Methods: In this study, comparative genome analysis was carried out using the G. boninense NJ3 genome to identify and characterize carbohydrate-active enzyme (CAZymes) including CWDE in the fungal genome. Augustus pipeline was employed for gene identification in G. boninense NJ3 and the produced protein sequences were analyzed via dbCAN pipeline and PhiBase 4.5 database annotation for CAZymes and plant-host interaction (PHI) gene analysis, respectively. Comparison of CAZymes from G. boninense NJ3 was made against G. lucidum, a well-studied model Ganoderma sp. and five selected pathogenic fungi for CAZymes characterization. Functional annotation of PHI genes was carried out using Web Gene Ontology Annotation Plot (WEGO) and was used for selecting candidate PHI genes related to cell wall degradation of G. boninense NJ3.
Results: G. boninense was enriched with CAZymes and CWDEs in a similar fashion to G. lucidum that corroborate with the lignocellulolytic abilities of both closely-related fungal strains. The role of polysaccharide and cell wall degrading enzymes in the hemibiotrophic mode of infection of G. boninense was investigated by analyzing the fungal CAZymes with necrotrophic Armillaria solidipes, A. mellea, biotrophic Ustilago maydis, Melampsora larici-populina and hemibiotrophic Moniliophthora perniciosa. Profiles of the selected pathogenic fungi demonstrated that necrotizing pathogens including G. boninense NJ3 exhibited an extensive set of CAZymes as compared to the more CAZymes-limited biotrophic pathogens. Following PHI analysis, several candidate genes including polygalacturonase, endo β-1,3-xylanase, β-glucanase and laccase were identified as potential CWDEs that contribute to the plant host interaction and pathogenesis.
Discussion: This study employed bioinformatics tools for providing a greater understanding of the biological mechanisms underlying the production of CAZymes in G. boninense NJ3. Identification and profiling of the fungal polysaccharide- and lignocellulosic-degrading enzymes would further facilitate in elucidating the infection mechanisms through the production of CWDEs by G. boninense. Identification of CAZymes and CWDE-related PHI genes in G. boninense would serve as the basis for functional studies of genes associated with the fungal virulence and pathogenicity using systems biology and genetic engineering approaches.
METHODS: All surgeries were performed by minimally invasive technique with either percutaneous monoaxial or percutaneous polyaxial screws inserted at adjacent fracture levels perpendicular to both superior end plates. Fracture reduction is achieved with adequate rod contouring and distraction maneuver. Radiological parameters were measured during preoperation, postoperation, and follow-up.
RESULTS: A total of 21 patients were included. Eleven patients were performed with monoaxial pedicle screws and 10 patients performed with polyaxial pedicle screws. Based on AO thoracolumbar classification system, 10 patients in the monoaxial group had A3 fracture type and 1 had A4. In the polyaxial group, six patients had A3 and four patients had A4. Total correction of anterior vertebral height (AVH) ratio was 0.30 ± 0.10 and 0.08 ± 0.07 in monoaxial and polyaxial groups, respectively (p < 0.001). Total correction of posterior vertebral height (PVH) ratio was 0.11 ± 0.05 and 0.02 ± 0.02 in monoaxial and polyaxial groups, respectively (p < 0.001). Monoaxial group achieved more correction of 13° (62.6%) in local kyphotic angle compared to 8.2° (48.0%) in polyaxial group. Similarly, in regional kyphotic angle, 16.5° (103.1%) in the monoaxial group and 8.1° (76.4%) in the polyaxial group were achieved.
CONCLUSIONS: Monoaxial percutaneous pedicle screws inserted at adjacent fracture levels provided significantly better fracture reduction compared to polyaxial screws in thoracolumbar fractures.
METHODS: All reported DENV protein sequence data for each serotype was retrieved from the NCBI Entrez Protein (nr) Database (txid: 12637). The downloaded sequences were then separated according to the individual serotype proteins by use of BLASTp search, and subsequently removed for duplicates and co-aligned across the serotypes. Shannon's entropy and mutual information (MI) analyses, by use of AVANA, were performed to measure the diversity within and between the serotype proteins to identify HCSS nonamers. The sequences were evaluated for the presence of promiscuous T-cell epitopes by use of NetCTLpan 1.1 and NetMHCIIpan 3.2 server for human leukocyte antigen (HLA) class I and class II supertypes, respectively. The predicted epitopes were matched to reported epitopes in the Immune Epitope Database.
RESULTS: A total of 2321 nonamers met the HCSS selection criteria of entropy 0.8. Concatenating these resulted in a total of 337 HCSS sequences. DENV4 had the most number of HCSS nonamers; NS5, NS3 and E proteins had among the highest, with none in the C and only one in prM. The HCSS sequences were immune-relevant; 87 HCSS sequences were both reported T-cell epitopes/ligands in human and predicted epitopes, supporting the accuracy of the predictions. A number of the HCSS clustered as immunological hotspots and exhibited putative promiscuity beyond a single HLA supertype. The HCSS sequences represented, on average, ~ 40% of the proteome length for each serotype; more than double of pan-DENV sequences (conserved across the four serotypes), and thus offer a larger choice of sequences for vaccine target selection. HCSS sequences of a given serotype showed significant amino acid difference to all the variants of the other serotypes, supporting the notion of serotype-specificity.
CONCLUSION: This work provides a catalogue of HCSS sequences in the DENV proteome, as candidates for vaccine target selection. The methodology described herein provides a framework for similar application to other pathogens.
METHODS: The cytotoxicity activity was measured using MTS assay. The mode of cell death was analysed by early (phosphatidylserine externalization) and late apoptosis (DNA fragmentation). The caspases 8, 9, 3/7 and apoptotic proteins bax, bcl-2 study were done by western blot and ELISA method.
RESULTS: The methanol extract was found to inhibit 50% growth of T-47D cells at the concentration of 79.43µg/ml respectively after 72hr. From seven fractions, fraction F1, F2 and F3 produced cytotoxicity effects in T-47D cell line with IC50 (72hr) < 30µg/ml. The results obtained by Annexin V/PI apoptosis detection assay and TUNEL assay suggest that active fractions of Vitex rotundifolia induced early and late apoptosis (DNA fragmentation) in T-47D cell line. Moreover, western blot analysis and Caspase GloTM luminescent assay demonstrated that fractions F2 and F3 triggered apoptotic cell death via activation of caspases -8, -9 and -3/7 and up-regulation of Bax and down-regulation of Bcl-2 protein. Furthermore, chemical profiling confirms the presence of potential metabolites (vitexicarpin) in fractions of Vitex rotundifolia.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in fractions of Vitex rotundifolia as future cancer therapeutic agent for the treatment of breast cancer.
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RESULT: An automated 3D modeling pipeline empowered by an Artificial Neural Network (ANN) was developed. This automated 3D modelling pipeline enables automated deformation of a generic 3D model of monogenean anchor into another target 3D anchor. The 3D modelling pipeline empowered by ANN has managed to automate the generation of the 8 target 3D models (representing 8 species: Dactylogyrus primaries, Pellucidhaptor merus, Dactylogyrus falcatus, Dactylogyrus vastator, Dactylogyrus pterocleidus, Dactylogyrus falciunguis, Chauhanellus auriculatum and Chauhanellus caelatus) of monogenean anchor from the respective 2D illustrations input without repeating the tedious modelling procedure.
CONCLUSIONS: Despite some constraints and limitation, the automated 3D modelling pipeline developed in this study has demonstrated a working idea of application of machine learning approach in a 3D modelling work. This study has not only developed an automated 3D modelling pipeline but also has demonstrated a cross-disciplinary research design that integrates machine learning into a specific domain of study such as 3D modelling of the biological structures.
METHODS: All adult patients admitted to the forensic wards who were able to understand Malay or English language and give written informed consent were included. Participants were assessed using the Conners Adult Attention-Deficit Diagnostic Interview for DSM-IV (for presence of adult ADHD and a history of childhood ADHD) and the Mini International Neuropsychiatric Interview (for psychiatric comorbidities). Sociodemographic and offence-related data were also collected.
RESULTS: Of 199 patients admitted, 120 were included for analysis. The mean age of participants was 36.3 years. 94.2% were men. 81.7% were single, divorced, or separated. 25% had a history of childhood ADHD. The prevalence of adult ADHD was 15.8%. The persistence rate was 63%. Among the 19 participants with adult ADHD, the most common psychiatric comorbidities were substance dependence (68.4%), lifetime depression (63.2%), and generalised anxiety disorder (47.4%). Compared with participants without ADHD, participants with adult ADHD were less likely to be married (0% vs 21.8%, p = 0.022) and more likely to have alcohol abuse (15.8% vs 2%, p = 0.028), lifetime manic/hypomanic episodes (42.1% vs 7.9%, p = 0.001), and generalised anxiety disorder (47.4% vs 19.8%, p = 0.017), and were of younger age at first offence (21.8 years vs 26.9 years, p = 0.021).
CONCLUSIONS: Adult ADHD is common in a Malaysian forensic mental hospital and is associated with unmarried status, alcohol abuse, lifetime manic/hypomanic episodes, generalised anxiety disorder, and younger age at first offence.
Methodology: Patients between 20 and 70 years of age, either gender, ASA I and II, and scheduled for elective open major bowel surgery were included in the study. Patients who underwent laparoscopic and other surgeries were excluded. After routine induction of general anaesthesia, the patients were randomised to either the control group (traditional fluid therapy), the FloTrac group (based on stroke volume variation), or the PVI group (based on pleth variability index). Fluid input and output, recovery characteristics, and complications were noted.
Results: 306 patients, with 102 in each group, were enrolled. Five patients (control (1), FloTrac (2), and PVI (2)) were inoperable and were excluded. Demographic data, ASA PS, anaesthetic technique, duration of surgery, and surgical procedures were comparable. The control group received significantly more crystalloids (3200 ml) than the FloTrac (2000 ml) and PVI groups (1875 ml), whereas infusion of colloids was higher in the FloTrac (400-700 ml) and PVI (200-500 ml) groups than in the control group (0-500 ml). The control group had significantly positive net fluid balance intraoperatively (2500 ml, 9 ml/kg/h) compared to the FloTrac (1515 ml, 5.4 ml/kg/h) and PVI (1420 ml, 6 ml/kg/h) groups. Days to ICU stay, HDU stay, return of bowel movement, oral intake, morbidity, duration of hospital stay, and survival rate were comparable. The total number of complications was not different between the three groups. Anastomotic leaks occurred more often in the Control group than in the others, but the numbers were small.
Conclusions: Use of goal-directed fluid management, either with FloTrac or pleth variability index results in a lower volume infusion and lower net fluid balance. However, the complication rate is similar to that of traditional fluid therapy. This trial is registered with CTRI/2018/04/013016.