Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Optimal Velocity Control for a Battery Electric Vehicle Driven by Permanent Magnet Synchronous Motors

The permanent magnet synchronous motor (PMSM) has high efficiency and high torque density. Field oriented control (FOC) is usually used in the motor to achieve maximum efficiency control. In the electric vehicle (EV) application, the PMSM efficiency model, combined with the EV and road load system model, is used to study the optimal energy-saving control strategy, which is significant for the economic operation of EVs. With the help of GPS, IMU, and other information technologies, the road conditions can be measured in advance. Based on this information, the optimal velocity of the EV driven by PMSM can be obtained through the analytical algorithm according to the efficiency model of PMSM and the vehicle dynamic model in simple road conditions. In complex road conditions, considering the dynamic characteristics, the economic operating velocity trajectory of the EV can be obtained through the dynamic programming (DP) algorithm. Simulation and experimental results show that the minimum energy consumption and global energy optimization can be achieved when the EV operates in the economic operation area

Pycnogenol® Induces Browning of White Adipose Tissue through the PKA Signaling Pathway in Apolipoprotein E-Deficient Mice

Beige adipocytes in white adipose tissue (WAT) have received considerable recognition because of their potential protective effect against obesity. Pycnogenol (PYC), extracted from French maritime pine bark, has anti-inflammatory and antioxidant properties and can improve lipid profiles. However, the effect of PYC on obesity has never been explored. In this study, we investigated the effects of PYC on obesity and WAT browning in apolipoprotein E- (ApoE-) deficient mice. The results showed that PYC treatment clearly reversed body weight and the mass of eWAT gain resulting from a high-cholesterol and high-fat diet (HCD), but no difference in food intake. The morphology results showed that the size of the adipocytes in the PYC-treated mice was obviously smaller than that in the HCD-fed mice. Next, we found that PYC upregulated the expression of genes related to lipolysis (ATGL and HSL), while it decreased the mRNA level of PLIN1. PYC significantly increased the expression of UCP1 and other genes related to beige adipogenesis. Additionally, PYC increased the expression of proteins related to the protein kinase A (PKA) signaling pathway. The findings suggested that PYC decreased obesity by promoting lipolysis and WAT browning. Thus, PYC may be a novel therapeutic target for obesity

Effects of sodium–glucose cotransporter 2 inhibitors in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients: A meta‐analysis of randomized controlled trials

Abstract Aims/Introduction In the present meta‐analysis, we aimed to determine the effects of sodium–glucose cotransporter 2 inhibitor (SGLT‐2i) in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients. Materials and Methods Randomized controlled trials were identified by searching the PubMed, Embase and Cochrane Library databases published before September 2017. The intervention group received SGLT‐2i as add‐on treatment to insulin therapy, and the control group received placebos in addition to insulin. We assessed pooled data, including weighted mean differences and 95% confidence intervals (CIs) using a random‐effects model. Results A total of 10 randomized controlled trials (n = 5,159) were eligible. The weighted mean differences for systolic blood pressure and diastolic blood pressure were −3.17 mmHg (95% CI −4.53, −1.80, I2 = 0%) and −1.60 mmHg (95% CI −2.52, −0.69, I2 = 0%) in the intervention groups. Glycosylated hemoglobin, fasting plasma glucose, postprandial glucose and daily insulin were also lower in the intervention groups, with relative weighted mean differences of −0.49% (95% CI −0.71, −0.28%, I2 = 92%), −1.10 mmol/L (95% CI −1.69, −0.51 mmol/L, I2 = 84%), −3.63 mmol/L (95% CI −4.36, −2.89, I2 = 0%) and −5.42 IU/day (95% CI −8.12, −2.72, I2 = 93%). The transformations of uric acid and bodyweight were −26.16 μmol/L (95% CI −42.14, −10.17, I2 = 80%) and −2.13 kg (95% CI −2.66, −1.60, I2 = 83%). The relative risk of hypoglycemia was 1.09 (95% CI 1.02, 1.17, P < 0.01). The relative risks of urinary tract and genital infection were 1.29 (95% CI 1.03, 1.62, P = 0.03) and 5.25 (95% CI 3.55, 7.74, P < 0.01). Conclusions The results showed that in the intervention group, greater reductions were achieved for blood pressure, glucose control, uric acid and bodyweight. This treatment regimen might therefore provide beneficial effects on the occurrence and development of cardiovascular events

A Five-Gene Signature for Recurrence Prediction of Hepatocellular Carcinoma Patients

Background. Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies with poor prognosis. There are many selectable treatments with good prognosis in Barcelona Clinic Liver Cancer- (BCLC-) 0, A, and B HCC patients, but the most crucial factor affecting survival is the high recurrence rate after treatments. Therefore, it is of great significance to predict the recurrence of BCLC-0, BCLC-A, and BCLC-B HCC patients. Aim. To develop a gene signature to enhance the prediction of recurrence among HCC patients. Materials and Methods. The RNA expression data and clinical data of HCC patients were obtained from the Gene Expression Omnibus (GEO) database. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen primarily prognostic biomarkers in GSE14520. Multivariate Cox regression analysis was introduced to verify the prognostic role of these genes. Ultimately, 5 genes were demonstrated to be related with the recurrence of HCC patients and a gene signature was established. GSE76427 was adopted to further verify the accuracy of gene signature. Subsequently, a nomogram based on gene signature was performed to predict recurrence. Gene functional enrichment analysis was conducted to investigate the potential biological processes and pathways. Results. We identified a five-gene signature which performs a powerful predictive ability in HCC patients. In the training set of GSE14520, area under the curve (AUC) for the five-gene predictive signature of 1, 2, and 3 years were 0.813, 0.786, and 0.766. Then, the relative operating characteristic (ROC) curves of five-gene predictive signature were verified in the GSE14520 validation set, the whole GSE14520, and GSE76427, showed good performance. A nomogram comprising the five-gene signature was built so as to show a good accuracy for predicting recurrence-free survival of HCC patients. Conclusion. The novel five-gene signature showed potential feasibility of recurrence prediction for early-stage HCC