Association between investigator-measured body-mass index and colorectal adenoma: a systematic review and meta-analysis of 168,201 subjects

The objective of this meta-analysis is to evaluate the odds of colorectal adenoma (CRA) in colorectal cancer screening participants with different body mass index (BMI) levels, and examine if this association was different according to gender and ethnicity. The EMBASE and MEDLINE were searched to enroll high quality observational studies that examined the association between investigator-measured BMI and colonoscopy-diagnosed CRA. Data were independently extracted by two reviewers. A random-effects meta-analysis was conducted to estimate the summary odds ratio (SOR) for the association between BMI and CRA. The Cochran’s Q statistic and I2 analyses were used to assess the heterogeneity. A total of 17 studies (168,201 subjects) were included. When compared with subjects having BMI < 25, individuals with BMI 25–30 had significantly higher risk of CRA (SOR 1.44, 95% CI 1.30–1.61; I2 = 43.0%). Subjects with BMI ≥ 30 had similarly higher risk of CRA (SOR 1.42, 95% CI 1.24–1.63; I2 = 18.5%). The heterogeneity was mild to moderate among studies. The associations were significantly higher than estimates by previous meta-analyses. There was no publication bias detected (Egger’s regression test, p = 0.584). Subgroup analysis showed that the magnitude of association was significantly higher in female than male subjects (SOR 1.43, 95% CI 1.30–1.58 vs. SOR 1.16, 95% CI 1.07–1.24; different among different ethnic groups (SOR 1.72, 1.44 and 0.88 in White, Asians and Africans, respectively) being insignificant in Africans; and no difference exists among different study designs. In summary, the risk conferred by BMI for CRA was significantly higher than that reported previously. These findings bear implications in CRA risk estimation

The Effects of Air Pollution on Mortality in Socially Deprived Urban Areas in Hong Kong, China

Background: Poverty is a major determinant of population health, but little is known about its role in modifying air pollution effects. Objectives: We set out to examine whether people residing in socially deprived communities are at higher mortality risk from ambient air pollution. Methods: This study included 209 tertiary planning units (TPUs), the smallest units for town planning in the Special Administrative Region of Hong Kong, China. The socioeconomic status of each TPU was measured by a social deprivation index (SDI) derived from the proportions of the population with a) unemployment, b) monthly household income < US$250, c) no schooling at all, d) one-person household, e) never-married status, and f) subtenancy, from the 2001 Population Census. TPUs were classified into three levels of SDI: low, middle, and high. We performed time-series analysis with Poisson regression to examine the association between changes in daily concentrations of ambient air pollution and daily number of deaths in each SDI group for the period from January 1996 to December 2002. We evaluated the differences in pollution effects between different SDI groups using a case-only approach with logistic regression. Results: We found significant associations of nitrogen dioxide, sulfur dioxide, particulate matter with aerodynamic diameter < 10 μm, and ozone with all nonaccidental and cardiovascular mortality in areas of middle or high SDI (p < 0.05). Health outcomes, measured as all nonaccidental, cardiovascular, and respiratory mortality, in people residing in high SDI areas were more strongly associated with SO 2 and NO 2 compared with those in middle or low SDI areas. Conclusions: Neighborhood socioeconomic deprivation increases mortality risks associated with air pollution.published_or_final_versio

Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Parenting approaches and digital technology use of preschool age children in a Chinese community

Background: Young children are using digital technology (DT) devices anytime and anywhere, especially with the invention of smart phones and the replacement of desktop computers with digital tablets. Although research has shown that parents play an important role in fostering and supporting preschoolers' developing maturity and decisions about DT use, and in protecting them from potential risk due to excessive DT exposure, there have been limited studies conducted in Hong Kong focusing on parent-child DT use. This study had three objectives: 1) to explore parental use of DTs with their preschool children; 2) to identify the DT content that associated with child behavioral problems; and 3) to investigate the relationships between approaches adopted by parents to control children's DT use and related preschooler behavioral problems. Methods. This exploratory quantitative study was conducted in Hong Kong with 202 parents or guardians of preschool children between the ages of 3 and 6 attending kindergarten. The questionnaire was focused on four aspects, including 1) participants' demographics; 2) pattern of DT use; 3) parenting approach to manage the child's DT use; and 4) child behavioral and health problems related to DT use. Multiple regression analysis was adopted as the main data analysis method for identifying the DT or parental approach-related predictors of the preschooler behavioral problems. Results: In the multiple linear regression model, the 'restrictive approach score' was the only predictor among the three parental approaches (B:1.66, 95% CI: [0.21, 3.11], p < 0.05). Moreover, the viewing of antisocial behavior cartoons by children also significantly increased the tendency of children to have behavioral problem (B:3.84, 95% CI: [1.66, 6.02], p < 0.01). Conclusions: Since preschool children's cognitive and functional abilities are still in the developmental stage, parents play a crucial role in fostering appropriate and safe DT use. It is suggested that parents practice a combination of restrictive, instructive and co-using approaches, rather than a predominately restrictive approach, to facilitate their child's growth and development. Further studies are needed to explore the parent-child relationship and parents' self-efficacy when managing the parent-child DT use, to develop strategies to guide children in healthy DT use. © 2014 WU et al.; licensee BioMed Central Ltd.Link_to_subscribed_fulltex

Radiomics from Various Tumour Volume Sizes for Prognosis Prediction of Head and Neck Squamous Cell Carcinoma: A Voted Ensemble Machine Learning Approach

Background: Traditionally, cancer prognosis was determined by tumours size, lymph node spread and presence of metastasis (TNM staging). Radiomics of tumour volume has recently been used for prognosis prediction. In the present study, we evaluated the effect of various sizes of tumour volume. A voted ensemble approach with a combination of multiple machine learning algorithms is proposed for prognosis prediction for head and neck squamous cell carcinoma (HNSCC). Methods: A total of 215 HNSCC CT image sets with radiotherapy structure sets were acquired from The Cancer Imaging Archive (TCIA). Six tumour volumes, including gross tumour volume (GTV), diminished GTV, extended GTV, planning target volume (PTV), diminished PTV and extended PTV were delineated. The extracted radiomics features were analysed by decision tree, random forest, extreme boost, support vector machine and generalized linear algorithms. A voted ensemble machine learning (VEML) model that optimizes the above algorithms was used. The receiver operating characteristic area under the curve (ROC-AUC) were used to compare the performance of machine learning methods, including accuracy, sensitivity and specificity. Results: The VEML model demonstrated good prognosis prediction ability for all sizes of tumour volumes with reference to GTV and PTV with high accuracy of up to 88.3%, sensitivity of up to 79.9% and specificity of up to 96.6%. There was no significant difference between the various target volumes for the prognostic prediction of HNSCC patients (chi-square test, p > 0.05). Conclusions: Our study demonstrates that the proposed VEML model can accurately predict the prognosis of HNSCC patients using radiomics features from various tumour volumes

Suppression of cGAS- and RIG-I-mediated innate immune signaling by Epstein-Barr virus deubiquitinase BPLF1.

Epstein-Barr virus (EBV) has developed effective strategies to evade host innate immune responses. Here we reported on mitigation of type I interferon (IFN) production by EBV deubiquitinase (DUB) BPLF1 through cGAS-STING and RIG-I-MAVS pathways. The two naturally occurring forms of BPLF1 exerted potent suppressive effect on cGAS-STING-, RIG-I- and TBK1-induced IFN production. The observed suppression was reversed when DUB domain of BPLF1 was rendered catalytically inactive. The DUB activity of BPLF1 also facilitated EBV infection by counteracting cGAS-STING- and TBK1-mediated antiviral defense. BPLF1 associated with STING to act as an effective DUB targeting its K63-, K48- and K27-linked ubiquitin moieties. BPLF1 also catalyzed removal of K63- and K48-linked ubiquitin chains on TBK1 kinase. The DUB activity of BPLF1 was required for its suppression of TBK1-induced IRF3 dimerization. Importantly, in cells stably carrying EBV genome that encodes a catalytically inactive BPLF1, the virus failed to suppress type I IFN production upon activation of cGAS and STING. This study demonstrated IFN antagonism of BPLF1 mediated through DUB-dependent deubiquitination of STING and TBK1 leading to suppression of cGAS-STING and RIG-I-MAVS signaling

Alternative splicing modulation by G-quadruplexes.

Alternative splicing is central to metazoan gene regulation, but the regulatory mechanisms are incompletely understood. Here, we show that G-quadruplex (G4) motifs are enriched ~3-fold near splice junctions. The importance of G4s in RNA is emphasised by a higher enrichment for the non-template strand. RNA-seq data from mouse and human neurons reveals an enrichment of G4s at exons that were skipped following depolarisation induced by potassium chloride. We validate the formation of stable RNA G4s for three candidate splice sites by circular dichroism spectroscopy, UV-melting and fluorescence measurements. Moreover, we find that sQTLs are enriched at G4s, and a minigene experiment provides further support for their role in promoting exon inclusion. Analysis of >1,800 high-throughput experiments reveals multiple RNA binding proteins associated with G4s. Finally, exploration of G4 motifs across eleven species shows strong enrichment at splice sites in mammals and birds, suggesting an evolutionary conserved splice regulatory mechanism

RNA G-Quadruplex Structures Mediate Gene Regulation in Bacteria

G-quadruplex in RNA (rG4) mediates various biological functions and cellular processes in eukaryotic organisms. However, the presence, locations, and functions of rG4 are still elusive in prokaryotes. Here, we found that rG4 is an abundant RNA secondary structure across a wide range of bacterial species. Subsequently, the transcriptome-wide rG4 structure sequencing (rG4-seq) revealed that the model E. coli strain and a major human pathogen, P. aeruginosa, have 168 and 161 in vitro rG4 sites, respectively, involved in virulence, gene regulation, cell envelope, and metabolism. We further verified the regulatory functions of two rG4 sites in bacteria (hemL and bswR). Overall, this finding strongly suggests that rG4s play key regulatory roles in a wide range of bacterial species.Guanine (G)-rich sequences in RNA can fold into diverse RNA G-quadruplex (rG4) structures to mediate various biological functions and cellular processes in eukaryotic organisms. However, the presence, locations, and functions of rG4s in prokaryotes are still elusive. We used QUMA-1, an rG4-specific fluorescent probe, to detect rG4 structures in a wide range of bacterial species both in vitro and in live cells and found rG4 to be an abundant RNA secondary structure across those species. Subsequently, to identify bacterial rG4 sites in the transcriptome, the model Escherichia coli strain and a major human pathogen, Pseudomonas aeruginosa, were subjected to recently developed high-throughput rG4 structure sequencing (rG4-seq). In total, 168 and 161 in vitro rG4 sites were found in E. coli and P. aeruginosa, respectively. Genes carrying these rG4 sites were found to be involved in virulence, gene regulation, cell envelope synthesis, and metabolism. More importantly, biophysical assays revealed the formation of a group of rG4 sites in mRNAs (such as hemL and bswR), and they were functionally validated in cells by genetic (point mutation and lux reporter assays) and phenotypic experiments, providing substantial evidence for the formation and function of rG4s in bacteria. Overall, our study uncovers important regulatory functions of rG4s in bacterial pathogenicity and metabolic pathways and strongly suggests that rG4s exist and can be detected in a wide range of bacterial species