METHODS AND MATERIALS: A MATLAB algorithm was developed to extract the setup errors in three translational directions (x, y, and z) from the data logged by the CBCT system during treatment delivery. The algorithm also calculates the resulted population setup error and PTV margin based on the van Herk margin recipe and subsequently estimates their respective values for no action level (NAL) and extended no action level (eNAL) offline correction protocols. The algorithm was tested on 25 head and neck cancer (HNC) patients treated using IG-IMRT.
RESULTS: The algorithms calculated that the HNC patients require a PTV margin of 3.1, 2.7, and 3.2 mm in the x-, y-, and z-direction, respectively, without IGRT. The margin can be reduced to 2.0, 2.2, and 3.0 mm in the x-, y-, and z-direction, respectively, with NAL and 1.6, 1.7, and 2.2 mm in the x-, y-, and z-direction, respectively, with eNAL protocol. The results obtained were verified to be the same with the margins calculated using an Excel spreadsheet. The algorithm calculates the weekly offline setup error correction values automatically and reduces the risk of input data error observed in the spreadsheet.
CONCLUSIONS: In conclusion, the algorithm provides an automated method for optimization and reduction of PTV margin using logged setup errors from CBCT-based IGRT.
OBJECTIVE: The aim of this study is to compare and assess interventions that address AMR across the One Health spectrum and determine what actions will help to build social and ecological capacity and readiness to sustainably tackle AMR.
METHODS: We will apply social-ecological resilience theory to AMR in an explicit One Health context using mixed methods and identify interventions that address AMR and its key pressure antimicrobial use (AMU) identified in the scientific literature and in the gray literature using a web-based survey. Intervention impacts and the factors that challenge or contribute to the success of interventions will be determined, triangulated against expert opinions in participatory workshops and complemented using quantitative time series analyses. We will then identify indicators using regression modeling, which can predict national and regional AMU or AMR dynamics across animal and human health. Together, these analyses will help to quantify the causal loop diagrams (CLDs) of AMR in the European and Southeast Asian food system contexts that are developed by diverse stakeholders in participatory workshops. Then, using these CLDs, the long-term impacts of selected interventions on AMR will be explored under alternate future scenarios via simulation modeling and participatory workshops. A publicly available learning platform housing information about interventions on AMR from a One Health perspective will be developed to help decision makers identify promising interventions for application in their jurisdictions.
RESULTS: To date, 669 interventions have been identified in the scientific literature, 891 participants received a survey invitation, and 4 expert feedback and 4 model-building workshops have been conducted. Time series analysis, regression modeling of national and regional indicators of AMR dynamics, and scenario modeling activities are anticipated to be completed by spring 2022. Ethical approval has been obtained from the University of Waterloo's Office of Research Ethics (ethics numbers 40519 and 41781).
CONCLUSIONS: This paper provides an example of how to study complex problems such as AMR, which require the integration of knowledge across sectors and disciplines to find sustainable solutions. We anticipate that our study will contribute to a better understanding of what actions to take and in what contexts to ensure long-term success in mitigating AMR and its impact and provide useful tools (eg, CLDs, simulation models, and public databases of compiled interventions) to guide management and policy decisions.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24378.
OBJECTIVE: This study investigated the anti-cancer effects of epigenetic drugs scriptaid and zebularine in human breast adenocarcinoma MDA-MB-231 and MCF-7 cells.
METHODS: First, the half maximal inhibitory concentration (IC50) of scriptaid, zebularine and the combination of both drugs on human breast adenocarcinoma MDA-MB-231 cells was determined. Next, MDA-MB-231 and MCF-7 cells were treated with scriptaid, zebularine and the combination of both. After treatments, the anti-cancer effects were evaluated via cell migration assay, cell cycle analysis and apoptotic studies, which included histochemical staining and reverse-transcriptase polymerase chain reaction (RT-PCR) of the apoptotic genes.
RESULTS: Both epigenetic drugs inhibited cell viability in a dose-dependent manner with 2 nM scriptaid, 8 µM zebularine and combination of 2 nM scriptaid and 2 µM zebularine. Both MDA-MB-231 and MCF-7 cells exhibited a reduction in cell migration after the treatments. In particular, MDA-MB-231 cells exhibited a significant reduction in cell migration (p < 0.05) after the treatments of zebularine and the combination of scriptaid and zebularine. Besides, cell cycle analysis demonstrated that scriptaid and the combination of both drugs could induce cell cycle arrest at the G0/G1 phase in both MDA-MB-231 and MCF-7 cells. Furthermore, histochemical staining allowed the observation of apoptotic features, such as nuclear chromatin condensation, cell shrinkage, membrane blebbing, nuclear chromatin fragmentation and cytoplasmic extension, in both MDA-MB-231 and MCF-7 cells after the treatments. Further apoptotic studies revealed that the upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2 and elevation of Bax/Bcl-2 ratio were found in MDA-MB-231 cells treated with zebularine and MCF-7 cells treated with all drug regimens.
CONCLUSION: Collectively, these findings suggest that scriptaid and zebularine are potential anti-cancer drugs, either single or in combination, for the therapy of breast cancer. Further investigations of the gene regulatory pathways directed by scriptaid and zebularine are definitely warranted in the future.
METHODS: A concurrent mixed-method approach was used. In the quantitative strand, a cross-sectional online survey was carried out via a Google form. Mann-Whitney U test and Chi-squared test were used for comparisons. In the qualitative strand, twelve participants were interviewed, based on a semi-structured interview guide and audio recorded. Transcribed data were evaluated with thematic content analysis.
RESULTS: A total of 225 final-year medical students were studied in the quantitative strand. Most were females. The mean score for knowledge was 3.35 ± 0.795 out of six. Of them, 31.6 % of participants scored below 3 points ( 80 %). Only 36.4 % reported "adequate" hand hygiene performance in all eight dimensions of the behavior domain. Noticeably, fewer participants reported to clean their hands after checking blood pressure (55.6 %), and only 66.2 % stated carrying a hand sanitizer in their pocket. Significant correlations were not found between reported behavior and attitudes (p = 0.821) or knowledge (p = 0.794). The qualitative strand with 12 respondents revealed the positive influence of both hierarchical and non-hierarchal role models. Time constraints, skin irritation, and workload pressures were the main barriers. Frequent reminders, supervision, and interactive teaching were suggested as methods to improve hand hygiene compliance. They also stated that increased enthusiasm was noted on hand hygiene during the COVID-19 pandemic compared to the pre-pandemic period.
CONCLUSIONS: Most of the participants had positive attitudes towards hand hygiene. Yet, a considerable gap between attitudes and knowledge and reported hand hygiene behavior was evident. Coupling educational programs that use cognitive and behavioral methods, including role modeling, supervision, and frequent reminders, is recommended to bridge the knowledge-attitude-behavior gap.
Methods: Three semi-synthetic series of compounds (C1-4, P1-4, and G1-4) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of Amaranthus spinosus L. (p-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities.
Results: Compounds C4 and G4 showed superior inhibitory activity against EGFR (IC50: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC50: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds C4 and G4 exhibited the highest cytotoxic activity with average IC50 values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites.
Discussion: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.
METHODS: A total of 266 healthcare workers working in a medical college in Nepal were studied using a questionnaire consisting of three sections: demographics, experiences and perception of COVID-19, and COVID-19 vaccine safety. Data were analyzed using IBM SPSS version 26. The total perception score was calculated by noting respondent's agreement with a set of eleven statements using a Likert-type scale. Non-parametric tests (Mann-Whitney U and Kruskal-Wallis) were used for analysis (p<0.05).
RESULTS: Altogether, 13.9% of respondents had been diagnosed COVID-19 positive prior to the survey. Many considered themselves to be at increased risk of contracting COVID-19. Only over one third (38.3%) were willing to be vaccinated. The most common reason for refusal/hesitancy was concern about vaccine safety. The median (interquartile range) total perception score was 36 (4) (maximum possible score=55). The score was significantly higher among those who had been diagnosed COVID positive, those who perceived the pandemic as being moderate or severe and among those willing to be vaccinated.
CONCLUSION: Addressing doubts related to vaccine safety and providing more data on the safety of vaccine may be helpful in overcoming hesitancy.