Background: The Covid-19 pandemic has globally impacted the lives of individuals, families, and children. In Italy, measures such as lockdowns and distance learning were implemented in schools, which affected the mental health of children and families. Methods: This article employs qualitative methodology to explore the experiences of children, parents, and teachers during the pandemic and lockdown, as well as the implementation of a death education project aimed at primary school children to help them process emotions and losses experienced during this period. Results: Distance learning posed challenges to the learning process and exacerbated social inequalities. Children suffered from limited social contact with friends and experienced negative emotions, including anger, fear, and concern for the health of their loved ones. The death education project provided a safe space for emotional expression and facilitated the acquisition of coping strategies. Open communication between adults and children about illness and death proved effective in mitigating the psychological impacts of loss and preventing traumatic bereavement. Conclusions: The findings highlight the utility of death education in enhancing children's ability to express their emotions and approach the topic of death morefrankly.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

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)

This study delves into the therapeutic potential of two natural compounds, Amentoflavone and Bilobetin, by investigating their interactions with the BPIFB4 protein. BPIFB4, a member of the BPI fold-containing superfamily, has been associated with various biological processes, particularly in longevity and cardioprotection( LAV-BPIFB4). Molecular docking analyses revealed promising binding energies for Amentoflavone and Bilobetin with BPIFB4, suggesting favorable interactions.Additionally by pKCSM database are showed the predicted toxicity properties of Amentoflavone and Bilobetin respectively.This research contributes to the growing body of knowledge on natural compounds and their therapeutic implications in the context of vital biological processes. However, these findings underscore the need for further investigations, including in vivo studies and clinical trials, to validate the observed effects and explore the translational potential of Amentoflavone and Bilobetin in promoting cardiovascular health and longevity.

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.

COPD is a "heterogeneous lung condition characterized by chronic respiratory symptoms. It is a leading cause of death and illness and is associated with a substantial economic burden worldwide. Furthermore, it is marked by frequent exacerbations, which significantly contribute to morbidity and mortality, as well as the overall burden. These exacerbations are frequently triggered by bacterial infections.So far, the most commonly implicated Bacteria are Pseudomonas aeruginosa, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.The advent of culture-independent techniques, such as next-generation sequencing techniques (NGS), allows us to characterise the lung microbiome in different disease states.

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.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

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.

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.

The paper is based on the research project P2Endure funded within the H2020-EE-2016-2017 call. The main aim of the research is to propose innovative solutions for deep renovation that are applicable and replicable for the widest range of building typologies, from public to residential and historic buildings. In this paper, the methodology adopted to perform the energy analyses and to verify the achievement of the expected targets in terms of savings is defined, based on a range of real case studies. The main aim is to promote a guideline for designers showing specific instruments to perform towards the attainment of the 60% threshold of the energy savings giving advice on how to further improve the energy performance of the buildings, basing on the overview of the energy analyses run for similar cases.

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

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

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.

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 tumours. 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 centre 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)

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

This comprehensive analysis aims to offer valuable insights into the safety profiles of these glucocorticoids, facilitating the identification of compounds with potentially reduced adverse effects. This study investigates the toxicity profiles of various glucocorticoids, utilizing predictions from the pKCSM Server. Among the glucocorticoids examined, Dexamethasone, Triamcinolone, Hydrocortisone hemisuccinate, Paramethasone, Fluprednisolone, and Flumethasone emerge as potentially less toxic, displaying favorable scores across diverse parameters such as Max. Tolerated Dose (human, MRT), Oral Rat Acute Toxicity (LD50), and Oral Rat Chronic Toxicity (LOAEL). Notably, Hydrocortisone hemisuccinate and Triamcinolone stand out for their high tolerability capacity based on the Max. Tolerated Dose (human, MRT), suggesting enhanced safety profiles. These findings contribute insights into selecting glucocorticoids with optimal safety and tolerability for potential therapeutic applications.Further research and clinical investigations are warranted to validate and refine these findings, ensuring the responsible and effective use of glucocorticoids in medical practice.

To evaluate the nutrient load due to the grazing of laying hens in outdoor runs, soil characteristics were monitored in three Italian organic farms. For each farm, soil samples were taken from three increasing distances from the hen house and two depths and different chemical parameters were evaluated. The comparison among the results from the different distances shows that N-NO3 and Olsen P are the most affected parameters by hen faeces: both present high values with a statistically significant difference in the area close to the poultry house and for the most superficial layer. Even TKN and TOC show significant differences between the concentrations of the first layer (more concentrated) and those of the second layer (less concentrated). In general, the surface soil layer closest to the chicken house is the portion of the outdoor run most affected by chicken droppings and represents the most critical point in terms of potential environmental impact. Therefore, it is necessary to intensify the management of the outdoor run with tools that can facilitate the grazing of animals and with vegetation that can absorb nutrients by limiting leaching and run-off.

Investigations are currently in progress to assess the potential of elevated FABP3 levels as biomarkers for assessing cardiac and cerebral injury post-stroke. Ongoing research endeavors are concentrated on elucidating the specific mechanisms by which FABPs, particularly FABP3, contribute to the complex processes involved in ischemic stroke. This study employs molecular docking techniques within a Virtual Screening framework to examine the interaction between various natural substances and the active site of human heart fatty acid-binding protein (PDB Code 4TKH). Utilizing Pyrx and Autodock Vina, the research aims to pinpoint compounds demonstrating robust binding interactions, characterized by high binding energy scores (kcal/mol) and the formation of multiple chemical bonds. The anticipated outcomes have the potential to yield valuable insights into the molecular interactions influencing human heart fatty acid-binding protein, suggesting possible implications for therapeutic interventions using these natural substances.From the docking and predicted toxicity results, Resistomycin has demonstrated superior characteristics compared to Morusin.

: This study was aimed at assessing adaptation and bonding of discontinuous (short) glass fiber-reinforced composite to intraradicular dentin EverX Flow (GC Corporation, Tokyo, Japan), when used as intracanal composite filling and anchorage instead of traditional fiber posts. (2) Methods: Seventy intact extracted human teeth were endodontically treated and randomly divided into 6 groups (n=10), depending on the materials used in the post space. In Group 1, a 2-bottle universal adhesive G2 Bond Universal + EverX Flow were tested. In group 2, a single-component universal adhesive G-Premio Bond + EverX Flow were used. In groups 3 and 4 the same materials are tested, but after cleaning of the canal walls with 17% EDTA and final irrigation with 5.25% NaOCl Ultrasound Activated. In the last three Groups (5-7) traditional prefabricated GC Fiber Posts 1.6 mm silanized with G-Multi Primer for 1 minute are cemented with a dual-cured composite resin cement (GradiaCore), after ultrasonic irrigation in the groups 6 and 7. In each group, 1 mm-thick slices from each sample (n=10) were cut for light microscope and SEM inspection for study materials adaption to the dentin and for measuring push-out strength of post / cemement material to the dentin / prefabricated post. These results were statistically analyzed: as the data distribution was not normal, the Kruskal-Wallis Analysis of Variance by Ranks had to be applied. The level of significance was set at p<0.05. Results: Push-out forces varied between 6.66-8.37 MPa. No statistically significant differences were recorded among the groups. Microscopic examination showed that ultrasonic irri-gation increased adaptation of the materials to the dentin surface. There was a trend of higher bond strength among the tested groups when EverX Flow was used. Also, the type of failure was more often cohesive when ultrasonic irrigation and two-step adhesive system were used. Conclusions: Within the limitations of this in vitro study, it may be concluded that when EverX Flow was used for intracanal anchorage in the post-endodontic recon-struction, similar push-out retentive forces and strength to those of traditional fiber posts cemented with particulate filler resin composite cements were achieved. Although further studies are necessary, EverX Flow represents an effective alternative to traditional fiber post adhesion in particular when used in combination with the two-step adhesive system and ultrasonic activation.

or the first time, this communication is intended to perform the possible biological role of natural compound Hypericin, in the Crystal Structure of dual-specificity tyrosine phosphorylation regulated kinase 2 (DYRK2), by Molecular and Dynamic Simulation. From Docking analysis by Autodock Vina and Autodock 4, Hypericin shows a significant ability to binds to DYRK2 protein, an important receptor for cell growth and development. Indeed, from docking studies Hypericin reports a binding energy value of about -13 kcal/mol and Estimated Inhibition Constant (Ki)of ca 1nM . Regarding MD simulation.From our results, this theoretical research it could has excellent future implications in the fight against cancer disease.

Use of porous titanium (Ti) and Ti alloys in orthopedic implants or in light structures requires processing routes that could generate an as-much-as possible control in the pores amount, shape, size and connectivity. In this work, a colloidal approach to the processing of Ti porous structures by the inside foaming of a porogen into a gelled high solid content aqueous suspension of Ti powders, is presented. The prepared slurries contained different amounts of Methyl Cellulose (MC) as gelling agent (8, 10 and 12 g/L) and ammonium bicarbonate (BA) as porogen (15, 20, 25 wt. %). The gel-casted samples were heated at mild temperatures ranging (60, 70 and 80 °C) to promote the gelation and produce, at the same time, the porosity by the thermal decomposition of the ammonium bicarbonate. Different structures are obtained depending on the combination of the study variables

Jealousy and mate retention have received attention in the research over the last decades. Despite this, most of the research examined male jealousy and male mate retention, emphasizing cost-inflicting behavior due to its role in relationship and domestic violence. The aim of this study was to investigate the relationship between jealousy and all mate retention strategies in romantic relationship among women during the COVID-19 pandemic. The sample consisted of 772 Croatian women aged 19 to 40 who were in a heterosexual relationship at the time. The study was conducted online, and the participants completed the Multidimensional jealousy scale and Mate Retention Inventory. The results showed that cognitive, emotional, and behavioral jealousy are positively correlated with all mate retention strategies which indicate that a stronger experience of jealousy can be expected to result in more frequent use of all partner retention strategies. We also found that all three dimensions of jealousy and relationship length positively predicted both cost-inflicting and benefit-provisioning mate retention behavior, whereas age was a negative predictor of benefit-provisioning behavior only. Findings of this study suggest that although jealousy can substantially explain interpersonally risky and damaging behavior in relationships, it can also explain affectionate and attentive behavior to some extent.

Load balancing, energy efficiency and fault tolerance are among the most important data dissemination issues in Wireless Sensor Networks (WSNs). In order to successfully cope with the mentioned issues, two main approaches (namely, Data-centric Storage and Distributed Data Storage) have been proposed in the literature. Both approaches suffer from data loss due to memory and/or energy depletion in the storage nodes. Even though several techniques have been proposed so far to overcome the mentioned problems, the proposed solutions typically focus on one issue at a time. In this paper, we integrate the Data-centric Storage (DCS) features into Distributed Data Storage (DDS) mechanisms and present a novel approach, denoted as Collaborative Memory and Energy Management (CoMEM), to overcome both problems and bring memory and energy efficiency to the data loss mechanism of WSNs. We also propose analytical and simulation frameworks for performance evaluation. Our results show that the proposed method outperforms existing approaches in various WSN scenarios.

Low temperatures in the autumn induce enhanced expression/relative accumulation of several cold-inducible transcripts/proteins with protective functions from Late-embryogenesis-abundant (LEA) superfamily including dehydrins. Several studies dealing with plants grown under controlled conditions revealed a correlation (significant quantitative relationship) between dehydrin transcript/protein relative accumulation and plant frost tolerance. However, to apply these results in breeding, field experiments are necessary. The aim of the review is to provide a summary of the studies dealing with the relationships between plant acquired frost tolerance and COR/LEA transcripts/proteins relative accumulation in cereals grown in controlled and in the field conditions. The impacts of cold acclimation and vernalization processes on the ability of winter-type Triticeae to accumulate COR/LEA proteins are discussed. The factors determining dehydrin relative accumulation under controlled cold acclimation treatments versus field trials during winter seasons are discussed. In conclusion, it can be stated that dehydrins could be used as suitable indicators of winter surival in field-grown winter cereals but only in plant prior to the fullfilment of vernalization requirement.

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.

Parkinson's disease is a neurodegenerative disorder resulting from progressive damage to specific brain regions. Key symptoms encompass involuntary movements (tremor), slowness of movements (bradykinesia), and muscle rigidity. Although the precise cause remains uncertain, a combination of genetic and environmental factors is believed to contribute to its development. This study focuses on the interaction of the E3 ubiquitin-protein ligase parkin with natural compounds. Docking investigations revealed that Amentoflavone exhibited an excellent binding energy score of approximately -10 kcal/mol. The E3 ubiquitin-protein ligase parkin displayed a robust binding affinity with docked amentoflavone, evident from a high binding energy of -10 kcal/mol. Nonetheless, additional biological studies are crucial not only to validate its potential efficacy against Parkinson's and assess safety in terms of toxicity but also to perform further computational analyses confirming these preliminary assessments.

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.

This theoretical study presents a novel perspective on the potential anti-inflammatory properties of Bromelain, a natural agent extracted from pineapple stems. The investigation explores the binding capabilities of Bromelain to Apoptosis-associated speck-like containing CARD (ASC), a crucial adapter molecule known for its involvement in inflammatory processes and inflammasome formation. For the first time, these findings suggest that Bromelain exhibits a notable affinity for ASC, indicating its promising role as a natural anti-inflammatory agent. This study sheds light on the molecular interactions that may contribute to Bromelain's therapeutic potential in modulating inflammatory responses.

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.

PIM1is involved in critical cellular processes, playing a key role in the regulation of the cell cycle, apoptosis, transcriptional activation, and broader signal transduction pathways . The exploration of PIM1inhibitors, such as small molecules or antibodies, represents a promising avenue in cancer research for developing novel treatment strategiess. Its significance in oncogenic signaling has led to extensive research on PIM1 as a target in cancer studies. Docking studies have revealed a robust interaction between hypericin and PIM1, suggesting a strong binding affinity (-12.5 kcal/mol). This research aims to explore the molecular dynamics of the hypericin-PIM1 interaction, identifying potential binding sites and elucidating the impact on PIM1-mediated cellular processes, such as cell cycle regulation and apoptosis. The findings may contribute valuable insights into developing hypericin-based therapies targeting PIM1, paving the way for novel and effective strategies in cancer research.

Heat Shock Proteins play a crucial role in maintaining cellular integrity during thermal stress conditions, acting as chaperones and participating in the regulation of cellular responses. The focus was to contribute valuable insights into the potential role of hypericin in modulating these heat shock proteins and its implications for anti-tumoral properties. This study employs computational methods, specifically molecular docking, to investigate the potential biological interactions between the chaperone proteins HSP90 and HSC70 and Hypericin, a natural compound recognized for its anti-tumor properties. Despite the limited existing studies in this domain, this research aims to uncover structural insights into the binding mechanisms between Hypericin and these heat shock proteins. In the docking assessments, hypericin demonstrated notable binding energy results, exhibiting a binding energy of -10.5 kcal/mol with Heat Shock Cognate 71 kDa protein and -11.2 kcal/mol with Heat Shock Protein HSP90-alpha.

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.

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.

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.

Cardiofaciocutaneous (CFC) syndrome, linked to mutations in genes including KRAS, BRAF, MEK1, and MEK2, leads to dysregulated RAS-MAPK signaling with limited therapeutic options. This study utilized molecular docking simulations to screen natural compounds against mutated KRAS, BRAF, MEK1, and MEK2 structures. Promising candidates such as Amentoflavone and Hypericin displayed strong binding affinities and favorable interactions with mutated sites, suggesting their potential as lead molecules for targeted therapies in CFC syndrome. This research offers novel insights into therapeutic interventions for this rare genetic disorder.

This theoretical study presents a novel perspective on the potential anti-inflammatory properties of Bromelain, a natural agent extracted from pineapple stems. The investigation explores the binding capabilities of Bromelain to Apoptosis-associated speck-like containing CARD (ASC), a crucial adapter molecule known for its involvement in inflammatory processes and inflammasome formation. For the first time, these findings suggest that Bromelain exhibits a notable affinity for ASC, indicating its promising role as a natural anti-inflammatory agent. This study sheds light on the molecular interactions that may contribute to Bromelain's therapeutic potential in modulating inflammatory responses.

This study investigates the potential inhibitory role of Amentoflavone against the Ebola virus, with a focus on the viral protein VP24 structure. Molecular docking simulations were conducted to assess the binding affinity and interaction between Amentoflavone and the VP24 protein. The results revealed promising docking scores, suggesting favorable binding of Amentoflavone to the VP24 structure. These findings provide valuable insights into the potential therapeutic efficacy of Amentoflavone against Ebola virus infection by targeting specific viral proteins. Further experimental validation is warranted to confirm these docking results and elucidate the mechanism of action underlying Amentoflavone's antiviral activity. This study contributes to the ongoing efforts to develop novel therapeutic strategies for combating Ebola virus disease.

Dengue virus infection poses a significant global health threat, particularly in tropical and subtropical regions. In this study, we employed molecular docking techniques to investigate potential inhibitors of Dengue virus type 1 envelope protein. Through a series of docking simulations, we identified Amentoflavone as a promising candidate with favorable binding affinity. Our results indicate that Amentoflavone exhibited a binding energy of -10 kcal/mol, suggesting strong interaction with the target protein. These findings highlight the potential of Amentoflavone as a therapeutic agent for combating Dengue virus infection. Further experimental validation is warranted to confirm its efficacy and safety profile. This study underscores the utility of in silico approaches in drug discovery and development against emerging infectious diseases like Dengue.

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.

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

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.

Astrocytes, the most abundant glial cells in the brain, are an integral part of the synaptic compartment and contribute to synaptic pruning, a key process for refining neural circuits during early postnatal development (PND). Dysregulations in this process are implicated in various neuropsychiatric disorders, including major depressive disorder (MDD). To investigate astrocyte functions in a physiologically relevant context, organotypic brain slice cultures (OBSCs) offer a powerful model, reproducing more closely in vivo conditions than traditional cell cultures and preserving complex brain architecture and interactions. Here, we present OBSCs as an ex vivo culturing method to provide a platform to explore astrocyte-mediated synaptic pruning dynamics in the rat prefrontal cortex (PFC) during PND. Our approach is based on assessing the role of MEGF10, a key protein involved in synaptic pruning, alongside the synaptic markers synaptophysin and PSD95, using Western blotting to analyse the expression levels of these markers in the cortex of developing rat pups. Additionally, we combine immunofluorescence staining with confocal imaging and IMARIS 9.8 software-assisted analysis to investigate the co-localization of the lysosomal marker LAMP1 with synaptic and astrocytic markers to evaluate the precise rate of synaptic engulfment. The methods presented here allow a deeper examination of an astrocyte-mediated synaptic remodelling in healthy and pathophysiological conditions.

In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel Atom Exchange Radical Cyclization (AERC) procedure. This method integrates the established Atom Transfer Radical Cyclization with halogen exchange in solution. The technique operates under mild conditions and requires little amounts of metallic copper, serving as both a supplemental activator and reducing agent.

The fossil record of the Ophiuroidea is still patchy, especially in the Cenozoic. Only four species have been described from the entire Oligocene, which is in stark contrast to the present-day diversity counting more than 2000 species. Here, we describe two new species of ophiuroid, Ophiura tankardi sp. nov. and Ophiodoris niersteinensis sp. nov., from the Lower Oligocene of the Mainz Basin. The species are based on microfossils extracted from the sieving residues of bulk sediment samples from a flush drill in Nierstein, Rhineland-Palatinate. The new species belong to extant genera and add to the poor Oligocene fossil record of the class. Based on present-day distributions, the occurrence of Ophiodoris suggests deep sublittoral to shallow bathyal palaeodepths for the Nierstein area of the Mainz Basin.

Phloem-feeding insects strive to offset the disadvantageous effects of stressors to sustain their offspring and survive. Adaptive responses to environmental stress are not well understood under complex influences of companion planting, natural enemies, and host gradient. In this study, under predation by lacewing Chrysoperla carnea Stephens (Neuroptera: Chrysopidae), we survey the responses of green peach aphid Myzus persicae Sulzer (Hemiptera: Aphididae), reared on different densities of cabbage Brassica oleracea L. (Brassicales: Brassicaceae) to its shallot companion Allium cepa (L.) var. aggregatum G. Don (Asparagales: Amaryllidaceae). Firstly, aphid aggregative abundance was strongly influenced by shallot perturbation, predator presence and changes in cabbage-host biomass, altering aphid phenotypic plasticity. Interestingly, the shallot and predation negative impacts can be of similar magnitudes. Secondly, changes in the cabbage-host availability and biomass, especially under predation, had a strong impact on aphid traits. Our study underscores the benefits of including shallots as crop-companions in augmenting pest control, but also suggests that the outcome of coupling companion planting with natural enemies is context-dependent and thus should be empirically applied. At the confluence of ecology and agronomy, this work provides insights on how manipulated functional biodiversity may function as an alternative strategy for pestilent herbivory management in model and green-house systems.

Inflammation is a vital aspect of the body's immune response, appearing either as an acute reaction that swiftly develops (e.g., after injury or during an infection) or as a chronic condition that persists over a prolonged period, often linked with autoimmune disorders or cancer. This study introduces potential TNF-alpha inhibitors investigated by Molecular Docking investigation. They are Dactolisib with a binding energy of -10.1 kcal/mol, Nilotinib with -9.6 kcal/mol, Eltrombopag with -9.7 kcal/mol, Radotinib with -9.6 kcal/mol, and Nilotinib again with -9.7 kcal/mol. Additionally, Hypericin exhibited a notable binding energy of -9.9 kcal/mol, suggesting its potential as a natural TNF-alpha inhibitor. While these computational results are preliminary, they provide a foundation for further biological studies to confirm their efficacy. The significance of these findings extends to the scientific community, offering potential applications in the field of inflammatory diseases.

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.

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.

Clinical and pre-clinical studies of neuropsychiatric (NP) disorders show altered astrocyte properties and synaptic networks. These are refined during early postnatal developmental (PND) stages. Thus, investigating early brain maturational trajectories is essential to understand NP disorders. However, animal experiments are highly time-/resource-consuming, thereby calling for alternative methodological approaches. The function of MEGF10 in astrocyte-mediated synapse elimination (pruning) is crucial to refine neuronal networks during development and adulthood. To investigate the impact of MEGF10 during PND in the rat prefrontal cortex (PFC) and its putative role in brain disorders, we established and validated an Organotypic Brain Slice Culture (OBSC) system.Using Western blot, we characterized the expression of MEGF10 and the synaptic markers synaptophysin and PSD95 in the cortex of developing pups. We then combined immunofluorescent-immunohistochemistry with Imaris-supported 3D-analysis to compare age- and sex-dependent astrocyte-mediated pruning within the PFC in pups and OBSCs. We thereby validated this system to investigate age-dependent astrocyte-mediated changes in pruning during PND. However, further optimizations are required to use OBSCs for revealing sex-dependent differences. In conclusion, OBSCs offer a valid alternative to study physiological astrocyte-mediated synaptic remodelling during PND and might be exploited to investigate pathomechanisms of brain disorders with aberrant synaptic development.

Probiotics are suggested to improve pig health, nutrient utilisation, performance, and may reduce nitrogen (N) pollution. However, the effectivity of a single-strain might be different from a multi-strain. The study was conducted to investigate the effect of a novel Bacillus multi-strain on nutrient digestibility, energy utilisation, and N retention in weaned piglets. The experiment consisted of a control diet (CD) and a supplemented diet (SD). The probiotic used for SD consisted of B. amyloliquefaciens - 516 and B. subtilis - 541. A total of 8 boars/ treatment were weaned (day 0; 8.5 kg bodyweight). Until day 10, piglets were fed ad libitum and were housed in pairs; from day 11, piglets were fed semi ad libitum and were housed individually. From day 14, faecal and urine were collected twice daily. Piglets were humanely euthanised at day 19 (15.0 kg bodyweight) after which the jejunum, ileum, and colon content were collected. In faeces the apparent total tract digestibility (ATTD) of, amongst others, DM, organic matter (OM), crude protein (CP), non-starch polysaccharides (NSP), and subsequently net energy (NE) were calculated using titanium dioxide as an indigestible marker. In jejunum and ileum, the apparent digestibility of CP was estimated and in ileum the apparent AA digestibility. In urine, N content was measured to determine N retention. The volatile fatty acid (VFA), branched-chain fatty acid (BCFA), and lactic acid content were analysed in colon and faeces. Apparent CP digestibility in jejunum and ileum were not affected by treatment (P&gt;0.05) and no effect was observed on apparent ileal digestibility of AA (P&gt;0.05). Supplementation with the multi-strain probiotic improved ATTD of DM (P=0.01; +1.3%) and OM (P=0.02; +1.2%) and tended to improved ATTD of CP (P=0.10; +2.2%) and NSP (P=0.07; +1.9%). The multi-strain probiotic also improved the NE value (P=0.02; +0.2 MJ/kg DM) and improved N retention (P=0.05; +1.6%). Supplementation did not influence VFA, BCFA, and lactic acid content in the faeces (P&gt;0.05). However, in colon, supplementation did influence lactic acid content (lower; P=0.01) and tended to influence valeric acid content (higher; P=0.09). In conclusion, results from the current study suggests that the multi-strain probiotic has the potential to contribute to improve nutrient efficiency in weaned piglets. More research needs to be done to identify the impact of the improved nutrient utilization on gut health in post-weaned pigs as well as environmental pollution.

Diabetes mellitus is acknowledged as a significant contributor to severe complications. The present work has explorated the potential role amentoflavone as an aldose reductase inhibitor through Docking Simulations. From these results this compound has shown excellent results with this enzyme with a high binding energy of -11 kcal/mol. If amentoflavone,a natural biflavonoid, proves effective in inhibiting aldose reductase, it could hold therapeutic promise for managing diabetic complications. However, it's crucial to emphasize that while computational studies offer valuable insights, experimental validation is essential to confirm the actual inhibitory effects and to establish the safety and efficacy of amentoflavone for this purpose. Further research and clinical studies are warranted to fully understand and harness the potential therapeutic benefits of amentoflavone in the context of diabetes.

Hundreds of millions of people on the planet are affected by malnourishment. This contributes to the vulnerability of large swaths of the population, especially children under five years old extremely vulnerable to diseases and even death in the least developed countries. Today, by providing a substantial share of global protein intake, as well as fatty acids and micronutrients, fisheries contribute to global food security. As fish stocks in the upper sea levels have already been over-exploited, there might not be enough in supplying food security, deep-sea fisheries have been increasingly discussed to address this problem. Some mesopelagic fishes show the potential to provide important nutrients. Another way of supplying food security might be through using mesopelagic fish as fish feed. However, fishing in the mesopelagic zone could lead to severe ecological problems and the impact on the biological carbon pump is uncertain. This paper highlights and juxtaposes different perspectives regarding exploitation pathways of the fish riches of deep seas and reviews best practice model projects that deal with uncertainties related to fishery management in the mesopelagic zone.

Past research suggests a continuity between perception and memory, as reflected in influences of orienting of spatial attention by cues presented after a visual target offset (post-target cues) on target perception. Conducting two experiments, we tested and confirmed this claim. Our study revealed an elevated reliance on post-target cues for target detection with diminishing target visibility, leading to better performance in validly versus invalidly cued trials, indicative for contrast gain. We demonstrated this post-target cueing impact on target perception without a postcue response prompt, meaning that our results truly reflected a continuity between perception and memory rather than a task-specific impact of having to memorize the target due to a response prompt. We further showed an influence of attention by the post-target cues with cues presented away from a clearly visible target, meaning that visual interactions at the target location provided no better explanation of our results. Our results generalize prior research with liminal targets and confirm the view of a perception-memory continuum, so that visual target processing is not shielded against visuospatial orienting of attention elicited by events following offset of the visual target.

Global rapidly evolving events, e.g., COVID-19, are usually followed by countermeasures and policies. As a reaction, the public tends to express their emotions on social media platforms. Therefore, predicting emotional responses to events is critical to put a plan to avoid risky behaviors. This paper proposes a machine learning-based framework to detect public emotions based on social media posts in response to specific events. It presents a precise measurement of population-level emotions which can aid governance in monitoring public response and guide it to put in place strategies such as targeted monitoring of mental health, to react to a rise in negative emotions in response to lockdowns, or information campaigns, for instance in response to elevated rates of fear in response to vaccination programs. We evaluate our framework by extracting 15,455 tweets. We annotate and categorize the emotions into 11 categories based on Plutchik’s study of emotion and extract the features using a combination of Bag of Words and Term Frequency-Inverse Document Frequency. We filter 813 COVID-19 vaccine-related tweets and use them to demonstrate our framework’s effectiveness. Numerical evaluation of emotions prediction using Random Forest and Logistic Regression shows that our framework predicts emotions with an accuracy up to 95%.

Understanding the structure and properties of MgCl2/TiCl4/ID nanoclusters is a key to uncover the origin of Ziegler-Natta catalysis. In this work MgCl2/TiCl4 nanoplatelets derived by machine learning and DFT calculations have been used to model the interaction with ethyl-benzoate EB (as internal donor) with available exposed sites of binary TixCly/MgCl2 systems. The influence of vicinal Ti2Cl8 and coadsorbed TiCl4 on energetic, structural and spectroscopic behaviour of EB has been considered. The adsorption of homogeneous-like TiCl4EB and TiCl4(EB)2 at the various surface sites have been also simulated. Calculations have been carried out by employing B3LYP-D2 and M06 functionals. The adducts have been characterized by computing IR and Raman spectra that have been found to provide specific fingerprints useful to identify surface species; IR spectra have been successfully compared to available experimental data.

N-acetyl-L-cysteine (NAC), a sulfhydryl-containing compound, is mainly used as a mucolytic and as an antidote for acetaminophen overdose. Flow injection and sequential injection systems were designed and optimized with the aim of providing precise, accurate and reliable flow methods for NAC determination in pharmaceuticals with very low sample and reagent consumption. Proposed methods are based on a redox reaction wherein NAC reduces a complex of Cu(II) and bathocuproine disulfonate (BCS) to orange [Cu(BCS)2]3– complex, which absorption was measured at λmax = 483 nm. The optimized FIA and SIA configuration yielded a linear calibration curve with correlation coefficients (R2 = 0.9999 and R2 = 0.9996) in the concentration range of 3.0 × 10–7 – 3.0 × 10–5 mol L–1 and analytical frequency of 120 h–1 for the FIA method and 4.0 × 10–7 – 4.0 × 10–5 mol L–1, at sampling rate 60 h–1 for the SIA method. The proposed flow methods were successfully applied for the determination of NAC in pharmaceutical products, as the results showed good agreement with the standard method prescribed by Pharmacopoeia. Recoveries were in the range from 98.4% to 101.9% for the FIA method and from 97.2% to 101.8% for the SIA method.

Inherited retinal diseases (IRD) comprise a heterogeneous set of clinical and genetic disorders that lead to blindness. Given the emerging opportunities in precision medicine and gene thera-py, it has become increasingly important to determine whether DNA variants with uncertain significance (VUS) are responsible for the patients’ IRD. This research was performed to assess the functional consequence of six VUS identified in patients with IRD. Clinical assessments in-cluded an ophthalmic examination, best corrected visual acuity, and kinetic perimetry. Imaging was acquired with the Optos ultra-widefield camera and spectral-domain optical coherence to-mography (SD-OCT). Genetic testing was performed by Molecular Vision Laboratories. VUS that were predicted to alter splicing were analyzed with a minigene assay which revealed that VUS in the genes OPA1, CNGB1, and CLUAP1 altered spicing mechanisms. Due to the emerging gene and cell therapies, these results expand the genotype-phenotype correlations for patients diag-nosed with an IRD.

As exemplified by the global response to the SARS-CoV-2 pandemic, whole genome sequencing played an important role in monitoring the evolution of novel viral variants and provided guidance on potential antiviral treatments. The recent rapid and extensive introduction and spread of highly pathogenic avian influenza virus in Europe, North America and elsewhere raises the need for similarly rapid sequencing to aid in appropriate response and mitigation activities. To facilitate this objective, we investigated a next generation sequencing platform that uses a portable nanopore sequencing device to generate and present data in real time. This platform offers the potential to extend in-house sequencing capacities to laboratories that may otherwise lack resources to adopt sequencing technologies requiring large benchtop instruments. We evaluated this platform for routine use in a diagnostic laboratory. In this study we evaluated different primer sets for the whole genome amplification of influenza A virus and evaluated five different library preparation approaches for sequencing on the nanopore platform using the MinION flow-cell. A limited amplification procedure and a rapid procedure were found to be best among the approaches taken.

Adaptive T cell immunotherapy holds great promise for the successful treatment of leukemia as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system allowing deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches.

Despite the recognized benefits of fecal occult blood test (FOBT) and mammography screenings, participation in breast (BC) and colorectal cancer (CRC) screening programs is still suboptimal. This study investigates municipal characteristics associated with their BC/CRC screening uptake profiles among women aged 55–69 years. Using data from 308 municipalities of Flanders from 2014 to 2017, a profile for each municipality based on its BC/CRC screening uptake compared with the median screening uptake was created. Logistic regression with generalized estimating equations was used to assess the associations between municipal characteristics and BC/CRC screening uptake profiles. The overall median uptake of cancer screening was higher for CRC (57.4%) than for BC (54.6%). The following municipal characteristics were associated with worse performance in terms of only CRC, only BC, or both CRC and BC screening uptake, respectively: foreign nationality, self-employment rate, (early) retirement rate, diabetes, disabilities; (early) retirement rate; age group 65–69, foreign nationality, self-employment rate, (early) retirement rate, wage-earners, diabetes. The following municipal characteristics were associated with better performance in terms of only CRC, only BC, or both CRC and BC screening uptake respectively: residential stability, having a partner, having children, jobseeker rate, GP visits, preventive dental visits; having children, GP visits; age group 55–59, residential stability, having a partner, having children, jobseeker rate, higher education, GP visits, preventive dental visits. This study’s results regarding the interrelation between the BC and CRC screening could be used to tailor interventions to improve the participation of the target population in both programs.

Within the Active Living and Well-Being Project (RRP3), funded by the Republic of Slovenia and the European Regional Development Fund Investing in Your Future programme, we aim to develop different approaches and prototypes to provide ICT solutions for the family in order to connect its members, communicate, promote quality family time, active life, a health-friendly lifestyle and well-being, and integrate various sensor and user-based data sources into a smart city ecosystem platform. A mixed methodology, combined qualitative and quantitative approaches, was selected to conduct a study. An online survey with a structured questionnaire as well as semi-structured interviews were performed. Through the analysis of the results we tried to establish a family-centred design approach that would be inclusive as much as possible, creating benefits for all generations in order to develop interactive prototypes that would allow us to further test and verify different use-case scenarios.

SARS-CoV-2 continues to widely circulate in populations globally. Underdetection is acknowledged and is problematic when attempting to capture the true prevalence. Seroprevalence studies, where blood samples from a population sample are tested for SARS-CoV-2 antibodies that react to the SARS-CoV-2 virus, are a common method for estimating the proportion of people previously infected with the virus in a given population. However, obtaining reliable estimates from seroprevalence studies is challenging for a number of reasons, and the uncertainty in the results is often overlooked by scientists, policy makers and the media. This paper reviews the methodological issues that arise in designing these studies, and the main sources of uncertainty that affect the results. We discuss the choice of study population, recruitment of subjects, uncertainty surrounding the accuracy of antibody tests themselves, and the relationship between antibodies and infection over time. Understanding these issues can help the reader to interpret and critically evaluate the results of seroprevalence studies.

Lactobacillus plantarum is a bacterium with promising applications to the food industry and agriculture and probiotic properties. So far, bacteriophages of this bacterium have been moderately addressed. We examined the diversity of five new L. plantarum phages via whole genome shotgun sequencing and in silico protein predictions. Moreover, we looked into their phylogeny and their potential genomic similarities to other complete phage genome records through extensive nucleotide and protein comparisons. These analyses revealed a high degree of similarity among the five phages, which extended to the vast majority of predicted virion-associated proteins. Based on these, we selected one of the phages as a representative and performed transmission electron microscopy and structural protein sequencing tests. Overall, the results suggested that the five phages belong to the family Myoviridae, they have a long genome of 137.973-141.344 bp, a G/C content of 36,3-36,6% that is quite distinct from their host’s, and, surprisingly, seven to 15 tRNAs. Only an average 41/174 of their predicted genes were assigned a function. The comparative analyses unraveled considerable genetic diversity for the five L. plantarum phages of this study. Hence, the new genus “Semelevirus” was proposed, which comprises exclusively the five phages. This novel lineage of Lactobacillus phages provides further insight into the genetic heterogeneity of phages infecting Lactobacillus sp.. The five new Lactobacillus phages have a potential value for the development of more robust starters through, for example, the selection of mutants insensitive to phage infections. The five phages could also form part of phage cocktails, which producers would apply in different stages of L. plantarum fermentations in order to create a range of organoleptic outputs.

The construction industry has witnessed the increasing use of digital tools and smart solutions, particularly, in the realm of buildings energy automation within the concept of smart cities. While to truly realize the potential benefits of smart cities, a broader scope of smart initiatives is required to support the transition from smart buildings towards smart neighbourhoods, appreciated as the critical unit of urban development. To support this interplay of smart solutions between buildings and neighbourhoods, this article aims to collect and review all smart solutions presented in existing scientific articles, technical literature, and realized European projects. These solutions are classified under two main sections of buildings and neighbourhoods, which are investigated through five domains: buildings energy-related uses, renewable energy sources, water, waste, and open space management. Showcasing the quantitative outcomes demonstrates the potential benefits of implementing smart solutions from buildings to neighbourhoods. Moreover, this research concludes that the true enhancement of energy conservation goes beyond the buildings’ energy component and can be genuinely achieved by integrating intelligent elements of the neighbourhood, due to their strong interdependencies. Future research is recommended to focus on assessing the effectiveness of these solutions towards resource conservation.

Upland lakes (ULs) of the Carajás, southeastern Amazonia, have been intensively studied to their evolution during the Quaternary, as well as the development of the associated biota. In this review, several classical and modern approaches from structural geology to the pollen rain and sedimentary data which cover an area of around 41,300 km² were compiled. Multi-elemental geochemistry indicates that the detrital sediments derived from weathered crusts and soils, while the sedimentary organic matter represent autochthonous (siliceous sponge spicules, algae, macrophytes) and allochthonous (C3 plants and freshwater DOC) sources. Modern pollen rain suggests that even small lakes and canga areas can reflect forest signal, which depends on the topographic control and prevailing wind direction on pollen deposition. Integrated data of the sedimentary cores indicate that the active lakes never dried up during the last 50 ka cal BP. However, subaerial exposure occurs on filled lakes such as ST02 Lake during the LGM, LB3 and R2 lakes at the mid-Holocene due to drier paleoclimate conditions. Considering the organic proxies, only LB3 Lake presents expansion of C4 canga (montane savanna) plants since ULs of the Serra da Bocaína does not present siderites. Siderite formation on ULs deposits also points to drier paleoenviromental conditions, interrupting predominantly wet conditions. However, there is no evidence for widespread expansion of savanna into Southeastern Amazonia during the late Pleistocene and Holocene.

The effect of Mg particles on PLA's thermal, chemical, physical, and mechanical properties has been studied. The thermal and physical properties have been studied by differential scanning calorimetry, analysing the stability of the α and α’-crystals of the PLA. A colloidal route was used to introduce Mg particles inside the PLA matrix, ensuring a good dispersion of the particles. Materials with Mg contents from 0 to 10 wt.% have been prepared, with additions of polyethyleneimine (PEI) and polyethylene glycol (PEG). Fourier Transform Infrared Spectroscopy has been used to confirm the influence of Mg, PEI, and PEG on PLA properties. The mechanical properties have been measured with a universal tensile test machine on printed filaments via Fused Filament Fabrication (FFF), which were naturally aged to stable conditions. Filaments with and without a notch were studied to obtain the materials' tensile strength, elastic modulus, and fracture toughness. Different analytical models to explain the results of the PLA-Mg were studied, in which the interface strength of the PLA-Mg composites was calculated.

The fish fauna of Rio de Janeiro has been extensively studied, resulting in a comprehensive database of species collected over more than three centuries. This study aimed to identify fish species, their locations, and compile scattered information to aid in climate action and freshwater conservation prioritization and an evaluation of the sampling effort to date, as well as to identify patterns of diversity and distribution of freshwater ichthyofauna, delineate biogeographic units, and explore similarity relationships between areas. Analyzing data from nearly 25 ichthyological collections and literature on original species descriptions revealed 346 fish species: 172 freshwaters native, 22 allochthonous, and 152 marine species. The checklist includes updated species names. The sampling effort in Rio de Janeiro is high, especially in coastal lowlands. The findings indicate that inventory work is still needed in certain areas. Five bioregions of freshwater ichthyofauna were identified, along with six major areas of higher species richness. This biogeographic assessment underscores the diverse and distinctive freshwater fish fauna in the basins of Rio de Janeiro, with well-defined biogeographic units.

Automated extraction of buildings from earth observation (EO) data is important for various applications, including updating of maps, risk assessment, urban planning, policy making. Combining data from different sensors such as high-resolution multispectral (HRI) and light detection and ranging (LiDAR) has shown great potential in building extraction. Deep learning (DL) is increasingly used in multimodal data fusion and urban object extraction. However, DL-based multimodal fusion networks may underperform due to insufficient learning of “joint features” from multiple sources and oversimplified approaches to fusing multimodal features. Recently, an hybrid attention-aware fusion network (HAFNet) has been proposed for building extraction from a dataset including co-located Very-High-Resolution (VHR) optical images and Light Detection And Ranging (LiDAR) joint data. The system reported good performances thanks to the adaptivity of the attention mechanism to the features of the information content of the three streams but suffered from model overparametrization, which inevitably leads to long training times and heavy computational load. In this paper the authors propose a restructuring of the scheme, which involved replacing VGG-16-like encoders with the recently proposed EfficientNet, whose advantages counteract exactly the issues found with the HAFNet scheme. The novel configuration was tested on multiple benchmark datasets, reporting great improvements in terms of processing times, and also in terms of accuracy. The new scheme, called HAFNetE (HAFNet with EfficientNet integration), appears indeed capable of achieving good results with less parameters, translating into better computational efficiency. Based on these findings, we can conclude that, given the current advancements in single-thread schemes, the classical multi-thread HAFNet scheme could be effectively transformed by the HAFNetE scheme by replacing VGG-16 with EfficientNet blocks on each single thread. The remarkable reduction achieved in computational requirements moves the system one step closer to on-board implementation in a possible, future “urban mapping” satellite constellation.

Background: Alfalfa, the most economically important forage legume worldwide, features modest genetic progress due to long selection cycles and large extent of non-additive genetic variance associated with its autotetraploid genome. Methods: To improve the efficiency of genomic selection in alfalfa, we explored the effects of genome parametrization (as autotetraploid and diploid dosage, plus allele ratios) and SNP marker subsetting (all available SNPs; only genic regions; only non-genic regions) on genomic regressions, together with various levels of filtering on reading depth and missing rates. We used Genotyping by Sequencing-generated data and focused on traits of different genetic complexity, i.e., dry biomass yield in moisture-favorable (FE) and drought stress (SE) environments, leaf size, and onset of flowering, assessed on 143 genotyped plants from a genetically-broad European reference population and their phenotyped half-sib progenies. Results: On average, allele ratio improved the predictive ability compared with other genome parametrizations (+7.9% vs. tetraploid dosage, +12.6% vs. diploid dosage), SNP subsetting offered an advantage compared with any tested subsettings (+3.7% vs. genic regions, +7.6% vs. non-genic regions). However, when focusing on specific traits, different combinations of genome parametrization and subsetting reached better performances. We also released Legpipe2, a SNP calling pipeline tailored for reduced representation (GBS, RAD) medium-sized genotyping experiments.

According to previous studies the median raphe region (MRR) is known to contribute significantly to social behavior. Beside serotonin, there are reports of a small population of dopaminergic neu-rons in this region. Dopamine is linked to reward and locomotion, but very little has been known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR) and humans (RT-PCR). Next, we used chemogenetic technology in mice containing Cre enzyme under the promoter of the dopamine transporter (DAT). With the help of an adeno-associated virus, artificial receptors were expressed in the dopaminergic cells of the MRR (DAT-MRR). Four weeks later, extensive behavioral charac-terization started 30 minutes after the injection of the artificial ligand (Clozapine-N-Oxide). Stimu-lation of DAT-MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social be-havior during social interaction test. No behavioral changes were detected in anxiety, memory and locomotion. All in all, dopaminergic cells were present both in the mice and human MRR, and manipulation of dopaminergic neurons of the MRR elicited a specific social response.

In the context of Inverse Analysis in Civil Engineering, parameter identification and model calibration, of a structural system, relying on dynamic measurements, are subjects of a growing research interest. In the present contribution, the topic is tackled with reference both to simplified structural numerical examples and to a specific case study, namely a historical road three-span reinforced concrete arched bridge, with vibrational data previously acquired by standard wired accelerometers on the deck, under operational traffic conditions. In particular, the present work aims at focussing on the identification issues, concerning the definition of a maximum allowable threshold number of sought material parameters (e.g., Young’s moduli and mass densities of different structural components), with respect to the amount of available measurement data, and the investigation of the inverse analysis discrepancy function to be optimised, in order to set the intrinsic issue of multiple “realizations”, in case of a plain use of modal properties, and in view of forming a well–posed optimisation problem. Structural modelling, sensitivity analysis and numerical optimisation approaches are herein combined toward a robust and efficient identification strategy, to be effectively employed in structural assessment and diagnosis, also with respect to originally available or enriched sets of experimental data. The proposed methodology, and collected results, shall outline an efficient identification procedure, in view of automated inverse analysis, practically oriented to the dynamic assessment and structural diagnosis in the Civil Engineering context, as applied e.g. to strategic bridge infrastructures.

In the broad field of Inverse Analysis and Structural Identification, it is nowadays of a large interest the study of Gaussian Processes, as a reliable and efficient optimisation method, particularly helpful toward the identification of a global optimum point, under the conditions of complicated functions to be optimised. In the present contribution, a specific case study is considered, focusing on a historical road reinforced concrete arched bridge, located in Northern Italy, employing dynamic modal properties, deciphered from in-situ measurements, previously acquired under operational traffic conditions, by a standard wired accelerometer system, placed at the deck level. Aiming at the identification and diagnosis of the bridge structure, three main methodological steps are herein considered: the adoption of a FEM model of the structure (in the linear dynamic framework), the definition of an appropriate discrepancy function, based on measured and numerically computed quantities (natural frequencies and mode shapes of the bridge), and the investigation of such a discrepancy function, toward a consistent selection of an optimisation strategy for the identification of sought parameters (Young’s moduli and mass densities of diverse elements of the structure). The presented developments, within the framework of methodological optimisation approach by Gaussian Processes, and achieved results display a rather efficient perspective, with reference to the considered case study, toward inverse analysis for structural diagnosis, in the context of strategic (historical) infrastructures.

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.

The ongoing expansion in volume, velocity and variety of geospatial data has stimulated the development of artificial intelligence applications and associated online cartographic visualizations. In this context, the cartographic communication through peer-reviewed media evolved to incorporate Findability, Accessibility, Interoperability and Re-usability (FAIR) principles. In this paper, we review the functionalities proposed by current international peer-reviewed media for accessing, exploring and re-using geospatial data, and situate them on a diagram conceived for peer-reviewed cartography in the artificial intelligence era. We then present an overview of the cartographic infrastructure and workflow currently available in the Terra Digitalis journal for the online publication of massive spatiotemporal data. This free and opensource based solution allows a smooth integration, from data submission to final peer reviewed publication, of dynamic, interactive 2D and 3D maps. As a proof of concept, we present two maps derived from massive spatiotemporal data, related, respectively, to a climate numerical model (raster data) and a bike sharing system’s origin-destination dataset (vector data). We argue that the combination of technologies used in the journal provides an efficient and low-cost solution, unmatched by other publication media, to boost the accessibility and FAIR principles for geospatial big data.

Gene electrotransfer is one of the main non-viral methods for intracellular delivery of plasmid DNA, wherein pulsed electric fields are used to transiently permeabilize the cell membrane allowing enhanced transmembrane transport. By localizing the electric field over small portions of the cell membrane using nanostructured substrates, it is possible to increase considerably the gene electrotransfer efficiency while preserving cell viability. In this study, we design an electrotransfer approach based on commercially available cell culture inserts with polyethylene-terephthalate (PET) porous substrate. We first use multiscale numerical modelling to determine the pulse parameters, substrate pore size, and other factors that are expected to result in successful gene electrotransfer. Based on numerical results we design a simple device combining an insert with substrates containing pores with 0.4 um and 1.0 um diameter, a multiwell plate, and a pair of wire electrodes. We test the device in three mammalian cell lines and obtain transfection efficiencies similar to those achieved with bulk electroporation, but with low-voltage pulses that do not require the use of expensive electroporators. Our combined theoretical and experimental analysis calls for further systematic studies that will investigate the influence of substrate pore size and porosity on gene electrotransfer efficiency and cell viability.

Graph databases (GDBs) are becoming increasingly popular across scientific disciplines, being highly suitable to store and connect complex heterogeneous data. In systems biology, they are used as a backend solution for biological data repositories, ontologies, networks, pathways, and knowledge graph (KG) databases. In this review, we analyse all publications using or mentioning graph databases retrieved from PubMed and PubMed Central full-text search, focusing on the top 16 available GDB technologies. Relevant publications are then categorised according to their domain and application. We detail different approaches and highlight advantages of outstanding resources, such as UniProtKB, Disease Ontology, and Reactome, which provide graph-based solutions. We discuss ongoing efforts of the systems biology community to standardise and harmonise KG creation and the maintenance of integrated resources. Outlining prospects, including the use of GDBs as a way of communication between biological data repositories, we conclude that efficient design, querying, and maintenance of GDBs will be key for knowledge generation in systems biology and other research fields with heterogeneous data.

People with specific TREM2 gene variants are more prone to develop Alzheimer's disease (AD). The TREM2 receptor regulates the number of myeloid cells, phagocytosis, and the inflammatory response via interacting with apolipoproteins and amyloid. Higher TREM2 expression has been found to protect against AD. When TREM2 activity increases, the activity of genes involved in the activation of microglia cells decreases. This can improve the efficiency of phagocytosis. When TREM2 is highly expressed and the inflammasome is activated, the results are not always congruent. Therefore, this study aimed to discover how sTREM2 levels in CSF and plasma samples relate to other indices of AD pathology. We examined 98 AD plasma samples, 35 plasma samples of subjects with mild cognitive impairment (MCI), 11 healthy controls (HC) plasma samples, as well as 155 AD CSF samples, 90 MCI CSF samples, and 50 HC CSF samples. CSF sTREM2 levels were higher in the AD group than in the MCI and HC groups, in contrast to plasma sTREM2. This shows that CSF sTREM2 levels could be used to distinguish between healthy and AD patients. CSF sTREM2 levels were significantly correlated with neurofibrillary changes, cognitive decline, and inflammasome activity in AD patients. While our findings are consistent with previous research, future studies will need to include more patients and employ standardized methodological approaches to add CSF sTREM2 to the list of biomarkers for AD.

Studies show that executive functions and motor development are associated among each other and with learning ability. A more technological lifestyle, related with digital culture, should be considered an important component to stimulate children. In addition, digital games constitute an element of the digital culture in which children are inserted. The aim of this study is to present a systematic mapping of the literature involving executive functions, motor development and the use of digital games in intervention programs for elementary school children, from 6 to 11 years old. Four databases were searched: PubMed, Scielo, Science Direct and SCOPUS, including publications between 2012 and March 2021. The initial results indicated 4881 works. After the selection process, 15 investigations that presented the central theme of the study were selected. The main results indicate that intervention strategies are quite heterogeneous. Most of the studies demonstrated significant positive effects after intervention protocols and were conducted in Europe and 46% of the studies were conducted in a school environment. No researches were identified that involved technological solutions involving executive functions, motor development and digital games in an integrated manner, constituting a field of future scientific research.

In the current context of worldwide honey bee colony losses, among which the varroa mite plays a major role, hope to improve honey bee health lies in part in the breeding of varroa resistant colonies. To do so, methods used to evaluate varroa resistance need better understanding. Repeatability and correlations between traits such as Mite Non-Reproduction (MNR), Varroa Sensitive Hygiene (VSH) and hygienic behaviour are poorly known, due to practical limitations and to their underlying complexity. We investigate (i) the variability, (ii) repeatability of the MNR score and (iii) its correlation with other resistance traits. To reduce the inherent variability of MNR scores, we propose to apply an Empirical Bayes correction. On the short-term (ten days) MNR had a modest repeatability of 0.4 whereas on the long- term (a month) it had a low repeatability of 0.2, similar to other resistance traits. Within our dataset there was no correlation between MNR and VSH. Although MNR is amongst the most popular varroa resistance estimates in field studies, its underlying complex mechanism is not fully understood. Its lack of correlation with better described resistance traits and low repeatability suggest that MNR need to be interpreted cautiously, especially when used for selection.

In recent years, the widespread introduction of bike-sharing systems in China has had a profound impact on the daily lives of Chinese citizens and the development of the urban transport system. This article attempts to analyse the impact of this phenomenon on sustainability. The gradual improvement of related monitoring measures has facilitated the maturation of the bike-sharing industry from the initial stage of uncontrolled growth to the current stage of standardised management. By tracing the global development of bike-sharing systems with a special focus on China, this study sheds light on the platformisation of bicycles and its multiple impacts on technical, environmental, cultural, economic and social sustainability. Furthermore, the study provides a comprehensive analysis of the transformation of bicycles in China and highlights the diverse impacts of platform-based bike sharing on various facets of Chinese society. The development of different bike-sharing systems in China is a unique and crucial case to interpret the current situation of bike-sharing and imagine future scenarios. In contrast to the prevailing and uniform approach derived from the experiences of Northern European countries, the massive and widespread experimentation with different bike-sharing schemes in China reveals not only potentials and aspects of sustainability, innovation and urban and social regeneration, but also some hidden shadows similar to those in small-scale contexts such as Northern Europe. Furthermore, the study emphasises the crucial role of sustainable development principles in addressing urban challenges specific to China.

Brain arteriovenous malformations (BAVMs) are a critical concern in hereditary hemorrhagic telangiectasia (HHT) patients, carrying the risk of life-threatening intracranial hemorrhage. While traditionally seen as congenital, the debate continues due to documented de novo cases. Our primary goal was to identify the precise postnatal window in which deletion of the HHT gene Endoglin (Eng) triggers BAVM development. We employed SclCreER(+);Eng2f/2f mice, enabling timed Eng gene deletion in endothelial cells via tamoxifen. Tamoxifen was given at four postnatal periods: P1-3, P8-10, P15-17, and P22-24. BAVM development was assessed at 2-3 months using latex dye perfusion. We examined angiogenic activity by assessing vascular endothelial growth factor receptor 2 (VEGFR2) expression via Western blotting and Flk1-LacZ reporter mice. Longitudinal magnetic resonance angiography (MRA) was conducted up to 9 months. BAVMs emerged in 88% (P1-3), 86% (P8-10), and 55% (P15-17) of cases, with varying localization. Notably, the P22-24 group did not develop BAVMs but exhibited skin AVMs. VEGFR2 expression peaked in the initial 2 postnatal weeks, coinciding with BAVM onset. These findings support the “second hit” theory, highlighting the role of early postnatal angiogenesis, in initiating BAVM development in HHT type I mice.

Degradation of intracellular components through autophagy is a fundamental process to maintain cellular integrity and homeostasis. Recently a glycogen-selective autophagy pathway has been described, termed ‘glycophagy’. Glycogen is a primary storage depot and regulator of glucose availability, and glycophagy is emerging as a critical physiological process involved in energy metabolism. Glycophagy-mediated degradation of glycogen appears to operate in parallel with the well-described canonical pathway of glycogenolysis involving glycogen phosphorylase. Evidence suggests that starch-binding domain protein-1 (Stbd1) is a key glycogen-binding protein involved in tagging glycogen for glycophagy, and that Gabarapl1 is primarily involved as the Atg8 family protein recruiting the Stbd1-glycogen complex into the forming glycophagosome. The nuances of glycophagy protein machinery, regulation and lysosomal glucose release are yet to be fully elucidated. In this mini-review, we critically analyze the current evidence base for glycophagy as a selective-autophagy process of physiological importance and highlight areas where further investigation is warranted.

Aim of this study was to evaluate the accuracy and usability of a novel continuous glucose moni-toring (CGM) system designed for needle-free insertion and reduced environmental impact. We assessed sensor performance of two GlucoMen® Day CGM systems worn simultaneously in eight participants with type 1 diabetes. Self-monitoring of blood glucose (SMBG) was performed reg-ularly over 14 days at home. Participants underwent two standardized 5-hour meal challenges with frequent plasma glucose (PG) measurements using a laboratory reference instrument at the research center. When comparing CGM to PG the overall mean absolute relative difference (MARD) was 9.7 [2.6-14.6]%. The overall MARD of CGM vs SMBG was 13.1 [3.5-18.6]%. In the consensus error grid (CEG) analysis, 98% of both CGM/PG and CGM/SMBG pairs were in the clinically acceptable zones A and B. The analysis confirms that GlucoMen® Day CGM meets the clinical requirements for state-of-the-art CGM. The needle-free insertion technology is well toler-ated by users and reduces medical waste compared to conventional CGM systems.

The introduction of innovative digital tools for supporting manufacturing processes has far-reaching effects on an organizational and an individual level due to the development of Industry 4.0. The FACTS4WORKERS project funded by H2020, i.e. Worker-Centric Workplaces in Smart Factories, aims to develop user-centered assistance systems in order to demonstrate their impact and applicability at the shop floor. To do so it is important to understand how to develop such tools and how to assess if advantages can be derived from the created ICT system. This study introduces the technology of a workplace solution that is linked to a specific industrial challenge. Subsequently, a 2-stepped approach to evaluate the presented system is discussed. Heuristics, which are an output of project “Heuristics for Industry 4.0”, are used to test if the developed solution covers critical aspects of socio-technical system design. Insights into the design, development and holistic evaluation of digital tools at the shop floor should be shown.

Background and objectives: Huntington disease (HD) is characterized by motor, cognitive and psychiatric manifestations and is caused by an expansion of CAG repeats over 35 triplets on the huntingtin (HTT) gene. However, expansions in the range 27-35 repeats (intermediate allele) can be associated with pathological phenotypes. The onset of HD is conventionally defined by the onset of motor symptoms, but psychiatric disturbances can precede the motor phase by up to twenty years. The aims of the present study are to identify HD patients in the pre-motor phase of the disease among patients diagnosed with bipolar disorders and to evaluate any differences between bipolar patients carrying normal HTT allele and patients with expanded HTT gene. Methods: We assessed the HTT genotype in an Italian cohort of 69 patients affected by bipolar disorder type 1 and type 2. Results: No patient was found to be a carrier of the pathological HTT allele, but 10% of bipolar subjects carried an intermediate allele. Carriers of the intermediate allele were older at onset of psychiatric symptoms than non-carriers. Conclusion: The pathological HTT gene was not associated with bipolar disorder, while we found a higher frequency of the intermediate allele among the bipolar population with respect to healthy controls.

Co-doped SnO2 nanocrystals with tetragonal rutile-type (space group P42/mnm) structure have been investigated using in-situ high-pressure synchrotron angle dis-persive X-ray diffraction till 20.9 GPa at ambient temperature. The analysis of ex-perimental results based on Rietveld refinements suggest that rutile-type SnO2 un-dergoes a structural phase transition at 14.2 GPa to an orthorhombic CaCl2-type phase (space group Pnnm) with no coexistence during the phase transition. No further phase transition is observed till 20.9 GPa. The low-pressure and high-pressure phases are related via a group/subgroup relationship. However, as a discontinuous change in the unit-cell volume is detected at the phase transition, thus, the phase transition can be classified as first-order type. On decompression the transition is found to be re-versible. The results are compared with previous high-pressure studies on SnO2.

Background: To compare the loss of preload in absence of loading and after a fixed number of ideal masticatory cycles in two different connection systems using all-on-four prosthetic model. Methods: Two equal models of an edentulous mandible rehabilitated with all-on-four technique with two types of abutment system (MUA and OT-Bridge) supporting a hybrid prosthesis, were used. Initial torque values of the prosthetic fixing screw, after ten minutes from initial screw tightening and after 400000 masticatory cycles were registered using a mechanical torque gauge. Differences between initial and final torque values were reported for each anchoring system and the two systems were finally compared. Results: No statistically significant differences regarding the loss of preload between MUA and OT-Bridge system were found after 400000 masticatory cycles; however, in MUA system it was found between anterior and posterior implant screws. A significant difference in preload loss was found only for MUA system comparing the initial screw torque to that measured after 10 minutes from the tightening in absence of cyclic loadings. Conclusions: MUA and OT-Bridge are reliable prosthetic anchoring systems able to tolerate repeated masticatory cycles also on distal cantilever in all-on-four rehabilitation model without any significant loss of preload in screw tightening

Radiomics represents the science of extraction and analysis of a multitude of quantitative features from medical imaging, unrevealing quantitative potentiality of Radiologic images. This scientific review aims to provide radiologists a comprehensive understanding of radiomics, emphasizing its principles, applications, challenges, limits, and future prospects. Limits of standardization of actual scientific production are analyzed with the possible solutions proposed by some papers reported and commented. As the continuous evolution of medical images is ongoing, radiologists must be aware of new perspective to perform a central role in patients management.

One of the most critical aspects in introral impression is the detection of the finish line, in particular in case of subgingival preparations. The aim of these in vitro study was to evaluate the accuracy among four different IntraOral Scanners (IOSs) in scanning a subgingival vertical margins preparation (VP). A reference maxillary typodont (MT) was fabricated with a VP for full crown on #16 and #21. The MT was scanned with a laboratory scanner (Aadva lab scanner, GC, Tokyo, Japan) to obtain a digital MT (dMT) in .stl format file. A group of 40 digital casts (dIOC) were obtained by scanning the MT 10 times with four different IOSs (Trios 3, 3Shape A/S), ( I700, Medit), (Vivascan, Ivoclar), (Experimental IOS, GC). All the obtained dIOCs were imported into an inspection software program (Geomagic Control X; 3D SYSTEMS) to be superimposed to the dMT, to calculate trueness. Therefore, in order to calculate precision all the scans of the same scanner group were superimposed onto the cast that obtained the best result of trueness. Results were collected as root mean square value (RMS) on #16 and #21 abutment surfaces and on a marginal area positioned 1 mm above and below the gingival margin. A nonparametric analysis Kruskal-Wallis test was performed to compare the RMS values obtained in the different iOS groups for trueness and precision. Statistically significance was set at 0.05. The trueness on #16 abutment, did not statistically differ in between the IOS, while on #21 abutment, Vivascan (56.0 ±12.1) and Experimental IOS, GC (59.2±2.7) performed statistically better than the others. Regarding precision Experimental IOS, GC and Trios 3 were significantly better than I700 and Vivascan both in the #16 (10.7±2,1; 15.8 ± 2,7) and in the #21 area (16.9±13.8 ; 18.0±2.7). At marginal level for both #16 and #21 all the IOS reported reduced accuracy compared to clinical acceptance.

The involved components of formulated blending, CNF and CuO NPs, were individually obtained by using a biorefinery strategy for agricultural waste valorization together with an optimized chemical precipitation, assisted by ultrasounds. The optimization of synthesis parameters for CuO NPs have avoided the presence of undesirable species which usually requires of later thermal treatment with associated costs. The aerogels-based structure, obtained by conventional freeze-drying, acted as 3D support for CuO NPs providing a good dispersion within the cross-linked structure of the nanocellulose and facilitating direct contact of the antibacterial phase against undesirable microorganisms. All samples showed a positive response against Escherichia coli and Staphylococcus aureus. An increase of the antibacterial response of the aerogels, measured by agar disk diffusion test, has been observed with the increase of CuO NPs incorporated, obtaining width of the antimicrobial “halo” (nwhalo) from 0 to 0.6 and 0.35 for S. aureus and E. coli, respectively. Furthermore, the aerogels have been able to deactivate S. aureus and E. coli in less than 5 hours when the antibacterial assays have been analyzed by broth dilution method. From CNF-50CuO samples, an overlap nanoparticles effect produced a decrease of the antimicrobial kinetic.

Aboriginal Australians have a fundamental human right to opportunities that lead to healthy and flourishing lives. While the impact of trauma on Aboriginal Australians is well-documented, a pervasive deficit narrative that focuses on problems and pathology persists in research and policy discourse. This narrative risks further exacerbating Aboriginal disadvantage, through a focus on ‘fixing what is wrong’ with Aboriginal Australians, and the internalising of these narratives by Aboriginal Australians. While a growing body of research adopts strength-based models, limited research has sought to explore Aboriginal flourishing. This conceptual paper seeks to contribute to a burgeoning paradigm shift in Aboriginal research, seeking to understand what can be learned from Aboriginal people who flourish, how we best determine this, and in what contexts this can be impactful. Within, we argue the case for a new approach to exploring Aboriginal wellbeing that integrates salutogenic, positive psychology concepts with complex systems theory to understand and promote Aboriginal wellbeing and flourishing, While deeper work may be required to establish the parameters of a strength-based, culturally aligned Aboriginal conceptualisation of positive psychology, we suggest the integration of Aboriginal and Western methodologies offer unique and potent means of shifting the dial on seemingly intractable problems.

Objective: The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on comorbid symptoms of depression, anxiety, and fatigue in migraine patients resistant to traditional prophylaxis. Methods: The study was an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis treated with anti-CGRP/R mAbs for 3 months. Results: 77 patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44% respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥ 50% of headache frequency. The two groups were highly homogeneous for investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms were reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. Conclusion: anti-CGRP/R antibodies improve pain together with affection, fatigue, and sensory sensitization in migraine patients.

Background. Cervical esophageal reconstruction is vital for improving the quality of life in cancer surgery patients. Microsurgery is crucial, providing vascularized tissue for defect repair, particularly in secondary cases with a higher risk of failure due to larger defects and damage from previous surgery and radiotherapy. The purpose of this study was to describe the clinical characteristics of a series of patients who underwent secondary repair of esophageal defects and provide practical information for the management and treatment of such cases based on the authors' experience and the literature review. Methods. We retrospectively reviewed the electronic medical records of the Plastic Surgery Clinic at the University of Trieste to identify cases of patients who underwent secondary esophageal microsurgical reconstructions following oncological surgery. Patient demographics, etiology of esophageal defects, previous surgical history, and preoperative assessments were collected from medical records. Surgical techniques employed for reconstruction, such as pedicled flaps or free tissue transfers, were documented along with intraoperative details. Postoperative outcomes, including complications, graft viability, and functional outcomes, were evaluated during follow-up. Results. We treated 13 cases of secondary esophageal reconstructions from 2011 to 2022. Most commonly, Antero-Lateral Thigh (ALT) flaps were used in 10 cases, while 2 cases employed Radial Forearm Flap (RFF), and 1 a chimeric parascapular flap. No flap failures occurred during a median 50-month follow-up. One ALT flap patient experienced post-op stricture but maintained swallowing ability. A single tracheoesophageal fistula occurred in a RFF patient with a history of radiotherapy and completion lymph node dissection. Conclusions. Cervical esophageal reconstruction significantly impacts patients' quality of life by restoring oral feeding and phonation. When local flaps fall short, microsurgical reconstruction with intestinal flaps is valuable, but burdened by limitations. For challenging secondary cases, ALT or RFF flaps emerge as safer options due to their robust pedicles, yielding low complication rates and positive functional outcomes.

Talking about sustainable development refers mainly to the environmental sphere, but the concept is much broader and also takes into account the social and economic conditions. The concept of sustainability, in this sense, is linked to the compatibility between the development of economic activities, the related social phenomena, and the protection of the environment. Therefore, the ability to balance social, economic and environmental sustainability is the very meaning of the concept of sustainable development. Firms that choose to develop policies and strategies to enhance and pursue sustainable development in the medium to long term have the burden of having to quantitatively document the improvements in production processes with the aim of sustainable development. As a result, one of the biggest challenges for European industry is to introduce sustainability principles into business models leading to competitive advantage. This is particularly important in raw material and energy intensive manufacturing sectors such as the ceramic industry. The present state of knowledge lacks a comprehensive operational tool for industry to support decision-making processes geared towards sustainability. In the ceramic sector, the economic and social dimensions of the product and processes have not yet been given sufficient importance. Moreover, the traditional research on industrial districts lacks an analysis of the relations between firms and the territory with a view to sustainability. Finally, the attention of scholars in the field of economic and social sustainability, has not yet turned to the analysis of the Sassuolo district. Therefore, in this paper we introduce the Life Cycle Sustainability Assessment (LCSA), as a method that can be a suitable tool to fill this gap, because through a mathematical model it is possible to obtain the information useful for decision makers to integrate the principles of sustainability both at the microeconomic level in enterprises, and at the meso-economic level for the definition of economic policies and territorial governance. Environmental and socio-economic analysis was performed from the extraction of raw materials to the packaging of the product on different product categories manufactured by the Italian ceramic industries of the Sassuolo district (northern Italy). For the first time the LCSA model, usually applied to unitary processes, is extended to the economic and industrial activities of the entire district, extending the prospect of investigation from the enterprise and its value chain to the integrated network of district enterprises.

An effective behavior changes program is the first-line of prevention for youth obesity. However, effectiveness in prevention of adolescent obesity requires several approaches, with special attention paid to disordered eating behaviors and psychological support among other environmental factors. The aim of this systematic review was to compare the impact of two types of obesity prevention programs, inclusive of behavior change components on weight outcomes. Energy-balance studies were aimed at reducing calories from high-energy sources and increasing PA levels, while “shared risk factors for obesity and eating disorders” focused on reducing disordered eating behaviors to promote a positive relationship with food and eating. A systematic search of ProQuest, PubMed, PsycInfo, SciELO, and Web of Science identified 8825 articles. Twenty were considered “energy-balance” and fifteen “shared-risk factors for obesity and eating disorders”. Overall, energy-balance studies were unable to support a maintenance weight status, diet, and PA over time. Shared risk factors programs also did not result in significant differences in weight status over time. However, the majority of shared risk factors studies demonstrated reduced body dissatisfaction, dieting, and weight-control behaviors. More research is needed to examine how a shared risk factor approach can address both obesity and eating disorder.

The human T-cell leukemia virus type 1 (HTLV-1) is the only known human oncogenic retrovirus. HTLV-1 can cause a cancer called adult T-cell leukemia/lymphoma (ATL). The virus is transmitted through body fluids of infected individuals, primarily breast milk, blood, and semen. At least 5–10 million people in the world are infected with HTLV-1. In addition to ATL, HTLV-1 infection can also cause HTLV-I-associated myelopathy (HAM /TSP). ATL is characterized by low viral ex-pression and poor prognosis. The oncogenesis triggered by HTLV-1 is extremely complex and the molecular mechanisms are not fully understood. However, viral regulatory proteins Tax and HTLV-1 bZIP factor (HBZ) have been shown to play key roles in the transformation of HTLV-1-infected T cells. Moreover, several studies have shown that the final fate of HTLV-1-infected transformed T cell clones is the result of a complex interplay of HTLV-1 oncogenic protein expression with cellular transcription factors that subvert the cell cycle and disrupt reg-ulated cell death, thereby exerting their transforming effects. This review provides updated in-formation on the mechanisms underlying the transforming action of HTLV-1 and the potential therapeutic targets to combat ATL.

Macro-autophagy is an essential cellular process involved in degradation of aberrant organelles and proteins. Initially proposed to be a ‘bulk’ degradation pathway, a more nuanced appreciation of selective autophagy pathways has emerged in recent years. The discovery of a glycogen-selective autophagy pathway (‘glycophagy’) has highlighted the importance of autophagy in regulating cellular metabolic homeostasis and identified a novel non-canonical major pathway of glycogen flux. The field of glycogen autophagy research is at an early evolutionary stage, but already it is clear that the implications of these discoveries are far-reaching and provide scope for multi-disciplinary investigations into the role of glycophagy in health and disease. With potential cognate protein partners identified, the opportunities for targeted intervention have become viable. Here we review the current evidence relating to specific protein mediators involved in glycophagy, and highlight areas of uncertainty that provide opportunity for further investigation.

To better understand anogenital warts (AGW) natural history and dynamic of HPV6/11 infection in regional hairs, 32 newly diagnosed AGW male patients and 32 age-matched healthy controls were closely followed. During enrollment and six follow-up visits (every 2.6 months) 43 AGW tissue and 1,232 anogenital and eyebrow hair samples were collected. This represents the closest longitudinal monitoring of AGW patients to date. Patients were treated according to standard-of-care. HPV6/11 prevalence was 19.9% in patients’ hair samples (HPV6 B1 in 87.5%) and 0% in controls. The highest HPV6/11 prevalence was found in pubic hairs (29.0%) and lowest in eyebrows (7.1%). Odds for HPV6/11-positive hairs increased with smoking, shaving anogenital region and age. A close association between HPV6/11 presence in hairs and clinically visible AGW was observed. The proportion of patients with visible AGW and HPV6/11-positive hairs declined during follow-up with similar trends. No particular HPV6/11 variant was linked with increased AGW recurrence, but sublineage HPV6 B1 showed significantly higher clearance from hairs. Despite treatment, 78.1% and 62.5% of AGW patients experienced one and two/more post-initial AGW episodes, respectively. Patients having HPV6/11-positive hairs or visible AGW at preceding visit demonstrated substantially higher odds for presenting with visible AGW in subsequent visit.