicting disease progression and optimizing treatment. The study employs retrospective, cross-sectional, and prospective designs, utilizing EEGs from various MS forms, cognitive assessments, serum/cerebrospinal fluid biomarkers and neuroimaging. The methodology involves time-based and spectral feature extraction, employing artificial intelligence classifiers and brain criticality-based approaches.The conceptual framework of an innovative modality is herein presented, that would EEG for early MS progression detection. Standardization of the methodology could lead to the creation of a digital tool for better prognostication and treatment strategy optimization.

Improving the level of farmers' participation in collective action is an important way to promote rural revitalization and improve the sustainable livelihood level of farmers in underdeveloped areas. Based on 312 questionnaires of farmers in Shanxi Province, this paper investigates the status of farmers' participation in collective action, their sustainable livelihood level and the sustainable livelihood effect of collective action participation. The results show that: farmers' willingness to participate in collective action is strong, and the participation effect is obvious, but the participation frequency is low, and the participation time is less; The farmers' sustainable livelihood level is relatively low, Empirical research shows that the level of collective action participation will have a significant positive impact on Farmers' livelihood risk prevention, livelihood capital accumulation, livelihood mode selection and livelihood income improvement, and the frequency, time and value perception of participation in collective action will have varying degrees of impact on Farmers' sustainable livelihoods. In order to promote farmers' active participation in collective action, it is proposed to strengthen the construction of collective organizations Provide incentives and improve the quality and skills of farmers to enhance the collective concept and other policy recommendations.

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol-gel transition. We started with the synthesis of three cationic azobenzenes (AZO A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV-Vis and ¹H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel-sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels.

A rare genetic disorder caused by col18.a1 mutations, inherited mostly in autosomal recessive and rarely in autosomal dominant pattern, giving rise to ocular abnormalities and other associated disorders, the condition is referred to as Knobloch syndrome. This paper overviews the anterior and posterior ocular symptoms in Knobloch patients, thus demonstrating the major findings in Knobloch cases including the mutational analysis which discusses the proteins involved and exon number on which mutations are detected. Animal modeling done by knocking out col18.a1 has also been discussed to determine the functions of this gene which have been identified based on anomalies found in knock-out mice.

Breast cancer brain metastasis (BCBM) is a challenging condition with limited treatment options and poor prognosis. Understanding the interactions between tumor cells and the blood-brain barrier (BBB) is critical for developing novel therapeutic strategies. One promising target is estrogen receptor β (ERβ), which promotes the expression of key tight junction proteins, sealing the BBB and reducing its permeability. In this study, we investigated the effects of 17β-estradiol (E2) and the selective ERβ agonist diarylpropionitrile (DPN) on endothelial and cancer cells. Western blot analysis revealed the expression patterns of ERs in these cell lines, and estrogen treatment upregulated claudin-5 expression in brain endothelial cells. Using in vitro models of the BBB, we found that DPN treatment significantly increased BBB tightness about suppressed BBB transmigration activity of representative HER2-positive (BT-474) and triple-negative (MDA-MB-231) breast cancer cell lines. However, the efficacy of DPN treatment decreased when cancer cells were pre-differentiated in the presence of E2. Our results support ERβ as a potential target for the prevention and treatment of BCBM and suggest that targeted vector-based approaches may be effective for future preventive and therapeutic implications.

The purpose of this paper is to explore the implementation of Retrieval-Augmented Gen- 14 eration (RAG) technology with open-source Large Language Models (LLMs). For this purpose, a 15 web-based application named PaSSER that integrates RAG with three models - Mistral:7b, 16 Llama2:7b: Orca2:7b, is developed. In its development various technologies are used, including 17 Blockchain for managing and storing assessment results of built-in testing modules. PaSSER em- 18 ploys a set of evaluation metrics for LLMs’ performance - METEOR, ROUGE, BLEU, Perplexity, 19 Cosine similarity, Pearson correlation, and F1 score. The specialized knowledge base is in the smart 20 agriculture domain. As an illustration, the paper presents results and analysis of two tests. First one 21 is assessing the performance of LLMs across different hardware configurations, the other is deter- 22 mining the model that delivers most accurate and contextually relevant responses within the RAG. 23 The paper also discusses the integration of blockchain technology with LLMs to manage and store 24 assessment results within a blockchain environment. The tests revealed that Mistral:7b demon- 25 strates the best results across most of the evaluated metrics. The discussion section comments on 26 technical and hardware considerations that affect the performance of LLMs. Future development 27 will focus in leveraging new larger pre-trained open-source LLMs, exploring different finetuning 28 approaches, and further integration with Blockchain and IPFS.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

HIV-1 transcribes only one kind of transcript – the full length genomic RNA. To make the mRNA transcripts for the accessory proteins Tat and Rev, the genomic RNA must completely splice. The mRNA transcripts for Vif, Vpr, and Env must splice but not completely. Genomic RNA (which also functions as mRNA for the Gag and Gag/Pro/Pol precursor polyproteins) must not splice at all. HIV-1 can tolerate a surprising range in the relative abundance of individual transcript types, and a surprising amount of aberrant and even odd splicing; however, it must not over-splice, which results in the loss of full length genomic RNA and has a dramatic fitness cost. Cells typically do not tolerate unspliced/incompletely spliced transcripts, so HIV-1 has to circumvent this cell policing mechanism to allow some splicing while suppressing most. Splicing is controlled by RNA secondary structure, cis-acting regulatory sequences which bind splicing factors, and the viral protein Rev. There is still much work to be done to clarify the combinatorial effects of these splicing regulators. These control mechanisms represent attractive targets to induce over-splicing as an antiviral strategy. Finally, splicing has been implicated in latency, but to date there is little supporting evidence for such a mechanism. In this review we apply what is known of cellular splicing to understand splicing in HIV-1, and also present data from our newer and more sensitive deep sequencing assays quantifying the different HIV-1 transcript types.

We will demonstrate that the photon energy density parameter Ωγ of the universe can be derived exactly in Rh = ct cosmology. We find that it must be Ωγ = 1/5760π ≈ 5.52621330180192× 10^(−5). This indicates that there is no uncertainty in the radiation density within at least somesub-classes of Rh = ct cosmology.

IMPORTANCE: On December 10, 2021, the FDA published a Determination Letter, along with a Statistical Review and Evaluation Report, and concluded that under the non-informative prior, the local Bayesian optimal interval design (BOIN) design, in its revised form, can be designated fit-for-purpose for identifying the maximum tolerated dose of a new drug, assuming that dose-toxicity relationship is monotonically increasing. Although setting the BOIN design parameter p.tox = 1.4 * target.DLT.rate is recommended in almost all BOIN methodology articles and is the default value in the R package BOIN, it's unclear if the choice of p.tox should only depend on the target DLT rate and if certain range of p.tox could produce the same BOIN boundary table. DESIGN: In this simulation study, following parameters were varied one at a time, using R package BOIN, to explore their effects on the equivalence intervals of p.saf and p.tox: 1) target DLT rate, 2) n.earlystop, 3) cutoff.eli, 4) cohortsize, and 5) ncohort. And a simple 3+3 design was used as an example to explore equivalent sets of BOIN design parameters that can generate the same boundary table. RESULTS: When the early stopping parameter n.earlystop is relatively small or the cohortsize value is not optimized via simulation, it might be better to use p.tox < 1.4 * target.DLT.rate, or try out different cohort sizes, or increase n.earlystop, whichever is both feasible and provides better operating characteristics. This is because if the cohortsize was not optimized via simulation, even when n.earlystop = 12 and cohortsize > 3, the BOIN escalation/de-escalation rules generated using p.tox = 1.4 * target.DLT.rate could be exactly the same as those calculated using p.tox > 3 * target.DLT.rate, which might not be acceptable for some pediatric trials targeting 10% DLT rate. The traditional 3+3 design stops the dose finding process when 3 patients have been treated at the current dose level, 0 DLT has been observed, and the next higher dose has already been eliminated. If additional 3 patients were required to be treated at the current dose in the situation described above, the decision rules of this commonly used 3+3 design could be generated using BOIN design with target DLT rates ranging from 18% to 29%, p.saf ranging from 8% to 26%, and different p.tox values ranging from 39% to 99%. These BOIN parameters also need to satisfy a set of conditions. Meaning: This study demonstrates the importance of interpreting BOIN design parameter p.tox as an interval of toxicity rates that are considered too toxic, rather than one prespecified value that corresponds to the lowest toxicity probability that is deemed overly toxic. When designing a dose-finding trial using BOIN, it is important to perform simulation studies to identify equivalent sets of BOIN design parameters that can generate the same boundary table so that we can better compare the safety properties of different boundary tables.

We will apply Pascal’s hydrostatic pressure law to black holes and also to the Hubble sphere. Haug has recently demonstrated how hydrostatic pressure in water can be utilized to determine the Planck length. One can conceptualize the energy in the Hubble sphere as a type of superfluid, and if this is correct, then Blaise Pascal’s hydrostatic pressure formula may also be applicable to such a superfluid, even within the Hubble sphere. By employing the same method on the Hubble sphere and considering it as a Schwarzschild black hole with the critical Friedmann mass, we can estimate the Planck length based on its hypothetical hydrostatic pressure.

The presence of the mite, Varroa destructor, requires the use of acaricide treatments in most honeybee colonies. Amitraz is one of the most common acaricide substances used by beekeepers. Some Varroa mite populations have developed resistance to amitraz leading to a loss of efficacy of amitraz-based treatments. Two products, Apivar and Supatraz were applied in the same apiary. Both treatments are amitraz-based but have a different galenics. Thanks to field data, a dynamic model was used to simulate the action of Apivar and Supatraz on the mite population. We consider two parameters to compare the products: daily mortality rate and treatment duration. In the field, the percentage of efficacy between the two products was not significantly different but Supatraz kills mite faster and decreases 90% of the mite infestation in 28.4 days compared to 50.9 days for Apivar. Thanks to modelling, we showed the daily impact of the two different products on mite population. Supatraz has a higher daily mortality rate during the first two weeks than Apivar. Supatraz requires a lower efficacy to stabilize the varroa mite population due to its faster release of active ingredient than Apivar, needing a shorter period to achieve the same result. Depending on the model, Supatraz conserve a good efficacy for low resistant mites but not for high resistant mites. These results show that the comparison of the efficacy of two products with different characteristics (duration of treatment and daily mortality rate) should be analyzed with caution.

In the field of delta-sigma modulators, reducing system power consumption without sacrificing accuracy has become a challenge. The summing circuit, as the main part of the cascade-of-integrator-in-feedforward delta-sigma modulator, consumes a significant amount of power in active summing. On the other hand, passive summing circuits have low power consumption but can cause attenuation in the summing results. This article proposes a low-power multi-bit delta-sigma modulator based on passive and attenuationless summation scheme. The summation circuit achieves multiplication of the voltage signal carried on the summation capacitor through bidirectional sampling technique, compensating for the inherent attenuation caused by passive summation, thus eliminating the need for active OTA to achieve perfect summation. A 2-order delta-sigma modulator based on 4-bit 1-order passive noise-shaping (NS) SAR quantizer is designed to verify the scheme. By combining a passive NS SAR as the 4-bit quantizer and the third-stage integrator of the system, and incorporating an energy-efficient cascode floating inverter amplifier (FIA) structure as the core active OTA, these elements have significantly enhanced the energy-efficiency of the modulator. Simulation results show that at a supply voltage of 1.2 V and a bandwidth of 20 kHz, the SNDR reaches 102.62 dB, power consumption is only 148.32 μW, and Schreier figure-of-merit (FoM) of SNDR is 183.92 dB.

Antibiotic prescription is the first line of treating bacterial diseases. But it affects the composition and function of non-targeted intestinal microbiota. Antimicrobial resistance will be the cause for the death of millions of people worldwide. By considering collateral damage of antibiotics, searching an alternative antimicrobial agent will be a solution to minimize the problems. Probiotics, prebiotics and synbiotics are an alternative to antibiotics. Thanks to GIT microbes as they are responsible for metabolism, energy production, protection from pathogens and immunomodulation. So, it is appreciable if the gut microbiota modulated through consumption of probiotics, prebiotics and synbiotics. Probiotic effects are genus and species specific. To get good health benefit of probiotics, safety of probiotics should be assessed before using them. This is mandatory for prebiotics and synbiotic selection. So this review paper gives information about side effects of antibiotics on gut microbiota, description of probiotics, prebiotics and synbiotics as alternative to antibiotics in modulating GIT microbiota, techniques of assessing safety of probiotics and health benefits of probiotics, prebiotics and synbiotics with scientific evidence in clinical trial and some disagreement and challenges of using probiotics, prebiotics and synbiotics.

Abstract—Hydraulic switching actuators are high efficiency, fast response, and low cost solutions for hydraulic control systems. One of the challenging problems is throttling losses during valve transitions. Previously the authors proposed a zero-flowrate switching method to reduce throttling energy loss of the switching valve, where a hydraulic resonator is applied to make the flowrates through the lines approaching zero before the valves are switched off. The major challenge of this approach is fast switching valves whose transition times are less than 2 ms. In this paper, an improved zero-flowrate switching method is presented. It utilizes the capacity with independent inlet/outlet ports to regulate flowrates through the lines. Models of capacity applied in a simple line with different pressure signals are developed to explore characteristics of the capacity, based on which a complete actuation system is developed. In the complete model, resistance and inductance are optimized to achieve desired flowrate response. The improved zero-flowrate switching method reduces throttling energy losses by 99.945% compared to a hard switching system. The simulation results demonstrated that the improved zero-flowrate switching method performs as expected in the design condition. A capacity with proper volume is able to regulate flowrates through all the lines to zero, with the help of appropriate resistance and inductance. Compared to previous zero-flowrate switching method, the novel strategy allows slower switching valves applied in hydraulic actuation systems and achieves better efficiency performance. This research paves a new avenue for reducing throttling energy losses and improves system efficiency in hydraulic switching actuators, as well as most of the hydraulic switch-mode circuits.

In the process of oil and gas development and production, when the flow rate in the wellbore is large, the materials underground will be eroded, causing the operation to be unable to proceed smoothly and reducing the efficiency of oil and gas production. Therefore, optimizing the anti-erosion coating under high-speed flow conditions in wellbore is a very interesting thing. It can greatly improve operational efficiency. In this paper, laser cladding was used to prepare the new coating used in the PDC drill bit. Then, the effects of tungsten carbide and multi-layer graphene on the microstructure and properties of the tungsten carbide coating were studied. The research results indicate that, for new coatings, 60% tungsten carbide and 0.3% graphene are the optimal ratios. After adding WC, the hardness has significantly improved. However, when the WC content further increases more than 30%, the increase in hardness is relatively small. In addition, when the content of graphene is more than 0.3%, the branched structure became thicker, and not only the segregation of Cr, Si and W became very obvious again, but also the segregation of Fe occurred at the Ni enrichment site. The research results contribute to improving oil and gas production and operational efficiency under high-speed fluid flow conditions in the wellbore.

The escalating demand for multifunctional and advanced materials for growing industries has turned scientific exploration to graphene-based hybrid filler polymer composites. The introduction of graphene with other fillers into polymer matrices results in astonishing properties and thus has gained significant attention in recent years. This study addresses the significance of graphene-based hybrid filler polymer composites in progressive materials science and engineering. The paper encloses some traditional and current preparation techniques employed in the fabrication of composites and a comprehensive review of successfully prepared graphene hybrid polymer composites with enhanced mechanical, thermal, and electrical properties reported in published research. The role of different factors, e.g., filler type, aspect ratios, filler-matrix compatibility, dispersion effects, homogeneity, filler orientation through polymer matrices, and curing conditions, are summarized. Finally, the applications in heavy industries, e.g., aerospace, electronics, energy storage, and automotive sectors were also analyzed. We hope this study will serve as a practical resource for new researchers and practitioners to understand and harness the full potential of these composites in various scientific and industrial fields.

Background –The brinjal is of much importance in the warm areas of Far East, being grown extensively in India, Bangladesh, Pakistan, China and the Philippines. It is also popular in Egypt, France, Italy and United States. Preserving soil fertility throughout time by preserving organic matter and soil biological diversity, mechanical intervention, as well as exercise is highly needed in upcoming future. Effect of six different fertilizer, five organic and one synthetic fertilizers listing vermicompost, poultry manure, mustard cake, neem cake, bonemeal and N:P:K study were main concern of this investigation to find out the most suitable fertilizer for the brinjal.Result - the final growth and development through N:P:K @ 1.5%(19:19:19) outperformed all the organic fertilizers but when considering only organic fertilizer performance vermicompost@5 ton/ha was outperforming all the other organic fertilizers. Coming close to it, mustard cake@1.5ton/ha has shown its inheritance in providing nutrients. Use of other organic fertilizers are also effective use of poultry manure can provide nitrogen in higher amount in short time. Higher temperature above 25 degree Celsius cause slow growth, temperature range between 21 to 14 degrees Celsius was found better in terms of growth of flower and fruit formation.Conclusion – our experiment demonstrate specific organic fertilizer use over other fertilizers in terms of brinjal different developemental parameters and there is even comparision between synthetic fertilizer with organic fertilizer readily available in market. Vermicompost showed promising result followed by mustard cake for this specific brinjal genotype in northern plain of Indian subcontinent.

The purpose of this project is to develop and build an extensible fixture. This fixture is ideal to milling, drilling, and shaping operations. Jigs and fittings are often the most cost-effective methods of mass fabricating a component. As a result, jigs and fittings are used and play a vital part in the mass production system. These are specialist work holding and tool-guiding devices. The quality of jigs and fixtures used in a process has a substantial impact on its performance. A fixture is distinctive because it is meant to fit a given area or shape. The basic purpose of a fixture is to find and, in certain instances, hold a workpiece throughout an operation. A jig differs from a fixture in that it leads the tool to the right position or movement during an operation, in addition to locating and supporting the workpiece. When a key is reproduced, the original key serves as a base for the path reader, which regulates the tool's movement to construct the duplicate key. In this situation, a CWC machine's route reader works as a jig, with the original being referred to as the template. Sometimes the template and jig refer to the same part of a production system.

This work addresses the intricate task of predicting the prices of diverse financial assets, including stocks, indices, and cryptocurrencies, each exhibiting distinct characteristics and behaviors under varied market conditions. To tackle the challenge effectively, a novel hybridized architecture, AE-GRU, integrating the encoder-decoder principle with GRU is designed. The experimentation involves multiple activation functions and hyperparameter tuning. With extensive experimentation and enhancements applied to AE-LSTM, the proposed AE-GRU architecture still demonstrates significant superiority in forecasting the annual prices of volatile financial assets from multiple sectors mentioned above. Thus, the novel AE-GRU architecture emerges as a superior choice for price prediction across diverse sectors and fluctuating market scenarios by extracting important non-linear features of financial data and retaining the long-term context from past observations.

Corrugated board is a composite material characterized by strong orthotropy in both the elastic and plastic phases. Additionally, due to its layered structure, which consists of alternately arranged flat and wavy layers of paper, its mechanics becomes complicated. Therefore, a precisely selected set of laboratory tests is needed to correctly identify all the necessary material parameters of cardboard. The work attempts to define a full set of laboratory tests in order to determine material parameters describing the linear-elastic, orthotropic behavior of cardboard and the basic parameters defining popular plasticity criteria, such as the asymmetric orthotropic Hoffman criterion. For this purpose, sensitivity analysis and numerical models of several selected basic laboratory tests were used. Since the aim of the work is to choose appropriate laboratory tests necessary to correctly determine the material parameters of corrugated board (not its individual layers), the numerical models do not contain detailed cardboard geometry, but only its homogenized representation in the form of the flat shell models. All numerical models are based on the nonlinear finite element method and constitutive modelling in the form of UMAT subroutines implemented in the ABAQUS software. Based on the analyses, appropriate measurements and laboratory tests were indicated that are most sensitive to the material parameters sought.

Precision farming is transforming how antibiotics get used on farms. It fights the overuse that creates superbugs and harms nature. Farmers now have high-tech tools to use antibiotics ultra-precisely. Drones, AI, and advanced watering equipment help them pinpoint only sick plants and animals needing treatment. This shields crops while avoiding environmental damage. More careful antibiotic use makes livestock healthier and boosts harvests too. And it prevents resistant germs, where antibiotics stop working altogether. The approach helps farms in multiple ways, using fewer resources for even better results. There are some growing pains, like high costs for small farms. And questions around data privacy also cause concern. But overcoming these hurdles could help precision farming spread far and wide. This technology promises safer, greener, and more productive agriculture. Targeted use of antibiotics protects both crops and people from drug-proof germs. And nature benefits when less medicine spreads into soil and water. The future looks bright for farming with precision.

Artifact metrics is a technology for authenticating artifacts based on their unique characteristics. The artifact-metric system offers "clone resistance," i.e., it makes it highly improbable to create another object exhibiting the same measured values as a genuine artifact. However, determined adversaries may still attempt to create imitations or clones with close physical characteristics to those of registered products, even if they cannot perfectly replicate the genuine product. Such clones serve to deceive users into believing they are genuine rather than counterfeits. Thus, in this study, we consider a scenario in which we measure raster-scanning-generated clones via a non-raster scanning method. Further, we employ image processing techniques to generate image data representing the clones and theoretically assess the filtering effects on these images. Our findings reveal that applying filters to specific frequency components in the spatial frequency domain can effectively highlight differences between raster-scanning-created clones and the corresponding genuine artifacts. Thus, we demonstrate directional emphasis filtering in artifact metrics as an effective approach for rejecting raster-scanning-created clones.

We discuss three key points: defining mathematically the notions of phase, symmetry breaking, topological defects and their stability in a formal language of homotopy theory and fiber bundle formalism; postulating and proving two theorems for successive symmetry breaking scenarios in condensed matter physics and cosmology, and demonstrating application of theorems to superfluid Helium 3 and Kibble-Lazarides-Shafi (KLS) walls, supporting and mathematically justifying the results of [Volovik, 2020].

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

Urbanization influences food culture, particularly in low- and middle-income countries, where there is an increasing consumption of processed and pre-packaged foods. This shift is contributing to a rise in non-communicable diseases. Food labeling standards are crucial for regulating manufacturing practices and aiding consumers in making healthy food choices. We aimed to assess the compliance of local and imported pre-packaged snacks with Tanzanian and international labeling standards in Dar es Salaam, Tanzania. A cross-sectional study was conducted on 180 snack products. A checklist based on Tanzanian and Codex labeling standards was used to evaluate adherence. We also examined factors influencing adherence, such as product origin, price, category, purchase location, and package size. The majority of the snacks demonstrated partial adherence to labeling standards. Imported products showed significantly better full adherence to both Tanzanian and International standards. Notably, over half of the products used English for labeling, and infrequently used the recommended World Health Organization Front-of-Pack nutrition Labeling. Product category, origin, and package size were significantly associated with higher levels of International standard adherence (p<0.05). The inadequate adherence to mandatory labeling standards, scarce use of Swahili and FoPL highlight the need to strengthen labeling practices and potential challenges faced by consumers in understanding nutritional information. Thus, strengthening and emphasizing good labeling practices is of urgency as we seek to address diet-related Non-communicable diseases.

Intelligent ship technology is currently an international research hotspot, and model predictive control is widely used in the path-tracking control of intelligent vehicles. To construct an intelligent ship anti-disturbance path-tracking control method, firstly, an environmental disturbance model was constructed with the actual meteorological data of the target sea area. Secondly, the Fossen ship equation of motion is linearized and discretized as the ship motion model. Thirdly, the expression of the prediction equation is derived from the ship motion model. Fourthly, the cost function is constructed by using the polar diameter and polar angle values of the ship. Fifth, the power function in the cost function is replaced with an exponential function to obtain an improved cost function. Sixthly, according to the Lyapunov theory and the MPC terminal constraint theory, the stability of the improved cost function is verified. Seventh, different test paths are set up, the environmental disturbance model is taken as the external disturbance, the ship motion model, the prediction equation, and the improved cost function are used to design the anti-disturbance path-tracking control algorithm according to the model prediction control idea for simulation experiments. Finally, different MATLAB simulation results show that the improved cost function can resist disturbance of the external wave, current, and wind, and effectively track the target path. Therefore, this study provides a reference for improving the navigation safety of ship path-tracking.

Permafrost covers about 23% ~ 25% of the land in the northern hemisphere, mainly in Russia, Canada, Alaska, Northeast and Qinghai Tibet Plateau (QTP) in China. Many engineering especially the transportation has been in the permafrost regions above. Under the action of highways construction and global warming, permafrost under infrastructures is degraded and causes serious damage. Two phases closed thermosyphon (TPCT) is a widely accepted green countermeasure against the problem in permafrost regions. Although it has been applied to prevent permafrost degradation, their application presents significant challenges on account of the stronger endothermic action of asphalt pavement. This paper focused on the thermosyphon technology and application in the permafrost. Moreover, the article highlighted the excellent working performance of the TPCT that improving the stability of the infrastructures and prevent it degrading due its excellent efficiency of heat transfer. The industrial applications of the TPCT were also summarized, along with their limitations. Finally, the results reported in this paper can provide a valuable guidance for the design of the TPCT and construction of the permafrost regions in the future.

The bioindicator potential of seagrass ecosystems in coastal trace metal monitoring is low for tropical island ecosystems. This study evaluated the bioindicator potential of six seagrass species exposed to anthropogenic trace metal pollution in the Andaman and Nicobar Islands (ANI) of India. Sediment and seagrass biomass, samples were analyzed for trace metals (Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Zn) from four locations of ANI exposed to anthropogenic contamination. Geo accumulation Index values indicated moderate trace metal contamination in seagrass sediment. Seagrass trace metal accumulation from sediment was both species-specific and location- specific for ANI. Small seagrass species such as H. ovalis, H. beccarii and H. uninervis accumulated the maximum concentration of six trace metals (Cr, Cu, Fe, Ni, Pb, Zn) in their tissues compared to big seagrass species like T. hemprichii and E. acoroides of ANI. This study indicates leaves of small seagrass and roots of big seagrass species can serve as short- and long-term bioindicators respectively, of coastal trace metal contamination in tropical islands of ANI.

Background: Waterborne diseases pose a significant global public health threat, compelling enhanced comprehensive surveillance. This study investigates the current infectious disease and antimicrobial resistance (AMR) surveillance systems, including wastewater and environmental surveillance (WES), in three sub-Saharan African countries: Tanzania, Burkina Faso, and the Democratic Republic of the Congo (DRC). The three countries have their specificities regarding wastewater networks and logistic systems. So, emphasizing the need to strengthen existing disease surveillance, the paper advocates for incorporating WES systems specifically designed for countries' context to monitor waterborne and re-emerging pathogens, as well as AMR.Methods: National workshops were conducted to assess the current clinical and environmental surveillance systems and identify priority pathogens for new environmental monitoring. Data were collected through surveys from experts in academia, research, policy, and healthcare. Results: Prioritized pathogens for WES include waterborne (poliovirus, Salmonella Typhi, Vibrio cholerae), respiratory (influenza A&B, SARS-CoV-2), other (Measles and Rubella, Mycobacterium tuberculosis). Recommended AMR pathogens include drug-resistant Mycobacterium tuberculosis, Salmonella spp., methicillin-resistant Staphylococcus aureus, and extended-spectrum beta-lactamase and carbapenemase-producing E. coli. Tanzania, Burkina Faso, and the DRC employ DHSI2-based centralized electronic systems for clinical data collection, complemented by Excel and paper-based registries. The WES approach is commonly employed for monitoring poliovirus and rarely for AMR and other pathogens. Discussion and conclusions: WES is a valuable tool for early detection of locally circulating human-derived pathogens, aiding in outbreak detection, data-driven epidemic response, and prevention. The availability of WES results underscores the importance of effective sanitation for safeguarding human, animal, and environmental health. WES is a pivotal tool for integrated risk management, preventing waterborne outbreaks, protecting drinking water sources, and ultimately gaining various UN Sustainable Development Goals. The study highlights the importance of customized WES systems in line with each country's context, emphasizing localized approaches for effective monitoring of waterborne pathogens and AMR.