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TAp63 is a p53 family member and potent tumor and metastasis suppressor. Here, we show that TAp63-/- mice exhibit an increased susceptibility to UVR-induced cutaneous squamous cell carcinoma (cuSCC). A human-to-mouse comparison of cuSCC tumors identified miR-30c-2* and miR-497 as underexpressed in TAp63-deficient cuSCC. Reintroduction of these microRNAs significantly inhibited the growth of cuSCC cell lines and tumors. Proteomic profiling of cells expressing either microRNA showed downregulation of cell cycle progression and mitosis associated proteins. A mouse to human and cross-platform comparison of RNA-Seq and proteomics data identified a 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC. Knockdown of these factors in cuSCC cell lines suppressed tumor cell proliferation and induced apoptosis. Additionally, selective inhibition of AURKA suppressed cuSCC cell proliferation, induced apoptosis, and showed anti-tumor effects in vivo. Finally, treatment with miR-30c-2* or miR-497 microRNA mimics was highly effective in suppressing cuSCC growth in vivo. Our data establishes TAp63 as an essential regulator of novel microRNAs that can be therapeutically targeted for potent suppression of cuSCC. Copyright ©2020, American Association for Cancer Research.CONTEXT Pneumococcal conjugate vaccines (PCVs) (pneumococcal 13-valent conjugate vaccine [PCV-13] and pneumococcal 10-valent conjugate vaccine [PCV-10]) are available for prevention of pneumococcal infections in children. OBJECTIVE To determine the vaccine effectiveness (VE) of PCV-13 and PCV-10 in preventing invasive pneumococcal disease (IPD) and acute otitis media (AOM) in children less then 5 years. DATA SOURCES Systematic searches of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Cochrane. STUDY SELECTION Eligible studies examined the direct effectiveness and/or efficacy of PCV-10 and PCV-13 in reducing the incidence of disease in healthy children less then 5 years. DATA EXTRACTION Two reviewers independently conducted data extraction and methodologic quality assessment. RESULTS Significant effectiveness against vaccine-type IPD in children ≤5 years was reported for ≥1 dose of PCV-13 in the 3 + 1 (86%-96%) and 2 + 1 schedule (67.2%-86%) and for PCV-10 for the 3 + 1 (72.8%-100%) and 2 + 1 schedules (92%-97%). In children less then 12 months of age, PCV-13 VE against serotype 19A post-primary series was significant for the 3 + 1 but not the 2 + 1 schedule. PCV-10 crossprotection against 19A was significant in children ≤5 years with ≥1 dose (82.2% and 71%). Neither PCVs were found effective against serotype 3. PCV-13 was effective against AOM (86%; 95% confidence interval [CI] 61 to 94). PCV-10 was effective against clinically defined (26.9%; 95% CI 5.9 to 43.3) and bacteriologically confirmed AOM (43.3%; 95% CI 1.7 to 67.3). LIMITATIONS Because of the large heterogeneity in studies, a meta-analysis for pooled estimates was not done. CONCLUSIONS Both PCVs afford protection against pneumococcal infections, with PCV-10 protecting against 19A IPD, but this VE has not been verified in the youngest age groups. Copyright © 2020 by the American Academy of Pediatrics.Photorespiration is an essential process in oxygenic photosynthetic organisms triggered by the oxygenase activity of ribulose-1,5-bisphosphate carboxylase/oxygenase. In peroxisomes, photorespiratory HYDROXYPYRUVATE REDUCTASE 1 (HPR1) catalyzes the conversion of hydroxypyruvate to glycerate together with the oxidation of a pyridine nucleotide cofactor. HPR1 regulation remains poorly understood; however, HPR1 phosphorylation at T335 has been reported. By comparing the kinetic properties of phospho-mimetic (T335D), non-phosphorylatable (T335A), and wild-type recombinant Arabidopsis thaliana HPR1, it was found that HPR1-T335D exhibits reduced NADH-dependent hydroxypyruvate reductase activity while showing improved NADPH-dependent activities. Complementation of the Arabidopsis hpr1-1 mutant by either wild-type HPR1 or HPR1-T335A fully complemented the photorespiratory growth phenotype of hpr1-1 in ambient air whereas HPR1-T335D containing hpr1-1 plants remained smaller and had lower photosynthetic CO2 assimilation rates. Metabolite analyses indicated that these phenotypes were associated with subtle perturbations in the photorespiratory cycle of HPR1-T335D-complemented hpr1-1 rosettes compared to all other HPR1-containing lines. Therefore, T335 phosphorylation may play a role in the regulation of HPR1 activity in planta although it was not required for growth under ambient air controlled conditions. Furthermore, improved NADP-dependent HPR1 activities in peroxisomes could not compensate for the reduced NADH-dependent HPR1 activity. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.OBJECTIVES To perform the cross-cultural adaption of the Breast Cancer Awareness Measurement (BCAM) and to test its psychometric properties among Chinese women. DESIGN This is a cross-sectional study. SETTINGS This study was conducted in communities, schools and institutions in Changchun, Jilin Province, China. PARTICIPANTS A total of 328 women voluntarily participated in and completed the Chinese version of the BCAM (C-BCAM), resulting in an effective response rate of 91.1%. PRIMARY AND SECONDARY OUTCOME MEASURES Psychometric properties, including item analysis (the extreme group comparison and item-total correlations), content validity (item-level content validity index (I-CVI) and scale-level content validity index (S-CVI)), construct validity (exploratory factor analysis (EFA) and confirmatory factor analysis (CFA)) and internal consistency (Cronbach's α and test-retest reliability), were measured. RESULTS The C-BCAM has excellent internal consistency (Cronbach's α=0.90), with alpha coefficients of 0.88, heir employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To understand the facilitators and barriers to the self-management of chronic obstructive pulmonary disease (COPD) in rural Nepal. SETTINGS Community and primary care centres in rural Nepal. PARTICIPANTS A total of 14 participants (10 people with COPD and 4 health care providers) were interviewed. PRIMARY AND SECONDARY OUTCOME MEASURES People with COPD and healthcare provider's experience of COPD self-management in rural Nepal. RESULTS Facilitators and barriers affecting COPD self-management in Nepal operated at the patient-family, community and service provider levels. People with COPD were found to have a limited understanding of COPD and medications. Some participants reported receiving inadequate family support and described poor emotional health. At the community level, widespread use of complementary and alternative treatment was found to be driven by social networks and was used instead of western medicine. There were limited quality controls in place to monitor the safe use of alternative tr020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE Overweight/obesity among women is associated with an increased risk of gestational diabetes, pre-eclampsia, postpartum haemorrhage, low birth weight, congenital malformation and neonatal deaths. Although the magnitude of overweight and obesity among the reproductive age group women is a common problem in Ethiopia, there are limited studies that determine the associated factors of overweight and obesity at the national level. Therefore, this study aimed to identify the determinant factors of overweight/obesity among reproductive age group women in Ethiopia. DESIGN Cross-sectional study design. SETTING Ethiopia. PARTICIPANTS Non-pregnant women aged 15-49 years. PRIMARY OUTCOME Overweight/obesity. METHODS The present study used the Ethiopia Demographic Health Survey (EDHS) data for 2016. A total of 10 938 non-pregnant reproductive age group women were included in the analysis. Both bivariable and multivariable multilevel logistic regression were performed to determine the determinants of overweight andmercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES In April 2017, the United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) released the electronic Maternal and Child Health Handbook, the e-MCH Handbook application. One of the first mobile health (m-Health) interventions in a refugee setting, the application gives pregnant women and mothers access to educational information and health records on smartphones. This study investigated factors associated with the dissemination and implementation of m-Health in the refugee setting. SETTING AND PARTICIPANTS A cross-sectional study was conducted in 9 of 25 UNRWA health centres for Palestine refugees in Jordan. Self-administered questionnaires were distributed for 1 week to pregnant women and mothers with children aged 0-5 years. learn more OUTCOME MEASURES The outcomes were whether participants knew about, downloaded or used the application. Multiple regression analyses were conducted to determine factors associated with application download and usage. RESULTS 1042 participants were ted factors may also play a role. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES To investigate women's understanding and attitudes towards the National Cervical Screening Program (NCSP) and to explore methods to improve screening participation. DESIGN Semi-structured face-to-face interviews were conducted through convenience and snowball sampling. Thematic analysis occurred using the interpretivist framework. SETTING A private general practice in North Queensland. PARTICIPANTS Women between the ages of 18 and 74 who attended the general practice were eligible to participate. Fourteen women between 20 and 58 years old were interviewed. RESULTS Participants were concerned that the new NCSP would miss cancer due to longer screening intervals and reliance on primary human papilloma virus (HPV) testing. They believed that young women are at increased risk of cervical cancer, due to perceived HPV vaccine ineffectiveness and parent objection to vaccination. Most participants were not agreeable to self-sampling and preferred their doctor to perform screening. Personal and practitioner beliefs influenced a woman's screening participation. Personal factors include being healthy for themselves and their family, previous abnormal smears and family history of cancer. Emphasis was placed on feeling 'comfortable' with their practitioner which included patient rapport and gender preference. Proposed methods to improve cervical screening included education programmes, advertising campaigns, general practitioner interventions and improving accessibility. CONCLUSIONS It is apparent that women are hesitant about the new NCSP. However, when provided with additional information they were more amenable to the changes. This highlights the need to improve awareness of cervical screening and the new NCSP. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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