Characteristics of Advanced Colorectal Cancer Detected by Fecal Immunochemical Test Screening in Participants with a Negative Result the Previous Year

Background: There is sufficient evidence to show the mortality reduction effect of colorectal cancer (CRC) screening programs using the fecal occult blood test (FOBT). However, we see cases that are found to be advanced CRC despite yearly FOBT screening. Methods: The aim of this study was to investigate the characteristics of advanced CRC detected by a fecal immunochemical test (FIT) screening program in participants with a negative screening result the previous year, which we call “Negative advanced CRC”. A total of 109,639 participants (10.0% required colonoscopy, of whom 76.9% received one) underwent a CRC screening program using a FIT from fiscal 2009 to 2017. Negative advanced CRC was compared with advanced CRC (First advanced CRC) found at the first visit in a person who had not had a FIT screening history for more than 3 years. In addition, we compared the characteristics of Negative advanced CRC with those of interval cancer: cancer cases detected after a negative screening result and before the date of the next recommended screening. Results: A total of 339 cases of CRC (175 male: 164 female, 173 early stage: 166 advanced stage) were detected in the nine-year CRC screening period. The rate of right-sided CRCs was significantly higher in female (P < 0.01), advanced stage (P < 0.01), negative result previous year (P < 0.01), and symptom-negative (P < 0.01) participants than in each counterpart, respectively. The ratio of female (22/35; 62.9%) patients in Negative advanced CRCs tended to be high compared with that (40/83; 48.2%) in First advanced CRCs (P = 0.145). Overall, 22 (62.9%) of 35 Negative advanced CRCs and 28 (33.7%) of 83 First advanced CRCs were located in the right-sided colon, and the rate was significantly higher in Negative advanced CRCs (P < 0.01). In addition, the frequency of female patients was significantly higher in right-sided Negative advanced CRCs than in right-sided First advanced CRCs (P = 0.03). Conclusion: The characteristics of Negative advanced CRC cases (female and right-sided colon) were similar to those of interval cancer reported so far. In the future, it will be necessary to introduce a screening program that is highly sensitive to right-sided CRC

Efficacy of pegylated interferon plus ribavirin in combination with corticosteroid for two cases of combined hepatitis C and autoimmune hepatitis

The treatment strategy for cases of combined autoimmune hepatitis (AIH) and chronic hepatitis C (CHC) has not yet been established. A 47-year-old woman and a 53-year-old-woman were hospitalized for treatment of CHC. Ultrasonography and histological findings revealed that their liver was not cirrhotic but did have chronic damage. The histological findings of both patients were suggestive of AIH. The patients were systematically treated with pegylated interferon-alpha 2b plus ribavirin which was preceded by and combined with corticosteroid (CS), and showed sustained virological responses and normal liver function. Although these two patients with combined AIH and CHC were successfully treated with this regimen, careful attention to exacerbation of hepatic inflammation is needed because hepatitis C viral load was increased due to immunosuppression during CS treatment

ARTADE2DB: Improved Statistical Inferences for Arabidopsis Gene Functions and Structure Predictions by Dynamic Structure-Based Dynamic Expression (DSDE) Analyses

Recent advances in technologies for observing high-resolution genomic activities, such as whole-genome tiling arrays and high-throughput sequencers, provide detailed information for understanding genome functions. However, the functions of 50% of known Arabidopsis thaliana genes remain unknown or are annotated only on the basis of static analyses such as protein motifs or similarities. In this paper, we describe dynamic structure-based dynamic expression (DSDE) analysis, which sequentially predicts both structural and functional features of transcripts. We show that DSDE analysis inferred gene functions 12% more precisely than static structure-based dynamic expression (SSDE) analysis or conventional co-expression analysis based on previously determined gene structures of A. thaliana. This result suggests that more precise structural information than the fixed conventional annotated structures is crucial for co-expression analysis in systems biology of transcriptional regulation and dynamics. Our DSDE method, ARabidopsis Tiling-Array-based Detection of Exons version 2 and over-representation analysis (ARTADE2-ORA), precisely predicts each gene structure by combining two statistical analyses: a probe-wise co-expression analysis of multiple transcriptome measurements and a Markov model analysis of genome sequences. ARTADE2-ORA successfully identified the true functions of about 90% of functionally annotated genes, inferred the functions of 98% of functionally unknown genes and predicted 1,489 new gene structures and functions. We developed a database ARTADE2DB that integrates not only the information predicted by ARTADE2-ORA but also annotations and other functional information, such as phenotypes and literature citations, and is expected to contribute to the study of the functional genomics of A. thaliana. URL: http://artade.org

水の光電気化学的酸化分解に活性な BiVO4薄膜光電極への Zr 添加効果

Effects of zirconium (Zr) doping into BiVO4 electrode on its structural properties and photoelectrochemical (PEC) property for water oxidation were examined. The BiVO4 electrodes with different Zr contents were prepared via a spin-coating process. Structural analyses using XRD and Raman spectroscopy indicated that all the samples consisted of mixtures of monoclinic scheelite (ms-BiVO4) and tetragonal scheelite (ts-BiVO4) structures. The highest PEC property for water oxidation was achieved when the sample doped with a relatively small amount of Zr (i.e., 0.5% of Zr-doped BiVO4); further doping caused a reduction of PEC property, probably due to the enhancement of carrier recombination induced by such excess Zr components

Identification of risk factors for elevated serum IgG4 levels in subjects in a large-scale health checkup cohort study

Introduction: To allow the identification of IgG4-related disease (IgG4-RD) from a subclinical phase as it is important to understand the risk of elevated serum IgG4 levels. We planned to evaluate serum IgG4 levels in the participants of the Nagasaki Islands Study (NaIS), a large-scale health checkup cohort study.Methods: This study included 3,240 individuals who participated in the NaIS between 2016 and 2018 and consented to participate in the study. Serum IgG4, IgG, and IgE levels and human leukocyte antigen (HLA) genotyping results of the NaIS subjects as well as lifestyle habits and peripheral blood test results were analyzed. The magnetic bead panel assay (MBA) and the standard nephelometry immunoassay (NIA) were used to measure serum IgG4 levels. The data were evaluated using multivariate analysis to identify lifestyle and genetic factors associated with elevated serum IgG4 levels.Results: Serum IgG4 levels measured with the NIA and MBA showed a tight positive correlation between the two groups (correlation coefficient 0.942). The median age of the participants in the NaIS was 69 years [63–77]. The median serum IgG4 level was 30.2 mg/dL [IQR 12.5–59.8]. Overall, 1019 (32.1%) patients had a history of smoking. When the subjects were stratified into three groups based on the smoking intensity (pack-year), the serum IgG4 level was significantly higher among those with a higher smoking intensity. Accordingly, the multivariate analysis identified a significant relationship between smoking status and serum IgG4 elevation.Conclusion: In this study, smoking was identified as a lifestyle factor correlating positively with elevated serum IgG4 levels

Molecular Evolutionary Analysis of the Influenza A(H1N1)pdm, May–September, 2009: Temporal and Spatial Spreading Profile of the Viruses in Japan

BACKGROUND: In March 2009, pandemic influenza A(H1N1) (A(H1N1)pdm) emerged in Mexico and the United States. In Japan, since the first outbreak of A(H1N1)pdm in Osaka and Hyogo Prefectures occurred in the middle of May 2009, the virus had spread over 16 of 47 prefectures as of June 4, 2009. METHODS/PRINCIPAL FINDINGS: We analyzed all-segment concatenated genome sequences of 75 isolates of A(H1N1)pdm viruses in Japan, and compared them with 163 full-genome sequences in the world. Two analyzing methods, distance-based and Bayesian coalescent MCMC inferences were adopted to elucidate an evolutionary relationship of the viruses in the world and Japan. Regardless of the method, the viruses in the world were classified into four distinct clusters with a few exceptions. Cluster 1 was originated earlier than cluster 2, while cluster 2 was more widely spread around the world. The other two clusters (clusters 1.2 and 1.3) were suggested to be distinct reassortants with different types of segment assortments. The viruses in Japan seemed to be a multiple origin, which were derived from approximately 28 transported cases. Twelve cases were associated with monophyletic groups consisting of Japanese viruses, which were referred to as micro-clade. While most of the micro-clades belonged to the cluster 2, the clade of the first cases of infection in Japan originated from cluster 1.2. Micro-clades of Osaka/Kobe and the Fukuoka cases, both of which were school-wide outbreaks, were eradicated. Time of most recent common ancestor (tMRCA) for each micro-clade demonstrated that some distinct viruses were transmitted in Japan between late May and early June, 2009, and appeared to spread nation-wide throughout summer. CONCLUSIONS: Our results suggest that many viruses were transmitted from abroad in late May 2009 irrespective of preventive actions against the pandemic influenza, and that the influenza A(H1N1)pdm had become a pandemic stage in June 2009 in Japan

Effect of CYP2C19 Polymorphism on Treatment Success in Lansoprazole-Based 7-Day Treatment Regimen for Cure of H. pylori Infection in Japan

Recently, Helicobacter pylori (H. pylori)-positive peptic ulcer patients were treated by a 1-week triple therapy [lansoprazole (LPZ) 30 mg, amoxicillin 750 mg and clarithromycin 200 or 400 mg, each twice daily] without the checking CYP2C19 genotype in Japan. This regimen was done to obtain sufficient cure rates for H. pylori infection using a high dose of LPZ (60 mg/day) without the great cost of having to determine the genotype. However, the failure rate for eradicating H. pylori was reported to be 12.5%. The reasons for this were studied in 33 Japanese patients with H. pylori-positive gastric or duodenal ulcer. Blood samples of the patients were collected to determine the genotype of CYP2C19 and plasma concentrations of LPZ and its metabolites at 3 h postdose on the morning of the 7th day of treatment. H. pylori infection was cured in 25 of the 33 patients (75.8%). The cure rate was highest in the group of poor metabolizers (PM), intermediate in the group of extensive metabolizers of the heterozygous type (htEM) and lowest in the group of extensive metabolizers of the homozygous type (hmEM). The relative ratio of mean plasma concentration for LPZ among the 3 groups was 1.00:1.43:2.93 (hmEM:htEM:PM groups). Our data suggest that success of the eradication is dependent on the CYP2C19-related genotypic status or the plasma concentrations of LPZ in a steady state condition after a multiple dosing regimen; that is to say, checking CYP2C19 is necessary even on occasions when treatment is done by H. pylori eradication methods as performed in Japan

Total and High Molecular Weight Adiponectin and Hepatocellular Carcinoma with HCV Infection

Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC), and liver fibrosis in patients with hepatitis C virus (HCV) infection.A case-control study was conducted on 97 HCC patients (cases) and 97 patients (controls) matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW) adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI), progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI).There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively) and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively). Interestingly, lower serum total (OR 11.76, 95% CI: 2.97–46.66 [P<0.001]) and HMW (OR 10.24, CI: 2.80–37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC.Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades

A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Geneenvironment interactions (G x E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G x E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G x E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G x E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant GxBMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer