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Article: Long Survival after Gastrointestinal Bleeding in a New-Onset Heyde's Syndrome Patient Treated with Multiple Endoscopic Hemostatic Procedures and Repeated Transfusions after Aortic Valve Replacement.

Notoya, Genso / Niikura, Ryota / Yamada, Atsuo / Ochi, Masanori / Kawai, Takashi / Koike, Kazuhiko

2021 Volume 15, Issue 3, Page(s) 819–824

Abstract: Heyde's syndrome, which is caused by aortic stenosis and subsequent acquired von Willebrand factor deficiency, is a gastrointestinal bleeding disease. Gastrointestinal bleeding develops in patients with Heyde's syndrome, which may have a different ... ...

Abstract	Heyde's syndrome, which is caused by aortic stenosis and subsequent acquired von Willebrand factor deficiency, is a gastrointestinal bleeding disease. Gastrointestinal bleeding develops in patients with Heyde's syndrome, which may have a different prognosis from general gastrointestinal bleeding; thus, it is important to understand the clinical course. We report a 76-year-old Japanese female who underwent aortic mechanical valve replacement 1 year ago and presented with recurrent gastrointestinal bleeding in angiodysplasia of the sigmoid colon. Endoscopic interventions achieved hemostasis. However, 6 rebleeding events occurred due to a sigmoid colon ulcer and gastric and jejunal angiodysplasia 7 years after first hemostasis. The patient underwent multiple endoscopic hemostatic procedures (upper, lower, and balloon-assisted endoscopy) and repeated transfusions (total of 394 units of red blood cells). The intensive treatment contributed to the survival time of 10 years. In addition, we performed a literature review of the prognosis of patients with Heyde's syndrome.
Language	English
Publishing date	2021-09-23
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2440540-1
ISSN	1662-0631
ISSN	1662-0631
DOI	10.1159/000519004
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Impaired Cognitive Function and Hippocampal Changes Following Chronic Diazepam Treatment in Middle-Aged Mice.

Furukawa, Tomonori / Nikaido, Yoshikazu / Shimoyama, Shuji / Masuyama, Nozomu / Notoya, Ayaka / Ueno, Shinya

Frontiers in aging neuroscience

2021 Volume 13, Page(s) 777404

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-11-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2021.777404
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Article ; Online: A Novel Acetyl-CoA Carboxylase 2 Selective Inhibitor Improves Whole-Body Insulin Resistance and Hyperglycemia in Diabetic Mice through Target-Dependent Pathways.

Takagi, Hiroyuki / Tanimoto, Keiichi / Shimazaki, Atsuyuki / Tonomura, Yutaka / Momosaki, Sotaro / Sakamoto, Shingo / Abe, Kohji / Notoya, Mitsuru / Yukioka, Hideo

The Journal of pharmacology and experimental therapeutics

2020 Volume 372, Issue 3, Page(s) 256–263

Abstract: Excess intramyocellular lipid (IMCL) deposition in skeletal muscle is closely associated with insulin resistance. Pharmacological inhibition of acetyl-CoA carboxylase (ACC) 2 offers a promising approach to treat insulin resistance through stimulation of ... ...

Abstract	Excess intramyocellular lipid (IMCL) deposition in skeletal muscle is closely associated with insulin resistance. Pharmacological inhibition of acetyl-CoA carboxylase (ACC) 2 offers a promising approach to treat insulin resistance through stimulation of mitochondrial fatty acid oxidation (FAO) and reduction of IMCL deposition. Previously reported experimental ACC2 inhibitors exhibited plasma glucose-lowering effects in diabetic rodents. However, their antidiabetic action may be potentially biased by off-target effects on triglyceride metabolism or by neurologic side effects. In this study, we investigated a safety profile, target dependency of its action, and antidiabetic efficacy of compound 2e, a novel olefin derivative potent ACC2 selective inhibitor. Four-day administration of suprapharmacological dose of compound 2e did not exhibit any obvious side effects in Sprague-Dawley rats. In db/db mice, single administration of compound 2e led to significantly elevated FAO and reduced IMCL deposition in skeletal muscle. In ACC2 knockout mice, treatment with pharmacological doses of compound 2e did not reduce plasma triglyceride levels, whereas A-908292, a previously reported ACC2 inhibitor, caused a significant triglyceride reduction, showing that compound 2e was devoid of off-target triglyceride-lowering activity. Chronic treatment of db/db mice with compound 2e improved hyperglycemia but did not decrease plasma triglyceride levels. Additionally, compound 2e showed significant improvements of whole-body insulin resistance in the clamp study and insulin tolerance test. Collectively, compound 2e demonstrated a good safety profile and significant antidiabetic effects through inhibition of ACC2-dependent pathways. These findings provide further evidence that selective inhibition of ACC2 is an attractive strategy against insulin resistance and type 2 diabetes. SIGNIFICANCE STATEMENT: This study shows that pharmacological inhibition of acetyl-CoA carboxylase (ACC) 2 leads to significant improvements in whole-body glucose homeostasis, independently of off-target metabolic pathways and toxicity, which were observed in previously reported ACC2 inhibitors. These findings support the concept that ACC2-selective inhibitors will be a novel remedy for treatment of type 2 diabetes.
MeSH term(s)	Acetyl-CoA Carboxylase/antagonists & inhibitors ; Acetyl-CoA Carboxylase/genetics ; Animals ; Blood Glucose/analysis ; Diabetes Mellitus, Experimental/blood ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/drug therapy ; Hyperglycemia/prevention & control ; Hypoglycemic Agents/pharmacokinetics ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Hypoglycemic Agents/toxicity ; Insulin/metabolism ; Insulin Resistance ; Mice, Knockout ; Muscle, Skeletal/enzymology ; Pancreas/drug effects ; Pancreas/metabolism ; Rats, Sprague-Dawley ; Toxicity Tests ; Triglycerides/blood
Chemical Substances	Blood Glucose ; Hypoglycemic Agents ; Insulin ; Triglycerides ; Acaca protein, mouse (EC 6.4.1.2) ; Acetyl-CoA Carboxylase (EC 6.4.1.2)
Language	English
Publishing date	2020-01-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.119.263590
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Article: [Dexmedetomidine for endoscopic submucosal dissection in a patient with severe chronic obstructive pulmonary disease].

Iizuka, Toru / Shimoyama, Naohito / Notoya, Atsuko

Masui. The Japanese journal of anesthesiology

2011 Volume 60, Issue 1, Page(s) 96–99

Abstract: Here we report an anesthetic management of a 74-year-old man with gastric cancer and severe chronic obstructive pulmonary disease (COPD) undergoing endoscopic submucosal dissection (ESD). We maintained spontaneous breathing during ESD under monitored ... ...

Abstract	Here we report an anesthetic management of a 74-year-old man with gastric cancer and severe chronic obstructive pulmonary disease (COPD) undergoing endoscopic submucosal dissection (ESD). We maintained spontaneous breathing during ESD under monitored anesthesia care with dexmedetomidine (DEX). ESD lasted 5.5 hours with sufficient analgesia, and he required no airway management with the exception of supplemental mask oxygen during the procedures. He tolerated the procedure well and recovered with no complications. He was discharged without sequelae on the fifth postoperative day. DEX is a selective alpha2 agonist that has both sedative and analgesic properties, and it does not suppress ventilation. It should be used judiciously, and understanding the potential adverse effects and how to treat them is of paramount importance. However, with vigilant monitoring of blood pressure, heart rate, and level of consciousness during the ESD, it can be administered safely, thus lessening the anesthetic requirements and possibly improving the surgical outcome of the high risk patients. Especially, patients with severe COPD have demonstrated an increased risk for oxygen desaturation following general anesthesia, and to avoid this complication, spontaneous breathing sedation with DEX during ESD is one of the suitable management methods for COPD patients.
MeSH term(s)	Adrenergic alpha-2 Receptor Agonists ; Aged ; Analgesics ; Anesthesia, General ; Dexmedetomidine ; Gastric Mucosa/surgery ; Gastroscopy ; Humans ; Hypnotics and Sedatives ; Male ; Monitoring, Intraoperative ; Pulmonary Disease, Chronic Obstructive/complications ; Severity of Illness Index ; Stomach Neoplasms/complications ; Stomach Neoplasms/surgery
Chemical Substances	Adrenergic alpha-2 Receptor Agonists ; Analgesics ; Hypnotics and Sedatives ; Dexmedetomidine (67VB76HONO)
Language	Japanese
Publishing date	2011-01
Publishing country	Japan
Document type	Case Reports ; English Abstract ; Journal Article
ZDB-ID	391878-6
ISSN	0021-4892
ISSN	0021-4892
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Article ; Online: WWP1 inactivation enhances efficacy of PI3K inhibitors while suppressing their toxicities in breast cancer models.

Kishikawa, Takahiro / Higuchi, Hiroshi / Wang, Limei / Panch, Nivedita / Maymi, Valerie / Best, Sachem / Lee, Samuel / Notoya, Genso / Toker, Alex / Matesic, Lydia E / Wulf, Gerburg M / Wei, Wenyi / Otsuka, Motoyuki / Koike, Kazuhiko / Clohessy, John G / Lee, Yu-Ru / Pandolfi, Pier Paolo

The Journal of clinical investigation

2021 Volume 131, Issue 24

Abstract: Activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is a pervasive event in tumorigenesis due to PI3K mutation and dysfunction of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Pharmacological inhibition of PI3K has ... ...

Abstract	Activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is a pervasive event in tumorigenesis due to PI3K mutation and dysfunction of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Pharmacological inhibition of PI3K has resulted in variable clinical outcomes, however, raising questions regarding the possible mechanisms of unresponsiveness and resistance to treatment. WWP1 is an oncogenic HECT-type ubiquitin E3 ligase frequently amplified and mutated in multiple cancers, as well as in the germ lines of patients predisposed to cancer, and was recently found to activate PI3K signaling through PTEN inactivation. Here, we demonstrate that PTEN dissociated from the plasma membrane upon treatment with PI3K inhibitors through WWP1 activation, whereas WWP1 genetic or pharmacological inhibition restored PTEN membrane localization, synergizing with PI3K inhibitors to suppress tumor growth both in vitro and in vivo. Furthermore, we demonstrate that WWP1 inhibition attenuated hyperglycemia and the consequent insulin feedback, which is a major tumor-promoting side effect of PI3K inhibitors. Mechanistically, we found that AMPKα2 was ubiquitinated and, in turn, inhibited in its activatory phosphorylation by WWP1, whereas WWP1 inhibition facilitated AMPKα2 activity in the muscle to compensate for the reduction in glucose uptake observed upon PI3K inhibition. Thus, our identification of the cell-autonomous and systemic roles of WWP1 inhibition expands the therapeutic potential of PI3K inhibitors and reveals new avenues of combination cancer therapy.
MeSH term(s)	Animals ; Breast Neoplasms/drug therapy ; Breast Neoplasms/enzymology ; Breast Neoplasms/genetics ; Female ; Humans ; MCF-7 Cells ; Mammary Neoplasms, Experimental/drug therapy ; Mammary Neoplasms, Experimental/enzymology ; Mammary Neoplasms, Experimental/genetics ; Mice ; Mice, Knockout ; Mice, Nude ; Mice, SCID ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors/adverse effects ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Neoplasm Proteins ; Phosphoinositide-3 Kinase Inhibitors ; WWP1 protein, human (EC 2.3.2.26) ; WWP1 protein, mouse (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2021-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI140436
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Article: [Effect of ulinastatin on microcirculation under excessive hemorrhage and fluid therapy].

Notoya, A

Masui. The Japanese journal of anesthesiology

1991 Volume 40, Issue 9, Page(s) 1387–1393

Abstract: Microcirculation during excessive hemorrhage and fluid therapy under anesthesia with or without associated treatment by ulinastatin (urinary trypsin inhibitor) was studied by using the rabbit ear chamber. Sixteen rabbits were divided into 2 groups; 8 ... ...

Abstract	Microcirculation during excessive hemorrhage and fluid therapy under anesthesia with or without associated treatment by ulinastatin (urinary trypsin inhibitor) was studied by using the rabbit ear chamber. Sixteen rabbits were divided into 2 groups; 8 rabbits without ulinastatin treatment (C group) and rabbits treated with ulinastatin (U group). After blood withdrawal, hemodynamic disturbance appeared in both groups. But the catecholamine concentration showed no increase in either groups. Significant differences between the groups were found only in urinary output and microcirculation. These were well maintained during hemorrhage in the ulinastatin treated group. It is concluded that ulinastatin is effective in maintaining microcirculation during excessive hemorrhage and fluid therapy.
MeSH term(s)	Animals ; Glycoproteins/pharmacology ; Glycoproteins/therapeutic use ; Hemodynamics/drug effects ; Microcirculation/drug effects ; Rabbits ; Shock, Hemorrhagic/drug therapy ; Shock, Hemorrhagic/physiopathology
Chemical Substances	Glycoproteins ; urinastatin (OR3S9IF86U)
Language	Japanese
Publishing date	1991-09
Publishing country	Japan
Document type	Journal Article
ZDB-ID	391878-6
ISSN	0021-4892
ISSN	0021-4892
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: [Tube introducer catheter as an adjunct to the airway scope for tracheal intubation in a manikin model].

Iizuka, Toru / Shimoyama, Naohito / Notoya, Atsuko

Masui. The Japanese journal of anesthesiology

2010 Volume 59, Issue 12, Page(s) 1534–1538

Abstract: Background: The Airway Scope (AWS) is a video laryngoscope and there are some problems associated with its use in insertion of the tracheal tube despite its ability to view the glottis. For the purpose of improving the problems, we devised the tube ... ...

Abstract	Background: The Airway Scope (AWS) is a video laryngoscope and there are some problems associated with its use in insertion of the tracheal tube despite its ability to view the glottis. For the purpose of improving the problems, we devised the tube introducer catheter (TIC) for use with AWS. Methods: Using the normal and fixed bent orotracheal tubes, wire-reinforced endotracheal tube, PORTEX and Phycon double lumen tubes, and Univent tube, TIC was attached to one of these tubes with AWS. And, we compared the efficacy and safety of the TIC with the AWS in facilitating tracheal intubation in a manikin model. Results: With about all tubes, correct placement of the endotracheal tube was achieved in the TIC-facilitated tracheal intubations. In addition, the TIC can administer oxygen to prevent desaturation during the intubation. Excessive secretions in the oropharynx were effectively removed under vision with the TIC connected to the suction catheter. The topical anesthetics were sprayed on the vocal cords through the spray channels of the TIC. Furthermore, it can be used for exchange of tracheal tube in a patient. Conclusions: The TIC was significantly effective in facilitating tracheal intubation using the AWS in a manikin model.
MeSH term(s)	Catheters ; Intubation, Intratracheal/instrumentation ; Laryngoscopes ; Manikins ; Video Recording
Language	Japanese
Publishing date	2010-12
Publishing country	Japan
Document type	English Abstract ; Journal Article
ZDB-ID	391878-6
ISSN	0021-4892
ISSN	0021-4892
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Article: [Acute pulmonary edema in adult caused by tonsillar hypertrophy following removal of laryngeal mask airway].

Iizuka, Toru / Shimoyama, Naohito / Notoya, Atsuko

Masui. The Japanese journal of anesthesiology

2010 Volume 59, Issue 12, Page(s) 1498–1501

Abstract: Negative pressure pulmonary edema (NPPE) has been described after acute airway obstruction. In the following case, we observed a rare occurrence of pulmonary edema caused by chronic tonsillar hypertrophy in a woman following removal of laryngeal mask ... ...

Abstract	Negative pressure pulmonary edema (NPPE) has been described after acute airway obstruction. In the following case, we observed a rare occurrence of pulmonary edema caused by chronic tonsillar hypertrophy in a woman following removal of laryngeal mask airway (LMA). A 38-year-old woman with breast cancer underwent mastectomy under general anesthesia using the LMA. With the patient fully awake, the LMA was removed. Abruptly 7 minutes afterward, she showed signs of intense dyspnea, generalized rhonchus and progressive desaturation, and obstructive tonsillar hypertrophy was noticed. Acute lung edema was suspected and treatment started with oxygen therapy, bronchodilators, intravenous corticoids and loop diuretics. She was then intubated to secure airway and provide adequate ventilation with PEEP. Fortunately, the symptoms progressively remitted satisfactorily, and she was subsequently extubated 18 hours later with no complications. NPPE is an infrequent medical emergency and its early diagnosis and recognition are likely to lead to successful management of this potentially serious complication.
MeSH term(s)	Acute Disease ; Adult ; Anesthesia, General ; Breast Neoplasms/surgery ; Bronchodilator Agents/therapeutic use ; Early Diagnosis ; Female ; Humans ; Hydrocortisone/administration & dosage ; Hyperbaric Oxygenation ; Hyperplasia ; Laryngeal Masks/adverse effects ; Palatine Tonsil/pathology ; Positive-Pressure Respiration ; Postoperative Complications/diagnosis ; Postoperative Complications/etiology ; Postoperative Complications/therapy ; Pulmonary Edema/diagnosis ; Pulmonary Edema/etiology ; Pulmonary Edema/therapy ; Treatment Outcome
Chemical Substances	Bronchodilator Agents ; Hydrocortisone (WI4X0X7BPJ)
Language	Japanese
Publishing date	2010-12
Publishing country	Japan
Document type	Case Reports ; English Abstract ; Journal Article
ZDB-ID	391878-6
ISSN	0021-4892
ISSN	0021-4892
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Article: [New lung isolation device, Fuggiano's bronchial blocker, facilitates lung isolation more effectively].

Iizuka, Toru / Shimoyama, Naohito / Fuggiano, Luigi / Notoya, Atsuko

Masui. The Japanese journal of anesthesiology

2010 Volume 59, Issue 12, Page(s) 1548–1551

Abstract: Background: One-lung ventilation and lung isolation are frequently required in thoracic surgery. In clinical practice, lung isolation is achieved by use of a double-lumen endotracheal tube and a bronchial blocker. A novel bagel shaped bronchial blocker, ...

Abstract	Background: One-lung ventilation and lung isolation are frequently required in thoracic surgery. In clinical practice, lung isolation is achieved by use of a double-lumen endotracheal tube and a bronchial blocker. A novel bagel shaped bronchial blocker, the Fuggiano's bronchial blocker, has been designed to prevent displacement of the blocker from its position in the bronchus. In this study, we evaluated the clinical performance of the Fuggiano's bronchial blocker for the lung isolation. Methods: In thirty patients undergoing thoracotomy or video-assisted thoracoscopic surgery, the Fuggiano's bronchial blockers were placed to the bronchus. Fifteen patients received a left-sided bronchial block, and fifteen a right-sided block. The position of the devices was checked using fibreoptic bronchoscope. Results: In all cases, successful lung isolation and the properly collapsed lung were achieved. It took significantly longer time to place a right bronchial block. Intraoperative repositioning of the device was not required. The quality of lung deflation was judged excellent in all patients. Conclusions: We conclude that, for routine use, the Fuggiano's bronchial blocker is preferable to achieve a lung isolation because of its facility in placement and a better quality of lung deflation. Fuggiano's bronchial blocker may be an alternative airway device for one-lung ventilation, and further work is required.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Intubation, Intratracheal/instrumentation ; Male ; Middle Aged ; Respiration, Artificial/instrumentation ; Thoracic Surgery, Video-Assisted ; Thoracotomy ; Young Adult
Language	Japanese
Publishing date	2010-12
Publishing country	Japan
Document type	English Abstract ; Evaluation Studies ; Journal Article
ZDB-ID	391878-6
ISSN	0021-4892
ISSN	0021-4892
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Article: Rheumatoid arthritis complicated with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis: a case report.

Goto, Akiko / Mukai, Masaya / Notoya, Atsushi / Kohno, Michifumi

Modern rheumatology

2006 Volume 15, Issue 2, Page(s) 118–122

Abstract: This article describes a patient with rheumatoid arthritis (RA) with crescentic glomerulonephritis (CrGN) associated with myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), who responded well to methotrexate (MTX). A 48-year-old woman with ...

Abstract	This article describes a patient with rheumatoid arthritis (RA) with crescentic glomerulonephritis (CrGN) associated with myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), who responded well to methotrexate (MTX). A 48-year-old woman with a 4-year history of RA was admitted with fever and elevated C-reactive protein. On laboratory evaluation, her level of MPO-ANCA was 422 EU, and urinalysis revealed proteinuria and hematuria. Because she was also suffering from episcleritis, vasculitis was considered. A renal biopsy was performed, which revealed necrotizing CrGN. We diagnosed RA complicated with MPO-ANCA-associated vasculitis. We considered treatment with high-dose oral prednisolone for vasculitis, but the patient refused this treatment. We started MTX at a dose of 8 mg/week for RA from the time of admission, and the patient responded immediately. Biochemical parameters, including C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and MPO-ANCA, improved. Seven months later, MPO-ANCA had decreased to 46 EU. In clinical studies, few patients have been reported with RA complicated with ANCA-associated CrGN. This case differs from previous cases in the treatment given. No high-dose steroid with intensive immunosuppression or plasma exchange was required.
Language	English
Publishing date	2006-08-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078157-X
ISSN	1439-7609 ; 1439-7595
ISSN (online)	1439-7609
ISSN	1439-7595
DOI	10.1007/pl00021709
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