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Nivolumab plus ipilimumab (NIVO+IPI) has a long-term response rate of 30% for patients with metastatic renal cell carcinoma (mRCC). However, 20% of patients develop primary resistant disease (PRD) to NIVO+IPI and show poor survival outcomes. In this study, we aimed to evaluate the effect of PRD as a second-line treatment in patients with mRCC. The data used in this multi-institutional, retrospective cohort were collected between August 2015 and January 2023. In total, 189 patients with mRCC were treated with NIVO+IPI and then with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor. Associations between PRD and progression-free survival of second-line treatment (PFS), progression-free survival 2 (PFS2), and overall survival (OS) were analyzed. The median age at NIVO+IPI initiation was 67 years in the male-dominant population (n = 140, 74.1%), and most patients had clear cell histology (n = 140, 74.1%). PRD was recorded in 42 (22.2%) of 189 patients during NIVO+IPI therapy. Patients who experienced PRD showed poor PFS (hazard ratio [HR], 1.788; 95% confidence interval [CI], 1.176-2.718; p = 0.007), PFS2 (HR, 4.127; 95% CI, 2.649-6.431; p < 0.001), and OS (HR, 3.330; 95% CI, 2.040-5.437; p < 0.001). Before starting second-line therapy, patients with PRD tended to have a poor performance status compared with non-PRD patients and a higher IMDC risk. Second-line drug therapy was not associated with treatment outcomes in patients with PRD. PRD in patients with mRCC receiving NIVO+IPI as first-line treatment was associated with poor clinical course, even with second-line therapy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Lung cancer is the leading cause of the global cancer incidence and mortality. It is important to obtain an accurate diagnosis of lymph-node metastasis before surgery to select the therapeutic strategy for non-small cell lung cancer (NSCLC) patients. Carbonic anhydrase 9 (CA9) is considered a marker of hypoxia and it has reported that CA9 is associated with tumor invasion and metastasis. In this study, the correlation between the CA9 expression for lymph-node metastases in NSCLC and [18F]FDG PET/CT results was investigated in order to clarify the efficacy of [18F]FDG PET/CT for detecting lymph-node metastases of NSCLC patients., Methods: Among the 564 patients who underwent surgical treatment for NSCLC between 2010 and 2016 at our hospital, a total of 338 patients who underwent preoperative [18F]FDG PET/CT were included in this study. CA9 expression was evaluated by immunochemistry. A lymph node with maximum standardized uptake value (SUVmax) ≥2.5 on [18F]FDG PET/CT was preoperatively defined as a metastatic lymph node., Result: CA9 positivity was detected in 122 patients; the other 216 patients were CA9-negative. The CA9-positive NSCLC cases significantly associated with pleural invasion (p = 0.0063), pT-factor (p = 0.0080), pN-factor (p = 0.036) and pStage (p = 0.043). CA9-positive patients presented significantly poorer survival rate for OS than that of the CA9-negative patients (p = 0.0024). In the multivariable analysis, histological SCC and CA9 positivity were independent poor-prognosis factors for OS. For the total patient population, the sensitivity and specificity of [18F]FDG PET/CT for lymph-node metastases were 54% and 89%, respectively. In contrast, the sensitivity and specificity were particularly low in the CA9-positive SCC cases (36% and 69%, respectively)., Conclusion: [18F]FDG PET/CT might not be useful for diagnosing lymph-node metastases of CA9-positive SCC cases of NSCLC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Suzuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Wearable devices are increasingly utilized to monitor physical activity and sedentary behaviors. Accurately determining wear/non-wear time is complicated by zero counts, where the acceleration-based indexes do not estimate activity intensity, often leading to misclassifications. We propose a novel synthetic classification algorithm that leverages both the probability and continuity of zero counts, aiming to enhance the accuracy of activity estimation. The physical activity data were obtained from 12 office workers wearing wearable devices with 3-axis accelerometers. The wear/non-wear times are classified by the commonly used current method (zero counts lasting longer than 60 minutes are classified as non-wear) and the proposed method. In the proposed method, only times that satisfy the following two criteria are classified as the wear time. (1) The appearance probability preceding and following 60 minutes must be less than the threshold value. (2) The number of consecutive zeros must be less than 10 minutes. The effectiveness of both the current and proposed classification methods was evaluated against the actual behavioral records. This evaluation utilized simulation-based augmented data, which was implemented to address the limited variability inherent in the original dataset. The range of recall, specificity, precisions, and accuracy classified by the current method were 0.93-1.00, 0.93-0.96, 0.85-0.88, and 0.94-0.97, respectively. Indeed, the proposed method shows 0.95-1.00, 0.99-1.00, 0.97-1.00, and 0.98-1.00, respectively. The reduction of misclassification of non-wear time as wear time was achieved by the synthetic classification algorithm. The performance of the proposed approach showed accurate classification of the wear/non-wear time of wearable sensors in office workers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nishiyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Titanium dioxide doped with Pt(IV) ions was synthesized via a sol-gel method, incorporating a sol purification process through dialysis. The doped Pt(IV) ions were reduced by UV light irradiation to obtain a transparent Pt-TiO 2 sol, with Pt(0) acting as a cocatalyst for hydrogen evolution. The hydrogen evolution activity of Pt-TiO 2 sol was evaluated under UV light irradiation using methanol as a sacrificial reagent. 0.05 atom % Pt-TiO 2 sol remained in the sol state without precipitation after 10 h of UV light irradiation. The amount of hydrogen produced after 10 h of light irradiation was 1195 μmol, with a turnover number (TON) of 664.1, a turnover frequency (TOF) of 66.4 h -1 , and an apparent quantum yield (AQY) of 0.86%. The sol-gel synthesis from the molecular level is thought to result in Pt ions being doped inside the TiO 2 particles, maintaining high dispersibility by suppressing particle growth due to the aggregation of Pt(0) during the UV reduction of Pt(IV) ions. These results show that the Pt-TiO 2 photocatalyst has a high renewable energy factor because it can be synthesized at room temperature, and the aggregation of Pt-TiO 2 particles is suppressed by making full use of a sol-gel method., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Aeromonas dhakensis is highly virulent but often misidentified in clinical settings. The entire genome sequence of a metallo-β-lactamase-producing A. dhakensis strain from a clinical specimen has been presented in this study. The genome comprised a single chromosome of 4.89 Mbp with 61.6% G + C content., Competing Interests: The authors declare no conflict of interest.

A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p < 0.0001) and PFS2 (HR 0.45, p < 0.0001) than those treated with vintage nonsteroidal antiandrogen agent (Vintage). The survival tree identified 4.65 months as the most prognostic PSADT cutoff point. Among the clinical and pathological factors PSADT of < 4.65 months remained an independent prognostic factor for OS (HR 2.96, p = 0.0003) and CSS (HR 3.66, p < 0.0001). Current data represented optimal cut-off of PSADT 4.65 months for a Japanese nmCRPC., (© 2024. The Author(s).)

Arterioureteral fistula represents a rare yet consequential urological complication characterized by persistent and refractory urinary tract bleeding. Its emergence typically involves aneurysm formation, presenting significant life-threatening implications. Nonetheless, its infrequency contributes to sparse documentation of incidences in post-kidney transplant recipients, thereby fostering numerous uncertainties concerning associated risks. A 67-year-old male patient, afflicted with end-stage renal failure and a history of urinary tract infection, underwent a living donor kidney transplant four months prior. Complications involving intraoperative bleeding necessitated the prolonged placement of a ureteral stent post-surgery. Subsequently, he experienced an abrupt onset of ureteral bleeding accompanied by shock, later diagnosed via contrast-enhanced computed tomography as pseudo-aneurysm formation in the right external iliac artery proximal to the allograft renal artery anastomosis, in conjunction with a fistula formation involving the donor ureter. Despite repeated attempts at intervention with covered stenting, the aneurysm persisted and proved refractory to resolution. Tragically, seven months later, the aneurysm ruptured, culminating in the demise of the patient. Our report details a case involving perioperative complications following kidney transplantation, persistent bacteriuria, and prolonged ureteral stenting, ultimately leading to the development of an arterioureteral fistula. Despite undergoing stent graft insertion as an intervention, the patient succumbed to aneurysm rupture associated with the arterioureteral fistula. This condition, though rare, can prove fatal following kidney transplantation. Consequently, future endeavors in this domain necessitate an emphasis on optimizing risk management, refining diagnostic approaches, and devising more effective therapeutic strategies to mitigate such complications., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Ceftriaxone is administered in regimens of either 2 g once-daily or 1 g twice-daily for the treatment of pneumonia caused by Streptococcus pneumoniae . Previous clinical study suggests the 2 g once-daily regimen is more effective, but comparison of antimicrobial efficacy between are lacking., Objectives: To assess the antimicrobial efficacy of these two ceftriaxone regimens against S. pneumoniae using a murine model of pneumonia., Methods: The study employed three S. pneumoniae isolates with ceftriaxone MICs of 1, 2 and 4 mg/L and two human-simulated regimens based on the blood concentration of ceftriaxone (1 g twice-daily and 2 g once-daily). Antimicrobial activity was quantified based on the change in bacterial counts (Δlog 10  cfu/lungs) observed in treated mice after 24 h, relative to the control mice at 0 h., Results: The human-simulated 2 g once-daily regimen of ceftriaxone exhibited significantly higher antimicrobial activity against S. pneumoniae isolates with MICs of 1 and 2 mg/L compared with the 1 g twice-daily regimen (1 mg/L, -5.14 ± 0.19 Δlog 10 cfu/lungs versus -3.47 ± 0.17 Δlog 10  cfu/lungs, P  < 0.001; 2 mg/L, -3.41 ± 0.31 Δ log 10  cfu/lungs versus -2.71 ± 0.37 Δlog 10  cfu/lungs, P  = 0.027). No significant difference in antimicrobial activity was observed against the S. pneumoniae isolate with a MIC of 4 mg/L between the two regimens (-0.33 ± 0.18 Δlog 10  cfu/lungs versus -0.42 ± 0.37 Δlog 10  cfu/lungs, P  = 0.684)., Conclusion: 2 g once-daily regimen of ceftriaxone is more effective for treating pneumonia caused by S. pneumoniae, with MICs of ≤2 mg/L., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

We performed molecular dynamics (MD) simulations of CO 2 + H 2 O systems by employing widely used force fields (EPM2, TraPPE, and PPL models for CO 2 ; SPC/E and TIP4P/2005 models for H 2 O). The phase behavior observed in our MD simulations is consistent with the coexistence lines obtained from previous experiments and SAFT-based theoretical models for the equations of state. Our structural analysis reveals a pronounced correlation between phase transitions and the structural orderliness. Specifically, the coordination number of Ow (oxygen in H 2 O) around other Ow significantly correlates with phase changes. In contrast, coordination numbers pertaining to the CO 2 molecules show less sensitivity to the thermodynamic state of the system. Furthermore, our data indicate that a predominant number of H 2 O molecules exist as monomers without forming hydrogen bonds, particularly in a CO 2 -rich mixture, signaling a breakdown in the hydrogen bond network's orderliness, as evidenced by a marked decrease in tetrahedrality. These insights are crucial for a deeper atomic-level understanding of phase behaviors, contributing to the well-grounded design of CO 2 injection under high-pressure and high-temperature conditions, where an atomic-scale perspective of the phase behavior is still lacking., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1β (IL-1β), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarify the roles of inositol-requiring enzyme 1 alpha (IRE1α), an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1β production in RPMs. In RPMs, CTB is incorporated into the ER and induces ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α-deficient RPMs show a significant impairment of CT- or CTB-induced IL-1β production, indicating that IRE1α is required for CT- or CTB-induced IL-1β production in RPMs. This study demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lipid nanoparticles (LNPs) coated with functional and biocompatible polymers have been widely used as carriers to deliver oligonucleotide and messenger RNA therapeutics to treat diseases. Poly(ethylene glycol) (PEG) is a representative material used for the surface coating, but the PEG surface-coated LNPs often have reduced cellular uptake efficiency and pharmacological activity. Here, we demonstrate the effect of pH-responsive ethylenediamine-based polycarboxybetaines with different molecular weights as an alternative structural component to PEG for the coating of LNPs. We found that appropriate tuning of the molecular weight around polycarboxybetaine-modified LNP, which incorporated small interfering RNA, could enhance the cellular uptake and membrane fusion potential in cancerous pH condition, thereby facilitating the gene silencing effect. This study demonstrates the importance of the design and molecular length of polymers on the LNP surface to provide effective drug delivery to cancer cells., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

Background: Intensity-modulated radiation therapy (IMRT) has been increasingly used as a new radiation modality for unresectable non-small cell lung cancer (NSCLC). The risk factors for radiation pneumonitis (RP) during consolidation durvalumab following concurrent chemoradiotherapy (CCRT) using IMRT have not been thoroughly investigated., Methods: This retrospective study analyzed medical record data from consecutive patients diagnosed with NSCLC who underwent CCRT and consolidation durvalumab at our institution between April 2018 and September 2022. Since we adopted IMRT for the treatment of NSCLC in April 2020, these patients were categorized into two groups: those treated with IMRT after April 2020 and those treated with three-dimensional conformal radiotherapy (3D-CRT) before April 2020., Results: A total of 31 patients underwent IMRT (the IMRT group), while 25 patients underwent 3D-CRT (the 3D-CRT group). In both groups, the total dose was 60 Gy in 30 fractions. The cumulative incidence of ≥ grade 2 RP at 12 months was significantly lower in the IMRT group than in the 3D-CRT group (27.0% vs. 64.0%, hazard ratio [HR]: 0.338, 95% confidence interval [CI]: 0.144-0.793, p = 0.013). In the multivariable analysis, V20 (≥ 25.6%, HR: 2.706, 95% CI: 1.168-6.269, p = 0.020) and radiotherapy technique (IMRT, HR: 0.414, 95% CI: 0.172-0.994, p = 0.048) were identified as significant risk factors for ≥ grade 2 RP., Conclusions: IMRT is associated with a lower rate of ≥ grade 2 RP in patients with NSCLC who received CCRT followed by durvalumab., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: Several guidelines recommended that second transurethral resection should be performed in patients with diagnosis of high-risk non-muscle-invasive bladder cancer. However, therapeutic benefits of second transurethral resection before bacillus Calmette-Guérin intravesical instillation were conflicting amongst previous studies. We investigated the prognostic impact of second transurethral resection before bacillus Calmette-Guérin instillation in high-risk non-muscle-invasive bladder cancer patients., Methods: This retrospective study included 3104 non-muscle-invasive bladder cancer patients who received bacillus Calmette-Guérin instillations between 2000 and 2019 at 31 collaborative institutions. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors of intravesical recurrence, disease progression, cancer-specific mortality and overall mortality., Results: In the entire population, patients undergoing second transurethral resection (33%, 1026/3104) had a lower risk of intravesical recurrence on univariate analysis (hazard ratio 0.85, 95% confidence interval 0.73-0.98, P = 0.027), although it did not remain significant on multivariate analysis (hazard ratio 0.90, 95% confidence interval 0.76-1.07, P = 0.24). Subgroup analysis revealed that, in pT1 patients (n = 1487), second transurethral resection was significantly correlated with a lower risk of intravesical recurrence on multivariate analysis (hazard ratio 0.80, 95% confidence interval 0.64-1.00, P = 0.048), but lower risks of disease progression (hazard ratio 0.75, 95% confidence interval 0.56-1.00, P = 0.049), cancer-specific mortality (hazard ratio 0.54, 95% confidence interval 0.35-0.85, P = 0.007) and overall mortality (hazard ratio 0.73, 95% confidence interval 0.55-0.97, P = 0.027) on univariate analysis., Conclusions: Second transurethral resection confers accurate pathological staging and could be used to safely select good candidates for intravesical bacillus Calmette-Guérin instillation. We further confirm that second transurethral resection could confer an oncological benefit in pT1 bladder cancer patients treated by bacillus Calmette-Guérin instillation, and so strongly recommend second transurethral resection in this patient population., (© The Author(s) 2023. Published by Oxford University Press.)

Nano-sized contrast agents (NCAs) hold potential for highly specific tumor contrast enhancement during magnetic resonance imaging. Given the quantity of contrast agents loaded into a single nano-carrier and the anticipated relaxation effects, the current molecular design approaches its limits. In this study, a novel molecular mechanism to augment the relaxation of NCAs is introduced and demonstrated. NCA formation is driven by the intramolecular self-folding of a single polymer chain that possesses systematically arranged hydrophilic and hydrophobic segments in water. Utilizing this self-folding molecular design, the relaxivity value can be elevated with minimal loading of gadolinium complexes, enabling sharp tumor imaging. Furthermore, the study reveals that this NCA can selectively accumulate into tumor tissues, offering effective anti-tumor results through gadolinium neutron capture therapy. The efficacy and versatility of this self-folding molecular design underscore its promise for cancer diagnosis and treatment., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

This study introduced design informatics using deep learning in a topological photonics system and applied it to a topological waveguide with a sharp bending structure to further reduce propagation loss. The sharp bend in the topological waveguide composed of two photonic crystals wherein dielectrics having C 6v symmetry were arranged in triangle lattices of hexagons, and the designing of parameters individually for 6 × 6 unit cells near the bending region using deep learning resulted in an output improvement of 60% compared to the initial structure. The proposed structural design method has high versatility and applicability for various topological photonic structures.

Purpose: This report reviews our experience with right lower sleeve lobectomy and describes our technique and approach to perioperative patient management., Methods: We retrospectively reviewed 11 patients who underwent right lower sleeve lobectomy for lung cancer. Surgical techniques and perioperative management were also investigated., Results: Bronchoplasty was performed using 4-0 absorbable monofilament sutures. The deepest portion was anastomosed using continuous sutures; interrupted sutures were used for the more superficial portions. The truncus intermedius and right middle lobe bronchus should be anastomosed in a natural position. Anastomosis patency was confirmed using intraoperative bronchoscopy. Separation of the right upper and middle lobes and pericardiotomy at the inferior edge of the superior pulmonary vein are useful for mobilizing the right middle lobe. Death during hospitalization and treatment-related death did not occur. One patient developed pneumonia, and another developed a bronchopleural fistula., Conclusion: We reported our technique of right lower sleeve lobectomy and our approach to perioperative patient management. Sharing knowledge is essential to completing this rare surgery.

Hideki Kobara,1 Hirohito Mori,1 Kazi Rafiq,2 Shintaro Fujihara,1 Noriko Nishiyama,1 Maki Ayaki,1 Tatsuo Yachida,1 Tae Matsunaga,1 Johji Tani,1 Hisaaki Miyoshi,1 Hirohito Yoneyama,1 Asahiro Morishita,1 Makoto Oryu,1 Hisakazu Iwama,3 Tsutomu Masaki1 1Department of Gastroenterology and Neurology, 2Department of Pharmacology, 3Life Science Research Center, Faculty of Medicine, Kagawa University, Miki-cho, Kita-Gun, Kagawa, Japan Abstract: Advances in endoscopic submucosal dissection include a submucosal tunneling technique, involving the introduction of tunnels into the submucosa. These tunnels permit safer offset entry into the peritoneal cavity for natural orifice transluminal endoscopic surgery. Technical advantages include the visual identification of the layers of the gut, blood vessels, and subepithelial tumors. The creation of a mucosal flap that minimizes air and fluid leakage into the extraluminal cavity can enhance the safety and efficacy of surgery. This submucosal tunneling technique was adapted for esophageal myotomy, culminating in its application to patients with achalasia. This method, known as per oral endoscopic myotomy, has opened up the new discipline of submucosal endoscopic surgery. Other clinical applications of the submucosal tunneling technique include its use in the removal of gastrointestinal subepithelial tumors and endomicroscopy for the diagnosis of functional and motility disorders. This review suggests that the submucosal tunneling technique, involving a mucosal safety flap, can have potential values for future endoscopic developments. Keywords: submucosal endoscopy, submucosal tunneling method, natural orifice transluminal endoscopic surgery, peroral endoscopic myotomy, gastrointestinal subepithelial tumor, functional and motility disorders

Background: Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) sheets have recently attracted attention as an alternative approach to injected cell suspensions for stem cell therapy. However, cell engraftment and cytokine expression levels between hUC-MSC sheets and their cell suspensions in vivo have not yet been compared. This study compares hUC-MSC in vivo engraftment efficacy and cytokine expression for both hUC-MSC sheets and cell suspensions., Methods: hUC-MSC sheets were prepared using temperature-responsive cell culture; two types of hUC-MSC suspensions were prepared, either by enzymatic treatment (trypsin) or by enzyme-free temperature reduction using temperature-responsive cell cultureware. hUC-MSC sheets and suspensions were transplanted subcutaneously into ICR mice through subcutaneous surgical placement and intravenous injection, respectively. hUC-MSC sheet engraftment after subcutaneous surgical transplantation was investigated by in vivo imaging while intravenously injected cell suspensions were analyzing using in vitro organ imaging. Cytokine levels in both transplant site tissues and blood were quantified by enzyme-linked immunosorbent assay., Results: After subcutaneous transplant, hUC-MSC sheets exhibited longer engraftment duration than hUC-MSC suspensions. This was attributed to extracellular matrix (ECM) and cell-cell junctions retained in sheets but enzymatically altered in suspensions. hUC-MSC suspensions harvested using enzyme-free temperature reduction exhibited relatively long engraftment duration after intravenous injection compared to suspensions prepared using trypsin, as enzyme-free harvest preserved cellular ECM. High HGF and TGF-β1 levels were observed in sheet-transplanted sites compared to hUC-MSC suspension sites. However, no differences in human cytokine levels in murine blood were detected, indicating that hUC-MSC sheets might exert local paracrine rather than endocrine effects., Conclusions: hUC-MSC sheet transplantation could be a more effective cell therapeutic approach due to enhanced engraftment and secretion of therapeutic cytokines over injected hUC-MSC suspensions., (© 2023. The Author(s).)

Precisely controlled heteroatom-doped metal-free carbon catalysts are highly desirable for use in various renewable energy conversion and storage devices. Herein, we report a nitrogen-doped metal-free carbon catalyst for the oxygen reduction reaction (ORR) using a facile and cost-effective synthetic method. The obtained catalysts (NC-1100) were synthesized in two steps via an amino-acid complex coating and high-temperature carbonization. The various physical characteristics revealed that NC-1100 has a unique morphology, a controlled nitrogen bonding configuration, and a uniform pore distribution. The resulting catalyst shows excellent catalytic performance toward direct 4-electron oxygen reduction reaction (ORR) in an alkaline electrolyte, with a high onset potential of 0.95 V versus RHE and limiting current density (4.5 mA cm -2 ). Furthermore, the developed catalysts showed superior long-term operating stability and methanol durability compared to those of commercial Pt/C. This study provides a promising guideline for the development of next-generation electrocatalysts for fuel cells and wider applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objective: The objective of this study is to validate the predictive ability of the 2021 European Association of Urology (EAU) risk model compared to that of existing risk models, including the 2019 EAU model and risk scoring tables of the European Organization for Research and Treatment of Cancer, Club Urologico Espanol de Tratamiento Oncologico, and Japanese Nishinihon Uro-oncology Extensive Collaboration Group., Patients and Methods: This retrospective multi-institutional database study included two cohorts-3024 patients receiving intravesical bacillus Calmette-Guerin (BCG) treatment (BCG cohort) and 789 patients not receiving BCG treatment (non-BCG cohort). The Kaplan-Meier estimate and log-rank test were used to visualize and compare oncological survival outcomes after transurethral surgery among the risk groups. Harrell's concordance index (C-index) was used to evaluate the predictive ability of the models., Results: We observed a risk shift from the 2019 EAU risk grouping to the 2021 EAU risk grouping in a substantial number of patients. For progression, the C-index of the 2021 EAU model was significantly higher than that of the 2019 EAU model in both the BCG (0.617 vs. 0.572; P  = 0.011) and non-BCG (0.718 vs. 0.560; P  < 0.001) cohorts. According to the 2021 EAU model, 731 (24%) and 130 (16%) patients in the BCG and non-BCG cohorts, respectively, were considered to have a very high risk. Survival analysis showed no significant differences among the five very high-risk subgroups in both cohorts. A major limitation was potential selection bias owing to the retrospective nature of this study., Conclusions: The updated 2021 EAU model showed better stratification than the three existing risk models, especially for progression, in both cohorts, determining the most appropriate postoperative treatment and identifying patients requiring intensified surveillance or early cystectomy., Competing Interests: The authors disclose no potential conflict of interest., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

A defect structure is proposed for enhancing the coupling efficiency of vertically incident circularly polarized light in a topological waveguide. In the topological edge-state waveguide based on triangle lattices of hexagons consisting of six nanoholes respecting C 6v symmetry in a silicon optical circuit, the vertical coupling rate is improved by removing the nanoholes from one hexagonal cell near the line. The coupling efficiency was evaluated with and without the defect structure. The introduced defect structure operates suitably for focused beams of left- and right-handed circularly polarized light, enhancing the optical communication wavelength bandwidth by up to 10 dB.

Background: The over-the-scope clip (OTSC) is a highly effective clipping device for refractory gastrointestinal disease. However, Japanese data from multicenter studies for anastomotic leakage (AL) involving a secondary fistula after gastrointestinal surgery are lacking. Therefore, this study evaluated the efficacy and safety of OTSC placement in Japanese patients with such conditions., Methods: We retrospectively collected data from 28 consecutive patients from five institutions who underwent OTSC-mediated closure for AL between July 2017 and July 2020., Results: The AL and fistula were located in the esophagus (3.6%, n = 1), stomach (10.7%, n = 3), small intestine (7.1%, n = 2), colon (25.0%, n = 7), and rectum (53.6%, n = 15). The technical success, clinical success, and complication rates were 92.9% (26/28), 71.4% (20/28), and 0% (0/28), respectively. An age of <65 years (85.7%), small intestinal AL (100%) and colonic AL (100%), defect size of <10 mm (82.4%), time to OTSC placement > 7 days (84.2%), and the use of simple suction (78.9%) and anchor forceps (80.0%) were associated with higher clinical success rates., Conclusion: OTSC placement is a useful therapeutic option for AL after gastrointestinal surgery.

Purpose: To evaluate the prognostic impact of restrictive ventilatory impairment in patients who undergo pulmonary resection of metachronous second primary lung cancer., Methods: The clinical characteristics and surgical outcomes of 70 patients with metachronous second primary lung cancer were analyzed., Results: The surgical procedures consisted of wedge resection in 40 patients, segmentectomy in 17, lobectomy in 12, and completion pneumonectomy in one. Patients who underwent ipsilateral pulmonary resection developed more perioperative complications (p = 0.0339). Three-year and 5-year overall survival rates were 78.2% and 69.2%, respectively. In univariate analysis, sex, restrictive ventilatory impairment, and histology of second primary lung cancer were significantly poor prognostic factors (all p <0.05). Multivariate analysis identified restrictive ventilatory impairment to be an independent predictor of a poor prognosis (p = 0.0193). In the 22 patients who died, the cause of death was lung cancer in 11 and other diseases, including pneumonia and respiratory failure, in 11. Death from another disease was significantly more common in patients with restrictive ventilatory impairment (p = 0.0216)., Conclusion: Restrictive ventilatory impairment was an independent predictor of a poor prognosis in patients with a second primary lung cancer. Restrictive ventilatory impairment as a result of repeated thoracic surgery may increase the likelihood of death from another disease.

The catalytic properties of conventional H-[Al]-ZSM-5 and gallium-substituted H-[Ga]-ZSM-5 were evaluated in the conversion of methanethiol to ethylene (CH 3 SH → 1/2C 2 H 4 + H 2 S). Dimethyl sulfide (DMS), aromatics, and CH 4 were formed as byproducts on the H-[Al]-ZSM-5 catalyst. The introduction of Ga into the ZSM-5 structure provided a high ethylene yield with relatively high selectivity for olefins. Based on the temperature-programmed desorption of NH 3 and pyridine adsorption on zeolites, the strength of acid sites was decreased by introducing Ga into the ZSM-5 structure. Undesirable reactions seemed less likely to occur at weakly acidic sites. The suppression of the formation of dimethyl sulfide (CH 3 SH → 1/2C 2 H 6 S + 1/2H 2 S) and the sequential reaction of ethylene to produce aromatics provided a high yield of ethylene over H-[Ga]-ZSM-5., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Detailed demographics play an important role in the development of smart cities. However, especially in developing countries, the maintenance and management of this data is incomplete, which hinders the promotion of smart cities. The objective of this study is to develop a method to create detailed building distribution maps from satellite images, which will serve as a basis for developing detailed demographic data to support the promotion of smart cities around the world. The target area is several areas of Tokyo where validation data is available. We first developed a method for extracting buildings from satellite images and then estimating the building use to determine the buildings where residents are distributed. Both methods use deep learning. As a result, it was possible to extract buildings with an extraction rate (the number of buildings in the automatically extracted building data divided by the number of buildings in the data for verification) of up to 60.3% for the entire target area. In addition, in the estimation of building use, our method was able to classify detached and non-detached buildings with an average accuracy of 78.7% for the entire target area. [ABSTRACT FROM AUTHOR]

Background: Moso bamboo (Phyllostachys edulis) is a typical East Asian bamboo that does not flower for > 60 years and propagates without seed reproduction. Thus, Moso bamboo can be propagated vegetatively, possibly resulting in highly heterozygous genetic inheritance. Recently, a draft genome of Moso bamboo was reported, followed by whole genome single nucleotide polymorphisms (SNP) analysis, which showed that the genome of Moso bamboo in China has regional characteristics. Moso bamboo in Japan is thought to have been introduced from China over the sea in 1736. However, it is unclear where and how Moso bamboo was introduced in Japan from China. Here, based on detailed analysis of heterozygosity in genome diversity, we estimate the spread of genome diversity and its pedigree of Moso bamboo., Results: We sequenced the whole genome of Moso bamboo in Japan and compared them with data reported previously from 15 regions of China. Only 4.1 million loci (0.37% of the analyzed genomic region) were identified as polymorphic loci. We next narrowed down the number of polymorphic loci using several filters and extracted more reliable SNPs. Among the 414,952 high-quality SNPs, 319,431 (77%) loci were identified as heterozygous common to all tested samples. The result suggested that all tested samples were clones via vegetative reproduction. Somatic mutations may accumulate in a heterozygous manner within a single clone. We examined common heterozygous loci between samples from Japan and elsewhere, from which we inferred that an individual closely related to the sample from Fujian, China, was introduced to Japan across the sea without seed reproduction. In addition, we collected 16 samples from four nearby bamboo forests in Japan and performed SNP and insertion/deletion analyses using a genotyping by sequencing (GBS) method. The results suggested that a small number of somatic mutations would spread within and between bamboo groves., Conclusions: High heterozygosity in the genome-wide diversity of Moso bamboo implies the vegetative propagation of Moso bamboo from China to Japan, the pedigree of Moso bamboo in Japan, and becomes a useful marker to approach the spread of genome diversity in clonal plants., (© 2023. The Author(s).)

Duodenal endoscopic submucosal dissection (ESD) is associated with high incidences of intraoperative complications and delayed adverse events (AEs). Delayed AEs can be reduced by closing the post-ESD defects. We developed a new method of closure after duodenal ESD, combining endoscopic ligation with O-ring closure (E-LOC) with an over-the-scope clip (OTSC) (Band OTSC; B-OTSC). Here, we conducted a single-center, retrospective, observational study to investigate the efficacy and safety of the B-OTSC method for preventing delayed AEs in patients undergoing duodenal ESD. The study included nine patients with superficial nonpapillary duodenal epithelial tumors who underwent ESD and were closed with B-OTSC from February 2021 to February 2023. There were no delayed AEs (0%), the mean (± standard deviation) closure time was 53 ± 21.6 min, the complete closure rate was 100%, and the mean hospital stay was 7.8 ± 1.8 days. The sustained closure rates at postoperative days 3 and 7 were 88.9% and 88.9%, respectively. The historical analysis indicated a significant difference in cost between B-OTSC and conventional OTSC ( p < 0.01). In conclusion, B-OTSC was a safe, secure, and cost-effective method of closure after duodenal ESD, even in patients with post-ESD defects of more than half the circumference.

Despite the promising efficacy of atezolizumab plus bevacizumab (atezo/bev), some patients with unresectable hepatocellular carcinoma (HCC) experience disease progression. This retrospective study, which included 154 patients, aimed to evaluate predictors of treatment efficacy of atezo/bev for unresectable HCC. Factors associated with treatment response were examined, focusing on tumor markers. In the high-alpha-fetoprotein (AFP) group (baseline AFP ≥ 20 ng/mL), a decrease in AFP level > 30% was an independent predictor of objective response (odds ratio, 5.517; p = 0.0032). In the low-AFP group (baseline AFP < 20 ng/mL), baseline des-gamma-carboxy prothrombin (DCP) level < 40 mAU/mL was an independent predictor of objective response (odds ratio, 3.978; p = 0.0206). The independent predictors of early progressive disease were an increase in AFP level ≥ 30% at 3 weeks (odds ratio, 4.077; p = 0.0264) and the presence of extrahepatic spread (odds ratio, 3.682; p = 0.0337) in the high-AFP group and up-to-seven criteria, OUT (odds ratio, 15.756; p = 0.0257) in the low-AFP group. In atezo/bev therapy, focusing on early AFP changes, baseline DCP, and tumor burden of up-to-seven criteria are useful in predicting response to treatment.

N-doped carbon materials have attracted considerable attention as highly functional materials because nitrogen doping distorts the carbon lattice, changes the charge density, and introduces additional defects. Among various positions of N atoms in N-doped carbon compounds, pyridinic-N, pyrrolic-N, and valley-N, which are doped at edge sites, exhibit specific electrocatalytic activities during the oxygen reduction reaction (ORR). However, it is difficult to selectively introduce these N atoms into a carbon matrix because the synthesis procedure typically includes high-temperature heat treatment. In this study, we applied a zeolite templating method to synthesize edge site-rich N-doped carbon materials. The sample fabricated using a zeolite template possessed high concentrations of pyridinic-N and valley-N atoms, demonstrating a significantly higher ORR catalytic activity than the sample synthesized without a zeolite template. Additional experiments conducted using various zeolites confirmed the positive effect of N-doped carbons on the ORR catalytic performance. This work demonstrated that the zeolite templating method not only increased the specific surface area and the number of active sites but also selectively created edge sites and improved the quality of the active sites., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A magneto-optical switch responding to signal with 200 ps rise time was demonstrated. The switch uses current-induced magnetic field to modulate the magneto-optical effect. Impedance-matching electrodes were designed to apply high-frequency current and accommodate the high-speed switching. A static magnetic field generated by a permanent magnet was applied orthogonal to the current-induced ones and acts as a torque and helps the magnetic moment reverse its direction which assist the high-speed magnetization reversal.