Cisplatin based therapy: The role of the mitogen activated protein kinase signaling pathway

Cisplatin is a widely used chemotherapeutic agent for treatment of various cancers. However, treatment with cisplatin is associated with drug resistance and several adverse side effects such as nephrotoxicity, reduced immunity towards infections and hearing loss. A Combination of cisplatin with other drugs is an approach to overcome drug resistance and reduce toxicity. The combination therapy also results in increased sensitivity of cisplatin towards cancer cells. The mitogen activated protein kinase (MAPK) pathway in the cell, consisting of extracellular signal regulated kinase, c-Jun N-terminal kinase, p38 kinases, and downstream mediator p90 ribosomal s6 kinase (RSK); is responsible for the regulation of various cellular events including cell survival, cell proliferation, cell cycle progression, cell migration and protein translation. This review article demonstrates the role of MAPK pathway in cisplatin based therapy, illustrates different combination therapy involving cisplatin and also shows the importance of targeting MAPK family, particularly RSK, to achieve increased anticancer effect and overcome drug resistance when combined with cisplatin. - 2018 The Author(s).Scopu

Clinical and Pharmacokinetic Outcomes of Peak–Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial

Background Vancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration–time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date. Objectives We aimed to compare clinical and pharmacokinetic outcomes between peak–trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates. Methods A multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak–trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations. Results Sixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak–trough-based-TDM (n = 30)]. Peak–trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak–trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak–trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak–trough-based group. Conclusion Maintenance of target vancomycin exposures and implementation of peak–trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.Open Access funding provided by the Qatar National Library. We would like to thank Dr. Hani Abdelaziz and Dr. Eman El-Mekaty for their efforts and contributions in the design and implementation of this study. We would also like to thank all staff at HMC who helped to conduct the study

Novel LiAlO2 Material for Scalable and Facile Lithium Recovery Using Electrochemical Ion Pumping

In this study, α-LiAlO2 was investigated for the first time as a Li-capturing positive electrode material to recover Li from aqueous Li resources. The material was synthesized using hydrothermal synthesis and air annealing, which is a low-cost and low-energy fabrication process. The physical characterization showed that the material formed an α-LiAlO2 phase, and electrochemical activation revealed the presence of AlO2* as a Li deficient form that can intercalate Li+. The AlO2*/activated carbon electrode pair showed selective capture of Li+ ions when the concentrations were between 100 mM and 25 mM. In mono salt solution comprising 25 mM LiCl, the adsorption capacity was 8.25 mg g−1, and the energy consumption was 27.98 Wh mol Li−1. The system can also handle complex solutions such as first-pass seawater reverse osmosis brine, which has a slightly higher concentration of Li than seawater at 0.34 ppm. © 2023 by the authors.This study is made possible by Qatar National Research Fund (QNRF) under National Priorities Research Program (NPRP) grant (#NPRP12S-0227-190166) and Graduate Student Research Award (GSRA) grant (#GSRA8-L-2-0411-21011).Scopu

Soil radioactivity levels, radiological maps and risk assessment for the state of Kuwait

An evaluation of the radioactivity levels associated with naturally occurring radioactive materials has been undertaken as part of a systematic study to provide a surface radiological map of the State of Kuwait. Soil samples from across Kuwait were collected, measured and analysed in the current work. These evaluations provided soil activity concentration levels for primordial radionuclides, specifically members of the (238)U and (232)Th decay chains and (40)K which. The (238)U and (232)Th chain radionuclides and (40)K activity concentration values ranged between 5.9 ↔ 32.3, 3.5 ↔ 27.3, and 74 ↔ 698 Bq/kg respectively. The evaluated average specific activity concentrations of (238)U, (232)Th and (40)K across all of the soil samples have mean values of 18, 15 and 385 Bq/kg respectively, all falling below the worldwide mean values of 35, 40 and 400 Bq/kg respectively. The radiological risk factors are associated with a mean of 33.16 ± 2.46 nG/h and 68.5 ± 5.09 Bq/kg for the external dose rate and Radium equivalent respectively. The measured annual dose rates for all samples gives rise to a mean value of 40.8 ± 3.0 μSv/y while the internal and internal hazard indices have been found to be 0.23 ± 0.02 and 0.19 ± 0.01 respectively

Creating language resources for under-resourced languages: methodologies, and experiments with Arabic

Language resources are important for those working on computational methods to analyse and study languages. These resources are needed to help advancing the research in fields such as natural language processing, machine learning, information retrieval and text analysis in general. We describe the creation of useful resources for languages that currently lack them, taking resources for Arabic summarisation as a case study. We illustrate three different paradigms for creating language resources, namely: (1) using crowdsourcing to produce a small resource rapidly and relatively cheaply; (2) translating an existing gold-standard dataset, which is relatively easy but potentially of lower quality; and (3) using manual effort with appropriately skilled human participants to create a resource that is more expensive but of high quality. The last of these was used as a test collection for TAC-2011. An evaluation of the resources is also presented

Assessment of radioactivity in some soil samples of qatar by gamma-ray spectroscopy and the derived dose rates

The activity concentrations of some natural and artificial radionuclides have been measured in soil samples by gamma-ray spectroscopy using a high purity germanium detector. From the obtained gamma-ray spectra, the activity concentrations of 238U and 232Th natural decay series and the long-lived naturally occurring radionuclide 40K have been determined, in addition to the fission product 137Cs. A wide range of different gamma-ray lines ranging from -100 keV up to 2.6 MeV, associated with the decay products of238U and232Th series have been analyzed independently to obtain more statistically significant overall results. The data have been analyzed, when secular equilibrium of the radionuclides is achieved within the samples. The weighted activity concentrations of 238U and232Th series vary from 4.4 to 64.4 and 0.8 to 7.6 Bq/kg, respectively. The activity concentrations of 40K and 137Cs have been found in the range of13.6 to 179.5 and 0.3 to 3.7 Bq/kg, respectively. Based on the measured activity concentrations, dose rate, radium equivalent, radiation hazard index and annual effective dose rates have been estimated. The values obtained are within the recommended safety limits

Assessment of radioactivity in some soil samples of qatar by gamma-ray spectroscopy and the derived dose rates

The activity concentrations of some natural and artificial radionuclides have been measured in soil samples by gamma-ray spectroscopy using a high purity germanium detector. From the obtained gamma-ray spectra, the activity concentrations of 238U and 232Th natural decay series and the long-lived naturally occurring radionuclide 40K have been determined, in addition to the fission product 137Cs. A wide range of different gamma-ray lines ranging from -100 keV up to 2.6 MeV, associated with the decay products of238U and232Th series have been analyzed independently to obtain more statistically significant overall results. The data have been analyzed, when secular equilibrium of the radionuclides is achieved within the samples. The weighted activity concentrations of 238U and232Th series vary from 4.4 to 64.4 and 0.8 to 7.6 Bq/kg, respectively. The activity concentrations of 40K and 137Cs have been found in the range of13.6 to 179.5 and 0.3 to 3.7 Bq/kg, respectively. Based on the measured activity concentrations, dose rate, radium equivalent, radiation hazard index and annual effective dose rates have been estimated. The values obtained are within the recommended safety limits

A systematic review for sustainability of global liquified natural gas industry: A 10-year update

This paper presents a comprehensive review and 10-years update of the sustainability research related to Liquefied Natural Gas (LNG) worldwide for the period between 2010 and 2020. Using the Scopus database, 467 articles, including journals, conference papers, and many other reports, were initially collected and screened. The filtered studies were categorized based on various factors such as author, year of publication, title, journal, method, country studied, analyzed system, the scope of the analysis, and period. It was found that only 168 (36% of the whole) studies have investigated the LNG sector's sustainability impacts with a detailed analysis. The collected literature was studied and categorized based on a proposed criterion. The findings showed that approximately 7 out of 46 countries performed such a massive number of LNG studies with a focus on LNG industries and sustainability. Moreover, it is observed that sustainability analysis research in LNG production concentrates mainly on the national level with 48% and the global level studies were found to be around 40% of total studies. The review also showed that there is no holistic life cycle environmental, economic, and social impact assessment for the LNG industry considering the entire value chain activities from gas extraction/processing to final consumption. This review finally discussed the lessons learned from the literature reviewed and industry best practices and several practical industry-specific policies are presented to enhance the long-term sustainability of LNG in support of sustainable development globally.Scopu

Using Data Analytics and Visualization Dashboard for Engineering, Procurement, and Construction Project's Performance Assessment

This study demonstrates the application of design principles for tools in Engineering, Procurement, and Construction (EPC) projects for project management purposes. It advocates the use of proper data analytics and visualization that can be implemented to support effective project progress reporting as well as performance monitoring. At first, an Entity Relationship Diagram (ERD) of the collected data was developed, and then the database was retrieved into the Microsoft Power BI for analysis and visualization. The project's relevant details were visualized and analyzed in terms of the major key performance indications that help evaluate the current situation of projects and aids in future decision making for project performance and portfolio management. A real case of a construction company has been selected and examined. Analytical results support finding the story behind the data. On the other hand, the effects point out that the use of the suitable facts analytics method coupled with the right analytics method and appropriate data visualization software would result in optimum use of information for future aspiration of project success and proper project progress reporting and performance evaluation. It will help companies to transfer from traditional data storage style to big data analytics and powerful use of enterprise business data for companies' growth and success in the field of EPC projects and the construction industries as a whole. Furthermore, it can be used for quicker and extra decisive choices aiming to keep projects on music about their security performance, scheduled time, cost, and great level. Using the proposed dashboard is creating a summary of the accessible records that prints a photo of how initiatives and portfolios are performing, permitting decision-makers to take their future strategic steps aiming for the improvement of their initiatives and accordingly success in their cutting-edge and future endeavors to reap the objective of all stakeholders of this organization. In this paper, it was demonstrated that the visualization of the contractor's performance and KPI are bringing assurance on contractor performance in addition to daily operational monitoring. Furthermore, it helps managers in organizing the workload to ensure the project's completion timely and meeting the customer demand as expected.Scopu