Publications by authors named "Yuki Sato"

410 Publications

Investigation of the Real-World Situation and Risk Factors Associated with Olanzapine Prescribed to Diabetes Patients by Using a Japanese Claims Database.

Biol Pharm Bull 2021 ;44(8):1151-1155

Department of Pharmacy, Hokkaido University Hospital.

Olanzapine is effective for schizophrenia management; however, it is contraindicated in diabetes patients. In addition, olanzapine is useful for treating nausea and vomiting, such as in the case of chemotherapy-induced nausea and vomiting (CINV). Therefore, we hypothesized that the contraindicated prescription of olanzapine likely occurs among cancer patients with diabetes, especially by non-psychiatric physicians. Hence, we conducted a nationwide survey to elucidate the situation of such contraindicated prescriptions and the associated risk factors. We extracted the data of patients who were newly prescribed olanzapine between April 2015 and March 2017 from the health insurance claims database developed by JMDC, Inc., Tokyo. The patients who were prescribed contraindicated olanzapine were defined as those who were prescribed olanzapine after a diagnosis of diabetes and diabetes drug prescription. In all, the data of 7181 patients were analyzed. We evaluated the proportion of diabetes patients who were prescribed contraindicated olanzapine from among those who were prescribed olanzapine. Furthermore, we investigated the background of patients who were prescribed olanzapine for information such as olanzapine prescribers and history of cancer chemotherapy. In all, 100 diabetes patients (1.39%) were prescribed olanzapine. In these patients, the frequency of olanzapine prescription was higher by non-psychiatry/neurology physicians than by psychiatry/neurology physicians (3.25 and 0.85%, respectively). Additionally, all olanzapine prescriptions in cancer chemotherapy-treated diabetes patients were issued by non-psychiatry/neurology physicians. Thus, our study revealed there were diabetes patients who were prescribed olanzapine. Additionally, olanzapine for CINV management was more likely to be a contraindicated prescription.
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http://dx.doi.org/10.1248/bpb.b21-00170DOI Listing
January 2021

cAMP Signaling Pathway Prevents Dasatinib-Induced Vascular Hyperpermeability.

Biol Pharm Bull 2021 ;44(8):1101-1110

Department of Pharmacy, Hokkaido University Hospital.

Dasatinib is a first-line pharmacotherapeutic treatment for chronic myeloid leukemia (CML). It is more effective than traditional treatments but causes adverse effects such as pleural effusion that limits its effective treatment cycle. Since pleural effusion is caused by vascular hyperpermeability and causes discontinuation of treatment with dasatinib, it is important to explore the mechanism of pleural effusion caused by dasatinib and how to prevent it. In this study, we investigated how dasatinib increase vascular permeability, and how it can be prevented. Cytotoxicity was observed in vascular endothelial cells or epithelial cells were exposed to high concentrations of dasatinib. Thus, it was observed in vascular endothelial cells such as human umbilical vascular endothelial cell (HUVEC). Vascular endothelial (VE)-cadherin is one of the important factors that control vascular permeability. When VE-cadherin expression decreases, vascular permeability increases, but it did not change with tyrosine kinase inhibitor exposure. Monolayer permeability significantly increased only with high concentration of dasatinib, but this increase was prevented by cAMP activation. Furthermore, dasatinib affects the cell morphology of HUVEC, with increased inter celluar space compared to control and bosutinib, which were also attenuated by cAMP activation. Dasatinib significantly affected permeability control of vascular endothelial cells compared to bosutinib and imatinib. These results indicated that the cAMP signaling pathway may be involved in the pleural effusion caused by dasatinib in CML patients.
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http://dx.doi.org/10.1248/bpb.b21-00270DOI Listing
January 2021

The use of the Sanuki airway™ in three patients with suspected difficult airway.

SAGE Open Med Case Rep 2021 9;9:2050313X211031311. Epub 2021 Jul 9.

Department of Anesthesiology, Fukushima Medical University Hospital, Fukushima, Fukushima, Japan.

The Sanuki airway is a single-use intubation oral airway designed for fiberoptic bronchoscope intubation. Sanuki airway has a bite block function and a wide lumen for the tracheal tube to pass through. Here, three cases are reported in which Sanuki airway was used for oral fiberoptic bronchoscope intubation. Case 1 is a patient who presented with reduced mouth opening and intraoral edema due to facial bone fracture. Case 2 is a patient who suffered from severe neck stiffness and had reduced mouth opening due to systemic psoriatic arthritis. Case 3 is a patient who suffered from multiple facial traumas and was in a full-stomach state. In all patients, advancing the tip of the bronchofiber into the larynx using Sanuki airway was possible under dexmedetomidine sedation, which contributed to the successful tracheal intubation. Using Sanuki airway may be considered an option for oral fiberoptic bronchoscope intubation in patients anticipated with difficult airways.
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http://dx.doi.org/10.1177/2050313X211031311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273519PMC
July 2021

Tertiary lymphoid tissues: a regional hub for kidney inflammation.

Nephrol Dial Transplant 2021 Jul 10. Epub 2021 Jul 10.

Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Tertiary lymphoid tissues (TLTs) are inducible ectopic lymphoid tissues that develop at sites of chronic inflammation in non-lymphoid organs. Same as lymph nodes, TLTs initiate adaptive immune responses and coordinate local tissue immunity. Although virtually ignored for decades, TLTs have recently received a great deal of attention for their ability to influence disease severity, prognosis and response to therapy in various diseases including cancer, autoimmune disorders and infections. TLTs are also induced in kidneys of patients with several CKDs such as IgA nephropathy and lupus nephritis. Nevertheless, TLTs in the kidney have not been extensively investigated, and their mechanism of development, functions and clinical relevance remain unknown, mainly because of the absence of adequate murine kidney TLT models and limited availability of human kidney samples containing TLTs. We recently found that aged kidneys, but not young kidneys, exhibit multiple TLTs after injury. Interestingly, although they are a minor component of TLTs, resident fibroblasts in the kidneys diversify into several distinct phenotypes that play crucial roles in TLT formation. Furthermore, the potential of TLTs as a novel kidney injury/inflammation marker as well as a novel therapeutic target for kidney diseases are also suggested. In this review article, we describe the current understanding of TLTs with a focus on age-dependent TLTs in the kidney and discuss their potential as a novel therapeutic target and kidney inflammation marker.
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http://dx.doi.org/10.1093/ndt/gfab212DOI Listing
July 2021

Evaluation of false positives in the SARS-CoV-2 quantitative antigen test.

J Infect Chemother 2021 Jun 25. Epub 2021 Jun 25.

Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan; Division of Infection Control, Sapporo Medical University Hospital, Sapporo, Japan; Department of Infection Control and Laboratory Medicine Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address:

Introduction: Highly sensitive reagents for detecting SARS-CoV-2 antigens have been developed for accurate and rapid diagnosis till date. In this study, we aim to clarify the frequency of false-positive reactions and reveal their details in SARS-CoV-2 quantitative antigen test using an automated laboratory device.

Methods: Nasopharyngeal swab samples (n = 4992) and saliva samples (n = 5430) were collected. We measured their SARS-CoV-2 antigen using Lumipulse® Presto SARS-CoV-2 Ag and performed a nucleic acid amplification test (NAAT) using the Ampdirect™ 2019 Novel Coronavirus Detection Kit as needed. The results obtained from each detection test were compared accordingly.

Results: There were 304 nasopharyngeal samples and 114 saliva samples were positive in the Lumipulse® Presto SARS-CoV-2 Ag test. All positive nasopharyngeal samples in the antigen test were also positive for NAAT. In contrast, only three (2.6%) of all the positive saliva samples in the antigen test were negative for NAAT. One showed no linearity with a dilute solution in the dilution test. Additionally, the quantitative antigen levels of all the three samples did not decrease after reaction with the anti-SARS-CoV-2 antibody.

Conclusions: The judgment difference between the quantitative antigen test and NAAT seemed to be caused by non-specific reactions in the antigen test. Although the high positive and negative predictive value of this quantitative antigen test could be confirmed, we should consider the possibility of false-positives caused by non-specific reactions and understand the characteristics of antigen testing. We recommend that repeating centrifugation before measurement, especially in saliva samples, should be performed appropriately.
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http://dx.doi.org/10.1016/j.jiac.2021.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226058PMC
June 2021

A cross-sectional survey of hospitalization and blood tests implementation status in patients who received tolvaptan under 75 years of age using a Japanese claims database.

Expert Opin Drug Saf 2021 Jul 19:1-10. Epub 2021 Jul 19.

Department of Pharmacy, Hokkaido University Hospital, Sapporo, Japan.

Background: Hypernatremia and liver injury are typical adverse effects of tolvaptan. Therefore, hospitalization and frequent monitoring of serum sodium concentration and liver function are necessary for tolvaptan initiation. We performed a cross-sectional survey to evaluate these situations.

Research Design And Methods: We employed the Japanese claims database, which contains data of patients aged < 75 years. Patients who were newly prescribed tolvaptan for fluid accumulation induced by chronic heart failure (FA-CHF) or liver cirrhosis (FA-LC) from January 2011 to June 2017 were included. We evaluated the hospitalization status and implementation of serum sodium and liver function tests in the evaluation period, based on the Japanese package insert.

Results: Of 1,173 patients, 347 and 117 were enrolled in FA-CHF and FA-LC groups, respectively. Among them, 10.7% (FA-CHF group) and 5.13% (FA-LC group) were prescribed tolvaptan without hospitalization. In the FA-CHF group, 11.0% and 17.6% did not undergo serum sodium and liver function tests even once in the evaluation period, respectively, compared with 12.0% and 12.8% in the FA-LC group.

Conclusions: Our results highlight the deviation from Japanese package insert recommendations. This approach can be applied to other drugs and provides important perspectives on pharmacovigilance research.
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http://dx.doi.org/10.1080/14740338.2021.1951219DOI Listing
July 2021

Intracellular oxidative stress induced by calcium influx initiates the activation of phagocytosis in keratinocytes accumulating at S-phase of the cell cycle after UVB irradiation.

J Dermatol Sci 2021 Jul 11;103(1):41-48. Epub 2021 Jun 11.

School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo, Japan.

Background: Phagocytosis is an essential process that maintains cellular homeostasis. In the epidermis, the phagocytosis of melanosomes into keratinocytes is important to protect their DNA against damage from ultraviolet B (UVB) radiation. Furthermore, it is considered that UVB activates the phagocytosis by keratinocytes but the detailed mechanism involved is not fully understood.

Objective: To clarify the mechanism of UVB-enhanced phagocytosis in keratinocytes, we investigated the relationship between the phagocytic ability of keratinocytes and the cell cycle stage of keratinocytes.

Methods: The phagocytic ability of keratinocytes was evaluated using the incorporation of fluorescent beads after exposure to UVB or oxidative stress. S-phase was evaluated by BrdU incorporation and immunostaining of cyclin D1. Intracellular calcium levels of keratinocytes were measured using the probe Fluo-4AM.

Results: The phagocytosis of fluorescent beads into keratinocytes was enhanced by UVB and also by oxidative stress. We found that keratinocytes exposed to UVB or oxidative stress were at S-phase of the cell cycle. Furthermore, keratinocytes synchronized to S-phase showed a higher phagocytic ability according to the increased intracellular ROS level. The UVB-enhanced phagocytosis and entrance into S-phase of keratinocytes was abolished by ascorbic acid, a typical antioxidant. Keratinocytes synchronized to S-phase and exposed to UVB or oxidative stress had increased levels of intracellular calcium and their enhanced phagocytic abilities were diminished by the calcium ion chelator BAPTA-AM.

Conclusion: Taken together, intracellular oxidative stress induced by intracellular calcium influx mediates the UVB-enhanced phagocytic ability of keratinocytes accumulating at S-phase of the cell cycle.
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http://dx.doi.org/10.1016/j.jdermsci.2021.06.005DOI Listing
July 2021

An imaging approach for determining the mechanism of enhancement of intestinal absorption of an L-theanine supplement.

PLoS One 2021 11;16(6):e0253066. Epub 2021 Jun 11.

Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.

Background & Objective: Theanine (L-glutamylethylamide) contained in green tea is a functional food component that has been attracting attention due to its relaxation effect. It was shown that the ingredients added to the theanine formulations increased the absorption of theanine. If this mechanism can be elucidated, it would be possible to contribute to development of evidence-based formulations. In this study, we investigated the effect of ingredients in the formulations on the absorption of theanine in detail.

Main Methods: After oral administration of a mixture of theanine and additional components to Wistar rats the plasma concentration was determined by an HPLC and the pharmacokinetic parameters were calculated. In addition, a new system for evaluating intestinal blood flow was developed since the involvement of intestinal blood flow was considered as a factor that increased absorption of theanine.

Key Findings: Plasma concentration of theanine increased significantly in the combined use group with eight ingredients containing piperine as compared with theanine only group. Piperine would increase theanine absorption by increased blood flow, not an inhibition of metabolism. We succeeded to develop a visual and quantitative system to evaluate the effect of these ingredients directly including piperine on the intestinal blood flow using indocyanine green while maintaining physiological conditions.

Significance: Increased intestinal blood flow by these ingredients including piperine enhanced the absorption of theanine. Other mechanisms may also be considered as the mechanism by which theanine absorption is increased in addition to increased blood flow.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253066PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195392PMC
June 2021

Time in range correlates glycated albumin measured immediately after 2 weeks of continuous glucose monitoring.

J Diabetes Complications 2021 Aug 25;35(8):107962. Epub 2021 May 25.

Department of Internal Medicine, Saitama Medical Center, Japan Community Healthcare Organization, 4-9-3 Kitaurawa, Urawa-ku, Saitama 330-0074, Japan. Electronic address:

Aims: Time in range (TIR), an index of glycemic control and also blood glucose fluctuation, obtained from continuous glucose monitoring (CGM), has been increasing its importance along with the spread of CGM in recent years. For a while, glycated albumin (GA) has been also used as a glycemic control index during about 2-weeks in routine clinical practice. It has not yet been confirmed under optimal condition whether TIR and GA correlates. Clarification of the correlation between TIR and GA, which was measured immediately after 2-weeks of CGM, might be a finding that further supports the utility of TIR.

Methods: GA was measured at the conclusion of 2-week CGM in 71 diabetes outpatients at our hospital, and the correlation between GA and indices such as TIR obtained from CGM was statistically analyzed.

Results: It was found that TIR and time above range (TAR) were significantly correlated with GA. Upon performing multiple regression analysis, TIR, TAR and BMI. indicated a significant regression coefficient with respect to GA.

Conclusions: These findings further support the utility of TIR as a marker of glycemic control that it might also be correlated with GA, and also suggest a relation between GA and blood glucose fluctuation.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.107962DOI Listing
August 2021

FKBP51 and FKBP52 regulate androgen receptor dimerization and proliferation in prostate cancer cells.

Mol Oncol 2021 May 31. Epub 2021 May 31.

Department of Biochemistry, Joint Faculty of Veterinary Science, Yamaguchi University, Japan.

The growth of prostate cancer is dependent on the androgen receptor (AR), which serves as a ligand-specific transcription factor. Although two immunophilins, FKBP51 and FKBP52, are known to regulate AR activity, the precise mechanism remains unclear. We found that depletion of either FKBP51 or FKBP52 reduced AR dimer formation, chromatin binding, and phosphorylation, suggesting defective AR signaling. Furthermore, the peptidyl-prolyl cis/trans isomerase activity of FKBP51 was found to be required for AR dimer formation and cancer cell growth. Treatment of prostate cancer cells with FK506, which binds to the FK1 domain of FKBPs, or with MJC13, an inhibitor of FKBP52-AR signaling, also inhibited AR dimer formation. Finally, elevated expression of FKBP52 was associated with a higher rate of prostate-specific antigen recurrence in patients with prostate cancer. Collectively, these results suggest that FKBP51 and FKBP52 might be promising targets for prostate cancer treatment through the inhibition of AR dimer formation.
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http://dx.doi.org/10.1002/1878-0261.13030DOI Listing
May 2021

Spontaneous disappearance of common bile duct stones following the insertion of a new dumbbell-shaped, covered self-expandable metallic stent in a patient with benign biliary stricture.

Clin Case Rep 2021 May 4;9(5):e04093. Epub 2021 May 4.

Department of Gastroenterology, School of Medicine Fukushima Medical University Fukushima Japan.

The new dumbbell-shaped, covered self-expanding metallic stent can efficiently remove the choledocholiths in cases with common bile duct (CBD) strictures; moreover, it may potentially prevent a positional displacement and contribute to the better improvement of the CBD stricture.
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http://dx.doi.org/10.1002/ccr3.4093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122123PMC
May 2021

Gastrointestinal perforation following dabrafenib and trametinib administration in non-small cell lung carcinoma with BRAF V600E mutation: a case report and literature review.

Invest New Drugs 2021 May 23. Epub 2021 May 23.

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-Ku, Kobe, 650-0047, Japan.

Gastrointestinal perforation related to mitogen-activated protein kinase kinase (MEK) inhibitors has been reported previously; however, there has been no case report of such a condition in patients with non-small cell lung cancer (NSCLC). Herein, we report a case of small intestinal perforation secondary to dabrafenib and trametinib administration, but not related to tumor regression. A 62-year-old man with non-small cell lung cancer harboring BRAF V600E mutation was treated with dabrafenib and trametinib. Four months after the initiation of treatment, a small intestinal perforation was diagnosed. Dabrafenib and trametinib rechallenge was performed after gastrointestinal perforation. The patient responded well to therapy and did not experience recurrence of gastrointestinal perforation. To the best of our knowledge, this is the first report of gastrointestinal perforation in a patient with NSCLC treated with a MEK inhibitor. The mechanism and risk factors of trametinib-induced perforation are currently unknown. Physicians should be aware of such severe gastrointestinal side effects of trametinib.
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http://dx.doi.org/10.1007/s10637-021-01135-0DOI Listing
May 2021

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions.

Beilstein J Org Chem 2021 20;17:866-872. Epub 2021 Apr 20.

Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan.

The homolytic cleavage of the P(O)-P bond in tetraphenyldiphosphine monoxide simultaneously provides both pentavalent and trivalent phosphorus-centered radicals with different reactivities. The method using V-40 as an initiator is successfully investigated for the regio- and stereoselective phosphinylphosphination of terminal alkynes giving the corresponding -isomers of 1-diphenylphosphinyl-2-diphenylthiophosphinyl-1-alkenes in good yields. The protocol can be applied to a wide variety of terminal alkynes including both alkyl- and arylalkynes.
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http://dx.doi.org/10.3762/bjoc.17.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077611PMC
April 2021

Fibroblast heterogeneity and tertiary lymphoid tissues in the kidney.

Immunol Rev 2021 Jul 5;302(1):196-210. Epub 2021 May 5.

Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Fibroblasts reside in various organs and support tissue structure and homeostasis under physiological conditions. Phenotypic alterations of fibroblasts underlie the development of diverse pathological conditions, including organ fibrosis. Recent advances in single-cell biology have revealed that fibroblasts comprise heterogeneous subpopulations with distinct phenotypes, which exert both beneficial and detrimental effects on the host organs in a context-dependent manner. In the kidney, phenotypic alterations of resident fibroblasts provoke common pathological conditions of chronic kidney disease (CKD), such as renal anemia and peritubular capillary loss. Additionally, in aged injured kidneys, fibroblasts provide functional and structural supports for tertiary lymphoid tissues (TLTs), which serve as the ectopic site of acquired immune reactions in various clinical contexts. TLTs are closely associated with aging and CKD progression, and the developmental stages of TLTs reflect the severity of renal injury. In this review, we describe the current understanding of fibroblast heterogeneity both under physiological and pathological conditions, with special emphasis on fibroblast contribution to TLT formation in the kidney. Dissecting the heterogeneous characteristics of fibroblasts will provide a promising therapeutic option for fibroblast-related pathological conditions, including TLT formation.
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http://dx.doi.org/10.1111/imr.12969DOI Listing
July 2021

PP1 regulatory subunit NIPP1 regulates transcription of E2F1 target genes following DNA damage.

Cancer Sci 2021 Jul 3;112(7):2739-2752. Epub 2021 May 3.

Department of Biochemistry, Joint Faculty of Veterinary Science, Yamaguchi University, Yamaguchi, Japan.

DNA damage induces transcriptional repression of E2F1 target genes and a reduction in histone H3-Thr phosphorylation (H3-pThr ) at E2F1 target gene promoters. Dephosphorylation of H3-pThr11 is partly mediated by Chk1 kinase and protein phosphatase 1γ (PP1γ) phosphatase. Here, we isolated NIPP1 as a regulator of PP1γ-mediated H3-pThr by surveying nearly 200 PP1 interactor proteins. We found that NIPP1 inhibits PP1γ-mediated dephosphorylation of H3-pThr both in vivo and in vitro. By generating NIPP1-depleted cells, we showed that NIPP1 is required for cell proliferation and the expression of E2F1 target genes. Upon DNA damage, activated protein kinase A (PKA) phosphorylated the NIPP1-Ser residue, adjacent to the PP1 binding motif (RVxF), and triggered the dissociation of NIPP1 from PP1γ, leading to the activation of PP1γ. Furthermore, the inhibition of PKA activity led to the activation of E2F target genes. Statistical analysis confirmed that the expression of NIPP1 was positively correlated with E2F target genes. Taken together, these findings demonstrate that the PP1 regulatory subunit NIPP1 modulates E2F1 target genes by linking PKA and PP1γ during DNA damage.
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http://dx.doi.org/10.1111/cas.14924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253265PMC
July 2021

Unique and abnormal subependymal pseudocysts in a newborn with mitochondrial disease.

Sci Prog 2021 Apr-Jun;104(2):368504211011873

Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.

Neonatal mitochondrial disease is occasionally observed in patients with intraventricular cysts in the brain. Atypical morphology is rarely seen in these cysts. Here, we report a case of neonatal lethal mitochondrial disease with gene mutation. We have, for the first time, described a subependymal pseudocyst (SEPC) with a fluctuating membrane. Our findings suggest that SEPCs with fluctuating membranes can be a potential diagnostic indicator of neonatal mitochondrial disease.
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http://dx.doi.org/10.1177/00368504211011873DOI Listing
April 2021

Activation of a Manganese Perovskite Oxygen Reduction Catalyst in Concentrated Alkaline Media.

J Am Chem Soc 2021 May 23;143(17):6505-6515. Epub 2021 Apr 23.

Faculty of Engineering, Hokkaido University, N13W8, Kita-ku, Sapporo, Hokkaido 060-8628, Japan.

The reaction pathway of the oxygen reduction reaction (ORR) is strongly affected by the electrolytic environment. Meanwhile, the ORR mechanism on transition-metal oxide catalysts has not been studied intensely in very concentrated alkaline solutions that are used in practical metal-air batteries. Herein, we report the activation of ORR catalysis on manganese perovskite in a concentrated alkaline solution, mediated by the spontaneous formation of oxygen vacancy sites. Electrochemical analyses of the (100) epitaxial film electrodes reveal that the exchange current and electron number of the ORR on LaSrMnNiO significantly increase with the duration of the ORR when the KOH concentration is greater than 4 M. However, these values remain unchanged with time at less than 1 M KOH concentration. Operando synchrotron X-ray spectroscopy of the (100) epitaxial film confirmed that LaSrMnNiO involves the oxygen vacancy sites with the reduction of Mn atoms in concentrated KOH solution via the hydroxylation decomposition of perhydroxyl intermediates. Hence, the O adsorption switched from an end-on to a bidentate mode because the cooperative active sites of the oxygen vacancy and neighboring Mn allow bidentate adsorption of the dissolved O. Due to the simultaneous interaction with the oxygen vacancy and Mn sites, the O-O bonds are activated and the potential barrier for the electron transfer to adsorbed O is lowered, resulting in a shift in the reaction mechanism from that involving an indirect "2 + 2" transfer pathway to a direct 4-electron pathway.
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http://dx.doi.org/10.1021/jacs.1c00449DOI Listing
May 2021

Localized gastric amyloidosis diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Clin J Gastroenterol 2021 Aug 22;14(4):1036-1041. Epub 2021 Apr 22.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

A 49-year-old man was found to have an elevated lesion on esophagogastroduodenoscopy (EGD) for gastric cancer screening. This lesion had been noted in EGD 13 years earlier, but the patient had not received EGD since then. Endoscopy showed a relatively soft subepithelial lesion (SEL) in the gastric antrum. In addition, endoscopic ultrasonography (EUS) showed a 20-mm-sized, slightly non-uniform hypoechoic mass in the submucosa. Since the diagnosis could not be confirmed by mucosal biopsy, EUS-guided fine-needle aspiration (EUS-FNA) was performed. Hematoxylin-eosin staining of EUS-FNA samples revealed deposition of acidophilic unstructured materials. The structure was positive on Congo red staining, and green polarized light was also observed under a polarizing microscope. Moreover, it was resistant to potassium permanganate reaction, negative for serum amyloid A protein, positive for anti-λ chain antibody, and negative for anti-κ chain, anti-amyloid A, anti-transthyretin, and anti-β2-microglobulin antibodies. Therefore, the lesion was diagnosed as AL-λ-type amyloidosis. No systemic amyloidosis findings were found; thus, the patient was finally diagnosed with localized gastric AL amyloidosis. If an SEL is seen without disease-specific endoscopic findings, amyloidosis should be included in the differential diagnosis, and EUS-FNA can contribute to obtaining tissue samples in such cases.
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http://dx.doi.org/10.1007/s12328-021-01416-4DOI Listing
August 2021

Association Between Sleep Characteristics and Asthma Control in Middle-Aged and Older Adults: A Prospective Cohort Study.

J Asthma Allergy 2021 6;14:325-334. Epub 2021 Apr 6.

Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan.

Background: Nocturnal asthma symptoms are a well-known feature of sleep disturbance. However, there are few reports on the association between sleep-related characteristics and asthma exacerbation. The aim of the current prospective observational study was to explore the factors while sleeping associated with future asthma exacerbation.

Materials And Methods: At baseline, adult asthmatics underwent home sleep monitoring by a Watch-PAT instrument and then they were prospectively followed-up for the occurrence of exacerbations. The number of asthma exacerbation was observed over a period of one year, and multivariable analyses of the factors associated with asthma exacerbation were performed.

Results: A total of 62 asthmatic subjects were enrolled (mean age 62.1 years), 59 of whom were finally included in the prospective observational study. Obstructive sleep apnea (defined by an apnea-hypopnea index based on peripheral arterial tone more than 5 times/hour) were observed in 81% of the subjects. During the one-year monitoring period, 14 of the 59 subjects (24%) used occasional systemic corticosteroids for their exacerbation asthma (worsened group) while the other 45 subjects did not experience asthma exacerbation (stable group). A comparison of the baseline clinical characteristics and sleep-related data between the two groups, mean forced expiratory volume one second percent (FEV/FVC), mean baseline Asthma Control Test (ACT) score, median pAHI value, and median oxygen desaturation index value were significantly lower in the worsened group than those in the stable group. Additionally, mean prevalence of the left lateral decubitus (LLD) position in sleep monitoring were significantly higher in the worsened group than that in the stable group. Among the independent variables, baseline asthma severity, ACT score, and the LLD position showed significant associations with asthma exacerbation.

Discussion/conclusion: The present study identified that sleeping in the LLD position was also associated with asthma exacerbation.
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http://dx.doi.org/10.2147/JAA.S301444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040693PMC
April 2021

A Pilot Randomized Crossover Trial of Wet Suction and Conventional Techniques of Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Upper Gastrointestinal Subepithelial Lesions.

Gastroenterol Res Pract 2021 22;2021:4913107. Epub 2021 Mar 22.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Methods: Twenty-six patients with UGI-SELs indicated for EUS-FNA were randomly assigned to the dry-first arm using the dry technique for the first two passes or the wet-first arm using the wet technique for the first two passes using a cross-over design with a ratio of 1 : 1. The primary endpoint was the cellularity score of the EUS-FNA specimens rated on a 4-point scale (0-3). The secondary endpoints were the factors influencing cellularity in each suction technique.

Results: The mean cellularity score was 1.65 ± 1.20 for the wet technique and 2.00 ± 0.98 for the dry technique ( = 0.068). Logistic regression analysis showed that higher cellularity may be related to the final diagnosis of gastrointestinal stromal tumors in the dry technique and the SEL location in the upper stomach in the wet technique.

Conclusion: The wet EUS-FNA technique failed to show a potential for improved cellularity of specimens compared to the dry technique for UGI-SELs.
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http://dx.doi.org/10.1155/2021/4913107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007354PMC
March 2021

Evaluation of two commercial molecular diagnostic assays: The Xpert Norovirus and the TRCReady NV.

J Infect Chemother 2021 Jul 1;27(7):1115-1118. Epub 2021 Apr 1.

Division of Laboratory Medicine, Sapporo Medical University Hospital, Japan; Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address:

Introduction: Norovirus is highly contagious, and a few particles of this virus are sufficient to make people sick. It is desirable to develop quick and accurate laboratory methods to detect norovirus.

Methods: We evaluated two commercial molecular diagnostic assays, the Xpert Norovirus and the TRCReady NV, using clinical fecal samples. A reference method was performed using in-house real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR).

Results: The results of the real-time RT-PCR analysis of 60 suspected cases of norovirus infection showed 5 cases of Genogroup I (GI) positives and 21 cases of GII positives, among which was 1 GI and GII coinfection. The viral titers of the norovirus-positive samples ranged from 1.54 × 10 to 3.14 × 10 copies/μL. Norovirus GII.17 (12 cases, 48%) was the most frequently detected genotype in this study, followed by GII.4 (6 cases, 24%), GII.13 (2 cases, 8%), GI.2 (2 cases, 8%), GI.3 (2 cases, 8%), GI.1 (1 case, 4%), and GII.2 (1 case, 4%). The kappa coefficient was 1.000 (95% CI: 1.000-1.000) for Xpert Norovirus and 0.966 (95% CI: 0.896-1.000) for TRCReady NV, indicating a strong agreement.

Conclusions: Norovirus detection using Xpert Norovirus and TRCReady NV is highly useful for diagnosis and infection control because these assays are easy to operate, quick, and exhibit almost the same performance as that of real-time RT-PCR.
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http://dx.doi.org/10.1016/j.jiac.2021.02.004DOI Listing
July 2021

Clinical Utility of Next-Generation Sequencing-Based Panel Testing under the Universal Health-Care System in Japan: A Retrospective Analysis at a Single University Hospital.

Cancers (Basel) 2021 03 5;13(5). Epub 2021 Mar 5.

Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.

Next-generation sequencing (NGS) assay is part of routine care in Japan owing to its reimbursement by Japan's universal health-care system; however, reimbursement is limited to patients who finished standard treatment. We retrospectively investigated 221 patients who underwent Foundation One CDX (F1CDx) at our hospital. Every F1CDx result was assessed at the molecular tumor board (MTB) for treatment recommendation. Based on patients' preferences, presumed germline findings were also assessed at the MTB and disclosed at the clinic. In total, 204 patients underwent F1CDx and 195 patients completed the analysis; however, 13.8% of them could not receive the report due to disease progression. Among 168 patients who received the results, 41.6% had at least one actionable alteration, and 3.6% received genomically matched treatment. Presumed germline findings were nominated in 24 patients, and 16.7% of them contacted a geneticist counselor. The NGS assay should be performed earlier in the clinical course to maximize the clinical benefit. Broader reimbursement for the NGS assay would enhance the delivery of precision oncology to patients. Access to clinical trials affects the number of patients who benefit from NGS. Additionally, the disclosure of presumed germline findings is feasible in clinical practice.
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http://dx.doi.org/10.3390/cancers13051121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961835PMC
March 2021

Disseminated carcinomatosis of the bone marrow from rectal cancer: A case report.

Clin Case Rep 2021 Mar 18;9(3):1483-1489. Epub 2021 Jan 18.

Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Hirosaki Japan.

A 66-year-old man presented with worsening dyspnea. A colonoscopy revealed an elevated lesion at the rectosigmoid junction. The biopsy specimen and bone marrow aspiration demonstrated adenocarcinoma, leading to a diagnosis of disseminated carcinomatosis of the bone marrow. Because chemotherapy proved effective, he survived until 333 days after admission.
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http://dx.doi.org/10.1002/ccr3.3810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981614PMC
March 2021

A preliminary study exploring the change in ankle joint laxity and general joint laxity during the menstrual cycle in cis women.

J Foot Ankle Res 2021 Mar 24;14(1):21. Epub 2021 Mar 24.

Institute for Human Movement and Medical Sciences, Niigata University of Health and Welfare, 950-3198, Shimami-cho 1398, Kita-Ku,, Niigata, Japan.

Background: The purpose of the present study was to examine the relationship between ankle joint laxity and general joint laxity (GJL) in relation to the menstrual cycle, which was divided into four phases based on basal body temperature and ovulation, assessed using an ovulation kit.

Methods: Participants were 14 female college students (21-22 years) with normal menstrual cycles (cis gender). Anterior drawer stress to a magnitude of 120 N was applied for all participants. Anterior talofibular ligament (ATFL) length was measured as the linear distance (mm) between its points of attachment on the lateral malleolus and talus using ultrasonography. Data on ATFL length from each subject were used to calculate each subject's normalized length change with anterior drawer stress (AD%). The University of Tokyo method was used for evaluation of GJL. AD% and GJL were measured once in each menstrual phase.

Results: There was no statistically significant difference between AD% in each phase. GJL score was significantly higher in the ovulation and luteal phases compared with the early follicular phase. AD% and GJL showed a positive correlation with each other in the ovulation phase.

Conclusions: Although it is unclear whether estrogen receptors are present in the ATFL, the present study suggests that women with high GJL scores might be more sensitive to the effects of estrogen, resulting in ATFL length change in the ovulation phase.
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http://dx.doi.org/10.1186/s13047-021-00459-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988940PMC
March 2021

A simple method for diagnosing gallbladder malignant tumors with subserosa invasion by endoscopic ultrasonography.

BMC Cancer 2021 Mar 17;21(1):288. Epub 2021 Mar 17.

Department of Gastroenterology, School of Medicine, Fukushima Medical University, Fukushima, Japan.

Background: If the depth of gallbladder malignant tumor (GBMT) invasion is deeper than the subserosa (ss), cholecystectomy is insufficient. In past reports that used endoscopic ultrasonography (EUS) to diagnose the depth of tumor invasion, it was difficult to diagnose GMBT invasion in the ss without a narrow or disrupted lateral hyperechoic layer (LHEL). Therefore, we developed a simple preoperative method to diagnose GBMTs with ss invasion.

Methods: Forty-nine GBMT patients who underwent both EUS and surgery were enrolled: 15 patients whose tumors invaded the mucosa (m) or muscularis propria (mp) were classified as the "shallow group", and 34 patients whose tumors invaded the ss were classified as the "deep group". The EUS findings were compared between the two groups.

Results: An irregular (narrow or thickened) LHEL was significantly more frequently observed on EUS in the deep group than in the shallow group. The diagnosis of ss invasion based on an irregular LHEL had the highest sensitivity and accuracy among the EUS imaging parameters (sensitivity 97.1% (33/34), specificity 86.7% (13/15), accuracy 93.8% (46/49)). When the deep group was limited to patients with a tumor depth of ss, the results were similar. When an irregular LHEL was used, the diagnostic accuracy of GBMTs with ss invasion was not significantly different between EUS specialists and beginners.

Conclusions: The observation of an irregular (thickened or narrow) LHEL observed on EUS could be a reliable and simple method of diagnosing GBMTs with ss invasion and could contribute to choosing an appropriate surgical method.
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http://dx.doi.org/10.1186/s12885-021-08017-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972348PMC
March 2021

Controlling Interfacial Ion-Transport Kinetics Using Polyelectrolyte Membranes for Additive- and Effluent-free, High-Performance Electrodeposition.

ACS Appl Mater Interfaces 2021 Mar 12;13(11):13896-13906. Epub 2021 Mar 12.

Electrification & Environment Material Engineering Div., Toyota Motor Corporation, Toyota-cho, Toyota, Aichi 471-8572, Japan.

The development of high-performance, environmentally friendly electrodeposition processes is critical for emerging coating technologies because current technologies use highly complex baths containing metal salts, supporting electrolytes, and various kinds of organic additives, which are problematic from both environmental and cost perspectives. Here, we show that a 200 μm-thin polyelectrolyte membrane sandwiched between electrodes effectively concentrates metal ions through interfacial penetration, which increases the conductance between the electrodes to 0.30 S and realizes solid-state electrodeposition that produces no mist, sludge, or even waste effluent. Both, experimental results and theoretical calculations, reveal that electrodeposition is controlled by ion penetration at the solution/polyelectrolyte interface, providing an intrinsically different ion-transport mechanism to that of conventional diffusion-controlled electrodeposition. The setup, which includes 0.50 mol L copper sulfate and no additives, delivers a maximum current density of 300 mA cm, which is nearly fivefold higher than that of a current commercial plating bath containing organic additives.
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http://dx.doi.org/10.1021/acsami.1c03608DOI Listing
March 2021

Two cases of gastric adenocarcinoma with enteroblastic differentiation resected by endoscopic submucosal dissection.

Clin J Gastroenterol 2021 Jun 24;14(3):736-744. Epub 2021 Feb 24.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is rare, highly malignant, and has higher vascular invasion and metastasis rates than conventional differentiated gastric cancer (CDGC). We report two cases of GAED that underwent curative resection by endoscopic submucosal dissection (ESD). Case 1 was an 82-year-old man with an elevated lesion in the gastric cardia. Biopsy revealed well-differentiated tubular adenocarcinoma. Pathological diagnosis of the ESD specimen revealed intramucosal gastric cancer without lymphovascular invasion (LVI). Although the surface layer of the lesion showed well and moderately differentiated tubular adenocarcinoma, clear cytoplasmic cancer cells positive for Sal-like protein-4 (SALL4) and Glypican-3 were found in a part of the deep layer. Therefore, GAED was diagnosed as present in a part of the whole lesion and covered with CDGC. Case 2 was an 83-year-old man with an elevated lesion in the gastric angulus. Biopsy revealed papillary and well-differentiated tubular adenocarcinomas. Pathological diagnosis of the ESD specimen revealed intramucosal gastric cancer without LVI. The entire lesion was occupied by papillary and tubular cancer cells, and had clear vesicles. Pure GAED was diagnosed, because the cells were SALL4 positive. In both cases, resection was curative despite the difference in pathological features.
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http://dx.doi.org/10.1007/s12328-021-01356-zDOI Listing
June 2021

Efficacy of Sodium Carboxymethylcellulose Compared to Sodium Hyaluronate as Submucosal Injectant for Gastric Endoscopic Submucosal Dissection: A Randomized Controlled Trial.

Digestion 2021 Feb 19:1-7. Epub 2021 Feb 19.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Introduction: Sodium hyaluronate (SH) is a useful submucosal injectant for gastric endoscopic submucosal dissection (ESD). On the other hand, sodium carboxymethylcellulose (SCMC), which has high viscosity, has also been applied clinically. We evaluated the efficacy of SCMC compared to that of SH in gastric ESD.

Methods: A prospective randomized controlled trial was conducted to assess the efficacy of 1.0% SCMC as the injectant (SCMC group) compared to 0.4% SH (SH group) for ESD of gastric neoplasms. The primary end point was the procedure time of ESD. Secondary end points were treatment outcomes such as en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment (visual analog scale, 1-10 points), adverse events, and rate of ulcer healing 8 weeks after ESD.

Results: A total of 60 patients were enrolled between October 2014 and October 2018, and 30 patients were allocated in each group. The procedure time (mean ± SD, minutes) was not significantly different between the SCMC (74.7 ± 54.5) and SH groups (67.1 ± 41.4) (p = 0.547). Furthermore, there were no differences between the 2 groups in terms of en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment, and rate of ulcer healing. No serious adverse events were observed in either group.

Conclusion: SCMC was comparable to SH in terms of procedure time, treatment outcome, and ease and safety of treatment in gastric ESD. Further studies are needed to demonstrate the differences between the 2 injectants.
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http://dx.doi.org/10.1159/000513148DOI Listing
February 2021

Scaling advantage over path-integral Monte Carlo in quantum simulation of geometrically frustrated magnets.

Nat Commun 2021 Feb 18;12(1):1113. Epub 2021 Feb 18.

D-Wave Systems, Burnaby, BC, Canada.

The promise of quantum computing lies in harnessing programmable quantum devices for practical applications such as efficient simulation of quantum materials and condensed matter systems. One important task is the simulation of geometrically frustrated magnets in which topological phenomena can emerge from competition between quantum and thermal fluctuations. Here we report on experimental observations of equilibration in such simulations, measured on up to 1440 qubits with microsecond resolution. By initializing the system in a state with topological obstruction, we observe quantum annealing (QA) equilibration timescales in excess of one microsecond. Measurements indicate a dynamical advantage in the quantum simulation compared with spatially local update dynamics of path-integral Monte Carlo (PIMC). The advantage increases with both system size and inverse temperature, exceeding a million-fold speedup over an efficient CPU implementation. PIMC is a leading classical method for such simulations, and a scaling advantage of this type was recently shown to be impossible in certain restricted settings. This is therefore an important piece of experimental evidence that PIMC does not simulate QA dynamics even for sign-problem-free Hamiltonians, and that near-term quantum devices can be used to accelerate computational tasks of practical relevance.
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http://dx.doi.org/10.1038/s41467-021-20901-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892843PMC
February 2021
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