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Viruses are ubiquitous in humans and various environments and continually mutate themselves. Identifying viruses in an environment without cultivation is challenging; however, promoting the screening of novel viruses and expanding the knowledge of viral space is essential. Homology-based methods that identify viruses using known viral genomes rely on sequence alignments, making it difficult to capture remote homologs of the known viruses. To accurately capture viral signals from metagenomic samples, models are needed to understand the patterns encoded in the viral genomes. In this study, we developed a hierarchical BERT model named ViBE to detect eukaryotic viruses from metagenome sequencing data and classify them at the order level. We pre-trained ViBE using read-like sequences generated from the virus reference genomes and derived three fine-tuned models that classify paired-end reads to orders for eukaryotic deoxyribonucleic acid viruses and eukaryotic ribonucleic acid viruses. ViBE achieved higher recall than state-of-the-art alignment-based methods while maintaining comparable precision. ViBE outperformed state-of-the-art alignment-free methods for all test cases. The performance of ViBE was also verified using real sequencing datasets, including the vaginal virome.

Background Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully. We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. Methods We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. Results No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. Conclusion We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer., Graphical Abstract

Background Diverse microbiome communities drive biogeochemical processes and evolution of animals in their ecosystems. Many microbiome projects have demonstrated the power of using metagenomics to understand the structures and factors influencing the function of the microbiomes in their environments. In order to characterize the effects from microbiome composition for human health, diseases, and even ecosystems, one must first understand the relationship of microbes and their environment in different samples. Running machine learning model with metagenomic sequencing data is encouraged for this purpose, but it is not an easy task to make an appropriate machine learning model for all diverse metagenomic datasets. Results We introduce MegaR, an R Shiny package and web application, to build an unbiased machine learning model effortlessly with interactive visual analysis. The MegaR employs taxonomic profiles from either whole metagenome sequencing or 16S rRNA sequencing data to develop machine learning models and classify the samples into two or more categories. It provides various options for model fine tuning throughout the analysis pipeline such as data processing, multiple machine learning techniques, model validation, and unknown sample prediction that can be used to achieve the highest prediction accuracy possible for any given dataset while still maintaining a user-friendly experience. Conclusions Metagenomic sample classification and phenotype prediction is important particularly when it applies to a diagnostic method for identifying and predicting microbe-related human diseases. MegaR provides various interactive visualizations for user to build an accurate machine-learning model without difficulty. Unknown sample prediction with a properly trained model using MegaR will enhance researchers to identify the sample property in a fast turnaround time.

Microorganisms play a vital role in living systems in numerous ways. In the soil or ocean environment, microbes are involved in diverse processes, such as carbon and nitrogen cycle, nutrient recycling, and energy acquisition. The relation between microbial dysbiosis and disease developments has been extensively studied. In particular, microbial communities in the human gut are associated with the pathophysiology of several chronic diseases such as inflammatory bowel disease and diabetes. Therefore, analyzing the distribution of microorganisms and their associations with the environment is a key step in understanding nature. With the advent of next-generation sequencing technology, a vast amount of metagenomic data on unculturable microbes in addition to culturable microbes has been produced. To reconstruct microbial genomes, several assembly algorithms have been developed by incorporating metagenomic features, such as uneven depth. Since it is difficult to reconstruct complete microbial genomes from metagenomic reads, contig binning approaches were suggested to collect contigs that originate from the same genome. To estimate the microbial composition in the environment, various methods have been developed to classify individual reads or contigs and profile bacterial proportions. Since microbial communities affect their hosts and environments through metabolites, metabolic profiles from metagenomic or metatranscriptomic data have been estimated. Here, we provide a comprehensive review of computational methods that can be applied to investigate microbiomes using metagenomic and metatranscriptomic sequencing data. The limitations of metagenomic studies and the key approaches to overcome such problems are discussed.

Background Microbial communities of the mouse gut have been extensively studied; however, their functional roles and regulation are yet to be elucidated. Metagenomic and metatranscriptomic analyses may allow us a comprehensive profiling of bacterial composition and functions of the complex gut microbiota. The present study aimed to investigate the active functions of the microbial communities in the murine cecum by analyzing both metagenomic and metatranscriptomic data on specific bacterial species within the microbial communities, in addition to the whole microbiome. Results Bacterial composition of the healthy mouse gut microbiome was profiled using the following three different approaches: 16S rRNA-based profiling based on amplicon and shotgun sequencing data, and genome-based profiling based on shotgun sequencing data. Consistently, Bacteroidetes, Firmicutes, and Deferribacteres emerged as the major phyla. Based on NCBI taxonomy, Muribaculaceae, Lachnospiraceae, and Deferribacteraceae were the predominant families identified in each phylum. The genes for carbohydrate metabolism were upregulated in Muribaculaceae, while genes for cofactors and vitamin metabolism and amino acid metabolism were upregulated in Deferribacteraceae. The genes for translation were commonly enhanced in all three families. Notably, combined analysis of metagenomic and metatranscriptomic sequencing data revealed that the functions of translation and metabolism were largely upregulated in all three families in the mouse gut environment. The ratio of the genes in the metagenome and their expression in the metatranscriptome indicated higher expression of carbohydrate metabolism in Muribaculum, Duncaniella, and Mucispirillum. Conclusions We demonstrated a fundamental methodology for linking genomic and transcriptomic datasets to examine functional activities of specific bacterial species in a complicated microbial environment. We investigated the normal flora of the mouse gut using three different approaches and identified Muribaculaceae, Lachnospiraceae, and Deferribacteraceae as the predominant families. The functional distribution of these families was reflected in the entire microbiome. By comparing the metagenomic and metatranscriptomic data, we found that the expression rates differed for different functional categories in the mouse gut environment. Application of these methods to track microbial transcription in individuals over time, or before and after administration of a specific stimulus will significantly facilitate future development of diagnostics and treatments.

A Case Report on 2 Cases of Patients with Uterine Fibroids Observed an Effective Result on Ultrasonography after Korean Traditional Medical TreatmentYu-Jin Gwak 1 , Sang-Hee Park 1 , Myung-Ju Jung 1 Sung-Woo Park 1 , Ung Park 1 , Hee-Guen Jo 21 Kyunghee Bogung Korean Medical Clinic 2 Sunchang Health Center and County Hospital Gurim Health SubcenterObjectives: We report two cases that have an effective result with Korean traditional medical treatment to two patients who have uterine fibroids, using transabdominal ultrasonography for checking the size of uterine fibroids. Methods: A 44-year-old patient and a 43-year-old patient were treated wi th an herbal medicine, acupuncture and cupping therapy. We followed up the symptoms and the size of uterine fibroids.Results: The 44-year-old patient was asymptomatic, her size of the uterine fibroid was reduced for 6 months. Also, the 43-year-old patient experienced that the symptoms such as urinary frequency, ovulation pain, heavy bleeding were improved and the size of the uterine fibroid was reduced. Conclusions: This results suggest that Korean traditional medical treatment if effective for both asymptomatic and symptomatic uterine fibroid s and ultrasonography is useful for checking the effect of Korean traditional medical treatment. Further case series and studies are warranted. Key Words: Uterine Fibroids, Korean Traditional Medicine, Ultrasonography

This study investigated the sensory characteristics of adlay tea favorably consumed by Korean consumers and analyzed the drivers behind for liking or disliking adlay tea. Six adlay tea products showing the highest market share in South Korea were selected. Sensory properties of the six products were analyzed using generic descriptive analysis. Among these, four products were further selected for consumer taste acceptance test. Sensory lexicons of adlay tea were developed by trained panelists, and the sensory characteristics of each adlay tea product were measured based on the perceived intensities of these attributes elicited from the samples. In the consumer taste acceptance test, frequent tea and coffee drinkers participated. Consumers rated the acceptance of each tea product on a 9-point hedonic scale and evaluated the reasons for liking or disliking each product based on the check-all-that-apply method. Analysis of Variance, principal component analysis, frequency analysis, and correspondence analysis were utilized for statistical analysis. Twenty sensory attributes were developed in order to characterize the six adlay tea products. The results of the descriptive analysis showed that attributes such as viscosity, black soybean flavor, goso flavor, peanut flavor, seaweed flavor, green, and presence of chunks were key factors differentiating the adlay tea products. In the consumer taste test, roasted flavor, goso flavor, peanut flavor, and presence of chunks were positive drivers for liking the adlay tea products, whereas seaweed and green flavors were negative attributes that drove consumers away.

The objectives of this study were to measure and validate the relative sweetness of various sweeteners and to identify the sweeteners having similar sensory quality to that of sucrose. Twelve types of bulk and intense sweeteners were investigated. The relative sweetness was measured by 2-alternative forced choice method with 5% sucrose solution and the results were validated using descriptive analysis. The relative sweetness of the novel sweeteners such as tagatose, erythritol, stevia, and rebaudioside A 97 were shown to be 0.85, 0.63, 64.1, and 227, respectively. Maltitol and tagatose were shown to elicit very similar sensory characteristics to that of sucrose.

Paraquat (1,1'-dimethyl-4, 4'-bipyridinium dichloride) is a nonselective herbicide that is extremely toxic after acute exposure. It was once widely used in North America and is still used in some countries, including the United States. Although there is little firm evidence that paraquat is a carcinogen, previous studies have suggested a potential relationship with some cancers. This prospective cohort study was performed to evaluate the association between lifetime paraquat exposure and cancer incidence among licensed pesticide applicators with 9.1 years of median follow-up. The lifetime ever-use of paraquat was evaluated in 56,224 subjects at baseline and exposure-response relationship was evaluated in 24,667 subjects (44%) who provided detailed information on total life-time paraquat exposure in a second questionnaire. Among the total subjects, the risk for non-Hodgkin's lymphoma (NHL) in the exposed group was marginally elevated (Relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) compared to the non-exposed group. However, among the 24,667 applicators who supplied total life-time exposure days, the highest tertile of lifetime exposure-days (LE) and intensity-weighted lifetime exposure-days (IWLE) was not significantly associated with NHL risk (RR, 1.57; 95%CI, 0.57-4.23 for LE; RR, 1.42; 95%CI, 0.40-4.71 for IWLE, respectively) and there was no significant exposure-response trend (p-trend > 0.1). There was some suggestion of a possible link between paraquat exposure and NHL risk in humans, but the inconsistency in exposure level trend suggests that this could be a chance finding.

This study was designed to compare the efficacy and tolerability of a new generic formulation of ramipril (test) and the branded formulation of ramipril (reference) to satisfy regulatory requirements for marketing of the generic product for use in Korean patients with mild to moderate hypertension.This was an 8-week, multicenter, prospective, randomized, open-label, parallel-group non-inferiority trial in adult patients (age18 years) with mild to moderate essential hypertension (sitting dia-stolic blood pressure [SiDBP] 90-109 mm Hg). After a 2-week washout of previous antihypertensive medications, eligible patients were randomized to receive either ramipril 5 mg/d in the morning (low-dose group: baseline SiDBP 90-99 mm Hg) or ramipril 10 mg/d (high-dose group: baseline SiDBP 100-109 mm Hg) for the first 4 weeks. If SiDBP wasor = 90 mm Hg after 4 weeks of treatment, the dose was increased to 10 mg/d for the remaining 4 weeks in the low-dose group, and hydrochlorothiazide 12.5 mg was added to the regimen for the remaining 4 weeks in the high-dose group. The primary end point was the change in SiDBP from baseline to week 8. Secondary end points included a noninferiority analysis of the test and reference formulations with respect to the change in mean sitting systolic blood pressure (SiSBP) from baseline to week 8; SiDBP and SiSBP response rates (proportion of patients achieving an SiDBP90 mm Hg and SiSBP140 mm Hg, respectively) at 8 weeks; and changes from baseline in SiSBP, pulse wave velocity (PWV), exercise capacity, left-ventricular diastolic function (LVDF), and levels of brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP). Laboratory and clinical adverse events (AEs) were monitored at each study visit (4 and 8 weeks).The modified intent-to-treat population consisted of 89 patients (45 test, 44 reference; 60 men, 29 women; mean age, 49.7 years; mean weight, 69.9 kg). At week 8, mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (test: from 145.0 [9.7]/98.1 [5.3] mm Hg to 132.2 [11.1]/ 91.8 [7.1] mm Hg [P0.001]; reference: from 145.1 [11.4]/98.0 [5.7] mm Hg to 134.0 [14.6]/92.5 [7.9] mm Hg [P0.001]). The changes in blood pressure at week 8 did not differ significantly between the test and reference groups or between the low- and highdose groups in a subgroup analysis. Blood pressure response rates at 8 weeks did not differ significantly between the groups receiving the test and reference formulations (SiDBP: 26.7% and 31.8%, respectively; SiSBP: 37.8% and 40.9%). In addition, there were no significant between-group differences in the change in PWV (-63.8 and -38.7 cm/sec), LVDF at rest or after exercise, or levels of BNP or hs-CRP. The incidence of AEs was 64.4% in the test formulation group and 68.2% in the reference group formulation (P = NS). The most common AE in both groups was cough (10/45 [22.2%] and 10/44 [22.7%]).There were no significant differences in the efficacy and tolerability of the test and reference formulations of ramipril in these Korean adults with mild to moderate hypertension. The new generic formulation was noninferior to the reference formulation in terms of the change in SiDBP at week 8.

BACKGROUND The present study cross-culturally investigated the drivers of liking for traditional and ethnic chicken marinades using descriptive analysis and consumer taste tests incorporating the check-all-that-apply (CATA) method. Seventy-three Koreans and 86 US consumers participated. The tested sauces comprised three tomato-based sauces, a teriyaki-based sauce and a Korean spicy seasoning-based sauce. Chicken breasts were marinated with each of the five barbecue sauces, grilled and served for evaluation. Descriptive analysis and consumer taste tests were conducted. Consumers rated the acceptance on a hedonic scale and checked the reasons for (dis)liking by the CATA method for each sauce. A general linear model, multiple factor analysis and chi-square analysis were conducted using the data. RESULTS The results showed that the preference orders of the samples between Koreans and US consumers were strikingly similar to each other. However, the reasons for (dis)liking the samples differed cross-culturally. The drivers of liking of two sauces sharing relatively similar sensory profiles but differing significantly in hedonic ratings were effectively delineated by reasons of (dis)liking CATA results. CONCLUSION Reasons for (dis)liking CATA proved to be a powerful supporting method to understand the internal drivers of liking which can be overlooked by generic descriptive analysis. © 2014 Society of Chemical Industry