Notes

Circ_0001667 knockdown prevents cancer malignancy further advancement and also attenuates adriamycin resistance simply by wearing NCOA3 through releasing miR-4458 within cancers of the breast.
Varicella zoster virus (VZV) is a herpesvirus that causes chickenpox and shingles. The biological mechanisms underpinning the multi-decadal latency of VZV in the body and subsequent viral reactivation-which occurs in approximately 30% of individuals-are largely unknown. Because chickenpox and shingles are endemic worldwide, understanding the relationship between VZV transmission and reactivation is important for informing disease treatment and control. While chickenpox is a vaccine-preventable childhood disease with a rich legacy of research, shingles is not a notifiable disease in most countries. To date, population-level studies of shingles have had to rely on small-scale hospital or community-level datasets. Here, we examined chickenpox and shingles notifications from Thailand and found strong seasonal incidence in both diseases, with a 3-month lag between peak chickenpox transmission season and peak shingles reactivation. We tested and fit 14 mathematical models examining the biological driversof chickenpox and shingles over an 8-year period to estimate rates of VZV transmission, reactivation, and immunity boosting, wherein re-exposure to VZV boosts VZV-specific immunity to reinforce protection against shingles. The models suggested the seasonal cycles of chickenpox and shingles have different underlying mechanisms, with ultraviolet radiation (UV) being correlated with shingles reactivation.Chromatin structures (and modulators thereof) play a central role in genome organization and function. Herein, we report that thymine DNA glycosylase (TDG), an essential enzyme involved in DNA repair and demethylation, has the capacity to alter chromatin structure directly through its physical interactions with DNA. Using chemically defined nucleosome arrays, we demonstrate that TDG induces decompaction of individual chromatin fibers upon binding and promotes self-association of nucleosome arrays into higher-order oligomeric structures (i.e. condensation). Chromatin condensation is mediated by TDG's disordered polycationic N-terminal domain, whereas its C-terminal domain antagonizes this process. Furthermore, we demonstrate that TDG-mediated chromatin condensation is reversible by growth arrest and DNA damage 45 alpha (GADD45a), implying that TDG cooperates with its binding partners to dynamically control chromatin architecture. Finally, we show that chromatin condensation by TDG is sensitive to the methylation status of the underlying DNA. This new paradigm for TDG has specific implications for associated processes, such as DNA repair, DNA demethylation, and transcription, and general implications for the role of DNA modification 'readers' in controlling chromatin organization.Increasing fertility and decreasing mortality are major response strategies in Russian demographic reform, which has led to significant decreases in both abortion rate (AR) and infant mortality. This study explores mechanisms influencing the socioeconomic conditions leading to abortion and infant mortality. Spatial panel economic analysis using data from the 83 regions of the country covering four time periods was applied. Every 1000 USD increase in per capita gross regional product (GRP) can lead to a decrease of the AR by 0.075, while one year life expectancy increase would lower it by 0.441. For infant mortality rate (IMR), GRP also shows a positive impact, particularly in recent years, while the population size of the region has a negative impact. Every 1000 USD increase in per capita GRP would result in a rate decrease of 0.064 in IMR, and every increase of 1000 added population would lead to an increased IMR by 2.05. The harvest effect between AR and infant mortality that was evident earlier, but not in the recent years, implies that the health care system in Russia is effective. A comprehensive improvement in wellbeing, income, etc. can contribute to mitigation of abortion and infant mortality. Theoretically, this study extends current research by comprehensively displaying the spatio-temporal patterns of abortion and infant mortality in Russia and qualifies the impact of regional socioeconomic disparities with regard to these two issues.The aim of this study was to assess the role of climate variability on the incidence of dengue fever (DF), an endemic arboviral infection existing in Jakarta, Indonesia. The work carried out included analysis of the spatial distribution of confirmed DF cases from January 2007 to December 2018 characterising the sociodemographical and ecological factors in DF high-risk areas. Spearman's rank correlation was used to examine the relationship between DF incidence and climatic factors. Spatial clustering and hotspots of DF were examined using global Moran's I statistic and the local indicator for spatial association analysis. Classification and regression tree (CART) analysis was performed to compare and identify demographical and socio-ecological characteristics of the identified hotspots and low-risk clusters. The seasonality of DF incidence was correlated with precipitation (r=0.254, P less then 0.01), humidity (r=0.340, P less then 0.01), dipole mode index (r= -0.459, P less then 0.01) and Tmin (r= -0.181, P less then 0.05). DF incidence was spatially clustered at the village level (I=0.294, P less then 0.001) and 22 hotspots were identified with a concentration in the central and eastern parts of Jakarta. CART analysis showed that age and occupation were the most important factors explaining DF clustering. Areaspecific and population-targeted interventions are needed to improve the situation among those living in the identified DF high-risk areas in Jakarta.The transition from the control phase to elimination of malaria in China through the national malaria elimination programme has focussed attention on the need for improvement of the surveillance- response systems. It is now understood that routine passive surveillance is inadequate in the parasite elimination phase that requires supplementation by active surveillance in foci where cluster cases have occurred. This study aims to explore the spatial clusters and temporal trends of malaria cases by the multivariate auto-regressive state-space model (MARSS) along the border to Myanmar in southern China. Data for indigenous cases spanning the period from 2007 to 2010 were extracted from the China's Infectious Diseases Information Reporting Management System (IDIRMS). The best MARSS model indicated that malaria transmission in the study area during 36 months could be grouped into three clusters. The estimation of malaria transmission patterns showed a downward trend across all clusters. The proposed methodology used in this study offers a simple and rapid, yet effective way to categorize patterns of foci which provide assistance for active monitoring of malaria in the elimination phase.Bone tumours are rarely found in children and adolescents (0- 19 years old), but there are reports from some provinces in Iraq indicating possible increases in the incidence of childhood bone cancer. Since counts are very low and often zero, or near zero, we fitted zero-inflated Poisson, zero-inflated negative binomial, Poisson hurdle, and negative binomial hurdle regression models to investigate these changes. Midostaurin We used data covering the 2000-2015 period taking age, gender and province into account with the aim of identifying potential health disparities. The results indicate that the zero-inflated Poisson is the most appropriate approach. We also found that, the incidence rate ratio of bone tumours for age groups of 5-9, 10-14 and 15-19 years were 134%, 490% and 723% higher, respectively, compared to the 0-4 year olds. The incidence rate was higher by 49% higher in males compared to females. Compared to 2000-2004, the rate was higher during 2005-2009 and 2010-2015 by 23% and 50%, respectively. In addition, the provinces Al-Muthana and Al-Diwaniyah in the South were found to have a higher incidence rate than other provinces. Join point analysis showed that the age-adjusted incidence rate had a significant, increasing trend, with an average percentage change of 3.1% during 2000-2015. The study suggests that further research into childhood tumours, bone tumours in particular, is needed. Reference to the effect of environmental factors in this group of medical disorders would be of special interest.
The hyperactivated neddylation pathway plays an important role in tumorigenesis and is emerging as a promising anticancer target. We aimed to study whether NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) might serve as a therapeutic target in esophageal squamous cell carcinoma (ESCC).

The clinical relevance of NEDD8 expression was evaluated by using The Cancer Genome Atlas (TCGA) database and tissue arrays. NEDD8-knockdown ESCC cells generated with the CRISPR/Cas9 system were used to explore the anticancer effects and mechanisms. Quantitative proteomic analysis was used to examine the variations in NEDD8 knockdown-induced biological pathways. The cell cycle and apoptosis were assessed with fluorescence activated cell sorting. A subcutaneous-transplantation mouse tumor model was established to investigate the anticancer potential of NEDD8 silencing
.

NEDD8 was upregulated at both the mRNA and protein expression levels in ESCC, and NEDD8 overexpression was associated with poorer overall patient survival (mRNA level
= 0.028, protein level
= 0.026, log-rank test). Downregulation of NEDD8 significantly suppressed tumor growth both
and
. Quantitative proteomic analysis revealed that downregulation of NEDD8 induced cell cycle arrest, DNA damage, and apoptosis in ESCC cells. Mechanistic studies demonstrated that NEDD8 knockdown led to the accumulation of cullin-RING E3 ubiquitin ligases (CRLs) substrates through inactivation of CRLs, thus suppressing the malignant phenotype by inducing cell cycle arrest and apoptosis in ESCC. Rescue experiments demonstrated that the induction of apoptosis after NEDD8 silencing was attenuated by DR5 knockdown.

Our study elucidated the anti-ESCC effects and underlying mechanisms of NEDD8 knockdown, and validated NEDD8 as a potential target for ESCC therapy.
Our study elucidated the anti-ESCC effects and underlying mechanisms of NEDD8 knockdown, and validated NEDD8 as a potential target for ESCC therapy.
Realist evaluation is increasingly used in healthcare research, and theories can provide plausible explanations of why interventions work or do not work in certain circumstances such as the effect of the opt-out hepatitis C virus (HCV) testing policy in English prisons.

To present the process of constructing the middle-range theories (MRTs) developed as part of an evaluation of hepatitis C test uptake in an English prison as a resource for researchers using realist evaluation.

MRTs are propositions that can explain a particular behaviour or outcome. In this evaluation, the MRTs emerged from a realist evaluation, a theory-driven approach for understanding what interventions work, in what circumstances and how. The mixed-methods data collected during the realist evaluation and the sociological theory of prisonisation were used to create the MRTs. Combining prisonisation with the qualitative data illustrates how healthcare interventions may be viewed by people in prison who may have adopted either the 'deprivation' or 'importation' processes of adaptation to cope with their incarceration.
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