Indirect influence in social networks as an induced percolation phenomenon.

Percolation theory has been widely used to study phase transitions in network systems. It has also successfully explained various macroscopic spreading phenomena across different fields. Yet, the theoretical frameworks have been focusing on direct interactions among nodes, while recent empirical observations have shown that indirect interactions are common in many network systems like social and ecological networks, among others. By investigating the detailed mechanism of both direct and indirect influence on scientific collaboration networks, here we show that indirect influence can play the dominant role in behavioral influence. To address the lack of theoretical understanding of such indirect influence on the macroscopic behavior of the system, we propose a percolation mechanism of indirect interactions called induced percolation. Surprisingly, our model exhibits a unique anisotropy property. Specifically, directed networks show first-order abrupt transitions as opposed to the second-order continuous transition in the same network structure but with undirected links. A mix of directed and undirected links leads to rich hybrid phase transitions. Furthermore, a unique feature of the nonmonotonic pattern is observed in network connectivities near the critical point. We also present an analytical framework to characterize the proposed induced percolation, paving the way to further understanding network dynamics with indirect interactions.

The associations between modifiable risk factors and nonalcoholic fatty liver disease: A comprehensive Mendelian randomization study.

BACKGROUND AND AIMS: Early identification of modifiable risk factors is essential for the prevention of nonalcoholic fatty liver disease (NAFLD). We aimed to systematically explore the relationships between genetically predicted modifiable risk factors and NAFLD. APPROACH AND RESULTS: We applied univariable and multivariable Mendelian randomization analyses to explore the relationships between 35 modifiable risk factors and NAFLD. We also evaluated the combined results in three independent large genome-wide association studies. Genetically predicted alcohol frequency, elevated serum levels of liver enzymes, triglycerides, C-reactive protein, and obesity traits, including body mass index, waist circumference, and body fat mass, were associated with increased risks of NAFLD (all with p < 0.05). Poor physical condition had a suggestive increased risk for NAFLD (odds ratio [OR] = 2.63, p  = 0.042). Genetically instrumented type 2 diabetes (T2DM), hypothyroidism, and hypertension all increased the risk for NAFLD, and the ORs (95% confidence interval) were 1.508 (1.20-1.90), 13.08 (1.53-111.65), and 3.11 (1.33-7.31) for a 1-U increase in log-transformed odds, respectively. The positive associations of T2DM and hypertension with NAFLD remained significant in multivariable analyses. The combined results from the discovery and two replication datasets further confirmed that alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension significantly increase the risk of NAFLD, whereas higher education and high-density lipoprotein cholesterol (HDL-cholesterol) could lower NAFLD risk. CONCLUSIONS: Genetically predicted alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension were associated with an increased risk of NAFLD, whereas higher education and HDL-cholesterol were associated with a decreased risk of NAFLD.

Causal association of nonalcoholic fatty liver disease with 22 extrahepatic cancers: A Mendelian randomization study.

AIM: It is unclear whether nonalcoholic fatty liver disease (NAFLD) acts as a direct contributing factor to multiple extrahepatic cancers. We aimed to systematically investigate the causal relationships of NAFLD with extrahepatic cancers. METHODS: We conducted a two-sample Mendelian randomization analysis to assess the causal effects of NAFLD on 22 extrahepatic cancers. We examined the association of NAFLD with extrahepatic cancers using multiple methods in the largest genome-wide association study meta-analysis to date. We also replicated the analyses and performed two independent sensitivity analysis in the largest genome-wide association study of UK Biobank. RESULTS: Using the weighted median method, genetically predicted NAFLD was significantly associated with female breast cancer risk (odds ratio [OR] 15.99; 95% confidence interval [CI] 9.58-26.69). Genetically predicted NAFLD is associated with cervical and laryngeal cancers using the inverse variance weighting method, and the ORs were 2.44 (95% CI 1.43-4.14) and 1.94 (95% CI 1.35-2.78), respectively. We observed that patatin-like phospholipase domain-containing protein 3-driven and transmembrane 6 superfamily member 2-driven NAFLD were associated with increased risks of leukemia, lung cancer, and prostate cancers (all with p < 0.05). Furthermore, we confirmed the causal association between NAFLD and breast cancer using five known single-nucleotide polymorphisms of NAFLD and six genome-wide association study-identified variants. The ORs of the weighted median estimator was 10.76 (95% CI 8.27-13.98) and 10.76 (95% CI 8.25-14.04), respectively (p < 0.001). CONCLUSION: Genetically predicted NAFLD is associated with an increased risk of female breast cancer, as well as cervical, laryngeal, leukemia, lung, and prostate cancers.

Causal association between inflammatory bowel disease and 32 site-specific extracolonic cancers: a Mendelian randomization study.

BACKGROUND: The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between IBD and extracolonic cancers. METHODS: Independent genetic variants strongly associated with IBD were extracted as instrumental variables from genome-wide association study (GWAS) conducted by the International IBD Genetics Consortium including 12,882 IBD patients, 5956 Crohn's disease (CD) patients, and 6968 ulcerative colitis (UC) patients. Three sources of cancer GWAS were selected as outcome data. Two-sample Mendelian randomization (MR) analysis was conducted to assess the causal effects of IBD on 32 extracolonic cancers. The meta-analysis was applied to assess the combined causal effect with multiple MR results. RESULTS: IBD, CD, and UC have potential causal associations with oral cavity cancer (IBD: OR = 1.180, 95% CI: 1.059 to 1.316, P = 0.003; CD: OR = 1.112, 95% CI: 1.008 to 1.227, P = 0.034; UC: OR = 1.158, 95% CI: 1.041 to 1.288, P = 0.007). Meta-analysis showed a significant positive causal relationship between IBD and breast cancer (OR = 1.059; 95% CI: 1.033 to 1.086; P < 0.0001) as well as a potential causal relationship between CD and breast cancer (OR = 1.029; 95% CI: 1.002 to 1.055; P = 0.032) based on combining multiple MR results. CONCLUSIONS: This comprehensive MR analysis suggested that genetically predicted IBD, as well as its subtypes, may be a risk factor in the development of oral cavity and breast cancer.

Minimal water exchange by the air-water valve versus left colon water exchange in unsedated colonoscopy: a randomized controlled trial.

BACKGROUND: Water exchange colonoscopy is the least painful method for unsedated colonoscopies. Simplified left colon water exchange (LWE) reduces the cecal intubation time but it is difficult to avoid the use of an additional pump. Minimal water exchange (MWE) is an improved novel method that eliminates the need for pumps, but it is not clear whether MWE has the same efficiency as LWE. METHODS: This was a prospective, randomized, controlled, noninferiority trial conducted in a tertiary hospital. Enrolled patients were randomized 1:1 to the LWE group or MWE group. The primary outcome was recalled insertion pain measured by a 4-point verbal rating scale. Secondary outcomes included adenoma detection rate (ADR), cecal intubation time, volume of water used, and patient willingness to repeat unsedated colonoscopy. RESULTS: 226 patients were included (LWE n = 113, MWE n = 113). The MWE method showed noninferior moderate/severe pain rates compared with the LWE method (10.6 % vs. 9.7 %), with a difference of 0.9 percentage points (99 % confidence interval [CI] -9.5 to 11.3; threshold, 15 %). ADR, cecal intubation time, and willingness to repeat unsedated colonoscopy were not significantly different between the two groups, but the mean volume of water used was significantly less with MWE than with LWE (163.7 mL vs. 407.2 mL; 99 %CI -298.28 to -188.69). CONCLUSION: Compared with LWE, MWE demonstrated a noninferior outcome for insertion pain, and comparable cecal intubation time and ADR, but reduced the volume of water used and eliminated the need for a water pump.

Associations of serum uric acid levels with liver disease-related morbidity and mortality: A prospective cohort study of the UK Biobank.

BACKGROUND AND AIMS: The association of serum uric acid (SUA) levels with liver-related morbidity and mortality remains undetermined. Therefore, we aimed to explore the association of SUA levels with liver-related morbidity and mortality. METHODS: The present cohort study included 459 619 adults from the UK Biobank. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SUA levels with morbidity and mortality of overall liver disease. Mendelian randomization (MR) analyses were conducted to explore the underlying causality. A polygenic risk score was generated to assess whether there was a gene-exposure interaction. RESULTS: During a median follow-up of 12.6 years, 14 302 nonfatal and 609 fatal cases of overall liver disease were identified. Compared to individuals in the lowest quartile, the HRs (95% CI) of incident overall liver disease were 1.08 (1.02-1.14), 1.13 (1.07-1.20) and 1.44 (1.36-1.53) for individuals with SUA levels in quartiles 2, 3 and 4 respectively. Similarly, the HRs (95% CI) of liver disease-associated mortality were 1.09 (0.78-1.52), 1.55 (1.14-2.13) and 1.96 (1.42-2.69) for individuals with SUA levels in quartiles 2, 3 and 4 respectively. The MR results did not support the causal association of SUA levels with liver disease. In addition, there was a significant modification effect of the polygenic risk score on the association of SUA levels with incident overall liver disease (pinteraction  = .003). CONCLUSIONS: Higher SUA levels were significantly associated with an increased risk of overall liver disease morbidity and mortality.

Causal relationship of sugar-sweetened and sweet beverages with colorectal cancer: a Mendelian randomization study.

BACKGROUND AND AIM: Prospective cohort studies have suggested that sugar-sweetened beverages (SSBs) intake is significantly associated with the risk of colorectal cancer (CRC). However, it remains unclear whether this observed association was susceptible to potential confounding factors due to the long-term development process of CRC, and the risk of CRC associated with sweet beverages has rarely been reported. We aimed to investigate the association between SSBs/sweet beverages and CRC risk. METHODS: We performed two-sample Mendelian randomization (MR) analysis using independent genetic variants for SSBs and sweet beverages from a published genome-wide association study (GWAS). Summary statistics for instrument-outcome associations from two databases for malignant neoplasms of the colon and the rectum (FinnGen and UK Biobank). The inverse weighted method (IVW) meta-analysis was the main method used to estimate the relationship, and sensitivity analyses were performed with Cochran's Q test, leave-one-out analysis, MR-Egger regression, Steiger filtering, and the MR PRESSO test. RESULTS: Genetically predicted SSBs intake was associated with a higher colonic malignant neoplasms risk (odds ratio (OR): 1.013; 95% confidence interval (CI) 1.001, 1.026; P = 0.036) in a combined sample size of 579,986 individuals (4029 cases). Such a significant causal effect of SSBs on rectal malignant neoplasms or sweet beverages on CRC was not observed. CONCLUSION: Our findings corroborated a causal association between SSBs and colonic malignant neoplasms risk but did not support such a relationship in the analysis of the rectal malignant neoplasms nor the sweet beverage intake, which might be interpreted with caution and further confirmed.

Different dietary carbohydrate component intakes and long-term outcomes in patients with NAFLD: results of longitudinal analysis from the UK Biobank.

BACKGROUND: This study aimed to investigate the association between the intake of different dietary carbohydrate components and the long-term outcomes of non-alcoholic fatty liver disease (NAFLD). METHODS: We used prospective data from 26,729 NAFLD participants from the UK Biobank cohort study. Dietary information was recorded by online 24-hour questionnaires (Oxford WebQ). Consumption of different carbohydrate components was calculated by the UK Nutrient Databank Food Composition Table. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). A substitution model was used to estimate the associations of hypothetical substitution for free sugars. RESULTS: During a median of 10.5 (IQR: 10.2-11.2) years and a total of 280,135 person-years of follow-up, 310 incident end-stage liver disease (ESLD) and 1750 deaths were recorded. Compared with the lowest quartile, the multi-adjusted HRs (95% CI) of incident ESLD in the highest quartile were 1.65 (1.14-2.39) for free sugars, 0.51 (0.35-0.74) for non-free sugars, and 0.55 (0.36-0.83) for fiber. For overall mortality, the multi-adjusted HRs (95% CI) in the highest quartile were 1.21 (1.04-1.39) for free sugars, 0.79 (0.68-0.92) for non-free sugars, and 0.79 (0.67-0.94) for fiber. Substituting free sugars with equal amounts of non-free sugars, starch or fiber was associated with a lower risk of incident ESLD and overall mortality. CONCLUSIONS: A lower intake of free sugars and a higher intake of fiber are associated with a lower incidence of ESLD and overall mortality in NAFLD patients. These findings support the important role of the quality of dietary carbohydrates in preventing ESLD and overall mortality in NAFLD patients.

Association between night shift work and NAFLD: a prospective analysis of 281,280 UK Biobank participants.

CONTEXT: This study aimed to investigate the association between night shift work and the risk of nonalcoholic fatty liver disease (NAFLD). METHODS: We conducted a prospective analysis of 281,280 UK Biobank participants. Cox proportional hazards models were used to estimate the association of night shift work with incident NAFLD. Polygenic risk score analyses were performed to assess whether a genetic predisposition to NAFLD modified the association. RESULTS: During a median follow-up of 12.1 years (3,373,964 person-years), 2,555 incident NAFLD cases were identified. Compared with workers who never/rarely worked night shifts, those who worked some night shifts or usual/permanent night shifts were 1.12 (95% CI: 0.96-1.31) and 1.27 (95% CI: 1.08-1.48) times more likely to develop NAFLD, respectively. Among the 75,059 participants who had reports on lifetime experience of night shift work, those with a longer duration, a higher frequency, more consecutive night shifts and a longer length per shift all showed higher risks of incident NAFLD. Further analyses showed that the association between night shift work and incident NAFLD was not modified by a genetic predisposition to NAFLD. CONCLUSIONS: Night shift work was associated with increased risks of incident NAFLD.

External validation of two prediction models for adequate bowel preparation in Asia: a prospective study.

BACKGROUND: Several models for predicting adequate bowel preparation are available but have never been externally validated. The aim of this study is to compare the available models in an independent population. METHODS: This study prospectively recruited 500 consecutive patients from August to December 2020 from the Endoscopy Center of a tertiary hospital. All patients underwent the same bowel preparation regimen. The discrimination of the prediction models was quantified with the area under the receiver operating characteristic curve (AUC), and the 95% confidence interval (CI) was calculated for each AUC. RESULTS: Finally, 461 patients were eligible for this study. A total of 110 (23.9%) patients were deemed to show inadequate bowel preparation during colonoscopy. There were significant differences between patients with and without adequate bowel preparation in terms of current hospitalization, procedure time, comorbidities (including diabetes and constipation), American Society of Anesthesiologists Physical Status Classification System score (ASA) ≥ 3, medication usage, and abdominal/pelvic surgery. The prediction models performed as follows: the Dik ≥ 2 model, the Dik ≥ 3 model, and the Antonio > 1.225 model had AUCs of 0.660 (95% CI = 0.604-0.717), 0.691 (95% CI = 0.646-0.733), and 0.645 (95% CI = 0.615-0.704), respectively. Comparison of the two prediction models showed no significant improvement (Antonio > 1.225 vs. Dik ≥ 3, 1.801, 95% CI = -0.004-0.096, P = 0.072). CONCLUSIONS: Both models are potentially helpful. However, it is necessary to develop or improve a prediction model to obtain a more suitable and detailed model. TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT04607161.

Face-to-Face Instruction and Personalized Regimens Improve the Quality of Inpatient Bowel Preparation for Colonoscopy.

BACKGROUND: Poor bowel preparation is commonly observed in inpatients undergoing colonoscopy, particularly those with higher risks for inadequate bowel preparation. AIMS: The objective of this study was to determine whether personalized bowel preparation regimens combined with face-to-face instruction (FFI) could improve the quality of bowel preparation for inpatient. METHODS: In this endoscopist-blinded, randomized controlled trial, 320 inpatients were enrolled and randomly allocated (1:1) to the control and intervention groups. The intervention group received FFI and personalized bowel preparation regimens, while the control group received the routine bowel preparation regimen and education. The primary outcome was adequate bowel preparation rate. Secondary outcomes included rates of procedure-related adverse events, incorrect diet restriction and laxative intake, etc. RESULTS: The adequate bowel preparation rate in the intervention group was significantly higher compared to control group [intention-to-treat (ITT) analysis: 70.0% vs 51.3%, P < 0.001; per-protocol (PP) analysis: 79.4% vs 58.6%, P < 0.001]. Bowel cleanliness was significantly improved in high-risk inpatients (ITT analysis: 65% vs 44.6%, P = 0.004; PP analysis: 73.0% vs 51.7%, P = 0.004) and in low-risk inpatients (ITT analysis: 80% vs 62.7%, P = 0.037; PP analysis: 92.3% vs 69.8%, P = 0.003). There were no significant differences between two groups regarding procedure-related adverse events. CONCLUSIONS: Personalized bowel preparation regimens combined with FFI improve the rate of adequate bowel preparation, especially for patients with high-risk factors. As such, inpatients could benefit from this novel approach for better bowel preparation to ultimately improve the quality of colonoscopies.

ZmCCT regulates photoperiod-dependent flowering and response to stresses in maize.

BACKGROUND: Appropriate flowering time is very important to the success of modern agriculture. Maize (Zea mays L.) is a major cereal crop, originated in tropical areas, with photoperiod sensitivity. Which is an important obstacle to the utilization of tropical/subtropical germplasm resources in temperate regions. However, the study on the regulation mechanism of photoperiod sensitivity of maize is still in the early stage. Although it has been previously reported that ZmCCT is involved in the photoperiod response and delays maize flowering time under long-day conditions, the underlying mechanism remains unclear. RESULTS: Here, we showed that ZmCCT overexpression delays flowering time and confers maize drought tolerance under LD conditions. Implementing the Gal4-LexA/UAS system identified that ZmCCT has a transcriptional inhibitory activity, while the yeast system showed that ZmCCT has a transcriptional activation activity. DAP-Seq analysis and EMSA indicated that ZmCCT mainly binds to promoters containing the novel motifs CAAAAATC and AAATGGTC. DAP-Seq and RNA-Seq analysis showed that ZmCCT could directly repress the expression of ZmPRR5 and ZmCOL9, and promote the expression of ZmRVE6 to delay flowering under long-day conditions. Moreover, we also demonstrated that ZmCCT directly binds to the promoters of ZmHY5, ZmMPK3, ZmVOZ1 and ZmARR16 and promotes the expression of ZmHY5 and ZmMPK3, but represses ZmVOZ1 and ZmARR16 to enhance stress resistance. Additionally, ZmCCT regulates a set of genes associated with plant development. CONCLUSIONS: ZmCCT has dual functions in regulating maize flowering time and stress response under LD conditions. ZmCCT negatively regulates flowering time and enhances maize drought tolerance under LD conditions. ZmCCT represses most flowering time genes to delay flowering while promotes most stress response genes to enhance stress tolerance. Our data contribute to a comprehensive understanding of the regulatory mechanism of ZmCCT in controlling maize flowering time and stress response.

CLA4 regulates leaf angle through multiple hormone signaling pathways in maize.

Leaf angle is an important agronomic trait in cereals and shares a close relationship with crop architecture and grain yield. Although it has been previously reported that ZmCLA4 can influence leaf angle, the underlying mechanism remains unclear. In this study, we used the Gal4-LexA/UAS system and transactivation analysis to demonstrate in maize (Zea mays) that ZmCLA4 is a transcriptional repressor that regulates leaf angle. DNA affinity purification sequencing (DAP-Seq) analysis revealed that ZmCLA4 mainly binds to promoters containing the EAR motif (CACCGGAC) as well as to two other motifs (CCGARGS and CDTCNTC) to inhibit the expression of its target genes. Further analysis of ZmCLA4 target genes indicated that ZmCLA4 functions as a hub of multiple plant hormone signaling pathways: ZmCLA4 was found to directly bind to the promoters of multiple genes including ZmARF22 and ZmIAA26 in the auxin transport pathway, ZmBZR3 in the brassinosteroid signaling pathway, two ZmWRKY genes involved in abscisic acid metabolism, ZmCYP genes (ZmCYP75B1, ZmCYP93D1) related to jasmonic acid metabolism, and ZmABI3 involved in the ethylene response pathway. Overall, our work provides deep insights into the ZmCLA4 regulatory network in controlling leaf angle in maize.

Impact of second forward-view examination on adenoma detection rate during unsedated colonoscopy: a randomized controlled trial.

OBJECTIVES: Colorectal cancer on the right side of the colon has been suggested to be harder to detect by colonoscopy. The aim of this study was to evaluate whether a second forward-view examination of the right side of the colon could increase the adenoma detection rate (ADR) and/or polyp detection rate (PDR). METHODS: This was a single-centre randomized controlled trial. Patients undergoing colonoscopy were recruited and randomly assigned to the second forward-view examination (SFE) group, in which the right side of the colon was examined twice or the traditional colonoscopy (TC) group in which the colonoscopy was performed in a standard manner. The primary outcome was the ADR of right colon. The overall PDR and ADR, PDR of the right colon, per-adenoma miss rate of the right colon, and advanced lesion detection rate were also recorded and compared. RESULTS: A total of 392 patients were included in the study (SFE group 197 vs. TC group 195). The ADR and PDR of the right colon in the SFE group were significantly higher than those in the TC group (ADR 10.7% vs. 5.1%; P = 0.042); PDR 17.8% vs. 9.7%, P = 0.021). No significant difference was found in overall PDR/ADR, or advanced lesion detection rate between the two groups. CONCLUSIONS: This prospective controlled study revealed that a second forward-view examination could modestly increase the ADR and PDR of the right colon during unsedated colonoscopies. This simple, safe and time-effective technique might be recommended for routine unsedated colonoscopy. TRIAL REGISTRATION: Clinical Trials.gov, NCT03619122. Registered on 7/8/2018.

Similar or dissimilar? Influence of similarity between distraction tasks and target tasks on unconscious thought.

Distraction tasks are known to affect the unconscious-thought (UT) effect. However, the relationship between two task types, namely distraction and target tasks, and their effect on UT effect have not been examined in previous studies. In this study, we assessed whether simultaneously performing dissimilar distraction and target tasks are beneficial to information processing by UT. In Experiment 1, the target task was an Alternate Use Task (speech task). For the similar-task test, the UT group was assigned the speech 1-back task (speech task) as the distraction task; for the dissimilar-task test, the UT group was assigned the spatial 1-back task (spatial task) as the distraction task. The results of the experiment revealed that under dissimilar tasks, the UT group not only provided more answers but also provided answers that were more novel. For Experiment 2, the target task was changed to Creative Mental Synthesis Task (spatial task) to replicate the results of Experiment 1. The results demonstrated that the dissimilarity between the distraction and target tasks facilitates the UT.

Light-to-Moderate Alcohol Consumption Is Associated With Increased Risk of Type 2 Diabetes in Individuals With Nonalcoholic Fatty Liver Disease: A Nine-Year Cohort Study.

OBJECTIVE: This study explored the association between light-to-moderate alcohol consumption (LMAC) and risk of type 2 diabetes mellitus (T2DM) in individuals with nonalcoholic fatty liver disease (NAFLD). METHODS: A 9-year cohort study was performed among Chinese men who underwent their annual health checkups between 2009 and 2018. NAFLD was diagnosed based on abdominal ultrasound with exclusion of excess alcohol intake and other causes of liver disease. Logistic regression and Cox proportional regression analyses were applied to identify the risk of prevalent and incident T2DM. RESULTS: Of the 7,079 participants enrolled, 243 had T2DM at baseline and 630 developed T2DM during the 45,456 person-years follow-up. Both at the baseline and by the end of the follow-up, LMAC was associated with a decreased risk of prevalent T2DM in NAFLD-free participants but with a significantly increased risk in patients with NAFLD. LMAC was also associated with a decreased risk of incident T2DM in NAFLD-free participants. The adjusted hazard ratios (95% confidence interval) of incident T2DM were 0.224 (0.115-0.437) and 0.464 (0.303-0.710) for NAFLD-free light drinkers and NAFLD-free moderate drinkers, respectively. Nondrinking, light-drinking, and moderate-drinking patients with NAFLD all showed significantly increased risks of incident T2DM. Compared with NAFLD-free nondrinkers, the adjusted hazard ratios (95% confidence interval) of incident T2DM were 1.672 (1.336-2.092), 2.642 (1.958-3.565), and 2.687 (2.106-3.427) for nondrinking, light-drinking, and moderate-drinking patients with NAFLD, respectively. DISCUSSION: LMAC decreased the risks of prevalent and incident T2DM in NAFLD-free participants. LMAC, however, was associated with an increased risk of T2DM in patients with NAFLD (ClinicalTrials.gov number: NCT03847116).

Underwater versus conventional endoscopic mucosal resection for small size non-pedunculated colorectal polyps: a randomized controlled trial : (UEMR vs. CEMR for small size non-pedunculated colorectal polyps).

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) is a recently developed technique and can be performed during water-aided or ordinary colonoscopy for the treatment of colorectal polyps. The objective of this clinical trial was to evaluate the efficacy and safety of UEMR in comparison with conventional endoscopic mucosal resection (CEMR) of small non-pedunculated colorectal polyps. METHODS: Patients with small size, non-pedunculated colorectal polyps (4-9 mm in size) who underwent colonoscopic polypectomy were enrolled in this multicenter randomized controlled clinical trial. The patients were randomly allocated to two groups, an UEMR group and a CEMR group. Efficacy and safety were compared between groups. RESULTS: In the intention-to-treat (ITT) analysis, the complete resection rate was 83.1% (59/71) in the UEMR group and 87.3% (62/71) in the CEMR group. The en-bloc resection rate was 94.4% (67/71) in the UEMR group and 91.5% (65/71) in the CEMR group (difference 2.9%; 90% CI - 4.2 to 9.9%), showed noninferiority (noninferiority margin - 5.7% < - 4.2%). No significant difference in procedure time (81 s vs. 72 s, P = 0.183) was observed. Early bleeding was observed in 1.4% of patients in the CEMR group (1/71) and 1.4% of patients in the UEMR group (1/71). None of the patients in the UEMR group complained of postprocedural bloody stool, whereas two patients in the CEMR group (2/64) reported this adverse event. CONCLUSION: Our results indicate that UEMR is safer and just as effective as CEMR in En-bloc resection for the treatment of small colorectal polyps as such, UEMR is recommended as an alternative approach to excising small and non-pedunculated colorectal adenomatous polyps. TRIAL REGISTRATION: Clinical Trials.gov, NCT03833492 . Retrospectively registered on February 7, 2019.

Evaluation of Carbazeran 4-Oxidation and O 6-Benzylguanine 8-Oxidation as Catalytic Markers of Human Aldehyde Oxidase: Impact of Cytosolic Contamination of Liver Microsomes.

The present study investigated the contribution of microsomal cytochrome P450 and cytosolic aldehyde oxidase-1 (AOX-1) to carbazeran 4-oxidation and O 6-benzylguanine 8-oxidation in human liver microsomal, cytosolic, and S9 fractions. Incubations containing carbazeran and human liver microsomes with or without exogenously added NADPH yielded comparable levels of 4-oxo-carbazeran. O 6-Benzylguanine 8-oxidation occurred in microsomal incubations, and the extent was increased by NADPH. Human recombinant CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 did not catalyze carbazeran 4-oxidation, whereas CYP1A2 was highly active in O 6-benzylguanine 8-oxidation. 1-Aminobenzotriazole, a pan-cytochrome P450 inhibitor, decreased O 6-benzylguanine 8-oxidation, but not carbazeran 4-oxidation, in microsomal incubations, whereas 1-aminobenzotriazole and furafylline (a CYP1A2-selective inhibitor) did not inhibit carbazeran 4-oxidation or O 6-benzylguanine 8-oxidation in human liver S9 fraction. Carbazeran 4-oxidation in incubations containing human liver microsomes (from multiple donors and commercial suppliers) was attributed to microsomal preparations contaminated with AOX-1, as suggested by liver microsomal experiments indicating a decrease in carbazeran 4-oxidation by an AOX-1 inhibitor (hydralazine), and to detection of AOX-1 protein (at one-third the level of that in liver cytosol). Cytosolic contamination of liver microsomes was further demonstrated by the formation of dehydroepiandrosterone sulfate (catalyzed by cytosolic sulfotransferases) in liver microsomal incubations containing dehydroepiandrosterone. In conclusion, carbazeran 4-oxidation and O 6-benzylguanine 8-oxidation are enzyme-selective catalytic markers of human AOX-1, as shown in human liver S9 fraction expressing cytochrome P450 and AOX-1. This study highlights the negative impact of cytosolic contamination of liver microsomes on the interpretation of reaction phenotyping data collected in an in vitro study performed in microsomal fractions.

Impact of visceral adiposity on severity of acute pancreatitis: a propensity score-matched analysis.

BACKGROUND: The relationship between visceral adiposity and acute pancreatitis (AP) has not been completely elucidated. This study evaluated the significance of visceral adipose tissue (VAT) and the ratio of VAT to skeletal muscle tissue (VAT/SMT) in the prognosis of AP patients. METHODS: Based on a 1:2 propensity score matching, 306 hospitalized patients were enrolled in the study analysis from 2010 to 2017. VAT, subcutaneous adipose tissue (SAT), and SMT were measured using unenhanced computed tomography (CT). Cox proportional hazards models were applied for the analysis. RESULTS: VAT and the VAT/SMT ratio were significantly higher in the severe AP (SAP) and moderately severe AP (MSAP) groups compared to the mild AP (MAP) group (both p < 0.001). Intensive care transfer, AP severity, systemic complications, and prognostic scores (Acute Physiology and Chronic Health Evaluation II [APACHE-II] score ≥ 8, Ranson's score ≥ 3, Bedside Index of Severity in Acute Pancreatitis [BISAP] score ≥ 3, and the systemic inflammatory response syndrome [SIRS] score ≥ 2) significantly correlated with VAT and the VAT/SMT ratio in AP patients. The multivariate adjusted hazard ratios (HRs) for VAT and the VAT/SMT ratio in the relationship of body parameters and AP mortality were 1.042 (95% confidence interval (CI), 1.019-1.066) and 7.820 (95% CI, 1.978-30.917), respectively. Compared with other prognostic scores, VAT had the highest area under the curve of receiver operating characteristics (ROC) (0.943, 95% CI, 0.909-0.976). CONCLUSION: High VAT and VAT/SMT ratio are independent negative prognostic indicators of AP. TRIAL REGISTRATION: Clinical study registration number: NCT03482921 . Date of registration: 03/23/2018.