24 results on '"Sakashita, T"'
Search Results
2. RWD78 Representativeness and Coverage of Death Data in the DeSC Healthcare Database in Japan
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Hamaguchi, A., Sano, H., Togase, Y., Kato, M., Sakashita, T., Pulfer, A., Koga, T., and Lambrelli, D.
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- 2024
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3. [Importance of early treatment and quantitative evaluation of enzyme replacement therapy for Pompe disease: alglucosidase alfa post-marketing surveillance additional analysis].
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Sunaga Y, Sakashita T, Koga T, Sawada T, Yamane S, and Ikeda M
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- Humans, Male, Female, Adult, Middle Aged, Vital Capacity, Adolescent, Time Factors, Child, Treatment Outcome, Young Adult, Aged, Time-to-Treatment, Glycogen Storage Disease Type II drug therapy, Enzyme Replacement Therapy, Product Surveillance, Postmarketing, alpha-Glucosidases administration & dosage, Walk Test
- Abstract
We conducted an additional analysis using the data from the post-marketing surveillance of Alglucosidase alfa for Pompe disease. We aimed to investigate the changes in the percentage of predicted forced vital capacity (%FVC) and the changes in the distance of the 6-min walk test (6MWT) by overall improvement and to investigate the %FVC change by the duration from symptom onset to survey registration (shorter/longer groups) using a linear mixed model. Thirty-seven and eighteen survey participants had %FVC and 6MWT data available, respectively; of the patients whose overall improvement was rated as "relatively improved," %FVC and 6MWT worsened in 71.4% and 66.7%, respectively. The %FVC at the survey registration estimated using a linear mixed model was significantly higher in the shorter group than in the longer group (P = 0.0413). The estimated slope of %FVC was significantly lower in the shorter group than in the longer group (P = 0.0051). These results suggest the importance of early treatment initiation and quantitative evaluation of each symptom.
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- 2024
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4. [Changes in attitudes toward suicide after brief gatekeeper education: Findings from population-based repeated cross-sectional surveys conducted among middle-aged and older adults].
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Oyama H, Harima Y, Sakashita T, Sasaki H, Oyama H, and Maguchi Y
- Abstract
Objective This study aimed to investigate changes in attitudes toward suicide following a universal home visitation program that included a brief face-to-face educational session focusing on gatekeeper roles in Japan.Methods Between 2015 and 2017, members of 169 households in an intervention district from a northern Japanese township were invited to attend an educational session during home visits. The participation rate was 72.8%, with 94.5% of the participants aged over 40. Repeated cross-sectional population-based surveys were conducted among adults in the towns in 2015 and 2021. Data from the surveys, focusing on individuals aged 40-79 years and residing in the intervention and matched control districts (where no visits occurred and only information was distributed through leaflets), were used to assess the prevalence of self-reported views toward suicide. The self-reported views encompassed "no substantial thoughts," "inevitable," "shameful," "annoying," "tragic," "must be managed," and "romantic" in addition to personal and perceived stigma, depressive symptoms (assessed using the Kessler Psychological Distress Scale-6), and suicidal ideation. Data were analyzed using generalized linear mixed models. The Cochran-Armitage test was used to analyze linear trends in the proportion of views that exhibited changes.Results Participation rates were 61.8% (n = 357) in 2015 and 52.8% (n = 257) in 2021. The intervention group showed a significant difference in the prevalence of the "inevitable" view between baseline and 4-year follow-up (P = 0.026). Marginal pre-post differences were observed among the two types of stigma; however, the symptoms remained unchanged. A marginally significant difference in the change of the "inevitable" view was observed between the two groups. In the follow-up, more knowledgeable respondents in the intervention group were less likely to view suicide as "inevitable," a trend not seen in the control group.Conclusions The universal home visitation program, including a face-to-face session focusing on the gatekeeper role, was associated with a decreased prevalence of the "inevitable" attitude between the baseline and 4-year follow-up among community-dwelling adults aged 40-79. This suggests that face-to-face interactions with healthcare professionals can reduce the tendency to condone suicide among middle-aged and older adults in community settings.
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- 2024
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5. Delayed onset septic pelvic thrombophlebitis treated by tissue-plasminogen activator following initial treatment for massive right ovarian vein thrombosis and methicillin-resistant Staphylococcus aureus bacteremia: A case report.
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Miyamori D, Shigemoto N, Une K, Kinoshita H, Harimoto S, Sakashita T, and Ito M
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- Humans, Female, Adult, Venous Thrombosis drug therapy, Fibrinolytic Agents administration & dosage, Fibrinolytic Agents therapeutic use, Pregnancy, Thrombophlebitis drug therapy, Thrombophlebitis microbiology, Methicillin-Resistant Staphylococcus aureus isolation & purification, Staphylococcal Infections drug therapy, Tissue Plasminogen Activator administration & dosage, Ovary, Bacteremia drug therapy, Bacteremia microbiology
- Abstract
Septic pelvic thrombophlebitis (SPT) is a rare condition that forms thrombosis in the pelvic veins, typically the ovarian veins, with subsequent infection and inflammation. We present a case of right ovarian vein thrombosis (ROVT), methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, and delayed onset of SPT symptoms, requiring tissue-plasminogen activator. A 40-year-old woman, G3P2, at 38 weeks' gestation, was admitted with a fever of 39°C. She had cervical insufficiency and had been often on bed rest. Blood culture revealed MRSA and computed tomography revealed a large ROVT. She received vancomycin and direct oral anticoagulant, and her fever resolved by day 3. On day 16, fever recurred with severe pain over the ROVT. Second computed tomography showed thickening of venous wall with enhancement around ROVT, consistent with SPT. Since pain and fever gradually exacerbated despite treatment with DOAC and antimicrobials, she was started on heparin and tissue plasminogen activator on days 23 and 25, respectively. Along with recanalization on the thrombosis by day 29, fever and abdominal pain resolved. We experienced a case of delayed onset SPT associated with MRSA bacteremia and a large ROVT. MRSA bacteremia might cause the originally existing ROVT to become an infection source, resulting in SPT with recurrent symptoms and long-term treatment. Early and strict anticoagulation is crucial in cases with a large thrombosis and bacteremia, due to the high risk of progression to SPT. This case highlights the importance of recanalization for the treatment of SPT and usefulness of administration of tissue-plasminogen activator for the massive thrombosis., (© 2024 The Author(s). Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)
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- 2024
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6. [Validation of Quantitative Accuracy and Variability in 177 Lu Imaging Using Monte Carlo Simulation].
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Daisaki H, Kubota C, Ishikawa K, Sato M, Yasumoto Y, Fukai S, and Sakashita T
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- Humans, Radioisotopes, Monte Carlo Method, Phantoms, Imaging, Tomography, Emission-Computed, Single-Photon methods, Lutetium
- Abstract
Purpose: To predict side effects and optimize injection doses in the dosimetry of
177 Lu imaging, highly accurate quantitative SPECT images are required. Monte Carlo simulations were performed to verify the accuracy and variability of quantitative values for177 Lu imaging under various imaging conditions., Methods: SPECT data of NEMA body phantom were assumed to simulate intrahepatic tumors 6 h after administration of 7.4 GBq of177 Lu-Dotatate. SPECT data were acquired using the SIMIND program with different combinations of collimators and energy windows. For variability evaluation, 30 SPECT images with Poisson noise were generated for each acquisition time. The relative error was evaluated for accuracy evaluation, and the coefficient of variation was estimated for variability evaluation., Results: The accuracy of BG quantification was less than 10% relative error. The accuracy of hot sphere quantification was highest with the combination of MEGP and an energy window of 208 keV±10%. However, the accuracy of hot sphere quantification decreased significantly with decreasing hot sphere diameter. Variability varied with imaging conditions and improved with longer acquisition time., Conclusion: Monte Carlo simulations revealed the accuracy and variability of quantitative values for each SPECT imaging condition for177 Lu imaging.- Published
- 2024
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7. [Usefulness of Delay Time Setting in Computed Tomography Pulmonary Angiography].
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Kuramochi K, Sakashita T, and Ogawa Y
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- Humans, Male, Female, Aged, Middle Aged, Aged, 80 and over, Time Factors, Adult, Contrast Media, Computed Tomography Angiography methods, Pulmonary Embolism diagnostic imaging, Pulmonary Artery diagnostic imaging
- Abstract
Purpose: During computed tomography pulmonary angiography (CTPA), a decrease in the CT value of the pulmonary artery may be observed due to poor contrast enhancement, even though the imaging is performed at the optimum timing while continuously injecting a contrast medium. This study focused on the increase in blood flow in the superior and inferior vena cava during inspiration that affects the decrease in the CT value of the pulmonary artery and investigated a radiography method in which a delay time was set after inspiration in clinical cases., Methods: A total of 50 patients who underwent CTPA for suspected pulmonary thromboembolism were included. Using the bolus tracking method, we monitored the pulmonary arteries before and after inspiration, and investigated the CT value changes., Results: A decrease in the CT value of the pulmonary artery after inspiration was observed in approximately 30% of cases. By setting the delay time, the contrast enhancement effect before and after inspiration became equivalent., Conclusion: As a result of this study, avoiding a decrease in the CT value of the pulmonary artery is possible by setting a delay time after inspiration, which is considered useful during CTPA.
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- 2024
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8. Correction: Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell carcinoma.
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Uchinami Y, Yasuda K, Kano S, Otsuka M, Hamada S, Suzuki T, Tsushima N, Takahashi S, Fujita Y, Miyazaki T, Higaki H, Taguchi J, Shimizu Y, Sakashita T, Homma A, and Aoyama H
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- 2024
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9. Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell carcinoma.
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Uchinami Y, Yasuda K, Kano S, Otsuka M, Hamada S, Suzuki T, Tsushima N, Takahashi S, Fujita Y, Miyazaki T, Higaki H, Taguchi J, Shimizu Y, Sakashita T, Homma A, and Aoyama H
- Abstract
Background: Tri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) but is sometimes challenging to complete in older patients. Weekly CDDP + RT has shown mild toxicity compared to tri-weekly CDDP + RT for LA-HNSCC and is a promising option for older adults. We aimed to report the treatment outcomes and prognostic factors in patients with LA-HNSCC treated with weekly CDDP + RT., Methods: We analyzed patients aged ≥ 70 years who started weekly CDDP + RT for LA-HNSCC between July 2006 and October 2022. LA-HNSCC includes cancer in the oropharynx, hypopharynx, or larynx with a clinical stage of 3 or 4 without distant metastases based on the Union for International Cancer Control staging system 8th edition. The radiation dose of 70 Gy was delivered in 35 fractions by 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, or proton beam therapy. The primary endpoint was the 3-year overall survival (OS), and the secondary endpoints were the 3-year progression-free survival (PFS) and 3-year cause-specific survival (CSS). The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to evaluate statistical significance. A Cox proportional hazards model was used for the multivariate analysis of prognostic factors., Results: The median age of the 49 patients was 72 (range: 70-78) years. The median CDDP dose was 200 (40-280) mg/ m
2 , and 47 patients completed scheduled radiotherapy. Forty-eight patients (98.0%) had a performance status of ≥ 1 at the initial visit. The 3-year OS, PFS, and CSS were 80.9% (95% confidence interval [CI]: 64.8-90.7), 68.3% (95% CI 51.8-81.2), and 85.0% (95% CI 68.7-93.4), respectively. In the multivariate analysis, the cumulative CDDP dose (< 200 or ≥ 200 mg/m2 ) was a significant factor for OS (hazard ratio: 0.29 [95% CI 0.08-0.97], p = 0.044). There was one case of early mortality. Grade 3 or higher late adverse events were observed in four patients (8.2%)., Conclusions: Weekly CDDP + RT in older patients led to good survival outcomes with an acceptable rate of adverse events. CDDP should be administered at a dose of at least 200 mg/m2 in older patients. Trial registration Retrospectively registered., (© 2023. The Author(s).)- Published
- 2023
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10. Utility of Color Doppler Ultrasonography in Monitoring of a Free Jejunal Flap.
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Maeda T, Ishikawa K, Oda Y, Kano S, Tsushima N, Sakashita T, Homma A, Yamamoto Y, and Funayama E
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- Humans, Retrospective Studies, Ultrasonography, Doppler, Color methods, Postoperative Complications, Ultrasonography, Doppler, Free Tissue Flaps, Thrombosis diagnostic imaging, Thrombosis surgery
- Abstract
Objectives: External color Doppler ultrasonography is reported to be a useful monitoring technique that is simple and noninvasive; however, details of imaging of the transferred free jejunal flap have not been reported. We reviewed our experience using external color Doppler ultrasonography to monitor a transferred free jejunal flap and examined its utility., Study Design: Retrospective study., Methods: Subjects were 43 patients who underwent total pharyngolaryngectomy, reconstruction with a free jejunal flap, and color Doppler ultrasonography before, during, and after surgery between September 2017 and December 2021., Results: During surgery, arterial thrombosis was detected up to 100% with the loss of continuous color signals in the entire circumference. After surgery, the positive predictive value was 100% for each of wiggling movement, dynamic intestinal movement, and continuous color signals in the entire circumference on color Doppler ultrasonography for detecting flap viability. Their negative predictive value was 100%, 7.1%, and 50%, respectively., Conclusions: During surgery, the continuous color signals in the entire circumference sign were useful with 100% negative predictive value for detecting the arterial thrombosis. After surgery, the wiggling movement sign very was useful with 100% positive and negative predictive values, enabling salvage surgery to be performed soon after detection of flap failure., Level of Evidence: 4 Laryngoscope, 133:3361-3369, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)
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- 2023
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11. Indications for sentinel lymph node biopsy in node-negative oral cancers.
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Ozawa T, Oze I, Matsuzuka T, Sasaki E, Yokoyama J, Sano Y, Tomifuji M, Araki K, Kogashiwa Y, Tateya I, Agena S, Sakashita T, Tsuzuki H, Terada H, Suzuki H, Nishikawa D, Beppu S, Matoba T, Mukoyama N, Oguri K, and Hasegawa Y
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- Humans, Lymphatic Metastasis pathology, Lymph Nodes surgery, Lymph Nodes pathology, Neck Dissection, Sentinel Lymph Node Biopsy, Mouth Neoplasms surgery, Mouth Neoplasms pathology
- Abstract
Background: We aimed to define the indications for sentinel lymph node biopsy (SLNB), the third option for cervical treatment in oral cancer with negative cervical lymph nodes., Methods: The greatest depth of invasion (DOI) and long diameter (LD) of the primary site were used as exposures. SLN metastasis was considered the outcome., Results: In three trials conducted between 2009 and 2016, 158 patients were eligible and reassigned to this study group. The scatterplot based on the respective values of DOI and LD would eventually be divided into three sections. In cases of sections T1, T2, and T3, the proportions of SLN metastasis positivity were 21.3%, 35.3%, and 51.2%, respectively. In certain cases of T1 with 2 mm < DOI ≤ 5 mm and 8 mm < LD ≤ 20 mm, the proportion of SLN metastasis positivity was 40.9%., Conclusions: SLNB-navigated or assisted neck dissection can be added as an effective procedure for N0 neck control., (© 2023 Wiley Periodicals LLC.)
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- 2023
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12. A case of coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ of the cervix.
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Habara K, Nishikori A, Kiyama J, Nakashima M, Koda M, Sasaki K, Sakashita T, Tanaka N, and Yonehara S
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- Female, Humans, Cervix Uteri surgery, Cervix Uteri pathology, Aged, Adenocarcinoma diagnosis, Adenocarcinoma surgery, Carcinoma, Adenosquamous diagnosis, Carcinoma, Adenosquamous surgery, Carcinoma, Adenosquamous complications, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell surgery, Papillomavirus Infections diagnosis, Papillomavirus Infections complications, Papillomavirus Infections pathology, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms surgery
- Abstract
Poorly differentiated adenosquamous carcinoma (glassy cell carcinoma) of the cervix is extremely rare, accounting for 1-2% of all cervical cancers. Herein, we report a case with coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), "usual-type" adenocarcinoma, and squamous cell carcinoma in situ of the cervix. A female patient in her 60 s was referred to our hospital and diagnosed with poorly differentiated adenosquamous carcinoma based on cervical cytology and biopsy. The tumor was classified as clinical stage IB1 cervical cancer following magnetic resonance imaging; radical hysterectomy was performed. Histopathological examination revealed poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ, all coexisting. All carcinoma regions showed identical sizes to high-risk human papillomavirus (HPV) in fragment analysis. The patient is currently alive, without evidence of recurrence, 31 months post surgery. In this case, three different carcinomas coexisted. Fragment analysis of the patient's HPV status suggested that all carcinomas were related to an infection with the same high-risk HPV type. To determine the precise mechanism of tumor development, i.e., whether the tumors were of the mixed or collision type, further studies are needed, including clonal analysis for the loss of heterozygosity pattern., (© 2023. The Author(s).)
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- 2023
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13. Correction: A case of coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ of the cervix.
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Habara K, Nishikori A, Kiyama J, Nakashima M, Koda M, Sasaki K, Sakashita T, Tanaka N, and Yonehara S
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- 2023
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14. Author Correction: Clustering of charged colloidal particles in the microgravity environment of space.
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Miki H, Ishigami T, Yamanaka J, Okuzono T, Toyotama A, Mata J, Komazawa H, Takeda Y, Minami M, Fujita M, Doi M, Higuchi T, Takase H, Adachi S, Sakashita T, Shimaoka T, Nagai M, Watanabe Y, and Fukuyama S
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- 2023
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15. An exa-scale high-performance molecular dynamics simulation program: MODYLAS.
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Andoh Y, Ichikawa SI, Sakashita T, Fujimoto K, Yoshii N, Nagai T, Tang Z, and Okazaki S
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A new version of the highly parallelized general-purpose molecular dynamics (MD) simulation program MODYLAS with high performance on the Fugaku computer was developed. A benchmark test using Fugaku indicated highly efficient communication, single instruction, multiple data (SIMD) processing, and on-cache arithmetic operations. The system's performance deteriorated only slightly, even under high parallelization. In particular, a newly developed minimum transferred data method, requiring a significantly lower amount of data transfer compared to conventional communications, showed significantly high performance. The coordinates and forces of 101 810 176 atoms and the multipole coefficients of the subcells could be distributed to the 32 768 nodes (1 572 864 cores) in 2.3 ms during one MD step calculation. The SIMD effective instruction rates for floating-point arithmetic operations in direct force and fast multipole method (FMM) calculations measured on Fugaku were 78.7% and 31.5%, respectively. The development of a data reuse algorithm enhanced the on-cache processing; the cache miss rate for direct force and FMM calculations was only 2.74% and 1.43%, respectively, on the L1 cache and 0.08% and 0.60%, respectively, on the L2 cache. The modified MODYLAS could complete one MD single time-step calculation within 8.5 ms for the aforementioned large system. Additionally, the program contains numerous functions for material research that enable free energy calculations, along with the generation of various ensembles and molecular constraints., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)
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- 2023
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16. Clustering of charged colloidal particles in the microgravity environment of space.
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Miki H, Ishigami T, Yamanaka J, Okuzono T, Toyotama A, Mata J, Komazawa H, Takeda Y, Minami M, Fujita M, Doi M, Higuchi T, Takase H, Adachi S, Sakashita T, Shimaoka T, Nagai M, Watanabe Y, and Fukuyama S
- Abstract
We conducted a charge-charge clustering experiment of positively and negatively charged colloidal particles in aqueous media under a microgravity environment at the International Space Station. A special setup was used to mix the colloid particles in microgravity and then these structures were immobilized in gel cured using ultraviolet (UV) light. The samples returned to the ground were observed by optical microscopy. The space sample of polystyrene particles with a specific gravity ρ (=1.05) close to the medium had an average association number of ~50% larger than the ground control and better structural symmetry. The effect of electrostatic interactions on the clustering was also confirmed for titania particles (ρ ~ 3), whose association structures were only possible in the microgravity environment without any sedimentation they generally suffer on the ground. This study suggests that even slight sedimentation and convection on the ground significantly affect the structure formation of colloids. Knowledge from this study will help us to develop a model which will be used to design photonic materials and better drugs., (© 2023. The Author(s).)
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- 2023
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17. Applicability of on-site disinfection of personal protective equipment by ozone gas.
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Ishiwata S, Hibino T, Sakashita T, Nishioka M, Inoue T, and Kotake T
- Abstract
On-site disinfection techniques are beneficial during a pandemic when there is a marked shortage of personal protective equipment (PPE), as experienced during the coronavirus disease 2019 outbreak. Ozone gas has been considered an alternative on-site disinfectant during a pandemic because it has antimicrobial activities, can be produced from air by electricity without the need for storage, and can be easily deactivated after use. However, ozone gas might become distributed at the lower layer because it has a larger molecular weight than air. This study aimed to reveal the applicability of ozone gas for the on-site disinfection of PPE. The lockers meant for changing dresses were used as ozone gas exposure boxes, and the distribution of ozone was assayed. Considering that the determined ozone levels were not consistent in the types of ozone analysers, we studied the chemical and biological activities of ozone, which were evenly detected in the locker. The gown in the locker was also uniformly exposed to ozone. Results showed that ozone gas could be used for the on-site disinfection of PPE in a closed box, such as a locker. This finding is valuable during a pandemic when PPE is in short supply., Competing Interests: The authors declare the following conflict of interests: S.I. received research grants from Tamura Teco Co., Ltd, Osaka, Japan. All other authors have no conflict of interest to declare., (© 2023 The Authors.)
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- 2023
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18. Comparison of the loci associated with HbA1c and blood glucose levels identified by a genome-wide association study in the Japanese population.
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Sakashita T, Nakamura Y, Sutoh Y, Shimizu A, Hachiya T, Otsuka-Yamasaki Y, Takashima N, Kadota A, Miura K, Kita Y, Ikezaki H, Otonari J, Tanaka K, Shimanoe C, Koyama T, Watanabe I, Suzuki S, Nakagawa-Senda H, Hishida A, Tamura T, Kato Y, Okada R, Kuriki K, Katsuura-Kamano S, Watanabe T, Tanoue S, Koriyama C, Oze I, Koyanagi YN, Nakamura Y, Kusakabe M, Nakatochi M, Momozawa Y, Wakai K, and Matsuo K
- Abstract
Aims: Hemoglobin A1c (HbA1c) levels are widely employed to diagnose diabetes. However, estimates of the heritability of HbA1c and glucose levels are different. Therefore, we explored HbA1c- and blood glucose-associated loci in a non-diabetic Japanese population., Methods: We conducted a two-stage genome-wide association study (GWAS) on variants associated with HbA1c and blood glucose levels in a Japanese population. In the initial stage, data of 4911 participants of the Japan Multi-Institutional Collaborative Cohort (J-MICC) were subjected to discovery analysis. In the second stage, two datasets from the Tohoku Medical Megabank project, with 8175 and 40,519 participants, were used for the replication study. Association of the imputed variants with HbA1c and blood glucose levels was determined via linear regression analyses adjusted for age, sex, body mass index (BMI), smoking, and genetic principal components (PC1-PC10). Moreover, we performed a BMI-stratified GWAS on HbA1c levels in the J-MICC. The discovery analysis and BMI-stratified GWAS results were validated with re-analyses of normalized HbA1c levels adjusted for site in addition to the above, and blood glucose adjusted for fasting time as an additional covariate., Results: Genetic variants associated with HbA1c levels were identified in KCNQ1 and TMC6 . None of the genetic variants associated with blood glucose levels in the discovery analysis were replicated. Association of rs2299620 in KCNQ1 with HbA1c levels showed heterogeneity between individuals with BMI ≥ 25 kg/m
2 and BMI < 25 kg/m2 ., Conclusions: The variant rs2299620 in KCNQ1 might affect HbA1c levels differentially based on BMI grouping in the Japanese population., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00618-0., Competing Interests: Conflict of interestTakuya Sakashita is an employee of Takara Bio, Inc., Japan. Dr. Hachiya is a board member of Genome Analytics Japan Inc. Dr. Nakatochi reports receiving grants from Boehringer Ingelheim outside the submitted work. All other authors declare that they have no conflicts of interest associated with this study., (© The Japan Diabetes Society 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)- Published
- 2023
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19. Comparative evaluation of radionuclide therapy using 90 Y and 177 Lu.
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Hanaoka H, Hashimoto K, Watanabe S, Matsumoto S, Sakashita T, Watanabe S, Ishioka NS, and Endo K
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- Mice, Animals, Tissue Distribution, Radiotherapy Dosage, Disease Models, Animal, Radiopharmaceuticals therapeutic use, Radioisotopes therapeutic use, Lutetium
- Abstract
Objective: Both
90 Y and177 Lu are attractive β-emitters for radionuclide therapy and have been used in clinical practice. Nevertheless, comparative evaluation between90 Y- and177 Lu-labeled molecules has not been fully conducted. Thus, in this study, the features of90 Y and177 Lu for radionuclide therapy were assessed in tumor-bearing mice., Methods: Two tumor cell lines with different growth rates were used. Biodistribution studies of177 Lu-labeled antibodies (177 Lu-Abs) were conducted in each tumor-bearing mouse model. Subsequently, the therapeutic effect of90 Y- and177 Lu-Ab were assessed in tumor-bearing mice. The absorbed radiation dose for the tumor was estimated using the Monte Carlo simulation., Results:177 Lu-Abs demonstrated high tumor accumulation in both tumor-xerograph. In the fast-growing tumor model,90 Y-Ab showed a better therapeutic effect than177 Lu-Ab, reflecting a higher absorbed radiation dose of90 Y-Ab than that of177 Lu-Ab. In the slow-growing tumor model, both90 Y- and177 Lu-Ab showed an excellent therapeutic effect; however,177 Lu-Ab had a longer efficacy period than90 Y-Ab, which could be attributed to the longer half-life and better dose uniformity of177 Lu than those of90 Y., Conclusions: To accomplish a maximum therapeutic effect, selecting90 Y or177 Lu, to depend on the growth rate of individual cancer, would be helpful., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)- Published
- 2023
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20. Fibroblast growth factor receptor 3 overexpression mediates ALK inhibitor resistance in ALK-rearranged non-small cell lung cancer.
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Sakashita T, Yanagitani N, Koike S, Low SK, Takagi S, Baba S, Takeuchi K, Nishio M, Fujita N, and Katayama R
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- Humans, Anaplastic Lymphoma Kinase genetics, Cell Line, Tumor, Drug Resistance, Neoplasm genetics, Mutation, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms metabolism, Receptor, Fibroblast Growth Factor, Type 3 genetics
- Abstract
The rearrangement of anaplastic lymphoma kinase (ALK) occurs in 3%-5% of patients with non-small cell lung cancer (NSCLC) and confers sensitivity to ALK-tyrosine kinase inhibitors (TKIs). For the treatment of patients with ALK-rearranged NSCLC, various additional ALK-TKIs have been developed. Ceritinib is a second-generation ALK-TKI and has shown great efficacy in the treatment of patients with both newly diagnosed and crizotinib (a first-generation ALK-TKI)-refractory ALK-rearranged NSCLC. However, tumors can also develop ceritinib resistance. This may result from secondary ALK mutations, but other mechanisms responsible for this have not been fully elucidated. In this study, we explored the mechanisms of ceritinib resistance by establishing ceritinib-resistant, echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive H3122 cells and ceritinib-resistant patient-derived cells. We identified a mechanism of ceritinib resistance induced by bypass signals that is mediated by the overexpression and activation of fibroblast growth factor receptor 3 (FGFR3). FGFR3 knockdown by small hairpin RNA or treatment with FGFR inhibitors was found to resensitize the resistant cells to ceritinib in vitro and in vivo. FGFR ligands from either human serum or fetal bovine serum were able to activate FGFR3 and induce ceritinib resistance. A detailed analysis of ceritinib-resistant patient-derived specimens confirmed that tyrosine-protein kinase Met (cMET) amplification induces ceritinib resistance. Amplified cMET counteractivated EGFR and/or Her3 and induced ceritinib resistance. These results reveal multiple ceritinib resistance mechanisms and suggest that ceritinib resistance might be overcome by identifying precise resistance mechanisms., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
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- 2022
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21. Organic cation transporter 3 mediates the non-norepinephrine transporter driven uptake of meta-[ 211 At]astato-benzylguanidine.
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Ohshima Y, Sasaki I, Watanabe S, Sakashita T, Higashi T, and Ishioka NS
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- 3-Iodobenzylguanidine metabolism, Animals, Cations metabolism, Desipramine, Guanidines, Humans, Hydrocortisone, Iodine Radioisotopes, Mice, Norepinephrine Plasma Membrane Transport Proteins metabolism, Phosphates metabolism, Prednisolone, RNA, Small Interfering, Rats, Tissue Distribution, Adrenal Gland Neoplasms metabolism, Pheochromocytoma diagnostic imaging, Pheochromocytoma genetics, Pheochromocytoma metabolism
- Abstract
Introduction: Meta-[
211 At]astato-benzylguanidine ([211 At]MABG) accumulates in pheochromocytoma via norepinephrine transporter (NET) and leads to a strong antitumor effect, but it also distributed in normal tissues non-specifically. Meta-[131 I]iodo-benzylguanidine ([131 I]MIBG), an iodine-labeled analog of [211 At]MABG, is known to be transported by not only NET but also organic cation transporter (OCT). The involvement of OCT in [211 At]MABG uptake is still largely unknown. We investigated the involvement of OCT in the non-NET-driven uptake of [211 At]MABG both in vitro and in vivo., Methods: [123 I]MIBG and [211 At]MABG uptake was investigated in PC-12 (rat pheochromocytoma cell line), NIH/3T3 (mouse fibroblasts cell line), ACHN (human renal cancer cell line), and BxPC-3 (human pancreatic cancer cell line). Herein, we used desipramine and dl-norepinephrine to inhibit NET, and we used steroids (hydrocortisone and prednisolone) to inhibit OCT3. The [211 At]MABG uptake in OCT3-knockdown cells established with OCT3-selective siRNA was also investigated. We investigated the biodistribution of [211 At]MABG in PC-12 tumor-bearing mice after a preloading of phosphate-buffered saline (PBS) or hydrocortisone solution., Results: The uptake of both [123 I]MIBG and [211 At]MABG was significantly inhibited by desipramine in PC-12 cells but not the other cell lines. The expression of OCT3 was relatively higher than those of the other OCT subtypes in ACHN and BxPC-3 cells. The expression of OCTs was not observed in NIH/3T3 cells. The uptake of both [123 I]MIBG and [211 At]MABG in ACHN and BxPC-3 cells was significantly inhibited by the steroid treatments. The [211 At]MABG uptake was also reduced in OCT3-knockdown cells (p < 0.001). The radioactivity of [211 At]MABG was significantly reduced in normal tissues by the preloading of hydrocortisone. In contrast, there was an increasing trend of [211 At]MABG uptake in the PC-12 tumors. The tumor-to-normal tissue ratio was significantly increased by the preloading of hydrocortisone compared to that of PBS., Conclusion: Our results suggest that OCT3 is involved in non-NET-driven [211 At]MABG uptake. The preloading of hydrocortisone selectively reduced [211 At]MABG accumulation in normal organs in vivo. OCT3 inhibition may therefore be beneficial for a reduction of the radiation risk in healthy organs in the treatment of malignant pheochromocytomas., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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22. Suicide Prevention Interventions and Their Linkages in Multilayered Approaches for Older Adults: A Review and Comparison.
- Author
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Sakashita T and Oyama H
- Subjects
- Aged, Female, Hong Kong epidemiology, Humans, Italy, Japan, Male, Suicidal Ideation, Suicide psychology, Suicide Prevention
- Abstract
Multilayered approaches to suicide prevention combine universal, selective, and indicated prevention interventions. These approaches may be more successful in reducing suicide rates among older adults if they link these layers more systematically: that is, if the programs are designed so that interventions at a lower level facilitate involvement at a higher level when appropriate. This study aimed to examine the effect on suicide rates of the structure of multilayered approaches, and in particular the types of interventions and the connections or linkages between them. We also wished to consider any different effects by sex. A literature search used PubMed and PsycINFO to identify systematic reviews of interventions in this age group. From the reference lists of these articles, we identified controlled studies assessing the impact of a multilayered program on suicide incidence among older adults. We were particularly interested in initiatives linking different kinds of prevention interventions. We found three relevant systematic reviews, and from these, we identified nine eligible studies. These included seven non-randomized controlled studies from rural areas in Japan (average eligible population: 3,087, 59% women, average duration: 8 years). We also found two cohort studies. The first was from a semi-urban area in Padua, Italy (18,600 service users, 84% women, duration: 11 years). The second was from urban Hong Kong, with 351 participants (57% women) over a 2-year follow-up period. We used a narrative synthesis of these studies to identify five different multilayered programs with different forms of connections or linkages between layers. Two studies/programs (Italy and Hong Kong) involved selective and indicated prevention interventions. One study/program (Yuri, Japan) included universal and selective prevention interventions, and the final six studies (two programs in northern Japan) involved linkages between all three layers. We also found that these linkages could be either formal or informal. Formal linkages were professional referrals between levels. Informal linkages included advice from professionals and self-referrals. Several of the studies noted that during the program, the service users developed relationships with services or providers, which may have facilitated movements between levels. All five programs were associated with reduced suicide incidence among women in the target groups or communities. Two programs were also associated with a reduction among men. The study authors speculated that women were more likely to accept services than men, and that the care provided in some studies did less to address issues that are more likely to affect men, such as suicidal impulsivity. We therefore suggest that it is important to build relationships between levels, especially between selective and indicated prevention interventions, but that these can be both formal and informal. Additionally, to reach older men, it may be important to create systematic methods to involve mental health professionals in the indicated prevention intervention. Universal interventions, especially in conjunction with systematically linked indicated and selective interventions, can help to disseminate the benefits across the community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sakashita and Oyama.)
- Published
- 2022
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23. Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer.
- Author
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Miura K, Kawakita D, Oze I, Suzuki M, Sugasawa M, Endo K, Sakashita T, Ohba S, Suzuki M, Shiotani A, Kohno N, Maruo T, Suzuki C, Iki T, Hiwatashi N, Matsumoto F, Kobayashi K, Toyoda M, Hanyu K, Koide Y, Murakami Y, and Hasegawa Y
- Subjects
- Humans, Neck pathology, Neck Dissection, Mouth Neoplasms pathology, Mouth Neoplasms surgery, Sentinel Lymph Node Biopsy methods
- Abstract
Prophylactic elective neck dissection (ND) with navigation surgery using radioisotope-based sentinel lymph node biopsy (SLNB) is non-inferior to elective ND in terms of survival but has an advantage in postoperative functional disability. We conducted a subgroup analysis to identify predictive factors for false-negative (FN)-SLNB in patients with early oral cavity cancer. This study is a supplementary analysis using the dataset of a previously reported randomized clinical trial on SLN navigation surgery for oral cancers. This study investigated the association of clinical and SLN-related factors with false-negative cases in the SLNB group. From 2011 to 2016, 275 patients were enrolled and randomly assigned to the ND and SLNB study groups, with 134 patients assigned to the SLNB group. In the SLNB group, seven cases with negative SLNs and neck recurrences were judged as FN-SLNBs according to the general definition. The number of detected SLNs with and without adjusting for the propensity score was significantly associated with FNs in the logistic analysis. FN-SLNB was associated with the number of identified SLNs, suggesting the need for careful postoperative monitoring for neck recurrence in patients with one or two identified SLNs after acquiring sufficient experience in the identification technique., (© 2022. The Author(s).)
- Published
- 2022
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24. Point Prevalence Surveys of Antimicrobial Prescribing in a Non-Acute Care Hospital in Saitama Prefecture, Japan.
- Author
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Ishibashi N, Pauwels I, Tomori Y, Gu Y, Yamaguchi T, Handa T, Yamaoka M, Ito D, Sakimoto T, Kimura T, Takizawa K, Sato R, Sakashita T, Ooyama A, Versporten A, Goossens H, Tarumoto N, Maesaki S, and Tanahashi N
- Abstract
Background: The global point prevalence survey (Global-PPS) is the standard for the surveillance of prescribed antimicrobials among inpatients and provides data for the development of hospital antimicrobial stewardship programs., Aim: To evaluate the prevalence and quality of antimicrobial prescriptions using the universally standardized Global-PPS protocol in a non-acute care hospital in Saitama Prefecture, Japan., Methods: Antimicrobial prescriptions for inpatients, staying at the hospital overnight, were surveyed on three separate week days in November 2018, January 2019, and May 2019. Information on the prescribed antimicrobials on the survey target day was obtained from the in-hospital pharmacy. Survey data were collected by physicians, based on the extracted information. Patient information was anonymized and entered in the Global-PPS Web application by physicians. We report the antimicrobial use prevalence, the indication for prescription, diagnosis, the most prescribed antimicrobials, and a set of quality indicators related to antimicrobial prescribing., Results: In total, 6.7% of the surveyed inpatients (120/1796) were prescribed antimicrobials on the survey day. Sulfamethoxazole/trimethoprim was the most commonly prescribed, with 20.0% of systemic antibiotic prescriptions (ATC J01). Of all antibiotics for systemic use, up to 58.4% were Watch antibiotics, as defined by the World Health Organization AWaRe classification. The most prescribed group of systemic antibiotics was non-penicillin beta-lactam antibiotics (34.4%), followed by penicillin antibiotics in combination with beta-lactamase inhibitors (25.6%), and sulfonamides with trimethoprim (20.8%). Healthcare-associated infections and medical prophylaxis were the most common indications reported in 69.3% and 26.3% of prescriptions, respectively. The most common diagnosis for systemic antibiotic prescriptions was pneumonia (49.6%). Reasons for antimicrobial prescriptions were indicated in the medical records for 67.1% of prescriptions, and the stop/review date was documented to be 50.3%. Compliance with local guidelines reached 66.7%., Conclusions: This study highlights important challenges related to antimicrobial prescription in a highly specific, non-acute care patient population., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Noriomi Ishibashi et al.)
- Published
- 2022
- Full Text
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