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Natural working fluid mixtures, including combinations of CO $$_{2}$$ , hydrocarbons, water, and ammonia, are expected to have applications in energy conversion processes such as heat pumps and organic Rankine cycles. However, the available literature data, much of which were published between 1975 and 1992, do not incorporate the recommendations of the Guide to the Expression of Uncertainty in Measurement. Therefore, new and more reliable thermodynamic property measurements obtained with state-of-the-art technology are required. The goal of the present study was to obtain accurate vapor-liquid equilibrium (VLE) properties for complex mixtures based on two different gases with significant variations in their boiling points. Precise VLE data were measured with a recirculation-type apparatus with a 380 cm $$^{3}$$ equilibration cell and two windows allowing observation of the phase behavior. This cell was equipped with recirculating and expansion loops that were immersed in temperature-controlled liquid and air baths, respectively. Following equilibration, the composition of the sample in each loop was ascertained by gas chromatography. VLE data were acquired for CO $$_{2}$$ /ethanol and CO $$_{2}$$ /isopentane binary mixtures within the temperature range from 300 K to 330 K and at pressures up to 7 MPa. These data were used to fit interaction parameters in a Helmholtz energy mixture model. Comparisons were made with the available literature data and values calculated by thermodynamic property models. [ABSTRACT FROM AUTHOR]

The article presents information on a study which described the use of an alkali-hydrolyzable cationic surfactant with a betaine ester group, (1-tetradecyloxycarbonylmethyl)trimethylammonium chloride (C14)B) as a cleavable emulsifier for emulsion polymerization of styrene. A review of the related literature is given. Reagents and chemicals used include Cetyltrimethylammonium chloride (CTAC) and 2,2'-azobis(2-aminidopropane) dihydrochloride. The research findings is discussed.

Resistance to potassium tellurite (PT) is an important indicator in isolating Shiga toxin-producing Escherichia coli (STEC) O157:H7 and other major STEC serogroups. Common resistance determinant genes are encoded in the ter gene cluster. We found an O157:H7 isolate that does not harbor ter but is resistant to PT. One nonsynonymous mutation was found in another PT resistance gene, tehA , through whole-genome sequence analyses. To elucidate the contribution of this mutation to PT resistance, complementation of tehA and the related gene tehB in isogenic strains and quantitative RT‒PCR were performed. The results indicated that the point mutation not only changed an amino acid of tehA , but also was positioned on a putative internal promoter of tehB and increased PT resistance by elevating tehB mRNA expression. Meanwhile, the amino acid change in tehA had negligible impact on the PT resistance. Comprehensive screening revealed that 2.3% of O157:H7 isolates in Japan did not harbor the ter gene cluster, but the same mutation in tehA was not found. These results suggested that PT resistance in E. coli can be enhanced through one mutational event even in ter -negative strains., Importance: Selective agents are important for isolating Shiga toxin-producing Escherichia coli (STEC) because the undesirable growth of microflora should be inhibited. Potassium tellurite (PT) is a common selective agent for major STEC serotypes. In this study, we found a novel variant of PT resistance genes, tehAB , in STEC O157:H7. Molecular experiments clearly showed that one point mutation in a predicted internal promoter region of tehB upregulated the expression of the gene and consequently led to increased resistance to PT. Because tehAB genes are ubiquitous across E. coli , these results provide universal insight into PT resistance in this species., Competing Interests: The authors declare no conflict of interest.

Objective: This study aimed to clarify the interactions between the tongue and primary afferent fibers in tongue cancer pain., Methods: A pharmacological analysis was conducted to evaluate mechanical hypersensitivity of the tongues of rats with squamous cell carcinoma (SCC). Changes in trigeminal ganglion (TG) neurons projecting to the tongue were analyzed using immunohistochemistry and western blotting., Results: SCC inoculation of the tongue caused persistent mechanical sensitization and tumor formation. Trypsin expression was significantly upregulated in cancer lesions. Continuous trypsin inhibition or protease-activated receptor 2 (PAR2) antagonism in the tongue significantly inhibited SCC-induced mechanical sensitization. No changes were observed in PAR2 and transient receptor potential vanilloid 4 (TRPV4) levels in the TG or the number of PAR2-and TRPV4-expressing TG neurons after SCC inoculation. In contrast, the relative amount of phosphorylated TRPV4 in the TG was significantly increased after SCC inoculation and abrogated by PAR2 antagonism in the tongue. TRPV4 antagonism in the tongue significantly ameliorated the mechanical sensitization caused by SCC inoculation., Conclusions: Our findings indicate that tumor-derived trypsin sensitizes primary afferent fibers by PAR2 stimulation and subsequent TRPV4 phosphorylation, resulting in severe tongue pain., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Genetically encoded caged amino acids can be used to control the dynamics of protein activities and cellular localization in response to external cues. In the present study, we revealed the structural basis for the recognition of O -(2-nitrobenzyl)-L-tyrosine ( o NBTyr) by its specific variant of Methanocaldococcus jannaschii tyrosyl-tRNA synthetase ( o NBTyrRS), and then demonstrated its potential availability for time-resolved X-ray crystallography. The substrate-bound crystal structure of o NBTyrRS at a 2.79 Å resolution indicated that the replacement of tyrosine and leucine at positions 32 and 65 by glycine (Tyr32Gly and Leu65Gly, respectively) and Asp158Ser created sufficient space for entry of the bulky substitute into the amino acid binding pocket, while Glu in place of Leu162 formed a hydrogen bond with the nitro moiety of o NBTyr. We also produced an o NBTyr-containing lysozyme through a cell-free protein synthesis system derived from the Escherichia coli B95. ΔA strain with the UAG codon reassigned to the nonnatural amino acid. Another crystallographic study of the caged protein showed that the site-specifically incorporated o NBTyr was degraded to tyrosine by light irradiation of the crystals. Thus, cell-free protein synthesis of caged proteins with o NBTyr could facilitate time-resolved structural analysis of proteins, including medically important membrane proteins.

Dibenzo[ g , p ]chrysene (DBC), which consists of a twisted naphthalene core with four fused benzene rings, is a promising framework for organic electronic materials. Therefore, the research for structure-property relationships is important for the design of DBC-based materials. Here, the electrochemical and spectroscopic properties of DBC derivatives were investigated, and the effects of substituents and torsion of the naphthalene moiety were examined based on density functional theory (DFT) calculations. All the substituted DBC derivatives showed higher oxidation potentials than that for DBC-H , even for compounds that contained an electron-donating group such as DBC-Me and DBC-SMe . DFT calculations clearly indicate that these higher oxidation potentials are due to the ineffective conjugation of the MeO group, which is oriented perpendicular to the benzene ring because of the steric repulsion of substituents on both sides. More specifically, the inductive effect of the MeO group is dominant rather than the mesomeric effect when the substituent is located at both sides of the MeO group. Concerning the torsion of the naphthalene moiety, the twisting results in a slight increase in the HOMO and a slight lowering of the LUMO. The twisting effect is much smaller than the conjugation effect of the MeO group. Absorption spectra of all the substituted DBC derivatives also showed a red-shift as compared to that for DBC-H . Concerning the luminescence, a strong photoluminescence was observed for DBC-H and DBC-Si ., (Copyright © 2022, Imai et al.)

Light-driven chloride-pumping rhodopsins actively transport anions, including various halide ions, across cell membranes. Recent studies using time-resolved serial femtosecond crystallography (TR-SFX) have uncovered the structural changes and ion transfer mechanisms in light-driven cation-pumping rhodopsins. However, the mechanism by which the conformational changes pump an anion to achieve unidirectional ion transport, from the extracellular side to the cytoplasmic side, in anion-pumping rhodopsins remains enigmatic. We have collected TR-SFX data of Nonlabens marinus rhodopsin-3 (NM-R3), derived from a marine flavobacterium, at 10-µs and 1-ms time points after photoexcitation. Our structural analysis reveals the conformational alterations during ion transfer and after ion release. Movements of the retinal chromophore initially displace a conserved tryptophan to the cytoplasmic side of NM-R3, accompanied by a slight shift of the halide ion bound to the retinal. After ion release, the inward movements of helix C and helix G and the lateral displacements of the retinal block access to the extracellular side of NM-R3. Anomalous signal data have also been obtained from NM-R3 crystals containing iodide ions. The anomalous density maps provide insight into the halide binding site for ion transfer in NM-R3., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

We present a novel methodology based on ion conductance to evaluate the perfusability of vascular vessels in microfluidic devices without microscopic imaging. The devices consisted of five channels, with the center channel filled with fibrin/collagen gel containing human umbilical vein endothelial cells (HUVECs). Fibroblasts were cultured in the other channels to improve the vascular network formation. To form vessel structures bridging the center channel, HUVEC monolayers were prepared on both side walls of the gel. During the culture, the HUVECs migrated from the monolayer and connected to the HUVECs in the gel, and vascular vessels formed, resulting in successful perfusion between the channels after culturing for 3-5 d. To evaluate perfusion without microscopic imaging, Ag/AgCl wires were inserted into the channels, and ion currents were obtained to measure the ion conductance between the channels separated by the HUVEC monolayers. As the HUVEC monolayers blocked the ion current flow, the ion currents were low before vessel formation. In contrast, ion currents increased after vessel formation because of creation of ion current paths. Thus, the observed ion currents were correlated with the perfusability of the vessels, indicating that they can be used as indicators of perfusion during vessel formation in microfluidic devices. The developed methodology will be used for drug screening using organs-on-a-chip containing vascular vessels.

Background and Aim: Underwater endoscopic mucosal resection (U-EMR) has been attracting much attention as treatment for patients with nonampullary duodenal epithelial tumors (NADETs). We aim to compare treatment outcomes, including submucosal resectability, between patients undergoing U-EMR and conventional endoscopic mucosal resection (C-EMR) for NADET., Methods: We conducted a retrospective review of 38 patients with NADET treated by U-EMR or C-EMR. In the resected specimens, we measured the horizontal length, the vertical distance from the muscularis mucosa to the margin at the deepest site, and the overall submucosal area. The submucosal index (SMI) was defined as the overall submucosal area divided by the largest horizontal length. These values and other treatment outcomes were compared between NADETs resected by U-EMR and C-EMR., Results: The median size of lesions was 7 mm with a range of 3-13 mm. Although the incidence of adverse events and the rates of en bloc and R0 resection were not different in the two groups, the median procedure time was significantly shorter in the U-EMR group (11 min vs 13 min; P = 0.045). The median submucosal depth at the deepest site (1.22 mm vs 1.08 mm; P = 0.38) and the median SMI (0.44 vs 0.41; P = 0.42) were not different between groups., Conclusions: The resectability between NADETs treated by U-EMR and C-EMR was comparable. These results, together with the shorter procedure time required for U-EMR, suggest that U-EMR may have the potential to be the first choice for small to medium-sized NADET., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: The aim of this study was to examine the predictive scoring system of advanced liver fibrosis in severely obese Japanese patients., Methods: Seventy-two patients underwent laparoscopic sleeve gastrectomy and intraoperative liver biopsies. We classified these patients into two groups: Brunt stage ≥ 2 (advanced fibrosis) and 0/1 (none/mild fibrosis). A logistic regression analysis was performed to identify the predictors of advanced fibrosis., Results: Sixteen patients had advanced fibrosis, while 56 had no/mild fibrosis. The prevalence of type 2 diabetes mellitus (T2DM) in advanced fibrosis group was significantly higher than in none/mild fibrosis. An univariate analysis of the factors predicting advanced fibrosis showed significant differences in AST/ALT ratio, serum insulin levels, HOMA-IR, and type IV collagen 7S in the T2DM group. According to a multivariate analysis, type IV collagen 7S was an independent predictor and the cutoff value was 5.6 ng/mL. We created a flow chart; high risk (T2DM and type IV collagen 7S ≥ 5.6 ng/mL), moderate risk (T2DM and type IV collagen 7S < 5.6 ng/mL), and low risk (non-DM). For those at high risk, the sensitivity, specificity, positive predictive value, and negative predictive value were 56.2%, 94.4%, 75.0%, and 87.9%, respectively., Conclusion: This classification system has the potential to accurately categorize the risk of liver fibrosis., (© 2021. Springer Nature Singapore Pte Ltd.)

Background/aims: Although colonic diverticular bleeding (CDB) is common, few reports have described the effects of antithrombotic agents (ATs) on CDB. This study aimed to clarify the risk factors of re-bleeding within a year in CDB patients., Methods: We retrospectively analyzed the risk of re-bleeding in CDB patients. Among 324 patients who were hospitalized for acute lower gastrointestinal bleeding at our institution during the period from 2015 to 2019, we used 76 patients who were diagnosed as CDB. Risk factors for re-bleeding were determined by Cox proportional hazard models., Results: Of 76 patients analyzed, 32 were taking ATs, nine of whom were taking multiple agents. Twenty-six patients re-bled within a year. Compared with the patients without re-bleeding, patients with re-bleeding within a year had been treated by antithrombotic therapy more frequently (62% vs. 32%, p = 0.013). Cox proportional hazard model revealed that treatment with ATs (hazard ratio 3.89, 95% confidence interval 1.53-10.74, p = 0.004) was an independent risk factor for re-bleeding within a year., Conclusion: ATs were found to be an independent risk factor related to re-bleeding within a year in patients with CDB., Competing Interests: Authors declare no conflict of interests for this article., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Clinical outcomes and prognostic factors for survival after endoscopic submucosal dissection (ESD) in older patients aged ≥ 85 years with early gastric cancer (EGC) are not well defined. The aim of this study was to investigate the clinical outcomes and prognostic factors for survival after ESD in older patients aged ≥ 85 years with EGC., Methods: Clinical outcomes of 70 patients aged ≥ 85 years with EGC treated with ESD were evaluated retrospectively. Prognostic factors for overall survival (OS) were analyzed with the Kaplan-Meier method and a Cox proportional hazards model., Results: During the follow-up period, 33 patients died from any cause, none of whom died from gastric cancer. OS probability after 3 years was 90.0%. Univariate analyses revealed that a neutrophil/lymphocyte ratio ≥ 2.6, a prognostic nutritional index (PNI) < 42.5 and low serum albumin value (< 3.5 g/dl) were associated with poor OS. Cox multivariate analysis revealed low PNI (< 42.5) to be an independent prognostic factor associated with OS (hazard ratio; 3.40, 95% confidence interval; 1.47-7.86, P = 0.004)., Conclusions: PNI may be a useful parameter for making the decision to perform ESD for older patients aged ≥ 85 years with EGC., (© 2021. The Author(s).)

Background and study aims  Some studies have reported an association between clinicopathological features and mucin phenotypes of non-ampullary duodenal epithelial tumors (NADETs). However, the association between clinical outcomes of endoscopic resection (ER) and mucin phenotypes has not been elucidated. The aim of this retrospective study was to analyze clinical outcomes of ER of NADETs with reference to mucin phenotypes. Patients and methods  We retrospectively evaluated the clinical outcomes of ER for NADETs performed from 2006 to 2019 and compared clinicopathological characteristics, ER procedures, and outcomes, including adverse events (AEs) among tumors classified by mucin phenotype. Mucin phenotypes were classified as gastric, gastrointestinal, and intestinal based on immunohistochemical examination. Grade of dysplasia was determined according to the Vienna classification (VCL). Results  The proportion of VCL 4/5 was higher in the gastric type (50 %) compared with that in the gastrointestinal (39.1 %, P  = 0.009) and intestinal types (5.4 %, P  = 0.008), respectively. With no statistical difference in tumor size and ER method among the three groups, no significant difference was observed for ER outcomes, i. e., en bloc and R0 resection rates. In the gastrointestinal and intestinal types, AEs occurred in four cases treated with ESD, but none developed in the gastric type. Conclusions  This study suggests that the mucin phenotype does not affect resection outcome. However, considering high malignant potential and tendency for low AE rates, the gastric type NADETs may be more appropriate for proactive ER than the others., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objectives: Epstein-Barr virus-associated gastric cancer (EBVGC) has been reported to be associated with a low risk for lymph node metastasis (LNM). However, the curative criteria for endoscopic submucosal dissection (ESD) for submucosal EBVGC (pT1b-EBVGC) remain unclear. Our study aimed to investigate the risk factors for LNM in pT1b-EBVGC., Methods: This was a retrospective multicenter study at five institutes in Japan. We reviewed medical records and extracted all pT1b-EBVGC cases that met the following criteria: (i) histologically proven submucosal gastric cancer; (ii) surgical or endoscopic resection between January 2000 and December 2016; and (iii) presence of Epstein-Barr virus (EBV) in tumor cells verified by EBV-encoded small RNA in situ hybridization (EBER-ISH). The association between clinicopathological factors and LNM were assessed using multivariable logistic regression analysis., Results: A total of 185 pT1b-EBVGC cases were included in the analysis. LNM was found in nine cases (4.9%). Multivariable logistic regression analysis demonstrated that lymphatic invasion (OR 9.1; 95% CI 2.1-46.1) and submucosal invasion ≥4000 μm (OR 9.2; 95% CI 1.3-110.3) were significant risk factors for LNM. When we focused on pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000 μm, the rate of LNM was 0% (0/96, 95% CI 0-3.8%)., Conclusions: Our findings indicated that lymphatic invasion and submucosal invasion ≥4000 μm were significant risk factors for LNM. ESD could be an appropriate option for pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000 μm., (© 2020 Japan Gastroenterological Endoscopy Society.)

Background: Intestinal metaplasias (IMs) are generally regarded as pre-neoplastic gastric lesions. However, molecular alterations including genetic and epigenetic changes occurring in individual IM glands are not well defined., Aims: We sought to identify DNA methylation status, microsatellite instability (MSI) and allelic imbalance (AI) occurring in individual IM glands and non-IM glands within the same mucosa., Methods: We divided examined isolated gland obtained from GC into 4 components: isolated cancer, antral isolated intestinal metaplastic tissue, antral isolated non-metaplastic gland and isolated non-metaplastic gland derived from the greater curvature of the most distant gastric body without mucosal atrophy. We examined AI and microsatellite instability statuses using PCR-based microsatellite analysis. Next, the DNA methylation status (high methylation epigenome [HME], intermediate methylation epigenome [IME], and low methylation epigenome [LME]) was investigated. DNA methylation analysis of CDKN2A, mir34-b/c and MLHI genes was also performed., Results: Although antral isolated IM glands were characterized by IME, isolated non-IM glands showed LME. In isolated cancer glands, HME was frequently found, compared with isolated non-IM glands. DNA methylation of mir34-b/c was common in isolated cancer and IM glands, whereas DNA methylation of CDKN2A was a rare event in isolated samples. The MLH1 gene was not methylated in isolated non-IM glands. Although multiple AIs were frequently found in isolated cancer glands, a few AIs were detected in isolated IM glands., Conclusions: We suggest that the DNA methylation status and the status of the mir34-b/c gene among isolated samples of IMs and isolated non-IM glands have an impact on IM development.

Objectives: Both potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) are known to be protective against bleeding after gastric endoscopic dissection (ESD) for early gastric cancers. The aim was to compare the effect of PPI and P-CAB treatment against bleeding after gastric ESD., Materials and Methods: This was a single-center, retrospective analysis. Among 541 patients who underwent gastric ESD during the period from 2014 to 2019, we recruited subjects who were treated with PPIs (intravenous lansoprazole followed by oral esomeprazole) or a P-CAB before and after ESD. The incidence of post-ESD bleeding was compared between treatment groups. The risks associated with post-ESD bleeding were examined by univariate and multivariate analyses after propensity score-matching., Results: The overall incidence of post-ESD bleeding was not significantly different between patients treated with PPIs ( n  = 362) and those treated with a P-CAB ( n  = 156) (3.0% vs 2.6%, respectively; p  = .77). Even after propensity score matching ( n  = 153 in each group), the incidence was not significantly different between groups (2.6% vs 2.6%, respectively; p  = 1.00). A multivariate analysis revealed that antithrombotic therapy (OR 4.85, 95% CI 1.14-20.57) was an independent factor associated with post-ESD bleeding., Conclusions: The incidence of post gastric ESD bleeding is not different between patients treated with PPI and patients treated with P-CAB. Antithrombotic therapy is an independent risk factor associated with post-ESD bleeding.

Objectives: Little is known about the usefulness of magnifying endoscopy with crystal violet staining (ME-CV) for the diagnosis of duodenal tumors. We assessed the ability of ME-CV to distinguish Vienna classification (VCL) category 4/5 (C4/5) from category 3 (C3) non-ampullary duodenal epithelial tumors (NADETs)., Methods: A total of 76 NADETs were studied. We retrospectively analyzed the diagnostic values of the white light endoscopy (WLE) scoring system and the ME-CV algorithm with receiver operating characteristic (ROC) curves, and three endoscopists calculated the sensitivity, specificity, accuracy, and the area under the curve (AUC) of each. The diagnostic values were tested among NADETs overall and among subgroups of tumors with gastric, gastrointestinal or intestinal mucin phenotypes. Inter-observer agreement of the diagnostic results was also calculated., Results: According to the VCL, 54 lesions (71.1%) were regarded as C3 and 22 lesions (28.9%) as C4/5. The sensitivity, specificity, accuracy and AUC of ME-CV were higher than those of the WLE scoring system (63.6 vs 54.5, 85.2 vs 75.9, 78.9 vs 69.7, 0.744 vs 0.652, respectively). Inter-observer agreements of the WLE scoring system and ME-CV were both moderate (kappa 0.45 and 0.41). ME-CV had higher sensitivity, specificity, accuracy and AUC than those of the WLE scoring system among the gastric and intestinal phenotypes of NADETs., Conclusions: ME-CV is appropriate for the diagnosis of C4/5 and C3 NADETs., (© 2020 Japan Gastroenterological Endoscopy Society.)

A 49 years old male, who had had postprandial dysphagia during the preceding 10 years, was referred to our hospital. Esophagogastroduodenoscopy (EGD) revealed longitudinal furrows and concentric rings in the mid to lower esophagus and stenosis in the lower esophagus. Histologic findings from esophageal biopsies showed eosinophilic infiltration (> 15 per high-power field). Under a diagnosis of eosinophilic esophagitis, an endoscopic bougie was performed, which resulted in symptomatic relief. Follow-up EGD revealed that the stenosis had improved, but histologic findings of eosinophilic esophagitis were remaining. Our case suggests that although rare, esophageal stenosis occurs in Japanese patients with EoE, and that the complication may be a consequence of prolonged disease. Other risks and the appropriate treatment for the prevention of stenosis need to be elucidated further.

Background: Crawling-type adenocarcinoma (CRA) is an important gastric cancer (GC) subtype that exhibits a specific histological pattern and has characteristic clinicopathological findings. Despite its characteristic histology, little is known about the molecular characteristics of CRA., Methods: We examined 177 GC cases, including 51 cases of CRA and 126 cases having conventional differentiated adenocarcinomas (CDAs). Results for immunohistochemistry (mucin phenotype; Muc5AC, Muc6, Muc2 and CD10, CDX-2, MLH-1, p53 and β-catenin), mutation analysis (TP53, KRAS and BRAF), microsatellite instability (BAT25, BAT26, D2S123, D5S346 and D17S250), DNA methylation status by a two-panel method (RUNX3, MINT31, LOX, NEUROG1, ELMO1 and THBD), MLH-1 promoter methylation, and allelic imbalance (AI; 1p, 3p, 4p, 5q, 8p, 9p, 13q, TP53, 18q and 22q) were examined., Results: CRAs were more likely to occur in the middle third of the stomach, in younger patients and to be macroscopically depressed. Nuclear accumulation of β-catenin and loss of MLH-1 expression were less frequent among CRA cases compared to CDA cases. At a molecular level, CRA is often characterized by the deletion mutation c.529&#95;546 (18-base pair deletion at codon 177-182 in exon 5) in the TP53 gene (10 cases). Although the low methylation epigenotype was significantly more frequent for CRAs compared to CDAs, multiple AIs were more often seen in CRAs relative to CDAs., Conclusions: The results demonstrated that TP53 mutations, particularly c.529&#95;546del, and multiple AIs are closely associated with CRA carcinogenesis. Our results suggest that CRA is an independent entity of GC in terms of clinicopathologic and molecular findings.

We present experimental measurements of the density, speed of sound, vapor pressure, and dew-point pressure of cis -1,1,1,4,4,4-hexafluorobutene, which is also known as R-1336mzz(Z). Vapor pressures were measured at temperatures from 330 to 440 K; the dew-point pressure was measured at T = 293.15 K. Densities were measured in the liquid and supercritical regions over the temperature range of 230 to 460 K, with pressures up to 36 MPa. Vapor-phase sound speeds were measured at temperatures between 280 and 480 K, with pressures from 0.021 to 2.2 MPa. Densities and dew points were measured in a two-sinker densimeter with a magnetic suspension coupling. Vapor pressures were measured with a static technique in the densimeter. Sound speed data were measured with a spherical acoustic resonator. An equation of state written in terms of the Helmholtz energy was developed based on these data together with additional data from the literature; it represents the present experimental data with relative average absolute deviations (AAD) of 0.0081% for densities, 0.027% for vapor pressure, and 0.017% for vapor-phase speed of sound. Literature data for liquid-phase speed of sound have an AAD of 0.023%, and for saturated liquid density data, the AAD is 0.049%., Competing Interests: The authors declare no competing financial interest.

We reviewed the records of patients with immune checkpoint inhibitor (ICI)-induced diarrhea during 2015 to 2019. ICI included nivolumab and ipilimumab. There were 11 patients with ICI-induced diarrhea aged 46-81 years (median, 63 years). On colonoscopy, four patients appeared normal, whereas loss of vascularity, erythema, granularity, erosions or ulcerations apparently mimicking ulcerative colitis were found in seven patients. Those seven patients had acute inflammation, cryptitis, crypt abscess and apoptosis, suggestive of ICI-induced colitis. Five of the seven patients were treated with prednisolone, two of whom were resistant to prednisolone and required infliximab. In contrast, none of the four patients without ICI-induced colitis required further treatment. Our observations suggest that diversity exists in the clinical, endoscopic and histological severity of patients with ICI-induced diarrhea. Colonoscopy together with biopsy is inevitable for the diagnosis of ICI-induced colitis, which requires intensive treatment., (© 2019 Japan Gastroenterological Endoscopy Society.)

Biofabrication is roughly defined as techniques producing complex 2D and 3D tissues and organs from raw materials such as living cells, matrices, biomaterials, and molecules. It is useful for tissue engineering, regenerative medicine, drug screening, and organs-on-a-chip. Biofabrication could be carried out by microfluidic techniques, optical methods, microfabrication, 3D bioprinting, etc. Meanwhile, electrochemical devices and/or systems have also been reported. In this progress report, the recent advances in applying these devices/systems for biofabrication are summarized. After introducing the concept of biofabrication, biofabrication strategies using electrochemical approaches are summarized. Then, various electrochemical systems such as probes and chip devices are described. Next, the biofabrication of hydrogels for 3D cell culture, electrochemical modification on cell culture surfaces, electrodeposition of conductive materials in hydrogels for cell culture, and biofabrication of cell aggregates using dielectrophoresis is discussed. In addition, electrochemical stimulation methods such as electrotaxis are mentioned as promising techniques for biofabrication. Finally, future research directions in this field and the application prospects are highlighted., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Little is known about the risk factors for post endoscopic submucosal dissection (post-ESD) bleeding with anticoagulant therapy., Aims: We aimed to investigate the risk factors for post-ESD bleeding for early gastric cancer (EGC) with an emphasis on anticoagulant therapy., Methods: We retrospectively analyzed 2355 EGCs, including 137 lesions in patients treated under anticoagulants. Clinicopathological findings were evaluated between lesions in patients with and without anticoagulant therapy with propensity score matching analysis. The factors associated with post-ESD bleeding were analyzed with multivariate analysis with a logistic regression method., Results: After propensity score matching, post-ESD bleeding was significantly more frequent in lesions of patients with than without anticoagulant therapy (11.7% vs 1.5%, respectively; P = 0.001). A univariate analysis revealed that anticoagulant therapy, heparin bridge therapy, undifferentiated type, deep submucosal invasion, and resected specimen size were associated with post-ESD bleeding. A multivariate analysis revealed anticoagulant therapy (OR 23.1, 95% CI 3.61-147.52) and resected specimen size (OR 1.03, 95% CI 1.00-1.06) to be independent factors associated with post-ESD bleeding., Conclusions: Anticoagulant therapy and resected specimen size were risk factors associated with post-ESD bleeding for EGC.

Background/aims: Magnifying endoscopic classification systems, such as the Japan narrow-band imaging (NBI) Expert Team (JNET) classification, have been widely used for predicting the histologic diagnosis and invasion depth of colorectal epithelial tumors. However, disagreement exists among observers regarding magnifying endoscopic diagnosis, because these classification systems are subjective. We herein investigated the utility of endoscopic microvascular density (eMVD) calculated from magnifying NBI endoscopic images in colorectal tumors., Methods: We reviewed magnifying NBI endoscopic images from 169 colorectal epithelial tumors (97 adenomas, 72 carcinomas/high-grade dysplasias) resected endoscopically or surgically. The eMVD on magnifying NBI endoscopic images was evaluated using image-editing software, and relationships between eMVD and clinical, endoscopic, and pathological findings were retrospectively analyzed., Results: The eMVD in carcinomas (0.152 ± 0.079) was significantly higher than that in adenomas (0.119 ± 0.059, P< 0.05). The best cutoff value for distinguishing carcinoma from adenoma was 0.133. Sensitivity, specificity, and accuracy were 56.9%, 67.0%, and 62.7%, respectively. In addition, JNET type 2B tumors showed significantly higher eMVD (0.162 ± 0.079) compared to type 2A tumors (0.111 ± 0.050, P< 0.05)., Conclusions: The eMVD as determined by magnifying NBI endoscopy is considered to be a possible objective indicator for differentiating colorectal carcinomas from adenomas.

Background/aims: To evaluate gastric early differentiate-type carcinogenesis, we attempted to identify clinicopathological and biological differences in differentiated-type minute intramucosal neoplasia (MIMN), which was defined as a tumor with a diameter of < 5 mm., Methods: We examined clinicopathological findings and biological factors, including TP53 overexpression, mucin phenotype, Ki-67-positive rate, MLH1, intranuclear accumulation of β-catenin, and DNA methylation status (low methylation epigenotype [LME], intermediate methylation epigenotype, and high methylation epigenotype [HME]) in MIMNs. In addition, non-MIMNs were also analyzed. In the present study, MIMN and non-MIMN were also examined based on low-grade dysplasia, high-grade dysplasia, and intramucosal cancer (IMC)., Results: In clinicopathological findings, there were significant differences in sex ratios and tumor locations between MIMNs and non-MIMNs. Among the examined biological factors, no significant differences in the frequencies of biological factors were observed between the 2 intramucosal neoplasia types. However, the frequency of intranuclear accumulation of β-catenin was higher in non-MIMNs than in MIMNs. Finally, although the frequency of HME was significantly lower in MIMNs than in non-MIMNs, the opposite was observed for LME., Conclusions: The current finding suggested that DNA methylation and accumulation of β-catenin were closely associated with tumor development from MIMN to non-MIMN., (© 2019 S. Karger AG, Basel.)

Objective Indigo naturalis (IN) is a traditional Chinese medicine that has recently been reported to be effective for ulcerative colitis (UC). The aim of this study was to evaluate the efficacy and safety of IN. Methods We performed a retrospective observational study for 14 patients with UC treated with IN from October 2015 to December 2016. Results After 8 weeks of oral administration of IN, the partial Mayo score decreased from 4 (2-5) to 1.5 (0-4) [median, interquartile range (IQR), p=0.015]. Among 10 active UC patients, 5 (50%) showed a clinical response, and 4 (40%) achieved clinical remission. Serial changes of endoscopic activity were evaluated in nine patients using the Mayo endoscopic subscore (MES), Rachmilewitz endoscopic index (REI), and UC endoscopy index of severity (UCEIS). The MES decreased from 2 (2-3) to 1 (1-2) [median (IQR), p=0.005], the REI decreased from 7 (5.5-11) to 3 (1-7) [median (IQR), p=0.008], and the UCEIS decreased from 3 (3-4.5) to 1 (0.5-3.5) [median (IQR), p=0.039]. One patient developed acute right-sided colitis with wall thickening and edematous change, and the remaining 13 showed no adverse events. Conclusion We conclude that IN is effective for patients with UC as a therapy for inducing remission.

Background: Little is known about the long-term outcomes and prognostic factors with non-curative endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer., Methods: Clinicopathological findings and long-term outcomes were evaluated in 87 patients with early gastric cancer (EGC) aged ≥ 75 years who were treated with non-curative ESD. Prognostic factors for overall survival (OS) were analyzed with the Kaplan-Meier method and a Cox proportional hazards model., Results: During the follow-up period, among 27 patients who died of any cause, only one patient died of gastric cancer. OS probabilities after 3 and 5 years were 89.7% and 79.3%, respectively. Univariate analyses revealed that Eastern Cooperative Oncology Group performance status 2-3, Charlson comorbidity index (CCI) ≥ 3, neutrophil/lymphocyte ratio ≥ 3.3, prognostic nutritional index < 44.8, distal tumor location and macroscopically depressed or flat configuration were associated with poor OS. Cox multivariate analysis revealed high CCI (≥ 3) to be an independent prognostic factor associated with OS (hazard ratio: 2.63, 95% confidence interval [CI] 1.06-6.49, P = 0.037)., Conclusions: CCI may be a useful parameter for decision-making regarding additional surgery for elderly patients with gastric cancer treated by non-curative ESD.

Aim: To determine appropriate fecal calprotectin cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with ulcerative colitis (UC)., Methods: We performed a cross-sectional observational study of 131 Japanese patients with UC and measured fecal calprotectin levels by fluorescence enzyme immunoassay. The clinical activity of UC was assessed with the partial Mayo score (PMS). Relapse was defined as increase of PMS by 2 points or more in stool frequency or rectal bleeding subscore. The endoscopic and histologic activities of UC were evaluated in 50 patients within a 2-mo period from fecal sampling. Endoscopic activity was determined by Mayo endoscopic subscore, Rachmilewitz endoscopic index, and ulcerative colitis endoscopic index of severity. The histologic grade of inflammation was evaluated with biopsy specimens obtained from the endoscopically most severely inflamed site, according to the scheme by Matts grade and Riley's score., Results: Fecal calprotectin levels varied from 1-20783 μg/g. There was a significant correlation between the partial Mayo score and fecal calprotectin levels ( r = 0.548, P < 0.001). In 50 patients who underwent colonoscopy with biopsy, levels were significantly correlated with the Mayo endoscopic subscore ( r = 0.574, P < 0.001), Rachmilewitz endoscopic index ( r = 0.628, P < 0.001), ulcerative colitis endoscopic index of severity ( r = 0.613, P < 0.001), Riley's histologic score ( r = 0.400, P = 0.006), and Matts grade ( r = 0.586, P < 0.001). Receiver-operating characteristic analyses identified the best cut-off value for the prediction of endoscopic remission as 288 μg/g, with an area under the curve of 0.777 or 0.823, while that for histologic remission was 123 or 125 μg/g, with an AUC of 0.881 or 0918, respectively. Of the 131 study patients, 88 patients in clinical remission were followed up 6 mo. During the follow-up period, 19 patients relapsed. The best fecal calprotectin cut-off value for predicting relapse was 175 μg/g., Conclusion: Fecal calprotectin is a predictive biomarker for endoscopic and histologic remission in Japanese patients with UC., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.