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Background & Aims: The revised Kyoto guidelines have a new catalog of high-risk stigmata and worrisome features for the risk stratification of intraductal papillary mucinous neoplasms (IPMNs). We aimed to validate the stratification system in terms of short- and long-term risks of pancreatic carcinoma., Methods: We included 3336 patients diagnosed with IPMNs in 2000-2021 and examined short-term (≤6 months) and long-term risks of pancreatic carcinoma diagnosis. We used the multivariable competing-risks proportional hazards regression model to calculate subdistribution hazard ratios for long-term incidence of pancreatic carcinoma with adjustment for potential confounders., Results: In short-term analyses, pancreatic carcinomas were prevalent predominantly in IPMNs with high-risk stigmata (49% vs 1.3% and 0.05% in IPMNs with worrisome features and no risk factors, respectively). In long-term analyses of worrisome features, the main pancreatic duct diameter of 5-9.9 mm, acute pancreatitis, and IPMN growth rate of 2.5 mm/y were associated with a high incidence with multivariable subdistribution hazard ratios of 3.46 (95% confidence interval [CI], 2.04-5.89), 5.65 (95% CI, 1.86-17.2), and 3.83 (95% CI, 2.14-6.86), respectively. An increasing number of worrisome features at baseline was associated with a higher prevalence and incidence of pancreatic carcinoma (P trend < .001). Patients with 1, 2, and 3-4 worrisome features had multivariable subdistribution hazard ratios for pancreatic cancer incidence of 1.43 (95% CI, 0.93-2.19), 2.17 (95% CI, 1.17-4.05), and 10.1 (95% CI, 4.20-24.5), respectively (vs no positive feature)., Conclusions: The revised Kyoto criteria stratify IPMN patients well in terms of the short- and long-term risks of pancreatic carcinoma diagnosis, potentially informing personalized patient management., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Stability and potency improvement have been reported by reacting levofloxacin (LF) with citric acid (CA) in a (1:1) molar ratio. However, CA is known to be irritant to the gastrointestinal tract and should be minimized. In a novel approach, this experiment aimed to prepare LF - CA salt with reduced CA, the (2:1) molar ratio, study the structure, and investigate its solubility, stability, and potency improvement. Solvent-dropped grinding and slow evaporation methods were used to prepare the new ratio composition salt, characterized by electrothermal, differential scanning calorimetry, and powder X-ray diffractometry to confirm the physically new solid-state formation. Next, Fourier transform spectrophotometry identified the chemical interaction between LF and CA. After that, a comprehensive structural study using single-crystal X-ray diffractometry determined the 3D structure of the new salt, which determined the solid physicochemical behavior. Finally, stability, solubility, and potency tests were done to investigate the benefits of the new LF-CA composition. As a result, this experiment successfully synthesized the salt, which bound 4.5 water molecules, named LFCA (2:1) - 4.5 hydrate. This new solid-state salt was comparable with the established (1:1) molar ratio in solubility, stability, and potency, higher than LF alone. Hereafter, with a reduced CA portion, this new composition holds potential for further development in drug formulation as a stable, safer, and more efficient antibiotic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and study aims Pancreatitis is a potentially lethal adverse event of endoscopic transpapillary placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction (MBO). Deep learning-based image recognition has not been investigated in predicting pancreatitis in this setting. Patients and methods We included 70 patients who underwent endoscopic placement of a SEMS for nonresectable distal MBO. We constructed a convolutional neural network (CNN) model for pancreatitis prediction using a series of pre-procedure computed tomography images covering the whole pancreas (≥ 120,960 augmented images in total). We examined the additional effects of the CNN-based probabilities on the following machine learning models based on clinical parameters: logistic regression, support vector machine with a linear or RBF kernel, random forest classifier, and gradient boosting classifier. Model performance was assessed based on the area under the curve (AUC) in the receiver operating characteristic analysis, positive predictive value (PPV), accuracy, and specificity. Results The CNN model was associated with moderate levels of performance metrics: AUC, 0.67; PPV, 0.45; accuracy, 0.66; and specificity, 0.63. When added to the machine learning models, the CNN-based probabilities increased the performance metrics. The logistic regression model with the CNN-based probabilities had an AUC of 0.74, PPV of 0.85, accuracy of 0.83, and specificity of 0.96, compared with 0.72, 0.78, 0.77, and 0.96, respectively, without the probabilities. Conclusions The CNN-based model may increase predictability for pancreatitis following endoscopic placement of a biliary SEMS. Our findings support the potential of deep learning technology to improve prognostic models in pancreatobiliary therapeutic endoscopy., Competing Interests: Conflict of Interest Y.N. and H.I. receive research funding and honoraria from Boston Scientific Japan. This work was not funded by this company. No other conflicts of interest exist. The other authors declare that they have no conflicts 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/).)

Aim: Comprehensive genomic profiling (CGP) test for solid tumors is now increasingly utilized in clinical practice, especially in pancreatobiliary cancer, and specimens obtained by endoscopic ultrasound-guided tissue acquisition (EUS-TA) are often submitted for tissue-based CGP test. In this study, we evaluated the feasibility of EUS-TA using a 22-gauge Franseen needle for the CGP test., Methods: Consecutive patients with solid tumors who underwent EUS-TA using a 22-gauge Franseen needle, and whose tissue samples were pre-checked for suitability for CGP test, were included in this single-center, retrospective analysis. The success rates of appropriate sample collection for CGP evaluated by pathologists (1st quality control) and CGP test (2nd quality control) were evaluated. In addition, The EUS-TA slides were evaluated for the tissue area and tumor area content, using the image software., Results: A total of 50 cases, with 78% of pancreatic cancer, were included in the analysis. A median of 3 passes of EUS-TA were performed with an adverse event rate of 4%. The success rates for 1st and 2nd quality control for CGP tests were 86% and 76%, respectively. The image analyses suggested EUS-TA specimen did not always fulfill CGP test criteria, with 18% of tissue area ≥16 mm 2 and 38% of tumor area content ≥20%, even in cases with successful CGP tests. The suction method yielded a significantly larger amount of DNA but without a significant difference in the multivariate analysis., Conclusions: The present study demonstrated the feasibility of EUS-TA using a 22-gauge Franseen needle for CGP test., Competing Interests: Yousuke Nakai is an Associate Editor of Digestive Endoscopy. YN received a research grant from Boston Scientific Japan, Fujifilm Corporation, and honoraria from Boston Scientific Japan, Fujifilm Corporation, and Olympus Corporation. MF received a research grant from Olympus Corporation, Fujifilm Corporation, and honoraria from Fujifilm Corporation, Olympus Corporation., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

The higher-order structure (HOS) is a critical quality attribute of recombinant adeno-associated viruses (rAAVs). Evaluating the HOS of the entire rAAV capsid is challenging because of the flexibility and/or less folded nature of the VP1 unique (VP1u) and VP1/VP2 common regions, which are structural features essential for these regions to exert their functions following viral infection. In this study, hydrogen/deuterium exchange mass spectrometry (HDX-MS) was used for the structural analysis of full and empty rAAV8 capsids. We obtained 486 peptides representing 85% sequence coverage. Surprisingly, the VP1u region showed rapid deuterium uptake even though this region contains the phospholipase A2 domain composed primarily of α-helices. The comparison of deuterium uptake between full and empty capsids showed significant protection from hydrogen/deuterium exchange in the full capsid at the channel structure of the 5-fold symmetry axis. This corresponds to cryo-electron microscopy studies in which the extended densities were observed only in the full capsid. In addition, deuterium uptake was reduced in the VP1u region of the full capsid, suggesting the folding and/or interaction of this region with the encapsidated genome. This study demonstrated HDX-MS as a powerful method for probing the structure of the entire rAAV capsid.

Background: The patella fracture involving of inferior pole fractures (IPF) may be associated with patella baja, However, the clinical impact of this condition remains unclear. This study aims to clarify 1) the incidence of patella baja following patellar fracture surgery, 2) the associated clinical outcomes with and without the presence of patella baja, and 3) the potential correlation between the detection of IPF on CT and the occurrence of patella baja., Methods: We conducted a retrospective multicenter study involving 251 patients who underwent surgical treatment for patellar fractures. Patients were divided into the patella baja (PB; n = 49) group and patella norma (PN; n = 202) group. Data collected included demographics, radiographic findings, surgical details, and postoperative complications. We compared these items between PB group and PN group. Logistic regression analyses were used to identify risk factors for patella baja., Results: Immediately following surgery, 36 (14.3%) patients presented with patella baja which increased to 49 cases (19.5%) at six months postoperatively. There is no statistically significant difference in the demographics, surgical details, clinical outcomes and complication between PB group and PN group. While, in the radiographical assessment, the prevalence of IPF on CT scan in the patella baja group was significantly higher than that in the patella norma group. By logistic regression analysis, IPFP on CT was identified as an independent risk factor for patella baja. (odds ratio 2.11, 95% confidence interval: 1.03-4.33, p = 0.042)., Conclusion: In patients with patellar fractures, the incidence of patella baja increased from 14.3% immediately post-surgery to 19.5% at the six-month check-up. No significant differences were observed in clinical outcomes between the patella baja group and the norma group. The patella fracture involving IPF on CT emerged as a predictive factor for patella baja., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The stigma of mental illness is a form of negative judgmental knowledge and is a barrier to individual seeking treatment. Contact-based educational interventions with first-person perspective (1PP) combined with immersive virtual reality (IVR) is promising as an anti-stigma intervention. This study aims to investigate the effectiveness of 1PP anti-stigma IVR intervention compared to video in enhancing depression knowledge and reducing stigma, as well as to examine the corresponding depression knowledge brain activity change using functional magnetic resonance imaging (fMRI). Participants engaged in a 1PP anti-stigma intervention using both IVR and conventional video, focusing on the daily life and recovery of a patient with mild depression. The change in depression knowledge, stigma-related behavioral, and brain activity using fMRI were measured at pre- and post-interventions. Depression knowledge improved for both interventions; however, only the IVR intervention reduced stigma. In the IVR intervention, depression knowledge score was positively associated with neural response in the right superior frontal gyrus activation, indicative of empathic concern. Conversely, the video intervention correlated with increased activity in the right anterior insula, suggesting a distress-related response. The findings demonstrate that the immersive nature of IVR can reduce stigma more effectively than video intervention. This effectiveness is underpinned by the change in depression knowledge on neural activity, with IVR fostering empathy-related behavioral responses. The results highlight the potential of IVR in enhancing empathic understanding and reducing stigma towards mental illness, emphasizing the need for further exploration into immersive technologies for mental health education., (© 2024. The Author(s).)

Purpose: Although venous drainage of the jejunal loop may be maintained after sacrifice of jejunal vein tributaries during pancreatoduodenectomy, risk of severe jejunal mesenteric congestion following division of these tributaries can be difficult to predict. This study considered how best to predict safety of jejunal vein tributary dissection., Methods: Preoperative imaging findings and results of intraoperative clamp tests of jejunal vein tributaries during pancreatoduodenectomy were analyzed in 121 patients with hepatobiliary and pancreatic disease to determine whether this information adequately predicted safety of resecting superior mesenteric vein branches., Results: Jejunal vein tributaries caudal to the inferior border of the pancreatic uncinate process tended to be fewer when tributaries cranial to this landmark were more numerous. Tributaries cranial to the border drained a relatively wide expanse of jejunal artery territory in the jejunal mesentery. The territory of jejunal tributaries cranial to the inferior border of the pancreas did not vary according to course of the first jejunal vein branch relative to the superior mesenteric artery. One patient among 30 (3%) who underwent intraoperative clamp tests of tributaries cranial to the border showed severe congestion in relation to a venous tributary coursing ventrally to the superior mesenteric artery., Conclusion: Jejunal venous tributaries drained an extensive portion of jejunal arterial territory, but tributaries located cranially to the inferior border of the pancreas could be sacrificed without congestion in nearly all patients. Intraoperative clamp testing of these tributaries can identify patients whose jejunal veins must be preserved to avoid congestion., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Genomic prediction was conducted using 2494 Japanese Black cattle from Hiroshima Prefecture and both single-nucleotide polymorphism information and phenotype data on monounsaturated fatty acid (MUFA) and oleic acid (C18:1) analyzed with gas chromatography. We compared the prediction accuracy for four models (A, additive genetic effects; AD, as for A with dominance genetic effects; ADR, as for AD with the runs of homozygosity (ROH) effects calculated by ROH-based relationship matrix; and ADF, as for AD with the ROH-based inbreeding coefficient of the linear regression). Bayesian methods were used to estimate variance components. The narrow-sense heritability estimates for MUFA and C18:1 were 0.52-0.53 and 0.57, respectively; the corresponding proportions of dominance genetic variance were 0.04-0.07 and 0.04-0.05, and the proportion of ROH variance was 0.02. The deviance information criterion values showed slight differences among the models, and the models provided similar prediction accuracy., (© 2024 Japanese Society of Animal Science.)

Objectives: Safe removal of extensive liver tumor burdens depends on regeneration of the remnant liver, which requires a large amount of zinc over a short period of time. We studied how zinc influences regeneration., Material and Methods: We measured perioperative serum zinc concentrations after liver cancer diagnosis in 77 patients undergoing hepatectomy to determine how serum zinc affected short-term outcomes and remnant liver regeneration., Results: Serum zinc concentration at diagnosis showed no correlation with inflammatory or nutritional parameters except for a weak correlation with the lymphocyte-to-monocyte ratio. When patients were divided into a high pre-hepatectomy zinc group (≥75 µg/dL, n= 39, H group) and a low zinc group (<75 µg/dL, n= 38, L group), short-term results such as mortality (p> 0.999), morbidity (p= 0.490), and hospital stay (p= 0.591) did not differ between groups. However, hypertrophy in the future liver remnant after hepatectomy in the H group (127.7 ± 24.7% of original volume) was greater than in the L group (115.9 ± 16.7%, p= 0.024). In a subgroup of patients with extended hepatectomy, hypertrophy was 130.9 ± 26.8% in the H group vs. 116.4 ± 16.5% in the L group (p= 0.037)., Conclusion: Greater serum zinc at diagnosis was associated with greater hypertrophy in the future liver remnant., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2023, Turkish Surgical Society.)

Tetrodotoxin (TTX)-bearing fish are thought to accumulate TTXs in their bodies through a food chain that begins with marine bacteria. However, the mechanism of TTXs transfer between prey and predators in the food chain remains unclear and the reasons for regional differences in pufferfish toxicity are also unknown. To investigate these matters, we collected juveniles of four species of pufferfish, Takifugu alboplumbeus, Takifugu flavipterus, Takifugu stictonotus, and Chelonodon patoca, from various locations in the Japanese Islands, and subjected them to liquid chromatography-tandem mass spectrometry analysis for TTX and its analog 5,6,11-trideoxyTTX (TDT). Concentrations of these substances tended to be higher in pufferfish juveniles collected from the Sanriku coastal area (Pacific coast of northern Japan) than in those from other locations. Juveniles had higher concentrations of TTX at all locations than of TDT. Mitochondrial cytochrome c oxidase subunit I (COI) sequences specific to the TTX-bearing flatworm, Planocera multitentaculata, were detected in the intestinal contents of up to 100% of pufferfish juveniles from various sampling sites, suggesting that P. multitentaculata was widely involved in the toxification of the juveniles in the coastal waters of Japan. A toxification experiment was conducted on three species of pufferfish juveniles (T. alboplumbeus, Takifugu rubripes and C. patoca) using TTX-bearing flatworm eggs harboring equal amounts of TTX and TDT. The TTX content of juveniles fed on flatworm eggs was found to be more than twice that of TDT, suggesting that pufferfish preferentially incorporate TTX compared to TDT., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Endoscopic self-expandable metal stent (SEMS) placement is a current mainstay for malignant gastric outlet obstruction (GOO), but symptomatic recurrence due to initial SEMS dysfunction commonly occurs. We aimed to compare the safety and effectiveness of second SEMS for recurrent GOO (RGOO). Methods: Between April 2006 and December 2022, a total of 95 cases with malignant RGOO undergoing second endoscopic SEMS placement were enrolled. Technical and clinical success rates, RGOO, time to RGOO (TRGOO), stent patency rate, adverse events (AE), and overall survival (OS) were retrospectively compared between covered and uncovered SEMS (cSEMS/uSEMS) groups. Risk factors for TRGOO were also explored. Results: Baseline characteristics were well balanced between cSEMS ( n = 48) and uSEMS ( n = 47) groups, except for the causes of the initial SEMS dysfunction. High technical and clinical success rates with a similar incidence of AE (15% vs. 17%, p = 0.78) and OS (median of 101 vs. 102 days, p = 0.68) were achieved in both groups. There were no statistical differences in cumulative incidence of RGOO (19% vs. 13%, p = 0.58), TRGOO (median, not reached in both groups, p = 0.57), and stent patency rates at 1, 2, and 3 months between the groups (60%, 47% and 26%, respectively vs. 70%, 55% and 38%, respectively). However, TRGOO tended to be longer in cSEMS in cases with RGOO due to tumor ingrowth (median, not reached vs. 111 days, p = 0.19). A Cox regression analysis demonstrated that chemotherapy after second SEMS placement was significantly associated with an improved TRGOO (the hazard ratio of 0.27 [95% confidence interval, 0.08-0.93], p = 0.03). Conclusions: Regardless of the type of SEMS, second SEMS placement was similarly safe and effective for RGOO. The type of second SEMS might be considered based on the cause of initial SEMS dysfunction.

Background: Esophageal thermal injury is a complication of atrial fibrillation (AF) ablation, and it can be avoided by esophageal deviation during left atrial posterior wall radiofrequency catheter ablation., Objective: This study aimed to evaluate the safety of a nitinol-based mechanical esophageal displacement device (MEDD) and its performance., Methods: This preclinical safety study was conducted on 20 pigs, with 10 undergoing radiofrequency AF ablation using the MEDD and 10 serving as a control group under anticoagulation but without radiofrequency application. Esophageal traumatic injuries were classified from 0 to 4 and were grouped as absent (grade 0), minor (grade 1 or 2), moderate (grade 3), or major risk lesions (grade 4) by anatomopathological study. Grades 1 and 2 were considered acceptable. Fluoroscopy was used to measure displacement., Results: Five (25%) pigs developed traumatic lesions, 4 with grade 1 and 1 with grade 2 (2-mm superficial ulcer). There was no difference in lesion occurrence between the radiofrequency and control groups (30% and 20%, respectively; P = .43). Under rightward displacement, the right edge moved 23.9 (interquartile range [IQR] 21.3-26.3) mm and the left edge moved 16.3 (IQR 13.8-18.4) mm ( P < .001) from baseline. Under leftward displacement, the right edge moved 13.5 (IQR 10.9-15.3) mm and the left edge moved 16.5 (IQR 12.3-18.5) mm ( P = .07). A perforation to the pharyngeal diverticulum occurred in 1 pig, related to an accidental extubation., Conclusion: In pigs, the MEDD demonstrated safety in relation to esophageal tissue, and successful deviation. Esophageal traumatic injuries were acceptable, but improper manipulation led to pharyngeal lesion., (© 2023 Published by Elsevier Inc. on behalf of Heart Rhythm Society.)

Background: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is widely used for the pathological diagnosis of solid pancreatic lesions but in cases with obstructive jaundice, transpapillary sampling can be performed during endoscopic retrograde cholangiopancreatography with transpapillary biliary stent placement. Thus, it is still controversial whether EUS-FNA should be performed prior to endoscopic retrograde cholangiopancreatography with biliary stent placement or only after negative transpapillary sampling., Methods: The accuracy, sensitivity, and specificity of EUS-FNA for solid pancreatic lesions with or without indwelling biliary stents were retrospectively studied in patients undergoing EUS-FNA between January 2017 and December 2021. We also conducted a meta-analysis including our data to compare the accuracy and sensitivity of EUS-FNA with or without biliary stents., Results: A total of 509 patients (40 with biliary stents and 469 without biliary stents) were included. The accuracy (77.5% vs. 94.5%, p < 0.001) and sensitivity (71.0% vs. 91.7%, p < 0.001) were lower in EUS-FNA with biliary stents. A meta-analysis confirmed that accuracy (odds ratio [OR] of 0.43, 95% confidence interval [CI] 0.29-0.62, p < 0.001) and sensitivity (OR of 0.46, 95% CI 0.33-0.64, p < 0.001) were lower in EUS-FNA with biliary stents. There were no statistically significant differences between plastic stents and self-expandable metallic stents for accuracy or sensitivity., Conclusions: The presence of biliary stents had a negative impact on the diagnostic performance of EUS-FNA, and EUS-FNA prior to endoscopic retrograde cholangiopancreatography with biliary stent placement should be considered in cases with obstructive jaundice., Competing Interests: Author Mitsuhiro Fujishiro has received honoraria from Fujifilm Corporation and Olympus Corporation and research grants from Fujifilm Corporation and Olympus Corporation. Author Yousuke Nakai is an editorial board member of Digestive Endoscopy and has received honoraria from Boston Scientific Japan, Gadelius medical corporation, Olympus Corporation, and research grants from Fujifilm Corporation and HOYA Corporation., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Regulation of α-synuclein (αS) fibril formation is a potent therapeutic strategy for αS-related neurodegenerative disorders. αS, an intrinsically disordered 140-residue intraneural protein, comprises positively charged N-terminal, hydrophobic non-amyloid β component (NAC), and negatively charged C-terminal regions. Although mouse and human αS share 95% sequence identity, mouse αS forms amyloid fibrils faster than human αS. To evaluate the kinetic regulation of αS fibrillation, we examined the effects of mismatched residues in human and mouse αS on fibril formation and intramolecular interactions. Thioflavin T fluorescence assay using domain-swapped or C-terminal-truncated αS variants revealed that mouse αS exhibited higher nucleation and fibril elongation than human αS. In mouse αS, S87N substitution in the NAC region rather than A53T substitution is dominant for enhanced fibril formation. Fӧrester resonance energy transfer analysis demonstrated that the intramolecular interaction of the C-terminal region with the N-terminal and NAC regions observed in human αS is perturbed in mouse αS. In mouse αS, S87N substitution is responsible for the perturbed interaction. These results indicate that the interaction of the C-terminal region with the N-terminal and NAC regions suppresses αS fibril formation and that the human-to-mouse S87N substitution in the NAC region accelerates αS fibril formation by perturbing intramolecular interaction., (© 2023. The Author(s).)

Background & Aims: Dilatation of the main pancreatic duct (MPD) has been a surgical indication for intraductal papillary mucinous neoplasms (IPMNs). Few studies have investigated long-term outcomes of IPMNs with MPD dilatation., Methods: Among 3610 patients diagnosed with pancreatic cysts between 1994 and 2021, we identified 2829 IPMN patients, including 282 patients with MPD ≥5 mm, and examined short-term (≤6 months) and long-term risks of pancreatic carcinoma. Utilizing competing risks proportional hazards models, we estimated subdistribution hazard ratios for incidence of pancreatic carcinoma with adjustment for potential confounders., Results: In analyses of short-term outcomes of the 282 patients with MPD dilatation, 72 (26%) patients were diagnosed with pancreatic carcinoma based on surgical or nonsurgical exploration. During long-term follow-up of 168 patients, we documented 24 (14%) patients diagnosed with pancreatic carcinoma (18 with IPMN-derived carcinoma and 6 with concomitant ductal adenocarcinoma). The patients with the MPD = 5-9.9 mm had cumulative incidence rates of pancreatic carcinoma diagnosis of 8.1% (95% confidence interval [CI], 4.3%-13.5%) and 10.0% (95% CI, 5.5%-15.9%) at 2 and 5 years, respectively; and the patients with the MPD ≥10 mm had the corresponding rates of 16.0% (95% CI, 3.6-36.5%) and 33.3% (95% CI, 10.3%-58.8%). The multivariable subdistribution hazard ratios were 2.78 (95% CI, 1.57-4.90) and 7.00 (95% CI, 2.58-19.0) for the MPD = 5-9.9 mm and ≥10 mm (vs <5 mm), respectively., Conclusions: IPMNs with MPD dilatation at baseline were associated with higher prevalence and incidence of pancreatic carcinoma compared with IPMNs with no MPD dilatation., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Tempe is a fermented food prepared by fermenting soybeans with Rhizopus species. However, there have recently been concerns about the stable supply of raw soybeans due to global warming and other factors. Moringa is a plant whose cultivation area is expected to expand in the future, and its seeds contain abundant proteins and lipids, and thus could be used as an alternative to soybeans. To develop a novel functional Moringa food, we fermented dehulled Moringa seeds with Rhizopus oligosporus and Rhizopus stolonifer using the solid fermentation method of tempe and investigated changes in the functional components, such as free amino acids and polyphenols, of the respective obtained Moringa tempe Rm and Rs. After 45 h of fermentation, the total content of free amino acids, mainly including gamma-aminobutyric acid and l-glutamic acid, in Moringa tempe Rm was about three times higher, while that in Moringa tempe Rs was almost the same, compared to that in unfermented Moringa seeds. Moreover, after 70 h of fermentation, both Moringa tempe Rm and Rs had approximately four times higher polyphenol content and significantly higher antioxidant activity than did unfermented Moringa seeds. Further, the content of each residual chitin-binding protein of defatted Moringa tempe Rm and Rs was almost the same as that of unfermented Moringa seeds. Taken together, Moringa tempe was rich in free amino acids and polyphenols, exhibited better antioxidant activity, and retained the levels of its chitin-binding proteins, suggesting that Moringa seeds could be used as an alternative to soybean for tempe preparation., (Copyright © 2023 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

We previously reported that Lys175 in the region of the active site of chymotrypsin (Csin) could be site-selectively modified by using an N -hydroxy succinimide (NHS) ester of the peptidyl derivative containing 1-amino-2-ethylphenylphosphonate diphenyl ester [NHS-Suc-Ala-Ala-Phe P (OPh) 2 ]. In this study, the Lys175-selective modification method was expanded to incorporate functional groups into Lys 175 in Csin. Two types of peptidyl phosphonate derivatives with the dansyl group (Dan) as a functional molecule, Dan-β-Ala-[Asp(NHS) or Glu(NHS)]-Ala-Ala-( R )-Phe P (OPh) 2 (DanD and DanE, respectively), were synthesized, and their action was evaluated when modifying Lys175 in Csin. Ion-exchange chromatography (IEC), fluorescence spectroscopy, and LC-MS/MS were used to analyze the products from the reaction of Csin with DanD or DanE. By IEC and LC-MS/MS, the results showed that DanE reacted with Csin more effectively than DanD to produce the modified Csin (DanMCsin) bearing Dan at Lys175. DanMCsin exhibited an enzymatic activity corresponding to 1/120 of Csin against Suc-Ala-Ala-Phe- p NA. In addition, an effect of Lys175 modification on the access of the proteinaceous Bowman-Birk inhibitor to the active site of DanMCsin was investigated. In conclusion, by using a peptidyl derivative containing 1-amino-2-ethylphenylphosphonate diphenyl ester, we demonstrated that a functional group could be incorporated into Lys175 in Csin.

Tetrodotoxin (TTX), also known as pufferfish toxin, is an extremely potent neurotoxin thought to be used as a biological defense compound in organisms bearing it. Although TTX was thought to function as a chemical agent for defense and anti-predation and an attractant for TTX-bearing animals including pufferfish, it has recently been demonstrated that pufferfish were also attracted to 5,6,11-trideoxyTTX, a related compound, rather than TTX alone. In this study, we attempted to estimate the roles of TTXs (TTX and 5,6,11-trideoxyTTX) in the pufferfish, Takifugu alboplumbeus , through examining the location of TTXs in various tissues of spawning pufferfish from Enoshima and Kamogawa, Japan. TTXs levels in the Kamogawa population were higher than those in the Enoshima population, and there was no significant difference in the amount of TTXs between the sexes in either population. Individual differences were greater in females than in males. However, the location of both substances in tissues differed significantly between sexes: male pufferfish accumulated most of their TTX in the skin and liver and most of their 5,6,11-trideoxyTTX in the skin, whereas females accumulated most of their TTX and 5,6,11-trideoxyTTX in the ovaries and skin.

Background: The public stigma related to mental illness is the general public's negative misconceptions about people with mental health conditions (PMHCs). The public stigma of mental illness is detrimental to PMHC as it leads to loss of opportunities and unemployment. The aim of the study was to clarify the status of public stigma related to PMHC, focusing on knowledge about mental illness and social distance concerning PMHC., Methods: A survey was conducted among 970 Japanese office workers aged 20 to 60 years. Accurate knowledge of mental illness was assessed using the Mental Illness and Disorder Understanding Scale (MIDUS). The Attitudinal Social Distance (ASD) was used to determine social distance in relation to PMHC. The demographic characteristics of the participants evaluated were sex, age group measured in years, employment position, employment status, and attendance at mental illness stigma training., Results: Regular employees (P = 0.03) and those having prior contact experience (P = 0.01) had more accurate knowledge. Participants between 50 to 59 years old (M = 15.87, standard deviation (SD) = 3.35) had greater social distance than those under 30 years old (M = 14.78, SD = 3.97, P < 0.05). The results of multiple linear regression analysis found that employment status (partial r = -0.07, P < 0.05) and prior contact experience (partial r = -0.15, P < 0.01) significantly affected the MIDUS score, whereas no variable had a significant effect on the ASD score., Conclusions: Accurate knowledge of mental illness was significantly higher among regular employees and those with contact experience. Social distance was significantly lower among those under the age of 30 years., Competing Interests: The authors declare that they have no competing interest., (Copyright 2023, Lem et al.)

Background: Rituximab, high-dose methotrexate (HD-MTX), procarbazine and vincristine (R-MPV), has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), but predictive factors for response to R-MPV have not yet been investigated. Herein, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R-MPV., Methods: We investigated the long-term clinical course and status of MYD88 and CD79B genes in 85 patients with PCNSL treated with R-MPV or HD-MTX treatment, and the correlation of these genetic mutations with prognosis., Results: R-MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5-year progression-free and overall survival rates, respectively). While MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (p < 0.05). However, the association of CD79B Y196 mutation with a better prognosis was not observed in the HD-MTX cohort, which indicated that CD79B Y196 mutation was a predictive marker for a favorable response to R-MPV. Furthermore, we established an all-in-one rapid genotyping system for these genetic mutations., Conclusions: In conclusion, CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in PCNSL. The rapid identification of MYD88 L265P and CD79B Y196 mutations can be helpful not only for the accurate molecular diagnosis of PCNSL but also for the prediction of response to R-MPV., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to the difficulty of its diagnosis. Because human satellite II (HSATII) RNA, a satellite repeat RNA, is highly and specifically expressed in human PDAC, the serum HSATII RNA level may be a biomarker of PDAC. To measure the serum HSATII RNA level with high sensitivity and reproducibility, we previously developed a convenient method, tandem repeat amplification by nuclease protection (TRAP) combined with droplet digital PCR (ddPCR). Here, we refined the original method by simultaneously measuring the serum miR-21-5p level to enhance the detection of PDAC. The resulting PDAC-Index, constructed using serum HSATII RNA and miR-21-5p levels, discriminated patients with PDAC with high accuracy. We verified the clinical usefulness of the PDAC-Index as a supportive test in difficult-to-diagnose cases. The PDAC-Index has satisfactory diagnostic performance and may routinely be applied for detecting PDAC., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Baker's yeast is an attractive host with established safety and stability characteristics. Many yeast-based biosensors have been developed, but transmembrane signal transduction has not been used to detect membrane-impermeable substances using antigen-antibody interactions. Therefore, we created Patrol Yeast, a novel yeast-based immunosensor of various targets, particularly toxic substances in food. A membrane-based yeast two-hybrid system using split-ubiquitin was successfully used to detect practically important concentration ranges of caffeine and aflatoxins using separated variable regions of an antibody. Moreover, enterohemorrhagic Escherichia coli O157 was detected using a specific single-chain antibody, in which Zymolyase was added to partially destroy the cell wall. The incorporation of secreted Cypridina luciferase reporter further simplified the signal detection procedures without cell lysis. The methodology is more cost-effective and faster than using mammalian cells. The ability to detect various targets renders Patrol Yeast a valuable tool for ensuring food and beverage safety and addressing other environmental and technological issues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aim: The incidence and prevalence of psychiatric disorders are elevated in patients with inflammatory bowel disease (IBD). Whether psychiatric disorders could affect the clinical course of IBD is uncertain and controversial. We aimed to evaluate the impact of psychiatric disorders, particularly depression, on the clinical course of IBD using a nationwide database in Japan., Methods: We collected data on admissions with IBD using the Diagnosis Procedure Combination database system introduced in Japan. We divided eligible admissions into IBD with and without depression groups using propensity score matching and compared the rates of surgery, use of molecular targeted drugs and biologics, systemic steroid administrations, and in-hospital death. We also conducted a logistic regression analysis to identify clinical factors affecting surgery, the use of molecular targeted drugs and biologics, and systemic steroid administrations., Results: The rates of surgery, use of two or more molecular targeted drugs, systemic steroid administrations, and in-hospital deaths in the ulcerative colitis (UC) with depression group were higher than in the UC without depression group. Multivariate analysis of UC showed that depression increased the odds of systemic steroid administrations, use of two or more molecular targeted drugs, and surgery. However, analysis of Crohn's disease showed that only steroid administrations were associated with depression., Conclusion: Our study demonstrated an association between a worse clinical course of UC and depression. Although this result indicates that depression might be associated with increased disease activity in patients with UC, the causal relationship is still unclear. Further prospective studies are warranted., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aim: Few studies have investigated the health-related quality of life (HRQoL) in long-stay inpatients with chronic schizophrenia in Japan. This study aimed to clarify the factors associated with HRQoL among these patients., Methods: Out of 238 patients with chronic schizophrenia admitted to three hospitals, 101 inpatients provided informed consent to participate in the study. The patients' HRQoL was assessed using two instruments: the EuroQol 5 dimensions (EQ-5D) as a generic index and the Subjective Well-being Under Neuroleptic Treatment Scale, Japanese Version (SWNS-J) as a disease-specific index. We examined the factors associated with these HRQoL indices using multiple linear regression models., Results: The patients' mean age was 62.9 years, and 51.5% were female. The mean (standard deviation) EQ-5D score and SWNS-J total score were 0.776 (0.177) and 83.5 (16.5), respectively. Multiple linear regression analysis indicated that the EQ-5D score was significantly and negatively associated with the female sex, benzodiazepine use, and Drug-Induced Extrapyramidal Symptoms Scale scores. In contrast, the SWNS-J total score was significantly and negatively associated with first-generation antipsychotics use, Brief Psychiatric Rating Scale scores, Drug-Induced Extrapyramidal Symptoms Scale scores, and Global Assessment of Functioning scale scores., Conclusion: This study identified the factors associated with two HRQoL indices among long-stay inpatients with chronic schizophrenia in Japan. Although the analyses showed differences in the associated factors between the generic EQ-5D and the disease-specific SWNS-J, extrapyramidal symptoms as adverse effects of antipsychotic treatment were found to be associated with both indices., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Soft-crystals are defined as flexible molecular solids with highly ordered structures and have attracted attention in molecular sensing materials based on external triggers and environments. Here, we show the soft-crystal copolymerization of green-luminescent Tb(III) and yellow-luminescent Dy(III) coordination centers. Soft-crystal polymerization is achieved via transformation of monomeric dinuclear complexes and polymeric structures with respect to coordination number and geometry. The structural transformation is characterized using single-crystal and powder X-ray diffraction. The connected Tb(III) crystal-Dy(III) crystal show photon energy transfer from the Dy(III) centre to the Tb(III) centre under blue light excitation (selective Dy(III) centre excitation: 460 ± 10 nm). The activation energy of the energy transfer is estimated using the temperature-dependent emission lifetimes and emission quantum yields, and time-dependent density functional theory (B3LYP) calculations. Luminescence-conductive polymers, photonic molecular trains, are successfully prepared via soft-crystal polymerization on crystal media with remarkable long-range energy migration., (© 2022. The Author(s).)

Background: Existing self-training materials are insufficient to learn open surgical procedures, and a new self-training system that provides three-dimensional procedural information is needed. The effectiveness and usability of a self-training system providing three-dimensional information by augmented reality (AR) were compared to those of an existing self-training system, instructional video, in self-learning of suturing in open surgery., Materials and Methods: This was a prospective, evaluator-blinded, randomized, controlled study. Medical students who were suturing novices were randomized into 2 groups: practice with the AR training system (AR group) or an instructional video (video group). Participants were instructed in subcuticular interrupted suture and each training system and watched the instructional video once. They then completed a pretest performing the suture on a skin pad. Participants in each group practiced the procedure 10 times using each training system, followed by a posttest. The pretest and posttest were video-recorded and graded by blinded evaluators using a validated scoring form composed of global rating (GR) and task-specific (TS) subscales. Students completed a post-study questionnaire assessing system usability, each system's usefulness, and their confidence and interest in surgery., Results: Nineteen participants in each group completed the trial. No significant difference was found between the AR and video groups on the improvement of the scores from pretest to posttest (GR: p = 0.54, TS: p = 0.91). The posttest scores of both GR and TS improved significantly from pretest in both groups (GR: both p < 0.001, TS: both p < 0.001). There was no significant difference between the groups in the system usability scale scores (p = 0.38). The motion provided in the AR system was more helpful for manipulating surgical instruments than the video (p = 0.02)., Conclusion: The AR system was considered as understandable and easy to use as the instructional video in learning suture technique in open surgery for novices., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Proton pump inhibitors (PPIs) are widely prescribed medications for gastric acid-induced diseases. Despite the effectiveness of PPIs, recent evidence suggested an increased risk of various bacterial infections in PPI users. The current study was conducted to evaluate the risk of biliary infection after endoscopic biliary stent placement in regular users of PPIs., Methods: Consecutive patients with a native papilla who underwent endoscopic retrograde cholangiopancreatography and stent placement for biliary stricture between January 2010 and August 2019 were included in this retrospective study. The cumulative incidences of biliary infection were compared between regular and non-regular PPI users., Results: During the study period, 270 regular PPI users and 146 non-regular PPI users were included in the analyses. Age, gender, and indication of endoscopic retrograde cholangiopancreatography were not different between the two groups. The incidences of biliary infection were 43% in regular PPI users and 36% in non-regular PPI users but the time to biliary infection was significantly shorter in regular PPI users than in non-regular users (28 vs. 87 days, p = 0.01). The cumulative incidence of biliary infection was significantly higher in regular PPI users compared with non-regular users ( p = 0.008). The multivariable Cox regression analysis also showed a significantly higher hazard ratio of biliary infection in regular PPI users (1.62 [95% confidence interval 1.16-2.26; p = 0.005])., Conclusions: Regular PPI use was associated with a higher risk of biliary infection after endoscopic biliary drainage. Inappropriate PPI use should be avoided., Competing Interests: Mitsuhiro Fujishiro received lecture honoraria from EA pharma, Takeda pharmaceuticals, Daiichi Sankyo Co., AstraZeneca Co., Olympus Co., and Fujifilm Co., and a research grant from Olympus Co, HOYA Pentax Co., Fujifilm Co., EA pharma, and Takeda pharmaceuticals, and scholarship grants from EA pharma, and Takeda Pharmaceuticals outside the submitted work.Yousuke Nakai received lecture honoraria from Olympus Co. and a research grant from HOYA Pentax Co., Fujifilm Co., and Boston Scientific Japan, and scholarship grants from Boston Scientific Japan, and Gadelius medical outside the submitted work. , (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Multilayered approaches to suicide prevention combine universal, selective, and indicated prevention interventions. These approaches may be more successful in reducing suicide rates among older adults if they link these layers more systematically: that is, if the programs are designed so that interventions at a lower level facilitate involvement at a higher level when appropriate. This study aimed to examine the effect on suicide rates of the structure of multilayered approaches, and in particular the types of interventions and the connections or linkages between them. We also wished to consider any different effects by sex. A literature search used PubMed and PsycINFO to identify systematic reviews of interventions in this age group. From the reference lists of these articles, we identified controlled studies assessing the impact of a multilayered program on suicide incidence among older adults. We were particularly interested in initiatives linking different kinds of prevention interventions. We found three relevant systematic reviews, and from these, we identified nine eligible studies. These included seven non-randomized controlled studies from rural areas in Japan (average eligible population: 3,087, 59% women, average duration: 8 years). We also found two cohort studies. The first was from a semi-urban area in Padua, Italy (18,600 service users, 84% women, duration: 11 years). The second was from urban Hong Kong, with 351 participants (57% women) over a 2-year follow-up period. We used a narrative synthesis of these studies to identify five different multilayered programs with different forms of connections or linkages between layers. Two studies/programs (Italy and Hong Kong) involved selective and indicated prevention interventions. One study/program (Yuri, Japan) included universal and selective prevention interventions, and the final six studies (two programs in northern Japan) involved linkages between all three layers. We also found that these linkages could be either formal or informal. Formal linkages were professional referrals between levels. Informal linkages included advice from professionals and self-referrals. Several of the studies noted that during the program, the service users developed relationships with services or providers, which may have facilitated movements between levels. All five programs were associated with reduced suicide incidence among women in the target groups or communities. Two programs were also associated with a reduction among men. The study authors speculated that women were more likely to accept services than men, and that the care provided in some studies did less to address issues that are more likely to affect men, such as suicidal impulsivity. We therefore suggest that it is important to build relationships between levels, especially between selective and indicated prevention interventions, but that these can be both formal and informal. Additionally, to reach older men, it may be important to create systematic methods to involve mental health professionals in the indicated prevention intervention. Universal interventions, especially in conjunction with systematically linked indicated and selective interventions, can help to disseminate the benefits across the community., 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 © 2022 Sakashita and Oyama.)