Summary
Background
Obesity, a comorbid medical condition, is usually observed in patients with established coronary artery disease. Paradoxically, patients with a higher body mass index (BMI) usually ...have better clinical outcomes after coronary revascularization.
Methods
We searched five online databases through December 2017. We identified studies reporting the rate of all‐cause mortality or cardiovascular‐related outcomes among patients after coronary revascularization with percutaneous coronary intervention or coronary artery bypass graft based on various BMI categories. Network meta‐analysis was performed using Bayesian methods.
Results
Sixty‐five records involving 865,774 participants were included in our study. A U‐shaped association was observed across BMI categories for all‐cause mortality. Using normal weight as the reference, all‐cause mortality was increased for (relative risk RR: 2.4; 95% credibility interval CrI: 2.1–2.7) patients with underweight, whereas it was lowered in patients with overweight, obese, and severely obese. This association remained significant in many subgroups. We also observed that the risk of major adverse cardiovascular events (MACE) was lowest among patients with overweight. Furthermore, patients with underweight were associated with greater risks of myocardial infarction (RR: 1.9; 95% CrI: 1.4–2.5), cardiovascular‐related mortality (RR: 2.8; 95% CrI: 1.6–4.7), stroke (RR: 2.0; 95% CrI: 1.3–3.3) and heart failure (RR: 1.7; 95% CrI: 1.1–2.7) compared with normal weight patients; no significant association was observed among individuals with higher BMI.
Conclusions
The ‘obesity paradox’ does exist in patients after coronary revascularization, especially for patients with post‐percutaneous coronary intervention. All‐cause mortality in patients with high BMI is significantly lower compared with patients with normal weight. Furthermore, patients with underweight experience higher rates of cardiovascular outcomes compared with patients with normal weight.
Alternative splicing (AS) allows generation of cell type–specific mRNA transcripts and contributes to hallmarks of cancer. Genome‐wide analysis for AS in human hepatocellular carcinoma (HCC), ...however, is limited. We sought to obtain a comprehensive AS landscape in HCC and define tumor‐associated variants. Single‐molecule real‐time long‐read RNA sequencing was performed on patient‐derived HCC cells, and presence of splice junctions was defined by SpliceMap‐LSC‐IDP algorithm. We obtained an all‐inclusive map of annotated AS variants and further discovered 362 alternative spliced variants that are not previously reported in any database (neither RefSeq nor GENCODE). They were mostly derived from intron retention and early termination codon with an in‐frame open reading frame in 81.5%. We corroborated many of these predicted unannotated and annotated variants to be tumor specific in an independent cohort of primary HCC tumors and matching nontumoral liver. Using the combined Sanger sequencing and TaqMan junction assays, unique and common expressions of spliced variants including enzyme regulators (ARHGEF2, SERPINH1), chromatin modifiers (DEK, CDK9, RBBP7), RNA‐binding proteins (SRSF3, RBM27, MATR3, YBX1), and receptors (ADRM1, CD44v8‐10, vitamin D receptor, ROR1) were determined in HCC tumors. We further focused functional investigations on ARHGEF2 variants (v1 and v3) that arise from the common amplified site chr.1q22 of HCC. Their biological significance underscores two major cancer hallmarks, namely cancer stemness and epithelial‐to‐mesenchymal transition–mediated cell invasion and migration, although v3 is consistently more potent than v1. Conclusion: Alternative isoforms and tumor‐specific isoforms that arise from aberrant splicing are common during the liver tumorigenesis. Our results highlight insights gained from the analysis of AS in HCC.
An inverted organic solar cell, consisting of an ultrathin Ca layer for electron transport, the blend of poly(3-hexylthiophene) and 1-(3-methoxycarbonyl)-propyl-1-phenyl-(6,6)C
61 for photon ...absorption, and a MoO
3 layer for hole transport, is optimized. The insertion of MoO
3 layer between photoactive layer and Ag anode has been demonstrated to improve both the photocurrent and the fill factor. By optical modeling and experiment, we find that the MoO
3 layer also functions as an optical spacer for thin devices. For the optimized device with an active layer thickness of 85
nm, Ca thickness of 0.5
nm, and MoO
3 layer thickness of 5
nm, a maximum power conversion efficiency of 3.86% was achieved.
Using a novel method of isochronous mass spectrometry, the masses of ^{62}Ge, ^{64}As, ^{66}Se, and ^{70}Kr are measured for the first time, and the masses of ^{58}Zn, ^{61}Ga, ^{63}Ge, ^{65}As, ...^{67}Se, ^{71}Kr, and ^{75}Sr are redetermined with improved accuracy. The new masses allow us to derive residual proton-neutron interactions (δV_{pn}) in the N=Z nuclei, which are found to decrease (increase) with increasing mass A for even-even (odd-odd) nuclei beyond Z=28. This bifurcation of δV_{pn} cannot be reproduced by the available mass models, nor is it consistent with expectations of a pseudo-SU(4) symmetry restoration in the fp shell. We performed ab initio calculations with a chiral three-nucleon force (3NF) included, which indicate the enhancement of the T=1 pn pairing over the T=0 pn pairing in this mass region, leading to the opposite evolving trends of δV_{pn} in even-even and odd-odd nuclei.
Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been ...termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
A coupled volume-of-fluid and level set (VOSET) method, which combines the advantages and overcomes the disadvantages of VOF and LS methods, is presented for computing incompressible two-phase flows. ...In this method VOF method is used to capture interfaces, which can conserve the mass and overcome the disadvantage of nonconservation of mass in LS method. An iterative geometric operation proposed by author is used to calculate the level set function
ϕ near interfaces, which can be applied to compute the accurate curvature
κ and smooth the discontinuous physical quantities near interfaces. By using the level set function
ϕ the disadvantages of VOF method, inaccuracy of curvature and bad smoothness of discontinuous physical quantities near interfaces, can be overcome. Finally the computing results made with VOSET method are compared with those made with VOF and LS methods.
Two α/β-fold hydrolases, KARRIKIN INSENSITIVE2 (KAI2) and Arabidopsis thaliana DWARF14 (AtD14), are necessary for responses to karrikins (KARs) and strigolactones (SLs) in Arabidopsis (Arabidopsis ...thaliana). Although KAI2 mediates responses to KARs and some SL analogs, AtD14 mediates SL but not KAR responses. To further determine the specificity of these proteins, we assessed the ability of naturally occurring deoxystrigolactones to inhibit Arabidopsis hypocotyl elongation, regulate seedling gene expression, suppress outgrowth of secondary inflorescences, and promote seed germination. Neither 5-deoxystrigol nor 4-deoxyorobanchol was active in KAI2-dependent seed germination or hypocotyl elongation, but both were active in AtD14-dependent hypocotyl elongation and secondary shoot growth. However, the nonnatural enantiomer of 5-deoxystrigol was active through KAI2 in growth and gene expression assays. We found that the four stereoisomers of the SL analog GR24 had similar activities to their deoxystrigolactone counterparts. The results suggest that AtD14 and KAI2 exhibit selectivity to the butenolide D ring in the 2'R and 2'S configurations, respectively. However, we found, for nitrile-debranone (CN-debranone, a simple SL analog), that the 2'R configuration is inactive but that the 2'S configuration is active through both AtD14 and KAI2. Our results support the conclusion that KAI2-dependent signaling does not respond to canonical SLs. Furthermore, racemic mixtures of chemically synthesized SLs and their analogs, such as GR24, should be used with caution because they can activate responses that are not specific to naturally occurring SLs. In contrast, the use of specific stereoisomers might provide valuable information about the specific perception systems operating in different plant tissues, parasitic weed seeds, and arbuscular mycorrhizae.
Venous thromboembolism is a significant cause of mortality
, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran ...Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought.
We report the superconductivity of PbTaS2 single crystals with the centrosymmetric structure. The systematic measurements of magnetization, electric transport and specific heat indicate that PbTaS2 ...is a weakly coupled type-II superconductor with transition temperature T c ∼ 2.6 K. Furthermore, the band structure calculations predicted four nodal lines near the Fermi energy with “drumhead-like” surface states, suggesting centrosymmetric PbTaS2 is a candidate of topological nodal line semimetals. These results demonstrate that PbTaS2 may open up another avenue for further exploring the properties of superconductivity and topological nodal-line states.
Using geometric phases to realize noise-resilient quantum computing is an important method to enhance the control fidelity. In this work, we experimentally realize a universal nonadiabatic geometric ...quantum gate set in a superconducting qubit chain. We characterize the realized single- and two-qubit geometric gates with both quantum process tomography and randomized benchmarking methods. The measured average fidelities for the single-qubit rotation gates and two-qubit controlled-Z gate are 0.9977(1) and 0.977(9), respectively. Besides, we also experimentally demonstrate the noise-resilient feature of the realized single-qubit geometric gates by comparing their performance with the conventional dynamical gates with different types of errors in the control field. Thus, our experiment proves a way to achieve high-fidelity geometric quantum gates for robust quantum computation.
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