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Abstract Background Despite initial delay, Japan’s COVID-19 vaccination accelerated remarkably from May to September 2021 under the leadership of Prime Minister Yoshihide Suga. His “campaign” for vaccination, however, did not yield uniform results nationwide. Methods To highlight political determinants for the regional variation, we employ ordinary least squares regression analyses to investigate how the share/presence of incumbent politicians belonging to the governing parties, the Liberal Democratic Party and Komei Party, influenced the varying progress of rollouts across prefectures as well as across cities/towns/villages. The data on the vaccination rate for all 47 prefectures was obtained from Government Chief Information Officer (CIO)’s Portal, Japan (GCPJ) approximately one month prior to the anticipated general election, the national election for the more important House of Representatives of Japan’s bicameral parliament (Diet). The data for lower administrative units, though its availability was limited to only three prefectures, was obtained from the respective governments of Kagawa and Ehime and from a local newspaper in Gifu. Results The findings reveal that at both prefectural and sub-prefectural administrative levels, the share/presence of the governing parties’ representation in the national parliament had a positive and statistically significant effect on the region’s vaccination progress, after controlling for the local proliferation of COVID-19 and demographic characteristics. Conclusion Our findings contribute insights into the understudied area of the contemporary COVID-19 health environment, namely how the political dynamics of democracy affect the pattern of vaccine dissemination in Japan. Trial registration : Not applicable.

The ∼74 ka Toba eruption was one of the largest volcanic events of the Quaternary. There is much interest in determining the impact of such a large event, particularly on the climate and hominid populations at the time. Although the Toba eruption has been identified in both land and marine archives as the Youngest Toba Tuff, its precise place in the ice core record is ambiguous. Several volcanic sulfate signals have been identified in both Antarctic and Greenland ice cores and span the Toba eruption 40Ar/39Ar age uncertainty. Here, we measure sulfur isotope compositions in Antarctic ice samples from the Dome C (EDC) and Dronning Maud Land (EDML) ice cores at high temporal resolution across 11 of these potential Toba sulfate peaks to identify candidates with sulfur mass-independent fractionation (S-MIF), indicative of an eruption whose plume reached altitudes at or above the stratospheric ozone layer. Using this method, we identify several candidate sulfate peaks that contain stratospheric sulfur. We further narrow down potential candidates based on the isotope signatures by identifying sulfate peaks that are due to a volcanic event at tropical latitudes. In one of these sulfate peaks at 73.67 ka, we find the largest ever reported magnitude of S-MIF in volcanic sulfate in polar ice, with a Δ33S value of −4.75 ‰. As there is a positive correlation between the magnitude of the S-MIF signal recorded in ice cores and eruptive plume height, this could be a likely candidate for the Toba super-eruption, with a plume top height in excess of 45 km. These results support the 73.7±0.3 ka (1σ) 40Ar/39Ar age estimate for the eruption, with ice core ages of our candidates with the largest magnitude S-MIF at 73.67 and 73.74 ka. Finally, since these candidate eruptions occurred on the transition into Greenland Stadial 20, the relative timing suggests that Toba was not the trigger for the large Northern Hemisphere cooling at this time although we cannot rule out an amplifying effect.

The Toba eruption that occurred some 74 ka ago in Sumatra, Indonesia, is among the largest volcanic events on Earth over the last 2 million years. Tephra from this eruption has been spread over vast areas in Asia, where it constitutes a major time marker close to the Marine Isotope Stage 4/5 boundary. As yet, no tephra associated with Toba has been identified in Greenland or Antarctic ice cores. Based on new accurate dating of Toba tephra and on accurately dated European stalagmites, the Toba event is known to occur between the onsets of Greenland interstadials (GI) 19 and 20. Furthermore, the existing linking of Greenland and Antarctic ice cores by gas records and by the bipolar seesaw hypothesis suggests that the Antarctic counterpart is situated between Antarctic Isotope Maxima (AIM) 19 and 20. In this work we suggest a direct synchronization of Greenland (NGRIP) and Antarctic (EDML) ice cores at the Toba eruption based on matching of a pattern of bipolar volcanic spikes. Annual layer counting between volcanic spikes in both cores allows for a unique match. We first demonstrate this bipolar matching technique at the already synchronized Laschamp geomagnetic excursion (41 ka BP) before we apply it to the suggested Toba interval. The Toba synchronization pattern covers some 2000 yr in GI-20 and AIM-19/20 and includes nine acidity peaks that are recognized in both ice cores. The suggested bipolar Toba synchronization has decadal precision. It thus allows a determination of the exact phasing of inter-hemispheric climate in a time interval of poorly constrained ice core records, and it allows for a discussion of the climatic impact of the Toba eruption in a global perspective. The bipolar linking gives no support for a long-term global cooling caused by the Toba eruption as Antarctica experiences a major warming shortly after the event. Furthermore, our bipolar match provides a way to place palaeo-environmental records other than ice cores into a precise climatic context.

Abstract  The accuracy of high-speed transient resistance measurements is an important issue particularly for measuring the thermal conductivity of high thermal-diffusivity (low-density) gases. This is because the hot-wire temperature rise against the logarithm of time is non-linear and can approach a steady state within the typical measurement time of 1 s. Two types of voltmeters are compared for use in the transient short-hot-wire method. Details of suitable procedures for taking accurate transient resistance measurements with either a two-channel high-speed analog/digital converter or a pair of integrating digital multimeters are presented. [ABSTRACT FROM AUTHOR]

We carried out 12CO(J = 1–0) observations of the Galactic gamma-ray supernova remnant (SNR) Kesteven 79 using the Nobeyama Radio Observatory 45 m radio telescope, which has an angular resolution of ∼20 arcsec. We identified molecular and atomic gas interacting with Kesteven 79, whose radial velocity is ∼80 km s−1. The interacting molecular and atomic gases show good spatial correspondence with the X-ray and radio shells, which have an expanding motion with an expanding velocity of ∼4 km s−1. The molecular gas associated with the radio and X-ray peaks also exhibits a high intensity ratio of CO 3–2/1–0 > 0.8, suggesting a kinematic temperature of ∼24 K, owing to heating by the supernova shock. We determined the kinematic distance to the SNR to be ∼5.5 kpc and the radius of the SNR to be ∼8 pc. The average interstellar proton density inside of the SNR is ∼360 cm−3, of which atomic protons comprise only ∼10%. Assuming a hadronic origin for the gamma-ray emission, the total cosmic-ray proton energy above 1 GeV is estimated to be ∼5 × 1048 erg. [ABSTRACT FROM AUTHOR]

We present Spitzer/IRS mid-infrared spectral maps of the Galactic star-forming region M17 as well as IRSF/SIRIUS Brγ and Nobeyama 45 m/FOREST 13CO (J = 1–0) maps. The spectra show prominent features due to polycyclic aromatic hydrocarbons (PAHs) at wavelengths of 6.2, 7.7, 8.6, 11.3, 12.0, 12.7, 13.5, and 14.2 μm. We find that the PAH emission features are bright in the region between the H ii region traced by Brγ and the molecular cloud traced by 13CO, supporting that the PAH emission originates mostly from photo-dissociation regions. Based on the spatially resolved Spitzer/IRS maps, we examine spatial variations of the PAH properties in detail. As a result, we find that the interband ratio of PAH 7.7 μm/PAH 11.3 μm varies locally near M17SW, but rather independently of the distance from the OB stars in M17, suggesting that the degree of PAH ionization is mainly controlled by local conditions rather than the global UV environments determined by the OB stars in M17. We also find that the interband ratios of the PAH 12.0 μm, 12.7 μm, 13.5 μm, and 14.2 μm features to the PAH 11.3 μm feature are high near the M17 center, which suggests structural changes of PAHs through processing due to intense UV radiation, producing abundant edgy irregular PAHs near the M17 center. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition caused by severe infection and often complicates acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) due to the collapse of the oxidative and inflammatory balance induced by microbial pathogens, including lipopolysaccharides (LPS). In sepsis-related ARDS/ALI, NADPH oxidase (NOX) and toll-like receptors (TLR) in neutrophils and macrophages are key players in initiating oxidative and inflammatory imbalances. Although NOX and TLR activation has been linked to carbon monoxide (CO), the mechanism by which CO affects sepsis-related ARDS/ALI through NOX and TLR remains unknown. Here, we demonstrate that CO reduces sepsis-related ARDS/ALI by inhibiting NOX in neutrophils and macrophages, which in turn suppresses the production of reactive oxygen species (ROS), TLR4-associated inflammatory responses, and macrophage polarization toward M1-like macrophages. CO-bound hemoglobin vesicle (CO-HbV) therapy, a hemoglobin-based CO donor, exerts a protective effect against LPS-induced ALI by suppressing exaggerated oxidative and inflammatory responses and neutrophil and M1-like macrophage infiltration in the bronchoalveolar lavage fluid (BALF). Through suppression of NOX activity, CO decreased ROS generation, the TLR4/NF-κB signaling pathway, and macrophage polarization toward M1-like macrophages, according to cellular experiments conducted with peripheral neutrophils, BALF cells, and Raw264.7 cells. Moreover, ALI was found to be more severe in Hmox1 +/- mice (mice with decreased endogenous CO production) than in the wild-type mice. Our findings suggest that both endogenously generated and exogenously supplied CO inhibit NOX-associated ROS generation, the TLR4/NF-κB signaling pathway, and macrophage polarization, thereby eliciting antioxidant and anti-inflammatory responses that prevent the onset and progression of LPS-induced ALI., 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 © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Systemic lupus erythematosus (SLE) is a systemic disease that affects several organs. The diagnosis was performed using the international classification criteria updated in 2019. The significance of antinuclear antibodies (ANAs) with a centromere pattern has not been clearly documented in these criteria. We herein report a patient with ANAs with a centromere pattern and anti-centromere antibodies, without anti-Sm antibodies or anti-dsDNA antibodies, who developed severe lupus nephritis, neuropsychiatric SLE, and lupus pleuritis. The patient was successfully treated with prednisolone, hydroxychloroquine, mycophenolate mofetil, cyclophosphamide, and belimumab, despite several relapses. Anti-centromere antibodies are not regarded as characteristics of SLE but can be detected in SLE patients with severe organ involvement.

A wide array of artificial O 2 carriers based on hemoglobin (Hb) has been developed to serve as substitutes for red blood cells (RBCs). Nevertheless, the prevention of heme-iron oxidation within Hb remains a critical challenge. In this study, we synthesized a nanoparticle O 2 carrier comprising a polymerized stromal-free Hb (SFHb) core covered with a human serum albumin shell, designated as SFHbNP. With an optimized particle size of approximately 30 nm, SFHbNPs are engineered to evade uptake by the reticuloendothelial system in various organs. We characterized the physicochemical properties and biochemical functions of SFHbNPs, demonstrating that the incorporation of trace amounts of the antioxidant enzyme catalase within the core effectively suppresses Hb autoxidation. The SFHbNP solution exhibited excellent compatibility with human blood and demonstrated no cytotoxicity toward human endothelial cells. Moreover, its extended circulatory retention enabled preclinical evaluation in animal models. In a rat model of 50% hemorrhagic shock, administration of SFHbNP solution achieved full resuscitation, as evidenced by the restoration of circulatory parameters. Serum biochemistry tests and histopathological analyses of major organs indicated no adverse effects. Comprehensive in vitro and in vivo studies confirm the safety and potential efficacy of SFHbNPs as a promising RBC alternative in transfusion medicine.

Background: Preoperative nivolumab combination chemotherapy has shown its efficacy in resectable stage II-III non-small cell lung cancer and become one of the standard treatments. While preoperative nivolumab combination chemotherapy is generally a regimen of three cycles, the efficacy of nivolumab combination chemotherapy when treatment is prematurely discontinued remains unclear., Case Presentation: An 81-year-old man was diagnosed as lung adenocarcinoma (cT3N1M0, cStage IIIA). A computed tomography (CT) showed a 58 mm mass in left upper lobe with an intrapulmonary metastasis, and a positron-emission tomography/CT suggested metastatic lymph nodes at the left pulmonary hilum. Preoperative nivolumab + carboplatin + paclitaxel were administered; however, after the first cycle, the treatment was discontinued due to grade 3 anorexia, grade 1 body weight loss, and grade 4 neutropenia. It was affair that continuation of preoperative therapy made him unsuitable for surgery, and CT scan showed a reduction in the tumor size to 20 mm. Then, we decided to discontinue the preoperative therapy and perform surgery. Video-assisted thoracoscopic left upper lobectomy and lymph node dissection were performed, and the postoperative course was uneventful. The pathological examination revealed 15% of residual tumor cell in primary lesion and no metastatic lymph nodes was diagnosed. The patient did not undergo adjuvant chemotherapy, and no recurrence was observed 1.5 years after surgery CONCLUSIONS: In this case, preoperative nivolumab combined chemotherapy was discontinued only one cycle due to adverse events; however, a significant treatment effect was achieved. Therefore, even it is unable to continue preoperative nivolumab combined therapy, it is important not to miss the chance of surgery, as good treatment effect may have been achieved., Competing Interests: Ethics approval and consent to participate: Informed consent to the patient in this case report has been obtained from the patient himself. Consent for publication: Consent for publication has been obtained from the patient himself. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: Although there are many reports on the efficacy of preoperative embolization for meningioma, such as a reduction in intraoperative blood loss, its efficacy for vestibular schwannoma remains unclear. Feeding arteries of vestibular schwannomas include branches from the anterior inferior cerebellar artery and internal carotid artery, in addition to the branches from the external carotid artery (ECA). However, it has been reported that the embolization of feeding arteries from the anterior inferior cerebellar artery and the internal carotid artery has a high risk of complications. Therefore, we retrospectively analyzed the effects of preoperative embolization of only the feeding arteries from the ECA for vestibular schwannomas, particularly regarding its volume reduction effect., Methods: Of the 805 patients with vestibular schwannoma who underwent tumor removal at our department between September 2013 and March 2022, a total of 15 patients who underwent preoperative embolization of only the feeding arteries from the ECA were analyzed. Tumor volume was measured based on contrast-enhanced T1-weighted imaging, and the effects of preoperative embolization on tumor volume reduction were analyzed., Results: Tumor volumes before and after embolization were 16.4 ± 9.2 mL and 14.1 ± 9.6 mL, respectively, indicating a volume reduction effect of 15.3 ± 10.3% (P < 0.001). The mean time from embolization to contrast-enhanced T1-weighted imaging was 5.1 ± 3.0 days., Conclusions: Preoperative embolization of only the feeding arteries from the ECA may be an effective adjunctive treatment for vestibular schwannomas, given the significant volume reduction effect achieved within several days after embolization, in addition to reducing intraoperative blood loss., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures: Takaki Akamine, Sho Wakasu, Taichi Matsubara, Masafumi Yamaguchi, Koji Yamazaki, Motoharu Hamatake, Takuro Kometani, Fumihiko Kinoshita, Mikihiro Kohno, Mototsugu Shimokawa, Tomoyoshi Takenaka, and Tomoharu Yoshizumi disclose no conflicts of interest that may be relevant to the contents of this study.

Introduction: Cognitive dysfunction after aneurysmal subarachnoid hemorrhage (aSAH) remains unclear due to various neurological impairments. This study aimed to evaluate the changes in hippocampal volume, cognitive function, and interictal epileptiform discharges after clipping in patients with aSAH of anterior circulation., Methods: Patients with modified Rankin Scale scores of 0-3 points who underwent clipping were evaluated. Aneurysmal locations were classified as middle cerebral artery (MCA), internal carotid artery (ICA), and anterior cerebral artery (ACA). Surgery was performed using the transsylvian approach or interhemispheric approach. Hippocampal volume measurement, neuropsychological assessments, and interictal electroencephalogram evaluations were performed postoperatively at the subacute phase. Epileptiform discharges were assessed using the spike index (SI)., Results: We included 60 patients (23 men, 37 women; median age, 57.4 years). Aneurysmal locations were found in the MCA, ICA, and ACA in 23, 19, and 18 patients, respectively. The postoperative hippocampal volume was significantly reduced on the clipping approach side in the MCA and ICA groups (MCA, p  < .001; ICA, p  < .001). There was no correlation between hippocampal volume and cognitive function. A significant difference was noted in elevated SI on the approach side of the MCA ( p  < .001), ICA ( p  < .001), and ACA ( p  < .001) in the transsylvian approach group. The elevated SI on the left approach side showed significant differences in some neuropsychological assessments (performance intellectual quotient, p  = .028; perceptual organization, p  = .045; working memory, p  = .003)., Discussion: Cognitive dysfunction in the subacute phase after clipping for aSAH was not correlated with hippocampal volume reduction but was correlated with interictal epileptiform discharges., 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., (© 2025 Otsuka, Sunaga, Jimbo, Suzuki and Kohno.)

Objectives: To update the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis (CPG for RA)., Methods: The recommendations were developed based on the evidence published until the end of June 2022 using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The steering committee, CPG panel, systematic review (SR) group, and SR support team were organised., Results: The treatment goal and drug treatment algorithm required no modifications; however, the footnotes of the drug treatment algorithm were modified. SR of 21 new or updated recommendations for subcutaneous methotrexate (n=1), biological disease-modifying antirheumatic drugs (n=1), rituximab (n=5), Janus kinase inhibitors (n=6), biosimilars (n=2), older patients (n=4), and pregnancy and lactation (n=2) was conducted. The recommendations for comorbidities and surgery and rehabilitation remained unchanged from the 2020 CPG for RA., Conclusion: The 2024 CPG for RA, which provide recommendations that reflect the current healthcare environment for RA in Japan, can be used effectively as a tool for shared decision-making between rheumatologists and patients in the treatment of RA., (© Japan College of Rheumatology 2025. 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.)

The Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders (LPDs). Additionally, EBV infection has correlated with diverse autoimmune diseases. However, the association between EBV and systemic small vessel vasculitis (SVV) remains controversial. Here, we report a case of SVV with pauci-immune glomerulonephritis accompanied by an EBV-positive polymorphic B-cell LPD, not otherwise specified. The intricate distinction between EBV-positive B-cell LPD and SVV was difficult, as both diseases demonstrated similar clinical presentations. Lymph node and kidney biopsies facilitated the accurate diagnosis of these two conditions. The administration of high-dose prednisolone, combined with rituximab, proved efficacious, with no instances of relapse over the subsequent 2-year period. This case indicates an association between EBV-positive B-cell LPD and SVV. The diligent execution of biopsies is a crucial diagnostic and interpretive strategy, generating precise comprehension of this condition and guiding its appropriate therapeutic management., (© Japan College of Rheumatology 2025. 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.)

The widespread adoption of preoperative embolization in highly vascularized brain tumors often involves the frequent use of Embosphere (Merit Medical Systems, South Jordan, Utah, USA). Nevertheless, inconsistency in size selection and dilution rates across different institutions requires comprehensive examination. This study explored the appropriate size and dilution rate of Embosphere microspheres. To assess catheter occlusion and Embosphere breakage, various dilutions (4-, 10-, 20-, 30-, and 60-fold) of Embosphere 300-500 and 500-700 μm were injected into the catheter in vitro. Results indicated that 20-fold or higher dilutions of Embosphere 300-500 μm and 30-fold or higher dilutions of Embosphere 500-700 μm showed no occlusion of the Excelsior SL-10 microcatheter (Stryker, Fremont, CA, USA) or Embosphere breakage. For embolization, to reduce the risk of Excelsior SL-10 occlusion further, a 30-fold dilution of Embosphere 300-500 μm and a 60-fold dilution of Embosphere 500-700 μm were employed. For 195 blood vessels in 107 patients (84 with meningioma and 23 with schwannoma), embolization was carried out using a 30-fold dilution of Embosphere 300-500 μm when the provocative test was negative and a 60-fold dilution of Embosphere 500-700 μm when the test was positive or when there was a risk of migration into neurotrophic vessels. Contrast-enhanced magnetic resonance imaging after embolization revealed a reduced enhancement effect in 69.1% of cases. Embolization using a 30-fold dilution of Embosphere 300-500 μm and a 60-fold dilution of Embosphere 500-700 μm with an Excelsior SL-10 catheter is safe and satisfactory, which minimizes microcatheter occlusion.

Explicit expressions for the leading chiral hyperon-nucleon-nucleon three-body forces have been derived by Petschauer et al (Phys Rev C93:014001, 2016). An important prerequisite for including these three-body forces in few- and many-body calculations is the accuracy and efficiency of their partial-wave decomposition. A careful benchmark of the Λ NN potential matrix elements, computed using two robust and efficient partial-wave decomposition methods, is presented. In addition, results of a first quantitative assessment for the contributions of Λ NN forces to the separation energies in A = 3 - 5 hypernuclei are reported., (© The Author(s) 2025.)

Background: Cluster of differentiation 155 (CD155) is expressed in many tumor types. CD155 is involved in the immune avoidance of tumor cells and contributes to tumor development and progression. Therefore, CD155 is a novel target for cancer immunotherapy. The clinical significance of CD155 expression in lung squamous cell carcinoma (LUSC) has not been fully elucidated., Materials and Methods: We performed a retrospective analysis of 264 patients with surgically resected LUSC. Immunohistochemistry was used to evaluate CD155 expression. The association of CD155 expression with clinicopathological features and clinical outcomes was assessed. We also analyzed the relationship between CD155 expression and programmed cell death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes., Results: Among the 264 patients, 137 patients (51.9%) were classified in the high CD155 expression group. High CD155 expression was significantly associated with pleural invasion, vascular invasion, PD-L1 positivity, and high CD3, CD4, and CD8 expressions. In multivariate analysis, the presence of pleural invasion and PD-L1 positivity were independent predictors of high CD155 expression. Kaplan-Meier curve analysis showed that high CD155 expression was significantly associated with shorter disease-free survival and overall survival. In multivariate analysis, high CD155 expression was an independent poor prognostic factor for overall survival, but not for disease-free survival. Subgroup analyses revealed that the prognostic effect of CD155 expression was observed in the PD-L1 positive group but not the PD-L1 negative group., Conclusion: Our analysis revealed that high CD155 expression significantly predicted poor prognosis in patients with surgically resected LUSC, especially in patients with PD-L1-positive tumors., Competing Interests: Declarations. Conflict of interest: The authors have no conflict of interest., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: The prognosis of patients with subarachnoid hemorrhage (SAH) who also develop cardiopulmonary arrest (CPA) is highly unfavorable, and hence they are often not aggressively treated. Presently, the therapeutic indications and factors that affect the prognosis of patients who experienced CPA remain unclear. Therefore, we analyzed SAH patients who experienced CPA, comparing the characteristics of the patients who survived with those who did not., Methods: The 36 patients were divided into the survivor group (n = 4) and the dead group (n = 32). The patient's age, sex, location of the aneurysm, the presence of intracranial hematoma, duration of cardiopulmonary resuscitation (CPR), the presence/absence of bystanders, initial electrocardiogram waveform, recovery of brainstem reflexes with motor response, and administration of vasopressors were compared between the 2 groups., Results: There were no significant differences in age, sex, location of the aneurysm, and presence of intracranial hematoma between the 2 groups. More than 90% of patients in the dead group had a non-shockable rhythm on the initial electrocardiogram waveform. The duration of CPR in the survivor group tended to be shorter than that in the dead group. Bystander CPR was performed on 14 patients, including all 4 of the survivors. All patients in the survivor group achieved recovery of brainstem reflexes with motor response. In the survivor group, all patients either did not need or only transiently needed the administration of vasopressors after the return of spontaneous circulation (ROSC)., Conclusion: Our analysis suggested the following as favorable prognostic factors in SAH patients with CPA: shockable arrhythmia on the initial electrocardiogram waveform, young age, bystander CPR, a short time from CPA to ROSC, recovery of brainstem reflexes with a motor response, and no or transient use of vasopressors. Our results indicate that aggressive treatment may be indicated in SAH patients with CPA who have stable vitals and show improvements in neurological symptoms., (©2025 The Japanese Society for Neuroendovascular Therapy.)

Background: Tumor microvasculature is an important component of the tumor microenvironment (TME), and it has been reported that tumor microvasculature induces TME to become immunosuppressive via vascular endothelial growth factor. However, the significance of this in adenocarcinoma with epidermal growth factor receptor (EGFR) common mutations has not been fully investigated., Methods: We analyzed 262 patients with adenocarcinoma harboring EGFR common mutations who underwent surgery at Kyushu University Hospital between 2006 and 2021. Microvessel density (MVD) was calculated by CD34 immunohistochemistry. Patients were categorized into high and low MVD status, which was compared with the clinicopathological characteristics., Results: A total of 136 (51.9%) patients had L858R mutation, and 126 (48.1%) had Exon 19 Del. Regarding MVD status; 133 patients (50.8%) were classified as high and 129 (49.2%) as low. Fisher's exact test revealed a significant association of high MVD status with high CD8+ tumor infiltrating lymphocytes (TILs) (p = 0.0187), low GZMB+ TILs (p = 0.0019), and high Foxp3+ TILs (p = 0.0003). On multivariate analysis, MVD status was significantly associated with Foxp3+ TILs and GZMB+ TILs. Fisher's exact test also revealed that tumors with L858R mutation had a high MVD status (p = 0.0136) compared with tumors with deletions of exon 19 (Exon 19 Del), and multivariate analysis revealed that L858R mutation was significantly associated with high MVD status., Conclusions: In adenocarcinomas harboring EGFR common mutations, abundant tumor microvasculature might induce the TME to be immunosuppressive. Tumors with L858R mutation compared with Exon 19 Del might be more likely to form an immunosuppressive TME owing to the abundance of tumor microvasculature., (© 2025. Society of Surgical Oncology.)

Objectives: Spread through air spaces (STAS) is considered a poor prognostic factor in patients with resected non-small lung cell cancer; however, the clinical significance of STAS extent remains unclear. We hypothesized that the further the tumour cells spread from the tumour edge, the worse the prognosis becomes., Methods: This study retrospectively reviewed the data of 642 patients with completely resected pathological stage I-III non-small lung cell cancer between 2008 and 2018. The maximum spread distance (MSD) from the tumour edge to the farthest STAS was quantitatively evaluated, and STAS was categorized as limited (MSD ≤1000 μm) or extended (MSD >1000 μm), based on the median MSD. Recurrence-free survival (RFS) and overall survival (OS) were compared among patients stratified by STAS classification., Results: Patients were classified into STAS-negative (n = 382, 59.6%), limited STAS (n = 130, 20.2%) and extended STAS (n = 130, 20.2%) groups. Extended STAS was associated with a high maximum standardized uptake value, advanced pathological stage and vascular invasion compared with limited STAS. The extended STAS group demonstrated significantly shorter RFS and OS than both the limited STAS and STAS-negative groups (both P < 0.001 for RFS; P = 0.007 and P < 0.001 for OS, respectively). Multivariable analysis showed that extended STAS was an independent prognostic factor for both RFS and OS (P < 0.001, P < 0.001, respectively)., Conclusions: The distance from tumour edge to STAS affects prognosis in patients with completely resected non-small lung cell cancer., Clinical Registration Number: IRB approval number: 2019-232., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Sublobar resection is the standard procedure for cT1N0 stage I non-small cell lung cancer (NSCLC) size ≤2 cm. However, its efficacy for high-risk pathologic stage I cases with a preoperative diagnosis of cT1N0 stage I NSCLC size ≤2 cm remains unclear. This study compared the outcomes of sublobar resection with those of lobectomy from a pathologic perspective., Methods: A multicenter retrospective analysis of patients with pathologic stage I NSCLC was performed following the eighth edition of tumor-node-metastasis (TNM) classification. The study enrolled patients with completely resected clinical stage I NSCLC and a tumor size of ≤2 cm determined by computed tomography. High-risk pathologic feature was defined as evidence of pleural invasion, lymphovascular invasion, or invasive component (>2 cm). Survival rates were compared between the patients who underwent sublobar resection and those who underwent lobectomy., Results: The study enrolled 875 patients (715 [81.7%] low-risk and 160 [18.3%] high-risk NSCLC patients). The high-risk patients in the lobectomy group had significantly better 5-year recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) rates than those in the sublobar resection group (RFS: 80.5% vs 44.3% [P < 0.001], OS: 84.9% vs 54.6% [P = 0.001], CSS: 91.6% vs 72.4% [P = 0.019]). In the low-risk group, lobectomy and sublobar resection resulted in equivalent 5-year RFS, OS, and CSS (RFS: 92.8% vs 88.6% [P = 0.13], OS: 93.8% vs 91.7% [P = 0.26], CSS: 98.9% vs 98.4% [P = 0.67]). Multivariate analysis indicated that sublobar resection was independently associated with poor RFS, OS, and CSS for the high-risk patients., Conclusions: Sublobar resection is feasible for low-risk pathologic stage I NSCLC, whereas lobectomy may have a prognostic benefit for high-risk NSCLC., Competing Interests: Disclosure: There are no conflicts of interest., (© 2024. Society of Surgical Oncology.)

Purposes: Polyglycolic acid (PGA) sheets, fibrin glue, and staple line reinforcement are frequently used to prevent air leakage during lung resection. However, the optimal staple-line reinforcement method remains unclear., Methods: Cranial lung lobes of pigs were used to evaluate different staple line reinforcement methods (n = 6). Ventilator-assisted manometry was used to measure the maximum resistance pressure at the time of rupture of the lung tissue after stapling., Results: The mean maximum resistance pressures at the time of lung tissue rupture after using the stapler alone, stapler with PGA sheet and fibrin glue, and stapler with reinforcement were 38.0 cmH 2 O, 51.3 cmH 2 O, and 62.7 cmH 2 O, respectively. A significant increase in the maximum resistance pressure was observed with stapler reinforcement (P < 0.001), while the differences between the other groups were not statistically significant (P = 0.055, P = 0.111). A histological assessment revealed disruption of alveolar structures near the needle-stitching site in the stapler alone, and in the stapler with PGA sheet and fibrin glue groups. Pleural rupture near the staple line was observed in the stapler with reinforcement group., Conclusions: The maximum resistance pressure before air leakage was significantly higher when using a stapler with reinforcement than when using a stapler alone., Competing Interests: Declarations. Conflict of interest: Shinkichi Takamori: no conflict of interest. Tomoyoshi Takenaka: no conflict of interest. Asato Hashinokuchi: no conflict of interest. Kyoto Matsudo: no conflict of interest. Taichi Nagano: no conflict of interest. Mikihiro Kohno: no conflict of interest. Naoko Miura: no conflict of interest. Tomoharu Yoshizumi: no conflict of interest., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Cluster of differentiation (CD) 155 is a transmembrane protein that belongs to the nectin-like molecule family, which is widely overexpressed in several types of cancer. However, the clinical significance of CD155 in pathologic stage I lung adenocarcinoma remains poorly understood., Methods: We analyzed 320 patients diagnosed with pathologic stage I lung adenocarcinoma who underwent surgical treatment at Kyushu University Hospital between 2006 and 2015. The number of tumor cells expressing CD155 was assessed by immunohistochemistry, and patients were categorized into high and low CD155 expression groups. We compared the clinical and pathologic characteristics and clinical outcomes between these groups., Results: Mutation status of the epidermal growth factor receptor gene (EGFR) was determined in 237 patients. A total of 106 patients (33.1%) had EGFR wild-type, and 131 patients (40.9%) had EGFR mutant-type. CD155 expression was classified as high in 77 patients (24.1%) and as low in 243 (75.9%) as low. Multivariate analysis identified pleural invasion and EGFR wild-type as independent predictors of high CD155 expression. The Kaplan-Meier plot demonstrated significantly poorer recurrence-free survival and overall survival in the high CD155 group compared with the low CD155 group. Multivariate analysis showed high CD155 expression was an independent poor prognostic factor for recurrence-free and overall survival. Subgroup analyses revealed that a prognostic difference related to CD155 expression was observed only in patients with EGFR wild-type but not in those with EGFR mutant-type., Conclusions: Our findings suggest that high expression of CD155 is associated with EGFR wild-type and could serve as a valuable prognostic marker in pathologic stage I lung adenocarcinoma, particularly in cases without EGFR mutation., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A 31-year-old man with neurofibromatosis type 1 (NF-1) had undergone resection of a malignant peripheral nerve sheath tumor (MPNST) on the buttock 3 months previously. He subsequently underwent mechanical thrombectomy for a hyperacute left middle cerebral artery embolism. Histopathologically, the emboli comprised neurofilament-positive pleomorphic tumor cells with geographic necrosis and conspicuous mitosis and were identified as MPNST. The patient died of respiratory failure due to lung MPNST metastasis on day 15 of hospitalization. To our knowledge, this is the first report of a spontaneous cerebral embolism due to MPNST in an NF-1 patient.

Background/aim: The dynamic interplay between cancer cells and the microenvironment involves a wide range of intricate relationships that evolve during different stages of tumor progression. Recent attention has focused on high endothelial venules (HEVs), specialized endothelial cells in tumors with a unique cuboidal shape similar to those in lymph nodes. Previous animal studies have shown that normalization of tumor angiogenesis through anti-VEGFR2 therapy promotes HEV formation. However, few reports exist regarding the relationship between HEVs and preexisting blood vessels or interstitial fibers. In this study, we histologically examined whether tumor vascular structure correlates with HEV neogenesis., Patients and Methods: A total of 109 patients with pathological stage I lung adenocarcinoma who had undergone curative lung resection at our Institute between 2012 and 2016 were included. HEVs were identified by anti-peripheral node addressin (PNAd) staining. Immunostaining and Elastica-Masson-Goldner staining were performed on tumor sections and quantified., Results: PNAd-positive cells were identified in 102 (93.6%) patients. Nearly all PNAd-positive cells were located within or near immune cell clusters. We investigated the correlation between microvessel structures or interstitial fibers and the number/density of PNAd-positive vessels, but no significant correlation was found. Since PNAd-positive cells were concentrated in immune cell aggregates, we focused our analysis specifically on these regions. Immune cell aggregates with abundant PNAd-positive vessels had a greater microvessel density along with by rich collagen fiber production, and displayed a more mature morphological phenotype of HEVs., Conclusion: The generation of PNAd-positive cells in tumors is governed by an angiogenetic mechanism distinct from that of broader tumor microenvironment. Furthermore, the accumulation of immune cells is associated with increased HEV maturation., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The use of metal nanoparticles such as cerium oxide nanoparticles (nanoceria) in living organisms is attracting increasing attention. We administered nanoceria to chronic kidney disease model rats, including a 5/6 nephrectomy model and adenine administration model rats, and reported high phosphorus adsorption capacity and renal function improvement effects of nanoceria. However, the iron ion concentration in the serum fluctuated significantly after administration. Therefore, we investigated changes in proteins related to iron metabolism following administration of nanoceria to normal mice without chronic kidney disease over different periods of time. Nanoceria were administered to 10-week-old C57BL/6 mice for 4 or 12 weeks. Another group was administrated lanthanum carbonate, which is currently used as a phosphorus adsorbent. The amount of iron in the serum and the concentration of transferrin in the liver were significantly increased following nanoceria administration, and the amount of iron in the liver was significantly decreased. There were no changes in serum hepcidin, ferroportin, cholesterol, or low-density lipoprotein levels. These results indicate that nanoceria administration can affect iron metabolism in mice. Although the detailed mechanism remains unknown, caution is warranted when considering biological utilization in the future., Competing Interests: MN is an employee of applause Co., Ltd., which sells a nanoceria product with a similar, but not identical formulation as the one used in this study. The nanoceria used in the study were not the commercially available product but rather one produced by applause Co., Ltd. For research use. The sponsor had no role in the data interpretation, writing, or publication of this work. The other authors declare no conflicts of interest., (Copyright © 2024 JCBN.)

Purpose: The embolization of vessels potentially involved in the vasa nervorum during brain tumor embolization is often a non-aggressive procedure. In this study, we aimed to investigate the safety and efficacy of embolization of vessels with positive provocative test results., Methods: Embosphere (Merit Medical Systems, South Jordan, Utah, USA) was the embolization material of choice. A provocative test was performed using 30 mg of 1% lidocaine, with a positive result if neurological symptoms appeared. A size of 500-700 µm was used for positive results and 300-500 µm for negative results. Embolization was performed five to seven days before resection, and contrast-enhanced MRI was performed three to five days after embolization to assess the embolic status., Results: Provocative tests were performed on 61 vessels from 55 patients. A total of 36 vessels (59.0%) were positive, and 25 vessels were negative. The petrosal branch of the middle meningeal artery and the neuro-meningeal branch of the ascending pharyngeal artery showed particularly high positivity rates (91.7% and 76.5%, respectively). Three patients (8.3%) out of the 36 who underwent embolization of the positive vessels had neurological symptoms after embolization; two had symptoms similar to those observed in the provocative test, and one had different symptoms. All symptoms were mild and transient. The postoperative contrast-enhanced MRI showed that the enhancing effect was attenuated in 18 of the 30 patients (60%) with provocative test-positive vessels., Conclusion: Embolization of provocative test-positive vessels can be performed safely and effectively with a larger Embosphere (500-700 μm)., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics Review Committee of Tokyo Medical University issued approval T2020-0030. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Hashimoto et al.)

Interstitial lung disease (ILD) is a serious complication of connective tissue diseases (CTDs). The heterogeneity of ILDs reflects differences in pathogenesis among diseases. This study aimed to clarify the characteristics of CTD-ILDs via a detailed analysis of the bronchoalveolar lavage fluid (BALF) and blood immune cells. BALF and blood samples were collected from 39 Japanese patients with newly diagnosed ILD: five patients with Sjögren's syndrome (SS), eight patients with dermatomyositis (DM), six patients with rheumatoid arthritis (RA), six patients with systemic sclerosis, four patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, and 10 patients with idiopathic interstitial pneumonia. We performed single-cell RNA sequencing to analyze the gene expression profiles in these patients' immune cells. In patients with SS, B cells in the BALF were increased and genes associated with the innate and acquired immunity were enriched in both the BALF and blood. In contrast, patients with DM showed an upregulation of genes associated with viral infection in both the BALF and blood. In patients with RA, neutrophils in the BALF tended to increase, and their gene expression patterns changed towards inflammation. These disease-specific characteristics may help us understand the pathogenesis for each disease and discover potential biomarkers., Competing Interests: Author KB was employed by the company Aimed Analytics GmbH. WF receives fundings from Nippon Boehringer Ingelheim Co., Ltd. and GlaxoSmithKline Consumer Healthcare Japan K.K., grants from Takeda Pharmaceutical Company Limited, and speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, and Chugai Pharmaceutical Co., Ltd. TT receives speaking fees from Asahi Kasei Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., and Novartis Pharma K.K. AO receives speaking fees from AbbVie GK, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., DAIICHI SANKYO COMPANY, LIMITED, Astellas Pharma Inc., AstraZeneca, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Asahi Kasei Pharma Corporation, Novartis Pharma K.K., Gilead Sciences, Inc., Janssen Pharmaceutical K.K., GlaxoSmithKline Consumer Healthcare Japan K.K., and Eli Lilly Japan K.K. TS receives consulting fees from Asahi Kasei Pharma and speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, GlaxoSmithKline Consumer Healthcare Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co., Ltd., and Pfizer Japan Inc. MW receives speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Gilead Sciences, Inc., GlaxoSmithKline Consumer Healthcare Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Pfizer Japan Inc. MK receives speaking fees from AbbVie GK, Asahi Kasei Pharma Corporation, Astellas Pharma Inc., GlaxoSmithKline Consumer Healthcare Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., and Pfizer Japan Inc. WF receives speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Gilead Sciences, Sawai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Pfizer Japan Inc. and represents committees supported by Astellas Pharma Inc. and AYUMI Pharmaceutical Corporation. KY receives supports for attending meetings from Shionogi Pharma Co., Ltd. KT receives grants from Chugai-Roche, Boehringer-Ingelheim, Ono Pharmaceutical, and Taiho Pharmaceutical, consulting fees from Ono Pharmaceutical, lecture fees from Eli Lilly, Ono Pharmaceutical, AstraZeneca, Chugai-Roche, Boehringer-Ingelheim, MSD-Merck, and Daiichi-Sankyo, and serves on the board member of Japan Lung Cancer Society. YuK receives grants from Asahi Kasei Pharma Corporation, AbbVie GK, AYUMI Pharmaceutical Corporation., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. and speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, AYUMI Pharmaceutical Corporation., GlaxoSmithKline Consumer Healthcare Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K. Pfizer Japan Inc., and Mylan Inc. Author KB was employed by the company Aimed Analytics GmbH. The remaining 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., (Copyright © 2024 Hirano, Sakashita, Fujii, Baßler, Tsuji, Kadoya, Omoto, Hiraoka, Imabayashi, Kaneko, Sofue, Maehara, Seno, Wada, Kohno, Fukuda, Yamada, Takayama and Kawahito.)

Bronchiolitis obliterans syndrome (BOS) is a chronic complication following lung transplantation that limits the long-term survival. Although the enhancer of zeste homolog 2 (EZH2) is involved in post-transplantation rejection, its involvement in BOS pathogenesis remains unclear. We aimed to investigate the therapeutic potential of EZH2 inhibition in BOS. 3-deazaneplanocin A (DZNep) was administered intraperitoneally to heterotopic tracheal transplant recipient model mice. Tracheal allografts were obtained on days 7, 14, 21, and 28 after transplantation. The obstruction ratios of the DZNep and control groups on days 7, 14, 21, and 28 were 15.1% ± 0.8% vs. 20.4% ± 3.6% ( p = 0.996), 16.9% ± 2.1% vs. 67.7% ± 11.5% ( p < 0.001), 47.8% ± 7.8% vs. 92.2% ± 5.4% ( p < 0.001), and 60.0% ± 9.6% vs. 95.0% ± 2.3% ( p < 0.001), respectively. The levels of interleukin (IL)-6 and interferon-γ on day 7 and those of IL-2, tumor necrosis factor, and IL-17A on days 14, 21, and 28 were significantly reduced following DZNep treatment. DZNep significantly decreased the number of infiltrating T-cells on day 14. In conclusion, DZNep-mediated EZH2 inhibition suppressed the inflammatory reactions driven by pro-inflammatory cytokines and T cell infiltration, thereby alleviating BOS symptoms., 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., (Copyright © 2024 Matsudo, Takamori, Takenaka, Shimokawa, Hashinokuchi, Nagano, Kinoshita, Akamine, Kohno, Toyokawa and Yoshizumi.)

Deep sea water (DSW) contains many trace minerals, and its applications, which include its use as drinking water, have gradually been expanding. Generally, humans tend to be lacking in mineral intake and deficiencies of trace minerals may increase the risk of several health problems. In recent years, the lack of exercise among the elderly has become an issue, leading to the onset of frailty and sarcopenia, which in turn increases the risk of dementia. Therefore, we investigated whether the daily intake of DSW-extract-added water (DSW; hardness 300 mg/L) impacted the training effect in aged mice. Treatment with DSW significantly induced a training effect in aged mice subjected to treadmill exercise. Locomotor function and metabolic capacity were also significantly increased in aged mice after DSW treatment. The results indicate that daily intake of DSW may enhance the training effect of exercise and affect locomotor performance., 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.)

Background: To address the need for short-term prognostic methods using objective measures, we developed a method to predict a 2- or 3-week prognosis using only six clinical tests (known as the WPCBAL score). However, the method has not yet been directly compared with globally accepted prognostic methods., Objectives: This study aimed to clarify the usefulness of the WPCBAL score by comparing it with other prediction methods., Setting/subjects: A prospective observational study was conducted with patients admitted to the palliative care unit of a Municipal Hospital in Japan between November 2017 and May 2021., Measurements: The primary endpoint was each prediction method's accuracy-the WPCBAL score, Glasgow Prognostic Score (GPS), Palliative Prognostic Index (PPI), Palliative Prognostic Score (PaP), Delirium-Palliative Prognostic Score (D-PaP), and Prognosis in Palliative Care Study predictor models (PiPS-A, PiPS-B)-in predicting a prognosis at 2 or 3 weeks. The secondary endpoints were sensitivity, specificity, positive and negative predictive values, area under the receiver operating characteristic curve, and each prediction method's feasibility rate., Results: In total, 181 patients were included in this study. For the 3-week prognosis, the PaP had the highest accuracy (0.746), followed by the D-PaP (0.735), WPCBAL (0.696), PPI (0.652), and GPS (0.575). For the 2-week prognosis, the PiPS-B had the highest accuracy (0.702), followed by the WPCBAL (0.696) and PiPS-A (0.641)., Conclusions: The WPCBAL score's accuracy in predicting a 2- or 3-week prognosis was comparable to that of commonly used prognostic methods, thus suggesting its usefulness as a short-term prognostic method., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Background: Intramuscular hemangioma is an uncommon benign tumor found mainly in the limbs of adolescents and young adults. The local recurrence rate is high, ranging from 30 to 50%, necessitating wide local excision of intercostal intramuscular hemangiomas. However, preoperative diagnosis of intramuscular hemangiomas is challenging. Herein, we report a rare case of an intramuscular hemangioma arising from the chest wall., Case Presentation: A healthy 29-year-old asymptomatic man was referred to our hospital after an abnormal shadow was observed on his chest radiography. Computed tomography and magnetic resonance imaging revealed a 30-mm-sized mass in the right second intercostal space. Neoplastic lesions, such as schwannomas or solitary fibrous tumors, were included in the preoperative differential diagnosis. Tumor resection was performed using video-assisted thoracoscopic surgery. The tumor, which had a smooth surface covered with parietal pleura, was dissected from the external intercostal muscle and costal bone. Postoperative histopathological examination revealed proliferation of spindle-shaped endothelial cells arranged in a capillary vascular structure accompanied by entrapped smooth muscle fibers, adipose tissue, and muscle vessels. The final diagnosis was an intramuscular hemangioma with negative surgical margins. There was no evidence of recurrence during the 1-year postoperative follow-up period., Conclusion: Intramuscular hemangiomas should be considered in the differential diagnosis of chest wall tumors, particularly in young people, owing to their potential for recurrence. Moreover, postoperative follow-up may be necessary for resected intramuscular intercostal hemangiomas., (© 2024. The Author(s).)

This preclinical study was conducted to investigate the efficacy of interstitial PDT (i-PDT) for malignant gliomas arising deep within the brain, which are difficult to remove. C6 glioma cells were implanted into the basal ganglia of rats, and 3 weeks later, the second-generation photosensitizer talaporfin sodium (TPS) was administered intraperitoneally. Ninety minutes after administration, a prototype fine plastic optical fiber was punctured into the tumor tissue, and semiconductor laser light was irradiated into the tumor from a 2-mm cylindrical light-emitting source under various conditions. The brain was removed 24 h after the i-PDT and analyzed pathologically. The optical fiber was able to puncture the tumor center in all cases, enabling i-PDT to be performed. Histological analysis showed that tumor necrosis was induced in areas close to the light source, correlating with the irradiation energy dose, whereas apoptosis was induced at some distance from the light source. Irradiation using high energy levels resulted in tissue swelling from strong tumor necrosis, and irradiation at 75 J/cm 2 was most suitable for inducing apoptosis. An experimental system of i-PDT using TPS was established using malignant glioma cells transplanted into the rat brain. Tumor cell death, which correlated with the light propagation, was induced in tumor tissue.

Introduction: High recurrence rate following curative surgery for non-small cell lung cancer (NSCLC) presents a major clinical challenge. Understanding the site and timing of recurrence and their impact on post-recurrence survival (PRS) is important for optimal postoperative surveillance and therapeutic intervention. In this study, we investigated the influence of the time to recurrence (TTR) and initial recurrence site on PRS., Materials and Methods: This multicentre prospective cohort study included patients who experienced recurrence after NSCLC resection between 2010 and 2015. The relationship between TTR and initial recurrence site, and their impact on PRS, was further evaluated. The hazard ratio (HR) for PRS was analysed using the Cox proportional hazards model., Results: Among 495 patients, the median TTR was 14 (range, 1-158) months; the mode of recurrence was 11 months. Early recurrence within 6 months was observed in 17 % of patients, and 68 % of patients showed recurrence within 2 years post-surgery. The HR for PRS was the highest in patients with a TTR within 6 months, and a noticeable decline was observed after the first 6 months. The HRs of TTRs beyond 2 years were not significantly different. The liver was a significantly unfavourable prognostic site for metastases (HR 2.2; P = 0.01), and metastases frequently recurred within 6 months after surgery. The timing of brain metastasis did not significantly impact the PRS., Conclusion: Earlier recurrence after surgery was associated with shorter PRS. In contrast, recurrences occurring >2 years after surgery do not significantly affect PRS., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (© 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Signal-regulatory protein alpha (SIRPα) is an immune checkpoint molecule expressed on macrophages that functions to inhibit phagocytosis by binding to CD47 expressed on tumor cells. SIRPα has attracted increasing attention as a novel target for cancer immunotherapy; however, the expression and immune function of SIRPα in lung squamous cell carcinoma (LUSC) remain unclear. Therefore, this study aimed to identify the clinical importance of SIRPα expression in LUSC and to explore the factors that elevate SIRPα expression., Patients and Methods: Primary LUSC specimens surgically resected from 172 patients underwent immunohistochemical evaluation of the association of SIRPα expression on tumor-associated macrophages with clinicopathological features and clinical outcomes. Furthermore, we analyzed the association of SIRPα expression with tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1). In vitro, monocytes were treated with cytokines, and SIRPα protein expression was assessed by flow cytometry., Results: There were no differences in SIRPα expression and clinicopathological factors. High SIRPα expression was significantly associated with PD-L1-positive expression, and high CD8, PD-1, and CD163 expression. The high SIRPα expression group showed significantly shorter recurrence-free survival (RFS) and overall survival (OS). On multivariate analysis, high SIRPα expression was an independent poor prognostic factor for RFS and OS. The expression of SIRPα protein in monocytes was upregulated by treatment with IFNγ., Conclusion: Our analysis revealed that high SIRPα expression significantly predicts poor prognosis in patients with surgically resected LUSC., (© 2024. Society of Surgical Oncology.)

Objectives: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA)., Methods: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used., Results: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively., Conclusion: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA., (© 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.)

Background: The preoperative serum creatine kinase (CK) concentration is a prognostic factor for malignant diseases. We investigated the significance of CK in surgically resected thymic epithelial tumors and the relationship between CK and clinicopathological factors., Methods: We retrospectively evaluated the relationship between preoperative CK levels and prognosis in 120 patients with thymic epithelial tumors who underwent surgical resection at two centers. The cutoff for CK was determined by the standard value in our institution (<62 IU/L for men and <45 IU/L for women). The paravertebral muscle at the Th12 level was used to assess skeletal muscle area to investigate sarcopenia., Results: Eighteen patients (15.0%) were categorized into the low CK group. The CK level was not associated with age, sex, performance status, myasthenia gravis, and pathological findings. Preoperative serum albumin and total cholesterol concentrations were significantly lower in the low CK group than in the normal CK group (both P<0.001). Moreover, the Th12 muscle index was lower in the low CK group (P=0.03), indicating that low CK was related to sarcopenia. Kaplan-Meier curve analysis illustrated that patients in the low CK group had significantly shorter disease-free survival (DFS) and overall survival (OS) than those in the normal CK group (P=0.03 and P=0.002, respectively). Multivariate analysis identified low CK as an independent prognostic factor for DFS (P=0.03) and OS (P=0.005)., Conclusions: Preoperative serum CK might reflect the host nutritional status in patients with resected thymic epithelial tumors; therefore, CK could be a biomarker of postoperative prognosis., 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-23-1797/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Objectives: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis., Methods: We retrospectively assessed patients with antibody-associated vasculitis who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes was also evaluated., Results: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly., Conclusion: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg)., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme with an important role in tumor progression in various cancers. However, the clinical significance of GPX2 in lung adenocarcinoma has not been clarified., Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze GPX2 mRNA expression. Then, we conducted immunohistochemistry (IHC) to assess GPX2 expression in specimens acquired from 351 patients with lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We investigated the association between GPX2 expression and clinicopathological characteristics and further analyzed the prognostic relevance., Results: qRT-PCR revealed that GPX2 mRNA expression was notably higher in tumor cells than in normal tissues. IHC revealed that high GPX2 expression (n = 175, 49.9%) was significantly correlated with male sex, smoking, advanced pathological stage, and the presence of pleural, lymphatic, and vascular invasion. Patients with high GPX2 expression exhibited significantly shorter recurrence-free survival (RFS) and overall survival. Multivariate analysis identified high GPX2 expression as an independent prognostic factor of RFS., Conclusions: GPX2 expression was significantly associated with pathological malignancy. It is conceivable that high GPX2 expression reflects tumor malignancy. Therefore, high GPX2 expression is a significant prognostic factor of poor prognosis for completely resected lung adenocarcinoma., (© 2024. Society of Surgical Oncology.)

During early development, the enteric nervous system forms from the migration of enteric neural crest cells (ENCCs) from the foregut to the hindgut, where they undergo proliferation and differentiation facilitated by interactions with enteric mesenchymal cells (EMCs). This study investigates the impact on ENCC migration of EMC-ENCC communication mediated by GFRA1b expressed in EMCs. GFRA1-expressing cells in day 11-12 (E11-12) mouse embryos differentiated into smooth muscle cells from E12 onwards. Observations at E12-13.5 revealed high levels of GFRA1 expression on the anti-mesenteric side of the hindgut, correlating with enhanced ENCC migration. This indicates that GFRA1 in EMCs plays a role in ENCC migration during development. Examining GFRA1 isoforms, we found high levels of GFRA1b, which lacks amino acids 140-144, in EMCs. To assess the impact of GFRA1 isoforms on EMC-ENCC communication, we conducted neurosphere drop assays. This revealed that GFRA1b-expressing cells promoted GDNF-dependent extension and increased neurite density in ENCC neurospheres. Co-culture of ENCC mimetic cells expressing RET and GFRA1a with EMC mimetic cells expressing GFRA1a, GFRA1b, or vector alone showed that only GFRA1b-expressing co-cultured cells sustained RET phosphorylation in ENCC-mimetic cells for over 120 min upon GDNF stimulation. Our study provides evidence that GFRA1b-mediated cell-to-cell communication plays a critical role in ENCC motility in enteric nervous system development. These findings contribute to understanding the cellular interactions and signaling mechanisms that underlie enteric nervous system formation and highlight potential therapeutic targets for gastrointestinal motility disorders., 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 Inc. All rights reserved.)

Patient-derived organoids (PDOs) retain the original tumor's characteristics to a large degree and allow direct evaluation of the drug sensitivity, thereby emerging as a valuable resource for both basic and preclinical researches. Whereas most past studies stereotypically adopted a single PDO as an avatar of the patient, it remains to be investigated whether this assumption can be justified even for the tumor with spatial diversity. To address this issue, we established and characterized multiple PDOs originating from various sites of a patient with advanced uterine carcinosarcoma (UCS). Specifically, cancer cells were separately sampled from three sites; resected UCS tumor tissue, the peritoneal lavage fluid, and an intra-uterine brushing of the tumor. The three derived PDOs were morphologically undistinguishable, displaying typical carcinoma organoids-like appearance, but two of them proliferated at a faster rate. The primary tumor harbored mutations in TP53 and STK11 along with amplifications in CCNE1, ERBB2, and KRAS. These two mutations and the CCNE1 amplification were detected in all PDOs, while either KRAS or ERBB2 amplification was selectively observed in each PDO in a mutually exclusive manner. Observed intra-tumor heterogeneity in HER2 expression was differentially reproduced in the PDOs, which mirrored each PDO's sensitivity to HER2 inhibitors. Inter-PDO heterogeneity was also evident in sensitivity to standard cytotoxic agents. Lastly, a drug screening identified four candidate reagents commonly effective to all PDOs. Collectively, we showed that multiple PDOs could help reproduce the spatial diversity of a tumor and serve as a valuable resource in UCS research in many respects., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

We report the first case of drug-induced interstitial lung disease attributed to lemborexant. A 66-year-old man reported to our hospital with the acute onset of cough and breathlessness with ground-glass opacity on radiological examination. Symptoms were identified after taking lemborexant for 2 consecutive days. The patient had undergone lemborexant treatment 2 years prior and had exhibited no symptoms at that time. The drug-induced lymphocyte stimulation test for lemborexant was positive. He showed rapid improvement upon treatment with steroid. With the rise in prescriptions of lemborexant for insomnia, lemborexant should be considered as a possible cause of drug-induced interstitial lung disease., Competing Interests: Non declared., (© 2024 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm 2 or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects., (© 2024. The Author(s).)

Aim: Cerium oxide, particularly in nanoparticle form (nanoceria), has been investigated for biomedical applications as a promising new agent for treating several pathologies. The aim of the present study was to characterize the pharmacologic effects of nanoceria in an animal model of chronic kidney disease., Methods: We created the chronic kidney disease animal model by feeding rats a 0.25% adenine diet. Male Wistar rats were divided into five groups: normal diet, 0.25% adenine diet, or adenine diet containing three different doses or durations of nanoceria treatment. Blood was collected weekly from the tail veins of each rat and analyzed for renal function markers. After 5 weeks, various biochemical markers in serum, plasma, and urine were also analyzed., Results: In the adenine-treated group, body weight was significantly decreased, and the kidneys lost much of their healthy reddish color and became lumpy and white in appearance. In addition, levels of serum creatinine, blood urea nitrogen, and plasma uremic toxins were significantly increased in adenine-treated rats compared with controls. Renal functional and structural damage in adenine diet model rats tended to be ameliorated by nanoceria ingestion. The high-dose cerium-treated group maintained reddish areas in the kidneys, and the increases in biomarker levels of creatinine, blood urea nitrogen, and inorganic phosphorus were markedly reduced, regardless of treatment duration., Conclusions: Ingestion of nanoceria may be effective for improving or preventing renal damage caused by adenine. Geriatr Gerontol Int 2024; 24: 88-95., (© 2023 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background: For malignant glioma, intraoperative photodynamic therapy (PDT) using talaporfin sodium is a powerful tool for local tumor control, when gross total removal is performed. However, the efficacy of PDT for non-totally resectable malignant glioma has not been clearly confirmed. Therefore, the purpose of this study was to clarify the usefulness of PDT using talaporfin sodium for non-totally resectable malignant glioma., Methods: Eighteen patients with malignant glioma (16 new onset, 2 recurrent) in whom gross total removal was judged to be difficult from the images obtained before surgery were evaluated. Fifteen patients had glioblastoma (14 newly diagnosed, 1 recurrent), and 3 patients had anaplastic oligodendroglioma (2 newly diagnosed, 1 recurrent). The whole resection cavity was subjected to PDT during the surgery. For newly diagnosed glioblastoma, postoperative therapy involved the combined use of radiation and temozolomide. Bevacizumab treatment was also started at an early stage after surgery., Results: In some patients, reduction of the residual tumor was observed at an early stage of chemoradiotherapy after the surgery, suggesting the positive effect of PDT. Recurrence occurred in 15 of the 18 patients during the course of treatment. Distant recurrence occurred in 8 of these 15 patients, despite good local tumor control. In the 14 patients with newly diagnosed glioblastoma, the median progression-free survival was almost 10.5 months, and the median overall survival was almost 16.9 months., Conclusions: PDT for malignant glioma is expected to slightly improve local tumor control for non-totally resectable lesions., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest in association with this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

A 72-year-old woman with dermatomyositis (DM) developed neurological manifestation, and magnetic resonance imaging (MRI) revealed multiple T2/fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions predominantly in the deep white matter of the cerebral hemisphere. Punctate or linear contrast enhancement was observed surrounding the T1-hypointense area. Multiple T2/FLAIR-hyperintense lesions were aligned along with the corona radiata. Malignant lymphoma was first suspected, and a brain biopsy was performed. Pathological investigation suggested the provisional diagnosis of "suspicious of malignant lymphoma." Owing to emergent clinical conditions, high-dose methotrexate (MTX) therapy was conducted, and then T2/FLAIR-hyperintense lesions were dramatically reduced. However, the diagnosis of malignant lymphoma was concerning since multiplex PCR demonstrated clonal restriction of the Ig H gene for B cells and TCR beta genes for T cells. Histopathology revealed the infiltration of both CD4 + and CD8 + T cells, and the CD4 + /CD8 + ratio was 4.0. Moreover, prominent plasma cells were observed, in addition to CD20 + B cells. Atypical cells with enlarged nuclei were present, and they were not hematopoietic but found as glial cells. JC virus (JCV) infection was verified with both immunohistochemistry and in situ hybridization; the final diagnosis was progressive multifocal leukoencephalopathy (PML). The patient was treated with mefloquine and discharged. This case is informative in understanding the host anti-viral response. Variable inflammatory cells were observed, including CD4 + and CD8 + T cells, plasma cells, and a small amount of perivascular CD20 + B cells. PD-1 and PD-L1 expression was observed in lymphoid cells and macrophages, respectively. PML with inflammatory reactions was thought fatal, and autopsy cases of PML with immune reconstitution inflammatory syndrome (IRIS) demonstrated excessive infiltration of only CD8 + T cells. However, this case revealed infiltration of variable inflammatory cells, and a favorable prognosis would be expected under PD-1/PD-L1 immune-checkpoint regulation., (© 2023 The Authors. Neuropathology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Neuropathology.)