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Introduction: The effectiveness and safety of 50 W, high-power, short-duration (HPSD) ablation in superior vena cava isolation (SVCI) for patients with atrial fibrillation (AF) have been reported. However, the acute outcomes of SVCI combined with 90 W/4 s, very high-power, short-duration (vHPSD) ablation remain unknown. In this study, we aimed to investigate a novel approach that combines 50 W-HPSD and 90 W/4 s-vHPSD ablation in SVCI and to elucidate the characteristics, outcomes, and safety of this approach by comparing SVCI with conventional ablation index (AI)-guided middle-power, middle-duration (MPMD) ablation., Methods: Overall, 126 patients who underwent AF ablation with SVCI using the QDOT MICRO TM catheter were retrospectively reviewed; one group underwent SVCI with a combined approach of HPSD and vHPSD ablation (50 W/90 W group, n = 73) and another group underwent AI-guided MPMD ablation (30-40 W group, n = 53). This study compared the procedural details, radiofrequency (RF) ablation profiles, and complications. The RF settings used in the 50 W/90 W group were 50 W/7 s for the lateral segment close to the phrenic nerve and 90 W/4 s for the nonlateral segment., Results: The 50 W/90 W group required a significantly shorter procedural time (3.2 vs. 5.9 min, p < .001), shorter RF duration (42.0 vs. 162.0 s, p < .001), and lower RF energy (2834 vs. 5480 J, p < .001) than the 30-40 W group. Procedural success, first-pass SVCI, number of RF applications, and SVC reconnection after isoproterenol loading were comparable between the groups. The maximum tip-electrode temperature of the multi-thermocouple system was significantly higher in the 50 W/90 W group than in the 30-40 W group (50.0°C vs. 47.0°C, p < .001). No complications, such as phrenic nerve injury or bleeding requiring transfusion, were observed in either group., Conclusions: The combined approach of 50 W/7 s-HPSD and 90 W/4 s-vHPSD ablation resulted in successful and safe SVCI with shorter procedural time, shorter RF duration, and lower RF energy., (© 2024 Wiley Periodicals LLC.)

A quadrivalent influenza vaccine (QIV) has been available in Japan since the 2015/2016 influenza season. Single radial immunodiffusion (SRID) assays are currently used worldwide to measure the hemagglutinin (HA) content of influenza vaccine components because they are simple, accurate, and the regulatory requirement, ensuring consistency in manufacture for the HA content. However, the cross-reactivity of antisera against the two lineages of the influenza B virus (IFVB) may cause inaccurate quantification of HA content in QIVs using the SRID assay. To examine cross-reactivity and develop an appropriate procedure for accurate measurement of vaccine potency, a collaborative study with four Japanese vaccine manufacturers was conducted to measure the HA contents of trivalent influenza vaccines (TIVs) and QIVs by SRID assay with a single and a mixture of reference antigens (refAgs) from each lineage of IFVB for seven influenza seasons from 2015/16 to 2021/22. The cross-reactivity of the two IFVB components in the SRID assay varied depending on the vaccine viruses. Our study demonstrated that it is useful to validate a suitable combination for each refAg and reference antiserum by selecting the combination showing similar HA contents between experimental TIV and QIV before lot release testing., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The necessity of a minimum volume of keratinized tissue around implants to maintain tissue stability remains a matter of debate. The aim of this case series is to showcase the outcome and long-term maintenance of dental implants that received soft tissue augmentation., Case Presentation: Three cases of second stage following dental implant placement were evaluated for amount of keratinized tissue. Based on the Ono-Nevins classification described here, treatment was rendered including keratinized tissue grafting. The cases were followed for 10, 18 and 28 years. Each case demonstrated maintenance of soft and hard tissue profile around the dental implants with no incidence of peri-implantitis as evidenced on clinical examination and use of peri-apical radiographs., Conclusion: Soft tissue management around dental implants may play a key role in long-term maintenance of peri-implant health and prevention of peri-implantitis.

Objective Adverse events such as bile leakage and bleeding are among the issues that need to be resolved in EUS-guided choledochoduodenostomy (EUS-CDS). To overcome this problem, we developed a new EUS-CDS technique using a 19-G Franseen needle without tract dilation. This study aimed to evaluate the safety and efficacy of the new EUS-CDS technique. Methods This single-center retrospective study included 20 consecutive patients who underwent EUS-CDS for primary drainage using a 19-G Franseen needle between March 2020 and May 2023. The primary endpoint was the technical success rate of EUS-CDS without tract dilation. Results The technical success rate of EUS-CDS was 20/20 (100%). None of the patients required any additional tract dilation, such as by using a balloon or electric cautery. The median procedure time was 7.8 [range, 3.2-19.4] min. No early adverse events were observed. Conclusion The 19-G Franseen needle appeared to have a sufficient dilatory effect during puncturing. This EUS-CDS technique appears to be safe and effective and has the advantages of no adverse events and it is also a simplified procedure, which suggests its potential for widespread use in primary drainage.

Background: Posterior sagittal anorectoplasty and laparoscopic-assisted anorectal pull-through are preferred for anorectal malformation (ARM) today, while careful pull-through procedures with sacroperineal approach yield excellent outcomes. This study focuses on a pull-through procedure emphasizing continence mechanism preservation and compares outcomes with historical studies with various procedures., Methods: Bowel function of patients with intermediate ARM followed up for over 10 years post-surgically was assessed. Data collected included ARM type with the Krickenbeck classification, comorbidities, complications, post-surgical examinations, follow-up, and bowel function at the latest clinic visit. The literature review collected original articles including more than 10 post-anorectoplasty cases which were followed for over 10 years., Results: Eleven cases were identified, with a median age at anorectoplasty and follow-up length of 6.9 months and 14.4 years. Two fistula recurrences required surgical treatment. Long-term incontinence and constipation were observed in 9% and 45% of the cohort, respectively. Good rectal angulation and a positive rectoanal inhibitory reflex were confirmed in most cases examined. A literature review identified eight studies with various outcome-measuring instruments., Conclusion: Outcomes of the introduced pull-through procedure were favorable, while the literature review highlights the variation in outcomes of various anorectoplasty., Evidence Level: Level IV., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aims: Dilation of the tract before stent deployment is a challenging step in endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD). In this study, we examined the effectiveness and safety of a novel spiral dilator, Tornus ES (Asahi Intec), for EUS-PDD., Methods: This was a retrospective, single-arm, observational study at Aichi Cancer Center Hospital. The punctured tract was dilated using a Tornus ES dilator in all EUS-PDD cases. Our primary endpoint was the technical success rate of initial tract dilation. Technical success was defined as successful fistula dilation using a Tornus ES followed by successful stent insertion. Secondary endpoints were procedure times and early adverse events., Results: A total of 12 patients were included between December 2021 and March 2023. EUS-PDD was performed in 11 patients for post-pancreaticoduodenectomy anastomotic strictures and one patient with pancreatitis with duodenal perforation. The technical success rates of stent insertion and fistula dilation using a Tornus ES dilator was 100%. The median procedure time was 24 minutes. No remarkable adverse events related to the procedure were observed, apart from fever, which occurred in 2 patients., Conclusions: Tract dilation in EUS-PDD using a Tornus ES is effective and safe.

Perforated esophageal cancer rarely results in the formation of mediastinal abscess. Endoscopic ultrasound (EUS)-guided abscess drainage (AD) has increasingly been used in the management of abscesses in locations that are difficult to treat percutaneously. We describe a case of EUS-AD for mediastinal abscess due to perforating esophageal cancer and successful bridge to surgery. A 71-year-old man with suspected esophageal issues was referred to our hospital. Computed tomography showed an esophageal cancer perforating the mediastinum, forming a mediastinal abscess. EUS-AD was planned before curative resection, because there was little improvement in inflammatory response with antimicrobial therapy. The mediastinal abscess cavity was confirmed on EUS and punctured using a 19-G needle, and then, a 0.025-inch guidewire was placed in the abscess cavity. The fistula was dilated with a 7-Fr dilator and a 6-Fr, single-pigtail nasobiliary tube was placed in the abscess cavity. One month later, clinical signs had improved and curative surgery was performed. Postoperative adjuvant therapy was administered using fluorouracil/cisplatin therapy. As of 2 years postoperatively, the patient remains free of recurrence., (© 2024. Japanese Society of Gastroenterology.)

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Background/aims: Endoscopic ultrasound (EUS)-guided pancreatic duct drainage is a well-established procedure for managing pancreaticojejunostomy anastomotic strictures (PJAS) post-Whipple surgery. In this study, we examined the effectiveness and safety of EUS-guided pancreaticojejunostomy (EUS-PJS)., Methods: This retrospective, single-arm study was performed at Aichi Cancer Center Hospital on 10 patients who underwent EUS-guided pancreaticojejunostomy through the afferent jejunal loop using a forward-viewing echoendoscope when endoscopic retrograde pancreatography failed. Our primary endpoint was technical success rate, defined as successful stent insertion. The secondary endpoints were early and late adverse events., Results: A total of 10 patients underwent EUS-PJS between February 2019 and October 2023. The technical success rate was 100%. The median procedure time was 23.5 minutes. No remarkable early or late adverse events related to the procedure, except for fever, occurred in two patients. The median follow-up duration was 9.5 months, and the median number of stent exchanges was two. A stent-free state was achieved in three patients., Conclusions: EUS-PJS for PJAS management after pancreaticoduodenectomy appears to be an effective and safe procedure with the potential advantages of fewer reinterventions and the creation of a permanent drainage fistula.

Background/aims: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) performed at the intrahepatic bile duct segment 3 (B3) is widely used for biliary drainage. Although performing post-puncture procedures is easier in the intrahepatic bile duct segment 2 (B2) when using a conventional oblique-viewing (OV) EUS scope, this method may cause transesophageal puncture and severe adverse events. We evaluated the safety and efficacy of B2 puncture using a novel OV-EUS scope., Methods: In this single-center retrospective study, we prospectively enrolled and collected data from 45 patients who consecutively underwent EUS-HGS procedures with a novel OV-EUS scope between September 2021 and December 2022 at our cancer center., Results: The technical success rates of B2-EUS-HGS and EUS-HGS were 93.3% (42/45) and 97.8% (44/45), respectively. The early adverse event rate was 8.9% (4/45) with no cases of scope changes or transesophageal punctures. The median procedure time was 13 minutes (range, 5-30)., Conclusions: B2-EUS-HGS can be performed safely with the novel EG-740UT (Fujifilm) OV-scope without transesophageal puncture and with a high success rate. B2-EUS-HGS using this novel OV scope may be the preferred strategy for EUS-HGS.

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) through ducts B2 or B3 is effective in most patients with biliary obstruction, because B2 and B3 commonly join together. However, in some patients, B2 and B3 do not join each other due to invasive hilar tumors; therefore, single-route drainage is insufficient. Here, we investigated the feasibility and efficacy of EUS-HGS through both B2 and B3 simultaneously in seven patients. We decided to perform EUS-HGS through both B2 and B3 to achieve adequate biliary drainage because these two ducts were separate from each other. Here, we report a 100% technical and overall clinical success rate. Early adverse effects were closely monitored. Minimal bleeding was reported in one patient (1/7) and mild peritonitis in one patient (1/7). None of the patients experienced stent dysfunction, fever, or bile leakage after the procedure. EUS-HGS through both B2 and B3 simultaneously is safe, feasible, and effective for biliary drainage in patients with separated ducts.

Conjugation of ATG8 to single membranes (CASM) at endolysosomal compartments has attracted attention as the non-autophagic function of the Atg8-family protein conjugation system, and the V-ATPase-ATG16L1 axis has emerged as a core mechanism. Our recent research has revealed that this mechanism contributes to the lysosomal recruitment and activation of LRRK2, a Parkinson disease-associated kinase that phosphorylates a subset of RAB GTPases. The activated LRRK2 under CASM-causing lysosomal stress acts to regulate lysosomal morphology and stimulate extracellular secretion of lysosomal contents, thereby promoting the lysosomal stress response.

Background: We hypothesized that high-resolution activation mapping during sinus rhythm (SR) in Koch's triangle (KT) can be used to describe the most delayed atrial potential around the atrioventricular node and evaluated whether ablation targeting of this potential is safe and effective for the treatment of patients with typical atrioventricular nodal reentrant tachycardia (AVNRT)., Methods: We conducted a prospective, non-randomized, observational study using high-resolution activation mapping from the sinus node to KT with a PENTARAY or OCTARAY catheter using the CARTO 3 cardiac mapping system (Biosense Webster) during SR in 62 consecutive patients (22 men; age [mean ± standard deviation] = 55 ± 14 years) treated for typical AVNRT at our institution from August 2021 to March 2023., Results: In all cases, the most delayed atrial potential was observed near the His potential within KT. Ablation targeting of this potential helped successfully treat each case of AVNRT, with a junctional rhythm observed at the ablation site. Initial ablation was deemed successful in 55/62 patients (89%); in the remaining seven patients, lesion expansion resolved AVNRT. One procedural complication occurred, namely, a transient atrioventricular block lasting 45 s. One patient experienced a transient tachycardic episode by the 1-month follow-up, but no further episodes were noted up to the 1-year follow-up., Conclusion: Activation mapping at KT during SR with the high-resolution CARTO system clearly revealed the most delayed atrial potential near the His potential within KT. Targeting this potential was a safe and effective treatment method for patients with typical AVNRT in our study., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Highly luminescent silver(I) coordination polymers [Ag 2 X 2 (PPh 3 ) 2 (Me 2 pyz)] n (X = I, Br, Cl; Me 2 pyz: 2,5-dimethylpyrazine) were prepared together with copper congeners [Cu 2 X 2 (PPh 3 ) 2 (Me 2 pyz)] n (X = I, Br). All the complexes showed thermally activated delayed fluorescence from the charge-transfer states in the visible region, from blue to red. The isomorphous relationship among the complexes allowed a detailed discussion of the effect of halogenido ligands and crystal packing on their luminescence energy. The relaxation in the emissive excited states (ESs) was determined to be more remarkable in silver complexes than in copper complexes despite their isomorphous structures, and the electronic effect of halogenido ligands was comparable to the effect of relaxation in emissive ESs.

Background/aims: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a standard diagnostic method for biliary tract cancer (BTC), and samples obtained in this manner may be used for comprehensive genomic profiling (CGP). This study evaluated the utility of EUS-TA for CGP in a clinical setting and determined the factors associated with the adequacy of CGP in patients with BTC., Methods: CGP was attempted for 105 samples from 94 patients with BTC at the Aichi Cancer Center, Japan, from October 2019 to April 2022., Results: Overall, 77.1% (81/105) of the samples were adequate for CGP. For 22-G or 19-G fine-needle biopsy (FNB), the sample adequacy was 85.7% (36/42), which was similar to that of surgical specimens (94%, p=0.45). Univariate analysis revealed that 22-G or larger FNB needle usage (86%, p=0.003), the target primary lesions (88%, p=0.015), a target size ≥30 mm (100%, p=0.0013), and number of punctures (90%, p=0.016) were significantly positively associated with CGP sample adequacy., Conclusions: EUS-TA is useful for CGP tissue sampling in patients with BTC. In particular, the use of 22-G or larger FNB needles may allow for specimen adequacy comparable to that of surgical specimens.

Background/aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a highly accurate method for diagnosing pancreatic neuroendocrine tumors (PNETs); however, some PNETs are difficult to diagnose. Recently, the efficacy of needle-based confocal laser endomicroscopy (nCLE) in diagnosing solid pancreatic masses has been reported. However, the efficacy of nCLE in the diagnosis of PNETs remains unknown and only a small number of cases have been reported. Hence, this study aimed to evaluate the efficacy of nCLE in the diagnosis of PNETs., Methods: This single-center retrospective study evaluated 30 consecutive patients with suspected PNETs on contrast-enhanced computed tomography, who consented to nCLE combined with EUS-FNA and were diagnosed using EUS-FNA or surgical resection. The diagnostic criteria for PNETs using nCLE were based on the nesting and trabecular and glandular arrangement of tumor cell clusters surrounded by capillary vessels and fibrosis, as reported in previous studies., Results: The diagnosis using nCLE was classified into three categories: misdiagnosis in three cases (10%), non-diagnostic in six cases (20%), and diagnostic in 21 cases (70%). nCLE was able to diagnose PNET in one of the two cases with inconclusive EUS-FNA., Conclusions: Although further development of the resolution and optimization of the diagnostic criteria are required, nCLE may constitute a useful diagnostic option in cases of inconclusive EUS-FNA for PNETs.

Boron doping of diamond-like carbon coatings has multiple effects on their tribological properties. While boron typically reduces wear in cutting applications, some B-doped coatings show poor tribological performance compared with undoped films. This is the case of the tribological tests presented in this work in which an alumina ball is placed in frictional contact with different undoped and B-doped amorphous carbon coatings in humid air. With B-doped coatings, a higher friction coefficient at a steady state with respect to their undoped counterparts was observed. Estimates of the average contact shear stress based on experimental friction coefficients, surface topographies, and Persson's contact theory suggest that the increased friction is compatible with the formation of a sparse network of interfacial ether bonds leading to a mild cold-welding friction regime, as documented in the literature. Tight binding and density functional theory simulations were performed to investigate the chemical effect of B-doping on the interfacial properties of the carbon coatings. The results reveal that OH groups that normally passivate carbon surfaces in humid environments can be activated by boron and form B-O dative bonds across the tribological interfaces, leading to a mild cold-welding friction regime. Simulations performed on different tribological pairs suggest that this mechanism could be valid for B-doped carbon surfaces in contact with a variety of materials. In general, this study highlights the impact that subtle modifications in surface and interface chemistry caused by the presence of impurities can have on macroscopic properties, such as friction and wear.

Background: The superior transseptal approach (STA) for mitral valve surgery is associated with a higher risk of developing macroreentrant incisional atrial flutter (AFL) than the left atrial approach. This study aimed to describe the linear lesions for the complex AFL circuit after the STA and to propose an option for the linear ablation target site., Methods: Of the 26 patients who underwent radiofrequency catheter ablation for AFL after mitral valve surgery, data from seven patients with STA incisions were retrospectively analyzed., Results: All patients who had undergone the STA had incisional AFL rotated in a long loop within the right atrium (RA) and cavo-tricuspid isthmus (CTI)-dependent AFL. The linear lesions were created in the CTI, the superior RA vestibule, and between the RA-free wall incision or the septal incision and the inferior vena cava. Procedural success was achieved with dual linear lesions in the CTI and superior RA vestibule. Two of seven patients had AFL recurrence during a mean observation period of 22.5 ± 16.7 months. The circuits of recurrent AFL were CTI-dependent AFL and perimitral AFL, respectively. No AFL recurrence was noted with reconduction of the superior RA vestibular lesion., Conclusion: Dual linear lesions in the CTI and superior RA vestibule are an effective treatment option for RA macroreentrant AFL after the STA., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The speed limit of information propagation is one of the most fundamental features in non-equilibrium physics. The region of information propagation by finite-time dynamics is approximately restricted inside the effective light cone that is formulated by the Lieb-Robinson bound. To date, extensive studies have been conducted to identify the shape of effective light cones in most experimentally relevant many-body systems. However, the Lieb-Robinson bound in the interacting boson systems, one of the most ubiquitous quantum systems in nature, has remained a critical open problem for a long time. This study reveals a tight effective light cone to limit the information propagation in interacting bosons, where the shape of the effective light cone depends on the spatial dimension. To achieve it, we prove that the speed for bosons to clump together is finite, which in turn leads to the error guarantee of the boson number truncation at each site. Furthermore, we applied the method to provide a provably efficient algorithm for simulating the interacting boson systems. The results of this study settle the notoriously challenging problem and provide the foundation for elucidating the complexity of many-body boson systems., (© 2024. The Author(s).)

Potency tests for influenza vaccines are currently performed using a single-radial immunodiffusion (SRID) assay, which requires a reference antigen and anti-hemagglutinin (HA) serum as reference reagents. Reagents must be newly prepared each time a strain used for vaccine production is modified. Therefore, establishing reference reagents of consistent quality is crucial for conducting vaccine potency tests accurately and precisely. Here, we established reference reagents for the SRID assay to conduct lot release tests of quadrivalent influenza vaccines in Japan during the 2022/23 influenza season. The potency of reference antigens during storage was confirmed. Furthermore, we evaluated the cross-reactivity of each antiserum raised against the HA protein of the 2 lineages of influenza B virus toward different lineages of influenza B virus antigens to select a suitable procedure for the SRID assay for accurate measurement. Finally, the intralaboratory reproducibility of the SRID assay using the established reference reagents was validated, and the SRID reagents had sufficient consistent quality, comparable to that of the reagents used for testing vaccines during previous influenza seasons. Our study contributes to the quality control of influenza vaccines.

Leucine-rich repeat kinase 2 (LRRK2), a Rab kinase associated with Parkinson's disease and several inflammatory diseases, has been shown to localize to stressed lysosomes and get activated to regulate lysosomal homeostasis. However, the mechanisms of LRRK2 recruitment and activation have not been well understood. Here, we found that the ATG8 conjugation system regulates the recruitment of LRRK2 as well as LC3 onto single membranes of stressed lysosomes/phagosomes. This recruitment did not require FIP200-containing autophagy initiation complex, nor did it occur on double-membrane autophagosomes, suggesting independence from canonical autophagy. Consistently, LRRK2 recruitment was regulated by the V-ATPase-ATG16L1 axis, which requires the WD40 domain of ATG16L1 and specifically mediates ATG8 lipidation on single membranes. This mechanism was also responsible for the lysosomal stress-induced activation of LRRK2 and the resultant regulation of lysosomal secretion and enlargement. These results indicate that the V-ATPase-ATG16L1 axis serves a novel non-autophagic role in the maintenance of lysosomal homeostasis by recruiting LRRK2., (© 2024 Eguchi et al.)

Therapeutic endoscopic ultrasonography (EUS) procedures using the forward-viewing convex EUS (FV-EUS) have been reviewed based on the articles reported to date. The earliest reported procedure is the drainage of pancreatic pseudocysts using FV-EUS. However, the study on drainage of pancreatic pseudocysts focused on showing that drainage is possible with FV-EUS rather than leveraging its features. Subsequently, studies describing the characteristics of FV-EUS have been reported. By using FV-EUS in EUS-guided choledochoduodenostomy, double punctures in the gastrointestinal tract can be avoided. In postoperative modified anatomical cases, using the endoscopic function of FV-EUS, procedures such as bile duct drainage from anastomosis, pancreatic duct drainage from the afferent limb, and abscess drainage from the digestive tract have been reported. When a perpendicular puncture to the gastrointestinal tract is required or when there is a need to insert the endoscope deep into the gastrointestinal tract, FV-EUS is considered among the options.

Background/aims: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) is useful for patients with biliary cannulation failure or inaccessible papillae. However, it can lead to serious complications such as bile peritonitis in patients with ascites; therefore, development of a safe method to perform EUS-HGS is important. Herein, we evaluated the safety of EUS-HGS with continuous ascitic fluid drainage in patients with ascites., Methods: Patients with moderate or severe ascites who underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after the procedure at our institution between April 2015 and December 2022, were included in the study. We evaluated the technical and clinical success rates, EUS-HGS-related complications, and feasibility of re-intervention., Results: Ten patients underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after completion of the procedure. Median duration of ascites drainage before and after EUS-HGS was 2 and 4 days, respectively. Technical success with EUS-HGS was achieved in all 10 patients (100%). Clinical success with EUS-HGS was achieved in 9 of the 10 patients (90 %). No endoscopic complications such as bile peritonitis were observed., Conclusion: In patients with ascites, continuous ascites drainage, which is initiated before EUS-HGS and terminated after completion of the procedure, may prevent complications and allow safe performance of EUS-HGS.

Background: We compared the results of preoperative pancreatic juice cytology (PJC) and final pathological diagnosis after resection in patients who underwent resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas to determine whether preoperative PJC can help determine therapeutic strategies., Methods: Of 1130 patients who underwent surgical resection IPMN at 11 Japanese tertiary institutions, the study included 852 patients who underwent preoperative PJC guided by endoscopic retrograde cholangiopancreatography (ERCP)., Results: The accuracy of preoperative PJC for differentiation between cancerous and noncancerous lesions were 55% for IPMN overall; 59% for the branch duct type; 49% for the main pancreatic duct type; 53% for the mixed type, respectively. On classifying IPMN according to the diameters of the mural nodule (MN) and main pancreatic duct (MPD), the corresponding values for diagnostic performance were 40% for type 1 (MN ≥5 mm and MPD ≥ 10 mm); 46% for type 2 (MN ≥5 mm and MPD < 10 mm); 61% for type 3 (MN < 5 mm and MPD ≥ 10 mm); 72% for type 4 (MN < 5 mm and MPD < 10 mm), respectively., Conclusions: PJC in IPMN is not a recommended examination because of its low overall sensitivity and no significant difference in diagnostic performance by type, location, or subclassification. Although the sensitivity is low, the positive predictive value is high, so we suggest that pancreatic juice cytology be performed only in cases where the patient is not sure about surgery., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Purpose: Cell-based therapy is a potential treatment option for neurointestinal diseases by serving as a source of neural progenitor cells to replace missing or abnormal enteric neurons. Using an ex vivo transplantation model, we recently demonstrated that treatment with collagenase and fibronectin promotes infiltration of transplanted enteric neural crest cells (ENCCs) toward the colon lumen. The aim of this study was to determine whether this new method also promotes colonization of transplanted ENCCs in vivo., Methods: Collagenase was applied locally on the anti-mesenteric area of the recipient colon using filter paper, followed by fibronectin. Neurospheres were generated from ENCCs isolated from fetal mouse intestines and transplanted into the collagenase and fibronectin-treated colon. Engraftment of neurospheres was confirmed by immunofluorescence., Results: Neurospheres transplanted onto PBS- or fibronectin-treated colons were not observed to infiltrate to the muscle layer. However, when used in combination with type I collagenase and fibronectin in the recipient colon, transplanted neurospheres reached Auerbach's plexus., Conclusion: We demonstrated that transplanted neurospheres grow into Auerbach's plexus in the recipient colon pretreated with collagenase and fibronectin., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tribological interfaces between silicon-based ceramics, such as Si 3 N 4 or SiC, are characterized by high friction and wear in unlubricated conditions. A solution to this problem is to use them in combination with a hydrogenated amorphous carbon (a-C:H) countersurface from which a passivating carbon film is transferred onto the ceramic surface. However, the mechanisms underlying a stable film transfer process and the conditions that favor it remain elusive. Here, we present friction experiments in ultrahigh vacuum in which friction coefficients lower than 0.01 are achieved by sliding Si 3 N 4 against a-C:H with 36 at. % hydrogen but not against a-C:H with 20 at. % hydrogen. Chemical surface analyses confirm that the superlubric interface forms via the transfer of a hydrocarbon nanofilm onto the Si 3 N 4 surface. Quantum-mechanical simulations reveal that a stable passivating a-C:H film can only be transferred if, after initial cold welding of the tribological interface, the plastic shear deformation is localized within the a-C:H coating. This occurs if the yield shear stress for plastic flow of a-C:H is lower than that of the ceramic and of the shear strength of the a-C:H-ceramic interface, i.e., if the a-C:H hydrogen content ranges between ∼30 and ∼50 at. %. While the importance of a relatively high hydrogen content to achieve an efficient passivation of a-C:H surfaces in a vacuum is well-documented, this work reveals how the hydrogen content is also crucial for obtaining a stable a-C:H transfer film. These results can be extended to glass, SiC, and steel, supporting the generality of the proposed mechanism.

Objectives: Endoscopic ultrasound-guided fine-needle aspiration and fine-needle biopsy (EUS-FNA/FNB) is not fully established as a pathological sampling tool for gallbladder lesions due to limited evidence. We therefore aimed to clarify the effectiveness and safety of this procedure in a large-population cohort., Methods: This study retrospectively evaluated the diagnostic yield of EUS-FNA/FNB for accurately differentiating between benign and malignant gallbladder lesions. Puncture targets included the gallbladder mass, lymph node, and liver mass. Adverse events and factors associated with diagnostic accuracy were analyzed as well., Results: In 187 patients with gallbladder lesions undergoing EUS-FNA/FNB, 18 benign lesions and 169 malignant lesions were identified. Overall sampling adequacy was 98% (184/187). The diagnostic accuracy of EUS-FNA/FNB was 97% (182/187), sensitivity was 97% (164/169), and specificity was 100% (18/18). A single postprocedural complication (minor bleeding) was recorded in one patient. In the 169 cases of malignancy, 203 sites were punctured for pathological sampling of the primary mass (n = 94), lymph node (n = 79), and metastatic liver mass (n = 30). No significant difference was found for diagnostic accuracy among the puncture sites (P = 0.70). In cases having specimens obtained from the primary mass, the accuracy of those targeting liver invasion sites was significantly higher than that of other sites (98% vs. 83%, P < 0.01)., Conclusion: EUS-FNA/FNB demonstrated clinical usefulness and safety for the pathological diagnosis of gallbladder lesions, with high diagnostic yield and a low incidence of adverse events. Targeting the site of liver infiltration may improve the diagnostic rate of EUS-FNA/FNB in the primary mass., (© 2023 Japan Gastroenterological Endoscopy Society.)

α-Synuclein and LRRK2 are associated with both familial and sporadic Parkinson's disease (PD), although the mechanistic link between these two proteins has remained elusive. Treating cells with lysosomotropic drugs causes the recruitment of LRRK2 and its substrate Rab10 onto overloaded lysosomes and induces extracellular release of lysosomal contents. Here we show that lysosomal overload elicits the release of insoluble α-synuclein from macrophages and microglia loaded with α-synuclein fibrils. This release occurred specifically in macrophage lineage cells, was dependent on the LRRK2-Rab10 pathway and involved exosomes. Also, the uptake of α-synuclein fibrils enhanced the LRRK2 phosphorylation of Rab10, which was accompanied by an increased recruitment of LRRK2 and Rab10 onto lysosomal surface. Our data collectively suggest that α-synuclein fibrils taken up in lysosomes activate the LRRK2-Rab10 pathway, which in turn upregulates the extracellular release of α-synuclein aggregates, leading to a vicious cycle that could enhance α-synuclein propagation in PD pathology., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Competing Interests: The authors declare that they have no financial conflict of interest with regard to the content of this report.

Acetaminophen (APAP) overdoses can cause severe liver injury. In this study, the protective effect of fasudil against APAP-induced liver injury was investigated. APAP (400 mg/kg) was administered to male C57BL/6J mice to induce liver injury, and fasudil (20 or 40 mg/kg) was injected 30 min before APAP administration. Fasudil markedly suppressed APAP-induced elevation in serum transaminase activity and hepatic necrosis and significantly reduced an increase in nitrotyrosine and DNA fragmentation. However, fasudil did not affect cytochrome P450 2E1 expression, N-acetyl-p-benzoquinone imine production or c-jun N-terminal kinase activation. In contrast, fasudil significantly inhibited an APAP-induced increase in expression of the transcription factor C/EBP homologous protein (CHOP) in the liver, accompanied by transcriptional suppression of ER stress-related molecules such as Ero1α, Atf4 and Grp78. These findings indicate that suppression of CHOP expression by fasudil exhibits a remarkable protective effect against APAP liver injury by regulating ER stress. We suggest that fasudil is a promising therapeutic candidate for treating APAP-induced liver injury., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

(+)-Negamycin, which is a dipeptide-like antibiotic containing a hydrazide structure, exhibits readthrough activity, resulting in the restoration of dystrophin in the mdx mouse model of Duchenne muscular dystrophy (DMD). In our previous structure-activity relationship study of negamycin, we found that its natural analogue 3- epi -deoxynegamycin (TCP-107), without antimicrobial activity, showed a higher readthrough activity than negamycin. In this study, we designed and synthesized cyclopropane-based conformationally restricted derivatives of TCP-107 and evaluated their readthrough activity in the cell-based reporter assay against a TGA-type mutation derived from DMD. As a result, a down- cis isomer, TCP-304, showed significant readthrough activity among the four isomers. Moreover, TCP-306, a derivative acylated by l-α-aminoundecanoic acid, possessed approximately 3 times higher activity than TCP-304. These down- cis derivatives showed dose-dependent readthrough activity and were effective for not only TGA but also TAG mutations. These results suggest that the conformational restriction of negamycin derivatives by the introduction of the cyclopropane ring is effective for an exhibition of potent readthrough activity., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Competing Interests: The authors declare that they have no conflict of interest.

Over the last decades, research on the pathobiology of neurodegenerative diseases has greatly evolved, revealing potential targets and mechanisms linked to their pathogenesis. Parkinson's disease (PD) is no exception, and recent studies point to the involvement of endolysosomal defects in PD. The endolysosomal system, which tightly controls a flow of endocytosed vesicles targeted either for degradation or recycling, is regulated by a number of Rab GTPases. Their associations with leucine-rich repeat kinase 2 (LRRK2), a major causative and risk protein of PD, has also been one of the hot topics in the field. Understanding their interactions and functions is critical for unraveling their contribution to PD pathogenesis. In this review, we summarize recent studies on LRRK2 and Rab GTPases and attempt to provide more insight into the interaction of LRRK2 with each Rab and its relationship to PD.

Background: The junction between the peristaltic and non-peristaltic bowel, which is named the "shore break" (SB), observed on endoscopy is thought to be the boundary between normal and abnormal motility in Hirschsprung's disease (HD). The transition zone (TZ), which is the histopathological border, does not have normal motility and should be resected. This study aimed to evaluate the histopathological findings of the SB and determine the association between the SB and TZ., Methods: A retrospective review of surgical specimens of patients with HD who underwent preoperative SB marking was conducted. The TZ was defined if nerve hypertrophy, myenteric hypoganglionosis, or partial circumferential aganglionosis was detected., Results: Ten patients (9 boys and 1 girl) were studied. The median age at surgery was 30 days. The median distance from the anal verge to the marked SB site was 14 cm. No patients manifested any obstructive symptoms resulting from a residual TZ bowel. In eight patients, nerve hypertrophy was identified at the proximal margin and at the SB. Myenteric hypoganglionosis was identified in three patients at the proximal margin and SB. Partial circumferential aganglionosis was identified at the SB in two patients. As a result, in all patients, the pull-through site and SB site had histopathological features indicating TZ., Conclusions: The SB is located in the TZ. Our results suggest that the proximal part of the TZ has normal motility and that functional border points may be present in the TZ., Level of Evidence: IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mobility is fundamental for human beings. In the current society, many personal mobility solutions have been invented to enable more time-efficient mobility, such as self-balancing vehicles, electric unicycles, and electric scooters. Personal mobility devices can provide flexibility to transportation. However, most personal mobility devices need to be carried by their users in the case that they climb stairs and steps. Therefore, many researchers have focused on developing stair-climbing vehicles, but due to the complicated mechanism, these devices are usually huge and heavy. To realize a new type of personal mobility device with more flexibility, we proposed a novel concept of a personal mobility device design that combines the agile mobility of a wheel type mechanism but does not limit a human's natural stair climbing ability. In this study, we introduced a compact personal mobility device, namely WeMo, under the concept of "wearing mobility", which extends humans' mobility in daily life. The developed hardware realizes "walking mode" and "driving mode". Users can move with the motorized driven wheels of the device during driving mode, and users can walk on their feet without any interference from the device during walking mode. In this manuscript, the detailed design of the hardware and control strategy were explained first.Then, we conducted fundamental user tests and discussed the ability of the developed device from test results. Finally, the conclusions and future work were provided.

Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a highly aggressive malignant neoplasm, with a median overall survival of <1 year, except for several surgical series. On the other hand, UC tissue sometimes contains non-neoplastic osteoclast-like giant cells (OGCs), and such cases have been reported to have relatively longer survival. Thus, the World Health Organization (WHO) classification histologically distinguishes UC with OGCs (UCOGCs) from UC, and UCs were subclassified into three subtypes: anaplastic UC, sarcomatoid UC and carcinosarcoma. However, still less is known about UC due to its rarity, and such situations lead to further difficulties in treatment for UC. To date, only surgical resection can offer curative treatment for patients with UC, and no clear evidence for chemotherapy exists for them. However, a retrospective cohort study and case reports showed that relatively promising results paclitaxel-containing regimens for treatment of patients with unresectable UC. Furthermore, high programmed cell death protein 1 expression has been reported in sarcomatoid UCs and UCOGCs, and promising responses to anti-programmed death-ligand 1 therapy have been described in case reports of UCOGCs. Recent advances in chemotherapeutic agents and molecular technologies are opening up the possibilities for expanded treatments., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Here, we report a novel photo-on-demand in situ phosgenation reaction that crosses three phases of a heterogeneous solution of chloroform (CHCl 3 ) and aqueous NaOH containing an aryl alcohol or amine. This reaction system enables the safe, convenient, and inexpensive synthesis of carbonate esters, polycarbonates, and N-substituted ureas from aryl alcohols, aryl diols, and primary/secondary amines, respectively, on a practical scale and with good yield. The photochemical oxidation of CHCl 3 to phosgene (COCl 2 ) occurs upon irradiation with UV light from a low-pressure mercury lamp of both the gas and liquid phases of the reaction system under O 2 bubbling of the vigorously stirred sample solution. The following reaction mechanisms are suggested: The aryl alcohol reacts in situ with the generated COCl 2 at the interfaces of the organic/aqueous phases and aqueous/gas phases, in competition with the decomposition of COCl 2 due to hydrolysis. Nucleophilicity and hydrophilicity are enhanced by the formation of aryl alkoxide ion through the reaction with NaOH, whereas the reaction of amine proceeds through neutralization of the generated HCl by the aqueous NaOH., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)