start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue= article-no= start-page=1 end-page=6 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The effects of cold compresses on itching in patients with atopic dermatitis: A cross-over controlled pilot trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=This cross-over controlled trial aimed to evaluate the effectiveness and safety of two types of cold compresses (towels and ice packs) in alleviating itching among patients with atopic dermatitis. The study recruited 19 participants diagnosed with atopic dermatitis and suffering from chronic itching for over 6 months. Each participant received both types of cold compress interventions. Itching sensations were assessed repeatedly using a visual analogue scale before and after the application of the cold compress. The mean and standard deviation of itching scores for the towel intervention were 16.9 ± 19.1 (baseline) and 11.4 ± 16.1 (post-application). For the ice pack intervention, the scores were 13.6 ± 14.7 (baseline) and 6.2 ± 9.8 (post-application). Although there was a reduction in mean itching scores following the application of cold compresses, the differences were not statistically significant for either intervention. Despite the lack of statistical significance, this study suggests that cold compresses, which are user-friendly and inexpensive, may safely reduce subjective itching in patients with atopic dermatitis without causing pain or discomfort. However, further research with a larger sample size is needed to confirm these findings. en-copyright= kn-copyright= en-aut-name=HIRAMIYuki en-aut-sei=HIRAMI en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HARADANahoko en-aut-sei=HARADA en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ONOMiho en-aut-sei=ONO en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KODAMasahide en-aut-sei=KODA en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FUKAIKiyoko en-aut-sei=FUKAI en-aut-mei=Kiyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Former Department of Nursing, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nursing Science, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Nursing, Faculty of Health, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=4 en-affil=Co-learning Community Healthcare Re-innovation Office, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Professor Emeritus, Okayama University, Graduate School of Nursing, The Jikei University School of Medicine kn-affil= en-keyword=Atopic Dermatitis kn-keyword=Atopic Dermatitis en-keyword=Pruritus kn-keyword=Pruritus en-keyword=Cryotherapy kn-keyword=Cryotherapy en-keyword=Quality of Life kn-keyword=Quality of Life en-keyword=Skin Temperature kn-keyword=Skin Temperature END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=845 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Seasonal Variations in the Risk of Outpatient Acute Kidney Injury in Patients with Chronic Kidney Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Acute kidney injury (AKI) frequently occurs in the outpatient setting and is associated with adverse renal and survival outcomes. However, there is no established definition of outpatient AKI, and the risk factors, especially seasonal variation, remain limited. This study aimed to investigate seasonal variation in the risk of outpatient AKI. Methods: This retrospective observational study used routinely collected clinical laboratory data from a single hospital in Japan between 2007 and 2022. Outpatient AKI was defined as ?35% relative decline in estimated glomerular filtration rate (eGFR) compared with a preceding outpatient measurement obtained within 14?90 days. Monthly and seasonal variations in outpatient AKI risk in patients with chronic kidney disease (CKD) were evaluated using logistic regression models. Subgroup analyses were performed according to AKI stage, age group, and CKD stage. Results: A total of 203,853 outpatient records were analyzed. The incidence of outpatient AKI was highest in August and lowest in November. Analyses demonstrated significantly increased odds ratios of outpatient AKI in January, February, July, and August. Seasonally, the risk was significantly higher during the summer. Stage-specific analyses showed that AKI stage 1 was more frequent in the summer, whereas AKI stage 2 tended to increase during the winter. Conclusions: Outpatient AKI exhibits distinct seasonal patterns, with increased risk during both summer and winter and differential associations according to AKI severity and baseline kidney function. Recognition of these patterns may help identify vulnerable populations and inform targeted preventive strategies for outpatient AKI. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute kidney injury kn-keyword=acute kidney injury en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=outpatients kn-keyword=outpatients en-keyword=seasons kn-keyword=seasons END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=e70168 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanosensitive Ion Channel PIEZO1 Suppresses BMP2-Induced Ossification of the Annulus Fibrosus Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Major cause of low-back pain is intervertebral disc degeneration (IVDD), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel, PIEZO1, is involved in various musculoskeletal tissues, but its role in the annulus fibrosus (AF) remains unclear. This study aimed to elucidate the function of PIEZO1 in AF cells under mechanical stimulation.
Methods: Primary rat AF cells were subjected to cyclic tensile strain (CTS) at low (2%) and high (12%) strain levels to investigate strain-dependent effects on osteogenic gene expression. We evaluated the effects of Piezo1, Piezo2, and Trpv4 knockdown by RNA interference to identify the upstream mechanotransducer. Furthermore, PIEZO1 was activated using the agonist Yoda1, followed by RNA-sequencing analysis and evaluation of its effects on BMP2-induced osteogenesis in rat AF cells. We also examined the effects of Yoda1 in primary human AF cells.
Results: Low-strain CTS significantly suppressed osteogenic marker expression, which was not observed with high strain. Piezo1 knockdown reversed this suppression, whereas Piezo2 and Trpv4 had no effect. Piezo1 activation by Yoda1 produced similar anti-osteogenic effects in both rat and human AF cells. RNA sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited BMP2-induced osteogenesis and nuclear translocation of p-Smad1/5/9.
Conclusions: Piezo1 maintains AF cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin-mediated inhibition of BMP signaling, which may represent a novel therapeutic target for IVDD. en-copyright= kn-copyright= en-aut-name=ShitozawaHisakazu en-aut-sei=Shitozawa en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamichiRyo en-aut-sei=Nakamichi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaMasataka en-aut-sei=Ueda en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoTaichi en-aut-sei=Saito en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakatoriRyo en-aut-sei=Takatori en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamashitaKazutaka en-aut-sei=Yamashita en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=annulus fibrosus kn-keyword=annulus fibrosus en-keyword=calcification kn-keyword=calcification en-keyword=ossification kn-keyword=ossification en-keyword=PIEZO1 kn-keyword=PIEZO1 END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=9 article-no= start-page=e772 end-page=e780 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Aging of the tricuspid valve annulus detected by photon-counting detector computed tomography: Importance of aortic root compression on occurrence of arrhythmias en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The aortic root compresses the heart in elderly patients, potentially influencing the conduction system and causing atrial tachyarrhythmias. However, actual anatomic alterations in the right side of the heart because of aortic root compression have not yet been fully evaluated.
Objective This study aimed to elucidate the alterations in the tricuspid valve annulus (TVA) caused by aortic root compression using a 3-dimensional endoscopic view of the heart constructed by photon-counting detector computed tomography, an emerging medical technology.
Methods We analyzed 147 consecutive patients who underwent photon-counting detector computed tomography at our institute after excluding those with diseases that directly influenced the right side of the heart.
Results Aortic root compression caused significant TVA deformation. We defined severe TVA compression as the length of the TVA compressed by the aortic root ?80% of the major axis of the TVA. Severe compression was more prevalent in elderly patients (age ?75 years [44%]; P < .01). The distance between the membranous septum and ostium of the coronary sinus was shortened, whereas the cavotricuspid isthmus was elongated in older patients. The regression analysis identified aging as a significant contributor to TVA compression. The short minor and long major axes of the TVA, incidence of atrial tachyarrhythmias (74% vs 45%; P < .01), and atrioventricular conduction disturbances (35% vs 15%; P < .01) were more frequently observed in patients with severe compression.
Conclusion Aortic root compression deforms the TVA and alters the anatomic relationship between the atrioventricular conduction system and the cavotricuspid isthmus. Therefore, aortic root compression may contribute to the occurrence of atrial tachyarrhythmias and conduction disturbances in older patients. en-copyright= kn-copyright= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaseSatoshi en-aut-sei=Nagase en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimotoYoshihisa en-aut-sei=Morimoto en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UeokaAkira en-aut-sei=Ueoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=3 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=11 en-affil=Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= en-keyword=Tricuspid valve annulus kn-keyword=Tricuspid valve annulus en-keyword=Aortic root kn-keyword=Aortic root en-keyword=Photon-counting detector computed tomography kn-keyword=Photon-counting detector computed tomography en-keyword=Atrial tachyarrhythmia kn-keyword=Atrial tachyarrhythmia en-keyword=Conduction abnormality kn-keyword=Conduction abnormality END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MMP-3 cleavage of Lamin A induces pro-migratory nuclear deformity, nucleophagy, and their autophagic secretion with extracellular vesicles in metastatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that cleave a plethora of substrates, including components of the extracellular matrix and cell-surface-associated proteins, as well as intracellular targets. MMPs have also been found in extracellular vesicles (EVs), such as exosomes. MMP-3 promotes tumor growth, epithelial-to-mesenchymal transition, genome instability, migration, invasion, and metastasis of cancer cells, and nuclear MMP-3 controls gene transcription. Intranuclear proteolysis by MMPs may significantly alter cancer progression. However, the nuclear substrates of MMP-3 have not been well investigated. In this study, we performed proteomic analyses to identify the nuclear substrates and EV proteins regulated by MMP-3. While rabidly metastatic colon cancer (LuM1) three-dimensionally cultured tumoroids secreted EVs containing 30 protein types, including Lamin A (LMNA), MMP-3, fibronectin (FN1), HSPA8 (Hsc70), β-actin (ACTB), and vimentin (VIM), CRISPR/Cas9-based knockout of MMP-3 reduced the secretion of these proteins in EVs. Notably, EV-bound cleaved Lamin secretion was confirmed by immunoelectron microscopy. Also, MMP-3 formed proteolytic dimers via its hemopexin-like repeat domains in nuclei. Many nuclear MMP-3-binding proteins, including Lamin A/C, histones, topoisomerases, and hnRNPs, were screened by co-immunoprecipitation followed by proteomics. Proteolytic MMP-3 overexpression generated a C-terminal 30-kDa fragment of Lamin A, whose cleavage site was defined via structural analysis. MMP-3 digestion of Lamin A induced nuclear deformity (atypia) required for cell migration in confined space. The cleaved Lamin A and MMP-3 were transported with autophagosomes (LC3B+), nucleophagosomes, and amphisomes (CD63?+?LC3B+) and co-secreted with EVs. Proteolytic MMP-3 also induced nuclear speckles of Lamin A, suggesting their roles in transcription and splicing. Clinical analysis revealed that high expressions of MMP3 and LMNA were significantly seen in head and neck squamous cell carcinoma (HNSC) than in the other 16 cancer types, and predicted poor prognosis of patients suffering from HNSC, pancreatic, rectum and lung adenocarcinomas at specific stages. Immunohistochemistry revealed that nuclear MMP-3 and cleaved Lamin were significantly higher expressed in stage IV metastatic HNSC cases than in stage I non-metastatic cases. Taken together, MMP3-cleavage of Lamin A induces nuclear deformity, nucleophagy, and their autophagic co-secretion with EVs in metastatic cancer. Also, high expression of MMP-3 and secretion of Lamin A can predict poor prognosis in multiple cancer types at specific stages. en-copyright= kn-copyright= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TahaEman A. en-aut-sei=Taha en-aut-mei=Eman A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TiwariVikas en-aut-sei=Tiwari en-aut-mei=Vikas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=XingLizi en-aut-sei=Xing en-aut-mei=Lizi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biochemistry, Faculty of Science, Ain Shams University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Council of Scientific & Industrial Research-Indian Institute of Toxicological Research kn-affil= affil-num=5 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology kn-affil= affil-num=9 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=Lamin A (LMNA) kn-keyword=Lamin A (LMNA) en-keyword=Matrix metalloprotease (MMP) kn-keyword=Matrix metalloprotease (MMP) en-keyword=Proteolysis kn-keyword=Proteolysis en-keyword=Extracellular vesicle (EV) kn-keyword=Extracellular vesicle (EV) en-keyword=Exosome kn-keyword=Exosome en-keyword=Autophagy kn-keyword=Autophagy en-keyword=Amphisome kn-keyword=Amphisome en-keyword=Proteome kn-keyword=Proteome en-keyword=Nuclear deformity kn-keyword=Nuclear deformity en-keyword=Migration kn-keyword=Migration en-keyword=Metastatic cancer kn-keyword=Metastatic cancer en-keyword=Head and neck squamous cell carcinoma kn-keyword=Head and neck squamous cell carcinoma en-keyword=Colorectal cancer kn-keyword=Colorectal cancer END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=27 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between the incidence of infusion-related reactions by obinutuzumab and the dose of corticosteroid as premedication: a multicenter retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Premedication with corticosteroids is recommended for prophylaxis against infusion-related reactions (IRRs) caused by obinutuzumab despite a lack of solid evidence regarding the dose of corticosteroids.
Methods The incidence rates of IRR in the high-dose and low-dose corticosteroid groups were investigated and compared using Student’s t-test.Univariable and multivariable logistic regression analyses were performed on patients to explore the risk of developing IRRs with obinutuzumab.
Results The incidence of IRRs in the high-dose and low-dose corticosteroid groups at the initial administration of obinutuzumab was 27.0% (41/152) and 48.4% (31/64), respectively, indicating that the high-dose group had a lower incidence of IRRs (p?=?0.002). The incidence of IRRs at the initial administration of obinutuzumab was significantly associated with the administration of first-generation histamine 1 receptor antagonist (OR?=?3.31, 95% CI: 1.16?9.47; reference: second-generation histamine 1 receptor antagonist), hydrocortisone (OR?=?7.21, 95% CI: 1.57?33.15; reference: dexamethasone), and methylprednisolone (OR?=?3.99, 95% CI :1.13?14.10; reference: dexamethasone), although no association was found with the lower dose of corticosteroids.
Conclusions Although no association was found between corticosteroid dosage and IRR when considering multiple factors, dexamethasone may be a better option than hydrocortisone or methylprednisolone for preventing IRR. Additionally, second-generation H1-receptor antagonists may be a better option than first-generation drugs. Certain combinations of premedications may influence infusion reaction incidence. en-copyright= kn-copyright= en-aut-name=OhtsuboTatsuya en-aut-sei=Ohtsubo en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatumotoSaori en-aut-sei=Matumoto en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoKaori en-aut-sei=Ito en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasaYuzuka en-aut-sei=Sasa en-aut-mei=Yuzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomishimaKosuke en-aut-sei=Tomishima en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoteSatoshi en-aut-sei=Dote en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakiharaKatuya en-aut-sei=Makihara en-aut-mei=Katuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WakasugiYoshinori en-aut-sei=Wakasugi en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MitsuieTsutomu en-aut-sei=Mitsuie en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamagiwaKouhei en-aut-sei=Yamagiwa en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatoKazuo en-aut-sei=Sato en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HasegawaHiroki en-aut-sei=Hasegawa en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UoshimaNobuhiko en-aut-sei=Uoshima en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TomoganeKanji en-aut-sei=Tomogane en-aut-mei=Kanji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Pharmacy, Japanese Red Cross Kyoto Daini Hospital kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Japanese Red Cross Osaka Hospital kn-affil= affil-num=4 en-affil=Faculty of Pharmacy, Meijo University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Kindai University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Japanese Red Cross Kyoto Daiichi Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Kyoto-Katsura Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Yodogawa Christian Hospital kn-affil= affil-num=9 en-affil=Department of Pharmacy, Shiga University of Medical Science Hospital kn-affil= affil-num=10 en-affil=Department of Pharmacy, Japanese Red Cross Otsu Hospital kn-affil= affil-num=11 en-affil=Department of Pharmacy, Saiseikai Shiga Hospital kn-affil= affil-num=12 en-affil=Department of Pharmacy, Japan Baptist Hospital kn-affil= affil-num=13 en-affil=Department of Pharmacy, Rakuwakai Otowa Hospital kn-affil= affil-num=14 en-affil=Department of Hematology, Japanese Red Cross Kyoto Daini Hospital kn-affil= affil-num=15 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=16 en-affil=Department of Pharmacy, Japanese Red Cross Kyoto Daini Hospital kn-affil= en-keyword=Obinutuzumab kn-keyword=Obinutuzumab en-keyword=Infusion-related reaction kn-keyword=Infusion-related reaction en-keyword=Premedication kn-keyword=Premedication en-keyword=Corticosteroids kn-keyword=Corticosteroids en-keyword=Histamine 1 receptor antagonists kn-keyword=Histamine 1 receptor antagonists END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=2339 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Concentration-Dependent Synergistic Interfacial Interactions Between Multifunctional Acrylate and Silane Coupling Agents in an Organic?Inorganic Nanohybrid Material en-subtitle= kn-subtitle= en-abstract= kn-abstract=Synergistic effects of a multifunctional acrylate and a long-chain silane coupling agent were investigated in an organic?inorganic nanohybrid material. We tested the bond strength of nanohybrid composites treated with experimental primers containing silane coupling agents?3-methacryloxypropyl trimethoxysilane (γ-MPTS) or 8-methacryloxyoctyl trimethoxysilane (8-MOTS)?with or without multifunctional acrylates?trimethylolpropane triacrylate (A-TMPT) or dipentaerythritol hexaacrylate (A-DPH). Shear bond strength was evaluated after 24 h of water storage at 37 °C. Untreated control and silane-only groups exhibited low shear bond strengths (e.g., control: 2.4 ± 2.0 MPa) and failed exclusively at the adhesive interface. While addition of A-TMPT did not significantly improve bond strength, addition of A-DPH produced significantly higher shear bond strengths. Highest strength was achieved with 30% 8-MOTS and A-DPH (22.4 ± 6.1 MPa), followed by 20% γ-MPTS and A-DPH (19.0 ± 7.0 MPa), and A-DPH groups produced cohesive failures. Regardless of the silane used (γ-MPTS or 8-MOTS), incorporating A-DPH in the primer consistently yielded superior bond strengths, indicating a promising strategy for improved adhesion for such nanohybrid systems. These findings provide new insights into optimizing resin?filler interfacial interactions and may contribute to the development of restorative materials with improved long-term clinical durability. en-copyright= kn-copyright= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IrieMasao en-aut-sei=Irie en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KodamaNaoki en-aut-sei=Kodama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshizaneMai en-aut-sei=Yoshizane en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkiyamaKentaro en-aut-sei=Akiyama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=2 en-affil=Health Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=3 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University kn-affil= affil-num=5 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=6 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=silane coupling kn-keyword=silane coupling en-keyword=multifunctional acrylate kn-keyword=multifunctional acrylate en-keyword=bond strength kn-keyword=bond strength en-keyword=resin kn-keyword=resin END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=e006392 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dental infection is associated with early relapse in patients with ANCA-associated vasculitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease where infections can trigger relapses. Dental infections, being common and associated with systemic inflammation, may play a role in AAV relapse, though their impact remains unclear. We aimed to evaluate the association between severe dental infections and early relapse in patients with AAV.
Methods This retrospective cohort study included patients newly diagnosed with AAV between January 2011 and July 2022. Patients with severe dental infections requiring tooth extraction were placed in the dental infection group, while the remaining patients were assigned to the control group. The primary outcome was defined as either vasculitis relapse or all-cause mortality within 1 year of treatment initiation. Adjusted HRs (aHRs) and 95% CIs were estimated using Cox proportional hazards models.
Results A total of 93 patients were enrolled with a median age of 74 years. 41 patients (44.1%) had severe dental infections in this cohort. Over the 1-year follow-up period, 13 patients experienced a relapse and two died, resulting in a composite event rate of 20.9 per 100 person-years. Dental infection was independently associated with the composite outcome (aHR, 3.78 (95% CI 1.13 to 12.66); p=0.031). Exploratory analysis indicated that composite outcome rates were similar regardless of tooth extraction among patients with dental infections.
Conclusions Severe dental infections were associated with increased risk of early relapse or mortality in AAV. These findings highlight the importance of early dental evaluation in AAV management. en-copyright= kn-copyright= en-aut-name=NawachiShoichi en-aut-sei=Nawachi en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Sakamoto-TokunagaMoe en-aut-sei=Sakamoto-Tokunaga en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TerajimaYuya en-aut-sei=Terajima en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoKazuya en-aut-sei=Matsumoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiroseKei en-aut-sei=Hirose en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakadoiTakato en-aut-sei=Nakadoi en-aut-mei=Takato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Hirata-WatanabeManami en-aut-sei=Hirata-Watanabe en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiKeigo en-aut-sei=Hayashi en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=Takano-NarazakiMariko en-aut-sei=Takano-Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TsujiShigetomo en-aut-sei=Tsuji en-aut-mei=Shigetomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue=3 article-no= start-page=117345 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of the cefazolin inoculum effect in blood culture-isolated methicillin-susceptible Staphylococcus aureus strains: A Japanese multicenter study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Cefazolin inoculum effect (CInE) is a microbiological phenomenon where the MIC of cefazolin against methicillin-susceptible Staphylococcus aureus (MSSA) strains increases with higher bacterial volumes.
Method: We retrospectively investigated the prevalence and characteristics of the CInE among MSSA strains isolated from blood cultures at three Japanese hospitals. The collected isolates were screened for blaZ using PCR, and the cefazolin minimum inhibitory concentration (MIC) for the blaZ-positive MSSA isolates was measured at standard and high inoculum volumes. CInE-positive MSSA strains were defined as those with a cefazolin MIC ?16 μg/mL at 107 CFU/mL and ?8 μg/mL at 105 CFU/mL. In these blaZ-positive strains, we performed blaZ typing and tested a modified nitrocefin-based rapid examination to detect the CInE.
Results: We collected 329 MSSA strains isolated from blood cultures. Of these, 96 (29.2%) were positive for the blaZ gene, with the following genotypes: type A (15, 15.6%), type B (3, 3.1%), type C (77, 80.2%), type D (0, 0.0%), and non-type (1, 1.0%). Among 96 blaZ-positive MSSA isolates, 11 exhibited the CInE, all of which harbored blaZ type A. The rapid nitrocefin test detected CInE positivity with high sensitivity (100%), specificity (94.1%), and diagnostic accuracy (94.8%).
Conclusion: This study highlighted the low prevalence of CInE-presenting MSSA isolates in Japan. When the cefazolin MIC is ?1 μg/mL or the penicillin G MIC is ?0.25 μg/mL, the rapid nitrocefin test may be useful for considering the CInE in patients with high bacterial volume MSSA infections. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaSakura en-aut-sei=Ogawa en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoyanagiNorihito en-aut-sei=Koyanagi en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoYuji en-aut-sei=Ito en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoganemaruHiroshi en-aut-sei=Koganemaru en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshidaAtsushi en-aut-sei=Yoshida en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Clinical Laboratory, Chutoen General Medical Center kn-affil= affil-num=7 en-affil=Department of General Internal Medicine, Chutoen General Medical Center kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=10 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=blaZ kn-keyword=blaZ en-keyword=Cefazolin inoculum effect kn-keyword=Cefazolin inoculum effect en-keyword=Methicillin-susceptible Staphylococcus aureus kn-keyword=Methicillin-susceptible Staphylococcus aureus en-keyword=Nitrocefin rapid test kn-keyword=Nitrocefin rapid test en-keyword=β-lactamase kn-keyword=β-lactamase END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=3 article-no= start-page=e198959 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collagen-binding C-type natriuretic peptide enhances chondrogenesis and osteogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=C-type natriuretic peptide (CNP) is known to promote chondrocyte proliferation and bone formation; however, CNP’s extremely short half-life necessitates continuous intravascular administration to achieve bone-lengthening effects. Vosoritide, a CNP analog designed for resistance to neutral endopeptidase, allows for once-daily administration. Nonetheless, it distributes systemically rather than localizing to target tissues, which may result in adverse effects such as hypotension. To enhance local drug delivery and therapeutic efficacy, we developed a potentially novel synthetic protein by fusing a collagen-binding domain (CBD) to CNP, termed CBD-CNP. This fusion protein exhibited stability under heat conditions and retained the collagen-binding ability and bioactivity as CNP. CBD-CNP localized to articular cartilage in fetal murine tibiae and promoted bone elongation. Spatial transcriptomic analysis revealed that the upregulation of chondromodulin expression may contribute to its therapeutic effects. Treatment of CBD-CNP mixed with collagen powder to a fracture site of a mouse model increased bone mineral content and bone volume compared with CNP-22. Intraarticular injection of CBD-CNP to a mouse model of knee osteoarthritis suppressed subchondral bone thickening. By addressing the limitations of CNP’s rapid degeneration, CBD-CNP leverages its collagen-binding capacity to achieve targeted, sustained delivery in collagen-rich tissues, offering a promising strategy for enhancing chondrogenesis and osteogenesis. en-copyright= kn-copyright= en-aut-name=HiraiKenta en-aut-sei=Hirai en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawamuraKenta en-aut-sei=Sawamura en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EsakiRyusaku en-aut-sei=Esaki en-aut-mei=Ryusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SawadaRyusuke en-aut-sei=Sawada en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AoyamaEriko en-aut-sei=Aoyama en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoHiroki en-aut-sei=Saito en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchidaKentaro en-aut-sei=Uchida en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MimaTakehiko en-aut-sei=Mima en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ImagamaShiro en-aut-sei=Imagama en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsushitaMasaki en-aut-sei=Matsushita en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HosonoYasuyuki en-aut-sei=Hosono en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=9 en-affil=Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences kn-affil= affil-num=10 en-affil=Department of Biochemistry and Molecular DentistryBacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world six-month outcomes after switching from aflibercept 2 mg to aflibercept 8 mg for neovascular age-related macular degeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose To investigate 6-month outcomes in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept 2 mg to intravitreal aflibercept 8 mg.
Study design Retrospective observational study.
Methods We reviewed records of consecutive nAMD eyes switched from aflibercept 2 mg to 8 mg. In eyes continuing aflibercept 8 mg, best-corrected visual acuity (BCVA), treatment intervals, and anatomical/exudative parameters were evaluated at 6 months. In eyes that could not continue, reasons for discontinuation were examined.
Results Forty-four eyes from 44 patients were included. At 6 months, 35 eyes (79.5%) continued and 9 (20.5%) discontinued aflibercept 8 mg. Discontinuing eyes had significantly shorter pre-switch treatment intervals and more frequent prior therapies than continuing eyes. In the continuation group, BCVA remained stable (median 0.05 to 0.00 logMAR, P = 0.351), while the treatment interval was significantly extended (median 7.0 to 9.0 weeks, P < 0.001). Central retinal thickness and pigment epithelial detachment height decreased significantly (P = 0.035 and P = 0.021, respectively). The proportion of eyes with subretinal fluid significantly decreased from 74.3 to 37.1% (P = 0.003). Of the discontinuations, 4 were due to worsening exudation and 5 to inability to extend to ?8 weeks as required by labeling. No intraocular inflammation or serious adverse events occurred.
Conclusions Switching to aflibercept 8?mg achieved anatomical improvements and longer treatment intervals in ~80% of nAMD cases, suggesting it may be a useful alternative to aflibercept 2 mg. However, continuation may be difficult in refractory cases requiring frequent injections before switching. en-copyright= kn-copyright= en-aut-name=KindoHiroya en-aut-sei=Kindo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosokawaMio Morizane en-aut-sei=Hosokawa en-aut-mei=Mio Morizane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OuchiChihiro en-aut-sei=Ouchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HayashiJunko en-aut-sei=Hayashi en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Aflibercept 8 mg kn-keyword=Aflibercept 8 mg en-keyword=Neovascular age-related macular degeneration kn-keyword=Neovascular age-related macular degeneration en-keyword=Treat-and-extend kn-keyword=Treat-and-extend en-keyword=Switching kn-keyword=Switching en-keyword=Treatment interval kn-keyword=Treatment interval END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=888 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skeletal muscle remodelling relies on muscle stem cells (MuSCs) for regeneration after injury and hypertrophy in response to mechanical loading. However, the mechanisms that trigger MuSC activation and proliferation remain unclear. Transient receptor potential vanilloid 2 (TRPV2) ion channels respond to insulin-like growth factor-1 and mechanical stimuli to regulate the biological characteristics of various cells. Using a temporally inducible MuSC-specific conditional knockout (cKO) mouse, we show that TRPV2 regulates MuSC function and is essential for muscle remodelling. In cultured myofibre, MuSCs express TRPV2 and exhibit Ca2+ responses to the TRPV2 agonists 2-aminoethoxydiphenyl borate and probenecid, which are abolished upon TRPV2 deletion. TRPV2-deficient MuSCs exhibit reduced paired box 7 (Pax7) expression and impaired proliferation, suggesting TRPV2 is a factor that regulates the early stage of MuSC function. Myotube formation in MuSCs was enhanced by overexpression of TRPV2 and suppressed by TRPV2 deficiency, suggesting that TRPV2 is a factor that promotes myogenesis. Muscle-administered cardiotoxin promoted muscle regeneration and resulted in the appearance of numerous Pax7-positive MuSCs between myofibres. MuSC-specific TRPV2 cKO mice exhibit substantially impaired muscle regeneration after cardiotoxin-induced injury, drastically reducing Pax7-positive MuSCs between myofibres. In floxed mice, mechanical loading via synergist ablation induces hypertrophy and greatly increases the number of myonuclei per myofibre. In contrast, MuSC-specific TRPV2 cKO mice show no changes in myofibre thickness or nuclear number, either at baseline or after mechanical loading. Mechanical loading of floxed mice increased TRPV2+/Pax7+ double-positive MuSCs, but MuSC-specific TRPV2 cKO mice showed no change. Additionally, MuSCs exhibit Ca2+ responses to hypo-osmotic stimuli, which are suppressed by TRPV2 inhibitors and TRPV2 deletion, suggesting that MuSCs exhibit TRPV2-dependent mechanical responses. These results establish TRPV2 as a critical regulator of MuSC-mediated muscle remodelling, an important finding that may lead to therapeutic strategies for muscle repair and adaptation. en-copyright= kn-copyright= en-aut-name=ChenYanzhu en-aut-sei=Chen en-aut-mei=Yanzhu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatanosakaKimiaki en-aut-sei=Katanosaka en-aut-mei=Kimiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShibuyaMakoto en-aut-sei=Shibuya en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DongYubing en-aut-sei=Dong en-aut-mei=Yubing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhangLidan en-aut-sei=Zhang en-aut-mei=Lidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanagawaMotoi en-aut-sei=Kanagawa en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukadaSo-ichiro en-aut-sei=Fukada en-aut-mei=So-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatanosakaYuki en-aut-sei=Katanosaka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka kn-affil= affil-num=6 en-affil=Department of Cell Biology and Molecular Medicine, Ehime University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka kn-affil= affil-num=8 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=411 cd-vols= no-issue=1 article-no= start-page=22 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The impact of liver transection depth on surgical difficulty in robotic versus laparoscopic limited liver resection (TAKUMI-5) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Although robotic liver resection (RLR) has gained popularity worldwide, limited liver resection remains the mainstay of RLR. This study aimed to investigate the effect of parameters, including liver transection depth (LTD), on surgical difficulty in limited RLR compared with limited laparoscopic liver resection (LLR).
Methods This retrospective study included 105 patients who underwent limited RLR (n?=?56) or LLR (n?=?49) at our institution between January 2018 and December 2024. After comparing outcomes of RLR and LLR, multivariate analyses were performed to examine effect of LTD on surgical difficulty (defined as prolonged operative time). Moreover, outcomes stratified by LTD cut-off values were compared between the groups.
Results Median LTD was similar between groups (RLR vs. LLR: 2.6 vs. 2.6 cm, P?=?0.77). LTD was significantly correlated with operative time for both procedures (RLR, R? = 0.07, P?=?0.042; LLR, R? = 0.08, P?=?0.046). Multivariate analyses demonstrated that LLR (odds ratio, 6.9; P??2.5 cm), the RLR group had significantly shorter operative time (145 vs. 231 min, P? Conclusion This study investigated impact of LTD on surgical outcomes in patients who underwent limited RLR compared to those who underwent limited LLR. LTD may be a useful parameter for estimating surgical difficulty in limited RLR. Moreover, robotic surgery may be favorable for deeper and limited liver resections. en-copyright= kn-copyright= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoAtene en-aut-sei=Ito en-aut-mei=Atene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YokoyamaShohei en-aut-sei=Yokoyama en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Robotic surgery kn-keyword=Robotic surgery en-keyword=Laparoscopic surgery kn-keyword=Laparoscopic surgery en-keyword=Limited liver resection kn-keyword=Limited liver resection en-keyword=Textbook outcome kn-keyword=Textbook outcome END start-ver=1.4 cd-journal=joma no-vol=411 cd-vols= no-issue=1 article-no= start-page=21 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged???90 years with resectable colon cancer.
Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS).
Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p?=?0.038) and lower ASA scores (p?=?0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p?=?0.046) but less intraoperative blood loss (10 vs. 78 mL, p? Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach. en-copyright= kn-copyright= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakanagaSatoe en-aut-sei=Takanaga en-aut-mei=Satoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InadaRyo en-aut-sei=Inada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToshimaToshiaki en-aut-sei=Toshima en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtaniTsuyoshi en-aut-sei=Ohtani en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaRyosuke en-aut-sei=Yoshida en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoriNaoto en-aut-sei=Hori en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShigemitsuKaoru en-aut-sei=Shigemitsu en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoSumiharu en-aut-sei=Yamamoto en-aut-mei=Sumiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KubotaTetsushi en-aut-sei=Kubota en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkanoYuka en-aut-sei=Okano en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NobuhisaTetsuji en-aut-sei=Nobuhisa en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IshikawaWataru en-aut-sei=Ishikawa en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsudaTatsuo en-aut-sei=Matsuda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UmeokaTatsuo en-aut-sei=Umeoka en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Setouchi Colorectal Neoplasm Registration study group collaborators en-aut-sei=Setouchi Colorectal Neoplasm Registration study group collaborators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Saiseikai Okayama Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Tottori Municipal Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Kobe Red Cross Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Onomichi City Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=15 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=16 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=17 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Matsuyama City Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=Oldest-old patients kn-keyword=Oldest-old patients en-keyword=Colon cancer kn-keyword=Colon cancer en-keyword=Laparoscopic surgery kn-keyword=Laparoscopic surgery en-keyword=Surgical outcome kn-keyword=Surgical outcome en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early C-reactive protein as a predictive biomarker for postoperative complications following robot-assisted surgery for rectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=This retrospective cohort study aimed to assess the predictive value of early postoperative C-reactive protein (CRP) levels for complications following robot-assisted rectal surgery (RARS) for rectal cancer. We analyzed data from 117 consecutive patients who underwent elective RARS at Okayama University Hospital between September 2020 and January 2025. Serum CRP levels were routinely measured preoperatively and on postoperative days (POD) 1 and 4. The primary outcome was the occurrence of any postoperative complication within 30 days, classified according to the Clavien?Dindo grading system. Postoperative complications were observed in 26 patients, representing 22.2% of the cohort. Univariate analysis revealed that several factors were significantly associated with complications, including older age, higher ASA score, neoadjuvant therapy, stoma creation, prolonged operative time, and elevated CRP levels on POD1 and POD4. Notably, multivariate logistic regression analysis identified POD1 CRP as a robust independent predictor of overall postoperative complications (adjusted odds ratio 0.77, 95% confidence interval (CI) [0.63?0.93], p? Methods In this retrospective study, morphologic mapping of sacral fracture lines was performed in 36 patients with FFP type IVb. Based on the mapping results, a finite element (FE) model of FFP type IVb was developed to evaluate the biomechanical stability of ilio-sacral screw (ISS) fixation, trans-sacral screw (TSS) fixation, spinopelvic fixation (SPF; On each side, L5 pedicle screw was connected to two iliac screws with a rod, and the bilateral constructs were linked using a cross-connector.), and bilateral triangular fixation (one TSS at S1 combined with SPF mentioned above) using finite element analysis (FEA).
Results Morphologic mapping showed that the sacrum fracture transverse line tended to pass between the S1-2 transverse lines. Although bilateral triangular fixation and SPF provided the highest stability in both U-type and H-type fractures, a TSS for U-type and two TSSs for H-type also demonstrated comparable levels of stability. ISS-based methods showed greater displacements.
Conclusion TSS-based fixation may provide stability comparable to bilateral triangular fixation and SPF in FFP type IVb, with less invasiveness when anatomy permits. Further studies are needed to optimize treatment strategies for this complex injury. en-copyright= kn-copyright= en-aut-name=NaniwaShuichi en-aut-sei=Naniwa en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YorimitsuMasanori en-aut-sei=Yorimitsu en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaTsubasa en-aut-sei=Hasegawa en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuokaShiro en-aut-sei=Fukuoka en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MochizukiYusuke en-aut-sei=Mochizuki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamakawaYasuaki en-aut-sei=Yamakawa en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HanakawaShiro en-aut-sei=Hanakawa en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Musculoskeletal Traumatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Emergency Health Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Kochi Health Sciences Center kn-affil= affil-num=9 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama Saidaiji Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Fragility fractures of the pelvis kn-keyword=Fragility fractures of the pelvis en-keyword=Spinopelvic dissociation kn-keyword=Spinopelvic dissociation en-keyword=Finite element analysis kn-keyword=Finite element analysis en-keyword=Internal fixation kn-keyword=Internal fixation END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=1 article-no= start-page=e70089 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lifestyle Factors and Current Alcohol Consumption Among Japanese Adolescents During the COVID-19 Pandemic: A Nationwide Cross-Sectional Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The COVID-19 pandemic may have influenced drinking behaviors in minors by disrupting daily routines and increasing psychosocial stress, although alcohol use among Japanese adolescents has declined in recent years. We aimed to clarify the relationships between current alcohol consumption and lifestyle factors during the COVID-19 pandemic based on a nationwide cross-sectional survey.
Methods: This cross-sectional study analyzed data from the 2021 Lifestyle Survey of Adolescents, a nationwide survey conducted in Japan during the COVID-19 pandemic. A total of 15?549 junior and senior high school students (7645 boys and 7904 girls) were included. Current alcohol consumption was defined as drinking on at least 1?day in the past 30?days. Multivariable logistic regression analyses were used to examine associations between current alcohol consumption and lifestyle factors, including irregular sleep patterns, irregular dietary habits, and increased screen time. Sex-stratified analyses and interaction tests were also performed.
Results: The overall prevalence of current alcohol consumption was 2.1%, with slightly higher rates among boys (2.2%) than girls (2.0%). Current alcohol consumption was significantly associated with irregular sleep patterns (odds ratio [OR]?=?1.51; 95% confidence interval [CI], 1.17?1.95) and irregular dietary habits (OR?=?1.68; 95% CI, 1.18?2.40). An association with increased screen time was also observed (OR?=?1.29; 95% CI, 1.00?1.69), particularly among boys. A significant interaction by sex was detected for irregular sleep patterns (p for interaction?=?0.013).
Conclusions: Alcohol consumption among Japanese adolescents was associated with irregular sleep and dietary habits and, among boys, with increased screen time. These findings highlight the importance of promoting regular routines and addressing lifestyle-related risks to prevent current alcohol consumption among adolescents during public health crises. en-copyright= kn-copyright= en-aut-name=NishiwakiMasatake en-aut-sei=Nishiwaki en-aut-mei=Masatake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KandaHideyuki en-aut-sei=Kanda en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaKeita en-aut-sei=Yoshida en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KinjoAya en-aut-sei=Kinjo en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuwabaraYuki en-aut-sei=Kuwabara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHongja en-aut-sei=Kim en-aut-mei=Hongja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ImamotoAya en-aut-sei=Imamoto en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshimotoHisashi en-aut-sei=Yoshimoto en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoTeruna en-aut-sei=Ito en-aut-mei=Teruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KasugaHideaki en-aut-sei=Kasuga en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MinobeRuriko en-aut-sei=Minobe en-aut-mei=Ruriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaesatoHitoshi en-aut-sei=Maesato en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=JikeMaki en-aut-sei=Jike en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OtsukaYuichiro en-aut-sei=Otsuka en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ItaniOsamu en-aut-sei=Itani en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KaneitaYoshitaka en-aut-sei=Kaneita en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HiguchiSusumu en-aut-sei=Higuchi en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OsakiYoneatsu en-aut-sei=Osaki en-aut-mei=Yoneatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=6 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=7 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=8 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=9 en-affil=Department of Family Medicine, General Practice and Community Health, Institute of Medicine, University of Tsukuba kn-affil= affil-num=10 en-affil=Department of Food and Nutrition, Koriyama Women's University kn-affil= affil-num=11 en-affil=Department of Hygiene and Preventive Medicine, Fukushima Medical University kn-affil= affil-num=12 en-affil=National Institute of Alcoholism, Kurihama National Hospital kn-affil= affil-num=13 en-affil=National Institute of Alcoholism, Kurihama National Hospital kn-affil= affil-num=14 en-affil=Department of Food Science and Nutrition, Faculty of Life and Environmental Science, Showa Women's University kn-affil= affil-num=15 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=16 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=17 en-affil=Division of Public Health, Department of Social Medicine, Nihon University School of Medicine kn-affil= affil-num=18 en-affil=National Institute of Alcoholism, Kurihama National Hospital kn-affil= affil-num=19 en-affil=Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= en-keyword=adolescent kn-keyword=adolescent en-keyword=alcohol drinking kn-keyword=alcohol drinking en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=Japan kn-keyword=Japan en-keyword=lifestyle kn-keyword=lifestyle END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=908 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic value of right atrial strain in patients with chronic heart failure en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims Right ventricular dysfunction is a well-established prognostic marker in patients with heart failure (HF). However, the prognostic significance of right atrial (RA) function remains unclear. Given its sensitivity to systemic congestion, RA function may provide additional insights into HF disease progression and management. This study aimed to investigate whether RA reservoir function serves as an independent prognostic indicator in patients with chronic HF.
Methods A total of 613 patients with chronic HF and a left ventricular (LV) ejection fraction of less than 50% who underwent echocardiographic assessment at Okayama University Hospital between January 2018 and March 2023 were included (median age: 68 (58?76) years; 69% male). RA reservoir function was quantified using two-dimensional speckle-tracking echocardiography. The primary endpoint was cardiovascular death or HF-related hospitalization. Kaplan?Meier survival analysis was performed to examine the association between RA reservoir function and clinical outcomes.
Results During a median follow-up period of 41 months (range: 12?91 months), 119 patients experienced cardiac events. Compared with event-free patients, those with cardiac events exhibited a significantly larger RA maximum volume index (38 mL/m2 vs. 31 mL/m2, P??20%, even without RA volume enlargement (log-rank test, P? Conclusions In patients who experienced adverse cardiac events, a reduced RASr and an increased RA maximum volume were observed. Furthermore, a reduced RASr was independently associated with an increased risk of cardiovascular death and HF-related hospitalization in patients with chronic HF and LV dysfunction. These findings indicate that RASr may serve as a valuable prognostic marker for the risk stratification and management of chronic HF. en-copyright= kn-copyright= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToruMiyoshi en-aut-sei=Toru en-aut-mei=Miyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= en-keyword=Right atrial function kn-keyword=Right atrial function en-keyword=Right atrial strain kn-keyword=Right atrial strain en-keyword=Chronic heart failure kn-keyword=Chronic heart failure en-keyword=Echocardiography kn-keyword=Echocardiography END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=50 article-no= start-page=e06926 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fibrosis is a significant barrier to drug delivery in pancreatic ductal adenocarcinoma (PDAC) and contributes to its dismal prognosis. Pancreatic stellate cells (PSCs) drive fibrosis by excessively secreting extracellular matrix proteins such as collagen I. Collagen I is thought to physically obstruct the delivery of macromolecules, such as albumin, antibodies, and nanomedicines. Apart from its structural role, collagen signals through dedicated cell surface receptors, such as the discoidin domain receptors (DDR) 1/2. However, whether and how collagen signaling contributes to fibrotic barrier generation remains uncharacterized. Here, a 3D culture model of PDAC fibrosis constructed from patient PSCs is used to assess the contribution of DDR1/2-mediated collagen signaling. DDR1/2 inhibition diminishes collagen I expression in PSCs to enhance macromolecular delivery. Moreover, MEK inhibitors exacerbate the fibrotic barrier by up-regulating collagen I, an effect reversed by inhibiting DDR1/2. Through isoform-specific targeting, inhibiting DDR1, but not DDR2, is shown to be effective. Downstream of DDR, the involvement of the PI3K/AKT/mTOR pathway is demonstrated, particularly alternative mTOR complexes involving MEAK7 and GIT1. Altogether, the results show in vitro that DDR1-mediated collagen signaling exacerbates the fibrotic barrier and may be targeted to enhance macromolecular drug delivery in PDAC. en-copyright= kn-copyright= en-aut-name=OhiraMayu en-aut-sei=Ohira en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamuraMoe en-aut-sei=Kitamura en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwasakiHiroyo en-aut-sei=Iwasaki en-aut-mei=Hiroyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Ohta‐OkanoHaruko en-aut-sei=Ohta‐Okano en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiiHiyori en-aut-sei=Tsujii en-aut-mei=Hiyori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraReika en-aut-sei=Nakamura en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakazawaTakuya en-aut-sei=Nakazawa en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiguchiAkihiro en-aut-sei=Nishiguchi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoMasaya en-aut-sei=Yamamoto en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OsadaKensuke en-aut-sei=Osada en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasamuneAtsushi en-aut-sei=Masamune en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KanoMitsunobu R. en-aut-sei=Kano en-aut-mei=Mitsunobu R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science kn-affil= affil-num=9 en-affil=Department of Materials Processing, Graduate School of Engineering, Tohoku University kn-affil= affil-num=10 en-affil=Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=13 en-affil=Division of Gastroenterology, Graduate School of Medicine, Tohoku University kn-affil= affil-num=14 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=15 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=collagen kn-keyword=collagen en-keyword=fibrosis kn-keyword=fibrosis en-keyword=nanomedicine kn-keyword=nanomedicine en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=pancreatic stellate cell kn-keyword=pancreatic stellate cell END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=2 article-no= start-page=e70170 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safety and efficacy of Rez?m water vapour energy therapy in BPH patients receiving antithrombotic therapy: A Japanese single‐centre experience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: The objective of this study is to evaluate the safety and efficacy of Rez?m water vapour energy therapy (WAVE) in Japanese patients with benign prostatic hyperplasia (BPH) continuing antithrombotic therapy and to validate the Okayama University Modified Clavien-Dindo classification (OU-mCD) for perioperative hematuria.
Patients and Methods: We retrospectively analysed 80 consecutive patients who underwent WAVE from August 2023 to July 2024, including 37 (46.2%) continuing antithrombotic therapy perioperatively. Hematuria within 30?days was graded using conventional Clavien-Dindo classification and the OU-mCD, a novel classification focusing on intervention necessity. We assessed clinically significant hematuria (Grade ? Ib), catheter-free rate, prostate volume reduction and haemoglobin change.
Results: Clinically significant hematuria occurred in 21.6% (8/37) of patients continuing antithrombotic therapy versus 4.7% (2/43) without (p?=?0.038). All 10 Grade ? Ib cases occurred during hospitalization with the catheter in place and were managed conservatively with continuous bladder irrigation (median 1 day); none required transfusion or surgical reintervention. Only one patient required temporary drug discontinuation. Treatment efficacy did not differ by antithrombotic status: 86.2% achieved PVR? Conclusion: WAVE can be safely performed with continued antithrombotic therapy. Whereas Grade ?Ib hematuria occurred in 25% of antiplatelet/anticoagulant users (vs. 5% without), 75% had no significant bleeding, and all complications were managed conservatively without transfusion. The OU-mCD provides precise complication stratification. These findings suggest outpatient procedures may be feasible with appropriate patient selection. en-copyright= kn-copyright= en-aut-name=MoriwakeTakatoshi en-aut-sei=Moriwake en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakuHaruki en-aut-sei=Kaku en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatayamaYasuhiro en-aut-sei=Katayama en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Urology, Okamura Isshindo Hospital kn-affil= affil-num=14 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=benign prostatic hyperplasia kn-keyword=benign prostatic hyperplasia en-keyword=hematuriaantithrombotic therapy kn-keyword=hematuriaantithrombotic therapy en-keyword=Japanese kn-keyword=Japanese en-keyword=OU-mCD kn-keyword=OU-mCD en-keyword=water vapour energy therapy kn-keyword=water vapour energy therapy END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=e87334 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Challenge of Diagnosing Scirrhous Gastric Cancer by Endoscopic Biopsy: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Scirrhous gastric cancer, also known as linitis plastica, is a rare and aggressive subtype of gastric carcinoma that poses significant diagnostic challenges due to its submucosal infiltration and often normal-appearing mucosa. We report a case involving a 30-year-old Japanese woman who presented with a six-month history of epigastric pain and postprandial vomiting. Initial endoscopic examination revealed erythema and mucosal swelling, with limited antral distensibility and resistance during duodenal intubation. Despite 12 mucosal biopsies, histopathological examination revealed no evidence of malignancy. Given the strong clinical and endoscopic suspicion of scirrhous gastric cancer, additional deep sections and immunohistochemical staining were performed. These revealed scattered signet-ring cell carcinoma and poorly differentiated adenocarcinoma, with positive immunostaining for p53 and Ki67. The patient underwent total gastrectomy, and the diagnosis of scirrhous gastric cancer was confirmed on the resected specimen. This case highlights the importance of a high index of clinical suspicion, close collaboration between endoscopists and pathologists, and the utility of ancillary diagnostic tools, such as immunohistochemistry, in identifying subepithelial gastric malignancies that may be missed on conventional biopsy. en-copyright= kn-copyright= en-aut-name=IkedaYuka en-aut-sei=Ikeda en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaNobumasa en-aut-sei=Ikeda en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Clinic IkedaDepartment of Internal Medicine, Clinic Ikeda kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Clinic Ikeda kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=endoscopic biopsy kn-keyword=endoscopic biopsy en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=immunohistochemistry kn-keyword=immunohistochemistry en-keyword=linitis plastica kn-keyword=linitis plastica en-keyword=scirrhous gastric cancer kn-keyword=scirrhous gastric cancer END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=2 article-no= start-page=284 end-page=293 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Characteristics and Spatial Transcriptome Analysis of Non?Small Cell Lung Cancers Exhibiting Early Alectinib Resistance: A Retrospective OLCSG Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some anaplastic lymphoma kinase (ALK) gene rearrangement?positive lung cancers show early resistance, within 3 months, to alectinib. This study investigated the clinical and molecular characteristics of these patients. We analyzed patients with unresectable stage III/IV disease without indications for radical radiotherapy and recurrent ALK-positive lung cancer who received alectinib as the primary ALK tyrosine kinase inhibitor between 2013 and 2021 at nine hospitals. In total, 103 patients were included. The median age was 65 years; 44 were male and 22 had brain metastases. The median progression-free survival and overall survival (OS) were 28.7 and 80.6 months. Nineteen patients treated for ?3 months and 84 treated for >3 months were categorized into the early resistance and responder groups, respectively. The early resistance group had significantly shorter OS (8.4 months vs. not estimable, P < 0.001) and was significantly more likely to have brain metastases (42% vs. 17%, P = 0.027). They also showed elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR). Univariate analysis identified brain metastases and high NLR as significant predictors of early resistance. Spatial transcriptome analysis and immunohistochemical staining revealed upregulation of annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein involved in inflammation and cancer progression, in the early resistance group. Interleukin 6 stimulation, prompted by elevated inflammatory markers, increased ANXA1 expression and reduced alectinib sensitivity. Knockdown of ANXA1 improved alectinib sensitivity in alectinib-resistant cells. In conclusion, brain metastases and high NLR are associated with early resistance. ANXA1 may play an important role in mediating early resistance. New treatment options for the early resistance group are required. en-copyright= kn-copyright= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoritaNaokatsu en-aut-sei=Horita en-aut-mei=Naokatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KayataniHiroe en-aut-sei=Kayatani en-aut-mei=Hiroe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SugimotoKeisuke en-aut-sei=Sugimoto en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization, Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Kure Kyosai Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=12 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=14 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=e70154 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitrofanoff Appendicovesicostomy With Boari Flap for Complete Female Urethral Transection: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Female urethral complete transection caused by pelvic trauma is extremely rare, and no standard management has been established when urethral reconstruction is not feasible.
Case Presentation: A woman in her twenties sustained an open pelvic fracture with perineal injury due to a traffic accident. Complete urethral transection was identified, and a suprapubic cystostomy was placed. After staged vaginal reconstruction and bladder function evaluation, a Mitrofanoff appendicovesicostomy was performed. Because the appendix was not enough to reach the umbilicus, a Boari flap was created to compensate for the length. Urodynamic evaluation showed improvement from a preoperative high-pressure bladder to increased compliance postoperatively, though pharmacological management was still required. Postoperatively, the patient achieved stable clean intermittent catheterization without complications.
Conclusion: The Mitrofanoff procedure can be an effective option in female urethral injuries where reconstruction is impossible. The addition of a Boari flap may expand its applicability by overcoming conduit length limitations. en-copyright= kn-copyright= en-aut-name=MoriKohei en-aut-sei=Mori en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamasakiYuichiro en-aut-sei=Yamasaki en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Kanagawa Children's Medical Center kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Boari flap kn-keyword=Boari flap en-keyword=female urethral transection kn-keyword=female urethral transection en-keyword=Mitrofanoff kn-keyword=Mitrofanoff END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue= article-no= start-page=100540 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Flow diverter treatment for internal carotid artery aneurysm following management of distal cerebral aneurysms: Technical note en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: In recent years, the effectiveness of flow diverters (FDs) for the treatment of intracranial aneurysms has been reported. While FDs are effective, their deployment involves advancing a delivery wire distally, which may pose a risk if a distal aneurysm exists within the same artery. In such cases, the delivery wire could potentially perforate the distal aneurysm. Here, we present two cases of tandem aneurysms in which an internal carotid artery (ICA) aneurysm was treated with an FD following the treatment of a distal cerebral aneurysm.
Case description: A 44-year-old woman and a 67-year-old woman underwent magnetic resonance imaging for headache or abducens nerve palsy. In both cases, two aneurysms were revealed: one at the ICA and the other either at the middle cerebral artery or the top of the ICA. Due to the risk of perforation by the delivery wire during FD deployment, the distal aneurysms were treated first?either with surgical neck clipping or stent-assisted coil embolization. One month after the initial treatment, FD placement for the ICA aneurysm was performed as planned without complications in either case.
Discussion: This is the first report where tandem aneurysms were successfully treated with treatment for distal cerebral aneurysms, followed by FDs for proximal ICA aneurysms. We emphasize the potential risk of perforation of the distal aneurysm by the delivery wire during FD placement.
Conclusion: Treatment of distal cerebral aneurysms beforehand can help ensure the safe and effective use of FDs in patients with tandem aneurysms. en-copyright= kn-copyright= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BabaFukiko en-aut-sei=Baba en-aut-mei=Fukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujitaJuntaro en-aut-sei=Fujita en-aut-mei=Juntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SotomeYuta en-aut-sei=Sotome en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawakamiMasato en-aut-sei=Kawakami en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KimuraRyu en-aut-sei=Kimura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EbisudaniYuki en-aut-sei=Ebisudani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HarumaJun en-aut-sei=Haruma en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HishikawaTomohito en-aut-sei=Hishikawa en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Flow diverter kn-keyword=Flow diverter en-keyword=Tandem aneurysms kn-keyword=Tandem aneurysms en-keyword=Complication kn-keyword=Complication en-keyword=Perforation kn-keyword=Perforation en-keyword=Delivery wire kn-keyword=Delivery wire END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=4591 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Calcium ions play a critical role in calcification of Corynebacterium matruchotii en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dental calculus is a hardened deposit composed of calcium phosphate precipitated within dental plaque. While the involvement of dental calculus in the progression of periodontal disease is well established, many aspects of its formation process remain poorly understood. In this study, we focused on Corynebacterium matruchotii, a key bacterium involved in dental calculus formation, and investigated the role of calcium ions in calcification, as well as the associated internal and external changes in the bacterium through long-term observation. In the absence of calcium ions, no intracellular calcification was observed, and the lipid bilayer with the formation of holes in bacterial body was evident. In contrast, in the presence of calcium ions, lipid bilayer remained intact, and intracellular needle- and plate- like crystals were formed. Furthermore, calcified C. matruchotii showed increased flocculation compared to non-calcified C. matruchotii. These results indicate that the influx of calcium ions is essential for intracellular calcification. Calcium ions entry appears to reinforce the integrity of the lipid bilayer, providing a stable intracellular environment conductive to calcification. Moreover, calcified C. matruchotii may contribute to the nucleation of dental calculus by forming aggregates composed of both bacterial components and calcified material. en-copyright= kn-copyright= en-aut-name=OharaNaoko en-aut-sei=Ohara en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaMidori en-aut-sei=Ogawa en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TosaIkue en-aut-sei=Tosa en-aut-mei=Ikue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnoSerina en-aut-sei=Ono en-aut-mei=Serina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoMitsumasa en-aut-sei=Saito en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Microbiology, School of Medicine, University of Occupational and Environmental Health kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Microbiology, School of Medicine, University of Occupational and Environmental Health kn-affil= affil-num=7 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Calcification kn-keyword=Calcification en-keyword=Corynebacterium matruchotii kn-keyword=Corynebacterium matruchotii en-keyword=Dental calculus kn-keyword=Dental calculus en-keyword=Calcium ions kn-keyword=Calcium ions END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=11 article-no= start-page=e97584 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Psoas Abscess Diagnosed With Oral Bacteria as the Causative Pathogen en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a rare case of a psoas abscess in an 87-year-old woman, in which oral commensal bacteria may have disseminated hematogenously from a chronic oral infection site and served as the causative pathogens. The patient presented with persistent left buttock pain, fever, and swelling, and imaging revealed a fracture of the left iliac bone with an associated psoas abscess. Bacterial cultures identified Streptococcus oralis and Pseudomonas aeruginosa. Her symptoms improved following antibiotic therapy and CT-guided drainage. Although the presence of P. aeruginosa in the oral cavity is generally considered transient, it has been isolated from the oral cavities of elderly and immunocompromised individuals. In the absence of lacerations or other direct portals of entry, and considering the identification of both pathogens, the oral cavity was regarded as the most likely source of infection. This case highlights the importance of correlating culture results with the most probable source of infection to improve the prognosis of systemic infections. en-copyright= kn-copyright= en-aut-name=UmemoriKoki en-aut-sei=Umemori en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaoMayumi en-aut-sei=Yao en-aut-mei=Mayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaKoji en-aut-sei=Fujita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Dentistry and Dental Surgery, Tsuyama Central Hospital kn-affil= affil-num=4 en-affil=General Internal Medicine and Infectious Diseases, Tsuyama Central Hospital kn-affil= affil-num=5 en-affil=Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine kn-affil= en-keyword=hematogenous spread kn-keyword=hematogenous spread en-keyword=oral diseases kn-keyword=oral diseases en-keyword=oral health care kn-keyword=oral health care en-keyword=pseudomonas aeruginosa kn-keyword=pseudomonas aeruginosa en-keyword=psoas muscle abscess kn-keyword=psoas muscle abscess en-keyword=streptococcus oralis kn-keyword=streptococcus oralis END start-ver=1.4 cd-journal=joma no-vol=94 cd-vols= no-issue=4 article-no= start-page=522 end-page=529 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Intermittent Low-temperature Storage Duration and Cycle on the Bolting and Flowering of Delphinium elatum in Summer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Early-bolting in summer is a major problem when growing delphinium seedlings in summer to produce cut flowers that will be shipped in autumn and winter. In this study, an intermittent low-temperature storage (ILTS) treatment that induces flower bud differentiation in strawberry and prevents rosette formation in Eustoma significantly increased the Delphinium elatum cut flower length. Moreover, ILTS was as effective as growing seedlings under cool conditions at preventing early-bolting. We analyzed the effects of six ILTS treatments that differed regarding the treatment temperature (5 and 10°C) and treatment cycle (3 days/3 days, 6 days/6 days, and 12 days/12 days; ambient conditions/cool and dark). Cut flowers were significantly longer with the 6 days/6 days treatment at 10°C than for the control treatment. Furthermore, repeating the ILTS treatment cycle (6 days ambient conditions/6 days at 10°C) a total of four times produced high-quality cut flowers regardless of the cultivar. Therefore, this ILTS treatment may be ideal for preventing early-bolting in D. elatum. en-copyright= kn-copyright= en-aut-name=KawaiMika en-aut-sei=Kawai en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuyasuMiwa en-aut-sei=Fukuyasu en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaYoshiyuki en-aut-sei=Tanaka en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitamuraYoshikuni en-aut-sei=Kitamura en-aut-mei=Yoshikuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasubaKen-ichiro en-aut-sei=Yasuba en-aut-mei=Ken-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaYuichi en-aut-sei=Yoshida en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotoTanjuro en-aut-sei=Goto en-aut-mei=Tanjuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=cool storage kn-keyword=cool storage en-keyword=cut flower quality kn-keyword=cut flower quality en-keyword=high ambient temperature kn-keyword=high ambient temperature en-keyword=long day kn-keyword=long day en-keyword=Ranunculaceae kn-keyword=Ranunculaceae END start-ver=1.4 cd-journal=joma no-vol=95 cd-vols= no-issue=1 article-no= start-page=10 end-page=20 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of Fruit Development, Ripening, and Transcriptome Dynamics in Taiwanese and Japanese Cultivars of Japanese Apricot (Prunus mume Sieb. et Zucc.) en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we compared changes in traits associated with fruit development and ripening in Taiwanese and Japanese cultivars of Japanese apricot (Prunus mume Sieb. et Zucc.). We also analyzed transcriptome profiles to comprehensively examine different fruit development and ripening patterns between the two groups in terms of fruit characteristics and gene expression. Early fruit development in Taiwanese cultivars ‘ST’ and ‘Ellching’ and the Japanese cultivar ‘Hakuo’ was ahead of that in other three Japanese cultivars (P1). From late April to early May, around the stone-hardening stage, the developmental differences decreased to the same level. Thereafter, Japanese cultivars showed rapid growth, whereas Taiwanese cultivars showed slower growth, reversing the developmental differences between these lines (P2). Ethylene production was not detected until the full ripening stage and was detected for the first time at this stage in five cultivars, except for ‘Ellching’ (P3). In contrast, no ethylene production was observed during the entire duration of fruit development in ‘Ellching’. A multidimensional scaling plot showed that the overall transcriptome profile changed according to the three stages (P1?P3) of fruit development and ripening. At P1, gene ontologies (GOs) related to cell division, such as the cell cycle and regulation of cyclin-dependent protein serine/threonine kinase activity, were enriched for differentially expressed genes downregulated in Taiwanese cultivars as compared with their expression in Japanese cultivars. At P2, GOs related to fruit development were not enriched, but some genes related to phytohormones, such as auxin, abscisic acid, and cytokinin, which are associated with fruit development and ripening, were differentially expressed. At P3, the expression of genes such as ACS, ACO, and PG, which are involved in ethylene biosynthesis, increased in response to increased ethylene production, but not in ‘Ellching’, which showed no ethylene production. Expression analysis of 115 NAC (NAM-ATAF1/2-CUC2) family genes, which are related to fruit ripening and ripening date in other fruit species, in the ‘Ellching’ genome revealed changes in expression of NAC056 and NAC073 corresponding to fruit development and ripening in Taiwanese and Japanese cultivars. We discuss the differences in fruit development and ripening behaviors between Taiwanese and Japanese cultivars in terms of physiological and transcriptome changes. en-copyright= kn-copyright= en-aut-name=KashiwamotoTomoaki en-aut-sei=Kashiwamoto en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiTakashi en-aut-sei=Kawai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OeTakaaki en-aut-sei=Oe en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NumaguchiKoji en-aut-sei=Numaguchi en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraYuto en-aut-sei=Kitamura en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuboYasutaka en-aut-sei=Kubo en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukudaFumio en-aut-sei=Fukuda en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UshijimaKoichiro en-aut-sei=Ushijima en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Japanese Apricot Laboratory, Wakayama Fruit Tree Experiment Station kn-affil= affil-num=4 en-affil=Japanese Apricot Laboratory, Wakayama Fruit Tree Experiment Station kn-affil= affil-num=5 en-affil=Faculty of Agriculture, Setsunan University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=cell division kn-keyword=cell division en-keyword=ethylene production kn-keyword=ethylene production en-keyword=NAC kn-keyword=NAC en-keyword=phytohormone kn-keyword=phytohormone en-keyword=stone hardening kn-keyword=stone hardening END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1716939 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural analysis of PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte alga Rhodomonas sp. NIES-2332 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Light energy is converted to chemical energy by two photosystems (PSI and PSII) in complex with their light-harvesting complex proteins (LHCI and LHCII) in photosynthesis. Rhodomonas is a member of cryptophyte alga whose LHCs contain unique chlorophyll a/c proteins (ACPs) and phycobiliproteins. We purified PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte Rhodomonas sp. NIES-2332 and analyzed their structures at high resolutions of 2.08 ? and 2.17 ?, respectively, using cryo-electron microscopy. These structures are largely similar to those reported previously from two other species of cryptophytes, but exhibited some differences in both the pigment locations and subunit structures. A part of the antenna subunits of both photosystems is shifted compared with the previously reported structures from other species of cryptophytes, suggesting some differences in the energy transfer rates from the antenna to the PSI and PSII cores. Newly identified lipids are found to occupy the interfaces between the antennae and cores, which may be important for assembly and stabilization of the supercomplexes. Water molecules surrounding three iron-sulfur clusters of the PSI core are found in our high-resolution structure, some of which are conserved from cyanobacteria to higher plants but some are different. In addition, our structure of PSII-ACPII lacks the subunits of oxygen-evolving complex as well as the Mn4CaO5 cluster, suggesting that the cells are in the S-growth phase, yet the PSI-ACPI structure showed the binding of PsaQ, suggesting that it is in an L-phase. These results suggest that the S-phase and L-phase can co-exist in the cryptophytic cells. The high-resolution structures of both PSI-ACPIs and PSII-ACPIIs solved in this study provide a more solid structural basis for elucidating the energy transfer and quenching mechanisms in this group of the organisms. en-copyright= kn-copyright= en-aut-name=ZhangWenyue en-aut-sei=Zhang en-aut-mei=Wenyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoneharaNozomi en-aut-sei=Yonehara en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiiMizuki en-aut-sei=Ishii en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JiangHaowei en-aut-sei=Jiang en-aut-mei=Haowei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=La RoccaRomain en-aut-sei=La Rocca en-aut-mei=Romain kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsaiPi-Cheng en-aut-sei=Tsai en-aut-mei=Pi-Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiHongjie en-aut-sei=Li en-aut-mei=Hongjie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=cryptophytes kn-keyword=cryptophytes en-keyword=Rhodomonas kn-keyword=Rhodomonas en-keyword=photosystem I kn-keyword=photosystem I en-keyword=photosystem II kn-keyword=photosystem II en-keyword=light-harvesting complex kn-keyword=light-harvesting complex en-keyword=photosynthesis kn-keyword=photosynthesis END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TeMPRA: advancing continuing professional development in pediatric rheumatology in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In the context of the global shortage of pediatric rheumatologists, mid-career specialists who can play key roles in regional education, research, and clinical practice have become increasingly important. In Japan, the Team of Mid-career Pediatric Rheumatologists Alliance (TeMPRA) was founded in 2014 to support continuing professional development (CPD) and foster collaboration among mid-career pediatric rheumatologists. The aim of this study was to characterize the current status and future perspectives of the TeMPRA members.
Methods In 2024, a cross-sectional, web-based survey was conducted among all 37 active members of the TeMPRA across Japan. Data were collected on career trajectories, educational roles, research activities, clinical practices, and international engagement. Categorical variables were compared using appropriate statistical tests, with a significance level of 0.05.
Results Responses were obtained from 35 members (response rate: 95%). Most respondents (71%) were affiliated with university hospitals, and 60% had?>?10 years of experience in pediatric rheumatology. Compared with those working in community hospitals, respondents affiliated with university hospitals were significantly more likely to be involved in research activities (50% vs. 0%, P?=?0.0261) and global professional contributions (88% vs. 0%, P? Conclusions This nationwide survey highlights the substantial educational roles, research activities, and clinical practices of mid-career pediatric rheumatologists in Japan and suggests that the TeMPRA framework can serve as a valuable model for supporting CPD and workforce sustainability. Similar alliance-based approaches may be applicable in other countries facing comparable challenges in pediatric rheumatology. en-copyright= kn-copyright= en-aut-name=WakiguchiHiroyuki en-aut-sei=Wakiguchi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashimotoKunio en-aut-sei=Hashimoto en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraKenichi en-aut-sei=Nishimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EbatoTakasuke en-aut-sei=Ebato en-aut-mei=Takasuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkamineKeiji en-aut-sei=Akamine en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UejimaYoji en-aut-sei=Uejima en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatoTomomi en-aut-sei=Sato en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamasakiYuichi en-aut-sei=Yamasaki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasumuraJunko en-aut-sei=Yasumura en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkazakiFumiko en-aut-sei=Okazaki en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KizawaToshitaka en-aut-sei=Kizawa en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasuokaRyuhei en-aut-sei=Yasuoka en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshikawaTomoaki en-aut-sei=Ishikawa en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamamotoTakeshi en-aut-sei=Yamamoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujitaYuji en-aut-sei=Fujita en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ItohNaohiro en-aut-sei=Itoh en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakasakiAsami en-aut-sei=Takasaki en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SakuraiNodoka en-aut-sei=Sakurai en-aut-mei=Nodoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuzukiKazuo en-aut-sei=Suzuki en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TamaiTasuku en-aut-sei=Tamai en-aut-mei=Tasuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HiranoNaoki en-aut-sei=Hirano en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=OkamotoNami en-aut-sei=Okamoto en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=ShimizuMasaki en-aut-sei=Shimizu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Yokohama City University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kitasato University kn-affil= affil-num=6 en-affil=Department of Nephrology and Rheumatology, Tokyo Metropolitan Children’s Medical Center kn-affil= affil-num=7 en-affil=Division of Infectious Diseases and Immunology, Saitama Children’s Medical Center kn-affil= affil-num=8 en-affil=Clinical Education Center for Physicians, Shiga University of Medical Science kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kagoshima University Hospital kn-affil= affil-num=10 en-affil=Department of Pediatrics, Hiroshima Prefectural Hospital Organization Futabanosato Prefectural Hospital kn-affil= affil-num=11 en-affil=Department of Pediatrics, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Japan Community Health Care Organization Sapporo Hokushin Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Hamamatsu University School of Medicine kn-affil= affil-num=14 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=15 en-affil=Department of Pediatrics, Chiba University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University kn-affil= affil-num=17 en-affil=Department of Pediatrics, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=18 en-affil=Department of Pediatrics, School of Medicine, University of Toyama kn-affil= affil-num=19 en-affil=Department of Pediatrics, NTT East Medical Center Sapporo kn-affil= affil-num=20 en-affil=Suzuki Kids Clinic kn-affil= affil-num=21 en-affil=Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine kn-affil= affil-num=22 en-affil=Department of Public Health and Epidemiology, Faculty of Medicine, Oita University kn-affil= affil-num=23 en-affil=Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety kn-affil= affil-num=24 en-affil=Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= en-keyword=Child kn-keyword=Child en-keyword=Education kn-keyword=Education en-keyword=Juvenile idiopathic arthritis kn-keyword=Juvenile idiopathic arthritis en-keyword=Practice kn-keyword=Practice en-keyword=Rheumatic diseases kn-keyword=Rheumatic diseases en-keyword=Systemic lupus erythematosus kn-keyword=Systemic lupus erythematosus en-keyword=Team of mid-career pediatric rheumatologists alliance kn-keyword=Team of mid-career pediatric rheumatologists alliance END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=100065 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of systemic ventricular assist combined with fenestration in failing Fontan: A theoretical analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Biventricular assist for failing Fontan circulation remains challenging. Because fenestration effectively reduces stressed blood volume and central venous pressure in Fontan patients with increased pulmonary vascular resistance (PVR), systemic ventricular assist device (VAD) combined with fenestration may improve hemodynamics in failing Fontan patients with increased PVR who would require biventricular assist. To validate this hypothesis, we performed a computational hemodynamic simulation of the failing Fontan circulation using a lumped parameter model. We compared hemodynamic variables between the models with and without fenestration while the PVR index was increased sequentially from 3.01 to 6.81 Wood Units m2. Following VAD initiation and stressed blood volume reduction, central venous pressure was maintained at a lower level in the fenestration models. This positive effect was greater in the model with larger fenestration diameter. However, excessive fenestration caused significant desaturation. In failing Fontan circulation with elevated PVR, systemic VAD combined with fenestration significantly improved hemodynamics. en-copyright= kn-copyright= en-aut-name=ShimizuShuji en-aut-sei=Shimizu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KotaniYasuhiro en-aut-sei=Kotani en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorioNaohiro en-aut-sei=Horio en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KisamoriEiri en-aut-sei=Kisamori en-aut-mei=Eiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyaharaYoshinori en-aut-sei=Miyahara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UemuraKoji en-aut-sei=Uemura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShishidoToshiaki en-aut-sei=Shishido en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=5 en-affil=Pediatric Heart Disease and Adult Congenital Heart Disease Center, Showa Medical University Hospital kn-affil= affil-num=6 en-affil=Department of Research Promotion and Management, National Cerebral and Cardiovascular Center kn-affil= affil-num=7 en-affil=Department of Research Promotion and Management, National Cerebral and Cardiovascular Center kn-affil= affil-num=8 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= en-keyword=Fontan circulation kn-keyword=Fontan circulation en-keyword=Hemodynamic simulation kn-keyword=Hemodynamic simulation en-keyword=Ventricular assist device kn-keyword=Ventricular assist device en-keyword=Fenestration kn-keyword=Fenestration en-keyword=Pulmonary vascular resistance kn-keyword=Pulmonary vascular resistance END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=12 article-no= start-page=8903 end-page=8905 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250818 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mesenteric Route Superior Mesenteric Artery First Approach in Robot-Assisted Pancreatoduodenectomy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. The superior mesenteric artery (SMA) approach is crucial for the successful implementation of robot-assisted pancreatoduodenectomy (RPD). Herein, we present a novel technique, the mesenteric route SMA-first approach, for RPD.
Patients and Methods. A 20-year-old woman with a 50 mm intraductal papillary mucinous neoplasm underwent RPD. As the tumor was large and located close to the mesenteric vessels, we developed the mesenteric route SMA-first approach.
Results. Following the mesenteric Kocher maneuver, the mesenteric route SMA-first approach was applied. With appropriate retraction of the pancreatic head, dissection around the mesenteric vessels was performed and their branches were divided. The uncinate process dissection (PL, ph II) was performed via the mesenteric route. This approach facilitated dorsal dissection, particularly around the large tumor. After dissection of the hepatoduodenal ligament, the remaining pancreatic nerve plexus (PL ph I) was dissected. Finally, the pancreas was divided on the superior mesenteric vein, and the specimen was resected. Operative time was 390 min with minimal blood loss.
Conclusions. The mesenteric route SMA-first approach enables uncinate process dissection via the mesenteric route. This technique may be a safe and feasible option for selected patients, such as nonobese individuals with a large pancreatic head tumor near major vessels. en-copyright= kn-copyright= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoAtene en-aut-sei=Ito en-aut-mei=Atene kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YanagiharaTsubasa en-aut-sei=Yanagihara en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Robotic pancreaticoduodenectomy kn-keyword=Robotic pancreaticoduodenectomy en-keyword=Superior mesenteric artery approach kn-keyword=Superior mesenteric artery approach en-keyword=Mesenteric route kn-keyword=Mesenteric route END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e84161 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudoachalasia Due to Malignant Pleural Mesothelioma Involving the Esophagus en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a rare case of pseudoachalasia secondary to malignant pleural mesothelioma involving the esophagus. A 66-year-old man presented with progressive dysphagia, weight loss, and postprandial hiccups. Endoscopic examination showed esophageal dilation with luminal narrowing at the esophagogastric junction, but no mucosal abnormalities. Computed tomography revealed an irregular-shaped mass extending from the peri-esophagogastric junction to the retroperitoneum, accompanied by pleural effusion, right-sided hydronephrosis, and multiple hepatic lesions. Endoscopic ultrasound-guided fine-needle aspiration from the mass lesion through the esophageal lumen revealed epithelioid malignant mesothelioma. This case highlights the importance of considering malignant mesothelioma in the differential diagnosis of pseudoachalasia, particularly when imaging reveals extrinsic esophageal compression without mucosal lesions. en-copyright= kn-copyright= en-aut-name=HondaManami en-aut-sei=Honda en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=endoscopic ultrasound-guided fine-needle aspiration kn-keyword=endoscopic ultrasound-guided fine-needle aspiration en-keyword=esophageal diseases kn-keyword=esophageal diseases en-keyword=esophagogastroduodenoscopy (egd) kn-keyword=esophagogastroduodenoscopy (egd) en-keyword=malignant mesothelioma kn-keyword=malignant mesothelioma en-keyword=pseudoachalasia kn-keyword=pseudoachalasia END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=4 article-no= start-page=e82046 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gastrointestinal Stromal Tumors in the Stomach With Tumor Growth and Hemorrhage During Conservative Management: A Report of Two Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastrointestinal stromal tumors (GISTs) are often detected incidentally during esophagogastroduodenoscopy. Although surgical resection is the standard treatment for GISTs, patients with significant comorbidities may not be eligible for surgery and are managed conservatively. Herein, we report two cases of gastric GISTs that were initially observed during the management of other comorbidities but subsequently became enlarged, resulting in gastrointestinal bleeding. These cases highlight the potential risks of tumor progression and bleeding in patients undergoing conservative management. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=conservative management kn-keyword=conservative management en-keyword=gastric subepithelial lesion kn-keyword=gastric subepithelial lesion en-keyword=gastrointestinal bleeding kn-keyword=gastrointestinal bleeding en-keyword=gastrointestinal stromal tumor kn-keyword=gastrointestinal stromal tumor en-keyword=tumor growth kn-keyword=tumor growth END start-ver=1.4 cd-journal=joma no-vol=3027 cd-vols= no-issue=1 article-no= start-page=012008 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fundamental examination of coherent structure model prediction using vortex cores in a two-dimensional Taylor’s analytical solution en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study focuses on the possibility that flow around vortex tubes in turbulence may resemble laminar flow, and aims to describe the characteristics of turbulent fields using analytical solutions to the governing equations. In the two-dimensional analytical Taylor solution, the velocity and pressure fields are expressed by trigonometric functions, and a structure in which counter-rotating vortices are arranged in a grid pattern is demonstrated. This solution is used to verify the accuracy of numerical analyses and is expected to contribute to a simple yet unambiguous description of turbulent fields based on vortex structures. Predictions of sub-grid scale components and validation of a coherent structure model using invariants of the velocity gradient tensor are also performed. en-copyright= kn-copyright= en-aut-name=GongXuanyou en-aut-sei=Gong en-aut-mei=Xuanyou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiHiroki en-aut-sei=Suzuki en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KouchiToshinori en-aut-sei=Kouchi en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaKento en-aut-sei=Tanaka en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue= article-no= start-page=1 end-page=8 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Branching Characteristics and Their Contribution to Yield in Everbearing Strawberry Cultivars under Forced Cultivation en-subtitle= kn-subtitle= en-abstract= kn-abstract=　Enhancing continuous flowering in cultivated strawberries may result in insufficient photosynthetic products due to the lower limit of leaf number on each lateral shoot, leading to reduced yield and fruit quality. If strawberries could differentiate an appropriate number of tillers and allow each tiller to grow autonomously with sufficient leaf number on each lateral shoot, rather than flowering continuously on the main bud alone, plants could achieve high yields while preventing plant weakening and fruit quality deterioration. Therefore, this study evaluated branching characteristics of everbearing strawberry cultivars under forcing cultivation to identify cultivars with moderate tillering and moderately low continuous flowering. Pot experiments revealed that the number of tillers was high in ‘Summer Princess’ and ‘Miyazaki-natsuharuka’ but low in ‘Summer Berry’ and ‘Suzuakane’. This trend was independent of total number of lateral shoots, nodal position of first inflorescence, and the number of leaves on each lateral shoot, which serve as indicators of continuous flowering ability. Among seven tested cultivars, ‘DT17’ and ‘Miyazaki-natsuharuka’ showed intermediate values with 2.1 - 2.5 tillers per plant and 6.7 - 7.7 leaves on each lateral shoots. These cultivars showed yields of 747.0 - 1,028.5 g per plant under forcing cultivation, which were higher than other cultivars, along with consistent fruit quality. These results suggest that improving branching characteristics is a practical approach to enhancing fruit productivity in strawberries. en-copyright= kn-copyright= en-aut-name=Hikawa-EndoMinori en-aut-sei=Hikawa-Endo en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SoneKazuyoshi en-aut-sei=Sone en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorishitaMasami en-aut-sei=Morishita en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Kyushu Okinawa Region Agricultural Research Center, NARO kn-affil= affil-num=2 en-affil=Kyushu Okinawa Region Agricultural Research Center, NARO kn-affil= affil-num=3 en-affil=Kyushu Okinawa Region Agricultural Research Center, NARO kn-affil= en-keyword=branching characteristics kn-keyword=branching characteristics en-keyword=continuous flowering ability kn-keyword=continuous flowering ability en-keyword=crown kn-keyword=crown en-keyword=strawberry kn-keyword=strawberry en-keyword=tiller kn-keyword=tiller END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue= article-no= start-page=41 end-page=56 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The Mediating Role of Self-Understanding in the Association Between Autistic Traits and Mental Health kn-title=自閉スペクトラム症特性と精神的健康の関連：自己理解による媒介効果の検討 en-subtitle= kn-subtitle= en-abstract=　This study examined whether positive and negative dimensions of self-understanding mediate the association between autistic traits and mental health in the general population. Analyzing cross-sectional data from 604 non-clinical Japanese adults, we found that higher autistic traits were significantly associated with poorer mental health. This association was partially mediated by the positive dimension of self-understanding, whereas the negative dimension did not mediate. Exploratory analyses suggested that this protective effect may be more pronounced in women than in men. These findings identify positive self-understanding as an actionable target for support and underscore the value of gender-informed approaches. kn-abstract= 本研究は、自閉スペクトラム症特性と精神的健康の関連において、自己理解がどのような役割を果たすかを明らかにすることを目的とした。日本の成人604名のデータを利用した二次分析の結果、自閉スペクトラム症特性の高さと精神的健康の悪化との間には関連が認められた。この関連は、自己理解の肯定的側面によって部分的に媒介されることが示された。特にこの自己理解の保護的な効果は、男性よりも女性においてより強い可能性が示唆された。一方で、自己理解の否定的側面は媒介効果を示さなかった。これらの結果から、自閉スペクトラム症特性を持つ人々への支援において、肯定的な自己理解を促進することが重要であり、性差を考慮したアプローチの必要性が示唆された。 en-copyright= kn-copyright= en-aut-name=NISHIMURAHiroki en-aut-sei=NISHIMURA en-aut-mei=Hiroki kn-aut-name=西村大樹 kn-aut-sei=西村 kn-aut-mei=大樹 aut-affil-num=1 ORCID= en-aut-name=UCHIDAAkihiro en-aut-sei=UCHIDA en-aut-mei=Akihiro kn-aut-name=内田晃裕 kn-aut-sei=内田 kn-aut-mei=晃裕 aut-affil-num=2 ORCID= affil-num=1 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil=岡山大学教育推進機構 affil-num=2 en-affil=Okayama Psychiatric Medical Center kn-affil=地方独立行政法人岡山県精神科医療センター en-keyword=自閉スペクトラム症 kn-keyword=自閉スペクトラム症 en-keyword=メンタルヘルス kn-keyword=メンタルヘルス en-keyword=精神的健康 kn-keyword=精神的健康 en-keyword=自己理解 kn-keyword=自己理解 en-keyword=性差 kn-keyword=性差 END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue= article-no= start-page=107048 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A cross-sectional study of the gut microbiota associated with urinary and serum equol production status in a general population of Japanese men en-subtitle= kn-subtitle= en-abstract= kn-abstract=Equol is a metabolite produced by the gut microbiota from the soy isoflavone daidzein. Previous studies identified bacteria capable of converting daidzein to equol. We investigated whether equol producers among Japanese with a high soy intake contained these bacteria. We also examined differences in equol production status between urine and serum and how the gut microbiota differs between these statuses. To minimize the potential confounding effects of hormonal variability in women, this cross-sectional study analyzed 853 Japanese men. Urinary and serum isoflavones were collected in the morning after fasting and were analyzed using LC-MS/MS. By applying a finite mixture model for each log10 equol/daidzein ratio, we defined equol producers and non-producers from urine and serum. Among 669 participants with fecal microbial measurements, the 16S rRNA gene was sequenced on a MiSeq System. The cut-off values for the log10 equol/daidzein ratio were ?0.94 for urine and ?0.95 for serum. Equol production status in urine and serum matched in 97 %, and equol producers from urine or serum were 42 %. The microbiota was more diverse in producers than in non-producers; the genus Senegalimassilia included strains with high sequence identity (>98 %) to daidzein reductase. The family Oscillospiraceae and class Clostridia also had approximately 46 %?48 % sequence identity. The equol production status of fasting urine and serum almost matched among a general population of Japanese men. Although we did not detect a microbiota with known daidzein reductase in equol producers, several shared similar sequences; these may include equol-producing bacteria that have not yet been identified. en-copyright= kn-copyright= en-aut-name=OkamiYukiko en-aut-sei=Okami en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ArimaHisatomi en-aut-sei=Arima en-aut-mei=Hisatomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BambaShigeki en-aut-sei=Bamba en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NamaiFu en-aut-sei=Namai en-aut-mei=Fu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoKeiko en-aut-sei=Kondo en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IdenoYuki en-aut-sei=Ideno en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SoejimaAyumi en-aut-sei=Soejima en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyakawaHaruna en-aut-sei=Miyakawa en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToriiSayuki en-aut-sei=Torii en-aut-mei=Sayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SegawaHiroyoshi en-aut-sei=Segawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhashiMizuki en-aut-sei=Ohashi en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawashimaMegumi en-aut-sei=Kawashima en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KadotaAya en-aut-sei=Kadota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SekikawaAkira en-aut-sei=Sekikawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiyoshiAkira en-aut-sei=Fujiyoshi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SESSA Research Group en-aut-sei=SESSA Research Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University kn-affil= affil-num=3 en-affil=Department of Fundamental Nursing, Shiga University of Medical Science kn-affil= affil-num=4 en-affil=Graduate School of Agricultural Science, Tohoku University kn-affil= affil-num=5 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Gunma University Center for Food Science and Wellness kn-affil= affil-num=7 en-affil=Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. kn-affil= affil-num=8 en-affil=Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. kn-affil= affil-num=9 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=11 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=12 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=15 en-affil=Department of Epidemiology, School of Public Health, University of Pittsburgh kn-affil= affil-num=16 en-affil=Department of Hygiene, Wakayama Medical University kn-affil= affil-num=17 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=18 en-affil= kn-affil= en-keyword=Equol kn-keyword=Equol en-keyword=Soy kn-keyword=Soy en-keyword=Isoflavone kn-keyword=Isoflavone en-keyword=Gut microbiota kn-keyword=Gut microbiota en-keyword=Men kn-keyword=Men en-keyword=Producers kn-keyword=Producers END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=57 end-page=66 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Piezo1-mediated mechanotransduction in cementocytes via protein kinase B and p38 mitogen-activated protein kinase signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/purpose: Cementocytes, terminally differentiated cells embedded within cellular cementum, are morphologically similar to osteocytes; however, their mechanosensory function remains poorly understood. This study aimed to investigate whether Piezo1, a mechanosensitive ion channel, contributes to the regulation of osteo/cementogenic gene expression in murine cementocyte-like IDG-CM6 cells.
Materials and methods: IDG-CM6 cells were subjected to cyclic stretch or treated with Piezo1-specific agonist Yoda1 or antagonist GsMTx4. Expression levels of osteo/cementogenic genes (Wnt1, Sost, Opg) and protein levels were analyzed. The involvement of intracellular signaling pathways was assessed using pharmacological inhibitors targeting mitogen-activated protein kinase and protein kinase B (PKB/AKT) pathways.
Results: Cyclic stretch upregulated Wnt1 and Opg, and downregulated Sost expression, without altering Piezo1 expression, suggesting an enhanced osteo/cementogenic potential. These effects were abolished by GsMTx4 and closely mimicked by Yoda1 stimulation. The Yoda1-induced gene expression changes were transient and diminished after withdrawal. Inhibitor experiments confirmed that Piezo1-mediated gene expression is modulated primarily through the AKT and p38 signaling pathways. Phosphorylation of AKT and p38 was rapidly induced by cyclic stretch.
Conclusion: Our findings demonstrate that Piezo1 functions as a mechanosensor in cementocytes, modulating the expression of osteo/cementogenic genes via the AKT and p38 pathways. This study provides new insight into the molecular mechanisms of cementocyte mechanotransduction and may inform strategies for periodontal regeneration and orthodontic treatment. en-copyright= kn-copyright= en-aut-name=XiongKaixin en-aut-sei=Xiong en-aut-mei=Kaixin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakisakaYukihiko en-aut-sei=Sakisaka en-aut-mei=Yukihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TenkumoTaichi en-aut-sei=Tenkumo en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NemotoEiji en-aut-sei=Nemoto en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaruyamaKentaro en-aut-sei=Maruyama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MuhammadFaisal en-aut-sei=Muhammad en-aut-mei=Faisal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiShigeki en-aut-sei=Suzuki en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TadaHiroyuki en-aut-sei=Tada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaSatoru en-aut-sei=Yamada en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Stomatology, Chengdu Integrated TCM and Western Medicine Hospital (Chengdu First People’s Hospital) kn-affil= affil-num=2 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=3 en-affil=Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry kn-affil= affil-num=4 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=5 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=7 en-affil=Department of Operative Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Division of Oral Microbiology and Immunology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=9 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= en-keyword=Cementocytes kn-keyword=Cementocytes en-keyword=Mechanotransduction kn-keyword=Mechanotransduction en-keyword=Piezo1 kn-keyword=Piezo1 en-keyword=Signal transduction kn-keyword=Signal transduction END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=11 article-no= start-page=e97962 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of Carboxyhemoglobin With Severity and Outcomes in Hypothermic Patients: A Retrospective Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
Carboxyhemoglobin (COHb), an endogenous marker of carbon monoxide production mediated by heme oxygenase-1, may reflect physiological stress responses in critically ill patients. However, its clinical relevance in accidental hypothermia remains unclear.

Methods
We conducted a single-center retrospective cohort study of adult patients admitted to the emergency ICU with accidental hypothermia between January 1, 2019, and March 31, 2025. Patients were categorized into low- and high-COHb groups based on median COHb levels upon emergency department arrival. Associations between COHb levels, disease severity (Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores), and 28-day mortality were analyzed using regression models adjusted for clinical confounders.

Results
Among the 88 patients, who had a median admission temperature of 28.7°C, 45 were classified into the low-COHb group and 43 into the high-COHb group, based on a median COHb level of 0.3%. Lower COHb levels on admission were significantly associated with higher APACHE II scores (β = ?4.20; 95% CI, ?7.56 to ?0.85), but not with SOFA scores. Admission and minimum COHb levels were not associated with 28-day mortality. However, higher maximum COHb levels within the first 24 hours were independently associated with lower 28-day mortality (adjusted OR, 0.17; 95% CI, 0.023 to 0.93).

Conclusions
Lower COHb levels were associated with greater disease severity, and higher maximum COHb levels were associated with lower 28-day mortality. COHb may reflect systemic stress in accidental hypothermia, but its prognostic value appears limited. en-copyright= kn-copyright= en-aut-name=MiyoshiYuya en-aut-sei=Miyoshi en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=carbon monoxide kn-keyword=carbon monoxide en-keyword=carboxyhemoglobin kn-keyword=carboxyhemoglobin en-keyword=heme oxygenase kn-keyword=heme oxygenase en-keyword=hypothermia kn-keyword=hypothermia en-keyword=sepsis kn-keyword=sepsis END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=5 article-no= start-page=372 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alpha-Ketoglutarate Drives an Osteogenic and Extracellular Matrix Gene Program in Periodontal Ligament Fibroblasts via Selective Reduction of H3K27me3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontal disease damages the tissues that support teeth and can ultimately lead to tooth loss, yet effective treatments to regenerate these tissues are still limited. Recent studies have shown that substances produced during normal cellular metabolism can influence how genes are regulated, but their role in periodontal regeneration has not been fully clarified. In this study, we investigated whether alpha-ketoglutarate, a naturally occurring metabolite involved in energy production, could promote periodontal tissue regeneration. We found that alpha-ketoglutarate enhanced bone-related and extracellular matrix-related gene expression in human periodontal ligament cells by reducing a repressive gene-regulatory signal that normally suppresses these genes. Importantly, alpha-ketoglutarate did not broadly alter chromatin accessibility, indicating that its effects were mediated through selective gene regulation. Furthermore, oral administration of alpha-ketoglutarate promoted alveolar bone regeneration and collagen-rich tissue formation in a mouse model of periodontal disease. Because alpha-ketoglutarate is a naturally occurring molecule in the body, these findings suggest that metabolite-based regulation of gene activity may represent a promising and safe approach for periodontal tissue regeneration. en-copyright= kn-copyright= en-aut-name=HasegawaRyu en-aut-sei=Hasegawa en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiShigeki en-aut-sei=Suzuki en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FahrezaRahmad Rifqi en-aut-sei=Fahreza en-aut-mei=Rahmad Rifqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsaiShin-Ho en-aut-sei=Tsai en-aut-mei=Shin-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DaidoujiYoshino en-aut-sei=Daidouji en-aut-mei=Yoshino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriMasato en-aut-sei=Omori en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KajikawaTetsuhiro en-aut-sei=Kajikawa en-aut-mei=Tetsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamadaSatoru en-aut-sei=Yamada en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=2 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=4 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=7 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=8 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= en-keyword=alpha-ketoglutarate kn-keyword=alpha-ketoglutarate en-keyword=periodontal ligament kn-keyword=periodontal ligament en-keyword=extracellular matrix kn-keyword=extracellular matrix en-keyword=epigenetic regulation kn-keyword=epigenetic regulation en-keyword=H3K27me3 kn-keyword=H3K27me3 END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=4 article-no= start-page=715 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antigen Remodeling in Colorectal Cancer: How Radiotherapy and Chemotherapy Enhance Immunotherapy Responsiveness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colorectal cancer (CRC) is traditionally considered a “cold tumor” characterized by low immunogenicity and limited responsiveness to immune checkpoint inhibitors (ICIs). However, recent findings reveal that cytotoxic modalities can reprogram this immunologically inert landscape. This review integrates these evolving concepts to guide the optimization of future treatments. Radiotherapy induces extensive DNA double-strand breaks, which may generate de novo mutations through error-prone repair while simultaneously exposing cryptic antigens via increased transcriptional instability, alternative splicing, and enhanced proteasomal processing. Chemoradiation also amplifies epigenetic and epitranscriptomic sources of neoepitope diversity, including RNA editing and stress-induced splicing alterations, expanding the immunopeptidome beyond canonical mutation-driven neoantigens. These changes collectively enhance antigen presentation and facilitate T-cell priming. Chemotherapy further reduces immunosuppressive cell populations and promotes dendritic cell activation, creating a permissive milieu for subsequent immune engagement. Clinically, the VOLTAGE studies demonstrated that long-course chemoradiotherapy can sensitize even mismatch repair?proficient rectal cancers to PD-1 blockade, yielding clinically meaningful pathological responses. In contrast, mismatch repair?deficient rectal tumors may respond completely to ICIs alone. Short-course radiotherapy combined with chemotherapy and ICIs has also shown encouraging activity in the setting of total neoadjuvant therapy. Collectively, these findings support a paradigm in which radiotherapy, chemotherapy, and epigenetic/epitranscriptomic alterations?including RNA editing?act as potent modulators of tumor antigenicity. By expanding the neoantigen repertoire and reshaping the tumor microenvironment, these strategies can transform CRC from a cold tumor into one that is increasingly responsive to immunotherapy. en-copyright= kn-copyright= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=immunotherapy kn-keyword=immunotherapy en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=neoantigens kn-keyword=neoantigens END start-ver=1.4 cd-journal=joma no-vol=164 cd-vols= no-issue= article-no= start-page=108315 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Global trends in Clostridioides difficile infection?related mortality, 2001-2023: An observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Clostridioides difficile infection (CDI) is a major public health concern, particularly in aging populations. The aim of this study was to evaluate global trends in CDI-related mortality to inform sustainable and cost-effective management strategies.
Methods: We conducted an observational study using mortality data from the World Health Organization (WHO) database spanning 2001 to 2023. Sixty-three countries with satisfactory data quality and at least 12 years of data between 2001 and 2023 were included. Crude and age-standardized CDI-related mortality rates per 1,000,000 individuals were calculated after stratification by age, sex, WHO region, and sociodemographic index (SDI). Global trends were analyzed using locally weighted regression.
Results: The global age-standardized CDI-related mortality rate was 0.76 per 1,000,000 individuals in 2001, peaked at 4.08 in 2010, and declined to 2.44 in 2023. The most notable downward trends were observed in the Americas and high-SDI countries. These improvements may reflect the impact of multidisciplinary efforts in CDI prevention and management.
Conclusions: Although CDI-related mortality has declined globally over the past decade, the disease remains a significant threat, especially in older populations. Ongoing global efforts are essential to further reduce CDI-related deaths. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoMaki en-aut-sei=Yamamoto en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=VuQuynh Thi en-aut-sei=Vu en-aut-mei=Quynh Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BelangoyKeith Pardillada en-aut-sei=Belangoy en-aut-mei=Keith Pardillada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OuddoudHanane en-aut-sei=Ouddoud en-aut-mei=Hanane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Hematology/Oncology, Mayo Clinic kn-affil= affil-num=3 en-affil=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=4 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Aging kn-keyword=Aging en-keyword=Locally weighted regression model kn-keyword=Locally weighted regression model en-keyword=Infection kn-keyword=Infection en-keyword=Clostridioides difficile kn-keyword=Clostridioides difficile en-keyword=Disparity kn-keyword=Disparity END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=3 article-no= start-page=102931 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tick-borne pathogens in ticks collected from Humans: A prospective clinical pilot study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tick-borne diseases (TBDs), particularly Japanese spotted fever, are an increasing public health concern in Japan. Data on pathogens carried by ticks removed directly from patients and their associated clinical outcomes remain limited. This prospective study investigated pathogen carriage in patient-derived ticks and evaluated the clinical risk of TBDs. Between April and October 2025, ticks were collected from patients presenting with tick bites at two medical institutions in Western Japan. Ticks were morphologically identified and spotted fever group rickettsiae (SFGR) was detected by nested PCR targeting the 17-kDa antigen gene, followed by sequence analysis. Clinical data, including patient background, antibiotic prescriptions, and outcomes, were reviewed. Clinical information was available for 70 patients (median age; 75 years), of whom 88.6% were prescribed prophylactic antibiotics. Ticks were collected from 60 patients (85.7%), and seven adults without antibiotic prophylaxis were followed for disease onset. Sixty-two ticks, predominantly Amblyomma testudinarium (88.7%), were analyzed. SFGR was detected in eight ticks (12.9%), including seven A. testudinarium and one Ixodes nipponensis, collected from seven patients. Two patients bitten by Rickettsia tamurae?carrying ticks were observed for one month without antibiotics and remained asymptomatic. In this prospective analysis, no clinically apparent rickettsiosis was observed following bites from R. tamurae?positive ticks without antibiotic prophylaxis; however, subclinical infection could not be excluded. Despite the small sample size, our findings suggest that the clinical risk associated with R. tamurae infection may be low. Direct analysis of removed ticks from patients may help characterize pathogen reservoirs and inform targeted approaches to TBDs. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SumidaTakaomi en-aut-sei=Sumida en-aut-mei=Takaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawamataOsamu en-aut-sei=Kawamata en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HidaniYoshimi en-aut-sei=Hidani en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Numakuma Hospital kn-affil= affil-num=3 en-affil=Numakuma Hospital kn-affil= affil-num=4 en-affil=Numakuma Hospital kn-affil= affil-num=5 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Epidemiology kn-keyword=Epidemiology en-keyword=Japanese spotted fever kn-keyword=Japanese spotted fever en-keyword=Spotted fever group rickettsiae kn-keyword=Spotted fever group rickettsiae en-keyword=Tick bite kn-keyword=Tick bite en-keyword=Tick-borne disease kn-keyword=Tick-borne disease END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=e100872 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Saliva as a Reliable and Non-invasive Sample for Detecting Influenza A in Severe Acute Respiratory Infection Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Nasopharyngeal swab sampling remains the gold standard for influenza diagnosis; however, it has several limitations, including dependence on medical staff, invasiveness, potential for nosocomial transmission, and occupational exposure risk. Non-invasive alternatives, such as saliva and nasal vestibular swabs, may improve patient comfort and participation in clinical studies. In addition, diagnosis with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Although rapid diagnostic devices such as the GenPad? offer potential alternatives to RT-qPCR, their performance with non-invasive samples remains insufficiently explored. This study addresses the two key questions for influenza detection in severe acute respiratory infection (SARI) cases: (i) whether saliva or nasal vestibular swab samples serve as suitable alternatives to nasopharyngeal swab samples, and (ii) whether the GenPad? provides a reliable option for detecting influenza using saliva samples.
Methodology
A prospective observational study was conducted with 16 inpatients classified as having SARIs and diagnosed with influenza between December 2024 and March 2025 in Japan. Paired saliva and nasal vestibular swab samples were collected 1-9 (median = 3.5) days after symptom onset. RT-qPCR testing was performed according to the National Institute of Infectious Diseases protocol. Saliva samples were also tested using the GenPad? system. Comparisons between sample types and diagnostic methods were analyzed using the exact McNemar's test.
Results
Among the 16 influenza-positive patients, saliva samples demonstrated higher sensitivity (87.5%) than nasal vestibular swabs (31.3%) in RT-qPCR when compared with the diagnostic results obtained from nasopharyngeal swabs. A comparison of RT-qPCR results between saliva and nasal vestibular swabs revealed a total agreement of 43.8%, with exact McNemar's test showing a significant difference (p = 0.0039). While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within seven days of symptom onset (100% positive agreement). The GenPad?, a rapid diagnostic device, showed promising performance (92.9%) using saliva samples compared to RT-qPCR.
Conclusions
Saliva is a reliable non-invasive alternative to nasopharyngeal swabs for influenza detection in SARI cases, particularly within seven days of symptom onset, whereas nasal vestibular swabs show lower sensitivity. Additionally, the GenPad? provides comparable performance to RT-qPCR using saliva samples, offering a rapid, portable diagnostic option. These approaches may mitigate discomfort, minimize infection risk for healthcare workers, and improve testing capacity. However, the absence of influenza-negative controls and the small sample size (n = 16) substantially limit the assessment of diagnostic accuracy and specificity. As a result, the broader applicability of our findings should be interpreted with caution, and further studies are required to validate these observations. en-copyright= kn-copyright= en-aut-name=TakeuchiJunko S en-aut-sei=Takeuchi en-aut-mei=Junko S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsunagaNobuaki en-aut-sei=Matsunaga en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukadaAi en-aut-sei=Tsukada en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwamotoNoriko en-aut-sei=Iwamoto en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuwaNoriko en-aut-sei=Fuwa en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IchikawaTakahiro en-aut-sei=Ichikawa en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoYasuyuki en-aut-sei=Kato en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TomitaYuka en-aut-sei=Tomita en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitagawaHiroki en-aut-sei=Kitagawa en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamatoMasaya en-aut-sei=Yamato en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AoyagiTetsuji en-aut-sei=Aoyagi en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HaseRyota en-aut-sei=Hase en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HatakeyamaShuji en-aut-sei=Hatakeyama en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InabaTohru en-aut-sei=Inaba en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IzumikawaKoichi en-aut-sei=Izumikawa en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakesueYoshio en-aut-sei=Takesue en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KimuraMoto en-aut-sei=Kimura en-aut-mei=Moto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OhmagariNorio en-aut-sei=Ohmagari en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=2 en-affil=Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security kn-affil= affil-num=3 en-affil=Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security kn-affil= affil-num=4 en-affil=Disease Control and Prevention Center, Japan Institute for Health Security kn-affil= affil-num=5 en-affil=Disease Control and Prevention Center, Japan Institute for Health Security kn-affil= affil-num=6 en-affil=Department of Infectious Diseases, Sapporo City General Hospital kn-affil= affil-num=7 en-affil=Department of Infectious Diseases, International University of Health and Welfare (IUHW) Narita Hospital kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Department of General Internal Medicine and Infectious Diseases, Rinku General Medical Center kn-affil= affil-num=11 en-affil=Department of Clinical Infectious Diseases, Tohoku University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Infectious Diseases, Japanese Red Cross Narita Hospital kn-affil= affil-num=14 en-affil=Division of Infectious Diseases, Jichi Medical University Hospital kn-affil= affil-num=15 en-affil=Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine kn-affil= affil-num=16 en-affil= kn-affil= affil-num=17 en-affil=Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=18 en-affil=Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=19 en-affil=Disease Control and Prevention Center, Japan Institute for Health Security kn-affil= en-keyword=influenza a kn-keyword=influenza a en-keyword=nasal vestibular swab kn-keyword=nasal vestibular swab en-keyword=nasopharyngeal swab kn-keyword=nasopharyngeal swab en-keyword=rapid diagnostics kn-keyword=rapid diagnostics en-keyword=rt-qpcr kn-keyword=rt-qpcr en-keyword=saliva kn-keyword=saliva en-keyword=sari kn-keyword=sari END start-ver=1.4 cd-journal=joma no-vol=112 cd-vols= no-issue=2 article-no= start-page=2301 end-page=2310 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear.
Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan?Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors.
Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group.
Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence. en-copyright= kn-copyright= en-aut-name=HayashiTatsuya en-aut-sei=Hayashi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OtsukaTomoaki en-aut-sei=Otsuka en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KurosakiTakeshi en-aut-sei=Kurosaki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamadaEiji en-aut-sei=Yamada en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsudaEisuke en-aut-sei=Matsuda en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HayashiTatsurou en-aut-sei=Hayashi en-aut-mei=Tatsurou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HayamaMakio en-aut-sei=Hayama en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HiramiYuji en-aut-sei=Hirami en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=WashioKazuhiro en-aut-sei=Washio en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MisaoTakahiko en-aut-sei=Misao en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SanoYoshifumi en-aut-sei=Sano en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KawamataOsamu en-aut-sei=Kawamata en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Center of Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=22 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=23 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=24 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=25 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=26 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=27 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=partial thymectomy kn-keyword=partial thymectomy en-keyword=real-world data analysis kn-keyword=real-world data analysis en-keyword=retrospective comparative cohort study kn-keyword=retrospective comparative cohort study en-keyword=thymic carcinoma kn-keyword=thymic carcinoma en-keyword=thymic epithelial tumors kn-keyword=thymic epithelial tumors en-keyword=total thymectomy kn-keyword=total thymectomy END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=4 article-no= start-page=1081 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Generative AI?Based Technical Data Extraction Tool for IoT Application Systems en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, Internet of Things (IoT) application systems play an essential role in smart cities, industry, healthcare, agriculture, and smart homes. For non-expert users, designing and implementing IoT application systems remains challenging, especially when configuring sensors, edge devices, and server platforms. To support configuration tasks of IoT application systems, we have developed an AI-based setup assistance tool. However, AI models still fail to reliably support newly released or previously unseen devices, sometimes producing incomplete or erroneous outputs that may lead to configuration failures. Incorporating their technical-document information into Retrieval-Augmented Generation (RAG) is an effective way to supplement AI knowledge and improve reliability. In this paper, we propose a generative AI-based technical data extraction tool to address the challenges. It extracts essential technical information using the schema-based extraction from given PDF or HTML datasheets and converts it into a structured format suitable for AI-supported configurations. A local vector database is used to enable semantic similarity retrieval and provide document-grounded evidence for RAG-based answering, ensuring consistent support for previously unseen IoT devices. For evaluations, we applied the proposal to several sensor and device datasheets and compared extracted specifications with ground-truth values to measure accuracy and completeness. Then, we compared end-to-end configuration QA reliability against a commercial baseline (ChatPDF) using the golden benchmark. The results show that the proposed tool reliably acquires key specifications and significantly improves end-to-end configuration QA reliability. Across 960 golden QA pairs, the proposed method improves Recall from 0.636 to 0.926 and Accuracy from 0.595 to 0.807 compared with ChatPDF. en-copyright= kn-copyright= en-aut-name=KongDezheng en-aut-sei=Kong en-aut-mei=Dezheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KyawHtoo Htoo Sandi en-aut-sei=Kyaw en-aut-mei=Htoo Htoo Sandi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KotamaI Nyoman Darma en-aut-sei=Kotama en-aut-mei=I Nyoman Darma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhuZihao en-aut-sei=Zhu en-aut-mei=Zihao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RahmadaniAlfiandi Aulia en-aut-sei=Rahmadani en-aut-mei=Alfiandi Aulia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= en-keyword=internet of things kn-keyword=internet of things en-keyword=AI kn-keyword=AI en-keyword=retrieval-augmented generation kn-keyword=retrieval-augmented generation en-keyword=vector database kn-keyword=vector database en-keyword=schema-based extraction kn-keyword=schema-based extraction en-keyword=data sheet kn-keyword=data sheet en-keyword=technical information kn-keyword=technical information END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=47 end-page=54 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Time Course of the Development and Loss of Delta-9-tetrahydrocannabinol Tolerance: Effects on Hypothermia and Spontaneous Locomotor Activity in Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Deregulation of cannabis use is gradually expanding in Europe and the United States. However, the biological processes driving tolerance to delta-9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component of cannabis, remain unclear. Thus, this study aimed to investigate the mechanisms and time course of tolerance development and loss to Δ9-THC in mice. Male ICR mice (7 weeks old) were administered Δ9-THC once daily for 3 days and then divided into three groups according to the washout period (3-, 10-, and 17-day washout groups). After each washout, changes in body temperature and locomotor activity were measured following re-exposure to Δ9-THC. Furthermore, the mRNA expression levels of CB1 and CB2 receptors in the brain were evaluated using real-time PCR. On day 1, significant hypothermia and reduced spontaneous locomotor activity were observed in the Δ9-THC-treated mice compared with the vehicle-treated mice. Tolerance to the hypothermic and locomotor-suppressing effects of Δ9-THC developed on days 2 and 3, respectively, and dissipated after 3 and 11 days of washout, respectively. These differences in the rates of tolerance development and recovery may reflect distinct underlying mechanisms. No significant changes in receptor mRNA expression were observed. These findings highlight the complexity of Δ9-THC tolerance and its potential implications for long-term cannabis use. en-copyright= kn-copyright= en-aut-name=EguchiYukiomi en-aut-sei=Eguchi en-aut-mei=Yukiomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IrieKeiichi en-aut-sei=Irie en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamashitaYuta en-aut-sei=Yamashita en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EguchiMiyu en-aut-sei=Eguchi en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoTakafumi en-aut-sei=Nakano en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MishimaKenichi en-aut-sei=Mishima en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=2 en-affil=Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=3 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=4 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=5 en-affil=Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=6 en-affil=Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=7 en-affil=Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= en-keyword=delta-9-tetrahydrocannabinol kn-keyword=delta-9-tetrahydrocannabinol en-keyword=cannabis kn-keyword=cannabis en-keyword=tolerance kn-keyword=tolerance en-keyword=locomotor kn-keyword=locomotor en-keyword=hypothermic kn-keyword=hypothermic END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=9 end-page=16 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel Nomogram that Predicts Chronic Hemodialysis Patients’ Survival Based on Their Sedentary Behavior en-subtitle= kn-subtitle= en-abstract= kn-abstract=Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patients’ survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patients’ sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7±11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patients’ sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patients’ 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients. en-copyright= kn-copyright= en-aut-name=SugaharaKentaro en-aut-sei=Sugahara en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoTakashi en-aut-sei=Kondo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyatakeNobuyuki en-aut-sei=Miyatake en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiHiroyuki en-aut-sei=Nishi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UjikeKazuhiro en-aut-sei=Ujike en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoumotoKiichi en-aut-sei=Koumoto en-aut-mei=Kiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NamioKeiichi en-aut-sei=Namio en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HishiiShuhei en-aut-sei=Hishii en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatayamaAkihiko en-aut-sei=Katayama en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuzukiHiromi en-aut-sei=Suzuki en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoYorimasa en-aut-sei=Yamamoto en-aut-mei=Yorimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Innoshima General Hospital kn-affil= affil-num=3 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=4 en-affil=Innoshima General Hospital kn-affil= affil-num=5 en-affil=Innoshima General Hospital kn-affil= affil-num=6 en-affil=Innoshima General Hospital kn-affil= affil-num=7 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=8 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Faculty of Social Studies, Shikokugakuin University kn-affil= affil-num=10 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=11 en-affil=Innoshima General Hospital kn-affil= en-keyword=nomogram kn-keyword=nomogram en-keyword=chronic hemodialysis kn-keyword=chronic hemodialysis en-keyword=sedentary behavior kn-keyword=sedentary behavior en-keyword=Cox proportional hazards model kn-keyword=Cox proportional hazards model en-keyword=Kaplan- Meier curve kn-keyword=Kaplan- Meier curve END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=1 end-page=7 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Usefulness of D-dimer Assay to Confirm the Course of Overt Venous Thromboembolism (VTE) in Cancer Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Venous thromboembolism (VTE) is a serious complication in patients with cancer. In this population, the presence of thrombi is often assessed at cancer diagnosis by measuring D-dimer levels, which have high sensitivity but low specificity for identifying VTE at this clinical time point. However, the usefulness of D-dimer measurement during anticoagulation therapy has not been fully established, despite its widespread use. In this retrospective observational study, we investigated whether D-dimer measurement during anticoagulation therapy in cancer patients could predict overt VTE at follow-up. The study included patients who underwent D-dimer testing and contrast-enhanced computed tomography between 30 and 100 days after initiation of anticoagulation therapy. Eighty-two patients were included: 60 with cancer and 22 without. The diagnostic performance of D-dimer for overt VTE was as follows: sensitivity, 85.7%; specificity, 87.2%; positive predictive value, 78.3%; and negative predictive value, 89.2%. These findings suggest that D-dimer measurement at follow-up has high sensitivity and specificity for overt VTE in cancer patients and may aid in assessing thrombotic status. Clinically, if anticoagulation therapy is continued until D-dimer levels become negative, the absence of overt VTE could be inferred without additional invasive testing. en-copyright= kn-copyright= en-aut-name=YamaokaHidenaru en-aut-sei=Yamaoka en-aut-mei=Hidenaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SarashinaToshihiro en-aut-sei=Sarashina en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MunemasaMitsuru en-aut-sei=Munemasa en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, IMS Tokyo Katsushika General Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Seisukai Kuroda Clinic kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=D-dimer kn-keyword=D-dimer en-keyword=venous kn-keyword=venous en-keyword=thromboembolism kn-keyword=thromboembolism en-keyword=cancer kn-keyword=cancer END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue= article-no= start-page=20 end-page=39 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Radiocarbon dating, dietary habits, and genetic characteristics of ancient skeletal remains excavated from the Inome Cave Site in Shimane Prefecture kn-title=島根県猪目洞窟遺跡出土人骨の年代・食性・遺伝的特徴 en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper reports on the integrative research findings of the human bones excavated from the Inome Cave Site in Shimane Prefecture, based on dietary estimation using carbon and nitrogen isotope analysis, radiocarbon dating, and whole genome analysis. The dates of the analyzed human bones span a wide range, from the Middle to Late Kofun period, the Nara period to the Early Heian period, and the Middle to Late Heian period, indicating that the Inome Cave Site was continuously used as a burial place. Dietary habits were a mixture of C3 resources (C3 plants and terrestrial animals that consumed C3 plants) and marine resources, with individual variations in the intake of marine and terrestrial resources. A correlation was observed between differences in dietary habits and individual variations in the Jomon ratio in the nuclear genome, with individuals who consumed higher amounts of marine resources tending to have a higher Jomon ratio. This suggests that individuals with different backgrounds were buried in the same site due to interactions with surrounding settlements. en-copyright= kn-copyright= en-aut-name=KANZAWA-KIRIYAMAHideaki en-aut-sei=KANZAWA-KIRIYAMA en-aut-mei=Hideaki kn-aut-name=神澤秀明 kn-aut-sei=神澤 kn-aut-mei=秀明 aut-affil-num=1 ORCID= en-aut-name=TAKIGAMIMai en-aut-sei=TAKIGAMI en-aut-mei=Mai kn-aut-name=瀧上舞 kn-aut-sei=瀧上 kn-aut-mei=舞 aut-affil-num=2 ORCID= en-aut-name=KAKUDATsuneo en-aut-sei=KAKUDA en-aut-mei=Tsuneo kn-aut-name=角田恒雄 kn-aut-sei=角田 kn-aut-mei=恒雄 aut-affil-num=3 ORCID= en-aut-name=SPEIDELLeo en-aut-sei=SPEIDEL en-aut-mei=Leo kn-aut-name=シュパイデルレオ kn-aut-sei=シュパイデル kn-aut-mei=レオ aut-affil-num=4 ORCID= en-aut-name=HELLENTHALGarrett en-aut-sei=HELLENTHAL en-aut-mei=Garrett kn-aut-name=ヘレンタールガレット kn-aut-sei=ヘレンタール kn-aut-mei=ガレット aut-affil-num=5 ORCID= en-aut-name=BIRDNancy en-aut-sei=BIRD en-aut-mei=Nancy kn-aut-name=バードナンシー kn-aut-sei=バード kn-aut-mei=ナンシー aut-affil-num=6 ORCID= en-aut-name=KAWAIYousuke en-aut-sei=KAWAI en-aut-mei=Yousuke kn-aut-name=河合洋介 kn-aut-sei=河合 kn-aut-mei=洋介 aut-affil-num=7 ORCID= en-aut-name=NCBN Controls WGS Consortium en-aut-sei=NCBN Controls WGS Consortium en-aut-mei= kn-aut-name=NCBN コントロール WGS コンソーシアム kn-aut-sei=NCBN コントロール WGS コンソーシアム kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SAKAMOTOMinoru en-aut-sei=SAKAMOTO en-aut-mei=Minoru kn-aut-name=坂本稔 kn-aut-sei=坂本 kn-aut-mei=稔 aut-affil-num=9 ORCID= en-aut-name=KAMEDAYuichi en-aut-sei=KAMEDA en-aut-mei=Yuichi kn-aut-name=亀田勇一 kn-aut-sei=亀田 kn-aut-mei=勇一 aut-affil-num=10 ORCID= en-aut-name=ADACHINoboru en-aut-sei=ADACHI en-aut-mei=Noboru kn-aut-name=安達登 kn-aut-sei=安達 kn-aut-mei=登 aut-affil-num=11 ORCID= en-aut-name=SHINODAKen-ichi en-aut-sei=SHINODA en-aut-mei=Ken-ichi kn-aut-name=篠田謙一 kn-aut-sei=篠田 kn-aut-mei=謙一 aut-affil-num=12 ORCID= en-aut-name=SAITOUNaruya en-aut-sei=SAITOU en-aut-mei=Naruya kn-aut-name=斎藤成也 kn-aut-sei=斎藤 kn-aut-mei=成也 aut-affil-num=13 ORCID= en-aut-name=HAMADATatsuhiko en-aut-sei=HAMADA en-aut-mei=Tatsuhiko kn-aut-name=M田竜彦 kn-aut-sei=M田 kn-aut-mei=竜彦 aut-affil-num=14 ORCID= affil-num=1 en-affil=Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture kn-affil= affil-num=2 en-affil=Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture kn-affil= affil-num=3 en-affil=Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi kn-affil= affil-num=4 en-affil=Center for Interdisciplinary Theoretical and Mathematical Sciences, RIKEN kn-affil= affil-num=5 en-affil=Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London kn-affil= affil-num=6 en-affil=Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London kn-affil= affil-num=7 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine, National Institute for Health Security kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=National Museum of Japanese History kn-affil= affil-num=10 en-affil=Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture kn-affil= affil-num=11 en-affil=Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi kn-affil= affil-num=12 en-affil=National Museum of Nature and Science kn-affil= affil-num=13 en-affil=National Institute of Genetics kn-affil= affil-num=14 en-affil=Research Institute for the Dynamics of Civilizations, Okayama University kn-affil= en-keyword=Inome Cave Site kn-keyword=Inome Cave Site en-keyword=human bone kn-keyword=human bone en-keyword=radiocarbon dating kn-keyword=radiocarbon dating en-keyword=dietary habits kn-keyword=dietary habits en-keyword=ancient genome kn-keyword=ancient genome END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=4 article-no= start-page=1422 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Perioperative Ozoralizumab Management for Patients with Rheumatoid Arthritis Who Underwent Orthopaedic Surgery: A Retrospective Case Series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Launched in Japan in 2022, ozoralizumab (OZR) is a novel, anti-tumour necrosis factor (TNF)-α inhibitor for treating rheumatoid arthritis (RA) that is refractory to conventional therapies. However, there is a lack of evidence regarding its perioperative management. Methods: This retrospective case series included nine patients with RA who underwent a total of 12 either RA-related (n = 9) or unrelated (n = 3) orthopaedic procedures. We reviewed patient demographics, surgical procedures, perioperative OZR discontinuation periods, and postoperative complications. Results: The mean preoperative OZR discontinuation period was 15.8 days (range, 2?25 days). Sutures were removed at a mean of 12.8 days postoperatively (range, 11?14 days) after adequate wound healing had been confirmed. The mean total discontinuation period was 34.9 days (range, 27?43 days). No cases of surgical site infection (SSI) or delayed wound healing (DWH) were observed during a minimum follow-up period of three months. One patient experienced a disease flare before OZR was restarted. Conclusions: Preoperative OZR discontinuation for up to four weeks appeared to be safe in this cohort. These findings may assist orthopaedic surgeons in determining an appropriate perioperative discontinuation strategy for OZR that minimises SSI and DWH risk while reducing the likelihood of RA flare. en-copyright= kn-copyright= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NasuYoshihisa en-aut-sei=Nasu en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaRyozo en-aut-sei=Harada en-aut-mei=Ryozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoritaMasahiro en-aut-sei=Horita en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NatsumedaMasamitsu en-aut-sei=Natsumeda en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaniwaShuichi en-aut-sei=Naniwa en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Locomotive Pain Center, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama City Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Kurashiki Sweet Hospital kn-affil= affil-num=4 en-affil=Locomotive Pain Center, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Locomotive Pain Center, Faculty of Medical Development Field, Okayama University kn-affil= affil-num=6 en-affil=Rheumatic Disease Center, Mabi Memorial Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=delayed wound healing kn-keyword=delayed wound healing en-keyword=discontinuation kn-keyword=discontinuation en-keyword=ozoralizumab kn-keyword=ozoralizumab en-keyword=orthopaedic surgery kn-keyword=orthopaedic surgery en-keyword=perioperative management kn-keyword=perioperative management en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis en-keyword=surgical site infection kn-keyword=surgical site infection END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=100731 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Insights into the taste of organic acids via TAS1Rs en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Organic acids contribute significantly to the flavor of fermented foods by imparting sourness. Although mice generally avoid sour taste, previous studies have reported greater consumption of l-lactic acid than its d-enantiomer, suggesting enantiomer-specific recognition. This behavior is hypothesized to involve TAS1Rs, which consists of sweet/umami receptors. However, it remains unclear whether TAS1Rs additionally contribute to the recognition of other chiral organic acids. This study aimed to evaluate the role of TAS1Rs, particularly TAS1R3, in the modulation of enantiomer-dependent behavioral responses to organic acids in mice.
Methods: Behavioral responses were evaluated using 48-h and 1-h 2-bottle tests. Binding of organic acids to TAS1Rs was investigated by differential scanning fluorimetry (DSF) with the ligand-binding domain (LBD) of medaka Tas1r2a/Tas1r3.
Results: Wild-type mice consumed more d-malic acid than l-malic acid in the 48-h test, whereas Tas1r3-KO mice showed no such difference. This pattern was not observed in the short-term 1-h test, which minimized the contribution of post-ingestion and learned effects. DSF analysis revealed no binding of any of the tested organic acids to the LBD of medaka Tas1r2a/Tas1r3.
Conclusions: Organic acids may elicit TAS1R3-dependent post-ingestion signals that contribute to enantiomer-selective consumption in mice. Electrostatic interactions and hydrogen-bonding networks within the orthosteric pocket of TAS1Rs may account for the differences in binding affinity to the LBD of medaka Tas1r2a/Tas1r3 between organic acids and L-alanine, a known ligand. en-copyright= kn-copyright= en-aut-name=YamaseYuko en-aut-sei=Yamase en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashitaAtsuko en-aut-sei=Yamashita en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Institute for Protein Research, The University of Osaka kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Taste detection kn-keyword=Taste detection en-keyword=Organic acid preference kn-keyword=Organic acid preference en-keyword=G-protein coupled receptor (GPCR) kn-keyword=G-protein coupled receptor (GPCR) en-keyword=Knockout mice kn-keyword=Knockout mice en-keyword=Surface electrostatic potential kn-keyword=Surface electrostatic potential END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=563 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Surface Morphology Formed by Additive Manufacturing on the Adhesion of Dental Cements to Zirconia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Durable bonding to zirconia remains difficult because its chemically inert surface resists acid etching. Additive manufacturing (AM) enables controlled surface morphology, which may enhance micromechanical retention without additional treatments. Methods: Zirconia specimens with three AM-derived surface designs?(1) concave?convex hemispherical patterns, (2) concave hemispherical patterns, and (3) as-printed surfaces?were fabricated using a slurry-based 3D printing system and sintered at 1500 °C. Zirconia specimens fabricated by subtractive manufacturing using CAD/CAM systems, polished with 15 ?m diamond lapping film and with or without subsequent alumina sandblasting, served as controls. Surface morphology was analyzed by FE-SEM, and shear bond strength (SBS) was tested after cementation with a resin-based luting agent. Results: SEM revealed regular layered textures and designed hemispherical structures (~300 ?m) in AM specimens, along with step-like irregularities (~40 ?m) at layer boundaries. The concave?convex AM group showed significantly higher SBS than both sandblasted and polished subtractive-manufactured zirconia (p < 0.05). Vertically printed specimens demonstrated greater bonding strength than those printed parallel to the bonding surface, indicating that build orientation affects resin infiltration and interlocking. Conclusion: AM-derived zirconia surfaces can provide superior and reproducible micromechanical retention compared with conventional treatments. Further optimization of printing parameters and evaluation of long-term durability are needed for clinical application. en-copyright= kn-copyright= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeeSungho en-aut-sei=Lee en-aut-mei=Sungho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SpirrettFiona en-aut-sei=Spirrett en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KiriharaSoshu en-aut-sei=Kirihara en-aut-mei=Soshu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Van MeerbeekBart en-aut-sei=Van Meerbeek en-aut-mei=Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute kn-affil= affil-num=2 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=3 en-affil=National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=4 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=5 en-affil=Joining and Welding Research Institute, Osaka University kn-affil= affil-num=6 en-affil=Joining and Welding Research Institute, Osaka University kn-affil= affil-num=7 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=8 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= en-keyword=additive manufacturing kn-keyword=additive manufacturing en-keyword=bond strength kn-keyword=bond strength en-keyword=dental crown kn-keyword=dental crown en-keyword=dental resin cement kn-keyword=dental resin cement en-keyword=dental zirconia kn-keyword=dental zirconia END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=12 article-no= start-page=5742 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250615 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Specific Heat-Killed Lactic Acid Bacteria Enhance Mucosal Aminopeptidase N Activity in the Small Intestine of Aged Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aminopeptidase N (APN), an enzyme expressed in the small intestinal mucosa, is involved in dietary protein digestion. Previous studies have shown that oral administration of fermented milk containing lactic acid bacteria (LAB) enhances mucosal APN activity in young mice. This study aimed to investigate whether LAB strains stimulate mucosal APN activity in aged mice and to evaluate its relevance to age-related changes in body composition. The underlying molecular mechanisms were also explored in vitro. Experiment 1: Aged C57BL/6J mice were fed diets supplemented with heat-killed LAB strains?Enterococcus faecalis OU-23 (EF), Leuconostoc mesenteroides OU-03 (LM), or Lactiplantibacillus plantarum SNK12 (LP). Compared to the aged Control group, the ileal APN activity was significantly higher in the LP group. LP administration also elevated serum Gla-osteocalcin levels and decreased serum CTX-1 levels. Experiment 2: IEC-6 cells were co-cultured with LP that had been treated with RNase, DNase, or lysozyme. APN activity was significantly lower in cells co-cultured with DNase- or lysozyme-treated LP compared to those co-cultured with untreated LP. A specific LAB strain may enhance mucosal APN activity in the aged intestine, potentially contributing to improved bone metabolism. This effect may be mediated by bacterial DNA and peptidoglycan. en-copyright= kn-copyright= en-aut-name=TsurutaTakeshi en-aut-sei=Tsuruta en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakisakaMami en-aut-sei=Wakisaka en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeTakumi en-aut-sei=Watanabe en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishijimaAoi en-aut-sei=Nishijima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaAkihito en-aut-sei=Ikeda en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeraokaMao en-aut-sei=Teraoka en-aut-mei=Mao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WangTianyang en-aut-sei=Wang en-aut-mei=Tianyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChenKuiyi en-aut-sei=Chen en-aut-mei=Kuiyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishinoNaoki en-aut-sei=Nishino en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Bio-Lab Co., Ltd. kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=aging kn-keyword=aging en-keyword=aminopeptidase N kn-keyword=aminopeptidase N en-keyword=bone metabolism kn-keyword=bone metabolism en-keyword=lactic acid bacteria kn-keyword=lactic acid bacteria en-keyword=small intestine kn-keyword=small intestine END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=4 article-no= start-page=300 end-page=309 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of biopterin and related pterin glycosides en-subtitle= kn-subtitle= en-abstract= kn-abstract=Certain pterins having a hydroxyalkyl side chain at C-6 have been found as glycosidic forms in certain prokaryotes, such as 2′-O-(α-D-glucopyranosyl)biopterin from various kinds of cyanobacteria, and limipterin from a green sulfur photosynthetic bacterium. Synthetic studies on glycosides of biopterin and related pterins have been made in view of the structural proof as well as for closer examination of their biological activities and functions. The syntheses of these natural pterin glycosides have effectively been achieved, mostly through appropriately protected N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]pterin derivatives as glycosyl acceptors, and are reviewed here. ? 2013 IUBMB Life 65(4):300?309, 2013. en-copyright= kn-copyright= en-aut-name=HanayaTadashi en-aut-sei=Hanaya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiroshi en-aut-sei=Yamamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=School of Pharmacy, Shujitsu University kn-affil= en-keyword=pteridine kn-keyword=pteridine en-keyword=pterin glycoside kn-keyword=pterin glycoside en-keyword=biopterin kn-keyword=biopterin en-keyword=ciliapterin kn-keyword=ciliapterin en-keyword=neopterin kn-keyword=neopterin en-keyword=limipterin kn-keyword=limipterin en-keyword=tepidopterin kn-keyword=tepidopterin en-keyword=asperopterin-A kn-keyword=asperopterin-A en-keyword=protecting group kn-keyword=protecting group en-keyword=glycosylation kn-keyword=glycosylation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pediatric autologous peripheral blood stem cell collection without heparin using a highly concentrated sodium citrate anticoagulant: A retrospective comparison with standard ACD-A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Heparin combined with sodium citrate has been used in leukocytapheresis for pediatric patients. Since 2022, we have performed leukocytapheresis using a highly concentrated sodium citrate solution (HSC, 5.32%) instead of acid citrate dextrose solution A (ACD-A). We conducted this study to determine whether HSC use reduces run time and the total amount of anticoagulant solution in children.
Study Design and Methods: We retrospectively analyzed data from consecutive autologous peripheral blood stem cell harvests (auto-PBSCHs) between June 2012 and May 2025, including patient characteristics, mobilization methods, protocol used, anticoagulant type, run time, total anticoagulant solution volume, and collection efficiency.
Results: Auto-PBSCH was performed using the mononuclear cell collection (MNC) protocol in 28 procedures and the continuous MNC protocol in 20 procedures. ACD-A was used in 35 procedures and HSC in 13. The run time was significantly shorter (204 [range, 117?302] vs. 157?min [range, 103?227], p?=?.02) in the HSC group and also confirmed in multivariable regression analysis (coefficient, ?55.6; 95% confidence interval, ?106.2 to ?5.04; p?=?.03). In a subgroup analysis of cMNC procedures, CD34+ collection efficiency showed a strong negative correlation with the proportion of run time devoted to establishing the initial interface (r?=??.73, p?=?.0003).
Conclusion: Delays in establishing the initial interface can reduce the duration of the effective MNC collection phase and may negatively affect collection efficiency. Careful attention to the initial interface phase is therefore warranted when using HSC. en-copyright= kn-copyright= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimonoJoji en-aut-sei=Shimono en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurakamiHiroyuki en-aut-sei=Murakami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Okayama University Hospital kn-affil= en-keyword=acid citrate dextrose solution kn-keyword=acid citrate dextrose solution en-keyword=autologous kn-keyword=autologous en-keyword=continuous mononuclear cell collection kn-keyword=continuous mononuclear cell collection en-keyword=highly concentrated sodium kn-keyword=highly concentrated sodium en-keyword=pediatric kn-keyword=pediatric en-keyword=peripheral blood stem cells kn-keyword=peripheral blood stem cells END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=12 article-no= start-page=2021 end-page=2029 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Improved Synthesis of a Key Intermediate for Glycosylation of Biopterin and Its Application for the First Synthesis of Microcystbiopterin B en-subtitle= kn-subtitle= en-abstract= kn-abstract=A key intermediate for the selective 2′-O-glycosylation of biopterin, N2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (12), was efficiently synthesized via a novel route starting from d-glucose, leading to an improved overall yield. This new pathway involves the preparation of a 5-deoxy-l-arabinose phenylhydrazone derivative (9) as a crucial intermediate in the construction of the pteridine ring. Utilizing compound 12, the first synthesis of microcystbiopterin B (4) was accomplished by glycosylation of 12 with 4,6-di-O-acetyl-2-O-(4-methoxybenzyl)-3-O-methyl-α-d-glucopyranosyl bromide (19) in the presence of silver triflate and tetramethylurea, followed by stepwise deprotection. en-copyright= kn-copyright= en-aut-name=HanayaTadashi en-aut-sei=Hanaya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaYuta en-aut-sei=Maeda en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwasakiKatsuya en-aut-sei=Iwasaki en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= en-keyword=microcystbiopterin B kn-keyword=microcystbiopterin B en-keyword=pteridine kn-keyword=pteridine en-keyword=pterin glycoside kn-keyword=pterin glycoside en-keyword=structural identification kn-keyword=structural identification END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A retrospective cohort study comparing periodontal regeneration using fibroblast growth factor‐2 versus autologous bone graft en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Fibroblast growth factor-2 (FGF-2) is a novel agent utilized in periodontal regeneration therapy. However, its clinical efficacy compared with autologous bone graft (ABG), a long-established treatment, remains unclear. This study aimed to compare the clinical outcomes of FGF-2 and ABG and to assess the impact of patient background factors on outcomes when using FGF-2.
Methods: We collected the subjects from January 2013 to September 2023. Clinical outcomes included the vertical bone defect improvement rate (VBDIR) and the probing pocket depth improvement (PPDI). Clinical outcomes between the two groups were compared using analysis of covariance (ANCOVA), adjusting for age, sex, smoking history, and hypertension. Additionally, a multilevel linear analysis was performed to assess factors influencing outcomes in FGF-2.
Results: A total of 180 sites from 141 patients (FGF-2: 150 sites; ABG: 30 sites) were evaluated. Both VBDIR and PPDI significantly improved postoperatively in both groups. There were no significant differences in clinical outcomes between FGF-2 and ABG. In FGF-2, smoking history was positively associated, while the preoperative bone defect angle (BDA) was negatively associated with clinical outcomes.
Conclusions: FGF-2 might exhibit clinical outcomes comparable to those of ABG, suggesting it is a clinically viable alternative for vertical bone defects. When using FGF-2, patient-specific factors such as smoking history and preoperative BDA should be considered carefully.
The name in the trial registry: A survey of clinical practice and evaluation of treatment outcomes of periodontal regenerative therapy using REGROTH at Okayama University Hospital en-copyright= kn-copyright= en-aut-name=MatsumotoToshiki en-aut-sei=Matsumoto en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraShin en-aut-sei=Nakamura en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Ito‐ShinodaYuki en-aut-sei=Ito‐Shinoda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoMai en-aut-sei=Sakamoto en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NonomuraYasuki en-aut-sei=Nonomura en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IdeguchiHidetaka en-aut-sei=Ideguchi en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkuboKeisuke en-aut-sei=Okubo en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Takeuchi‐HatanakaKazu en-aut-sei=Takeuchi‐Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=autologous bone graft kn-keyword=autologous bone graft en-keyword=fibroblast growth factor-2 kn-keyword=fibroblast growth factor-2 en-keyword=periodontal pocket kn-keyword=periodontal pocket en-keyword=periodontal regeneration kn-keyword=periodontal regeneration en-keyword=periodontitis kn-keyword=periodontitis en-keyword=vertical bone defect kn-keyword=vertical bone defect END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=e2025-0068 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Is Saline Sealing of Needle Tract Effective to Prevent Pneumothorax after Computed Tomography-guided Lung Biopsy? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To evaluate the efficacy of needle tract sealing using normal saline instillation for decreasing the risk of pneumothorax after computed tomography-guided lung biopsy.
Material and Methods: This retrospective, single-institution study included 391 computed tomography-guided lung biopsies performed by 12 operators between January 2022 and October 2024. After exclusion, 298 biopsies were analyzed by comparing the saline seal (n = 138) and control (n = 160) groups. A 17/18-gauge or 19/20-gauge coaxial biopsy system was used, and tract sealing was performed by instilling 1-5 mL of normal saline during the withdrawal of the introducer needle in the saline seal group; tract sealing was not performed in the control group. After 1:1 propensity score matching was performed to balance baseline characteristics, the incidences of pneumothorax and chest tube placement were compared between the two groups using Fisher's exact test.
Results: After propensity score matching, 108 pairs (mean lesion size: 17 mm) were well balanced. The incidence of pneumothorax did not differ significantly between the control and saline seal groups (50.0% vs. 60.2%, respectively; p = 0.171). Similarly, the incidence of chest tube placement was not significantly different between the two groups (7.4% vs. 13.0%, respectively; p = 0.260).
Conclusions: According to the propensity score-matched analysis, normal saline instillation for tract sealing did not significantly reduce the incidence of pneumothorax or chest tube placement. In our cohort, which had a high prevalence of small lesions, saline sealing alone may be insufficient to reduce post-biopsy pneumothorax risk. Hence, combined strategies require further investigation. en-copyright= kn-copyright= en-aut-name=OkamotoSoichiro en-aut-sei=Okamoto en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MunetomoKazuaki en-aut-sei=Munetomo en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=pneumothorax kn-keyword=pneumothorax en-keyword=lung biopsy kn-keyword=lung biopsy en-keyword=image-guided biopsy kn-keyword=image-guided biopsy en-keyword=needle tract sealing kn-keyword=needle tract sealing END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=7 article-no= start-page=102730 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of full-time equivalent allocation on the effectiveness of antimicrobial stewardship activities: A multicenter study in Okayama, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Optimized administration of antimicrobial agents is critical for mitigating the emergence of antimicrobial resistance. This study aimed to elucidate the relationship between antimicrobial stewardship (AS) activities and antimicrobial prescription trends and patterns.
Methods: This retrospective, multicenter, longitudinal study was conducted between April 2014 and March 2023 (9-year fiscal period). A structured, questionnaire survey, regarding institutional infrastructure and environmental parameters, service modalities provided by AS activities, resource allocation and systemic support, and data on the use of broad-spectrum antimicrobial agents, was distributed to co-investigators working at seven hospitals in Okayama, Japan. Full-time equivalent (FTE) allocation for each healthcare facility were calculated and subsequently compared among the hospitals. Temporal variations in the proportional distribution of broad-spectrum antimicrobial agents were statistically evaluated using joinpoint regression analysis.
Results: Two hospitals where pharmacists were exclusively dedicated to AS activities and met the recommended FTE allocation showed a statistically significant reduction in the proportion of broad-spectrum antibiotic administration, with average annual percentage changes of ?8.0 % (95 % confidence interval [CI]: ?10.5 to ?5.8) and ?3.1 % (95 % CI: ?5.5 to ?0.7), respectively. In contrast, two other hospitals with full-time AS members but insufficient FTE allocation exhibited inconsistent and statistically nonuniform trends. The remaining three healthcare institutions with poorly resourced AS teams demonstrated no statistically significant trends in their broad-spectrum antimicrobial prescriptions.
Conclusion: Our findings uncovered that hospitals with adequate FTE staffing metrics for AS activities exhibited statistically significant downward trends in the consumption of broad-spectrum antimicrobial agents. en-copyright= kn-copyright= en-aut-name=KajitaShiho en-aut-sei=Kajita en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkitaAtsushi en-aut-sei=Okita en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HarukiYuto en-aut-sei=Haruki en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaHaruto en-aut-sei=Yamada en-aut-mei=Haruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueYasurou en-aut-sei=Inoue en-aut-mei=Yasurou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashionnaTsukasa en-aut-sei=Higashionna en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatouKana en-aut-sei=Satou en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TorigoeFumihiro en-aut-sei=Torigoe en-aut-mei=Fumihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwamotoShinobu en-aut-sei=Iwamoto en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaMika en-aut-sei=Yoshida en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamaneYumiko en-aut-sei=Yamane en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KenmotsuHiroki en-aut-sei=Kenmotsu en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SugimuraSatoru en-aut-sei=Sugimura en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraYutaka en-aut-sei=Fujiwara en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IkedaFusao en-aut-sei=Ikeda en-aut-mei=Fusao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YoshidaChikamasa en-aut-sei=Yoshida en-aut-mei=Chikamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AndouShinichirou en-aut-sei=Andou en-aut-mei=Shinichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuwakiToshimitsu en-aut-sei=Suwaki en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Antimicrobial Stewardship Team, Okayama City Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Setouchi City Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Tsuyama Chuo Hospital kn-affil= affil-num=5 en-affil=Antimicrobial Stewardship Team, Okayama City Hospital kn-affil= affil-num=6 en-affil=Antimicrobial Stewardship Team, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Pharmacy, Kurashiki Central Hospital kn-affil= affil-num=9 en-affil=Division of Pharmacy, Kurashiki Central Hospital kn-affil= affil-num=10 en-affil=Division of Pharmacy, Okayama Kyoritsu Hospital kn-affil= affil-num=11 en-affil=Infection Control Team, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=12 en-affil=Infection Control Team, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=13 en-affil=Division of Pharmacy, Okayama Saiseikai Hospital kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Okayama Kyoritsu Hospital kn-affil= affil-num=15 en-affil=Infection Control Team, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=16 en-affil=Department of Hepatology, Okayama Saiseikai Hospital kn-affil= affil-num=17 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Infection Control Team, Okayama City Hospital kn-affil= affil-num=19 en-affil=Infection Control Team, Okayama City Hospital kn-affil= affil-num=20 en-affil=Infection Control Team, Okayama City Hospital kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Antimicrobial stewardship kn-keyword=Antimicrobial stewardship en-keyword=Full-time equivalent kn-keyword=Full-time equivalent en-keyword=Infection prevention and control kn-keyword=Infection prevention and control en-keyword=Trend analysis kn-keyword=Trend analysis END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=e101143 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic Topical Application (ETA) Therapy for Refractory Overactive Bladder: A First-in-Human Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Refractory overactive bladder (OAB) remains a clinical challenge despite established therapies, such as anticholinergics, β3-agonists, and intradetrusor botulinum toxin (BTX). Emerging evidence suggests that sensory mechanisms within the bladder, including those involving the trigone where superficial afferent networks are present, may contribute to persistent urinary urgency and frequency in some patients. Although intradetrusor BTX injection is effective in selected patients, its impact on these superficial pathways may be limited because the injected drug predominantly distributes within the detrusor. Endoscopic topical application (ETA) therapy delivers BTX directly to the trigone under air cystoscopy, potentially providing targeted modulation of sensory hyperexcitability. We report a 72-year-old woman with long-standing refractory OAB who experienced only partial improvement with repeated intradetrusor BTX injections but achieved clinically meaningful symptom relief after ETA therapy. Nocturia, urgency, urgency urinary incontinence, and voided volume were improved, with no complications other than transient postoperative urethral pain. This case suggests that ETA therapy may represent a promising sensory-focused option for refractory OAB. en-copyright= kn-copyright= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiharaMasahiro en-aut-sei=Sugihara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Surgery, Nishi Fukuyama Hospital kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bladder trigone kn-keyword=bladder trigone en-keyword=botulinum toxin kn-keyword=botulinum toxin en-keyword=endoscopic topical application kn-keyword=endoscopic topical application en-keyword=new drug delivery systems kn-keyword=new drug delivery systems en-keyword=refractory overactive bladder kn-keyword=refractory overactive bladder END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=11 article-no= start-page=1023 end-page=1032 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bioconversion and Metabolic Fate of the n-1 Polyunsaturated Fatty Acids, 6,9,12,15- Hexadecatetraenoic (C16:4 n-1) and 8,11,14,17- Octadecatetraenoic (C18:4 n-1) Acids, in HepG2 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fish oil contains not only major fatty acids with double bonds at the n-3, n-6, n-7, and n-9 positions but also those with a double bond at the n-1 position, such as 6,9,12,15-hexadecatetraenoic acid (C16:4 n-1; HDTA). However, intracellular bioconversion and metabolic fate of n-1 polyunsaturated fatty acids (PUFA) remain unclear. Therefore, in this study, we aimed to assess the intracellular bioconversion and metabolic fate of HDTA and its metabolite, 8,11,14,17- octadecatetraenoic acid (C18:4 n-1; ODTA), using HepG2 cells. Based on the results of cell viability and cytotoxicity assays for HDTA and ODTA, the concentration of each fatty acid supplemented in the experiments was set at 10 μM. HepG2 cell culture with HDTA revealed C20:4 n-1 as a new HDTA metabolite, along with previously reported ODTA. Our findings suggest that the HDTA taken up by HepG2 cells undergoes elongation to form ODTA and C20:4 n-1. Following supplementation with HDTA, ODTA, and 5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; EPA), fatty acids disappeared from the culture medium within 24 h. Notably, the total relative level of HDTA and its metabolites, including ODTA and C20:4 n-1 in HDTA- and ODTA-supplemented cells were significantly lower than the total relative level of EPA and its metabolites, including 7,10,13,16,19-docosapentaenoic acid (C22:5 n-3), C24:6 n-3, and 4,7,10,13,16,19-docosahexaenoic acid (C22:6 n-3) in the EPA-supplemented cells. Except for a portion that was intracellularly elongated, most HDTA was taken up by HepG2 cells and may undergo rapid fatty acid β-oxidation. However, RNA-sequencing and real-time polymerase chain reaction analysis revealed no significant changes in fatty acid β-oxidation?related gene expression levels in HDTA-supplemented cells. Collectively, these results provide novel insights into the intracellular bioconversion mechanisms and metabolic fate of HDTA and ODTA in HepG2 cells, suggesting that the metabolic fate of n-1 PUFA is distinct from that of common PUFA. en-copyright= kn-copyright= en-aut-name=SugimotoKoki en-aut-sei=Sugimoto en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiguchiHideto en-aut-sei=Nishiguchi en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HosomiRyota en-aut-sei=Hosomi en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanizakiToshifumi en-aut-sei=Tanizaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsushimaTadahiro en-aut-sei=Tsushima en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BabaNaomichi en-aut-sei=Baba en-aut-mei=Naomichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MisawaYoshihisa en-aut-sei=Misawa en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MurakamiYuki en-aut-sei=Murakami en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KandaSeiji en-aut-sei=Kanda en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FukunagaKenji en-aut-sei=Fukunaga en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Faculty of Food and Nutritional Sciences, Toyo University kn-affil= affil-num=2 en-affil=Faculty of Chemistry, Materials, and Bioengineering, Kansai University kn-affil= affil-num=3 en-affil=Faculty of Chemistry, Materials, and Bioengineering, Kansai University kn-affil= affil-num=4 en-affil=Bizen Chemical Co., Ltd. kn-affil= affil-num=5 en-affil=Bizen Chemical Co., Ltd. kn-affil= affil-num=6 en-affil=Bizen Chemical Co., Ltd. kn-affil= affil-num=7 en-affil=Bizen Chemical Co., Ltd. kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hygiene and Public Health, Kansai Medical University kn-affil= affil-num=11 en-affil=Department of Hygiene and Public Health, Kansai Medical University kn-affil= affil-num=12 en-affil=Faculty of Chemistry, Materials, and Bioengineering, Kansai University kn-affil= en-keyword=n-1 polyunsaturated fatty acids kn-keyword=n-1 polyunsaturated fatty acids en-keyword=hexadecatetraenoic acid kn-keyword=hexadecatetraenoic acid en-keyword=octadecatetraenoic acid kn-keyword=octadecatetraenoic acid en-keyword=HepG2 kn-keyword=HepG2 END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=12 article-no= start-page=102853 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and molecular characteristics of urinary catheter-associated Pseudomonas aeruginosa prostatic infection: A case series of four postoperative nosocomial infections en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudomonas aeruginosa is a causative pathogen of nosocomial catheter-associated urinary tract infections (CAUTI), but prostate involvement, including prostatitis and prostatic abscess, is rare. The clinical characteristics of P. aeruginosa-associated CAUTI with prostatic lesions, as well as the contribution of genetic backgrounds remain unclear. We describe four cases of urinary catheter-associated prostatic infection caused by P. aeruginosa following postoperative catheterization. All patients developed fever within 10 days after surgery, and three of the four patients developed bacteremia. Three patients were diagnosed with prostatic abscess by contrast-enhanced computed tomography or magnetic resonance imaging, while one case presented with prostatitis without abscess formation. Prostate-specific antigen levels were elevated over 20 ng/mL in all three measured cases. All patients were treated successfully with prolonged antibiotic therapy (28?39 days) without surgical drainage. Notably, all three abscess cases were successfully managed with fluoroquinolone-based combination therapy, highlighting its potential role in the management of prostatic abscesses. Three of four isolates were submitted for molecular investigations. All isolates harbored exoT and exoY, whereas exoU was absent. Biofilm-associated genes were detected in two cases, but not in the remaining case. Our findings suggested that P. aeruginosa strains carrying T3SS genes (exoT and exoY) potentially develop prostatic infections, independent of biofilm-associated genes. Host and iatrogenic factors, such as catheter manipulation, may play more critical roles in the development of prostatic pathology than strain-specific determinants. Assessment of prostate-specific antigen levels and early imaging may facilitate appropriate diagnosis and effective management when P. aeruginosa is detected as a cause of CAUTI. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SanoTakayuki en-aut-sei=Sano en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashimotoTakashige en-aut-sei=Kashimoto en-aut-mei=Takashige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University kn-affil= affil-num=3 en-affil=Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Pseudomonas aeruginosa kn-keyword=Pseudomonas aeruginosa en-keyword=Catheter-associated urinary tract infection kn-keyword=Catheter-associated urinary tract infection en-keyword=Prostatic abscess kn-keyword=Prostatic abscess en-keyword=Type III secretion system kn-keyword=Type III secretion system END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=e70066 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Procedural Transhiatal Approach for the Thoracic Para‐Aortic Lymph Node: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=The thoracic posterior para-aortic lymph node (TPAN) is classified as an extra-regional lymph node in esophageal cancer, with metastasis indicating poor prognosis. However, some cases with suspected TPAN metastasis may benefit from esophagectomy with lymph node dissection, including TPAN. This report presents the case of a 58-year-old man with upper thoracic esophageal squamous cell carcinoma and suspected simultaneous TPAN metastasis who underwent neoadjuvant chemotherapy followed by thoracoscopic subtotal esophagectomy and procedural transhiatal TPAN dissection. This transhiatal approach provided direct access to the lymph node without additional thoracic incisions, ensuring safe resection in coordination with the assistant and following anatomical landmarks systematically. Pathological examination showed a false-positive TPAN finding, though the patient later developed distant recurrence. Compared with conventional approaches, this transhiatal technique allows for procedural and reproducible lymphadenectomy while minimizing respiratory burden. This case highlights the feasibility of a transhiatal approach for TPAN dissection. en-copyright= kn-copyright= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=112aoP kn-keyword=112aoP en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=thoracic posterior para-aortic lymph node kn-keyword=thoracic posterior para-aortic lymph node END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=5 article-no= start-page=101 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prolonged exposure to axitinib alters the molecular profile of Caki?2 renal cell carcinoma cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Axitinib, an oral second?generation multitargeted tyrosine kinase inhibitor, is used as a second?line treatment for metastatic renal cell carcinoma (RCC). However, patients often develop resistance after initial responsiveness, necessitating the elucidation of the underlying resistance mechanisms. Therefore, the present study aimed to investigate the mechanisms underlying axitinib resistance using the Caki?2 human papillary RCC model cells. Cells tolerating 0.1 ?M axitinib were designated as Caki/AX cells. Cell viability was assessed using the water?soluble tetrazolium salt assay. Notably, the 50% inhibitory concentration (IC50) values of axitinib and sunitinib were significantly higher in Caki/AX cells than those in Caki?2 cells, indicating 2.83? and 1.2?fold resistance, respectively. By contrast, the IC50 values of sorafenib and erlotinib were decreased in Caki/AX cells. Moreover, Caki/AX cells showed resistance to everolimus, temsirolimus and rapamycin, and decreased sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin and SN?38 compared with Caki?2 cells. Notably, etoposide, 5?fluorouracil, cisplatin and carboplatin sensitivities were comparable in both cell types. Reverse transcription?quantitative polymerase chain reaction (PCR) analysis revealed that the mRNA levels of the ATP?binding cassette subfamily B member 1 and subfamily G member 2 were significantly higher in Caki/AX cells than those in Caki?2 cells. A PCR array related to vascular endothelial growth factor signalling showed that the mRNA levels of FIGF (also known as vascular endothelial growth factor D) and sphingosine kinase 1 were upregulated, whereas those of Rac family small GTPase 2 were downregulated in Caki/AX cells. Overall, these findings suggested that the upregulation of the ATP?binding cassette subfamily B member 1, FIGF and sphingosine kinase 1 mRNA levels, and downregulation of the Rac family small GTPase 2 mRNA levels may contribute to acquired resistance in Caki/AX cells. en-copyright= kn-copyright= en-aut-name=NakayamaYuko en-aut-sei=Nakayama en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoAya en-aut-sei=Ino en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaraKohji en-aut-sei=Takara en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University kn-affil= affil-num=2 en-affil=Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University kn-affil= affil-num=3 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University kn-affil= en-keyword=axitinib kn-keyword=axitinib en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=drug resistance kn-keyword=drug resistance en-keyword=ABC transporter kn-keyword=ABC transporter END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251117 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Daytime Bladder Control Status in Toddlerhood Is Associated With Subsequent Bedwetting in Preschool Years: A Nationwide Cohort Study of Over 30?000 Japanese Children en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Nocturnal enuresis is common in early childhood. While daytime bladder control typically precedes nighttime continence, the temporal relationship between early daytime bladder control and subsequent bedwetting remains unclear. We investigated whether daytime bladder control status at age 2.5?years?as indicated by diaper use?is associated with bedwetting at age 4.5?years in a Japanese nationwide cohort.
Methods: We analyzed data from the Japanese Longitudinal Survey of Newborns in the 21st Century (2010 cohort). Daytime bladder control was assessed at age 2.5?years through caregiver-reported diaper use, and bedwetting frequency at age 4.5?years through parental questionnaires. Modified Poisson regression estimated risk ratios (RRs), adjusting for birth-related factors, socioeconomic status, daycare attendance, and developmental milestones.
Results: Among 32?168 children, 26?651 (82.8%) still used diapers at 2.5?years. Bedwetting prevalence at 4.5?years was 42.2%: 34.5% in children who achieved daytime bladder control at 2.5?years versus 43.9% in those still using diapers. After multivariable adjustment, incomplete daytime bladder control at 2.5?years was associated with higher bedwetting risk (adjusted RR 1.25; 95% CI, 1.20?1.31). Multinomial regression revealed dose?response relationships: odds ratios 1.41 (95% CI, 1.30?1.52) for “sometimes” and 1.58 (95% CI, 1.42?1.77) for “often” bedwetting.
Conclusions: Daytime bladder control status at 2.5?years was associated with a 25% increased bedwetting risk at 4.5?years. This association likely reflects individual differences in bladder control maturation rather than causal effects. While daytime bladder control may serve as a developmental marker, its validity as an intervention target remains unestablished. en-copyright= kn-copyright= en-aut-name=MoriwakeTakatoshi en-aut-sei=Moriwake en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Urology Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan kn-affil= affil-num=10 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bedwetting kn-keyword=bedwetting en-keyword=cohort study kn-keyword=cohort study en-keyword=daytime bladder control kn-keyword=daytime bladder control en-keyword=nocturnal enuresis kn-keyword=nocturnal enuresis END start-ver=1.4 cd-journal=joma no-vol=113 cd-vols= no-issue=4 article-no= start-page=117030 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Time to positivity for differentiating blood culture contamination: A 20-hour cutoff for major contaminants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Blood culture remains the gold standard for diagnosing bacteremia; however, contamination inevitably occurs in 2-3% of cases, requiring differentiation between true bacteremia and contamination. Although time to positivity (TTP) aids in this clinical decision, with detection after 24 hours generally indicating contamination, technological advances in blood culture systems may have shortened this threshold interval.
Methods: This study retrospectively analyzed blood culture data in our hospital from April 2023 to January 2025 to determine the optimal TTP cutoff. Patients with positive blood cultures for major contaminating bacteria were included. Cases were classified as true bacteremia or contamination based on a comprehensive chart review conducted by the antimicrobial stewardship audit, and TTP was compared between the groups. Sensitivity, specificity, and Youden index at various TTP cutoffs were utilized to determine the optimal threshold using the receiver operating characteristic curve analysis.
Results: Seventy-one patients were enrolled, with 34 cases classified as true bacteremia and 37 as contamination. Identified bacteria included coagulase-negative staphylococci (70.4%), viridans group streptococci (18.3%), and others (11.3%). The median TTP was significantly shorter in the true bacteremia group compared with the contamination group (18.6 vs.25.8 hours, p < 0.001). In the contamination group, 43.2% of the cases demonstrated positive growth within 24 hours. Based on sensitivity, specificity, and Youden index, the optimal threshold was estimated to be 20 hours. A subgroup analysis of the CNS-only cohort yielded concordant results.
Conclusion: This study suggests that a 20-hour TTP threshold could help effectively differentiate true bacteremia from contamination in current clinical settings. en-copyright= kn-copyright= en-aut-name=ManabeYohei en-aut-sei=Manabe en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujitaYasushi en-aut-sei=Fujita en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KiguchiTakashi en-aut-sei=Kiguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Nursing, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Nursing, Okayama University Hospital kn-affil= affil-num=9 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= en-keyword=Bacteremia kn-keyword=Bacteremia en-keyword=Blood stream infection kn-keyword=Blood stream infection en-keyword=Contamination kn-keyword=Contamination en-keyword=Incubation time kn-keyword=Incubation time en-keyword=Time to positivity kn-keyword=Time to positivity END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=10 article-no= start-page=e71249 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recurrent Septic Shock in Immunosuppressed Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cytomegalovirus gastroenteritis presents with diarrhea and abdominal pain in immunosuppressed patients, and histopathological examination is essential by endoscopy. This case illustrates that cytomegalovirus enteritis may develop insidiously and possibly invoke shock in immunocompromised patients, warranting its inclusion in the differential diagnosis of recurrent septic shock. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaKoji en-aut-sei=Fujita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Medicine and Infectious Diseases, Tsuyama Chuo Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=bacteremia kn-keyword=bacteremia en-keyword=compromised host kn-keyword=compromised host en-keyword=cytomegalovirus kn-keyword=cytomegalovirus en-keyword=septic shock kn-keyword=septic shock END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hospital-acquired pneumonia caused by multidrug-resistant Streptococcus pneumoniae serotype 15A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Streptococcus pneumoniae remains a common cause of community-acquired pneumonia but is an infrequent pathogen in hospital-acquired pneumonia (HAP). Non-vaccine serotypes of multidrug-resistant (MDR) S. pneumoniae strains have been emerging globally, posing an increased risk of nosocomial infection.
Case A 71 year-old man developed pneumonia on postoperative day 4 following spinal fusion surgery. Despite initial treatment with ampicillin/sulbactam, his condition deteriorated, requiring ICU admission and mechanical ventilation. Microbiological testing confirmed S. pneumoniae as a causative pathogen, and ceftriaxone was empirically administered based on the local antibiogram. However, antimicrobial susceptibility testing revealed resistant profiles to penicillin (minimum inhibitory concentration [MIC], 8 ?g/mL), ceftriaxone (MIC, 16 ?g/mL), meropenem (MIC, 1 ?g/mL), macrolides, and clindamycin, while demonstrating susceptibility to levofloxacin and vancomycin. The therapeutic regimen was subsequently adjusted to levofloxacin, resulting in clinical improvement. The isolate was later identified as serotype 15A, sequence type 63 (ST63).
Conclusion This case highlights that MDR S. pneumoniae can cause early-onset HAP and may not be covered by standard empiric therapies, emphasizing the need for careful evaluation of treatment response. Continued surveillance of infections caused by vaccine-escape clones like MDR serotype 15A is essential, given their increasing clinical relevance. en-copyright= kn-copyright= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimbeMadoka en-aut-sei=Shimbe en-aut-mei=Madoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChangBin en-aut-sei=Chang en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkedaYukihiro en-aut-sei=Akeda en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=7 en-affil=Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Multidrug-resistant kn-keyword=Multidrug-resistant en-keyword=Nosocomial infection kn-keyword=Nosocomial infection en-keyword=Sequence type 63 kn-keyword=Sequence type 63 en-keyword=Serotype 15A kn-keyword=Serotype 15A en-keyword=Streptococcus pneumoniae kn-keyword=Streptococcus pneumoniae END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=6 article-no= start-page=e70230 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Corynebacterium striatum-Associated Pyogenic Osteomyelitis With Direct Extension From Postoperative Empyema en-subtitle= kn-subtitle= en-abstract= kn-abstract=Corynebacterium striatum can cause postoperative empyema. C. striatum-associated empyema may be associated with osteomyelitis. Rifampicin is a viable therapeutic option for C. striatum infection. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Corynebacterium striatum kn-keyword=Corynebacterium striatum en-keyword=empyema kn-keyword=empyema en-keyword=osteomyelitis kn-keyword=osteomyelitis en-keyword=rifampicin kn-keyword=rifampicin END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=2 article-no= start-page=100820 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feasibility and Diagnostic Utility of Mucosal T-Cell Flow Cytometry for Intestinal Graft-Versus-Host Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aims: Timely diagnosis of intestinal complications after hematopoietic stem cell transplantation (HSCT), including graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy, and cytomegalovirus infection, is essential for appropriate management. This study evaluated whether mucosal T-cell profiling from endoscopic biopsies could support the diagnosis of these post-transplant conditions.
Methods: We prospectively analyzed 58 intestinal biopsy specimens from 21 post-HSCT patients. Paired samples were obtained from the stomach and duodenum during upper endoscopy and from the ileum and large intestine during colonoscopy. Lymphocytes were isolated from each specimen and analyzed using flow cytometry. These data were integrated with those of a previously collected cohort (35 patients, 51 samples) for comparative immunophenotypic analysis across histologically defined groups.
Results: Duodenal biopsies yielded more lymphocytes than did gastric biopsies (mean ± standard deviation: 532 ± 823 vs 233 ± 392 cells; P = .070), with comparable yields between the ileum and colon. Among 41 evaluable cases, the CD56+:CD3+ ratio was significantly lower in patients with GVHD (5.5 ± 2.2%) than in those with nonspecific or no inflammation (28.4 ± 16.3%; P = .006). A cutoff value of <11% provided 85.7% sensitivity and 83.3% specificity for diagnosing GVHD (area under the curve = 0.91).
Conclusion: Mucosal T-cell profiling using endoscopic biopsies is feasible and may aid in the diagnosis of GVHD after HSCT. A decreased CD56+:CD3+ ratio is a promising marker for distinguishing GVHD from other post-transplant intestinal conditions. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiramatsuMai en-aut-sei=Hiramatsu en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirabataAraki en-aut-sei=Hirabata en-aut-mei=Araki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiTakahide en-aut-sei=Takahashi en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=cytomegalovirus infection kn-keyword=cytomegalovirus infection en-keyword=flow cytometry kn-keyword=flow cytometry en-keyword=graft-versus-host disease kn-keyword=graft-versus-host disease en-keyword=hematopoietic stem cell transplantation kn-keyword=hematopoietic stem cell transplantation en-keyword=T lymphocytes kn-keyword=T lymphocytes END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=5 article-no= start-page=733 end-page=743 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT. Seven male patients (all male; mean age: 43.3 years) received HLC-001 and three completed the trial. The survival rate at day 56 (primary endpoint) was 71.4% (5/7 patients; 95% confidence interval: 29.0%?96.3%) and was sustained at day 100, suggesting that HLC-001 was more effective than previously reported treatment. Three of the five patients with ??100 days of follow-up died. Five patients experienced at least one adverse drug reaction, none of which were serious. These findings indicate that HLC-001 was potentially effective and generally well tolerated in Japanese patients with steroid-dependent or refractory IPS after HSCT. Given there is no effective cure for steroid-dependent or refractory IPS, HLC-001 may be a promising treatment option and further clinical evaluation is warranted.
Trial registration: Japan Registry of Clinical Trials identifier: jRCT2063220014. en-copyright= kn-copyright= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakoShinichi en-aut-sei=Kako en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaidaEmiko en-aut-sei=Sakaida en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=4 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=5 en-affil=Division of Hematology, Department of Medicine, Jichi Medical University kn-affil= en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Hematopoietic stem cell transplantation kn-keyword=Hematopoietic stem cell transplantation en-keyword=Idiopathic pneumonia syndrome kn-keyword=Idiopathic pneumonia syndrome en-keyword=Overall survival kn-keyword=Overall survival en-keyword=Umbilical cord-derived mesenchymal stromal cells kn-keyword=Umbilical cord-derived mesenchymal stromal cells END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=376 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Health-Related Quality of Life and Self-Reported Oral Health Status Are Associated with Change in Self-Reported Depression Status: A Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Oral health-related quality of life (OHRQoL) may influence mental health outcomes, yet longitudinal evidence on its association with depression remains limited. This study aimed to examine whether oral health status and OHRQoL are associated with a change in self-reported depression status among adults in Japan. Methods: We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), conducted in 2022 and 2023. A total of 15,068 participants aged ?20 years without depression at baseline were included. Depression status was identified by self-reported measures between the two survey waves. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for change in self-reported depression status in relation to OHRQoL and oral health status, adjusting for sociodemographic and behavioral factors. Results: During follow-up, 218 participants (1.45%) reported a change in self-reported depression status. Poorer OHRQoL was significantly associated with a change in self-reported depression status (OR: 1.018; 95% CI: 1.001?1.036; p = 0.039). Additional risk factors included younger age (OR: 0.974; 95% CI: 0.964?0.985), participation in hobbies and cultural activities (OR: 2.224; 95% CI: 1.498?3.302), habitual use of sleeping pills or anxiolytics (current use OR: 3.512; 95% CI: 2.267?5.442), increased loneliness (OR: 1.217; 95% CI: 1.140?1.299), lower life satisfaction (OR: 0.900; 95% CI: 0.836?0.969), and poor self-rated health (OR: 2.921; 95% CI: 1.810?4.715). Conclusions: Impaired OHRQoL was associated with a change in self-reported depression status, potentially through psychosocial mechanisms. These findings suggest that oral health and OHRQoL may be relevant factors to consider in integrated oral and mental health approaches in clinical practice. en-copyright= kn-copyright= en-aut-name=TakeuchiNoriko en-aut-sei=Takeuchi en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsubeYuzuki en-aut-sei=Katsube en-aut-mei=Yuzuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TabuchiTakahiro en-aut-sei=Tabuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Dental School, Okayama University kn-affil= affil-num=5 en-affil=Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=oral health-related quality of life kn-keyword=oral health-related quality of life en-keyword=depression status kn-keyword=depression status en-keyword=cohort study kn-keyword=cohort study END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue= article-no= start-page=100857 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A multi-institutional dummy run on segmentation variability and plan quality of stereotactic body radiotherapy for oligometastatic disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and purpose: Oligometastatic disease represents limited metastatic burden, and local ablative therapies such as stereotactic body radiotherapy (SBRT) may improve survival. However, inter-institutional variability in target segmentation and treatment planning can compromise treatment quality. This study aimed to evaluate the segmentation variability and dose distribution quality of SBRT in oligometastatic settings using a multi-institutional dummy run approach.
Methods and materials: Sixty-nine institutions were provided with two anonymized cases of adrenal and spine metastases to delineate targets and organs at risk (OARs) and create intensity-modulated radiotherapy plans following a protocol. Variability was quantified using the Dice similarity coefficient (DSC), Hausdorff distance, and mean distance to agreement. Plan qualities were assessed using the Paddick conformity index, modified gradient index, and a new three-dimensional conformity?gradient index (3D-CGI). Knowledge-based planning (KBP) was applied to explore potential improvements in OAR sparing.
Results: All submitted plans met protocol dose constraints. However, substantial segmentation variability was observed, particularly for the spine case. Among 136 plans, 79% demonstrated acceptable conformity and dose gradients, with 3D-CGI < 6 correlating with favorable distributions. Mean DSC was 0.93 for the clinical target volume and 0.76 for the cauda equina, which showed the highest variability. KBP reduced OAR doses for the adrenal case but showed limited impact for the spine case.
Conclusions: Although dose constraints were achieved, segmentation variability remained substantial, particularly for the cauda equina in the spine case. These findings emphasize inter-institutional differences and the need for standardization and tools to improve SBRT consistency. en-copyright= kn-copyright= en-aut-name=HirashimaHideaki en-aut-sei=Hirashima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoYukinori en-aut-sei=Matsuo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshikuraSatoshi en-aut-sei=Ishikura en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraMitsuhiro en-aut-sei=Nakamura en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishibuchiIkuno en-aut-sei=Nishibuchi en-aut-mei=Ikuno kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaharaDaisuke en-aut-sei=Kawahara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimadaYoshihisa en-aut-sei=Shimada en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakaharaYoshiro en-aut-sei=Nakahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishioTeiji en-aut-sei=Nishio en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShikamaNaoto en-aut-sei=Shikama en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeShun-ichi en-aut-sei=Watanabe en-aut-mei=Shun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkamotoIsamu en-aut-sei=Okamoto en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MizowakiTakashi en-aut-sei=Mizowaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Radiation Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Radiation Oncology, St. Luke’s International Hospital, St. Luke’s International University kn-affil= affil-num=4 en-affil=Department of Advanced Medical Physics, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University kn-affil= affil-num=7 en-affil=Department of Surgery, Tokyo Medical University kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Kitasato University Hospital kn-affil= affil-num=9 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= affil-num=10 en-affil=Department of Radiation Oncology, Juntendo University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=13 en-affil=Department of Breast Surgery, Institute of Science Tokyo kn-affil= affil-num=14 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=15 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=Oligometastatic disease kn-keyword=Oligometastatic disease en-keyword=Dummy run kn-keyword=Dummy run en-keyword=Segmentation variability kn-keyword=Segmentation variability en-keyword=Dose distribution accuracy kn-keyword=Dose distribution accuracy END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=12 article-no= start-page=e00740-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic portrayal of emerging carbapenem-resistant El Tor variant Vibrio cholerae O1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The escalating prevalence of carbapenem-resistant (CR) enteric pathogens elicits significant challenges to public health management and effective antimicrobial therapy. While carbapenem resistance is rare in Vibrio cholerae O1 (VC), the recent emergence of CR strains reveals a concerning shift in their antimicrobial resistance (AMR) landscape. This study aims to characterize the resistance mechanisms in newly identified El Tor CRVC isolated from cholera patients in Gujarat, India during 2019. Fifty VC isolates were screened for major virulence-associated genes along with the determination of their antibiotic resistance profiles using Kirby-Bauer disk diffusion and MIC assays. Whole-genome sequencing (WGS) was employed to investigate the underlying mechanisms of CR. All the isolates exhibited hypervirulent Haitian alleles of major virulence genes and AMR profiles of typical multidrug resistance (MDR). Strikingly, 12% (6/50) of them were resistant to carbapenems and other antibiotics. Molecular analysis revealed that these CR isolates were clonally related and harbored a 142 kbp IncA/C type conjugative mega-plasmid with several AMR encoding genes, including blaNDM-1, that can be easily transferred to other bacterial species and confer donor AMR patterns. The plasmid’s competence for horizontal gene transfer presents a significant risk of dissemination to other enteric pathogens and thereby may complicate the treatment. This finding emphasizes the urgent need for enhanced genomic surveillance and robust antimicrobial stewardship programs aimed at curbing the spread of CRVC strains and mitigating their impact on cholera treatment and containment strategies. en-copyright= kn-copyright= en-aut-name=ShawSreeja en-aut-sei=Shaw en-aut-mei=Sreeja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PragasamAgila Kumari en-aut-sei=Pragasam en-aut-mei=Agila Kumari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SamantaProsenjit en-aut-sei=Samanta en-aut-mei=Prosenjit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RoyDeboleena en-aut-sei=Roy en-aut-mei=Deboleena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GhoshDebjani en-aut-sei=Ghosh en-aut-mei=Debjani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RamamurthyThandavarayan en-aut-sei=Ramamurthy en-aut-mei=Thandavarayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KariaJigna en-aut-sei=Karia en-aut-mei=Jigna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NinamaGovind en-aut-sei=Ninama en-aut-mei=Govind kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AkedaYukihiro en-aut-sei=Akeda en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KoleyHemanta en-aut-sei=Koley en-aut-mei=Hemanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MukhopadhyayAsish Kumar en-aut-sei=Mukhopadhyay en-aut-mei=Asish Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=2 en-affil=V. Ramalingaswami Bhawan, Indian Council of Medical Research kn-affil= affil-num=3 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=4 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=6 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=7 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=8 en-affil=Medical College Baroda kn-affil= affil-num=9 en-affil=Medical College Baroda kn-affil= affil-num=10 en-affil=Okayama University kn-affil= affil-num=11 en-affil=National Institute of Infectious Diseases kn-affil= affil-num=12 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=13 en-affil=ICMR-National Institute for Research in Bacterial Infections kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae en-keyword=blaNDM-1 kn-keyword=blaNDM-1 en-keyword=carbapenem resistance kn-keyword=carbapenem resistance en-keyword=horizontal gene transfer kn-keyword=horizontal gene transfer en-keyword=IncA/C plasmid kn-keyword=IncA/C plasmid END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=20 article-no= start-page=4309 end-page=4317 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251009 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characterization of Autonomous and Ca2+/Calmodulin-Dependent Activities of CaMKK Isoforms In Vitro and in Mouse Tissues en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ca2+/CaM-dependent protein kinase kinase (CaMKK) phosphorylates and activates downstream kinases, including CaMKI, CaMKIV, PKB, and AMPK, regulating various cellular functions such as neuronal morphogenesis, metabolic control, and pathophysiological pathways, such as cancer progression. CaMKKα/1 is tightly regulated by an autoinhibitory mechanism. CaMKKβ/2 activity is highly Ca2+/CaM-independent (autonomous activity) in vitro and Ca2+/CaM-dependent in cultured cells. Whether these two activity states of CaMKKβ/2 exist in vivo and the detailed regulatory mechanisms for the transition of both activity states remain unclear due to the difficulty in distinguishing the two activity states. In this study, we detected Ca2+-dependent and autonomous CaMKK activity in HeLa cells and successfully separated both activity states of CaMKKβ/2 in mouse brain and testis extracts using a recently developed CaMKK inhibitor (TIM-063)-coupled sepharose, which binds to the catalytic domain in the active state but not in the autoinhibited state. Furthermore, lambda protein phosphatase treatment converted the Ca2+/CaM-dependent form to the autonomous form of CaMKKβ/2, which was not affected by Ala mutation of Ser128, Ser132, and Ser136. The two activity forms of CaMKKβ/2 had equivalent Ca2+/CaM-binding ability. The findings demonstrate the presence of autonomous and Ca2+/CaM-dependent forms of CaMKKβ/2 independently in mouse tissues and cultured cells. The transition of these states of CaMKKβ/2 may be dynamically regulated by the phosphorylation/dephosphorylation of serine residues in the N-terminal regulatory domain. en-copyright= kn-copyright= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenYerun en-aut-sei=Chen en-aut-mei=Yerun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshikawaTeruhiko en-aut-sei=Ishikawa en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakagamiHiroyuki en-aut-sei=Sakagami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuizuFutoshi en-aut-sei=Suizu en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=5 en-affil=Department of Anatomy, Kitasato University School of Medicine kn-affil= affil-num=6 en-affil=Clinical Examination Department, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=695 cd-vols= no-issue= article-no= start-page=123031 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Flash vaporization and migration of iodine in the oceanic plate subduction zone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Crustal fluids in subduction zones, such as subsurface aquifers, submarine seeps, and gas hydrate waters, are often rich in iodine (I2) and methane (CH4). Large-scale aquifers in the Kanto subduction zone, where the Pacific Plate (PAC) and the Philippine Sea Plate (PHS) are subducting, also exhibit high concentrations of I2 and CH4. However, the origin and behavior of I2 in the subduction zone are unclear, and its coexistence with CH4 remains unresolved. To investigate this, we compiled the I2 phase diagram under high-pressure and high-temperature (P?T) conditions to predict its physicochemical properties in the subduction zone. We then applied the P?T paths of subducted PAC and PHS sediments to the I2 phase diagram. Our findings reveal that I2 can exist as a liquid in the young and hot PHS subduction zone. Transient decompressions during earthquake ruptures can cause liquid iodine to flash-vaporize and be expelled from subducted sediments. Along with I2, thermogenic CH4 and hydrogen (H2) generated in the subducted sediments are also released and transported upward, likely by slab-dehydrated fluids. Additionally, H2 may enhance microbial CH4 production through hydrogenotrophic methanogenesis. In subduction zones of young and hot oceanic plates such as the PHS, crustal fluids are enriched in I2 and coexist with CH4 owing to the simultaneous expulsion of I2, CH4, and H2 from the same subducted sediments and their migration via deep fluids. Large subsurface aquifers can act as traps and reservoirs for migrating I2 and CH4, forming large-scale I2 and CH4 deposits. en-copyright= kn-copyright= en-aut-name=SuzukiNoriyuki en-aut-sei=Suzuki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamedaJun en-aut-sei=Kameda en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AmoMiki en-aut-sei=Amo en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Earth and Planetary Sciences, Faculty of Science, Hokkaido University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Geology and Geophysics Division, Technology Department, Japan Organization for Metals and Energy Security kn-affil= en-keyword=Iodine circulation kn-keyword=Iodine circulation en-keyword=Flash vaporization kn-keyword=Flash vaporization en-keyword=Microbial methane kn-keyword=Microbial methane en-keyword=Thermogenic methane kn-keyword=Thermogenic methane en-keyword=Thermogenic hydrogen kn-keyword=Thermogenic hydrogen en-keyword=Subducted sediments kn-keyword=Subducted sediments END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=8 article-no= start-page=938 end-page=943 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical outcomes of Japanese patients treated with out-of-specification tisagenlecleucel in a phase 3b trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The final manufactured tisagenlecleucel product should meet the commercial product release specifications to ensure the quality in terms of safety, purity, identity, and potency. However, it may occasionally fail to meet these specifications due to the nature of patient-derived cells with variable properties as starting material and the complex manufacturing process. The final product that does not meet at least one of the commercial release specifications is referred to as “out-of-specification” (OOS). However, the benefit-risk profile of OOS tisagenlecleucel has not yet been fully elucidated.
Aims: To evaluate the safety and efficacy of OOS tisagenlecleucel in Japanese patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (B-ALL).
Methods: This is a single-arm, open-label, multicenter phase 3b study (NCT04094311). Patients consistent with label indication were enrolled and followed-up for 3 months.
Results: Of the 29 patients enrolled between December 2019 and May 2022 across 13 qualified sites in Japan, 28 received tisagenlecleucel, and of these, 23 had r/r DLBCL and 5 had r/r B-ALL. The primary reasons for OOS were low cell viability (15 of 24 batches) and low dose (8 of 23 batches) tisagenlecleucel in the r/r DLBCL group, and high dose (4 of 5 batches) in the r/r B-ALL group. In patients with r/r DLBCL, the grade 3 or 4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 3 and 1 patients, respectively. Response assessments were performed for 15 of 23 patients with r/r DLBCL: 6 achieved a complete response, and 1 achieved a partial response as the best response within 3 months.
Conclusions: Despite the limited patient sample size, our findings affirm that the infusion of OOS tisagenlecleucel is a viable option, with no observed increase in toxicity and outcomes comparable to those of in-specification products in clinical and real-world studies. en-copyright= kn-copyright= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoJun en-aut-sei=Kato en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotoHideki en-aut-sei=Goto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiTakeshi en-aut-sei=Kobayashi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiYoshiyuki en-aut-sei=Takahashi en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakaidaEmiko en-aut-sei=Sakaida en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiramatsuHidefumi en-aut-sei=Hiramatsu en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoMasahide en-aut-sei=Yamamoto en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AndoJun en-aut-sei=Ando en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KohKatsuyoshi en-aut-sei=Koh en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FukushimaKentaro en-aut-sei=Fukushima en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IwamotoFumiko en-aut-sei=Iwamoto en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TiwariRanjan en-aut-sei=Tiwari en-aut-mei=Ranjan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital kn-affil= affil-num=2 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital kn-affil= affil-num=4 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics, Graduate School of Medicine, Kyoto University kn-affil= affil-num=8 en-affil=Department of Hematology, Institute of Science Tokyo Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=10 en-affil=Department of Cell Therapy and Transfusion Medicine, Juntendo University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Hematology/Oncology, Saitama Children’s Medical Center kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Osaka University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Medical Affairs, Novartis Pharma K.K. kn-affil= affil-num=14 en-affil=Development Advance Quantitative Sciences, Novartis Healthcare Private Limited kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=CAR-T kn-keyword=CAR-T en-keyword=DLBCL kn-keyword=DLBCL en-keyword=Out-of-specification kn-keyword=Out-of-specification en-keyword=Safety kn-keyword=Safety en-keyword=Tisagenlecleucel kn-keyword=Tisagenlecleucel END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=12 article-no= start-page=1811 end-page=1825 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250926 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Fentanyl-Emerged Adverse Events and Pharmacokinetics in Neonates: A Physiologically Based Pharmacokinetic Modeling Approach en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Despite its common use for analgesia in neonatal intensive care units, the optimal dosing and safety profile of fentanyl, particularly regarding suspected fentanyl-emerged adverse events (FEAEs), such as hypotension, desaturation, and oliguria, are not well-defined.
Objective This study aimed to develop an optimal therapeutic monitoring and dosing strategy for fentanyl for neonates. A physiologically based pharmacokinetic (PBPK) model for predicting fentanyl pharmacokinetics across various populations, including preterm and term neonates, was developed, and the relationship between predicted fentanyl exposure and FEAE incidence in neonates was assessed.
Methods A PBPK model was developed and validated against the observed values in the literature. The model’s predictive accuracy for fentanyl pharmacokinetics and association with FEAE incidence in an external retrospective cohort of Japanese neonates was evaluated using the predicted concentrations and pharmacokinetic parameters estimated by PBPK simulation.
Results The PBPK model exhibited reasonable predictive performance for serum fentanyl concentrations in actual neonatal patients (mean error: 9.27% [standard error: 5.06%], root mean squared error: 54.7%). The incidence of any FEAE, particularly oxygen desaturation, was associated with the fentanyl concentration-to-dose ratio, but not with some exposure parameters, such as the area under the curve and maximum concentration. The recommended reduced infusion rate allowed serum fentanyl concentrations to fall within the ranges established by the reported values and our data.
Conclusions Our PBPK model and proposed dosing strategy may contribute to safer and more effective fentanyl use in neonates. en-copyright= kn-copyright= en-aut-name=MahdyWalaa Yousef Bassyouni en-aut-sei=Mahdy en-aut-mei=Walaa Yousef Bassyouni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JojiRisa en-aut-sei=Joji en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoMari en-aut-sei=Hashimoto en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakasoneRuka en-aut-sei=Nakasone en-aut-mei=Ruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiokaKazumichi en-aut-sei=Fujioka en-aut-mei=Kazumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoharaKotaro en-aut-sei=Itohara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Graduate School of Medicine, Kobe University kn-affil= affil-num=6 en-affil=Department of Pediatrics, Graduate School of Medicine, Kobe University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=9 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=10 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue= article-no= start-page=107077 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibitory effect of cyclodextran on the induction of dental caries by Streptococcus mutans en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cyclodextrans (CIs) are cycloisomaltooligosaccharides that are known to function as dextran analogues and are possible inhibitors of dental plaque formation. CIs have a structure in which 7 to 12 glucose molecules are cyclically linked by α-1,6 bonds. We examined the inhibitory effects of CIs on the induction of dental caries by Streptococcus mutans. The inhibitory effects for bacterial growth, anti-enzymatic activity, and biofilm formation were analyzed. Additionally, the inhibitory effect of CIs on the induction of dental caries was investigated using a rat caries model. The presence of CIs resulted in reduced bacterial growth and biofilm formation. Kinetic analysis of the results showed that the inhibitory effect of CIs on anti-enzymatic activity is competitive. Furthermore, the caries scores with CIs were lower than those without CIs in both diet and drinking experiments. These results suggest that CIs possess strong anticaries activity and may be useful as a dietary supplement. en-copyright= kn-copyright= en-aut-name=AsaumiHaruka en-aut-sei=Asaumi en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuuraSakuya en-aut-sei=Matsuura en-aut-mei=Sakuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotoKana en-aut-sei=Goto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuokaDaiki en-aut-sei=Matsuoka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TabataKeiko en-aut-sei=Tabata en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakaShuhei en-aut-sei=Naka en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Matsumoto-NakanoMichiyo en-aut-sei=Matsumoto-Nakano en-aut-mei=Michiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Streptococcus mutans kn-keyword=Streptococcus mutans en-keyword=glucosyltransferase kn-keyword=glucosyltransferase en-keyword=dental caries kn-keyword=dental caries en-keyword=cyclodextran kn-keyword=cyclodextran en-keyword=animal experiments kn-keyword=animal experiments END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=11 article-no= start-page=e43440 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Suppression of defect in plated film on AMed metal products by electron beam polishing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Additively manufactured (AMed) metal products with high shape accuracy can be produced by laser powder bed fusion (LPBF). However, the AMed metal products have large surface roughness due to the arrangement of bead shape. Surface irregularities such as spatter and small cavity are also generated on the surface. Furthermore, elemental composition of AMed metal products may be changed from that of original metal powder due to oxidation of surface. On the other hand, electroless plating has been applied to improvement of surface functions. However, defect is often generated in the plated film due to surface irregularities and oxidation of base material. Therefore, surface smoothing methods are required for suppression of defect in plated film.
In this study, surface smoothing and surface repairing of AMed aluminum (Al) alloy were performed by electron beam (EB) polishing with large-area EB. After the EB polishing, electroless plating was conducted on the AMed Al alloy, and suppression of defect in plated film was proposed. Experimental results show that surface smoothing, surface repairing and removal of oxidization layer of AMed Al alloy can be done simultaneously by the EB polishing. Furthermore, the plated film without defect can be successfully formed on the EB polished Al alloy. en-copyright= kn-copyright= en-aut-name=ShinonagaTogo en-aut-sei=Shinonaga en-aut-mei=Togo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsudaYuki en-aut-sei=Matsuda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaAkira en-aut-sei=Okada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Additive manufacturing kn-keyword=Additive manufacturing en-keyword=Electron beam kn-keyword=Electron beam en-keyword=Surface smoothing kn-keyword=Surface smoothing en-keyword=Surface repairing kn-keyword=Surface repairing en-keyword=Electroless plating kn-keyword=Electroless plating en-keyword=Defect kn-keyword=Defect END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=German Chamomile (Matricaria chamomilla) Induces Cytochrome P450 Expression Through Increased BMAL1 Protein Expression in Liver Nuclei en-subtitle= kn-subtitle= en-abstract= kn-abstract=German chamomile (Matricaria chamomilla) is a medicinal herb that promotes improved digestion and reduces insomnia. Although it is widely used worldwide, the mechanism of induction of drug-metabolizing enzymes is unknown. We found that German chamomile extracts induced cytochrome P450 expression at the transcriptional stage. Cyp3a11 expression is decreased at night in wild-type mice, but German chamomile extract induced nocturnal Cyp3a11 and Cyp1a2 expression. German chamomile extract increased the nuclear protein expression of the clock gene BMAL1, which drives and abolishes the rhythm of Cyp3a11 expression. By contrast, German chamomile extract did not significantly alter clock gene expression in the suprachiasmatic nucleus (SCN). Similarly, it did not affect the mRNA expression of the clock genes in the kidneys. Because it did not induce the mRNA expression of ATP-binding cassette (ABC) transporters (Abcb1a, Abcc2, Abcc4, and Abcg2) in the kidney, German chamomile extract had no effect on the transcription of pharmacokinetics-related molecules other than CYPs. German chamomile extract promoted liver-selective nuclear transfer rhythm changes in clock genes and induced the expression of CYPs. This study may help to explain the mechanism of drug interactions associated with chronic German chamomile extract consumption. en-copyright= kn-copyright= en-aut-name=IkedaMoka en-aut-sei=Ikeda en-aut-mei=Moka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsurudomeYuya en-aut-sei=Tsurudome en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EnrinMai en-aut-sei=Enrin en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WadaYukiyo en-aut-sei=Wada en-aut-mei=Yukiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoriguchiMichiko en-aut-sei=Horiguchi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UshijimaKentaro en-aut-sei=Ushijima en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University kn-affil= affil-num=2 en-affil=Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University kn-affil= affil-num=3 en-affil=Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University kn-affil= affil-num=4 en-affil=Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University kn-affil= affil-num=5 en-affil=Department of Regenerative and Therapeutic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University kn-affil= en-keyword=Circadian clock kn-keyword=Circadian clock en-keyword=German chamomile kn-keyword=German chamomile en-keyword=Xenobiotic transporter kn-keyword=Xenobiotic transporter en-keyword=Metabolic enzyme kn-keyword=Metabolic enzyme en-keyword=Clock gene kn-keyword=Clock gene END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=cr.25-00065 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Surgical Treatment of a Spontaneous Rupture of the Left Iliac Vein: What Is the Optimal and Radical Treatment? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spontaneous rupture of the iliac vein (SRIV) requires surgical hemostasis and venous return restoration. We herein report a case treated with initial thrombus removal and direct venous repair. Because of early occlusion, a 2nd surgery was performed for iliac vein reconstruction using a 14-mm ringed Gore-Tex graft (W. L. Gore & Associates, Newark, DE, USA), and a 4-mm Gore-Tex arteriovenous shunt was created between the femoral artery and the femoral vein to prevent reocclusion. The patient had an uneventful recovery without recurrence. A single-stage procedure including hemostasis, vein replacement, and arteriovenous bypass may be ideal for radical SRIV treatment. en-copyright= kn-copyright= en-aut-name=MoriokaKei en-aut-sei=Morioka en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirotaMasanori en-aut-sei=Hirota en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Surgery, Showa Medical University Fujigaoka Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Surgery, Okayama University Hospital kn-affil= en-keyword=spontaneous rupture of the iliac vein kn-keyword=spontaneous rupture of the iliac vein en-keyword=deep vein thrombosis kn-keyword=deep vein thrombosis en-keyword=arteriovenous shunt kn-keyword=arteriovenous shunt END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=1720 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n?=?1808; replication cohort: n?=?207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p?=?4.60 × 10-8); this finding has been confirmed in the replication cohort (p?=?0.0068) and meta-analysis (p?=?1.08 × 10?9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p?=?0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset. en-copyright= kn-copyright= en-aut-name=NakamuraRyoichi en-aut-sei=Nakamura en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TohnaiGenki en-aut-sei=Tohnai en-aut-mei=Genki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AtsutaNaoki en-aut-sei=Atsuta en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsudaYumi en-aut-sei=Matsuda en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorimotoSatoru en-aut-sei=Morimoto en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoDaisuke en-aut-sei=Ito en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatsunoMasahisa en-aut-sei=Katsuno en-aut-mei=Masahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IzumiYuishin en-aut-sei=Izumi en-aut-mei=Yuishin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaMitsuya en-aut-sei=Morita en-aut-mei=Mitsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwataIkuko en-aut-sei=Iwata en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YabeIchiro en-aut-sei=Yabe en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakazatoTomoko en-aut-sei=Nakazato en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HattoriNobutaka en-aut-sei=Hattori en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirayamaTakehisa en-aut-sei=Hirayama en-aut-mei=Takehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KanoOsamu en-aut-sei=Kano en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TamuraAsako en-aut-sei=Tamura en-aut-mei=Asako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SuzukiNaoki en-aut-sei=Suzuki en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AokiMasashi en-aut-sei=Aoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShibuyaKazumoto en-aut-sei=Shibuya en-aut-mei=Kazumoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KuwabaraSatoshi en-aut-sei=Kuwabara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OdaMasaya en-aut-sei=Oda en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HashimotoRina en-aut-sei=Hashimoto en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=AibaIkuko en-aut-sei=Aiba en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=IshiharaTomohiko en-aut-sei=Ishihara en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=OnoderaOsamu en-aut-sei=Onodera en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=BokudaKota en-aut-sei=Bokuda en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ShimizuToshio en-aut-sei=Shimizu en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=IkedaYoshio en-aut-sei=Ikeda en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=HasegawaKazuko en-aut-sei=Hasegawa en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TanakaFumiaki en-aut-sei=Tanaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=YokotaTakanori en-aut-sei=Yokota en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KanaiKazuaki en-aut-sei=Kanai en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NotoYu-ichi en-aut-sei=Noto en-aut-mei=Yu-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=KajiRyuji en-aut-sei=Kaji en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=WatanabeHirohisa en-aut-sei=Watanabe en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KonishiTomoko en-aut-sei=Konishi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=HasegawaMikiko en-aut-sei=Hasegawa en-aut-mei=Mikiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=FukayaHozuki en-aut-sei=Fukaya en-aut-mei=Hozuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=NiwaJun-ichi en-aut-sei=Niwa en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=DoyuManabu en-aut-sei=Doyu en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=OkadaYohei en-aut-sei=Okada en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=NakamuraShiho en-aut-sei=Nakamura en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=OzawaFumiko en-aut-sei=Ozawa en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=OkanoHideyuki en-aut-sei=Okano en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=NakatochiMasahiro en-aut-sei=Nakatochi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=SobueGen en-aut-sei=Sobue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= affil-num=1 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=2 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=3 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=4 en-affil=Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=6 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Division of Neurology, Department of Internal Medicine, Jichi Medical University kn-affil= affil-num=10 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=11 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=12 en-affil=Department of Neurology, Juntendo University School of Medicine kn-affil= affil-num=13 en-affil=Department of Neurology, Juntendo University School of Medicine kn-affil= affil-num=14 en-affil=Department of Neurology, Toho University Faculty of Medicine kn-affil= affil-num=15 en-affil=Department of Neurology, Toho University Faculty of Medicine kn-affil= affil-num=16 en-affil=Department of Neurology, Mie University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Neurology, Tohoku University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neurology, Tohoku University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=20 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=21 en-affil=Department of Neurology, Vihara Hananosato Hospital kn-affil= affil-num=22 en-affil=Department of Neurology, NHO Higashinagoya National Hospital kn-affil= affil-num=23 en-affil=Department of Neurology, NHO Higashinagoya National Hospital kn-affil= affil-num=24 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=25 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=26 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=27 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=28 en-affil=Department of Neurology, Tokyo Metropolitan Neurological Hospital kn-affil= affil-num=29 en-affil=Department of Neurology, Tokyo Metropolitan Neurological Hospital kn-affil= affil-num=30 en-affil=Department of Neurology, Gunma University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Division of Neurology, NHO Sagamihara National Hospital kn-affil= affil-num=32 en-affil=Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine kn-affil= affil-num=33 en-affil=Department of Neurology and Neurological Science, NucleoTIDE and PepTIDE Drug Discovery Center (TIDE), Institute of Science Tokyo kn-affil= affil-num=34 en-affil=Department of Neurology, Fukushima Medical University School of Medicine kn-affil= affil-num=35 en-affil=Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=36 en-affil=Department of Neurology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=37 en-affil=Department of Neurology, Fujita Health University kn-affil= affil-num=38 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=39 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=40 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= affil-num=41 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=42 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=43 en-affil=Department of Neurology, Aichi Medical University School of Medicine kn-affil= affil-num=44 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=45 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=46 en-affil=Keio University Regenerative Medicine Research Center, Kawasaki kn-affil= affil-num=47 en-affil=Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine kn-affil= affil-num=48 en-affil=Division of ALS Research, Aichi Medical University School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=12 article-no= start-page=e100045 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sequential Bilateral Central Retinal Vein Occlusion With Differential Long-Term Outcomes Following Cardiac Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bilateral central retinal vein occlusion (CRVO) is rare and is associated with systemic diseases such as hypertension, diabetes, dyslipidemia, and coagulopathy. In this study, we showed that the sequential development of bilateral CRVO in an elderly patient was related to increased venous pressure in the right heart system. A 71-year-old man developed CRVO in the right eye, and one year later, he developed CRVO in the left eye. He had undergone pacemaker implantation for sick sinus syndrome 10 years earlier and had started hemodialysis three months prior for chronic renal failure, probably caused by hypertensive nephrosclerosis. The right CRVO resulted in neovascular glaucoma and loss of light perception despite intensive treatment with panretinal laser photocoagulation, intravitreal bevacizumab injection, and additional laser therapy. In contrast, the left CRVO remained at an impending stage, was treated only with panretinal laser photocoagulation, and had a favorable outcome for 11 years until his death. In retrospect, half a year after the onset of left CRVO, the patient underwent open-heart surgery to repair aortic, mitral, and tricuspid valve regurgitation through aortic valve replacement, mitral valve annuloplasty, and tricuspid valve annuloplasty, respectively. Based on the temporal sequence of events, elevated venous pressure due to right heart dysfunction may have contributed to the poor outcome of the right CRVO, whereas improvement of venous stasis after cardiac surgery may have led to the better long-term outcome of the left CRVO. Venous stasis in the right heart system should therefore be considered an underlying factor in the development of bilateral CRVO. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasudaZenichi en-aut-sei=Masuda en-aut-mei=Zenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiyamaHiroki en-aut-sei=Sugiyama en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University Hospital kn-affil= affil-num=2 en-affil=Cardiovascular Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Cardiovascular Medicine and Center for Advanced Heart Failure, Okayama University Hospital kn-affil= en-keyword=aortic valve regurgitation kn-keyword=aortic valve regurgitation en-keyword=aortic valve replacement kn-keyword=aortic valve replacement en-keyword=bevacizumab kn-keyword=bevacizumab en-keyword=bilateral central retinal vein occlusion kn-keyword=bilateral central retinal vein occlusion en-keyword=intravitreal injection kn-keyword=intravitreal injection en-keyword=mitral valve annuloplasty kn-keyword=mitral valve annuloplasty en-keyword=mitral valve regurgitation kn-keyword=mitral valve regurgitation en-keyword=panretinal laser photocoagulation kn-keyword=panretinal laser photocoagulation en-keyword=tricuspid valve annuloplasty kn-keyword=tricuspid valve annuloplasty en-keyword=tricuspid valve regurgitation kn-keyword=tricuspid valve regurgitation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dorsolateral Cervical Cord T2 Hyperintensity in KIF1C-Related Disease (Spastic Paraplegia 58): Two Long-Duration Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pathogenic variants in KIF1C cause Spastic Paraplegia 58 (SPG58), typically presenting with cerebellar ataxia and spastic paraparesis. We report two unrelated patients with spastic paraparesis, cerebellar ataxia, and tremor. Whole-exome sequence analysis identified novel homozygous variants in the motor domain of KIF1C (NM_006612.6): c.921G>A (p.Trp307Ter) and c.607C>T (p.Arg203Trp). In addition to the canonical brain MRI showing leukoencephalopathy with posterior dominance and hyperintensity along the corticospinal tracts, both patients showed symmetric T2 hyperintensity confined to the lateral and dorsal columns of the cervical cord. Given the long disease durations (22 and 51?years), these findings may represent late-emerging or previously overlooked spinal cord involvement and broaden the neuroradiological spectrum of SPG58. en-copyright= kn-copyright= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OsakiMasao en-aut-sei=Osaki en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsakoMiho en-aut-sei=Osako en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeuchiChisen en-aut-sei=Takeuchi en-aut-mei=Chisen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KurokawaRyo en-aut-sei=Kurokawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriHarushi en-aut-sei=Mori en-aut-mei=Harushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakahashiYuji en-aut-sei=Takahashi en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=GotoJun en-aut-sei=Goto en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled kn-affil= affil-num=5 en-affil=Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Radiology, School of Medicine, Jichi Medical University kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=cerebellar ataxia kn-keyword=cerebellar ataxia en-keyword=hereditary spastic paraplegia kn-keyword=hereditary spastic paraplegia en-keyword=KIF1C kn-keyword=KIF1C en-keyword=leukoencephalopathy kn-keyword=leukoencephalopathy END start-ver=1.4 cd-journal=joma no-vol=468 cd-vols= no-issue= article-no= start-page=109497 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surface exposure ages of middle?late Pleistocene marine and fluvial terraces along the northern and southern Sanriku coasts, Northeast Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=To estimate long-term rates of coastal uplift along the northern Pacific coast of Northeast Japan, we determined the surface exposure ages of marine and fluvial terraces based on terrestrial in situ cosmogenic radionuclide dating of exposed bedrock surfaces. Based on reinterpretation of marine and fluvial terraces, we collected samples from the northern and southern Sanriku coast. The surface exposure ages from 10Be concentrations in quartz calculated from the measured 10Be/9Be ratios commonly suggest MIS 5 and MIS 7 for the marine and fluvial terraces and averaged coastal uplift rates of ca. 0.25?±?0.15 and 0.4?mm/yr along the northern and southern Sanriku coast at intermediate timescales. The results may demonstrate different styles of crustal strain accommodation in the northern Northeast Japan arc above the subducting Pacific plate. en-copyright= kn-copyright= en-aut-name=WakasaSachi en-aut-sei=Wakasa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiyamaTatsuya en-aut-sei=Ishiyama en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirouchiDaisuke en-aut-sei=Hirouchi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MattaNobuhisa en-aut-sei=Matta en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujitaNatsuko en-aut-sei=Fujita en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EchigoTomoo en-aut-sei=Echigo en-aut-mei=Tomoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Regional Innovation, Hirosaki University kn-affil= affil-num=2 en-affil=Earthquake Research Institute, University of Tokyo kn-affil= affil-num=3 en-affil=Faculty of Education, Shinshu University kn-affil= affil-num=4 en-affil=Faculty of Education, Okayama University kn-affil= affil-num=5 en-affil=Tono Geoscience center, Japan Atomic Energy Agency kn-affil= affil-num=6 en-affil=Kankyo Chisitsu, Co. kn-affil= en-keyword=Marine terrace kn-keyword=Marine terrace en-keyword=Exposure age kn-keyword=Exposure age en-keyword=10Be kn-keyword=10Be en-keyword=Coastal uplift kn-keyword=Coastal uplift END start-ver=1.4 cd-journal=joma no-vol=198 cd-vols= no-issue=1 article-no= start-page=kiaf196 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of polar localization of the silicon transporter OsLsi1 in metalloid uptake by rice roots en-subtitle= kn-subtitle= en-abstract= kn-abstract=Low silicon (Si) rice 1 (OsLsi1) is a key transporter mediating Si uptake in rice (Oryza sativa). It is polarly localized at the distal side of the root exodermis and endodermis. Although OsLsi1 is also permeable to other metalloids, such as boron (B), germanium (Ge), arsenic (As), antimony (Sb), and selenium (Se), the role of its polar localization in the uptake of these metalloids remains unclear. In this study, we investigated the role of OsLsi1 polar localization in metalloid uptake by examining transgenic rice plants expressing polarly or nonpolarly localized OsLsi1 variants. Loss of OsLsi1 polar localization resulted in decreased accumulation of Ge, B, and As in shoots but increased Sb accumulation, while Se accumulation remained unaffected under normal conditions. Experiments with varying B concentrations revealed that B uptake is significantly lower at low B concentrations (0.3 to 3?μm) but higher at high B concentrations (300?μm) in plants expressing nonpolarly localized OsLsi1, despite the similar B permeability of both OsLsi1 variants in Xenopus oocytes and their comparable protein abundance in roots. Additionally, the loss of OsLsi1 polarity did not affect the abundance, localization, or high B-induced degradation of the borate transporter 1 (OsBOR1), an efflux transporter that cooperates with OsLsi1 for B uptake. Taken together, our findings demonstrate that the polar localization of OsLsi1 plays a critical role in regulating metalloid uptake, depending on the presence or absence of efflux transporters cooperating with OsLsi1. en-copyright= kn-copyright= en-aut-name=KonishiNoriyuki en-aut-sei=Konishi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Mitani-UenoNamiki en-aut-sei=Mitani-Ueno en-aut-mei=Namiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=4 article-no= start-page=e70082 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Retinopathy?Sensory Neuropathy Syndrome With a Novel Compound Heterozygous FLVCR1 Variant en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aims: Retinopathy?sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic variants in FLVCR1. Here, we report a case of a Japanese patient with RETSNS.
Methods: Clinical, neuroradiological, and electrophysiological findings were documented. Whole-genome sequencing was performed. Subcloning was carried out to confirm compound heterozygosity. A functional assay was performed to assess the pathogenicity of the variants.
Results: The patient showed retinitis pigmentosa and sensory ataxia. Over the course of the disease, autonomic dysfunction has become increasingly evident. Despite consanguinity in the family, whole-genome sequencing identified two heterozygous variants in FLVCR1 (c.369T>G, p.Phe123Leu and c.733A>G, p.Asn245Asp). Cloning of the PCR product followed by Sanger sequencing indicated compound heterozygosity of the variants. Immunocytochemistry of HEK293FT cells transfected with plasmids containing wild-type or variant FLVCR1 cDNA demonstrated altered subcellular localization of the variant FLVCR1 proteins, characterized by reduced membrane localization.
Interpretation: We report a novel variant in FLVCR1 causing RETSNS. The functional assay supports the pathogenicity of the variants. en-copyright= kn-copyright= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoTomohito en-aut-sei=Kawano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TairaYuki en-aut-sei=Taira en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuoAyaka en-aut-sei=Matsuo en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsakadaYosuke en-aut-sei=Osakada en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama City General Medical Center kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=FLCVR1 kn-keyword=FLCVR1 en-keyword=functional analysis kn-keyword=functional analysis en-keyword=posterior column ataxia with retinitis pigmentosa kn-keyword=posterior column ataxia with retinitis pigmentosa en-keyword=subcellular localization kn-keyword=subcellular localization END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=4 article-no= start-page=244 end-page=249 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of New Repeat Expansion Diseases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Through a genetic study of benign adult familial myoclonus epilepsy (BAFME) type 1, TTTCA and TTTTA repeat expansions have been identified in intron 4 of SAMD12. Lengths of expanded repeats inversely correlated with age at onset of epilepsy. Gain-of-toxic function mechanisms are suggested by the presence of UUUCA-repeat-containing RNA foci. From families with BAFME who did not have repeat expansions in SAMD12, we identified expanded TTTCA and TTTTA repeats in TNRC6A and RAPGEF2. These findings indicated a strong correlation between the repeat motif and the phenotype, leading to the identification of other types of BAFME. We then conducted genetic analysis of neuronal intranuclear inclusion disease (NIID), oculopharyngeal myopathy with leukoencephalopathy (OPML), and oculopharyngodistal myopathy (OPDM). From the observation that NIID, OPML, and OPDM, in addition to fragile X-associated tremor/ataxia syndrome, have shared clinical features, a direct search for CGG repeat expansions successfully led to the identification of the causative genes. Here, I review recent studies on repeat expansions. en-copyright= kn-copyright= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama UniversityGraduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=463 end-page=468 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MRI Images of a Case of Adenocarcinoma, Human Papillomavirus-Independent, Mesonephric Type, of the Uterine Cervix en-subtitle= kn-subtitle= en-abstract= kn-abstract=We present a case of a woman in her 70s who was diagnosed with mesonephric adenocarcinoma of the uterine cervix, following biopsy and surgery. Preoperative MRI revealed a 7-cm, well-defined circumferential cervical mass with left lateral wall predominance, bulging into the uterine cavity and vagina. The lesion showed intermediate signal intensity on T2-weighted images, diffusion restriction, and early contrast enhancement weaker than that of the myometrium, followed by washout on contrast-enhanced imaging. The circumferential growth pattern with the lateral wall predominance and its imaging characteristics may suggest this rare entity be routinely included in the differential diagnosis of cervical cancers. en-copyright= kn-copyright= en-aut-name=AsanoYudai en-aut-sei=Asano en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiharaChika en-aut-sei=Nishihara en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitayamaTakahiro en-aut-sei=Kitayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkawaNanako en-aut-sei=Okawa en-aut-mei=Nanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakimotoSatoko en-aut-sei=Makimoto en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KojimaKatsuhide en-aut-sei=Kojima en-aut-mei=Katsuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=mesonephric adenocarcinoma kn-keyword=mesonephric adenocarcinoma en-keyword=cervical cancer kn-keyword=cervical cancer en-keyword=MRI imaging characteristics kn-keyword=MRI imaging characteristics en-keyword=HPV-independent adenocarcinoma kn-keyword=HPV-independent adenocarcinoma END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=457 end-page=461 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exacerbation of Proteinuria in a Patient with Beh?et’s Disease and IgA Nephropathy Following Colchicine Discontinuation en-subtitle= kn-subtitle= en-abstract= kn-abstract=This case involves a 23-year-old male who was diagnosed with Beh?et’s disease 5 years ago and managed with colchicine. Two months ago, he underwent renal biopsy due to abnormal urinalysis and kidney dysfunction, leading to a diagnosis of IgA nephropathy. He subsequently underwent tonsillectomy followed by glucocorticoid pulse therapy. However, after the tonsillectomy, discontinuing colchicine led to increased proteinuria, despite the glucocorticoid pulse therapy. Upon reintroducing colchicine, urinary protein excretion decreased, achieving incomplete remission. These findings suggest that colchicine may be effective in decreasing proteinuria in patients with Beh?et’s disease complicated by IgA nephropathy. en-copyright= kn-copyright= en-aut-name=AsakawaTomohiko en-aut-sei=Asakawa en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakurabuYoshimasa en-aut-sei=Sakurabu en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaKatsuyoshi en-aut-sei=Katayama en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Matsuoka-UchiyamaNatsumi en-aut-sei=Matsuoka-Uchiyama en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UmebayashiRyoko en-aut-sei=Umebayashi en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakemotoRika en-aut-sei=Takemoto en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Beh?et’s disease kn-keyword=Beh?et’s disease en-keyword=IgA nephropathy kn-keyword=IgA nephropathy en-keyword=colchicine kn-keyword=colchicine END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=413 end-page=419 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=COVID-19 and the Risks of Migraine and Headache: A Mendelian Randomization Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Several observational studies suggested that migraine headache attacks were associated with coronavirus disease 2019 (COVID-19). We investigated genetic causal links between COVID-19 phenotypes and the development of headache and migraine, including migraine with aura (MA) and migraine without aura (MO). We conducted a two-sample Mendelian randomization (MR) analysis to estimate the genetic association in European populations. The inverse-variance weighted (IVW) method was used as the main approach in the MR analyses, together with weighted median and MR-Egger methods. We also performed a series of sensitivity tests to assess the robustness of the MR results. The MR results demonstrated that COVID-19 severity, hospitalization, and susceptibility had no causal effect on the risks of headache, migraine, MA, or MO. No horizontal pleiotropy was detected, and the results were robust as supported by the sensitivity analysis findings. Our analyses identified no casual effect of COVID-19 severity, hospitalization, or susceptibility on the risks of headache or migraine in European populations. en-copyright= kn-copyright= en-aut-name=JiangZhiyun en-aut-sei=Jiang en-aut-mei=Zhiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=XiYing en-aut-sei=Xi en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University kn-affil= en-keyword=headache kn-keyword=headache en-keyword=migraine kn-keyword=migraine en-keyword=Mendelian randomization kn-keyword=Mendelian randomization en-keyword=COVID-19 kn-keyword=COVID-19 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=405 end-page=412 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration in Patients Aged 85 or Older en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the treatment outcomes of patients aged ?85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ? 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes. en-copyright= kn-copyright= en-aut-name=OuchiChihiro en-aut-sei=Ouchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Morizane HosokawaMio en-aut-sei=Morizane Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anti-vascular endothelial growth factor therapy kn-keyword=anti-vascular endothelial growth factor therapy en-keyword=neovascular age-related macular degeneration kn-keyword=neovascular age-related macular degeneration en-keyword=age kn-keyword=age en-keyword=treat-and-extend kn-keyword=treat-and-extend en-keyword=pro re nata kn-keyword=pro re nata END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=11 article-no= start-page=1178 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sensory Modality-Dependent Interplay Between Updating and Inhibition Under Increased Working Memory Load: An ERP Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Working memory (WM) performance relies on the coordination of updating and inhibition functions within the central executive system. However, their interaction under varying cognitive loads, particularly across sensory modalities, remains unclear. Methods: This study examined how sensory modality modulates flanker interference under increasing WM loads. Twenty-two participants performed a visual n-back task at three load levels (1-, 2-, and 3-back) while ignoring visual (within-modality) or auditory (cross-modality) flankers. Results: Behaviorally, increased WM load (2- and 3-back) led to reduced accuracy (AC) and prolonged reaction times (RTs) in both conditions. In addition, flanker interference was observed under the 2-back condition in both the visual within-modality (VM) and audiovisual cross-modality (AVM) tasks. However, performance impairment emerged at a lower load (2-back) in the VM condition, whereas in the AVM condition, it only emerged at the highest load (3-back). Significant performance impairment in the AVM condition occurred at higher WM loads, suggesting that greater WM load is required to trigger interference. Event-related potential (ERP) results showed that N200 amplitudes increased significantly for incongruent flankers under the highest WM load (3-back) in the visual within-modality condition, reflecting greater inhibitory demands. In the cross-modality condition, enhanced N200 was not observed across all loads and even reversed at low load (1-back). Moreover, the results also showed that P300 amplitude increased with load in the within-modality condition but decreased in the cross-modality condition. Conclusions: These results demonstrated that the interaction between updating and inhibition is shaped by both WM load and sensory modality, further supporting a sensory modality-specific resource allocation mechanism. The cross-modality configurations may enable more efficient distribution of cognitive resources under high load, reducing interference between concurrent executive demands. en-copyright= kn-copyright= en-aut-name=LuoYuxi en-aut-sei=Luo en-aut-mei=Yuxi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GuoAo en-aut-sei=Guo en-aut-mei=Ao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WuJinglong en-aut-sei=Wu en-aut-mei=Jinglong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YangJiajia en-aut-sei=Yang en-aut-mei=Jiajia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Psychology, Institute of Education, China West Normal University kn-affil= affil-num=3 en-affil=Faculty of Biomedical Engineering, Shenzhen University of Advanced Technology kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=workingmemory load kn-keyword=workingmemory load en-keyword=attentional resource allocation kn-keyword=attentional resource allocation en-keyword=modality-specific interference kn-keyword=modality-specific interference en-keyword=inhibitory control kn-keyword=inhibitory control en-keyword=executive function kn-keyword=executive function en-keyword=sensory modality kn-keyword=sensory modality END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=32 article-no= start-page=105347 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Guide Tip Damage Due to Rotablation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The rotational atherectomy system can effectively debulk calcified coronary lesions. However, rare complications specific to that system have been reported.
Case Summary: A 77-year-old man with a heavily calcified lesion in the right coronary artery (RCA) ostium underwent percutaneous coronary intervention in an 8-F system. During the procedure, rotablation with a 2.25-mm burr was required. After the percutaneous coronary intervention, partial loss of the tip of the guide was observed. He had no clinical sequelae despite the presumed retained catheter material in his body.
Discussion: Although insufficient guide coaxiality has been suggested as the primary cause of guide tip fracture during RCA ostial ablation, other factors may have contributed: the application of force to the tip and a small difference in size between the guide and the burr.
Take-Home Message: When ablating RCA ostial lesions, positioning the burr platform outside the guide may help prevent similar complications in future cases. en-copyright= kn-copyright= en-aut-name=TayaSatoshi en-aut-sei=Taya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaMasatoki en-aut-sei=Yoshida en-aut-mei=Masatoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TodaHironobu en-aut-sei=Toda en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=complication kn-keyword=complication en-keyword=coronary angiography kn-keyword=coronary angiography en-keyword=imaging kn-keyword=imaging END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=2 article-no= start-page=101482 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amelioration of Cd-induced bone deterioration by orally administered calcium phosphate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cadmium (Cd) is a heavy metal that accumulates in the body, primarily through daily grain intake, and has a high affinity for bone, leading to skeletal diseases such as osteomalacia and fractures. Hydroxyapatite (HAp), a major bone mineral component, is highly pH-sensitive and is known to incorporate Cd, as observed in studies of Itai-itai disease. Based on these findings, we hypothesized that HAp could serve as an effective oral detoxification material for heavy metals. This study investigated the efficacy of orally administered HAp in inhibiting Cd-induced changes in bone physical and chemical properties, comparing its effects to those of activated charcoal (AC), a common detoxifying agent. Six-week-old male ICR mice were exposed to cadmium via drinking water containing CdCl2 and subsequently given diets containing either HAp or AC for four weeks. Three-point bending tests, micro-CT analysis, and histological observations of the femurs demonstrated that mice receiving HAp exhibited improved mechanical strength and enhanced bone quality protection compared to the control and other Cd-treated groups. Activated charcoal also contributed to bone quality improvement at low concentrations, but its effect diminished at high concentrations. These results suggest that the oral administration of HAp may be a promising therapeutic strategy for suppressing cadmium-induced osteomalacia. en-copyright= kn-copyright= en-aut-name=SungPing-chin en-aut-sei=Sung en-aut-mei=Ping-chin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BikharudinAhmad en-aut-sei=Bikharudin en-aut-mei=Ahmad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MusaRanda en-aut-sei=Musa en-aut-mei=Randa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UchidaKenta en-aut-sei=Uchida en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtakaAkihisa en-aut-sei=Otaka en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsusakaTadaaki en-aut-sei=Matsusaka en-aut-mei=Tadaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsugakiAira en-aut-sei=Matsugaki en-aut-mei=Aira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoTakayoshi en-aut-sei=Nakano en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University kn-affil= affil-num=8 en-affil=Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University kn-affil= affil-num=9 en-affil=Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University kn-affil= affil-num=10 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cadmium kn-keyword=Cadmium en-keyword=Bone deterioration kn-keyword=Bone deterioration en-keyword=Calcium phosphate kn-keyword=Calcium phosphate en-keyword=Bone quality kn-keyword=Bone quality END start-ver=1.4 cd-journal=joma no-vol=163 cd-vols= no-issue=22 article-no= start-page=224312 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fourier-transform infrared spectroscopy of hydrogen fluoride dimers in solid parahydrogen en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigate the Fourier-transform infrared spectra of hydrogen fluoride dimers in solid parahydrogen, the detailed analysis of which has remained unexplored. We propose a plausible analysis based on concentration dependence, light polarization, annealing, and time evolution. The absorption lines exhibited multiple peaks, with intensity ratios significantly altered by annealing and by time evolution at a constant temperature. The spectral patterns and isotopic effects suggest that the dimers do not rotate freely in solid parahydrogen, while multiple peaks arise from different stable structures, including single and double substitution sites. Unlike in the gas phase and helium droplets, no tunneling splitting was observed. The broad ν1 band suggests that some dimer structures may exhibit axial rotation. Spectral changes due to annealing likely result from site conversion, while observed IR-induced changes indicate preferential dissociation of dimers in double substitution sites. These findings still remain tentative, necessitating further experimental and theoretical studies. en-copyright= kn-copyright= en-aut-name=MiyamotoYuki en-aut-sei=Miyamoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OoeHiroki en-aut-sei=Ooe en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KumaSusumu en-aut-sei=Kuma en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Physics, Rikkyo University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=9 article-no= start-page=1068 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Evaluation of Oxidative Stress Markers in Patients with Long COVID During the Omicron Phase in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=To characterize changes in markers of oxidative stress for the clinical evaluation of patients with long COVID, we assessed oxidative stress and antioxidant activity based on serum samples from patients who visited our clinic between May and November 2024. Seventy-seven patients with long COVID (41 [53%] females and 36 [47%] males; median age, 44 years) were included. Median [interquartile range] serum levels of diacron-reactive oxygen metabolites (d-ROM; CARR Unit), biological antioxidant potential (BAP; μmol/L), and oxidative stress index (OSI) were 533.8 [454.9?627.6], 2385.8 [2169.2?2558.1] and 2.0 [1.7?2.5], respectively. Levels of d-ROMs (579.8 vs. 462.2) and OSI (2.3 vs. 1.8), but not BAP (2403.4 vs. 2352.6), were significantly higher in females than in males. OSI levels positively correlated with age and body mass index, whereas BAP levels negatively correlated with these parameters. d-ROM and OSI levels were significantly associated with inflammatory markers, including C-reactive protein (CRP) and fibrinogen, whereas BAP levels were inversely correlated with CRP and ferritin levels. Notably, serum free thyroxine levels were negatively correlated with d-ROMs and OSI, whereas cortisol levels were positively correlated with d-ROMs. Among long COVID symptoms, patients reporting brain fog exhibited significantly higher OSI levels (2.2 vs. 1.8), particularly among females (d-ROMs: 625.6 vs. 513.0; OSI: 2.4 vs. 2.0). The optimal OSI cut-off values were determined to be 1.32 for distinguishing long COVID from healthy controls and 1.92 for identifying brain fog among patients with long COVID. These findings suggest that oxidative stress markers may serve as indicators for the presence or prediction of psycho-neurological symptoms associated with long COVID in a gender-dependent manner. en-copyright= kn-copyright= en-aut-name=MeseOsamu en-aut-sei=Mese en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakuradaYasue en-aut-sei=Sakurada en-aut-mei=Yasue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SoejimaYoshiaki en-aut-sei=Soejima en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaSatoru en-aut-sei=Morita en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HondaHiroyuki en-aut-sei=Honda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EguchiAkiko en-aut-sei=Eguchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukudaSanae en-aut-sei=Fukuda en-aut-mei=Sanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NojimaJunzo en-aut-sei=Nojima en-aut-mei=Junzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Biobank Center, Mie University Hospital kn-affil= affil-num=10 en-affil=Department of Health Welfare Sciences, Kansai University of Welfare Sciences kn-affil= affil-num=11 en-affil=Department of Laboratory Medicine, Yamaguchi University kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biological antioxidant potential (BAP) kn-keyword=biological antioxidant potential (BAP) en-keyword=Coronavirus disease 2019 (COVID-19) kn-keyword=Coronavirus disease 2019 (COVID-19) en-keyword=diacron-reactive oxygen metabolites (d-ROM) kn-keyword=diacron-reactive oxygen metabolites (d-ROM) en-keyword=Long COVID kn-keyword=Long COVID en-keyword=oxidative stress index (OSI) kn-keyword=oxidative stress index (OSI) END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=4 article-no= start-page=104195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors affecting the development of hypokalemia during apheresis in healthy donors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite being generally safe, apheresis for peripheral blood stem cell collection potentially disrupts electrolyte balance owing to the use of citric acid as an anticoagulant. As prior research has primarily studied hypocalcemia, information on the kinetics of potassium levels during apheresis in healthy donors is scarce. We investigated the fluctuation in potassium levels during apheresis and the risk factors for hypokalemia. This subanalysis used data from an open-label, randomized controlled trial of “oral calcium supplementation versus placebo in mitigating citrate toxicity” conducted between January 2021 and July 2022, at Okayama University Hospital. Potassium levels were significantly reduced after 5-day granulocyte colony-stimulating factor (G-CSF) administration (p??15?% reduction in potassium levels from baseline was associated with age and the acid citrate dextrose solution A (ACD-A) volume in univariate analysis. In the multivariable analysis, both factors were associated (hazard ratio [HR], 11.60; 95?% confidence interval [CI], 1.60?83.70; p?=?0.02 and HR, 17.50; 95?% CI, 1.07?136.00; p?=?0.04). In conclusion, G-CSF administration and apheresis ultimately induced hypokalemia in two-thirds of the donors. Older age and higher ACD-A volume may affect potassium levels during apheresis in healthy donors. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukumiTakuya en-aut-sei=Fukumi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=Allogeneic kn-keyword=Allogeneic en-keyword=Peripheral blood stem cells kn-keyword=Peripheral blood stem cells en-keyword=Hypokalemia kn-keyword=Hypokalemia en-keyword=Acid citrate dextrose solution A kn-keyword=Acid citrate dextrose solution A en-keyword=Healthy donors kn-keyword=Healthy donors END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=14 article-no= start-page=4918 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Symptomatic Trends and Time to Recovery for Long COVID Patients Infected During the Omicron Phase en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Since the pathophysiology of long COVID is not yet fully understood, there are no specific methods for its treatment; however, its individual symptoms can currently be treated. Long COVID is characterized by symptoms that persist at least 2 to 3 months after contracting COVID-19, although it is difficult to predict how long such symptoms may persist. Methods: In the present study, 774 patients who first visited our outpatient clinic during the Omicron period from February 2022 to October 2024 were divided into two groups: the early recovery (ER) group (370 cases; 47.8%), who recovered in less than 180 days (median 33 days), and the persistent-symptom (PS) group (404 cases; 52.2%), who had symptoms that persisted for more than 180 days (median 437 days). The differences in clinical characteristics between these two groups were evaluated. Results: Although the median age of the two groups did not significantly differ (40 and 42 in ER and PS groups, respectively), the ratio of female patients was significantly higher in the PS group than the ER group (59.4% vs. 47.3%). There were no significant differences between the two groups in terms of the period after infection, habits, BMI, severity of COVID-19, and vaccination history. Notably, at the first visit, female patients in the PS group had a significantly higher rate of complaints of fatigue, insomnia, memory disturbance, and paresthesia, while male patients in the PS group showed significantly higher rates of fatigue and headache complaints. Patients with more than three symptoms at the first visit were predominant in the PS groups in both genders. Notably, one to two symptoms were predominant in the male ER group, while two to three symptoms were mostly reported in the female PS group. Moreover, the patients in the PS group had significantly higher scores for physical and mental fatigue and for depressive symptoms. Conclusions: Collectively, these results suggest that long-lasting long COVID is related to the number of symptoms and presents gender-dependent differences. en-copyright= kn-copyright= en-aut-name=AkiyamaHiroshi en-aut-sei=Akiyama en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakuradaYasue en-aut-sei=Sakurada en-aut-mei=Yasue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HondaHiroyuki en-aut-sei=Honda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsudaYui en-aut-sei=Matsuda en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaseRyosuke en-aut-sei=Takase en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OmuraDaisuke en-aut-sei=Omura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UedaKeigo en-aut-sei=Ueda en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=fatigue kn-keyword=fatigue en-keyword=headache kn-keyword=headache en-keyword=insomnia kn-keyword=insomnia en-keyword=long COVID kn-keyword=long COVID en-keyword=Omicron variants kn-keyword=Omicron variants en-keyword=recovery kn-keyword=recovery END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=3 article-no= start-page=e220018 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Origin of the unique topology of the triangular water cluster in <i>Rubrobacter xylanophilus</i> rhodopsin en-subtitle= kn-subtitle= en-abstract= kn-abstract=The crystal structure of Rubrobacter xylanophilus rhodopsin (RxR) reveals a triangular cluster of three water molecules (W413, W415, and W419) at the extracellular proton-release site, near Glu187 and Glu197. Using a quantum mechanical/molecular mechanical approach, we identified the structural nature of this unique water cluster. The triangular shape is best reproduced when all three water molecules are neutral H2O with protonated Glu187 and deprotonated Glu197. Attempts to place H3O+ at any of these water molecules result in spontaneous proton transfer to one of the acidic residues and significant distortion from the crystal structure. The plane defined by the triangular water cluster extends into the guanidinium plane of Arg71, with both aligned along the W413...W419 axis. This extended plane lies nearly perpendicular to a five-membered, ring-like H-bond network involving two carboxyl oxygen atoms from Glu187 and one from Glu197. The resulting bipartite planar architecture, defined by the water triangle, Arg71, and the Glu187/Glu197 network may reflect the exceptional thermal stability in RxR. en-copyright= kn-copyright= en-aut-name=NojiTomoyasu en-aut-sei=Noji en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujimuraMasaki en-aut-sei=Tsujimura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoKeisuke en-aut-sei=Saito en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshikitaHiroshi en-aut-sei=Ishikita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Advanced Interdisciplinary Studies, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=4 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=microbial rhodopsin kn-keyword=microbial rhodopsin en-keyword=proton transfer pathway kn-keyword=proton transfer pathway en-keyword=H3O+ kn-keyword=H3O+ en-keyword=pKa kn-keyword=pKa en-keyword=proton release group kn-keyword=proton release group END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=4 article-no= start-page=116 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Drip Fertigation in Greenhouse Eggplant Cultivation: Reducing N2O Emissions and Nitrate Leaching en-subtitle= kn-subtitle= en-abstract= kn-abstract=Drip fertigation (DF) is a sustainable agricultural management technique that optimizes water and nutrient usage, enhances crop productivity, and reduces environmental impact. Herein, we compared the effects of DF and conventional fertilization (CF) with a basal fertilizer on yield, soil inorganic nitrogen dynamics, N2O emissions, and nitrogen leaching during facility-grown eggplant cultivation. The experiment was conducted in a greenhouse from September 2023 to May 2024, with treatments arranged in three rows and three replicates. Soil, gas, and water samples were collected and analyzed throughout the growing season. The results revealed that the DF treatment produced yields comparable to those obtained with the CF treatment while significantly reducing nitrogen and phosphorus inputs. DF effectively prevented excessive nitrogen accumulation in the soil and reduced nitrogen loss through leaching and gas emissions. N2O emissions were significantly lower by more than 60% under DF than under CF. Precise nutrient management in DF suppressed nitrification and denitrification processes, mitigating N2O emissions. DF also significantly reduced nitrogen leaching by more than 70% compared with that in CF. These findings demonstrate that DF effectively enhances agricultural sustainability by improving nutrient use efficiency, reducing greenhouse gas emissions, and minimizing nitrogen leaching during the cultivation of facility-grown eggplant. en-copyright= kn-copyright= en-aut-name=ShiraishiWataru en-aut-sei=Shiraishi en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraShion en-aut-sei=Nishimura en-aut-mei=Shion kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UenoHideto en-aut-sei=Ueno en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Kochi Prefectural Agricultural Research Center kn-affil= affil-num=2 en-affil=Department of Bioresource Production Science, United Graduate School of Agriculture, Ehime University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Bioresource Production Science, United Graduate School of Agriculture, Ehime University kn-affil= en-keyword=drip fertigation kn-keyword=drip fertigation en-keyword=eggplant kn-keyword=eggplant en-keyword=greenhouse cultivation kn-keyword=greenhouse cultivation en-keyword=nitrogen leaching kn-keyword=nitrogen leaching en-keyword=nitrogen use efficiency kn-keyword=nitrogen use efficiency en-keyword=nitrous oxide emissions kn-keyword=nitrous oxide emissions END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=5 article-no= start-page=547 end-page=555 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase. en-copyright= kn-copyright= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KiyotaNaomi en-aut-sei=Kiyota en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikawaYuichiro en-aut-sei=Kikawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoKyoko en-aut-sei=Kato en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubotaKaoru en-aut-sei=Kubota en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TateishiRyosuke en-aut-sei=Tateishi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakataAkinobu en-aut-sei=Nakata en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaritaYukiya en-aut-sei=Narita en-aut-mei=Yukiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShimozumaKojiro en-aut-sei=Shimozuma en-aut-mei=Kojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MuroKei en-aut-sei=Muro en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IwamotoTetsuya en-aut-sei=Iwamoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakumotoYuki en-aut-sei=Takumoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShiroiwaTakeru en-aut-sei=Shiroiwa en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaTakashi en-aut-sei=Fukuda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamaguchiTakuhiro en-aut-sei=Yamaguchi en-aut-mei=Takuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HagiwaraYasuhiro en-aut-sei=Hagiwara en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MinamiHironobu en-aut-sei=Minami en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Kansai Medical University kn-affil= affil-num=4 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medical Oncology, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=6 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University kn-affil= affil-num=13 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=14 en-affil=Department of Biomed Sciences, College of Life Sciences, Ritsumeikan University kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=17 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=18 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=19 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=20 en-affil=Division of Biostatistics, Tohoku University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Biostatistics, Division of Health Sciences and Nursing, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=22 en-affil=Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Graduate School of Medicine kn-affil= en-keyword=electronic patient-reported outcomes monitoring kn-keyword=electronic patient-reported outcomes monitoring en-keyword=advanced cancers kn-keyword=advanced cancers en-keyword=systemic chemotherapy kn-keyword=systemic chemotherapy en-keyword=randomized controlled study kn-keyword=randomized controlled study en-keyword=quality of life kn-keyword=quality of life en-keyword=overall survival kn-keyword=overall survival END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=577 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of miR-128-3p on Renal Inflammation in a Rat Periodontitis Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: The study aim was to investigate the effects of extracellular vesicles (EVs) derived miR-128-3p on renal inflammation using a rat periodontitis model. Methods: Ten-week-old male Wistar rats were divided into two groups: a control (n = 8) and a lipopolysaccharides (LPS) group (n = 8). The LPS group received LPS (Porphyromonas gingivalis) injection in the gingiva for 7 days. At the end of the experiment, plasma, gingival tissue, and kidney samples were collected. Hematoxylin and eosin staining was performed to evaluate the glomerular tissue injury score. Bioinformatic analysis was conducted to identify potential target genes of miR-128-3p. The reverse transcription-quantitative polymerase chain reaction was performed to evaluate miR-128-3p, inflammatory, pro-inflammatory cytokine, chemokine and predicting gene’s expression. The control and LPS groups were compared using Welch’s t-test. p-values < 0.05 were considered to indicate statistical significance. Results: The kidney glomerular tissue injury score was significantly higher in the LPS than in the control group. miR-128-3p expression in the LPS group was significantly higher in the gingival tissue and plasma. mRNAs (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, C-X3-C motif chemokine ligand 1 [CX3CL1], and C-X-C motif chemokine ligand 7 [CXCL7]) expression was higher in the kidney of the LPS group. The potential target genes of activin A receptor type I (Acvr1), ribosomal protein S6 kinase B1 (Rps6kb1), and transforming growth factor beta receptor type 1 (Tgfbr1) were significantly lower in the kidneys of the LPS group. Conclusions: EVs-derived miR-128-3p in LPS induced periodontitis may cause kidney inflammation which may be mediated by, Rps6kb1, Tgfbr1, and Acvr1. en-copyright= kn-copyright= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhangYixuan en-aut-sei=Zhang en-aut-mei=Yixuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakaharaMomoko en-aut-sei=Nakahara en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagashimaYosei en-aut-sei=Nagashima en-aut-mei=Yosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Health, Takarazuka University of Medical and Health Care kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=extracellular vesicles kn-keyword=extracellular vesicles en-keyword=miR-128-3p kn-keyword=miR-128-3p en-keyword=mRNA kn-keyword=mRNA en-keyword=inflammation kn-keyword=inflammation en-keyword=periodontitis kn-keyword=periodontitis en-keyword=renal inflammation kn-keyword=renal inflammation en-keyword=lipopolysaccharide kn-keyword=lipopolysaccharide END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue= article-no= start-page=111782 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Robotic posterior radical antegrade modular pancreatosplenectomy for left-sided pancreatic cancer using the ligament of Treitz first approach: A case report and technical note en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Radical antegrade modular pancreatosplenectomy (RAMPS) is the standardized open surgical technique for treating left-sided pancreatic cancer. However, studies reporting the surgical approaches for robotic RAMPS are limited. Here, we present a robotic posterior RAMPS using the ligament of Treitz first approach.
Presentation of case: A 46-year-old male patient with initially unresectable pancreatic body cancer underwent robotic posterior RAMPS as a conversion surgery after 1-year of chemotherapy with modified FOLFIRINOX.
Discussion: Following evaluation of resectability, the ligament of Treitz first approach was applied. The transverse colon was lifted cranially, and the left renal vein was exposed after dissection around the ligament of Treitz. The left adrenal vein was divided, and the left adrenal gland was resected with special caution to avoid injury to the left renal artery. Retroperitoneal dissection was performed with lymphadenectomy around the superior mesenteric and celiac arteries using the ligament of Treitz first approach. After repositioning the transverse colon, the gastrocolic and gastrosplenic ligaments were dissected. Following the division of the pancreas and splenic vessels, the retroperitoneal dissection line was connected with those of the ligament of Treitz first approach. The operative time was 303 min, and the estimated blood loss was 150 mL.
Conclusion: The ligament of Treitz first approach may be an option for robotic RAMPS for left-sided pancreatic cancer. Surgeons should select the best approach for performing robotic RAMPS. en-copyright= kn-copyright= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Radical antegrade modular pancreatosplenectomy kn-keyword=Radical antegrade modular pancreatosplenectomy en-keyword=Distal pancreatectomy kn-keyword=Distal pancreatectomy en-keyword=Robotic surgery kn-keyword=Robotic surgery en-keyword=Ligament of Treitz kn-keyword=Ligament of Treitz en-keyword=Surgical approach kn-keyword=Surgical approach END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=2 article-no= start-page=103274 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimization of the reconstruction kernel for temporal bone imaging using photon-counting detector CT: A combined physical and visual evaluation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Photon-counting detector CT (PCD-CT) offers superior spatial resolution and noise characteristics compared to conventional CT. However, optimal reconstruction parameters for temporal bone imaging, especially kernel selection, remain unclear. This study aimed to identify the optimal reconstruction kernel using both objective physical image quality metrics and subjective expert assessments.
Methods: In phantom experiments, the system performance function (SPF) based on the task-based transfer function (TTF) and noise power spectrum (NPS) was calculated across 11 reconstruction kernels (Hr60?Hr98). Based on the results of the physical evaluation and clinical considerations from clinical practice, a subset of kernels was selected for visual assessment. For clinical images, two diagnostic radiologists evaluated three fine anatomical structures (i.e., stapes footplate, incudomalleolar joint, and cochlea) and overall image quality using both a ranking method and a 5-point Likert scale.
Results: TTF analysis indicated that Hr96 had the highest spatial resolution, while Hr60 showed the lowest noise in the NPS. SPF analysis identified Hr72 as providing the optimal balance between resolution and noise. Visual assessment using four reconstruction kernels (Hr60, Hr72, Hr76, and Hr84) showed that Hr76 consistently received the highest preference for overall image quality and visualization of fine structures. Statistically significant differences were observed among the kernels, with Hr60 consistently rated the lowest (p < 0.05).
Conclusion: The kernel Hr76 was found suitable for middle and inner ear diagnoses using PCD-CT, providing a good balance between spatial resolution and image noise. This finding provides a foundation for standardized reconstruction protocols in high-resolution temporal bone imaging.
Implications for practice: These findings support the use of Hr76 as a standard kernel for high-resolution temporal bone imaging and may contribute to protocol optimization in clinical PCD-CT practice. en-copyright= kn-copyright= en-aut-name=NishiiS. en-aut-sei=Nishii en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsaharaT. en-aut-sei=Asahara en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimitsuY. en-aut-sei=Morimitsu en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KajisakiS. en-aut-sei=Kajisaki en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkagiN. en-aut-sei=Akagi en-aut-mei=N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HondaM. en-aut-sei=Honda en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayashiH. en-aut-sei=Hayashi en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugayaA. en-aut-sei=Sugaya en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MunetomoK. en-aut-sei=Munetomo en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HigakiF. en-aut-sei=Higaki en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirakiT. en-aut-sei=Hiraki en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IguchiT. en-aut-sei=Iguchi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=7 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= affil-num=8 en-affil=Department of Otolaryngology, Head & Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=10 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=11 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= en-keyword=Photon-counting CT kn-keyword=Photon-counting CT en-keyword=Temporal bone imaging kn-keyword=Temporal bone imaging en-keyword=Reconstruction kernel kn-keyword=Reconstruction kernel en-keyword=Image quality kn-keyword=Image quality END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue= article-no= start-page=28 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Airway management during sedation for dental treatment in people with intellectual disabilities: a review en-subtitle= kn-subtitle= en-abstract= kn-abstract=The oral health of people with intellectual disabilities remains poor due to a complex combination of physical and social problems, and often requires invasive dental treatment. However, it can be difficult to obtain their cooperation for dental treatment because they may not fully understand the need for treatment or may experience high levels of anxiety due to lack of understanding and/or sensory aversions to stimuli present in the dental environment, and behavioral management is often necessary during such treatment. Sedation is a very useful patient management method for dental treatment for people with intellectual disabilities; however, the dental treatment-related sedation of people with intellectual disabilities has different characteristics to the dental treatment-related sedation of others or other procedure-related sedation. For example, deep sedation is required for behavioral management; drug interactions between the patient’s regular medications, such as antiepileptic and antipsychotic drugs, and anesthetics may make the depth of sedation deeper; and the prevalence rate of obesity is higher among people with intellectual disabilities. The fact that the patient is in the supine position with their mouth open also makes airway management during sedation for dental treatment more difficult. It is therefore imperative that airway management during dental treatment for people with intellectual disabilities be conducted with the utmost precision and vigilance. Various attempts have been made to improve airway management during such sedation, and new technologies, such as capnography, nasal high-flow systems, and acoustic respiration monitors, may help. The objective of this review is to enhance comprehension of the attributes of airway management in dental sedation for people with intellectual disabilities and to properly understand the usefulness of the techniques that have been attempted thus far to ensure safer and more secure airway management for this population. The ultimate goal is to provide them with safe and secure medical care and improve their health outcomes. en-copyright= kn-copyright= en-aut-name=HiguchiHitoshi en-aut-sei=Higuchi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiokaYukiko en-aut-sei=Nishioka en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyakeSaki en-aut-sei=Miyake en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Dentistry kn-keyword=Dentistry en-keyword=sedation kn-keyword=sedation en-keyword=airway management kn-keyword=airway management en-keyword=people with intellectual disabilities kn-keyword=people with intellectual disabilities END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=191 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Palladium-Catalyzed Decarbonylative Nucleophilic Halogenation of Acid Anhydrides en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we developed a palladium-catalyzed decarbonylative nucleophilic halogenation reaction using inexpensive and readily available acid anhydrides as substrates. This approach effectively circumvents the instability of acyl chlorides and the low reactivity of acyl fluorides. The Pd/Xantphos catalyst system exhibited excellent compatibility with the thermodynamically and kinetically challenging reductive elimination of C?X bonds (X = I, Br, and Cl) from Pd(II) intermediates. Notably, for electron-donating substrates, adopting an open system significantly improved the reaction efficiency. The positive effect of the open system may be due to the reversible nature of CO insertion and deinsertion, which helps direct the reaction toward the desired pathway by allowing the generated CO to exit the reaction system. Mechanistic studies suggest that the reaction proceeds through a highly reactive acyl halide intermediate, followed by a unimolecular fragment coupling (UFC) pathway via decarbonylation or an alternative pathway involving the formation of an activated anionic palladate complex in the presence of lithium halide. en-copyright= kn-copyright= en-aut-name=TianTian en-aut-sei=Tian en-aut-mei=Tian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UeiShuhei en-aut-sei=Uei en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanWeidan en-aut-sei=Yan en-aut-mei=Weidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiharaYasushi en-aut-sei=Nishihara en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= en-keyword=reductive elimination of C?X bond kn-keyword=reductive elimination of C?X bond en-keyword=nucleophilic halogenation kn-keyword=nucleophilic halogenation en-keyword=unimolecular fragment coupling (UFC) kn-keyword=unimolecular fragment coupling (UFC) en-keyword=acid anhydrides kn-keyword=acid anhydrides en-keyword=aryl halides kn-keyword=aryl halides END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=ycaf192 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Proliferation of a bloom-forming phytoplankton via uptake of polyphosphate-accumulating bacteria under phosphate-limiting conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Harmful algal blooms negatively impact the ecosystem and fisheries in affected areas. Eutrophication is a major factor contributing to bloom occurrence, and phosphorus is particularly important in limiting the growth of bloom-forming algae. Although algae efficiently utilize orthophosphate (Pi) as a phosphorous source over other molecular forms, Pi is often limited in the marine environment. While uptake and utilization of soluble inorganic and organic phosphorous by bloom-forming algae has been extensively studied, the details of geochemical and biological phosphorous cycling remain to be elucidated. Here, we report for the first time that the bloom-forming alga Heterosigma akashiwo can phagocytose bacteria and grow under phosphate-depleted conditions. The addition of Vibrio comitans to Pi-depleted H. akashiwo enabled the alga propagate to high cell densities, whereas other bacterial strains had only a minor effect. Importantly, V. comitans accumulates polyphosphate?a linear polymer of Pi?at high levels. The extent of algal proliferation induced by the addition of Vibrio species and polyphosphate-accumulating Escherichia coli correlated strongly with their polyphosphate content, indicating that bacterial polyphosphate served as an alternative PO43? source for H. akashiwo. The direct uptake of polyphosphate-accumulating bacteria through algal phagocytosis may represent a novel biological phosphorous-cycling pathway in marine ecosystems. The role of polyphosphate-accumulating marine bacteria as a hidden phosphorous source required for bloom formation warrants further investigation. en-copyright= kn-copyright= en-aut-name=FukuyamaSeiya en-aut-sei=Fukuyama en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UsamiFumiko en-aut-sei=Usami en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirotaRyuichi en-aut-sei=Hirota en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OharaShizuka en-aut-sei=Ohara en-aut-mei=Shizuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoKen en-aut-sei=Kondo en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GomibuchiYuki en-aut-sei=Gomibuchi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasunagaTakuo en-aut-sei=Yasunaga en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OndukaToshimitsu en-aut-sei=Onduka en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KurodaAkio en-aut-sei=Kuroda en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoikeKazuhiko en-aut-sei=Koike en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UekiShoko en-aut-sei=Ueki en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=6 en-affil=Research Institute of Environment, Agriculture and Fisheries , Osaka Prefecture kn-affil= affil-num=7 en-affil=Department of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=8 en-affil=Department of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=9 en-affil=Hatsukaichi Branch, Fisheries Technology Institute , Fisheries Research and Education Agency kn-affil= affil-num=10 en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=11 en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=12 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=40522 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long intervals between repetitive concussions reduce risk of cognitive impairment and limit microglial activation, astrogliosis, and tauopathy in adolescent rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although previous studies have demonstrated the effects of concussions do not accumulate as the time interval between injuries increases, little is known about the relationship between this interval and the effects of repetitive concussions. The objective of this study is to explore the relationship between the time interval and changes in behavior and histology following repetitive concussions. Male adolescent rats received concussions by weight drop and were randomly assigned to one of five experimental groups, receiving concussions three times either daily, every other day, once per week, once every 2 weeks, or receiving sham procedures. Only rats that received daily concussions exhibited cognitive impairment, while the other groups did not. No groups showed motor or anxiety-like impairments. Histological analysis revealed accumulation of microglia, as well as astrogliosis, in the prefrontal cortex, corpus callosum, dentate gyrus, and cornu Ammonis 1 region of the hippocampus in rats subjected to daily concussions. Accumulation of phosphorylated tau was also observed in the prefrontal cortex and cornu Ammonis 1. Longer intervals between concussions may reduce the risk of cognitive impairment and limit microglial activation, astrogliosis, and phosphorylated tau accumulation. These findings may help guide decisions on the appropriate timing for return to play in humans. en-copyright= kn-copyright= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaseTakayuki en-aut-sei=Nagase en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugaharaChiaki en-aut-sei=Sugahara en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiKoji en-aut-sei=Kawai en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanimotoShun en-aut-sei=Tanimoto en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyakeHayato en-aut-sei=Miyake en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaijoTomoya en-aut-sei=Saijo en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Yasuhara Clinic kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= en-keyword=Concussion kn-keyword=Concussion en-keyword=Return to play kn-keyword=Return to play en-keyword=Sports-related head injury kn-keyword=Sports-related head injury en-keyword=Microglia kn-keyword=Microglia en-keyword=Astrocyte kn-keyword=Astrocyte en-keyword=Tauopathy kn-keyword=Tauopathy END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=219 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Does perioperative discontinuation of anti-rheumatic drugs increase postoperative complications in orthopedic surgery for rheumatoid arthritis? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery.
Methods A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events.
Results A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor α and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers.
Conclusion In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context. en-copyright= kn-copyright= en-aut-name=ItoHiromu en-aut-sei=Ito en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaHajime en-aut-sei=Ishikawa en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiShigeyoshi en-aut-sei=Tsuji en-aut-mei=Shigeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MochizukiTakeshi en-aut-sei=Mochizuki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EbinaKosuke en-aut-sei=Ebina en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoTakumi en-aut-sei=Matsumoto en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KubotaAyako en-aut-sei=Kubota en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakajimaArata en-aut-sei=Nakajima en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KanekoAtsushi en-aut-sei=Kaneko en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsushitaIsao en-aut-sei=Matsushita en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HaraRyota en-aut-sei=Hara en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakurabaKoji en-aut-sei=Sakuraba en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AkasakiYukio en-aut-sei=Akasaki en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsubaraTsukasa en-aut-sei=Matsubara en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MochidaYuichi en-aut-sei=Mochida en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KanbeKatsuaki en-aut-sei=Kanbe en-aut-mei=Katsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NakagawaNatsuko en-aut-sei=Nakagawa en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MurataKoichi en-aut-sei=Murata en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MomoharaShigeki en-aut-sei=Momohara en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Kurashiki Central Hospital kn-affil= affil-num=2 en-affil=Department of Rheumatology, Niigata Rheumatic Center kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Osaka Minami Medical Center kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, International University of Health and Welfare kn-affil= affil-num=5 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Kamagaya General Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Osaka University Faculty of Medicine Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Nagoya University Hospital kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, University of Tokyo kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Toho University Omori Medical Center kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery and Rehabilitation, Toho University Sakura Medical Center kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Nagoya Medical Center kn-affil= affil-num=13 en-affil=Department of Rehabilitation Medicine, Kanazawa Medical University kn-affil= affil-num=14 en-affil=The Center for Rheumatic Diseases, Nara Medical University kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery, Kyushu Medical Center kn-affil= affil-num=16 en-affil=Department of Orthopaedic Surgery, Kyushu University kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Matsubara Mayflower Hospital kn-affil= affil-num=18 en-affil=Department of Orthopaedic Surgery, Yokohama City University Medical Center kn-affil= affil-num=19 en-affil=Department of Orthopaedic Surgery, Nippori Orthopaedics and Rheumatic Clinic kn-affil= affil-num=20 en-affil=Department of Orthopaedic Surgery, Kakogawa Medical Center kn-affil= affil-num=21 en-affil=Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Endowed Course for Advanced Therapy for Musculoskeletal Disorders, Keio University School of Medicine kn-affil= en-keyword=Rheumatoid arthritis kn-keyword=Rheumatoid arthritis en-keyword=Orthopaedic surgery kn-keyword=Orthopaedic surgery en-keyword=DMARD kn-keyword=DMARD en-keyword=Perioperative complications kn-keyword=Perioperative complications END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Is Pain Intensity Related to Psychosocial Factors in Chronic Non‐Nociceptive Orofacial Pain Patients? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: In order to understand the psychological aspects of chronic pain, it is important to consider the relationships between pain and psychosocial factors in patients with chronic pain. While psychosocial factors are known to affect pain intensity in temporomandibular disorders, few studies have evaluated them in patients with other types of chronic orofacial pain.
Objective: The purpose of the present study was to evaluate the relationships between pain intensity and patient characteristics, diagnostic categories and psychosocial factors in chronic non-nociceptive orofacial pain patients.
Methods: In a retrospective, cross-sectional study, we collected information from the medical records of 123 patients with chronic non-nociceptive orofacial pain. Pain intensity was measured using the Brief Pain Inventory (BPI) total score. Analysis of the correlations among the variables revealed several strong correlations. Principal component analysis identified two components: the psychological distress and self-efficacy/quality of life (QOL) components. Multiple linear regression analyses of the overall study population and each ICOP pain category were also performed.
Results: In the overall sample, higher BPI scores were significantly associated with a greater psychological distress component and lower self-efficacy/QOL component. The pain category was not a significant predictor of the BPI score. In the subgroup analyses, both components were significant predictors of the BPI score in myofascial orofacial pain; whereas, only the self-efficacy/QOL component was in idiopathic orofacial pain.
Conclusion: The results indicated that pain intensity in chronic non-nociceptive orofacial pain is related to the self-efficacy/QOL psychosocial factor component. These findings suggest that assessing psychosocial factors may be clinically important for the diagnosis and treatment of chronic orofacial pain. en-copyright= kn-copyright= en-aut-name=KawaseAkiko en-aut-sei=Kawase en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiguchiHitoshi en-aut-sei=Higuchi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoFumika en-aut-sei=Hashimoto en-aut-mei=Fumika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeSaki en-aut-sei=Miyake en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiokaYukiko en-aut-sei=Nishioka en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueMidori en-aut-sei=Inoue en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UjitaHitomi en-aut-sei=Ujita en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawauchiAki en-aut-sei=Kawauchi en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaShigeru en-aut-sei=Maeda en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=9 en-affil=Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=10 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic pain kn-keyword=chronic pain en-keyword=International Classification of Orofacial Pain kn-keyword=International Classification of Orofacial Pain en-keyword=orofacial pain kn-keyword=orofacial pain en-keyword=psychological distress component kn-keyword=psychological distress component en-keyword=psychosocial factors kn-keyword=psychosocial factors en-keyword=self-efficacy/ QOL component kn-keyword=self-efficacy/ QOL component END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=166 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PEGylation of liposome-encapsulated midazolam does not improve the bioavailability of midazolam when administered orally en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Liposomes are closed vesicles made of the same phospholipid bilayer as biological membranes and are capable of containing drugs, and so they have been investigated as useful drug carriers for drug delivery. We previously developed liposome-encapsulated midazolam (LE-midazolam) for oral administration, but midazolam is metabolized in the liver, and for clinical use the encapsulation of the liposomes needed to be improved to increase the bioavailability of midazolam. The surfaces of pharmaceutical liposomes are generally coated with polyethylene glycol (PEGylation) because it prevents their capture by phagocytes and helps them to avoid the reticuloendothelial system. Therefore, we considered that PEGylation could reduce the metabolism of orally administered encapsulated midazolam in the liver.
Methods Midazolam solution, LE-midazolam solution, and PEGylated liposome-encapsulated midazolam (PEG-LE-midazolam) solution were prepared, and the characteristics of the liposomes in these solutions were evaluated. Furthermore, these solutions were orally administered to rabbits, and the resultant plasma midazolam concentrations were measured. The effects of the PEGylation of LE-midazolam on the plasma concentration and bioavailability of orally administered midazolam were also evaluated.
Results The PEG-LE-midazolam solution contained a higher percentage of larger liposomes than the LE-midazolam solution. The area under the concentration-time curve (AUC) of the LE-midazolam solution was significantly higher than that of the midazolam solution, but there was no difference between the AUC values of the PEG-LE-midazolam and midazolam solutions.
Conclusions These findings suggest that liposome encapsulation may reduce the first-pass effect following oral administration, but PEGylation is not expected to improve the bioavailability of orally administered midazolam. en-copyright= kn-copyright= en-aut-name=NishiokaYukiko en-aut-sei=Nishioka en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LuYanyin en-aut-sei=Lu en-aut-mei=Yanyin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiguchiHitoshi en-aut-sei=Higuchi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeSaki en-aut-sei=Miyake en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimotoMaki en-aut-sei=Fujimoto en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Hamaoka-InoueMidori en-aut-sei=Hamaoka-Inoue en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanimuraHiroshi en-aut-sei=Tanimura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UjitaHitomi en-aut-sei=Ujita en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaShigeru en-aut-sei=Maeda en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=PEGylation kn-keyword=PEGylation en-keyword=Liposome kn-keyword=Liposome en-keyword=Midazolam kn-keyword=Midazolam en-keyword=Oral administration kn-keyword=Oral administration en-keyword=Bioavailability kn-keyword=Bioavailability END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=12 article-no= start-page=1455 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of ROS and NO in Plant Responses to Individual and Combined Salt Stress and Waterlogging en-subtitle= kn-subtitle= en-abstract= kn-abstract=During the climate change era, plants are increasingly exposed to multiple environmental challenges occurring simultaneously or sequentially. Among these, salt stress and waterlogging are two major factors that severely constrain crop productivity worldwide and often occur together. To survive under such conditions, plants have evolved sophisticated systems to scavenge harmful levels of reactive oxygen species (ROS). Despite their cytotoxic potential, ROS also act as key signaling molecules that interact with nitric oxide (NO), Ca2+, protein kinases, ion homeostasis pathways, and plant hormones. These signaling and acclimatory mechanisms are closely associated with the functions of energy-regulating organelles?chloroplasts and mitochondria?which are major sources of ROS under both individual and combined stresses. While many of these responses are shared between salt stress, waterlogging and their combination, it is likely that specific signaling mechanisms are uniquely activated when both stresses occur together?mechanisms that cannot be inferred from responses to each stress alone. Such specificity may depend on precise coordination among organelle-derived signals and the tight regulation of their cross-communication. Within this network, ROS and NO likely serve as central hubs, fine-tuning the integration of multiple signaling pathways that enable plants to adapt to complex and fluctuating stress environments. en-copyright= kn-copyright= en-aut-name=AneeTaufika Islam en-aut-sei=Anee en-aut-mei=Taufika Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SewelamNasser A. en-aut-sei=Sewelam en-aut-mei=Nasser A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BautistaNonnatus S. en-aut-sei=Bautista en-aut-mei=Nonnatus S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakashi en-aut-sei=Hirayama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University kn-affil= affil-num=2 en-affil=Botany Department, Faculty of Science, Tanta University kn-affil= affil-num=3 en-affil=Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University kn-affil= en-keyword=chloroplasts kn-keyword=chloroplasts en-keyword=mitochondria kn-keyword=mitochondria en-keyword=nitric oxide (NO) kn-keyword=nitric oxide (NO) en-keyword=reactive oxygen species (ROS) kn-keyword=reactive oxygen species (ROS) en-keyword=salt stress kn-keyword=salt stress en-keyword=stress combination waterlogging kn-keyword=stress combination waterlogging END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A rare case of supratentorial ependymosarcoma harboring ZFTA::RELA fusion en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ependymosarcoma is an exceedingly rare variant of ependymoma characterized by a mixture of ependymomatous and sarcomatous components. We report a case of supratentorial ependymosarcoma harboring a ZFTA::RELA fusion in a 10-year-old girl. Histologically, the tumor comprised an ependymomatous component resembling clear cell ependymoma and a sarcomatous component. ZFTA::RELA fusion was confirmed in both components. Genome-wide methylation profiling classified both components as supratentorial ependymoma, ZFTA fusion?positive by the German Cancer Research Center (DKFZ) CNS tumor classifier v12b8. However, their copy number alteration profiles were distinct. The ependymomatous component exhibited a gain of chromosome 1q and a loss of chromosomes 1p, 9, and 19q, while the sarcomatous component showed a loss of chromosome 14. These findings suggest that both components may have differentiated from a common precursor despite their distinct morphologies. The patient underwent gross total resection followed by adjuvant chemoradiotherapy and remains recurrence-free eight years post-treatment. Further investigation of additional cases is warranted to better understand the pathogenesis of this rare tumor. en-copyright= kn-copyright= en-aut-name=MatsumotoYuji en-aut-sei=Matsumoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SurugaYasuki en-aut-sei=Suruga en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatomiKaishi en-aut-sei=Satomi en-aut-mei=Kaishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueYohei en-aut-sei=Inoue en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HattoriYasuhiko en-aut-sei=Hattori en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurozumiKazuhiko en-aut-sei=Kurozumi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NobusawaSumihito en-aut-sei=Nobusawa en-aut-mei=Sumihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiratoJunko en-aut-sei=Hirato en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IchimuraKoichi en-aut-sei=Ichimura en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchikawaTomotsugu en-aut-sei=Ichikawa en-aut-mei=Tomotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Pathology, Faculty of Medicine, Kyorin University kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Neurosurgery, Hamamatsu University Hospital kn-affil= affil-num=8 en-affil=Department of Human Pathology, Gunma University School of Medicine kn-affil= affil-num=9 en-affil=Department of Pathology, Public Tomioka General Hospital kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Pathology, Faculty of Medicine, Kyorin University kn-affil= affil-num=14 en-affil=Department of Neurosurgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Ependymoma kn-keyword=Ependymoma en-keyword=Ependymosarcoma kn-keyword=Ependymosarcoma en-keyword=ZFTA kn-keyword=ZFTA en-keyword=RELA kn-keyword=RELA en-keyword=Methylation profiling kn-keyword=Methylation profiling END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=6 article-no= start-page=104265 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel leukocytapheresis method using highly concentrated sodium citrate solution for the manufacturing of tisagenlecleucel en-subtitle= kn-subtitle= en-abstract= kn-abstract=For the manufacturing of tisagenlecleucel (tisa-cel) requires the non-mobilized mononuclear cell collection (MNC). CD3+ cell collection is performed using the same protocol as autologous peripheral blood stem cell harvest (auto-PBSCH), but this procedure necessitates the same target CD3+ cell yields regardless of age or body weight, which may take several days especially in pediatric and small female patients with low white blood cell counts. We previously demonstrated a novel method using highly concentration sodium citrate (HSC), which reduced the need for an anticoagulant (AC) solution and shortened the procedure time in auto-PBSCH. This novel method was expected to offer advantages for smaller patients, prompting us to investigate its application in leukocytapheresis for the manufacturing of tisa-cel. We retrospectively analyzed consecutive leukocytapheresis data obtained using Spectra Optia continuous MNC mode between November 2022 and June 2024 at our institution (n?=?9). In six of nine patients, pre-leukocytapheresis CD3+ cell counts were less than 500 /μL, but all could obtain the target CD3+ cell yields in one day upon processing blood volume adjustment. When we compared patients who had received CD3+ cell collection using normal-concentration sodium citrate (NSC) as our previously reported using propensity score-matched pair analysis, the total AC solution volume was significantly lower (1168 vs. 316?mL, p? Study Design and Methods: We retrospectively analyzed consecutive auto-PBSCH data obtained using the Spectra Optia continuous mononuclear cell collection mode between May 2017 and May 2025 at our institution.
Results: Leukocytapheresis was performed using NSC in 36 patients and HSC in 22. In the HSC group, patients tended to be younger, had significantly lower body weight, and had significantly fewer hematopoietic tumors as primary diseases compared to the NSC group. After propensity score-matched cohort adjusted for patient background, the total amount of AC solution was significantly lower (694 [range, 77?1648] vs. 298?mL [range, 64?797], p?=?.02), and procedure time was significantly shorter (224 [range, 117?395] vs. 181?min [range, 103?309], p?=?.048) in the HSC group. Furthermore, the loss rates of magnesium and potassium were lower in the HSC group.
Conclusion: This novel leukocytapheresis method demonstrated the efficacy and safety in auto-PBSCH, while minimizing the patient burden. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimonoJoji en-aut-sei=Shimono en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=acid citrate dextrose solution A kn-keyword=acid citrate dextrose solution A en-keyword=anticoagulant kn-keyword=anticoagulant en-keyword=autologous kn-keyword=autologous en-keyword=highly concentrated sodium citrate kn-keyword=highly concentrated sodium citrate en-keyword=peripheral blood stem cell kn-keyword=peripheral blood stem cell END start-ver=1.4 cd-journal=joma no-vol=82 cd-vols= no-issue=2 article-no= start-page=26-1566 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=放射線治療装置の回転座標系誤差が軸外targetの照射精度に及ぼす影響とTG142のトレランスの評価 en-subtitle= kn-subtitle= en-abstract=Purpose: The aim of this study was to quantitatively evaluate the impact of gantry, collimator, and couch rotational errors in a linear accelerator on the irradiation accuracy of off-isocenter targets, and to assess the validity of the rotational error tolerance (±1.0°) specified in American Association of Physicists in Medicine TG142. Methods: Using an Elekta linear accelerator (Elekta, Stockholm, Sweden) and the MultiMet-WL QA phantom (Sun Nuclear, Melbourne, FL, USA), an off-isocenter Winston?Lutz test was performed on six targets. In addition to baseline measurements, six conditions were evaluated by intentionally introducing rotational errors of +0.5° and +1.0° in the collimator, gantry, and couch. The vector distance (S value) between the field center and the target center, as well as positional deviations in each direction (gantry-target: GT, left-right: LR, anterior-posterior: AP), were analyzed. Results: Targets located farther from the isocenter exhibited more significant positional deviations. The collimator rotation had the greatest impact; at 7 cm from the isocenter, even a 0.5° error resulted in a maximum S value of 1.24 mm. Couch rotation had the next largest effect, while gantry rotation had relatively smaller effects, likely because most targets were located near the gantry’s rotational axis. The rotational errors mainly caused geometric deviations with direction-dependent positional shifts. Conclusion: The effects of the collimator and couch were substantial, with positional deviations exceeding 1 mm even for a 0.5° rotation error. The influence of the gantry was relatively small and dependent on the target configuration. For irradiation of off-axis targets, the TG142 tolerance of ±1.0° should be regarded as a minimum standard that must be strictly observed regardless of the type of linear accelerator. However, depending on the target arrangement, clinically adequate margins may not be ensured. These findings suggest the necessity of applying stricter criteria according to target configuration and emphasize the importance of regular quality assurance. kn-abstract=【目的】放射線治療装置の回転座標系の誤差が軸外targetの照射精度に及ぼす影響を定量的に評価し，TG142における回転座標系誤差（±1.0°）のトレランスの妥当性を検討する．【方法】Elekta社製放射線治療装置（Elekta, Stockholm, Sweden）とMultiMet-WL QAファントム（Sun Nuclear, Melbourne, FL, USA）を用いて，6個のtargetに対してoff isocenterのWinston?Lutz test（WL test）を実施した．Baselineの測定に加え，意図的にcollimator，gantry，couchに+0.5°, +1.0°回転誤差を加えた6条件で測定を行い，照射野中心とtarget中心のベクトル距離（S値）および各方向（gantry-target: GT, left-right: LR, anterior-posterior: AP）の位置ずれを解析した．【結果】Isocenterからの距離が大きいtargetほど位置ずれが顕著であった．特にcollimator回転誤差の影響が最も大きく，isocenterから7?cm離れたtargetでは0.5°の回転誤差でもS値が最大1.24?mmに達した．次に影響が大きかったのはcouch回転であり，gantry回転はtargetの配置が回転軸に近いものが多く相対的に影響が少なかった．回転座標系の誤差は幾何学的誤差の影響が強く，位置ずれに方向依存性があった．【結語】Collimatorやcouchの影響が大きく，0.5°の誤差でも1?mm以上の位置ずれが生じることがあった．Gantryの影響はtargetの配置依存があり，相対的に小さかった．軸外targetの照射において，TG142の±1.0°のトレランスは放射線治療装置の種類にかかわらず最低限遵守するべき基準であり，targetの配置次第では臨床的に十分なマージンを保証できない可能性が示された．Target配置に応じたより厳格な基準と定期的quality assurance（QA）の重要性が示唆された． en-copyright= kn-copyright= en-aut-name=NakayamaTakahiro en-aut-sei=Nakayama en-aut-mei=Takahiro kn-aut-name=中山貴裕 kn-aut-sei=中山 kn-aut-mei=貴裕 aut-affil-num=1 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name=田辺悦章 kn-aut-sei=田辺 kn-aut-mei=悦章 aut-affil-num=2 ORCID= en-aut-name=FujiiYasushi en-aut-sei=Fujii en-aut-mei=Yasushi kn-aut-name=藤井康志 kn-aut-sei=藤井 kn-aut-mei=康志 aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Radiology, Public Mutual Aid Association Chugoku Central Hospital kn-affil=公立学校共済組合中国中央病院放射線科 affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil=岡山大学学術研究院保健学域放射線技術科学専攻 affil-num=3 en-affil=Department of Radiology, Public Mutual Aid Association Chugoku Central Hospital kn-affil=公立学校共済組合中国中央病院放射線科 en-keyword=off-isocenter Winston?Lutz test kn-keyword=off-isocenter Winston?Lutz test en-keyword=rotation error kn-keyword=rotation error en-keyword=off-axis targets kn-keyword=off-axis targets en-keyword=Elekta kn-keyword=Elekta en-keyword=TG142 kn-keyword=TG142 END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=8 article-no= start-page=e90112 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250814 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conversion to Hip Arthroplasty After Internal Fixation Failure in an Intertrochanteric Femoral Fracture: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intertrochanteric femoral fractures are mainly managed by internal fixation. However, failures such as over-telescoping, cut-out, nonunion, or implant failure can occur, especially in osteoporotic elderly patients. We report the case of a patient in whom we performed artificial hip replacement surgery after fixation failure following internal fixation of an intertrochanteric femoral fracture. We report the case of an 85-year-old woman who sustained a left intertrochanteric femoral fracture treated with a dynamic hip screw (DHS). One week postoperatively, radiographs revealed over-telescoping of the lag screw. The patient did not complain of pain, but she underwent conversion to cemented bipolar hemiarthroplasty under general anesthesia. One possible cause of over-telescoping of the lag screw after surgery was that the longitudinal fracture line in the calcar of the proximal bone fragment, as seen in the initial CT image, may have extended horizontally at the neck level. During surgery, a fracture at the same site caused the anterior medial fragment to fail, resulting in a coronal shear fracture and fixation failure. When a longitudinal fracture line is observed in the calcar of the proximal fragment, it is necessary to keep in mind that it may extend horizontally at the neck level. en-copyright= kn-copyright= en-aut-name=FukuokaShiro en-aut-sei=Fukuoka en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueTomoo en-aut-sei=Inoue en-aut-mei=Tomoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiMotoki en-aut-sei=Takahashi en-aut-mei=Motoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawasakiKeisuke en-aut-sei=Kawasaki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthopedics, Kagawa Prefectural Central Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedics, Kagawa Prefectural Central Hospital kn-affil= affil-num=3 en-affil=Department of Orthopedics, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=arthroplasty kn-keyword=arthroplasty en-keyword=coronal shear fracture kn-keyword=coronal shear fracture en-keyword=double jaws sign kn-keyword=double jaws sign en-keyword=fixation failure kn-keyword=fixation failure en-keyword=intertrochanteric femoral fracture kn-keyword=intertrochanteric femoral fracture END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ベトナムにおける保護区政策と地域コミュニティへの影響 kn-title=Protected Areas and Their Effects on Local Communities: Insights from Vietnam en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MAI THI KHANH VAN en-aut-sei=MAI THI KHANH VAN en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=本邦における小児肥満トレンドの変化：2012年から2021年の全国観察研究 kn-title=Trends in childhood obesity in Japan: A nationwide observational study from 2012 to 2021 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FUJIWARAShintaro en-aut-sei=FUJIWARA en-aut-mei=Shintaro kn-aut-name=藤原進太郎 kn-aut-sei=藤原 kn-aut-mei=進太郎 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=小腸腺癌における相同組換え修復遺伝子変異のゲノムプロファイルと臨床的影響 kn-title=Genomic landscape and clinical impact of homologous recombination repair gene mutation in small bowel adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OZATOToshiki en-aut-sei=OZATO en-aut-mei=Toshiki kn-aut-name=大里俊樹 kn-aut-sei=大里 kn-aut-mei=俊樹 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=抗石灰化グルタールアルデヒド処置を施した三次元培養軟骨組織の物理的特性の評価と加工 kn-title=Evaluation and processing of physical properties of anti-calcified glutaraldehyde-treated three-dimensional cultured cartilage tissues en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KITAGUCHIYohei en-aut-sei=KITAGUCHI en-aut-mei=Yohei kn-aut-name=北口陽平 kn-aut-sei=北口 kn-aut-mei=陽平 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=出生順位が小児アレルギー疾患に及ぼす影響： 日本における全国出生コホート kn-title=Impact of Birth Order on Paediatric Allergic Diseases: A National Birth Cohort in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KOBAYASHIMitsuro en-aut-sei=KOBAYASHI en-aut-mei=Mitsuro kn-aut-name=小林光郎 kn-aut-sei=小林 kn-aut-mei=光郎 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=19 article-no= start-page=3144 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utility of Same-Modality, Cross-Domain Transfer Learning for Malignant Bone Tumor Detection on Radiographs: A Multi-Faceted Performance Comparison with a Scratch-Trained Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases like malignant bone tumors is limited by scarce annotated data. This study evaluates same-modality cross-domain transfer learning by comparing an AI model pretrained on chest radiographs with a model trained from scratch for detecting malignant bone tumors on knee radiographs. Methods: Two YOLOv5-based detectors differed only in initialization (transfer vs. scratch). Both were trained/validated on institutional data and tested on an independent external set of 743 radiographs (268 malignant, 475 normal). The primary outcome was AUC; prespecified operating points were high-sensitivity (?0.90), high-specificity (?0.90), and Youden-optimal. Secondary analyses included PR/F1, calibration (Brier, slope), and decision curve analysis (DCA). Results: AUC was similar (YOLO-TL 0.954 [95% CI 0.937?0.970] vs. YOLO-SC 0.961 [0.948?0.973]; DeLong p = 0.53). At the high-sensitivity point (both sensitivity = 0.903), YOLO-TL achieved higher specificity (0.903 vs. 0.867; McNemar p = 0.037) and PPV (0.840 vs. 0.793; bootstrap p = 0.030), reducing ~17 false positives among 475 negatives. At the high-specificity point (~0.902?0.903 for both), YOLO-TL showed higher sensitivity (0.798 vs. 0.764; p = 0.0077). At the Youden-optimal point, sensitivity favored YOLO-TL (0.914 vs. 0.892; p = 0.041) with a non-significant specificity difference. Conclusions: Transfer learning may not improve overall AUC but can enhance practical performance at clinically crucial thresholds. By maintaining high detection rates while reducing false positives, the transfer learning model offers superior clinical utility. Same-modality cross-domain transfer learning is an efficient strategy for developing robust AI systems for rare diseases, supporting tools more readily acceptable in real-world screening workflows. en-copyright= kn-copyright= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaYujiro en-aut-sei=Otsuka en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeuchiKoichi en-aut-sei=Takeuchi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraYusuke en-aut-sei=Nakamura en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkutaKunihiro en-aut-sei=Ikuta en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OsakiShuhei en-aut-sei=Osaki en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TamiyaHironari en-aut-sei=Tamiya en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiwaShinji en-aut-sei=Miwa en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhshikaShusa en-aut-sei=Ohshika en-aut-mei=Shusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishimuraShunji en-aut-sei=Nishimura en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KaharaNaoaki en-aut-sei=Kahara en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Medical Informatics and Clinical Support Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Juntendo University School of Medicine kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Plusman LCC kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University kn-affil= affil-num=7 en-affil=Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute, kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Kindai University Hospital kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Mizushima Central Hospital kn-affil= affil-num=13 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=malignant bone tumors kn-keyword=malignant bone tumors en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=transfer learning kn-keyword=transfer learning en-keyword=YOLO kn-keyword=YOLO en-keyword=radiographs kn-keyword=radiographs en-keyword=cross-domain learning kn-keyword=cross-domain learning en-keyword=diagnostic imaging kn-keyword=diagnostic imaging END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=42195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elucidation of puberulic acid?induced nephrotoxicity using stem cell-based kidney organoids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent cases of acute kidney injury (AKI) in Japan have been linked to Beni-koji CholesteHelp supplements, with puberulic acid identified as a potential nephrotoxic contaminant. To address the need for a reliable in vitro nephrotoxicity testing platform, we developed a screening model using kidney organoids derived from adult rat kidney stem (KS) cells. The organoids were exposed to known nephrotoxicants, including cisplatin and gentamicin, to validate the system. Puberulic acid toxicity was evaluated in both KS cell-derived organoids and wild-type mice. The organoids recapitulated tubular injury induced by known nephrotoxins and showed significant Kim-1 mRNA upregulation. Puberulic acid-treated organoids and mice exhibited morphological features of acute tubular necrosis (ATN), mitochondrial damage, and reduced cytochrome c oxidase subunit IV (COX-IV) expression. Markers of oxidative stress and apoptosis, such as 8-hydroxy-2’-deoxyguanosine (8-OHdG) and cleaved caspase-3, were also elevated. These findings suggest that puberulic acid induces mitochondrial dysfunction and oxidative stress, leading to tubular cell death. Puberulic acid-induced nephrotoxicity was demonstrated using our kidney organoid model. KS cell-derived kidney organoids may provide a simple, reproducible, and rapid platform for nephrotoxicity assessment, which may complement conventional animal experiments. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Kidney organoid kn-keyword=Kidney organoid en-keyword=Kidney stem cell kn-keyword=Kidney stem cell en-keyword=Puberulic acid kn-keyword=Puberulic acid en-keyword=Nephrotoxicity kn-keyword=Nephrotoxicity en-keyword=Mitochondrial dysfunction kn-keyword=Mitochondrial dysfunction END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=10 article-no= start-page=1342 end-page=1353 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=First-time diagnosis and referral practices for individuals with CKD by primary care physicians: a study of electronic medical records across multiple clinics in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Chronic kidney disease (CKD) is a major public health burden in Japan. Japanese primary care physicians (PCPs) are expected to play an important role in the early diagnosis and management of CKD, but comprehensive data on their role are limited.
Methods This observational study examined data from individuals who underwent tests for CKD diagnosis between January 2017 and September 2023 in the Japan Medical Data Survey (JAMDAS) database of primary care clinics in Japan. The primary outcome was the proportion of individuals with CKD without the registration of a CKD-related disease code. Time to CKD diagnosis and referral were also assessed.
Results Among 1,188,543 eligible individuals who underwent kidney-related laboratory tests, 183,473 (15.4%) met CKD diagnosis criteria according to the Japanese Clinical Practice Guideline for CKD. The mean (±?SD) age was 77.4?±?11.0 years, 57.1% were female, and 71.8% had CKD stage 3a. Over 98% of individuals who met CKD diagnosis criteria did not receive an insurance diagnosis code within 90 days after meeting the criteria. Among referrable individuals, 89.7% did not receive a referral within 90 days of meeting the referral criteria.
Conclusion These results suggest CKD may be underdiagnosed and under-referred in Japanese clinics. Measures should be taken to increase detection and diagnosis according to the Japanese Clinical Practice Guideline for CKD. en-copyright= kn-copyright= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaoYuji en-aut-sei=Nagao en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IharaKatsuhito en-aut-sei=Ihara en-aut-mei=Katsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Medicine Division, Nippon Boehringer Ingelheim Co., Ltd. kn-affil= affil-num=4 en-affil=Medicine Division, Nippon Boehringer Ingelheim Co., Ltd. kn-affil= en-keyword=Chronic kidney disease kn-keyword=Chronic kidney disease en-keyword=Electronic medical records kn-keyword=Electronic medical records en-keyword=Japan kn-keyword=Japan en-keyword=Primary care physician kn-keyword=Primary care physician en-keyword=Disease code kn-keyword=Disease code END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=5 article-no= start-page=e70057 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Features Miyu Kanazawa, en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18?years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7?g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5?months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features. en-copyright= kn-copyright= en-aut-name=KanazawaMiyu en-aut-sei=Kanazawa en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiRyoya en-aut-sei=Aoki en-aut-mei=Ryoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SueMihiro en-aut-sei=Sue en-aut-mei=Mihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Okayama University Medical School kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Gd-IgA1 kn-keyword=Gd-IgA1 en-keyword=IgA nephropathy kn-keyword=IgA nephropathy en-keyword=membranoproliferative glomerulonephritis kn-keyword=membranoproliferative glomerulonephritis en-keyword=nephrotic syndrome kn-keyword=nephrotic syndrome en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=5762 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Patients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion. Other endogenous sulfides compounds which accumulated as in the renal failure also increased glucose-stimulated insulin secretion from β?-cell. With RNA-seq analyses and gene knock down, we demonstrated that insulin secretion evoked by PS was mediated by Ddah2. In addition, we also found that PS increased insulin resistance through lncRNA expression and Erk phosphorylation in the adipocytes. To confirm the relationship between PS and glucose metabolism in human, we recruited 2 clinical cohort studies (DKD and CKD) including 462 patients, and found that there was a weak negative correlation between PS and HbA1c. Because these trials did not measure fasting insulin level, we alternatively used the urinary C-peptide/creatinine ratio (UCPCR) as an indicator of insulin resistance. We found that PS may induce insulin resistance in patients with eGFR? Methods: Fourteen MDA5-DM patients with multiple adverse prognostic factors were studied. Seven received the BRT-Tx regimen, and the remaining seven, previously treated with TC-Tx, served as historical controls. Twelve-month survival was assessed. Transcriptome analysis was performed for six patients (BRT=3, TC=3), beginning with cluster analysis to evaluate whether changes in peripheral blood gene expression varied according to treatment or prognosis. Gene ontology analysis characterized expression profiles in survivors and distinguished treatment effects. Alterations in the type I, II, and III interferon signatures were also assessed.
Results: In the TC-Tx group, four of seven patients succumbed to RP-ILD, whereas all seven BRT-Tx patients survived the 12-month observation period. Only one BRT-Tx patient required combined rescue therapies, including plasma exchange, and one case of unexplained limbic encephalitis (LE) occurred. Cytomegalovirus reactivation was observed in both groups (BRT: 5/7; TC: 6/7). Transcriptomic analysis revealed no treatment-specific clustering of differentially expressed genes (DEGs) before and after therapy. However, survivors and nonsurvivors formed distinct clusters, with survivors showing significant posttreatment suppression of B-cell-related gene expression. Moreover, interferon signature scores were significantly lower after treatment in survivors than in nonsurvivors. BRT-Tx effectively suppressed B-cell-mediated immune responses and maintained a low interferon signature, while TC-Tx resulted in nonspecific gene suppression, and in nonsurvivors, an elevated interferon signature was observed.
Conclusion: BRT-Tx has the potential to improve survival in MDA5-DM patients by effectively targeting hyperactive immune pathways. The combination of rituximab and tacrolimus is expected to disrupt B-cell?T-cell interactions and reduce autoantibody production, whereas baricitinib may suppress both IFN and GM-CSF signaling, regulating excessive autoimmunity mediated by cells such as macrophages. Unlike TC-Tx, BRT-Tx avoids cyclophosphamide-associated risks such as infertility and secondary malignancies. Future randomized controlled trials are warranted to validate its efficacy and safety. en-copyright= kn-copyright= en-aut-name=TokunagaMoe en-aut-sei=Tokunaga en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaiYu en-aut-sei=Nakai en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoYoshiharu en-aut-sei=Sato en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiratsukaMitori en-aut-sei=Hiratsuka en-aut-mei=Mitori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakatsueTakeshi en-aut-sei=Nakatsue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaekiTakako en-aut-sei=Saeki en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmayaharaTakatsune en-aut-sei=Umayahara en-aut-mei=Takatsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KoyamaYoshinobu en-aut-sei=Koyama en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=DNA Chip Research Inc., Medical Laboratory kn-affil= affil-num=4 en-affil=DNA Chip Research Inc., Medical Laboratory kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital kn-affil= affil-num=7 en-affil=Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital kn-affil= affil-num=8 en-affil=Division of Dermatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= en-keyword=anti-MDA5 antibody-positive dermatomyositis (MDA5-DM) kn-keyword=anti-MDA5 antibody-positive dermatomyositis (MDA5-DM) en-keyword=JAK inhibitor kn-keyword=JAK inhibitor en-keyword=baricitinib kn-keyword=baricitinib en-keyword=rituximab kn-keyword=rituximab en-keyword=multitargeted treatment kn-keyword=multitargeted treatment en-keyword=IFN signature kn-keyword=IFN signature en-keyword=transcriptome analysis kn-keyword=transcriptome analysis END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e94951 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251019 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bladder Trigone as a Sensory Hub: A Narrative Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=The bladder trigone is an anatomically and functionally distinct region within the lower urinary tract (LUT), characterized by a dense network of afferent sensory fibers, specialized urothelial interactions, and prominent mechanotransduction mechanisms. Its intricate neuroarchitecture enables precise detection of bladder filling and coordination of micturition, whereas dysregulation of these pathways contributes to lower urinary tract symptoms (LUTS), including urgency, frequency, and bladder pain. Despite its recognized clinical relevance, the structural and functional basis of trigonal sensory signaling - and its role - remain incompletely understood.
This review synthesizes current evidence on trigonal afferent organization, integrating data from anatomical mapping, receptor profiling, electrophysiological characterization, and translational research. Seminal anatomical observations are combined with recent advances in mechanotransduction and purinergic, peptidergic, and transient receptor potential (TRP) signaling to provide a comprehensive perspective. The trigone exhibits three principal afferent classes: (1) intraepithelial fibers penetrating umbrella cells, marked by P2X purinoceptor 3 (P2X3), transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP), and substance P (SP); (2) subepithelial plexuses surrounding microvasculature, enriched in vasoactive neuropeptides and exhibiting plastic hypertrophy in overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS); and (3) encapsulated corpuscular endings at the lamina propria-detrusor junction, expressing PIEZO1/2 and acid-sensing ion channels (ASICs) for rapid adaptation. In trigeminal dorsal root ganglion (DRG) neurons, high expression of PIEZO2, P2RX3, and voltage-gated sodium channel, type 1.8 (Nav1.8) was observed, revealing their role as the foundation for multisensory information processing. Functional assays highlight distinct mechanotransductive and chemosensory pathways, with aging, inflammation, and neurotrophic factors driving afferent plasticity underlying abnormal bladder sensation, such as urgency, frequency, and pain. Early clinical trials of P2X3 antagonists and intravesical TRPV1 inhibitors demonstrate promising symptomatic benefits. Collectively, evidence positions the bladder trigone as a critical sensory hub where neuronal, urothelial, and immune signals converge to regulate bladder sensation. Understanding its molecular and structural specialization may inform the development of region-specific neuromodulatory therapies targeting sensory urgency and afferent-driven bladder dysfunction. en-copyright= kn-copyright= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bladder trigone kn-keyword=bladder trigone en-keyword=botulinum toxin kn-keyword=botulinum toxin en-keyword=lower urinary tract symptoms kn-keyword=lower urinary tract symptoms en-keyword=sensory afferents kn-keyword=sensory afferents en-keyword=varicosities kn-keyword=varicosities END start-ver=1.4 cd-journal=joma no-vol=786 cd-vols= no-issue= article-no= start-page=152753 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury.
Methods: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed.
Results: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1α and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion.
Conclusions: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions. en-copyright= kn-copyright= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MengYing en-aut-sei=Meng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinoriKosaki en-aut-sei=Yoshinori en-aut-mei=Kosaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeAkihiro en-aut-sei=Watanabe en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaTaihei en-aut-sei=Yamada en-aut-mei=Taihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=10 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Intestinal ischemia-reperfusion injury kn-keyword=Intestinal ischemia-reperfusion injury en-keyword=Molecular hydrogen kn-keyword=Molecular hydrogen en-keyword=Hydrogen gas therapy kn-keyword=Hydrogen gas therapy en-keyword=Caco-2 cells kn-keyword=Caco-2 cells en-keyword=Mitochondrial function kn-keyword=Mitochondrial function en-keyword=Hypoxia-inducible factor-1α (HIF1α) kn-keyword=Hypoxia-inducible factor-1α (HIF1α) END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=1 article-no= start-page=e70221 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pediatric stroke risk and neurotrauma from roller coasters in amusement parks en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although rare, neurotrauma has been documented as a potential risk of high-speed, high-acceleration amusement park rides such as roller coasters. These attractions generate rapid acceleration, deceleration, sharp turns, and significant gravitational forces, which may stress the central nervous system and cerebrovascular structures. This review analyzed pediatric stroke cases (children 15?years old or younger) linked to roller-coaster rides reported in PubMed and summarized the key mechanisms and clinical features associated with such neurotrauma. Documented complications include internal and vertebral carotid artery dissections, with or without stroke, subdural hemorrhage, intraparenchymal hemorrhage, and post-traumatic migraines. The aim of this review is to alert healthcare providers to the possibility of stroke induced by roller-coaster rides, emphasizing the importance of timely diagnosis and management to prevent adverse outcomes. Key considerations include the recognition of risk factors, public education on potential risks, and strategies for preventing complications in at-risk populations. Although intracranial hemorrhage from roller-coaster rides is rare, individuals with predisposing conditions, such as prior head trauma or vascular abnormalities, should be evaluated carefully when presenting with neurological symptoms after such activities. en-copyright= kn-copyright= en-aut-name=MorikawaTomoki en-aut-sei=Morikawa en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokiokaKohei en-aut-sei=Tokioka en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=amusement parks kn-keyword=amusement parks en-keyword=brain injuries kn-keyword=brain injuries en-keyword=carotid artery dissection kn-keyword=carotid artery dissection en-keyword=stroke kn-keyword=stroke en-keyword=vertebral artery dissection kn-keyword=vertebral artery dissection END start-ver=1.4 cd-journal=joma no-vol=254 cd-vols= no-issue= article-no= start-page=108998 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cellulose nanofibers boost soil water availability, plant growth, and irrigation water use efficiency under deficit irrigation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Under climate change, even previously rainfall-prone areas may experience droughts, and effective strategies are vital for soil conservation. Owing to their cutting-edge water absorption and storage properties, cellulose nanofibers (CNF) are expected to increase soil water availability and help plants resist water stress. However, the role of CNF in improving plant growth and soil water retention under various irrigation regimes is not yet known. We evaluated the effects of CNFs on plant available water (PAW), germination, plant growth, and irrigation water use efficiency (IWUE) under both adequate and deficit irrigation conditions. Plant cultivation experiments were conducted using different CNF dosages (0%, 0.1%, 0.5%, and 1.0%), irrigation levels (I100, I50, and I25), and soil types (sandy and silty loam). The results indicated that CNF significantly increased field capacity (FC) and PAW in both soil types, with PAW in CNF-amended soils increasing by up to 110% and 88% in sandy and silty loam soil, respectively, at 1% CNF dosage. In germination tests, CNF showed no phytotoxicity and supported the germination process during water stress, with enhancements of up to 64% and 163% at I50 and up to 125% and 214% at I25 in germination percentage and germination index, respectively. Plant growth experiments revealed that CNF addition helped plants resist water stress, maintaining plant height and weight close to those under full irrigation, while using 50% less water. IWUE analyses demonstrated that CNF enhanced IWUE, with increases of up to 56% under sufficient watering (I100), 169% under moderate water stress (I50), and 120% under severe water stress (I25), at 1% CNF dosage. These findings highlight the potential of CNF as a multifaceted amendment, offering practical solutions for addressing water scarcity challenges and contributing to more resilient and sustainable agricultural practices. en-copyright= kn-copyright= en-aut-name=NgoAn Thuy en-aut-sei=Ngo en-aut-mei=An Thuy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NguyenManh Cong en-aut-sei=Nguyen en-aut-mei=Manh Cong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriYasushi en-aut-sei=Mori en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Nong Lam University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Cellulose nanofibers kn-keyword=Cellulose nanofibers en-keyword=Available water kn-keyword=Available water en-keyword=Plant growth kn-keyword=Plant growth en-keyword=Irrigation water use efficiency kn-keyword=Irrigation water use efficiency en-keyword=Deficit irrigation kn-keyword=Deficit irrigation en-keyword=Water stress kn-keyword=Water stress END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=185 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tattoo-associated toxic shock syndrome: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Toxic shock syndrome (TSS) is a rare but life-threatening complication occasionally reported after tattooing.
Case presentation: : A 29-year-old Japanese man was admitted to Okayama University Hospital, Okayama, Japan, in early spring 2025, one week after receiving a tattoo on his right shoulder and upper arm in Osaka. He presented with fever, gastrointestinal symptoms, hypotension, and multi-organ failure. Despite a failure to isolate a causative pathogen, he met clinical criteria for TSS. Supportive care and broad-spectrum antibiotics led to full recovery.
Conclusions: TSS can occur after tattooing, even in individuals without apparent immunodeficiency. Pathogenic organisms may be unidentifiable; however, clinical diagnosis should not be delayed, and early therapeutic interventions are essential to improve outcomes. en-copyright= kn-copyright= en-aut-name=KuboTakuya en-aut-sei=Kubo en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Blood culture kn-keyword=Blood culture en-keyword=Critically ill kn-keyword=Critically ill en-keyword=Septic shock kn-keyword=Septic shock en-keyword=Tattooing kn-keyword=Tattooing en-keyword=Toxic shock syndrome kn-keyword=Toxic shock syndrome END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=17 article-no= start-page=2770 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250825 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Refining the Role of Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the tumor microenvironment, various immune and stromal cells, such as fibroblasts and vascular endothelial cells, contribute to tumor growth and progression by interacting with cancer cells. Tumor-associated macrophages (TAMs) have attracted attention as major players in the tumor microenvironment. The origin of TAMs is believed to be the infiltration of monocytes derived from bone marrow progenitor cells into tumor tissues and their differentiation into macrophages, whereas tissue-resident macrophages derived from yolk sacs have recently been reported. TAMs infiltrating tumor tissues act in a tumor-promoting manner through immunosuppression, angiogenesis, and the promotion of cancer cell invasion. Reflecting the nature of TAMs, increased TAM invasion and TAM-specific gene expression in tumor tissues may be the new biomarkers for cancer. Moreover, new therapeutic strategies targeting TAMs, such as transformation into immunostimulatory macrophages, suppression of TAM infiltration, and promotion of phagocytosis, are being investigated, and many clinical trials are underway. As the origin and function of TAMs are further elucidated, TAM-targeted therapy is expected to become a new option for the immunotherapy of various cancers, including oral cancers. en-copyright= kn-copyright= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TianyanPiao en-aut-sei=Tianyan en-aut-mei=Piao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArashimaTakuma en-aut-sei=Arashima en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChangAnqi en-aut-sei=Chang en-aut-mei=Anqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiMasae en-aut-sei=Fujii en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=tumor-associated macrophage (TAM) kn-keyword=tumor-associated macrophage (TAM) en-keyword=oral squamous cell carcinoma (OSCC) kn-keyword=oral squamous cell carcinoma (OSCC) en-keyword=macrophage polarity kn-keyword=macrophage polarity en-keyword=invasion kn-keyword=invasion en-keyword=carcinogenesis kn-keyword=carcinogenesis END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=14 article-no= start-page=4055 end-page=4070 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CXCR4 Inhibition Induces Tumor Necrosis by Selectively Targeting the Proliferating Blood Vessels in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The C-X-C chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor that contributes to tumor growth and angiogenesis. While prior studies have primarily focused on CXCR4 expression in cancer cells and its role in metastasis, a few have examined its involvement in tumor-associated vasculature. In this study, we reported for the first time that CXCR4 expression within the tumor vasculature is significantly associated with higher pathological grades of human oral squamous cell carcinoma (OSCC) (p<0.03). A previous study reported that inhibiting CXCR4 with AMD3100 induces tumor cell death and enhances the efficacy of the chemotherapeutic agent cisplatin. These findings suggest that CXCR4 is an important target for cancer treatment. However, the tumor vascular system is known to be heterogeneous within the tumor microenvironment (TME), which may influence the treatment outcomes. Therefore, this study aimed to explore the effect of CXCR4 antagonism on various blood vessels present within the oral squamous cell carcinoma (OSCC) tumor stroma. Although the efficiency of AMD3100 was not significant in MOC cancer cells, necrosis was induced in the TME when applied to a poorly differentiated OSCC model, highlighting the role of the TME. Notably, CXCR4 is found to be highly overlapped with CD105+ angiogenic tumor vessels among various vascular markers. Treatment with AMD3100 leads to a marked reduction in the CD105+ vessels and impairs the maturation of tumor micro-vessels, explaining the cause of observed necrosis. Thus, CXCR4 serves as a promising biomarker in OSCC, and its inhibition with AMD3100 offers the therapeutic potential, particularly in cases with advanced pathological grades. en-copyright= kn-copyright= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=CXCR4 kn-keyword=CXCR4 en-keyword=tumor angiogenesis kn-keyword=tumor angiogenesis en-keyword=chemokine receptors kn-keyword=chemokine receptors en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=oral squamous cell carcinoma (OSCC) kn-keyword=oral squamous cell carcinoma (OSCC) en-keyword=AMD3100 kn-keyword=AMD3100 END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=3 article-no= start-page=965 end-page=970 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decreased homovanillic acid and 5‐hydroxyindoleacetic acid levels in the cerebrospinal fluid of patients with Dravet syndrome with parkinsonism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy characterized by drug-resistant seizures and multiple comorbidities. It has been reported that in adulthood, it may be accompanied by parkinsonism, but the pathogenesis of this condition remains unclear. We performed dopamine transporter single-photon emission computed tomography (DAT SPECT) and measured monoamine metabolite levels in the cerebrospinal fluid (CSF) in two adult patients with DS who developed parkinsonism around the age of 30?years. DAT SPECT showed no abnormalities in either patient, whereas CSF tests revealed significant decreases in the levels of homovanillic and 5-hydroxyindoleacetic acids. One patient with severe symptoms was treated with levodopa?carbidopa, which improved parkinsonism manifestations. The other patient initiated treatment with a low dose and has been continuing the treatment without any reported side effects. In conclusion, CSF testing can detect a decrease in dopamine synthesis and may be useful in monitoring the efficacy of levodopa treatment in patients with DS and parkinsonism.
Plain Language Summary: Dravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy. DS can lead to the development of parkinsonism in adulthood, a clinical syndrome characterized by tremor, slowed movements, and rigidity. Although parkinsonism is a significant issue for patients, its underlying pathology has not yet been elucidated. In this study, we confirmed that the levels of monoamine metabolites in the CSF were low in two patients, potentially shedding light on the pathology involved. en-copyright= kn-copyright= en-aut-name=SugiyamaRyo en-aut-sei=Sugiyama en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoTakashi en-aut-sei=Saito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsumotoAtsuko en-aut-sei=Katsumoto en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YonenoShota en-aut-sei=Yoneno en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KomakiHirofumi en-aut-sei=Komaki en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry kn-affil= affil-num=2 en-affil=Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry kn-affil= affil-num=3 en-affil=Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry kn-affil= affil-num=4 en-affil=Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry kn-affil= affil-num=5 en-affil=Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry kn-affil= en-keyword=dopamine transporter kn-keyword=dopamine transporter en-keyword=levodopa kn-keyword=levodopa en-keyword=monoamine metabolites kn-keyword=monoamine metabolites en-keyword=single-photon emission computed tomography kn-keyword=single-photon emission computed tomography END start-ver=1.4 cd-journal=joma no-vol=98 cd-vols= no-issue= article-no= start-page=103224 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The vicious cycle between nutrient deficiencies and antibiotic-induced nutrient depletion at the host cell-pathogen interface: Coenzyme Q10 and omega-6 as key molecular players en-subtitle= kn-subtitle= en-abstract= kn-abstract=The increasing prevalence of antibiotic resistance and pathological inflammation underscores the importance of understanding the underlying biochemical and immune processes that govern the host-pathogen interface. Nutrient deficiency, compounded by antibiotic-induced nutrient depletion, forms a vicious cycle of overt inflammation, contributing to bacterial toxin translocation in human inter-organ and intra-organs milieus. Coenzyme Q10 (CoQ10) and omega-6 linoleic acid (LA 18:2ω6) are integral to cellular membrane integrity and immune defense. However, the complex enzymatic steps at the host cell-pathogen interface remain poorly understood. This study is particularly timely, as it explores these knowledge gaps, which can inform the development of nutritional and therapeutic strategies that modulate or target these mechanisms. Using an infectious-inflamed cell co-culture model of the gut-liver axis, we exposed triple cell co-cultures of human intestinal epithelial cells (T84), macrophage-like THP-1 cells, and hepatic cells (Huh7) to linoleic acid-producing Lactobacillus casei (L. casei) and Pseudomonas aeruginosa strain PAO1 (PAO1). The cultures were incubated for 6?h in medium with or without ceftazidime antibiotic. PAO1 and L. casei exerted opposing effects on the secretion of Th1 cytokines IL-1β, IL-6, and the Th 2-type cytokine IL-10. Inoculation with PAO1 decreased CoQ10 and linoleic acid levels compared to uninfected controls. L. casei restored cellular health and biofunctionality impaired by PAO1, indicating its benefit to the host's well-being. The antibiotic ceftazidime exerted dual effects, alleviating PAO1 toxicity while marginally disrupting the beneficial effects of L. casei. Our results show how the vicious cycle of nutrient deficiency and antibiotic-induced nutrient loss reinforces pathological inflammation at the host cell-pathogen interface and highlights the need for more appropriate targeted antibiotic use that preserves essential nutrients like CoQ10 and omega-6 fatty acids. Inflammatory responses driven by opportunistic pathogens and LA-producing bacteria represent opposing immunometabolic pathways that may provide insights into novel approaches for treating infection and reducing antibiotic resistance. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Bl?merSophia en-aut-sei=Bl?mer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=?ahi?n KayaAysel en-aut-sei=?ahi?n Kaya en-aut-mei=Aysel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Kr?gerSandra en-aut-sei=Kr?ger en-aut-mei=Sandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=R?ckenChristoph en-aut-sei=R?cken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Sch?ferHeiner en-aut-sei=Sch?fer en-aut-mei=Heiner kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Faculty of Medicine, Christian-Albrechts-University of Kiel kn-affil= affil-num=3 en-affil=Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University kn-affil= affil-num=4 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel kn-affil= affil-num=7 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=9 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Antibiotics kn-keyword=Antibiotics en-keyword=Coenzyme Q10 kn-keyword=Coenzyme Q10 en-keyword=Infection kn-keyword=Infection en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Micronutrients kn-keyword=Micronutrients en-keyword=Oxidative stress kn-keyword=Oxidative stress END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=670 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neoadjuvant chemotherapy strategies for optimizing safety and efficacy in elderly patients with locally advanced gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The completion rate of adjuvant chemotherapy for gastric cancer (GC) is suboptimal, particularly in elderly patients. While neoadjuvant chemotherapy (NAC) for locally advanced GC has shown promise, data on elderly patients remain limited. Given the considerable physical burden of NAC, optimizing its administration is crucial. This study evaluates the safety and efficacy of a modified approach for elderly patients.
Methods A retrospective analysis was conducted on 38 patients with cStage II/III GC who received NAC between November 2015 and December 2023. Additionally, 25 patients aged???75 years with cStage III who underwent upfront surgery during the same period were analyzed.
Results The NAC group was divided into non-elderly ( Conclusions NAC can be safely administered to elderly patients by increasing cycles while reducing per-cycle dosage. It may also serve as a viable alternative to upfront surgery. en-copyright= kn-copyright= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HanzawaShunya en-aut-sei=Hanzawa en-aut-mei=Shunya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Neoadjuvant chemotherapy kn-keyword=Neoadjuvant chemotherapy en-keyword=Elderly kn-keyword=Elderly en-keyword=Adverse events kn-keyword=Adverse events END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative Analysis of a Dual DNA?RNA Panel and a DNA-Only Panel for Sarcoma: Real-World Data From a Nationwide Genomic Database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Next-generation sequencing-based comprehensive cancer genomic profiling is promising in cancer management; however, most studies rely on tumor-only DNA panels from single institutions. In 2023, Japan introduced an insurance-covered cancer genomic profiling test?the GenMine TOP Cancer Genome Profiling System?a dual DNA?RNA panel with matched tumor?normal testing. This study evaluated its utility compared to a conventional DNA-only test (FoundationOne CDx) in managing sarcoma patients using a nationwide genetic profiling database provided by the Center for Cancer Genomics and Advanced Therapeutics. This study included 1046 patients registered between August 2023 and October 2024. The dual DNA?RNA test identified significantly more fusion genes (20.3% vs. 7.4%, p? Material and Methods: This retrospective study included 17 patients with 17 renal cell carcinomas who underwent transarterial ethiodized-oil marking before cryoablation. Tumor feeders were automatically detected on transarterial renal computed tomography angiography images using the automated feeder-detection software with three virtual-target definitions: small (ellipsoidal area maximized within the tumor contour), medium (ellipsoidal area covering the entire tumor with a minimal peripheral margin), and large (ellipsoidal area including the tumor and a 5-mm peripheral margin). The detected feeders were classified as true or false positives according to the findings of selective renal arteriography, by consensus of two interventional radiologists. Feeder-detection sensitivity and the mean number of false-positive feeders per tumor were calculated for each virtual-target definition.
Results: For 17 tumors, 25 feeding arteries were identified on the arteriography. The feeder-detection sensitivity of the software was 80.0% (20/25), 88.0% (22/25), and 48.0% (12/25) for small, medium, and large virtual targets, respectively. The mean ± standard deviation number of false-positive feeders per tumor was 0.82 ± 1.3, 1.41 ± 1.1, and 2.82 ± 1.6 when using small, medium, and large virtual-target definitions, respectively.
Conclusions: The detection rate of renal cell carcinoma feeders with the automated feeder-detection software varies according to the virtual-target definition. Using a medium virtual target, covering the entire tumor with a minimal peripheral margin, may provide the highest sensitivity and an acceptable number of false-positive feeders. en-copyright= kn-copyright= en-aut-name=OkamotoSoichiro en-aut-sei=Okamoto en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawabataTakahiro en-aut-sei=Kawabata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MunetomoKazuaki en-aut-sei=Munetomo en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Tsuyama Chuo Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=computed tomography angiography kn-keyword=computed tomography angiography en-keyword=kidney kn-keyword=kidney en-keyword=software kn-keyword=software en-keyword=therapeutic embolization kn-keyword=therapeutic embolization END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=127 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical predictors of extubation failure in postoperative critically ill patients: a post-hoc analysis of a multicenter prospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Postoperative patients constitute majority of critically ill patients, although factors predicting extubation failure in this group of patients remain unidentified. Aiming to propose clinical predictors of reintubation in postoperative patients, we conducted a post-hoc analysis of a multicenter prospective observational study.
Methods This study included postoperative critically ill patients who underwent mechanical ventilation for >?24 h and were extubated after a successful 30-min spontaneous breathing trial. The primary outcome was reintubation within 48 h after extubation, and clinical predictors for reintubation were investigated using logistic regression analyses.
Results Among the 355 included patients, 10.7% required reintubation. Multivariable logistic regression identified that the number of endotracheal suctioning episodes during the 24 h before extubation and underlying respiratory disease or pneumonia occurrence were significantly associated with reintubation (adjusted odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05?1.18, p? Conclusions Endotracheal suctioning frequency and respiratory complications were identified as independent predictors of reintubation. These readily obtainable predictors may aid in decision-making regarding the extubation of postoperative patients. en-copyright= kn-copyright= en-aut-name=HattoriJun en-aut-sei=Hattori en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaAiko en-aut-sei=Tanaka en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KosakaJunko en-aut-sei=Kosaka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraoOsamu en-aut-sei=Hirao en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurushimaNana en-aut-sei=Furushima en-aut-mei=Nana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MakiYuichi en-aut-sei=Maki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KabataDaijiro en-aut-sei=Kabata en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaAkinori en-aut-sei=Uchiyama en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EgiMoritoki en-aut-sei=Egi en-aut-mei=Moritoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MizobuchiSatoshi en-aut-sei=Mizobuchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KotakeYoshifumi en-aut-sei=Kotake en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShintaniAyumi en-aut-sei=Shintani en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KoyamaYukiko en-aut-sei=Koyama en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshidaTakeshi en-aut-sei=Yoshida en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujinoYuji en-aut-sei=Fujino en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Faculty of Medicine, Osaka University kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology, Osaka General Medical Center kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Intensive Care Medicine, Kobe University Hospital kn-affil= affil-num=6 en-affil=Department of Anesthesiology, Toho University Ohashi Medical Center kn-affil= affil-num=7 en-affil=Center for Mathematical and Data Science, Kobe University kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Anesthesia, Kyoto University Hospital kn-affil= affil-num=10 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Anesthesiology and Intensive Care Medicine, Kobe University Hospital kn-affil= affil-num=12 en-affil=Department of Anesthesiology, Toho University Ohashi Medical Center kn-affil= affil-num=13 en-affil=Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=14 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= en-keyword=Reintubation kn-keyword=Reintubation en-keyword=Extubation failure kn-keyword=Extubation failure en-keyword=Endotracheal suctioning kn-keyword=Endotracheal suctioning en-keyword=Postoperative patient kn-keyword=Postoperative patient en-keyword=Clinical predictor kn-keyword=Clinical predictor en-keyword=Critical care kn-keyword=Critical care END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Anorexia nervosa (AN) is a metabolic-psychiatric disorder characterized by severe weight loss, hypercortisolemia, and hypothalamic?pituitary?adrenal (HPA) axis activation. In this study, we investigated the effect of inhibiting cortisol regeneration via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on the pathophysiology of AN.
Method: Female C57BL/6J mice underwent a 7-day activity-based anorexia (ABA) paradigm, involving 3?h daily feeding and free access to wheels, until 25% body weight loss or experiment completion. Mice were orally treated once daily with a potent 11β-HSD1 inhibitor, DSOK-0011, or vehicle. Body weight, food intake, and activity transitions were recorded; plasma corticosterone and cholesterol levels were measured using a fluorometric assay; gut microbiota were analyzed using 16S rRNA sequencing; and hippocampal glial cells were analyzed using immunohistochemistry.
Results: DSOK-0011-treated mice exhibited a modest but significant increase in postprandial wheel-running activity compared to baseline (4?5?p.m., p?=?0.018; 5?6?p.m., p?=?0.043), whereas vehicle-treated mice showed higher preprandial activity (9?10?a.m., p?=?0.0229). Gut microbiota analysis revealed increased alpha diversity in ABA mice, with a specific enrichment of the Lachnospiraceae family in the DSOK-0011 group. However, DSOK-0011 did not significantly affect body weight, food intake, corticosterone, and lipid levels, or hippocampal glial cell populations.
Conclusion: Inhibition of 11β-HSD1 by DSOK-0011 was associated with microbiota alterations and subtle shifts in activity timing under energy-deficient conditions. These findings suggest that peripheral glucocorticoid metabolism may influence microbial and behavioral responses in the ABA model, although its metabolic impact appears limited in the acute phase. en-copyright= kn-copyright= en-aut-name=KawaiHiroki en-aut-sei=Kawai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaNanami en-aut-sei=Wada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyazakiKenji en-aut-sei=Miyazaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTaro en-aut-sei=Kato en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriuchiYoshihiro en-aut-sei=Horiuchi en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiriiHiroshi en-aut-sei=Kirii en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NguyenHoang Duy en-aut-sei=Nguyen en-aut-mei=Hoang Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HinotsuKenji en-aut-sei=Hinotsu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhyaYoshio en-aut-sei=Ohya en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsadaTakahiro en-aut-sei=Asada en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkahisaYuko en-aut-sei=Okahisa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=5 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=6 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=7 en-affil=Department of Animal Applied Microbiology, Okayama University Graduate School of Environmental, Life, Natural Science and Technology kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=11β-HSD1 kn-keyword=11β-HSD1 en-keyword=activity-based anorexia kn-keyword=activity-based anorexia en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=corticosterone kn-keyword=corticosterone en-keyword=eating disorders kn-keyword=eating disorders en-keyword=microbiota kn-keyword=microbiota END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=1 article-no= start-page=22 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective impact of landiolol against acute lung injury following hemorrhagic shock and resuscitation in rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation, leading to acute lung injury (ALI). Notably, blocking β1 receptors can lead to organ protection through anti?inflammatory and anti?apoptotic effects. Additionally, although the β1 receptor pathway is blocked by the β1 blocker, the β2 receptor pathway may be preserved and activate the 5' adenosine monophosphate?activated protein kinase (AMPK) pathway. The present study aimed to examine whether administration of the β1 blocker landiolol could achieve lung protection in a model of HSR?ALI, alongside improvements in inflammation and apoptosis. Male Sprague?Dawley rats underwent hemorrhage keeping their mean arterial pressure at 30 mmHg for 1 h. Resuscitation by reinfusion was initiated to restore blood pressure to pre?hemorrhage levels for >15 min, followed by a 45?min stabilization period to create the HSR?ALI model. Landiolol (100 mg/kg/min) or saline was continuously administered after resuscitation. The lung tissues, which were collected for assessing inflammation and apoptosis?related damage, underwent analyses, including histological examination, neutrophil count, assessment of lung wet/dry weight ratio, detection of the mRNA levels of tumor necrosis factor?α (TNF?α) and inducible nitric oxide synthase (iNOS), identification of terminal deoxynucleotidyl transferase dUTP nick?end labeling (TUNEL)?positive cells, and evaluation of caspase?3 expression. In addition, phosphorylated AMPKα (pAMPKα) expression was tested via western blotting. Compared with the HSR/saline group, the HSR/landiolol group demonstrated a reduction in lung tissue damage score, and significant reductions in neutrophil count, lung wet/dry weight ratio, lung TNF?α and iNOS mRNA levels, TUNEL?positive cells and cleaved caspase?3 expression. Furthermore, landiolol administration following HSR treatment increased pAMPKα expression. No significant hypotension occurred between the HSR/landiolol and HSR/saline groups; and blood loss did not differ significantly between the groups. In conclusion, landiolol administration after HSR reduced lung inflammation and apoptosis, suggesting a potential improvement in tissue damage. Furthermore, pAMPKα activation in the HSR/landiolol group may be the mechanism underlying the pulmonary protective effects of landiolol. en-copyright= kn-copyright= en-aut-name=SakamotoRisa en-aut-sei=Sakamoto en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraRyu en-aut-sei=Nakamura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LuYifu en-aut-sei=Lu en-aut-mei=Yifu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiYaqiang en-aut-sei=Li en-aut-mei=Yaqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriEmiko en-aut-sei=Omori en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Human Anatomy, Shantou University Medical College kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Okayama Saidaiji Hospital kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=HSR kn-keyword=HSR en-keyword=lung injury kn-keyword=lung injury en-keyword=landiolol kn-keyword=landiolol en-keyword=β1 blocker kn-keyword=β1 blocker en-keyword=inflammation kn-keyword=inflammation en-keyword=apoptosis kn-keyword=apoptosis END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=565 end-page=569 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utilization of the pericapsular nerve group block in preoperative rehabilitation of patients with femoral neck fractures -a case series- en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Elderly patients with femoral neck fractures, particularly those with severe comorbidities or living in regions with limited medical resources, may experience delays in surgical treatment. Although the benefits of preoperative rehabilitation (prehabilitation) in hip arthroplasty have been reported, pain management remains a challenge. The pericapsular nerve group (PENG) block, known for its exceptional analgesic effect and motor function preservation, may be a promising intervention during prehabilitation in these patients.
Case: We enrolled ten patients with Garden classification 3?4 femoral neck fractures scheduled for hip arthroplasty. After receiving a PENG block with 20 ml of 0.375% ropivacaine, all patients underwent initial prehabilitation sessions comprising 9 mobility levels, ranging from bed-sitting to walking. One patient was excluded due to experiencing high blood pressure during prehabilitation. Six of the nine remaining patients (66.7%) were successfully transferred from bed to wheelchair.
Conclusions: The PENG block enhanced prehabilitation for patients with femoral neck fractures undergoing hip arthroplasty. en-copyright= kn-copyright= en-aut-name=JinZhuan en-aut-sei=Jin en-aut-mei=Zhuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaDaisuke en-aut-sei=Sugiyama en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigoFumiya en-aut-sei=Higo en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirataTakahiro en-aut-sei=Hirata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiOsamu en-aut-sei=Kobayashi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UedaKenichi en-aut-sei=Ueda en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=3 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=5 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= en-keyword=Conduction anesthesia kn-keyword=Conduction anesthesia en-keyword=Femoral neck fractures kn-keyword=Femoral neck fractures en-keyword=Hip fractures kn-keyword=Hip fractures en-keyword=Nerve block kn-keyword=Nerve block en-keyword=Prehabilitation kn-keyword=Prehabilitation en-keyword=Preoperative exercise kn-keyword=Preoperative exercise en-keyword=Preoperative rehabilitation kn-keyword=Preoperative rehabilitation en-keyword=Regional anesthesia kn-keyword=Regional anesthesia END start-ver=1.4 cd-journal=joma no-vol=215 cd-vols= no-issue= article-no= start-page=110706 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Compression only CPR and mortality in pediatric out-of-hospital cardiac arrest during COVID-19 pandemic en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The COVID-19 pandemic influenced resuscitation practices worldwide, leading to a notable decline in rescue breathing cardiopulmonary resuscitation (RB-CPR), even in pediatric out-of-hospital cardiac arrest (OHCA). Understanding the impact of this decline is important to assess the role of rescue breathing in pediatric resuscitation. This study aimed to evaluate the impact of the reduced RB-CPR during the COVID-19 pandemic on mortality and neurological outcomes among pediatric OHCA patients in Japan.
Methods: This retrospective cohort study utilized data from the nationwide All-Japan Utstein Registry for pediatric OHCA patients (?17 years) who received bystander CPR between January 2017 and December 2021. Data were compared in pre-COVID-19 (2017?2019) versus pandemic (2020?2021) periods. Bystander CPR were classified as RB-CPR or chest compression-only CPR (CO-CPR). The primary outcome was 30-day mortality, with secondary outcomes including the absence of return of spontaneous circulation and unfavorable neurological outcomes (Cerebral Performance Category scores of 3?5). Adjusted risk ratios (aRR) with 95 % confidence intervals (CI) were estimated using Poisson regression.
Results: Of 7,162 pediatric OHCA cases, 3,352 (46.8 %) received bystander CPR. RB-CPR decreased from 33.0 % pre-pandemic to 21.1 % during the pandemic. CO-CPR was associated with higher 30-day mortality (aRR: 1.16; 95 % CI: 1.08?1.24) and unfavorable neurological outcomes (aRR: 1.10; 95 % CI: 1.05?1.16). These trends were consistent across age groups and arrest etiologies, particularly for non-cardiac causes. More significantly, the decrease in RB-CPR was estimated to contribute to 10.7 excess deaths annually during the pandemic.
Conclusions: The findings highlight the importance of rescue breathing in pediatric OHCA. CO-CPR, while suitable for adults, may compromise outcomes in children. Emphasizing rescue breathing in pediatric resuscitation training and integrating infection control measures is essential for future public health emergencies. en-copyright= kn-copyright= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cardiopulmonary resuscitation kn-keyword=Cardiopulmonary resuscitation en-keyword=Out-of-hospital kn-keyword=Out-of-hospital en-keyword=Pediatrics kn-keyword=Pediatrics en-keyword=Artificial respiration kn-keyword=Artificial respiration en-keyword=COVID-19 pandemic kn-keyword=COVID-19 pandemic END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=8 article-no= start-page=e101809 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurological outcomes with hypothermia versus normothermia in patients with moderate initial illness severity following resuscitation from out-of-hospital cardiac arrest: protocol for a multicentre randomised controlled trial (R-CAST OHCA) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Temperature control is a fundamental intervention for neuroprotection following resuscitation from cardiac arrest. However, evidence regarding the efficacy of hypothermia in post-cardiac arrest syndrome (PCAS) remains unclear. Retrospective studies suggest that the clinical effectiveness of hypothermia may depend on the severity of PCAS. The R-CAST OHCA trial aims to compare the efficacy of hypothermia versus normothermia in improving 30-day neurological outcomes in patients with moderately severe PCAS following out-of-hospital cardiac arrest.
Methods and analysis The multicentre, single-blind, parallel-group, superiority, randomised controlled trial (RCT) is conducted with the participation of 35 emergency and critical care centres and/or intensive care units at academic and non-academic hospitals. The study enrols moderately severe PCAS patients, defined as those with a revised post-Cardiac Arrest Syndrome for induced Therapeutic Hypothermia score of 5.5?15.5. A target number of 380 participants will be enrolled. Participants are randomised to undergo either hypothermia or normothermia within 3?hours after return of spontaneous circulation. Patients in the hypothermia group are cooled and maintained at 34°C until 28 hours post-randomisation, followed by rewarming to 37°C at a rate of 0.25°C/hour. Patients in the normothermia group are maintained at normothermia (36.5°C?37.7°C). Total periods of intervention, including the cooling, maintenance and rewarming phases, will occur 40 hours after randomisation. Other treatments for PCAS can be determined by the treating physicians. The primary outcome is a favourable neurological outcome, defined as Cerebral Performance Category 1 or 2 at 30 days after randomisation and compared using an intention-to-treat analysis.
Ethics and dissemination This study has been approved by the Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, Ethics Committee (approval number: R2201-001). Written informed consent is obtained from all participants or their authorised surrogates. Results will be disseminated via publications and presentations.
Trial registration number jRCT1062220035. en-copyright= kn-copyright= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishikimiMitsuaki en-aut-sei=Nishikimi en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaYohei en-aut-sei=Okada en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaeyamaHiroki en-aut-sei=Maeyama en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KiguchiTakeyuki en-aut-sei=Kiguchi en-aut-mei=Takeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishidaKazuki en-aut-sei=Nishida en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuiShigeyuki en-aut-sei=Matsui en-aut-mei=Shigeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurodaYasuhiro en-aut-sei=Kuroda en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishiyamaKei en-aut-sei=Nishiyama en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwamiTaku en-aut-sei=Iwami en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=JAAM R-CAST OHCA Trial Group en-aut-sei=JAAM R-CAST OHCA Trial Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=3 en-affil=Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University kn-affil= affil-num=4 en-affil=Department of Emergency and Critical Care Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=5 en-affil=Division of Trauma and Surgical Critical Care, Osaka General Medical Center kn-affil= affil-num=6 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University kn-affil= affil-num=8 en-affil=Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University kn-affil= affil-num=9 en-affil=Emergency and Critical Care Center, TMG Asaka Medical Center kn-affil= affil-num=10 en-affil=Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science kn-affil= affil-num=11 en-affil=Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=10 article-no= start-page=e0332595 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship between obesity indices and cognitive function in Japanese men: A cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=We aimed to investigate the associations among various obesity indices, including visceral (VAT) and subcutaneous adipose tissue (SAT), and cognitive function in community-dwelling Japanese men. This population-based cross-sectional study used data of 853 men who participated in the follow-up examinations of the Shiga Epidemiological Study of Subclinical Atherosclerosis. Among them, we analyzed data of 776 men who completed the Cognitive Abilities Screening Instrument (CASI) and had abdominal VAT and SAT areas measured using computed tomography. The VAT-to-SAT ratio (VSR) was calculated; participants were categorized into VSR quartiles. Using analysis of covariance, we computed crude and adjusted means of the CASI total and domain scores across VSR quartiles, adjusting for potential confounders. No significant differences were observed in total CASI scores among body mass index, VAT, or SAT quartiles. However, in the multivariable-adjusted model, participants in the lowest VSR quartile (Q1) had significantly lower CASI total scores than those in the third quartile (Q3) (Q1: 89.5, Q3: 90.9). Low VSR was independently associated with lower cognitive function in a community-based sample of middle-aged and older Japanese men. In summary, VSR may be associated with cognitive function in Japanese men, highlighting the importance of fat distribution in cognitive health and highlighting VSR as a useful indicator. en-copyright= kn-copyright= en-aut-name=MatsunoSatoshi en-aut-sei=Matsuno en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OzekiYuji en-aut-sei=Ozeki en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadowakiSayaka en-aut-sei=Kadowaki en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ToriiSayuki en-aut-sei=Torii en-aut-mei=Sayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoKeiko en-aut-sei=Kondo en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyagawaNaoko en-aut-sei=Miyagawa en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimaAzusa en-aut-sei=Shima en-aut-mei=Azusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhashiMizuki en-aut-sei=Ohashi en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyazawaItsuko en-aut-sei=Miyazawa en-aut-mei=Itsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SegawaHiroyoshi en-aut-sei=Segawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KadotaAya en-aut-sei=Kadota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Psychiatry, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=Department of Psychiatry, Shiga University of Medical Science kn-affil= affil-num=3 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=4 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=5 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Department of Preventive Medicine and Public Health, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Clinical Nursing, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=9 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=11 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=38590 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. en-copyright= kn-copyright= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HanzawaShunya en-aut-sei=Hanzawa en-aut-mei=Shunya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KadowakiDaisuke en-aut-sei=Kadowaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhtaniTomoko en-aut-sei=Ohtani en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KumonKento en-aut-sei=Kumon en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle en-keyword=Liquid biopsy kn-keyword=Liquid biopsy en-keyword=Predictive biomarker kn-keyword=Predictive biomarker en-keyword=Stealth effect kn-keyword=Stealth effect END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and chemoresistance poses a significant challenge in its treatment. Neutrophil extracellular traps (NETs) have emerged as key players in the tumour microenvironment, but their role in chemoresistance remains unclear.
Methods: We investigated the involvement of NETs in PDAC chemoresistance using patient tumour samples, in vitro assays with gemcitabine (GEM)-treated PDAC cells, and in vivo mouse models. We evaluated cytokine production, NET formation and tumour response to GEM, with or without the CXCR1/2 inhibitor navarixin.
Results: NETs are significantly accumulated in the tumours of PDAC patients exhibiting poor response to chemotherapy. GEM-treated PDAC cells secrete pro-inflammatory cytokines such as interleukin-8 (IL-8). IL-8 promote the formation of chemotherapy-induced NETs (chemoNETosis) through activation of CXCR 1/2 on neutrophils. Importantly, treatment with navarixin significantly suppressed chemoNETosis, restored sensitivity to GEM, and significantly reduced tumour growth in vivo.
Conclusions: Our findings reveal that NETs contribute to chemoresistance in PDAC and that IL-8?mediated chemoNETosis plays a pivotal role in this process. Inhibition of CXCR1/2-mediated NET formation enhances the efficacy of GEM. This approach may represent a promising therapeutic strategy for overcoming chemoresistance in PDAC. These results support further clinical investigation of anti-NETs therapies. en-copyright= kn-copyright= en-aut-name=NogiShohei en-aut-sei=Nogi en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiAtsuki en-aut-sei=Taniguchi en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=13 article-no= start-page=CASE25483 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endovascular treatment for a symptomatic dissecting ophthalmic artery aneurysm occurring in the orbit: illustrative case en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND: Peripheral ophthalmic artery aneurysms (POAAs) arising from the main trunk or branches of the ophthalmic artery (OphA) are extremely rare. However, their epidemiology and optimal management remain poorly understood. The authors report a rare case of a symptomatic POAA caused by arterial dissection that was successfully treated using endovascular therapy, leading to favorable visual recovery.
OBSERVATIONS: A 77-year-old woman presented with sudden-onset visual impairment in the right eye. Ophthalmological examination revealed a defect in the right visual field. CT angiography revealed a fusiform aneurysm in the right intraorbital OphA. Digital subtraction angiography revealed a pearl and string sign, consistent with a dissecting aneurysm. A balloon test occlusion (BTO) of the OphA origin confirmed collateral circulation from the external carotid artery. Internal trapping of the OphA was performed under general anesthesia. Postoperatively, the patient’s visual function gradually improved, and complete recovery was achieved within 3 months.
LESSONS: Although POAAs are exceptionally rare, they may lead to significant visual dysfunction owing to optic nerve compression. When visual symptoms are present, prompt intervention may reverse the symptoms. Preoperative assessment of collateral circulation using BTO is essential for treatment planning. Internal trapping may be an effective strategy when sufficient collateral flow is confirmed. en-copyright= kn-copyright= en-aut-name=IzumiharaKohei en-aut-sei=Izumihara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HarumaJun en-aut-sei=Haruma en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BabaFukiko en-aut-sei=Baba en-aut-mei=Fukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujitaJuntaro en-aut-sei=Fujita en-aut-mei=Juntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SotomeYuta en-aut-sei=Sotome en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawakamiMasato en-aut-sei=Kawakami en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KimuraRyu en-aut-sei=Kimura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ophthalmic artery kn-keyword=ophthalmic artery en-keyword=dissecting aneurysm kn-keyword=dissecting aneurysm en-keyword=visual impairment kn-keyword=visual impairment en-keyword=endovascular treatment kn-keyword=endovascular treatment END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=33014 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250926 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=iTRAQ-based quantitative proteomics reveals reduced expression of KRT19, KRT7, and PTGDS in cutaneous specimens after kidney transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Clinical improvement in pigmentation is frequently observed after kidney transplantation. However, the underlying molecular and histological mechanisms remain unclear. We conducted a study to quantify the skin color change using a handheld reflected light colorimeter and to investigate protein expression changes in the skin before and after kidney transplantation. Paired skin biopsies were obtained from three patients who underwent kidney transplantation before and one month after transplantation. Protein expression was analyzed using iTRAQ-based quantitative proteomics. Differentially expressed proteins were identified and visualized using hierarchical clustering and volcano plots. Histopathological evaluation included hematoxylin and eosin (H&E), Masson’s trichrome, and immunohistochemical (IHC) staining for keratin (KRT) 7, KRT19, and MelanA. Skin pigmentation of the arms, ankles, and abdomen had significant L-value improvement after kidney transplantation. Proteomic profiling identified 2148 proteins, with six proteins showing significant differential expression after transplantation. Among them, KRT7, KRT19, and prostaglandin D2 synthase (PTGDS) were significantly downregulated, potentially reflecting reduced epithelial stress and systemic inflammation. H&E and Masson’s trichrome staining revealed a post-transplantation reduction in dermal pigmentation and collagen content. IHC showed decreased KRT7, KRT19, and MelanA expression after transplantation. Our results suggest that targeting KRT or prostaglandin pathways may offer new treatments for ESRD-related skin symptoms. en-copyright= kn-copyright= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic kn-affil= affil-num=6 en-affil=Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic kn-affil= affil-num=7 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Cutaneous manifestations kn-keyword=Cutaneous manifestations en-keyword=Keratin kn-keyword=Keratin en-keyword=Skin color kn-keyword=Skin color en-keyword=Pigmentation kn-keyword=Pigmentation en-keyword=Prostaglandin D2 synthase kn-keyword=Prostaglandin D2 synthase en-keyword=Renal transplantation kn-keyword=Renal transplantation en-keyword=Dialysis kn-keyword=Dialysis END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251006 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Netherton Syndrome/SPINK5-Syndromic Epidermal Differentiation Disorder Evaluated by Serial Tape-Stripping: Persistent Elevation of Serine Protease Activities Despite Clinical Improvement en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaAnri en-aut-sei=Morita en-aut-mei=Anri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HasuiKen‐Ichi en-aut-sei=Hasui en-aut-mei=Ken‐Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HondaHiroyuki en-aut-sei=Honda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=kallikrein-related peptidase kn-keyword=kallikrein-related peptidase en-keyword=lympho- epithelial Kazal-type-related inhibitor kn-keyword=lympho- epithelial Kazal-type-related inhibitor en-keyword=Netherton syndrome/SPINK5-syndromic epidermaldifferentiation disorder kn-keyword=Netherton syndrome/SPINK5-syndromic epidermaldifferentiation disorder en-keyword=RNA sequencing kn-keyword=RNA sequencing en-keyword=serine protease activity kn-keyword=serine protease activity en-keyword=tape-stripping kn-keyword=tape-stripping END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Admission prognostic nutritional index predicts prolonged hospitalization in severe odontogenic deep neck infections en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives Severe odontogenic deep neck infections (DNIs) can be life threatening. This study investigated the nutritional status of affected patients and evaluated the usefulness of the Prognostic Nutritional Index (PNI) at admission in helping maxillofacial surgeons identify, at presentation, those likely to require extended hospitalization.
Methods A total of 112 patients treated for odontogenic deep neck abscesses and necrotizing soft tissue infections at five hospitals in Japan. Patients were included. Patients were categorized by length of hospitalization duration and factors associated with prolonged hospitalization were analyzed using propensity score matching to minimize bias. Spearman’s rank correlation analysis was also performed to assess the relationship between PNI and hospitalization duration.
Results Fifty patients (44.6%) required hospitalization for more than 14 days. Multivariate analysis identified PNI???41.2 (odds ratio [OR]?=?2.79) and the presence of abscesses in multiple deep neck spaces (OR?=?2.76) as significant predictors of prolonged hospitalization. Propensity score analysis confirmed the significant association between PNI and length of hospitalization duration (P?=?0.048). In addition, Spearman’s rank correlation coefficient was r?=???0.471 (P? Conclusion The admission PNI may serve as a useful adjunctive indicator for predicting prolonged hospitalization in patients with severe odontogenic DNIs, as it reflects both nutritional status and systemic inflammation. en-copyright= kn-copyright= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikutaShogo en-aut-sei=Kikuta en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanekoNaoki en-aut-sei=Kaneko en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKotaro en-aut-sei=Sato en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitagawaNorio en-aut-sei=Kitagawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuoKatsuhisa en-aut-sei=Matsuo en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SameshimaJunsei en-aut-sei=Sameshima en-aut-mei=Junsei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TachibanaAkira en-aut-sei=Tachibana en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawanoShintaro en-aut-sei=Kawano en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KusukawaJingo en-aut-sei=Kusukawa en-aut-mei=Jingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AkashiMasaya en-aut-sei=Akashi en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=4 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=9 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital kn-affil= affil-num=11 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=12 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=15 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Odontogenic deep neck infections kn-keyword=Odontogenic deep neck infections en-keyword=Nutrition status kn-keyword=Nutrition status en-keyword=Prognostic nutritional index kn-keyword=Prognostic nutritional index en-keyword=Prolonged hospitalization kn-keyword=Prolonged hospitalization en-keyword=Multiple spaces with abscess kn-keyword=Multiple spaces with abscess END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Upgrading Recycle Technology for Iron Removal in ADC12 Alloy Using Gravity and Magnetic Force en-subtitle= kn-subtitle= en-abstract= kn-abstract=As there is a technical issue to remove iron elements during aluminum recycling process, an attempt was made to evaluate the effectiveness of magnetic and gravitational separation methods for removing iron from Al-Si-Cu alloy (ADC12). A rare-earth samarium?cobalt (SmCo) magnet was employed during the solidification process to attract Fe-rich eutectic structures. The microstructural analysis revealed that block-like Fe-Cr-Si-based phases formed preferentially near the magnet and at the bottom of the crucible, suggesting that magnetic and gravity attraction contributed to the localized segregation of these phases. However, other Fe-based phases, including Fe-Si-based ones, are not strongly affected by magnet. Additionally, prolonged heating in the solid?liquid coexistence (SLC) region at 577 °C for 10 h led to the settling of a largely grown Fe-Cr-Si-rich crystal at the bottom of the crucible due to gravity. Other structures, such as Si-rich eutectic phases, were not influenced by gravity, which may be caused by the low density of Si compared to Fe one. From this approach, combining magnetic attraction and gravitational settling is a promising method to promote the removal of iron impurities from aluminum alloys. en-copyright= kn-copyright= en-aut-name=OkayasuM. en-aut-sei=Okayasu en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiS. en-aut-sei=Takeuchi en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SyahidM. en-aut-sei=Syahid en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkedaT. en-aut-sei=Ikeda en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Mechanical Systems and Engineering, Okayama University kn-affil= affil-num=2 en-affil=Department of Mechanical Systems and Engineering, Okayama University kn-affil= affil-num=3 en-affil=Department of Mechanical Engineering, Hasanuddin University kn-affil= affil-num=4 en-affil=Department of Mechanical Systems and Engineering, Okayama University kn-affil= en-keyword=aluminum alloy kn-keyword=aluminum alloy en-keyword=upgrade recycle kn-keyword=upgrade recycle en-keyword=iron kn-keyword=iron en-keyword=microstructure kn-keyword=microstructure en-keyword=mechanical property kn-keyword=mechanical property END start-ver=1.4 cd-journal=joma no-vol=281 cd-vols= no-issue= article-no= start-page=111174 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=N-terminal domains and site-specific glycosylation regulate the secretion of avian melanocortin inverse agonists, agouti signaling protein (ASIP) and agouti-related protein (AGRP) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Agouti signaling protein (ASIP) and agouti-related protein (AGRP) are paralogous inverse agonists of melanocortin receptors with distinct physiological roles, but their structural and biochemical properties in birds remain poorly understood. Here, we characterized chicken ASIP and AGRP proteins. Analysis of available sequences revealed that a motif resembling the mammalian proprotein convertase 1/3 (PC1/3, also known as PCSK1) cleavage site is conserved across a broad range of avian orders, but Western blot analysis of transfected Chinese hamster ovary (CHO-K1) cells and chicken hypothalamus detected no cleavage, suggesting that avian AGRP may not be post-translationally processed at this site. Chicken ASIP mRNA contains an in-frame upstream ATG (uATG) and a putative N-linked glycosylation site at Asn-42, both conserved across multiple avian orders. Overexpression in CHO-K1 cells showed that ASIP translated from either ATG produces a mature protein of the same size that is N-glycosylated at Asn-42 and exhibits markedly lower secretion efficiency than AGRP. Domain-swapping experiments revealed that the N-terminal domain reduces secretion, whereas a naturally occurring ASIP-b variant with an additional N-glycan at Asn-47 shows enhanced secretion. Proteasome inhibition increased intracellular ASIP, and endoglycosidase H (Endo H) sensitivity indicated endoplasmic reticulum (ER) retention, suggesting that the N-terminal domain limits secretion via ER-associated proteasomal degradation. These findings reveal species-specific post-translational regulation of avian melanocortin inverse agonists, in which N-terminal features and site-specific N-glycosylation determine secretion efficiency, likely contributing to their distinct roles in pigmentation and hypothalamic energy balance. en-copyright= kn-copyright= en-aut-name=FukuchiHibiki en-aut-sei=Fukuchi en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeRyoya en-aut-sei=Watanabe en-aut-mei=Ryoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IidaYuna en-aut-sei=Iida en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakanoSaya en-aut-sei=Nakano en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MizutaniAya en-aut-sei=Mizutani en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AboTatsuhiko en-aut-sei=Abo en-aut-mei=Tatsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Agouti signaling protein kn-keyword=Agouti signaling protein en-keyword=Agouti-related protein kn-keyword=Agouti-related protein en-keyword=Avian melanocortin inverse agonists kn-keyword=Avian melanocortin inverse agonists en-keyword=Post-translational modification kn-keyword=Post-translational modification en-keyword=N-linked glycosylation kn-keyword=N-linked glycosylation en-keyword=Protein secretion kn-keyword=Protein secretion END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=11 article-no= start-page=1680 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251029 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Kidney Organoids: Current Advances and Applications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Kidney organoids, derived from stem cells, including pluripotent stem cells and adult progenitor cells, have been reported as three-dimensional in vitro models that reflect key aspects of kidney development, structure, and function. Advances in differentiation protocols and tissue engineering have enabled the generation of organoids that exhibit nephron-like structures, including glomerular and tubular structures. Kidney organoids have been widely applied in several directions, including disease modeling and therapeutic screening, drug nephrotoxicity evaluation, and regenerative medicine. In particular, kidney organoids offer a promising platform for studying genetic kidney diseases, such as polycystic kidney disease and congenital anomalies of the kidney and urinary tract (CAKUT), by allowing patient-specific modeling for the analysis of pathophysiology and therapeutic screening. Despite several current limitations, such as incomplete maturation, lack of full nephron segmentation, and variability between protocols and cell conditions, further technological innovations such as microfluidics and bioengineering may refine kidney organoid systems. This review highlights recent advances in kidney organoid research, outlines major applications, and discusses future directions to enhance their physiological relevance, functional maturity, and translational integration into preclinical and clinical nephrology. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=kidney organoid kn-keyword=kidney organoid en-keyword=stem cell kn-keyword=stem cell en-keyword=disease modeling kn-keyword=disease modeling en-keyword=drug toxicity kn-keyword=drug toxicity en-keyword=drug screening kn-keyword=drug screening en-keyword=regenerative medicine kn-keyword=regenerative medicine END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=e92587 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Intranasal Administration of Semaphorin 3A Inhibitor in a Mouse Model of Olfactory Disorder en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the effects of intranasal administration of a semaphorin 3A inhibitor (Sema3A-I) in a mouse model of olfactory disorder, where olfactory sensory neuron (OSN) axons had been severely damaged. We performed axotomy (transection of OSN axons) of the OSNs in mice and administered Sema3A?I intranasally to seven mice and saline to another seven mice. Following treatment, we assessed the thickness of the olfactory epithelium and the regeneration ratio of OSN axons. Intranasal administration of Sema3A-I did not significantly promote OSN regeneration, axonal outgrowth, or improve axonal projection compared to saline administration. Although Sema3A-I administration showed some promotion of axonal outgrowth, the difference was not statistically significant. Continuous subcutaneous administration of Sema3A-I in rats after axotomy promotes OSN regeneration and axonal outgrowth. Given that intranasal administration is minimally invasive, we believe that it may still be a feasible route when combined with additional treatment strategies. Further investigation into administration methods and therapeutic combinations is warranted. en-copyright= kn-copyright= en-aut-name=MuraiAya en-aut-sei=Murai en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NodaMinori en-aut-sei=Noda en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimizuAiko en-aut-sei=Shimizu en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaharaJunko en-aut-sei=Takahara en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Technical Support for Medical Science, Department of Comprehensive Technical Solutions, Okayama University kn-affil= affil-num=5 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University kn-affil= en-keyword=axon growth kn-keyword=axon growth en-keyword=intranasal administration kn-keyword=intranasal administration en-keyword=olfactory disorder kn-keyword=olfactory disorder en-keyword=olfactory sensory neurons kn-keyword=olfactory sensory neurons en-keyword=semaphorin3a kn-keyword=semaphorin3a END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=10 article-no= start-page=1483 end-page=1493 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biologics and Small‐Molecule Therapies in Netherton Syndrome: A Comprehensive Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Netherton syndrome (NS) is a rare congenital ichthyosis caused by loss-of-function mutations in the SPINK5 gene, leading to defective expression of the serine protease inhibitor LEKTI. Dysregulated epidermal protease activity results in impaired skin barrier function and chronic inflammation, accompanied by complex immune profiles. NS patients commonly show activation of the inflammatory axis, centered on IL-17 and IL-36, in the skin and blood, and show a psoriasis-like shift to Th17. Conversely, the immune profile differs depending on the clinical type, with ichthyosis linearis circumflexa type characterized by complement activation and Th2-type allergic responses, and scaly erythroderma type characterized by a type I IFN signature and Th9-type allergic responses. While symptomatic treatments such as emollients and topical corticosteroids have been the mainstay of care, recent advances have opened new therapeutic avenues involving biologic agents and oral small-molecule immunomodulators. This review provides a comprehensive overview of the current clinical landscape and future directions of biologics (e.g., dupilumab, secukinumab, ustekinumab) and small-molecule therapies (e.g., JAK inhibitors such as tofacitinib, baricitinib, and upadacitinib) in the treatment of NS. Though evidence remains limited to case reports and small series, preliminary data suggest that cytokine-targeted interventions?particularly those inhibiting IL-4, IL-13, IL-17, IL-36, and JAK pathways?may offer tangible clinical benefits. Well-designed clinical trials and mechanistic investigations are crucial to establishing their place in NS management. en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasuiKen‐ichi en-aut-sei=Hasui en-aut-mei=Ken‐ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaAnri en-aut-sei=Morita en-aut-mei=Anri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=20 article-no= start-page=3351 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tertiary Lymphoid Structures Are Associated with Favorable Clinical Outcomes and Negatively Correlated with Cancer-Associated Fibroblasts in Esophageal Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Esophageal cancer remains a highly aggressive malignant tumor with poor prognosis, despite advances in combination therapies and novel immunotherapies. Tertiary lymphoid structures (TLSs), characterized by densely packed CD20+ B cells in a germinal-center-like structure, have recently been recognized as immune-stimulating components within the tumor microenvironment. In contrast, cancer-associated fibroblasts (CAFs) are stromal cells expressing fibroblast-activating protein (FAP) involved in immunosuppression. Methods: In this retrospective study, 124 clinical samples from patients who underwent radical surgery for esophageal cancer at our institute were analyzed. We investigated whether TLSs could serve as a prognostic factor and examined their association with tumor microenvironment factors. Results: The presence of TLSs was an independent prognostic factor for overall and progression-free survival in multivariate analyses. A high level of TLS formation correlated with better nutritional status, fewer M2 macrophages, and greater plasma cell infiltration. Additionally, little TLS formation was observed in areas with abundant CAFs, and quantitative analyses revealed a significant negative correlation between TLSs and CAFs. Conclusions: TLSs enhance antitumor immunity via macrophages and plasma cells and can be a valuable prognostic indicator in patients undergoing surgery for esophageal cancer. Targeting CAFs may prove to be a promising therapeutic strategy to enhance tumor-immunity-related TLSs. en-copyright= kn-copyright= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiTatsuya en-aut-sei=Takahashi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkaiMasaaki en-aut-sei=Akai en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=tertiary lymphoid structures (TLSs) kn-keyword=tertiary lymphoid structures (TLSs) en-keyword=cancer-associated fibroblasts (CAFs) kn-keyword=cancer-associated fibroblasts (CAFs) en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=prognosis kn-keyword=prognosis END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=e70318 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ??2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n?=?510), statin use was associated with a significantly lower incidence of Grade ??2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p?=?0.029). Our findings indicate that statins may protect against OIPN in patients with CRC. en-copyright= kn-copyright= en-aut-name=TakechiKenshi en-aut-sei=Takechi en-aut-mei=Kenshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawashiriTakehiro en-aut-sei=Kawashiri en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MineKeisuke en-aut-sei=Mine en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HidaNoriko en-aut-sei=Hida en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MomoKenji en-aut-sei=Momo en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaMasanobu en-aut-sei=Uchiyama en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaMami en-aut-sei=Uchida en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaMamoru en-aut-sei=Tanaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HidakaNoriaki en-aut-sei=Hidaka en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuiHideki en-aut-sei=Yasui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UedaMasahiro en-aut-sei=Ueda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiRyohei en-aut-sei=Fujii en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HashimotoMisaki en-aut-sei=Hashimoto en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakamotoYasutaka en-aut-sei=Sakamoto en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UyamaKana en-aut-sei=Uyama en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HanaiYuki en-aut-sei=Hanai en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TsuboyaAyaka en-aut-sei=Tsuboya en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SuzukiKeisuke en-aut-sei=Suzuki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KamiyamaNaoya en-aut-sei=Kamiyama en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HagiwaraHiromi en-aut-sei=Hagiwara en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OkadaNaoto en-aut-sei=Okada en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Research and Development, Graduate School of Pharmacy, SHOWA Medical University kn-affil= affil-num=7 en-affil=Department of Hospital Pharmaceutics, Graduate School of Pharmacy, SHOWA Medical University kn-affil= affil-num=8 en-affil=Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Fukuoka University Hospital kn-affil= affil-num=10 en-affil=Division of Pharmacy, Ehime University Hospital kn-affil= affil-num=11 en-affil=Division of Pharmacy, Ehime University Hospital kn-affil= affil-num=12 en-affil=Center for Clinical Research, Hamamatsu University Hospital kn-affil= affil-num=13 en-affil=Faculty of Pharmaceutical Sciences, Setsunan University kn-affil= affil-num=14 en-affil=Department of Pharmacy, Kansai Medical University Hospital kn-affil= affil-num=15 en-affil=Department of Pharmacy, Kansai Medical University Hospital kn-affil= affil-num=16 en-affil=Department of Pharmacy, Yokohama City University Hospital kn-affil= affil-num=17 en-affil=Department of Pharmacy, Yokohama City University Hospital kn-affil= affil-num=18 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=19 en-affil=Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University kn-affil= affil-num=20 en-affil=Department of Pharmacy, Kawasaki Municipal Tama Hospital kn-affil= affil-num=21 en-affil=Innovation Center for Translational Research, National Center for Geriatrics and Gerontology kn-affil= affil-num=22 en-affil=Asahikawa Medical University Hospital kn-affil= affil-num=23 en-affil=Nagoya City University Hospital kn-affil= affil-num=24 en-affil=Pharmacy Department, Yamaguchi University Hospital kn-affil= affil-num=25 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=26 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= en-keyword=cancer kn-keyword=cancer en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=oxaliplatin kn-keyword=oxaliplatin en-keyword=peripheral neuropathy kn-keyword=peripheral neuropathy en-keyword=statins kn-keyword=statins END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=e88699 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevalence of Locomotive Syndrome in Perioperative Patients With Localized Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
Many patients with cancer experience reduced activities of daily living due to muscle weakness and fatigue caused by underlying symptoms and treatment side effects. However, the incidence of locomotive syndrome, which may reduce mobility due to motor dysfunction in patients with cancer, has not been sufficiently explored. Therefore, we aimed to investigate the incidence of locomotive syndrome and identify its risk factors in perioperative patients with cancer.

Methods
We included 636 perioperative patients with localized cancer who were treated between 2020 and 2023. The severity of locomotive syndrome was classified into stages 1, 2, and 3.

Results
The overall locomotive syndrome rate was 88.1%, with distribution across stages: stage 1 (56.8%), stage 2 (17.5%), and stage 3 (13.8%). Among men, the overall incidence was 86.5%, with stage 1 (60.3%), stage 2 (15.5%), and stage 3 (10.7%). Among women, the overall incidence was 90.6%, with stage 1 (50.6%), stage 2 (20.9%), and stage 3 (19.1%). Half of patients in their 20s and two-thirds in their 30s had locomotive syndrome. The rates were 58.6%, 80.4%, 81.8%, 93.2%, and 97.8% in the 40s, 50s, 60s, 70s, and 80s age groups, respectively. Individuals in their 40s had significantly lower rates than those in older groups. Age, grip strength, and percent vital capacity were identified as risk factors.

Conclusion
A high prevalence of locomotive syndrome was observed among patients with localized cancer. Age, reduced grip strength, and lower respiratory capacity were identified as associated factors. While the findings suggest possible implications for postoperative recovery, further validation through longitudinal studies is required. en-copyright= kn-copyright= en-aut-name=KatayamaYoshimi en-aut-sei=Katayama en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkezakiYoshiteru en-aut-sei=Akezaki en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Physical Therapy, Kochi Professional University of Rehabilitation kn-affil= affil-num=5 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= en-keyword=aging kn-keyword=aging en-keyword=cancer kn-keyword=cancer en-keyword=locomotive syndrom kn-keyword=locomotive syndrom en-keyword=muscle strength kn-keyword=muscle strength en-keyword=perioperative system kn-keyword=perioperative system en-keyword=physical function kn-keyword=physical function en-keyword=risk factors kn-keyword=risk factors END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=5 article-no= start-page=e200293 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vanishing White Matter Disease With EIF2B2 c.254T >A Variant en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives
Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges.
Methods
We describe 2 of 3 individuals carrying the homozygous c.254T >A variant in EIF2B2 identified at our hospital, excluding 1 previously reported case.1 Genetic analyses were performed using whole-genome sequence or whole-exome sequence analysis, and detected variants were confirmed by direct nucleotide sequence analysis. Brain MRI findings and clinical features were reviewed for the 2 individuals along with other cases in the literature with the same variant.
Results
A 69-year-old woman presented with recurrent transient dizziness and secondary amenorrhea. MRI of the brain revealed small T2-hyperintense lesions confined to the subcortical white matter with hyperintensities on diffusion-weighted images and mildly elevated apparent diffusion coefficient values. A 28-year-old woman presented with transient dizziness and secondary amenorrhea. MRI of the brain showed mild T2-hyperintense lesions in the cerebral white matter with frontal predominance.
Discussion
This report highlights the clinically mild cases of VWM with subtle abnormalities on brain MRI who had the homozygous c.254T >A in EIF2B2, further expanding the clinical spectrum of VWM and underscoring the importance of genetic assessments in the diagnosis of individuals with mild clinical and MRI findings. en-copyright= kn-copyright= en-aut-name=KakumotoToshiyuki en-aut-sei=Kakumoto en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokimuraRyo en-aut-sei=Tokimura en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboyamaYoko en-aut-sei=Tsuboyama en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HayashiYasufumi en-aut-sei=Hayashi en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataAtsushi en-aut-sei=Iwata en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaMeiko Hashimoto en-aut-sei=Maeda en-aut-mei=Meiko Hashimoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimizuJun en-aut-sei=Shimizu en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GonoiWataru en-aut-sei=Gonoi en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=417 end-page=431 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of?a?Startup Program Identification for?Efficient and?Accurate IoT Security Investigations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Not all file in firmware are executed while using Internet of Things (IoT) devices and hundreds to approximately a thousand executable and linkable format files exist in one firmware. Therefore, security investigations without prioritization may lead to investigate programs that are not executed while using IoT devices first. This has resulted in inefficient security investigations. To perform efficient security investigations, we proposed a method that can identify programs executed during the startup process. However, only two firmware were used for the evaluation which can only evaluate one of the two startup sequences in the OpenWrt-based firmware. In addition, security investigations to validate whether the proposed method addresses the problem of inefficient security investigations were limited to OpenWrt-based firmware. In this study, we use more firmware data for evaluation and validation. We use nine firmware not used in previous studies including startup methods that have not previously been used for evaluation. In addition, we increase the number of firmware used for validation to 225. The evaluation results demonstrate that the proposed method can identify with only few false positives. The validation demonstrates that efficiency can be improved and prioritizing investigations by considering the proposed method result is worthwhile. en-copyright= kn-copyright= en-aut-name=ShimamotoYuta en-aut-sei=Shimamoto en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PhinyodomJiratchaya en-aut-sei=Phinyodom en-aut-mei=Jiratchaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshimotoRyota en-aut-sei=Yoshimoto en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UekawaHiroyuki en-aut-sei=Uekawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkiyamaMitsuaki en-aut-sei=Akiyama en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=School of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=NTT Social Informatics Laboratories kn-affil= affil-num=5 en-affil=NTT Social Informatics Laboratories kn-affil= affil-num=6 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Internet of Things kn-keyword=Internet of Things en-keyword=Firmware kn-keyword=Firmware en-keyword=Startup script kn-keyword=Startup script en-keyword=SysVinit kn-keyword=SysVinit END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=20 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Natural Effects and Separable Effects: Insights into Mediation Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose of Review We compare natural effects and separable effects under nonparametric structural equation models with independent errors, highlighting their similarities and differences. By examining their required properties and sufficient conditions for identification, we aim to provide deeper insights into mediation analysis.
Recent Findings If certain assumptions about confounding, positivity, and consistency are met, we can identify natural direct and indirect effects under nonparametric structural equation models with independent errors. However, these effects have been criticized because they rely on a specific cross-world quantity, and the so-called cross-world independence assumption cannot be empirically verified. Furthermore, interventions on the mediator may sometimes be challenging to even conceive. As an alternative approach, separable effects have recently been proposed and applied in mediation analysis, often under finest fully randomized causally interpretable structured tree graph models. These effects are defined without relying on any cross-world quantities and are claimed to be identifiable under assumptions that are testable in principle, thereby addressing some of the challenges associated with natural direct and indirect effects.
Summary To conduct meaningful mediation analysis, it is crucial to clearly define the research question of interest, and the choice of methods should align with the nature of the question and the assumptions researchers are willing to make. Examining the underlying philosophical perspectives on causation and manipulation can provide valuable insights. en-copyright= kn-copyright= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShinozakiTomohiro en-aut-sei=Shinozaki en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoEiji en-aut-sei=Yamamoto en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Interfaculty Initiative in Information Studies, the University of Tokyo kn-affil= affil-num=3 en-affil=Okayama University of Science kn-affil= en-keyword=Causality kn-keyword=Causality en-keyword=Counterfactuals kn-keyword=Counterfactuals en-keyword=Cross-world independence assumption kn-keyword=Cross-world independence assumption en-keyword=Directed acyclic graphs kn-keyword=Directed acyclic graphs en-keyword=Mediation analysis kn-keyword=Mediation analysis en-keyword=Nonparametric structural equation models with independent errors kn-keyword=Nonparametric structural equation models with independent errors END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of flight behaviors among laboratory and field strains in Tribolium castaneum (Coleoptera: Tenebrionidae) using a simple method to measure flight ability en-subtitle= kn-subtitle= en-abstract= kn-abstract=Most insects can fly. The acquisition of flight is a factor that allows insects to prosper on Earth. On the other hand, in the same species and population, individual differences in flight ability may occur. Flight ability can vary due to geographical conditions and cumulative rearing. Investigating these changes in flight performance is important for understanding dispersal polymorphism and the evolution of flight performance. Thus, in the present study, the flight behaviors between cumulative rearing and field strains and changes in flight behaviors between strains of the red flour beetle, Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), which is distributed around the world were compared. Tribolium castaneum is a worldwide pest of stored grains. Its body length is about 3?4 mm. Previous studies have investigated the influence of environmental and physiological factors on the flight of this species, but no studies have examined individual differences or polymorphism in flight behaviors within this species. In this study, we developed a simple apparatus that can quantify the flight behavior of this species. The experimental apparatus was set up as a double structure with two different size containers. This apparatus was able to assess the flight activity of insects by counting individuals in a big container because insects transfer to the big container only by flight. Moreover, upward flight ability was possible to be assessed by the apparatus adding the barrier. Then, the flight behavior was compared between strains of this species that have been bred in the laboratory for more than 45 years and several strains of this species collected in the field. The results showed no variation in flight activity between strains, but flying ability was higher in strains originating from warmer regions. Here, we discussed the variations in flight behavior of T. castaneum. en-copyright= kn-copyright= en-aut-name=SoneSota en-aut-sei=Sone en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environment, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Dispersal kn-keyword=Dispersal en-keyword=Flight behavior kn-keyword=Flight behavior en-keyword=Red flour beetle kn-keyword=Red flour beetle en-keyword=Upward flight kn-keyword=Upward flight END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e95411 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary Lacrimal Sac Diffuse Large B-cell Lymphoma Treated With Local Radiotherapy Alone: A Case With No Relapse After 21 Years of Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary lacrimal sac lymphoma is rare and diagnosed as diffuse large B-cell lymphoma in a predominant histopathological type. Systemic chemotherapy would be the standard of care, but local radiotherapy may be a treatment option toward a localized lesion. The present patient is a 54-year-old otherwise healthy woman with a right lacrimal sac mass, which was proven by excisional biopsy to be diffuse large B-cell lymphoma. Since she did not have any other systemic lesions on gallium scintigraphy and neck-to-abdominal computed tomography scans, which were the standard procedure at that time, she underwent local radiotherapy at 40 Gy. Two years later, at the age of 56 years, she developed radiation retinopathy with macular edema in the right eye and had spotty laser photocoagulation in the nasal half of the fundus. At the age of 57 years, she developed radiation cataract and underwent cataract surgery with intraocular lens implantation in the right eye. At the age of 58 years, the macular edema in the right eye became worse and remained active, resulting in poor visual acuity of 0.1. She thus underwent 25-gauge vitrectomy in the right eye to peel off the adhering posterior vitreous surface, together with the internal limiting membrane, as the standard procedure at that time. The visual acuity in the right eye was elevated to 0.6. She maintained the visual acuity afterward and had no relapse of lymphoma in 21 years from the diagnosis of primary right lacrimal sac diffuse large B-cell lymphoma. Local radiotherapy would still be a treatment option for localized lymphoma lesions such as primary lacrimal sac lymphoma. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakemotoMitsuhiro en-aut-sei=Takemoto en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Radiotherapy, Himeji Red Cross Hospital kn-affil= en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=excisional biopsy kn-keyword=excisional biopsy en-keyword=lacrimal sac kn-keyword=lacrimal sac en-keyword=laser photocoagulation kn-keyword=laser photocoagulation en-keyword=macular edema kn-keyword=macular edema en-keyword=pathology kn-keyword=pathology en-keyword=radiation cataract kn-keyword=radiation cataract en-keyword=radiation retinopathy kn-keyword=radiation retinopathy en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=vitrectomy kn-keyword=vitrectomy END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=20 article-no= start-page=3287 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Neoadjuvant Chemotherapy with Gemcitabine Plus S-1 in Patients with Resectable Pancreatic Ductal Adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Although neoadjuvant chemotherapy (NAC) is not universally recommended for resectable pancreatic ductal adenocarcinoma (PDAC), NAC with gemcitabine plus S-1 (NAC-GS) has become a commonly used regimen for resectable PDAC in Japan. Furthermore, the impact of achieving textbook outcomes (TO) in patients receiving NAC-GS remains unclear. Methods: This retrospective study included 265 patients who were diagnosed with resectable PDAC at our institution between January 2009 and December 2023. Patients were categorized into two groups: the NAC-GS group (n = 81; 2019?2023) and the upfront surgery (UFS) group (n = 164; 2009?2018). After comparing the clinical outcomes between groups, multivariate analyses for survival were performed. Additionally, outcomes stratified by the achievement of the modified TO were analyzed in the NAC-GS group. Results: The completion rate of NAC-GS was 90.1%. Patients in the NAC-GS group exhibited significantly longer survival than those in the UFS group (2-year recurrence-free survival: 61.4% vs. 37.9%, p < 0.01; 2-year overall survival: 83.2% vs. 61.2%, p < 0.01). Multivariate analyses identified lymph node metastasis, NAC-GS induction, and completion of adjuvant chemotherapy as factors significantly associated with improved survival. Moreover, among patients who received NAC-GS, those who achieved modified TO demonstrated significantly longer survival than those who did not. Conclusions: This study demonstrated the clinical efficacy of NAC-GS in patients with resectable PDAC. Induction of NAC-GS was significantly associated with improved long-term outcomes. In multidisciplinary treatment strategies for PDAC, achieving a modified TO may lead to improved survival of patients undergoing NAC-GS. en-copyright= kn-copyright= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=neoadjuvant chemotherapy kn-keyword=neoadjuvant chemotherapy en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=resectable kn-keyword=resectable en-keyword=textbook outcome kn-keyword=textbook outcome END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=3 article-no= start-page=215 end-page=227 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Root-exuded sugars as drivers of rhizosphere microbiome assembly en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sugars in root exudates play a pivotal role in shaping plant-microbe interactions in the rhizosphere, serving as carbon sources and signaling molecules that orchestrate microbial behavior, community structure, and plant resilience. Recent research has shed light on the dynamics of sugar levels in root exudates, the factors that influence their secretion, and the mechanisms by which these sugars drive microbial colonization and community assembly in the rhizosphere. Microbial communities, in turn, contribute to plant physiological changes that enhance growth and stress tolerance. While well-studied sugars such as glucose, sucrose, and fructose are known to promote chemotaxis, motility, and biofilm formation, emerging evidence suggests that less-studied sugars like arabinose and trehalose may also play significant roles in microbial interactions and stress resilience. Key challenges remain, including the accurate measurement of labile sugars that are rapidly metabolized by microbes, and the elucidation of genetic mechanisms underlying rhizosphere metabolic interactions in both host plants and microbes. Addressing these challenges will advance our understanding of sugar-mediated interactions and inform the development of sustainable agricultural innovations. en-copyright= kn-copyright= en-aut-name=HemeldaNiarsi Merry en-aut-sei=Hemelda en-aut-mei=Niarsi Merry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Biology, Faculty of Mathematics and Natural Sciences, University of Indonesia kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=carbon sources kn-keyword=carbon sources en-keyword=plant-derived sugars kn-keyword=plant-derived sugars en-keyword=plant-microbe interactions kn-keyword=plant-microbe interactions en-keyword=rhizosphere kn-keyword=rhizosphere en-keyword=root exudate kn-keyword=root exudate END start-ver=1.4 cd-journal=joma no-vol=108 cd-vols= no-issue= article-no= start-page=104508 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Introduction to the “Japanese and Western approaches to psychotrauma” symposium en-subtitle= kn-subtitle= en-abstract= kn-abstract=Understandings of psychotrauma have changed throughout medical history, shaped by cultural and social factors. Reviewing transcultural perspectives of psychotrauma helps understand its complexities and contextual impacts. This paper summarizes the Japan?Netherlands symposium on psychotrauma held on March 1, 2024. Despite experiencing psychological trauma from World War II and numerous natural disasters, Japan did not actively research post-traumatic stress disorder (PTSD) for nearly 50 years after the war. The Great Hanshin-Awaji Earthquake and the Tokyo subway Sarin gas attack (1995) popularized the term PTSD in Japan and triggered related research. The absence of psychotrauma research in Japan may reflect a form of state-level PTSD, characterized by avoidance. Japan’s collectivist culture, stigma against seeking psychological help, view of patience as a virtue, survivor guilt, and moral injury were potential related factors. Additionally, sociocultural factors (e.g., insufficient collective grieving and focusing on post-war reconstruction) were discussed as potential hinderances to discussing war experiences. From a European perspective, we examined how “Konzentrationslager” (KZ) syndrome, a trauma-related disorder, evolved independently into diverse conceptual frameworks, ultimately contributing to the acceptance of PTSD following its introduction in 1980. Beyond state compensation for concentration camp survivors, advocacy by feminist movements and veterans' groups increased awareness of psychotrauma across Europe, fostering scholarly research and public discourse. Both PTSD and KZ syndromes are diagnostic categories shaped by specific historical and cultural contexts and should not be regarded as simple, universally applicable medical conditions. They reflect how trauma is interpreted and responded to differently depending on cultural, political, and historical factors. en-copyright= kn-copyright= en-aut-name=NagamineMasanori en-aut-sei=Nagamine en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaoTomoyo en-aut-sei=Nakao en-aut-mei=Tomoyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=van BergenLeo en-aut-sei=van Bergen en-aut-mei=Leo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShigemuraJun en-aut-sei=Shigemura en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoTaku en-aut-sei=Saito en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=van der DoesFlorentine H.S. en-aut-sei=van der Does en-aut-mei=Florentine H.S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitanoMasato en-aut-sei=Kitano en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GiltayErik J. en-aut-sei=Giltay en-aut-mei=Erik J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=van der WeeNic J. en-aut-sei=van der Wee en-aut-mei=Nic J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=VermettenEric en-aut-sei=Vermetten en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Behavioral Science, National Defense Medical College Research Institute kn-affil= affil-num=2 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=3 en-affil=Freelance Medical Historian kn-affil= affil-num=4 en-affil=Faculty of Health Sciences, Mejiro University kn-affil= affil-num=5 en-affil=Division of Behavioral Science, National Defense Medical College Research Institute kn-affil= affil-num=6 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= affil-num=7 en-affil=Division of Behavioral Science, National Defense Medical College Research Institute kn-affil= affil-num=8 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= affil-num=9 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= affil-num=10 en-affil=Department of Psychiatry, Leiden University Medical Center (LUMC) kn-affil= en-keyword=Psychotrauma kn-keyword=Psychotrauma en-keyword=World War II kn-keyword=World War II en-keyword=Japan kn-keyword=Japan en-keyword=Europe kn-keyword=Europe en-keyword=KZ syndrome kn-keyword=KZ syndrome en-keyword=Post-traumatic stress disorder kn-keyword=Post-traumatic stress disorder END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=399 end-page=404 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epstein-Barr Virus-Associated Early Gastric Carcinoma with Lymphoid Stroma Mimicking a Submucosal Tumor: A Typical Case Diagnosed by Endoscopic Resection and Treated by Local Resection with Sentinel Node Navigation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastric cancer with lymphoid stroma (GCLS) accounts for 1%-7% of gastric cancers; ~80% are Epstein-Barr virus (EBV)-positive. The rate of lymph node metastasis is relatively low, even when an early GCLS has invaded the submucosa. We report an early GCLS with massive submucosal invasion mimicking a submucosal tumor (SMT), diagnosed by endoscopic submucosal resection (ESD) and treated with local resection and sentinel node navigation surgery (SNNS). The patient was a 40-year-old Japanese man. A protruding lesion on the greater curvature of the middle part of his stomach was detected by X-ray, and an endoscopic examination revealed a 2.5-cm protruding tumor covered with a normal mucosa and small ulcers at the apex. ESD was performed for a diagnosis. The pathological diagnosis was lymphoepithelioma-like gastric cancer (GCLS), pT1b(SM2), Ly0, V0, pHM1, pVM1. EBV infection in the cancer cells was confirmed pathologically by EBV-encoded RNA. The local resection was performed using SNNS. The patient has had no recurrence or post-gastrectomy syndrome 4 years postsurgery. EBV-associated early GCLS resembling an SMT is relatively rare, and clinicians need to be aware of this disease. Local resection using SNNS may be a surgical option for GCLS cases with a low rate of lymphatic metastasis. en-copyright= kn-copyright= en-aut-name=IsozakiHiroshi en-aut-sei=Isozaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoSasau en-aut-sei=Matsumoto en-aut-mei=Sasau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakamaTakehiro en-aut-sei=Takama en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IsozakiYuka en-aut-sei=Isozaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShigeki en-aut-sei=Murakami en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Oomoto Hospital kn-affil= en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=gastric cancer with lymphoid stroma kn-keyword=gastric cancer with lymphoid stroma en-keyword=lymphoepithelioma-like carcinoma kn-keyword=lymphoepithelioma-like carcinoma en-keyword=Epstein Barr virus kn-keyword=Epstein Barr virus en-keyword=sentinel node navigation surgery kn-keyword=sentinel node navigation surgery END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=339 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Scleral Adjustment Method: A Novel Adjustable Suture Technique in Strabismus Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=To determine whether passing a pole suture through the sclera at two points provides fixation comparable to that of a sliding noose, we measured the tensile strength of the suture?sclera interface during simulated traction. In this in vitro study, three suture patterns were evaluated in porcine eyeballs, using 6-0 polyglycolic acid sutures. Patterns A (control), B (second suture pass perpendicular), and C (second suture pass in the same direction) were compared. The tensile strength of each pattern was measured 20 times using a KANON TK300CN, and the results were analyzed using the Kruskal?Wallis test. Pattern A showed a tensile strength of 2±4 gram-force (gf) (range: 0-12). Pattern B showed 112±38 gf (range: 61-184). Pattern C showed 139±31 gf (range: 97-204). Patterns B and C had significantly higher tensile strengths than Pattern A (p<0.001). Although Pattern C was not significantly different from Pattern B (p=0.363), it exhibited the highest tensile strength. Lifting the suture between the first and second suture passes allows for an adjustable suture length, suggesting that adjustability can be achieved using only the sclera. This scleral adjustment method with a second suture pass offers a durable means of securing extraocular muscles and may represent a valuable addition to adjustable suturing techniques. en-copyright= kn-copyright= en-aut-name=HamasakiIchiro en-aut-sei=Hamasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShibataKiyo en-aut-sei=Shibata en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Lino Eye Clinic kn-affil= affil-num=2 en-affil=Lino Eye Clinic kn-affil= en-keyword=scleral adjustment method kn-keyword=scleral adjustment method en-keyword=adjustable suture technique kn-keyword=adjustable suture technique en-keyword=hang-loose method kn-keyword=hang-loose method en-keyword=tensile strength kn-keyword=tensile strength en-keyword=polyglycolic acid sutures kn-keyword=polyglycolic acid sutures END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=329 end-page=337 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary graft dysfunction (PGD) is one of the major risk factors affecting patients’ short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patient’s need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology. en-copyright= kn-copyright= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=primary graft dysfunction kn-keyword=primary graft dysfunction en-keyword=extracorporeal membrane oxygenation kn-keyword=extracorporeal membrane oxygenation en-keyword=ex vivo lung perfusion kn-keyword=ex vivo lung perfusion END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=10 article-no= start-page=417 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Guided Self-Study Platform of Integrating Documentation, Code, Visual Output, and Exercise for Flutter Cross-Platform Mobile Programming en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, Flutter with the Dart programming language has become widely popular in mobile developments, allowing developers to build multi-platform applications using one codebase. An increasing number of companies are adopting these technologies to create scalable and maintainable mobile applications. Despite this increasing relevance, university curricula often lack structured resources for Flutter/Dart, limiting opportunities for students to learn it in academic environments. To address this gap, we previously developed the Flutter Programming Learning Assistance System (FPLAS), which supports self-learning through interactive problems focused on code comprehension through code-based exercises and visual interfaces. However, it was observed that many students completed the exercises without fully understanding even basic concepts, if they already had some knowledge of object-oriented programming (OOP). As a result, they may not be able to design and implement Flutter/Dart codes independently, highlighting a mismatch between the system’s outcomes and intended learning goals. In this paper, we propose a guided self-study approach of integrating documentation, code, visual output, and exercise in FPLAS. Two existing problem types, namely, Grammar Understanding Problems (GUP) and Element Fill-in-Blank Problems (EFP), are combined together with documentation, code, and output into a new format called Integrated Introductory Problems (INTs). For evaluations, we generated 16 INT instances and conducted two rounds of evaluations. The first round with 23 master students in Okayama University, Japan, showed high correct answer rates but low usability ratings. After revising the documentation and the system design, the second round with 25 fourth-year undergraduate students in the same university demonstrated high usability and consistent performances, which confirms the effectiveness of the proposal. en-copyright= kn-copyright= en-aut-name=KinariSafira Adine en-aut-sei=Kinari en-aut-mei=Safira Adine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AungSoe Thandar en-aut-sei=Aung en-aut-mei=Soe Thandar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KyawHtoo Htoo Sandi en-aut-sei=Kyaw en-aut-mei=Htoo Htoo Sandi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= en-keyword=Flutter kn-keyword=Flutter en-keyword=Dart kn-keyword=Dart en-keyword=cross-platform kn-keyword=cross-platform en-keyword=self-learning kn-keyword=self-learning en-keyword=introductory kn-keyword=introductory END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=34964 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Periodontitis associated with Porphyromonas gingivalis infection is a risk factor for infertility through uterine hypertrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontitis has recently been recognized as a potential risk factor for infertility due to its adverse effect on conception, although the underlying mechanisms remain unclear. This study investigated serum IgG antibody titers against periodontopathogenic bacteria in women with unexplained infertility and investigated how periodontal inflammation affects pregnancy and uterine function using a ligature-induced periodontitis mouse model infected with Porphyromonas gingivalis (Pg). IgG antibody titers against seven periodontopathogenic bacteria strains were measured by ELISA in 76 spontaneously pregnant women and 70 women undergoing infertility treatment. In the in vivo study, periodontitis mice were bred four weeks after periodontitis induction. Birth numbers, newborn weights, and gestation periods were assessed. To evaluate periodontal inflammation, alveolar bone, serum, and uterus was collected before mating. Uterine tissue was evaluated through histological and immunohistochemical staining. Women receiving infertility treatment were significantly older and had higher IgG titers against three Pg strains. Periodontitis mice had fewer births, lower newborn weights, and increased uterine cross-sectional areas. Additionally, elevated estrogen receptor α and progesterone receptor expression levels were observed in endometrial and stromal tissues. These results suggest that periodontitis may cause uterine hypertrophy and hormone receptor changes, potentially impairing pregnancy. en-copyright= kn-copyright= en-aut-name=Kamei-NagataChiaki en-aut-sei=Kamei-Nagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakoHidefumi en-aut-sei=Sako en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaidaKyosuke en-aut-sei=Sakaida en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakayamaMasa-aki en-aut-sei=Nakayama en-aut-mei=Masa-aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Kubota-TakamoriMoyuka en-aut-sei=Kubota-Takamori en-aut-mei=Moyuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KiyamaFumiko en-aut-sei=Kiyama en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraiKimito en-aut-sei=Hirai en-aut-mei=Kimito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Takeuchi-HatanakaKazu en-aut-sei=Takeuchi-Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=Tai-TokuzenMasako en-aut-sei=Tai-Tokuzen en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakamotoAi en-aut-sei=Sakamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiyokawaMachiko en-aut-sei=Kiyokawa en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamanishiTomomi en-aut-sei=Yamanishi en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OdaTakashi en-aut-sei=Oda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakigawaMasayuki en-aut-sei=Takigawa en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MiyakeTakahito en-aut-sei=Miyake en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=17 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=18 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=19 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=20 en-affil=Miyake Hello Dental Clinic, Pediatric Dentistry and Orthodontics kn-affil= affil-num=21 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=22 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=23 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Infertility kn-keyword=Infertility en-keyword=Periodontitis kn-keyword=Periodontitis en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=Chronic inflammation kn-keyword=Chronic inflammation en-keyword=Uterus kn-keyword=Uterus en-keyword=Sex hormone receptor kn-keyword=Sex hormone receptor END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=4 article-no= start-page=51 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target. en-copyright= kn-copyright= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HikitaTakao en-aut-sei=Hikita en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MashimaTomoha en-aut-sei=Mashima en-aut-mei=Tomoha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TorigataKosuke en-aut-sei=Torigata en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoSachio en-aut-sei=Ito en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=School of Medicine, Kobe University kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Thoracic Surgery, National Hospital Organization, Shikoku Cancer Center kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cancer-associated fibroblast kn-keyword=Cancer-associated fibroblast en-keyword=Superoxide dismutase 3 kn-keyword=Superoxide dismutase 3 en-keyword=Lymphangiogenesis kn-keyword=Lymphangiogenesis en-keyword=Angiogenesis kn-keyword=Angiogenesis en-keyword=Metastasis kn-keyword=Metastasis en-keyword=Lung adenocarcinoma kn-keyword=Lung adenocarcinoma END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Computed tomography versus aortography for transcatheter patent ductus arteriosus closure in adults en-subtitle= kn-subtitle= en-abstract= kn-abstract=Accurate sizing of the patent ductus arteriosus (PDA) is essential for successful transcatheter closure. While aortography is the standard imaging modality, computed tomography (CT) may offer superior anatomical visualization. This study aimed to compare the accuracy and procedural outcomes of preprocedural CT versus aortography alone in adult patients undergoing transcatheter PDA closure. We retrospectively analyzed 54 adult patients who underwent PDA closure using the Amplatzer? Duct Occluder between 2009 and 2024. Nineteen patients were treated based on aortography alone and 35 based on preprocedural CT. We compared procedural characteristics and outcomes, including device size exchange and procedure time. A simulation study was also conducted in which two blinded implanters independently predicted occluder size based on CT and aortography, with actual implanted device size used as the reference. The CT group had significantly larger PDA sizes and implanted device sizes. Device replacement was required in three patients in the aortography group but none in the CT group. Procedure time was shorter in the CT group (60?±?9 vs. 70?±?14 min, p?=?0.003). Simulation results showed that CT more accurately predicted the actual implanted device size (85% vs. 63%, p?=?0.008). PDA size at the pulmonary artery end was significantly underestimated by aortography. Preprocedural CT improved procedural efficiency and device selection accuracy in adult PDA closure. These findings suggest that CT imaging may enhance planning and safety in transcatheter PDA interventions. en-copyright= kn-copyright= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkagiTeiji en-aut-sei=Akagi en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Patent ductus arteriosus kn-keyword=Patent ductus arteriosus en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Aortography kn-keyword=Aortography en-keyword=Transcatheter closure kn-keyword=Transcatheter closure END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=1333 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250816 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phosphorylated pullulan as a local drug delivery matrix for cationic antibacterial chemicals to prevent oral biofilm en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Preventing oral infections, such as oral caries and periodontal disease, helps reduce the risks of various systemic diseases. In this study, the polysaccharide pullulan produced by the black yeast Aureobasidium pullulans was modified in combination with the cationic surfactant cetylpyridinium chloride (CPC) to create a local drug delivery system, and its antibacterial potential on oral bacteria was examined in vitro.
Methods Pullulan was phosphorylated at the CH2OH residue of α6 in the maltotriose structure and mixed with CPC. Bacterial attachment of cariogenic Streptococcus mutans on hydroxyapatite plates (HAPs) treated with the phosphorylated pullulan (PP) and CPC compound (0.01% PP and 0.001? 0.03% CPC, and vice versa) was assessed by observing bacteria using a field emission scanning electron microscope (FE-SEM) and quantified through 16 S rRNA amplification via real-time polymerase chain reaction (PCR). Additionally, the quartz crystal microbalance (QCM) method was employed to evaluate the sustained release of CPC.
Results PP-CPC compound maintained significant bactericidal activity even at 0.01%, which is one-fifth of the conventional applicable concentration of CPC. Additionally, a residual mixture was detected by the hydroxyapatite sensor of the crystal oscillator microbalance detector, suggesting an unknown molecular interaction that enables the sustained release of CPC after attachment to hydroxyapatite.
Conclusions The combination of PP and CPC may contribute to the low concentration and effective prevention of oral infections, such as dental caries. en-copyright= kn-copyright= en-aut-name=Namba-KoideNaoko en-aut-sei=Namba-Koide en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkiharaTakumi en-aut-sei=Okihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawataYusuke en-aut-sei=Kawata en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoMasahiro en-aut-sei=Ito en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoTakashi en-aut-sei=Ito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Takeuchi-HatanakaKazu en-aut-sei=Takeuchi-Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Phosphorylated Pullulan kn-keyword=Phosphorylated Pullulan en-keyword=Local drug delivery system kn-keyword=Local drug delivery system en-keyword=Cationic antimicrobial agents kn-keyword=Cationic antimicrobial agents en-keyword=Cetylpyridinium chloride kn-keyword=Cetylpyridinium chloride en-keyword=Oral biofilm kn-keyword=Oral biofilm END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Disruption of the Enterococcus faecalis?Induced Biofilm on the Intraocular Lens Using Bacteriophages en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To compare the effects of bacteriophages (phages) and vancomycin on Enterococcus faecalis?induced biofilms on the intraocular lens.
Methods: E. faecalis strains EF24, GU02, GU03, and phiEF14H1 were used. The expression of the enterococcus surface protein (esp) gene was analyzed using polymerase chain reaction. Phages or vancomycin was added to the biofilms formed on culture plates or acrylic intraocular lenses. The biofilms were quantified after staining with crystal violet. The structure of the biofilms was analyzed using scanning electron microscopy.
Results: E. faecalis strains EF24, GU02, and GU03 formed biofilms on cell culture plates; however, the esp-negative GU03 strain had a significantly lower biofilm-forming ability than the esp-positive strains EF24 and GU02. The addition of phiEF14H1 resulted in a significant reduction in biofilm mass produced by both EF24 and GU02 compared with the untreated control. However, the addition of vancomycin did not degrade the biofilms. Phages significantly degraded biofilms and reduced the viable EF24 and GU02 bacteria on the intraocular lens.
Conclusions: Phages can degrade biofilms formed on the intraocular lens and destroy the bacteria within it. Thus, phage therapy may be a new treatment option for refractory and recurrent endophthalmitis caused by biofilm-forming bacteria.
Translational Relevance: Phage therapy, a novel treatment option for refractory and recurrent endophthalmitis caused by biofilm-forming bacteria, effectively lyses E. faecalis?induced biofilms. en-copyright= kn-copyright= en-aut-name=KishimotoTatsuma en-aut-sei=Kishimoto en-aut-mei=Tatsuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukudaKen en-aut-sei=Fukuda en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshidaWaka en-aut-sei=Ishida en-aut-mei=Waka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwanaAozora en-aut-sei=Kuwana en-aut-mei=Aozora kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TodokoroDaisuke en-aut-sei=Todokoro en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamashiroKenji en-aut-sei=Yamashiro en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= affil-num=2 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= affil-num=3 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= affil-num=4 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Gunma University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=8 en-affil=Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University kn-affil= en-keyword=biofilm kn-keyword=biofilm en-keyword=bacteriophage kn-keyword=bacteriophage en-keyword=intraocular lens kn-keyword=intraocular lens en-keyword=endophthalmitis kn-keyword=endophthalmitis en-keyword=cataract kn-keyword=cataract en-keyword=enterococcus faecalis kn-keyword=enterococcus faecalis END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=6 article-no= start-page=065001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240613 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inert structural transition in 4H and 6H SiC at high pressure and temperature: a Raman spectroscopy study en-subtitle= kn-subtitle= en-abstract= kn-abstract=We conducted Raman spectroscopy measurements of 4H-SiC and 6H-SiC up to 69 GPa and 1023 K to assess the stability and bonding of SiC at high pressure and temperature. Both optic and acoustic modes were observed at wide pressure and temperature ranges. The temperature shifts of the Raman frequencies were fitted by the equation with the Bose?Einstein distribution function, and we found that the shifts were almost insensitive to the pressure. The mode Gr?neisen coefficients weakly depend on the pressure and temperature, suggesting the sluggish transition of the crystal structure, unlike the previous experiments showing the transition or decomposition of SiC at high pressure and temperature conditions. Inert transitions are confirmed by Raman measurements and annealing experiments using multiple high-pressure apparatuses. The crystallinity may be a hidden critical parameter in the experiments to determine the stable polytypes of SiC under high pressure and temperature. en-copyright= kn-copyright= en-aut-name=MaitaniShuhou en-aut-sei=Maitani en-aut-mei=Shuhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SinmyoRyosuke en-aut-sei=Sinmyo en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YozaKenji en-aut-sei=Yoza en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Physics, School of Science and Technology, Meiji University kn-affil= affil-num=2 en-affil=Department of Physics, School of Science and Technology, Meiji University kn-affil= affil-num=3 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Bruker Japan kn-affil= en-keyword=SiC kn-keyword=SiC en-keyword=Raman kn-keyword=Raman en-keyword=phase transitions kn-keyword=phase transitions en-keyword=high pressure kn-keyword=high pressure en-keyword=high temperature kn-keyword=high temperature en-keyword=diamond anvil cell kn-keyword=diamond anvil cell en-keyword=crystal structure kn-keyword=crystal structure END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=17 article-no= start-page=6049 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250826 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Photon-Counting CT Enhances Diagnostic Accuracy in Stable Coronary Artery Disease: A Comparative Study with Conventional CT en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Coronary CT angiography (CCTA) is a cornerstone in evaluating stable coronary artery disease (CAD), but conventional energy-integrating detector CT (EID-CT) has limitations, including calcium blooming and limited spatial resolution. Photon-counting detector CT (PCD-CT) may overcome these drawbacks through enhanced spatial resolution and improved tissue characterization. Methods: In this retrospective, propensity score?matched study, we compared CCTA findings from 820 patients (410 per group) who underwent either EID-CT or PCD-CT for suspected stable CAD. Primary outcomes included stenosis severity, high-risk plaque features, and downstream invasive coronary angiography (ICA) referral and yield. Results: The matched cohorts were balanced in demographics and cardiovascular risk factors (mean age 67 years, 63% male). PCD-CT showed a favorable shift in stenosis severity distribution (p = 0.03). High-risk plaques were detected less frequently with PCD-CT (22.7% vs. 30.5%, p = 0.01). Median coronary calcium scores did not differ (p = 0.60). Among patients referred for ICA, those initially evaluated with PCD-CT were more likely to undergo revascularization (62.5% vs. 44.1%), and fewer underwent potentially unnecessary ICA without revascularization (3.7% vs. 8.0%, p = 0.001). The specificity in diagnosing significant stenosis requiring revascularization was 0.74 with EID-CT and 0.81 with PCD-CT (p = 0.04). Conclusions: PCD-CT improved diagnostic specificity for CAD, reducing unnecessary ICA referrals while maintaining detection of clinically significant disease. This advanced CT technology holds promise for more accurate, efficient, and patient-centered CAD evaluation. en-copyright= kn-copyright= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraShohei en-aut-sei=Hara en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyagiRyosuke en-aut-sei=Miyagi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=photon-counting CT kn-keyword=photon-counting CT en-keyword=coronary CT angiography kn-keyword=coronary CT angiography en-keyword=diagnostic accuracy kn-keyword=diagnostic accuracy en-keyword=invasive coronary angiography kn-keyword=invasive coronary angiography END start-ver=1.4 cd-journal=joma no-vol=1869 cd-vols= no-issue=12 article-no= start-page=130860 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol?disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats. en-copyright= kn-copyright= en-aut-name=BabaTakumi en-aut-sei=Baba en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UenoGo en-aut-sei=Ueno en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OheChika en-aut-sei=Ohe en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SajiShuku en-aut-sei=Saji en-aut-mei=Shuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoSachiko en-aut-sei=Yamamoto en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaHiroshi en-aut-sei=Nakagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiNobuo en-aut-sei=Okazaki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Kawasaki-OhmoriIori en-aut-sei=Kawasaki-Ohmori en-aut-mei=Iori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeshitaKohei en-aut-sei=Takeshita en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=2 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=3 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=4 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=5 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=6 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=7 en-affil=Materials Sciences Research Center, Japan Atomic Energy Agency kn-affil= affil-num=8 en-affil=Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS) kn-affil= affil-num=9 en-affil=Department of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University kn-affil= affil-num=11 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= en-keyword=Txn kn-keyword=Txn en-keyword=Thioredoxin kn-keyword=Thioredoxin en-keyword=Protein instability kn-keyword=Protein instability en-keyword=Thermosensitivity kn-keyword=Thermosensitivity en-keyword=Crystal structure kn-keyword=Crystal structure en-keyword=Molecular dynamics simulation kn-keyword=Molecular dynamics simulation END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=9 article-no= start-page=1135 end-page=1151 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Heart failure-specific cardiac fibroblasts contribute to cardiac dysfunction via the MYC?CXCL1?CXCR2 axis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heart failure (HF) is a growing global health issue. While most studies focus on cardiomyocytes, here we highlight the role of cardiac fibroblasts (CFs) in HF. Single-cell RNA sequencing of mouse hearts under pressure overload identified six CF subclusters, with one specific to the HF stage. This HF-specific CF population highly expresses the transcription factor Myc. Deleting Myc in CFs improves cardiac function without reducing fibrosis. MYC directly regulates the expression of the chemokine CXCL1, which is elevated in HF-specific CFs and downregulated in Myc-deficient CFs. The CXCL1 receptor, CXCR2, is expressed in cardiomyocytes, and blocking the CXCL1?CXCR2 axis mitigates HF. CXCL1 impairs contractility in neonatal rat and human iPSC-derived cardiomyocytes. Human CFs from failing hearts also express MYC and CXCL1, unlike those from controls. These findings reveal that HF-specific CFs contribute to HF via the MYC?CXCL1?CXCR2 pathway, offering a promising therapeutic target beyond cardiomyocytes. en-copyright= kn-copyright= en-aut-name=KomuroJin en-aut-sei=Komuro en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashimotoHisayuki en-aut-sei=Hashimoto en-aut-mei=Hisayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsukiToshiomi en-aut-sei=Katsuki en-aut-mei=Toshiomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KusumotoDai en-aut-sei=Kusumoto en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatohManami en-aut-sei=Katoh en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoToshiyuki en-aut-sei=Ko en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoMasamichi en-aut-sei=Ito en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatagiriMikako en-aut-sei=Katagiri en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KubotaMasayuki en-aut-sei=Kubota en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaShintaro en-aut-sei=Yamada en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraTakahiro en-aut-sei=Nakamura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkibaYohei en-aut-sei=Akiba en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KoukaThukaa en-aut-sei=Kouka en-aut-mei=Thukaa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KomuroKaoruko en-aut-sei=Komuro en-aut-mei=Kaoruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimuraMai en-aut-sei=Kimura en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ItoShogo en-aut-sei=Ito en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NomuraSeitaro en-aut-sei=Nomura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KomuroIssei en-aut-sei=Komuro en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaKeiichi en-aut-sei=Fukuda en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IedaMasaki en-aut-sei=Ieda en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Frontier Cardiovascular Science, Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Frontier Cardiovascular Science, Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=12 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=16 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Frontier Cardiovascular Science, Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=3 article-no= start-page=394 end-page=403 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240802 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis and Crystal Structure of Ilmenite-Type Silicate with Pyrope Composition en-subtitle= kn-subtitle= en-abstract= kn-abstract=Akimotoite, ilmenite-type MgSiO3 high-pressure polymorph can be stable in the lower-mantle transition zone along average mantle and subducting slab geotherms. Significant amounts of Al2O3 can be incorporated into the structure, having the pyrope (Mg3Al2Si3O12) composition. Previous studies have investigated the effect of Al2O3 on its crystal structure at nearly endmember compositions. In this study, we synthesized high-quality ilmenite-type Mg3Al2Si3O12 phase at 27 GPa and 1073 K by means of a Kawai-type multi-anvil press and refined the crystal structure at ambient conditions using a synchrotron X-ray diffraction data via the Rietveld method to examine the effect of Al2O3. The unit-cell lattice parameters were determined to be a = 4.7553(7) ?, c = 13.310(2) ?, and V = 260.66(6) ?3, with Z = 6 (hexagonal, R3? ). The volume of the present phase was placed on the akimotoite-corundum endmember join. However, the refined structure showed a strong nonlinear behavior of the a- and c-axes, which can be explained by Al incorporation into the MgO6 and SiO6 octahedral sites, which are distinctly different each other. Ilmenite-type Mg3Al2Si3O12 phase may be found in shocked meteorites and can be a good indicator for shock conditions at relatively low temperatures of 1027?1127 K. en-copyright= kn-copyright= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SinmyoRyosuke en-aut-sei=Sinmyo en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsuraTomoo en-aut-sei=Katsura en-aut-mei=Tomoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Department of Physics, School of Science and Technology, Meiji University kn-affil= affil-num=3 en-affil=Bavarian Research Institute of Experimental Geochemistry and Geophysics, University of Bayreuth kn-affil= en-keyword=ilmenite kn-keyword=ilmenite en-keyword=akimotoite kn-keyword=akimotoite en-keyword=pyrope kn-keyword=pyrope en-keyword=high pressure kn-keyword=high pressure en-keyword=X-ray diffraction kn-keyword=X-ray diffraction en-keyword=crystal structure kn-keyword=crystal structure en-keyword=Rietveld analysis kn-keyword=Rietveld analysis en-keyword=mantle kn-keyword=mantle en-keyword=subducting slab kn-keyword=subducting slab en-keyword=corundum kn-keyword=corundum END start-ver=1.4 cd-journal=joma no-vol=198 cd-vols= no-issue=1 article-no= start-page=kiaf137 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The thylakoid membrane remodeling protein VIPP1 forms bundled oligomers in tobacco chloroplasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=The thylakoid membrane (TM) serves as the scaffold for oxygen-evolving photosynthesis, hosting the protein complexes responsible for the light reactions and ATP synthesis. Vesicle inducing protein in plastid 1 (VIPP1), a key protein in TM remodeling, has been recognized as essential for TM homeostasis. In vitro studies of cyanobacterial VIPP1 demonstrated its ability to form large homo-oligomers (2?MDa) manifesting as ring-like or filament-like assemblies associated with membranes. Similarly, VIPP1 in Chlamydomonas reinhardtii assembles into rods that encapsulate liposomes or into stacked spiral structures. However, the nature of VIPP1 assemblies in chloroplasts, particularly in Arabidopsis, remains uncharacterized. Here, we expressed Arabidopsis thaliana VIPP1 fused to GFP (AtVIPP1-GFP) in tobacco (Nicotiana tabacum) chloroplasts and performed transmission electron microscopy (TEM). A purified AtVIPP1-GFP fraction was enriched with long filamentous tubule-like structures. Detailed TEM observations of chloroplasts in fixed resin-embedded tissues identified VIPP1 assemblies in situ that appeared to colocalize with GFP fluorescence. Electron tomography demonstrated that the AtVIPP1 oligomers consisted of bundled filaments near membranes, some of which appeared connected to the TM or inner chloroplast envelope at their contact sites. The observed bundles were never detected in wild-type Arabidopsis but were observed in Arabidopsis vipp1 mutants expressing AtVIPP1-GFP. Taken together, we propose that the bundled filaments are the dominant AtVIPP1 oligomers that represent its static state in vivo. en-copyright= kn-copyright= en-aut-name=GachieSarah W en-aut-sei=Gachie en-aut-mei=Sarah W kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MuhireAlexandre en-aut-sei=Muhire en-aut-mei=Alexandre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiDi en-aut-sei=Li en-aut-mei=Di kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawamotoAkihiro en-aut-sei=Kawamoto en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Takeda-KamiyaNoriko en-aut-sei=Takeda-Kamiya en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GotoYumi en-aut-sei=Goto en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoMayuko en-aut-sei=Sato en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToyookaKiminori en-aut-sei=Toyooka en-aut-mei=Kiminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshimuraRyo en-aut-sei=Yoshimura en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakamiTsuneaki en-aut-sei=Takami en-aut-mei=Tsuneaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ZhangLingang en-aut-sei=Zhang en-aut-mei=Lingang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurisuGenji en-aut-sei=Kurisu en-aut-mei=Genji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TerachiToru en-aut-sei=Terachi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SakamotoWataru en-aut-sei=Sakamoto en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=5 en-affil=Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=6 en-affil=Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=7 en-affil=Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=8 en-affil=Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=11 en-affil=School of Life Sciences, Inner Mongolia University/Key Laboratory of Herbage and Endemic Crop Biotechnology kn-affil= affil-num=12 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=13 en-affil=Faculty of Life Sciences, Kyoto Sangyo University kn-affil= affil-num=14 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=17 article-no= start-page=8643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anti-HMGB1 Antibody Therapy Ameliorates Spinal Cord Ischemia?Reperfusion Injury in Rabbits en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spinal cord ischemia?reperfusion (SCI/R) injury remains a major clinical challenge with limited therapeutic options. High-mobility group box 1 (HMGB1), a proinflammatory mediator released during cellular stress, has been implicated in the pathogenesis of ischemia?reperfusion-induced neural damage. In this study, we investigated the neuroprotective potential of the anti-HMGB1 monoclonal antibody (mAb) in a rabbit model of SCI/R injury. Male New Zealand White rabbits were anesthetized and subjected to 11 min of abdominal aortic occlusion using a micro-bulldog clamp following heparinization. Anti-HMGB1 mAb or control IgG was administered intravenously immediately after reperfusion and again at 6 h post-reperfusion. Neurological function was assessed at 6, 24, and 48 h after reperfusion using the modified Tarlov scoring system. The rabbits were euthanized 48 h after reperfusion for spinal cord and blood sampling. Treatment with anti-HMGB1 mAb significantly improved neurological outcomes, reduced the extent of spinal cord infarction, preserved motor neuron viability, and decreased the presence of activated microglia and infiltrating neutrophils. Furthermore, it attenuated apoptosis, oxidative stress, and inflammatory responses in the spinal cord, and helped maintain the integrity of the blood?spinal cord barrier. These findings suggest that anti-HMGB1 mAb may serve as a promising therapeutic agent for SCI/R injury. en-copyright= kn-copyright= en-aut-name=MuraokaGenya en-aut-sei=Muraoka en-aut-mei=Genya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiYasuhiro en-aut-sei=Fujii en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QiaoHandong en-aut-sei=Qiao en-aut-mei=Handong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OozawaSusumu en-aut-sei=Oozawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Translational Research, Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Technology, Faculty of Science, Okayama University of Science kn-affil= affil-num=7 en-affil=Division of Medical Safety Management, Safety Management Facility, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Translational Research and Drug Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=thoracoabdominal aortic aneurysm kn-keyword=thoracoabdominal aortic aneurysm en-keyword=spinal cord ischemia?reperfusion injury kn-keyword=spinal cord ischemia?reperfusion injury en-keyword=high mobility group box 1 kn-keyword=high mobility group box 1 en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=blood?spinal cord barrier kn-keyword=blood?spinal cord barrier en-keyword=aortic surgery kn-keyword=aortic surgery END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=1 article-no= start-page=56 end-page=22 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250911 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The Ethnic Integration and Security Issues in Estonia : In light of the results of the “Social Awareness Survey”（May 2023） kn-title=エストニアの民族間統合と安全保障問題 ― 「社会意識調査」（2023年５月）の結果に照らして― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KawaharaY. en-aut-sei=Kawahara en-aut-mei=Y. kn-aut-name=河原祐馬 kn-aut-sei=河原 kn-aut-mei=祐馬 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学学術研究院社会文化科学学域 END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=6 article-no= start-page=103174 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of a method to predict positioning errors in orthopantomography using cephalography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Various radiographic examinations are used to diagnose diseases and determine treatment plans, and the quality of radiographic images affects diagnostic accuracy. This study assessed the relationship between orthopantomography and cephalometric analysis in predicting positioning errors before orthopantomography.
Methods: This study evaluated four human head phantom types and included 300 patients aged ?18 years who underwent orthopantomography. The correlation between the Frankfort horizontal plane and occlusal plane angles in the orthopantomogram was analyzed. The occlusal plane angle at a Frankfort horizontal plane of 0° was estimated using a linear approximation formula. Frankfort horizontal plane and occlusal plane angles were measured on the cephalograms, and their differences were analyzed for correlation with the occlusal plane angle at a Frankfort horizontal plane of 0° in the corresponding orthopantomograms. The cephalogram’s condylar plane?corpus line angle was also compared with orthopantomogram measurements.
Results: Frankfort horizontal and occlusal plane angles demonstrated a strong negative correlation (r < ?0.9) in phantom studies and moderate negative correlation (r < ?0.4) in clinical orthopantomograms. In the phantoms, the occlusal plane at a Frankfort horizontal of 0° in the orthopantomogram strongly correlated with the difference between the Frankfort horizontal and condylar plane?corpus line angles in the cephalogram.
Conclusion: Adjusting patient positioning based on individual skeletal differences and angles may reduce positioning errors and improve image quality. Cephalogram analysis could help determine an appropriate Frankfort plane angle for each patient when acquiring orthopantomograms.
Implications for practice: Integrating cephalometric analysis into positioning protocols enhances radiographic accuracy, reduces retakes, and improves diagnostic reliability in clinical positioning. This research could improve image quality by identifying reference indicators for orthopantomography by incorporating data from images other than cephalograms, such as computed tomography and magnetic resonance imaging. en-copyright= kn-copyright= en-aut-name=ImajoS. en-aut-sei=Imajo en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HondaM. en-aut-sei=Honda en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanabeY. en-aut-sei=Tanabe en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Division of Radiology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Radiology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=3 en-affil=Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Cephalogram kn-keyword=Cephalogram en-keyword=Orthopantomogram kn-keyword=Orthopantomogram en-keyword=Panoramic radiography kn-keyword=Panoramic radiography en-keyword=Frankfort horizontal plane kn-keyword=Frankfort horizontal plane en-keyword=Occlusal plane angle kn-keyword=Occlusal plane angle en-keyword=Patient positioning kn-keyword=Patient positioning END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Double-blind randomized noninferiority study of the effect of pharyngeal lidocaine anesthesia on EUS en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objectives: EUS is typically performed under sedation, often with concomitant analgesics to reduce pain. Traditionally used pharyngeal anesthesia, commonly with lidocaine, may cause pharyngeal discomfort and allergic reactions. This study investigated whether lidocaine-based pharyngeal anesthesia is necessary for EUS under sedation with analgesics.
Methods: A double-blind, randomized, noninferiority study was conducted on EUS cases that met the selection criteria. Patients were randomly assigned to receive either 5 sprays of 8% lidocaine (lidocaine group: LG) or saline spray (placebo group: PG) as endoscopy pretreatment. The primary outcome was EUS tolerability, analyzed separately for endoscopists and patients, with a noninferiority margin set at 15%. Secondary outcomes included endoscopist and patient satisfaction, midazolam/pethidine doses, number of gag events, number of esophageal insertion attempts, use of sedative/analgesic antagonists, interruptions due to body movements, throat symptoms after endoscopy, and sedation-related adverse events.
Results: Favorable tolerance was 85% in LG and 88% for PG among endoscopists (percent difference: 3.0 [95% confidence interval, ?6.6 to 12.6]) and 90% in LG and 91% in PG among patients (percent difference, 0.94 [95% confidence interval, ?7.5 to 9.4]). Both groups exceeded the noninferiority margin (P = 0.0002 for endoscopists and patients). Patient satisfaction was significantly higher in PG (P = 0.0080), but no intergroup differences were found in other secondary outcomes.
Conclusions: PG was noninferior to LG for pharyngeal anesthesia during EUS with sedation and analgesics. These results suggest that pharyngeal anesthesia with lidocaine can be omitted when performing EUS under sedation with concomitant analgesics. Omitting pharyngeal anesthesia with lidocaine may prevent discomfort and complications caused by pharyngeal anesthesia, shorten examination times, and reduce medical costs. en-copyright= kn-copyright= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKei en-aut-sei=Harada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HattoriNao en-aut-sei=Hattori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=EUS kn-keyword=EUS en-keyword=Lidocaine kn-keyword=Lidocaine en-keyword=Tolerance kn-keyword=Tolerance END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activation en-subtitle= kn-subtitle= en-abstract= kn-abstract=S100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis. However, the exact mechanisms by which S100A8/A9 contributes to GC pathogenesis remain unclear. This study investigates the role of S100A8/A9 and its receptor in GC. Immunohistochemical analysis was performed on GC tissue samples to assess the expression of the S100A8/A9 receptor melanoma cell adhesion molecule (MCAM). In vitro transwell migration and invasion assays were used to evaluate the motility and invasiveness of GC cells. Cell proliferation was assessed using a growth assay, and Western blotting (WB) was employed to examine downstream signaling pathways, including ERK and the transcription factor c-Jun, in response to S100A8/A9?MCAM interaction. S100A8/A9 stimulation enhanced both proliferation and migration through MCAM binding in GC cell lines. These cellular events were accompanied by ERK activation and c-Jun induction. Downregulation of MCAM suppressed both ERK phosphorylation and c-Jun expression, highlighting the importance of the S100A8/A9?MCAM?ERK?c-Jun axis in promoting GC progression. These findings indicate that S100A8/A9 contributes to GC progression via MCAM, which activates the ERK?c-Jun pathway. The S100A8/A9?signaling axis may represent a novel therapeutic target in GC. en-copyright= kn-copyright= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YangXu en-aut-sei=Yang en-aut-mei=Xu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PanBo en-aut-sei=Pan en-aut-mei=Bo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WuFangping en-aut-sei=Wu en-aut-mei=Fangping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangXu en-aut-sei=Zhang en-aut-mei=Xu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SagayamaKazumi en-aut-sei=Sagayama en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SunBei en-aut-sei=Sun en-aut-mei=Bei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=6 en-affil=School of Pharmaceutical Sciences, Zhejiang Chinese Medical University kn-affil= affil-num=7 en-affil=Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=8 en-affil=Faculties of Educational and Research Management Field, Okayama University kn-affil= affil-num=9 en-affil=Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=S100 protein kn-keyword=S100 protein en-keyword=MCAM kn-keyword=MCAM en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Metastasis kn-keyword=Metastasis END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=16 article-no= start-page=2634 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic Impact of Gastrointestinal Immune-Related Adverse Events Depends on Nutritional Status in Cancer Patients Treated with Immune Checkpoint Inhibitors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Gastrointestinal immune-related adverse events (GI-irAEs) are recognized complications of immune checkpoint inhibitors (ICIs), but their prognostic relevance and associated risk factors remain unclear. This study aimed to assess whether baseline nutritional status, measured using the prognostic nutritional index (PNI), modifies the prognostic impact of GI-irAEs, and to identify clinical factors associated with their occurrence. Methods: We retrospectively analyzed 1104 cancer patients treated with ICIs at a single institution. GI-irAEs were defined as gastrointestinal symptoms requiring clinical intervention. Patients were stratified by irAE type and PNI (?40 vs. <40), and differences in survival and treatment response were evaluated. Potential risk factors for developing GI-irAEs were also examined. Results: GI-irAEs occurred in 2.7% of patients and were associated with prolonged overall survival (median: 28.7 vs. 14.0 months) among those with PNI ? 40. This survival advantage was not observed in patients with PNI < 40. The PNI-dependent prognostic pattern was specific to GI-irAEs and not observed for non-GI irAEs. Similar trends were confirmed in 4- and 8-week landmark analyses. Differences in objective response rate and disease control rate by PNI status were most pronounced in patients with GI-irAEs. The use of anti-CTLA-4 antibodies was significantly associated with GI-irAE development (odds ratio 4.24; 95% confidence interval 1.73?10.39). Conclusions: GI-irAEs appear to confer a survival benefit primarily in patients with preserved nutritional status. PNI may serve as a useful tool to contextualize the clinical relevance of GI-irAEs and help identify patients most likely to benefit from immune activation during ICI therapy. en-copyright= kn-copyright= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaEmi en-aut-sei=Tanaka en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SueMasahiko en-aut-sei=Sue en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeuchiYasuto en-aut-sei=Takeuchi en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshikawaTomoki en-aut-sei=Yoshikawa en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakiYoshie en-aut-sei=Maki en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KametakaDaisuke en-aut-sei=Kametaka en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuedaKatsunori en-aut-sei=Matsueda en-aut-mei=Katsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaguchiChihiro en-aut-sei=Sakaguchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=gastrointestinal immune-related adverse events kn-keyword=gastrointestinal immune-related adverse events en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=prognostic nutrition index kn-keyword=prognostic nutrition index END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=17 article-no= start-page=8145 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250822 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Augmentation of the Benzyl Isothiocyanate-Induced Antiproliferation by NBDHEX in the HCT-116 Human Colorectal Cancer Cell Line en-subtitle= kn-subtitle= en-abstract= kn-abstract=Increased drug metabolism and elimination are prominent mechanisms mediating multidrug resistance (MDR) to not only chemotherapy drugs but also anti-cancer natural products, such as benzyl isothiocyanate (BITC). To evaluate the possibility of combined utilization of a certain compound to overcome this resistance, we focused on glutathione S-transferase (GST)-dependent metabolism of BITC. The pharmacological treatment of a pi-class GST-selective inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), significantly increased BITC-induced toxicity in human colorectal cancer HCT-116 cells. However, NBDHEX unexpectedly increased the level of the BITC?glutathione (GSH) conjugate as well as BITC-modified proteins, suggesting that NBDHEX might increase BITC-modified protein accumulation by inhibiting BITC?GSH excretion instead of inhibiting GST. Furthermore, NBDHEX significantly potentiated BITC-induced apoptosis with the enhanced activation of apoptosis-related pathways, such as c-Jun N-terminal kinase and caspase-3 pathways. These results suggested that combination treatment with NBDHEX may be an effective way to overcome MDR with drug efflux and thus induce the biological activity of BITC at lower doses. en-copyright= kn-copyright= en-aut-name=SunRuitong en-aut-sei=Sun en-aut-mei=Ruitong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanoAina en-aut-sei=Yano en-aut-mei=Aina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=benzyl isothiocyanate kn-keyword=benzyl isothiocyanate en-keyword=multidrug resistance kn-keyword=multidrug resistance en-keyword=glutathione S-transferase kn-keyword=glutathione S-transferase en-keyword=NBDHEX kn-keyword=NBDHEX en-keyword=apoptosis kn-keyword=apoptosis en-keyword=c-Jun N-terminal kinase kn-keyword=c-Jun N-terminal kinase END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=27047 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevalence of Streptococcus mutans harboring the cnm gene encoding cell surface protein Cnm in Japanese children en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dental caries is a highly prevalent infectious disease primarily caused by the pathogenic bacterium Streptococcus mutans, which has also been associated with systemic disease. A 120-kDa collagen-binding protein (Cnm) produced by S. mutans contributes to cardiovascular disease pathogenicity. Few studies have addressed the current prevalence of S. mutans and the cnm gene in Japanese children or examined caries pathology in relation to cnm presence. Here, we investigated the prevalence of S. mutans and the distribution of cnm-positive S. mutans among 490 children who visited two university hospitals in Japan. The caries experience index (dmft/DMFT) was calculated, and the collagen-binding ability of cnm-positive S. mutans strains was assessed. S. mutans was isolated from the oral cavities of 158 patients (36.8%); 10.1% (16/158) harbored cnm-positive S. mutans. When caries experience indices were compared across dentitions, patients harboring cnm-positive strains had significantly higher dmft/DMFT scores than those with cnm-negative strains (P? Objective: To identify different elements of patient data that are significant predictors of early and late-onset or delayed cardio-inflammatory irAEs through various predictive modeling strategies.
Methods: A cohort of patients receiving ICI therapy from January 1, 2010 to May 1, 2022 was identified from TriNetX meeting inclusion/exclusion criteria. Patient data collected included occurrence of early and later cardio-inflammatory irAEs, patient survival time, patient demographic information, ICI therapies, comorbidities, and medication histories. Predictive and statistical modeling approaches identified unique risk factors for early and later developing cardio-inflammatory irAEs.
Results: A cohort of 66,068 patients on ICI therapy were identified in the TriNetX platform; 193 (0.30%) experienced early cardio-inflammatory irAEs and 175 (0.26%) experienced later cardio-inflammatory irAEs. Significant predictors for early irAEs included: anti-PD-1 therapy at index, combination ICI therapy at index, and history of peripheral vascular disease. Significant predictors for later irAEs included: a history of myocarditis and/or pericarditis, cerebrovascular disease, and history of non-steroidal anti-inflammatory medication use.
Conclusions: Cardio-inflammatory irAEs can be divided into clinically meaningful categories of early and late based on time since initiation of ICI therapy. Considering distinct risk factors for early-onset and late-onset events may allow for more effective patient monitoring and risk assessment. en-copyright= kn-copyright= en-aut-name=SayerMichael en-aut-sei=Sayer en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagasakaMisako en-aut-sei=Nagasaka en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LeeBenjamin J. en-aut-sei=Lee en-aut-mei=Benjamin J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DohJean en-aut-sei=Doh en-aut-mei=Jean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PatelPranav M. en-aut-sei=Patel en-aut-mei=Pranav M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OzakiAya F. en-aut-sei=Ozaki en-aut-mei=Aya F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=2 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Hematology and Oncology, University of California kn-affil= affil-num=4 en-affil=Department of Pharmacy, University of California Irvine Health kn-affil= affil-num=5 en-affil=Department of Pharmacy, University of California Irvine Health kn-affil= affil-num=6 en-affil=Division of Cardiology, Department of Medicine, University of California kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Immune-Related adverse events kn-keyword=Immune-Related adverse events en-keyword=Myocarditis kn-keyword=Myocarditis en-keyword=Pericarditis kn-keyword=Pericarditis en-keyword=Predictive modeling kn-keyword=Predictive modeling en-keyword=TriNetx kn-keyword=TriNetx END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neutrophil-to-lymphocyte ratio affects the impact of proton pump inhibitors on efficacy of immune checkpoint inhibitors in patients with non?small-cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The neutrophil-to-lymphocyte ratio (NLR) at the initiation of immune checkpoint inhibitor (ICI) therapy is a known predictor of prognosis. Proton pump inhibitors (PPIs) reportedly attenuate the therapeutic efficacy of ICIs. However, the attenuation effects are not consistently observed across all patients. This study aimed to evaluate whether NLR serves as a stratification factor to determine the impact of PPI on the efficacy of ICI.
Methods This retrospective study was conducted in patients with NSCLC treated with ICI monotherapy. Patients were stratified into two groups (higher NLR (??4) and lower NLR ( Results Among the 132 patients included, PPI users exhibited significantly shorter median PFS and OS than non-PPI users. In the higher NLR group (n?=?61), PPI users had a markedly shorter PFS and OS than non-PPI users (median PFS: 1.6 vs. 8.2 months; p? Conclusion NLR may be a significant stratification factor for evaluating the impact of PPI on PFS and OS in patients with NSCLC undergoing ICI monotherapy. en-copyright= kn-copyright= en-aut-name=HoriTomoki en-aut-sei=Hori en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoTakefumi en-aut-sei=Ito en-aut-mei=Takefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkushimaShigeki en-aut-sei=Ikushima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Nara Prefecture General Medical Center kn-affil= affil-num=4 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=5 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor en-keyword=Neutrophil-to-lymphocyte ratio kn-keyword=Neutrophil-to-lymphocyte ratio en-keyword=Non-small-cell lung cancer kn-keyword=Non-small-cell lung cancer en-keyword=Proton pump inhibitor kn-keyword=Proton pump inhibitor END