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Type I X-ray bursts are rapid-brightening transient phenomena on the surfaces of accreting neutron stars (NSs). Some X-ray bursts, called clocked bursters, exhibit regular behavior with similar light-curve profiles in their burst sequences. The periodic nature of clocked bursters has the advantage of constraining X-ray binary parameters and physics inside the NS. In the present study, we compute numerical models, based on different equations of state and NS masses, which are compared with the observations of a recently identified clocked burster, 1RXS J180408.9−342058. We find that the relation between the accretion rate and the recurrence time is highly sensitive to the NS mass and radius. We determine, in particular, that 1RXS J180408.9−342058 appears to possess a mass less than 1.7 M _⊙ and favors a stiffer nuclear equation of state (with an NS radius ≳12.7 km). Consequently, the observations of this new clocked burster may provide additional constraints for probing the structure of NSs.

Background: The diurnal rhythm in water and solute diuresis is known to be disturbed in older adults with nocturia due to nocturnal polyuria. We estimated the prevalence of increased natriuresis in nocturia due to nocturnal polyuria by comparing individuals with and without nocturnal polyuria., Methods: We calculated the night-to-day ratio of excreted urinary sodium and potassium concentrations adjusted for urinary creatinine concentration and urinary osmolality using spot urine samples collected at 2 PM (daytime) and 6 AM (nighttime) and compared results among controls with nocturia and paitents with nocturia with and without nocturnal polyuria., Results: Among 83 patients aged 50 to 86 years, the mean night-to-day ratio of excreted urinary sodium and potassium concentrations in the nocturia group with nocturnal polyuria (n = 40) was 2.5, which was significantly higher (p = 0.034) than those in the control group (n = 23; 0.7) and the nocturia group without nocturnal polyuria (n = 20; 0.9). After adjustment for age, no difference in potassium and urinary osmolality existed among groups. Thirteen patients (33%) in the nocturia group with nocturnal polyuria showed increased natriuresis when a 2.0 night-to-day ratio of excreted urinary sodium was applied as a cut-off for increased natriuresis, whereas only 3 (7%) patients in the combined groups without nocturnal polyuria had increased natriuresis (p = 0.005)., Conclusions: One-third of patients with nocturia due to nocturnal polyuria had increased natriuresis. Assessment of a night-to-day ratio of excreted urinary sodium using spot urine samples could facilitate a better understanding of the underlying pathophysiology and optimal management of nocturnal polyuria., (© 2025 Wiley Periodicals LLC.)

Objective: We investigated the impact of intraoperative tumor capsule injury (TCI) during robot-assisted partial nephrectomy (RAPN) or laparoscopic partial nephrectomy (LPN) on oncological outcomes, as well as underlying factors of intraoperative TCI for improving surgical outcomes., Methods: A total of 253 patients who underwent RAPN or LPN between 2010 and 2022 were retrospectively analyzed and were divided into two groups: non-TCI and TCI groups. The background was compared between two groups. We investigated the surgical records or video to evaluate TCI and seek the possible causes for TCI. Multivariate logistic regression analysis was performed to identify prognostic factors for cancer recurrence., Results: Of the 253 patients, 227 have renal cell carcinoma (RCC), with 29 patients having TCI. The TCI group had larger tumors, a lower rate of trifecta achievement, higher bleeding, higher T stage, and a lower rate of clear cell RCC (ccRCC) histological types as compared to non-TCI group. Disease recurrence rate was 13.8% with TCI and 1.0% with non-TCI (odds ratio 15.7; 95% confidence interval, 2.73-90.1; p = 0.003). Univariate and multivariate analyses confirmed TCI as an independent prognostic factor for disease-free survival. Compared with ccRCC, non-clear cell RCC (non-ccRCC) was found to have a higher probability of TCI and a significantly thinner capsule thickness on pathological evaluation., Conclusion: TCI had a negative impact on oncological outcomes. Surgeons should consider thickness of tumor capsules, especially in cases with non-ccRCC, to minimize the risk of TCI during partial nephrectomy., (© 2025 The Japanese Urological Association.)

Background : Hydrogen gas (H 2 ) has been shown to be effective in the treatment of various clinical conditions, from acute illnesses to chronic illnesses. However, its clinical indications and the corresponding appropriate hydrogen delivery methods have yet to be determined. This is due to the fact that the pharmacokinetics and pharmacodynamics of hydrogen in each delivery method have not been experimentally proven. Here, we verified the pharmacokinetics of hydrogen after the infusion of hydrogen-saturated saline. Methods : Hydrogen-saturated saline was prepared and checked for sterility and component specifications. Hydrogen-saturated saline was administered intravenously (125 mL/h) through the left internal jugular vein of pigs, and the blood hydrogen concentration was measured over time. Results : It was confirmed that hydrogen can be safely mixed under pressure into intravenous solutions (pharmaceutical products) without the contamination of foreign substances by using a needle-less vial access cannula. No change in the PH or composition of the solution was observed due to hydrogen filling. The hydrogen concentrations of blood samples collected from the left internal jugular vein 3 cm to the heart from the tip of the infusion line were 6.4 (30 min), 4.7 (60 min), 4.9 (90 min), and 5.3 (120 min) ppb w / w , respectively. The hydrogen concentrations of blood samples collected from the right atrium were 0.7 (30 min), 0.5 (60 min), 0.7 (90 min), and 0.7 (120 min) ppb, respectively. The hydrogen concentration of blood samples collected from the right internal carotid artery were 0.1 (pre), 0.2 (30 min), 0.3 (60 min), 0.0 (90 min), and 0.0 (120 min) ppb w / w , respectively. Conclusions : We confirmed that hydrogen could be safely pressurized and filled into intravenous (pharmaceutical) solution without contamination by foreign objects using a needle-free vial access cannula. When saturated hydrogen saline was dripped intravenously, almost all of the hydrogen was expelled during its passage through the lungs and could not be supplied to the arterial side.

Lysophosphatidylethanolamine (LPE) is a bioactive lipid mediator involved in diverse cellular functions. In this study, we investigated the effects of three LPE species, 1-palmitoyl LPE (16:0 LPE), 1-stearoyl LPE (18:0 LPE), and 1-oleoyl LPE (18:1 LPE) on pre-osteoblast MC3T3-E1 cells. All LPE species stimulated cell proliferation and activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1/2. MAPK/ERK1/2 activation by 16:0 LPE and 18:1 LPE was inhibited by the Gq/11 inhibitor YM-254890, while activation by 18:0 LPE was blocked by the Gi/o inhibitor pertussis toxin. Intracellular Ca 2+ transients were triggered by 16:0 LPE and 18:1 LPE but not by 18:0 LPE, with YM-254890 suppressing these responses. These results suggest that 16:0 and 18:1 LPE act via Gq/11-coupled G protein coupled receptors (GPCRs), and 18:0 LPE acts via Gi/o-coupled GPCRs. Furthermore, receptor desensitization experiments suggested that each LPE acts through distinct GPCRs. Interestingly, 18:0 LPE suppressed osteogenic differentiation, reducing mineralization, alkaline phosphatase activity, and osteogenic gene expression, whereas 16:0 LPE and 18:1 LPE had no such effects. These results suggest the physiological significance of LPEs in bone formation and indicate that different LPE species and their receptors play distinctive roles in this process., Competing Interests: Declarations. Competing interests: The 24-well plates with a special surface modification used in this study were generously provided free of charge by the Stella Chemifa Corporation. T.U. and N.S. are patent holders for the 24-well plates featuring the special surface modification. Additionally, a separate collaborative research agreement, including funding support, has been established with Stella Chemifa Corporation; however, the agreement is unrelated to the present study., (© 2024. The Author(s).)

Introduction: Limited evidence exists regarding differences in post-operative renal function and ileal conduit-related complications, including ureteroenteric anastomotic stricture (UAS) and parastomal hernia (PH), between radical cystectomy (RC) with extracorporeal urinary diversion (ECUD) and robot-assisted RC with intracorporeal UD (ICUD)., Methods: We retrospectively collected the baseline and post-RC follow-up data from 179 patients receiving RC with ileal conduit UD (152 ECUD and 27 ICUD). The estimated glomerular filtration rate (eGFR, mL/min/1.73 m 2 ) and occurrence of UAS and PH were post-operatively monitored. Chronic kidney disease (CKD) stages were determined based on eGFR level. UD-related complications were evaluated using the Clavien-Dindo system. Time-course changes in eGFR level and CKD-related survival rates were compared in both the original and propensity score-matched cohorts., Results: Although the original ECUD group had higher eGFR levels (median, 60.9 vs. 52.1), comparison of the adjusted cohorts revealed no significant difference at any time points, CKD upstaging-free survival, and CKD stage 3b-free survival. Out of 179 patients, three (1.7%), eight (4.5%), and 14 (7.8%) experienced grade I, II, and IIIa UAS, respectively. Thirteen (7.3%) developed PH during follow-up. No significant differences were observed in UAS rates (p = 0.38), PH rates (p = 0.69), CKD upstaging-free survival, and CKD stage 3b-free survival between two groups., Conclusion: No significant difference was observed in post-operative renal function and UD-related complication rates among the different types of surgery in patients undergoing RC in our institute. Further research is needed to determine the optimal surgical approach for each patient to minimize risks of CKD upstaging, UAS, and PH., (© 2025 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Objectives: This study aimed to describe the treatment selection for systemic lupus erythematosus (SLE) using data from the Kyushu Collagen Disease Network for SLE (KCDN-SLE) registry, a multicentre prospective registry in Japan., Methods: This study used data from patients registered between August 2022 and November 2023. Clinical characteristics, purpose of agent initiation, other candidate agents, and short-term efficacy and safety were evaluated., Results: We analysed 69 previously treated patients with SLE (mean age 43.7 years; 62 females, 7 males). Hydroxychloroquine, biological agents, and immunosuppressive agents were initiated during the maintenance phase in 12, 41, and 16 patients, respectively. In patients with active organ involvement, hydroxychloroquine and biological agents were widely used for initiation. In those who already achieved treatment goals, biological agents alone were predominantly selected. The SLE Disease Activity Index 2000 score and prednisolone dose declined significantly over a 6-month follow-up period. Among 48 patients with active disease, 22 achieved a lupus low disease activity state, but this had no evident association with the initiation of a biological agent. In total, 14 adverse events, predominantly infections, were observed., Conclusions: Biological agents were used preferentially, and the therapeutic agents were appropriately effective and mostly achieved the purpose of agent initiation., (© Japan College of Rheumatology 2024. Published by Oxford University Press. 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.)

In almost all cancers, the p53 pathway is disabled and cancer cells survive. Hence, it is crucially important to induce cell death independent of p53 in the treatment of cancers. The transcription factor E2F1 is controlled by binding of the tumor suppressor pRB, and induces apoptosis by activating the ARF gene, an upstream activator of p53, when deregulated from pRB by loss of pRB function. Deregulated E2F1 can also induce apoptosis, independent of p53, via other targets such as TAp73 and BIM . We searched for novel E2F1-interacting proteins and identified the RNA helicase DEAD/H box 5 (DDX5), which also functions as a transcriptional coactivator. In contrast to the reported growth-promoting roles of DDX5, we show that DDX5 suppresses cell growth and survival by augmentation of deregulated E2F1 activity. Over-expression of DDX5 enhanced E2F1 induction of tumor suppressor gene expression and cell death. Conversely, shRNA-mediated knockdown of DDX5 compromised both. Moreover, DDX5 modulated E2F1-mediated cell death independent of p53, for which DDX5 also functions as a coactivator. Since p53 function is disabled in almost all cancers, these results underscore the roles of DDX5 in E2F1-mediated induction of cell death, independent of p53, and represent novel aspects for the treatment of p53-disabled cancer cells.

Background/Objectives : The standard recommendation for patients with non-muscle invasive bladder cancer is 5-aminolevulinic acid-mediated photodynamic diagnosis. The intensity of the fluorescence caused by the intracellular accumulation of protoporphyrin IX (PPIX) varies among tumors and patients. This study investigated the circadian rhythm of intracellular PPIX accumulation in bladder urothelial cancer cells exposed to 5-aminolevulinic acid. Methods : The expression of two clock genes, PER2 and BMAL1 , and their impact on intracellular PPIX accumulation were evaluated in two bladder cancer cell lines, UM-UC-3 and J82, and mouse xenograft models. We evaluated the enzymes involved in the heme synthesis pathway that potentially affect the circadian rhythm of intracellular PPIX accumulation. The red fluorescence intensity of the images captured during photodynamic diagnosis-assisted transurethral resection of bladder tumors was quantified and compared among the four groups according to surgery start time: 9 a.m.-11 a.m., 11 a.m.-1 p.m., 1-3 p.m., and 3-5 p.m. Results : We observed the circadian rhythm of intracellular PPIX accumulation, which was potentially regulated by the clock genes PER2 and BMAL1 . Two enzymes involved in the heme synthesis pathway, coproporphyrinogen oxidase and ferrochelatase, exhibit a circadian rhythm. The fluorescence intensity started gradually increasing at 12 p.m., and the highest level was observed in patients who underwent surgery between 3 and 5 p.m. Conclusions : Our findings suggest that it may be possible to optimize the timing of the photodynamic diagnosis in photodynamic diagnosis-assisted transurethral resection of bladder cancer based on the circadian rhythm to improve tumor detection and treatment outcomes.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for 30% of non-Hodgkin lymphomas. Although comprehensive analysis of genetic abnormalities has led to the classification of lymphomas, the exact mechanism of lymphomagenesis remains elusive. The Ets family transcription factor, PU.1, encoded by Spi1, is essential for the development of myeloid and lymphoid cells. Our previous research illustrated the tumor suppressor function of PU.1 in classical Hodgkin lymphoma and myeloma cells. In the current study, we found that patients with DLBCL exhibited notably reduced PU.1 expression in their lymphoma cells, particularly in the non-germinal center B-cell-like (GCB) subtype. This observation suggests that downregulation of PU.1 may be implicated in DLBCL tumor growth. To further assess PU.1's role in mature B cells in vivo, we generated conditional Spi1 knockout mice using Cγ1-Cre mice. Remarkably, 13 of the 23 knockout mice (56%) showed splenomegaly, lymphadenopathy, or masses, with some having histologically confirmed B-cell lymphomas. In contrast, no wild-type mice developed B-cell lymphoma. In addition, RNA-seq analysis of lymphoma cells from Cγ1-Cre Spi1 F/F mice showed high frequency of each monoclonal CDR3 sequence, indicating that these lymphoma cells were monoclonal tumor cells. When these B lymphoma cells were transplanted into immunodeficient recipient mice, all mice died within 3 weeks. Lentiviral-transduced Spi1 rescued 60% of the recipient mice, suggesting that PU.1 has a tumor suppressor function in vivo. Collectively, PU.1 is a tumor suppressor in mature B cells, and decreased PU.1 results in mature B-cell lymphoma development., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), a Stachybotrys microspora triprenyl phenol family member, may extend this therapeutic window., Methods: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study, JX10 or placebo was administered as a single intravenous infusion to Japanese patients with acute ischemic stroke who were unable to receive tissue-type plasminogen activator or thrombectomy within 12 hours of last known normal. Primary end point was incidence of symptomatic intracranial hemorrhage with a worsening National Institutes of Health Stroke Scale score of ≥4 points within 24 hours of drug administration (symptomatic intracranial hemorrhage incidence)., Results: Ninety patients received either placebo (n=38; female 26.3%) or JX10 at 1, 3, or 6 mg/kg (n=6, 18, 28; female 0%, 33.3%, and 42.9%, respectively). Median age (range) and baseline median (range) National Institutes of Health Stroke Scale scores were respectively 76.5 (42-87) and 8 (6-21) for the combined JX10 cohort (JX10 Cohorts) and 75.0 (34-85) and 8 (6-22) for placebo. Median (range) dosing time since last known normal was 9.5 (5.0-12.1) and 10.0 (3.7-12.0) hours for JX10 Cohorts and placebo, respectively. Symptomatic intracranial hemorrhage incidence was 0% (0/52 [95% CI, 0.0-5.6]) for JX10 Cohorts versus 2.6% (1/38 [95% CI, 0.1-13.8]) for placebo ( P =0.42). Vessel patency at 24 hours (secondary end point) in patients with baseline arterial occlusive lesion score <3 (39/90) improved in 58.3% (14/24) of patients in JX10 Cohorts versus 26.7% (4/15) for placebo (odds ratio, 4.23 [95% CI, 0.99-18.07]). In JX10 Cohorts, a significantly higher proportion of patients had modified Rankin Scale scores of 0 to 1 on day 90 (secondary end point) versus placebo (JX10: 21/52, 40.4% versus placebo: 7/38, 18.4%; P =0.03)., Conclusions: JX10 was well tolerated and may expand the acute ischemic stroke therapeutic window as a novel thrombolytic agent., Registration: URL: https://rctportal.niph.go.jp/en; Unique identifier: jRCT2080223786., Competing Interests: Dr Niizuma reports study funding and article processing charges from TMS Co, Ltd. Dr Nishimura was a TMS Co, Ltd, employee during the conduct of the study, owns TMS Co, Ltd, stocks and stock options, and reports consulting fees from TMS Co, Ltd, as well as recipient of license fees for JX10-related patents. K. Hasegawa is an employee and shareholder of TMS Co, Ltd, and reports license fees for JX10-related patents. Dr Hasumi is a Director of the Board and shareholder of TMS Co, Ltd, an employee of Tokyo University of Agriculture and Technology, and reports grants from TMS Co, Ltd, and EPS Corporation, as well as license fees for JX10-related patents. Dr Wald is an employee and shareholder of Biogen. Dr Bell is a former employee of Biogen Inc. Drs Kuribayashi and Toda are employees of Biogen Japan Ltd and shareholders of Biogen Inc. Dr Tominaga declares consulting fees and license fees for a JX10-related patent from TMS Co, Ltd. The other authors report no conflicts.

Aim: Esophagogastric varices (EGV) are a serious complication of hepatitis C virus (HCV)-related liver cirrhosis (HCV-LC). In most cases, portal hypertension improves after a sustained virologic response (SVR) is achieved with direct-acting antiviral (DAA) treatment; however, in some cases, EGV exacerbation occurs after HCV elimination. We investigated whether von Willebrand factor (VWF) and a disintegrin-like metalloproteinase with thrombospondin type-1 motif 13 (ADAMTS13) can predict EGV progression with HCV-LC after SVR achievement., Methods: This retrospective study enrolled 47 patients with HCV-LC who achieved an SVR after DAA treatment. Eighteen patients experienced EGV progression after the SVR was achieved (EGV progression group). Twenty-nine patients did not experience EGV progression after the SVR was achieved (non-EGV progression group). Plasma VWF antigen levels and ADAMTS13 activity were measured the day before DAA treatment., Results: The EGV progression group had significantly higher plasma VWF antigen levels (p = 0.00331) and VWF-to-ADAMTS13 ratios (p = 0.000249) than the non-EGV progression group. Multivariate logistic regression models found that a VWF-to-ADAMTS13 ratio >2.3 was the only risk factor for EGV progression after the SVR was achieved (hazard ratio [HR], 18.4; 95% confidence interval [CI], 3.08-109; p = 0.00138). During the observation period, patients with a VWF-to-ADAMTS13 ratio >2.3 had a significantly higher cumulative incidence of EGV progression after SVR achievement than patients with a VWF-to-ADAMTS13 ratio ≤2.3 (HR, 6.4; 95% CI, 1.78-22.96; p = 0.0044)., Conclusions: The VWF-to-ADAMTS13 ratio before DAA treatment for HCV could predict EGV progression after SVR achievement., (© 2024 Japan Society of Hepatology.)

Imeglimin promotes glucose-stimulated insulin secretion in the pancreas in a glucose-dependent manner and inhibits gluconeogenesis in the liver. Meanwhile, imeglimin can improve mitochondrial function in hepatocytes. We used a nondiabetic metabolic dysfunction-associated steatohepatitis (MASH) model to examine the effects of imeglimin on MASH independent of its glucose-lowering action. Mice fed a choline-deficient high-fat diet (CDA-HFD) were orally administered imeglimin (100 and 200 mg/kg twice daily), and MASH pathophysiology was evaluated after 8 weeks. Moreover, an in vitro study investigated the effects of imeglimin on palmitic acid (PA)-stimulated lipid accumulation, apoptosis, and mitochondrial dysfunction in human hepatocytes. CDA-HFD-fed mice showed hepatic steatosis, inflammation, and fibrosis without hyperglycemia. Imeglimin reduced hepatic steatosis in response to increased expression of β-oxidation-related markers. Imeglimin reduced reactive oxygen species accumulation and increased mitochondrial biogenesis in CDA-HFD-fed mice. Consequently, imeglimin suppressed hepatocyte apoptosis and decreased macrophage infiltration with reduced proinflammatory cytokine expression, suppressing hepatic fibrosis development. PA-stimulated hepatocytes induced lipogenesis, inflammatory cytokine production, and apoptosis, which were significantly suppressed by imeglimin. In mitochondrial function, imeglimin improved PA-stimulated decrease in mitochondrial membrane potential, mitochondrial complexes activity, oxygen consumption rate, and mitochondrial biogenesis marker expression. In conclusion, imeglimin could contribute to prevention of MASH progression through suppressing de novo lipogenesis and enhancing fatty acid oxidation.

Rationale: Equivocal interstitial lung abnormality (ILA) involves less than 5% of any lung zone or presents unilaterally without satisfying the diagnostic criteria for ILA; however, the prevalence and prognosis of equivocal ILA are unknown., Objectives: To investigate the prevalence and long-term prognosis of equivocal ILA., Methods: This retrospective cohort study included individuals who underwent chest CT as part of a health check-up program in 2010 at St. Luke's International Hospital in Tokyo, Japan. ILA and equivocal ILA were diagnosed using the Fleischner Society criteria. The primary outcome was the annual rate of forced vital capacity (FVC) decline in the ILA, Equivocal ILA, and No ILA groups, evaluated using a mixed-effects model. Radiological progression was also evaluated., Results: Among the 20,896 individuals included in the study, ILA and equivocal ILA were present in 2.0% (95% CI: 1.8-2.2%) and 0.4% (95% CI: 0.4-0.5%) of individuals, respectively. Follow-up pulmonary function tests were available for 18,101 (87%) individuals, with a median follow-up time of 8.3 (interquartile range: 4.0-9.0) years. Individuals with equivocal ILA showed a significantly greater rate of FVC decline than those without ILA (-36.7 vs. -27.7 mL/year, P = 0.008). Of the 86 individuals with equivocal ILA, 20 (23%) exhibited progression during the follow-up period; of these, 19 progressed to definite ILA., Conclusions: Individuals with equivocal ILA showed a significant tendency for FVC decline compared to those without ILA. A considerable number of cases progressed to definite ILA, warranting careful attention. Clinicians should be aware that even mild interstitial changes that do not meet the current criteria for ILA may deteriorate.

Objective To investigate the clinical course of ulcerative colitis (UC) during pregnancy, focusing on their mutual influence. Methods We retrospectively reviewed the medical records of 58 patients with UC who had 73 pregnancies and 3 patients with newly developed UC during pregnancy. We recorded the rate of relapse of UC; the relationship between medication use and UC relapse during pregnancy; treatment for relapse; and the incidence of pregnancy, childbirth, and newborn abnormalities. Results UC was in remission at conception in 78% of the patients. The relapse rate during pregnancy was 27.3%, with most relapses occurring during the second and third trimesters. The relapse rate in patients in whom any UC drug had been discontinued was 50%, a rate significantly higher than the 20.5% of patients for whom all medications were continued (p = 0.016). Thiopurine was discontinued in 60% (6/10) of patients at conception, and the disease relapsed in 50% (3/6) of the patients. Most relapses were successfully treated with 5-aminosalicylic acid or corticosteroids. UC relapse occurred in 26.1% (18/70) of the patients after delivery, mostly within 2 months. Pregnancy, delivery, or neonatal abnormalities occurred in 23.3% (17/73) of patients. In two of the three patients with new-onset UC, UC was severe and required intensive care; however, the pregnancies continued uneventfully. Conclusion Although the progress of pregnancies complicated by UC was mostly uneventful, discontinuing medication carries the risk of UC relapse. Thus, appropriate management of medical treatments for UC during pregnancy is important.

A 72-year-old Japanese woman presented to our hospital with progressive hearing loss and dysphagia. Blood tests revealed elevated C-reactive protein and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Contrast-enhanced magnetic resonance imaging of the head showed hypertrophic pachymeningitis of the left middle cranial fossa with compression of the cranial nerves, including the trigeminal (V), facial (VII), glossopharyngeal (IX), and vagal (X) nerves, resulting in cranial nerve palsy. She was diagnosed with Garcin syndrome associated with otitis media with ANCA-associated vasculitis (OMAAV) and treated with high-dose glucocorticoid therapy followed by intravenous cyclophosphamide and rituximab. Therefore, OMAAV should be considered in the differential diagnosis of refractory otitis media with unilateral cranial nerve involvement.

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) varies widely in clinical presentation, and some patients experience hemoptysis. Bronchial artery embolization (BAE) is a treatment option for hemoptysis caused by NTM-PD. However, the association between post-BAE rebleeding risk and the presence of cavitary lesions has not been fully elucidated., Methods: A retrospective observational study was conducted on patients with NTM-PD who had undergone BAE at our institution. Patients were classified into Cavitary and Non-cavitary groups, and baseline characteristics and clinical outcomes were compared., Results: Among the 155 BAE cases between 2013 and 2023, 18 were included in the analysis, and four experienced rebleeding. The Cavitary group tended to have a higher rebleeding rate 24 months after BAE (37.5% vs. 10.0%, p = 0.27). Furthermore, the Cavitary group showed a significantly higher number of non-bronchial arteries involved (median number: 1.5 vs. 0.0, p = 0.02), a higher proportion of patients with a prior antibiotic treatment history (100% vs. 20%, p = 0.001), and longer duration from diagnosis to BAE (median year: 9.0 vs. 0.6, p = 0.02). The Kaplan-Meier curves showed a tendency for shorter rebleeding-free survival in the Cavitary group (p = 0.10)., Conclusions: Cavitary lesions in patients with NTM-PD may predict higher rebleeding rates after BAE. Further research with larger cohorts is needed to better understand rebleeding risk factors in BAE for NTM-PD., Competing Interests: Conflict of interest statement The authors have no conflict of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background/aim: Radiotherapy is one of the most frequently used options for prostate cancer (PCa). However, adverse effects related to irradiation of surrounding normal organs are significant clinical concerns. Specifically, genitourinary toxicity can dramatically reduce the quality of life. This clinical trial investigated the efficacy of oral 5-aminolevulinic acid phosphate combined with sodium ferrous citrate (ALA-SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source., Patients and Methods: The AMBER study was a prospective single-center trial involving patients with localized PCa who underwent LDR-BT without external-beam radiotherapy (jRCTs051190077). Fifty patients were included and instructed to take capsules of ALA-SFC twice a day (200 mg phosphate salt and 229.42 mg per day) for six months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data were collected before implantation, during ALA-SFC treatment, and at 1, 3, 6, 9, and 12 months post-LDR-BT. The primary endpoint of this trial was urinary frequency at three months. Other patient-reported outcomes, investigator-reported adverse events, and oncological outcomes were secondary endpoints., Results: Of 50 enrolled cases (45 in the per-protocol analysis, 49 in the safety analysis), urinary frequency and its increase from baseline did not differ from 141 historical controls at any time point, including at three months post-LDR-BT. Propensity score matched analysis confirmed no time-course differences in frequency, volume, or urinary symptom scores between groups. Biochemical failure-free and metastasis-free survival also remained similar., Conclusion: Oral supplementation of ALA-SFC to LDR-BT did not alleviate radiation-induced toxicity or improve oncological outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: The impact of individual biological/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) on kidney function in patients with rheumatoid arthritis (RA) remains unclear. This study aimed to determine the comparative effects of b/tsDMARDs on chronic kidney disease (CKD) incidence in patients with RA., Methods: This multicentre cohort study included patients with RA who had baseline estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m2 and started a tumor necrosis factor inhibitor (TNFi), cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig), interleukin-6 receptor inhibitor (IL-6Ri), or Janus kinase inhibitor (JAKi) in Japan. Multiple propensity score-based inverse probability weighting (IPW) was used to adjust confounders. The incidence of CKD was compared among b/tsDMARDs using IPW mixed-effect Cox proportional hazards models and linear mixed-effect models with IPW examined trajectories of eGFR., Results: Among 2187 patients with 3068 treatment courses and up to 11 years of follow-up, CKD occurred in 275 cases. Compared with the CTLA4-Ig group, the TNFi group had a significantly lower CKD incidence (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.46-0.97, p= 0.04), whereas the JAKi group had a significantly higher incidence (HR 2.16, 95% CI 1.23-3.79, p= 0.01). The trajectory of eGFR was significantly greater in the JAKi group than in the CTLA4-Ig group (CTLA4-Ig: -1.28 mL/min/1.73 m2/year, JAKi: -2.29 mL/min/1.73 m2/year, p< 0.001)., Conclusions: TNFi use was associated with reduced CKD incidence, whereas JAKi showed a less protective association for kidney function in patients with RA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor-Cre drivers resulted in motor freezing when placed in a magnetic resonance imaging machine or adjacent to a transcranial magnetic stimulation device. Functional imaging and fiber photometry confirmed activation in response to magnetic fields. Expression of the same construct in the striatum of wild-type mice along with a second injection of an AAVretro expressing Cre into the globus pallidus led to similar circuit specificity and motor responses. Last, a mutation was generated to gate chloride and inhibit neuronal activity. Expression of this variant in the subthalamic nucleus in PitX2-Cre parkinsonian mice resulted in reduced c-fos expression and motor rotational behavior. These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits noninvasively in vivo using clinically available devices.

Over the past decade, the photovoltaic (PV) performance of perovskite solar cells (PSCs) has been considerably improved with the development of perovskite photoabsorbers. Among these, formamidinium-lead-iodide (FAPbI 3 ) is a promising photoabsorber owing to its narrow bandgap and is mainly used in n-i-p-structured PSCs. The property modulation of FAPbI 3 photoabsorbers while retaining their narrow bandgap is imperative for further development of PSCs. Molecular tetrafluoroborate anion (BF 4 - )-based materials can be used as additives in perovskite layers to prevent bandgap widening, while facilitating perovskite crystal growth; thus, they are suitable for FAPbI 3 photoabsorbers in principle. However, BF 4 - -based additives for narrow-bandgap FAPbI 3 photoabsorbers have not been developed. This is presumably because of the higher temperatures required for FAPbI 3 formation than that for other wide-bandgap perovskites, which likely changes the effects of BF 4 -based additives from those for wide-bandgap perovskites. In this study, we verified the applicability of methylammonium tetrafluoroborate (MABF 4 ) as an additive in narrow-bandgap FAPbI 3 photoabsorbers for improving their PV performance primarily via the spontaneous modulation of the heterointerfaces between FAPbI 3 and carrier-transport materials, rather than the bulk quality improvement of FAPbI 3 perovskite. At the interface of the hole-transport material and FAPbI 3 , MABF 4 addition effectively eliminates the surface defects in all FAPbI 3 components, even in the absence of BF 4 - over the heated FAPbI 3 surface, suggesting a defect-suppression mechanism that differs from that observed in conventional ones. Moreover, at the interface of FAPbI 3 and the TiO 2 electron-transport material, the BF 4 -derived species, which likely includes decomposed BF 4 - owing to the high-temperature heating, spontaneously segregates upon deposition, thereby modulating the heterointerface. Furthermore, in addition to the carrier mobility ratio in FAPbI 3 (e - :h + ≈ 7:3), a time-resolved microwave conductivity measurement revealed that MABF 4 addition eliminates carrier traps at the heterointerfaces. Our findings provide insights into promising FAPbI 3 -based PSCs, offering a valuable tool for their further development.

Real-world data on health-related quality of life (HRQoL) in advanced urothelial carcinoma (aUC) receiving immune checkpoint inhibitors (ICIs) are limited. This study included 42 patients with aUC who received second-line or later pembrolizumab (n = 19), maintenance avelumab followed by first-line chemotherapy (n = 13), or adjuvant nivolumab after radical surgery (n = 10). Time-course changes in the domains and scales related to HRQoL were evaluated using the EORTC QLQ-C30, FACT-G, and SF-8 questionnaires during ICI therapy. Anchor-based approaches for minimally important differences were determined as 'improved', 'stable', and 'deteriorated'. We found significant improvements after the start of pembrolizumab treatment on many scales. Almost none of the scales changed significantly in the avelumab and nivolumab groups. Approximately 80% of the pembrolizumab group had deteriorated social/family well-being in FACT-G. Approximately 60% of the patients in the avelumab group had deteriorated general health and vitality in SF-8. In the nivolumab group, none of the scales deteriorated in > 50% of the patients. Deterioration of physical function in the SF-8 was associated with occurrence of treatment-related adverse events ≥ grade 2 during ICI therapy (P = 0.013). Our findings demonstrated that majority of patients with aUC who received ICI therapy had a stable HRQoL, which was consistent with evidence from clinical trials., (© 2024. The Author(s).)

Introduction: Needle-track seeding of prostate cancer into the rectal wall following transrectal prostate biopsy is exceedingly rare. We report a case of mucinous prostate cancer recurrence in the rectal wall due to biopsy needle seeding, discovered after robot-assisted radical prostatectomy., Case Presentation: A 67-year-old man underwent robot-assisted radical prostatectomy for mucinous prostate cancer (clinical stage T2cN0M0, Gleason score of 4 + 4, and initial prostate-specific antigen level of 8.8 ng/mL). Five years postoperatively, endoscopy revealed a rectal tumor, which was diagnosed as needle-track seeding from the previous transrectal prostate biopsy. Following resection of this rectal tumor, the patient's prostate-specific antigen level fell to <0.008 ng/mL. No signs of recurrence or metastasis were observed 3 months postoperatively., Conclusion: While rare, transrectal prostate biopsies can pose a small risk of needle-track seeding into the rectal wall. Endorectal examination should be considered if biochemical recurrence of prostate cancer occurs following radical prostatectomy., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Background & Aims: Excess sucrose intake induces metabolic syndrome. In human, abnormal lipids metabolism like obesity, hyperlipidemia and fatty liver are induced. However, excess sucrose causes different phenotypes in different species. Based on our previous study, excess sucrose induced fatty liver and hyperlipidemia in rats. The phenotypes and mechanism of abnormal lipid metabolism in mice is unclear. We investigated the different phenotypes in 5 strains of mice and the relationship between gut microbiome and abnormal lipid metabolism in C57BL/6N mice., Methods: We examined the effect of a high sucrose diet in 5 different strains of mice. Besides, to find out the relationship between gut microbiome and metabolic disorder induced by excess sucrose, C57BL/6N mice were fed with a high sucrose diet with or without antibiotics cocktail., Results: A high sucrose diet induced obesity and fatty liver in inbred mice, whereas did not induce hyperlipidemia in all strains of mice. Moreover, a high sucrose diet changed the composition of gut microbiota in C57BL/6N mice. Antibiotics treatment alleviated the abnormal lipid metabolism induced by high sucrose diet by changing the composition of gut short chain fatty acids., Conclusions: These results indicates that the phenotypes of metabolic syndrome are influenced by genetic factors. Furthermore, the dysbiosis of gut microbiome caused by excess sucrose may contribute to the development of abnormal lipid metabolism via its metabolites., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Cabozantinib, a multiple tyrosine kinase inhibitor targeting AXL, vascular endothelial growth factor receptor (VEGFR), and MET, is used clinically to treat certain cancers, including hepatocellular carcinoma. This study aimed to assess the impact of cabozantinib on liver fibrosis and hepatocarcinogenesis in a rat model of metabolic dysfunction-associated steatohepatitis (MASH). MASH-based liver fibrosis and hepatocarcinogenesis were induced in rats by feeding them a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for eight and 16 weeks, respectively. Cabozantinib (1 or 2 mg/kg, daily) was administered concurrently with the diet in the fibrosis model and after eight weeks in the carcinogenesis model. Treatment with cabozantinib significantly attenuated hepatic inflammation and fibrosis without affecting hepatocyte steatosis and ballooning in CDAHFD-fed rats. Cabozantinib-treated rats exhibited a marked reduction in α-smooth muscle actin + activated hepatic stellate cell (HSC) expansion, CD68 + macrophage infiltration, and CD34 + pathological angiogenesis, along with reduced hepatic AXL, VEGF, and VEGFR2 expression. Consistently, cabozantinib downregulated the hepatic expression of profibrogenic markers ( Acta2 , Col1a1 , Tgfb1 ), inflammatory cytokines ( Tnfa , Il1b , Il6 ), and proangiogenic markers ( Vegfa , Vwf , Ang2 ). In a cell-based assay of human activated HSCs, cabozantinib inhibited Akt activation induced by GAS6, a ligand of AXL, leading to reduced cell proliferation and profibrogenic activity. Cabozantinib also suppressed lipopolysaccharide-induced proinflammatory responses in human macrophages, VEGFA-induced collagen expression and proliferation in activated HSCs, and VEGFA-stimulated proliferation in vascular endothelial cells. Meanwhile, administration of cabozantinib did not affect Ki67 + hepatocyte proliferation or serum albumin levels, indicating no negative impact on regenerative capacity. Treatment with cabozantinib also reduced the placental glutathione transferase + preneoplastic lesions in CDAHFD-fed rats. In conclusion, cabozantinib shows promise as a novel option for preventing MASH progression., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objective: To assess the feasibility of a nurse-initiated brief cognitive behavioral strategy (CBS) intervention program targeting pain and fatigue symptoms among the pain and fatigue/anorexia symptom clusters experienced by patients with advanced non-small cell lung cancer (NSCLC)., Methods: In this single-group, pre-post test study, 15 NSCLC outpatients undergoing medical treatment participated. After providing informed consent, participants completed a baseline questionnaire and received a booklet detailing brief cognitive-behavioral techniques (e.g., relaxation, symptom-management strategies), exercise therapy, and related tools. Follow-up calls were made five times over a 10-week period to monitor adherence and assess symptom severity changes., Results: Ten participants (66.7%) completed the program. For pain management, 86.7% of participants chose deep breathing as a relaxation technique, and 80.0% used exercise to alleviate fatigue. Median symptom severities decreased from baseline to week 10 as follows: pain (2.00 to 1.00), sadness (1.00 to 0.00), and anxiety (1.00 to 0.50)., Conclusions: The naurse-initiated brief CBS intervention program is feasible and clinically relevant for patients with advanced NSCLC undergoing standard treatment in Japan., Competing Interests: The authors declare no conflict of interest., (© 2024 Asian Oncology Nursing Society. Published by Elsevier Inc.)

A 24-year-old woman was referred to our hospital with joint pain, fever, abdominal pain, and diarrhea. A colonoscopy revealed longitudinal ulcers with a cobblestone appearance throughout the entire colon, suggestive of Crohn's disease. However, treatment with 5-aminosalicylic acid, azathioprine, and infliximab failed to achieve clinical remission. A colonoscopy 5 months later revealed a diffusely spreading granular mucosa without visible vasculature, compatible with active ulcerative colitis. Based on these serial changes in colonic lesions, we tested the patient for MEFV gene mutations and found variants E148Q and L110P in exon 2. Administration of colchicine resulted in complete clinical remission. Our experience suggests that drastic changes in the features of colonic inflammation may be a clue to the diagnosis of enterocolitis associated with familial Mediterranean fever., Competing Interests: Takayuki Matsumoto is a responsible and executive JGES member for DEN Open. 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.)

Introduction: Retrocaval ureter is a rare congenital anomaly that causes ureteral obstruction. Because of the rarity of retrocaval ureter, only a few cases of open, laparoscopic, or robot-assisted surgery have been reported. We herein report a case of retrocaval ureter that was successfully reconstructed with robot-assisted surgery., Case Presentation: A 24-year-old woman was incidentally diagnosed with right hydronephrosis on ultrasonography. Computed tomography revealed retrocaval ureter, and the right hydronephrosis was attributed to the retrocaval ureter. The patient underwent robot-assisted right ureteral reconstruction in the left lateral decubitus position. No intraoperative or postoperative complications occurred, and no right hydronephrosis was observed 6 months after the operation., Conclusion: The present case demonstrated the feasibility and efficacy of robot-assisted ureteral reconstruction for retrocaval ureter., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Objectives: The objectives of the study are to evaluate the oncological and functional outcomes of three bladder preservation regimens: radiotherapy alone (RT-alone group), concurrent chemoradiotherapy (CRT) using gemcitabine plus platinum (GP-RT group), and low-dose gemcitabine (LD-Gem-RT group) for muscle-invasive bladder cancer., Methods: The three oncological outcomes, bladder-intact distant metastasis-free survival (BI-DMFS), cancer-specific survival, and overall survival (OS), were compared among RT alone ( n = 10), GP-RT ( n = 16), and LD-Gem-RT ( n = 11) groups. Treatment-related adverse events were evaluated against the Common Terminology Criteria for Adverse Events (version 5.0). In the LD-Gem-RT group, time-course changes in the domains and scales related to the quality of life were evaluated by utilizing three questionnaires., Results: Age was significantly higher in the RT alone group (84 ± 7.2 years old) than in the GP-RT (74 ± 9.0) and LD-Gem-RT (75 ± 6.7) groups ( P = 0.016). At a median follow-up of 26 months, the 2-year BI-DMFS rates were 80, 81, and 55% in the RT alone, GP-RT, and LD-Gem-RT groups, respectively, and the 2-year OS rates were 69, 62, and 81%, respectively. In the CRT groups, only the baseline CRP ≥ 1.0 mg/dL was associated with poor survival outcomes. Common early-onset adverse events included diarrhea, urinary frequency, and hematotoxicity. A questionnaire survey in the LD-Gem-RT group revealed patients experienced significant deterioration in the global health status/quality of life and the physical component summary score., Conclusion: We reported the oncological and functional outcomes of bladder preservation therapy using three different regimens, yielding acceptable outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bladder, All rights reserved.)

A halogen-substituted cyclic disilene compound, bromocyclotrisilene, Si 3 Br(Eind) 3 ( 3a ), bearing fused-ring bulky Eind ( a : R 1 = R 2 = Et) groups, has been synthesized as an extraordinarily air-stable compound by the reduction of 1,2-dibromodisilene, (Eind)BrSi═SiBr(Eind) ( 2a ), or tribromosilane, (Eind)SiBr 3 ( 1a ), with the Mg or Li metal. The X-ray diffraction analysis of 3a showed that the disilene moiety has an almost planar, but slightly trans -bent structure. Even though 3a is quite air-stable both in solutions and in the solid state, its Si-Br bond is reactive under reducing conditions. The further treatment of 3a with the Li metal leads to the formation of room-temperature thermally stable silicon homologues of the cyclopropyl radical, i.e., the cyclotrisilanyl radicals ( 6a ) [ 6a ( syn ) and 6a ( anti )], via intramolecular C-H bond activation in a transient silicon homologue of the cyclopropenyl radical, i.e., the cyclotrisilenyl radical, [Si 3 (Eind) 3 ] • ( 5a ). The formation mechanism of 6a from 5a is discussed based on the theoretical calculations. The unique structural and electronic properties of these Si 3 three-membered ring species incorporating the Eind groups have been experimentally and theoretically investigated.

Introduction: In facial motor-evoked potential monitoring, efforts to reduce peripheral stimulation are necessary because it can cause false-negatives. The effects of peripheral stimulation on Cz-C3/C4 and C3-C4 montages were compared., Methods: Facial motor-evoked potentials were recorded from bilateral orbicularis oculi (Oculi) and oris (Oris) muscles. The double-train approach combining single-pulse and five-train pulse stimulation was used to determine the effect of peripheral stimulation. If the five-train pulse produced a significant waveform, it was defined as "total success." In total success cases, "true success" was defined as a case in which no waveform appeared after the single pulse at the threshold level of the five-train pulse. The total and true success rates and the threshold value of Oculi and Oris were compared between Cz-C3/C4 and C3-C4 montages., Results: Thirty-six muscles each of Oculi and Oris of 18 patients were used for the analysis. True success was more likely to be obtained by the Cz-C3/C4 montage than the C3-C4 montage in Oculi (42% vs. 22%, p = 0.039). Both Oculi and Oris had higher thresholds to elicit facial motor-evoked potentials with the Cz-C3/C4 montage (Oculi: 101.7 vs. 71.4 mA, p = 0.038; Oris: 94.8 vs. 73.1 mA, p = 0.016)., Conclusions: Cz-C3/4 montage is more effective at reducing peripheral stimulation compared with the C3-4 montage. This effect was primarily seen in the orbicularis oculi muscle. It should be noted that the Cz-C3/C4 montage has a higher threshold than the C3-C4 montage in facial muscles. In facial motor-evoked potential monitoring, the Cz-C3/C4 montage may be more suitable to eliminate peripheral stimulation., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 by the American Clinical Neurophysiology Society.)

Background: Maintenance avelumab is currently recommended for patients with unresectable and/or metastatic (mUC) achieving at least stable disease (SD) on first-line platinum-based chemotherapy (1L-CT). Pembrolizumab is an alternative therapeutic avenue for this patient cohort in clinical practice. We investigated real-world data, focusing on the correlation between response to 1L-CT and oncological efficacy of subsequent immune checkpoint inhibitor (ICI) therapy with avelumab or pembrolizumab., Methods: A multicenter database registered 626 patients with mUC diagnosed from 2008-2023; among these, 175 receiving 2-6 cycles of 1L-CT followed by ICI therapy. Patients were categorized based on response to 1L-CT using the Response Evaluation Criteria in Solid Tumors (v1.1). Objective response rate on ICI, progression to ICI-free survival (ICI-PFS), and overall survival from start of 1L-CT were compared between avelumab-treated and pembrolizumab-treated patients in each response subgroup., Results: ICI-PFS was significantly longer in patients achieving partial response on 1L-CT and subsequently receiving pembrolizumab compared to those receiving avelumab. Notably, patients achieving SD on 1L-CT and subsequently receiving pembrolizumab manifested significantly higher objective response rate (14% and 41%, respectively) and prolonged ICI-PFS relative to those receiving avelumab. In contrast, overall survival did not delineate difference between patients treated with avelumab versus pembrolizumab. Similar findings were discerned in the subanalysis of patients having favorable SD (tumor shrinkage, from - 29 to 0%) and unfavorable SD (tumor enlargement, from + 1 to + 19%) on 1L-CT., Conclusions: Our study provides real-world evidence regarding difference of oncological efficacy between maintenance avelumab and subsequent pembrolizumab in patients with mUC who achieved partial response or SD on 1L-CT., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Pulmonary sclerosing pneumocytoma (PSP) is a rare, benign tumor. Given the challenges of a bronchoscopic diagnosis, surgery is performed during the early stages of the disease. Therefore, little is known about the growth pattern of PSP. This case of PSP was not diagnosed despite bronchoscopy, resulting in lung resection eight years after the anomaly was first identified on computed tomography (CT). This report compares the long-term follow-up of CT and pathological findings and discusses the difficulty in making a diagnosis using a bronchoscopic forceps biopsy to aid in future PSP diagnoses and treatment planning.

Alzheimer's disease (AD) is marked by the aggregation of extracellular amyloid-β (Aβ) and astrocyte dysfunction. For Aβ oligomers or aggregates to be formed, there must be Aβ monomers present; however, the roles of monomeric Aβ (mAβ) and oligomeric Aβ (oAβ) in astrocyte pathogenesis are poorly understood. We cultured astrocytes in a brain-mimicking three-dimensional (3D) extracellular matrix and revealed that both mAβ and oAβ caused astrocytic atrophy and hyper-reactivity, but showed distinct Ca 2+ changes in astrocytes. This 3D culture evolved into a microfluidic glymphatics-on-chip model containing astrocytes and endothelial cells with the interstitial fluid (ISF). The glymphatics-on-chip model not only reproduced the astrocytic atrophy, hyper-reactivity, and Ca 2+ changes induced by mAβ and oAβ, but recapitulated that the components of the dystrophin-associated complex (DAC) and aquaporin-4 (AQP4) were properly maintained by the ISF, and dysregulated by mAβ and oAβ. Collectively, mAβ and oAβ cause distinct AD pathophysiological characteristics in the astrocytes.

In partial onset epilepsy, seizures arise focally in the brain and often propagate. Patients frequently become refractory to medical management, leaving neurosurgery, which can cause neurologic deficits, as a primary treatment. In the cortex, focal seizures spread through horizontal connections in layers II/III, suggesting that severing these connections can block seizures while preserving function. Focal neocortical epilepsy is induced in mice, sub-surface cuts are created surrounding the seizure focus using tightly-focused femtosecond laser pulses, and electrophysiological recordings are acquired at multiple locations for 3-12 months. Cuts reduced seizure frequency in most animals by 87%, and only 5% of remaining seizures propagated to the distant electrodes, compared to 80% in control animals. These cuts produced a modest decrease in cortical blood flow that recovered and left a ≈20-µm wide scar with minimal collateral damage. When placed over the motor cortex, cuts do not cause notable deficits in a skilled reaching task, suggesting they hold promise as a novel neurosurgical approach for intractable focal cortical epilepsy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objectives: The aim of this study was to compare clinical outcomes between patients receiving second TUR after initial white-light transurethral resection of bladder tumor (WL-TURBT) and initial photodynamic diagnosis (PDD)-assisted TURBT., Methods: A total of 1007 patients were divided into four groups based on the treatment pattern: WL-TURBT with second TUR (161 patients, WL-second group) or without second TUR (540 patients, WL-alone group) and PDD-TURBT with second TUR (112 patients, PDD-second group) or without second TUR (194 patients, PDD-alone group). Oncologic outcomes (bladder cancer recurrence, progression, urothelial cancer-specific mortality) and rates of residual tumor and risk stratification of non-muscle-invasive bladder cancer (NMIBC) after second TUR were evaluated., Results: After propensity score-matching 121 patients were included each in the WL-alone and WL-second groups, and 63 patients each in the PDD-alone and PDD-second groups. In the WL group, the second TUR was significantly associated with improved progression-free (p = 0.012) and urothelial cancer-specific free survival (p = 0.011), but not with recurrence-free survival (p = 0.93). Patients initially treated with PDD-TURBT, and with a tumor diameter <30 mm and multifocality had a relatively high benefit from second TUR. The rates of residual tumor and risk stratification of NMIBC did not significantly differ between WL-TURBT and PDD-TURBT groups., Conclusions: Our findings suggested that a second TUR could be omitted after an initial PDD-TURBT in selected patients with high-risk NMIBC., (© 2024 The Japanese Urological Association.)