Infinium Methylation BeadChip arrays remain one of the most popular platforms for epigenome-wide association studies, but tools for downstream pathway analysis have their limitations. Functional class scoring (FCS) is a group of pathway enrichment techniques that involve the ranking of genes and evaluation of their collective regulation in biological systems, but the implementations described for Infinium methylation array data do not retain direction information, which is important for mechanistic understanding of genomic regulation. Here, we evaluate several candidate FCS methods that retain directional information. According to simulation results, the best-performing method involves the mean aggregation of probe limma t-statistics by gene followed by a rank-ANOVA enrichment test using the mitch package. This method, which we call 'LAM,' outperformed an existing over-representation analysis method in simulations, and showed higher sensitivity and robustness in an analysis of real lung tumour-normal paired datasets. Using matched RNA-seq data, we examine the relationship of methylation differences at promoters and gene bodies with RNA expression at the level of pathways in lung cancer. To demonstrate the utility of our approach, we apply it to three other contexts where public data were available. First, we examine the differential pathway methylation associated with chronological age. Second, we investigate pathway methylation differences in infants conceived with in vitro fertilization. Lastly, we analyse differential pathway methylation in 19 disease states, identifying hundreds of novel associations. These results show LAM is a powerful method for the detection of differential pathway methylation complementing existing methods. A reproducible vignette is provided to illustrate how to implement this method.

This study investigates the impact of different work paces on cardiorespiratory outcomes, perceived effort and carried load (CL) in industrial workers.

Research and development of military-required innovations are usually funded through the issuance of grants and contracts. The limitations of these funding methods are the a priori specifications and objectives that limit creativity and often do not produce capabilities beyond the desired outcomes or leverage the best ideas and solutions available. This limited engagement of commercial industry to develop military-required innovations usually relies solely on government funding and receipt of proposals from companies whose business model is built on receiving government grants and contracts, with the government owning most of the risks. Because the produced capabilities or products are designed to be military-unique, there is a limited or no commercial market available, usually driving the price per unit extremely high to the point that the military cannot afford to procure products in quantities sufficient to enable businesses to keep production lines open, however, for military-required or desired capabilities or products that have a commercial market, there are other funding pathways available to develop products by partnering with industry, academia, and other non-government organizations and leveraging their ideas and funding. One such way of engaging the commercial industry is through the use of prize competitions. This often under-utilized pathway has several notable strengths such as (1) reduced risks and costs for the military to develop novel capabilities and products; (2) new and novel creative solutions to solve military problems; (3) utilizing a results-oriented approach that funds the successful achievement of acceptance criteria versus funding of potential to achieve; (4) enticing investors by increased competition for a successful product or capability; and (5) delivery of a commercially available, affordable, field-tested, and viable capabilities and products. Prize competitions may be used by any/all federal agencies as authorized by Congressional Public Laws and Federal regulations. The specifics of this pathway for funding pathway and applications for use by medical researchers, developers, and project/program managers are spelled out in the article, along with the regulatory guidance and resources for finding out more about current and past prize competitions.

Breast cancer is a major public health concern. Proteomics enables identification of proteins with aberrant properties. Here, we identified proteins with abnormal expression levels in breast cancer tissues and systematically analyzed and validated the data to locate potential diagnostic and therapeutic targets.

This trial aimed to investigate the influence of graded replacing fish meal (D1: 0.00%, D2: 27.27%, and D3: 54.55%) with mixed protein ingredients (i.e., chicken meal, krill meal, fermented soybean meal, and soy protein concentrate) on the growth performance, muscle nutritional composition, blood biochemical indices, gut bacterial community, and transcriptome of Chinese perch. Two hundred seventy Chinese perch were divided into three groups (90 per group) and the diet lasted for 56 days. Results showed that the weight gain rate and specific growth rate were significantly lower, and the feed conversion ratio was significantly higher in the D3 group than in fish fed D1 ( < 0.05), with no significant differences between the D1 and D2 groups ( > 0.05). The muscle crude protein content was highest in the D2 group, and the crude fat content was significantly different in the order: D3 > D1 > D2 ( < 0.05). The levels of serum triglycerides (TG) and low-density lipoprotein cholesterol in the D2 group were significantly lower than those in the D1 group ( < 0.05), but there was no significant difference compared to the D3 group ( > 0.05). The microbial community structure changed significantly. showed the highest abundance in the D1 and D2 groups ( < 0.05), and peaked in D2 group, and significantly higher than that in D1 group ( < 0.05). Network analysis and cohesion index calculation showed that both network complexity and cohesion peaked in D2 group, and was highly correlated with the cohesion index ( < 0.05). Further, muscle transcriptome analysis results showed that compared with the control group, differentially expressed genes were clustered ( < 0.05) in the arginine and proline metabolism pathways in D2 group. Fish in D3 group significantly ( < 0.05) affected genes involved in KEGG pathways of ribosome, circadian rhythm, thermogenesis, insulin signaling pathway, fatty acid degradation, oxidative phosphorylation, and apoptosis. In conclusion, under the experimental conditions, the replacement of 27.27% of fish meal by the compound protein did not have a negative impact on the growth performance of Chinese perch and could improve muscle quality, lipid metabolism, and the interaction of intestinal microbiota.