Inbreeding and Gallbladder Cancer Risk: Homozygosity Associations Adjusted for Indigenous American Ancestry, BMI, and Genetic Risk of Gallstone Disease.

Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (F) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans.

Small-RNA sequencing reveals potential serum biomarkers for gallbladder cancer: Results from a three-stage collaborative study of large European prospective cohorts.

Gallbladder cancer (GBC) is an aggressive disease with limited treatment options but high prevention potential. GBC tumours take 10-20 years to develop, a timeframe that holds potential for early detection. MicroRNAs (miRNAs) play a central role in abnormal cell processes, and circulating miRNAs may constitute valuable biomarkers of early disease.

Cholecystectomy and digestive cancer in Chile: Complementary results from interrupted time series and aggregated data analyses.

Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality.

Molecular and Serological Studies on Potential SARS-CoV-2 Infection among 43 Lemurs under Human Care-Evidence for Past Infection in at Least One Individual.

In the setting of the recent COVID-19 pandemic, transmission of SARS-CoV-2 to animals has been reported in both domestic and wild animals and is a matter of concern. Given the genetic and functional similarities to humans, non-human primates merit particular attention. In the case of lemurs, generally considered endangered, they are believed to be susceptible to SARS-CoV-2 infection.

Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers.

Background: Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk.

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association.

Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models.

Gallstones, Cholecystectomy, and Kidney Cancer: Observational and Mendelian Randomization Results Based on Large Cohorts.

Background & Aims: Gallstones (cholelithiasis) constitute a major health burden with high costs related to surgical removal of the gallbladder (cholecystectomy), generally indicated for symptomatic gallstones. The association between gallstones and cholecystectomy and kidney cancer is controversial. We comprehensively investigated this association, considering age at cholecystectomy and time from cholecystectomy to kidney cancer diagnosis, and assessed the causal effect of gallstones on kidney cancer risk by Mendelian randomization (MR).

Ceramic Crowns and Sleep Bruxism: First Results from a Randomized Trial.

Background: This randomized clinical trial was conducted to assess whether sleep bruxism (SB) is associated with an increased rate of technical complications (ceramic defects) in lithium disilicate (LiDi) or zirconia (Z) molar single crowns (SCs). Methods: Adult patients were classified as affected or unaffected by SB based on structured questionnaires, clinical signs, and overnight portable electromyography (BruxOff) and block randomized into four groups according to SB status and crown material (LiDi or Z): LiDi-SB (n = 29), LiDi-no SB (n = 24), Z-SB (n = 23), and Z-no SB (n = 27). Differences in technical complications (main outcome) and survival and success rates (secondary outcomes) one year after crown cementation were assessed using Fisher’s exact test with significance level α = 0.

Development of an Application for Electronic Retrieval of Patient and Sample Information in Latin American Regions with a High Incidence of Gallbladder Cancer.

The European-Latin American Consortium towards Eradication of Preventable Gallbladder Cancer, EULAT Eradicate GBC, is collecting high-quality data and samples in four Latin American countries with high gallbladder cancer incidence (Argentina, Bolivia, Chile, and Peru) to build a unique biorepository integrated into a tailored IT platform, to identify, validate, and functionally characterize new risk biomarkers, and to develop prediction models that integrate epidemiological and genetic-molecular risk factors. We decided to develop an application for electronic data collection to facilitate the retrieval of sociodemographic, clinical, lifestyle, dietary, and sample-related information from 15,000 Latin American study participants. The application EULAT eCollect will facilitate the work of study nurses, reduce time spent by participants, limit the use of paper and ink, minimize costs and errors associated with filling out written forms and subsequent digitisation, and support the monitoring of local recruitment rates and data quality.

The serotonin receptor 3E variant is a risk factor for female IBS-D.

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT receptor family. 5-HTRs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular.

Time trends and persistence in PM in 20 megacities: evidence for the time period 2018-2020.

The degree of persistence in daily data for PM in 20 relevant megacities such as Bangkok, Beijing, Mumbai, Calcutta, Canton, Dhaka, Delhi, Jakarta, London, Los Angeles, Mexico City, Moscow, New York, Osaka. Paris, Sao Paulo, Seoul, Shanghai, Tientsin, and Tokyo is examined in this work. The analysis developed is based on fractional integration techniques.

NGS allele counts versus called genotypes for testing genetic association.

Unlabelled: RNA sequence data are commonly summarized as read counts. By contrast, so far there is no alternative to genotype calling for investigating the relationship between genetic variants determined by next-generation sequencing (NGS) and a phenotype of interest. Here we propose and evaluate the direct analysis of allele counts for genetic association tests.

Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression.

Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer () using robust linear and logistic regression techniques.

Inbreeding, Native American ancestry and child mortality: linking human selection and paediatric medicine.

The children of related parents show increased risk of early mortality. The Native American genome typically exhibits long stretches of homozygosity, and Latin Americans are highly heterogeneous regarding the individual burden of homozygosity, the proportion and the type of Native American ancestry. We analysed nationwide mortality and genome-wide genotype data from admixed Chileans to investigate the relationship between common causes of child mortality, homozygosity and Native American ancestry.

Atmospheric pollution in the ten most populated US cities. Evidence of persistence.

The degree of persistence in daily PM and O in the ten most populated US cities, namely New York, Los Angeles, Chicago, Houston, Phoenix, Philadelphia, San Antonio, San Diego, Dallas and San Jose is examined in this work. We employ a methodology based on fractional integration, using the order of integration as a measure of the degree of persistence. Using data for the time period from January 1, 2019 to December 31, 2020, our results indicate that fractional integration and long memory features are both present in all the examined cases, with the integration order of the series being constrained in the (0, 1) interval.

A New Pipeline for the Normalization and Pooling of Metabolomics Data.

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.

Survival and success of tooth-implant-supported and solely implant-supported double-crown-retained overdentures: A prospective study over a period of up to 11 years.

Objectives: To investigate the long-term performance, over a period of up to 11 years, of tooth-implant-supported and solely implant-supported double-crown-retained overdentures (DCRDs) for complete restoration of the jaw.

Materials And Methods: Between 2002 and 2015, patients were consecutively enrolled in the study at Heidelberg University Hospital's Department of Prosthodontics. Scheduled and unscheduled visits were both documented on standardized forms.

Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes.

Background & Aims: Gallbladder cancer (GBC) is the most common type of biliary tract cancer, but the molecular mechanisms involved in gallbladder carcinogenesis remain poorly understood. In this study, we applied integrative genomics approaches to characterise GBC and explore molecular subtypes associated with patient survival.

Methods: We profiled the mutational landscape of GBC tumours (whole-exome sequencing on 92, targeted sequencing on 98, in total 190 patients).

Genotype-Based Gene Expression in Colon Tissue-Prediction Accuracy and Relationship with the Prognosis of Colorectal Cancer Patients.

Colorectal cancer (CRC) survival has environmental and inherited components. The expression of specific genes can be inferred based on individual genotypes-so called expression quantitative trait loci. In this study, we used the PrediXcan method to predict gene expression in normal colon tissue using individual genotype data from 91 CRC patients and examined the correlation ρ between predicted and measured gene expression levels.

Robust Huber-LASSO for improved prediction of protein, metabolite and gene expression levels relying on individual genotype data.

Least absolute shrinkage and selection operator (LASSO) regression is often applied to select the most promising set of single nucleotide polymorphisms (SNPs) associated with a molecular phenotype of interest. While the penalization parameter λ restricts the number of selected SNPs and the potential model overfitting, the least-squares loss function of standard LASSO regression translates into a strong dependence of statistical results on a small number of individuals with phenotypes or genotypes divergent from the majority of the study population-typically comprised of outliers and high-leverage observations. Robust methods have been developed to constrain the influence of divergent observations and generate statistical results that apply to the bulk of study data, but they have rarely been applied to genetic association studies.

Epigenome-Wide Analysis of Methylation Changes in the Sequence of Gallstone Disease, Dysplasia, and Gallbladder Cancer.

Background And Aims: Gallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract. Most cases of GBC are diagnosed in low-income and middle-income countries, and research into this disease has long been limited. In this study we therefore investigate the epigenetic changes along the model of GBC carcinogenesis represented by the sequence gallstone disease → dysplasia → GBC in Chile, the country with the highest incidence of GBC worldwide.