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Dysfunction of apoptosis and DNA damage response pathways often drive cancer, and so a better understanding of these pathways can contribute to new cancer therapeutic strategies. Diverse discovery approaches have identified many apoptosis regulators, DNA damage response, and DNA damage repair proteins; however, many of these approaches rely on indirect detection of DNA damage. Here, we describe a novel discovery platform based on the comet assay that leverages previous technical advances in assay precision by incorporating high-throughput robotics. The high-throughput screening (HTS) CometChip is the first high-throughput-compatible assay that can directly detect physical damage in DNA. We focused on DNA double-strand breaks (DSBs) and utilized our HTS CometChip technology to perform a first-of-its-kind screen using an shRNA library targeting 2564 cancer-relevant genes. Conditions of the assay enable detection of DNA fragmentation from both exogenous (ionizing radiation) and endogenous (apoptosis) sources. Using this approach, we identified LATS2 as a novel DNA repair factor as well as a modulator of apoptosis. We conclude that the HTS CometChip is an effective assay for HTS to identify modulators of physical DNA damage and repair.The Nursing Working Group of the International Society of Pediatric Oncology developed baseline standards for pediatric oncology nursing care in low- and middle-income countries. The standards represent the foundational support required to provide quality nursing care and address barriers such as inadequate staffing, lack of support, limited access to education, and unsafe nursing environments. The purpose of the current study was to develop and validate an instrument to accurately measure the standards. Content validity was assessed by a panel of expert pediatric oncology nurses from all geographical regions of the World Health Organization. The experts were informed about the study's purpose and provided the publications used to develop the instrument. The experts rated how well each criterion measured the corresponding standard by using a 4-point scale. A content validity index (CVI) was computed by using the percentage of total standards given a score of 3 or 4 by the experts. selleck compound A CVI of .98 was obtained from the panel's evaluation. A CVI of more than .80 is recommended for a newly developed instrument. On the basis of the panel's recommendations, minor modifications were made to the instrument. We developed and validated the content of an instrument to accurately measure baseline standards for pediatric oncology nursing care. This instrument will aid future research on the effect of nursing standards on clinical outcomes, including mortality and abandonment of treatment, with the potential to influence health policy decisions and improve nursing support in low- and middle-income countries.Background Bacillary dysentery (BD) remains a significant public health issue, especially in developing countries. Evidence assessing the risk of BD from temperature is limited, particularly from national studies including multiple locations with different climatic characteristics. Objectives We estimated the effect of temperature on BD across China, assessed heterogeneity and attributable risks across cities and regions, and projected the future risk of BD under climate change. Methods Daily BD surveillance and meteorological data over 2014-2016 were collected from the Chinese Center for Disease Control and Prevention and the China Meteorology Administration, respectively. A two-stage statistical model was used to estimate city-specific temperature-BD relationships that were pooled to derive regional and national estimates. The risk of BD attributable to temperature was estimated, and the future burden of BD attributable to temperature was projected under different climate change scenarios. Results A positivd the projection for increased risk due to climate change, support efforts to mitigate future risks. https//doi.org/10.1289/EHP5779.Background The purpose of our research was to recommend the initial tacrolimus dosage for Chinese pediatric patients undergoing kidney transplantation based on population pharmacokinetics and pharmacogenetics. Methods Demographic data, laboratory results, drug combinations, and pharmacogenetics from Chinese pediatric patients undergoing kidney transplantation were analyzed using non-linear mixed-effects modeling. A Monte Carlo simulation was performed to evaluate the optimal initial dose of tacrolimus. Results Body weight and post-transplant days, combined with wuzhi-capsule (WZ, extracted from schisandra sphenanthera, whose primary efficient constituents are schisantherin A, schisandrol B, schisandrin, etc., and often used to treat drug-induced hepatitis in Chinese organ transplant patients) and CYP3A5 polymorphisms, influenced the clearance of tacrolimus in these patients. With same weight and post-transplant days, tacrolimus clearance rates from patients carrying CYP3A5*3/*3 and without WZ, carrying CYP3A5*1 allele and without WZ, carrying CYP3A5*3/*3 and with WZ, carrying CYP3A5*1 allele and with WZ were 1, 1.6, 0.72, and 1.152, respectively. In addition, the initial dose for each condition is recommended. Conclusions The initial dosage recommendations in the tacrolimus instructions were not individualized, and we have developed more accurate initial doses based on weight and the CYP3A5 genotype. In addition, lower initial doses are recommended with concurrent use of WZ.People with a mental illness may be exposed to stigma which, when internalised, negatively influences self-esteem, personal goal attainment and quality of life. Avoiding the use of stigmatising language and using terminology that does not exclude the positive characteristics of the individual may play an important role in challenging stigma. This study involved a mixed method approach to identify the terminology preferences of people with a mental illness in Australia. N = 173 participants were recruited via convenience sampling. The humanistic terms 'individual' and 'person with lived experience' were identified as the preferred terms. Qualitatively there was a wide variation in how the terms made the respondents think or feel, with only one of the terms - 'survivor,' having solely negative themes. When contrasting the two most commonly used clinical terms, 'client' was significantly preferred to 'patient'. The term 'consumer' was one of the least preferred terms. This suggests that the use of this term, which is in regular use in Australia, should be reconsidered.
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