Miracle-dz/UniFAR-FTUs huggingface dataset:
Future Incidence of Malignant Mesothelioma in South Korea: Updated Projection to 2038

Malignant mesothelioma (MM) is a cancer that is largely caused by exposure to asbestos. Although asbestos is no longer used in South Korea, the incidence of MM continues to increase due to its long latent period. We aimed to update the previous prediction of MM incidence until 2038. We predicted the incidence of MM over the next 20 years (2019–2038) in South Korea using Møller’s age–period–cohort (APC) model and a Poisson regression model based on asbestos consumption. The APC model predicted that the crude incidence rate would increase sharply in men and slowly in women. Despite the sex discrepancy in the rate of increase, the incidence rate for both sexes is expected to continue increasing until 2038. In the Poisson model, the crude incidence rate was predicted to increase continuously until 2038, and far more cases of MM were predicted to occur compared with the results of the APC model. When compared with actual incidence data, the APC model was deemed more suitable than the Poisson model. The APC model predicted a continuous increase over the next 20 years with no peak, suggesting that the incidence of MM will continue to rise far into the future.
eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.
Determining Factors Affecting the Acceptance of Medical Education eLearning Platforms during the COVID-19 Pandemic in the Philippines: UTAUT2 Approach

eLearning has been the medium of delivery of medical educational institutions to address the scarcity of medical professionals during the COVID-19 pandemic. In this study, the Unified Theory of Acceptance and Use of Technology (UTAUT2) was extended to determine the factors affecting the acceptance of eLearning platforms to medical education in the Philippines during the COVID-19 pandemic. A total of 360 medical students voluntary participated and answered an online questionnaire that consisted of 40 questions. Structural Equation Modeling (SEM) indicated that performance expectancy was found to have the highest effect on behavioral intention, which was followed by learning value and instructor characteristics. A high behavioral intention was found to affect the actual use of eLearning platforms. Interestingly, social influence and habit were found not to be significant to behavioral intentions. This study is the first study that has explored the acceptance of eLearning platforms among medical students in the Philippines during the COVID-19 pandemic. The findings can be a theoretical guideline of the Commission on Higher Education of the Philippines for eLearning platforms. Finally, the framework would be very valuable for enhancing the open innovation in eLearning platforms in medical fields worldwide.
Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties

Adenovirus vector-based genetic vaccines have emerged as a powerful strategy against the SARS-CoV-2 health crisis. This success is not unexpected because adenoviruses combine many desirable features of a genetic vaccine. They are highly immunogenic and have a low and well characterized pathogenic profile paired with technological approachability. Ongoing efforts to improve adenovirus-vaccine vectors include the use of rare serotypes and non-human adenoviruses. In this review, we focus on the viral capsid and how the choice of genotypes influences the uptake and subsequent subcellular sorting. We describe how understanding capsid properties, such as stability during the entry process, can change the fate of the entering particles and how this translates into differences in immunity outcomes. We discuss in detail how mutating the membrane lytic capsid protein VI affects species C viruses’ post-entry sorting and briefly discuss if such approaches could have a wider implication in vaccine and/or vector development.
Potency- and Selectivity-Enhancing Mutations of Conotoxins for Nicotinic Acetylcholine Receptors Can Be Predicted Using Accurate Free-Energy Calculations

Nicotinic acetylcholine receptor (nAChR) subtypes are key drug targets, but it is challenging to pharmacologically differentiate between them because of their highly similar sequence identities. Furthermore, α-conotoxins (α-CTXs) are naturally selective and competitive antagonists for nAChRs and hold great potential for treating nAChR disorders. Identifying selectivity-enhancing mutations is the chief aim of most α-CTX mutagenesis studies, although doing so with traditional docking methods is difficult due to the lack of α-CTX/nAChR crystal structures. Here, we use homology modeling to predict the structures of α-CTXs bound to two nearly identical nAChR subtypes, α3β2 and α3β4, and use free-energy perturbation (FEP) to re-predict the relative potency and selectivity of α-CTX mutants at these subtypes. First, we use three available crystal structures of the nAChR homologue, acetylcholine-binding protein (AChBP), and re-predict the relative affinities of twenty point mutations made to the α-CTXs LvIA, LsIA, and GIC, with an overall root mean square error (RMSE) of 1.08 ± 0.15 kcal/mol and an R2 of 0.62, equivalent to experimental uncertainty. We then use AChBP as a template for α3β2 and α3β4 nAChR homology models bound to the α-CTX LvIA and re-predict the potencies of eleven point mutations at both subtypes, with an overall RMSE of 0.85 ± 0.08 kcal/mol and an R2 of 0.49. This is significantly better than the widely used molecular mechanics—generalized born/surface area (MM-GB/SA) method, which gives an RMSE of 1.96 ± 0.24 kcal/mol and an R2 of 0.06 on the same test set. Next, we demonstrate that FEP accurately classifies α3β2 nAChR selective LvIA mutants while MM-GB/SA does not. Finally, we use FEP to perform an exhaustive amino acid mutational scan of LvIA and predict fifty-two mutations of LvIA to have greater than 100X selectivity for the α3β2 nAChR. Our results demonstrate the FEP is well-suited to accurately predict potency- and selectivity-enhancing mutations of α-CTXs for nAChRs and to identify alternative strategies for developing selective α-CTXs.
The Impact of COVID-19 on Smoking Behaviours and Support for Smoke-Free Zones in Saudi Arabia

This article focuses on the impact of COVID-19 on smoking and smoking cessation behaviours and support for smoke-free zones in Jeddah, Saudi Arabia. A pre-tested structured survey was distributed by email in October–November 2020 to students and staff at the University of Jeddah. Responses were analysed using descriptive statistics with summative content analysis of open text. Participants providing open text comments (n = 374/666; 56.4%) were non-smokers (n = 293; 78.3%), former smokers (n = 26; 7.0%) and current smokers (n = 55; 14.7%). Some had household members (n = 220; 58.8%) and friends who smoke (n = 198; 52.9%) plus daily exposure to secondhand smoke at home (n = 125; 33.4%). There was an awareness during COVID-19 of: smoking inside cafes/restaurants and other indoor and outdoor public places; exposure to warnings in the media both against and promoting smoking; widespread support for smoke-free zones. Smokers plans for accessing smoking cessation support are inconsistent with retrospective reports. Many express positivity highlighting reductions in smoking but there were also negative reports of increased smoking. The COVID-19 pandemic has affected every aspect of society worldwide. People have been at home more with restricted freedom of movement and limitations on social liberty. These individual accounts can help to focus evidence-based smoking prevention and cessation programmes during and post-COVID-19.
Subtyping Cryptosporidium xiaoi, a Common Pathogen in Sheep and Goats

Cryptosporidiosis is a significant cause of diarrhea in sheep and goats. Among the over 40 established species of Cryptosporidium, Cryptosporidium xiaoi is one of the dominant species infecting ovine and caprine animals. The lack of subtyping tools makes it impossible to examine the transmission of this pathogen. In the present study, we identified and characterized the 60-kDa glycoprotein (gp60) gene by sequencing the genome of C. xiaoi. The GP60 protein of C. xiaoi had a signal peptide, a furin cleavage site of RSRR, a glycosylphosphatidylinositol anchor, and over 100 O-glycosylation sites. Based on the gp60 sequence, a subtyping tool was developed and used in characterizing C. xiaoi in 355 positive samples from sheep and goats in China. A high sequence heterogeneity was observed in the gp60 gene, with 94 sequence types in 12 subtype families, namely XXIIIa to XXIIIl. Co-infections with multiple subtypes were common in these animals, suggesting that genetic recombination might be responsible for the high diversity within C. xiaoi. This was supported by the mosaic sequence patterns among the subtype families. In addition, a potential host adaptation was identified within this species, reflected by the exclusive occurrence of XXIIIa, XXIIIc, XXIIIg, and XXIIIj in goats. This subtyping tool should be useful in studies of the genetic diversity and transmission dynamics of C. xiaoi.
A Possible Role for HSV-1-Specific Humoral Response and PILRA rs1859788 Polymorphism in the Pathogenesis of Parkinson’s Disease

The etiology of Parkinson’s disease (PD), a progressive nervous system disorder that affects movement, is still unknown; both genetic and environmental factor are believed to be involved in onset of the disease and its development. Herpes simplex virus type 1 (HSV-1), in particular, is suspected to have a role in PD. Paired Immunoglobulin-like type 2 receptor alpha (PILRA) is an inhibitory receptor that down-regulates inflammation and is expressed on innate immune cells. The PILRA rs1859788 polymorphism is protective against Alzheimer’s disease, even in relation with HSV-1 antibody titers, but no data are available in PD. We analyzed HSV-1 antibody titers and PILRA rs1859788 in PD (n = 51) and age-and sex-matched healthy controls (HC; n = 73). Results showed that HSV-1, but not cytomegalovirus (CMV) or human herpes virus type 6 (HHV-6) antibody titers were significantly higher in PD compared to HC (p = 0.045). The rs1859788 polymorphism was not differentially distributed between PD and HC, but the minor allele A was more frequently carried by PD (68%) compared to HC (50%) (p = 0.06). Notably, the rs1859788 minor allele A was statically more frequent in male PD (65%) compared to male HC (37%) (p = 0.036). Finally, no relation was found between HSV-1 antibody titers and PILRA genotype. Results herein suggest an involvement of HSV-1 in PD and indicate a possible interaction between PILRA gene polymorphisms and this neuropathology.
Heart rate variability analysis for the assessment of immersive emotional arousal using virtual reality: Comparing real and virtual scenarios

Many affective computing studies have developed automatic emotion recognition models, mostly using emotional images, audio and videos. In recent years, virtual reality (VR) has been also used as a method to elicit emotions in laboratory environments. However, there is still a need to analyse the validity of VR in order to extrapolate the results it produces and to assess the similarities and differences in physiological responses provoked by real and virtual environments. We investigated the cardiovascular oscillations of 60 participants during a free exploration of a real museum and its virtualisation viewed through a head-mounted display. The differences between the heart rate variability features in the high and low arousal stimuli conditions were analysed through statistical hypothesis testing; and automatic arousal recognition models were developed across the real and the virtual conditions using a support vector machine algorithm with recursive feature selection. The subjects’ self-assessments suggested that both museums elicited low and high arousal levels. In addition, the real museum showed differences in terms of cardiovascular responses, differences in vagal activity, while arousal recognition reached 72.92% accuracy. However, we did not find the same arousal-based autonomic nervous system change pattern during the virtual museum exploration. The results showed that, while the direct virtualisation of a real environment might be self-reported as evoking psychological arousal, it does not necessarily evoke the same cardiovascular changes as a real arousing elicitation. These contribute to the understanding of the use of VR in emotion recognition research; future research is needed to study arousal and emotion elicitation in immersive VR.
The Odorant-Binding Proteins of the Spider Mite Tetranychus urticae

Spider mites are one of the major agricultural pests, feeding on a large variety of plants. As a contribution to understanding chemical communication in these arthropods, we have characterized a recently discovered class of odorant-binding proteins (OBPs) in Tetranychus urticae. As in other species of Chelicerata, the four OBPs of T. urticae contain six conserved cysteines paired in a pattern (C1–C6, C2–C3, C4–C5) differing from that of insect counterparts (C1–C3, C2–C5, C4–C6). Proteomic analysis uncovered a second family of OBPs, including twelve members that are likely to be unique to T. urticae. A three-dimensional model of TurtOBP1, built on the recent X-ray structure of Varroa destructor OBP1, shows protein folding different from that of insect OBPs, although with some common features. Ligand-binding experiments indicated some affinity to coniferyl aldehyde, but specific ligands may still need to be found among very large molecules, as suggested by the size of the binding pocket.
Investigating In Vitro and Ex Vivo Properties of Artemether/Lumefantrine Double-Fixed Dose Combination Lipid Matrix Tablets Prepared by Hot Fusion

Highly lipophilic antimalarial drugs, artemether and lumefantrine, whilst an effective fixed-dose combination treatment to lower the malarial disease burden, are therapeutically hindered by low aqueous solubility and varied bioavailability. This work investigates the plausibility of directly compressed lipid matrix tablets, their role as lipid-based formulations and their future standing as drug delivery systems. Lipid matrix tablets were manufactured from solid lipid dispersions in various lipid:drug ratios employing hot fusion—the melt mixing of highly lipophilic drugs with polymer(s). Sequential biorelevant dissolution media, multiple mathematical models and ex vivo analysis utilizing porcine tissue samples were employed to assess drug release kinetics and more accurately predict in vitro performance. Directly compressed stearic acid tablets in a 0.5:1 lipid:drug ratio were deemed optimal within investigated parameters. Biorelevant media was of immense value for artemether release analysis, with formulation SA0.5C1 (Stearic Acid:double fixed dose in a 0.5:1 ratio (i.e., Stearic acid 70 mg + Lumefantrine 120 mg + Artemether 20 mg); CombiLac® as filler (q.s.); and 1% w/w magnesium stearate) yielding a higher percentage of artemether release (97.21%) than the commercially available product, Coartem® (86.12%). However, dissolution media lacked the specificity to detect lumefantrine. Nonetheless, stearic acid lipid:drug ratios governed drug release mechanisms. This work demonstrates the successful utilization of lipids as pharmaceutical excipients, particularly in the formulation of lipid matrix tablets to augment the dissolution of highly lipophilic drugs, and could thus potentially improve current malarial treatment regimens.
Childhood Personality Assessment Q-Sort (CPAP-Q): A Clinically and Empirically Procedure for Assessing Traits and Emerging Patterns of Personality in Childhood

Background: Despite increasing research confirming the existence of childhood personalities, which are recognizable from a developmental perspective, controversies over the possibility to assess personality in childhood have continued. The purpose of this study was to provide initial data on the validation of the Childhood Personality Assessment Q-Sort (CPAP-Q), a clinician report instrument that can be employed to evaluate children’s personalities and address the gap in the field of emerging personality in children classification. Method: A sample of 135 clinicians completed the CPAP-Q to assess the personality features of 135 children (ages 4–11) who had been in their care between two and 12 months. The clinicians completed a clinical questionnaire to collect information on them, the children, and their families, as well as the Child Behavior Checklist (CBCL), to evaluate the children’s behavioral problems and social competencies. Results: Q-factor analysis identified seven specific emerging personality patterns: psychological health, borderline/impulsive, borderline/dysregulated, schizoid, inhibited/self-critical, obsessive, and dysphoric/dependent. These patterns revealed good levels of validity and reliability. Conclusions: These findings are preliminary, but seem to support the possibility of evaluating emerging personality patterns in childhood and their developmental pathways that may lead to personality disorders in adolescence and adulthood. The CPAP-Q promises to significantly contribute to less explored research areas and encourage systematic studies of children assessment, promoting best practices for individualized diagnoses.
Combining Molecular Dynamic Information and an Aspherical-Atom Data Bank in the Evaluation of the Electrostatic Interaction Energy in Multimeric Protein-Ligand Complex: A Case Study for HIV-1 Protease

Computational analysis of protein–ligand interactions is of crucial importance for drug discovery. Assessment of ligand binding energy allows us to have a glimpse of the potential of a small organic molecule to be a ligand to the binding site of a protein target. Available scoring functions, such as in docking programs, all rely on equations that sum each type of protein–ligand interactions in order to predict the binding affinity. Most of the scoring functions consider electrostatic interactions involving the protein and the ligand. Electrostatic interactions constitute one of the most important part of total interactions between macromolecules. Unlike dispersion forces, they are highly directional and therefore dominate the nature of molecular packing in crystals and in biological complexes and contribute significantly to differences in inhibition strength among related enzyme inhibitors. In this study, complexes of HIV-1 protease with inhibitor molecules (JE-2147 and darunavir) were analyzed by using charge densities from the transferable aspherical-atom University at Buffalo Databank (UBDB). Moreover, we analyzed the electrostatic interaction energy for an ensemble of structures, using molecular dynamic simulations to highlight the main features of electrostatic interactions important for binding affinity.
PD-L1 Expression Associated with Epstein—Barr Virus Status and Patients’ Survival in a Large Cohort of Gastric Cancer Patients in Northern Brazil

Simple Summary The programmed death ligand 1 (PD-L1) tumor expression is a manifestation of immune evasion and is used as a biomarker for treatment by immunotherapy and appears as a promising therapeutical option for Gastric Cancer (GC). The aim of this study was to evaluate the correlation between EBV status, PD-L1 expression and overall survival in a cohort of a thousand GC patients. Of the thousand tumors, 190 were EBV-positive and presented a high relative expression of PD-L1. the PD-L1 low expression was a characteristic of GC patients EBV-negative. We also show that the high expression of PD-L1 impacts on the survival probability and increase overall survival in GC patients. No EBV-negative GC patients had expression of PD-L1 protein, which suggests that the low expression is related to low overall survival. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine. Abstract Gastric cancer (GC) is a worldwide health problem, making it one of the most common types of cancer, in fifth place of all tumor types, and the third highest cause of cancer deaths in the world. There is a subgroup of GC that consists of tumors infected with the Epstein–Barr virus (EBV) and is characterized mainly by the overexpression of programmed cell death protein-ligand-1 (PD-L1). In the present study, we present histopathological and survival data of a thousand GC patients, associated with EBV status and PD-L1 expression. Of the thousand tumors analyzed, 190 were EBV-positive and the vast majority (86.8%) had a high relative expression of mRNA and PD-L1 protein (p < 0.0001) in relation to non-neoplastic control. On the other hand, in EBV-negative samples, the majority had a low PD-L1 expression of RNA and protein (p < 0.0001). In the Kaplan–Meier analysis, the probability of survival and increased overall survival of EBV-positive GC patients was impacted by the PD-L1 overexpression (p < 0.0001 and p = 0.004, respectively). However, the PD-L1 low expression was correlated with low overall survival in those patients. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine.