Quality and reporting of clinical guidelines for breast cancer treatment: A systematic review

Background: High-quality, well-reported clinical practice guidelines (CPGs) and consensus statements (CSs) underpinned by systematic reviews are needed. We appraised the quality and reporting of CPGs and CSs for breast cancer (BC) treatment. Methods: Following protocol registration (Prospero no: CRD42020164801), CPGs and CSs on BC treatment were identified, without language restrictions, through a systematic search of bibliographic databases (MEDLINE, EMBASE, Web of Science, Scopus, CDSR) and online sources (12 guideline databases and 51 professional society websites) from January 2017 to June 2020. Data were extracted in duplicate assessing overall quality using AGREE II (% of maximum score) and reporting compliance using RIGHT (% of total 35 items); reviewer agreement was 98% and 96% respectively. Results: There were 59 relevant guidance documents (43 CPGs, 16 CSs), of which 20 used systematic reviews for evidence synthesis. The median overall quality was 54.0% (IQR 35.9e74.3) and the median overall reporting compliance was 60.9% (IQR 44.5e84.4). The correlation between quality and reporting was 0.9. Compared to CSs, CPGs had better quality (55.4% vs 44.2%; p ¼ 0.032) and reporting (67.18% vs 44.5%; p ¼ 0.005). Compared to subjective methods of evidence analysis, guidance documents that used systematic reviews had better quality (76.3% vs 51.4%; p ¼ 0.001) and reporting (87.1% vs 59.4%; p ¼ 0.001). Conclusion: The quality and reporting of CPGs and CSs in BC treatment were moderately strong. Systematic reviews should be used to improve the quality and reporting of CPGs and CSs.Beatriz Galindo (senor modality) Program by the Ministry of Science, Innovation, and Universities of the Spanish Governmen

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

Peer reviewe

An Initial Implementation of the Turing Tournament to Learning in Repeated Two

National Science Foundation (Grant #SES-0079301) for help in funding the experiments

Microarray-predicted marker genes and molecular pathways indicating crowding stress in rainbow trout (Oncorhynchus mykiss)

STATEMENT OF RELEVANCE: The comprehensive recording of animal-based biomarkers is becoming increasingly important for the further development of the aquaculture industry with importance for fish well-being and consumer opinion. Previous studies on crowding stress in rainbow trout have used single or multi-gene approaches to assess the relevance of putative biomarkers, but transcriptomic approaches to define crowding stress-induced pathways in salmonids are overdue. The present study compares the transcriptomic profiles of rainbow trout exposed to different stocking densities and correlates these data sets with classical plasma parameters and behavioural observations.Stocking density is considered as a key factor determining the productivity of fish aquaculture systems. The transcriptomic response to crowding stress is, however, still poorly investigated. We aimed to identify potential biomarker genes via microarray analyses to gain insight into molecular pathways modulated by density-induced stress in farmed rainbow trout Oncorhynchus mykiss. Transcriptome profiling in the liver, kidney, and gills was complemented by analysis of classical plasma parameters and behavioural observations. Individuals of two trout strains were exposed for nine days to definite stocking densities, ~ 10 kg/m3 (low density); ~ 30 kg/m3 (moderate); ~ 60 kg/m3 (elevated); and ~ 120 kg/m3 (high). Only the PYGMA gene, encoding the key enzyme of glycogenolysis, was upregulated in gills and kidney, while about 90 genes were differentially regulated in the liver of trout exposed to high density compared with the moderate-density group. Pathway enrichment analyses predicted the upregulation of HIF1A signalling in liver, contributing to glucose homeostasis during stress conditions. This is consistent with the increased plasma glucose levels detected in crowding-stressed trout. The mTOR and PI3K/AKT signalling pathways were impaired in liver at higher stocking densities indicating stress at the cellular level. Contrary to our expectations, protein ubiquitination and cholesterol biosynthesis pathways were found to be underexpressed. Cholesterol is a precursor of the stress hormone cortisol, whose plasma concentrations were indeed within the normal physiological range in all treatment groups. In addition, we did not observe any aggressive interactions, which are known to be triggered through cortisol release. Taken together, we identified a relatively modest number of rainbow trout-specific crowding markers suggesting that farmed rainbow trout have gained enhanced stress-tolerant phenotypes through decades of selective breeding