Transcriptome Analysis by RNA Sequencing of Mouse Embryonic Stem Cells Stocked on International Space Station for 1584 Days in Frozen State after Culture on the Ground.

As a space project, in "Stem Cells" by the Japan Aerospace Exploration Agency (JAXA), frozen mouse ES cells were stored on the International Space Station (ISS) in the Minus Eighty Degree Laboratory Freezer for ISS (MELFI) for 1584 days. After taking these cells back to the ground, the cells were thawed and cultured, and their gene expressions were comprehensively analyzed using RNA sequencing in order to elucidate the early response of the cells to long-time exposure to space radiation consisting of various ionized particles. The comparisons of gene expression involved in double-stranded break (DSB) repair were examined. The expressions of most of the genes that were involved in homologous recombination (HR) and non-homologous end joining (NHEJ) were not significantly changed between the ISS-stocked cells and ground-stocked control cells. However, the transcription of Trp53inp1 (tumor protein 53 induced nuclear protein-1), Cdkn1a (p21), and Mdm2 genes increased in ISS-stocked cells as well as Fe ion-irradiated cells compared to control cells. This suggests that accumulated DNA damage caused by space radiation exposure would activate these genes, which are involved in cell cycle arrest for repair and apoptosis in a p53-dependent or -independent manner, in order to prevent cells with damaged genomes from proliferating and forming tumors.

The Prognostic Impact of Follow-up Cardiac MIBG Imaging on LV trajectory After Acute Decompensation.

AIMS: Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure. Recently, the trajectory of left ventricular ejection fraction (LVEF) has been a focus in patients with reduced LVEF admitted for acute decompensated heart failure (ADHF). We sought to investigate the prognostic value of follow-up cardiac MIBG imaging in ADHF patients with reduced LVEF in relation to LVEF trajectory. METHODS AND RESULTS: We prospectively studied 145 ADHF patients with reduced LVEF<40%. The cardiac MIBG heart-to-mediastinum ratio (late HMR) was measured on the delayed image at discharge and at the 6-month follow-up (6FUP). At 6 months after discharge, 54 (37%) patients had complete recovery of LVEF≥50% (HFcorEF), and 43 (30%) patients had partial recovery of LVEF: 40%-50% (HFparEF), while the remaining 48 (33%) patients had no functional recovery of LVEF (HFnorEF). The late HMR at 6 FUP in HFcorEF patients was significantly greater than that in HFparEF and HFnorEF patients. During a follow-up period of 4.3 ± 2.6 years, 43 patients had cardiac events, defined as the composite of readmission for worsening HF and cardiac death. Patients with lower late HMR at 6 FUP had a greater risk of cardiac events than those with higher late HMR at 6 FUP in the group with recovered LVEF, especially HFparEF, which was not observed in the HFnorEF subgroup. CONCLUSION: Follow-up MIBG imaging after discharge could provide additional prognostic information in ADHF patients with recovered left ventricular function.

A Rare Case of a Common Inferior Pulmonary Vein Presumed to Be a Remnant of the Common Pulmonary Vein.

A 74-year-old woman with an implanted physiological DDD pacemaker visited our department complaining of palpitations due to atrial fibrillation (AF). Catheter ablation therapy for AF was scheduled. Preoperative multidetector computed tomography showed that the inferior pulmonary vein (PV) was a common trunk, and the left and right superior PVs branched from the center of the left atrial roof. In addition, mapping of the left atrium before AF ablation revealed no potential in either the inferior PV or common trunk. We performed left and right superior PV and posterior wall isolation. After ablation, AF was not observed on pacemaker recordings.

The clinical relevance of mild cognitive impairment in acute heart failure: A comparison with cognitive impairment.

BACKGROUND: Although mild cognitive impairment (MCI) has received much attention as a precursor of dementia, its prognostic role has not been fully clarified in patients with heart failure (HF). METHODS AND RESULTS: We studied 274 patients admitted for acute decompensated HF. Cognitive function was evaluated using Mini Mental State Examination (MMSE). According to the previous definition, MMSE of 0-23, 24-27, and 28-30 were classified as CI (n = 132), MCI (n = 81), and normal cognitive function (n = 61). The primary endpoint was cardiac events, defined as the composite of unplanned HF hospitalization and cardiovascular mortality. During a mean follow-up period of 4.9 ±â€¯3.1 years, 145 patients experienced cardiac events. Multivariable logistic regression analysis showed that hypertension (p = 0.043), low cardiac index (p = 0.022), and low serum albumin level (p = 0.041) had a significant association with cognitive abnormalities. Both CI and MCI were significantly associated with cardiac events after Cox multivariable adjustment [CI: p = 0.001, adjusted HR 2.66 (1.48-4.77); MCI: p = 0.025, adjusted HR 1.90 (1.09-3.31), normal cognitive function group: reference]. Patients with MCI had a significantly higher risk of unplanned HF hospitalization [p = 0.033, adjusted HR 1.91 (1.05-3.47)], but not all-cause mortality (p = 0.533) or cardiovascular mortality (p = 0.920), while CI was significantly associated with all-cause mortality (p = 0.025) and cardiovascular mortality (p = 0.036). CONCLUSION: Even MCI had a significant risk of cardiac events in patients with acute decompensated HF. This risk was mainly derived from unplanned HF hospitalization.

Dietary habits in Japanese patients with bullous pemphigoid: low intake of retinol.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Dietary habits may modulate the pathogenesis of BP. OBJECTIVES: We evaluated dietary habits in Japanese patients with BP and compared their results to those of age- and sex-matched healthy controls. We also examined the relationship between dietary habits versus IgG anti-BP180NC16A antibody or parameters of BP disease area index (BPDAI); cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. MATERIALS & METHODS: Dietary habits were assessed by the validated, Brief-type self-administered Diet History Questionnaire. Severity of disease was assessed with BPDAI. RESULTS: Patients with BP showed a lower intake of retinol (vitamin A1) and beverages, and a higher intake of seasoning/spices, compared to controls. The bivariate and multivariable logistic regression analysis showed that BP was associated with a low intake of retinol and beverages. There were no significant correlations between IgG anti-BP180NC16A antibody levels and intake of nutrients/foods. The BPDAI score for cutaneous blisters/erosions significantly positively correlated with intake of carbohydrate and negatively with intake of retinol, vitamin A, animal fat, cholesterol, phosphorus, and vitamin B2. The BPDAI score for cutaneous urticaria/erythema significantly negatively correlated with intake of vitamin A. BP patients with mucosal blisters/erosions had a higher intake of cholesterol, n-6 polyunsaturated fatty acid, and eggs, and lower intake of seasoning/spices, compared to patients without BP. CONCLUSION: The supplementation of vitamin A might have prophylactic and/or therapeutic effects on BP.

Shorter door-to-balloon time, better long-term clinical outcomes in ST-segment elevation myocardial infarction patients: J-MINUET substudy.

BACKGROUND: The impact of shorter door-to-balloon (DTB time on long-term outcomes in ST-segment elevation myocardial infarction (STEMI treated with primary percutaneous coronary intervention (PPCI has not been fully elucidated. METHODS: We investigated 3283 consecutive patients with acute myocardial infarction selected from a prospective, nationwide, multicenter registry (J-MINUET database comprising 28 institutions in Japan between July 2012 and March 2014. Among the study population, we analyzed 1639 STEMI patients who had PPCI within 12 h of onset. Patients were stratified into four groups (DTB time < 45 min, 45-60 min, 61-90 min, >90 min. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. We performed landmark analysis for incidence of the primary endpoint from 31 days to 3 years among the four groups. RESULTS: The primary endpoint rate from 31 days to 3 years increased significantly and time-dependently with DTB time (10.2 % vs. 15.3 % vs. 16.2 % vs. 19.3 %, respectively; log-rank p = 0.0129. Higher logarithm-transformed DTB time was associated with greater risk of a primary endpoint from 31 days to 3 years, and the increased number of adverse long-term clinical outcomes persisted even after adjusting for other independent variables. CONCLUSION: Shorter DTB time was associated with better long-term clinical outcomes in STEMI patients treated with PPCI in contemporary clinical practice. Further efforts to shorten DTB time are recommended to improve long-term clinical outcomes in STEMI patients. TRIAL REGISTRATION: UMIN Unique trial Number: UMIN000010037.

Clinical impact of beta-blockers at discharge on long-term clinical outcomes in patients with non-reduced ejection fraction after acute myocardial infarction.

BACKGROUND: Beta-blockers are associated with several clinical benefits in patients with reduced left ventricular ejection fraction (REF) after acute myocardial infarction (AMI), such as lower rates of mortality, recurrence of myocardial infarction, and heart failure. However, the long-term prognosis of beta-blockers has rarely been investigated in patients with non-REF after AMI. This study aimed to investigate the clinical benefits of beta-blockers in these patients. METHODS: A total of 3281 consecutive patients who were hospitalized within 48 h after AMI were registered in the J-MINUET study. Patients who underwent primary percutaneous coronary intervention (PCI) and had a left ventricular ejection fraction ≥40 % were enrolled, and patients who died during admission were excluded. Included patients were divided into two groups according to the prescription of beta-blockers at discharge. Their characteristics and clinical outcomes were compared. RESULTS: The number of AMI patients treated with beta-blockers was 1353 (70.4 %). Patients who received beta-blockers were younger and had a higher incidence of hypertension, dyslipidemia, and ST-segment elevation myocardial infarction than those who did not receive beta-blockers. The peak creatine kinase level after primary PCI was significantly higher in patients who received beta-blockers. These patients also had a lower incidence of a composite of all-cause death, myocardial infarction, and stroke compared to those that did not receive beta-blockers (7.3 % vs. 11.9 %, p = 0.001). Multivariate analysis showed that beta-blocker use was an independent factor for better clinical outcomes. CONCLUSIONS: The J-MINUET study revealed the clinical benefit of beta-blockers in AMI patients with non-REF after primary PCI.

Multi-Kernel Temporal and Spatial Convolution for EEG-Based Emotion Classification.

Deep learning using an end-to-end convolutional neural network (ConvNet) has been applied to several electroencephalography (EEG)-based brain-computer interface tasks to extract feature maps and classify the target output. However, the EEG analysis remains challenging since it requires consideration of various architectural design components that influence the representational ability of extracted features. This study proposes an EEG-based emotion classification model called the multi-kernel temporal and spatial convolution network (MultiT-S ConvNet). The multi-scale kernel is used in the model to learn various time resolutions, and separable convolutions are applied to find related spatial patterns. In addition, we enhanced both the temporal and spatial filters with a lightweight gating mechanism. To validate the performance and classification accuracy of MultiT-S ConvNet, we conduct subject-dependent and subject-independent experiments on EEG-based emotion datasets: DEAP and SEED. Compared with existing methods, MultiT-S ConvNet outperforms with higher accuracy results and a few trainable parameters. Moreover, the proposed multi-scale module in temporal filtering enables extracting a wide range of EEG representations, covering short- to long-wavelength components. This module could be further implemented in any model of EEG-based convolution networks, and its ability potentially improves the model's learning capacity.

Comparison of biological measurement and physical estimates of space radiation in the International Space Station.

Nowadays, ordinary people can travel in space, and the possibility of extended durations in an environment such as moon of the Earth and Mars with higher space radiation exposures compared to past missions, is increasing. Until now, the physical doses of space radiation have been measured, but measurement of direct biological effects has been hampered by its low dose and low dose-rate effect. To assess the biological effects of space radiation, we launched and kept frozen mouse embryonic stem (ES) cells in minus eighty degree Celsius freezer in ISS (MELFI) on the International Space Station (ISS) for a maximum of 1,584 days. The passive dosimeter for life science experiments in space (PADLES) was attached on the surface of the sample case of the ES cells. The physical dosimeter measured the absorbed dose in water. After return, the frozen cells were thawed and cultured and their chromosome aberrations were analyzed. Comparative experiments with proton and iron ion irradiation were performed at particle accelerators on Earth. The wild-type ES cells showed no differences in chromosomal aberrations between the ground control and ISS exposures. However, we detected an increase of chromosome aberrations in radio-sensitized histone H2AX heterozygous-deficient mouse ES cells and found that the rate of increase against the absorbed dose was 1.54-fold of proton irradiation at an accelerator. On the other hand, we estimated the quality factor of space radiation as 1.48 ± 0.2. using formulas of International Commission of Radiation Protection (ICRP) 60. The relative biological effectiveness (RBE) observed from our experiments (1.54-fold of proton) was almost equal (1.04-fold) to the physical estimation (1.48 ± 0.2). It should be important to clarify the relation between biological effect and physical estimates of space radiation. This comparative study paves a way to reveal the complex radiation environments to reduce the uncertainty for risk assessment of human stay in space.

Loop Diuretic Use is Associated With Adverse Clinical Outcomes in Acute Myocardial Infarction Patients With Low Volume Status.

To investigate the difference in the prognostic impact of loop diuretics in patients with acute myocardial infarction (AMI) based on plasma volume status, a total of 3,364 survivors of AMI who were registered in the large database of the Osaka Acute Coronary Insufficiency Study (OACIS) were studied. Plasma volume status was assessed by the estimated plasma volume status (ePVS) that was calculated based on a weight- and hematocrit-based formula at discharge. The endpoint was a composite endpoint of all-cause death and rehospitalization due to heart failure for 5 years. During a median follow-up period of 1.9 years, 90 and 223 patients had events in the groups with low ePVS (

Bitiscetin-3, a Novel C-Type Lectin-like Protein Cloned from the Venom Gland of the Viper Bitis arietans, Induces Platelet Agglutination and Inhibits Binding of Von Willebrand Factor to Collagen.

Bitiscetin-1 (aka bitiscetin) and bitiscetin-2 are C-type lectin-like proteins purified from the venom of Bitis arietans (puff adder). They bind to von Willebrand factor (VWF) and-at least bitiscetin-1-induce platelet agglutination via enhancement of VWF binding to platelet glycoprotein Ib (GPIb). Bitiscetin-1 and -2 bind the VWF A1 and A3 domains, respectively. The A3 domain includes the major site of VWF for binding collagen, explaining why bitiscetin-2 blocks VWF-to-collagen binding. In the present study, sequences for a novel bitiscetin protein-bitiscetin-3-were identified in cDNA constructed from the B. arietans venom gland. The deduced amino acid sequences of bitiscetin-3 subunits α and ß share 79 and 80% identity with those of bitiscetin-1, respectively. Expression vectors for bitiscetin-3α and -3ß were co-transfected to 293T cells, producing the heterodimer protein recombinant bitiscetin-3 (rBit-3). Functionally, purified rBit-3 (1) induced platelet agglutination involving VWF and GPIb, (2) did not compete with bitiscetin-1 for binding to VWF, (3) blocked VWF-to-collagen binding, and (4) lost its platelet agglutination inducing ability in the presence of an anti-VWF monoclonal antibody that blocked VWF-to-collagen binding. These combined results suggest that bitiscetin-3 binds to the A3 domain, as does bitiscetin-2. Except for a small N-terminal fragment of a single subunit-which differs from that of both bitiscetin-3 subunits-the sequences of bitiscetin-2 have never been determined. Therefore, by identifying and analyzing bitiscetin-3, the present study is the first to present the full-length α- and ß-subunit sequences and recombinant expression of a bitiscetin-family toxin that blocks the binding of VWF to collagen.

Long-Term Outcomes and Clinical Predictors of Mortality Following Occurrence of Stent Thrombosis.

Background Stent thrombosis (ST) remains a significant medical issue. In particular, longer-term mortality and clinical predictors after ST occurrence have yet to be elucidated. Methods and Results This was a multicenter, retrospective, observational study. A total of 187 definite ST cases from January 2008 to December 2017 were enrolled, and the long-term clinical outcomes were investigated. The primary outcome measure was the cumulative mortality after ST occurrence. In addition, independent predictors of mortality were assessed. Among the stent types causing ST, bare-metal stent, first-generation drug-eluting stent, second-generation drug-eluting stent, and third-generation drug-eluting stent comprised 31.0%, 19.3%, 36.9%, and 6.4% of cases, respectively. Median duration from stent implantation to ST was 680.5 (interquartile range, 33.8-2450.5) days. Cumulative mortality was 14.6%, 17.4%, 21.2%, 24.4%, and 33.8% at 1, 2, 3, 5 and 10 years, respectively. The cumulative mortality did not significantly differ by type of stent, and mortality of late ST was higher than that of early ST and very late ST; however, it did not reach statistical significance after the multivariate analysis. Independent predictors of mortality were hemodialysis (hazard ratio [HR], 7.80; 95% CI, 3.07-19.81; P<0.001), culprit lesions in the left main trunk (HR, 8.14; 95% CI, 1.71-38.75; P=0.008), culprit lesions in the left coronary artery (HR, 2.77; 95% CI, 1.10-6.96; P=0.030), and peak creatine kinase (HR, 1.017; 95% CI, 1.011-1.022; P<0.001). Conclusions The 10-year cumulative mortality after ST reached 33.8%. Close follow-up is thus mandatory for patients with ST, especially with hemodialysis, culprit lesions in the left main trunk and left coronary artery, and high peak creatine kinase.

Usefulness of the 2-year iodine-123 metaiodobenzylguanidine-based risk model for post-discharge risk stratification of patients with acute decompensated heart failure.

PURPOSE: A four-parameter risk model that included cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging and readily available clinical parameters was recently developed for prediction of 2-year cardiac mortality risk in patients with chronic heart failure. We sought to validate the ability of this risk model to predict post-discharge clinical outcomes in patients with acute decompensated heart failure (ADHF) and to compare its prognostic value with that of the Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines-Heart Failure (GWTG-HF) risk scores. METHODS: We studied 407 consecutive patients who were admitted for ADHF and survived to discharge, with definitive 2-year outcomes (death or survival). Cardiac MIBG imaging was performed just before discharge. The 2-year cardiac mortality risk was calculated using four parameters, namely age, left ventricular ejection fraction, New York Heart Association functional class, and cardiac MIBG heart-to-mediastinum ratio on delayed images. Patients were stratified into three groups based on the 2-year cardiac mortality risk: low- (< 4%), intermediate- (4-12%), and high-risk (> 12%) groups. The ADHERE and GWTG-HF risk scores were also calculated. RESULTS: There was a significant difference in the incidence of cardiac death among the three groups stratified using the 2-year cardiac mortality risk model (p < 0.0001). The 2-year cardiac mortality risk model had a higher C-statistic (0.732) for the prediction of cardiac mortality than the ADHERE and GWTG-HF risk scores. CONCLUSION: The 2-year MIBG-based cardiac mortality risk model is useful for predicting post-discharge clinical outcomes in patients with ADHF. TRIAL REGISTRATION NUMBER: UMIN000015246, 25 September 2014.

Galectin-3 promotes the adipogenic differentiation of PDGFRα+ cells and ectopic fat formation in regenerating muscle.

Worldwide prevalence of obesity is associated with the increase of lifestyle-related diseases. The accumulation of intermuscular adipose tissue (IMAT) is considered a major problem whereby obesity leads to sarcopenia and metabolic disorders and thus is a promising target for treating these pathological conditions. However, whereas obesity-associated IMAT is suggested to originate from PDGFRα+ mesenchymal progenitors, the processes underlying this adipogenesis remain largely unexplored. Here, we comprehensively investigated intra- and extracellular changes associated with these processes using single-cell RNA sequencing and mass spectrometry. Our single-cell RNA sequencing analysis identified a small PDGFRα+ cell population in obese mice directed strongly toward adipogenesis. Proteomic analysis showed that the appearance of this cell population is accompanied by an increase in galectin-3 in interstitial environments, which was found to activate adipogenic PPARγ signals in PDGFRα+ cells. Moreover, IMAT formation during muscle regeneration was significantly suppressed in galectin-3 knockout mice. Our findings, together with these multi-omics datasets, could unravel microenvironmental networks during muscle regeneration highlighting possible therapeutic targets against IMAT formation in obesity.

Prognostic Significance of Cardiac 123I-MIBG SPECT Imaging in Heart Failure Patients With Preserved Ejection Fraction.

OBJECTIVES: The authors sought to elucidate the prognostic value of cardiac sympathetic nerve dysfunction as evaluated using iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) single-photon emission computed tomography (SPECT) imaging in patients with heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). BACKGROUND: Cardiac sympathetic nerve dysfunction assessed by 123I-MIBG imaging is associated with poor outcomes in chronic HF patients with reduced left ventricular ejection fraction (HFrEF). However, no information is available on the prognostic vale of cardiac 123I-MIBG SPECT imaging in patients with HFpEF. METHODS: We studied 148 patients admitted for acute decompensated HF (ADHF) with nonischemic HFpEF and who underwent cardiac 123I-MIBG imaging at discharge. The cardiac 123I-MIBG heart-to-mediastinum ratio (H/M) was measured on the delayed planar image (late H/M). SPECT analysis of the delayed image was conducted, and the tracer uptake in all 17 regions on the polar map was scored on a 5-point scale by comparison with a sex-matched normal control database. The total defect score (TDS) was calculated by summing the score of each of the 17 segments. The primary endpoint was the association between TDS and cardiac events (the composite of emergent HF hospitalization and cardiac death). RESULTS: During a mean follow-up period of 2.4 ± 1.6 years, 61 patients experienced cardiac events. TDS was significantly associated with cardiac events after multivariate Cox adjustment (P < 0.0001). Patients with high TDS levels had a significantly greater risk of cardiac events than those with middle or low TDS levels (63% vs 40% vs 20%, respectively; P < 0.0001; HR: 4.69; 95% CI: 2.29 to 9.61; and HR: 2.46; 95% CI: 1.14 to 5.29). C-statistic of TDS was 0.730 (95% CI: 0.651 to 0.799), which was significantly higher than that of late H/M (0.607; 95% CI: 0.524 to 0.686; P = 0.0228). CONCLUSIONS: Cardiac 123I-MIBG SPECT imaging provided useful prognostic information in nonischemic ADHF patients with HFpEF. (Clinical Trial: Osaka Prefectural Acute Heart Failure Syndrome Registry [OPAR]: UMIN000015246).

A serial optical frequency-domain imaging study of early and late vascular responses to bioresorbable-polymer sirolimus-eluting stents for the treatment of acute myocardial infarction and stable coronary artery disease patients: results of the MECHANISM-ULTIMASTER study.

The purpose of this study was to assess early and late vascular healing in response to bioresorbable-polymer sirolimus-eluting stents (BP-SESs) for the treatment of patients with ST-elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). A total of 106 patients with STEMI and 101 patients with stable-CAD were enrolled. Optical frequency-domain images were acquired at baseline, at 1- or 3-month follow-up, and at 12-month follow-up. In the STEMI and CAD cohorts, the percentage of uncovered struts (%US) was significantly and remarkably decreased during early two points and at 12-month (the STEMI cohort: 1-month: 18.75 ± 0.78%, 3-month: 10.19 ± 0.77%, 12-month: 1.80 ± 0.72%; p < 0.001, the CAD cohort: 1-month: 9.44 ± 0.78%, 3-month: 7.78 ± 0.78%, 12-month: 1.07 ± 0.73%; p < 0.001 respectively). The average peri-strut low-intensity area (PLIA) score in the STEMI cohort was significantly decreased during follow-up period (1.90 ± 1.14, 1.18 ± 1.25, and 1.01 ± 0.72; p ≤ 0.001), whereas the one in the CAD cohort was not significantly changed (0.89 ± 1.24, 0.67 ± 1.07, and 0.64 ± 0.72; p = 0.59). In comparison with both groups, differences of %US and PLIA score at early two points were almost disappeared or close at 12 months. The strut-coverage and healing processes in the early phase after BP-SES implantation were significantly improved in both cohorts, especially markedly in STEMI patients. At 1 year, qualitatively and quantitatively consistent neointimal coverage was achieved in both pathogenetic groups.

Coronary vasomotion after treatment with drug-coated balloons or drug-eluting stents: a prospective, open-label, single-centre randomised trial.

BACKGROUND: Although recent studies have reported that drug-coated balloons (DCB) are non-inferior to drug-eluting stents (DES) for the treatment of native coronary arteries in a specific population, there is no available information concerning vasomotion after treatment with DCB. AIMS: The aim of this study was to prospectively compare coronary vasomotion in patients with small coronary artery disease treated with DCB versus DES. METHODS: Forty-two native lesions (2.0-3.0 mm) treated in our institution were randomly assigned to the DCB arm (n=19) or the bioabsorbable polymer everolimus-eluting stents arm (n=23) after successful predilation. At eight months after treatment, endothelium-dependent and -independent vasomotion was evaluated with intracoronary infusions in incremental doses of acetylcholine (right coronary artery: low dose 5 µg, high dose 50 µg; left coronary artery: low dose 10 µg, high dose 100 µg) and nitroglycerine (200 µg). The mean lumen diameter of the distal segment, beginning 5 mm and ending 15 mm distal to the edge of the treated segment, was quantitatively measured by angiography. RESULTS: The luminal dimension in the treated segment did not differ between groups at the follow-up angiography. The vasoconstriction after acetylcholine infusion was less pronounced in the DCB arm than in the DES arm (low-dose: 6±13% vs -3±18%, p=0.060; high-dose: -4±17% vs -21±29%, p=0.035). The response to nitroglycerine did not differ between groups (17±13% vs 17±22%, p=0.929). CONCLUSIONS: Vasoconstriction after acetylcholine infusion in the peri-treated region was less pronounced in the DCB arm than in the DES arm, suggesting that endothelial function in treated coronary vessels could be better preserved by DCB than by new-generation DES.

Measuring context dependency in birdsong using artificial neural networks.

Context dependency is a key feature in sequential structures of human language, which requires reference between words far apart in the produced sequence. Assessing how long the past context has an effect on the current status provides crucial information to understand the mechanism for complex sequential behaviors. Birdsongs serve as a representative model for studying the context dependency in sequential signals produced by non-human animals, while previous reports were upper-bounded by methodological limitations. Here, we newly estimated the context dependency in birdsongs in a more scalable way using a modern neural-network-based language model whose accessible context length is sufficiently long. The detected context dependency was beyond the order of traditional Markovian models of birdsong, but was consistent with previous experimental investigations. We also studied the relation between the assumed/auto-detected vocabulary size of birdsong (i.e., fine- vs. coarse-grained syllable classifications) and the context dependency. It turned out that the larger vocabulary (or the more fine-grained classification) is assumed, the shorter context dependency is detected.

Impact of Chronic Kidney Disease on In-Hospital and 3-Year Clinical Outcomes in Patients With Acute Myocardial Infarction Treated by Contemporary Percutaneous Coronary Intervention and Optimal Medical Therapy　- Insights From the J-MINUET Study.

BACKGROUND: The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in debate.Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m2); moderate CKD (60>eGFR≥30 mL/min/1.73 m2); and severe CKD (eGFR <30 mL/min/1.73 m2). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788-0.841) to 0.831 (0.806-0.857), as well as 0.731 (0.708-0.755) to 0.740 (0.717-0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement [NRI] 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively. CONCLUSIONS: CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.

Long-Term Clinical Impact of Cardiogenic Shock and Heart Failure on Admission for Acute Myocardial Infarction.

Long-term clinical outcomes among patients with cardiogenic shock (CS) and heart failure (HF) who survive the early phase of acute myocardial infarction (AMI) remain uncertain. We investigated 3283 consecutive patients with AMI, selected from a prospective, nation-wide multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014. The 3263 eligible patients were divided into the following three groups: CS-/HF- group (n = 2467, 75.6%); CS-/HF+ group (n = 479, 14.7%); and CS+ group (n = 317, 9.7%). The thirty-day mortality rate in CS+ patients was 32.8%, significantly higher than in CS- patients. Among CS+ patients, multivariate logistic regression analysis identified statin use before admission (Odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14-0.66, P = 0.002), renal deficiency (OR 8.72, 95%CI 2.81-38.67, P < 0.0001) and final thrombolysis in myocardial infarction flow grade (OR 0.42, 95%CI 0.18-0.99, P = 0.046) were associated with 30-day mortality. Landmark Kaplan-Meier analysis showed that mortality rates after 30 days were comparable between CS+ and CS-/HF+ groups but were lower in the CS-/HF- group. Multivariate Cox hazard analysis also showed that hazard risk of mortality after 30 days was comparable between the CS+ and CS-/HF+ groups (Hazard ratio (HR) 1.03, 95%CI 0.63-1.68, P = 0.90), and significantly lower in the CS-/HF- group (HR 0.44, 95%CI 0.32-059, P < 0.0001). In conclusion, AMI patients with CS who survived 30 days experienced worse long-term outcomes compared with those without CS up to 3 years. Attention is required for patients who show HF on admission without CS to improve long-term AMI outcomes.