Bayesian inference for a semi-parametric copula-based Markov chain

This paper presents a method to specify a strictly stationary univariate time series model with particular emphasis on the marginal characteristics (fat tailedness, skewness etc.). It is the first time in time series models with specified marginal distribution, a non-parametric specification is used. Through a Copula distribution, the marginal aspect are separated and the information contained within the order statistics allow to efficiently model a discretely-varied time series. The estimation is done through Bayesian method. The method is invariant to any copula family and for any level of heterogeneity in the random variable. Using count times series of weekly rearm homicides in Cape Town, South Africa, we show our method efficiently estimates the copula parameter representing the first-order Markov chain transition density

Vitamin E δ-tocotrienol Sensitizes Human Pancreatic Cancer Cells to TRAIL-induced Apoptosis Through Proteasome-Mediated Down-Regulation of c-FLIP

Background: Vitamin E δ-tocotrienol (VEDT), a vitamin E compound isolated from sources such as palm fruit and annatto beans, has been reported to have cancer chemopreventive and therapeutic effects. Methods: We report a novel function of VEDT in augmenting tumor necrosis factor-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis in pancreatic cancer cells. The effects of VEDT were shown by its ability to trigger caspase-8-dependent apoptosis in pancreatic cancer cells. Results: When combined with TRAIL, VEDT significantly augmented TRAIL-induced apoptosis of pancreatic cancer cells. VEDT decreased cellular FLICE inhibitory protein (c-FLIP) levels without consistently modulating the expression of decoy death receptors 1, 2, 3 or death receptors 4 and 5. Enforced expression of c-FLIP substantially attenuated VEDT/TRAIL-induced apoptosis. Thus, c-FLIP reduction plays an important part in mediating VEDT/TRAIL-induced apoptosis. Moreover, VEDT increased c-FLIP ubiquitination and degradation but did not affect its transcription, suggesting that VEDT decreases c-FLIP levels through promoting its degradation. Of note, degradation of c-FLIP and enhanced TRAIL-induced apoptosis in pancreatic cancer cells were observed only with the anticancer bioactive vitamin E compounds δ-, γ-, and β-tocotrienol but not with the anticancer inactive vitamin E compounds α-tocotrienol and α-, β-, γ-, and δ-tocopherol. Conclusions: c-FLIP degradation is a key event for death receptor-induced apoptosis by anticancer bioactive vitamin E compounds in pancreatic cancer cells. Moreover, VEDT augmented TRAIL inhibition of pancreatic tumor growth and induction of apoptosis in vivo. Combination therapy with TRAIL agonists and bioactive vitamin E compounds may offer a novel strategy for pancreatic cancer intervention

Axial Globe Position Measurement: A Prospective Multicenter Study by the International Thyroid Eye Disease Society

Identify a reproducible measure of axial globe position (AGP) for multicenter studies on patients with thyroid eye disease (TED)

Multi-Omic Data Interpretation to Repurpose Subtype Specific Drug Candidates for Breast Cancer

Triple-negative breast cancer (TNBC), which is largely synonymous with the basal-like molecular subtype, is the 5th leading cause of cancer deaths for women in the United States. The overall prognosis for TNBC patients remains poor given that few treatment options exist; including targeted therapies (not FDA approved), and multi-agent chemotherapy as standard-of-care treatment. TNBC like other complex diseases is governed by the perturbations of the complex interaction networks thereby elucidating the underlying molecular mechanisms of this disease in the context of network principles, which have the potential to identify targets for drug development. Here, we present an integrated “omics” approach based on the use of transcriptome and interactome data to identify dynamic/active protein-protein interaction networks (PPINs) in TNBC patients. We have identified three highly connected modules, EED, DHX9, and AURKA, which are extremely activated in TNBC tumors compared to both normal tissues and other breast cancer subtypes. Based on the functional analyses, we propose that these modules are potential drivers of proliferation and, as such, should be considered candidate molecular targets for drug development or drug repositioning in TNBC. Consistent with this argument, we repurposed steroids, anti-inflammatory agents, anti-infective agents, cardiovascular agents for patients with basal-like breast cancer. Finally, we have performed essential metabolite analysis on personalized genome-scale metabolic models and found that metabolites such as sphingosine-1-phosphate and cholesterol-sulfate have utmost importance in TNBC tumor growth

Patterns of tobacco use in the United Arab Emirates healthy future (UAEHFS) pilot study

© 2018 Al-Houqani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Self-reported tobacco use in the United Arab Emirates is among the highest in the region. Use of tobacco products other than cigarettes is widespread, but little is known about specific behavior use patterns. There have been no studies that have biochemically verified smoking status. Methods The UAE Healthy Future Study (UAEHFS) seeks to understand the causes of non-communicable diseases through a 20,000-person cohort study. During the study pilot, 517 Emirati nationals were recruited to complete a questionnaire, provide clinical measurements and biological samples. Complete smoking data were available for 428 participants. Validation of smoking status via cotinine testing was conducted based on complete questionnaire data and matching urine samples for 399 participants, using a cut-off of 200ng/ml to indicate active smoking status. Results Self-reported tobacco use was 36% among men and 3% among women in the sample. However, biochemical verification of smoking status revealed that 42% men and 9% of women were positive for cotinine indicating possible recent tobacco use. Dual and poly-use of tobacco products was fairly common with 32% and 6% of the sample reporting respectively. Conclusions This is the first study in the region to biochemically verify tobacco use self-report data. Tobacco use in this study population was found to be higher than previously thought, especially among women. Misclassification of smoking status was more common than expected. Poly-tobacco use was also very common. Additional studies are needed to understand tobacco use behaviors and the extent to which people may be exposed to passive tobacco smoke. Implications This study is the first in the region to biochemically verify self-reported smoking status

Association between pediatric asthma and adult polycystic ovarian syndrome (PCOS): a cross-sectional analysis of the UAE healthy future Study (UAEHFS)

Asthma and polycystic ovarian syndrome (PCOS) are linked in several possible ways. To date, there has been no study evaluating whether pediatric asthma is an independent risk factor for adult PCOS. Our study aimed to examine the association between pediatric asthma (diagnosed at 0-19 years) and adult PCOS (diagnosed at ≥20 years). We further assessed whether the aforementioned association differed in two phenotypes of adult PCOS which were diagnosed at 20-25 years (young adult PCOS), and at \u3e25 years (older adult PCOS). We also evaluated whether the age of asthma diagnosis (0-10 vs 11-19 years) modified the association between pediatric asthma and adult PCOS. This is a retrospective cross-sectional analysis using the United Arab Emirates Healthy Future Study (UAEHFS) collected from February 2016 to April 2022 involving 1334 Emirati females aged 18-49 years. We fitted a Poisson regression model to estimate the risk ratio (RR) and its 95% confidence interval (95% CI) to assess the association between pediatric asthma and adult PCOS adjusting for age, urbanicity at birth, and parental smoking at birth. After adjusting for confounding factors and comparing to non-asthmatic counterparts, we found that females with pediatric asthma had a statistically significant association with adult PCOS diagnosed at ≥20 years (RR=1.56, 95% CI: 1.02-2.41), with a stronger magnitude of the association found in the older adult PCOS phenotype diagnosed at \u3e25 years (RR=2.06, 95% CI: 1.16-3.65). Further, we also found females reported thinner childhood body size had a two-fold to three-fold increased risk of adult PCOS diagnosed at ≥20 years in main analysis and stratified analyses by age of asthma and PCOS diagnoses (RR=2.06, 95% CI: 1.08-3.93 in main analysis; RR=2.74, 95% CI: 1.22-6.15 among those diagnosed with PCOS \u3e 25 years; and RR=3.50, 95% CI: 1.38-8.43 among those diagnosed with asthma at 11-19 years). Pediatric asthma was found to be an independent risk factor for adult PCOS. More targeted surveillance for those at risk of adult PCOS among pediatric asthmatics may prevent or delay PCOS in this at-risk group. Future studies with robust longitudinal designs aimed to elucidate the exact mechanism between pediatric asthma and PCOS are warranted

Types of tobacco consumption and the oral microbiome in the United Arab Emirates Healthy Future (UAEHFS) Pilot Study

© 2018, The Author(s). Cigarette smoking alters the oral microbiome; however, the effect of alternative tobacco products remains unclear. Middle Eastern tobacco products like dokha and shisha, are becoming globally widespread. We tested for the first time in a Middle Eastern population the hypothesis that different tobacco products impact the oral microbiome. The oral microbiome of 330 subjects from the United Arab Emirates Healthy Future Study was assessed by amplifying the bacterial 16S rRNA gene from mouthwash samples. Tobacco consumption was assessed using a structured questionnaire and further validated by urine cotinine levels. Oral microbiome overall structure and specific taxon abundances were compared, using PERMANOVA and DESeq analyses respectively. Our results show that overall microbial composition differs between smokers and nonsmokers (p = 0.0001). Use of cigarettes (p = 0.001) and dokha (p = 0.042) were associated with overall microbiome structure, while shisha use was not (p = 0.62). The abundance of multiple genera were significantly altered (enriched/depleted) in cigarette smokers; however, only Actinobacillus, Porphyromonas, Lautropia and Bifidobacterium abundances were significantly changed in dokha users whereas no genera were significantly altered in shisha smokers. For the first time, we show that smoking dokha is associated to oral microbiome dysbiosis, suggesting that it could have similar effects as smoking cigarettes on oral health

High prevalence of cardiometabolic risk factors amongst young adults in the United Arab Emirates: the UAE Healthy Future Study

BackgroundCardiovascular disease (CVD) is the leading cause of death in the world. In the United Arab Emirates (UAE), it accounts for 40% of mortality. CVD is caused by multiple cardiometabolic risk factors (CRFs) including obesity, dysglycemia, dyslipidemia, hypertension and central obesity. However, there are limited studies focusing on the CVD risk burden among young Emirati adults. This study investigates the burden of CRFs in a sample of young Emiratis, and estimates the distribution in relation to sociodemographic and behavioral determinants.MethodsData was used from the baseline data of the UAE Healthy Future Study volunteers. The study participants were aged 18 to 40 years. The study analysis was based on self-reported questionnaires, anthropometric and blood pressure measurements, as well as blood analysis.ResultsA total of 5167 participants were included in the analysis; 62% were males and the mean age of the sample was 25.7 years. The age-adjusted prevalence was 26.5% for obesity, 11.7% for dysglycemia, 62.7% for dyslipidemia, 22.4% for hypertension and 22.5% for central obesity. The CRFs were distributed differently when compared within social and behavioral groups. For example, obesity, dyslipidemia and central obesity in men were found higher among smokers than non-smokers (p \u3c 0.05). And among women with lower education, all CRFs were reported significantly higher than those with higher education, except for hypertension. Most CRFs were significantly higher among men and women with positive family history of common non-communicable diseases.ConclusionsCRFs are highly prevalent in the young Emirati adults of the UAE Healthy Future Study. The difference in CRF distribution among social and behavioral groups can be taken into account to target group-specific prevention measures