Hepatoprotective and Antioxidant Effects of Nanopiperine against Cypermethrin via Mitigation of Oxidative Stress, Inflammations and Gene Expression Using qRT-PCR.

Cypermethrin (Cyp) is a pyrethroid that has been associated with the toxicity of various organs. The aim of our study was to evaluate the hepatoprotective and antioxidant activities of nano-piperine (NP) against Cyp toxicity. Cyp (50 mg/kg) was administered orally in all animals of groups III-VI for 15 days. Groups IV-VI each received three doses of NP (125, 250, and 500 µg/kg/day) for 10 days after receiving the Cyp dosage, which was given after 1 h. A rise in serum biomarkers (ALT, AST, ALP, total protein, and albumin), which are indicators of toxicity alongside anomalous oxidative stress indices (lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD) and catalase), was detected. After Cyp treatment, we observed upregulated cytokines, caspase expression, and histological analysis that the showed distortion of cell shape. However, the administration of NP dramatically reversed all of the Cyp-induced alterations, inducing reductions in serum marker levels, stress level, the production of cytokines, and caspase expression. Additionally, all of the histopathological alterations were minimized to values that were comparable to normal levels. The present findings suggested that NP exhibits potent antioxidant and anti-inflammatory activities that can protect rats' livers against Cyp-induced liver damage through hepatoprotective activities.

Renoprotective effects of cinnamon oil against APAP-Induced nephrotoxicity by ameliorating oxidative stress, apoptosis and inflammation in rats.

Acetaminophen (APAP) is used as a primary medication in relieving moderate pain and fever. However, APAP is associated with toxic effects in renal tissue that appear because of its free radicals property. The principle goal of the present work is to assess the kidney damage by APAP and its restore antioxidative property of cinnamon oil (CO). Animals were distributed into six animals each in six groups. Rats were administered with three varying doses of CO from 50 to 200 mg/kg b.w. respectively and only a single dose of APAP. APAP induced an alteration in serum biochemical markers, imbalance in oxidative parameters, morphological changes in kidney tissue along with increased interleukins cytokines (IL-1ß & 6) and caspase (3, 9) levels. CO administration significantly ameliorates all the parameters and histopathological changes were restored. Moreover, it also restored the activities of antioxidative enzymes. Our work proved that an variance of oxidative markers in the kidney by APAP is ameliorated by CO in rats. Thus, CO could be used in reducing APAP-induced nephrotoxicity.

Design, synthesis, and cytotoxic screening of novel azole derivatives on hepatocellular carcinoma (HepG2 Cells).

Novel azole derivatives 3-30 were designed, synthesized, and screened for their antitumor activity on HepG2 cell line. The cytotoxicity screening demonstrated that imidazolone 8 and triazoles 25 and 29 exhibited more potent cytotoxic activities by 1.21-, 4.75-, and 1.8-fold compared to Sorafenib (SOR). Furthermore, vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme inhibition assay declared that compounds 25 and 29 had inhibitory activity at the nanomolar concentration. Moreover, the tested compounds exhibited good ß-tubulin (TUB) polymerization inhibition percentages. In addition, DNA flow cytometry analysis over HepG2 cells indicated that triazoles 25 and 29 demonstrated arrest at G1 and G2/M phase of the cell cycle and induced apoptotic activity by increasing sub-G1 phase. Finally, mechanistic studies of the proapoptotic activities of compounds 8, 10, 11, 25, and 29 indicated that they induced upregulation of P53, Fas/Fas-ligand, and BAX/BCL-2 ratio expression that resulted in increasing the active caspase 3/7 percentages and trigger apoptosis.

Design, synthesis, and cytotoxicity screening of 5-aryl-3-(2-(pyrrolyl) thiophenyl)-1, 2, 4-oxadiazoles as potential antitumor molecules on breast cancer MCF-7 cells.

The work representing the design and the cytotoxic screening of synthetic small molecules (SSMs) such as carbonitriles 3a-c, carboximidamides 4a-c, and oxadiazoles 5-19 as antitumor molecules. Molecules 4c, 9, 12, and 14 show promising cytotoxicity profiles against two cell lines higher than prodigiosin (PG). The results of topoisomerase enzyme inhibition assay show that compounds 4c and 14 display potent inhibitory activity in nano-molar concentration. In addition, DNA-flow cytometry and annexin V analysis also display that compounds 4c, 9, 12, and 14 exhibit antiproliferative activities over MCF-7 cells by cell cycle arrest at G1 phase and apoptosis-inducing activity by increasing cell percentages at pre G1 phase. Moreover, Elisa measurement of p53 and apoptosis mediators, show that carboximidamide 4c and oxadiazoles 9, 12, and 14 significantly up-regulate p53 and cell death mediators as puma and Bax/Bcl-2 ratio levels. Subsequently, pro-apoptotic activities are confirmed by active caspase 3/7 percentages green fluorescence assay.

SLC5A1 Mutations in Saudi Arabian Patients With Congenital Glucose-Galactose Malabsorption.

Congenital glucose-galactose malabsorption (cGGM) is a rare autosomal recessive disorder, caused by mutations in the SLC5A1 gene, encoding the sodium/glucose cotransporter 1, which may result in severe life-threatening osmotic diarrhea due to the accumulation of unabsorbed sugars in the intestinal lumen. If treated early with elimination of glucose and galactose from the diet, patients usually recover and develop normally. We present clinical and molecular data from 16 unrelated cGGM diagnosed Saudi patients from consanguineous families with majority of them having previous positive family history of cGGM. Sanger sequencing for the full coding regions of SLC5A1 for all patients resulted in the identification of 4 allelic variants in a homozygous state. Two mutations are novel; c.265G>A (p.G89R) and c.1304 G>A (p.G435D), and 2 have been previously reported to cause cGGM, c.765 C>G (p.C255W) and c.1136 G>A (p.R379Q). This is the first report delineating the clinical and molecular basis of cGGM in patients from this region.

Thiazolidinediones as antidiabetic agents: A critical review.

Thiazolidinediones (TZDs) or Glitazones are an important class of insulin sensitizers used in the treatment of Type 2 diabetes mellitus (T2DM). TZDs were reported for their antidiabetic effect through antihyperglycemic, hypoglycemic and hypolipidemic agents. In time, these drugs were known to act by increasing the transactivation activity of Peroxisome Proliferators Activated Receptors (PPARs). The clinically used TZDs that suffered from several serious side effects and hence withdrawn/updated later, were full agonists of PPAR-γ and potent insulin sensitizers. These drugs were developed at a time when limited data were available on the structure and mechanism of PPARs. In recent years, however, PPAR-α/γ, PPAR-α/δ and PPAR-δ/γ dual agonists, PPAR pan agonists, selective PPAR-γ modulators and partial agonists have been investigated. In addition to these, several non PPAR protein alternatives of TZDs such as FFAR1 agonism, GPR40 agonism and ALR2, PTP1B and α-glucosidase inhibition have been investigated to address the problems associated with the TZDs. Using these rationalized approaches, several investigations have been carried out in recent years to develop newer TZDs devoid of side effects. This report critically reviews TZDs, their history, chemistry, mechanism mediated through PPAR, recent advances and future prospects.

Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2Inhibitors.

In this work, design, synthesis, and screening of thiophene carboxamides 4-13 and 16-23 as dual vascular endothelial growth factor receptors (VEGFRs) and mitotic inhibitors was reported. All compounds were screened against two gastrointestinal solid cancer cells, HepG-2 and HCT-116 cell lines. The most active cytotoxic derivatives 5 and 21 displayed 2.3- and 1.7-fold higher cytotoxicity than Sorafenib against HepG-2 cells. Cell cycle and apoptosis analyses for compounds 5 and 21 showed cells accumulation in the sub-G1 phase, and cell cycle arrest at G2/M phase. The apoptotic inducing activities of compounds 5 and 21were correlated to the elevation of p53, increase in Bax/Bcl-2 ratio, and increase in caspase-3/7.Compounds 5 and 21 showed potent inhibition againstVEGFR-2 (IC50 = 0.59 and 1.29 µM) and ß-tubulin polymerization (73% and 86% inhibition at their IC50 values).Molecular docking was performed with VEGFR-2 and tubulin binding sites to explain the displayed inhibitory activities.

Design, Synthesis and Screening of 4,6-Diaryl Pyridine and Pyrimidine Derivatives as Potential Cytotoxic Molecules.

A new series of pyridine and pyrimidine derivatives is designed and synthesized as potential antitumor molecules. The tested compounds show promising in vitro cytotoxic activity against HL-60 cell line as eight compounds: 4, 6, 11, 13, 14, 15, 18 and 21 exhibit potent cytotoxic activity in sub-micromolar concentration higher than the combretastatin A4 (CA-4). Compound 21 shows a cytotoxic activity 5-fold more potent than CA-4 on HL-60 cells. DNA-Flow cytometry cell cycle analysis and annexin-V assay on HL-60 cells show that compounds 4, 18 and 21 exhibit potent cell growth inhibition, cell cycle arrest at G2/M phase and pro-apoptotic inducing activities. The percentage inhibition assay of ß-tubulin polymerization on HL-60 cells shows that the antitumor activity of the tested compounds appears to correlate well with its ability to inhibit ß-tubulin polymerization. In addition, enzyme-linked immunosorbene assay (ELlSA) measurement for compound 21 shows apoptotic inducing activities through significant up regulation of p53, Bax/Bcl-2 ratio and caspase-3 proteins parallel to down regulation of the level of survivin proteins.

The invasome of Salmonella Dublin as revealed by whole genome sequencing.

BACKGROUND: Salmonella enterica serovar Dublin is a zoonotic infection that can be transmitted from cattle to humans through consumption of contaminated milk and milk products. Outbreaks of human infections by S. Dublin have been reported in several countries including high-income countries. A high proportion of S. Dublin cases in humans are associated with invasive disease and systemic illness. The genetic basis of virulence in S. Dublin is not well characterized. METHODS: Whole genome sequencing was applied to a set of clinical invasive and non-invasive S. Dublin isolates from different countries in order to characterize the putative genetic determinants involved in the virulence and invasiveness of S. Dublin in humans. RESULTS: We identified several virulence factors that form the bacterial invasome and may contribute to increasing bacterial virulence and pathogenicity including mainly Gifsy-2 prophage, two different type 6 secretion systems (T6SSs) harbored by Salmonella pathogenicity islands; SPI-6 and SPI-19 respectively and virulence genes; ggt and PagN. Although Vi antigen and the virulence plasmid have been reported previously to contribute to the virulence of S. Dublin we did not detect them in all invasive isolates indicating that they are not the main virulence determinants in S. Dublin. CONCLUSION: Several virulence factors within the genome of S. Dublin might contribute to the ability of S. Dublin to invade humans' blood but there were no genomic markers that differentiate invasive from non-invasive isolates suggesting that host immune response play a crucial role in the clinical outcome of S. Dublin infection.

Beyond urinalysis: evaluation of various clinical and laboratory reflex criteria to warrant urine culture collection in the emergency department.

BACKGROUND: Clinical criteria are essential for diagnosing urinary tract infections (UTIs) followed by urine testing, including urinalysis (UA). No study has evaluated the potential related factors that may guide the appropriate collection of urine cultures. Therefore, we aimed to assess the factors that may guide the appropriate collection of urine cultures. METHODS: This was a case-control study of patients for whom a urine culture and a UA were ordered in the emergency department (ED) between February 2018 and December 2022. The cases included patients with positive cultures, whereas the controls included patients without growth. Patients were excluded if they were pregnant, underwent any urological procedure, received antibiotics within 3 days before ED presentation, or before culture collection. RESULTS: Of the 263 patients, 123 had growth and 140 did not have growth in urine cultures. In the univariate analysis, female gender, urinary symptoms, urinary white blood cell (WBC) count > 5 cells/hpf, and nitrite in urine were significantly associated with growth (P < 0.05). However, only female gender (aOR, 1.86; 95% CI, 1.06-3.24), urinary WBC count > 5 cells/hpf (aOR, 4.60; 95% CI, 2.21-9.59), and positive nitrite in urine (aOR, 21.90; 95% CI, 2.80-171.00) remained significant in the multivariable analysis. These factors also remained significant in the subgroup of patients with urinary symptoms, except for the female gender. CONCLUSION: A high urinary WBC count and positive nitrite in UA should be utilized as a guide to collect urine culture, particularly in female patients, to limit the unnecessary ordering of urine culture in the ED. These factors can be used as evidence-based UA reflex criteria as an antimicrobial stewardship intervention.

Genomic analysis of Anderson typing phages of Salmonella Typhimrium: towards understanding the basis of bacteria-phage interaction.

The Anderson phage typing scheme has been successfully used worldwide for epidemiological surveillance of Salmonella enterica serovar Typhimurium. Although the scheme is being replaced by whole genome sequence subtyping methods, it can provide a valuable model system for study of phage-host interaction. The phage typing scheme distinguishes more than 300 definitive types of Salmonella Typhimurium based on their patterns of lysis to a unique collection of 30 specific Salmonella phages. In this study, we sequenced the genomes of 28 Anderson typing phages of Salmonella Typhimurium to begin to characterize the genetic determinants that are responsible for the differences in these phage type profiles. Genomic analysis of typing phages reveals that Anderson phages can be classified into three different groups, the P22-like, ES18-like and SETP3-like clusters. Most Anderson phages are short tailed P22-like viruses (genus Lederbergvirus); but phages STMP8 and STMP18 are very closely related to the lambdoid long tailed phage ES18, and phages STMP12 and STMP13 are related to the long noncontractile tailed, virulent phage SETP3. Most of these typing phages have complex genome relationships, but interestingly, two phage pairs STMP5 and STMP16 as well as STMP12 and STMP13 differ by a single nucleotide. The former affects a P22-like protein involved in DNA passage through the periplasm during its injection, and the latter affects a gene whose function is unknown. Using the Anderson phage typing scheme would provide insights into phage biology and the development of phage therapy for the treatment of antibiotic resistant bacterial infections.

PARADOXICAL DUAL ROLES OF SOME CYTOKINES INTERPRETED BY CYTOGENETICS INVESTIGATIONS IN IRRADIATED HUMAN BLOOD CULTURES.

Four different cytokines (IL1-ß, IL-6, IL-10 and TNF-α) and the cytokinesis-block micronucleus (CBMN) cytome assay investigations were evaluated in six human blood samples. They were divided into the control (nonirradiated) and five gamma-irradiated groups which were exposed to five different doses (0.5, 1, 2, 4 and 8 Gy). Blood groups were cultured in triplets for 72 h following 1 h of irradiation. Immunological and cytogenetics were investigated parallelly at different irradiation doses to understand the connection between them. Our aim is anchoring the active proliferation action of cytokines by presence of binucleated cells and resting immune system by mononuclear cell. Also, cell death by increasing necrotic cell count and TNF-α concentration. When compared with the control group, 0.5, 1, 2 and 4 Gy irradiation groups recorded a gradual increase in the cytokines levels, an increase in the total micronucleated cells (binucleated and mononucleated cells), an increase in necrotic and apoptotic cells counts. While 8 Gy irradiation leads to depletion in TNF-α concentration, although the number of necrotic cells was high.

The Influence of Different γ-Irradiation Patterns on Factors that May Affect Cell Cycle Progression in Male Rats.

Most studies of the biological effects of ionizing radiation have been done on a single acute dose, while clinically and environmentally exposures occur under chronic/repetitive conditions. It is important to study effects of different patterns of ionizing radiation. In this study, a rat model was used to compare the effects of repetitive and acute exposure. Groups: (I) control, (II, III) were exposed to fractionated doses (1.5 GyX4) and (2 GyX4), respectively/24h interval, and (IV, V) were exposed to 6 Gy and 8 Gy of whole-body gamma irradiation, respectively. The gene expression of MAPT and tau phosphorylation increased in all irradiated groups but the gene expression of PKN not affected. TGFß% increased at dose of 2 GyX4 only. In addition, the cell cycle was arrested in S phase. Micronucleus (MN) increased and cell proliferation decreased. In conclusion, the dose and pattern of ionizing radiation do not affect the MAPT and PKN gene expression, but TGF-ß, p-tau, MN assay and cell proliferation are significantly affected. The dose of 2 GyX4 showed distinctive effect. Repetitive exposure may increase TGF-ß%, which causes radio-resistance and, G2/M delay. Thus, the cell cycle could be regulated in a different manner according to the dose and pattern of irradiation.

Characterisation of Phage Susceptibility Variation in Salmonellaenterica Serovar Typhimurium DT104 and DT104b.

The surge in mortality and morbidity rates caused by multidrug-resistant (MDR) bacteria prompted a renewal of interest in bacteriophages (phages) as clinical therapeutics and natural biocontrol agents. Nevertheless, bacteria and phages are continually under the pressure of the evolutionary phage-host arms race for survival, which is mediated by co-evolving resistance mechanisms. In Anderson phage typing scheme of Salmonella Typhimurium, the epidemiologically related definitive phage types, DT104 and DT104b, display significantly different phage susceptibility profiles. This study aimed to characterise phage resistance mechanisms and genomic differences that may be responsible for the divergent phage reaction patterns in S. Typhimurium DT104 and DT104b using whole genome sequencing (WGS). The analysis of intact prophages, restriction-modification systems (RMS), plasmids and clustered regularly interspaced short palindromic repeats (CRISPRs), as well as CRISPR-associated proteins, revealed no unique genetic determinants that might explain the variation in phage susceptibility among the two phage types. Moreover, analysis of genes coding for potential phage receptors revealed no differences among DT104 and DT104b strains. However, the findings propose the need for experimental assessment of phage-specific receptors on the bacterial cell surface and analysis of bacterial transcriptome using RNA sequencing which will explain the differences in bacterial susceptibility to phages. Using Anderson phage typing scheme of Salmonella Typhimurium for the study of bacteria-phage interaction will help improving our understanding of host-phage interactions which will ultimately lead to the development of phage-based technologies, enabling effective infection control.

1,3,4-Thiadiazolo (3,2-Α) Pyrimidine-6-Carbonitrile Scaffold as PARP1 Inhibitors.

BACKGROUND: 1,3,4-thiadiazolo pyrimidine is a lead molecule that is versatile for a wide variety of biological activities and in continuation of our interest in establishing some novel heterocyclic compounds for antitumor activity. OBJECTIVE: The objective of the study was to synthesize a series of 5-amino-7-(substituted aldehyde)-2[(naphthalene- 2-yloxy)methyl] -[1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivatives and evaluate their possible in vitro and in vivo anticancer activity. METHODS: Herein, we report the synthetic scheme, which was followed for the preparation of a series of title compounds B1- B9 outlined in scheme 1. The intermediate 5-[(naphthalen-2- yloxy)methyl]-1,3,4-thiadiazolo- 2-amine was prepared by heating 2-naphthoxyacetic acid and thiosemicarbazide in the presence of phosphoryl chloride at a temperature of 65-75°C. The obtained compound reacted with malononitrile and an appropriate amount of aromatic and heteroaromatic aldehydes in refluxing ethanol yielded 5-amino-7-(substituted aldehyde)-2[(naphthalene-2-yloxy)methyl] -[1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivatives (B1 - B9). The purity of the synthesized compounds was ensured by various spectral analyses. RESULTS: In in silico molecular docking studies, compounds B3 and B9 show binding affinity like known PARP1 inhibitor olaparib. The cellular evaluation indicates that the anticancer profile of compounds B1, B3, and B9 is significant when compared to the standard drug (olaparib) against MDA-MB-232 cell line and compounds B3, B6, and B7 are the most active against MCF-7 cell lines. The most active compound B3 was subjected to acute oral toxicity studies by OECD 423 guidelines and in vivo anti-cancer studies were carried out using DMBA induced model. CONCLUSION: The in silico docking study of the newly synthesized compounds was performed; the results showed good binding mode in the active site of PARP1 enzyme. In silico ADME properties of synthesized compounds were also studied and showed good drug-like properties.

Design, synthesis and screening of benzimidazole containing compounds with methoxylated aryl radicals as cytotoxic molecules on (HCT-116) colon cancer cells.

A novel series of benzimidazole derivatives with methoxylated aryl groups was designed and synthesized as molecules with potential cytotoxic activity. In vitro cytotoxic activity over HCT-116 cells showed that N-(benzimidazothiazolone)acetamides 11a, 11b and 11c were found to be the most cytotoxic compounds compared camptothecin (CPT). The tested compounds had a dual topoisomerase I-ß (Topo I-ß) and tubulin inhibiting activities when compared to CPT and Podophyllotoxin (Podo) where, compounds l0a, l0b, 11a and 11b exhibited a potent inhibitory activity on Topo I-ß enzyme in nano-molar concentration, on the other hand, compounds 12b and 13b exhibited the best inhibitory activity ß-tubulin polymerization. Results of the cell cycle analysis as well as the results of annexin-V on HCT-116 cells showed that benzimidazothiazoles 12b and 13b had a pro-apoptotic activity higher than CPT by 1.33- and 1.30-folds, respectively. Moreover, the concentration of p53, Bax/Bcl-2 ratio and caspase 3/7 increased in compounds l0b, 11b, l2b, 13b, especially, compounds 11b and 13b exhibited an increased level of these mediators than CPT. Finally, compound 11b regulated the radiosensitizing activity of the HCT-116 cells by modulating the chromosomal instability.

Evaluation of WGS-subtyping methods for epidemiological surveillance of foodborne salmonellosis.

BACKGROUND: Salmonellosis is one of the most common foodborne diseases worldwide. Although human infection by non-typhoidal Salmonella (NTS) enterica subspecies enterica is associated primarily with a self-limiting diarrhoeal illness, invasive bacterial infections (such as septicaemia, bacteraemia and meningitis) were also reported. Human outbreaks of NTS were reported in several countries all over the world including developing as well as high-income countries. Conventional laboratory methods such as pulsed field gel electrophoresis (PFGE) do not display adequate discrimination and have their limitations in epidemiological surveillance. It is therefore very crucial to use accurate, reliable and highly discriminative subtyping methods for epidemiological characterisation and outbreak investigation. METHODS: Here, we used different whole genome sequence (WGS)-based subtyping methods for retrospective investigation of two different outbreaks of Salmonella Typhimurium and Salmonella Dublin that occurred in 2013 in UK and Ireland respectively. RESULTS: Single nucleotide polymorphism (SNP)-based cluster analysis of Salmonella Typhimurium genomes revealed well supported clades, that were concordant with epidemiologically defined outbreak and confirmed the source of outbreak is due to consumption of contaminated mayonnaise. SNP-analyses of Salmonella Dublin genomes confirmed the outbreak however the source of infection could not be determined. The core genome multilocus sequence typing (cgMLST) was discriminatory and separated the outbreak strains of Salmonella Dublin from the non-outbreak strains that were concordant with the epidemiological data however cgMLST could neither discriminate between the outbreak and non-outbreak strains of Salmonella Typhimurium nor confirm that contaminated mayonnaise is the source of infection, On the other hand, other WGS-based subtyping methods including multilocus sequence typing (MLST), ribosomal MLST (rMLST), whole genome MLST (wgMLST), clustered regularly interspaced short palindromic repeats (CRISPRs), prophage sequence profiling, antibiotic resistance profile and plasmid typing methods were less discriminatory and could not confirm the source of the outbreak. CONCLUSIONS: Foodborne salmonellosis is an important concern for public health therefore, it is crucial to use accurate, reliable and highly discriminative subtyping methods for epidemiological surveillance and outbreak investigation. In this study, we showed that SNP-based analyses do not only have the ability to confirm the occurrence of the outbreak but also to provide definitive evidence of the source of the outbreak in real-time.

Question classification based on Bloom's taxonomy cognitive domain using modified TF-IDF and word2vec.

The assessment of examination questions is crucial in educational institutes since examination is one of the most common methods to evaluate students' achievement in specific course. Therefore, there is a crucial need to construct a balanced and high-quality exam, which satisfies different cognitive levels. Thus, many lecturers rely on Bloom's taxonomy cognitive domain, which is a popular framework developed for the purpose of assessing students' intellectual abilities and skills. Several works have been proposed to automatically handle the classification of questions in accordance with Bloom's taxonomy. Most of these works classify questions according to specific domain. As a result, there is a lack of technique of classifying questions that belong to the multi-domain areas. The aim of this paper is to present a classification model to classify exam questions based on Bloom's taxonomy that belong to several areas. This study proposes a method for classifying questions automatically, by extracting two features, TFPOS-IDF and word2vec. The purpose of the first feature was to calculate the term frequency-inverse document frequency based on part of speech, in order to assign a suitable weight for essential words in the question. The second feature, pre-trained word2vec, was used to boost the classification process. Then, the combination of these features was fed into three different classifiers; K-Nearest Neighbour, Logistic Regression, and Support Vector Machine, in order to classify the questions. The experiments used two datasets. The first dataset contained 141 questions, while the other dataset contained 600 questions. The classification result for the first dataset achieved an average of 71.1%, 82.3% and 83.7% weighted F1-measure respectively. The classification result for the second dataset achieved an average of 85.4%, 89.4% and 89.7% weighted F1-measure respectively. The finding from this study showed that the proposed method is significant in classifying questions from multiple domains based on Bloom's taxonomy.

Botulinum Toxin A Injection in Treatment of Upper Limb Spasticity in Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Cerebral palsy (CP) is the most common cause of childhood disability globally. Botulinum toxin A injections are widely used to manage limb spasticity in children with CP. Intramuscular botulinum toxin A has been used in the upper limbs of children with CP to manage preoperative and postoperative pain, facilitate nursing, and achieve functional and/or cosmetic improvement of hand position. These goals are achieved primarily through reduction of spasticity. The aim of this review was to assess the evidence for the effect of botulinum toxin A injections used to manage upper limb spasticity in children with spastic CP. Specifically, we examined the role of botulinum toxin A as an adjunctive treatment to other physical therapy modalities. Additionally, we analyzed the associated complications. METHODS: The literature extraction process involved 4 phases: identification, screening, eligibility, and inclusion. We used a combination of Google Scholar, PubMed, and ScienceDirect. The choice of the search terms was based on the Medical Subject Headings. We extracted the relevant studies using a combination of words or terms related to (1) patient population, (2) pathology, (3) clinical intervention, and (4) anatomical distribution of pathology. Studies were included if they were randomized controlled trials conducted on children and/or adolescents with CP targeting the upper extremities in which botulinum toxin A was used as an adjunctive treatment to a primary intervention. RESULTS: The literature extraction process yielded 15 randomized controlled trials for inclusion in this review. The total number of participants enrolled in the included studies was 499, with 255 in the intervention group (51%) and 244 controls (49%). All participants in the eligible studies had unilateral spastic CP except for those in 4 studies (27%) with 198 participants (40%) that included a heterogeneous sample of unilateral and bilateral spastic CP. The mean age of participants in the intervention group ranged from 2.6 to 10.7 years among the individual studies. The mean age of participants in the control group ranged from 3.1 to 10.55 years among the individual studies. This review indicated that botulinum toxin A had a positive effect on the degree of spasticity and cosmetic appearance of the injected upper limb. The results with respect to functional gains and quality of life were either conflicting or not significant. CONCLUSIONS: Randomized controlled trials of botulinum toxin A injection in the treatment of upper limb spasticity in children with CP used variable outcome measures and yielded mixed results. Overall, there is some evidence to support the use of botulinum toxin A as an adjuvant treatment to other physical therapy regimens or placebo to reduce spasticity in the short term. There is insufficient evidence to support its use as an adjunctive treatment to improve upper limb function or quality of life. The complications were acceptable and did not outweigh the clinical gains incurred. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Whole-Genome Sequences of Two Salmonella enterica Serovar Dublin Strains That Harbor the viaA, viaB, and ompB Loci of the Vi Antigen.

Here, we report the genome sequences of two Salmonella enterica serovar Dublin strains, 03EB8736SAL and 03EB8994SAL, isolated from raw-milk cheese and milk filtrate, respectively. Analysis of the draft genomes of the two isolates reveals the presence of the viaA, viaB, and ompB loci of the Vi capsular polysaccharide antigen (Vi antigen).