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1 ng/mL) in both groups. A high-normal CEA level was an independent risk factor for DFS in both groups, and was associated with inferior DFS in patients with stage II and III disease and in never or former smokers. The correlation between DFS and CEA levels was more distinct in left-sided colon and rectal cancer. CONCLUSIONS A high-normal preoperative CEA level (≥ 2.1 ng/mL), even within the normal range, was an independent prognosticator for poor DFS in CRC. The usefulness of CEA was influenced by smoking status and tumor location in addition to tumor stage.BACKGROUND Gamma-aminobutyric acid (GABA) is a non-protein amino acid present in all living things. GABA is mainly synthesized from glutamate by glutamate decarboxylase (GAD). In plants the enzymatic activity of GAD is activated by Ca2+/calmodulin binding (CaMBD) at the C-terminus in response to various stresses, allowing rapid GABA accumulation in cells. GABA plays a central role in not only stress responses but also many aspects of plant growth and development as a signaling molecules. Furthermore, it is known to be a health-promoting functional substance that exerts improvements in life-style related diseases such as hypertension, diabetes, hyperlipidemia, and so on. Previous reports indicated that CaMBD found plant GADs possess an autoinhibitory function because truncation of GAD resulted in extreme GABA accumulation in plant cells. Therefore, we attempted a genetic modification of rice GAD via genome editing technology to increase GABA levels in the edible part of rice. RESULTS In this study, we focused air deletion in the N-terminal coding region of the CaMBD. Free amino acid analysis of the seeds (T2) indicated that the former line contained seven-fold higher levels of GABA than wild-type, whereas the latter line had similar levels to the wild-type, although in vitro enzyme activities of recombinant GAD proteins based on the GAD3 amino acid sequence elucidated from these two lines in the absence of Ca2+/bovine CaM were both higher than wild-type counterpart. In addition to high level of GABA in #8_8, the average seed weight per grain and protein content were superior to wild-type and #8_1. CONCLUSIONS We have successfully established GABA-fortified rice by using CRISPR/Cas9 genome editing technology. Modified rice contained seven-fold higher GABA content and furthermore displayed significantly higher grain weight and protein content than wild-type brown rice. This is the first report of the production of GABA-enriched rice via a genome editing.Atrial fibrillation (AF) is the most common cardiac arrhythmia. We designed an umbrella review to systematically assess the epidemiological credibility of the associations of non-genetic factors with risk of AF. We searched PubMed and EMBASE from inception to December 31, 2018 to identify systematic reviews and meta-analyses of observational studies for the association of non-genetic factors with risk of AF. For each meta-analysis, we used the random-effects model, and we estimated the 95% confidence and prediction intervals. We also assessed between-study heterogeneity, small-study effects and excess significance bias. We identified 34 eligible papers that examined 51 associations of 42 unique non-genetic factors with risk of AF. Eighteen associations remained statistically significant at P value  30 units vs.  less then  30 units, per 5 units increase), waist circumference, body weight, type 2 diabetes mellitus, and smoking (ever vs. never, per 10 cigarettes/day increase) were supported by convincing or highly suggestive evidence in meta-analyses of prospective cohort studies. Type 2 diabetes mellitus, markers of adiposity, alcohol consumption, smoking, and corrected QT interval constitute credible risk factors of AF. Our proposed grading may guide the design of future studies, including Mendelian randomization studies, to assess whether these associations are causal.Conceptual concreteness and categorical specificity are two continuous variables that allow distinguishing, for example, justice (low concreteness) from banana (high concreteness) and furniture (low specificity) from rocking chair (high specificity). The relation between these two variables is unclear, with some scholars suggesting that they might be highly correlated. In this study, we operationalize both variables and conduct a series of analyses on a sample of > 13,000 nouns, to investigate the relationship between them. selleck Concreteness is operationalized by means of concreteness ratings, and specificity is operationalized as the relative position of the words in the WordNet taxonomy, which proxies this variable in the hypernym semantic relation. Findings from our studies show only a moderate correlation between concreteness and specificity. Moreover, the intersection of the two variables generates four groups of words that seem to denote qualitatively different types of concepts, which are, respectively, highly specific and highly concrete (typical concrete concepts denoting individual nouns), highly specific and highly abstract (among them many words denoting human-born creation and concepts within the social reality domains), highly generic and highly concrete (among which many mass nouns, or uncountable nouns), and highly generic and highly abstract (typical abstract concepts which are likely to be loaded with affective information, as suggested by previous literature). These results suggest that future studies should consider concreteness and specificity as two distinct dimensions of the general phenomenon called abstraction.This study assesses factors influencing the capacity to maintain a steady rhythm during explicit counting activities. There are three counting paces (count every 800, 1200, or 1600 ms) and three experimental conditions (count silently, aloud and aloud in the presence of someone). The study also assesses the effect of a speech disorder, namely stuttering, on this counting ability by comparing the performance of a group of adult stutterers (n = 21) to that of a group of adult non-stutterers (n = 24). For temporal variability, in addition to replicating the fact that counting more slowly leads to lower performance, the results show that there are benefits to expect when participants count aloud instead of silently. There is no main effect of group, but the interaction between the experimental condition, the counting pace, and the group is significant. Adult non-stutterers are better than adult stutterers in the silent and long time-interval conditions (1600 ms). The significantly higher variability at 1600 ms indicates a loss of efficiency in the capacity to keep time constant when counting is slow, and it is in this condition that stutterers will gain the most benefits from counting aloud instead of silently.