699 research outputs found
phytochemicals targeting EGFR: molecular docking, molecular dynamics simulation and density functional theory studies
No full textEpidermal growth factor receptor (EGFR) is a prominent target for anticancer therapy due to its role in activating several cell signaling cascades. Clinically approved EGFR inhibitors are reported to show treatment resistance and toxicity, this study, therefore, investigates Moringa oleifera phytochemicals to find potent and safe anti-EGFR compounds. For that, phytochemicals were screened based on drug-likeness and molecular docking analysis followed by molecular dynamics simulation, density functional theory analysis and ADMET analysis to identify the effective inhibitors of EGFR tyrosine kinase (EGFR-TK) domain. Known EGFR-TK inhibitors (1-4 generations) were used as control. Among 146 phytochemicals, 136 compounds showed drug-likeness, of which Delta 7-Avenasterol was the most potential EGFR-TK inhibitor with a binding energy of -9.2 kcal/mol followed by 24-Methylenecholesterol (-9.1 kcal/mol), Campesterol (-9.0 kcal/mol) and Ellagic acid (-9.0 kcal/mol). In comparison, the highest binding affinity from control drugs was displayed by Rociletinib (-9.0 kcal/mol). The molecular dynamics simulation (100 ns) exhibited the structural stability of native EGFR-TK and protein-inhibitor complexes. Further, MM/PBSA computed the binding free energies of protein complex with Delta 7-Avenasterol, 24-Methylenecholesterol, Campesterol and Ellagic acid as -154.559 ± 18.591 kJ/mol, -139.176 ± 19.236 kJ/mol, -136.212 ± 17.598 kJ/mol and -139.513 ± 23.832 kJ/mol, respectively. Non-polar interactions were the major contributors to these energies. The density functional theory analysis also established the stability of these inhibitor compounds. ADMET analysis depicted acceptable outcomes for all top phytochemicals without displaying any toxicity. In conclusion, this report has identified promising EGFR-TK inhibitors to treat several cancers that can be further investigated through laboratory and clinical tests
Do market conditions affect interconnectedness pattern of socially responsible equities?
No full textWe assess the interconnectedness pattern of sustainability leaders from United States market during stable, boom and crisis situations for the period 01-Oct-2005 to 31-May-2021 using Qian et al. (2020) methodology. The purpose is to assess the hedging properties of sustainable firms. We find that sampled firms exhibit high connectedness during tail events. Also, they offer hedge against the market conditions. Moreover, the small and growth-oriented firms contribute to the total connectedness for all market conditions. The sampled SRI network appears favorable for forming portfolio as the average connectedness is negative for all economic conditions
Improving Perception of Usability Through User Interface Design Patterns to Optimize Information Architecture for Cognitive Benefits and User Satisfaction in Massive Open Online Courses
No full textThis study explores the impact of user interface design patterns on usability, cognitive load, and user satisfaction for Massive Open Online Courses using small-screen devices. An empirical approach was adopted, involving 232 university students who voluntarily participated in the experiment. Prototypes of three well-known Massive Open Online Courses platforms (i.e., Coursera, Udemy, and edX) were developed to assess how various user interface design patterns influence user experience. The findings revealed that the aesthetic design of Coursera, including color scheme, content organization, was perceived as the most visually appealing, while Udemy received higher ratings for its typography, i.e, font size, type, and button shape. Coursera also outperformed the other platforms in terms of navigation (e.g., tab navigation, hamburger menu, drop-down, floating action button, listview), customization features (e.g., search filters, font, and background settings), and feedback mechanisms (e.g., toast messages, error alerts, progress indicators, confirmation prompts, and system status updates). Overall, participants reported higher satisfaction with Coursera, and its interface was associated with a lower cognitive load compared to Udemy and edX. These results underscore the importance of thoughtful user interface design in enhancing usability and reducing cognitive effort in mobile learning applications
Serum amyloid P and endocrine markers in a cohort of obese children
No full textObjectives: Obesity in children can lead to morbidity and mortality due to metabolic and inflammatory comorbidities. Aims: The objective of the study was to investigate the alterations in acute inflammatory markers, serum amyloid P (SAP) and cortisol, and endocrine markers, leptin and insulin, in obese children. Materials and Methods: Serum leptin, insulin, cortisol, and amyloid P concentrations were measured in obese (BMI percentile >85, n = 17) and nonobese (BMI percentile < 75, n = 20) children using ELISA and Bio-Plex Bead-based assay. Statistical Analysis Used: Serum concentrations of analytes were compared between normal and obese groups using 2-tailed student's t-test. Results: Mean leptin, insulin, and SAP serum concentrations were significantly higher in obese children as compared to the controls (97.19 vs. 4.06, P < 0.05; 21.31 vs 3.56, P < 0.05; 46.77 vs. 17.89, P < 0.05; respectively). No difference was found in mean serum cortisol levels of the two groups. However, cortisol values were higher in obese subjects compared to the control group (7.89 vs 6.30, P = 0.15). Leptin corelated with insulin (r = 0.42, P = 0.043) and cortisol (r = 0.48, P = 0.025) levels in the obese group. Furthermore, leptin, insulin, and SAP levels were corelated with BMI (r = 0.80, P < 0.000; r = 0.67, P = 0.015, respectively) and body weight (r = 0.52, P = 0.01; r = 0.52, P = 0.002; r = 0.54, P = 0.01, respectively) in the obese group but did not demonstrate a significant relationship in the nonobese group. Conclusion: Elevated SAP levels and increase in leptin and insulin indicated a preeminent disposition of morbidly obese children to the development of low-grade inflammation and metabolic syndrome
Etiology and characteristics of burn injuries in patients admitted at Burns Center, Civil Hospital Karachi
No full textBackground: Morbidity and mortality by burns are alarmingly high among the developing countries due to inadequate care facilities. Among these nations, Pakistan has one of the highest burn-related incidents. The dilemma is that most of these deaths and disabilities are curable and preventable. Therefore, there is an urgent need of creating an effective infrastructure to cut down these high number of cases. Methods: We conducted a cross-sectional study at Burns Center, Civil Hospital Karachi. Two hundred and seventy-five patients participated in the study. Data were analyzed using SPSS version 17.0. Results: Among these 275 patients interviewed 63.6% (n = 175) were males whereas 36.4% (n = 100) were females. The mean age of our participants was found to be 26.36 years. A large proportion of the population belonged to the urban areas, i.e. 76.4% (210), whereas only 23.6% (65) were from rural areas, with P = 0.001. About 63.6% of the burn injuries occurred at home (175) while 25.1% (69) got injured at the place of work. Most of the cases were found to be accidental 93.8% (258). About 53.1% (146) had <20% of the total body surface area effected, whereas 16.7% (46) had more than 40% burns. Conclusion: By introducing an effective awareness program regarding burns and teaching first aid techniques to general population, a high number of burn-related accidents could be prevented
Attitude toward blood donation among medical and nonmedical students across Karachi
No full textAim: To evaluate the factors that motivate and discourage medical and nonmedical students from donating blood voluntarily and to assess the level of awareness and knowledge regarding blood donation. Materials and Methods: We conducted a cross-sectional descriptive study from August 2011 to May 2012 across different universities of Karachi covering both private and public sector. Predesigned questionnaires were filled by students. A total of 690 students participated in the study, 345 from each. Data collected was analyzed using SPSS Version 17.0. Simple frequencies and percentages were calculated, and Pearson Chi-square and Fisher's exact tests were applied to calculate association between different variables with P value set as significant when <0.05. Results: Mean age of the students was found to be between 21 and 23 (64.6%) in medical, whereas in nonmedical, 66.7% fell in this age group. Astonishingly, blood donors in nonmedical (27%) were quite more than that in medical group, where they were only 18%. Males constituted the majority in both of the groups. Most commonly reported factor that motivated blood donation in medical group was feeling of self-satisfaction (40.2%), whereas in nonmedical group, 32.9% reported that they had only donated blood when their friends/family were in need. When asked about the adverse effects after blood donation, weakness was common among both medical and nonmedical, i.e. 46.8% and 46.7%, respectively. Among the factors that impeded our subjects from donating blood were primarily health concerns in medical students (19%), whereas in nonmedical students they claimed they were not approached by anyone and were unaware of the importance of blood donation (34.8%). Conclusion: Proportion of blood donors was significantly low in both medical and nonmedical students, especially in females. Most important motivating factor in medical students was feeling of self–satisfaction, whereas in nonmedical students, it was family/friend in need of blood transfusion. Never approached by anyone/awareness about the importance of donating blood was the major discouragement factor seen in both medical and nonmedical groups
Experience with macrophage activation syndrome associated with systemic lupus erythematosus: A single-center study from Pakistan
No full textObjective: The objective of the study was to evaluate the clinical, laboratory manifestations, and associations of macrophage activation syndrome (MAS) in a cohort of Pakistani patients with systemic lupus erythematous and to compare it with a well-characterized cohort of active systemic lupus erythematosus (SLE) without MAS.
Materials and Methods: Patients with a diagnosis of SLE admitted from January 2017 to July 2019 were retrospectively reviewed. MAS ascertained by either clinical criteria or bone marrow biopsy were studied. Demographics, clinical, and laboratory parameters of MAS patients were evaluated and compared with a cohort of non-MAS active SLE.
Results: A total of 305 patients of SLE were evaluated, out of these 18 patients had a diagnosis of MAS, making a MAS prevalence of 5.9%. Mean age of the patients was 27.25 ± 10.16 years. Female comprised 13 (72%) of MAS group. Fever was the most common clinical presentation (100%), followed by splenomegaly (38.9%) and lymphadenopathy (33.3%). At least 5 (27.8%0 patients had MAS as their initial manifestation. Anemia (88.9%), thrombocytopenia (88.9%), leukopenia (72%), and pancytopenia (55.6%) were prominent laboratory parameters. Mean serum ferritin of 1584 ng/ml and mean triglyceride of 270 mg/dl were reported. On comparing with non-MAS cohort; younger age, fever, lymphadenopathy, splenomegaly, mucocutaneous features, any type of cytopenia, high aspartate aminotransferase (AST), low albumin, and lactate dehydrogenase, all showed significant association with MAS (P < 0.05).
Conclusion: Fever and associated cytopenias coupled with raised AST are strong predictors of MAS in patients with SLE
Test order for quantitative sensory testing (QST) and its impact on the test outcome
No full textQuantitative Sensory Testing (QST) is a group of different tests used to evaluate the sensory function of nerve fibers. This sensory profiling of the nerves is obtained by different QST tests with a specific sequence proposed by The German Research Network on Neuropathic Pain (DFNS)1. In the proposed sequence by DFNS thermal testing comes before the mechanical. Later, Grone et al suggested that if mechanical test is preceded by heat testing, it can change the mechanical test values significantly from the reference values which were proposed by DFNS2. In this study, we used 3 different tests: Heat Pain Threshold (HPT), Cold Pain Threshold (CPT) and Mechanical Pain Threshold (MPT) which are used to evaluate sensory nerve fibers namely A-beta, A-delta and C fibers on two different testing sites i.e., trigeminal (Infraorbital) and extra-trigeminal (Volar forearm). Subjects were examined on any of the testing sites, one week apart. These 3 QST tests were used in 6 possible sequences, with a washout period of 10 minutes between each sequence, to evaluate if these tests depict sequence dependent values. Results: We performed the single factor ANOVA test to analyze any significant difference among the values of QST tests in different sequences. We observed no significant differences in QST values for any sequence for both the testing sites with respective P values were higher than 0.05 (Volar forearm MPT P=0.943, Volar forearm CPT P=0.320, Volar forearm HPT P=0.986, Infraorbital MPT P=0.958, Infraorbital CPT P=0.344 and Infraorbital HPT P=0.986). In our study, we concluded that there was statistically no significant difference among any QST test sequence and QST tests used in our study are independent of sequence.Ph.D.Includes bibliographical reference
Do market conditions affect interconnectedness pattern of socially responsible equities?
No full textWe assess the interconnectedness pattern of sustainability leaders from United States market
during stable, boom and crisis situations for the period 01-Oct-2005 to 31-May-2021 using Qian
et al. (2020) methodology. The purpose is to assess the hedging properties of sustainable firms.
We find that sampled firms exhibit high connectedness during tail events. Also, they offer hedge
against the market conditions. Moreover, the small and growth-oriented firms contribute to the
total connectedness for all market conditions. The sampled SRI network appears favorable for
forming portfolio as the average connectedness is negative for all economic conditions
The abolishment of death penalty as capital punishment: A comparative study of death penalty between Malaysia and Australia / Siti Adzlin Mohd Anwer … [et al.]
No full textThroughout the world, the subject of the relevancy of death penalty has become a polemic issue that will never be ceased from being debated unless all the countries in the world has finally come to a resolution that the imposition of death penalty should be completely abolished be it in law or in practice. Malaysia is among the nations that still preserve the imposition of death penalty in its criminal justice system. The method of execution is by hanging the criminals to death and a mandatory death sentence will be imposed towards the criminals who are guilty of the offence of discharging firearms at public, intentional murder and trafficking in dangerous drugs. While Malaysia is still practicing this gruesome law, most of the world's nations especially in the big part of Europe had already taken away this type of punishment from their laws. According to these 'civilised' nations, death penalty is a cruel punishment that denies the right to life of human beings. Besides, the punishment is being condemned for it is prone to establish unfairness and miscarriage of justice especially in a situation where an innocent man is being put to death and he will only be exonerated after several years of his execution. In order to know whether these arguments are valid and justified, a comparative study will be conducted between Malaysia and Australia. We choose to compare the law of Malaysia with Australia since both are applying common law principle
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