Improving Accuracy of Somatic Mutation Profiling in Large Epidemiologic Studies: Addressing Cases without Matched Normal Samples.

Ideally, detection of somatic mutations in a tumor is accomplished using a patient-matched sample of normal cells as the benchmark. In this way somatic mutations can be distinguished from rare germline mutations. In large retrospective studies, archival tissue collection can pose challenges in obtaining samples of normal DNA.

DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance.

Purpose: Patients with stage II and III cutaneous primary melanoma vary considerably in their risk of melanoma-related death. We explore the ability of methylation profiling to distinguish primary melanoma methylation classes and their associations with clinicopathologic characteristics and survival.

Materials And Methods: InterMEL is a retrospective case-control study that assembled primary cutaneous melanomas from American Joint Committee on Cancer (AJCC) 8th edition stage II and III patients diagnosed between 1998 and 2015 in the United States and Australia.

Lactulose with synergists supplementation improving a health of chicks and reducing the environmental burden in poultry industry.

Objective: The study aims to understand the effect of new antibiotic-substituting supplements in feeding chickens of the Hisex Brown cross in industrial conditions.

Materials And Methods: A total of 216 hatched chicks were randomly selected and distributed into Control, Test I, and Test II groups, with 3 replicates of 24 birds in three treatments.

Results: At the end of the experiment, BW of T1/T2 birds was higher by 6.

Effects of dietary Silybum marianum powder on growth performance, egg and carcass characteristics, immune response, intestinal microbial population, haemato-biochemical parameters and sensory meat quality of laying quails.

The study aimed to assess the effects of different dietary Silybum marianum (SM, milk thistle) powder levels on growth performance, productivity, immunity, small intestine, haemato-biochemical parameters, meat quality, and egg and carcass characteristics of laying quails. The experimental subjects consisted of one hundred and eight 43-day-old quails divided into 3 treatments (0, 0.75, and 1.

Strength of selection in lung tumors correlates with clinical features better than tumor mutation burden.

Single nucleotide substitutions are the most common type of somatic mutations in cancer genome. The goal of this study was to use publicly available somatic mutation data to quantify negative and positive selection in individual lung tumors and test how strength of directional and absolute selection is associated with clinical features. The analysis found a significant variation in strength of selection (both negative and positive) among tumors, with median selection tending to be negative even though tumors with strong positive selection also exist.

Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.

Background: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.

Methods: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants.

Identification of genetically predicted DNA methylation markers associated with non-small cell lung cancer risk among 34,964 cases and 448,579 controls.

Background: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated.

Methods: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established.

Immunomodulatory Effects of Natural Feed Additives for Meat Chickens.

Broiler chickens are increasingly kept in large numbers in intensive housing conditions that are stressful, potentially depleting the immune system. With the prohibition of the use of antibiotics in poultry feed spreading worldwide, it is necessary to consider the role of natural feed additives and antibiotic alternatives to stimulate the chickens' immune systems. We review the literature to describe phytogenic feed additives that have immunomodulatory benefits in broilers.

Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From the INTEGRAL-ILCCO Cohort Analysis.

Introduction: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer.

Methods: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls.

Immune Infiltration in Tumor and Adjacent Non-Neoplastic Regions Codetermines Patient Clinical Outcomes in Early-Stage Lung Cancer.

Introduction: In recent years, the proportion of patients with NSCLC diagnosed at an early stage has increased continuously.

Methods: In this study, we analyzed samples and data collected from 119 samples from 67 early stage patients with NSCLC, including 52 pairs of tumor and adjacent non-neoplastic samples, and performed RNA-sequencing analysis with high sequencing depth.

Results: We found that immune-related genes were highly enriched among the differentially expressed genes and observed significantly higher inferred immune infiltration levels in adjacent non-neoplastic samples than in tumor samples.

A Comparison of the Effects of Raw and Processed Amaranth Grain on Laying Hens' Performance, Egg Physicochemical Properties, Blood Biochemistry and Egg Fatty Acids.

In order to investigate the effects of using different levels of either raw or processed amaranth () grain on performance productivity, egg physicochemical properties, blood biochemistry and egg fatty acids, a trial was conducted using 168 Hy-line W-36 laying hens (67 week of age) in a completely randomized design with seven treatments and six replications of four birds for eight weeks. The trial treatments included the control group receiving no amaranth and the test groups receiving 5, 10 and 15% of raw or autoclaved (120 °C for 5 min) amaranth grain based on dry matter. The results showed that the use of processed amaranth up to the level of five and ten percent of the diet compared to raw amaranth resulted in a better performance than the control group ( < 0.

InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma.

Introduction: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients.

Pathway Alterations in Stage II/III Primary Melanoma.

Purpose: Genomic classification of melanoma has thus far focused on the mutational status of , , and . The clinical utility of this classification remains limited, and the landscape of alterations in other oncogenic signaling pathways is underexplored.

Methods: Using primary samples from the InterMEL study, a retrospective cohort of cases with specimens collected from an international consortium with participating institutions throughout the United States and Australia, with oversampling of cases who ultimately died of melanoma, we examined mutual exclusivity and co-occurrence of genomic alterations in 495 stage II/III primary melanomas across 11 cancer pathways.

Why does the X chromosome lag behind autosomes in GWAS findings?

The X-chromosome is among the largest human chromosomes. It differs from autosomes by a number of important features including hemizygosity in males, an almost complete inactivation of one copy in females, and unique patterns of recombination. We used data from the Catalog of Published Genome Wide Association Studies to compare densities of the GWAS-detected SNPs on the X-chromosome and autosomes.

Effect of Dietary Amaranth () Supplemented with Enzyme Blend on Egg Quality, Serum Biochemistry and Antioxidant Status in Laying Hens.

A feeding trial was performed to assess the effects of dietary raw amaranth () grain (RAG), with or without an enzyme blend, on the productive performance, blood biochemistry, and antioxidant status in laying hens. The trial was conducted following a completely randomized design by factorial method, including five levels of RAG (0, 10, 20, 30, and 40%, respectively) and two levels of enzyme blend (0 and 0.025 %).

Methylation of nonessential genes in cutaneous melanoma - Rule Out hypothesis.

Differential methylation plays an important role in melanoma development and is associated with survival, progression and response to treatment. However, the mechanisms by which methylation promotes melanoma development are poorly understood. The traditional explanation of selective advantage provided by differential methylation postulates that hypermethylation of regulatory 5'-cytosine-phosphate-guanine-3' dinucleotides (CpGs) downregulates the expression of tumor suppressor genes and therefore promotes tumorigenesis.

Effects of Using Processed Amaranth Grain with and without Enzyme on Performance, Egg Quality, Antioxidant Status and Lipid Profile of Blood and Yolk Cholesterol in Laying Hens.

The objective of this study was to investigate the effects of feeding Amaranthus hybridus chlorostachys grain (AG) with (+E) and without enzyme (−E) on performance, egg quality, antioxidant status and lipid profile of blood serum and yolk cholesterol in laying hens. A total of 960 white leghorn (Hy-line W-36) commercial layers (56 weeks) were divided into 10 groups with 8 replicates per group (12 birds per replicate, including 3 adjacent cages with 4 birds each). A completely randomized design was implemented with a 5 × 2 factorial arrangement of treatments consisting of five levels of AG (0, 100, 200, 300 and 400 g/kg) and two levels of multienzyme complex addition (0 −E and 0.

The effects of peppermint ( L.) and chicory ( L.) in comparison with a prebiotic on productive performance, blood constituents, immunity and intestinal microflora in broiler chickens.

A total of 320 one-day-old broiler chickens were used in a 42-day feeding trial to evaluate the effects of peppermint ( L.) and chicory ( L.) in comparison with a prebiotic on-growth performance, blood constitutes, immunity and intestinal microflora.

The effects of green tea in the diet of broilers challenged with coccidiosis on their performance, carcass characteristics, intestinal mucosal morphology, blood constituents and ceca microflora.

Background: Coccidiosis is an endemic protozoal disease of chickens normally controlled by ionophores. However, coccidiostats are also antibiotics, and evidence of resistance in both coccidia and bacteria may develop and reduce antibacterial activity in humans. This has led to a search for natural coccidiostats, such as green tea.

Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity.

Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study.

It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments.

Identification of lung cancer drivers by comparison of the observed and the expected numbers of missense and nonsense mutations in individual human genes.

Largely, cancer development is driven by acquisition and positive selection of somatic mutations that increase proliferation and survival of tumor cells. As a result, genes related to cancer development tend to have an excess of somatic mutations in them. An excess of missense and/or nonsense mutations in a gene is an indicator of its cancer relevance.