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Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by cognitive deterioration and changes in behavior. Acetylcholinesterase (AChE), which hydrolyzes acetylcholine, is a key drug target for treating AD. This research aimed to identify new AChE inhibitors using the IMPPAT database. We used known drugs as a basis to search for similar chemicals in the IMPPAT database and created a library of 127 plant-based compounds. Initial screening of these compounds was performed using molecular docking, followed by an analysis of their drug-likeness and ADMET properties. Compounds with favorable properties underwent density functional theory (DFT) calculations to assess their electronic properties such as HOMO-LUMO gap, electron density, and molecular orbital distribution. These descriptors provided insights into each compound's reactivity, stability, and binding potential with AChE. Promising candidates were further evaluated through molecular dynamics (MD) simulations over 100 ns and MMPBSA analysis for the last 30 ns. Two compounds, Biflavanone (IMPHY013027) with a binding free energy of − 130.394 kcal/mol and Calomelanol J (IMPHY007737) with − 107.908 kcal/mol, demonstrated strong binding affinities compared to the reference molecule HOR, which has a binding free energy of − 105.132 kcal/mol. These compounds exhibited promising drug-ability profiles in both molecular docking and MD simulations, indicating their potential as novel AChE inhibitors for AD treatment. However, further experimental validation is necessary to verify their effectiveness and safety. [ABSTRACT FROM AUTHOR]

Purpose: Subperiosteal abscess (SPA) can lead to devastating morbidity and mortality. Prompt management is important; however, the choice of management route is controversial. This study investigates factors associated with surgical management and defines a cut-off abscess volume prompting surgical intervention. Methods: SPA cases presented to King Saud University Medical City (KSUMC) from 2014 to 2023 were reviewed. The surgical approach was studied in association with factors including age, gender, symptoms and signs, laboratory results, computed tomography (CT) characteristics, medications, and surgical approach. Multiple statistical tests were used for analysis, including student t-test, chi-square, multiple logistic regression analysis, and receiver operating characteristic (ROC) analysis. Results: Patients were managed medically (n = 14, 45.16%) or surgically (n = 17, 54.84%). The average duration of antibiotics was 15 days. Superior SPA favors surgical management (OR = 6.722, CI [1.332–33.913], p = 0.029), along with the use of steroids (OR = 5.625, CI [0.915–34.572], p = 0.049), and abscess volume (OR = 10.003, CI [1.418–70.540], p < 0.001). However, the only factor attributing to a surgical decision on multivariate logistic regression analysis was abscess volume (OR = 5.126, CI [1.023–25.694], p = 0.047). SPA volume of ≥ 0.648 ml strongly prompts surgical management, with a sensitivity of 94.1% and a specificity of 71.4% (p = 0.000). Conclusion: SPA volume increases the likelihood of surgical intervention by five times, especially when abscess volume is ≥ 0.648 ml. [ABSTRACT FROM AUTHOR]

Blood coagulation is a vital physiological process involving a complex network of biochemical reactions, which converge to form a blood clot that repairs vascular injury. This process unfolds in three phases: initiation, amplification, and propagation, ultimately leading to thrombin formation. Coagulation begins when tissue factor (TF) is exposed on an injured vessel's wall. The first step is when activated factor VII (VIIa) in the plasma binds to TF, forming complex TF:VIIa, which activates factor X. Activated factor X (Xa) is necessary for coagulation, so the regulation of its activation is crucial. Tissue Factor Pathway Inhibitor (TFPI) is a critical regulator of the initiation phase as it inhibits the activation of factor X. While previous studies have proposed two pathways—direct and indirect binding—for TFPI's inhibitory role, the specific biochemical reactions and their rates remain ambiguous. Many existing mathematical models only assume an indirect pathway, which may be less effective under physiological flow conditions. In this study, we revisit datasets from two experiments focused on activated factor X formation in the presence of TFPI. We employ an adaptive Metropolis method for parameter estimation to reinvestigate a previously proposed biochemical scheme and corresponding rates for both inhibition pathways. Our findings show that both pathways are essential to replicate the static experimental results. Previous studies have suggested that flow itself makes a significant contribution to the inhibition of factor X activation. We added flow to this model with our estimated parameters to determine the contribution of the two inhibition pathways under these conditions. We found that direct binding of TFPI is necessary for inhibition under flow. The indirect pathway has a weaker inhibitory effect due to removal of solution phase inhibitory complexes by flow. Author summary: After vascular injury, a large complex network of biochemical reactions leads to clot formation to repair vessel damage. Three vital biochemical components in the early phase of this process are coagulation factor X (X), the activated coagulation factor VII and tissue factor (TF) complex (TF:VIIa) that activates X, and tissue factor pathway inhibitor (TFPI), which regulates X activation. The mechanism of this TFPI regulation remains ambiguous. Here, we develop a mathematical model of the biochemical reactions involved in this process and calibrate our model to published data from two experimental studies of factor X activation. To explain the experimental data, we find that TFPI acts through two distinct biochemical pathways: direct and indirect binding, the latter being a multi-step process involving Xa re-binding to TF:VIIa. We extend our model to study TFPI's regulatory effects under flow and, in contrast to a previous study, demonstrate that the direct pathway of regulation is essential in the presence of flow. Incorporating our findings into larger models that include later phases of the clotting process could enhance our understanding of clotting disorders and aid in the development of targeted therapies. [ABSTRACT FROM AUTHOR]

Objective: This study offered an updated meta-analysis of randomized controlled trials (RCTs) that assessed preoperative misoprostol compared to control (matched placebos or no treatment) during abdominal myomectomies. Methods: Six databases underwent screening until 7 April 2024. The risk of bias was assessed using the Cochrane Collaboration tool. The results were presented as mean differences (MDs) or risk ratios (RRs) along with 95% confidence intervals (CIs) using the random-effects model. Results: Sixteen RCTs were analyzed, involving 975 women. The overall quality of the studies was rated as "low" or had "some concerns" of bias in seven and eight RCTs, respectively; one RCT had an overall "high" risk of bias. For primary endpoints, the misoprostol intervention had significantly lower mean intraoperative blood loss (n = 15, MD = −180.2 mL, 95% CI [−224.04, −136.35], p < 0.001), mean hemoglobin drop (n = 13, MD = −0.58 g/dl, 95% CI [−0.82, −0.35], p < 0.001), and rate of perioperative blood transfusion (n = 13, RR = 0.43, 95% CI [0.29, 0.63], p < 0.001) compared to the control intervention. For secondary endpoints, the misoprostol intervention had significantly lower mean hematocrit drop (MD = 2.15, 95% CI −3.34, −0.96], p < 0.001), mean operative time (MD = −12.95 min, 95% CI [−19.89, −6.01], p < 0.001), and mean hospital stay (MD = −0.14 days, 95% CI [−0.25, −0.02], p = 0.02) compared to the control intervention. Nonetheless, no significant change was indicated between both interventions regarding the rate of postoperative fever. Conclusions: During abdominal myomectomy, the administration of preoperative misoprostol was generally safe and yielded statistically significant reductions in intraoperative blood loss, hemoglobin drop, and perioperative blood transfusion. [ABSTRACT FROM AUTHOR]

Burn wounds are associated with infections, drug resistance, allergic reactions, odour, bleeding, excess exudates, and scars, requiring prolonged hospital stay. It is crucial to develop wound dressings that can effectively combat allergic reactions and drug resistance, inhibit infections, and absorb excess exudates to accelerate wound healing. To overcome the above-mentioned problems associated with burn wounds, SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers incorporated with Capparis sepiaria plant extract were prepared using an electrospinning technique. Fourier-transform infrared spectroscopy confirmed the successful incorporation of the extract into the nanofibers without any interaction between the extract and the polymers. The nanofibers displayed porous morphology and a rough surface suitable for cellular adhesion and proliferation. SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers demonstrated significant antibacterial effects against wound infection-associated bacterial strains: Pseudomonas aeruginosa, Enterococcus faecalis, Mycobaterium smegmatis, Escherichia coli, Enterobacter cloacae, Proteus vulgaris, and Staphylococcus aureus. Cytocompatibility studies using HaCaT cells revealed the non-toxicity of the nanofibers. SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers exhibited hemostatic properties, resulting from the synergistic effect of the plant extract and polymers. The in vitro scratch wound healing assay showed that the SA/PVA/Capparis sepiaria nanofiber wound-healing capability is more than the plant extract and a commercially available wound dressing. The wound-healing potential of SA/PVA/Capparis sepiaria nanofiber is attributed to the synergistic effect of the phytochemicals present in the extract, their porosity, and the ECM-mimicking structure of the nanofibers. The findings suggest that the electrospun nanofibers loaded with Capparis sepiaria extract are promising wound dressings that should be explored for burn wounds. [ABSTRACT FROM AUTHOR]

Seismic data is commonly acquired sparsely and irregularly, which necessitates the regularization of seismic data with anti-aliasing and anti-leakage methods during seismic data processing. We propose a novel method of 4D anti-aliasing and anti-leakage Fourier transform using a cube-removal strategy to address the combination of irregular sampling and aliasing in high-dimensional seismic data. We compute a weighting function by stacking the spectrum along the radial lines, apply this function to suppress the aliasing energy, and then iteratively pick the dominant amplitude cube to construct the Fourier spectrum. The proposed method is very efficient due to a cube removal strategy for accelerating the convergence of Fourier reconstruction and a well-designed parallel architecture using CPU/GPU collaborative computing. To better fill the acquisition holes from 5D seismic data and meanwhile considering the GPU memory limitation, we developed the anti-aliasing and anti-leakage Fourier transform method in 4D with the remaining spatial dimension looped. The entire workflow is composed of three steps: data splitting, 4D regularization, and data merging. Numerical tests on both synthetic and field data examples demonstrate the high efficiency and effectiveness of our approach. [ABSTRACT FROM AUTHOR]

Background: Effective wound dressing is the key solution to combating the increased death rate and prolonged hospital stay common to patients with wounds. Methods: Sodium alginate-based single- and double-layer membranes incorporated with Capparis sepiaria root extract were designed using the solvent-casting method from a combination of polyvinyl alcohol (PVA), Pluronic F127 (PF127), and gum acacia. Results: The successful preparation of the membranes and loading of the extract were confirmed using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The prepared membranes were biodegradable and non-toxic to human skin cells (HaCaT), with high biocompatibility of 92 to 112% cell viability and good hemocompatibility with absorbance ranging from 0.17 to 0.30. The membrane's highest water vapor transmission rate was 1654.7333 ± 0.736 g/m2/day and the highest % porosity was 76%. The membranes supported cellular adhesion and migration, with the highest closure being 68% after 4 days compared with the commercial wound dressings. This membrane exhibited enhanced antimicrobial activity against the pathogens responsible for wound infections. Conclusions: The distinct features of the membranes make them promising wound dressings for treating infected wounds. [ABSTRACT FROM AUTHOR]

According to the United Nations Convention on the Rights of the Child, children have the right to voice their opinions and participate in decision-making in matters affecting their lives. Furthermore, professionals working with children have the responsibility to always make the best interests of the child the priority when contemplating decisions that have an impact on the child, including by ensuring that the child's concerns are paid attention to and their opinion is taken into consideration. However, studies indicate that the opposite occurs in practice and that decision-making in child protection cases often excludes children's views, especially in alternative care. In this qualitative study, 31 foster children's perspectives were gathered through in-depth semi-structured and focus group interviews with the aim of exploring the children's participation and perspectives based on their lived experiences within the context of child protection removal practice in Estonia. Findings indicate several obstacles that hinder children's meaningful participation, including not receiving adequate or truthful information about their removal and placement. Furthermore, they had no trustworthy adult to talk to and, therefore, they lacked opportunities to discuss their views or concerns with someone capable of acting on them. These findings suggest that children's active and meaningful participation in alternative care requires more attention and implications in practice. [ABSTRACT FROM AUTHOR]

The [ P S I + ] prion phenotype in yeast manifests as a white, pink, or red color pigment. Experimental manipulations destabilize prion phenotypes, and allow colonies to exhibit [ p s i - ] (red) sectored phenotypes within otherwise completely white colonies. Further investigation of the size and frequency of sectors that emerge as a result of experimental manipulation is capable of providing critical information on mechanisms of prion curing, but we lack a way to reliably extract this information. Images of experimental colonies exhibiting sectored phenotypes offer an abundance of data to help uncover molecular mechanisms of sectoring, yet the structure of sectored colonies is ignored in traditional biological pipelines. In this study, we present [PSI]-CIC, the first computational pipeline designed to identify and characterize features of sectored yeast colonies. To overcome the barrier of a lack of manually annotated data of colonies, we develop a neural network architecture that we train on synthetic images of colonies and apply to real images of [ P S I + ] , [ p s i - ] , and sectored colonies. In hand-annotated experimental images, our pipeline correctly predicts the state of approximately 95% of colonies detected and frequency of sectors in approximately 89.5% of colonies detected. The scope of our pipeline could be extended to categorizing colonies grown under different experimental conditions, allowing for more meaningful and detailed comparisons between experiments. Our approach streamlines the analysis of sectored yeast colonies providing a rich set of quantitative metrics and provides insight into mechanisms driving the curing of prion phenotypes. [ABSTRACT FROM AUTHOR]

The evolution of Sb2Se3 heterojunction devices away from CdS electron transport layers (ETL) to wide bandgap metal oxide alternatives is a critical target in the development of this emerging photovoltaic material. Metal oxide ETL/Sb2Se3 device performance has historically been limited by relatively low fill factors, despite offering clear advantages with regards to photocurrent collection. In this study, TiO2 ETLs are fabricated via direct current reactive sputtering and tested in complete Sb2Se3 devices. A strong correlation between TiO2 ETL processing conditions and the Sb2Se3 solar cell device response under forward bias conditions is observed and optimized. Numerical device models support experimental evidence of a spike‐like conduction band offset, which can be mediated, provided a sufficiently high conductivity and low interfacial defect density can be achieved in the TiO2 ETL. Ultimately, a SnO2:F/TiO2/Sb2Se3/P3HT/Au device with the reactively sputtered TiO2 ETL delivers an 8.12% power conversion efficiency (η), the highest TiO2/Sb2Se3 device reported to‐date. This is achieved by a substantial reduction in series resistance, driven by improved crystallinity of the reactively sputtered anatase‐TiO2 ETL, whilst maintaining almost maximum current collection for this device architecture. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the effects of amino acid (histidine and L-Tyrosine) on in vitro maturation (IVM), in vitro fertilization (IVF), cleavage (CR) rates, and in vitro embryonic cultivation (IVC; Morula and Blastocyst stage) in buffaloes. Within two hours of buffalo slaughter, the ovaries were collected and transported to the laboratory. Follicles with a diameter of 2 to 8 mm were aspirated to recover the cumulus oocyte complexes (COCs). Histidine (0.5, 1, and 3 mg/ml) or L-Tyrosine (1, 5, and 10 mg/ml) were added to the synthetic oviductal fluid (SOF) and Ferticult media. The IVM, IVF, CR, and IVC (Morula and Blastocyst) rates were evaluated. The results showed that SOF maturation media containing histidine at 0.5 mg/ml significantly (P ≤ 0.01) improved the oocyte maturation when compared to control and other concentrations. The addition of histidine to FertiCult media at 0.5, 1, and 3 mg/ml did not improve the IVM, IVF, CR, or IVC percentages. However, the embryos in the control group were unable to grow into a morula or blastocyst in the SOF or Ferticult, while addition of L-Tyrosine to the SOF or Ferticult at various concentrations improved IVC (morula and blastocyst rates). There was a significant (P ≤ 0.01) increase in IVM when histidine was added to SOF medium at a concentration of 0.5 mg/ml compared with L-Tyrosine. Also, there were significant (P ≤ 0.01) increases in IVC when L-Tyrosine was added to SOF medium at concentrations of 1 and 10 mg/ml compared with histidine. In conclusion, the supplementation of the SOF and FertiCult with the amino acids histidine and L-Tyrosine improve the maturation rate of oocytes and development of in vitro-produced buffalo embryos. [ABSTRACT FROM AUTHOR]

In this paper, Nonlinear Model Predictive Control (NMPC) and Nonlinear Moving Horizon Estimator (NMHE) are combined to control, in a distributed way, a heterogeneous fleet composed of a steering car and a quadcopter. In particular, the ground vehicle in the role of the leader communicates its one-step future position to the drone, which keeps the formation along the desired trajectory. Inequality constraints are introduced in a switching control fashion to the leader's NMPC formulation to avoid obstacles. In the literature, few works using NMPC and NMHE deal with these two vehicles together. Moreover, the presented scheme can tackle noisy, partial, and missing measurements of the agents' state. Results show that the ground car can avoid detected obstacles, keeping the tracking errors of both robots in the order of a few centimeters, thanks to trustworthy NMHE estimates and NMPC predictions. [ABSTRACT FROM AUTHOR]

Trauma-informed care (TIC) is a relatively new topic in the Estonian child protection system, but it has become the particular focus of substitute care. The Estonian child protection system focuses on protecting children from maltreatment, and neglects the adult carers' right to adequate information about the child's trauma experience. This makes trauma-informed care vague. This article is based on focus groups conducted for a wider study that aims to develop the basis for a TIC training course for foster parents and staff members working as direct caregivers in residential substitute care. The foster parents and staff members participated in four focus groups, with special attention on their experiences with TIC. The participants eagerly shared their experiences, and thematic narrative analysis was used during the data analysis. The central theme of the participants' stories was the need for information about the child's traumatic past. The findings indicate that a complex interplay exists between the needs of children entering substitute care and the capacity of the foster parents and residential care staff to meet those needs. It is complicated for a child to heal from trauma if the child's past is hidden from their carers. This could result in re-traumatisation and hinder the child from making sense of past trauma. Estonia's child protection system needs greater awareness of the impact of trauma on the child's behaviour and how to help the child heal. This is directly connected to the need for clear and precise information, which is one of the basic rights of the child. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dental education is considered as a complex, challenging and often stressful educational procedure. Acquisition of psychomotor skills by undergraduate students is an important step in many health professions to become a successful professional. During under graduation, class II cavity preparation exercise is of utmost important in dentistry. OBJECTIVE: To compare class II cavities prepared by students after hands-on live demonstration and pre-recorded video demonstration using well-organised evaluation rubrics. METHOD: Preclinical dental students (n = 50) were divided into two groups. The students in group I (n = 25) attended a hands-on live demonstration performed by one faculty while students in group II (n = 25) watched a 15-minute pre-recorded procedural video on the projector. Both groups were appealed to prepare class II cavity for amalgam involving disto-occlusal surface of mandibular second molar articulated on jaw model (TRU LON study model, Jayna industries, Ghaziabad U.P., India). Following completion of the preparations, all teeth were collected, and labelled grades of prepared cavities were given according to prespecified rubrics. The data of scores were presented as means and standard deviation. Statistical analysis of data was executed using SPSS software. A paired t-test was used to compare scores between groups. RESULTS: The study shows that the video-supported demonstration of a cavity preparation was better than the live hands-on demonstration. A higher mean response for the procedural video group was found compared to the live demonstration group (p = 0.000133). CONCLUSION: Pre-recorded video-supported demonstration along with guidance by a tutor may be a viable alternative to hands-on live demonstration in cavity preparation procedures during undergraduate dental training. Moreover, rubric methods can be implemented in the teaching of various preclinical exercises for conservative dentistry and endodontics. [ABSTRACT FROM AUTHOR]

Purpose: Healthcare practitioners in Saudi Arabia sometimes experience workplace bullying (WPB). However, more research on this issue must be carried out in the country. This study aimed to investigate the prevalence of WPB and how individual factors among nurses contribute to different experiences of WPB in clinical settings. Methods: This cross-sectional quantitative study occurred among registered nurses in Riyadh, Saudi Arabia. A self-administered questionnaire was used, and nurses filled it out via a Google survey that included sociodemographic details such as age, gender, education, and the WBS to gauge the prevalence of workplace bullying in hospital settings. Results: Of 416 nurses, 58.7% were aged between 31 and 40, and 76.9% were women. The prevalence of WPB was found to be 54.8%. WPB was higher among middle-aged nurses, men, charge/managerial nurses, nurses with higher education, those with 3 to 6 years of experience, and those working in specialty units. Conclusions: More than half of the nurses had experienced WPB at some point. Middle-aged nurses, especially men with higher education and more experience in specialty units, were the most common victims of WPB compared to other registered nurses. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis—including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio—and MetS. In this descriptive cross-sectional study, 209 participants aged 24–70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment—Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS. [ABSTRACT FROM AUTHOR]

Introduction: Global inequality in clinical research capacity and service delivery can be indicated simply by the proportion of clinical trials that a country or region has registered in clinical trial registry databases. The proportion of clinical trials registered in Africa is very low at 0.02%, even though the region accounts for approximately 15% of the world's population. Despite the economic challenges in most African countries, they have shown potential for growth and change in recent years. Methods: We conducted desk reviews on the interventional clinical trials done in Kenya, Ethiopia, and Nigeria between 2015 to May 2023. The search was done in clinical trials repositories, and journal repositories. The search focused on intervention clinical trials. Data was extracted by screening through the publications and clinical trial platforms. The data extracted from the publications included the type of clinical trial, clinical trial phase, diseases, etc. The data extracted from the reports included: challenges in conducting clinical trials, capacity-building efforts, and the impact of the clinical trial. Results: The number of clinical trial studies identified in Kenya was 113 (28 were on infant clinical trials). The study identified 97 clinical trials in Nigeria, of which 11 studies were on infant clinical trials. In Ethiopia, there were 28 clinical trials and only five were on infant clinical trials. The landscape review also expanded to capacity and gaps in clinical trials in the three countries. The largest proportion of clinical trials carried out in Kenya was on injury, occupational disease, and poisoning, 30.5% (n = 18) and the smallest proportion was on kidney disease, neonatal disease, obstetrics, and gynecology. Most Infant clinical trials were carried out in the area of infections and infestations 33.3% (n=7). Most of the challenges faced by clinical trials in the three countries include a lack of infrastructure, a lack of human resources, and a lack of financial resources. Implications: There is a need to map clinical trials done by African researchers based in Africa to exclude the trials done by non-African researchers based in Africa. Opportunities for clinical trials should be supported and challenges addressed. [ABSTRACT FROM AUTHOR]

Nuclear receptor binding SET domain protein 2 (NSD2) significantly contributes to the development of cancer, making it a promising target for cancer drug discovery. This research explores natural compounds as potential selective inhibitors for NSD2 in cancer treatment. Employing a comprehensive in silico approach, the study utilized pharmacophore modeling, molecular docking, pharmacokinetic profiling, and molecular dynamics simulations. An e-pharmacophore model-based screening using the first selective and potent ligand bound to NSD2 identified 49,248 natural compounds from the SuperNatural 3.0 database (containing 449,008 molecules) with acceptable alignment with the developed pharmacophore hypotheses. Subsequently, molecular docking was executed to assess the standout compounds which led to the selection of ten candidates that surpassed the reference inhibitor in accordance w the binding affinity expressed as a G score. Ligand-residue interaction analyses of the top three hits (SN0450102, SN0410255, and SN0142336) revealed diverse crucial interactions with the NSD2 active site, including hydrogen bonds, pi-pi stacking, and hydrophobic contacts with key amino acid residues in the NSD2-PWWP1 domain. Pharmacokinetic profiling confirmed the drug-likability for the refined hits, indicating good cellular permeability and minimal blood-brain barrier penetration. Molecular dynamics simulations for 200 nanoseconds affirmed the stability of protein-ligand complexes, with minimal fluctuations in root mean square deviation and root mean square fluctuation analyses. Overall, this study identified promising natural compounds as potential pharmaceutical agents in the treatment of NSD2-associated cancers. [ABSTRACT FROM AUTHOR]

Prion variants are self-perpetuating conformers of a single protein that assemble into amyloid fibers and confer unique phenotypic states. Multiple prion variants can arise, particularly in response to changing environments, and interact within an organism. These interactions are often competitive, with one variant establishing phenotypic dominance over the others. This dominance has been linked to the competition for non-prion state protein, which must be converted to the prion state via a nucleated polymerization mechanism. However, the intrinsic rates of conversion, determined by the conformation of the variant, cannot explain prion variant dominance, suggesting a more complex interaction. Using the yeast prion system [PSI+], we have determined the mechanism of dominance of the [PSI+]Strong variant over the [PSI+]Weak variant in vivo. When mixed by mating, phenotypic dominance is established in zygotes, but the two variants persist and co-exist in the lineage descended from this cell. [PSI+]Strong propagons, the heritable unit, are amplified at the expense of [PSI+]Weak propagons, through the efficient conversion of soluble Sup35 protein, as revealed by fluorescence photobleaching experiments employing variantspecific mutants of Sup35. This competition, however, is highly sensitive to the fragmentation of [PSI+]Strong amyloid fibers, with even transient inhibition of the fragmentation catalyst Hsp104 promoting amplification of [PSI+]Weak propagons. Reducing the number of [PSI+]Strong propagons prior to mating, similarly promotes [PSI+]Weak amplification and conversion of soluble Sup35, indicating that template number and conversion efficiency combine to determine dominance. Thus, prion variant dominance is not an absolute hierarchy but rather an outcome arising from the dynamic interplay between unique protein conformations and their interactions with distinct cellular proteostatic niches. [ABSTRACT FROM AUTHOR]

Purpose: Diagnosing oral and maxillofacial lesions is a multi-step, multidisciplinary process. If a clinical diagnosis is achievable, then a histopathological diagnosis is indicated to support and confirm the diagnosis. Histopathological examination of tissue biopsies is therefore an essential part of the diagnosis and/or treatment plan. The purpose of this study was to investigate the agreement between the clinical and histopathological diagnoses of oral and maxillofacial lesions and the patient, lesion, and healthcare provider factors that may affect this agreement. Patients and Methods: This was an observational, cross-sectional study of all patients who had been referred to the Oral Pathology Central Laboratory at the Faculty of Dentistry and University Dental Hospital at King Abdulaziz University in Jeddah, Saudi Arabia, between 2018 and 2022 for diagnosis of oral and maxillofacial lesions. Data extracted included information about the referring dental provider such as their clinical experience (number of years), specialty, certification, and education. Agreement between the clinical and histopathological diagnoses was evaluated, and logistic regression was used to assess provider characteristics associated with the accuracy of diagnosis. Results: The clinical and pathological diagnoses were concordant in 44.1% (n=378) of cases, and concordance was highest for odontogenic tumors (72.7%, n=24), significantly higher than for inflammatory lesions (37.3%, n=111). The anatomical locations with the highest diagnostic accuracy were the ventral surface of the tongue (71.4%, n=5), followed by the lips (52.6%, n=20). Patient age and sex and the dentist's years of experience were not associated with diagnostic agreement (p=0.2, p=0.9, and p=0.08, respectively). However, concordant diagnoses were significantly associated with the dentist's rank (p=0.02) and specialty (p=0.01). Clinical diagnoses made by oral surgeons at the time of biopsy were 1.6-times more likely (p=0.01) to agree with the pathological diagnosis compared with those made by other specialties when controlling for education, certification, and years of experience. Conclusion: These data are a reminder that a clinical diagnosis alone is not sufficient to secure the final diagnosis and to plan treatment. Histopathological examination remains essential for most oral and maxillofacial lesions. [ABSTRACT FROM AUTHOR]

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Since Malaysian authorities developed the Maid Online System (MOS) to recruit foreign domestic workers remotely, including Indonesian workers, the government of Indonesia has enacted a moratorium policy. The system allows Malaysian employers to have low-cost overseas workers. Nevertheless, it offends the bilateral agreement signed in the Memoranda of Understanding between Indonesia and Malaysia. Within the system, the sending countries like Indonesia cannot appropriately protect the workers who utilize MOS independently. In contrast, the host countries dominate the process from pre-departure to arrival. Without proper protection from the country of origin, the workers are more likely to become victims of human trafficking and slavery. This study investigates the positive support of online Indonesian public opinion for Indonesia's moratorium policy concerning Malaysia's Maid Online System (MOS) to recruit foreign domestic workers, including Indonesians. The paper focuses on secondary data from YouTube, Instagram, and online news. The data analysis of this paper utilizes netnography to elaborate on domestic politics in which public opinion (comments on YouTube, Instagram, and online news) strongly supports Indonesia's moratorium policy. Considering Putnam's two-level game theory, this article argues that netizens support Indonesia's moratorium policy because of cost and benefits considerations, rivalry among states, and meritocratic authorities. [ABSTRACT FROM AUTHOR]

Natural deep eutectic solvents (NADES) are emerging, environment-friendly solvents that have garnered attention for their application in extracting phenolic compounds. This study investigated the effects of four synthetic NADES on polyphenols extracted from date seeds (DS) using choline chloride (ChCl) as a hydrogen-bond acceptor and lactic acid (La), citric acid (Citri), glycerol (Gly), and fructose (Fruc) as hydrogen-bond donors, in comparison with DS extracts extracted by conventional solvents (water, 70% methanol, and 70% ethanol). The antioxidant activity (DPPH), total phenolic content (TPC) and 6 phenolic compounds were determined using HPLC. The results showed that the ChCl–La and ChCl–Citri systems exhibited a high extraction efficiency regarding TPC, and DPPH in the DS extracts extracted by NADES compare to those DS extracts extracted with conventional solvents (p ˂ 0.001). HPLC results demonstrated that DS extracted by ChCl–La contained all measured phenolic compounds. Also gallic acid and catechin were the major compounds identified in the DS extracts. In addition DS extracted by ChCl–Citri and ChCl–Gly had the highest concentration of catechin. In conclusion, combining NADES is a promising and environment-friendly alternative to the conventional solvent extraction of phenolic compounds from DS. [ABSTRACT FROM AUTHOR]

Cancer is a threatening disease that needs strong therapy with fewer side effects. A lot of different types of chemotherapy or chemo-drugs are used in cancer treatments but have many side effects. The increasing number of antibiotic-resistant microorganisms requires more study of new antimicrobial compounds and delivery and targeting strategies. This work aims to isolate and identify Azotobacter sp., and extract alginate from Azotobacter sp. As well as fabricating selenium nanoparticles using ascorbic acid as reducing agent (As/Se-NPs), and loading extracted alginate with selenium nanoparticles (Alg-Se-NCMs). The As/Se-NPs and Alg-Se-NCMs were categorized by TEM, EDX, UV–Vis spectrophotometry, FT-IR, and zeta potential. The antifungal activities of both As/Se-NPs and Alg-Se-NCMs were investigated against some human pathogen fungi that cause skin infection such as Aspergillus niger (RCMB 002005), Aspergillus fumigatus (RCMB 002008), Cryptococcus neoformans (RCMB 0049001), Candida albicans (RCMB 005003), and Penicillium marneffei (RCMB 001002). The anticancer activities were determined against HCT-116 colorectal cancer and Hep G2 human liver cancer cells. UV spectra of As/Se-NPs and Alg-Se-NCMs confirmed a surface plasmon resonance at 269 and 296 nm, and zeta potential has negative charges −37.2 and −38.7 mV,. Both As/Se-NPs and Alg-Se-NCMs were hexagonal, size ranging from 16.52 to 97.06 and 17.29 to 44.2. Alg-Se-NCMs had anticancer activities against HCT-116 and HepG2. The Alg-Se-NCMs possessed the highest antifungal activities against Cryptococcus neoformans, followed by Aspergillus niger, but did not possess any activities against Penicillium marneffei. Alginate-capped selenium nanoparticles can be used as antifungal and anticancer treatments. [ABSTRACT FROM AUTHOR]

This study explores the utilization of Spent Coffee Grounds (SCG), a residual product of the coffee industry, as a microfiller reinforcement in Poly‐3‐hydroxybutyrate‐co‐3‐hydroxyvalerate (PHBV) biopolymer composites at varying concentrations (1%, 3%, 5%, and 7%). Melt compounding via a twin‐screw extruder and subsequent compression molding were employed in the fabrication process. The SCG microfiller, with particle diameters ranging from 1.11 to 1.28 μm, exhibited a significant negative charge (zeta potential: −20 mV). Hydrophobicity increased up to 5% filler concentration, as indicated by higher water contact angles, but diminished at highest concentration likelihood of agglomeration of the spent coffee grounds within the biopolymer matrix. The addition of SCG enhanced overall mechanical properties, particularly at a 5% filler concentration. Field Emission Scanning Electron Microscopy (FE‐SEM) and Atomic Force Microscopy (AFM) confirmed the successful incorporation of SCG microfiller, improving structural characteristics. Schematic drawings illustrated the interphase bonding of microfiller and matrix. However, properties diminished at the highest filler content (7%) due to coffee grounds' agglomeration. Despite this, SCG incorporation enhanced functional properties, making the biopolymer composite a promising material for sustainable packaging and various applications. Highlights: Enhancement of properties of spent coffee grounds in PHBV biocomposites.Characterization of Biocomposites for multifunctional properties.Fracture and 2D analysis of the tensile fractured surface of biocomposites.A promising material for sustainable and biodegradable packaging. [ABSTRACT FROM AUTHOR]

Background: Multimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer's disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them. Method: A 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records. Results: The dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake. Conclusion: These results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density. Trial registration: ClinicalTrials.gov NCT03249688, 2017–07-08. [ABSTRACT FROM AUTHOR]

Today, with the presence of 5G communication systems, including Internet of Things (IoT) technology, there is a high demand for mobile devices (especially smartphones, tablets, wearable technology, and so on). Regarding this proliferation and high demand, the massive adoption of mobile devices (MDs) has led to an exponential increase in network latency; the heavy demand for cloud servers causes the degradation of data traffic, which considerably impacts the real-time communication and computing aspects of mobile devices. As a result, mobile edge computing (MEC), an efficient framework capable of enhancing processing, optimizing energy usage, and offloading computation tasks, is considered a promising solution. In current research, numerous models have been implemented to achieve resource allocation and task offloading. However, these techniques are ineffective due to privacy issues and a lack of sufficient resources. Hence, this study proposes secure task offloading and resource allocation strategies in mobile devices using the Probit Mish–Gated Recurrent Unit (PM-GRU) and Entropic Linear Interpolation-Serval Optimization Algorithm (ELI-SOA). Primarily, the tasks to be offloaded and their attributes are gathered from mobile users and passed to a local computing model to identify the edge server. Here, the task attributes and the server attributes are compared with a cache table using the Sorensen–Dice coefficient. If the attributes match, then details about the appropriate edge server are produced. If the attributes do not match, then they are inputted into a global scheme that analyzes the attributes and predicts the edge server based on the Probit Mish-Gated Recurrent Unit (PM-GRU). Then, the server information is preserved and updated in the cache table in the local scheme. Further, the attributes, along with the predicted edge server, are inputted into a system for privacy-preserving smart contract creation by using Exponential Earth Mover's Distance Matrix-Based K-Anonymity (EEMDM-KA) to develop a secure smart contract. Subsequently, the traffic attributes in the smart contract are extracted, and the request load is balanced by using HCD-KM. Load-balanced requests are assigned to the edge server, and the optimal resources are allocated in the cloud server by using the Entropic Linear Interpolation-Serval Optimization Algorithm (ELI-SOA). Finally, the created smart contract is hashed based on KECCAK-512 and stored in the blockchain. With a high accuracy of 99.84%, the evaluation results showed that the proposed approach framework performed better than those used in previous efforts. [ABSTRACT FROM AUTHOR]

This study offers valuable insights into family needs and interaction patterns regarding the use of information and communications technologies (ICT) in everyday life. Given that ICT has become an important part of everyday family life, it is essential to comprehensively explore family interactions related to experiences with digital technologies. Within the DigiGen project, 30 interviews involving 10 families were conducted with children aged 5 to 10 years and their family members in Estonia. The aim of the study was to identify the interaction patterns regarding ICT use that emerge between family members in daily life and the daily family needs that are accompanied by ICT use. Thematic analysis was carried out to identify the main themes in the data. Four primary themes of family needs and interaction patterns regarding the use of ICT in everyday life – satisfying needs in family life, the roles of family members, conflicts/disagreements in family life and family rules and negotiation – are discussed. [ABSTRACT FROM AUTHOR]

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Purpose: To examine the factors that affect graft healing after laryngotracheal reconstruction (LTR). Methods: We conducted a retrospective chart review at King Abdulaziz University Hospital, Riyadh, Saudi Arabia, between January-2008 and October-2023. We included all patients who underwent LTR and required anterior and/or posterior graft placement, while those who underwent procedures without graft placement and those with incomplete information were excluded. Results: Forty-nine patients were analyzed. Most patients were pediatric (65.3%), male (65.3%), had no coexisting comorbidities (55.1%), and harbored grade 3–4 stenosis (59.2%). Thirty patients (61.2%) underwent open surgery. Various graft complications occurred including infection (n = 1, 2%), dehiscence (n = 3, 6.1%), scar (n = 6, 12.2%), and granulation (n = 29, 59.2%). Only 15 patients (30.65%) achieved the composite status of "healthy" graft. Among 43 patients who had postoperative cultures, positive results for Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus were observed in 10 and four patients, respectively. Open surgery and double-stage procedure were significantly associated with higher rates of granulation tissue formation. Pediatric-age group had significantly higher rate of complete epithelization compared to adult-age group. A significantly greater proportion of patients who had unhealthy grafts had open surgery. The rate of double-stage LTR was significantly higher in unhealthy grafts compared to healthy grafts. Prolonged stent duration was linked to various graft-related complications. Multivariate logistic regression analyses showed no statistically significant correlations between various factors and postoperative graft-related complications. Conclusion: Open surgery, double-stage procedure, pediatric age group, and stent duration were not significant risk factors associated with postoperative graft-related complications during LTR in multivariate analysis. [ABSTRACT FROM AUTHOR]

Background: Consumption of beverages and processed foods with high fructose content has increased recently. This condition increases the risk of metabolic syndrome, which include insulin resistance, impaired lipid profile, and elevated blood pressure. Moringa leaves (Moringa Oleifera), with their bioactive compounds that function as antioxidants, are known to improve fat metabolism and blood glucose. Objectives: The purpose of this study is to analyze the effect of Moringa Oleifera leaf powder and quercetin in controlling metabolic syndrome conditions by improving lipid profiles and aortic thickness in prediabetes mellitus (pre DM). Methods: This experimental research used a post-test-only control group design approach. A total of 35 male Wistar rats were divided into 5 groups such as group K0 (standard feed), E1 (66% fructose probe for 16 weeks), E2 (66% fructose probe for 12 weeks), E3 (66% fructose probe + quercetin 50 mg/kgBW), and E4 (66% fructose probe + Moringa leaf powder 500 mg/kgBW). The examination method for lipid profiles involved serum extraction and enzymatic tests, weighing for white fat tissue mass, while the aorta was examined using a light microscope and histological image analysis. Data analysis used the One-Way ANOVA test. Results: This research showed there are no difference in triglycerides, Low-Density Lipoprotein (LDL) cholesterol, and white adipose tissue significantly between the treatment groups. Level of High-Density Lipoprotein (HDL) cholesterol, total cholesterol, and aortic thickness between the treatment groups are significant differences, with the best results sequentially in groups E2, E1, and K0. Conclusions: The administration of Moringa leaf powder for 4 weeks showed improvements in lipid profiles and aortic thickness in prediabetes mellitus conditions. [ABSTRACT FROM AUTHOR]

The research was motivated by the researcher's interest in tourism in the city of Curup, especially the hot spring suban tourist destination. Various natural resources in Curup City such as mountains, hills, lakes, or waterfalls, and others have the potential to become tourist attractionsthat attract tourists to visit. Suban Air Panas is a touristattraction managed by the Rejang Lebong Regency Culture and Tourism Office. Suban Air Panas is one of themainstay attractions of Curup City which is the main destination for visitors on holidays and weekdays. The study aims to examine what factors are related to touristinterest in visiting tourist destinations in the city of Curupusing the Social Exchange Theory by George C. Homansas the basis for analysis. Homans as the basis for analysis. The type of research conducted in this study is quantitativeresearch method. Data obtained through literature study, documentation and questionnaires, observation andutilization of secondary data. Informants were selectedusing purposive sampling technique and using accidentalsampling method where the sampling technique wascarried out by chance from visitors to Suban Hot Springstourist attraction. The analysis model used in this researchis multiple linear regression with tourist interest as thedependent variable, while there are three variables as independent variables, namely tourist attraction, facilities, and accessibility. The results of this study indicate that thethree independent variables in the regression equationhave a significant effect on tourist interest in visiting. So, these variables greatly affect the number of tourists whocome to Suban Hot Springs. The tourism sector shouldcontribute to PAD can be increased again by consideringsupporting factors such as accommodation facilities (hotels and tourist lodges), restaurants, travel agencies, tourism, tourism attractions, and tourism educationinstitutions. [ABSTRACT FROM AUTHOR]

Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. Methods: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. Results: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions. Conclusions: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial. Trial registration: ClinicalTrials.gov NCT03249688. [ABSTRACT FROM AUTHOR]

Objectives A comparable performance between bulk-fill composites (BFCs) and progressively inserted conventional resin composite (CRC) has been observed in previous studies. However, a significant number of dental institutions in India continue to employ incremental techniques for RC restorations during preclinical studies. But as BFCs are gaining popularity, they may soon be a part of the curriculum for dental students. The aim of this study was to assess the microhardness and the polymerization efficiency of bulk-fill composites versus CRC in class II slot preparations restored by second-year dental students on ivorine mandibular first molar teeth with high-intensity (HI) and low-intensity (LI) light-curing units using the standard mesial slot preparation technique. Material and Methods Fifty preclinical dental students of second year of a dental college were recruited for the study on a voluntary basis. During their preclinical instructions, all participants were taught and made to practice the handling and curing techniques for two-surface RC restorations for 4 months. Each student was asked to perform four RC restorations: CRC-HI, CRC-LI, BFC-HI, and BFC LI. Assessment of microhardness was done using the Vickers microhardness (VMH) test. Statistical analysis One-way and multivariate analysis of variance and Bonferroni 's post hoc test tests were used for data analysis. Results The results showed a significant decrease in the VMH readings in the horizontal axis, progressing from the uppermost to the lowermost positions (p > 0.05). In all the examined groups, the VMH values at the deepest reading locations were found to be higher than 80% of the values observed at the occlusal surface reading locations. Statistically significant associations were seen between the RC type and the light source used in the VMH readings conducted (p > 0.05). However, no significant correlation was identified between the type of light source and the vertical VMH readings (p > 0.05). Conclusion Instructing dental students to place RC restorations using CRC or BFC materials together with both HI and LI light-curing protocols is safe and can be considered for preclinical studies. [ABSTRACT FROM AUTHOR]