Search

Mermithidae is a family of nematodes that parasitize a wide range of invertebrates worldwide. Herein, we report nematodes that were unexpectedly found in three of 486 adult stable flies (Stomoxys calcitrans) captured from three farms (F1, F2, and F3) in different regions of Gifu Prefecture, Japan. We aimed to characterize these nematodes both at the morphological and molecular level. Morphological studies revealed that the nematodes were juveniles of Mermithidae. Phylogenetic analysis based on 18S and 28S rDNA indicated that the mermithids from farms F1 and F2 could be categorized into the same cluster as Ovomermis sinensis and Hexamermis sp., whereas the mermithid from farm F3 clustered with Amphimermis sp. Additionally, these mermithids could be categorized within the same clusters as related mermithids detected in Japan that parasitize various arthropod orders. Our findings suggest that these stable flies may have been parasitized by mermithids already present in the region and that genetically distinct species of mermithids occur across Japan. To the best of our knowledge, this is the first report of mermithids parasitizing adult stable flies in Japan.

Microbubble-enhanced ultrasound provides a noninvasive physical method to locally overcome major obstacles to the accumulation of blood-borne therapeutics in the brain, posed by the blood-brain barrier (BBB). However, due to the highly nonlinear and coupled behavior of microbubble dynamics in brain vessels, the impact of microbubble resonant effects on BBB signaling and function remains undefined. Here, combined theoretical and prospective experimental investigations reveal that microbubble resonant effects in brain capillaries can control the enrichment of inflammatory pathways that are sensitive to wall shear stress and promote differential expression of a range of transcripts in the BBB, supporting the notion that microbubble dynamics exerted mechanical stress can be used to establish molecular, in addition to spatial, therapeutic windows to target brain diseases. Consistent with these findings, a robust increase in cytotoxic T-cell accumulation in brain tumors was observed, demonstrating the functional relevance and potential clinical significance of the observed immuno-mechano-biological responses., (© 2024. The Author(s).)

This retrospective cohort study aimed to investigate the association between alcohol consumption and the onset of type 2 diabetes in middle-aged Japanese individuals. Participants were aged 40 and above from Panasonic Corporation, Osaka, Japan's medical health checkup program from 2008 to 2021. Alcohol consumption was calculated by converting the quantity consumed into daily ethanol consumption. We assessed the association between alcohol consumption and the onset of type 2 diabetes using Cox regression analysis. The total and median follow-up duration was 13 years and 7 (3-13) years (748,090 person-years). Among 102,802 participants, 7,510 participants (7.3%) developed type 2 diabetes during the study period. Alcohol consumption at the level of 0 < to < 22 g/day and 22 to < 39 g/day were negatively associated with developing type 2 diabetes compared to complete alcohol abstainers. Alcohol consumption at levels of 39 to < 66 g/day and at levels of ≥ 66 g/day were positively associated with developing type 2 diabetes in participants with BMI < 25 kg/m 2 . All levels of alcohol consumption were negatively associated with developing type 2 diabetes in participants with BMI ≥ 25 kg/m 2 . Moderate-to-heavy alcohol consumption were positively associated with developing type 2 diabetes for participants with BMI < 25 kg/m 2 , whereas alcohol intake was negatively associated with developing type 2 diabetes among participants with BMI ≥ 25 kg/m 2 ., (© 2024. The Author(s).)

Objectives: This study aimed to investigate the regulatory mechanisms governing dental mesenchymal cell commitment during tooth development, focusing on odontoblast differentiation and the role of epigenetic regulation in this process., Methods: We performed single-cell RNA sequencing (scRNA-seq) of dental cells from embryonic day 14.5 (E14.5) mice to understand the heterogeneity of developing tooth germ cells. Computational analyses including gene regulatory network (GRN) assessment were conducted. We validated our findings using immunohistochemistry (IHC) and in vitro loss-of-function analyses using the DNA methyltransferase 1 (DNMT1) inhibitor Gsk-3484862 in primary dental mesenchymal cells (DMCs) isolated from E14.5 mouse tooth germs. Bulk RNA-seq of Gsk-3484862-treated DMCs was performed to identify potential downstream targets of DNMT1., Results: scRNA-seq analysis revealed diverse cell populations within the tooth germs, including epithelial, mesenchymal, immune, and muscle cells. Using single-cell regulatory network inference and clustering (SCENIC), we identified Dnmt1 as a key regulator of early odontoblast development. IHC analysis showed the ubiquitous expression of DNMT1 in the dental papilla and epithelium. Bulk RNA-seq of cultured DMCs showed that Gsk-3484862 treatment upregulated odontoblast-related genes, whereas genes associated with cell division and the cell cycle were downregulated. Integrated analysis of bulk RNA-seq data with scRNA-seq SCENIC profiles was used to identify the potential Dnmt1 target genes., Conclusions: Dnmt1 may negatively affect odontoblast commitment and differentiation during tooth development. These findings contribute to a better understanding of the molecular mechanisms underlying tooth development and future development of hard-tissue regenerative therapies., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

The C797S mutation is one of the major factors behind resistance to the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Herein, we describe the discovery of DS06652923, a novel, potent, and orally available EGFR-triple-mutant inhibitor. Through scaffold hopping from the previously reported nicotinamide derivative, a novel biaryl scaffold was obtained. The potency was successfully enhanced by the introduction of basic substituents based on analysis of the docking study results. In addition, the difluoromethoxy group on the pyrazole ring improved the kinase selectivity by inducing steric clash with the other kinases. The most optimized compound, DS06652923, achieved tumor regression in the Ba/F3 allograft model upon its oral administration., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Hideaki Kageji, Takayuki Momose, Masayuki Ebisawa, Yusuke Nakazawa, Hiroyuki Okada, Noriko Togashi, Yasuhito Nagamoto, Wataru Obuchi, Isao Yasumatsu, Kawori Kihara, Kumiko Hiramoto, Megumi Minami, Naomi Kasanuki, Takeshi Isoyama, Hiroyuki Naito, and Naoki Tanaka report that they are employees of Daiichi Sankyo Co., Ltd]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest None.

Food allergens in processed foods are affected by heating, processing, and the food matrix. To conduct highly reliable tests, extracting allergens into test solutions is necessary for appropriate detection. In addition to the commonly used enzyme-linked immunosorbent assay (ELISA), liquid chromatography-mass spectrometry (LC-MS), which has the advantage of simultaneously detecting multiple allergens in foods, is being increasingly used. When managing food allergens at food manufacturing sites, obtaining the same measured values is desirable, regardless of the analytical method used. Therefore, in this study, we focused on the importance of pretreatment steps for LC-MS when examining food allergens in processed foods, which can be difficult to analyze. The ELISA method uses food extracts optimized for analyzing allergens in processed foods. We developed a high-resolution accurate mass spectrometry (HRAM)-LC-MS/MS method using the same food extract used in the ELISA method and an MS sample preparation kit. Multiple food allergen analysis was performed using 1, 5, 10, and 20 ppm of allergen-incurred processed foods. Overall, a strong correlation was observed between the measured values of HRAM-LC-MS/MS and ELISA, demonstrating the applicability of multi-allergen analysis using LC-MS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: For the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5-1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients., Methods: We analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal., Results: Our analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review., Conclusion: The results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors., (© 2024. The Author(s).)

Background: Interleukin (IL)-23 is involved in the pathogenesis of ulcerative colitis (UC). A genome-wide significant association between IL23R p.G149R (rs76418789) and UC was previously identified in Japan and Korea. This case-control study aims to examine this association within the Japanese population., Methods: The study included 384 cases diagnosed with UC within the past 4 years and 661 control subjects. Adjustment was made for sex, age, and smoking., Results: The frequency of the AA genotype of rs76418789 was 0.0 % in cases and 0.5 % in control subjects. In comparison to study subjects with the GG genotype of rs76418789, those with the GA or AA genotype had a significantly reduced risk of UC, with an adjusted odds ratio of 0.67 (95 % confidence interval: 0.44-0.999). A significant multiplicative interaction was observed between rs76418789 and having ever smoked influencing UC (p for interaction = 0.03). A significant positive association was found between having ever smoked and UC in individuals with at least one A allele, while no such positive relationship was observed in those with the GG genotype., Conclusion: IL23R SNP rs76418789 showed a significant association with UC. This study provides new evidence regarding the interaction between rs76418789 and smoking in relation to UC., 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 Elsevier Ltd. All rights reserved.)

Uterine myomas can cause infertility. Studies are attempting to determine the indications for myomectomy. However, the multiplicity and localization of myomas complicate this issue. We aimed to develop a visualization tool to aid patients with infertility in their decision-making for myomectomy. We included 191 women with uterine myoma attending an outpatient infertility clinic, of whom 124 patients underwent myomectomy. Of these, 65 (52.4%) patients became pregnant within 17.6 months after surgery, and 54 (83.1%) of them had a live birth. A logistic regression model predicting the pregnancy rate (area under the curve, 0.82; 95% confidence interval, 0.74-0.89; validation value, 74.6%) was generated using the leave-one-out cross-validation method. This model incorporated five factors: age, maximum level of infertility intervention following myomectomy, presence of submucosal myoma, maximum diameter of the myoma, and type of myomas (multiple or single). We successfully visualized the degree of involvement of each factor in the pregnancy rate by developing a nomogram based on this model. We expanded the data from the preoperative magnetic resonance images and applied machine learning using a convolutional neural network. The classification accuracy was 71.4% for sensitivity and 77.7% for specificity. Heatmap images, generated using gradient-weighted class activation mapping to show the classification results of this model, could distinguish between myomas that required enucleation and those that did not. Although a larger sample size is needed to further validate our findings, this innovative pilot study demonstrates the potential of machine learning to refine assessment criteria and improve patient decision-making., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Safety data of the latest radiofrequency (RF) technologies during atrial fibrillation (AF) ablation in real-world clinical practice are limited., Objectives: We sought to evaluate the acute procedural safety of the four latest ablation catheters commonly used for AF ablation., Methods: A total of 3957 AF ablation procedures performed between January 2022 and December 2023 at 20 centers with either the THERMOCOOL SMARTTOUCH SF (STSF), TactiCath (TC), QDOT Micro (QDM), or TactiFlex (TF) were retrospectively analyzed., Results: In total, QDM, STSF, TF, and TC were used in 343 (8.7%), 1793 (45.3%), 1121 (28.4%), and 700(17.7%) procedures. Among 2406 index procedures, electrical pulmonary vein isolations were successfully achieved in 99.5%. Despite similar total procedure times in the four groups, the total fluoroscopic time was significantly shorter for QDM/STSF with CARTO than TF/TC with EnSite (18.7 ± 14 vs. 27.6 ± 20.6 min, p < .001) and longest in the TF group. The incidence of cardiac tamponade was 0.7% (0.5% and 0.9% during index and redo procedures, 0.8% and 0.3% for paroxysmal and non-paroxysmal AF) and was significantly lower for QDM/STSF than TF/TC (0.2% vs. 1.1%, p = .008) and highest in the TF group. The incidence of cardiac tamponade was higher for TF than TC and STSF than QDM. In the multivariate analysis, TF/TC with EnSite was a significant independent predictor of cardiac tamponade during both the index (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3-17.5, p = .02) and all procedures (OR = 3.0, 95% CI = 1.3-7.2, p = .01)., Conclusions: The incidence of cardiac tamponade and the fluoroscopic time during AF ablation significantly differed among the latest RF catheters and mapping systems in real-world clinical practice., (© 2024 Wiley Periodicals LLC.)

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline mutations in tumor suppressor gene TP53 . Perivascular epithelioid cell tumors (PEComas) are a group of tumors by the World Health Organization Classification as mesenchymal tumors composed of histologically and immunohistochemically distinctive PECs. The present study reports a rare case of PEComa associated with LFS. A 32-year-old female patient was referred to Tokyo Metropolitan Tama Medical Center (Tokyo, Japan) in March 2022 for a detailed examination of a liver mass. The patient had received a diagnosis of LFS based on a history of sarcoma and germline variants of TP53 7 years previously. Magnetic resonance imaging revealed a ring-enhanced mass in the liver segment 8 (S8). This was observed in the arterial phase, followed by washout of contrast media in the venous phase. Owing to the possibility of malignancy (such as metastatic liver tumor or hepatocellular carcinoma), the patient was referred for diagnostic surgery. In August 2022, a laparoscopic partial hepatectomy of S8 was performed without complications and she was discharged on postoperative day 7. The pathological findings led to the diagnosis of PEComa. The patient is currently under follow-up at 1 year and 4 months postoperative. Laparoscopic hepatectomy was useful as a diagnostic treatment because it was relatively non-invasive. Mutations in TP53 are involved in the development of PEComa. Further cases and studies are required to clarify the relationship between LFS and PEComa., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Takada et al.)

Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article.

A 38-day-old infant was referred to our hospital for evaluation of apnea, fever, and pyuria. Invasive bacterial infection, including meningitis, was suspected because of the presence of apnea. A contrast-enhanced CT scan revealed acute localized bacterial nephritis, and meningitis was ruled out. Gram-positive cocci and Gram-negative rods, ie, Enterococcus raffinosus and Escherichia coli, were isolated from a urine culture at the referring hospital. This case report describes the youngest case of E. raffinosus infection. Apnea was the main complaint, but the origin of fever was infant acute focal bacterial nephritis (AFBN) with mixed infection. In infants, bacterial infections, especially invasive bacterial infections, can result in poor outcomes and require careful evaluation and treatment. Furthermore, the possibility of AFBN should not be overlooked, because bacteriuria or leukocyturia may be absent and can flare up if antimicrobials are not administered for an adequate duration. Although ampicillin-susceptible E. raffinosus infection in our patient responded well to treatment, there have been reports of vancomycin-resistant enterococci, which highlights the importance of proper use of antimicrobial agents to avoid producing drug-resistant bacteria.

Although outcomes have improved with new-generation drug-eluting stents, few reports have analyzed the risk factors associated with chronic outcomes of chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). This study aimed to investigate the independent risk factors for target lesion revascularization (TLR) and major adverse cardiac and cerebrovascular events (MACCEs) after CTO-PCI using Japanese multicenter data. A total of 3,666 patients, who underwent CTO-PCI and completed a 1-year follow-up, registered at the Japanese CTO-PCI Expert Registry from 2014 to 2019, were examined. The primary outcome was defined as TLR, and the secondary outcome was MACCEs at the 1-year follow-up. TLRs and MACCEs occurred in 175 (4.8%) and 524 (14.3%) patients, respectively. Multivariate logistic regression analysis demonstrated that in-stent occlusion (ISO) (odds ratio [OR] 2.604, 95% confidence interval [CI] 1.695 to 4.001), hemodialysis (OR 1.784, 95% CI 1.062 to 2.997), diabetes mellitus with insulin use (OR 1.741, 95% CI 1.060 to 2.861), moderate-to-severe calcification (OR 1.726, 95% CI 1.197 to 2.487), and the right coronary artery as the target vessel (OR 1.468, 95% CI 1.018 to 2.117) were significantly associated with TLR. Hemodialysis (OR 2.214, 95% CI 1.574 to 3.113), ISO (OR 1.499, 95% CI 1.127 to 1.993), arteriosclerosis obliterans (OR 1.414, 95% CI 1.074 to 1.863), and multivessel disease (OR 1.356, 95% CI 1.117 to 1.647) were significantly associated with MACCEs. One-year outcomes of new-generation drug-eluting stents for CTO-PCI were favorable, and ISO as a lesion factor and hemodialysis as a patient factor were strongly associated with TLR and MACCEs, respectively., Competing Interests: Declaration of competing interest Dr. Tsuchikane is a consultant for Asahi Intecc, Boston Scientific, and Kaneka. Dr. Osamu Katoh is a consultant for Asahi Intecc, Nipro, and Canon Medical. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Cold snare polypectomy (CSP) and underwater endoscopic mucosal resection (UEMR) have been developed recently, in addition to conventional methods, but adverse events of each method have not been fully clarified. We compared the outcomes of each method for the appropriate choice., Methods: Patients who underwent CSP, endoscopic mucosal resection (EMR)/hot snare polypectomy (HSP), or UEMR for small and intermediate-sized colorectal polyps between April 2017 and June 2020 were retrospectively examined. The rate of adverse events and recurrences due to each method were determined as the main outcomes. Clinical factors related to adverse events were examined., Results: A total of 1,025 patients with 3,163 polyps underwent polypectomy using any of the methods. CSP, EMR/HSP, and UEMR were performed for 704 (22.2%), 2,145 (67.8%), and 314 polyps (9.9%), and the median size for each method was 4, 6, and 7 mm, respectively. Delayed bleeding for CSP, EMR/HSP, and UEMR was 0%, 0.2%, and 0.6% (p = 0.15), and perforation was 0%, 0.1%, and 0%, respectively (p = 0.62). Recurrence after CSP, EMR/HSP, and UEMR was 0.3%, 0.09%, and 1.3%, respectively (p &lt; 0.01). Recurrence for UEMR was significantly higher in the early stage of procedure introduction (p = 0.015). Oral anticoagulants were the risk factor for delayed bleeding (p &lt; 0.01, respectively)., Conclusion: There was no significant difference regarding adverse events among each method for small and intermediate-sized polyps, although the recurrence rate after UEMR was higher than other methods., (© 2024 S. Karger AG, Basel.)

Background: Glioblastoma (GBM) has a highly immunosuppressive tumor immune microenvironment (TIME), largely mediated by myeloid-derived suppressor cells (MDSCs). Here, we utilized a retroviral replicating vector (RRV) to deliver Interferon Regulatory Factor 8 (IRF8), a master regulator of type 1 conventional dendritic cell (cDC1) development, in a syngeneic murine GBM model. We hypothesized that RRV-mediated delivery of IRF8 could "reprogram" intratumoral MDSCs into antigen-presenting cells (APCs) and thereby restore T-cell responses., Methods: Effects of RRV-IRF8 on survival and tumor growth kinetics were examined in the SB28 murine GBM model. Immunophenotype was analyzed by flow cytometry and gene expression assays. We assayed functional immunosuppression and antigen presentation by ex vivo T-cell-myeloid co-culture., Results: Intratumoral injection of RRV-IRF8 in mice bearing intracerebral SB28 glioma significantly suppressed the tumor growth and prolonged survival. RRV-IRF8 treated tumors exhibited significant enrichment of cDC1s and CD8+ T-cells. Additionally, myeloid cells derived from RRV-IRF8 tumors showed decreased expression of the immunosuppressive markers Arg1 and IDO1 and demonstrated reduced suppression of naïve T-cell proliferation in ex vivo co-culture, compared to controls. Furthermore, DCs from RRV-IRF8 tumors showed increased antigen presentation compared to those from control tumors. In vivo treatment with azidothymidine (AZT), a viral replication inhibitor, showed that IRF8 transduction in both tumor and non-tumor cells is necessary for survival benefit, associated with a reprogrammed, cDC1- and CD8 T-cell-enriched TIME., Conclusions: Our results indicate that reprogramming of glioma-infiltrating myeloid cells by in vivo expression of IRF8 may reduce immunosuppression and enhance antigen presentation, achieving improved tumor control., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

When a neuroendocrine tumor with abundant blood flow is located in the pancreatic tail, it is difficult to distinguish it from accessory spleen. The patient was a 71-year-old woman who was admitted with impaired consciousness and hypoglycemia, raising suspicion of insulinoma. The selective arterial calcium injection test suggested a lesion in the pancreatic tail. Contrast-enhanced computed tomography and magnetic resonance imaging (MRI) showed a mass in the splenic hilum; however, its continuity with the pancreas was unclear. Contrast-enhanced MRI using super paramagnetic iron oxide (SPIO) showed no SPIO uptake in the splenic hilar mass. SPIO contrast-enhanced MRI is considered useful for differentiating pancreatic endocrine tumors from paraspleen tumors.

Pancreatic cancer is one of the most refractory malignancies. In situ vaccines (ISV), in which intratumorally injected immunostimulatory adjuvants activate innate immunity at the tumor site, utilize tumor-derived patient-specific antigens, thereby allowing for the development of vaccines in patients themselves. Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapy that selectively kills cancer cells exclusively in the NIR-irradiated region. Extending our previous research showing that ISV using the unique nanoparticulate Toll-like receptor 9 (TLR9) ligand K3-SPG induced effective antitumor immunity, here we incorporated NIR-PIT into K3-SPG-ISV so that local tumor destruction by NIR-PIT augments the antitumor effect of ISV. In the mouse model of pancreatic cancer, the combination of K3-SPG-ISV and CD44-targeting NIR-PIT showed synergistic systemic antitumor effects and enhanced anti-programmed cell death-1 (PD-1) blockade. Mechanistically, strong intratumoral upregulation of interferon-related genes and dependency on CD8 + T cells were observed, suggesting the possible role of interferon and cytotoxic T cell responses in the induction of antitumor immunity. Importantly, this combination induced immunological memory in therapeutic and neoadjuvant settings. This study represents the first attempt to integrate NIR-PIT with ISV, offering a promising new direction for cancer immunotherapy, particularly for pancreatic cancer., 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 Inc. All rights reserved.)

Despite recent advancements in cancer immunotherapy, many patients with gliomas and glioblastomas have yet to experience substantial therapeutic benefits. Modulating the tumor microenvironment (TME) of gliomas, which is typically "cold", is crucial for improving treatment outcomes. Clinical tumor specimens obtained post-immunotherapy provide invaluable insights. However, access to such post-immunotherapy samples remains limited, even in clinical trials, as tumor tissues are often collected only at tumor relapse. Recent studies of neoadjuvant immunotherapy provided important insights by incorporating surgical resections of post-treatment tumors. Moreover, pre-surgical immunotherapies are increasingly integrated into clinical trial designs to evaluate treatment efficacy. These investigations reveal critical information, particularly regarding the delivery success of therapeutic agents, the expansion and persistence of immune products, and the cellular and molecular changes induced in the TME. In this review, we assess the findings on post-treatment tumor specimens obtained from recent immunotherapy clinical trials on gliomas, highlight the importance of these samples for understanding therapeutic impacts, and discuss proactive investigation approaches for future clinical trials.

Background: Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients., Methods: This is an analysis of the Japan Chronic Kidney Disease Database Ex　(J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m 2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression., Results: The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium., Conclusion: Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background and Aims: Killian-Jamieson diverticulum (KJD) is a relatively uncommon variant of pharyngoesophageal diverticula, distinct from the more prevalent Zenker diverticulum. However, literature on endoscopic management of KJD remains limited. This study aimed to elucidate the efficacy and safety of peroral endoscopic septotomy (POES) as a treatment approach for symptomatic KJD., Methods: In this retrospective observational study, we investigated the outcomes of nine consecutive patients who underwent POES for KJD between January 2019 and May 2023. Follow-up data of at least 2 months post-treatment were analyzed. The primary outcome measure was the technical success rate of POES. Secondary outcomes encompassed the clinical success rate, defined as symptomatic improvement 2 months after POES, and the incidence of adverse events., Results: All patients presented with dysphagia, with a median symptom duration of 6 months (interquartile range [IQR]: 3-12 months). The median diverticulum size was 32 mm (IQR: 24-42 mm). The median duration of the operation time was 66 min (IQR: 60-109). A 100% technical success rate was achieved, with complete closure of the defect in all cases. There were no adverse events related to this treatment. The median hospitalization duration was 5 days (IQR: 4-6), and the clinical success rate was 88.9%. Follow-up barium esophagograms exhibited significant improvement in the flow of the barium for all patients., Conclusions: Despite the relatively limited case volume, our findings underscore that POES is a safe and efficacious approach for managing symptomatic KJD., (© 2023 Japan Gastroenterological Endoscopy Society.)

Aims: Renal dysfunction in patients with chronic heart failure predicts a poor prognosis. Tolvaptan has a diuretic effect in patients with chronic kidney disease and heart failure without adverse effects on renal function. We aimed to determine the effects of tolvaptan and predictors of worsening renal function in patients with heart failure., Methods and Results: This post hoc analysis was a sub-analysis of a single-centre prospectively randomized trial on the early and short-term tolvaptan administration. We enrolled 201 participants with decompensated heart failure between January 2014 and March 2019 (early group, n = 104; age: 79.0 ± 12.8 years; late group, n = 97; age: 80.3 ± 10.8 years). Renal ultrasonography was performed before and after the administration of tolvaptan. Urine output and oral water intake significantly increased during tolvaptan administration. The difference between water intake and urine volume increased during tolvaptan administration. Changes in body weight, blood pressure, heart rate, and estimated glomerular filtration rate (eGFR) in both groups were comparable. The changes in peak-systolic velocity (PSV), acceleration time (AT) of the renal arteries, and resistance index were comparable. The changes in PSV and end-diastolic velocity (EDV) of the interlobar arteries increased following tolvaptan administration (Δmax PSV: 0.0 ± 14.8 cm/s before tolvaptan vs. 5.6 ± 15.7 cm/s after tolvaptan, P = 0.002; Δmean PSV: 0.4 ± 12.3 vs. 4.9 ± 12.7 cm/s, P = 0.002; Δmax EDV: -0.2 ± 3.5 vs. 1.4 ± 4.0 cm/s, P = 0.001; Δmean EDV: -0.0 ± 3.1 vs. 1.1 ± 3.4 cm/s, P = 0.003). The renal artery AT was negatively correlated with the eGFR (Δmax AT: beta = -0.2354, P = 0.044; Δmean AT: beta = -0.2477, P = 0.035)., Conclusions: Tolvaptan increased the PSV and EDV of the interlobar artery, which may mean tolvaptan increased renal blood flow. The renal artery AT may be a surrogate for worsening renal function., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim/introduction: This historical cohort study sought to research the relationship between eating behaviors and the incidence of type 2 diabetes in a large, long-term cohort of Japanese subjects., Materials and Methods: Panasonic Corporation employees who had no history of diabetes and attended yearly health surveys between 2008 and 2018 were included in this study. The main outcome measure was diabetes onset., Results: This study included 128,594 participants and 6,729 participants who developed type 2 diabetes in the study period. Skipping breakfast, fast eating, snacking after dinner, and eating meals before sleeping were linked with the risk of the incidence of type 2 diabetes. In individuals with a BMI < 25 kg/m 2 , fast eating (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.37-1.90), and eating meals before sleeping (HR: 1.09, 95% CI: 1.02-1.17) were likewise associated with an increased risk of incident type 2 diabetes. Nevertheless, fast eating (HR: 1.08, 95% CI: 0.89-1.30) and meals before sleeping (HR: 0.94, 95% CI: 0.88-1.01) were not related to the occurrence of type 2 diabetes in individuals with a BMI ≥25 kg/m 2 (P value for interaction = 0.0007 [fast eating] and 0.007 [meals before sleeping], respectively). No significant interaction effect between sex and eating behavior was found., Conclusions: With respect to Japanese people, especially in people with a BMI < 25 kg/m 2 , eating behaviors may be a risk factor for the occurrence of type 2 diabetes., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Erythromelalgia is a rare disease characterized by a triad of recurrent burning pain, redness with pain, and hot flashes in the legs during attacks. We report the case of a 40-year-old woman who suffered from refractory erythromelalgia for 15 years and was successfully managed with Kampo medicine and acupuncture. Her pain was refractory to seven types of oral medications and intravenous lidocaine injections. Byakkokaninjinto was also administered for concomitant polydipsia in addition to acupuncture, unseiin, orengedokuto, and sokeikakketsuto. Because erythromelalgia has no established treatment, traditional Kampo medicine combined with acupuncture may help improve the quality of life of affected patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kumada et al.)

Background: We found that conventional controlling nutritional status (CONUT) score can serve as a sensitive prognostic marker. Some prognostic indicators do include C-reactive protein (CRP), such as the CRP-lymphocyte ratio (CLR), CRP-albumin-lymphocyte index (CALLY), and CRP-albumin ratio (CAR). However, CRP has not been combined with the CONUT score, which we believe could result in a more sensitive marker. This study evaluated the combined use of the CONUT score and CRP to predict prognostic outcomes in elderly non-small cell lung cancer (NSCLC) patients undergoing surgical resection., Methods: This study involved the retrospective analysis of 114 NSCLC patients who were over 80 years old and underwent curative resection. The summation of the CRP score and CONUT score was defined as the combined CRP and controlling nutritional status (C-CONUT) score. The capacity of CRP, CONUT score, and C-CONUT score to predict overall survival (OS) was evaluated via receiver operating characteristics (ROC) curves. Prognostic markers for OS were then identified using the Cox proportional hazards regression model., Results: The ROC curves identified the C-CONUT score as the most reliable marker of prognosis (area under the curve =0.745). Forty-seven patients were included in the high C-CONUT (≥3) group, while 67 patients were included in the low C-CONUT (0 to 2) group. Worse prognosis rates were observed in the high C-CONUT group in comparison to the low C-CONUT group in terms of OS (five-year OS: 39.8% versus 87.4%, P<0.001). Lymphatic invasion (P<0.001), histological findings (P=0.02), and C-CONUT score [hazard ratio (HR): 5.07, 95% confidence interval (CI): 2.39-10.8, P<0.001] were identified as exclusive markers for OS prognosis in the multivariate analysis., Conclusions: Our current findings indicate that C-CONUT score may serve as an innovative prognostic marker in the elderly NSCLC population., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-435/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Introduction: Isodicentric Y chromosomes are relatively common structural variants of the human genome. The underlying mechanism of isodicentric Y chromosomes with short arm breakpoints [idic(Yq)] remains to be clarified., Case Presentation: We encountered a Japanese man with azoospermia and mild short stature. G-banding and array-based comparative genomic hybridization indicated that his karyotype was 45,X/46,X,idic(Y)(qter→p11.32::p11.32→qter) with a ∼1.8 Mb terminal deletion. Whole-genome sequencing suggested that the Y chromosome had four breakpoints in a ∼7 kb region of the pseudoautosomal region 1 (PAR1)., Conclusion: This case was assumed to have an idic(Yq) resulting from multiple DNA double-strand breaks in PAR1. This rearrangement may have been facilitated by the PAR1-specific chromatin architecture. The clinical features of the patient can be ascribed to SHOX haploinsufficiency and the presence of a 45,X cell line, although copy-number gains of some Yq genes and the size reduction of PAR1 may also contribute to his spermatogenic failure., (© 2024 S. Karger AG, Basel.)

Background: Over the past 2 years, researchers have used various medical licensing examinations to test whether ChatGPT (OpenAI) possesses accurate medical knowledge. The performance of each version of ChatGPT on the medical licensing examination in multiple environments showed remarkable differences. At this stage, there is still a lack of a comprehensive understanding of the variability in ChatGPT's performance on different medical licensing examinations., Objective: In this study, we reviewed all studies on ChatGPT performance in medical licensing examinations up to March 2024. This review aims to contribute to the evolving discourse on artificial intelligence (AI) in medical education by providing a comprehensive analysis of the performance of ChatGPT in various environments. The insights gained from this systematic review will guide educators, policymakers, and technical experts to effectively and judiciously use AI in medical education., Methods: We searched the literature published between January 1, 2022, and March 29, 2024, by searching query strings in Web of Science, PubMed, and Scopus. Two authors screened the literature according to the inclusion and exclusion criteria, extracted data, and independently assessed the quality of the literature concerning Quality Assessment of Diagnostic Accuracy Studies-2. We conducted both qualitative and quantitative analyses., Results: A total of 45 studies on the performance of different versions of ChatGPT in medical licensing examinations were included in this study. GPT-4 achieved an overall accuracy rate of 81% (95% CI 78-84; P<.01), significantly surpassing the 58% (95% CI 53-63; P<.01) accuracy rate of GPT-3.5. GPT-4 passed the medical examinations in 26 of 29 cases, outperforming the average scores of medical students in 13 of 17 cases. Translating the examination questions into English improved GPT-3.5's performance but did not affect GPT-4. GPT-3.5 showed no difference in performance between examinations from English-speaking and non-English-speaking countries (P=.72), but GPT-4 performed better on examinations from English-speaking countries significantly (P=.02). Any type of prompt could significantly improve GPT-3.5's (P=.03) and GPT-4's (P<.01) performance. GPT-3.5 performed better on short-text questions than on long-text questions. The difficulty of the questions affected the performance of GPT-3.5 and GPT-4. In image-based multiple-choice questions (MCQs), ChatGPT's accuracy rate ranges from 13.1% to 100%. ChatGPT performed significantly worse on open-ended questions than on MCQs., Conclusions: GPT-4 demonstrates considerable potential for future use in medical education. However, due to its insufficient accuracy, inconsistent performance, and the challenges posed by differing medical policies and knowledge across countries, GPT-4 is not yet suitable for use in medical education., Trial Registration: PROSPERO CRD42024506687; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=506687., (©Mingxin Liu, Tsuyoshi Okuhara, XinYi Chang, Ritsuko Shirabe, Yuriko Nishiie, Hiroko Okada, Takahiro Kiuchi. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 25.07.2024.)

Aims/introduction: Efficacy of long-term low-carbohydrate diets (LCD) to improve glycemic management for type 2 diabetes remains controversial. Thus, we investigated the association between long-term LCD and glycemic control in individuals with type 2 diabetes., Materials and Methods: We searched PubMed, Embase and the Cochrane Database for articles published up to June 2023, and included randomized controlled trials conducted on LCD interventions for >12 months in adults with type 2 diabetes. Primary outcome was the difference in glycated hemoglobin between long-term LCD and control groups. Additionally, we evaluated the differences in changes in systolic and diastolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and weight between long-term LCD and control groups., Results: Six studies were identified and met the inclusion criteria. This study did not show significant differences in changes in glycated hemoglobin between long-term LCD and control diets (standardized mean difference -0.11, 95% confidence interval -0.33 to 0.11, P = 0.32). As with glycemic control, there were no significant differences in the changes in weight loss, blood pressure, and low-density lipoprotein cholesterol between long-term LCD and control diets. However, long-term LCD were associated with greater elevation in high-density lipoprotein cholesterol (standardized mean difference 0.22, 95% confidence interval 0.04-0.41; P = 0.02) and decrease in triglyceride (standardized mean difference -0.19; 95% confidence interval -0.37 to 0.02; P = 0.03) than that in control diets., Conclusions: Our findings suggest efficacy of long-term LCD in treating dyslipidemia in individuals with type 2 diabetes, but do not recommend long-term LCD for glycemic control in the individuals., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Mutations in isocitrate dehydrogenase (IDH) genes, an early step in the ontogeny of lower-grade gliomas, induce global epigenetic changes characterized by a hypermethylation phenotype and are critical to tumor classification, treatment decision making, and estimation of patient prognosis. The introduction of IDH inhibitors to block the oncogenic neomorphic function of the mutated protein has resulted in new therapeutic options for these patients. To appreciate the implications of these recent IDH inhibitor results, it is important to juxtapose historical outcomes with chemoradiotherapy. Herein, we rationally evaluate recent IDH inhibitor data within historical precedents to guide contemporary decisions regarding the role of observation, maximal safe resection, adjuvant therapies, and the import of patient and tumor variables. The biological underpinnings of the IDH pathway and the mechanisms, impact, and limitations of IDH inhibitors, the actual magnitude of tumor regression and patient benefit, and emergence of resistance pathways are presented to guide future trial development. Management in the current, molecularly defined era will require careful patient selection and risk factor assessment, followed by an open dialog about the results of studies such as INDIGO, as well as mature data from legacy trials, and a discussion about risk-versus-benefit for the choice of treatment, with multidisciplinary decision making as an absolute prerequisite.

In the context of local injection techniques, there are infectious complications such as epidural abscesses and pyogenic spondylitis. An 83-year-old female who received an injection into the paraspinal muscles for lower back pain four years ago developed a paraspinal muscle abscess accompanied bymethicillin-susceptible Staphylococcus aureus bacteremia and multiple sites of pyogenic spondylitis. Non-surgical treatment was followed with 73 days of antibiotic therapy by cefazoline. We noted an improvement in inflammatory response in blood tests and findings of inflammation on imaging tests. Instances of delayed-onset infectious complications several years after simple local injection techniques are rare., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shinta et al.)

Objectives: The endoscopic pressure study integrated system (EPSIS) is an endoscopic diagnostic system utilized for evaluation of lower esophageal sphincter function. Although previous studies have determined that EPSIS was effective as a tool for the diagnosis of achalasia, it remains uncertain if EPSIS can detect significant changes before and after peroral endoscopic myotomy (POEM), which is the premier treatment for achalasia. This study aimed to evaluate the effectiveness of EPSIS as an objective diagnostic tool for assessing the clinical effect of POEM., Methods: We conducted a retrospective analysis of patients who underwent POEM from January 2022 to December 2023. The patients underwent EPSIS preoperatively and 2 months postoperatively. Intragastric pressure (IGP) parameters, including the maximum IGP, IGP difference, and waveform gradient were compared pre- and post-POEM. These parameters also were compared between two groups: the postoperative gastroesophageal reflux disease (GERD) group and the non-GERD group., Results: A total of 50 patients were analyzed. The mean maximum IGP was significantly lower postoperatively than preoperatively (15.0 mmHg vs. 19.8 mmHg, P < 0.001). The mean IGP difference and waveform gradient were also significantly lower postoperatively than preoperatively (8.0 mmHg vs. 12.2 mmHg, P < 0.001; and 0.26 mmHg/s vs. 0.43 mmHg/s, P < 0.001, respectively). The mean postoperative waveform gradient was significantly lower in the GERD group (17 patients, 34%) than in the non-GERD group (33 patients, 66%) (0.207 mmHg vs. 0.291 mmHg, P = 0.034)., Conclusion: The results supported the use of EPSIS as an effective diagnostic tool for assessing the effect of POEM., (© 2024 Japan Gastroenterological Endoscopy Society.)

Background: The International Committee of Medical Journal Editors (ICMJE) has published Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals. These provide a global standard for writing and editing medical articles, including research integrity. However, no study has examined the research integrity-related content of Japanese medical journals' Instructions for Authors. We therefore compared research integrity content in ICMJE member journals with those in the English- and Japanese-language journals of the Japanese Association of Medical Sciences (JAMS)., Materials and Methods: This was a descriptive literature study. We obtained Instructions for Authors from English- and Japanese-language journals listed on the JAMS website and the ICMJE member journals listed on the ICMJE website as of September 1, 2021. We compared the presence of 20 topics (19 in the ICMJE Recommendations plus compliance with ICMJE) in the Instructions for Authors, and analyzed the content of the conflict of interest disclosure., Results: We evaluated 12 ICMJE member journals, and 82 English-language and 99 Japanese-language subcommittee journals. The median number of topics covered was 10.5 for ICMJE member journals, 10 for English-language journals, and three for Japanese-language journals. Compliance with ICMJE was mentioned by 10 (83%) ICMJE member journals, 75 (91%) English-language journals, and 29 (29%) Japanese-language journals. The ICMJE Conflicts of Interest Disclosure Form was requested by seven (64%) ICMJE member journals, 15 (18%) English-language journals, and one (1%) Japanese-language journal., Conclusions: Although the topics in the JAMS English-language journals resembled those in the ICMJE member journals, the median value of ICMJE-related topic inclusion was approximately one-third lower in JAMS Japanese-language journals than in ICMJE member journals. It is hoped that Japanese-language journals whose conflict of interest disclosure policies differ from ICMJE standards will adopt international standards to deter misconduct and ensure publication quality., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KI received research grants from The Nippon Foundation – Osaka University Project for Infectious Disease Prevention, the Watanabe Memorial Foundation for the Advancement of New Technology, (R2-524), the Inamori Foundation, and the Japan Society for the Promotion of Science (Grant-in-Aid for Early-Career Scientists, 23K12845); and received honoraria from Mimir, Inc., outside the submitted work. YN reports donation from Datack, outside the submitted work. HO reports research grants from I&H Co., Ltd., KRAFT Inc., donation from Neo Plus Pharma Co., Ltd., and YUYAMA Co., Ltd. TN reports research grants from I&H Co., Ltd., Cocokarafine Co., Ltd., and Konica Minolta Inc.; consulting fees from Otsuka Pharmaceutical; honoraria from Pfizer Japan, Merck Sharp & Dohme, Chugai Pharmaceutical, Takeda Pharmaceutical, Janssen Pharmaceutical K.K., Boehringer Ingelheim, Eli Lilly Japan K.K., Maruho, Mitsubishi Tanabe Pharma, Novartis Pharma, Allergan Japan, Novo Nordisk Pharma, Toa Eiyo, Dentsu, and GlaxoSmithKline, Abbott; Stock options from Bon Bon Inc.; and donations from CancerScan and YUYAMA Co., Ltd. All other authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous five years; no other relationships or activities that could appear to have influenced the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Koizumi 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.)

Background: Compartment syndrome commonly occurs in patients with forearm and lower leg fractures. Compartment syndromes of the gluteal and thigh muscles are less common. It is imperative that compartment syndrome be diagnosed and treated with fasciotomy as soon as possible. However, there are few reports on the diagnosis and treatment strategies for compartment syndromes that occur simultaneously in multiple anatomical regions or in the ipsilateral gluteal region and thigh., Case Presentation: We report on a 76-year-old man who was obliquely crushed under a tree extending from the right forearm to the left groin. He was brought to our emergency room, where he was diagnosed with compartment syndrome of the right forearm and left lower leg and crush syndrome. Emergency fasciotomy was performed. On the day after admission, swelling and tightness of the left gluteal thigh became apparent, and intracompartmental pressures were elevated, which led to an additional diagnosis of these compartment syndromes. A fasciotomy was performed, the gluteal skin incision was made according to the Kocher-Langenbeck approach (one of the posterior approaches for hip fractures), and the thigh was approached by extending the incision laterally. This surgical approach enabled the decompression of the compartments through a single incision and allowed for easier wound treatment and closure., Conclusion: This case highlights the diagnosis and treatment of compartment syndrome in four anatomical regions. Extension of the Kocher-Langenbeck approach to the lateral thigh can be a useful surgical approach for ipsilateral gluteal and thigh compartment syndrome., (© 2024. The Author(s).)

Objectives: Endoscopic resection (ER) for gastric submucosal tumors (SMTs) has gained prominence in recent years, with studies emerging from various countries. However, there is a paucity of reports from Japan. We aimed to elucidate the efficacy and safety of ER for gastric SMT in Japan., Methods: In this retrospective observational study, we investigated the outcomes of consecutive patients who underwent ER for gastric SMT from January 2017 to May 2023. The outcome variables assessed included the complete resection rate, procedure time, closure-related outcomes, and the incidence of adverse events., Results: A total of 13 patients were included in the analysis. The median procedure time was 163 (55-283) min. Complete full-thickness resection was performed in seven cases, while in four cases, the serosa remained, and in two cases, the outer layer of the muscularis propria remained. In two cases where the SMT was located on the anterior side, conversion to laparoscopic surgery became necessary, resulting in a procedural success rate of 84.6% (11/13). Excluding these two cases, endoscopic closure of the defect was successfully accomplished in the remaining 11 cases. R0 resection was achieved in 12 out of 13 cases (92.3%). Although one patient had peritonitis, which was successfully treated conservatively, no other treatment-related adverse events were encountered., Conclusions: Although ER for SMT on the anterior side may be challenging, our experience revealed that ER is a safe and efficacious approach for gastric SMT., Competing Interests: Author Haruhiro Inoue is an advisor for Olympus Corporation and Top Corporation. He has also received educational grants from Olympus Corporation and Takeda Pharmaceutical Co. The other authors declare no conflict of interest., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Dysgonomonas capnocytophagoides shows multidrug resistance to antibiotics and causes opportunistic infections in immunocompromised hosts. The drug resistance mechanisms of D. capnocytophagoides have not yet been identified. In this work, we analyzed D. capnocytophagoides isolated from a fatal case of peritonitis to clarify its drug resistance mechanisms. Whole genome sequencing revealed that our isolate harbored a chromosomally encoded metallo-beta-lactamase (designated bla DYB-1 ) and a chromosomally encoded ermFS gene. Phylogenetic analysis, primary sequence comparison, and structural modeling analysis of DYB-1 showed it was highly similar to CfiA in Bacteroides fragilis and belonged to the B1 MBL family. Transformation analysis into Escherichia coli TOP10 showed that a recombinant plasmid containing bla DYB-1 increased the minimum inhibitory concentration of beta-lactams, including carbapenem. We identified a novel chromosomally encoded class B1 metallo-beta-lactamase gene designated bla DYB-1 and an ermFS gene that contributed to multidrug resistance. This study indicates the importance of further surveillance for D. capnocytophagoides harboring bla DYB-1 ., Competing Interests: Declarations of Competing Interest The authors declare that they have no conflicts of interests, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME., Methods: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant. Bispecific IL-13Rα2/TGF-β CAR-T cells were evaluated for efficacy and safety against both patient-derived GBM xenografts and syngeneic models of murine glioma., Results: Treatment with IL-13Rα2/TGF-β CAR-T cells leads to greater T-cell infiltration and reduced suppressive myeloid cell presence in the tumor-bearing brain compared to treatment with conventional IL-13Rα2 CAR-T cells, resulting in improved survival in both patient-derived GBM xenografts and syngeneic models of murine glioma., Conclusion: Our findings demonstrate that by reprogramming tumor-specific T-cell responses to TGF-β, bispecific IL-13Rα2/TGF-β CAR-T cells resist and remodel the immunosuppressive TME to drive potent anti-tumor responses in GBM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A three-dimensional convolutional neural network model was developed to classify the severity of chronic kidney disease (CKD) using magnetic resonance imaging (MRI) Dixon-based T1-weighted in-phase (IP)/opposed-phase (OP)/water-only (WO) imaging. Seventy-three patients with severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m 2 , CKD stage G4-5); 172 with moderate renal dysfunction (30 ≤ eGFR < 60 mL/min/1.73 m 2 , CKD stage G3a/b); and 76 with mild renal dysfunction (eGFR ≥ 60 mL/min/1.73 m 2 , CKD stage G1-2) participated in this study. The model was applied to the right, left, and both kidneys, as well as to each imaging method (T1-weighted IP/OP/WO images). The best performance was obtained when using bilateral kidneys and IP images, with an accuracy of 0.862 ± 0.036. The overall accuracy was better for the bilateral kidney models than for the unilateral kidney models. Our deep learning approach using kidney MRI can be applied to classify patients with CKD based on the severity of kidney disease., (© 2024. The Author(s).)

Background: The Banff Working Group has updated the histological classification of BK virus nephropathy (BKVN), highlighting the importance of early detection. However, an early detection strategy for BKVN using biopsy has not yet been established. Our investigation aimed to assess the efficacy of protocol biopsy for the diagnosis of BKVN., Methods: We performed a retrospective cohort study of 314 patients who had undergone kidney transplantation between 2006 and 2021. Kidney allograft biopsies were performed as part of a protocol biopsy at 3 months and 1 year post-transplantation. Following the diagnosis of BKVN, the immunosuppressant dose was reduced., Results: Twelve patients (3.8%) were diagnosed with BKVN by biopsy. Most diagnoses are established during the early stages of BKVN (polyomavirus nephropathy class 1 in six, class 2 in five, and class 3 in one). Following the reduction in immunosuppressant dose, kidney allograft function did not deteriorate in any patients. Additionally, test for BK virus DNA in the blood was negative. All but one patient demonstrated histological resolution of BKVN, and the other had a very slight positivity for the simian virus 40 large T antigen. The median follow-up time after BKVN diagnosis was 6 years. One patient developed de novo donor-specific antibody and subclinical acute antibody-mediated rejection that was successfully cured., Conclusions: Our analysis indicates that protocol biopsy may enable the early detection of BKVN, resulting in the preservation of kidney function., (© 2024 Wiley Periodicals LLC.)

Objective The characteristics of gastric cancer in patients with atrophic mucosa and no apparent history of Helicobacter pylori eradication have not been thoroughly investigated. Therefore, this study examined the clinicopathological characteristics of gastric cancer in these patients. Methods We retrospectively examined the endoscopic and pathological characteristics of gastric cancer in patients who underwent endoscopic submucosal dissection. Patients or Materials We divided the patients into 2 groups: those with gastric atrophy and no history of eradication (group A; n =102) and those with a history of eradication (group B; n =161). In group A, patients were further divided into mild atrophy (group C) and severe atrophy (group D) groups, while group B was further divided into those who underwent eradication treatment >5 years ago (group E) and those who underwent eradication 1-5 years ago (group F). Results Group A comprised significantly older individuals (75±8.0 vs. 71±7.5 years old, p <0.001) with a higher frequency of elevated gastric cancer than group B (32.4% vs. 17.4%, p =0.006). Compared with group E, group A was older and had a greater incidence of elevated gastric cancer. The incidence of gastric cancer in the U or M region was lower in group C than in group D. Conclusion Gastric cancer in patients with gastric atrophy and no history of eradication was associated with an older age and higher frequency of elevated-type morphology than in those with a history of eradication.

Objective: The development of acquired middle ear cholesteatoma is associated with a single nucleotide polymorphism, 538G>A, in the human adenosine triphosphate-binding cassette transporter C11 (ABCC11) gene, which is a determinant of the earwax morphotype, such as wet- and dry-type earwax; however, the mechanism underlying this association is unclear. We focused on the earwax pH and aimed to elucidate the mechanism between ABCC11 genotypes and acquired middle ear cholesteatoma., Study Design: Prospective observational study., Setting: Single-center, academic hospital., Methods: We recruited 40 patients with acquired middle ear cholesteatoma who underwent surgery and 115 controls with no history of middle ear cholesteatoma. We assessed the earwax pH and ABCC11 genotypes in all participants. Clinical information was collected from the patients with cholesteatoma., Results: The earwax pH was significantly less acidic in patients with cholesteatoma and those carrying wet earwax genotypes (ABCC11 538G/G or 538G/A) than in the controls and those carrying the dry earwax genotype (ABCC11 538A/A), respectively. Furthermore, earwax pH was significantly positively correlated with high preoperative cholesteatoma stages in the patients with cholesteatoma., Conclusion: Our results show that the less acidic earwax pH was significantly related to the development and progression of acquired middle ear cholesteatoma. The less acidic earwax pH may play an important role in the mechanism underlying the association between acquired middle ear cholesteatoma and the ABCC11 gene at site 538., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

[Purpose] This study aimed to determine whether applying electrical stimulation to the deltoid and extensor digitorum muscles could lead to a reduction in fixation force during shoulder joint adduction and grip strength. [Participants and Methods] Fifteen healthy adult males participated in this study. In the shoulder adduction force experiment, the middle fibers of the deltoid muscle of the dominant arm were electrically stimulated. In the grip strength experiment, the extensor digitorum muscle of the dominant arm was electrically stimulated. The forces exerted with and without the electrical stimulation were measured. [Results] The torque of the shoulder adduction force decreased significantly with electrical stimulation, while no significant change was observed in normalized grip strength with electrical stimulation. [Conclusion] The response of antagonist muscles to electrical stimulation varied according to location., Competing Interests: The authors declare no competing interests., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Competing Interests: Declaration of competing interest None.