Miracle-dz/UniFAR-FTUs huggingface dataset:
Views of Community Pharmacists on Antimicrobial Resistance and Antimicrobial Stewardship in Jordan: A Qualitative Study

The Center for Disease Control and Prevention and the World Health Organization issued a practical approach and Global Action Plan to control the threatening emerging antibacterial resistance. One of the main bases of this plan is the Antimicrobial Stewardship Program (ASPs). This study aimed to evaluate community pharmacists’ awareness and perception towards antimicrobial resistance and ASPs in Jordan. Thus, a qualitative study was conducted through in-depth interviews with twenty community pharmacists. Convenience sampling was used in the study. Qualitative analysis of the data yielded four themes and eleven sub-themes. All the respondents showed a good understanding of the causes of antimicrobial resistance. The most important cause reported by them was the non-restricted prescription of antimicrobials. Most of the pharmacists believed that they are competent to provide ASPs, however, they believed that there are several barriers against the implementation of ASPs in community pharmacies in Jordan. Barriers demonstrated by the pharmacists, included organizational obstacles, resources obstacles, and personal obstacles. In conclusion, this study revealed several barriers against the implementation of ASPs in community pharmacies in Jordan. Incorporating ASPs in the community pharmacy settings requires proper pharmacist training, several academic disciplines team efforts, and good pharmacy practice of antimicrobial guidelines.
Synergistic Protection by Isoquercitrin and Quercetin against Glutamate-Induced Oxidative Cell Death in HT22 Cells via Activating Nrf2 and HO-1 Signaling Pathway: Neuroprotective Principles and Mechanisms of Dendropanax morbifera Leaves

Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial superoxide generation, Ca2+ dysregulation, mitochondrial dysfunction, and nuclear translocation of apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin and quercetin, both of whom showed prominent synergism, as assessed by drug–drug interaction analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway.
The Incidence of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

Simple Summary The worldwide prevalence of Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL) is undetermined. There is no clearly defined cut-off for EBV-encoded RNA (EBER) positivity in tumor cells by in situ hybridization. A lack of common criteria for positive expression of EBER has been raised as a limitation for interpreting and understanding the geographic and ethnic disparity of prevalence of EBV+ DLBCL. We conducted a systematic literature review and meta-analysis to establish the proportions of EBV+ DLBCL patients. Results showed that the pooled proportion of EBER positivity was 7.9% in patients with de novo DLBCL. The prevalence of EBV+ DLBCL was significantly higher in Asia and South America compared with Western countries. A tendency for lower pooled proportions was observed in studies using a higher cut-off for EBER positivity. The patients’ age did not significantly affect the prevalence. These findings may improve our current knowledge of the EBV+ DLBCL. Abstract The worldwide prevalence of Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL) is undetermined. There is no clearly defined cut-off for EBV-encoded RNA (EBER) positivity in tumor cells by in-situ hybridization. The purpose of this study was to establish the proportions of EBV+ DLBCL patients and influence of the different cut-offs for EBER positivity, geographical location, and age on the prevalence of EBV+ DLBCL. PubMed and EMBASE were searched for studies published up to May 28, 2020 that reported proportions of EBER positivity in immunocompetent and de novo DLBCL patients. The pooled proportions were computed by an inverse variance method for calculating the weights and the DerSimonian–Laird method. Multiple subgroup analyses were conducted to explore any heterogeneity. Thirty-one studies (8249 patients) were included. The pooled proportion of EBV+ DLBCL was 7.9% (95% CI, 6.2–10.0%) with significant heterogeneity among studies (p < 0.001). The prevalence of EBV+ DLBCL was significantly higher in Asia and South America compared with Western countries (p < 0.01). The cut-offs for EBER positivity (10%, 20%, 50%) and patients’ age (≥50 years vs. <50 years) did not significantly affect the prevalence (p ≥ 0.10). EBV+ DLBCL is rare with a pooled proportion of 7.9% in patients with DLBCL and the geographic heterogeneity was confirmed.
Concomitant Swine Influenza A Virus Infection Alters PRRSV1 MLV Viremia in Piglets but Does Not Interfere with Vaccine Protection in Experimental Conditions

Modified-live vaccines (MLVs) against porcine reproductive and respiratory syndrome viruses (PRRSVs) are usually administrated to piglets at weaning when swine influenza A virus (swIAV) infections frequently occur. SwIAV infection induces a strong interferon alpha (IFNa) response and IFNa was shown to abrogate PRRSV2 MLV replication and an inherent immune response. In this study, we evaluated the impacts of swIAV infection on the replication of a PRRSV1 MLV (MLV1), post-vaccine immune responses and post-challenge vaccine efficacy at both the systemic and pulmonary levels. Piglets were either swIAV inoculated and MLV1 vaccinated 6 h apart or singly vaccinated or mock inoculated and mock vaccinated. Four weeks after vaccination, the piglets were challenged with a PRRSV1 field strain. The results showed that swIAV infection delayed MLV1 viremia by six days and post-vaccine seroconversion by four days. After the PRRSV1 challenge, the swIAV enhanced the PRRSV1-specific cell-mediated immunity (CMI) but the PRRSV1 field strain viremia was not better controlled. High IFNa levels that were detected early after swIAV infection could have been responsible for both the inhibition of MLV1 replication and CMI enhancement. Thus, whereas swIAV infection had a negative impact on humoral responses post-vaccination, it did not interfere with the protective effectiveness of the PRRSV MLV1 in our experimental conditions.
Bromelain a Potential Bioactive Compound: A Comprehensive Overview from a Pharmacological Perspective

Bromelain is an effective chemoresponsive proteolytic enzyme derived from pineapple stems. It contains several thiol endopeptidases and is extracted and purified via several methods. It is most commonly used as an anti-inflammatory agent, though scientists have also discovered its potential as an anticancer and antimicrobial agent. It has been reported as having positive effects on the respiratory, digestive, and circulatory systems, and potentially on the immune system. It is a natural remedy for easing arthritis symptoms, including joint pain and stiffness. This review details bromelain’s varied uses in healthcare, its low toxicity, and its relationship to nanoparticles. The door of infinite possibilities will be opened up if further extensive research is carried out on this pineapple-derived enzyme.
High-Sensitivity Dual Electrochemical QCM for Reliable Three-Electrode Measurements

An electrochemical quartz crystal microbalance (EC-QCM) is a versatile gravimetric technique that allows for parallel characterization of mass deposition and electrochemical properties. Despite its broad applicability, simultaneous characterization of two electrodes remains challenging due to practical difficulties posed by the dampening from fixture parasitics and the dissipative medium. In this study, we present a dual electrochemical QCM (dual EC-QCM) that is employed in a three-electrode configuration to enable consequent monitoring of mass deposition and viscous loading on two crystals, the working electrode (WE) and the counter electrode (CE). A novel correction approach, along with a three standard complex impedance calibration, is employed to overcome the effect of dampening while keeping high spectral sensitivity. Separation of viscous loading and rigid mass deposition is achieved by robust characterization of the complex impedance at the resonance frequency. Validation of the presented system is done by cyclic voltammetry characterization of Ag underpotential deposition on gold. The results indicate mass deposition of 412.2 ng for the WE and 345.6 ng for the CE, reflecting a difference of the initially-present Ag adhered to the surface. We also performed higher harmonic measurements that further corroborate the sensitivity and reproducibility of the dual EC-QCM. The demonstrated approach is especially intriguing for electrochemical energy storage applications where mass detection with multiple electrodes is desired.
Combined Ubisol-Q10 and Ashwagandha Root Extract Target Multiple Biochemical Mechanisms and Reduces Neurodegeneration in a Paraquat-Induced Rat Model of Parkinson’s Disease

Parkinson’s disease (PD) is characterized by progressive neurodegeneration in the substantia nigra (SN) region resulting in loss of movement coordination. Current therapies only provide symptomatic relief, and there is no agent to halt the progression of PD. Previously, Ubisol-Q10, a water-soluble formulation of coenzyme-Q10, and ethanolic root extract of ashwagandha (ASH) have been shown to inhibit PD pathology in rodent models when used alone. Here, we evaluated the neuroprotective efficacy of oral administration of ASH and Ubisol-Q10 alone and in combination in a paraquat-induced PD rat model. The combined treatment resulted in better-preserved neuron morphology compared to Ubsiol-Q10 or ASH alone. The combination treatment enhanced activation of pro-survival astroglia and inhibited pro-inflammatory microglia. While anti-oxidative effects were seen with both agents, Ubisol-Q10 activated autophagy, whereas ashwagandha showed a better anti-inflammatory response. Thus, the combined treatment caused inhibition of oxidative stress, autophagy activation, inhibition of pro-inflammatory microglia, and activation of pro-survival astroglia. Consequently, paraquat (PQ)-treated rats given the combination treatment in drinking water did not show motor impairment. Based on these interesting observations, the combined treatment containing two well-tolerated natural compounds could be a more effective strategy to halt the progression of PD.
Sex and Race-Related DNA Methylation Changes in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer and fourth leading cause of cancer-related death worldwide. The number of HCC cases continues to rise despite advances in screening and therapeutic inventions. More importantly, HCC poses two major health disparity issues. First, HCC occurs more commonly in men than women. Second, with the global increase in non-alcoholic fatty liver diseases (NAFLD), it has also become evident that HCC is more prevalent in some races and/or ethnic groups compared to others, depending on its predisposing etiology. Most studies on HCC in the past have been focused on genetic factors as the driving force for HCC development, and the results revealed that genetic mutations associated with HCC are often heterogeneous and involve multiple pathogenic pathways. An emerging new research field is epigenetics, in which gene expression is modified without altering DNA sequences. In this article, we focus on reviewing current knowledge on HCC-related DNA methylation changes that show disparities among different sexes or different racial/ethnic groups, in an effort to establish a point of departure for resolving the broader issue of health disparities in gastrointestinal malignancies using cutting-edge epigenetic approaches.
Dynamic Analyses of Contagion Risk and Module Evolution on the SSE A-Shares Market Based on Minimum Information Entropy

The interactive effect is significant in the Chinese stock market, exacerbating the abnormal market volatilities and risk contagion. Based on daily stock returns in the Shanghai Stock Exchange (SSE) A-shares, this paper divides the period between 2005 and 2018 into eight bull and bear market stages to investigate interactive patterns in the Chinese financial market. We employ the Least Absolute Shrinkage and Selection Operator (LASSO) method to construct the stock network, compare the heterogeneity of bull and bear markets, and further use the Map Equation method to analyse the evolution of modules in the SSE A-shares market. Empirical results show that (1) the connected effect is more significant in bear markets than bull markets and gives rise to abnormal volatilities in the stock market; (2) a system module can be found in the network during the first four stages, and the industry aggregation effect leads to module differentiation in the last four stages; (3) some stocks have leading effects on others throughout eight periods, and medium- and small-cap stocks with poor financial conditions are more likely to become risk sources, especially in bear markets. Our conclusions are beneficial to improving investment strategies and making regulatory policies.
Internet of Things Geosensor Network for Cost-Effective Landslide Early Warning Systems

Worldwide, cities with mountainous areas struggle with an increasing landslide risk as a consequence of global warming and population growth, especially in low-income informal settlements. Landslide Early Warning Systems (LEWS) are an effective measure to quickly reduce these risks until long-term risk mitigation measures can be realized. To date however, LEWS have only rarely been implemented in informal settlements due to their high costs and complex operation. Based on modern Internet of Things (IoT) technologies such as micro-electro-mechanical systems (MEMS) sensors and the LoRa (Long Range) communication protocol, the Inform@Risk research project is developing a cost-effective geosensor network specifically designed for use in a LEWS for informal settlements. It is currently being implemented in an informal settlement in the outskirts of Medellin, Colombia for the first time. The system, whose hardware and firmware is open source and can be replicated freely, consists of versatile LoRa sensor nodes which have a set of MEMS sensors (e.g., tilt sensor) on board and can be connected to various different sensors including a newly developed low cost subsurface sensor probe for the detection of ground movements and groundwater level measurements. Complemented with further innovative measurement systems such as the Continuous Shear Monitor (CSM) and a flexible data management and analysis system, the newly developed LEWS offers a good benefit-cost ratio and in the future can hopefully find application in other parts of the world.
Human Endogenous Retroviruses in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor. It is primarily diagnosed in the elderly and has a 5-year survival rate of less than 6% even with the most aggressive therapies. The lack of biomarkers has made the development of immunotherapy for GBM challenging. Human endogenous retroviruses (HERVs) are a group of viruses with long terminal repeat (LTR) elements, which are believed to be relics from ancient viral infections. Recent studies have found that those repetitive elements play important roles in regulating various biological processes. The differentially expressed LTR elements from HERVs are potential biomarkers for immunotherapy to treat GBM. However, the understanding of the LTR element expression in GBM is greatly lacking. Methods: We obtained 1077.4 GB of sequencing data from public databases. These data were generated from 111 GBM tissue studies, 30 GBM cell lines studies, and 45 normal brain tissues studies. We analyzed repetitive elements that were differentially expressed in GBM and normal brain samples. Results: We found that 48 LTR elements were differentially expressed (p-value < 0.05) between GBM and normal brain tissues, of which 46 were HERV elements. Among these 46 elements, 34 significantly changed HERVs belong to the ERV1 superfamily. Furthermore, 43 out of the 46 differentially expressed HERV elements were upregulated. Conclusion: Our results indicate significant differential expression of many HERV LTR elements in GBM and normal brain tissues. Expression levels of these elements could be developed as biomarkers for GBM treatments.
Alternative σ Factors Regulate Overlapping as Well as Distinct Stress Response and Metabolic Functions in Listeria monocytogenes under Stationary Phase Stress Condition

Listeria monocytogenes can regulate and fine-tune gene expression, to adapt to diverse stress conditions encountered during foodborne transmission. To further understand the contributions of alternative sigma (σ) factors to the regulation of L. monocytogenes gene expression, RNA-Seq was performed on L. monocytogenes strain 10403S and five isogenic mutants (four strains bearing in-frame null mutations in three out of four alternative σ factor genes, ΔCHL, ΔBHL, ΔBCL, and ΔBCH, and one strain bearing null mutations in all four genes, ΔBCHL), grown to stationary phase. Our data showed that 184, 35, 34, and 20 genes were positively regulated by σB, σL, σH, and σC (posterior probability > 0.9 and Fold Change (FC) > 5.0), respectively. Moreover, σB-dependent genes showed the highest FC (based on comparisons between the ΔCHL and the ΔBCHL strain), with 44 genes showing an FC > 100; only four σL-dependent, and no σH- or σC-dependent genes showed FC >100. While σB-regulated genes identified in this study are involved in stress-associated functions and metabolic pathways, σL appears to largely regulate genes involved in a few specific metabolic pathways, including positive regulation of operons encoding phosphoenolpyruvate (PEP)-dependent phosphotransferase systems (PTSs). Overall, our data show that (i) σB and σL directly and indirectly regulate genes involved in several energy metabolism-related functions; (ii) alternative σ factors are involved in complex regulatory networks and appear to have epistatic effects in stationary phase cells; and (iii) σB regulates multiple stress response pathways, while σL and σH positively regulate a smaller number of specific pathways.
Laboratory Investigation and Numerical Modelling of Concrete Reinforced with Recycled Steel Fibers

In the last decades, fiber reinforced concrete have emerged as the possible key to revolutionize civil engineering. Among different types of fibers employed in concrete technology to date, the application of recycled steel fibers produced from end-of-life car tires appears to be a viable approach towards environmentally friendly construction. In this study, we demonstrate the laboratory research and numerical analysis of concrete reinforced with waste steel fibers recovered during the recycling process of end-of-life car tires. Concrete mixes with the following fiber contents: 0.5%, 0.75%, 1.0%, 1.25%, and 1.5% per volume were prepared and then tested in three-point bending conditions. The laboratory investigation revealed highly boosted properties of concrete under flexure. We further performed the finite element method (FEM) analysis of 2D models using Atena software in order to develop a material model allowing the numerical modelling of recycled steel fibers reinforced concrete (RSFRC) behavior. The parameters of RSFRC material model have been modified using the inverse analysis until matching the experimental performance of the material. The results, being in good agreement with the laboratory investigation, have indicated a high potential of RSFRC for real scale construction applications.
CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes

Simple Summary CYP2C19 is known as an enzyme primarily responsible for metabolizing various drugs, such as proton pump inhibitor, antiplatelet, anti-epileptic, and anticoagulant. CYP2C19 is known to be polymorphic and can result in the clinical efficacy of drugs. To examine the prevalence and the distribution of the CYP2C19 genetic polymorphisms in Indonesia, we performed polymerase chain reaction-restriction fragment length polymorphism to the genomic DNA of Indonesian participants. In addition, we also analyzed the distribution of CYP2C19 polymorphisms among ethnicities and clinical outcomes. We found that the prevalence of intermediate metabolizers were the highest in Indonesia, followed by rapid metabolizers and poor metabolizers, respectively. The distribution of metabolizer groups were different between ethnic groups in Indonesia. Therefore, dosage adjustment should be considered when administering drugs-affected by CYP2C19 in Indonesia. The results presented in this study showed the distribution of CYP2C19 variant alleles at the population level in Indonesia and might be used as a consideration for providing personalized treatment in clinical practice. Abstract CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.