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We conclude that MEK1/2 inhibition may be a promising approach to suppress ovarian cancer growth as a maintenance therapy. Promotion of stem-like properties upon MEK1/2 inhibition suggests a possible mechanism of resistance, so a combination with CSC-targeting drugs should be considered.Methylmercury (MeHg) toxicity is a major environmental concern. In the aquatic reservoir, MeHg bioaccumulates along the food chain until it is consumed by riverine populations. There has been much interest in the neurotoxicity of MeHg due to recent environmental disasters. Studies have also addressed the implications of long-term MeHg exposure for humans. The central nervous system is particularly susceptible to the deleterious effects of MeHg, as evidenced by clinical symptoms and histopathological changes in poisoned humans. Zimlovisertib order In vitro and in vivo studies have been crucial in deciphering the molecular mechanisms underlying MeHg-induced neurotoxicity. A collection of cellular and molecular alterations including cytokine release, oxidative stress, mitochondrial dysfunction, Ca2+ and glutamate dyshomeostasis, and cell death mechanisms are important consequences of brain cells exposure to MeHg. The purpose of this review is to organize an overview of the mercury cycle and MeHg poisoning events and to summarize data from cellular, animal, and human studies focusing on MeHg effects in neurons and glial cells. This review proposes an up-to-date compendium that will serve as a starting point for further studies and a consultation reference of published studies.Although there has been extensive research on the corporate social responsibility (CSR)-performance link, full understanding is still elusive. A possible reason for this is the limited understanding of the underlying processes that affect the relationship. Grounded in institutional theory, which emphasizes the importance of micro-level intermediating processes (e.g., employees' perceptions and attitudes) to explain a macro-level association (i.e., CSR to organizational performance), we built a moderated mediation model where (i) organization commitment mediated the influence of CSR on organizational performance, and (ii) an employee's prosocial motivation moderated the relationship between CSR and organizational commitment. Using three-wave time-lagged survey data obtained from 302 Korean workers, we found that organizational commitment is an important micro-level process in the CSR-performance link, and that the level of an employee's prosocial motivation can positively moderate that link. We discuss theoretical and practical implications, along with limitations and future research directions.The transportation system has evolved into a complex cyber-physical system with the introduction of wireless communication and the emergence of connected travelers and connected automated vehicles. Such applications create an urgent need to develop high-fidelity transportation modeling tools that capture the mutual interaction of the communication and transportation systems. This paper addresses this need by developing a high-fidelity, large-scale dynamic and integrated traffic and direct cellullar vehicle-to-vehicle and vehicle-to-infrastructure (collectively known as V2X) modeling tool. The unique contributions of this work are (1) we developed a scalable implementation of the analytical communication model that captures packet movement at the millisecond level; (2) we coupled the communication and traffic simulation models in real-time to develop a fully integrated dynamic connected vehicle modeling tool; and (3) we developed scalable approaches that adjust the frequency of model coupling depending on the number of concurrent vehicles in the network. The proposed scalable modeling framework is demonstrated by running on the Los Angeles downtown network considering the morning peak hour traffic demand (145,000 vehicles), running faster than real-time on a regular personal computer (1.5 h to run 1.86 h of simulation time). Spatiotemporal estimates of packet delivery ratios for downtown Los Angeles are presented. This novel modeling framework provides a breakthrough in the development of urgently needed tools for large-scale testing of direct (C-V2X) enabled applications.In the United States, overweight/obesity is more prevalent among those with low-income; higher income is related to greater leisure time physical activity (LTPA) and sedentary behavior (SB), which are inversely related to overweight/obesity. This study aimed to evaluate the role of LTPA and SB simultaneously in the income-overweight/obesity relationship. Cross-sectional data from the National Health and Nutrition Examination Survey (2007-2014) were utilized (n = 10,348 non-older adults (aged 20-59 years)). A multiple mediator structural equation model was conducted to evaluate the indirect effects from income to overweight/obesity (Body Mass Index ≥25 kg/m2) through LTPA and SB simultaneously, controlling for confounding variables, including diet, smoking, and alcohol consumption. As expected, greater income was negatively associated with overweight/obesity. Income indirectly influenced overweight/obesity through LTPA (Indirect effect B = -0.005; CI = -0.01, -0.003), and through SB (Indirect effect B = 0.008; CI = 0.005, 0.01), in opposing directions. The direct effect from income to overweight/obesity remained statistically significant. LTPA partially accounted for the negative relationship between income and overweight/obesity; SB reduced the strength of the negative relationship between income and overweight/obesity. Targeted behavior approaches for weight management may be beneficial. Increasing LTPA among adults with lower income and decreasing SB among adults with higher income may provide some overweight/obesity protection.Autism Spectrum Disorder (ASD) is a constellation of social deficits and repetitive sensory-motor behaviours. Aquatic therapy (AT) may be effective in improving the social interactions and behaviours in children with ASD. The objective of this study was to evaluate the effects of an AT program on social competence and quality of life and to understand participant's experiences related to the intervention by obtaining qualitative data. A mixed methods intervention study was conducted among 6 children with ASD and their parents, with two research phases in a concurrent embedded design (an aquatic intervention as the quantitative design and a qualitative design in second step). The intervention and qualitative design followed international guidelines and were integrated into the method and reporting subheadings. Significant improvement was observed in the physical competence (p = 0.026) and important improvements in school functioning and aquatic skills, with no adverse events. Qualitative findings described the meaning of AT intervention, patterns of behaviour and activities changes, social communication and social interaction.

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