Dual Channel H2O2 Photosynthesis in Pure Water over S-Scheme Heterojunction Cs3PMo12/CC Boosted by Proton and Electron Reservoirs.

Dual channel photo-driven H2O2 production in pure water on small-scale on-site setups is a promising strategy to provide low-concentrated H2O2 whenever needed. This process suffers, however, strongly from the fast recombination of photo-generated charge carriers and the sluggish oxidation process. Here, insoluble Keggin-type cesium phosphomolybdate Cs3PMo12O40 (abbreviated to Cs3PMo12) is introduced to carbonized cellulose (CC) to construct S-scheme heterojunction Cs3PMo12/CC. Dual channel H2O2 photosynthesis from both H2O oxidation and O2 reduction in pure water has been thus achieved with the production rate of 20.1 mmol L-1 gcat. -1 h-1, apparent quantum yield (AQY) of 2.1% and solar-to-chemical conversion (SCC) efficiency of 0.050%. H2O2 accumulative concentration reaches 4.9 mmol L-1. This high photocatalytic activity is guaranteed by unique features of Cs3PMo12/CC, namely, S-scheme heterojunction, electron reservoir, and proton reservoir. The former two enhance the separation of photo-generated charge carriers, while the latter speeds up the torpid oxidation process. In situ experiments reveal that H2O2 is formed via successive single-electron transfer in both channels. In real practice, exposing the reaction system under natural sunlight outdoors successfully results in 0.24 mmol L-1 H2O2. This work provides a key practical strategy for designing photocatalysts in modulating redox half-reactions in photosynthesis.

A Positioning and Navigation Method Combining Multimotion Features Dead Reckoning with Acoustic Localization.

Accurate location information can offer huge commercial and social value and has become a key research topic. Acoustic-based positioning has high positioning accuracy, although some anomalies that affect the positioning performance arise. Inertia-assisted positioning has excellent autonomous characteristics, but its localization errors accumulate over time. To address these issues, we propose a novel positioning navigation system that integrates acoustic estimation and dead reckoning with a novel step-length model. First, the features that include acceleration peak-to-valley amplitude difference, walk frequency, variance of acceleration, mean acceleration, peak median, and valley median are extracted from the collected motion data. The previous three steps and the maximum and minimum values of the acceleration measurement at the current step are extracted to predict step length. Then, the LASSO regularization spatial constraint under the extracted features optimizes and solves for the accurate step length. The acoustic estimation is determined by a hybrid CHAN-Taylor algorithm. Finally, the location is determined using an extended Kalman filter (EKF) merged with the improved pedestrian dead reckoning (PDR) estimation and acoustic estimation. We conducted some comparative experiments in two different scenarios using two heterogeneous devices. The experimental results show that the proposed fusion positioning navigation method achieves 8~56.28 cm localization accuracy. The proposed method can significantly migrate the cumulative error of PDR and high-robustness localization under different experimental conditions.

Deep Neural Network-Based Fusion Localization Using Smartphones.

Indoor location-based services (LBS) have tremendous practical and social value in intelligent life due to the pervasiveness of smartphones. The magnetic field-based localization method has been an interesting research hotspot because of its temporal stability, ubiquitousness, infrastructure-free nature, and good compatibility with smartphones. However, utilizing discrete magnetic signals may result in ambiguous localization features caused by random noise and similar magnetic signals in complex symmetric and large-scale indoor environments. To address this issue, we propose a deep neural network-based fusion indoor localization system that integrates magnetic and pedestrian dead reckoning (PDR). In this system, we first propose a ResNet-GRU-LSTM neural network model to achieve magnetic localization more accurately. Afterward, we put forward a multifeatured-driven step length estimation. A hierarchy GRU (H-GRU) neural network model is proposed, and a multidimensional dataset using acceleration and a gyroscope is constructed to extract more valid characteristics. Finally, more reliable and accurate pedestrian localization can be achieved under the particle filter framework. Experiments were conducted at two trial sites with two pedestrians and four smartphones. Results demonstrate that the proposed system achieves better accuracy and robustness than other traditional localization algorithms. Moreover, the proposed system exhibits good generality and practicality in real-time localization with low cost and low computational complexity.

A Low-Cost and Efficient Indoor Fusion Localization Method.

Accurate indoor location information has considerable social and economic value in applications, such as pedestrian heatmapping and indoor navigation. Ultrasonic-based approaches have received significant attention mainly since they have advantages in terms of positioning with temporal correlation. However, it is a great challenge to gain accurate indoor localization due to complex indoor environments such as non-uniform indoor facilities. To address this problem, we propose a fusion localization method in the indoor environment that integrates the localization information of inertial sensors and acoustic signals. Meanwhile, the threshold scheme is used to eliminate outliers during the positioning process. In this paper, the estimated location is fused by the adaptive distance weight for the time difference of arrival (TDOA) estimation and improved pedestrian dead reckoning (PDR) estimation. Three experimental scenes have been developed. The experimental results demonstrate that the proposed method has higher localization accuracy in determining the pedestrian location than the state-of-the-art methods. It resolves the problem of outliers in indoor acoustic signal localization and cumulative errors in inertial sensors. The proposed method achieves better performance in the trade-off between localization accuracy and low cost.

[A comparison of magnetic resonance spectroscopy and diffusion weighted imaging for diagnosing prostate cancer].

OBJECTIVE: To compare the clinical values of magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) in diagnosing prostate cancer. METHODS: A 1. 5T MR scanner was used in this study. We measured 274 regions of interest (ROI) in the images produced by MRS and DWI from 53 patients. The biopsy confirmed 150 ROI as cancers and 124 ROI as non-cancers. The results of MRS and DWI were compared using receiver operating characteristic (ROC) curves. RESULTS: Significant differences (P<0. 05) between malignant and benign tumors were found in signal intensity (b= 0,100,800 s/mm, in DWI), ADC value(in DWI), Cit content integral, Cho content integral and (Cho+Cr)/Cit ratio (in MRS). The ROC curves showed that ADC value, signal intensity (b=800 s/mm2) and the ratio of (Cho+Cr)/Cit performed better in distinguishing prostate cancers from benign tumors. The optimal operating point (OOP) of ADC value was determined as 1. 027 x 10(-3) mm2/s, with 0. 887 specificity, 0. 953 sensitivity, 0. 84 Youden index, and the area under curve (AUC) of 0. 966. The OOP of signal intensity (b=800 s/mm2) was determined as 47. 1, with 0. 806 specificity, 0. 72 sensitivity, 0. 53 Youden index, and the AUC of 0.782; The OOP of (Cho+Cr)/Cit ratio was determined as 0.78, with 0. 806 specificity, 0. 793 sensitivity, 0. 60 Youden index, and the AUC of 0. 844. CONCLUSION: DWI is a better method than MRS in differentiating prostate cancers from benign tumors.

Major inducing factors of hypertensive complications and the interventions required to reduce their prevalence: an epidemiological study of hypertension in a rural population in China.

BACKGROUND: The complications of hypertension cause severe health problems in rural areas in China. We (i) screened the major factors inducing hypertensive complications and provided intervention measures; and (ii) verified the efficacy of the New Rural Cooperative Medical Scheme (NRCMS; a medical insurance scheme for rural residents) for hypertension management. METHODS: A survey was conducted in the villages of Yunnan (an underdeveloped province in southwest China). The NRCMS was initiated there in 2005. Data were collected through questionnaires, physical examination, electrocardiography, as well as blood and urine tests. To detect factors inducing hypertension complications, a generalized estimating equations model was developed. Multivariable logistic regression was used to analyze influencing factors for hypertension control. RESULTS: Poor management of hypertension was observed in women. Being female, old, poorly educated, a smoker, ignorant of the dangerousness of hypertension, and having uncontrolled hypertension made patients more prone to hypertension complications. Combination therapy with ≥ 2 drugs helped control hypertension, but most rural patients disliked multidrug therapy because they considered it to be expensive and inconvenient. The NRCMS contributed little to reduce the prevalence of complications and improve control of hypertension. CONCLUSIONS: The present study suggested that the NRCMS needs to be reformed to concentrate on early intervention in hypertension and to concentrate on women. To increase hypertension control in rural areas in China, compound products containing effective and inexpensive drugs (and not multidrug therapy) are needed.

Indoor Acoustic Signals Enhanced Algorithm and Visualization Analysis.

A pure acoustic signal can be easy to realize signal analysis and feature extraction. However, the surrounding noises will affect the content of acoustic signals as well as auditory fatigue to the audience. Therefore, it is vital to overcome the problem of noises that affect the acoustic signal. An indoor acoustic signal enhanced method based on image source (IS) method, filtered-x least mean square (FxLMS) algorithm, and the combination of Delaunay triangulation and fuzzy c-means (FCM) clustering algorithm is proposed. In the first stage of the proposed system, the IS method was used to simulate indoor impulse response. Next, the FxLMS algorithm was used to reduce the acoustic signals with noise. Lastly, the quiet areas are optimized and visualized by combining the Delaunay triangulation and FCM clustering algorithm. The experimental analysis results on the proposed system show that better noise reduction can be achieved than the most widely used least mean square algorithm. Visualization was validated with an intuitive understanding of the indoor sound field distribution and the quiet areas.

Can machine learning-based analysis of multiparameter MRI and clinical parameters improve the performance of clinically significant prostate cancer diagnosis?

PURPOSE: To establish machine learning(ML) models for the diagnosis of clinically significant prostate cancer (csPC) using multiparameter magnetic resonance imaging (mpMRI), texture analysis (TA), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantitative analysis and clinical parameters and to evaluate the stability of these models in internal and temporal validation. METHODS: The dataset of 194 men was split into training (n = 135) and internal validation (n = 59) cohorts, and a temporal dataset (n = 58) was used for evaluation. The lesions with Gleason score ≥ 7 were defined as csPC. Logistic regression (LR), stepwise regression (SR), classical decision tree (cDT), conditional inference tree (CIT), random forest (RF) and support vector machine (SVM) models were established by combining mpMRI-TA, DCE-MRI and clinical parameters and validated by internal and temporal validation using the receiver operating characteristic (ROC) curve and Delong's method. RESULTS: Eight variables were determined as important predictors for csPC, with the first three related to texture features derived from the apparent diffusion coefficient (ADC) mapping. RF, LR and SR models yielded larger and more stable area under the ROC curve values (AUCs) than other models. In the temporal validation, the sensitivity was lower than that of the internal validation (p < 0.05). There were no significant differences in specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) and AUC (p > 0.05). CONCLUSIONS: Each machine learning model in this study has good classification ability for csPC. Compared with internal validation, the sensitivity of each machine learning model in temporal validation was reduced, but the specificity, accuracy, PPV, NPV and AUCs remained stable at a good level. The RF, LR and SR models have better classification performance in the imaging-based diagnosis of csPC, and ADC texture-related parameters are of the highest importance.

PPARgamma gene C161T substitution alters lipid profile in Chinese patients with coronary artery disease and type 2 diabetes mellitus.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor, which regulates gene expression of the key proteins involved in lipid metabolism, vascular inflammation, and proliferation. PPARgamma may contribute to attenuating atherogenesis and postangioplasty restenosis. PPARgamma C161-->T substitution is associated with a reduced risk of coronary artery disease (CAD). Whether or not the gene substitution alters the risk of CAD in type 2 diabetes mellitus (T2DM) patients remains unclear. METHODS: A total of 556 unrelated subjects from a Chinese Han population, including 89 healthy subjects, 78 CAD patients, 86 T2DM patients, and 303 CAD combined with T2DM patients, were recruited to enroll in this study. PPARgammaC161-->T gene polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphisms. Plasma levels of lipoproteins, apolipoproteins, glucose, and insulin were measured by ELISA or radioimmunoassay (RIA). The coronary artery lesions were evaluated by coronary angiography. RESULTS: The frequency of the 161T allele in CAD, T2DM, and CAD combined with T2DM patients was similar to that observed in the healthy control group. However, in CAD combined with T2DM patients, the group with angiographically documented moderate stenoses had a higher frequency of the 161T allele in comparison to the group with severe stenoses (P < 0.05). Moreover, in CAD with T2DM patients, the triglyceride levels and apoB in CC homozygote carriers were significantly higher than those in "T" allele carriers. CONCLUSIONS: PPARgammaC161-->T genotypes weren't significantly associated with the risk of CAD, but were markedly correlated with severity of disease vessels in patients with CAD and T2DM. Furthermore, PPARgammaC161-->T substitution was associated with an altered adipose, but not glucose metabolism. These results indicate that the PPARgamma C161-->T polymorphism may reduce the risk of severe atherogenesis by modulation of adipose metabolism, especially triglycerides and apoB, in Chinese patients with CAD and T2DM.

[Extracorporeal cardiac shock wave therapy for treatment of coronary artery disease].

OBJECTIVE: To evaluate the feasibility and efficiency of extracorporeal cardiac shock wave therapy (CSWT) for treatment of coronary artery disease. METHODS: Twenty-five patients with 1 - 16 years history of chronic angina pectoris underwent the CSWT. Before and after the treatment, low-dose Dobutamine stress echocardiography and (99)Tc(m)-MIBI myocardial perfusion SPECT were applied to locate the ischemic segments, detect the viable myocardium and evaluate the effect of CSWT. Under the guidance of echocardiography, CSWT was applied in R-wave-triggered manner with low energy (0.09 mJ/mm(2)) at 200 shoots/spot for 9 spots (-1-0-+1 combination). Patients were divided group A and group B. Sixteen patients in group A were applied 9 sessions on 29 segments within 3 month and nine patients in group B were applied 9 sessions on 13 segments within 1 month. Ten chronic angina pectoris patients receiving standard medication served as controls. RESULTS: All patients completed the 9 sessions without procedural complications or adverse effects. CSWT significantly improved symptoms as evaluated by NYHA, Canadian Cardiovascular Society (CCS) class sores, Seattle angina questionnaire (SAQ), 6-min walk and the use of nitroglycerin (P < 0.05). CSWT also improved myocardial perfusion and regional myocardium function as evaluated by rest SPECT and stress peak systolic strain rate (PSSR) (P < 0.01). Myocardial perfusion improvement was more significant in group A compared with group B (1.21 ± 0.86 vs. 0.83 ± 0.80, P < 0.01). All parameters remained unchanged in control group during follow up. CONCLUSION: These preliminary results indicate that CSWT is safe and effective on ameliorating anginal symptoms for chronic angina pectoris patients.

Extracorporeal cardiac shock waves therapy promotes function of endothelial progenitor cells through PI3K/AKT and MEK/ERK signaling pathways.

Previous studies have demonstrated extracorporeal cardiac shock waves (ECSW) could induce angiogenesis and improves myocardial function in patients with coronary heart diseases as a safe, effective, and non-invasive angiogenic approach. The endothelial progenitor cells (EPCs) can migrate to the ischemic myocardium and differentiate into vascular endothelial cells, thus promoting the angiogenesis. Whether ECSW can improve the angiogenic ability of EPCs is unclear. This topic studied the effects of ECSW Therapy on EPCs functions and related signal transduction pathways. The bone marrow-derived EPCs of SD rats were isolated by the density centrifugation method. After treatment with ECSW (500 shots at 0.09 mJ/mm2), the cell viability, anti-apoptosis, migration, and tube formation of EPCs were significantly improved. In addition, the expressions of phosphorylated AKT and ERK were increased after ECSW treatment, the expressions of downstream signaling molecules eNOS and Bcl-2 were also increased, but the expressions of Bax and Caspase3 were decreased. However, these beneficial effects can be inhibited by PI3K/AKT inhibitor LY294002 and MEK/ERK inhibitor PD98059. Together, ECSW can promote the cell viability, migration, and angiogenic ability of EPCs and inhibit the apoptosis of EPCs through the PI3K/AKT and MEK/ERK signaling pathways. The mechanism may be related to promoting the expressions of downstream p-eNOS and anti-apoptotic protein Bcl-2 and inhibiting the expressions of pro-apoptotic protein Bax and Caspase3 through the PI3K/AKT and MEK/ERK signaling pathways.

Improving myocardial fractional flow reserve in coronary atherosclerosis via CX37 gene silence: a preclinical validation study in pigs.

OBJECTIVES: The purpose of this study was to evaluate the effect of CX37 gene silence on myocardial fractional flow reserve (FFR). METHODS: A total of 90 male pigs were randomly divided into saline, mock and 3 different doses (5, 10 and 20 µl) of CX37 viral suspension groups that could induce coronary plaque formation with high-fat diet. After performing myocardial FFR by intravascular ultrasound, different doses of CX37 viral suspension, saline and mock small interfering RNA (siRNA) were transfected into the related coronary. The FFR, the myocardial enzymes and the cardiac structures and functions of the pigs were detected at baseline, 4th, 8th and 12th week after transfection, respectively. RESULTS: Repeated measures analysis of variance comparison showed that the difference in the FFR among the 5 groups was statistically significant (F = 27.0, P < 0.01). Post hoc analysis showed that FFR were highest in the siRNA CX37 group (20 µl), followed by the siRNA CX37 group (10 µl) and the siRNA CX37 group (5 µl), and lowest in the mock and saline groups. Left ventricular end-diastolic diameter was significantly smaller and ejection fraction was obviously higher in the 3 siRNA CX37 groups compared with the untreated groups. CONCLUSIONS: Our study showed that FFR levels increased along with decreased doses of siRNA CX37 lentivirus, indicating that siRNA CX37 lentivirus may reduce the risk of coronary atherosclerosis and provide a potential approach to treat coronary heart disease.

Effect of varying hypoxia reoxygenation times on autophagy of cardiomyocytes.

PURPOSE: To investigate the impact of different hypoxia reoxygenation (HR) times on autophagy of rat cardiomyocytes (H9C2). METHODS: Rat cardiomyocytes were randomly divided into normal control group (group A), hypoxia group (group B), 2 h HR group (group C), 12 h HR group (group D), and 24 h HR group (group E). LC3 II/LC3 I was determined via western blotting, and cell viabilities of cardiomyocytes were measured using methyl thiazolyl tetrazolium (MTT) assay. RESULTS: Cell viabilities in HR model groups were significantly lower than those of group A (P<0.05). LC3 II/LC3 I levels in groups B to D were significantly higher than those of group A (P<0.05), and group D showed the highest LC3 II/LC3 I levels. Cell viabilities in groups B to D were significantly lower than those of group A (P<0.05), with group D showing the lowest cell viabilities (P<0.05). CONCLUSIONS: Hypoxia can induce autophagy in rat cardiomyocytes, which can be further activated by reoxygenation; most notable after 12 h. Hypoxia-induced cell injury can be aggravated by reoxygenation. The lowest cell viability was observed at 12 h after reoxygenation; however, cell viability can be recovered after 24 h.

Burnout is associated with poor recovery of physical performance and low quality of life in patients after their first episode of acute coronary syndrome: A hospital-based prospective cohort study.

OBJECTIVES: "Burnout" is an affective response that is different to depression or anxiety. Studies on the relationship between burnout and physical recovery after acute coronary syndrome (ACS) in the long-term are lacking, hence the rationale of this study. METHODS: Participants were patients after their first onset of ACS divided into the high burnout group (HBG) and low burnout group (LBG) based on the upper quartile of their burnout score on the day before discharge. At three times (1month, 6months, and 1year) after ACS, participants were scheduled for assessment of physical function and quality of life (QoL). To determine the association between burnout and physical function at different times, as well as for burnout and the QoL scores, generalized estimating equations were conducted. RESULTS: Of the 208 participants, 68 participants were assigned to HBG, and 140 were assigned to LBG. QoL scores in both groups at three times showed that HBG had lower scores than LBG (p<0.01). HBG had lower physical scores at three times (z=7.28, p<0.001). Even after adjustment for confounding factors (age, sex, marital status, socioeconomic status, cigarette/alcohol consumption, ACS type, Killip class upon hospital admission), the difference was significant (z=7.78, p<0.001). CONCLUSIONS: Patients with high burnout have poor physical recovery and low quality of life after ACS.

Cardiac shockwave therapy improves myocardial function in patients with refractory coronary artery disease by promoting VEGF and IL-8 secretion to mediate the proliferation of endothelial progenitor cells.

Cardiac shockwave therapy (CSWT) is a potential and effective remedy to promote revascularization in the ischemic myocardium of patients with refractory coronary heart disease (CHD). The technique is both safe and non-invasive; however, the underlying molecular mechanism remains unclear. The aim of this study was to evaluate the efficacy of CSWT in treating CHD patients and investigate a potential mechanism. A total of 26 patients with CHD were enrolled in the study, and CSWT was performed over a 3-month period. The efficacy of CSWT was assessed using several clinical parameters. Peripheral blood (PB) was collected prior to and following treatment. The number of circulating endothelial progenitor cells (EPCs) in the PB was counted using a flow cytometer, and the levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), stromal cell-derived factor 1 and matrix metalloproteinase 9 in the PB were analyzed. Mononuclear cells were isolated from the PB and cultured in vitro. The EPCs and EPC-colony forming units (EPC-CFUs) in the PB mononuclear cell culture were counted using an inverted phase contrast microscope. Following CSWT, the tested clinical parameters were significantly improved. The levels of circulating EPCs, VEGF and IL-8 in the PB were significantly increased, as were the EPCs and EPC-CFUs from the PB mononuclear cell culture. We suggest that EPC proliferation, mediated by VEGF and IL-8 secretion, may be among the potential mechanisms associated with CSWT.

Effect of varying hypoxia reoxygenation times on autophagy of cardiomyocytes

Abstract Purpose: To investigate the impact of different hypoxia reoxygenation (HR) times on autophagy of rat cardiomyocytes (H9C2). Methods: Rat cardiomyocytes were randomly divided into normal control group (group A), hypoxia group (group B), 2 h HR group (group C), 12 h HR group (group D), and 24 h HR group (group E). LC3 II/LC3 I was determined via western blotting, and cell viabilities of cardiomyocytes were measured using methyl thiazolyl tetrazolium (MTT) assay. Results: Cell viabilities in HR model groups were significantly lower than those of group A (P<0.05). LC3 II/LC3 I levels in groups B to D were significantly higher than those of group A (P<0.05), and group D showed the highest LC3 II/LC3 I levels. Cell viabilities in groups B to D were significantly lower than those of group A (P<0.05), with group D showing the lowest cell viabilities (P<0.05). Conclusions: Hypoxia can induce autophagy in rat cardiomyocytes, which can be further activated by reoxygenation; most notable after 12 h. Hypoxia-induced cell injury can be aggravated by reoxygenation. The lowest cell viability was observed at 12 h after reoxygenation; however, cell viability can be recovered after 24 h.

Cardiac shock wave therapy reduces angina and improves myocardial function in patients with refractory coronary artery disease.

BACKGROUND: Safe and effective therapeutic management of refractory coronary artery disease (CAD) in heart patients is critical to enhance cardiovascular function and improve quality of life. Current therapies for refractory CAD are inadequate in ameliorating angina and promoting revascularization of ischemic myocardium. HYPOTHESIS: Cardiac shock wave therapy (CSWT) is a safe and effective noninvasive intervention in the management of patients with refractory CAD. METHODS: The study enrolled 9 male patients age 50 to 70 years (5.11 ± 5.46 years) with a diagnosis of CAD and stent implantation (3.00 ± 2.24 stents). CSWT was carried out for 3 months at 3 intervals during the first week of each month (first, third, and fifth day), for a total of 9 therapies per patient. Dobutamine stress echocardiography and radionuclide angiography identified the myocardial ischemic segments. The effects of CSWT on myocardial perfusion and systolic function were examined. Other outcome measures included myocardial injury enzyme markers, angina scale, nitroglycerin dosage, and cardiopulmonary fitness assessments. RESULTS: Improved myocardial blood flow and regional systolic function (stress peak systolic strain rate - 1.10 to - 1.60 s(-1), P = 0.002) were detected in patients following CSWT. Reductions in creatine kinase (87.89 ± 36.69 to 86.22 ± 35.96 IU/L, P = 0.046), creatine kinase MB (10.89 ± 5.73 to 10.11 ± 5.93 IU/L, P = 0.008), aspartate transaminase (interquartile range [IQR], 28.00 to 27.00 IU/L, P = 0.034) were also found. Angina (Canadian Cardiovascular Society scale IQR 3.0 to 2.0, P = 0.035) and nitroglycerin dose reduction (IQR 3.0 to 1.0 times/wk, P = 0.038) were reported. CONCLUSIONS: This study is a preliminary assessment of CSWT in patients with refractory CAD. We report that CSWT is a noninvasive, effective, and safe intervention in the treatment of refractory CAD.