Search

Abstract Background Pathogenic missense variants in the dystrophin (DMD) gene are rarely reported in dystrophinopathies. Most DMD missense variants are of uncertain significance and their pathogenicity interpretation remains complicated. We aimed to investigate whether DMD missense variants would cause aberrant splicing and re-interpret their pathogenicity based on mRNA and protein studies. Methods Nine unrelated patients who had an elevated serum creatine kinase level with or without muscle weakness were enrolled. They underwent a detailed clinical, imaging, and pathological assessment. Routine genetic testing and muscle-derived mRNA and protein studies of dystrophin and sarcoglycan genes were performed in them. Results Three of the 9 patients presented with a Duchenne muscular dystrophy (DMD) phenotype and the remaining 6 patients had a suspected diagnosis of Becker muscular dystrophy (BMD) or sarcoglycanopathy based on their clinical and pathological characteristics. Routine genetic testing detected only 9 predicted DMD missense variants in them, of which 6 were novel and interpreted as uncertain significance. Muscle-derived mRNA studies of sarcoglycan genes didn’t reveal any aberrant transcripts in them. Dystrophin mRNA studies confirmed that 3 predicted DMD missense variants (c.2380G > C, c.4977C > G, and c.5444A > G) were in fact splicing and frameshift variants due to aberrant splicing. The 9 DMD variants were re-interpreted as pathogenic or likely pathogenic based on mRNA and protein studies. Therefore, 3 patients with DMD splicing variants and 6 patients with confirmed DMD missense variants were diagnosed with DMD and BMD, respectively. Conclusion Our study highlights the importance of muscle biopsy and aberrant splicing for clinical and genetic interpretation of uncertain DMD missense variants.

Abstract A drug conjugate consists of a cytotoxic drug bound via a linker to a targeted ligand, allowing the targeted delivery of the drug to one or more tumor sites. This approach simultaneously reduces drug toxicity and increases efficacy, with a powerful combination of efficient killing and precise targeting. Antibody‒drug conjugates (ADCs) are the best-known type of drug conjugate, combining the specificity of antibodies with the cytotoxicity of chemotherapeutic drugs to reduce adverse reactions by preferentially targeting the payload to the tumor. The structure of ADCs has also provided inspiration for the development of additional drug conjugates. In recent years, drug conjugates such as ADCs, peptide‒drug conjugates (PDCs) and radionuclide drug conjugates (RDCs) have been approved by the Food and Drug Administration (FDA). The scope and application of drug conjugates have been expanding, including combination therapy and precise drug delivery, and a variety of new conjugation technology concepts have emerged. Additionally, new conjugation technology-based drugs have been developed in industry. In addition to chemotherapy, targeted therapy and immunotherapy, drug conjugate therapy has undergone continuous development and made significant progress in treating lung cancer in recent years, offering a promising strategy for the treatment of this disease. In this review, we discuss recent advances in the use of drug conjugates for lung cancer treatment, including structure-based drug design, mechanisms of action, clinical trials, and side effects. Furthermore, challenges, potential approaches and future prospects are presented.

To solve the problems that the network intrusion detection system in the Internet of things couldn’t identify new attacks and has limited flexibility, a network intrusion detection system based on honeyfarm was proposed, which could effectively identify abnormal traffic and have continuous learning ability.Firstly, considering the characteristics of the convolutional block attention module, an abnormal traffic detection model was developed, focusing on both channel and spatial dimensions, to enhance the model’s recognition abilities.Secondly, a model training scheme utilizing federated learning was employed to enhance the model’s generalization capabilities.Finally, the abnormal traffic detection model at the edge nodes was continuously updated and iterated based on the honeyfarm, so as to improve the system’s accuracy in recognizing new attack traffic.The experimental results demonstrate that the proposed system not only effectively detects abnormal behavior in network traffic, but also continually enhances performance in detecting abnormal traffic.

Abstract This letter presents a Ku‐band horizontally polarized (HP) omnidirectional antenna based on single‐ridge trapezoidal waveguide (STW). Four groups of longitudinal slots are etched on a pair of back‐to‐back arranged STWs to achieve the HP omnidirectional radiation performance. The number and distribution of each radiation slot group are optimized to reduce the gain variation. An out‐of‐phase stripline power divider cascaded with two probe‐based vertical power dividers is used to excite all radiating slots in a series‐parallel hybrid structure, which helps to enhance the boresight radiation bandwidth. For demonstration, a prototype covering 14.5 to 15.5 GHz is designed, fabricated, and measured. Experimental results show that the good impedance matching (|S11|←14 dB) and the measured out‐of‐roundness for the omnidirectional radiation pattern are less than 4.4 dB within the desired frequency band. High gain and wideband omnidirectional radiation characteristics can provide a wide range of coverage and good signal transmission performance for outdoor wireless communication systems.

Abstract Background Daylength is a key seasonal cue for animals and plants. In cereals, photoperiodic responses are a major adaptive trait, and alleles of clock genes such as PHOTOPERIOD1 (PPD1) and EARLY FLOWERING3 (ELF3) have been selected for in adapting barley and wheat to northern latitudes. How monocot plants sense photoperiod and integrate this information into growth and development is not well understood. Results We find that phytochrome C (PHYC) is essential for flowering in Brachypodium distachyon. Conversely, ELF3 acts as a floral repressor and elf3 mutants display a constitutive long day phenotype and transcriptome. We find that ELF3 and PHYC occur in a common complex. ELF3 associates with the promoters of a number of conserved regulators of flowering, including PPD1 and VRN1. Consistent with observations in barley, we are able to show that PPD1 overexpression accelerates flowering in short days and is necessary for rapid flowering in response to long days. PHYC is in the active Pfr state at the end of the day, but we observe it undergoes dark reversion over the course of the night. Conclusions We propose that PHYC acts as a molecular timer and communicates information on night-length to the circadian clock via ELF3.

With the emergence and development of application requirements such as data analysis and publishing, it is particularly important to use differential privacy protection technology to provide more reliable, secure, and compliant datasets for research in the field of children’s health. This paper focuses on the differential privacy protection of the ultrasound examination health dataset of adolescents in southern Texas from three aspects: differential privacy protection with output perturbation on basic statistics, publication of differential privacy marginal histogram and synthesized data, and a machine learning differential privacy learning algorithm. Firstly, differential privacy protection results with output perturbation show that Laplace and Gaussian mechanisms for numerical data, as well as the exponential mechanism for non-numerical data, can achieve the goal of protecting privacy. The exponential mechanism provides higher privacy protection. Secondly, a differential privacy marginal histogram with four attributes can be obtained with an appropriate privacy budget that approximates the marginal histogram of the original data. In order to publish synthetic data, we construct a synthetic query to obtain the corresponding differential privacy histogram for two attributes. Further, a synthetic dataset can be constructed by following the data distribution of the original dataset and the quality of the synthetic data publication can also be evaluated by the mean square error and error rate. Finally, consider a differential privacy logistic regression model under machine learning to predict whether children have fatty liver in binary classification tasks. The experimental results show that the model combined with quadratic perturbation has better accuracy and privacy protection. This paper can provide differential privacy protection models under different demands, which provides important data release and analysis options for data managers and research organizations, in addition to enriching the research on child health data releasing and mining.

Aim: To evaluate the costs and consequences of two front-line atrial fibrillation (AF) treatments from Chinese healthcare system perspective: radiofrequency catheter ablation (RFCA) using ThermoCool SmartTouch Catheter guided by Ablation Index (STAI), in comparison to antiarrhythmic drugs (AADs). Patients & methods: We simulated clinical and economic consequences for AF patients initially receiving STAI or AADs using a short-term decision tree model leading to a 10-year long-term Markov model. The model projected both clinical consequences and costs associated with, among others, AF, heart failure (HF), strokes, and deaths due to AF or AF related complications. Data informing the models included combination of a local real-world study and published clinical studies. Results: STAI was advantageous versus AADs on all 4 main clinical outcomes evaluated; AF: 25.83% lower (12.84% vs 38.67%), HF: 2.22% lower (1.33% vs 3.55%), stroke or post stroke: 1.82% lower (10.00% vs 11.82%) and deaths due to AF or AF related complications: 0.64% lower (4.11% vs 4.75%). The average total cost per patient in STAI group was ¥16,682 lower (¥123,124 vs ¥139,806). The one-way sensitivity analysis indicated that the difference in total cost was most sensitive to annual AF recurrence probability in AADs-treated patients. Probabilistic sensitivity analysis indicated a 98.5% probability that RFCA treatment would result in cost savings by the end of the 10th year. Conclusion: Radiofrequency catheter ablation using SmartTouch catheter guided by Ablation Index was superior to AADs as the first-line AF treatment in Chinese setting with better clinical outcomes and at lower costs over a 10-year time horizon.

Abstract With the introduction of emerging technologies such as cloud computing, the railway communication network has the characteristics of complex structure and blurred boundaries, which leads to a series of security threats including information leakage and malicious access. Specifically, the third-party cloud services are difficult to be supervised, and network traffic is untrustworthy. To ensure system security, we propose a zero-trust security model in this paper. Then, we introduce blockchain and Merkle tree to build a distributed identity storage scheme for guaranteeing reliable, confidential and efficient data updates, and improving authentication efficiency. Furthermore, the proxy was introduced for two-way authentication with cloud servers, so that internal and external threats could be counteracted. Moreover, reputation assessment mechanism has been adopted to reduce the possibility of nodes accessing malicious cloud services. Performance analysis demonstrated that the proposed security model is able to enhance the security, efficiency and stability of the system, and consequently can guarantee the safety and reliability of railway transportation.

The Internet of Vehicles (IoV) has a significant impact on improving traffic efficiency and driving safety. In this paper, we propose an intelligent transportation credit system based on blockchain, and design a crossroad passing smart contract that allows time-sensitive convoys to pass a crossroad earlier by paying traffic tokens for right-of-way trade. Second, this paper formulates the time–cost optimization problem under the premise of protecting the privacy of preceding convoys. Based on game theory with incomplete information, two right-of-way optimal bid strategies are given. Both theoretical analysis and simulation prove that the strategy proposed in this paper effectively reduces the waiting time of time-sensitive vehicles at a crossroad and increases the trade success probability, which, in turn, improves the expected total profit of convoys and achieves Pareto improvement.

With the increasing contribution of the marine economy to the national economy, it is of great significance to carry out the assessment and analysis of the high-quality development of the marine economy to promote the construction of a marine power. Based on the "six high-quality" framework of Jiangsu Province, this paper constructed a high-quality development evaluation index system of marine economy. Based on the weight of coefficient of variation method and entropy weight, TOPSIS proximity was calculated respectively, and the high-quality development of Jiangsu marine economy in 2015-2019 was compared and analyzed. The research found that: the dynamic trend and ranking of the quality of marine economic development calculated by the two weights were 2019>2015>2018>2017>2016. The remarkable optimization in 2019 was mainly due to the fact that the throughput of foreign trade goods of coastal and riverside ports, the environmental quality of coastal waters, the retention rate of natural shorelines and the per capita net income of fishermen were significantly better than the other evaluation years. Finally, some suggestions were put forward to promote the high-quality development of marine economy.

The development of selective estrogen receptor degraders (SERDs) has brought new ideas for the clinical treatment of ER-positive advanced breast cancer. The successful application of combinational therapy inspired the exploration of other targets to prevent breast cancer progression. Thioredoxin reductase (TrxR) is an important enzyme that can regulate redox balance in cells and it was considered as a potential target for anticancer treatment. In this study, we firstly combine a clinical SERD candidate——G1T48 (NCT03455270), with a TrxR inhibitor——N-heterocyclic carbene gold(I) [NHC-Au(I)] to form dual targeting complexes that can regulate both signaling pathways. The most efficacious complex 23 exhibited significant antiproliferative profile through degrading ER and inhibiting TrxR activity. Interestingly, it can induce immunogenic cell death (ICD) caused by ROS. This is the first evidence to elucidate the role of ER/TrxR-ROS-ICD axis in ER positive breast cancer and this research may inspire new drug development with novel mechanisms. The in vivo xenograft study demonstrated that complex 23 had excellent antiproliferative activity toward MCF-7 cells in mice model.

Abstract Background Observational studies have suggested that obstructive sleep apnea (OSA) is in relation to atrial fibrillation (AF); however, these studies might be confounded and whether the relationship is causal remains unclear. We conducted a bidirectional Mendelian randomization (MR) study to clarify the causal inference between OSA and AF. Methods Genetic instruments for OSA and AF were obtained from genome-wide association studies. The fixed-effects inverse-variance weighted (IVW) method was used as the main method, supplemented by several sensitivity analyses. For replication, another AF dataset was used to validate the causal effect of OSA on AF. Furthermore, multivariable MR analyses were performed to obtain direct estimates adjusting for potential confounders. Results Genetic liability to OSA was found to be significantly associated with a higher AF risk in the fixed-effects IVW method [odds ratio (OR) 1.210; 95% CI 1.119–1.307; P = 1.51 × 10–6]. The results were consistent in MR sensitivity analyses as well as in replication analyses, and the significance remained after adjusting for potential confounders. In the reverse MR analyses, there was no causal effect of AF on OSA. Conclusions Our study strengthened the causal evidence of genetically predicted OSA with a higher AF risk. Early screening and appropriate management of OSA might show anti-arrhythmic benefits.

BackgroundObservational studies have indicated that psychosocial factors contribute to hypertension; however, the causality of these associations remains unclear due to reverse causality and confounders. We aim to assess the causal associations of mental health disorders with hypertension.MethodsInstrumental variables of anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, depression, obsessive–compulsive disorder, post-traumatic stress disorder, schizophrenia, and subjective well-being measure were obtained from the corresponding largest genome-wide association studies. Summary statistics for the association of essential hypertension were obtained from the FinnGen Study (42,857 cases and 162,837 controls) and UK Biobank cohort (54,358 cases and 408,652 controls). The multiplicative random-effects inverse-variance weighted method was utilized as the primary analysis and three other statistical methods were conducted in the supplementary analyses. The results were combined using the fixed-effects method.ResultsIn the pooled analyses, genetic liability to depression was associated with higher risk of hypertension (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.17–1.35; p

Abstract Aims We performed a Mendelian randomization (MR) study to elucidate the associations of ever smoking, lifelong smoking duration, and smoking cessation with heart failure (HF) risk. Methods and results We extracted genetic variants associated with smoking initiation, age at initiation of regular smoking, cigarettes per day, and smoking cessation from the genome‐wide association study and Sequencing Consortium of Alcohol and Nicotine use (1.2 million individuals), as well as a composite lifetime smoking index from the UK Biobank (462 690 individuals). The associations between smoking phenotypes and HF were explored in the Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium (47 309 cases; 930 014 controls) employing inverse variance‐weighted meta‐analysis and multivariable MR. The mediation effects of coronary artery disease and atrial fibrillation on smoking–HF risk were explored using mediation analysis. The odds ratios (ORs) for HF were 1.28 [95% confidence interval (CI), 1.22–1.36; P = 1.5 × 10−18] for ever regular smokers compared with never smokers and 1.25 (95% CI, 1.09–1.44; P = 1.6 × 10−3) for current smokers vs. former smokers. Genetic liability to smoking more cigarettes per day (OR, 1.37; 95% CI, 1.20–1.58; P = 6.4 × 10−6) and a higher composite lifetime smoking index (OR, 1.49; 95% CI, 1.31–1.70; P = 2.5 × 10−9) were associated with a higher risk of HF. The results were robust and consistent in all sensitivity analyses and multivariable MR after adjusting for HF risk factors, and their associations were independent of coronary artery disease and atrial fibrillation. Conclusions Genetic liability to ever smoking and a higher lifetime smoking burden are associated with a higher risk of HF.

The nonnegligible reason for the poor prognosis of hepatocellular carcinoma (HCC) is resistance to conventional chemotherapy. Immunogenic cell death (ICD) is a rare immunostimulatory form of cell death that can reengage the tumor-specific immune system. ICD can improve the clinical outcomes of chemotherapeutics by promoting a long-term cancer immunity. The discovery of potential ICD inducers is emerging as a promising direction. In the present study, micheliolide (MCL), a natural guaianolide sesquiterpene lactone, was screened out by the virtual screening strategies, identified as an inhibitor of thioredoxin reductase (TrxR) and was evaluated to have high potential to induce ICD. Here, we showed that MCL induced ICD-associated DAMPs (damage-associated molecular patterns, such as CRT exposure, ATP secretion and HMGB1 release). MCL significantly triggered the regression of established tumors in an immunocompetent mouse vaccine model, and induced ICD (DCs maturation, the stimulation of CD4+, and CD8+ T-cells responses) in vivo. Mechanistically, we found that the magnitude of ICD-associated effects induced upon exposure of HCC cells to MCL was dependent on the generation of reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ERS). In addition, the suppression of ROS normalized MCL-induced ERS, in contrast, the downregulation of TrxR synergized with the ERS driven by MCL. We also systematically detected the H2O2 generation using Hyper7 sensors in HCC cells exposed to MCL. Notably, MCL inhibited the development of HCC organoids. Collectively, our results reveal a potential association between the TrxR inhibitors and ICD, presenting valuable insights into the MCL-activated ICD in HCC cells.

Abstract Background The causality between the use of alcohol and cigarettes and atrial fibrillation (AF) remains controversial. We conducted a Mendelian randomization (MR) study to evaluate the association of genetic variants related to tobacco and alcohol use with AF. Methods Single nucleotide polymorphisms (SNPs) related to smoking initiation (N = 374), age at initiation of regular smoking (N = 10), cigarettes per day (N = 55), and smoking cessation (N = 24) were derived from a genome-wide association studies (GWAS) of tobacco use (N = 1.2 million individuals). SNPs related to heavy alcohol use (N = 6) were derived from a GWAS of UK biobank (N = 125,249 individuals). The genetically matching instrumented variables were obtained from the GWAS of AF (N = 588,190 individuals). The estimates between tobacco and alcohol use and AF were combined by inverse-variance weighted (IVW), simple median, weighted median, MR-robust adjusted profile score method, MR-PRESSO, and multivariable MR. Results A total of 65,446 AF patients and 522,744 referents were included. In the IVW analysis, the odds ratio per one-unit increase of smoking initiation was 1.11 (95% CI, 1.06–1.16; P = 3.35 × 10−6) for AF. Genetically predicted age at initiation of regular smoking, cigarettes per day and smoking cessation were not associated with AF. The IVW estimate showed that heavy alcohol consumption increased AF risk (OR, 1.11; 95% CI, 1.04–1.18; P = 0.001). The results were consistent in complementary analyses and multivariable MR. Conclusion Our MR study indicated that regular smoking was associated with increased risk of AF, no matter the age at initiation of regular smoking, or the number of cigarettes smoked per day. Genetically predicted heavy alcohol consumption increased the risk of AF.

Games have long been benchmarks and testbeds for AI research. In recent years, with the development of new algorithms and the boost in computational power, many popular games played by humans have been solved by AI systems. Mahjong is one of the most popular games played in China and has been spread worldwide, which presents challenges for AI research due to its multi-agent nature, rich hidden information, and complex scoring rules, but it has been somehow overlooked in the community of game AI research. In 2020 and 2022, we held two AI competitions of Official International Mahjong, the standard variant of Mahjong rules, in conjunction with a top-tier AI conference called IJCAI. We are the first to adopt the duplicate format in evaluating Mahjong AI agents to mitigate the high variance in this game. By comparing the algorithms and performance of AI agents in the competitions, we conclude that supervised learning and reinforcement learning are the current state-of-the-art methods in this game and perform much better than heuristic methods based on human knowledge. We also held a human-versus-AI competition and found that the top AI agent still could not beat professional human players. We claim that this game can be a new benchmark for AI research due to its complexity and popularity among people.

Loss reduction to improve the power efficiency in active integrated antenna (AIA) is a key design drive. This paper first analyzes the loss mechanism in a convention AIA structure. A new integration scheme of a GaN power amplifier (PA) transistor with an antenna without using any output matching network (OMN) and harmonic tuning network (HTN) is then proposed to construct a seamlessly integrated AIA. This is achieved by a novel design of a slot antenna with optimized input impedance at its fundamental frequency as well as for harmonic tuning, which essentially absorbs the OMN and HTN functions in the conventional Class-F power amplifier design. By eliminating these passive networks between the transistor and the antenna, the associated insertion and mismatch losses as well as the overall circuit size are reduced. For verification, two prototypes are designed, fabricated and measured, one with the integrated design and the other with a conventional design for comparison. Both AIAs operate between 3.4 and 3.6 GHz. Experimental results show that the power-added efficiency (PAE) of the seamlessly integrated AIA is over 52% within the operating band. Compared with the conventional cascaded design of a PA and an antenna, the PAE is improved by 14.2%.

A batch variable learning rate gradient descent algorithm is proposed to efficiently train a neuro-fuzzy network of zero-order Takagi-Sugeno inference systems. By using the advantages of regularization, the smoothing L1/2 regularization is utilized to find more appropriate sparse network. Combining the second-order information of the smoothing error function, a variable learning rate is chosen along the steep descent direction, which avoids line search procedure and may reduce the cost of computation. In order to appropriately adjust the Lipschitz constant of the smoothing error function in the learning rate, a new scheme is proposed by introducing a hyper-parameter. Also the article applies the modified secant equation for estimating the Lipschitz constant, which makes the algorithm greatly reduce the oscillating phenomenon and improve the robustness. Under appropriate assumptions, a convergent result of the proposed algorithm is also given. Simulation results for two identification and classification problems show that the proposed algorithm has better numerical performance and promotes the sparsity capability of the network, compared with the common batch gradient descent algorithm and a variable learning rate gradient-based algorithm.

Background: This paper performs a detailed ordinal logistic regression study in an evaluation of a survey at a university in South Texas, USA. We show that, for categorical data in our case, ordinal logistic regression works well. Methods: The survey was designed according to the guidelines in diet and lifestyle from the American Heart Association and the United States Department of Agriculture and was sent out to all registered students at Texas A&M International University in Laredo, Texas. Data analysis included 601 students’ results from the survey. Data analysis was conducted in Rstudio. Results: The results showed that, compared with students who do not have enough whole grain food and exercise, those who have enough in both tend to have normal BMIs. As age increases, BMI tends to be out of the normal range. Conclusions: Because BMI in this research has three categories, applying an ordinal logistic regression model to describe the relationship between an ordered categorical response variable and more explanatory variables has several advantages compared with other models, such as the linear regression model.

Aim: The structural and electrical changes in the atrium, also known as atrial remodeling, are the main characteristics of atrial fibrillation (AF). Fibroblast growth factor 21 (Fgf21) is an important endocrine factor, which has been shown to play an important role in cardiovascular diseases. However, the effects of Fgf21 on atrial remodeling have not been addressed yet. The purpose of the present study is to evaluate the effects of Fgf21 on atrial remodeling.Methods and Results: Adult mice were treated with Ang II, and randomly administrated with or without Fgf21 for 2 weeks. The susceptibility to AF was assessed by electrical stimulation and optical mapping techniques. Here, we found that Fgf21 administration attenuated the inducibility of atrial fibrillation/atrial tachycardia (AF/AT), improved epicardial conduction velocity in the mice atria. Mechanistically, Fgf21 protected against atrial fibrosis and reduced oxidative stress of the atria. Consistently, in vitro study also demonstrated that Fgf21 blocked the upregulation of collagen by Tgf-β in fibroblasts and attenuated tachypacing-induced oxidative stress including reactive oxygen species (ROS), Tgf-β, and ox-CaMKII in atrial myocytes. We further found that Fgf21 attenuated oxidative stress by inducing antioxidant genes, such as SOD2 and UCP3. Fgf21 also improved tachypacing-induced myofibril degradation, downregulation of L-type calcium channel, and upregulation of p-RyR2, which implicated protective effects of Fgf21 on structural and electrical remodeling in the atria. Moreover, Nrf2 was identified as a downstream of Fgf21 and partly mediated Fgf21-induced antioxidant gene expression in atrial myocytes.Conclusion: Fgf21 administration effectively suppressed atrial remodeling by reducing oxidative stress, which provides a novel therapeutic insight for AF.

Background: Although some observational studies have shown that physical activity may have a positive relationship with cardiovascular diseases, the causal effect remains uncertain. We conducted a Mendelian randomization (MR) study to identify the potential causal effect between physical activity and cardiovascular diseases.Methods: Summary statistics of genome-wide association studies on four physical activity phenotypes and cardiovascular diseases were utilized. MR analysis was performed using inverse-variance weighted (IVW) and multivariable MR. Multiple sensitivity analysis was further conducted to identify the robustness of our results.Results: Genetically predicted self-reported vigorous physical activity (VPA) was significantly associated with lower risk of myocardial infarction (IVW OR: 0.24, 95% CI: 0.08–0.68, p-value: 0.007). Additionally, the causal effect of VPA with myocardial infarction was robust after adjusting for several cardiovascular risk factors through using the multivariable MR. There were no apparent causal associations between physical activity with other cardiovascular diseases. Results were consistent with the sensitivity analysis.Conclusion: The present study supports a protective role of self-reported vigorous physical activity in the initiation of myocardial infarction and highlights the importance of activity levels of physical activity. Further studies are required to elucidate the potential biological pathways of physical activity with cardiovascular diseases.

Background: Previous observational studies have reported an association between psychiatric traits and cardiovascular diseases (CVDs). In this two-sample Mendelian randomization (MR) study, we aimed to investigate the causality between psychiatric traits and CVDs.Methods: Single-nucleotide polymorphisms (SNPs) associated with autism spectrum disorder (ASD), neuroticism, and subjective well-being at genome-wide significance (P < 1 × 10−8) were identified from genome-wide association studies. Summary-level data of the outcomes, including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF), were obtained from several largest datasets. The inverse-variance weighted (IVW) method was used as our main analyses to conduct this MR study. Sensitivity analyses included the weighted median, the MR-robust adjusted profile score (MR-RAPS), and the MR pleiotropy residual sum and outlier (MR-PRESSO) method. Repeated MR analyses using a more relaxed threshold (P < 1 × 10−6) for instruments selection and multivariable MR analyses were also applied to evaluate the robustness of results.Results: The MR analyses showed that genetic predisposition to ASD was associated with a higher risk of AF [odds ratio (OR), 1.109; 95% confidence interval (CI), 1.023–1.201; P = 0.011] and HF (OR, 1.138; 95% CI, 1.036–1.251; P = 0.007). Neuroticism was casually associated with an increased risk of AF (OR, 1.201; 95% CI, 1.037–1.392; P = 0.015), whereas subjective well-being had a protective effect on HF (OR, 0.732; 95% CI, 0.574–0.933; P = 0.012). No other causal association between psychiatric traits and CVDs was observed. Consistent results were obtained in sensitivity analyses.Conclusion: This study provided evidence of causal associations of ASD with a higher risk of AF and HF. Besides, neuroticism was casually associated with an increased risk of AF, and subjective well-being was associated with a decreased risk of HF.

Games have long been benchmarks and test-beds for AI algorithms. With the development of AI techniques and the boost of computational power, modern game AI systems have achieved superhuman performance in many games played by humans. These games have various features and present different challenges to AI research, so the algorithms used in each of these AI systems vary. This survey aims to give a systematic review of the techniques and paradigms used in modern game AI systems. By decomposing each of the recent milestones into basic components and comparing them based on the features of games, we summarize the common paradigms to build game AI systems and their scope and limitations. We claim that deep reinforcement learning is the most general methodology to become a mainstream method for games with higher complexity. We hope this survey can both provide a review of game AI algorithms and bring inspiration to the game AI community for future directions.

Chitosan-based composite films with good biodegradability, biocompatibility, and sustainability are extensively employed in the field of food packaging. In this study, novel chitosan/tannic acid (CTA) and chitosan/oxidized tannic acid (COTA) composite films with excellent mechanical and antibacterial properties were prepared using a tape casting method. The results showed that, when 20% tannic acid (TA) was added, the tensile strength of the CTA composite film was 80.7 MPa, which was 89.4% higher than that of the pure chitosan (CS) film. TA was oxidized to oxidized tannic acid (OTA) with laccase, and the phenolic hydroxyl groups were oxidized to an o-quinone structure. With the addition of OTA, a Schiff base reaction between the OTA and CS occurred, and a dual network structure consisting of a chemical bond and hydrogen bond was constructed, which further improved the mechanical properties. The tensile strength of 3% COTA composite film was increased by 97.2% compared to that of pure CS film. Furthermore, these CTA films with significant antibacterial effects against Escherichia coli (E. coli) are likely to find uses in food packaging applications.

Background Observational studies have indicated that depression is associated with coronary artery disease (CAD) and myocardial infarction. Nevertheless, causal associations between depression and cardiovascular diseases remain controversial. Hence, we conducted a Mendelian randomization and mediation analysis to evaluate the associations of depression‐related genetic variants with CAD and myocardial infarction. Methods and Results Summary statistics from genome‐wide association studies of depression (807 553 individuals), and CAD (60 801 cases, including 43 676 with myocardial infarction, and 123 504 controls) were used. We pooled Mendelian randomization estimates using a fixed‐effects inverse‐variance weighted meta‐analysis and multivariable Mendelian randomization. The mediation effects of potential cardiovascular risk factors on depression‐CAD and myocardial infarction risk were investigated by using mediation analysis. We also explored the relationship of genetic liability to depression with heart failure, atrial fibrillation, and ischemic stroke. Genetic liability to depression was associated with higher CAD (odds ratio [OR], 1.14; 95% CI, 1.06–1.24; P=1.0×10−3) and myocardial infarction (OR, 1.21; 95% CI, 1.11–1.33; P=4.8×10−5) risks. Results were consistent in all sensitivity analyses. Type 2 diabetes mellitus and smoking demonstrated significant mediation effects. Furthermore, our Mendelian randomization analyses revealed that the genetic liability to depression was associated with higher risks of heart failure and small vessel stroke. Conclusions Genetic liability to depression is associated with higher CAD and myocardial infarction risks, partly mediated by type 2 diabetes mellitus and smoking. The potential preventive value of depression treatment on cardiovascular diseases should be investigated in the future.

This paper presents a design of dual-polarized antenna with embedded filtering circuits by using a printed Jerusalem-cross radiator and a ring slot-coupled feed structure. A square ring slot has been adopted to implement the coupling mechanism. It is excited by two orthogonal microstrip feedlines to achieve dual polarizations. Meanwhile, the slot-coupled feed network and printed Jerusalem-cross radiator form a coupled-resonator circuit that realizes a second-order bandpass filtering performance. Consequently, a dual-polarized antenna with a filtering performance is obtained without using extra filtering circuits. To demonstrate the idea, an antenna prototype operating at LTE bands 42 and 43 (3.4-3.8 GHz) is designed, fabricated, and measured. Measured results show that the proposed antenna provides good filtering and dual-polarized radiation performances. Furthermore, a four-element dual-polarized linear array is designed for high-gain applications.

Data leakage is a growing insider threat in information security among organizations and individuals. A series of methods has been developed to address the problem of data leakage prevention (DLP). However, large amounts of unstructured data need to be tested in the big data era. As the volume of data grows dramatically and the forms of data become much complicated, it is a new challenge for DLP to deal with large amounts of transformed data. We propose an adaptive weighted graph walk model to solve this problem by mapping it to the dimension of weighted graphs. Our approach solves this problem in three steps. First, the adaptive weighted graphs are built to quantify the sensitivity of the tested data based on its context. Then, the improved label propagation is used to enhance the scalability for fresh data. Finally, a low-complexity score walk algorithm is proposed to determine the ultimate sensitivity. Experimental results show that the proposed method can detect leaks of transformed or fresh data fast and efficiently.

A Ka-band waveguide continuous transverse stub antenna array with full-corporate-feed network is presented in this paper. Multiple-section stepped-impedance transformers are used for wideband impedance matching of the radiation slots. The required high-quality quasi-TEM wave excitation is generated by a wideband plane-wave generator (WPWG). Compared with the conventional pillbox structure, the WPWG produces a quasi-TEM wave with more uniform amplitude distribution. By using the combination of these design features, significant increases both in bandwidth and antenna aperture efficiency are achieved. For demonstration, a prototype is designed, fabricated, and measured. Excellent agreement is achieved between simulations and measurements. The antenna is matched over the entire Ka-band of 26-40 GHz. A high antenna aperture efficiency of over 75% and a low cross-polarization of less than -46 dB are achieved over the entire bandwidth. The demonstrated features of wideband, high aperture efficiency, and low cross-polarization have great potentials for millimeter-wave applications.

A new trust region method is presented, which combines nonmonotone line search technique, a self-adaptive update rule for the trust region radius, and the weighting technique for the ratio between the actual reduction and the predicted reduction. Under reasonable assumptions, the global convergence of the method is established for unconstrained nonconvex optimization. Numerical results show that the new method is efficient and robust for solving unconstrained optimization problems.

A new self-adaptive rule of trust region radius is introduced, which is given by a piecewise function on the ratio between the actual and predicted reductions of the objective function. A self-adaptive trust region method for unconstrained optimization problems is presented. The convergence properties of the method are established under reasonable assumptions. Preliminary numerical results show that the new method is significant and robust for solving unconstrained optimization problems.