Miracle-dz/UniFAR-FTUs huggingface dataset:
Knowledge, Attitude, and Practice of General Population toward Complementary and Alternative Medicines in Relation to Health and Quality of Life in Sungai Petani, Malaysia

Purpose: The demand of complementary and alternative medicine (CAM) has increased drastically over the past few decades. The perceptions about CAMs among general population are positive. However, the literature highlights that effectiveness and acceptance of alternative therapies among the general population is still a subject of debate. Materials and Methods: This is a cross-sectional study and the response along with demographic details was collected through a validated questionnaire; the results were analyzed by using a validated data collection tool. The results were concluded based on good, moderate, and poor responses, which were evaluated through data analysis by using the Statistical Package for the Social Sciences software version 20.0. , SPSS Inc., Chicago, III, USA. A value of P < 0.05 was considered statistically significant. Results: In total, 182 (44.4%) of male and 228 (55.6%) of female respondents were selected for this study. Studies showed that a greater knowledge level was observed among female respondents (15.55 ± 2.7, P < 0.001). The selected Chinese population had relatively good knowledge (i.e., 15.63, P = 0.006). People practicing Buddhism had also good knowledge. Rural population had lesser family income and showed a good practice pattern and understanding (P = 0.006). The positive attitude was identified among women ( P < 0.001) with a mean score of 15.55 ± 2.7. Postgraduate participants were found to have diverse results with SD ± 6.23, and 77.1% had a good attitude. A statistically significant association was observed between religion and attitude of respondents (P < 0.001). Conclusion: Although a better practice was noticed in Malaysian population, more awareness is required and knowledge should be disseminated among the population to improve the overall health and quality of life in Malaysia.
Impact of guidelines implementation for the rational use of prophylactic antibiotics in elective cesarean sections at Elqutainah Teaching Hospital

Background: The clinical pharmacists have a sensible role in the implementation of guidelines by ensuring proper patient selection and medication use. This study aimed to implement a hospital guideline for the rational use of prophylactic antibiotics in elective cesarean sections (ECS) by establishing compliance with international guidelines regarding prophylactic antibiotic use in ECS at Elqutainah Teaching Hospital in White Nile State, Sudan, and define the area of medication cost-saving. Methods: A quasi-experimental design without control group was used from April to June 2018. 195 participants were included, 94 participants before and 101 participants after the intervention and data were collected using a designed checklist by the researchers. The intervention is based on withdrawal metronidazole dosage forms from prophylactic antibiotics for ECS according to international guidelines in antibiotics prophylaxis toward ECS. Finally, the data were compared between pre- and post-intervention. Findings: Before intervention; all participants had received intravenous cefuroxime and metronidazole infusions prior ECS and oral cefuroxime or amoxicillin-clavulanic acid, and metronidazole for 7 days upon discharge. While after the intervention, all participants didn't receive any metronidazole dosage forms before and after ECS also didn't receive amoxicillin-clavulanic acid. However, the dosage regimen of cefuroxime didn't change. This intervention was meaningful in minimizing overuse of antibiotics prophylaxis in the ECS, and reducing staff workload along with medication cost. Conclusions: Clinical pharmacist intervention was concisely changing the physicians' practice toward using updated guidelines of the rational use of prophylactic antibiotics for ECS.
Antibacterial activity of Syzygium aromaticum (clove) against uropathogens producing ESBL, MBL, and AmpC beta-lactamase: Are we close to getting a new antibacterial agent?

Introduction: The present study was done to access the antibacterial activity of clove (Syzygium aromaticum) against extended-spectrum beta-lactamase (ESBL), metallo-beta-lactamase (MBL), and AmpC beta-lactamase-producing gram-negative bacteria causing urinary tract infection. Methods: A total of 221 gram-negative uropathogens were isolated and screened for beta-lactamase (ESBL, MBL, and AmpC) production and further tested against ethanolic extract of clove (S. aromaticum) for its antibacterial activity. Results: Clove was effective against all gram-negative isolates but the best antibacterial activity was shown against Proteus species with 19 mm zone of inhibition, 0.39 mg/ml minimum inhibitory concentration (MIC) and 0.19 mg/ml minimum bactericidal concentration (MBC). Conclusions: Clove extract showed different antibacterial potential against all gram-negative uropathogens. Clove activity for particular strain was found to be similar between isolates producing beta-lactamase and non beta-lactamase.
Discovery of in vivo Virulence Genes of Obligatory Intracellular Bacteria by Random Mutagenesis

Ehrlichia spp. are emerging tick-borne obligatory intracellular bacteria that cause febrile and sometimes fatal diseases with abnormal blood cell counts and signs of hepatitis. Ehrlichia HF strain provides an excellent mouse disease model of fatal human ehrlichiosis. We recently obtained and established stable culture of Ehrlichia HF strain in DH82 canine macrophage cell line, and obtained its whole genome sequence and annotation. To identify genes required for in vivo virulence of Ehrlichia, we constructed random insertional HF strain mutants by using Himar1 transposon-based mutagenesis procedure. Of total 158 insertional mutants isolated via antibiotic selection in DH82 cells, 74 insertions were in the coding regions of 55 distinct protein-coding genes, including TRP120 and multi-copy genes, such as p28/omp-1, virB2, and virB6. Among 84 insertions mapped within the non-coding regions, seven are located in the putative promoter region since they were within 50 bp upstream of the seven distinct genes. Using limited dilution methods, nine stable clonal mutants that had no apparent defect for multiplication in DH82 cells, were obtained. Mouse virulence of seven mutant clones was similar to that of wild-type HF strain, whereas two mutant clones showed significantly retarded growth in blood, livers, and spleens, and the mice inoculated with them lived longer than mice inoculated with wild-type. The two clones contained mutations in genes encoding a conserved hypothetical protein and a staphylococcal superantigen-like domain protein, respectively, and both genes are conserved among Ehrlichia spp. , but lack homology to other bacterial genes. Inflammatory cytokine mRNA levels in the liver of mice infected with the two mutants were significantly diminished than those infected with HF strain wild-type, except IL-1β and IL-12 p40 in one clone. Thus, we identified two Ehrlichia virulence genes responsible for in vivo infection, but not for infection and growth in macrophages.
Flux Growth and Superconducting Properties of (Ce,Pr)OBiS2 Single Crystals

Ce1−xPrxOBiS2 (0. 1 ≤ x ≤ 0.9) single crystals were grown using a CsCl flux method. Their structural and physical properties were examined by X-ray diffraction, X-ray absorption, transmission electron microscopy, and electrical resistivity. All of the Ce1−xPrxOBiS2 single crystals with 0.1 ≤ x ≤ 0.9 exhibited tetragonal phase. With increasing Pr content, the a-axis and c-axis lattice parameters decreased and increased, respectively. Transmission electron microscope analysis of Ce0.1Pr0.9OBiS2 (x = 0.9) single crystal showed no stacking faults. Atomic-resolution energy dispersive X-ray spectrometry mapping revealed that Bi, Ce/Pr, O, and S occupied different crystallographic sites, while Ce and Pr randomly occupied the same sites. X-ray absorption spectra showed that an increase of the Pr ratio increased the ratio of Ce4+/Ce3+. All of the Ce1−xPrxOBiS2 crystals showed superconducting transition, with a maximum transition temperature of ~4 K at x = 0.9.
Ammonium Transporter (BcAMT1.2) Mediates the Interaction of Ammonium and Nitrate in Brassica campestris

The provision of ammonium (NH4 +) and nitrate (NO3 −) mixture increases the total nitrogen (N) than the supply of sole NH4 + or NO3 – with the same concentration of total N; thus, the mixture contributes to better growth in Brassica campestris. However, the underlying mechanisms remain unknown. In this study, we analyzed NH4 + and NO3 – fluxes using a scanning ion-selective electrode technique to detect under different N forms and levels in B. campestris roots. We observed that the total N influxes with NH4 + and NO3 − mixture were 1.25- and 3.53-fold higher than those with either sole NH4 + or NO3 −. Furthermore, NH4 + and NO3 – might interact with each other under coexistence. NO3 – had a positive effect on net NH4 + influx, whereas NH4 + had a negative influence on net NO3 – influx. The ammonium transporter (AMT) played a key role in NH4 + absorption and transport. Based on expression analysis, BcAMT1.2 differed from other BcAMT1s in being upregulated by NH4 + or NO3 −. According to sequence analysis and functional complementation in yeast mutant 31019b, AMT1.2 from B. campestris may be a functional AMT. According to the expression pattern of BcAMT1.2, β-glucuronidase activity, and the cellular location of its promoter, BcAMT1.2 may be responsible for NH4 + transport. Following the overexpression of BcAMT1.2 in Arabidopsis, BcAMT1.2-overexpressing lines grew better than wildtype lines at low NH4 + concentration. In the mixture of NH4 + and NO3 –, NH4 + influxes and NO3 – effluxes were induced in BcAMT1.2-overexpressing lines. Furthermore, transcripts of N assimilation genes (AtGLN1.2, AtGLN2, and AtGLT1) were significantly upregulated, in particular, AtGLN1.2 and AtGLT1 were increased by 2.85–8.88 times in roots, and AtGLN1.2 and AtGLN2 were increased by 2.67–4.61 times in leaves. Collectively, these results indicated that BcAMT1.2 may mediate in NH4 + fluxes under the coexistence of NH4 + and NO3 – in B. campestris.
Biomass, Morphology, and Dynamics of the Fine Root System Across a 3,000-M Elevation Gradient on Mt. Kilimanjaro

Fine roots (≤2 mm) consume a large proportion of photosynthates and thus play a key role in the global carbon cycle, but our knowledge about fine root biomass, production, and turnover across environmental gradients is insufficient, especially in tropical ecosystems. Root system studies along elevation transects can produce valuable insights into root trait-environment relationships and may help to explore the evidence for a root economics spectrum (RES) that should represent a trait syndrome with a trade-off between resource acquisitive and conservative root traits. We studied fine root biomass, necromass, production, and mean fine root lifespan (the inverse of fine root turnover) of woody plants in six natural tropical ecosystems (savanna, four tropical mountain forest types, tropical alpine heathland) on the southern slope of Mt. Kilimanjaro (Tanzania) between 900 and 4,500 m a.s. l. Fine root biomass and necromass showed a unimodal pattern along the slope with a peak in the moist upper montane forest (~2,800 m), while fine root production varied little between savanna and upper montane forest to decrease toward the alpine zone. Root:shoot ratio (fine root biomass and production related to aboveground biomass) in the tropical montane forest increased exponentially with elevation, while it decreased with precipitation and soil nitrogen availability (decreasing soil C:N ratio). Mean fine root lifespan was lowest in the ecosystems with pronounced resource limitation (savanna at low elevation, alpine heathland at high elevation) and higher in the moist and cool forest belt (~1,800–3,700 m). The variation in root traits across the elevation gradient fits better with the concept of a multi-dimensional RES, as root tissue density and specific root length showed variable relations to each other, which does not agree with a simple trade-off between acquisitive and conservative root traits. In conclusion, despite large variation in fine root biomass, production, and morphology among the different plant species and ecosystems, a general belowground shift in carbohydrate partitioning is evident from 900 to 4,500 m a.s. l. , suggesting that plant growth is increasingly limited by nutrient (probably N) shortage toward higher elevations.
Renal Glomerular Mitochondria Function in Salt-Sensitive Hypertension

Salt-sensitive (SS) hypertension is accompanied with an early onset of proteinuria, which results from the loss of glomerular podocytes. Here, we hypothesized that glomerular damage in the SS hypertension occurs in part due to mitochondria dysfunction, and we used a unique model of freshly isolated glomeruli to test this hypothesis. In order to mimic SS hypertension, we used Dahl SS rats, an established animal model. Animals were fed a 0.4% NaCl (normal salt, NS) diet or challenged with a high salt (HS) 4% NaCl diet for 21 days to induce an increase in blood pressure (BP). Similar to previous studies, we found that HS diet caused renal hypertrophy, increased BP, glomerulosclerosis, and renal lesions such as fibrosis and protein casts. We did not observe changes in mitochondrial biogenesis in the renal cortex or isolated glomeruli fractions. However, Seahorse assay performed on freshly isolated glomeruli revealed that basal mitochondrial respiration, maximal respiration, and spare respiratory capacity were lower in the HS compared to the NS group. Using confocal imaging and staining for mitochondrial H2O2 using mitoPY1, we detected an intensified response to an acute H2O2 application in the podocytes of the glomeruli isolated from the HS diet fed group. TEM analysis showed that glomerular mitochondria from the HS diet fed group have structural abnormalities (swelling, enlargement, less defined cristae). Therefore, we report that glomerular mitochondria in SS hypertension are functionally and structurally defective, and this impairment could eventually lead to loss of podocytes and proteinuria. Thus, the glomerular–mitochondria axis can be targeted in novel treatment strategies for hypertensive glomerulosclerosis.
Development of a Novel mcr-6 to mcr-9 Multiplex PCR and Assessment of mcr-1 to mcr-9 Occurrence in Colistin-Resistant Salmonella enterica Isolates From Environment, Feed, Animals and Food (2011–2018) in Germany

The polymyxin antibiotic colistin has been used in decades for treatment and prevention of infectious diseases in livestock. Nowadays, it is even considered as last-line treatment option for severe human infections caused by multidrug- and carbapenem-resistant Gram-negative bacteria. Therefore, the discovery of plasmid-mediated mobile colistin resistance (mcr) genes raised major public health concern. The aim of our study was to analyze colistin-resistant Salmonella enterica strains from animals, food, feed and the environment collected at the National Reference Laboratory for Salmonella in Germany on the presence of mcr-1 to mcr-9 genes. Altogether 407 colistin-resistant (MIC >2 mg/L) Salmonella isolates received between 2011 and 2018 were selected and screened by PCR using a published mcr-1 to mcr-5 as well as a newly developed mcr-6 to mcr-9 multiplex PCR protocol. 254 of 407 (62.4%) isolates harbored either mcr-1 (n = 175), mcr-4 (n = 53), mcr-5 (n = 18) or mcr-1 and mcr-9 (n = 8). The number of mcr-positive isolates ranged from 19 (2017) to 64 (2012) per year. WGS revealed that none of our isolates harbored the mcr-9.1 gene. Instead, two novel mcr-9 variants were observed, which both were affected by frameshift mutations and are probably non-functional. The mcr-harboring isolates were mainly derived from animals (77.2%) or food (20.1%) and could be assigned to ten different Salmonella serovars. Many of the isolates were multidrug-resistant. Co-occurrence of mcr-1 and AmpC or ESBL genes was observed in eight isolates. Our findings suggest that mcr genes are widely spread among colistin-resistant Salmonella isolates from livestock and food in Germany. Potential transfer of mcr-harboring isolates along the food chain has to be considered critically.
Varying Architecture of Heat Shock Elements Contributes to Distinct Magnitudes of Target Gene Expression and Diverged Biological Pathways in Heat Stress Response of Bread Wheat

The heat shock transcription factor (HSF) binds to cis-regulatory motifs known as heat shock elements (HSEs) to mediate the transcriptional response of HSF target genes. However, the HSF–HSEs interaction is not clearly understood. Using the newly released genome reference sequence of bread wheat, we identified 39,478 HSEs (95.6% of which were non-canonical HSEs) and collapsed them into 30,604 wheat genes, accounting for 27.6% wheat genes. Using the intensively heat-responsive transcriptomes of wheat, we demonstrated that canonical HSEs have a higher propensity to induce a response in the closest downstream genes than non-canonical HSEs. However, the response magnitude induced by non-canonical HSEs was comparable to that induced by canonical HSEs. Significantly, some non-canonical HSEs that contain mismatched nucleotides at specific positions within HSEs had a larger response magnitude than that of canonical HSEs. Consistently, most of the HSEs identified in the promoter regions of heat shock proteins were non-canonical HSEs, suggesting an important role for these non-canonical HSEs. Lastly, distinct diverged biological processes were observed between genes containing different HSE types, suggesting that sequence variation in HSEs plays a key role in the evolution of heat responses and adaptation. Our results provide a new perspective to understand the regulatory network underlying heat responses.
The TRPM2 Ion Channel Regulates Inflammatory Functions of Neutrophils During Listeria monocytogenes Infection

During infection, phagocytic cells pursue homeostasis in the host via multiple mechanisms that control microbial invasion. Neutrophils respond to infection by exerting a variety of cellular processes, including chemotaxis, activation, phagocytosis, degranulation and the generation of reactive oxygen species (ROS). Calcium (Ca2+) signaling and the activation of specific Ca2+ channels are required for most antimicrobial effector functions of neutrophils. The transient receptor potential melastatin-2 (TRPM2) cation channel has been proposed to play important roles in modulating Ca2+ mobilization and oxidative stress in neutrophils. In the present study, we use a mouse model of Listeria monocytogenes infection to define the role of TRPM2 in the regulation of neutrophils' functions during infection. We show that the susceptibility of Trpm2−/− mice to L. monocytogenes infection is characterized by increased migration rates of neutrophils and monocytes to the liver and spleen in the first 24 h. During the acute phase of L. monocytogenes infection, Trpm2−/− mice developed septic shock, characterized by increased serum levels of TNF-α, IL-6, and IL-10. Furthermore, in vivo depletion of neutrophils demonstrated a critical role of these immune cells in regulating acute inflammation in Trpm2−/− infected mice. Gene expression and inflammatory cytokine analyses of infected tissues further confirmed the hyperinflammatory profile of Trpm2−/− neutrophils. Finally, the increased inflammatory properties of Trpm2−/− neutrophils correlated with the dysregulated cytoplasmic concentration of Ca2+ and potentiated membrane depolarization, in response to L. monocytogenes. In conclusion, our findings suggest that the TRPM2 channel plays critical functional roles in regulating the inflammatory properties of neutrophils and preventing tissue damage during Listeria infection.
Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae

The primary function of the respiratory system of gas exchange renders it vulnerable to environmental pathogens that circulate in the air. Physical and cellular barriers of the respiratory tract mucosal surface utilize a variety of strategies to obstruct microbe entry. Physical barrier defenses including the surface fluid replete with antimicrobials, neutralizing immunoglobulins, mucus, and the epithelial cell layer with rapidly beating cilia form a near impenetrable wall that separates the external environment from the internal soft tissue of the host. Resident leukocytes, primarily of the innate immune branch, also maintain airway integrity by constant surveillance and the maintenance of homeostasis through the release of cytokines and growth factors. Unfortunately, pathogens such as influenza virus and Streptococcus pneumoniae require hosts for their replication and dissemination, and prey on the respiratory tract as an ideal environment causing severe damage to the host during their invasion. In this review, we outline the host-pathogen interactions during influenza and post-influenza bacterial pneumonia with a focus on inter- and intra-cellular crosstalk important in pulmonary immune responses.
CAR T Cells Redirected to CD44v6 Control Tumor Growth in Lung and Ovary Adenocarcinoma Bearing Mice

The main challenge of adoptive therapy with Chimeric Antigen Receptor modified T cells (CAR T) is the application to the field of solid tumors, where the identification of a proper antigen has emerged as one of the major drawbacks to CAR T cell treatment success. CD44 is a glycoprotein involved in cell-cell and cell-matrix interactions. The isoform containing the variant domain 6 of CD44 gene (CD44v6) has been implicated in tumorigenesis, tumor cell invasion and metastasis and represents an attractive target for CAR T cell therapies. Targeting CD44v6 antigen has been shown to control tumor growth in acute myeloid leukemia and multiple myeloma mouse models. While CAR T approach for the treatment of B cell malignancies has shown great success, response rates among patients with solid cancer are less favorable. The purpose of our study was to test the efficacy of CD44v6.CAR T cells, produced in compliance with Good Manufacturing Practice (GMP), in adenocarcinoma tumor models. We generated a bicistronic retroviral vector containing the CD44v6 CAR and the HSV-TK Mut2 suicide gene to enhance the safety of the proposed CAR T cell therapy. CD44v6 transduced CAR T cells were homogeneously positive for ΔLNGFR selection marker, were enriched in T central memory (TCM) and T memory stem cells (TSCM) and displayed a highly activated phenotype. In vitro assays revealed antigen-specific activation and cytotoxicity of human CD44v6.CAR T cells against CD44v6 expressing tumor cell lines. When infused in immunodeficient tumor bearing mice, human CD44v6.CAR T cells were able to reach, infiltrate and proliferate at tumor sites, finally resulting in tumor growth control. Next, we checked if cells produced in compliance with GMP grade standards retained the same antitumor activity of those produced with research grade materials and protocols. Noteworthy, no differences in the potency of the CAR T obtained with the two manufacturing processes were observed. In conclusion, our preclinical results suggest that CD44v6.CAR T based adoptive therapy could be a promising strategy in solid cancer treatment.