655 results on '"Shinya T"'
Search Results
2. Evaluation of a newly developed low reflection dummy load for high power millimeter waves
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Yamazaki, H., Kobayashi, T., Hiranai, S., Sawahata, M., Toida, N., Sato, F., Hinata, J., Terakado, M., Ishita, K., Ikeda, R., Shinya, T., Yajima, S., and Kajiwara, K.
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- 2023
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3. High power experiment and heat load evaluation of transmission line for the ECH/CD system in JT-60SA
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Kobayashi, T., Yamazaki, H., Hiranai, S., Sawahata, M., Terakado, M., Ishita, K., Hinata, J., Sato, F., Wada, K., Ikeda, R., Shinya, T., Yajima, S., Kajiwara, K., Takahashi, K., and Moriyama, S.
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- 2022
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4. Estimation of RF power absorption and stray distribution at plasma breakdown based on the design of ITER ECH&CD equatorial launcher
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Yajima, S., Kajiwara, K., Isozaki, M., Kobayashi, N., Ikeda, R., Kobayashi, T., Shinya, T., Yamazaki, H., and Takahashi, K.
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- 2021
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5. Development of calorimetry methodology for beam current measurement of the Linear IFMIF Prototype Accelerator (LIPAc)
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Nishiyama, K., Knaster, J., Okumura, Y., Marqueta, A., Pruneri, G., Scantamburlo, F., Sakamoto, K., Sugimoto, M., Kasugai, A., Hirata, Y., Kondo, K., Ikeda, Y., Maebara, Sunao, Ichimiya, R., Shinya, T., Ihara, A., Kitano, T., Beauvais, Pierre-Yves, Gobin, R., and Bolzon, B.
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- 2018
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6. Successful mediastinal teratoma resection in a child by assisted VATS: a case report
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Masato Kojima, Ryo Touge, Sho Kurihara, Isamu Saeki, and Shinya Takahashi
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Mediastinal teratoma ,Video-assisted thoracic surgery ,Pediatrics ,Surgery ,RD1-811 ,Anesthesiology ,RD78.3-87.3 - Abstract
Abstract Background Video-assisted thoracic surgery (VATS) is widely used for thoracic lesions in pediatric patients. VATS is also applied to pediatric mediastinal tumors if there is no adhesion or invasion between the tumor and adjacent neuronal and cardiovascular structures. Here, we present a pediatric case of mediastinal teratoma in which the tumor adhered to the superior vena cava, and resection was safely completed using assisted VATS, an integrated surgical approach comprising mini-thoracotomy with video assistance. Case presentation A 9 year-old girl presented with right shoulder pain. Chest radiography and computed tomography revealed a 5.4 × 5.1 × 5.8 cm mass in the right upper anterior mediastinum. She was presumed with a mature teratoma, and resection was performed by assisted VATS with muscle sparing axillar skin crease incision (MSASCI) for a mini-thoracotomy. The procedure was safely completed, with the patient discharged on postoperative day 5. At 1 year postoperatively, there was no recurrence with excellent motor and cosmetic results. Conclusions The combination of MSASCI and VATS would be useful not only for mediastinal teratomas but also for other mediastinal tumors and almost all other thoracic lesions in pediatric patients.
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- 2024
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7. SR-TWAS: leveraging multiple reference panels to improve transcriptome-wide association study power by ensemble machine learning
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Randy L. Parrish, Aron S. Buchman, Shinya Tasaki, Yanling Wang, Denis Avey, Jishu Xu, Philip L. De Jager, David A. Bennett, Michael P. Epstein, and Jingjing Yang
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Science - Abstract
Abstract Multiple reference panels of a given tissue or multiple tissues often exist, and multiple regression methods could be used for training gene expression imputation models for transcriptome-wide association studies (TWAS). To leverage expression imputation models (i.e., base models) trained with multiple reference panels, regression methods, and tissues, we develop a Stacked Regression based TWAS (SR-TWAS) tool which can obtain optimal linear combinations of base models for a given validation transcriptomic dataset. Both simulation and real studies show that SR-TWAS improves power, due to increased training sample sizes and borrowed strength across multiple regression methods and tissues. Leveraging base models across multiple reference panels, tissues, and regression methods, our real studies identify 6 independent significant risk genes for Alzheimer’s disease (AD) dementia for supplementary motor area tissue and 9 independent significant risk genes for Parkinson’s disease (PD) for substantia nigra tissue. Relevant biological interpretations are found for these significant risk genes.
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- 2024
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8. Bimodal machine learning model for unstable hips in infants: integration of radiographic images with automatically-generated clinical measurements
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Hirokazu Shimizu, Ken Enda, Hidenori Koyano, Tomohiro Shimizu, Shun Shimodan, Komei Sato, Takuya Ogawa, Shinya Tanaka, Norimasa Iwasaki, and Daisuke Takahashi
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Medicine ,Science - Abstract
Abstract Bimodal convolutional neural networks (CNNs) are frequently combined with patient information or several medical images to enhance the diagnostic performance. However, the technologies that integrate automatically generated clinical measurements within the images are scarce. Hence, we developed a bimodal model that produced automatic algorithm for clinical measurement (aaCM) from radiographic images and integrated the model with CNNs. In this multicenter research project, the diagnostic performance of the model was investigated with 813 radiographic hip images of infants at risk of developmental dysplasia of the hips (232 and 581 images of unstable and stable hips, respectively), with the ground truth defined by provocative examinations. The results indicated that the accuracy of aaCM was equal or higher than that of specialists, and the bimodal model showed better diagnostic performance than LightGBM, XGBoost, SVM, and single CNN models. aaCM can provide expert’s knowledge in a high level, and our proposed bimodal model has better performance than the state-of-art models.
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- 2024
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9. Evaluation of the Accuracy of Intraocular Lens Power Calculation Formulas in Phacovitrectomy
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Yuichiro Tanaka, Kazutaka Kamiya, Akihito Igarahi, Nobuyuki Shoji, Hiroshi Tsuchiya, Shinya Takahashi, Eri Ishikawa, and Tadahiko Kozawa
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Phacovitrectomy ,Rhegmatogenous retinal detachment ,Barrett Universal II ,Prediction error ,Gas ,IOL position ,Ophthalmology ,RE1-994 - Abstract
Abstract Introduction The aim of this study was to evaluate the refractive error in patients undergoing combined phacovitrectomy with and without gas tamponade. Methods This was a retrospective chart review including patients undergoing phacoemulsification alone (Group 1), combined phacovitrectomy for epiretinal membrane (Group 2), and combined phacovitrectomy with gas tamponade for rhegmatogenous retinal detachment (RRD) (Group 3). Axial length and keratometry were measured using an optical biometric system (Argos, Alcon Laboratories. Inc.), and a three-piece intraocular lens (IOL; NX-70S) was implanted in all groups. In each group, the prediction error at 3 months was calculated using IOL power calculation formulas (SRK/T, Hill-RBF, Kane, and Barrett Universal II) for each eye. Outcome measures included the mean prediction error (MPE), its standard deviation (SD), and the mean absolute error (MAE). The change in IOL position at 3 months was also assessed using anterior segment optical coherence tomography. Results A total of 104 eyes were included (Group 1: 30; Group 2: 34; Group 3: 40 eyes). The MPE was −0.08 ± 0.37 diopters (D), −0.26 ± 0.32 D, and −0.59 ± 0.34 D in Group 1, Group 2, and Group 3, respectively, using the Barrett Universal II formula (P
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- 2024
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10. Severe hypotension and postoperative cardiac arrest caused by 5-aminolevulinic acid: a case report
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Taishi Miyazaki, Shinya Taguchi, Norihiko Obata, and Satoshi Mizobuchi
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5-Aminolevulinic acid ,Cardiac arrest ,Hypotension ,Bladder tumor ,Medicine - Abstract
Abstract Background Although 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of postoperative cardiac arrest in addition to severe intraoperative hypotension, probably owing to the use of 5-aminolevulinic acid. Case presentation An 81-year-old Japanese man was scheduled to undergo transurethral resection of bladder tumor. The patient took 5-aminolevulinic acid orally 2 hours before entering the operating room. After the induction of anesthesia, his blood pressure decreased to 47/33 mmHg. The patient’s hypotension did not improve even after noradrenaline was administered. After awakening from anesthesia, the patient’s systolic blood pressure increased to approximately 100 mmHg, but approximately 5 hours after returning to the ward, cardiac arrest occurred for approximately 12 seconds. Conclusion We experienced a case of postoperative cardiac arrest in a patient, probably owing to the use of 5-aminolevulinic acid. Although the cause of cardiac arrest is unknown, perioperative hemodynamic management must be carefully performed in patients taking 5-aminolevulinic acid.
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- 2024
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11. Fatal COVID-19 pulmonary disease involves ferroptosis
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Baiyu Qiu, Fereshteh Zandkarimi, Anjali Saqi, Candace Castagna, Hui Tan, Miroslav Sekulic, Lisa Miorin, Hanina Hibshoosh, Shinya Toyokuni, Koji Uchida, and Brent R. Stockwell
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Science - Abstract
Abstract SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.
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- 2024
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12. G-protein coupled estrogen receptor 1, amyloid-β, and tau tangles in older adults
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Shahram Oveisgharan, Lei Yu, Katia de Paiva Lopes, Vladislav A. Petyuk, Shinya Tasaki, Ricardo Vialle, Vilas Menon, Yanling Wang, Philip L. De Jager, Julie A. Schneider, and David A. Bennett
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Biology (General) ,QH301-705.5 - Abstract
Abstract Accumulation of amyloid-β (Aβ) and tau tangles are hallmarks of Alzheimer’s disease. Aβ is extracellular while tau tangles are typically intracellular, and it is unknown how these two proteinopathies are connected. Here, we use data of 1206 elders and test that RNA expression levels of GPER1, a transmembrane protein, modify the association of Aβ with tau tangles. GPER1 RNA expression is related to more tau tangles (p = 0.001). Moreover, GPER1 expression modifies the association of immunohistochemistry-derived Aβ load with tau tangles (p = 0.044). Similarly, GPER1 expression modifies the association between Aβ proteoforms and tau tangles: total Aβ protein (p = 0.030) and Aβ38 peptide (p = 0.002). Using single nuclei RNA-seq indicates that GPER1 RNA expression in astrocytes modifies the relation of Aβ load with tau tangles (p = 0.002), but not GPER1 in excitatory neurons or endothelial cells. We conclude that GPER1 may be a link between Aβ and tau tangles driven mainly by astrocytic GPER1 expression.
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- 2024
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13. Regulation of cytokine and chemokine expression by histone lysine methyltransferase MLL1 in rheumatoid arthritis synovial fibroblasts
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Keita Okamoto, Yasuto Araki, Yoshimi Aizaki, Shinya Tanaka, Yuho Kadono, and Toshihide Mimura
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Rheumatoid arthritis ,Synovial fibroblast ,Histone lysine methylation ,Cytokine ,Chemokine ,Medicine ,Science - Abstract
Abstract Histone lysine methylation is thought to play a role in the pathogenesis of rheumatoid arthritis (RA). We previously reported aberrant expression of the gene encoding mixed-lineage leukemia 1 (MLL1), which catalyzes methylation of histone H3 lysine 4 (H3K4), in RA synovial fibroblasts (SFs). The aim of this study was to elucidate the involvement of MLL1 in the activated phenotype of RASFs. SFs were isolated from synovial tissues obtained from patients with RA or osteoarthritis (OA) during total knee joint replacement. MLL1 mRNA and protein levels were determined after stimulation with tumor necrosis factor α (TNFα). We also examined changes in trimethylation of H3K4 (H3K4me3) levels in the promoters of RA-associated genes (matrix-degrading enzymes, cytokines, and chemokines) and the mRNA levels upon small interfering RNA-mediated depletion of MLL1 in RASFs. We then determined the levels of H3K4me3 and mRNAs following treatment with the WD repeat domain 5 (WDR5)/MLL1 inhibitor MM-102. H3K4me3 levels in the gene promoters were also compared between RASFs and OASFs. After TNFα stimulation, MLL1 mRNA and protein levels were higher in RASFs than OASFs. Silencing of MLL1 significantly reduced H3K4me3 levels in the promoters of several cytokine (interleukin-6 [IL-6], IL-15) and chemokine (C–C motif chemokine ligand 2 [CCL2], CCL5, C-X-C motif chemokine ligand 9 [CXCL9], CXCL10, CXCL11, and C-X3-C motif chemokine ligand 1 [CX3CL1]) genes in RASFs. Correspondingly, the mRNA levels of these genes were significantly decreased. MM-102 significantly reduced the promoter H3K4me3 and mRNA levels of the CCL5, CXCL9, CXCL10, and CXCL11 genes in RASFs. In addition, H3K4me3 levels in the promoters of the IL-6, IL-15, CCL2, CCL5, CXCL9, CXCL10, CXCL11, and CX3CL1 genes were significantly higher in RASFs than OASFs. Our findings suggest that MLL1 regulates the expression of particular cytokines and chemokines in RASFs and is associated with the pathogenesis of RA. These results could lead to new therapies for RA.
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- 2024
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14. Relationship between Treatment Choices according to the Modified Osteoporotic Fracture Score and Posttreatment Radiographic Outcomes
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Shinya Tokunaga, Toshiyuki Takahashi, Koki Mitani, Tomoo Inoue, Ryo Kanematsu, Manabu Minami, Izumi Suda, Sho Nakamura, and Junya Hanakita
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osteoporotic fractures ,conservative treatment ,kyphoplasty ,surgery ,Medicine - Abstract
Study Design Retrospective observational study. Purpose To evaluate the modified osteoporotic fracture (mOF) scores in three treatment groups and compare imaging findings in patients treated and not treated according to the mOF score-based treatment recommendation. Overview of Literature The osteoporotic fracture (OF) score was established by the AO Spine to guide therapeutic decisions. To enhance its applicability, a mOF score was recently introduced. Methods Consecutive patients diagnosed with OFs at Fujieda Heisei Memorial Hospital were divided into three groups: nonsurgical therapy, balloon kyphoplasty (BKP), and open surgery groups. The mOF score was calculated, and the levels of independence and posttreatment imaging data were compared between patients treated and not treated according to the mOF score-based treatment recommendation. Results In total, 118 patients were included (nonsurgical therapy, n=57; BKP, n=48; open surgery, n=13), of whom 100 (85%) received treatment consistent with the mOF score-based treatment recommendation. In the BKP and open surgery groups, the mOF score-based treatment recommendations were consistent with the actual treatment in 93% of the patients. However, in the nonsurgical group, the mOF score-based treatment recommendation was not consistent with the actual treatment in 25% of the patients. In this group, patients not treated according to the mOF score had significantly shorter vertebral body height, greater local kyphosis, and smaller sacral slope after treatment than patients treated according to the mOF score-based treatment recommendation. Conclusions In the BKP and open surgery groups, the mOF scores were consistent with actual clinical selection. In the nonsurgical therapy group, patients not treated according to the mOF score-based treatment recommendation exhibited severe vertebral body deformity and a less well-balanced spine shape after treatment. The mOF score may help in selecting suitable treatments for OFs.
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- 2024
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15. Digital quantification of the MMSE interlocking pentagon areas: a three-stage algorithm
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Namhee Kim, Timothy Truty, S. Duke Han, Moonseong Heo, Aron S. Buchman, David A. Bennett, and Shinya Tasaki
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Mini-mental state examination ,Pentagon copying test ,Aging ,Perceptual speed ,Medicine ,Science - Abstract
Abstract The Mini-Mental State Examination (MMSE) is a widely employed screening tool for the severity of cognitive impairment. Among the MMSE items, the pentagon copying test (PCT) requires participants to accurately replicate a sample of two interlocking pentagons. While the PCT is traditionally scored on a binary scale, there have been limited developments of granular scoring scale to assess task performance. In this paper, we present a novel three-stage algorithm, called Quantification of Interlocking Pentagons (QIP) which quantifies PCT performance by computing the areas of individual pentagons and their intersection areas, and a balance ratio between the areas of the two individual pentagons. The three stages of the QIP algorithm include: (1) detection of line segments, (2) unraveling of the interlocking pentagons, and (3) quantification of areas. A set of 497 PCTs from 84 participants including their baseline and follow-up PCTs from the Rush Memory and Aging Project was selected blinded about their cognitive and clinical status. Analysis of the quantified data revealed a significant inverse relationship between age and balance ratio (beta = − 0.49, p = 0.0033), indicating that older age was associated with a smaller balance ratio. In addition, balance ratio was associated with perceptual speed (r = 0.71, p = 0.0135), vascular risk factors (beta = − 3.96, p = 0.0269), and medical conditions (beta = − 2.78, p = 0.0389). The QIP algorithm can serve as a useful tool for enhancing the scoring of performance in the PCT.
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- 2024
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16. Successful repair of recurrent ventricular septal perforation after myocardial infarction using double patch technique via right ventriculotomy: a case report
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Khoirur Rijal Ashsholih, Taiichi Takasaki, Mayu Tomota, Taika Tokumoto, Seimei Go, Shogo Emura, Masamichi Ozawa, and Shinya Takahashi
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VSP after MI ,Recurrent VSP ,Double patch technique ,Surgery ,RD1-811 ,Anesthesiology ,RD78.3-87.3 - Abstract
Abstract Background Post-myocardial infarction (MI) ventricular septal perforation (VSP) is a rare but life-threatening complication. Surgical repair is challenging and carries significant risks, particularly in the context of recurrent VSPs. This case study presents a patient with recurrent VSP after initial surgical repair following myocardial infarction. Case presentation A 65-year-old male were re-administered to our hospital due to recurrent VSP. He was during follow up after undergone emergency VSP closure surgery 2 months earlier, utilizing the bovine double patch technique via left ventriculostomy. The initial VSP was located in the apical part of the interventricular septum, while the recurrent VSP appeared in the upper middle portion of the interventricular septum (Fig. 1). As the previous patch remained intact, the second surgery employed the bovine double patch technique via right ventriculostomy. The patient’s condition remained stable without the development of heart failure symptoms. Conclusion Repairing recurrent VSPs remains a challenge, necessitating the mastery of appropriate approaches to achieve optimal outcomes. Further research and guidelines are required to refine management strategies for recurrent VSPs.
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- 2024
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17. Preliminary comparative study of lower extremity pressure measurements under the conditions using former models and new lithotomy stirrups in rectal cancer surgery
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Takayuki Ochi, Hidetoshi Katsuno, Hiroyuki Kato, Shinya Takagi, Kenji Kikuchi, Kenichi Nakamura, Tomoyoshi Endo, Kazuhiro Matsuo, Hironobu Yasuoka, Akihiro Nishimura, Akihiko Horiguchi, and Zenichi Morise
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Lithotomy stirrups-2 ,Well-leg compartment syndrome ,Deep venous thrombosis ,Robot-assisted rectal surgery ,Surgery ,RD1-811 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background This study aimed to investigate the effect of the use of new lithotomy stirrups-2 on the pressure dispersal on lower limbs, which may lead to the prevention of well-leg compartment syndrome (WLCS) and deep venous thrombosis (DVT), which are the most commonly associated adverse events with laparoscopic and robot-assisted rectal surgery. Methods A total of 30 healthy participants were included in this study. The pressure (mmHg) applied on various lower limb muscles when using conventional lithotomy stirrups-1 and new type stirrups-2 was recorded in various lithotomy positions; 1) neutral position, 2) Trendelenburg position (15°) with a 0° right inferior tilt, and 3) Trendelenburg position (15°) with a 10° right inferior tilt. Using a special sensor pad named Palm Q®, and the average values were compared between two types of stirrups. Results The use of new lithotomy stirrups-2 significantly reduced the pressure applied on the lower limb muscles in various lithotomy positions compared with the use of lithotomy stirrups-1. The most pressured lower limb muscle when using both lithotomy stirrups was the central soleus muscle, which is the most common site for the development of WLCS and DVT. In addition, when using the conventional lithotomy stirrups-1, the pressure was predominantly applied to the proximal soleus muscle; however, when using lithotomy stirrups-2, the pressure was shifted to the more distal soleus muscle. Conclusion These results suggest that the new lithotomy stirrups-2 is useful in reducing the pressure load on leg muscles, especially on the proximal to central soleus, and may reduce the incidence of WLCS and DVT after rectal surgery performed in the lithotomy position. Further clinical studies are needed to determine whether the use of lithotomy stirrups-2 prevents these complications in various clinical settings.
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- 2024
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18. Development of high-power, long-pulse, multi-frequency ECH/CD system for JT-60SA
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Kobayashi, T., primary, Yamazaki, H., additional, Hiranai, S., additional, Sawahata, M., additional, Terakado, M., additional, Ishita, K., additional, Hinata, J., additional, Sato, F., additional, Wada, K., additional, Toida, N., additional, Ikeda, R., additional, Shinya, T., additional, Yajima, S., additional, Kajiwara, K., additional, Takahashi, K., additional, and Moriayama, S., additional
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- 2022
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19. Ferroptosis in health and disease
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Carsten Berndt, Hamed Alborzinia, Vera Skafar Amen, Scott Ayton, Uladzimir Barayeu, Alexander Bartelt, Hülya Bayir, Christina M. Bebber, Kivanc Birsoy, Jan P. Böttcher, Simone Brabletz, Thomas Brabletz, Ashley R. Brown, Bernhard Brüne, Giorgia Bulli, Alix Bruneau, Quan Chen, Gina M. DeNicola, Tobias P. Dick, Ayelén Distéfano, Scott J. Dixon, Jan B. Engler, Julia Esser-von Bieren, Maria Fedorova, José Pedro Friedmann Angeli, Manuel A. Friese, Dominic C. Fuhrmann, Ana J. García-Sáez, Karolina Garbowicz, Magdalena Götz, Wei Gu, Linda Hammerich, Behrouz Hassannia, Xuejun Jiang, Aicha Jeridi, Yun Pyo Kang, Valerian E. Kagan, David B. Konrad, Stefan Kotschi, Peng Lei, Marlène Le Tertre, Sima Lev, Deguang Liang, Andreas Linkermann, Carolin Lohr, Svenja Lorenz, Tom Luedde, Axel Methner, Bernhard Michalke, Anna V. Milton, Junxia Min, Eikan Mishima, Sebastian Müller, Hozumi Motohashi, Martina U. Muckenthaler, Shohei Murakami, James A. Olzmann, Gabriela Pagnussat, Zijan Pan, Thales Papagiannakopoulos, Lohans Pedrera Puentes, Derek A. Pratt, Bettina Proneth, Lukas Ramsauer, Raphael Rodriguez, Yoshiro Saito, Felix Schmidt, Carina Schmitt, Almut Schulze, Annemarie Schwab, Anna Schwantes, Mariluz Soula, Benedikt Spitzlberger, Brent R. Stockwell, Leonie Thewes, Oliver Thorn-Seshold, Shinya Toyokuni, Wulf Tonnus, Andreas Trumpp, Peter Vandenabeele, Tom Vanden Berghe, Vivek Venkataramani, Felix C.E. Vogel, Silvia von Karstedt, Fudi Wang, Frank Westermann, Chantal Wientjens, Christoph Wilhelm, Michele Wölk, Katherine Wu, Xin Yang, Fan Yu, Yilong Zou, and Marcus Conrad
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Cell death ,Lipid peroxidation ,Iron ,Ischemia/reperfusion ,Cancer ,Neurodegeneration ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells’ susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with – or caused by – ferroptosis.
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- 2024
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20. Evaluation of antimicrobial selective pressure using the multicenter semiautomatic surveillance system Japan surveillance for infection prevention and healthcare epidemiology
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Kayoko Hayakawa, Yusuke Asai, Taichi Tajima, Mio Endo, Jun Kawabata, Naoki Fujii, Mikiyo Sakaguchi, Haruhiko Ishioka, Shinya Tsuzuki, Nobuaki Matsunaga, Norio Ohmagari, and Haruhisa Fukuda
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Selective pressure antimicrobial ,Resistance ,Carbapenem ,J-SIPHE ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Background: Evaluating the selective pressure of antimicrobials on bacteria is important for promoting antimicrobial stewardship programs (ASPs). The aim of this study was to assess the selective pressure of antimicrobials by evaluating their use (carbapenem [CBP] and CBP-sparing therapy) over time and the detection status of CBP-resistant organisms using multicenter data. Methods: Among the facilities whose data were registered in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology from 2017 to 2020, those that had data on the use of CBP and CBP-sparing therapy (fluoroquinolones [FQs], cefmetazole [CMZ], piperacillin–tazobactam [PIP/TAZ], ampicillin–sulbactam [ABPC/SBT], ceftriaxone/cefotaxime [CTRX/CTX], CAZ (ceftazidime), cefepime [CFPM], and aminoglycosides [AGs]) as well as on CBP-resistant Enterobacterales (CRE) and CBP-resistant Pseudomonas aeruginosa (CRPA) detection were included. Alcohol-based hand rubbing (ABHR) usage was also analyzed. Regression analyses, including multivariable regression analysis, were performed to evaluate trends. The association of antimicrobial use density (AUD) with CRE and CRPA detection rates was evaluated. Results: In 28 facilities nationwide, CBP, FQ, CAZ, AG, and PIP/TAZ use decreased over the 3-year period, whereas the use of CMZ, ABPC/SBT, CTRX/CTX, CFPM, and ABHR as well as the rates of CRE and CRPA detection increased. The average AUD did not significantly correlate with CRE and CRPA detection rates. The multivariable regression analysis did not reveal any significant correlation between each AUD or ABHR and CRE or CRPA detection. Conclusion: CBP and ABHR use showed a decreasing and an increasing trend, respectively, while CRPA and CRE detection rates exhibited a gradual increase. The considerably low CRE and CRPA detection rates suggest that slight differences in numbers may have been observed as excessive trend changes. Further investigation is warranted to evaluate selective pressure while considering the characteristics of ASP and the mechanisms underlying resistance.
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- 2024
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21. Editorial: Methods in artificial intelligence for dementia 2024
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Roozbeh Sadeghian, Fasih Haider, Kathleen Fraser, Shinya Tasaki, and Graciela Muniz-Terrera
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digital biomarkers ,machine learning ,dementia ,active living ,cognitive impairment ,intervention ,Medicine - Published
- 2024
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22. Experimental study of mechanical behavior of unsaturated silty clay in different loading sequences under constant water content condition
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Rasool, A, primary, Jiro, K, additional, and Shinya, T, additional
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- 2015
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23. Completion of JT-60SA construction and contribution to ITER
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Kamada Y., Di Pietro E., Hanada M., Barabaschi P., Ide S., Davis S., Yoshida M., Giruzzi G., Sozzi C., Abdel Maksoud W., Abe H., Aiba N., Akiyama T., Ayllon-Guerola J., Arai T., Artaud J. -F., Asakura N., Ashikawa N., Balbinot L., Bando T., Baulaigue O., Belonohy E., Bin W., Bombarda F., Bolzonella T., Bonne F., Bonotto M., Botija J., Cabrera-Perez S., Cardella A., Carraro L., Cavalier J., Chernyshova M., Chiba S., Clement-Lorenzo S., Cocilovo V., Coda S., Coelho R., Coffey I., Collin B., Corato V., Cucchiaro A., Czarski T., Dairaku M., Day C., de la Luna E., De Tommasi G., Decool P., Di Pace L., Dibon M., Disset G., Ejiri A., Endo Y., Ezumi N., Falchetto G., Fassina A., Fejoz P., Ferro A., Fietz W., Figini L., Fornal T., Frello G., Fujita T., Fukuda T., Fukui K., Fukumoto M., Furukawa M., Futatani S., Gabellieri L., Gaio E., Galazka K., Garcia J., Garcia-Dominguez J., Garcia-Lopez J., Garcia-Munoz M., Garzotti L., Gasparini F., Gharafi S., Giacomelli L., Ginoulhiac G., Giudicotti L., Guillen Gonzalez R., Hajnal N., Hall S., Hamada K., Hanada K., Hasegawa K., Hatae T., Hatakeyama S., Hauer V., Hayashi N., Hayashi T., Heller R., Higashijima S., Hinata J., Hiranai S., Hiratsuka J., Hiwatari R., Hoa C., Homma H., Honda A., Honda M., Horiike H., Hoshino K., Hurzlmeier H., Iafrati M., Ibano K., Ichige H., Ichikawa M., Ichimura M., Ida K., Idei H., Iijima T., Iio S., Ikeda R., Ikeda Y., Imai T., Imazawa R., Inagaki S., Inomoto M., Inoue S., Isayama A., Ishida S., Ishii Y., Isobe M., Janky F., Joffrin E., Jokinen A., Kado S., Kajita S., Kajiwara K., Kamata I., Kaminaga A., Kamiya K., Kanapienyte D., Kashiwa Y., Kashiwagi M., Katayama K., Kawamata Y., Kawamura G., Kawano K., Kawashima H., Kin F., Kitajima S., Kiyono K., Kizu K., Kobayashi K., Kobayashi M., Kobayashi S., Kobayashi T., Kocsis G., Koide Yo., Koide Yu., Kojima A., Kokusen S., Komuro K., Konishi S., Kovacsik A., Ksiazek I., Kubkowska M., Kuhner G., Kuramochi M., Kurihara K., Kurki-Suonio T., Kurniawan A. B., Kuwata T., Lacroix B., Lamaison V., Lampasi A., Lang P., Lauber P., Lawson K., Louzguiti A., Maekawa R., Maekawa T., Maeyama S., Maffia G., Maget P., Mailloux J., Maione I., Maistrello A., Malinowski K., Marchiori G., Marechal J. -L., Massaut V., Masuzaki S., Matsunaga G., Matsunaga S., Mayri Ch., Mattei M., Medrano M., Mele A., Meyer I., Michel F., Minami T., Miyata Y., Miyazawa J., Miyo Y., Mizuuchi T., Mogaki K., Morales J., Moreau P., Mori M., Morisaki T., Morishima S., Moriyama S., Moro A., Murakami H., Murayama M., Murakami S., Nagasaki K., Naito O., Nakamura S., Nakano T., Nakashima Y., Nardino V., Narita E., Narushima Y., Natsume K., Nemoto S., Neu R., Nicollet S., Nishikawa M., Nishimura S., Nishiura M., Nishiyama T., Nocente M., Nobuta Y., Novello L., Nunio F., Ochoa S., Ogawa T., Ogawa Y., Ohdachi S., Ohmori Y., Ohno N., Ohtani Y., Ohzeki M., Oishi T., Okano F., Okano J., Okano K., Onishi Y., Osakabe M., Oshima T., Ostuni V., Oya M., Oya Y., Oyama N., Ozeki T., Pasqualotto R., Pelli S., Peretti E., Phillips G., Piccinni C., Pigatto L., Pironti A., Pizzuto A., Plockl B., Polli G., Poncet J. -M., Ponsot P., Puiatti M., Radloff D., Raimondi V., Ramos F., Rancsik P., Ricci D., Ricciarini S., Rincon E., Romano A., Rossi P., Roussel P., Rubino G., Saeki H., Sagara A., Sakakibara S., Sakamoto H., Sakamoto M., Sakamoto Y., Sakasai A., Sakata S., Sakuma T., Sakurai S., Salanon B., Salmi A., Sannazzaro G., Sano R., Sanpei A., Sasajima T., Sasaki S., Sasao H., Sato F., Sato M., Sawahata M., Scherber A., Scully S., Seki M., Seki S., Shibama Y., Shibata Y., Shikama T., Shimada K., Shimono M., Shinde J., Shinya T., Shinohara K., Shirai H., Shiraishi J., Soare S., Soleto A., Someya Y., Streciwilk-Kowalska E., Strobel H., Sueoka M., Sukegawa A., Sulistyanintyas D., Sumida S., Sunaoshi H., Suzuki H., Suzuki M., Suzuki S., Suzuki T., Suzuki Y., Svoboda J., Szabolics T., Szepesi T., Takahashi K., Takase Y., Takechi M., Takeda K., Takeiri Y., Takenaga H., Taliercio C., Tamura N., Tanaka H., Tanaka K., Tani K., Tanigawa H., Tardocchi M., Terakado A., Terakado M., Terakado T., Teuchner B., Tilia B., Tobita K., Toi K., Toida N., Tojo H., Tokitani M., Tokuzawa T., Tormarchio V., Tomine M., Torre A., Totsuka T., Tsuchiya K., Tsujii N., Tsuru D., Tsutsui H., Uchida M., Ueda Y., Uno J., Urano H., Usui K., Utoh H., Valisa M., Vallar M., Vallcorba-Carbonell R., Vallet J. -C., Varela J., Vega J., Verrecchia M., Vieillard L., Villone F., Vincenzi P., Wada K., Wada R., Wakatsuki T., Wanner M., Watanabe F., Watanabe K., Wauters T., Wiesen S., Wischmeier M., Yagi M., Yagyu J., Yajima M., Yokooka S., Yokoyama M., Yamamoto S., Yamanaka H., Yamauchi K., Yamauchi Y., Yamazaki H., Yamazaki K., Yamazaki R., Yamoto S., Yanagi S., Yanagihara K., Yoshizawa N., Zani L., Zito P., Kamada, Y., Di Pietro, E., Hanada, M., Barabaschi, P., Ide, S., Davis, S., Yoshida, M., Giruzzi, G., Sozzi, C., Abdel Maksoud, W., Abe, H., Aiba, N., Akiyama, T., Ayllon-Guerola, J., Arai, T., Artaud, J. -F., Asakura, N., Ashikawa, N., Balbinot, L., Bando, T., Baulaigue, O., Belonohy, E., Bin, W., Bombarda, F., Bolzonella, T., Bonne, F., Bonotto, M., Botija, J., Cabrera-Perez, S., Cardella, A., Carraro, L., Cavalier, J., Chernyshova, M., Chiba, S., Clement-Lorenzo, S., Cocilovo, V., Coda, S., Coelho, R., Coffey, I., Collin, B., Corato, V., Cucchiaro, A., Czarski, T., Dairaku, M., Day, C., de la Luna, E., De Tommasi, G., Decool, P., Di Pace, L., Dibon, M., Disset, G., Ejiri, A., Endo, Y., Ezumi, N., Falchetto, G., Fassina, A., Fejoz, P., Ferro, A., Fietz, W., Figini, L., Fornal, T., Frello, G., Fujita, T., Fukuda, T., Fukui, K., Fukumoto, M., Furukawa, M., Futatani, S., Gabellieri, L., Gaio, E., Galazka, K., Garcia, J., Garcia-Dominguez, J., Garcia-Lopez, J., Garcia-Munoz, M., Garzotti, L., Gasparini, F., Gharafi, S., Giacomelli, L., Ginoulhiac, G., Giudicotti, L., Guillen Gonzalez, R., Hajnal, N., Hall, S., Hamada, K., Hanada, K., Hasegawa, K., Hatae, T., Hatakeyama, S., Hauer, V., Hayashi, N., Hayashi, T., Heller, R., Higashijima, S., Hinata, J., Hiranai, S., Hiratsuka, J., Hiwatari, R., Hoa, C., Homma, H., Honda, A., Honda, M., Horiike, H., Hoshino, K., Hurzlmeier, H., Iafrati, M., Ibano, K., Ichige, H., Ichikawa, M., Ichimura, M., Ida, K., Idei, H., Iijima, T., Iio, S., Ikeda, R., Ikeda, Y., Imai, T., Imazawa, R., Inagaki, S., Inomoto, M., Inoue, S., Isayama, A., Ishida, S., Ishii, Y., Isobe, M., Janky, F., Joffrin, E., Jokinen, A., Kado, S., Kajita, S., Kajiwara, K., Kamata, I., Kaminaga, A., Kamiya, K., Kanapienyte, D., Kashiwa, Y., Kashiwagi, M., Katayama, K., Kawamata, Y., Kawamura, G., Kawano, K., Kawashima, H., Kin, F., Kitajima, S., Kiyono, K., Kizu, K., Kobayashi, K., Kobayashi, M., Kobayashi, S., Kobayashi, T., Kocsis, G., Koide, Yo., Koide, Yu., Kojima, A., Kokusen, S., Komuro, K., Konishi, S., Kovacsik, A., Ksiazek, I., Kubkowska, M., Kuhner, G., Kuramochi, M., Kurihara, K., Kurki-Suonio, T., Kurniawan, A. B., Kuwata, T., Lacroix, B., Lamaison, V., Lampasi, A., Lang, P., Lauber, P., Lawson, K., Louzguiti, A., Maekawa, R., Maekawa, T., Maeyama, S., Maffia, G., Maget, P., Mailloux, J., Maione, I., Maistrello, A., Malinowski, K., Marchiori, G., Marechal, J. -L., Massaut, V., Masuzaki, S., Matsunaga, G., Matsunaga, S., Mayri, Ch., Mattei, M., Medrano, M., Mele, A., Meyer, I., Michel, F., Minami, T., Miyata, Y., Miyazawa, J., Miyo, Y., Mizuuchi, T., Mogaki, K., Morales, J., Moreau, P., Mori, M., Morisaki, T., Morishima, S., Moriyama, S., Moro, A., Murakami, H., Murayama, M., Murakami, S., Nagasaki, K., Naito, O., Nakamura, S., Nakano, T., Nakashima, Y., Nardino, V., Narita, E., Narushima, Y., Natsume, K., Nemoto, S., Neu, R., Nicollet, S., Nishikawa, M., Nishimura, S., Nishiura, M., Nishiyama, T., Nocente, M., Nobuta, Y., Novello, L., Nunio, F., Ochoa, S., Ogawa, T., Ogawa, Y., Ohdachi, S., Ohmori, Y., Ohno, N., Ohtani, Y., Ohzeki, M., Oishi, T., Okano, F., Okano, J., Okano, K., Onishi, Y., Osakabe, M., Oshima, T., Ostuni, V., Oya, M., Oya, Y., Oyama, N., Ozeki, T., Pasqualotto, R., Pelli, S., Peretti, E., Phillips, G., Piccinni, C., Pigatto, L., Pironti, A., Pizzuto, A., Plockl, B., Polli, G., Poncet, J. -M., Ponsot, P., Puiatti, M., Radloff, D., Raimondi, V., Ramos, F., Rancsik, P., Ricci, D., Ricciarini, S., Rincon, E., Romano, A., Rossi, P., Roussel, P., Rubino, G., Saeki, H., Sagara, A., Sakakibara, S., Sakamoto, H., Sakamoto, M., Sakamoto, Y., Sakasai, A., Sakata, S., Sakuma, T., Sakurai, S., Salanon, B., Salmi, A., Sannazzaro, G., Sano, R., Sanpei, A., Sasajima, T., Sasaki, S., Sasao, H., Sato, F., Sato, M., Sawahata, M., Scherber, A., Scully, S., Seki, M., Seki, S., Shibama, Y., Shibata, Y., Shikama, T., Shimada, K., Shimono, M., Shinde, J., Shinya, T., Shinohara, K., Shirai, H., Shiraishi, J., Soare, S., Soleto, A., Someya, Y., Streciwilk-Kowalska, E., Strobel, H., Sueoka, M., Sukegawa, A., Sulistyanintyas, D., Sumida, S., Sunaoshi, H., Suzuki, H., Suzuki, M., Suzuki, S., Suzuki, T., Suzuki, Y., Svoboda, J., Szabolics, T., Szepesi, T., Takahashi, K., Takase, Y., Takechi, M., Takeda, K., Takeiri, Y., Takenaga, H., Taliercio, C., Tamura, N., Tanaka, H., Tanaka, K., Tani, K., Tanigawa, H., Tardocchi, M., Terakado, A., Terakado, M., Terakado, T., Teuchner, B., Tilia, B., Tobita, K., Toi, K., Toida, N., Tojo, H., Tokitani, M., Tokuzawa, T., Tormarchio, V., Tomine, M., Torre, A., Totsuka, T., Tsuchiya, K., Tsujii, N., Tsuru, D., Tsutsui, H., Uchida, M., Ueda, Y., Uno, J., Urano, H., Usui, K., Utoh, H., Valisa, M., Vallar, M., Vallcorba-Carbonell, R., Vallet, J. -C., Varela, J., Vega, J., Verrecchia, M., Vieillard, L., Villone, F., Vincenzi, P., Wada, K., Wada, R., Wakatsuki, T., Wanner, M., Watanabe, F., Watanabe, K., Wauters, T., Wiesen, S., Wischmeier, M., Yagi, M., Yagyu, J., Yajima, M., Yokooka, S., Yokoyama, M., Yamamoto, S., Yamanaka, H., Yamauchi, K., Yamauchi, Y., Yamazaki, H., Yamazaki, K., Yamazaki, R., Yamoto, S., Yanagi, S., Yanagihara, K., Yoshizawa, N., Zani, L., and Zito, P.
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assembly ,Cryostat ,Nuclear and High Energy Physics ,Materials science ,Tokamak ,Nuclear engineering ,Plasma ,Condensed Matter Physics ,Field coil ,ITER risk mitigation ,Overcurrent ,law.invention ,Control theory ,law ,Electromagnetic coil ,research plan ,broader approach ,Voltage - Abstract
Construction of the JT-60SA tokamak was completed on schedule in March 2020. Manufacture and assembly of all the main tokamak components satisfied technical requirements, including dimensional accuracy and functional performances. Development of the plasma heating systems and diagnostics have also progressed, including the demonstration of the favourable electron cyclotron range of frequency (ECRF) transmission at multiple frequencies and the achievement of long sustainment of a high-energy intense negative ion beam. Development of all the tokamak operation control systems has been completed, together with an improved plasma equilibrium control scheme suitable for superconducting tokamaks including ITER. For preparation of the tokamak operation, plasma discharge scenarios have been established using this advanced equilibrium controller. Individual commissioning of the cryogenic system and the power supply system confirmed that these systems satisfy design requirements including operational schemes contributing directly to ITER, such as active control of heat load fluctuation of the cryoplant, which is essential for dynamic operation in superconducting tokamaks. The integrated commissioning (IC) is started by vacuum pumping of the vacuum vessel and cryostat, and then moved to cool-down of the tokamak and coil excitation tests. Transition to the super-conducting state was confirmed for all the TF, EF and CS coils. The TF coil current successfully reached 25.7 kA, which is the nominal operating current of the TF coil. For this nominal toroidal field of 2.25 T, ECRF was applied and an ECRF plasma was created. The IC was, however, suspended by an incident of over current of one of the superconducting equilibrium field coil and He leakage caused by insufficient voltage holding capability at a terminal joint of the coil. The unique importance of JT-60SA for H-mode and high-β steady-state plasma research has been confirmed using advanced integrated modellings. These experiences of assembly, IC and plasma operation of JT-60SA contribute to ITER risk mitigation and efficient implementation of ITER operation.
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- 2022
24. Effects of acute phase intensive electrical muscle stimulation in COVID-19 patients requiring invasive mechanical ventilation: an observational case-control study
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Yohei Tsuchikawa, Shinya Tanaka, Daisuke Kasugai, Riko Nakagawa, Miho Shimizu, Takayuki Inoue, Motoki Nagaya, Takafumi Nasu, Norihito Omote, Michiko Higashi, Takanori Yamamoto, Naruhiro Jingushi, Atsushi Numaguchi, and Yoshihiro Nishida
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Neuromuscular electrical stimulation ,Physical performance ,Intensive care unit acquired weakness ,SARS-CoV-2 ,Ventilator ,Medicine ,Science - Abstract
Abstract We investigated the effects of acute-phase intensive electrical muscle stimulation (EMS) on physical function in COVID-19 patients with respiratory failure requiring invasive mechanical ventilation (IMV) in the intensive care unit (ICU). Consecutive COVID-19 patients requiring IMV admitted to a university hospital ICU between January and April 2022 (EMS therapy group) or between March and September 2021 (age-matched historical control group) were included in this retrospective observational case–control study. EMS was applied to both upper and lower limb muscles for up to 2 weeks in the EMS therapy group. The study population consisted of 16 patients undergoing EMS therapy and 16 age-matched historical controls (median age, 71 years; 81.2% male). The mean period until initiation of EMS therapy after ICU admission was 3.2 ± 1.4 days. The EMS therapy group completed a mean of 6.2 ± 3.7 EMS sessions, and no adverse events occurred. There were no significant differences between the two groups in Medical Research Council sum score (51 vs. 53 points, respectively; P = 0.439) or ICU mobility scale at ICU discharge. Addition of upper and lower limb muscle EMS therapy to an early rehabilitation program did not result in improved physical function at ICU discharge in severe COVID-19 patients.
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- 2024
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25. Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant
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Tomokazu Tamura, Takashi Irie, Sayaka Deguchi, Hisano Yajima, Masumi Tsuda, Hesham Nasser, Keita Mizuma, Arnon Plianchaisuk, Saori Suzuki, Keiya Uriu, Mst Monira Begum, Ryo Shimizu, Michael Jonathan, Rigel Suzuki, Takashi Kondo, Hayato Ito, Akifumi Kamiyama, Kumiko Yoshimatsu, Maya Shofa, Rina Hashimoto, Yuki Anraku, Kanako Terakado Kimura, Shunsuke Kita, Jiei Sasaki, Kaori Sasaki-Tabata, Katsumi Maenaka, Naganori Nao, Lei Wang, Yoshitaka Oda, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Terumasa Ikeda, Akatsuki Saito, Keita Matsuno, Jumpei Ito, Shinya Tanaka, Kei Sato, Takao Hashiguchi, Kazuo Takayama, and Takasuke Fukuhara
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Science - Abstract
Abstract Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.
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- 2024
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26. Real-world effectiveness of full and booster mRNA vaccination for coronavirus disease 2019 against disease severity during the delta- and omicron-dominant phases: A propensity score-matched cohort study using the nationwide registry data in Japan
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Tetsuya Suzuki, Yusuke Asai, Shinya Tsuzuki, Hidetoshi Nomoto, Nobuaki Matsunaga, Eiichi N. Kodama, Kayoko Hayakawa, and Norio Ohmagari
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Booster vaccination ,Coronavirus ,Delta variant ,Omicron variant ,Vaccine effectiveness ,Microbiology ,QR1-502 - Abstract
Background: To date, few studies from the Asian region have reported the effectiveness of messenger ribonucleic acid coronavirus disease 2019 (COVID-19) vaccines against disease progression and death after hospitalization. Methods: We evaluated the data from the COVID-19 registry in Japan during the delta- and omicron-dominant phases. A propensity score-matched cohort study was conducted between the incompletely (0–1 dose) and fully (2 doses) vaccinated groups during the delta-dominant phase and among the incompletely, fully, and booster (3 doses) vaccinated groups during the omicron-dominant phase. Results: In the delta-dominant phase, 411 pairs were matched. The fully vaccinated group showed a significantly lower oxygen supplementation rate (24.1 % vs. 41.1 %, p
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- 2024
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27. Cavin‐2 promotes fibroblast‐to‐myofibroblast trans‐differentiation and aggravates cardiac fibrosis
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Yusuke Higuchi, Takehiro Ogata, Naohiko Nakanishi, Masahiro Nishi, Yumika Tsuji, Shinya Tomita, Simon J. Conway, and Satoaki Matoba
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Cardiac fibrosis ,Cavin‐2 ,Fibroblasts ,TGF‐β/Smad signalling ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Transforming growth factor β (TGF‐β) signalling is one of the critical pathways in fibroblast activation, and several drugs targeting the TGF‐β/Smad signalling pathway in heart failure with cardiac fibrosis are being tested in clinical trials. Some caveolins and cavins, which are components of caveolae on the plasma membrane, are known for their association with the regulation of TGF‐β signalling. Cavin‐2 is particularly abundant in fibroblasts; however, the detailed association between Cavin‐2 and cardiac fibrosis is still unclear. We tried to clarify the involvement and role of Cavin‐2 in fibroblasts and cardiac fibrosis. Methods and results To clarify the role of Cavin‐2 in cardiac fibrosis, we performed transverse aortic constriction (TAC) operations on four types of mice: wild‐type (WT), Cavin‐2 null (Cavin‐2 KO), Cavin‐2flox/flox, and activated fibroblast‐specific Cavin‐2 conditional knockout (Postn‐Cre/Cavin‐2flox/flox, Cavin‐2 cKO) mice. We collected mouse embryonic fibroblasts (MEFs) from WT and Cavin‐2 KO mice and investigated the effect of Cavin‐2 in fibroblast trans‐differentiation into myofibroblasts and associated TGF‐β signalling. Four weeks after TAC, cardiac fibrotic areas in both the Cavin‐2 KO and the Cavin‐2 cKO mice were significantly decreased compared with each control group (WT 8.04 ± 1.58% vs. Cavin‐2 KO 0.40 ± 0.03%, P
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- 2024
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28. Impact of radiation doses on clinical relapse of biochemically recurrent prostate cancer after prostatectomy
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Seiya Takano, Natsuo Tomita, Masanari Niwa, Akira Torii, Taiki Takaoka, Nozomi Kita, Kaoru Uchiyama, Mikiko Nakanishi-Imai, Shiho Ayakawa, Masato Iida, Yusuke Tsuzuki, Shinya Otsuka, Yoshihiko Manabe, Kento Nomura, Yasutaka Ogawa, Akifumi Miyakawa, Akihiko Miyamoto, Shinya Takemoto, Takahiro Yasui, and Akio Hiwatashi
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Medicine ,Science - Abstract
Abstract The relationship between radiation doses and clinical relapse in patients receiving salvage radiotherapy (SRT) for biochemical recurrence (BCR) after radical prostatectomy (RP) remains unclear. We identified 292 eligible patients treated with SRT between 2005 and 2018 at 15 institutions. Clinical relapse-free survival (cRFS) between the ≥ 66 Gy (n = 226) and
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- 2024
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29. The Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling in pulmonary hypertension by interfering with BMPR2/Caveolin-1 binding
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Shinya Tomita, Naohiko Nakanishi, Takehiro Ogata, Yusuke Higuchi, Akira Sakamoto, Yumika Tsuji, Takaomi Suga, and Satoaki Matoba
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Biology (General) ,QH301-705.5 - Abstract
Abstract Caveolin-1 (CAV1) and Cavin-1 are components of caveolae, both of which interact with and influence the composition and stabilization of caveolae. CAV1 is associated with pulmonary arterial hypertension (PAH). Bone morphogenetic protein (BMP) type 2 receptor (BMPR2) is localized in caveolae associated with CAV1 and is commonly mutated in PAH. Here, we show that BMP/Smad signaling is suppressed in pulmonary microvascular endothelial cells of CAV1 knockout mice. Moreover, hypoxia enhances the CAV1/Cavin-1 interaction but attenuates the CAV1/BMPR2 interaction and BMPR2 membrane localization in pulmonary artery endothelial cells (PAECs). Both Cavin-1 and BMPR2 are associated with the CAV1 scaffolding domain. Cavin-1 decreases BMPR2 membrane localization by inhibiting the interaction of BMPR2 with CAV1 and reduces Smad signal transduction in PAECs. Furthermore, Cavin-1 knockdown is resistant to CAV1-induced pulmonary hypertension in vivo. We demonstrate that the Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling and is a promising target for the treatment of PAH.
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- 2024
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30. Structure-changeable luminescent Eu(III) complex as a human cancer grade probing system for brain tumor diagnosis
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Mengfei Wang, Masaya Kono, Yusaku Yamaguchi, Jahidul Islam, Sunao Shoji, Yuichi Kitagawa, Koji Fushimi, Sora Watanabe, Go Matsuba, Akihisa Yamamoto, Motomu Tanaka, Masumi Tsuda, Shinya Tanaka, and Yasuchika Hasegawa
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Medicine ,Science - Abstract
Abstract Accurate determination of human tumor malignancy is important for choosing efficient and safe therapies. Bioimaging technologies based on luminescent molecules are widely used to localize and distinguish active tumor cells. Here, we report a human cancer grade probing system (GPS) using a water-soluble and structure-changeable Eu(III) complex for the continuous detection of early human brain tumors of different malignancy grades. Time-dependent emission spectra of the Eu(III) complexes in various types of tumor cells were recorded. The radiative rate constants (k r), which depend on the geometry of the Eu(III) complex, were calculated from the emission spectra. The tendency of the k r values to vary depended on the tumor cells at different malignancy grades. Between T = 0 and T = 3 h of invasion, the k r values exhibited an increase of 4% in NHA/TS (benign grade II gliomas), 7% in NHA/TSR (malignant grade III gliomas), and 27% in NHA/TSRA (malignant grade IV gliomas). Tumor cells with high-grade malignancy exhibited a rapid upward trend in k r values. The cancer GPS employs Eu(III) emissions to provide a new diagnostic method for determining human brain tumor malignancy.
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- 2024
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31. The Number of Microbubbles Generated During Cardiopulmonary Bypass Can Be Estimated Using Machine Learning From Suction Flow Rate, Venous Reservoir Level, Perfusion Flow Rate, Hematocrit Level, and Blood Temperature
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Satoshi Miyamoto, Zu Soh, Shigeyuki Okahara, Akira Furui, Taiichi Takasaki, Keijiro Katayama, Shinya Takahashi, and Toshio Tsuji
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Cardiac surgery ,cardiopulmonary bypass ,microbubbles ,neural network ,online detection ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Medical technology ,R855-855.5 - Abstract
Goal: Microbubbles (MBs) are known to occur within the circuits of cardiopulmonary bypass (CPB) systems, and higher-order dysfunction after cardiac surgery may be caused by MBs as well as atheroma dispersal associated with cannula insertion. As complete MB elimination is not possible, monitoring MB count rates is critical. We propose an online detection system with a neural network-based model to estimate MB count rate using five parameters: suction flow rate, venous reservoir level, perfusion flow rate, hematocrit level, and blood temperature. Methods: Perfusion experiments were performed using an actual CPB circuit, and MB count rates were measured using the five varying parameters. Results: Bland–Altman analysis indicated a high estimation accuracy (R2 > 0.95, p < 0.001) with no significant systematic error. In clinical practice, although the inclusion of clinical procedures slightly decreased the estimation accuracy, a high coefficient of determination for 30 clinical cases (R2 = 0.8576) was achieved between measured and estimated MB count rates. Conclusions: Our results highlight the potential of this system to improve patient outcomes and reduce MB-associated complication risk.
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- 2024
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32. Effect of body fat mass loss on prognosis of radical resection for pancreatic ductal adenocarcinoma based on bioelectrical impedance analysis
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Yoshiyuki Shibata, Takeshi Sudo, Sho Tazuma, Haruki Sada, Naoki Tanimine, Norimitsu Shimada, Hirofumi Tazawa, Takahisa Suzuki, Takashi Onoe, Yosuke Shimizu, Hirotaka Tashiro, Atsushi Yamaguchi, and Shinya Takahashi
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Bioelectrical impedance analysis ,Body composition ,BFM ,Prognosis ,Pancreatic ductal adenocarcinoma ,Surgery ,RD1-811 - Abstract
Abstract Background Few reports have performed a prognostic analysis based on bioelectrical impedance analysis in patients with radical resection of pancreatic ductal adenocarcinoma (PDAC), and its usefulness in prognostic analysis remains unclear. This study aimed to evaluate body composition changes in patients undergoing radical resection for PDAC and analyze its impact on prognosis. Methods The medical records of radical resection for patients with PDAC were retrospectively reviewed, and the parameters of body composition, including body weight, skeletal muscle mass, body fat mass (BFM), and extracellular water-total body water ratio, from preoperatively to 12 months postoperatively, for each surgical procedure were measured based on direct segmental multifrequency bioelectrical impedance analysis with an InBody 770 (InBody Inc., Tokyo, Japan) device. The clinicopathological and prognostic factors were analyzed. Results Among 79 patients who underwent radical resection for PDAC, 36 (46%), 7 (8%), and 36 (46%) underwent pancreatoduodenectomy, total pancreatectomy, and distal pancreatectomy, respectively. The multivariate overall survival analysis demonstrated that BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021), lymph node metastasis (p = 0.014), and non-adjuvant chemotherapy (p
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- 2024
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33. Outcome of surgical parathyroidectomy for tertiary hyperparathyroidism in kidney transplant recipients: tertiary hyperparathyroidism should not be ignored, for the sake of precious allografts
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Michio Nakamura, Shinya Takiguchi, Saeko Uehara, and Yusuke Tomita
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Tertiary hyperparathyroidism ,kidney transplantation ,parathyroidectomy ,calcimimetics ,allograft function ,allograft survival ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Tertiary hyperparathyroidism is a complication of kidney transplantation. This complicated condition carries over from the dialysis period and varies according to the function of the transplanted allograft. Treatments include pharmacotherapy (mainly using calcimimetics) and parathyroidectomy, but calcimimetics are currently not covered by the national insurance system in Japan. Two types of parathyroidectomy can be performed: subtotal parathyroidectomy; and total parathyroidectomy with partial autograft. Both types can be expected to improve hypercalcemia. Concerns about the postoperative deterioration of allograft function are influenced by preoperative allograft function, which is even more likely to be affected by early surgery after kidney transplantation. In general, transient deterioration of allograft function after surgery is not expected to affect graft survival rate in the medium to long term. Tertiary hyperparathyroidism in kidney transplant recipients negatively impacts allograft and patient survival rates, and parathyroidectomy can be expected to improve prognosis in both kidney recipients and dialysis patients. However, studies offering high levels of evidence remain lacking.
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- 2024
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34. Strontium isotope analysis identifies the source and transport of fluvial suspended solids in the Fuji River Basin, Japan
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Shinya Takano, Tomoya Iwata, Ki-Cheol Shin, and Ichiro Tayasu
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Sr isotopic composition ,Riverine SS ,Soil erosion ,Turbidity ,River water ,Fluvial sediments ,Physical geography ,GB3-5030 ,Geology ,QE1-996.5 - Abstract
Study region: The middle and lower reaches of the Fuji River system, Central Japan Study focus: The increase in turbidity over the last decade is considered a major cause of habitat degradation of aquatic organisms in the Fuji River and the adjacent coastal area of Suruga Bay. This study identifies the source and fate of suspended solids (SS) in the Fuji River system based on an investigation of the isotopic composition of strontium (87Sr/86Sr) in river water, SS, and fluvial sediments. New hydrological insights for the region: The Sr isotope mass-balance model revealed that the strong turbidity (SS > 500 mg L−1) observed in a major tributary system—the Hayakawa River—accounted for 65 % of riverine SS in the Fuji River; however, the Hayakawa River water contributed only 24 % to the total river water flow in the Fuji River. In contrast, riverbed sediments in the Fuji River contained only 11 % of the sediments derived from the Hayakawa River system. These results suggest that the Hayakawa River SS could be a major source of turbidity in the Fuji River but most of it flowing into Suruga Bay without significant sedimentation. The present Sr isotope ratio, depends on host rock types in geologically heterogeneous catchments, can be used for fingerprinting of fluvial SS and improving ecosystem management planning in watersheds susceptible to frequent soil erosion and landslides.
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- 2024
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35. Challenge of fabricating difficult-to-nitride materials: Formation of martensitic phase in (Fe0.8Co0.2)8N foil based on industrially suitable gas-nitriding process
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Tomohiro Tabata, Matahiro Komuro, Yusuke Asari, Shinya Tamura, Masafumi Nojima, Tomio Iwasaki, and Shohei Terada
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Physics ,QC1-999 - Abstract
Nitrogen-martensitic phase (Fe0.8Co0.2)8N was successfully synthesized by using an industrially suitable gas-nitriding process of a bulk foil. So far, the nitrogen-martensitic phase of the bulk material has not been synthesized at such a high Co content. We found that this is because the nitride was easily denitrided by elevating temperature. In this work, by exploiting a NH3 gas-nitriding process combined with quenching at a rapid cooling rate (>800 °C/s) in NH3 atmosphere, we found that nitrogen stayed at the surface layer of the foil. By using cross-sectional laser microscopy, the nitride region was observed as a 7-μm-thick layered shape at the surface of the 100-μm-thick foil. An x-ray diffraction technique revealed that the nitride layer was a martensitic phase that was characterized as a body-centered tetragonal structure with c/a = 1.04. These findings can be applied to nitriding and surface treatments for alloy systems in which a nitrogen solid solution is hardly formed. Our developed method is promising because the martensitic phase is expected to be formed in whole bulk by further optimizing parameters clarified in this work.
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- 2024
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36. Lipid metabolites and nitric oxide production in the cerebrospinal fluid and plasma of dogs with meningoencephalitis of unknown origin and idiopathic epilepsy: a pilot study
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Tomohiro Yonezawa, Shinya Takenouchi, Tomoki Motegi, Michiyo Miyazaki, Nanae Nagata, Koji Kobayashi, Masaki Yamada, and Takahisa Murata
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epileptic seizures ,nitric oxide ,prostaglandin ,arachidonic acid ,cerebrospinal fluid ,Veterinary medicine ,SF600-1100 - Abstract
IntroductionIdiopathic epilepsy (IE) and meningoencephalomyelitis of unknown origin (MUO) are common causes of brain diseases leading to seizures in dogs. In this study, the concentrations of 196 lipid metabolites and nitrogen oxide (NO) production in the cerebrospinal fluid (CSF) and plasma of dogs with MUO or IE were measured using a LC-MS/MS and a NOx analyzer, respectively.MethodsNine clinically healthy dogs and 11 and 12 dogs with IE and MUO, respectively, were included in the study.ResultsLipid analysis revealed variations in the levels of four and six lipid metabolites in CSF and plasma, respectively, between the groups. The levels of 6-keto-prostaglandin (PG) F1α (PGF1α), 20-carboxy arachidonic acid (20-carboxy-AA), 9-hydroxyoctadecadienoic acid, and lyso-platelet-activating factor were high in the CSF of dogs with MUO. In addition, the plasma levels of 11,12-dihydroxyeicosatrienoic acid, 20-carboxy-AA, and oleoylethanolamide were high in dogs with IE, and those of PGF1α were high in dogs with MUO. NO production levels were high in CSF but not in plasma in dogs with MUO or IE.DiscussionIt remains unknown whether these changes represent the cause or effect of diseases of the central nervous system; however, lipid metabolites and NO production in CSF and plasma may be used as diagnostic biomarkers and could be exploited for treating idiopathic or inflammatory epilepsy in dogs.
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- 2024
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37. Akaluc bioluminescence offers superior sensitivity to track in vivo dynamics of SARS-CoV-2 infection
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Tomokazu Tamura, Hayato Ito, Shiho Torii, Lei Wang, Rigel Suzuki, Shuhei Tsujino, Akifumi Kamiyama, Yoshitaka Oda, Masumi Tsuda, Yuhei Morioka, Saori Suzuki, Kotaro Shirakawa, Kei Sato, Kumiko Yoshimatsu, Yoshiharu Matsuura, Satoshi Iwano, Shinya Tanaka, and Takasuke Fukuhara
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Virology ,Methodology in biological sciences ,Science - Abstract
Summary: Monitoring in vivo viral dynamics can improve our understanding of pathogenicity and tissue tropism. Because the gene size of RNA viruses is typically small, NanoLuc is the primary choice for accommodation within viral genome. However, NanoLuc/Furimazine and also the conventional firefly luciferase/D-luciferin are known to exhibit relatively low tissue permeability and thus less sensitivity for visualization of deep tissue including lungs. Here, we demonstrated in vivo sufficient visualization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using the pair of a codon-optimized Akaluc and AkaLumine. We engineered the codon-optimized Akaluc gene possessing the similar GC ratio of SARS-CoV-2. Using the SARS-CoV-2 recombinants carrying the codon-optimized Akaluc, we visualized in vivo infection of respiratory organs, including the tissue-specific differences associated with particular variants. Additionally, we could evaluate the efficacy of antivirals by monitoring changes in Akaluc signals. Overall, we offer an effective technology for monitoring viral dynamics in live animals.
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- 2024
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38. Epidemiological shifts in and impact of COVID-19 on streptococcal toxic shock syndrome in Japan: A genotypic analysis of group A Streptococcus isolates
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Tadayoshi Ikebe, Rumi Okuno, Yumi Uchitani, Takahiro Yamaguchi, Junko Isobe, Emi Maenishi, Yoshimi Date, Hitoshi Otsuka, Yu Kazawa, Shohei Fujita, Ayaka Kobayashi, Mami Takano, Shinya Tsukamoto, Yoshiko Kanda, Makoto Ohnishi, and Yukihiro Akeda
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Streptococcus pyogenes ,Group A Streptococcus ,Streptococcal toxic shock syndrome ,Invasive infection ,COVID-19 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: Streptococcal toxic shock syndrome (STSS) is caused by group A Streptococcus (GAS; Streptococcus pyogenes) strains. In Japan, the number of STSS cases has decreased; however, the underlying reason remains unclear. Moreover, information on distribution and prevalence of specific emm types in STSS cases is scarce. Hence, we investigated the reason for the decreased number of STSS cases in Japan. Methods: We genotyped emm of 526 GAS isolates obtained from 526 patients with STSS between 2019 and 2022. The distributions of emm types in each year were compared. Results: The emm1 type was predominant, with the highest proportion in 2019, which decreased after 2020 following the onset of the coronavirus disease 2019 (COVID-19) pandemic. Strains isolated during the pandemic correlated with strains associated with skin infection, whereas those isolated during the prepandemic period correlated with strains associated with both throat and skin infections. The decrease in the annual number of STSS cases during the COVID-19 pandemic could be due to a decreased proportion of strains associated with pharyngeal infections. Conclusions: Potential associations between pandemic and STSS numbers with respect to public health measures, such as wearing masks and changes in healthcare-seeking behavior, may have affected the number of GAS-induced infections.
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- 2024
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39. Feasibility of comprehensive genomic profiling using endoscopic ultrasound‐guided tissue acquisition with a 22‐gauge Franseen needle
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Kazunaga Ishigaki, Yousuke Nakai, Go Endo, Kohei Kurihara, Kota Ishida, Shuichi Tange, Rintaro Fukuda, Shinya Takaoka, Yurie Tokito, Yukari Suzuki, Hiroki Oyama, Sachiko Kanai, Tatsunori Suzuki, Tatsuya Sato, Ryunosuke Hakuta, Tomotaka Saito, Tsuyoshi Hamada, Naminatsu Takahara, Aya Shinozaki‐Ushiku, and Mitsuhiro Fujishiro
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comprehensive genomic profiling ,endoscopic ultrasound‐guided fine needle aspiration ,Franseen needle ,image analysis ,pancreatobiliary cancer ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Aim Comprehensive genomic profiling (CGP) test for solid tumors is now increasingly utilized in clinical practice, especially in pancreatobiliary cancer, and specimens obtained by endoscopic ultrasound‐guided tissue acquisition (EUS‐TA) are often submitted for tissue‐based CGP test. In this study, we evaluated the feasibility of EUS‐TA using a 22‐gauge Franseen needle for the CGP test. Methods Consecutive patients with solid tumors who underwent EUS‐TA using a 22‐gauge Franseen needle, and whose tissue samples were pre‐checked for suitability for CGP test, were included in this single‐center, retrospective analysis. The success rates of appropriate sample collection for CGP evaluated by pathologists (1st quality control) and CGP test (2nd quality control) were evaluated. In addition, The EUS‐TA slides were evaluated for the tissue area and tumor area content, using the image software. Results A total of 50 cases, with 78% of pancreatic cancer, were included in the analysis. A median of 3 passes of EUS‐TA were performed with an adverse event rate of 4%. The success rates for 1st and 2nd quality control for CGP tests were 86% and 76%, respectively. The image analyses suggested EUS‐TA specimen did not always fulfill CGP test criteria, with 18% of tissue area ≥16 mm2 and 38% of tumor area content ≥20%, even in cases with successful CGP tests. The suction method yielded a significantly larger amount of DNA but without a significant difference in the multivariate analysis. Conclusions The present study demonstrated the feasibility of EUS‐TA using a 22‐gauge Franseen needle for CGP test.
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- 2024
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40. The impact of biliary stents on the diagnostic yield of endoscopic ultrasound‐guided fine needle aspiration for solid pancreatic lesions: A single‐center retrospective study and meta‐analysis
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Go Endo, Kazunaga Ishigaki, Tsuyoshi Hamada, Yousuke Nakai, Kota Ishida, Kohei Kurihara, Shuichi Tange, Shinya Takaoka, Yurie Tokito, Yukari Suzuki, Hiroki Oyama, Sachiko Kanai, Tatsunori Suzuki, Tatsuya Sato, Ryunosuke Hakuta, Tomotaka Saito, Naminatsu Takahara, and Mitsuhiro Fujishiro
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cholangiopancreatography ,endoscopic retrograde ,endoscopic ultrasound‐guided fine needle aspiration ,jaundice ,obstructive ,pancreatic neoplasms ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is widely used for the pathological diagnosis of solid pancreatic lesions but in cases with obstructive jaundice, transpapillary sampling can be performed during endoscopic retrograde cholangiopancreatography with transpapillary biliary stent placement. Thus, it is still controversial whether EUS‐FNA should be performed prior to endoscopic retrograde cholangiopancreatography with biliary stent placement or only after negative transpapillary sampling. Methods The accuracy, sensitivity, and specificity of EUS‐FNA for solid pancreatic lesions with or without indwelling biliary stents were retrospectively studied in patients undergoing EUS‐FNA between January 2017 and December 2021. We also conducted a meta‐analysis including our data to compare the accuracy and sensitivity of EUS‐FNA with or without biliary stents. Results A total of 509 patients (40 with biliary stents and 469 without biliary stents) were included. The accuracy (77.5% vs. 94.5%, p < 0.001) and sensitivity (71.0% vs. 91.7%, p < 0.001) were lower in EUS‐FNA with biliary stents. A meta‐analysis confirmed that accuracy (odds ratio [OR] of 0.43, 95% confidence interval [CI] 0.29–0.62, p < 0.001) and sensitivity (OR of 0.46, 95% CI 0.33–0.64, p < 0.001) were lower in EUS‐FNA with biliary stents. There were no statistically significant differences between plastic stents and self‐expandable metallic stents for accuracy or sensitivity. Conclusions The presence of biliary stents had a negative impact on the diagnostic performance of EUS‐FNA, and EUS‐FNA prior to endoscopic retrograde cholangiopancreatography with biliary stent placement should be considered in cases with obstructive jaundice.
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- 2024
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41. Switching from FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab based on early tumor shrinkage in RAS wild‐type metastatic colorectal cancer: A phase II trial (HYBRID)
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Hiroyuki Arai, Takashi Tsuda, Yu Sunakawa, Mototsugu Shimokawa, Kohei Akiyoshi, Shinya Tokunaga, Hirokazu Shoji, Kenji Kunieda, Masahito Kotaka, Toshihiko Matsumoto, Yusuke Nagata, Takuro Mizukami, Fumitaka Mizuki, Kathleen D. Danenberg, Narikazu Boku, and Takako Eguchi Nakajima
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bevacizumab ,cetuximab ,early tumor shrinkage ,metastatic colorectal cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Long‐term anti‐EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single‐arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild‐type metastatic colorectal cancer (mCRC). Methods Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS‐negative patients switched to FOLFIRI plus bevacizumab, whereas ETS‐positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression‐free survival. Results This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS‐negative and 22 were ETS‐positive. Two ETS‐negative patients and 17 ETS‐positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression‐free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients. Conclusions Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities.
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- 2024
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42. Detection of factors related to treatment reduction in docetaxel and ramucirumab for non-small cell lung cancer treatment
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Yoshitaka Saito, Shinya Tamaki, Daisuke Hirate, Shinya Takada, Kenta Takahashi, Yoh Takekuma, Jun Sakakibara-Konishi, Yasushi Shimizu, Ichiro Kinoshita, and Mitsuru Sugawara
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Medicine ,Science - Abstract
Abstract Treatment using docetaxel (DOC) and ramucirumab (RAM) is an effective regimen in second or later line advanced non-small cell lung carcinoma (NSCLC) treatment. However, it induces severe adverse effects, resulting in treatment reduction such as dose reduction and/or discontinuation. This study aimed to reveal the factor(s) associated with treatment reduction in DOC + RAM. We retrospectively evaluated patients with advanced NSCLC (n = 155). Treatment reduction of the second course due to severe adverse effects was conducted in 25.8% of the participants, and relative dose intensity at the second course was 95.7 ± 8.4% for DOC and 91.9 ± 24.8% for RAM. Multivariate logistic regression analyses identified that baseline anemia and prophylactic granulocyte colony-stimulating factor (G-CSF) administration are preventive factors for the reduction (adjusted odds ratio, 0.29; 95% confidence interval, 0.12–0.66; P = 0.004 for baseline anemia, 0.18; 0.08–0.42; P
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- 2023
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43. Therapeutic Prediction of Osteoporotic Vertebral Compression Fracture Using the AO Spine-DGOU Osteoporotic Fracture Classification and Classification-Based Score: A Single-Center Retrospective Observational Study
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Koki Mitani, Toshiyuki Takahashi, Shinya Tokunaga, Tomoo Inoue, Ryo Kanematsu, Manabu Minami, and Junya Hanakita
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osteoporotic fracture ,retrospective study ,vertebral compression fracture ,of score ,of classification ,osteoporosis ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Objective The treatment of osteoporotic vertebral compression fractures (OVCFs) is based on their severity; however, an efficient prediction tool is lacking. We aimed to evaluate the validity of the osteoporotic fracture classification (OF classification) and scoring system (OF score) in predicting the treatment strategy for patients with OVCF, defined according to the Japanese criteria. Methods We retrospectively investigated 487 consecutive patients diagnosed with vertebral body fractures between January 2018 and December 2022. Only patients with their fresh vertebral fracture episode during the study period were included. Patients were classified into 3 groups: conservative treatment, balloon kyphoplasty (BKP), and open surgery. OF classification and OF scores were assessed for each patient. Results A total of 237 patients with OVCF were included. There were 127, 81, and 29 patients in the conservative, BKP, and open surgery groups, respectively. The OF score was significantly higher in the BKP and open surgery groups than in the conservative group (p < 0.001). Multivariate logistic regression analysis showed that antiosteoporotic drug use, OF classification, progressive deformity, neurological symptoms and mobilization were independent risk factors for operative treatment (all p < 0.001). Receiver operating characteristic analysis showed that the cutoff OF score for operative indication was 5.5, with a sensitivity of 91.9%, specificity of 56.5%, and area under the curve of 0.820 (95% confidence interval, 0.769–0.871). Conclusion The OF score identified patients who required operative treatment with a high degree of accuracy. This is especially important for ruling out patients who definitely require operative treatment.
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- 2023
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44. Wnt activation disturbs cell competition and causes diffuse invasion of transformed cells through NF-κB-MMP21 pathway
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Kazuki Nakai, Hancheng Lin, Shotaro Yamano, Shinya Tanaka, Sho Kitamoto, Hitoshi Saitoh, Kenta Sakuma, Junpei Kurauchi, Eilma Akter, Masamitsu Konno, Kojiro Ishibashi, Ryo Kamata, Akihiro Ohashi, Jun Koseki, Hirotaka Takahashi, Hideshi Yokoyama, Yukihiro Shiraki, Atsushi Enomoto, Sohei Abe, Yoku Hayakawa, Tetsuo Ushiku, Michihiro Mutoh, Yasuyuki Fujita, and Shunsuke Kon
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Science - Abstract
Abstract Normal epithelial cells exert their competitive advantage over RasV12-transformed cells and eliminate them into the apical lumen via cell competition. However, the internal or external factors that compromise cell competition and provoke carcinogenesis remain elusive. In this study, we examine the effect of sequential accumulation of gene mutations, mimicking multi-sequential carcinogenesis on RasV12-induced cell competition in intestinal epithelial tissues. Consequently, we find that the directionality of RasV12-cell extrusion in Wnt-activated epithelia is reversed, and transformed cells are delaminated into the basal lamina via non-cell autonomous MMP21 upregulation. Subsequently, diffusively infiltrating, transformed cells develop into highly invasive carcinomas. The elevated production of MMP21 is elicited partly through NF-κB signaling, blockage of which restores apical elimination of RasV12 cells. We further demonstrate that the NF-κB-MMP21 axis is significantly bolstered in early colorectal carcinoma in humans. Collectively, this study shows that cells with high mutational burdens exploit cell competition for their benefit by behaving as unfit cells, endowing them with an invasion advantage.
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- 2023
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45. Factors Associated with Geographical Variability of Antimicrobial Use in Japan
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Taito Kitano, Shinya Tsuzuki, Ryuji Koizumi, Kensuke Aoyagi, Yusuke Asai, Yoshiki Kusama, and Norio Ohmagari
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Antimicrobials ,Antimicrobial stewardship ,Upper respiratory infection ,Gender ,Education ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Introduction Evidence regarding the factors affecting the geographical variation of antimicrobial use (AMU) is relatively scarce. This study aimed to evaluate factors potentially associated with geographical variability of AMU per day per 1000 habitants in the 47 prefectures of Japan. Methods This is an observational ecological study using the Japanese national database in 2019. The outcome was the defined daily doses per 1000 inhabitants per day by prefecture. Multivariable negative binomial regression analysis was conducted using patient- and physician-level variables. Results The study included 605,391,054 defined daily doses of AMU in 2019 from the 47 prefectures. In the multivariable negative binomial regression analyses for the outcome of total AMU, the proportion of female individuals (adjusted rate ratio [aRR] 1.04 [1.01–1.08] per 1% increase, p = 0.021), the proportion of upper secondary graduates going to further education (aRR 1.01 [1.00–1.01] per 1% increase, p = 0.005), and the annual number of diagnoses related to upper respiratory infections (URIs) per 1000 inhabitants per day (aRR 1.21 [1.10–1.34], p
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- 2023
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46. Trends in teicoplanin loading dose implementation from 2010 to 2019 and evaluation of safety and efficacy factors: a retrospective cohort study based on a Japanese administrative claims database
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Ryota Goto, Yuichi Muraki, Ryo Inose, Moeno Ichii, Keisuke Sawada, Kanako Mizuno, Ryuji Koizumi, Shinya Tsuzuki, Masahiro Ishikane, and Norio Ohmagari
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Teicoplanin ,Database ,Loading dose ,Liver injury ,Mortality ,Methicillin-resistant Staphylococcus aureus ,Therapeutics. Pharmacology ,RM1-950 ,Pharmacy and materia medica ,RS1-441 - Abstract
Abstract Background The loading dose of teicoplanin (TEIC) is recommended for implementation. However, there is significant discrepancy between the dose settings in the package insert and, in the guidelines, and the actual status of loading doses in Japan is unclear. Furthermore, TEIC causes liver injury as side effect. Although the risk of developing liver injury has not been reported to be increased following a loading dose based on the guidelines, there is a lack of reports in large populations. Therefore, we evaluated the trend in the loading dose and factors affecting the efficacy and safety of TEIC administration. Methods A Japanese administrative claims database was used in this study. Trends in loading doses were evaluated in target populations administered TEIC between 2010 and 2019. Patient characteristics were adjusted by propensity score matching based on the guideline group (total dose of 3 days > 1,600 mg) and non-guideline group (≤ 1,600 mg) of the loading dose. Finally, univariable and multivariable conditional logistic regression analysis was performed to evaluate factors affecting 30-day mortality and liver injury. Results A total of 10,030 patients were selected based on these criteria. The proportion of loading doses based on the recommended guidelines showed an increase over time, regardless of the implementation of therapeutic drug monitoring (TDM), but especially so in cases where TDM was implemented, the loading doses were administered in accordance with the recommendations of the guidelines. Conditional logistic regression analysis showed a relationship between drug management and guidance fees (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.36‒0.55), a reimbursement indicating pharmacist intervention, and a reduction in 30-day mortality. In addition, loading doses based on the recommended guidelines had no influence on liver injury, and other factors were not significantly associated with increased incidence of liver injury. Conclusion Thus, this study implies the benefits of pharmacological management as indicated by drug management and guidance fee and supports the implementation of loading doses based on the guideline on TEIC administration.
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- 2023
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47. Dynamics of Myers-Perry black holes with almost equal angular momenta in odd dimensions
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Ryotaku Suzuki and Shinya Tomizawa
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Black Holes ,Classical Theories of Gravity ,Black Holes in String Theory ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract We investigate the nonlinear dynamics of D = 2N + 3 Myers-Perry black holes with almost equal angular momenta, which have N equal spins out of possible N + 1 spins. In particular, we study the ultraspinning instability and the fate of its nonlinear evolution using the large D effective theory approach. We find that every stationary phase can be mapped to the counterpart in the singly rotating phase within the leading order effective theory. From the known results of singly rotating solutions, we obtain the phase diagram of almost equally rotating black holes. We also obtain a certain implication for the possible topology changing transition.
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- 2023
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48. Risk factor analysis for cisplatin-induced nephrotoxicity with the short hydration method in diabetic patients
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Yoshitaka Saito, Masaki Kobayashi, Shinya Tamaki, Katsuyuki Nakamura, Daisuke Hirate, Kenta Takahashi, Yoh Takekuma, Jun Sakakibara-Konishi, Yasushi Shimizu, Ichiro Kinoshita, and Mitsuru Sugawara
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Medicine ,Science - Abstract
Abstract The occurrence of cisplatin (CDDP)-induced nephrotoxicity (CIN) has decreased with advancements in supportive care. In contrast, we reported that baseline diabetes mellitus (DM) complications significantly worsen CIN. This study aimed to determine further risk factors associated with CIN development in DM patients. Patients with thoracic cancer requiring DM pharmacotherapy, who received CDDP (≥ 60 mg/m2)-containing regimens using the short hydration method (n = 140), were enrolled in this retrospective multicenter observational study. The primary endpoint of the present study was the elucidation of risk factors (patient factors, DM medication influence, and treatment-related factors) associated with CIN development in patients with DM. Cisplatin-induced nephrotoxicity occurred in 22.1% of patients with DM. The median worst variation of serum creatinine levels and creatinine clearance (worst level − baseline level) was 0.16 mg/dL (range: − 0.12–1.41 mg/dL) and − 15.9 mL/min (− 85.5–24.3 mL/min), respectively. Multivariate logistic regression analyses identified female sex as the singular risk factor for CIN development in the DM population (adjusted odds ratio; 2.87, 95% confidence interval; 1.08–7.67, P = 0.04). Diabetes mellitus medication and treatment-related factors did not affect CIN development. In conclusion, our study revealed that female sex is significantly associated with CIN development in patients with DM and thoracic cancer.
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- 2023
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49. Robust, scalable, and informative clustering for diverse biological networks
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Chris Gaiteri, David R. Connell, Faraz A. Sultan, Artemis Iatrou, Bernard Ng, Boleslaw K. Szymanski, Ada Zhang, and Shinya Tasaki
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Biology (General) ,QH301-705.5 ,Genetics ,QH426-470 - Abstract
Abstract Clustering molecular data into informative groups is a primary step in extracting robust conclusions from big data. However, due to foundational issues in how they are defined and detected, such clusters are not always reliable, leading to unstable conclusions. We compare popular clustering algorithms across thousands of synthetic and real biological datasets, including a new consensus clustering algorithm—SpeakEasy2: Champagne. These tests identify trends in performance, show no single method is universally optimal, and allow us to examine factors behind variation in performance. Multiple metrics indicate SpeakEasy2 generally provides robust, scalable, and informative clusters for a range of applications.
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- 2023
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50. Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis
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Yuichi Tsuchiya, Takao Seki, Kenta Kobayashi, Sachiko Komazawa-Sakon, Shigeyuki Shichino, Takashi Nishina, Kyoko Fukuhara, Kenichi Ikejima, Hidenari Nagai, Yoshinori Igarashi, Satoshi Ueha, Akira Oikawa, Shinya Tsurusaki, Soh Yamazaki, Chiharu Nishiyama, Tetuo Mikami, Hideo Yagita, Ko Okumura, Taketomo Kido, Atsushi Miyajima, Kouji Matsushima, Mai Imasaka, Kimi Araki, Toru Imamura, Masaki Ohmuraya, Minoru Tanaka, and Hiroyasu Nakano
- Subjects
Science - Abstract
Abstract Liver fibrosis results from chronic liver injury triggered by factors such as viral infection, excess alcohol intake, and lipid accumulation. However, the mechanisms underlying liver fibrosis are not fully understood. Here, we demonstrate that the expression of fibroblast growth factor 18 (Fgf18) is elevated in mouse livers following the induction of chronic liver fibrosis models. Deletion of Fgf18 in hepatocytes attenuates liver fibrosis; conversely, overexpression of Fgf18 promotes liver fibrosis. Single-cell RNA sequencing reveals that overexpression of Fgf18 in hepatocytes results in an increase in the number of Lrat + hepatic stellate cells (HSCs), thereby inducing fibrosis. Mechanistically, FGF18 stimulates the proliferation of HSCs by inducing the expression of Ccnd1. Moreover, the expression of FGF18 is correlated with the expression of profibrotic genes, such as COL1A1 and ACTA2, in human liver biopsy samples. Thus, FGF18 promotes liver fibrosis and could serve as a therapeutic target to treat liver fibrosis.
- Published
- 2023
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