Publications by authors named "Takayuki Nagai"

138 Publications

Restricted left atrial dilatation can visually differentiate cardiac amyloidosis from hypertrophic cardiomyopathy.

ESC Heart Fail 2021 May 27. Epub 2021 May 27.

Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Japan.

Aims: Cardiac amyloidosis (CA) is an infiltrative myocardial disease that occasionally mimics hypertrophic cardiomyopathy (HCM). The aim of this study is to investigate the discriminatory ability of visual assessment of left atrial (LA) function between CA and HCM on echocardiography.

Methods And Results: In total, 93 patients with cardiac magnetic resonance imaging (CMR)-confirmed HCM and 34 with cardiac biopsy-confirmed CA were retrospectively assessed. LA dilatation was assessed via echocardiography in an apical four-chamber view. Visual assessment was performed to identify LA dilatation grade (preserved = 1, abnormal = 2, and restricted = 3) based on the extent of outward expansion in the LA reservoir phase. Regarding the reproducibility of visually assessing LA dilatation grade, the kappa values between intra- and inter-observer measurements were 0.82 and 0.70, respectively. Of 127 participants, 57 (45%), 42 (33%), and 28 (22%) presented with LA dilatation Grades 1, 2, and 3, respectively. All 57 patients with preserved LA dilatation (Grade 1) had HCM, and 20 of 28 patients (71%) with restricted LA dilatation (Grade 3) presented with CA. Patients with CA had a higher LA dilatation grade than those with HCM (P < 0.01). LA emptying fraction and reservoir strain were also quantitatively evaluated. The area under the curves of LA dilatation grade (0.88) and LA emptying fraction (0.88) for differentiation of these two diseases were higher than that of LA reservoir strain (0.73) (P < 0.01, respectively). During follow-up, nine patients with HCM and 16 with CA experienced cardiac event (cardiac death or hospitalization due to heart failure). In Kaplan-Meier analysis including both groups of HCM and CA, the incidence of cardiac events was higher in patients with restricted LA dilatation than in those with preserved or abnormal LA dilatation (log-rank test, P < 0.01).

Conclusions: Restricted LA dilatation is an indicator for the diagnosis of CA. Further, visual assessment of abnormal LA motion may facilitate diagnosis in patients with CA and high-risk patients with HCM.
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http://dx.doi.org/10.1002/ehf2.13442DOI Listing
May 2021

Scoring system for identifying Japanese patients with COVID-19 at risk of requiring oxygen supply: A retrospective single-center study.

J Infect Chemother 2021 May 11. Epub 2021 May 11.

Department of Infectious Diseases, Osaka Habikino Medical Center, Habikino, Osaka, 583-8588, Japan.

Introduction: Japan is facing the threat of medical system collapse due to the rapid spread of coronavirus disease 2019 (COVID-19). The present scoring system may help assess disease severity and oxygen supply requirements in COVID-19 patients.

Methods: Data on patient characteristics at baseline and throughout hospitalization for COVID-19 were extracted from medical records. Disease severity was dichotomized into two categories without or with oxygen supply as asymptomatic, mild, and moderate illness (AMMI), and severe and critical illness (CSI). The AMMI and CSI groups were compared. Predictors of disease severity, previously identified in the outpatient setting, were included in multivariable logistic regression analysis; the obtained coefficients were converted to integers and assigned a score.

Results: A total of 206 patients diagnosed with COVID-19 were included in this study. Correlation between COVID-19 severity and medical information was examined by comparing AMMI and CSI. Age, hemodialysis, and C-reactive protein (CRP) levels were candidate predictors of the need for oxygen supply in patients with COVID-19. Coefficients associated with age, hemodialysis, and CRP were as follows: 1 × age (in years, coded as 0 for values of <50, and as 1 for values of ≥50) + 1 × hemodialysis (coded as 0 for "no", and as 1 for "yes") + 1 × CRP (in mg/dL, coded as 0 for values of <1.0, and as 1 for values of ≥1.0). Patients with scores of ≥2 points required oxygen supply (sensitivity, 68.4%; specificity, 79.0%) CONCLUSION: The present model can help predict disease severity and oxygen requirements in COVID-19 patients in Japan.
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http://dx.doi.org/10.1016/j.jiac.2021.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112289PMC
May 2021

Editorial: Language and Robotics.

Front Robot AI 2021 12;8:674832. Epub 2021 Apr 12.

Graduate School of Engineering Science, Osaka University, Suita, Japan.

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http://dx.doi.org/10.3389/frobt.2021.674832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072269PMC
April 2021

Clinical COVID-19 diagnostic methods: Comparison of reverse transcription loop-mediated isothermal amplification (RT-LAMP) and quantitative RT-PCR (qRT-PCR).

J Clin Virol 2021 06 26;139:104813. Epub 2021 Mar 26.

Department of Infectious Diseases, Osaka Habikino Medical Center, Habikino, Osaka, 583-8588, Japan.

Background: The coronavirus disease 2019 (COVID-19) pandemic is a major public health concern. Accurate and rapid diagnosis of COVID-19 is critical for disease control. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a nucleic acid amplification assay similar to reverse transcription-polymerase chain reaction (RT-PCR), the former being a simple, low cost, and rapid method.

Objectives: This study aimed to compare the RT-LAMP assay with RT-PCR using the Loopamp™ SARS-CoV-2 Detection Kit.

Study Design: One hundred and fifty-one nasopharyngeal swab and 88 sputum samples obtained from individuals with suspected or confirmed COVID-19 were examined.

Results: RT-LAMP had high specificity (98.5 % (95 % CI: 96.9-100 %)), sensitivity (87.0 % (95 % CI: 82.8-91.3 %)), positive predictive value (97.9 % (95 % CI: 96.1-99.7 %)), negative predictive value (90.2 % (95 % CI: 86.4-94.0 %)), and concordance rate (93.3 % (95 % CI: 90.1-96.5 %)). Nasopharyngeal and sputum samples positive in RT-LAMP contained as few as 10.2 and 23.4 copies per 10 μL, respectively. RT-LAMP showed similar performance to RT-PCR for samples with cycle threshold value below 36.

Conclusions: These results indicate that RT-LAMP is a highly reliable and at least equivalent to RT-PCR in utility, and potentially applicable in settings that are more diverse as a point-of-care tool.
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http://dx.doi.org/10.1016/j.jcv.2021.104813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997201PMC
June 2021

Cost-Effectiveness of Obstructive Sleep Apnea Screening and Treatment Before Catheter Ablation for Symptomatic Atrial Fibrillation.

Circ Rep 2020 Aug 27;2(9):507-516. Epub 2020 Aug 27.

Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Toon Japan.

Although management of obstructive sleep apnea (OSA) has been recommended to improve outcomes of catheter ablation (CA) in patients with symptomatic atrial fibrillation (AF), the most cost-effective way of preprocedural OSA screening is undetermined. This study assessed the cost-effectiveness of OSA management before CA for symptomatic AF. A Markov model was developed to assess the cost-effectiveness of 3 OSA detection strategies before CA: no screening; Type 3 portable monitor (PM)-guided screening; and polysomnography (PSG)-guided screening. The target population consisted of a hypothetical cohort of patients aged 65 years with symptomatic AF, with 50% prevalence of OSA. We used a 5-year horizon, with sensitivity analyses for significant variables and scenario analyses for lower and higher OSA prevalence (30% and 70%, respectively). In the base-case, both types of OSA screening were dominant (less costly and more effective) relative to no screening. Although PSG-guided management was more effective than PM-guided management, it was more costly and therefore did not show clear benefit. These findings were replicated in cohorts with lower and higher OSA risks. OSA screening before CA is cost-effective in patients with symptomatic AF, with PM screening being the most cost-effective. Physicians should consider OSA management using this simple tool in the decision making for treatment of symptomatic AF.
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http://dx.doi.org/10.1253/circrep.CR-20-0074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819651PMC
August 2020

Quantitative analysis of spontaneous sociality in children's group behavior during nursery activity.

PLoS One 2021 2;16(2):e0246041. Epub 2021 Feb 2.

Faculty of Information and Human Sciences, Kyoto Institute of Technology, Kyoto, Kyoto, Japan.

Sociality is the tendency to spontaneously interact with others to establish and maintain relationships. Some approaches, including questionnaires, tests, controlled experiments, and qualitative field research, cannot capture complex social interactions, such as in children during nursery activities, because of problems with ecological validity and the labor cost of analysis. Here, we introduced a new methodology for the quantitative analysis of spontaneous social movement and investigated children's group behavior using position data. We periodically visited a nursery and recorded videos of eurhythmics, in which children move in tune with music, in different classes. The results revealed that children in the six-year-old class approached others in a short period of time (within one second) and established group behavior like that in a game of tag. It can be interpreted that such social behavior may include actions related to the cognition of anticipating others' behaviors in a complex situation. Although only a small amount of data could be acquired, this study suggests one of the characteristics of social behaviors in the classroom considering an ecological approach.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246041PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853442PMC
February 2021

Chemical profile of Cimicifuga heracleifolia Kom. And immunomodulatory effect of its representative bioavailable component, cimigenoside on Poly(I:C)-induced airway inflammation.

J Ethnopharmacol 2021 Mar 24;267:113615. Epub 2020 Nov 24.

College of Pharmacy, Jinan University, Guangzhou, 510632, PR China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, Jinan University, Guangzhou, 510632, PR China. Electronic address:

Ethnopharmacological Relevance: The dried rhizome of Cimicifuga heracleifolia Kom. (C. heracleifolia) is a popular traditional Chinese medicine, which has been extensively used in Asian countries for its anti-inflammatory, antipyretic and analgesic activities. However, further utilization and application of C. heracleifolia have been hampered due to a lack of full understanding of its active ingredients.

Aim Of Study: The present study aims for clarification of the systematical chemical profile of C. heracleifolia and the immunomodulatory effect of its main bioavailable component.

Materials And Methods: Comprehensive chemical profile of C. heracleifolia was systematically analyzed by ultra-performance liquid chromatography hyphenated with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). Xenobiotics after oral administration of C. heracleifolia extracts were investigated to hunt for bioavailable components. The immunomodulatory activity evaluation of cimigenoside was achieved on poly(I:C)-induced airway inflammation mouse and BEAS-2B cell models from aspects of neutrophil infiltration, lung inflammation by using microscope analysis, quantification of production and expression of inflammatory cytokine and chemokines by using ELISA and quantitative PCR.

Results: By UPLC-Q-TOF/MS analysis, 110 compounds (including 81 triterpenoids, 21 cinnamic acid derivatives, and 8 other structure types) were identified or tentatively characterized in ethanolic extract of C. heracleifolia. Based on the data of chemical profile, xenobiotics of C. heracleifolia were subsequently analyzed, and triterpene glycosides were detected as the major bioavailable ingredients. Oral administration of cimigenoside, a representative triterpene glycoside, could prevent neutrophils infiltration in the lung due to suppression of the production of CXCL2 and CXCL10, and the expression of P-selectin, VCAM1 in poly(I:C)-induced airway inflammation model mice. Moreover, cimigenoside also inhibited the productions of inflammatory cytokines and chemokines from human airway epithelial cell line (BEAS-2B cells) induced by poly(I:C).

Conclusion: Triterpene glycosides were the main components of C. heracleifolia extract, and cimigenoside was considered as the effective component with immunomodulatory effect on the pulmonary immune system by oral administration.
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http://dx.doi.org/10.1016/j.jep.2020.113615DOI Listing
March 2021

Gallstone impaction at the orifice of the duct of Wirsung successfully treated via needle-knife papillotomy.

Endoscopy 2020 Nov 11. Epub 2020 Nov 11.

Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan.

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http://dx.doi.org/10.1055/a-1290-6691DOI Listing
November 2020

Neuroinflammaging underlies emotional disturbances and circadian rhythm disruption in young male senescence-accelerated mouse prone 8 mice.

Exp Gerontol 2020 12 16;142:111109. Epub 2020 Oct 16.

Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.

Aging causes psychological dysfunction and neurodegeneration, and can lead to cognitive impairments. Although numerous studies have reported that neurodegeneration and subsequent cognitive impairments are involved in neuroinflammation, relationship between psychological disturbance and neuroinflammation with aging (neuroinflammaging) remains unclear. Here, to clarify the relationship, we examined whether neuroinflammaging affects emotional behaviors in senescence-accelerated mouse prone 8 (SAMP8) mice. Microglial inflammatory responses to a subsequent lipopolysaccharide (LPS) challenge were significantly enhanced in male SAMP8 mice relative to normal aging senescence-accelerated mouse resistant 1 (SAMR1) mice at 17 weeks, but not 8 weeks of age. LPS injection also significantly increased brain and systemic inflammation in SAMP8 mice at 17 weeks. In a battery of behavioral tests, SAMP8 mice at 17 weeks, but not 8 weeks, exhibited anxiety- and depression-like behaviors and circadian rhythm disruption. Taken together, SAMP8 mice at 17 weeks possess a brain microenvironment in which it is easier to trigger neuroinflammatory priming; this may lead to an emergence of anxiety- and depression-like behaviors and circadian rhythm disruption. These findings provide new insights into the temporal relationship between neuroinflammaging and emotion.
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http://dx.doi.org/10.1016/j.exger.2020.111109DOI Listing
December 2020

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study.

J Infect Chemother 2021 Jan 10;27(1):76-82. Epub 2020 Oct 10.

Department of Infectious Diseases, Osaka Habikino Medical Center, Osaka Prefectural Hospital, Habikino, Osaka, 583-3588, Japan.

Introduction: The severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020.

Methods: All patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients' records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software.

Results: Data from 61 patients (16 Pt-CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt-CSI were significantly older and had hypertension or diabetes than Pt-MMI (P < 0.001, 0.014 and < 0.001, respectively). Serum albumin levels were significantly lower in Pt-CSI than in Pt-MMI (P < 0.001), whereas the neutrophil-to-lymphocyte ratio and C-reactive protein level were significantly higher in Pt-CSI than in Pt-MMI (P < 0.001 and P < 0.001, respectively). In the CT images of 60 patients, bilateral lung lesions were more frequently observed in Pt-CSI than in Pt-MMI (P = 0.013). Among the 16 Pt-CSI, 15 received antiviral therapy, 12 received tocilizumab, five underwent methylprednisolone treatment, six received mechanical ventilation, and one died.

Conclusions: The illness severity of Japanese COVID-Pts was associated with older age, hypertension and/or diabetes, low serum albumin, high neutrophil-to-lymphocyte ratio, and C-reactive protein.
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http://dx.doi.org/10.1016/j.jiac.2020.09.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547613PMC
January 2021

Transbronchial Cryobiopsy for Miliary Tuberculosis Mimicking Hypersensitivity Pneumonitis.

Intern Med 2021 Feb 19;60(3):445-448. Epub 2020 Sep 19.

Department of Infectious Diseases, Osaka Habikino Medical Center, Japan.

Miliary tuberculosis is a potentially lethal type of tuberculosis that results from the hematogenous dissemination of Mycobacterium tuberculosis bacilli. We herein describe the case of a 34-year-old man that presented with a one-month history of cough and fever, while his sputum smear results were negative. Chest computed tomography revealed bilateral centrilobular ground-glass opacification (GGO), suggestive of hypersensitivity pneumonitis; thus, bronchoscopy was performed. Cryobiopsy specimens revealed necrotic granulomas. A re-examination of sputum after bronchoscopy identified Mycobacterium tuberculosis, and miliary tuberculosis was diagnosed. A cryobiopsy might be useful for diagnosing miliary tuberculosis pathologically, particularly when miliary nodules may be masked by GGO.
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http://dx.doi.org/10.2169/internalmedicine.4511-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925263PMC
February 2021

Impact of right ventricular contractile reserve during low-load exercise on exercise intolerance in heart failure.

ESC Heart Fail 2020 Sep 13. Epub 2020 Sep 13.

Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.

Aims: Traditional criteria for heart transplantation by cardiopulmonary exercise testing (CPX) include peak oxygen uptake (VO ) < 14 mL/kg/min. Reaching a sufficient exercise load is challenging for patients with refractory heart failure (HF) because of their exercise intolerance. Recently, a substantial impact of right ventricular (RV) dysfunction was highlighted on urgent heart transplantation and mortality. This study aims to investigate the impact of RV contractile reserve, assessed by low-load exercise stress echocardiography (ESE), on exercise intolerance defined as peak VO  < 14 mL/kg/min, in patients with HF.

Methods And Results: We prospectively examined 67 consecutive patients hospitalized for HF who underwent ESE and CPX under a stabilized HF condition. Although low-load ESE was defined as 25 W load exercise, an increment in RV systolic (s') velocity was regarded as the preservation of RV contractile reserve. All patients completed low-load ESE. During low-load ESE, the variation in RV s' velocity significantly correlated with peak VO (r = 0.787, P < 0.001). The change in RV s' velocity during low-load ESE accurately identified patients with peak VO  < 14 mL/kg/min (area under the curve, 0.95; sensitivity, 92%; specificity, 85%). The intraclass correlation coefficient for intra-observer and inter-observer agreement for the change in RV s' velocity was 0.96 (95% confidence interval, 0.88-0.99, P < 0.001) and 0.86 (95% confidence interval, 0.64-0.95, P < 0.001), respectively. The RV-to-pulmonary circulation (PC) coupling, which was assessed by the slope of the relationship between RV s' velocity and pulmonary artery systolic pressure at rest and low-load exercise, was worse in the low-peak VO group (<14 mL/kg/min) than the preserved-peak VO group (≥14 mL/kg/min).

Conclusions: The change in RV s' velocity during low-load ESE could estimate the exercise capacity in HF patients. The assessments of RV contractile reserve and RV-to-PC coupling could be clinically beneficial to distinguish high-risk HF patients.
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http://dx.doi.org/10.1002/ehf2.12968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755000PMC
September 2020

Colitis cystica profunda mimicking mucinous adenocarcinoma of the rectum diagnosed by endoscopic submucosal dissection.

Endoscopy 2021 Apr 20;53(4):E157-E159. Epub 2020 Aug 20.

Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan.

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http://dx.doi.org/10.1055/a-1224-3347DOI Listing
April 2021

Development of diffuse large B-cell lymphoma from duodenal type follicular lymphoma: a retrospective study of 23 cases.

Int J Hematol 2020 Nov 1;112(5):658-665. Epub 2020 Aug 1.

Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, 1-1 Hasama Idaigaoka, Yuhu City, Oita, 879-5593, Japan.

The incidence and clinical characteristics of histological transformation (HT) from duodenal type follicular lymphoma (DFL) are unclear. A retrospective analysis was conducted to identify the incidence and clinical features of HT from DFL in 23 cases with DFL. The median follow-up duration was 4.6 years (range, 0.8-20 years). HT to diffuse large B-cell lymphoma was observed in 2 of 23 cases during follow-up (8.7%). One of two cases transformed at 21 months later with increased serum lactate dehydrogenase (LDH; 1655 U/L) and abdominal lymphadenopathy. Partial response was achieved after R-THP (pirarubicin)-COP therapy, but the disease progressed. The other case transformed at 8.3 years with an increase of serum LDH (4022 U/L), abdominal lymphadenopathy, and bone marrow involvement. The disease was refractory to DA-EPOCH-R and a high-dose methotrexate/cytarabine regimen. The patient received allogenic peripheral blood stem cell transplantation and finally achieved complete response. Both cases developed HT at nodal or other intestinal lesions with no progression of the primary duodenal lesion. No significant factors for the occurrence of HT were identified. Although the incidence is low, HT could occur in DFL with aggressive clinical manifestations.
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http://dx.doi.org/10.1007/s12185-020-02957-zDOI Listing
November 2020

Atrial tachycardia with multiple reconductions across the surgical incision.

J Cardiovasc Electrophysiol 2020 09 1;31(9):2526-2529. Epub 2020 Aug 1.

Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Incisional atrial tachycardia (AT) with multiple penetrating points on one surgical incision has not been reported yet. We present a case of incisional AT following mitral valve annuloplasty with a superior transseptal approach, in which two reconduction sites were parts of the reentrant circuit. Radiofrequency ablation at the reconduction site successfully terminated the tachycardia. A total of four penetrating points were found on the incision line, and radiofrequency ablation at these sites was completed. Detailed mapping of possible reconduction sites along the incision line should be performed to avoid further instances of AT following open heart surgery.
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http://dx.doi.org/10.1111/jce.14690DOI Listing
September 2020

Endoscopic band ligation and over-the-scope clip placement for refractory bleeding of Dieulafoy ulcer in the jejunum.

Endoscopy 2021 Mar 26;53(3):E85-E86. Epub 2020 Jun 26.

Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan.

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http://dx.doi.org/10.1055/a-1195-1795DOI Listing
March 2021

Follicular lymphoma Grade 1 of the minor duodenal papilla successfully diagnosed by endoscopic papillectomy.

Endoscopy 2021 Jan 29;53(1):E35-E37. Epub 2020 May 29.

Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan.

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http://dx.doi.org/10.1055/a-1173-8418DOI Listing
January 2021

Diagnostic accuracy of stress myocardial computed tomography perfusion imaging to detect myocardial ischemia: a comparison with coronary flow velocity reserve derived from transthoracic Doppler echocardiography.

J Cardiol 2020 09 27;76(3):251-258. Epub 2020 Apr 27.

Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Japan.

Background: Our aim was to evaluate the ability of adenosine triphosphate (ATP)-stress myocardial computed tomography perfusion (CTP) imaging to detect myocardial ischemia in the left anterior descending artery (LAD) territory, and to compare this method with coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography (TTDE).

Methods: ATP-stress CTP and CFVR were performed in 50 patients with stable angina pectoris. Myocardial ischemia assessed from CTP imaging was defined as qualitative visual perfusion defects and reduced myocardial blood flow (MBF) based on quantitative assessment. A cut-off value of CFVR of 2.0 was used.

Results: The mean CFVR was 1.9 ± 0.6 in ischemic regions by CTP, whereas it was 2.9 ± 0.8 in non-ischemic regions (p < 0.001). CTP imaging could accurately predict CFVR <2.0 with 84.0% diagnostic accuracy (94.7% sensitivity, 77.4% specificity, 72.0% positive predictive value, and 96.0% negative predictive value). When receiver operating characteristic curve analysis of the MBF data was performed to detect CFVR <2.0, the area under the curve was 0.89, and the optimal MBF cut-off value was 1.43 mL/g/min.

Conclusions: This study suggests that qualitative and quantitative assessment of ATP-stress CTP exhibits a good correlation with CFVR for evaluation of myocardial ischemia.
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http://dx.doi.org/10.1016/j.jjcc.2020.03.003DOI Listing
September 2020

An Information Theoretic Approach to Reveal the Formation of Shared Representations.

Front Comput Neurosci 2020 29;14. Epub 2020 Jan 29.

Basic Research Group, Araya Inc., Tokyo, Japan.

Modality-invariant categorical representations, i.e., shared representation, is thought to play a key role in learning to categorize multi-modal information. We have investigated how a bimodal autoencoder can form a shared representation in an unsupervised manner with multi-modal data. We explored whether altering the depth of the network and mixing the multi-modal inputs at the input layer affect the development of the shared representations. Based on the activation of units in the hidden layers, we classified them into four different types: visual cells, auditory cells, inconsistent visual and auditory cells, and consistent visual and auditory cells. Our results show that the number and quality of the last type (i.e., shared representation) significantly differ depending on the depth of the network and are enhanced when the network receives mixed inputs as opposed to separate inputs for each modality, as occurs in typical two-stage frameworks. In the present work, we present a way to utilize information theory to understand the abstract representations formed in the hidden layers of the network. We believe that such an information theoretic approach could potentially provide insights into the development of more efficient and cost-effective ways to train neural networks using qualitative measures of the representations that cannot be captured by analyzing only the final outputs of the networks.
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http://dx.doi.org/10.3389/fncom.2020.00001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001587PMC
January 2020

Integrated Cognitive Architecture for Robot Learning of Action and Language.

Front Robot AI 2019 29;6:131. Epub 2019 Nov 29.

Graduate School of Engineering Science, Osaka University, Osaka, Japan.

The manner in which humans learn, plan, and decide actions is a very compelling subject. Moreover, the mechanism behind high-level cognitive functions, such as action planning, language understanding, and logical thinking, has not yet been fully implemented in robotics. In this paper, we propose a framework for the simultaneously comprehension of concepts, actions, and language as a first step toward this goal. This can be achieved by integrating various cognitive modules and leveraging mainly multimodal categorization by using multilayered multimodal latent Dirichlet allocation (mMLDA). The integration of reinforcement learning and mMLDA enables actions based on understanding. Furthermore, the mMLDA, in conjunction with grammar learning and based on the Bayesian hidden Markov model (BHMM), allows the robot to verbalize its own actions and understand user utterances. We verify the potential of the proposed architecture through experiments using a real robot.
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http://dx.doi.org/10.3389/frobt.2019.00131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805838PMC
November 2019

HVGH: Unsupervised Segmentation for High-Dimensional Time Series Using Deep Neural Compression and Statistical Generative Model.

Front Robot AI 2019 20;6:115. Epub 2019 Nov 20.

Center for Mathematical Modeling and Data Science, Osaka University, Osaka, Japan.

Humans perceive continuous high-dimensional information by dividing it into meaningful segments, such as words and units of motion. We believe that such unsupervised segmentation is also important for robots to learn topics such as language and motion. To this end, we previously proposed a hierarchical Dirichlet process-Gaussian process-hidden semi-Markov model (HDP-GP-HSMM). However, an important drawback of this model is that it cannot divide high-dimensional time-series data. Furthermore, low-dimensional features must be extracted in advance. Segmentation largely depends on the design of features, and it is difficult to design effective features, especially in the case of high-dimensional data. To overcome this problem, this study proposes a hierarchical Dirichlet process-variational autoencoder-Gaussian process-hidden semi-Markov model (HVGH). The parameters of the proposed HVGH are estimated through a mutual learning loop of the variational autoencoder and our previously proposed HDP-GP-HSMM. Hence, HVGH can extract features from high-dimensional time-series data while simultaneously dividing it into segments in an unsupervised manner. In an experiment, we used various motion-capture data to demonstrate that our proposed model estimates the correct number of classes and more accurate segments than baseline methods. Moreover, we show that the proposed method can learn latent space suitable for segmentation.
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http://dx.doi.org/10.3389/frobt.2019.00115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805757PMC
November 2019

Editorial: Machine Learning Methods for High-Level Cognitive Capabilities in Robotics.

Front Neurorobot 2019 22;13:83. Epub 2019 Oct 22.

Department of Electrical and Electronic Engineering, Imperial College London, London, United Kingdom.

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http://dx.doi.org/10.3389/fnbot.2019.00083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817914PMC
October 2019

Successful endoscopic retrieval of a toothpick stuck in the small intestine using double-balloon enteroscopy.

Endoscopy 2020 02 9;52(2):E45-E46. Epub 2019 Sep 9.

Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan.

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http://dx.doi.org/10.1055/a-0992-8959DOI Listing
February 2020

Effect of ingesting yogurt fermented with OLL1073R-1 on influenza virus-bound salivary IgA in elderly residents of nursing homes: a randomized controlled trial.

Acta Odontol Scand 2019 Oct 16;77(7):517-524. Epub 2019 May 16.

Division of Environmental Pathology, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University , Yokosuka , Japan.

The purpose of this study was to clarify the influence of consuming yogurt fermented with OLL1073R-1 (1073R-1-yogurt) on influenza virus-bound salivary immunoglobulin A (IgA) levels, in the elderly residents of nursing homes. A double-blind, parallel-group, randomized controlled trial was conducted with 96 elderly volunteers residing in 2 nursing homes. During the trial, participants consumed 100 g of 1073R-1-yogurt every morning for 12 weeks, whereas the control participants consumed yogurt fermented with a different strain (control yogurt). Saliva was collected before the trial and after 4, 8 and 12 weeks of yogurt ingestion. Our data indicated that consumption of 1073R-1-yogurt affected influenza A virus subtype H3N2-bound IgA levels in saliva ( = .001). In addition, saliva flow rate and total IgA levels increased in response to the yogurt intake period in both the 1073R-1 and control yogurt groups ( = .04). Our study suggests that continuous daily ingestion of 1073R-1-yogurt may help prevent infection with influenza A virus subtype H3N2 in elderly subjects with weakened immunity, by increasing the production of influenza A virus subtype of H3N2-bound salivary IgA.
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http://dx.doi.org/10.1080/00016357.2019.1609697DOI Listing
October 2019

Peyer's patch-immunomodulating glucans from sugar cane enhance protective immunity through stimulation of the hemopoietic system.

Int J Biol Macromol 2019 Mar 22;124:505-514. Epub 2018 Nov 22.

Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan; Kitasato Institute for Life Sciences, Kitasato University, Tokyo 108-8641, Japan; Oriental Medicine Research Center, Kitasato University, Tokyo 108-8642, Japan. Electronic address:

The aim of the present study was chemical clarification of in vitro Peyer's patch-immunomodulating polysaccharides in sugar cane molasses, and evaluation of in vivo modulating activity on immune function of T lymphocytes in Peyer's patches and on microenvironment of hemopoietic system. Five kinds of glucans, comprising of dextranase-sensitive and activity-related d-glucosyl moieties, were purified as in vitro Peyer's patch-immunomodulating polysaccharides from the molasses. Oral administration of a glucan-enriched subfraction induced IL-2 and GM-CSF-producing T lymphocytes in Peyer's patches, resulting in enhancement of IL-6 production in a hemopoietic microenvironment to boost neutrophil numbers in the peripheral blood stream. Oral administration of purified glucan or glucan-enrich sub-fraction of sugar cane reduced the number of Plasmodium berghei- or P. yoelii-infected erythrocytes in a murine infection model, using polysaccharide alone or via co-administration with the antimalarial drug, artesunate. These results suggested that Peyer's patch-immunomodulating glucans enhanced protective immunity through axis of Peyer's patches-hemopoietic system.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.11.180DOI Listing
March 2019

Efficacy and safety of concurrent anti-Cancer and anti-tuberculosis chemotherapy in Cancer patients with active Mycobacterium tuberculosis: a retrospective study.

BMC Cancer 2018 Oct 12;18(1):975. Epub 2018 Oct 12.

Departments of Infectious Diseases, Osaka Habikino Medical Center, 3-7-1 Habikino, Habikino City, Osaka, 583-8588, Japan.

Background: In our previous study, colorectal cancer (CRC) patients with active Mycobacterium tuberculosis (MTB) tolerated concurrent anti-cancer chemotherapy (anti-CCT) and anti-MTB chemotherapy. In this study, we retrospectively confirmed the efficacy and safety of concurrent chemotherapy in a greater number of patients with different types of malignancies.

Methods: We enrolled 30 patients who were treated concurrently with anti-CCT and anti-MTB regimens between January 2006 and February 2016. Cancer and MTB treatments were administered according to the approved guidelines.

Results: Patient demographics included: men/woman: 24/6; median age: 66.5 years; Eastern Cooperative Oncology Group performance status 0-1/2/3-4: 24/4/2; Stage IIB-IIIC/IV/recurrence: 6/22/2; lung cancer (LC)/CRC/other: 15/10/5; and MTB diagnosis (before or during anti-CCT): 20/10 (LC: 8/7; CRC: 8/2; other: 4/1). For anti-CCT, 23 patients received two cytotoxic agents with or without targeted agents and 7 patients received a single cytotoxic or targeted agent. The overall response rate was 36.7%. Regarding anti-MTB chemotherapy, 22 patients received a daily drug combination containing isoniazid, rifampicin, and ethambutol, plus pyrazinamide in 15 of the 22 patients, followed by daily isoniazid and rifampicin; the remaining 8 patients received other combinations. Hematological adverse events of Grade ≥ 3 were observed in 19 (67.9%) of 28 patients; laboratory data were lost for the remaining 2. Grade 3 lymphopenia and higher were significantly more frequent in LC compared to other malignancies (P < 0.005). Non-hematological adverse events of Grade ≥ 3 were observed in 5 (16.7%) of 30 patients. One CRC patient experienced Grade 3 hemoptysis and another 2 experienced Grade 3 anaphylaxis. One patient with cholangiocellular carcinoma and gastric cancer experienced Grade 3 pseudomembranous colitis as a result of a Clostridium difficile infection. One patient (3.3%) died of pemetrexed-induced pneumonitis. The success of the anti-MTB chemotherapy was 70.0%. There were no MTB-related treatment failures. The median overall survival (months, 95.0% confidence interval) was 10.5 (8.7-36.7), 8.7 (4.7-10.0), 36.7 (minimum 2.2), and 14.4 (minimum 9.6) for all patients combined, LC, CRC, and Other malignancies, respectively. LC patients experienced delayed MTB diagnosis and shorter overall survival.

Conclusions: Concurrent chemotherapy is effective and safe for treating cancer patients with active MTB.
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http://dx.doi.org/10.1186/s12885-018-4889-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186130PMC
October 2018

Paradoxical response in a patient with non-small cell lung cancer who received nivolumab followed by anti-Mycobacterium tuberculosis agents.

J Infect Chemother 2019 Jan 25;25(1):54-58. Epub 2018 Jul 25.

Department of Thoracic Oncology, Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, 3-7-1, Habikino, Habikino City, Osaka, 583-8588, Japan.

Anti-programmed cell death-1 (PD-1) agents enhance the antitumor immunoresponse. A number of reports have indicated that patients with malignancies who receive anti-PD-1 agents are at risk for tuberculosis (TB) infection. In this report, we present a patient with non-small cell lung cancer who developed pulmonary tuberculosis while receiving the anti-PD-1 agent nivolumab, and who subsequently demonstrated a paradoxical response (PR) 10 days after initiation of anti-MTB treatment. We suggest that anti-PD-1 agents not only induce the development of pulmonary TB, but also development of PR after anti-MTB treatment, through upregulation of the immune response. Furthermore, based on their radiological and immunological similarity, we speculate that the schema of development of PR closely resembles that of pseudoprogression in non-small cell lung cancer patients after anti-PD-1 treatment.
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http://dx.doi.org/10.1016/j.jiac.2018.06.016DOI Listing
January 2019

SERKET: An Architecture for Connecting Stochastic Models to Realize a Large-Scale Cognitive Model.

Front Neurorobot 2018 26;12:25. Epub 2018 Jun 26.

Department of Information Science and Engineering, Ritsumeikan University, Shiga, Japan.

To realize human-like robot intelligence, a large-scale cognitive architecture is required for robots to understand their environment through a variety of sensors with which they are equipped. In this paper, we propose a novel framework named Serket that enables the construction of a large-scale generative model and its inferences easily by connecting sub-modules to allow the robots to acquire various capabilities through interaction with their environment and others. We consider that large-scale cognitive models can be constructed by connecting smaller fundamental models hierarchically while maintaining their programmatic independence. Moreover, the connected modules are dependent on each other and their parameters must be optimized as a whole. Conventionally, the equations for parameter estimation have to be derived and implemented depending on the models. However, it has become harder to derive and implement equations of large-scale models. Thus, in this paper, we propose a parameter estimation method that communicates the minimum parameters between various modules while maintaining their programmatic independence. Therefore, Serket makes it easy to construct large-scale models and estimate their parameters via the connection of modules. Experimental results demonstrated that the model can be constructed by connecting modules, the parameters can be optimized as a whole, and they are comparable with the original models that we have proposed.
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http://dx.doi.org/10.3389/fnbot.2018.00025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028621PMC
June 2018

Incremental value of left atrial active function measured by speckle tracking echocardiography in patients with hypertrophic cardiomyopathy.

Echocardiography 2018 08 12;35(8):1138-1148. Epub 2018 Apr 12.

Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Purpose: Hypertrophic cardiomyopathy (HCM) impairs left ventricular (LV) diastolic function leading to left atrial (LA) dilatation. Because Doppler echocardiography cannot accurately assess LV diastolic function in hearts with heterogeneous hypertrophy, assessment of LA function might be useful for risk stratification of patients with HCM. This study aimed to elucidate the impact of LA function on outcome in patients with patients.

Methods: Seventy-six patients with HCM who underwent echocardiographic and cardiac magnetic resonance imaging were retrospectively enrolled. Twenty-six control subjects were also included. Using speckle tracking echocardiography, LA function was divided into active and passive strain indices based on the timing of the second positive peak of LA strain rate that occurred during LV systole.

Results: Left atrial strain indices of active and passive function were significantly impaired concomitantly with increased LA volume index in HCM patients compared with controls. During follow-up (2.6 ± 1.7 years), 14 patients with HCM developed cardiac events (heart failure hospitalization or atrial fibrillation). The association of LA active strain with cardiac events was independent of and incremental to clinical and echocardiographic parameters (age, gender, E/e', LV global longitudinal strain, and LA volume index) in sequential models. Cardiac events were more frequent in HCM patients with LA active strain <20.3% than with active strain ≥20.3% (P = .01).

Conclusion: Loss of LA active function was associated with increased cardiac events in patients with HCM.
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http://dx.doi.org/10.1111/echo.13886DOI Listing
August 2018