TP53 structure-function relationships in metastatic castrate-sensitive prostate cancer and the impact of APR-246 treatment.

PURPOSE: Despite well-informed work in several malignancies, the phenotypic effects of TP53 mutations in metastatic castration-sensitive prostate cancer (mCSPC) progression and metastasis are not clear. We characterized the structure-function and clinical impact of TP53 mutations in mCSPC. PATIENTS AND METHODS: We performed an international retrospective review of men with mCSPC who underwent next-generation sequencing and were stratified according to TP53 mutational status and metastatic burden. Clinical outcomes included radiographic progression-free survival (rPFS) and overall survival (OS) evaluated with Kaplan-Meier and multivariable Cox regression. We also utilized isogenic cancer cell lines to assess the effect of TP53 mutations and APR-246 treatment on migration, invasion, colony formation in vitro, and tumor growth in vivo. Preclinical experimental observations were compared using t-tests and ANOVA. RESULTS: Dominant-negative (DN) TP53 mutations were enriched in patients with synchronous (vs. metachronous) (20.7% vs. 6.3%, p < 0.01) and polymetastatic (vs. oligometastatic) (14.4% vs. 7.9%, p < 0.01) disease. On multivariable analysis, DN mutations were associated with worse rPFS (hazards ratio [HR] = 1.97, 95% confidence interval [CI]: 1.31-2.98) and overall survival [OS] (HR = 2.05, 95% CI: 1.14-3.68) compared to TP53 wild type (WT). In vitro, 22Rv1 TP53 R175H cells possessed stronger migration, invasion, colony formation ability, and cellular movement pathway enrichment in RNA sequencing analysis compared to 22Rv1 TP53 WT cells. Treatment with APR-246 reversed the effects of TP53 mutations in vitro and inhibited 22Rv1 TP53 R175H tumor growth in vivo in a dosage-dependent manner. CONCLUSIONS: DN TP53 mutations correlated with worse prognosis in prostate cancer patients and higher metastatic potential, which could be counteracted by APR-246 treatment suggesting a potential future therapeutic avenue.

Genetically predicted dietary intake and risks of colorectal cancer: a Mendelian randomisation study.

BACKGROUND: Effects of confounders on associations between diet and colorectal cancer (CRC) in observational studies can be minimized in Mendelian randomization (MR) approach. This study aimed to investigate observational and genetically predicted associations between dietary intake and CRC using one-sample MR. METHODS: Using genetic data of over 93 million variants, we performed a genome-wide association study to find genomic risk loci associated with dietary intake in participants from the UK Biobank. Then we calculated genetic risk scores of diet-related variants and used them as instrumental variables in the two-stage least square MR framework to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations. We also performed observational analyses using age as a time-scale in Cox proportional hazard models. RESULTS: Allele scores were calculated from 399 genetic variants associated with the consumption of of red meat, processed meat, poultry, fish, milk, cheese, fruits, vegetables, coffee, tea, and alcohol in participants from the UK Biobank. In MR analysis, genetically predicted fruit intake was significantly associated with a 21% decreased risk of CRC (HR = 0.79, 95% CI = 0.66-0.95), and there was a marginally inverse association between vegetable intake and CRC (HR = 0.85, 95% CI = 0.71-1.02). However, null findings were observed in multivariable analysis, with HRs (95% CIs) of 0.99 (0.98-1.01) and 0.99 (0.98-1.00) per increment of daily servings of fruits and vegetables, respectively. CONCLUSION: Dietary habits were attributable to genetic variations, which can be used as instrumental variables in the MR framework. Our study supported a causal relationship between fruit intake and a decreased risk of CRC and suggested an effective strategy of consuming fruits in the primary prevention of CRC.

Effects of mixed traffic flow and time pressure on violated driving behaviors of bus drivers.

This study aimed to examine the effects of mixed traffic flow (MTF) environments with time pressure (TP) on violated driving behaviours (VDBs) of bus drivers. A questionnaire-based survey was conducted among bus drivers. Factor analyses, partial correlation and linear regression analyses were utilised to explore the associations among VDB, MTF and TP. Our results proposed two novel measurements of MTF and TP and one modified VDB scale. Bus drivers who perceived a higher presence of motorcycles and more dangerous interactions among vehicles were less likely to participate in VDB. Those who perceived motorcyclists as aggressive, road users' traffic habits as unsafe, and bus routes' punctuality and organisation as very strict were more likely to engage in VDB. The predictive models indicated a higher influence of MTF and TP on VDB among bus drivers involved in an accident over the last 3 years compared to other groups.

This study explores the impact of MTF environments with TP on bus drivers' VDB. Questionnaire surveys were conducted to investigate bus drivers' VDB and their perceptions of MTF and TP. The results indicate that MTF conditions discourage bus drivers' VDB. Conversely, road users' unsafe traffic habits, aggressive driving behaviours and TP encourage bus drivers' VDB.

Dysbiotic microbiome variation in colorectal cancer patients is linked to lifestyles and metabolic diseases.

BACKGROUND: Differences in the composition and diversity of the gut microbial communities among individuals are influenced by environmental factors. However, there is limited research on factors affecting microbiome variation in colorectal cancer patients, who display lower inter-individual variations than that of healthy individuals. In this study, we examined the association between modifiable factors and the microbiome variation in colorectal cancer patients. METHODS: A total of 331 colorectal cancer patients who underwent resection surgery at the Department of Surgery, Seoul National University Hospital between October 2017 and August 2019 were included. Fecal samples from colorectal cancer patients were collected prior to the surgery. Variations in the gut microbiome among patients with different lifestyles and metabolic diseases were examined through the network analysis of inter-connected microbial abundance, the assessment of the Anna Karenina principle effect for microbial stochasticity, and the identification of the enriched bacteria using linear discrimination analysis effect size. Associations of dietary diversity with microbiome variation were investigated using the Procrustes analysis. RESULTS: We found stronger network connectivity of microbial communities in non-smokers, non-drinkers, obese individuals, hypertensive subjects, and individuals without diabetes than in their counterparts. The Anna Karenina principle effect was found for history of smoking, alcohol consumption, and diabetes (with significantly greater intra-sample similarity index), whereas obesity and hypertension showed the anti-Anna Karenina principle effect (with significantly lower intra-sample similarity index). We found certain bacterial taxa to be significantly enriched in patients of different categories of lifestyles and metabolic diseases using linear discrimination analysis. Diversity of food and nutrient intake did not shape the microbial diversity between individuals (pProcrustes>0.05). CONCLUSIONS: Our findings suggested an immune dysregulation and a reduced ability of the host and its microbiome in regulating the community composition. History of smoking, alcohol consumption, and diabetes were shown to affect partial individuals in shifting new microbial communities, whereas obesity and history of hypertension appeared to affect majority of individuals and shifted to drastic reductions in microbial compositions. Understanding the contribution of modifiable factors to microbial stochasticity may provide insights into how the microbiome regulates effects of these factors on the health outcomes of colorectal cancer patients.

Assessments of dietary intake and polygenic risk score in associations with colorectal cancer risk: evidence from the UK Biobank.

BACKGROUND: This study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk. METHODS: We analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term. RESULTS: During a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05-1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18-1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HRT3vsT1 = 2.12, 95% CI = 1.97-2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08-1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00-1.19 for low vs. high WCRF dietary scores). CONCLUSION: Dietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk.

Facile preparation of porphyrin@g-C3N4/Ag nanocomposite for improved photocatalytic degradation of organic dyes in aqueous solution.

In the quest of improving the photocatalytic efficiency of photocatalysts, the combination of two and more semiconductors recently has garnered significant attention among scientists in the field. The doping of conductive metals is also an effective pathway to improve photocatalytic performance by avoiding electron/hole pair recombination and enhancing photon energy absorption. This work presented a design and fabrication of porphyrin@g-C3N4/Ag nanocomposite using acid-base neutralization-induced self-assembly approach from monomeric porphyrin and g-C3N4/Ag material. g-C3N4/Ag material was synthesized by a green reductant of Cleistocalyx operculatus leaf extract. Electron scanning microscopy (SEM), X-ray diffraction (XRD), FT-IR spectroscopy, and UV-vis spectrometer were utilized to analyse the properties of the prepared materials. The prepared porphyrin@g-C3N4/Ag nanocomposite showed well integration of porphyrin nanostructures on the g-C3N4/Ag's surface, in which porphyrin nanofiber was of the diameter in nanoscales and the length of several micrometers, and Ag NPs had an average particle size of less than 20 nm. The photocatalytic behavior of the resultant nanocomposite was tested for the degradation of Rhodamine B dye, which exhibited a remarkable RhB photodegrading percentage. The possible mechanism for photocatalysis of the porphyrin@g-C3N4/Ag nanocomposite toward Rhodamine B dye was also proposed and discussed.

Nutrition-wide association study of microbiome diversity and composition in colorectal cancer patients.

BACKGROUND: The effects of diet on the interaction between microbes and host health have been widely studied. However, its effects on the gut microbiota of patients with colorectal cancer (CRC) have not been elucidated. This study aimed to investigate the association between diet and the overall diversity and different taxa levels of the gut microbiota in CRC patients via the nutrition-wide association approach. METHODS: This hospital-based study utilized data of 115 CRC patients who underwent CRC surgery in Department of Surgery, Seoul National University Hospital. Spearman correlation analyses were conducted for 216 dietary features and three alpha-diversity indices, Firmicutes/Bacteroidetes ratio, and relative abundance of 439 gut microbial taxonomy. To identify main enterotypes of the gut microbiota, we performed the principal coordinate analysis based on the ß-diversity index. Finally, we performed linear regression to examine the association between dietary intake and main microbiome features, and linear discriminant analysis effect size (LEfSe) to identify bacterial taxa phylogenetically enriched in the low and high diet consumption groups. RESULTS: Several bacteria were enriched in patients with higher consumption of mature pumpkin/pumpkin juice (ρ, 0.31 to 0.41) but lower intake of eggs (ρ, -0.32 to -0.26). We observed negative correlations between Bacteroides fragilis abundance and intake of pork (belly), beef soup with vegetables, animal fat, and fatty acids (ρ, -0.34 to -0.27); an inverse correlation was also observed between Clostridium symbiosum abundance and intake of some fatty acids, amines, and amino acids (ρ, -0.30 to -0.24). Furthermore, high intake of seaweed was associated with a 6% (95% CI, 2% to 11%) and 7% (95% CI, 2% to 11%) lower abundance of Rikenellaceae and Alistipes, respectively, whereas overall beverage consumption was associated with an 10% (95% CI, 2% to 18%) higher abundance of Bacteroidetes, Bacteroidia, and Bacteroidales, compared to that in the low intake group. LEfSe analysis identified phylogenetically enriched taxa associated with the intake of sugars and sweets, legumes, mushrooms, eggs, oils and fats, plant fat, carbohydrates, and monounsaturated fatty acids. CONCLUSIONS: Our data elucidates the diet-microbe interactions in CRC patients. Additional research is needed to understand the significance of these results in CRC prognosis.

Association between dietary intake networks identified through a Gaussian graphical model and the risk of cancer: a prospective cohort study.

PURPOSE: In this study, we aimed to investigate the association between dietary communities identified by a Gaussian graphical model (GGM) and cancer risk. METHODS: We performed GGM to identify the dietary communities in a Korean population. GGM-derived communities were then scored and investigated for their association with cancer incidence in the entire population as well as in the 1:1 age- and sex-matched subgroup using a Cox proportional hazards model. In the sensitivity analysis, GGM-derived communities were compared to dietary patterns (DPs) that were identified by principal component analysis (PCA) and reduced rank regression (RRR). RESULTS: During a median time to follow-up of 6.6 years, 397 cancer cases were newly diagnosed. The GGM identified 17 and 16 dietary communities for the total and matched populations, respectively. For each one-unit increase in the standard deviation of the community-specific score of the community that was composed of dairy products and bread, there was a reduced risk of cancer according to the fully adjusted model (HR: 0.80, 95% CI: 0.66-0.96). In the matched population, the third tertile of the community-specific score of the community composed of poultry, seafood, bread, cakes and sweets, and meat by-products showed a significantly reduced risk of cancer compared to that of the lowest tertile in the fully adjusted model (HR: 0.66, 95% CI: 0.50-0.86, p-trend = 0.002). CONCLUSION: We found that the GGM-identified community composed of dairy products and bread showed a reduced risk of cancer. Further population-based prospective studies should be conducted to examine possible associations of dietary intake and specific cancer types.

A Lesson Learnt from a Dural Carotid Cavernous Fistula-induced Superior Ophthalmic Vein Occlusion with Posterior Ischaemic Optic Neuropathy.

We report a 64-year-old male patient without any contributory medical history who visited the eye clinic due to right-sided headache for 1 month and then loss of vision for 3 days. The clinical presentation suggested a cavernous sinus syndrome and acute optic nerve ischaemia in his right eye. The left eye was normal. Orbit and brain magnetic resonance (MR) imaging demonstrated restricted diffusion of the posterior orbital segment of the right optic nerve, suggesting an acute posterior ischaemic optic neuropathy. Three-dimensional time-of-flight MR angiography showed high flow in the right cavernous sinus, indicating a carotid cavernous fistula (CCF). In the arterial phase of digital subtraction angiography (DSA), a fistula in the right cavernous sinus was revealed which was fed by meningeal branches from both the external and internal carotid arteries, confirming an indirect CCF. The origin of the right ophthalmic artery was seen, but its branches were not detected. Right common carotid artery DSA showed a superior ophthalmic vein occlusion and the drainage vein of the CCF ran through the inferior petrosal sinus to the internal jugular vein. The right cavernous sinus was embolised using platinum coils and glue to occlude the feeding vessels from the branches of both the external and internal carotid arteries. Post-embolisation imaging showed complete closure of the fistula.

Night shift work and breast cancer risk: a meta-analysis of observational epidemiological studies.

Previous observational epidemiological studies have reported inconsistently the association between night shift work (NSW) and the risk of breast cancer (BC). This study aimed to investigate those associations by using a meta-analysis of observational epidemiological studies. We searched PubMed and EMBASE using keywords related to this topic from inception till November 2020. The pooled effect sizes such as odds ratio (OR), hazard ratio (HR) or relative risk (RR) with 95% confidence interval (CI) were calculated using a random-effects model. In the meta-analysis of a total of 32 observational studies including 13 case-control studies, 4 nested case-control studies and 15 cohort studies, NSW significantly increased the risk of BC (OR/RR/HR, 1.11; 95% CI, 1.04-1.20; I2 = 72.4%). In the subgroup meta-analysis by type of study, NSW was also associated with the increased risk of BC in case-control studies (OR, 1.34; 95% CI, 1.17-1.53; I2 = 63.8%). However, no significant association was found in both nested case-control studies (OR, 1.14; 95% CI, 0.89-1.46; I2 = 65.8%) and cohort studies (RR/HR, 0.98; 95% CI, 0.93-1.03; I2 = 25.3%). Besides, there was no significant association between NSW for over 20 years and the risk of BC (OR/RR/HR, 1.03; 95% CI, 0.95-1.11; I2 = 36.6%, n = 14). Given that cohort studies provide higher evidence than case-control studies, there is no association between NSW and the risk of BC.

Systematic review and meta-analysis of factors associated with re-positive viral RNA after recovery from COVID-19.

Previous studies reported the positive viral RNA among coronavirus disease-2019 (COVID-19) recovered patients. This study aimed to summarize the current evidence of factors associated with the risk of disease recurrence. PubMed and Embase were searched until September 2020 to identify studies assessing characteristics of recurrence and nonrecurrence subjects after discharge. Random-effect meta-analysis was used to pool estimates of odds ratio (OR) or weighted mean difference (WMD) and their 95% confidence intervals (CIs) across studies. Meta-analysis data were available for age, sex, hospital duration, disease severity, seven comorbidities, five symptoms, five indexes of blood routine, nine indexes of blood biochemistry, four treatment therapies, two antibodies, and history of high-risk contact. Among them, hospital duration of recurrence cases was significantly shorter than nonrecurrence subjects (WMD, -1.55 days; 95% CI, -2.66 to -0.45). Fatigue, positive Immunoglobulin M (IgM), and positive IgG were associated with an increased risk of recurrence cases, with ORs and 95% CIs of 4.06 (1.14-14.4), 2.95 (1.15-7.61), and 3.45 (1.58-7.54), respectively. In contrast, the odds of recurrence cases were observed to significantly lower in subjects with elevated lactate dehydrogenase and C-reactive protein, low lymphocyte count, steroid and arbidol use, with ORs (95% CIs) of 1.08 (0.27-4.37), 0.49 (0.27-0.97), 0.64 (0.42-0.97), 0.48 (0.25-0.96), and 0.48 (0.25-0.92), respectively. This study provided up-to-date evidence of several clinical and epidemiological characteristics in the association with COVID-19 recurrence cases. Further in-depth analyses for the causal effect of factors on re-positive viral RNA are needed for the management of discharged patients with COVID-19.

Ambient air pollution, meteorology, and COVID-19 infection in Korea.

The outbreak of novel pneumonia coronavirus disease has become a public health concern worldwide. Here, for the first time, the association between Korean meteorological factors and air pollutants and the COVID-19 infection was investigated. Data of air pollutants, meteorological factors, and daily COVID-19 confirmed cases of seven metropolitan cities and nine provinces were obtained from 3 February 2020 to 5 May 2020 during the first wave of pandemic across Korea. We applied the generalized additive model to investigate the temporal relationship. There was a significantly nonlinear association between daily temperature and COVID-19 confirmed cases. Each 1°C increase in temperature was associated with 9% (lag 0-14; OR = 1.09; 95% CI = 1.03-1.15) increase of COVID-19 confirmed cases when the temperature was below 8°C. A 0.01 ppm increase in NO2 (lag 0-7, lag 0.14, and lag 0-21) was significantly associated with increases of COVID-19 confirmed cases, with ORs (95% CIs) of 1.13 (1.02-1.25), 1.19 (1.09-1.30), and 1.30 (1.19-1.41), respectively. A 0.1 ppm increase in CO (lag 0-21) was associated with the increase in COVID-19 confirmed cases (OR = 1.10, 95% CI = 1.04-1.16). There was a positive association between per 0.001 ppm of SO2 concentration (lag 0, lag 0-7, and lag 0-14) and COVID-19 confirmed cases, with ORs (95% CIs) of 1.13 (1.04-1.22), 1.20 (1.11-1.31), and 1.15 (1.07-1.25), respectively. There were significantly temporal associations between temperature, NO2 , CO, and SO2 concentrations and daily COVID-19 confirmed cases in Korea.

Short-term exposure to ambient air pollution in association with COVID-19 of two clusters in South Korea.

OBJECTIVES: This study aimed to examine the association between six air pollutants and COVID-19 infection in two main clusters, which accounted for 83% of total confirmed cases in Korea. METHODS: We collected the data on daily confirmed cases between February 24, 2020 and September 12, 2020. Data on six air pollutants (PM2.5 , PM10 , O3 , NO2 , CO and SO2 ) and four meteorological factors (temperature, wind speed, humidity and air pressure) were obtained on seven days prior to the research period. The generalised additive model and the distributed lag nonlinear model were applied to generate the relative risks (RRs) and 95% confidence intervals (CIs) for the associations. Pooled estimates for clusters were obtained by applying a random-effects model. RESULTS: We found that NO2 concentration was positively associated with daily confirmed cases in both Seoul-Gyeonggi and Daegu-Gyeongbuk clusters, with RRs (95% CIs) of 1.22 (1.03-1.44) and 1.66 (1.25-2.19), respectively. However, SO2 concentration was observed to be associated with daily confirmed cases in the Seoul-Gyeonggi cluster only (RR = 1.30, 95% CI = 1.10-1.54), whereas PM2.5 and CO concentrations were observed to be associated with daily confirmed cases in the Daegu-Gyeongbuk cluster only (RR = 1.14, 95% CI = 1.02-1.27 and RR = 1.30, 95% CI = 1.15-1.48, respectively). CONCLUSIONS: Our data found that NO2 concentration was positively associated with daily confirmed cases in both clusters, whereas the effect of PM2.5 , CO and SO2 on COVID-19 infection in two clusters was different.

Acute Complete Oculomotor Nerve Palsy in a Young Male Due to a Skull Base Myofibroma.

ABSTRACT: A 25-year-old male patient visited the ophthalmology clinic because of upper eye lid ptosis in the right eye, binocular double vision, and light sensitivity. He was diagnosed with a complete third nerve palsy caused by a skull base myofibroma, a rare clinical entity that has not been described before in oculomotor nerve palsy.

Phytonutrient supplements and metabolic biomarkers of cardiovascular disease: An umbrella review of meta-analyses of clinical trials.

Phytonutrients exert several pharmacological effects on humans. In this study, we performed an umbrella review of the association of phytonutrient supplements (PNSs) with biomarkers of cardiovascular disease. Relevant published systematic reviews and meta-analyses of clinical trials were identified by searching PubMed, Embase, and Cochrane Library until July 4, 2020. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) for summarized effects and I2 statistics of heterogeneity were extracted from individual studies or reanalyzed using a random-effects model. Of the 50 included studies, pooled effects of PNSs on blood pressure, lipid profiles, and glycemic control were reported in 16, 25, and 14 articles, respectively. The findings appeared to be highly heterogeneous among individual trials of included systematic reviews and meta-analyses. Ginger (WMD = -6.36 mmHg, 95% CI = -11.27, -1.46) and Hibiscus sabdariffa (WMD = -7.58 mmHg, 95% CI = -9.69, -5.46) were associated with lowered systolic blood pressure, whereas Aloe vera, Nigella sativa, and spirulina were associated with beneficial effects on both lipid profiles and glycemic control. In summary, this umbrella review has provided up-to-date evidence for the effect of PNSs on biomarkers related to hypertension, dyslipidemia, and diabetes. The results must be interpreted with caution due to potential heterogeneity.

Splice sites detection using chaos game representation and neural network.

A novel method is proposed to detect the acceptor and donor splice sites using chaos game representation and artificial neural network. In order to achieve high accuracy, inputs to the neural network, or feature vector, shall reflect the true nature of the DNA segments. Therefore it is important to have one-to-one numerical representation, i.e. a feature vector should be able to represent the original data. Chaos game representation (CGR) is an iterative mapping technique that assigns each nucleotide in a DNA sequence to a respective position on the plane in a one-to-one manner. Using CGR, a DNA sequence can be mapped to a numerical sequence that reflects the true nature of the original sequence. In this research, we propose to use CGR as feature input to a neural network to detect splice sites on the NN269 dataset. Computational experiments indicate that this approach gives good accuracy while being simpler than other methods in the literature, with only one neural network component. The code and data for our method can be accessed from this link: https://github.com/thoang3/portfolio/tree/SpliceSites_ANN_CGR.

Gynecological cancer and omega-3 fatty acid intakes: Meta-analysis.

BACKGROUND AND OBJECTIVES: Previous observational epidemiological studies have reported inconsistent findings on the association between dietary intake of omega-3 fatty acids and endocrine-related gynecological cancer including ovarian cancer and endometrial cancer. This study aimed to investigate this association using a metaanalysis of observational studies. METHODS AND STUDY DESIGN: We searched PubMed, EMBASE, and Cochrane library by using keywords related to the topic in December 2019. The pooled odd ratios (pORs), pooled relative risks (pRRs), or pooled hazard ratios (pHRs) with 95% confidence intervals (CIs) were calculated based on a random- effects model. Also, we performed subgroup analyses by methodological quality, type of cancer, study design, and type of omega-3 fatty acids. RESULTS: A total of 10 observational studies with six case-control and four prospective cohort studies were included in the current meta-analysis. In the meta-analysis of all studies, dietary intake of omega-3 fatty acids was not significantly associated with the risk of endometrial and ovarian cancers (pOR/HR, 0.87; 95% CI, 0.73-1.04; I2=67.2%) (highest versus lowest intake). In the subgroup analysis by type of study, no significant association was found in cohort studies (pHR, 1.03; 95% CI, 0.63-1.67, I2=81.9%), whereas dietary intake of omega-3 fatty acids was associated with the decreased risk of endocrine-related gynecological cancers in case-control studies (pOR, 0.81; 95% CI, 0.67 to 0.98, I2=55.7%). CONCLUSIONS: The current metaanalysis of observational studies suggests that dietary intake of omega-3 fatty acids is not significantly associated with the risk of endocrine-related gynecological cancer.

Determination of picomolar levels of methylmercury complexes with low molecular mass thiols by liquid chromatography tandem mass spectrometry and online preconcentration.

Methylmercury (MeHg) is one of the most potent neurotoxins. It is produced in nature through the methylation of inorganic divalent mercury (HgII) by phylogenetically diverse anaerobic microbes. The mechanistic understanding of the processes that govern the extent of bacterial export of MeHg, its bioaccumulation, and bio-toxicity depends on accurate quantification of its species, especially its complexation with low molecular mass thiols; organometallic complexes that are difficult to detect and measure in natural conditions. Here, we report the development of a novel analytical method based on liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine 13 MeHg complexes with important thiol compounds which have been observed in the environment and in biological systems. By using online preconcentration via solid phase extraction (SPE), the method offers picomolar (12-530 pM) detection limits, the lowest reported so far for the determination of MeHg compounds. Among three different SPE materials, a weak cation exchange phase showed the best efficiency at a low pH of 2.5. We further report the presence of MeHg-cysteine, MeHg-cysteamine, MeHg-penicillamine, MeHg-cysteinylglycine, and MeHg-glutamylcysteine as the predominant MeHg-thiol complexes in the extracellular milieu of an important HgII methylating bacterium, Geobacter sulfurreducens PCA, exposed to 100 nM of HgII.

Parameterized optical properties of InxAl1-xP alloys.

We report values of parametric-model (PM) parameters that can be used to obtain dielectric functions (refractive indices) from 1.5 to 6.0 eV for ${{\rm In}_x}{{\rm Al}_{1 - x}}{\rm P}$InxAl1-xP alloys of arbitrary compositions $x$x. Using reported pseudo-dielectric data for several In compositions, we extract their dielectric functions by multilayer calculations, then parameterize them with PM lineshapes that well describe the asymmetric nature of their critical point (CP) contributions. We follow the ${E_0}$E0 fundamental bandgap as a function of $x$x, and determine the composition of the indirect-to-direct crossover.

Novel dual regulators of Pseudomonas aeruginosa essential for productive biofilms and virulence.

Gene regulation network in Pseudomonas aeruginosa is complex. With a relatively large genome (6.2 Mb), there is a significant portion of genes that are proven or predicted to be transcriptional regulators. Many of these regulators have been shown to play important roles in biofilm formation and maintenance. In this study, we present a novel transcriptional regulator, PA1226, which modulates biofilm formation and virulence in P. aeruginosa. Mutation in the gene encoding this regulator abolished the ability of P. aeruginosa to produce biofilms in vitro, without any effect on the planktonic growth. This regulator is also essential for the in vivo fitness and pathogenesis in both Drosophila melanogaster and BALB/c mouse lung infection models. Transcriptome analysis revealed that PA1226 regulates many essential virulence genes/pathways, including those involved in alginate, pili, and LPS biosynthesis. Genes/operons directly regulated by PA1226 and potential binding sequences were identified via ChIP-seq. Attempts to confirm the binding sequences by electrophoretic mobility shift assay led to the discovery of a co-regulator, PA1413, via co-immunoprecipitation assay. PA1226 and PA1413 were shown to bind collaboratively to the promoter regions of their regulons. A model is proposed, summarizing our finding on this novel dual-regulation system.