Nanoscrolls of Janus Monolayer Transition Metal Dichalcogenides.

Tubular structures of transition metal dichalcogenides (TMDCs) have attracted attention in recent years due to their emergent physical properties, such as the giant bulk photovoltaic effect and chirality-dependent superconductivity. To understand and control these properties, it is highly desirable to develop a sophisticated method to fabricate TMDC tubular structures with smaller diameters and a more uniform crystalline orientation. For this purpose, the rolling up of TMDC monolayers into nanoscrolls is an attractive approach to fabricating such a tubular structure. However, the symmetric atomic arrangement of a monolayer TMDC generally makes its tubular structure energetically unstable due to considerable lattice strain in curved monolayers. Here, we report the fabrication of narrow nanoscrolls by using Janus TMDC monolayers, which have an out-of-plane asymmetric structure. Janus WSSe and MoSSe monolayers were prepared by the plasma-assisted surface atom substitution of WSe2 and MoSe2 monolayers, respectively, and then were rolled by solution treatment. The multilayer tubular structures of Janus nanoscrolls were revealed by scanning transmission electron microscopy observations. Atomic resolution elemental analysis confirmed that the Janus monolayers were rolled up with the Se-side surface on the outside. We found that the present nanoscrolls have the smallest diameter of about 5 nm, which is almost the same as the value predicted by the DFT calculation. The difference in work functions between the S- and Se-side surfaces was measured by Kelvin probe force microscopy, which is in good agreement with the theoretical prediction. Strong interlayer interactions and anisotropic optical responses of the Janus nanoscrolls were also revealed by Raman and photoluminescence spectroscopy.

Evaluation of a Novel Easy Loop-Forming Guidewire to Reduce Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis for Serial Pancreatic Juice Aspiration Cytologic Examination: A Propensity Score Matching Analysis.

OBJECTIVE: This study aimed to investigate whether a novel, easy loop-forming guidewire could reduce post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) in patients undergoing endoscopic nasopancreatic drainage tube placement for serial pancreatic juice aspiration cytologic examination (SPACE). METHODS: We evaluated patients with suspected pancreatic cancer who underwent SPACE at our institution between January 2015 and April 2023 retrospectively. The patients were divided into 2 groups based on the type of guidewire used, namely, easy loop-forming and control groups. Propensity score matching was used to compare the incidence of PEP between the groups. RESULTS: We included 101 patients, with 51 and 50 in the easy loop-forming and control groups, respectively. After propensity score matching, 29 pairs of patients were selected from each group. Intraductal ultrasonography of the pancreas was performed more frequently in the easy loop-forming group than in the control group (27.6% vs 0%; P = 0.004); however, PEP incidence was significantly lower in the easy loop-forming group than in the control group (3.4% vs 27.6%; odds ratio, 0.097; 95% confidence interval, 0.002-0.82; P = 0.025). CONCLUSIONS: The use of the novel easy loop-forming guidewire decreased PEP occurrence in patients who underwent endoscopic nasopancreatic drainage tube placement for SPACE.

Physical activity in idiopathic pulmonary fibrosis: Longitudinal change and minimal clinically important difference.

BACKGROUND AND OBJECTIVE: Reference values of physical activity to interpret longitudinal changes are not available in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to define the minimal clinical important difference (MCID) of longitudinal changes in physical activity in patients with IPF. METHODS: Using accelerometry, physical activity (steps per day) was measured and compared at baseline and 6-months follow-up in patients with IPF. We calculated MCID of daily step count using multiple anchor-based and distribution-based methods. Forced vital capacity and 6-minute walk distance were applied as anchors in anchor-based methods. Effect size and standard error of measurement were used to calculate MCID in distribution-based methods. RESULTS: One-hundred and five patients were enrolled in the study (mean age: 68.5 ± 7.5 years). Step count significantly decreased from baseline to 6-months follow-up (-461 ± 2402, p = .031). MCID calculated by anchor-based and distribution-based methods ranged from 570-1358 steps. CONCLUSION: Daily step count significantly declined over 6-months in patients with IPF. MCID calculated by multiple anchor-based and distribution-based methods was 570 to 1358 steps/day. These findings contribute to interpretation of the longitudinal changes of physical activity that will assist its use as a clinical and research outcome in patients with IPF.

High-throughput dry transfer and excitonic properties of twisted bilayers based on CVD-grown transition metal dichalcogenides.

van der Waals (vdW) layered materials have attracted much attention because their physical properties can be controlled by varying the twist angle and layer composition. However, such twisted vdW assemblies are often prepared using mechanically exfoliated monolayer flakes with unintended shapes through a time-consuming search for such materials. Here, we report the rapid and dry fabrication of twisted multilayers using chemical vapor deposition (CVD) grown transition metal chalcogenide (TMDC) monolayers. By improving the adhesion of an acrylic resin stamp to the monolayers, the single crystals of various TMDC monolayers with desired grain size and density on a SiO2/Si substrate can be efficiently picked up. The present dry transfer process demonstrates the one-step fabrication of more than 100 twisted bilayers and the sequential stacking of a twisted 10-layer MoS2 single crystal. Furthermore, we also fabricated hBN-encapsulated TMDC monolayers and various twisted bilayers including MoSe2/MoS2, MoSe2/WSe2, and MoSe2/WS2. The interlayer interaction and quality of dry-transferred, CVD-grown TMDCs were characterized by using photoluminescence (PL), cathodoluminescence (CL) spectroscopy, and cross-sectional electron microscopy. The prominent PL peaks of interlayer excitons can be observed for MoSe2/MoS2 and MoSe2/WSe2 with small twist angles at room temperature. We also found that the optical spectra were locally modulated due to nanosized bubbles, which are formed by the presence of interface carbon impurities. The present findings indicate the widely applicable potential of the present method and enable an efficient search of the emergent optical and electrical properties of TMDC-based vdW heterostructures.

Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by worsening dyspnoea and exercise intolerance. RESEARCH QUESTION: Does a long-term pulmonary rehabilitation improve exercise tolerance in patients with IPF treated with standard antifibrotic drugs, which are expected to reduce disease progression? METHODS: This open-label randomised controlled trial was performed at 19 institutions. Stable patients receiving nintedanib were randomised into pulmonary rehabilitation and control groups (1:1). The pulmonary rehabilitation group underwent initial rehabilitation which included twice-weekly sessions of monitored exercise training for 12 weeks, followed by an at-home rehabilitation programme for 40 weeks. The control group received usual care only, without pulmonary rehabilitation. Both groups continued to receive nintedanib. The primary and main secondary outcomes were change in 6 min walking distance (6MWD) and change in endurance time (using cycle ergometry) at week 52. RESULTS: Eighty-eight patients were randomised into pulmonary rehabilitation (n=45) and control (n=43) groups. Changes in 6MWD were -33 m (95% CI -65 to -1) and -53 m (95% CI -86 to -21) in the pulmonary rehabilitation and control groups, respectively, with no statistically significant difference (mean difference, 21 m (95% CI -25 to 66), p=0.38). Changes in endurance time were significantly better in the pulmonary rehabilitation (64 s, 95% CI -42.3 to 171)) than in the control (-123 s (95% CI -232 to -13)) group (mean difference, 187 s (95% CI 34 to 153), p=0.019). INTERPRETATION: Although pulmonary rehabilitation in patients taking nintedanib did not improve 6MWD in the long term, it led to prolonged improvement in endurance time. TRIAL REGISTRATION NUMBER: UMIN000026376.

Distinguishing the papilla of Vater during biliary cannulation using texture and color enhancement imaging: A pilot study.

Objectives: Understanding the exact morphology of the bile duct opening is important for determining the success of bile duct cannulation. Texture and color enhancement imaging (TXI) has been reported to enhance slight changes in color tone and structure that are difficult to see with white light imaging. This study investigated whether TXI mode1 could improve papillary recognition by trainees inexperienced in endoscopic retrograde cholangiopancreatography. Methods: We included 31 patients with naive papilla of Vater at a single institution in the study. Trainee endoscopists (n = 4) evaluated and identified the papilla according to the Inomata classification using white light imaging and TXI. The degree of agreement with the evaluation of supervising physicians (n = 4) was examined using the McNemar test. Results: In the trainee group, the kappa coefficient agreements were κ = 0.346 and κ = 0.754 for white light imaging and TXI, respectively. When further evaluated, the separate and septal types of papilla groups showed an increased concordance rate in one of the four trainees (76.67%-96.67%, p = 0.031, respectively). Moreover, comparison for two-group evaluation showed an increased kappa coefficient in two of four trainees (0.34-0.92, p = 0.010, 0.45-0.92, p = 0.024). Conclusions: Observation of the duodenal papilla using TXI improved papillary differentiation and suggested the potential of TXI as a clinical tool. Further study of this method is necessary; it is expected to help reduce cannulation time and the incidence of pancreatitis.

Comparison of Fork-tip and Franseen needles for endoscopic ultrasound-guided fine-needle biopsy in pancreatic solid lesions: A propensity-matched analysis.

Objectives: There is no unanimity regarding the most appropriate needle to use for an endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). To date, new types of FNB needles have been designed, including the Fork-tip and Franseen needles. This study primarily aimed to compare the diagnostic accuracy and histological quality between the use of the Franseen and Fork-tip needles in EUS-FNB for solid pancreatic lesions. Materials and methods: We retrospectively analyzed 147 patients at our center for solid pancreatic lesions, 75 of whom underwent EUS-FNB using a 22-G Franseen needle, and 72 using a 22-G Fork-tip needle, from December 2019 to September 2021. The present study conducted a propensity-matched analysis and confounder adjustment. Results: The diagnostic accuracy of the Fork-tip group (93.3%, 42/45) was the same as that of the Franseen group. For the core tissue and blood scores, no significant difference was observed (p = 0.58, 0.25) between the two groups. The rate of changes in the operator from that of a trainee to an expert was less in the Fork-tip group (4.4%, 2/45) than in the Franseen group (15.6%, 7/45), but not significantly different (p = 0.16). Conclusions: In both groups, the diagnostic accuracy and histological quality were not significantly different. Additionally, there were no significant differences in the rate of operator changes. As both needles are useful, the choice of using either of them is equally good.

Safety of early oral intake after endoscopic ultrasound-guided hepaticoenterostomy.

BACKGROUND: Techniques and devices for endoscopic ultrasound (EUS)-guided hepaticoenterostomy (EUS-HES) procedures, including EUS-guided hepaticogastrostomy (EUS-HGS) and EUS-guided hepaticojejunostomy (EUS-HJS), have been developed; however, the optimal timing to begin oral intake after EUS-HES remains unknown. This study aimed to evaluate the safety of early oral intake after EUS-HES. METHODS: We retrospectively investigated patients who underwent EUS-HES (EUS-HGS or EUS-HJS) between March 2015 and March 2022. Patients who had no problems with the results of blood tests and computed tomography examinations on the morning of day 1 after EUS-HES were classified as either the early intake group (started oral intake on day 1 after EUS-HES) or the late intake group (started oral intake on day 2 or later after EUS-HES). Patients' characteristics, procedure characteristics, and early postprocedural adverse events (within 14 days after the procedure) were compared between groups. RESULTS: Fifty patients were enrolled in this study. Forty-three patients had no problems with the results of examinations performed on the morning of day 1 after EUS-HES. Twenty-one patients comprised the early intake group and 22 comprised the late intake group. Adverse events that developed within 14 days after EUS-HES were not significantly different between groups (early 4.7% vs. late 9.0%; odds ratio, 0.50; 95% confidence interval, 0.0080-10.49; P = 1.00). CONCLUSIONS: Starting oral intake on day 1 after EUS-HES did not increase postprocedural adverse events compared with starting oral intake on day 2 or later after EUS-HES.

Successful endoscopic resection by using gel immersion and the technique of endoscopic papillectomy for a tumor adjacent to the papilla of Vater.

Video 1Successful endoscopic resection using gel immersion for a tumor adjacent to the papilla of Vater.

Factors affecting complete stone extraction in the initial procedure in short type single-balloon enteroscopy-assisted endoscopic retrograde cholangiography for patients with Roux-en-Y gastrectomy.

OBJECTIVES: This study aimed to evaluate the efficacy and safety of stone extraction in patients who underwent Roux-en-Y gastrectomy using short-type single-balloon enteroscopy (SBE) and to clarify the factors affecting complete stone extraction in the initial procedure. METHODS: The data of patients with Roux-en-Y gastrectomy who underwent endoscopic stone extraction using short SBE between September 2011 and January 2022 was analyzed. RESULTS: Overall, 85 patients were scheduled to undergo stone extraction. 77 patients were intended stone extraction after successful biliary cannulation. The complete stone extraction success in the initial procedure, overall complete stone extraction success including repeated procedures, and adverse event rates were 68.2% (95% confidence interval [CI], 57.2%-77.9%), 87.1% (95% CI, 78.0%-93.4%), and 8.2% (95% CI, 3.4%-16.2%), respectively. Multiple logistic regression analysis indicated that bile duct diameter affected the success of complete stone extraction after successful biliary cannulation in the initial procedure (odds ratio 0.53, 95% CI, 0.30-0.94, p = .03). CONCLUSIONS: Stone extraction in patients with Roux-en-Y gastrectomy using short SBE was effective. Patients with a large diameter bile duct required several sessions for complete stone extraction, suggesting that more dedicated devices are warranted for patients with surgically altered anatomy.

Effectiveness of a multi-loop traction device for colorectal endoscopic submucosal dissection performed by trainees: a pilot study.

Colorectal endoscopic submucosal dissection (ESD) is a difficult procedure, and its introduction to trainees has been debated. Although the criteria for performing colorectal ESD vary among institutions, it is often allowed after gaining experience performing surgeries in animals and upper gastrointestinal ESD. This pilot study aimed to compare the treatment outcomes of ESD performed by trainees using the multi-loop traction device (MLTD group) and those of conventional ESD performed by experts (control group). It also aimed to determine whether the MLTD can be used to safely introduce colorectal ESD to trainees. We included 26 colorectal ESD patients (13 in the MLTD group and 13 in the control group) treated at our hospital from October to December 2021. There were no significant differences in the procedure time (50 min vs. 30 min), dissection speed (19.9 mm2/min vs. 28.7 mm2/min), and intraoperative perforation (0% vs. 0%) of the two groups. Furthermore, the rate of ESD self-completion in the MLTD group was 100%. Therefore, the use of the MLTD allowed the safe introduction of colorectal ESD, even among endoscopists with no experience performing colorectal ESD. Consequently, the use of the MLTD may replace animal and upper gastrointestinal ESD when introducing colorectal ESD to trainees.

Competence development of trainees performing short-type single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy.

OBJECTIVES: This study aimed to evaluate the trainees' practice and learning curve in short-type single-balloon enteroscopy (short SBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) for patients with surgically altered anatomy (SAA) and determine how to train these trainees. METHODS: The data of short SBE-assisted ERCP procedures between September 2011 and June 2021 were analyzed. RESULTS: Three trainees and 180 cases were included in the analysis. Each trainee performed 60 cases between April 2016 and June 2021. The trainees' completion rate was 73.9% (95% confidence interval [CI], 66.8-80.1%). Adverse events occurred in 5.0% of cases (95% CI, 2.3-9.3%). The trainee who experienced colonoscopy and ERCP the most achieved better outcomes of enteroscopy success (reaching the target site) and trainee's completion rates than those of the others (P = .03 and .02, respectively). The learning curve for trainee's completion showed a significant improvement after 60 cases (P = .001). Multiple logistic regression analysis indicated that Roux-en-Y reconstruction was the factor affecting trainees' completion failure. CONCLUSIONS: Short SBE-assisted ERCP trainees has a substantial learning curve. If trainees do not have much experience with colonoscopy and ERCP procedures, it may be beneficial for them to start performing short SBE-assisted ERCP procedures on non-Roux-en-Y reconstruction cases.

Xenotransplantation of cryopreserved human clumps of mesenchymal stem cells/extracellular matrix complexes pretreated with IFN-γ induces rat calvarial bone regeneration.

Introduction: Three-dimensional (3D) clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes, composed with cells and self-produced intact ECM, can be grafted into defect areas without artificial scaffold to induce successful bone regeneration. Moreover, C-MSCs pretreated with IFN-γ (C-MSCsγ) increased the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) expression and thereby inhibited T cell activity. Xenotransplantation of human C-MSCsγ suppressed host T cell immune rejection and induced bone regeneration in mice. Besides, we have also reported that C-MSCs retain the 3D structure and bone regenerative property even after cryopreservation. To develop the "off-the-shelf" cell preparation for bone regenerative therapy that is promptly provided when needed, we investigated whether C-MSCsγ can retain the immunosuppressive and osteogenic properties after cryopreservation. Methods: Confluent human MSCs that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. The round cell clumps were incubated with a growth medium for 3 days, and then C-MSCs were obtained. To generate C-MSCsγ, after 2 days' culture, C-MSCs were stimulated with 50 ng/ml of IFN-γ. Both C-MSCs and C-MSCsγ were cryopreserved for 2 days and then thawed to obtain Cryo-C-MSCs and Cryo-C-MSCsγ, respectively. The biological properties of those cell clumps were assessed in vitro. In addition, to test whether human Cryo-C-MSCsγ attenuates immune rejection to induce bone regeneration, a xenograft study using a rat calvarial defect was performed. Results: Both IFN-γ pretreatment and cryopreservation process did not affect the 3D structure and cell viability in all human cell clumps. Interestingly, Cryo-C-MSCsγ showed significantly increased IDO mRNA expression equivalent to C-MSCsγ. More importantly, xenotransplantation of human C-MSCsγ and Cryo-C-MSCsγ induced rat calvarial bone regeneration by suppressing rat T cells infiltration and the grafted human cells reduction in the grafted area. Finally, there were no human donor cells in the newly formed bone, implying that the bone reconstruction by C-MSCsγ and Cryo-C-MSCsγ can be due to indirect host osteogenesis. Conclusion: These findings implied that Cryo-C-MSCsγ can be a promising bone regenerative allograft therapy that can be certainly and promptly supplied on demand.

Endoscopic closure using an over-the-scope clip for pancreatobiliary endoscopy-related large gastrointestinal perforation (with video).

Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) for pancreatobiliary diseases require advanced techniques. We usually use an oblique-viewing endoscope in such procedures. Sometimes, tumor invasion causes gastrointestinal strictures. Crossing a stricture using an oblique-viewing endoscope is more difficult than using a forward-viewing scope. Therefore, the frequency of scope perforation is higher than other endoscopic procedures. Although surgical repair for gastrointestinal perforations caused by endoscopes has been performed, patients with pancreatobiliary diseases are often elderly and in poor general condition; therefore, patients are hesitant to undergo surgical treatments. Recently, the usefulness of over-the-scope clipping (OTSC) as a minimally invasive rescue method has also been reported. In this study, we report cases of successful endoscopic closure using OTSC for gastrointestinal perforations caused by endoscopes in ERCP and EUS-related procedures. After those procedures, all cases showed no abnormalities in blood tests or symptoms, and emergency surgery was successfully avoided. Thus, endoscopic closure using OTSC for pancreatobiliary endoscopy-related gastrointestinal perforations is safe and effective. However, OTSC requires some expertise. A good assessment of defect size and careful insertion of the scope using OTSC attached to the upper esophagus are needed to avoid clip migration or disinsertion and esophageal tears. Therefore, endoscopic closure using OTSC could be the first choice of treatment for pancreatobiliary endoscopy-related gastrointestinal perforations. We should be familiar with its indication and perform it carefully and rapidly.

Effectiveness of clip-and-thread traction-assisted duodenal endoscopic submucosal dissection: a propensity score-matched study (with video).

BACKGROUND AND AIMS: The indications for endoscopic submucosal dissection (ESD) in superficial nonampullary duodenal epithelial tumors (SNADETs) remain controversial because the procedure is technically challenging. Moreover, the effectiveness of clip-and-thread traction-assisted ESD (TA-ESD) for SNADETs has not been assessed. The aim of the current study was to compare the effectiveness of duodenal TA-ESD and conventional ESD for SNADETs. METHODS: SNADETs treated with conventional ESD or TA-ESD between April 2017 and March 2021 at Saitama Medical University International Medical Center were evaluated retrospectively. RESULTS: There were 49 cases of conventional ESD and 32 cases of TA-ESD for SNADETs. Using a propensity score-matched design, we selected 26 pairs of cases with conventional ESD and TA-ESD. In the unmatched cohort, patients treated with TA-ESD were characterized by a higher R0 (no tumor identified at the lateral or vertical margins) resection rate (P = .004), more frequent poor submucosal lifting because of fibrosis (P = .014), and shorter follow-up period (P = .0004) than patients treated with conventional ESD. In the propensity score-matched pairs, patients treated with TA-ESD were characterized by a higher rate of R0 resection (P = .021) and a shorter follow-up period (P = .0061). The findings regarding R0 resection rates were confirmed by multivariate logistic regression models, which found a higher odds ratio (OR) for R0 resection in patients who underwent TA-ESD than in patients who underwent conventional ESD both in the unmatched cohort (OR, 17.0; 95% confidence interval, 1.6-178.8; P = .018) and in the propensity score-matched pairs (OR, 26.7; 95% confidence interval, 1.5-460.2; P = .024). CONCLUSIONS: Our findings suggest TA-ESD may increase the rate of R0 resection in patients with SNADETs in comparison with conventional ESD.

A Prospective Multicenter Randomized Feasibility Trial of Double-guidewire Techniques for Difficult Biliary Cannulation Comparing a New Double-guidewire-supported Sphincterotome (MagicTome) to a Conventional Device.

Objective To evaluate the effectiveness and safety of the double-guidewire technique (DGT) using a new double-guidewire-supported sphincterotome (MagicTome) for patients who required endoscopic retrograde cholangiopancreatography (ERCP) for biliary cannulation. Methods This prospective multicenter randomized feasibility trial involved patients with difficult biliary cannulation at any of the three study sites from June 2017 to October 2018. Patients were assigned to the DGT with MagicTome (MDGT) initially performed group and the conventional DGT (CDGT) initially performed group. The success rates of biliary cannulation by MDGT and CDGT and the ERCP-related complications were evaluated. Results Twenty-eight patients were included in this study. No significant difference was observed in the success rates of first attempts and crossover attempts between the groups (p=0.69 and p=1.00). Furthermore, no significant difference was observed in the success rate of biliary cannulation between MDGT and CDGT (62.5% and 75.0%, respectively; p=0.48). CDGT was successful in two of four patients with malignant biliary obstruction. MDGT was successful in all four patients with malignant biliary obstruction, including the two for whom CDGT was unsuccessful. Post-ERCP pancreatitis occurred in only one MDGT case. Conclusion MDGT is safe for biliary cannulation and can be used in cases where biliary cannulation by CDGT is difficult.