THE NEW GENETIC ASPECTS OF ATRIAL FIBRILLATION IN PERSONS OF THE RUSSIAN POPULATION

2020 ◽  
pp. 27-33
Author(s):  
Aksyutina N.V. ◽  
Shulman V.A. ◽  
Aldanova E.E. ◽  
Nikulina S.Yu. ◽  
Mordovskii V.S. ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Chronic Heart Failure ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Heart Rhythm ◽  
Control Group ◽  
Atrial Remodeling ◽  
Cardiovascular Pathology ◽  
Heart Rhythm Disorders

Atrial fibrillation (AF) is one of the most common and dangerous heart rhythm disorders. Lone AF is due to a genetic predisposition. Foreign studies have proven the association of rs2200733 polymorphism of chromosome 4q25 with AF. No such studies have been conducted in the Russian Federation. Purpose of the study: to determine the association of the rs2200733 polymorphism of chromosome 4q25 with the development of AF, and to exclude the possible connection of the studied polymorphic marker with concomitant cardiovascular pathology. A total of 247 patients with AF were examined (113 from lone AF, 134 from secondary). Control group - 182 healthy people. Behavior: ECG, EchoCG, Holter ECG monitoring, blood test for thyroid hormones, VEM, CAG, molecular genetic research. In the group of patients with AF, the TT genotype was detected in 12.95%, which is statistically significant more often than in the control group (4.94%), p<0.05. In the presence of a genotype with a rare T allele, the risk of developing AF increases by 1.5 times. The TT genotype was statistically significant more often in the subgroup of patients with isolated AF (17.70%) in comparison with the control group (4.94%), p<0.05. The risk of developing isolated AF in the presence of a genotype with a rare allele T is 1.8 times increased. Chronic heart failure, no statistically significant differences were found (p>0.05). In patients with the TT genotype, the mean LA size was 3.738 ± 0.494 cm, it was statistically significantly smaller than in patients with the CC genotype, which corresponded to 3.925 ± 0.629 cm, p<0.05; and than in individuals with a heterozygous CT genotype, its value in this subgroup is 4.018 ± 0.639 cm, p<0.05. Conclusions: Homozygous genotype for the rare TT allele and the T allele of the rs2200733 polymorphism of chromosome 4q25 are predictors of lone AF. The rs2200733 polymorphism has no association with any cardiovascular pathology, such as hypertension, ischemic heart disease and chronic heart failure. The TT genotype and the T allele of the rs2200733 polymorphism do not affect left atrial remodeling in patients with AF.

scholarly journals Clinical and laboratory associations of liver fibrosis indexes in patients with decompensated Chronic Heart Failure II-IV Functional Classes

Kardiologiia ◽  
2020 ◽  
Vol 60 (5) ◽  
pp. 90-99
Author(s):  
S. K. Stolbova ◽  
N. A. Dragomiretskaya ◽  
I. G. Beliaev ◽  
V. I. Podzolkov
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Heart Rhythm ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Heart Rhythm Disorders ◽  
High Liver

Aim To study clinical and laboratory associations of hepatic fibrosis indexes in patients with decompensated NYHA functional class II-IV chronic heart failure (CHF).Material and methods The study included 128 patients admitted to the cardiological or therapeutic department of the University Clinical Hospital #4 at the I. M. Sechenov First Moscow State Medical University (Sechenov University) with symptoms of CHF associated with ischemic heart disease (IHD) and/or arterial hypertension (AH). All patients had signs of liver disease (liver enlargement on physical examination ± diffuse changes in hepatic tissue according to ultrasound data). Mean age was 70.59±10.71 years. Along with general clinical examination, severity of hepatic fibrosis was evaluated by calculated indexes, FIB-4, APRI, MELD-XI, and BARD. All calculations were based on laboratory data obtained within the first two days of hospitalization for decompensated CHF, at the onset of active therapy with intravenous diuretics. Statistical analyses were performed with the R programming language (3.6.1).Results In patients with NYHA FC II–IV CHF, the FIB-4 index significantly increased with the increase in NYHA FC (р<0.05). Also, the high liver density by most fibrosis indexes correlated with the probability of LV EF decrease to <40 % (FIB-4: RR, 1.32 at 95 % CI from 0.53 to 3.28, р=0.079; MELD-XI: RR, 1.62 at 95 % CI from 1.19 to 2.20, р=0.004; BARD: median LV EF, 42.5 % vs. 56 %, р=0.019), and a tendency to heart rhythm disorders was observed (FIB-4: RR, 1.92 at 95 % CI from 0.75 to 4.90, р=0.218; BARD: RR, 1.09 at 95 % CI from 0.97 to 1.22, р=0.174; MELD-XI: RR, 1.34 at 95 % CI from 0.94 to 1.90, р=0.101). Increases in liver fibrosis indexes correlated with other multiorgan disorders in CHF patients evident as a decrease in platelet count (FIB-4: р<0.01; APRI: р=0.045) and a tendency to a decrease in hemoglobin (FIB-4: 127 g/l vs. 137 g/l, p=0.249; APRI: 127 g/l vs. 136 g/l, p=0.749). Patients with a high liver density more frequently had cardiorenal syndrome diagnosed by reduced glomerular filtration rate (GFR) estimated by CKD-EPI to less than 60 ml/min / 1.73 m2 (FIB-4: р<0.03; MELD-XI: p=0.0001; BARD: р=0.005). In comparing liver fibrosis indexes in subgroups of CHF patients with preserved and reduced left ventricular ejection fraction (LV EF), significant differences were found only for MELD-XI (12.08 vs. 9.32, р=0.001).Conclusions For all studied indexes, correlations were observed with LV EF, decreases in hemoglobin, and incidence of heart rhythm disorders. For the BARD, FIB-4, and MELD-XI indexes, high results of calculations correlated with the presence of other predictors for unfavorable prognosis and disease severity (LV EF, NYHA FC, presence of type 2 diabetes mellitus, chronic kidney disease, and lower GFR). Liver fibrosis indexes are a new and promising but understudied instrument for evaluation of prognosis in CHF patients, which requires further study to determine most appropriate prognostic formulas.

scholarly journals Cardiovascular Pathology in Patients With COVID-19

Kardiologiia ◽  
2020 ◽  
Vol 60 (8) ◽  
pp. 23-26
Author(s):  
E. K. Serezhina ◽  
A. G. Obrezan
Keyword(s):  
Heart Failure ◽  
Chest Pain ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Myocardial Injury ◽  
Heart Rhythm ◽  
Hospitalized Patients ◽  
Cardiovascular Pathology ◽  
Heart Rhythm Disorders ◽  
Coronavirus Infection

In the recent months of the COVID-19 pandemics, the cardiological society has faced a new challenge, myocardial injury by the coronavirus infection. According to statistics, 20-40% of hospitalized patients have chest pain, heart rhythm disorders, heart failure, and sudden cardiac death syndrome. This review focuses on recent studies and clinical cases related with this issue.

scholarly journals Clinical manifestation features of chronic heart failure with comorbid obesity in consideration of cytochrome P450 system CYP2D6*4 gene polymorphism

2020 ◽  
Vol 86 (1) ◽  
pp. 9-16
Author(s):  
I.C. Gasanov ◽  
I.S. Ryduk ◽  
O.O. Medentseva ◽  
T.V. Lozyk
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Cytochrome P450 ◽  
Chronic Heart Failure ◽  
Clinical Manifestation ◽  
Genetic Research ◽  
Main Group ◽  
Control Group ◽  
Cytochrome P450 System

In order to assess the characteristics of the clinical manifestation of CHF with obesity, taking into account the polymorphism of the CYP2D6*4 gene of the cytochrome P450 system in terms of patient’s quality of life a prospective randomized controlled trial was conducted, 127 people (93 men and 34 women) aged 32-87 (61) years with CHF of II—III stages, 1^1 functional class according to the classification of the New York Heart Association (NYHA) have been examined. The main group consisted of 73 patients with obesity of 1 degree and higher, the comparison group consisted of 54 patients without obesity, the control group consisted of 21 people without cardiovascular disorders. Research methods included estimation of clinical symptom score scale, 6-minute walk test, quality of life (with the Minnesota questionnaire for patients with heart failure), assessment of subjective symptoms and course of the disease, anthropometric data, determination of objective signs of the disease; instrumental methods (Doppler echocardiography, basic laboratory examination, etc.), as well as genetic research (G1846A variants of the CYP2D6 gene real-time polymerase chain reaction), statistical non-parametric methods (with 0.05 p-value thresold). It is shown, that in the clinical aspect, patients of the main group have been characterized by a tendency to more expressive pathological manifestations of CHF, especially in carriers of the heterozygous GA variant of the CYP2D6*4 gene of the cytochrome P450 system. According to the Minnesota questionnaire, the clinical condition of patients and the quality of life in case of GG polymorphism variant was better than in GA carriers of the CYP2D6*4 genotype variant of the cytochrome P450 system. Keywords: chronic heart failure, quality of life, obesity, genetic polymorphism, treatment, prognosis.

FUNCTIONAL AND INSTRUMENTAL EXAMINATION OF ELDERLY PATIENTS WITH CARDIOVASCULAR PATHOLOGY

2021 ◽  
pp. 134-138
Author(s):  
Михаил Олегович Паршин ◽  
Антон Александрович Титов ◽  
Татьяна Игоревна Субботина ◽  
Борис Дмитриевич Жидких ◽  
Елена Ефимовна Атлас
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Chronic Heart Failure ◽  
Elderly Patients ◽  
Arterial Hypertension ◽  
The Elderly ◽  
Functional Study ◽  
Economic Damage ◽  
Control Group ◽  
Cardiovascular Pathology

Сердечно-сосудистые заболевания в пожилом возрасте представляют актуальную проблему многих стран и на протяжении ряда последних десятилетий выступают ведущей причиной преждевременной смерти, нанося значительный экономический ущерб обществу и здравоохранению. Сердечно-сосудистые заболевания и, в частности, хроническая сердечная недостаточность в сочетании с артериальной гипертензией у пожилых встречаются часто, и такая тенденция сохранится и в ближайшие годы. Рассматриваемая патология у пожилых протекает нередко атипично и поэтому выявление ее требует комплексного функционального и инструментального обследования пациентов. Цель исследования - анализ и совершенствование функционального и инструментального обследования пожилых пациентов с сердечно-сосудистой патологией. Диагностическое обследование 86 пациентов 60-74 лет включало функциональное изучение интерлейкинового статуса и эхокардиографию при наличии хронической сердечной недостаточности и артериальной гипертензии. Диагноз хронической сердечной недостаточности устанавливался с учетом критериев NYHA и в соответствии с Рекомендациями Европейского общества кардиологов по диагностике и лечению острой и хронической сердечной недостаточности. Артериальная гипертензия верифицировалась в соответствии с «Национальными рекомендациями по диагностике, профилактике и лечению артериальной гипертензии». Контрольную группу составили 42 пациента пожилого возраста с отсутствием вышеназванных сердечно-сосудистых заболеваний. В ходе исследования установлено, что развитие сочетанной сердечно-сосудистой патологии сопровождается статистически значимым изменением ряда параметров инструментального (эхокардиографического) обследования. Одновременно при развитии сердечно-сосудистой патологии наблюдались изменения в системном интерлейкиновом профиле пациентов пожилого возраста. Они сопровождались преимущественно увеличением содержания в сыворотке крови провоспалительных интерлейкинов и особенно IL-8 до 48,6±2,5 пг/мл против 6,1±1,3 нг/мл в контрольной группе и IL-1β до 78,6±1,9 нг/мл против 13,5±1,0 пг/мл. Вместе с тем наблюдалось у пожилых пациентов с сердечно-сосудистой патологией снижение противовоспалительных интерлейкинов IL-4 и IL-10. Полученные результаты свидетельствуют о важности комплексного обследования пациентов с сердечно-сосудистой патологией Cardiovascular diseases in old age are an urgent problem in many countries and over the past few decades have been the leading cause of premature death, causing significant economic damage to society and public health. Cardiovascular diseases and, in particular, chronic heart failure in combination with arterial hypertension in the elderly are common and this trend will continue in the coming years. The pathology under consideration in the elderly is often isolated, and therefore its detection requires a comprehensive functional and instrumental examination of patients. The aim of the study was to analyze and improve the functional and instrumental examination of elderly patients with cardiovascular pathology. Diagnostic examination of 86 patients aged 60-74 years included functional study of interleukin status and echocardiography in the presence of chronic heart failure and arterial hypertension. The diagnosis of chronic heart failure was established taking into account the NYHA criteria and in accordance with the Recommendations of the European Society of Cardiology for the Diagnosis and Treatment of Acute and Chronic Heart Failure. Arterial hypertension was verified in accordance with the"National guidelines for the diagnosis, prevention and treatment of arterial hypertension". The control group consisted of 42 elderly patients with the absence of the above-mentioned cardiovascular diseases. The study found that the development of combined cardiovascular pathology is accompanied by a statistically significant change in a number of parameters of the instrumental (echocardiographic) examination. At the same time, changes in the systemic interleukin profile of elderly patients were observed with the development of cardiovascular pathology. They were accompanied mainly by an increase in the serum content of proinflammatory interleukins and especially IL-8 to 48.6±2.5 pg / ml versus 6.1±1.3 ng/ml in the control group and IL-1β to 78.6±1.9 ng/ml versus 13.5±1.0 pg / ml. At the same time, a decrease in anti-inflammatory interleukins IL-4 and IL-10 was observed in elderly patients with cardiovascular pathology. The results obtained indicate the importance of a comprehensive examination of patients with cardiovascular pathology

Abstract 740: Statin Prevents Structural and Electrical Atrial Remodeling in Rat Hypertensive Heart Failure Induced by Chronic Inhibition of NO Synthesis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Hidetoshi Okazaki ◽  
Tetsuo Minamino ◽  
Masakatsu Wakeno ◽  
Osamu Tsukamoto ◽  
Jiyoong Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Pressure Control ◽  
Control Group ◽  
High Dose ◽  
Atrial Remodeling ◽  
Dependent Manner ◽  
Oxidative Stresses ◽  
Wistar Kyoto

Background: The prevalence of atrial fibrillation (AF) increases in patients with hypertension and heart failure in which endothelial function is impaired. Oxidative stress in atrial tissues is involved in the development of AF. Statins have pleiotropic effects including antioxidant effects. Thus, we developed hypertensive heart failure in rats by the chronic inhibition of NO synthesis and we investigated the role of the statin in atrial remodeling. Methods and Results: Ten-week-old male Wistar-Kyoto rats were randomly divided into four groups: the control (no treatment), the L-NAME (received L-NAME, an inhibitor of NO synthase, 1 g/L in drinking water), the L-NAME+atorvastatin (L(a low dose)) (5 mg/kg/day) and the L-NAME+atorvastatin (H(a high dose)) (20 mg/kg/day). Chronic inhibition of NO synthesis increased systolic blood pressure (control group: 138±5 mmHg; L-NAME group: 212±8 mmHg L+atorvastatin (L) group: 210±6 seconds , L+atorvastatin (H): 208±6 seconds) and decreased LV dP/dt max/LVSP (control group: 54±3, L-NAME group: 36±8, L+atorvastatin (L) group: 40±3, L+atorvastatin (H) group: 38±6 1/second), whereas co-administration of atorvastatin did not affect them. The sustained duration of AF was always induced by transesophageal burst pacing (The pacing pulse used for induction of AF was rectanglar in shape, of 60V and 6ms-width. The atrium was paced at a cycle length of 12ms (83Hz) for 30seconds) and it was prolonged by L-NAME, which was prevented by atorvastatin in a dose-dependent manner (control: 8.8 ± 1.0 seconds, L-NAME: 20.7 ± 3.0 seconds, L+atorvastatin (L): 12.8 ± 3.2 seconds , L+atorvastatin (H): 8.8 ± 2.6 seconds). The chronic inhibition of NO synthesis increased the extent of fibrosis and markers of oxidative stresses such as proteins modified with 4-hydroxy-trans-2-nonenal and p47phox and rac1 in left atrial tissue, either of which was prevented by atorvastatin. Conclusion: Atorvastatin attenuates oxidative stresses in atrium and prevents atrial electrical and morphological remodeling in rat hypertensive failing hearts without hemodynamic changes. Statin may be beneficial in patients with coronary heart disease and atrial fibrillation, and may contribute to the prevention of the onset of heart failure.

scholarly journals Atrial edema in patients with atrial fibrillation with chronic heart failure

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
VV Kirillova ◽  
OV Mochula ◽  
AA Garganeeva ◽  
VYU Usov ◽  
RE Batalov ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Skeletal Muscle ◽  
Chronic Heart Failure ◽  
Interventricular Septum ◽  
Myocardial Edema ◽  
Interatrial Septum ◽  
Atrial Septum ◽  
Control Group ◽  
Constant Form

Abstract Funding Acknowledgements Type of funding sources: None. Objective to investigate the intensity of the atrial septum by T2-weighted magnetic resonance imaging (MRI) in patients with chronic heart failure (CHF), with and without atrial fibrillation (AF). Materials and methods. In patients with CHF with atrial fibrillation (n = 23, including 11 patients with paroxysmal form, and 12 patients with constant forms) and without (n = 9) of arrhythmias in the control group – almost healthy (n = 6) we evaluated the signal intensity (SI) of the interatrial septum, the interventricular septum, and skeletal muscle at MRI T-2 weighted images. An increase in the value of SI in 2 times or more compared with the SI of skeletal muscle was regarded as an MRI signs of myocardial edema. Results. The SI of the atrial septum in patients with CHF who have constant forms of atrial fibrillation is higher than in the control (2775.58 ± 383.61 relative to the control - 1448.57 ± 291.30, p &lt; 0.05). The MPP gain index in patients with paroxysmal AF equal to 1.59 ± 0.10 did not differ in comparison with patients with CHF who do not have rhythm disorders - 1.53 ± 0.12. An index of atrial septal enhancement greater than 2, indicating the presence of MRI signs of atrial septal myocardial edema  was detected only in patients with a constant form of AF (2.39 ± 0.18) than in patients with CHF with paroxysmal AF, in patients with CHF without rhythm disturbances and in the control group (1.59 ± 0.23; 1.53 ± 0.28 and 1.15 ± 0.16, respectively,  p &lt; 0.05). Summary. In patients with CHF who have a constant form of atrial fibrillation, according to T2-weighted MRI images, signs of edema of the myocardium of the atrial septum were revealed in comparison with the control group and patients with CHF who have a paroxysmal form of atrial fibrillation and without rhythm disturbances.

scholarly journals Clinical course of chronic heart failure with preserved ejection fraction after radiofrequency catheter ablation for atrial fibrillation

2020 ◽  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Radiofrequency Catheter Ablation ◽  
Clinical Course ◽  
Nyha Class ◽  
Control Group ◽  
Preserved Ejection Fraction

Introducrion. Recent randomized controlled trials suggest that catheter ablation of atrial fibrillation (AF) in heart failure (HF) patients leads to improvements in left ventricular function, exercise capacity, and quality of life, but focused on HF with reduced left ventricle ejection fraction (LVEF). Aim. To study the clinical course of chronic heart failure with preserved ejection fraction after radiofrequency catheter ablation for atrial fibrillation. Materials and methods. 194 patients with AF and chronic HF with preserved ejection fraction were included in the study: 136 patients – underwent catheter ablation (CA) for AF; 58 − control group, who continued pharmacological therapy (PT) for rhythm control strategy. All the patients had New York Heart Association (NYHA) class I, II or III HF, LVEF > 40 %. Baseline characteristics comprised demographic and clinical data, medical history echocardiography and ECG results of the included patients. Results. Patients on PT were significantly more symptomatic for HF in comparison to CA patients (the average value of NYHA class HF 2,2 ± 07 versus (vs.) 1,8 ± 0,6; p = 0,019), but AF for itself were more symptomatic in CA group (the average value of EHRA 3,1 ± 0,5 vs. 2,9 ± 0,6; p = 0,001). Among patients with HF with preserved LVEF who underwent CA and were followed-up 24 months 52,9 % of patients remained free of AF recurrence; while in the control group only 7 %. At the 24 months follow-up NYHA class significantly improved in ablation group, as well as EHRA score. Conclusions. Radiofrequency catheter ablation was associated with improved the clinical course of chronic heart failure with preserved left ventricle ejection fraction and AF – related symptoms itself.

scholarly journals Efficacy of cardiac rehabilitation with motion assistance from wearable cyborg hybrid assistive limb in patients with chronic heart failure: a randomized controlled trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Watanabe ◽  
A Koike ◽  
H Kato ◽  
L Wu ◽  
K Hayashi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Rehabilitation ◽  
Exercise Therapy ◽  
Knee Extensor ◽  
Control Group ◽  
Cardiac Events ◽  
Rehabilitation Programs ◽  
Sit To Stand ◽  
Knee Extensor Strength

Abstract Background Recent Cochrane Systematic Review suggested that the participation in cardiac rehabilitation is associated with approximately 20% lower cardiovascular mortality and morbidity. Exercise therapy is the key component of cardiac rehabilitation programs. In recent years, innovative technologies have been introduced into the field of rehabilitation, and a typical example is the wearable cyborg Hybrid Assistive Limb (HAL). The wearable cyborg HAL provides motion assistance based on detection of bioelectrical signals on the skin surface when muscle forces are generated. The lumbar-type HAL is expected to expand the therapeutic options for severe cardiac patients who have difficulty in performing usual cardiac rehabilitation programs, such as bicycle pedaling or walking. Purpose We aim to compare the efficacy of exercise therapy performed with motion assistance from a lumbar-type HAL versus conventional training (sit-to-stand exercise without HAL) in patients with chronic heart failure. Methods This clinical trial is a randomized, non-blinded, and controlled study. Twenty-eight heart failure patients (73.1±13.8 years) who have difficulty in walking at the usual walking speed of healthy subjects were randomly assigned to 2 groups (HAL group or control group) with a 1:1 allocation ratio and performed sit-to stand exercise either with HAL or without HAL for 5 to 30 minutes once a day, and 6 to 10 days during the study period. The brain natriuretic peptide (BNP), isometric knee extensor strength, standing ability (30-seconds chair-stand test: CS-30), short physical performance battery (SPPB) and 6-minute walking distance (6MWD) were measured before and after the completion of cardiac rehabilitation. Cardiac events such as death, re-hospitalization, myocardial infarction and worsening of angina pectoris and heart failure during 1 year after discharge were evaluated. Results There was no significant difference in the number of days of exercise therapy between the two groups. BNP, SPPB and 6MWD were improved in both groups. In the HAL group, the isometric knee extensor strength (0.29±0.11 vs 0.35±0.11 kgf/kg, p=0.003) significantly improved and CS-30 (5.5±5.1 vs 8.2±5.3, p=0.054) tended to improve. However, in the control group, either the isometric knee extensor strength (0.35±0.11 vs 0.36±0.14 kgf/kg, p=0.424) or CS-30 (6.0±4.3 vs 9.2±6.2, p=0.075) did not significantly change. HAL group showed significantly more improvement in the isometric knee extensor strength than control group (p=0.045). Cardiac events occurred in 20% in the HAL group and 43% in the control group. Conclusion The improvement in isometric knee extensor strength with the assistance from lumbar-type HAL suggests that exercise therapy using this device may be useful in chronic heart failure patients with flail or sarcopenia, a strong poor prognostic factor in these patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported in part by a grant-in-aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (JSPS KAKENHI grant number JP17K09485) and funded by the ImPACT Program of the Council for Science, Technology and Innovation (Cabinet Office, Government of Japan) (grant number 2017-PM05-03-01).

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