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Texture and color enhancement imaging (TXI) may improve the visibility of gastric tumors and allow their early detection. However, few reports have examined the utility of TXI. Between June 2021 and October 2022, 56 gastric tumors in 51 patients undergoing endoscopic submucosal dissection at Fukuchiyama City Hospital were evaluated preoperatively using conventional white light imaging (WLI), narrow-band imaging (NBI), and TXI modes 1 and 2. The color differences of the tumors and surrounding mucosae were evaluated using the CIE 1976 L*a*b color space, Additionally, the visibility scores were scaled. Of the 56 gastric tumors, 45 were early gastric cancers, and 11 were adenomas. Overall, the color difference in TXI mode 1 was considerably higher compared to WLI (16.36 ± 7.05 vs. 10.84 ± 4.05; p < 0.01). Moreover, the color difference in early gastric cancers was considerably higher in TXI mode 1 compared to WLI, whereas no significant difference was found in adenomas. The visibility score in TXI mode 1 was the highest, and it was significantly higher compared to WLI. Regarding adenomas, the visibility score in TXI mode 1 was also significantly higher compared to that in WLI. TXI may provide improved gastric tumor visibility., (© 2024. The Author(s).)

Objectives: We aimed to conduct a systematic review and meta-analysis to assess the value of image-enhanced endoscopy including blue laser imaging (BLI), linked color imaging, narrow-band imaging (NBI), and texture and color enhancement imaging to detect and diagnose gastric cancer (GC) compared to that of white-light imaging (WLI)., Methods: Studies meeting the inclusion criteria were identified through PubMed, Cochrane Library, and Japan Medical Abstracts Society databases searches. The pooled risk ratio for dichotomous variables was calculated using the random-effects model to assess the GC detection between WLI and image-enhanced endoscopy. A random-effects model was used to calculate the overall diagnostic performance of WLI and magnifying image-enhanced endoscopy for GC., Results: Sixteen studies met the inclusion criteria. The detection rate of GC was significantly improved in linked color imaging compared with that in WLI (risk ratio, 2.20; 95% confidence interval [CI], 1.39-3.25; p < 0.01) with mild heterogeneity. Magnifying endoscopy with NBI (ME-NBI) obtained a pooled sensitivity, specificity, and area under the summary receiver operating curve of 0.84 (95 % CI, 0.80-0.88), 0.96 (95 % CI, 0.94-0.97), and 0.92, respectively. Similarly, ME-BLI showed a pooled sensitivity, specificity, and area under the curve of 0.81 (95 % CI, 0.77-0.85), 0.85 (95 % CI, 0.82-0.88), and 0.95, respectively. The diagnostic efficacy of ME-NBI/BLI for GC was evidently high compared to that of WLI, However, significant heterogeneity among the NBI studies still existed., Conclusions: Our meta-analysis showed a high detection rate for linked color imaging and a high diagnostic performance of ME-NBI/BLI for GC compared to that with WLI., Competing Interests: Osamu Dohi received research funding from Fujifilm Co., Ltd. Naohisa Yoshida received research funds and lecture fees from Fujifilm Co., Ltd. The other authors declare no conflict of interest., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Introduction: Esophagogastroduodenoscopy is the most important tool to detect gastric cancer (GC). In this study, we developed a computer-aided detection (CADe) system to detect GC with white light imaging (WLI) and linked color imaging (LCI) modes and aimed to compare the performance of CADe with that of endoscopists., Methods: The system was developed based on the deep learning framework from 9,021 images in 385 patients between 2017 and 2020. A total of 116 LCI and WLI videos from 110 patients between 2017 and 2023 were used to evaluate per-case sensitivity and per-frame specificity., Results: The per-case sensitivity and per-frame specificity of CADe with a confidence level of 0.5 in detecting GC were 78.6% and 93.4% for WLI and 94.0% and 93.3% for LCI, respectively (p &lt; 0.001). The per-case sensitivities of nonexpert endoscopists for WLI and LCI were 45.8% and 80.4%, whereas those of expert endoscopists were 66.7% and 90.6%, respectively. Regarding detectability between CADe and endoscopists, the per-case sensitivities for WLI and LCI were 78.6% and 94.0% in CADe, respectively, which were significantly higher than those for LCI in experts (90.6%, p = 0.004) and those for WLI and LCI in nonexperts (45.8% and 80.4%, respectively, p &lt; 0.001); however, no significant difference for WLI was observed between CADe and experts (p = 0.134)., Conclusions: Our CADe system showed significantly better sensitivity in detecting GC when used in LCI compared with WLI mode. Moreover, the sensitivity of CADe using LCI is significantly higher than those of expert endoscopists using LCI to detect GC., (© 2024 S. Karger AG, Basel.)

Competing Interests: Osamu Dohi received a collaboration research grant from Fujifilm Co., Ltd. All other authors have no conflict of interest to be disclosed.

The ATP-dependent RNA helicase UPF1 plays a crucial role in various mRNA degradation pathways, most importantly in nonsense-mediated mRNA decay (NMD). Here, we show that UPF1 is upregulated during the early stages of B cell development and is important for early B cell development in the bone marrow. B-cell-specific Upf1 deletion in mice severely impedes the early to late LPre-B cell transition, in which V H -D H J H recombination occurs at the Igh gene. Furthermore, UPF1 is indispensable for V H -D H J H recombination, without affecting D H -J H recombination. Intriguingly, the genetic pre-arrangement of the Igh gene rescues the differentiation defect in early LPre-B cells under Upf1 deficient conditions. However, differentiation is blocked again following Ig light chain recombination, leading to a failure in development into immature B cells. Notably, UPF1 interacts with and regulates the expression of genes involved in immune responses, cell cycle control, NMD, and the unfolded protein response in B cells. Collectively, our findings underscore the critical roles of UPF1 during the early LPre-B cell stage and beyond, thus orchestrating B cell development., (© 2024. The Author(s).)

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare. Therefore, there is a lack of comprehensive information regarding their pathogenesis. We herein present the case of a patient with a 5-mm ampullary NET who demonstrated the presence of lymphatic invasion after undergoing endoscopic papillectomy. A 44-year-old woman was referred to our hospital for treatment of a grade 1 NET in the ampulla of Vater. Endoscopic ultrasonography revealed a hypoechoic mass within the submucosal layer without obvious infiltration into the common bile duct or the main pancreatic duct. We performed underwater endoscopic papillectomy (UEP) to remove the tumor with a negative margin. Pathological evaluation of the resected specimen showed a grade 1 NET with a negative margin. However, pancreaticoduodenectomy was subsequently performed because of the risk of lymph node metastasis, which was expected due to the significant number of NET cells infiltrating the endothelium of the lymphatic vessels. No lymph node metastasis or recurrence was observed during the 26-month follow-up period. UEP is a useful method to achieve complete resection for diagnostic and therapeutic purposes. UEP may be a novel option for endoscopic treatment of ampullary NET., (© 2024. Japanese Society of Gastroenterology.)

Background and Aims: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors., Patients and Methods: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups., Results: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed., Conclusion: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objective: Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion., Methods: This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching., Results: Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate., Conclusions: Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Conventional clip closure of mucosal defects after duodenal endoscopic submucosal dissection decreases the incidence of delayed adverse events, but may result in incomplete closure, depending on size or location. This study aimed to assess the effectiveness of the underwater clip closure method for complete duodenal defect closure without the difficulties associated with conventional closure methods. We investigated 19 patients with 20 lesions who underwent endoscopic submucosal dissection of the duodenum and subsequent mucosal defect closure in underwater conditions at our facility between February 2021 and January 2022. The success rate of the underwater clip closure method was defined as the complete endoscopic closure of the mucosal defect; a success rate of 100% was achieved. The median resected specimen size was 34.3 mm, the median procedure time for mucosal defect closure was 14 min, and the median number of clips used per patient was 12. No delayed adverse events were observed. The underwater clip closure method is a feasible option for complete closure of mucosal defects, regardless of the size or location of a duodenal endoscopic submucosal dissection., (© 2023 Japan Gastroenterological Endoscopy Society.)

Advanced gastric cancer is a highly aggressive malignancy. The available literature does not provide the prognostic value of ascites based on their degree, because most clinical trials exclude patients who present with massive ascites. Therefore, this study examined whether the presence or degree of ascites has a prognostic value in 124 patients with advanced gastric cancer. The degree of ascites was assessed using computed tomography and classified as none, small, moderate or massive. The overall survival (OS) was compared based on the presence or degree of ascites. Furthermore, a Cox proportional hazards analysis was performed to ascertain the predictors of OS. The cumulative 1-year and 2-year OS rates in patients without ascites were 43.5 and 20.2%, respectively, whereas those in patients with ascites were 29.1 and 13.6%, respectively (P=0.116). The cumulative 1-year and 2-year OS rates in patients without moderate or massive ascites were 39.5 and 20.9%, respectively; however, those in patients with moderate or massive ascites were 28.0 and 4.0%, respectively (P=0.027). Multivariate analysis showed that diffuse-type [hazard ratio (HR), 1.532; 95% confidence interval (CI), 1.002-2.343; P=0.049], moderate or massive ascites (HR, 2.153; 95% CI, 1.301-3.564; P=0.003) and chemotherapy (HR, 0.189; 95% CI, 0.101-0.352; P<0.001) were significant predictive factors of OS. In conclusion, the present study indicated that moderate or massive ascites may influence the OS of patients with advanced gastric cancer., Competing Interests: All authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

After endoscopic treatment for esophageal cancer, a 65-year-old male underwent surveillance esophagogastroduodenoscopy. A 12-mm discolored flat lesion was noted on the greater curvature of the middle gastric body. Magnifying endoscopy with blue laser imaging demonstrated an irregular papillary surface. Biopsy revealed atypical cells with mucus and irregularly distributed nuclei. The lesion was diagnosed as a gastric-type neoplasm with low atypia. Thereafter, endoscopic submucosal dissection (ESD) was conducted and specimen was sent for biopsy. The ESD specimen suggested a signet-ring cell carcinoma with MUC5AC-positive phenotype and adenocarcinoma of the fundic gland type, with MUC6 positivity and pepsinogen I positivity in the shallow and deeper layers, respectively. Moreover, the cervical region of fundic glands demonstrated a transformation zone of the signet-ring cell carcinoma into an adenocarcinoma of the fundic gland type. Herein, we report this rare case along with a literature review.

Exploring the timing of life-history transitions has been a pivotal focus in the field of evolutionary ecology. Studies on amphibian metamorphosis are well suited to investigate this aspect. We propose a species-specific model to predict the optimal metamorphosis point for frog individuals with different larval growth trajectories. Because overall fitness will be determined throughout both aquatic and terrestrial stages, we included growth and survival rates of aquatic and terrestrial stages in the fitness equation. Then we conducted a rearing experiment on a brown frog, Rana ornativentris, as an example to obtain the size at metamorphosis, larval period, and larval growth trajectory. Based on these results, we determined the model's parameters to fit the actual metamorphosis patterns. Because the parameters are supposed to be evolutionarily maintained, our data-driven approach enabled obtaining fundamental ecological information (evolutionally-based life-history parameters) of the target species. Comparing the parameters among species will allow us to understand the mechanisms in determining life-history transition more deeply., (© 2023. Springer Nature Limited.)

Objectives: To investigate possible associations between diffusion-weighted imaging (DWI) parameters derived from a non-Gaussian model fitting and Ki-67 status in patients with oral squamous cell carcinoma (OSCC)., Methods: Twenty-four patients with newly diagnosed OSCC were prospectively recruited. DWI was performed using six b-values (0-2500). The diffusion-related parameters of kurtosis value (K), kurtosis-corrected diffusion coefficient (D K ), diffusion heterogeneity (α), distributed diffusion coefficient (DDC), slow diffusion coefficient (D slow ), and apparent diffusion coefficient (ADC) were calculated from four diffusion fitting models. Ki-67 status was categorized as low (Ki-67 percentage score < 20%), middle (20-50%), or high (> 50%). Kruskal-Wallis tests were performed between each non-Gaussian diffusion model parameters and Ki-67 grade., Results: The Kruskal-Wallis tests revealed that multiple parameters (K, ADC, D k , DDC and D slow ) showed statistically significant differences between the three levels of Ki-67 status (K: p = 0.020, ADC: p = 0.012, D k : p = 0.027, DDC: p = 0.007 and D slow : p = 0.026)., Conclusions: Several non-Gaussian diffusion model parameters and ADC values were significantly associated with Ki-67 status and have potential as promising prognostic biomarkers in patients with OSCC., (© 2023. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

Background: The therapeutic approach after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) diagnosed as pathological T1a-muscularis mucosa (pT1a-MM) without lymphovascular involvement (LVI) remains uncertain. We aimed to determine whether observation after ESD is acceptable for patients without LVI showing pT1a-MM cancer., Methods: We retrospectively registered 566 ESCC patients who were treated with ESD at ten institutions between January 2007 and December 2015. Of those, 447 cases showing pT1a-epithelium/lamina propria mucosa (EP/LPM) without LVI and vertical margin (VM) (EP/LPM group), and 41 cases showing pT1a-MM without LVI and VM (MM group) were analyzed in this investigation. The clinical outcomes were assessed between the groups., Results: The 5 year cumulative incidence of metastatic recurrence was 0.5% and 3.3% in the EP/LPM and MM groups, respectively (P = 0.121). Two cases showing pT1a-EP/LPM and one showing pT1a-MM experienced lymph node recurrence. The 5 year cumulative incidence of local recurrence was 1.5% and 3.8% in the EP/LPM and MM groups, respectively (P = 0.455). The 5 year disease-specific survival (DSS) rate was 99.3% and 96.6% in the EP/LPM and MM groups, respectively (P = 0.118), whereas the 5 year overall survival rate was significantly higher in the EP/LPM group than in the MM group (92.6% versus 81.1%, respectively; P = 0.021)., Conclusions: As regards metastatic recurrence and DSS, ESCC patients with pT1a-MM without LVI showed favorable outcomes that were equivalent to those with pT1a-EP/LPM, even when they were not treated with additional therapy after ESD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A 67-year-old woman presented with a history of upper abdominal pain and weight loss. Physical examination revealed a lump in the right lower quadrant. She had undergone esophagogastroduodenoscopy at another hospital ten years ago, which showed a 15-mm elevated lesion in the duodenal bulb. The patient had not undergone further examinations or received treatment during the 10 years. Esophagogastroduodenoscopy conducted in our hospital revealed an enlarged tumor that was difficult to assess on the whole image. The tumor was diagnosed as a well-differentiated adenocarcinoma based on a biopsy specimen. Enhanced computed tomography revealed a hypervascular duodenal tumor with liver and lymph node metastases. The patient was treated with capecitabine plus oxaliplatin for the duodenal cancer. Lymph node metastases increased markedly after 2 courses of chemotherapy. The patient died 3 months after the initiation of chemotherapy. The natural history of sporadic non-ampullary duodenal epithelial tumors remains to be fully elucidated due to the low incidence rate. This case suggests that sporadic non-ampullary duodenal epithelial tumors have a biological potential for invasive malignancy.

Advances in culture-independent microbial analysis, such as metagenomics and single-cell genomics, have significantly increased our understanding of microbial lineages. While these methods have uncovered a large number of novel microbial taxa, many remain uncultured, and their function and mode of existence in the environment are still unknown. This study aims to explore the use of bacteriophage-derived molecules as probes for detecting and isolating uncultured bacteria. Here, we proposed multiplex single-cell sequencing to obtain massive uncultured oral bacterial genomes and searched prophage sequences from over 450 obtained human oral bacterial single-amplified genomes (SAGs). The focus was on the cell wall binding domain (CBD) in phage endolysin, and fluorescent protein-fused CBDs were generated based on several CBD gene sequences predicted from Streptococcus SAGs. The ability of the Streptococcus prophage-derived CBDs to detect and enrich specific Streptococcus species from human saliva while maintaining cell viability was confirmed by magnetic separation and flow cytometry. The approach to phage-derived molecule generation based on uncultured bacterial SAG is expected to improve the process of designing molecules that selectively capture or detect specific bacteria, notably from uncultured gram-positive bacteria, and will have applications in isolation and in situ detection of beneficial or pathogenic bacteria., (Copyright © 2023 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Objectives: Esophagogastroduodenoscopy (EGD) is important for the detection of curable gastric cancer (GC). However, there are no appropriate surveillance data during routine endoscopic inspections. This study aimed to clarify the risk factors of pT1b or deeper GC detection during surveillance endoscopy., Methods: This was a retrospective, multicenter, cross-sectional study conducted in 15 Japanese hospitals. We retrospectively analyzed patients with GC who had previously undergone surveillance endoscopy at each institution from January 2014 to March 2020. Patients who had undergone gastrectomy, non-infection of Helicobacter pylori (Hp), and those with intervals <3 months or >10 years from a previous endoscopy were excluded., Results: In total, 1085 patients with GCs detected during surveillance endoscopy were enrolled. The multivariate logistic analysis revealed that current Hp infection (odds ratio [OR] 2.18; 95% confidence interval [CI] 1.50-3.16) and a surveillance interval of >1.5 years (OR 1.96; 95% CI 1.35-2.84) were independent risk factors for pT1b or deeper GC. The 5-year disease-specific survival (5y-DSS) rate of GC was significantly lower in patients with surveillance interval of >1.5 years than in those with surveillance interval of ≤1.5 years (93.7% vs. 98.3%, P < 0.001). Similarly, the 5y-DSS rate of GC was significantly lower in patients with active Hp infection than in those without (93.7% vs. 99.4%, P < 0.001)., Conclusion: In this study, a surveillance interval of >1.5 years and current Hp infection were independent risk factors for detecting pT1b or deeper GC. Additionally, these factors were poor prognostic factors of the detected GC during surveillance endoscopy., (© 2022 Japan Gastroenterological Endoscopy Society.)

Bleeding frequently occurs during gastric endoscopic submucosal dissection (ESD) and bleeding points are sometimes difficult to detect. Red dichromatic imaging (RDI) was recently developed to improve the visibility of bleeding. Our study aimed at examining the efficacy of RDI in improving the visibility of bleeding during gastric ESD. We retrospectively evaluated the visibility score and color difference of bleeding spot during gastric ESD during September 2020-January 2021. The visibility score was evaluated as four numeric values by operators, and the color difference between the bleeding spot and surroundings was evaluated using RDI and white light imaging (WLI). A further analysis to evaluate bleeding characteristics was performed to evaluate the possible beneficial effects of RDI. Twenty patients with a total of 85 bleedings were analyzed. The mean visibility score in RDI was significantly higher than that in WLI (3.69 ± 0.60 vs 3.20 ± 0.84, p < 0.01). The color difference with RDI was also significantly higher than that with WLI (19.51 ± 15.18 vs 14.80 ± 7.41, p < 0.01). Furthermore, in the bleedings with a higher visibility score in RDI, the color difference in RDI was significantly higher than that in WLI (23.99 ± 19.29 vs 14.33 ± 7.08, p < 0.01). The multivariate analysis of visibility scores revealed that submergence of bleeding points was independently associated with the superiority of RDI (odds ratio 10.35, 95% confidence interval: 2.76-38.81, p < 0.01). Our study demonstrates that RDI can improve the visibility of bleeding during gastric ESD., (© 2023. The Author(s).)

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a popular technique; however, post-ERCP pancreatitis (PEP) remains a major adverse event. The administration of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) is reportedly effective in preventing PEP. However, the recommended dose varies and the efficacy of low-dose rectal NSAIDs remains unclear. Therefore, we decided to investigate the effectiveness of low-dose rectal diclofenac on PEP prevention, using propensity score matching., Methods: This single-center retrospective study included 401 patients who underwent ERCP between July 2015 and March 2020. After December 2016, we administered rectal diclofenac within 30 min before the ERCP procedure as widely as possible. Patients were divided into those who did (diclofenac group) and did not (control group) receive rectal diclofenac. Patients weighing ≥ 50 kg were administered a 50 mg dose, while those weighing < 50 kg were administered a 25 mg dose. The incidence and severity of PEP in the two groups were assessed by propensity score matching analysis., Results: Among 401 patients undergoing ERCP, 367 fulfilled the inclusion criteria. Overall, 187 patients received rectal diclofenac (diclofenac group) and 180 did not (control group). After propensity score matching, 105 pairs were selected for evaluation. Overall, seven (6.7%) patients in the diclofenac group and 10 (9.5%) in the control group developed PEP (P = 0.45). Moderate or severe PEP occurred in four (3.8%) patients in the diclofenac group and six (5.7%) in the control group (P = 0.52)., Conclusions: The administration of low-dose rectal diclofenac could not reduce the incidence and severity of PEP., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

During hemodialysis (HD), blood pressure (BP) changes are frequently observed. However, the mechanism of BP changes during HD has not been fully clarified. The cardio-ankle vascular index (CAVI) reflects the arterial stiffness of the arterial tree from the origin of the aorta to the ankle independent from BP during measurement. Additionally, CAVI reflects functional stiffness in addition to structural stiffness. We aimed to clarify the role of CAVI in regulating the BP system during HD. We included 10 patients undergoing 4-hour HD (total 57 HD sessions). Changes in the CAVI and various hemodynamic parameters were evaluated during each session. During HD, BP decreased and CAVI significantly increased (CAVI, median [interquartile range]; 9.1 [8.4-9.8] [0 min] to 9.6 [9.2-10.2] [240 min], p < 0.05). Changes in CAVI from 0 min to 240 min were significantly correlated with water removal rate (WRR) (r = -0.42, p = 0.002). Changes in CAVI at each measurement point were negatively correlated with ΔBP (Δsystolic BP each MP , r = -0.23, p < 0.0001; Δdiastolic BP each MP , r = -0.12, p = 0.029). Whereas one patient exhibited a simultaneous decrease in BP and CAVI during the initial 60 min of HD. Arterial stiffness monitored with CAVI generally increased during HD. CAVI elevation is associated with decreased WWR and BP. An increase in CAVI during HD may reflect the contraction of smooth muscle cells and play an important role in BP maintenance. Hence, measuring CAVI during HD may distinguish the cause of BP changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sato, Shimizu, Takahashi, Masai, Nagakawa, Uchino, Suzuki, Sato, Iwai and Shirai.)

Purpose: Anamorelin, a ghrelin receptor agonist, has recently been approved for gastric, pancreatic, and colorectal cancer patients with cachexia in Japan. However, only few studies have investigated the predictors of response to anamorelin in clinical settings. Thus, our study aimed to investigate the predictors of the response, in addition to its efficacy and safety., Methods: The clinical outcomes of 20 patients were evaluated during administration. They were divided into two groups based on lean body mass, responders and non-responders, and their clinical characteristics were compared., Results: The mean ± standard error (SE) variations at 12 weeks in lean body mass and handgrip strength were 2.63 ± 0.79 kg and - 1.53 ± 1.20 kg, respectively. The mean ± SE variations at 8 weeks in fasting blood glucose and hemoglobin A1c were 32.88 ± 13.77 mg/dL and 0.90 ± 0.18%, respectively. Total protein, albumin, transferrin, and prognostic nutritional index at baseline were significantly higher in responders (n = 8) than in non-responders (n = 12), whereas the neutrophil/lymphocyte and C-reactive protein/albumin ratios at baseline were significantly higher in non-responders than in responders., Conclusion: The study confirmed the efficacy and safety of anamorelin and identified nutritional or systemic inflammatory markers as predictors of anamorelin response in advanced gastrointestinal cancer patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS., Patients and Methods: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients., Results: In 325 patients, the rates of moderate/severe anemia (hemoglobin &lt; 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p &lt; 0.0001) and active bleeding (23.4% vs. 0%; p &lt; 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10)., Conclusions: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The number of older people is increasing rapidly, and the number of older people with care needs who live at home is also increasing in Japan. Maintaining their life satisfaction has been a primary challenge. This study aimed to identify factors affecting the life satisfaction of older people with care needs. The study was conducted among older people using homecare services; 126 participants (mean age, 79.33 ± 7.51 years, 54 male) were included in the analysis. Logistic regression analysis with adjustment for age, sex, and economic status was conducted with life satisfaction as the objective variable and the Japanese version of occupational gaps questionnaire (OGQ-J), sense of coherence, functional independence measure, and environmental factors as explanatory variables. The variables that significantly affected life satisfaction were the OGQ-J ( p = 0.0352, OR 0.90, 95% CI 0.81-0.99) and environmental factors ( p = 0.0083, OR 4.41, 95% CI 1.52-14.11). This study's results indicate the importance of focusing on environmental factors and facilitating the participation of older people with care needs in activities they want to do to maintain and improve their life satisfaction.

A man in his 70s, with a history of dementia and aplastic anemia, was diagnosed with a gastric tumor. Thrombocytopenia due to aplastic anemia may cause bleeding after endoscopic submucosal dissection. Then, ulcer closure using the over-the-scope clip system was performed for prevention of post-operative bleeding., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The antibiotic alaremycin has a structure that resembles that of 5-aminolevulinic acid (ALA), a universal precursor of porphyrins, and inhibits porphyrin biosynthesis. Genome sequencing of the alaremycin-producing bacterial strain and enzymatic analysis revealed that the first step of alaremcyin biosynthesis is catalysed by the enzyme, AlmA, which exhibits a high degree of similarity to 5-aminolevulinate synthase (ALAS) expressed by animals, protozoa, fungi, and α-proteobacteria. Site-directed mutagenesis of AlmA revealed that the substitution of two amino acids residues around the substrate binding pocket transformed its substrate specificity from that of alaremycin precursor synthesis to ALA synthesis. To estimate the evolutionary trajectory of AlmA and ALAS, we performed an ancestral sequence reconstitution analysis based on a phylogenetic tree of AlmA and ALAS. The reconstructed common ancestral enzyme of AlmA and ALAS exhibited alaremycin precursor synthetic activity, rather than ALA synthetic activity. These results suggest that ALAS evolved from an AlmA-like enzyme. We propose a new evolutionary hypothesis in which a non-essential secondary metabolic enzyme acts as an 'evolutionary seed' to generate an essential primary metabolic enzyme., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Nitric oxide (NO) functions in cell protection or cell death, depending on its concentration. Therefore, regulation of the intracellular concentrations of NO by its degradation systems is important for cellular functions. One of the NO degrading enzymes, flavohemoglobin (FHb), which has NO dioxygenase (NOD) activity, is a promising target for antibiotics, based on the finding that FHb-deficient pathogens exhibited reduced host toxicity. Here, we developed a high-throughput method to measure the NOD activity. Our newly developed method could contribute to the screening of potential antibiotics with NOD inhibitory activity.

The ability to distinguish between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) is of ongoing interest due to differences in transmissibility, responses to vaccination, clinical prognosis, and therapy. Although detailed genetic characterization requires whole-genome sequencing (WGS), targeted nucleic acid amplification tests can serve a complementary role in clinical settings, as they are more rapid and accessible than sequencing in most laboratories. We designed and analytically validated a two-reaction multiplex reverse transcription-quantitative PCR (RT-qPCR) assay targeting spike protein mutations L452R, E484K, and N501Y in reaction 1 and del69-70, K417N, and T478K in reaction 2. This assay had 95 to 100% agreement with WGS for 502 upper respiratory tract swab samples collected between 26 April 2021 and 1 August 2021, consisting of 43 Alpha, 2 Beta, 20 Gamma, 378 Delta, and 59 non-VOC infections. Validation in a separate group of 230 WGS-confirmed Omicron variant samples collected in December 2021 and January 2022 demonstrated 100% agreement. This RT-qPCR-based approach can be implemented in clinical laboratories already performing SARS-CoV-2 nucleic acid amplification tests to assist in local epidemiological surveillance and clinical decision-making.

Background: Long-term outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) have not been assessed in a large, multicenter cohort. We aimed to evaluate long-term outcomes of ESD for ESCC in a real-world setting., Methods: We retrospectively recruited 659 patients who underwent ESD for ESCC at ten institutions from January 2007 to December 2015. Of these, 566 patients were analyzed and classified into three groups according to the pathologic invasion depth after ESD: epithelium/lamina propria mucosa (EP/LPM group: 454 patients), muscularis mucosa/submucosa invasion ≤ 200 μm below the inferior margin of the muscularis mucosa (MM/SM1 group: 81 patients), and submucosa invasion > 200 μm below the MM inferior margin (SM2 group: 31 patients)., Results: The 5-year overall survival rates in the EP/LPM, MM/SM1, and SM2 groups were 92.6%, 80.0%, and 62.7%, respectively, while the 5-year disease-specific survival rates were 99.7%, 96.9%, and 88.3%, respectively. Multivariate analyses revealed that the invasion depth, Charlson Comorbidity Index (CCI), and prognostic nutritional index (PNI) were independent prognostic factors. Hazard ratios in the MM/SM1 and SM2 groups were 2.25 (95% confidence interval [CI] 1.04-4.83; P = 0.038) and 3.18 (95% CI 1.08-9.34; P = 0.036), respectively, compared to those in the EP/LPM group, while those for patients with a CCI ≥ 3 and PNI ≤ 47.75 were 3.25 (95% CI 1.79-5.89; P < 0.001) and 2.42 (95% CI 1.26-4.65; P = 0.008), respectively., Conclusions: This study identified that invasion depth, presence of comorbid diseases and preoperative nutritional status are independent prognostic risk factors associated with ESCC patients undergoing ESD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Cleft palate (CP) in children is frequently complicated by otitis media with effusion (OME) due to Eustachian tube dysfunction. Although tympanostomy tube (TT) placement can be beneficial in the treatment of OME to prevent short-term hearing loss, there is no consensus regarding the indications for and timing of TT insertion. The present study was performed to define the safety and effectiveness of simultaneous TT placement with palatoplasty during the language-acquisition period., Methods: We retrospectively reviewed the medical charts of pediatric patients who underwent palatoplasty for CP in a tertiary medical center, Kyoto University Hospital, from June 2010 to October 2018. The TT retention time was estimated using the Kaplan-Meier method. The incidence of OME recurrence was compared among four Veau classification groups based on the patients' sex, type of CP, median TT retention time, and type of fluid., Results: Seventy-six subjects (150 ears) were enrolled in the study. The median follow-up duration was 48.7 months (range, 18.2-108.0 months) after the first TT placement. A first TT retention time of <20.1 months was a significant risk factor for OME recurrence. Subjects with maxillofacial anomaly complex and subjects with cleft lip and palate and an alveolar cleft showed a significantly higher OME recurrence rate than subjects with clefts only in the hard and/or soft palate. There was no significant difference in the occurrence of sequelae between subjects with only a single TT placement and subjects with more than one TT placement., Conclusions: Based on the findings of the present study, it is reasonable to perform TT insertion at the same time as palatoplasty on patients who meet the indications. This technique may reduce the number of times the patient requires general anesthesia and maintain good middle ear condition during the period of language acquisition between 1 and 3 years of age., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell-cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor subunit of the kinesin superfamily protein 3 (KIF3), a motor protein, is specifically decreased in SRCC of the stomach. CRISPR/Cas9-mediated gene knockout experiments indicated that loss of KAP3 impairs the formation of circumferential actomyosin cables by inactivating RhoA, leading to the weakening of cell-cell adhesion. Furthermore, in KAP3 knockout cells, post-Golgi transport of laminin, a key component of the basement membrane, was inhibited, resulting in impaired basement membrane formation. Together, these findings uncover a potential role for KAP3 in the pathogenesis of SRCC of the stomach., (© 2022. The Author(s).)

Background: Knowledge of the bacterial spectrum involved in acute cholangitis is essential for adequate empiric antibiotic treatment. There is a lack of published data comparative data between patients with first and recurrent episodes of acute cholangitis. This study aimed to analyze the microbial spectrum in patients with first and second episodes of acute cholangitis., Methods: We retrospectively assessed 251 patients with first episodes of acute cholangitis between January 2014 to September 2020., Results: At the first episode of acute cholangitis, the predominant strains belonged to Escherichia coli (17.9%), followed by Klebsiella spp. (15.5%), Enterobacter spp. (6.4%), and Enterococcus spp. (5.6%). During follow-up, acute cholangitis recurred in 109 patients; at the second episode, the predominant strains belonged to Enterococcus spp. (35.8%), followed by Klebsiella spp. (27.5%), Enterobacter spp. (22.9%), and Escherichia coli (15.6%). Enterococcus spp. were the most common pathogen in patients with second episode of acute cholangitis, regardless of whether the cholangitis was caused by a malignant tumor or a benign disease., Conclusions: Unlike in patients with a first episode of acute cholangitis, clinicians should consider empirical treatment with anti-enterococcal antibiotics in patients with recurrent episodes of acute cholangitis., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Studies have reported the feasibility of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in elderly people with respect to both short- and long-term outcomes. As the elderly population in society increases, the requirement for managing super-elderly patients aged ≥85 years with EGC will also increase. This study aims to identify the long-term clinical outcomes of ESD for clinical T1N0 EGC in patients aged ≥85 years., Methods: A total of 370 consecutive patients aged ≥85 years with clinical T1N0 EGC who were managed in 11 institutions were reviewed retrospectively. On the basis of treatment strategy, we compared the overall survival (OS) and disease-specific survival (DSS) after performing propensity score-matched analysis between patients undergoing ESD (ESD group) and those not undergoing treatment (conservative treatment group). The potential prognostic factors were also investigated in the propensity score-matched patients., Results: After propensity score matching, we found that the 3-year OS and DSS rates were significantly higher in the ESD group than in the conservative treatment group (OS, 82.2% vs. 50.5%; p < 0.001; DSS, 100% vs. 80.1%; p = 0.008). Furthermore, ESD was identified as a significant factor for prolonged OS, whereas Charlson comorbidity index (CCI) ≥3 and prognostic nutritional index (PNI) <36.2 were associated with reduced OS., Conclusion: ESD was associated with improved OS in patients with clinical T1N0 EGC aged ≥85 years compared with the absence of treatment. Furthermore, CCI and PNI were helpful for patient selection., (© 2022 S. Karger AG, Basel.)

Bacterial small RNAs regulate the expression of multiple genes through imperfect base-pairing with target mRNAs mediated by RNA chaperone proteins such as Hfq. GcvB is the master sRNA regulator of amino acid metabolism and transport in a wide range of Gram-negative bacteria. Recently, independent RNA-seq approaches identified a plethora of transcripts interacting with GcvB in Escherichia coli. In this study, the compilation of RIL-seq, CLASH, and MAPS data sets allowed us to identify GcvB targets with high accuracy. We validated 21 new GcvB targets repressed at the posttranscriptional level, raising the number of direct targets to >50 genes in E. coli. Among its multiple seed sequences, GcvB utilizes either R1 or R3 to regulate most of these targets. Furthermore, we demonstrated that both R1 and R3 seed sequences are required to fully repress the expression of gdhA, cstA, and sucC genes. In contrast, the ilvLXGMEDA polycistronic mRNA is targeted by GcvB through at least four individual binding sites in the mRNA. Finally, we revealed that GcvB is involved in the susceptibility of peptidase-deficient E. coli strain (Δpeps) to Ala-Gln dipeptide by regulating both Dpp dipeptide importer and YdeE dipeptide exporter via R1 and R3 seed sequences, respectively., (© 2021 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Aim: Mortality rate of maintenance hemodialysis patients is known to be high. Cardio-ankle vascular index (CAVI) is an index reflecting the proper stiffness of the arterial tree from the origin of the aorta to the ankle. We aimed to clarify the utility of CAVI as a predictor of mortality in hemodialysis patients. The roles of age and nutritional conditions on survival were also examined., Methods: We followed 242 patients undergoing hemodialysis for 6 consecutive years. Data from 209 patients (mean age was 60 ± 11 years) excluding those with ankle-brachial index <0.90 were then analyzed. CAVI and heart to ankle pulse wave velocity (haPWV) were measured using Vasera 1500., Results: Thirty-eight hemodialysis patients who died during the 6-year period had higher age, cardiothoracic ratio (CTR), CAVI, and haPWV, and lower diastolic blood pressure, albumin, phosphate, and calcium phosphate product. The Kaplan-Meier curves for cumulative survival among the tertile groups showed that the mortality rate was higher in the highest tertile (T3) compared to T1/T2 for both CAVI and haPWV. Receiver operating characteristic (ROC) analysis revealed that CAVI had better discriminatory power for all-cause mortality compared to haPWV. In the Cox-proportional hazards analyses, 1 SD increase in both parameters contributed independently to all-cause mortality [CAVI: HR 1.595 (95% CI 1.108-2.297), haPWV: HR 1.695 (95% CI 1.185-2.425)], as well as age and CTR. Both parameters above the cut-offs estimated in the ROC analysis (CAVI ≥ 9.2, haPWV ≥ 8.9) also had independent contributions to mortality., Conclusion: Through the 6 consecutive years of follow-up in 209 HD patients, increased CAVI might represent a major modifiable risk factor for all-cause mortality. Further research is needed to examine whether CAVI-lowering interventions contribute to improved prognosis., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 Murakami et al.)

Regnase-1 is an endoribonuclease crucial for controlling inflammation by degrading mRNAs encoding cytokines and inflammatory mediators in mammals. However, it is unclear how Regnase-1-mediated mRNA decay is controlled in interleukin (IL)-1β- or Toll-like receptor (TLR) ligand-stimulated cells. Here, by analyzing the Regnase-1 interactome, we found that IL-1β or TLR stimulus dynamically induced the formation of Regnase-1-β-transducin repeat-containing protein (βTRCP) complex. Importantly, we also uncovered a novel interaction between Regnase-1 and 14-3-3 in both mouse and human cells. In IL-1R/TLR-stimulated cells, the Regnase-1-14-3-3 interaction is mediated by IRAK1 through a previously uncharacterized C-terminal structural domain. Phosphorylation of Regnase-1 at S494 and S513 is critical for Regnase-1-14-3-3 interaction, while a different set of phosphorylation sites of Regnase-1 is known to be required for the recognition by βTRCP and proteasome-mediated degradation. We found that Regnase-1-14-3-3 and Regnase-1-βTRCP interactions are not sequential events. Rather, 14-3-3 protects Regnase-1 from βTRCP-mediated degradation. On the other hand, 14-3-3 abolishes Regnase-1-mediated mRNA decay by inhibiting Regnase-1-mRNA association. In addition, nuclear-cytoplasmic shuttling of Regnase-1 is abrogated by 14-3-3 interaction. Taken together, the results suggest that a novel inflammation-induced interaction of 14-3-3 with Regnase-1 stabilizes inflammatory mRNAs by sequestering Regnase-1 in the cytoplasm to prevent mRNA recognition., Competing Interests: KA, KO, YY, NI, KT, FH, AM, YI, TM, OT No competing interests declared, (© 2021, Akaki et al.)

A 49-year-old man underwent treatment with glecaprevir plus pibrentasvir (G/P) for chronic hepatitis C infection. Six weeks later, he was admitted to our hospital because of jaundice and fatigue with no accompanying skin rash. A laboratory examination and evaluation of the patient's history resulted in a diagnosis of acute liver injury. Discontinuation of G/P and a rigorous medical protocol, including plasma exchange and hemodiafiltration, successfully mitigated the liver damage. The patient was also found to be allergic to two drugs other than the G/P therapy. In such cases with a history of drug allergy, careful observation may be required to detect serious adverse events.

The impact of the psoas muscle mass index (PMI) on survival is still poorly understood in unresectable pancreatic cancer. Thus, we aimed to investigate whether the PMI at diagnosis or its decrease during chemotherapy can influence the prognosis of unresectable pancreatic cancer. The data of 100 patients were analyzed, and they were divided into two groups according to the median PMI in each sex. Subsequently, 72 patients undergoing computed tomography (CT) within 30-100 days from CT at diagnosis were evaluated in terms of PMI change rate, and divided into two groups based on the median. We evaluated the clinical characteristics and outcomes in terms of the PMI at diagnosis or its decrease during chemotherapy. The median PMI was 5.00 in males, and 3.66 in females. The median overall survival (OS) was 278.0 days in the high-PMI group and 221.0 days in the low-PMI group ( p = 0.329). The median PMI change rate was -2.4%. The median OS was 347.0 days in the group without PMI decrease and 172.0 days in the group with PMI decrease ( p = 0.001). We determined that a pivotal prognostic factor was not the PMI at diagnosis, but rather PMI decrease during chemotherapy in unresectable pancreatic cancer.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with concerning phenotypic mutations is of public health interest. Genomic surveillance is an important tool for a pandemic response, but many laboratories do not have the resources to support population-level sequencing. We hypothesized that a nucleic acid amplification test (NAAT) to genotype mutations in the viral spike protein could facilitate high-throughput variant surveillance. We designed and analytically validated a one-step multiplex allele-specific reverse transcriptase PCR (RT-qPCR) to detect three nonsynonymous spike protein mutations (L452R, E484K, N501Y). Assay specificity was validated with next-generation whole-genome sequencing. We then screened a large cohort of SARS-CoV-2-positive specimens from our San Francisco Bay Area population. Between 1 December 2020 and 1 March 2021, we screened 4,049 unique infections by genotyping RT-qPCR, with an assay failure rate of 2.8%. We detected 1,567 L452R mutations (38.7%), 34 N501Y mutations (0.84%), 22 E484K mutations (0.54%), and 3 (0.07%) E484K plus N501Y mutations. The assay had perfect (100%) concordance with whole-genome sequencing of a validation subset of 229 specimens and detected B.1.1.7, B.1.351, B.1.427, B.1.429, B.1.526, and P.2 variants, among others. The assay revealed the rapid emergence of the L452R variant in our population, with a prevalence of 24.8% in December 2020 that increased to 62.5% in March 2021. We developed and clinically implemented a genotyping RT-qPCR to conduct high-throughput SARS-CoV-2 variant screening. This approach can be adapted for emerging mutations and immediately implemented in laboratories already performing NAAT worldwide using existing equipment, personnel, and extracted nucleic acid.

RNA in extracellular vesicles (EVs) are uptaken by cells, where they regulate fundamental cellular functions. EV-derived mRNA in recipient cells can be translated. However, it is still elusive whether "naked nonvesicular extracellular mRNA" (nex-mRNA) that are not packed in EVs can be uptaken by cells and, if so, whether they have any functions in recipient cells. Here, we show the entrance of nex-mRNA in the nucleus, where they exert a translation-independent function. Human nex-interleukin-1β (IL1β)-mRNA outside cells proved to be captured by RNA-binding zinc finger CCCH domain containing protein 12D (ZC3H12D)-expressing human natural killer (NK) cells. ZC3H12D recruited to the cell membrane binds to the 3'-untranslated region of nex-IL1β-mRNA and transports it to the nucleus. The nex-IL1β-mRNA in the NK cell nucleus upregulates antiapoptotic gene expression, migration activity, and interferon-γ production, leading to the killing of cancer cells and antimetastasis in mice. These results implicate the diverse actions of mRNA.

The human SOX2 gene was recently identified as a novel major oncogene, recurrently amplified and overexpressed in esophageal squamous cell carcinoma (ESCC). However, the role and molecular mechanism of SOX2 in the carcinogenesis of ESCC remain to be elucidated. The present study investigated the effect of SOX2 on ESCC cell survival and resistance to apoptosis under serum starvation conditions. An adenoviral vector-mediated expression system and RNA interference were used to study the effect of SOX2. The present results revealed that SOX2 promoted ESCC cell survival and enhanced resistance to apoptosis under serum starvation conditions, but not in culture conditions with serum. Mechanistically, SOX2 increased the expression levels of phosphorylated AKT and glycogen synthase kinase-3β (GSK-3β), a downstream factor of AKT, under serum starvation conditions, leading to the promotion of ESCC cell survival. Additionally, SOX2 activated AKT through the PTEN/PI3K/phosphoinositide-dependent protein kinase 1 and mammalian target of rapamycin complex 2 signaling pathways. Therefore, SOX2 may facilitate the survival of ESCC cells under poor nutrient conditions by activating the AKT/GSK-3β signaling pathway., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021, Spandidos Publications.)

Hitachimycin is a macrolactam antibiotic with an ( S )-β-phenylalanine (β-Phe) at the starter position of its polyketide skeleton. ( S )-β-Phe is formed from l-α-phenylalanine by the phenylananine-2,3-aminomutase HitA in the hitachimycin biosynthetic pathway. In this study, we produced new hitachimycin analogs via mutasynthesis by feeding various ( S )-β-Phe analogs to a Δ hitA strain. We obtained six hitachimycin analogs with F at the ortho , meta , or para position and Cl, Br, or a CH 3 group at the meta position of the phenyl moiety, as well as two hitachimycin analogs with thienyl substitutions. Furthermore, we carried out a biochemical and structural analysis of HitB, a β-amino acid-selective adenylation enzyme that introduces ( S )-β-Phe into the hitachimycin biosynthetic pathway. The K M values of the incorporated ( S )-β-Phe analogs and natural ( S )-β-Phe were similar. However, the K M values of unincorporated ( S )-β-Phe analogs with Br and a CH 3 group at the ortho or para position of the phenyl moiety were high, indicating that HitB functions as a gatekeeper to select macrolactam starter units during mutasynthesis. The crystal structure of HitB in complex with ( S )-β-3-Br-phenylalanine sulfamoyladenosine (β- m -Br-Phe-SA) revealed that the bulky meta- Br group is accommodated by the conformational flexibility around Phe328, whose side chain is close to the meta position. The aromatic group of β- m -Br-Phe-SA is surrounded by hydrophobic and aromatic residues, which appears to confer the conformational flexibility that enables HitB to accommodate the meta -substituted ( S )-β-Phe. The new hitachimycin analogs exhibited different levels of biological activity in HeLa cells and multidrug-sensitive budding yeast, suggesting that they may target different molecules.

Identifying the depth of invasion (DOI) of superficial esophageal squamous cell carcinoma (SESCC) is crucial to determine the indication for endoscopic resection. This retrospective, single-center study aimed to evaluate the diagnostic efficacy of magnifying blue laser imaging (M-BLI) compared with white-light imaging (WLI) or magnifying narrow-band imaging (M-NBI) for identifying the DOI of SESCC. A total of 160 consecutive patients with SESCCs who underwent endoscopic submucosal dissection were enrolled in this study. Still images of the lesion were obtained using WLI, M-BLI and M-NBI prior to endoscopic submucosal dissection. Three endoscopists retrospectively evaluated the DOI using WLI according to non-magnifying findings and using M-BLI and M-NBI images according to the magnifying endoscopic classification of the Japan Esophageal Society. The diagnostic accuracy of each modality was compared using the chi-square test. The DOIs in 160 SESCCs evaluated pathologically were as follows: invasion to the epithelium or lamina propria mucosa in 130, invasion to the lamina muscularis mucosa or submucosa to a depth ≤ 200 μm in 18, and invasion to the submucosa to a depth > 200 μm in 12. The overall diagnostic accuracy rates of WLI, M-BLI, M-NBI, WLI with M-BLI (WLI + M-BLI), and WLI with M-NBI (WLI + M-NBI) were 86.9, 91.2, 90.6, 95.6 and 94.4%, respectively. Significant differences were found between WLI and WLI + M-BLI or WLI + M-NBI (P = 0.006 and P = 0.021, respectively). The concordance of intrapapillary capillary loops between M-BLI and M-NBI was 91.2%. The kappa coefficients for interobserver variability of the three endoscopists for M-BLI and M-NBI were 0.728/0.649/0.792 and 0.729/0.666/0.791, respectively, while those for intraobserver variability were 0.919/0.746/0.778 and 0.736/0.720/0.745, respectively. Similar to M-NBI, M-BLI was useful in predicting the DOI of SESCCs., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Colon cancer with mucinous components was accompanied by bacterial infection and abscess formation., (© 2021 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: We frequently encounter early gastric cancer (EGC) that could not be detected in the previous esophagogastroduodenoscopy even if the procedure was annually performed. However, little evidence exists regarding the characteristics of false-negative EGCs. Our aim was to reveal the clinical features of false-negative EGCs., Methods: We retrospectively reviewed cases of endoscopic submucosal dissection (ESD) for EGCs in Fukuchiyama City Hospital between January 2013 and May 2019. False-negative EGCs were defined as EGCs within 3 years of negative endoscopy. We evaluated the clinical characteristics of false-negative and initially detected EGCs and the difference in the detected and last missed endoscopy in false-negative EGCs. The miss rates of false-negative EGCs were compared between trainees (nonboard-certified endoscopists) and experienced endoscopists (board-certified endoscopists); thereafter, the characteristics of false-negative EGCs missed by trainees were investigated., Results: Of 219 cases, 119 were classified as false-negative EGCs. False-negative EGCs were characterized as smaller lesions, which presented with normal color or gastritis-like appearance, and were diagnosed after ESD and H. pylori eradication ( P < 0.01). The rate of trainees in the last missed endoscopy was significantly higher than that in the detected endoscopy. The miss rate of false-negative EGC by trainees was higher than that of experienced endoscopists but not significantly different (0.70% vs. 0.57%, P = 0.08). The false-negative EGCs missed by trainees were characterized as reddish or well-differentiated lesions, which were located in the lower or lesser curvature of the stomach ( P < 0.05)., Conclusion: The characteristics of false-negative EGCs were similar to those of H. pylori -eradicated EGC. Procedures with shortened examination time and those performed by trainees were risk factors of missing false-negative EGCs. Trainees should pay attention to reddish or well-differentiated EGCs located in the lower or lesser curvature of the stomach., Competing Interests: Kohei Oka, Naoto Iwai, Takashi Okuda, Tasuku Hara, Yutaka Inada, Toshifumi Tsuji, Toshiyuki Komaki, Junichi Sakagami, Yuji Naito, Keizo Kagawa, and Yoshito Itoh have no conflicts of interest pertaining to this study., (Copyright © 2021 Kohei Oka et al.)

Reflections of academic pediatric surgery in Japan are shared by the authors. As in most areas of surgical practice committement and life long dedication are emphasized as the key(s) to success. An enquiring mind is always an advantage., (Copyright © 2021. Published by Elsevier Inc.)