Long-term antiplatelet therapy in medically managed non-ST-segment elevation acute coronary syndromes: The EPICOR Asia study

OBJECTIVES: To describe long-term antithrombotic management patterns (AMPs) in medically managed Asian patients with non-ST-segment myocardial infarction (NSTEMI) or unstable angina (UA). BACKGROUND: Current guidelines support an early invasive strategy in NSTEMI and UA patients, but many are medically managed, and data are limited on long-term AMPs in Asia. METHODS: Data were analyzed from medically managed NSTEMI and UA patients included in the prospective, observational EPICOR Asia study (NCT01361386). Survivors to hospital discharge were enrolled (June 2011 to May 2012) from 8 countries/regions across Asia. Baseline characteristics and AMP use up to 2 years post-discharge were collected. Outcomes were major adverse cardiovascular events (MACE: myocardial infarction, ischemic stroke, and death) and bleeding. RESULTS: Among 2289 medically managed patients, dual antiplatelet therapy (DAPT) use at discharge was greater in NSTEMI than in UA patients (81.8% vs 65.3%), and was significantly associated with male sex, positive cardiac markers, and prior cardiovascular medications (p < 0.0001). By 2 years, 57.9% and 42.6% of NSTEMI and UA patients, respectively, were on DAPT. On multivariable Cox regression analysis, risk of MACE at 2 years was most significantly associated with older age (HR [95% CI] 1.85 [1.36, 2.50]), diagnosis of NSTEMI vs UA (1.96 [1.47, 2.61]), and chronic renal failure (2.14 [1.34, 3.41]), all p ≤ 0.001. Risk of bleeding was most significantly associated with region (East Asia vs Southeast/South Asia) and diabetes. CONCLUSIONS: Approximately half of all patients were on DAPT at 2 years. MACE were more frequent in NSTEMI than UA patients during follow-up

The association of long-term trajectories of BMI, its variability, and metabolic syndrome: a 30-year prospective cohort study

Background Limited data exists on how early-life weight changes relate to metabolic syndrome (MetS) risk in midlife. This study examines the association between long-term trajectories of body mass index (BMI), its variability, and MetS risk in Chinese individuals. Methods In the Hanzhong Adolescent Hypertension study (March 10, 1987–June 3, 2017), 1824 participants with at least five BMI measurements from 1987 to 2017 were included. Using group-based trajectory modeling, different BMI trajectories were identified. BMI variability was assessed through standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Logistic regression analyzed the relationship between BMI trajectory, BMI variability, and MetS occurrence in midlife (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02734472). Findings BMI trajectories were categorized as low-increasing (34.4%), moderate-increasing (51.8%), and high-increasing (13.8%). Compared to the low-increasing group, the odds ratios (ORs) [95% CIs] for MetS were significantly higher in moderate (4.27 [2.63–6.91]) and high-increasing groups (13.11 [6.30–27.31]) in fully adjusted models. Additionally, higher BMI variabilities were associated with increased MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 2.30 [2.02–2.62], 1.22 [1.19–1.26], and 4.29 [3.38–5.45]). Furthermore, BMI trajectories from childhood to adolescence were predictive of midlife MetS, with ORs in moderate (1.49 [1.00–2.23]) and high-increasing groups (2.45 [1.22–4.91]). Lastly, elevated BMI variability in this period was also linked to higher MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 1.24 [1.08–1.42], 1.00 [1.00–1.01], and 1.21 [1.05–1.38]). Interpretation Our study suggests that both early-life BMI trajectories and BMI variability could be predictive of incident MetS in midlife

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Numerical Investigation on the Electrical Performance Optimization of a Tubular Thermoelectric Generator for Waste Heat Recovery

In the waste heat utilization of automobile exhaust, the tubular thermoelectric generator (TTEG) has structural advantages compared with the flat-plate thermoelectric generator. A kind of TTEG that is composed of Bi0.5Sb1.5Te3 and Ni conical rings alternately attracts researchers' attention, and it generates electrical power based on the transverse thermoelectric effect. However, the electrical performance of such TTEG still needs to be improved for industrial utilization. In this study, the performance of TTEG was optimized through numerical simulation by changing its related structural parameters, including the tilt angle, the thickness of the conical ring, and the relative content of Ni. It is confirmed that the optimal tilt angle with maximum open-circuit voltage (OCV) is 27.3°; on this basis, it is found that a thinner thickness corresponds to a larger OCV; furthermore, when using a conical rings’ thickness of 0.75 mm and increasing the relative content of Ni in the Bi0.5Sb1.5Te3/Ni layered pair from 10% to 90%, the OCV decreases from 198mV to 105mV while the power density increases from 413W/m2 to 1350W/m2. It is believed that these findings can help to develop TTEGs with better electrical performance

Identification of SPRYD4 as a tumour suppressor predicts prognosis and correlates with immune infiltration in cholangiocarcinoma

Abstract Cholangiocarcinoma (CCA) is an aggressive solid tumour with a 5-year survival rate ranging from 7% to 20%. It is, therefore, urgent to identify novel biomarkers and therapeutic targets to improve the outcomes of patients with CCA. SPRY-domain containing protein 4 (SPRYD4) contains SPRY domains that modulate protein–protein interaction in various biological processes; however, its role in cancer development is insufficiently explored. This study is the first to identify that SPRYD4 is downregulated in CCA tissues using multiple public datasets and a CCA cohort. Furthermore, the low expression of SPRYD4 was significantly associated with unfavourable clinicopathological characteristics and poor prognosis in patients with CCA, indicating that SPRYD4 could be a prognosis indicator of CCA. In vitro experiments revealed that SPRYD4 overexpression inhibited CCA cells proliferation and migration, whereas the proliferative and migratory capacity of CCA cells was enhanced after SPRYD4 deletion. Moreover, flow cytometry showed that SPRYD4 overexpression triggered the S/G2 cell phase arrest and promoted apoptosis in CCA cells. Furthermore, the tumour-inhibitory effect of SPRYD4 was validated in vivo using xenograft mouse models. SPRYD4 also showed a close association with tumour-infiltrating lymphocytes and important immune checkpoints including PD1, PD-L1 and CTLA4 in CCA. In conclusion, this study elucidated the role of SPRYD4 during CCA development and highlighted SPRYD4 as a novel biomarker and tumour suppressor in CCA

Epileptic Seizure Prediction Using Deep Neural Networks Via Transfer Learning and Multi-Feature Fusion

International audienceEpilepsy is one of the most common neurological diseases, which can seriously affect the patient’s psychological well-being and quality of life. An accurate and reliable seizure prediction system can generate alarm before epileptic seizures to provide patients and their caregivers with sufficient time to take appropriate action. This study proposes an efficient seizure prediction system based on deep learning in order to anticipate the onset of the seizure as early as possible. Handcrafted features extracted based on the prior knowledge and hidden deep features are complementarily fused through the feature fusion module, and then the hybrid features are fed into the multiplicative long short-term memory (MLSTM) to explore the temporal dependency in EEG signals. A one-dimensional channel attention mechanism is implemented to emphasize the more representative information in the multi-channel output of the MLSTM. Finally, a transfer learning strategy is proposed to transfer the weights of the base model trained on the EEG data of all patients to the target patient model, and the latter is then continuously trained using the EEG data of the target patient. The proposed method achieves an average sensitivity of 95.56% and a false positive rate (FPR) of 0.27/h on the SWEC-ETHZ intracranial EEG data. For the more challenging CHB-MIT scalp EEG database, an average sensitivity of 89.47% and a FPR of 0.34/h are obtained. Experimental results demonstrate that the proposed method has good robustness and generalization ability in both intracranial and scalp EEG signals

Electrophysiological brain imaging based on simulation-driven deep learning in the context of epilepsy

International audienceIdentifying the location, the spatial extent and the electrical activity of distributed brain sources in the context of epilepsy through ElectroEncephaloGraphy (EEG) recordings is a challenging task because of the highly ill-posed nature of the underlying Electrophysiological Source Imaging (ESI) problem. To guarantee a unique solution, most existing ESI methods pay more attention to solve this inverse problem by imposing physiological constraints. This paper proposes an efficient ESI approach based on simulation-driven deep learning. Epileptic High-resolution 256-channels scalp EEG (Hr-EEG) signals are simulated in a realistic manner to train the proposed patient-specific model. More particularly, a computational neural mass model developed in our team is used to generate the temporal dynamics of the activity of each dipole while the forward problem is solved using a patient-specific three-shell realistic head model and the boundary element method. A Temporal Convolutional Network (TCN) is considered in the proposed model to capture local spatial patterns. To enable the model to observe the EEG signals from different scale levels, the multi-scale strategy is leveraged to capture the overall features and fine-grain features by adjusting the convolutional kernel size. Then, the Long Short-Term Memory (LSTM) is used to extract temporal dependencies among the computed spatial features. The performance of the proposed method is evaluated through three different scenarios of realistic synthetic interictal Hr-EEG data as well as on real interictal Hr-EEG data acquired in three patients with drug-resistant partial epilepsy, during their presurgical evaluation. A performance comparison study is also conducted with two other deep learning-based methods and four classical ESI techniques. The proposed model achieved a Dipole Localization Error (DLE) of 1.39 and Normalized Hamming Distance (NHD) of 0.28 in the case of one patch with SNR of 10 dB. In the case of two uncorrelated patches with an SNR of 10 dB, obtained DLE and NHD were respectively 1.50 and 0.28. Even in the more challenging scenario of two correlated patches with an SNR of 10 dB, the proposed approach still achieved a DLE of 3.74 and an NHD of 0.43. The results obtained on simulated data demonstrate that the proposed method outperforms the existing methods for different signal-to-noise and source configurations. The good behavior of the proposed method is also confirmed on real interictal EEG data. The robustness with respect to noise makes it a promising and alternative tool to localize epileptic brain areas and to reconstruct their electrical activities from EEG signals

3D geophysical characterization of the Sulu–Dabie orogen and its environs

In an effort to further advance our understanding of the evolution of the Sulu–Dabie orogen and its complex interactions with the Tanlu fault, and to tackle non-unique geophysical interpretations, we characterize the 3D geological structures and dynamics of the Sulu–Dabie orogen and its environs using various data processing and interpretation of a very large suite of gravimetric, magnetic, magnetotelluric, geothermal, and seismic data. We have modeled regional geothermal field of the lithosphere by incorporating both surface heat flow and Curie-point depths inverted from magnetic anomalies. This gives better constraints on regional thermal lithospheric thicknesses, which are found to be small (mostly between 55 and 95 km), conformable to other geophysical results, and supportive of lithospheric de-rooting. From regional geotherms and Bouguer gravity anomalies, we assess depths, temperatures and heat flow of the Moho, and find that mantle contributes a little over 70% of the total surface heat flow. Large differences in thermal lithospheric thicknesses and geothermal activities are found between the Sulu and the Dabie segments of the Sulu–Dabie orogen. These differences result, at least partially, from large vertical differential movement at the lithospheric scale across the Tanlu fault, as seen from both reflection seismic sections and gravity anomalies. Within the Sulu–Dabie orogenic belt, reduction to the pole and 3D analytic signal analysis on magnetic anomalies reveal that positive magnetic anomalies associated with this belt are most due to gneiss, migmatite and Mesozoic granites, whereas ultrahigh-pressure metamorphic zones show weak or negative magnetic anomalies. This interesting magnetic contrast between ultrahigh-pressure metamorphic rocks and surrounding rocks suggests that ultrahigh-pressure metamorphic minerals are either only weakly magnetized, or possibly retrograded and remagnetized over a long time span or in a period of reversed magnetization. High-pressure metamorphic minerals of blueschist facies appear to be less susceptive than ultrahigh-pressure metamorphic minerals. Highlights ► Ultrahigh-pressure metamorphic rocks are correlated to weak or negative magnetic anomalies. ► Regional surface heat flow measurements are negatively correlated with Curie-point depths. ► Geothermal field modeling is constrained by both surface heat flow and Curie-point depths. ► Thermal lithosphere is thin and mantle contributes to over 70% of the total surface heat flow. ► Large-scale and persistent late Mesozoic uplift and exhumation occurred east of the Tanlu fault

Combined Value of Red Blood Cell Distribution Width and Global Registry of Acute Coronary Events Risk Score for Predicting Cardiovascular Events in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Global Registry of Acute Coronary Events (GRACE) risk score and red blood cell distribution width (RDW) content can both independently predict major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). We investigated the combined predictive value of RDW and GRACE risk score for cardiovascular events in patients with ACS undergoing percutaneous coronary intervention (PCI) for the first time. We enrolled 480 ACS patients. During a median follow-up time of 37.2 months, 70 (14.58%) patients experienced MACEs. Patients were divided into tertiles according to the baseline RDW content (11.30-12.90, 13.00-13.50, 13.60-16.40). GRACE score was positively correlated with RDW content. Multivariate Cox analysis showed that both GRACE score and RDW content were independent predictors of MACEs (hazard ratio 1.039; 95% confidence interval [CI] 1.024-1.055; p < 0.001; 1.699; 1.294-2.232; p < 0.001; respectively). Furthermore, Kaplan-Meier analysis demonstrated that the risk of MACEs increased with increasing RDW content (p < 0.001). For GRACE score alone, the area under the receiver operating characteristic (ROC) curve for MACEs was 0.749 (95% CI: 0.707-0.787). The area under the ROC curve for MACEs increased to 0.805 (0.766-0.839, p = 0.034) after adding RDW content. The incremental predictive value of combining RDW content and GRACE risk score was significantly improved, also shown by the net reclassification improvement (NRI = 0.352, p < 0.001) and integrated discrimination improvement (IDI = 0.023, p = 0.002). Combining the predictive value of RDW and GRACE risk score yielded a more accurate predictive value for long-term cardiovascular events in ACS patients who underwent PCI as compared to each measure alone

Pioglitazone stabilizes atherosclerotic plaque by regulating the Th17/Treg balance in AMPK-dependent mechanisms

Abstract Background Pioglitazone (PIO), a thiazolidinediones drug, is a well-known anti-diabetic medicine, but its anti-atherosclerotic effects remain controversial. Thus it is important to investigate the effects of PIO on atherogenesis and the relevant mechanisms. Methods For in vitro studies, primary cultured or AMP-activated protein kinase (AMPK) inhibited splenocytes were treated with oxidized low density lipoprotein (ox-LDL) or ox-LDL plus PIO. Percentage of T helper 17 (Th17) and regulatory T (Treg) cells were determined by flow cytometry. Expression of AMPK, interleukin-17 (IL-17) and forkhead box P3 (FoxP3) were detected by Western blots. For in vivo studies, apolipoprotein E–deficient (apoE−/−) mice fed with western diet were treated with PIO or vehicle for 8 weeks respectively. Percentage of Th17 and Treg cells in spleen were measured by immunohistochemical analysis. The atherosclerotic lesions were analyzed using oil red O staining, and collagen types I and III in atherosclerotic lesions were stained by Sirius red. Expression of IL-17 and FoxP3 were determined by quantitative polymerase chain reaction. Results In cultured primary splenocytes, PIO dramatically inhibited Th17 and raised Treg. Intriguingly, pharmacological and genetic AMPK inhibitions abolished PIO-induced Treg elevation and Th17 inhibition. Moreover, PIO significantly induced AMPK phosphorylation, decreased IL-17+ and increased FoxP3+ cells in spleen of apoE−/− mice. Finally, PIO did not alter plaque area, but intriguingly, stabilized atherosclerotic plaque through collagen induction in apoE−/− mice. PIO treatment also improved Th17/Treg balance in atherosclerotic lesions. Conclusions PIO exhibits anti-atherosclerotic effects for stabilization of atherosclerotic plaque through regulating the Th17/Treg balance in an AMPK-dependent manner