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With the rapid development of 5G, Mobile Edge Computing (MEC) paradigm has emerged to enable various devices or servers at the network edge to contribute their computing capacity for reducing communication delay. A fundamental problem is to preserve satisfactory quality-of-service (QoS) for mobile users in light of densely dispersed wireless communication environment and capacity-constrained MEC nodes. Such user-perceived QoS, typically in terms of the end-to-end delay, is highly vulnerable to both access network bottleneck and communication delay. Previous works primarily focused on optimizing the communication delay through dynamic service placement, while ignoring the critical effect of access network selection on the access delay. This paper studies the problem of jointly optimizing the access network selection and service placement for MEC, with the objective of improving QoS in a cost-efficient manner by judiciously balancing the access delay, communication delay, and service switching cost. We propose an efficient online framework to decompose this long-term time-varying optimization problem into a series of one-shot subproblems. To address the NP-hardness of the one-shot problem, we design a computationally-efficient two-phase algorithm, which achieves a near-optimal solution. Both theoretical analysis on the optimality gap and trace-driven simulations are conducted to validate the efficacy of our proposed solution.

The accelerating convergence of artificial intelligence (AI) and Internet-of-Things (IoT) has sparked a recent wave of interest in Artificial-Intelligence-of-Things (AIoT). By exploiting the novel paradigm of edge intelligence, emerging computational intensive and resource demanding AIoT applications can be efficiently supported at the network edge. However, due to the limited resource capacity and/or power budget of the edge node, AIoT applications typically deploy compressed AI models to achieve the goal of low-latency and energy-efficient model inference. However, compressed models inherently suffer from the curse of data drift, i.e., the inference data at the deployment stage diverges from the training data at the training stage, leading to reduced model inference accuracy. To handle this issue, continuous learning has been proposed to periodically retrain the AI models on new data in an incremental manner. In this paper, we investigate how to coordinate the edge and the cloud resources to perform cost-efficient continuous learning, with the goal of simultaneously optimize the model performance (in terms of accuracy and robustness) and resource cost. Leveraging Lyapunov optimization theory, we design and analyze a cost-efficient optimization framework for making online decisions upon admission control, transmission scheduling, and resource provisioning, for the dynamically arrived new data samples of various AIoT applications. We examine the effectiveness of the proposed framework on navigating the performance-cost tradeoff theoretically and empirically through trace-driven simulations.

To design simple and efficient inductive power transfer (IPT) systems, minimum number of conversion stages and effective maximum efficiency tracking (MET) are the primary design criteria. The MET control uses a fast mutual inductance estimation (MIE) algorithm to achieve fast tracking of the maximum efficiency point especially when the variation of the gap distance and misalignment of the magnetic coupler are significant. The feedback control of the MET-MIE IPT system should be designed without a wireless communication channel to improve stability and robustness. In this paper, a novel MET-MIE control strategy is proposed for achieving simplicity and high efficiency in IPT systems. Verifications are provided by simulations and experiments. It is shown that maximum efficiency can be tracked with less than 4% error in MIE under significant variation of the gap distance and misalignment of the magnetic coupler.

Purpose Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED). Patients and methods From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM). Results Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9%vs.36.5%, P=0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4%vs.21.7%, P=0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P Conclusion Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.

Due to the power interaction between the phase-shifted dual active bridges (PSDABs) and series resonant dual active bridges (SRDABs) in the hybrid modular dc Transformer (HMDCT), it is difficulty to optimize current stress based on the transferred power. An extended-state-observer based model predictive control (ESO-MPC) strategy with the extended phase shift (EPS) is proposed to optimize the current stress of the PSDABs in the HMDCT. The MPC is employed to calculate the optimal transferred power of the PSDABs. Moreover, a first-order ESO is introduced to observe the uncertain output current of the PSDABs. Based on the calculated transferred power, the optimal phase-shifted duty ratios of each PSDAB under EPS, which achieves optimal current stress, are obtained by the Lagrange multiplier method. Because of the ESO-MPC strategy, it enables to achieve the current sensorless control of the HMDCT. Simulations on a four-cell 3kV/500V HMDCT and the extensive experiments of a downscale laboratory platform, using DSP OMPL138 -EZW + FPGA XC7A75T as the core controller, validate the feasibility of the proposed control strategy.

Serverless computing is becoming a promising paradigm for Distributed Deep Neural Network (DDNN) training in the cloud, as it allows users to decompose complex model training into a number of $functions$ without managing virtual machines or servers. Though provided with a simpler resource interface ( $i.e.,$ function number and memory size), inadequate function resource provisioning (either under-provisioning or over-provisioning) easily leads to $unpredictable$ DDNN training performance in serverless platforms. Our empirical studies on AWS Lambda indicate that, such $unpredictable performance$ of serverless DDNN training is mainly caused by the resource bottleneck of Parameter Servers (PS) and small local batch size. In this paper, we design and implement $\lambda DNN$ , a cost-efficient function resource provisioning framework to provide predictable performance for serverless DDNN training workloads, while saving the budget of provisioned functions. Leveraging the PS network bandwidth and function CPU utilization, we build a $lightweight$ analytical DDNN training performance model to enable our design of $\lambda DNN$ resource provisioning strategy, so as to guarantee DDNN training performance with serverless functions. Extensive prototype experiments on AWS Lambda and complementary trace-driven simulations demonstrate that, $\lambda DNN$ can deliver predictable DDNN training performance and save the monetary cost of function resources by up to 66.7%, compared with the state-of-the-art resource provisioning strategies, yet with an acceptable runtime overhead.

BACKGROUND Neurosurgical treatment of severe bilateral occipital lobe epilepsy usually involves two operations several mos apart. AIM To evaluate surgical resection of bilateral occipital lobe lesions during a single operation as a treatment for bilateral occipital lobe epilepsy. METHODS This retrospective case series included patients with drug-refractory bilateral occipital lobe epilepsy treated surgically between March 2006 and November 2015. RESULTS Preoperative evaluation included scalp video-electroencephalography (EEG), magnetic resonance imaging, and PET-CT. During surgery (bilateral occipital craniotomy), epileptic foci and important functional areas were identified by EEG (intracranial cortical electrodes) and cortical functional mapping, respectively. Patients were followed up for at least 5 years to evaluate treatment outcome (Engel grade) and visual function. The 20 patients (12 males) were aged 4-30 years (median age, 12 years). Time since onset was 3-20 years (median, 8 years), and episode frequency was 4-270/mo (median, 15/mo). Common manifestations were elementary visual hallucinations (65.0%), flashing lights (30.0%), blurred vision (20.0%) and visual field defects (20.0%). Most patients were free of disabling seizures (Engel grade I) postoperatively (18/20, 90.0%) and at 1 year (18/20, 90.0%), 3 years (17/20, 85.0%) and ≥ 5 years (17/20, 85.0%). No patients were classified Engel grade IV (no worthwhile improvement). After surgery, there was no change in visual function in 13/20 (65.0%), development of a new visual field defect in 3/20 (15.0%), and worsening of a preexisting defect in 4/20 (20.0%). CONCLUSION Resection of bilateral occipital lobe lesions during a single operation may be applicable in bilateral occipital lobe epilepsy.

Human epidermal growth factor receptor 2 (HER2) amplification or activating mutations are found in 1.6%–4% of non-small cell lung cancer (NSCLC). Pyrotinib has been reported to have better potency in NSCLC patients with HER2 exon 20 insertion (ex20ins) mutations; however, more clinical evidence is urgently needed to guide pyrotinib-based therapy in NSCLC with HER2 amplification or heterogeneous mutations. We retrospectively analyzed advanced NSCLC patients with HER2 amplification or mutations who were treated with pyrotinib-based therapy between September 25, 2018 and October 30, 2020 in our hospital. Molecular dynamics simulation was used to explore the bioactive conformation and binding mechanisms of pan-ErbB tyrosine kinase inhibitors (TKIs) including pyrotinib for different HER2 ex20ins variants. In this study, 79 eligible patients were included with 70 ex20ins variants, 6 missense mutations and 3 primary HER2 amplifications identified. A775_G776insYVMA insertion was the most common observed subtype. The median progression-free survival (mPFS) was 5.8 (95% CI: 4.1–7.4) months. Use of pyrotinib-based therapy in first-/second-line settings showed a significantly better prognosis than that observed in third-line settings or above (mPFS: 9.1 vs. 4.4 months; P = 0.0003). Compared with HER2 amplification and exon 20 non-YVMA insertion variants, patients with HER2 missense mutations had a visible mPFS benefit (12.2 vs. 6.8 vs. 5.2 months). Computational docking simulations revealed that pyrotinib failed to interact with the specific insertion variant P780_Y781insGSP. These results indicated that pyrotinib-based therapy exhibited good anti-tumor activity and acceptable safety profile in HER2-altered advanced NSCLC.

The traditional object detection model based on convolutional neural network contains a large amount of parameters, so it has poor performance when applied to high-real-time and high-precision scenes. To solve the problem, this paper proposes a deep recurrent attention object detection dynamic model (DRA-ODM). The model based on time domain attention mechanism is constructed by using recurrent neural network and dynamic sampling point mechanism, it simulates the way that human-eyes ignore irrelevant information and pay attention to key information when observing things. DRA-ODM model completes object detection on the premise of extracting only part of image features. In addition, this paper visualizes the position in each sampling, thus, it is convenient to observe the position of sampling points during each cycle. Extensive experiment results demonstrate that DRA-ODM model achieves object detection within 5 time steps using about 20 M parameters, its average accuracy could reach 87. 4%.

Background: The B-Raf proto-oncogene (BRAFV600E) gene mutation has been identified in a variety of malignancies, but no evidence of the efficacy of vemurafenib treatment in BRAFV600E mutant breast cancer (BC) has been reported. Case Presentation: We reported a 60-year-old woman with confirmed triple-negative BC with BRAFV600E mutation. Progression-free survival (PFS) for first-line chemotherapy was 7 months. The patient received vemurafenib and albumin-bound paclitaxel as second-line therapy, exhibiting regression of some pulmonary metastatic lesions with concomitant progression of other lesions, and achieved 4.4 months of PFS. Genetic testing of the progressed pulmonary lesion revealed the BRAFV600E mutation, and acquired new mutations and AR amplification. The patient ultimately died of multiple organ failure and achieved 12 months of overall survival. Conclusions: The BRAFV600E mutation may be a potential prognostic factor and therapeutic target for BC.

Jointed network simulations tend to be more random in nature due to the uncertainty of rock mass structures. In this paper, a series of jointed network models can be established in batches using Monte Carlo simulation (MSC) and loop iteration. Taking the joints, tunnel profile and their intersections as the edges E and vertices V of graph G, the jointed network model can serve as an unweighted undigraph. Then, the breadth-first search is introduced to search the closed paths around the tunnel profile, such as the potential key blocks. With batch simulation of network models, the spatial distribution characteristics and probability distribution rules of blocks can be automatically analysed during the search process. For comparison, the Laohushan tunnel of the Jinan Belt Expressway in China has been analysed using the breadth-first search, discontinuous deformation analysis method and procedure of “Finding the Key Blocks-Unrolled Tunnel Joint Trace Maps”. Each simulation starts from the same probabilistic model of geometrical parameters of joints but develops differently with different outcomes. The spatial distribution rule of potential key blocks simulated by the aforementioned batch jointed network models is essentially identical to the actual rockfall during tunnel excavation.

Purpose: There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy. Patients and Methods: We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses. Results: A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n = 196) or trastuzumab plus chemotherapy (CT group, n = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0–44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7–21.7)] in the ET group and 14.8 months (12.8–16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71–1.09; Pnoninferiority < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group. Conclusions: Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR+HER2+ MBC.

The prevalence of diabetes has increased rapidly throughout the world in recent years. Currently, approximately 463 million people are living with diabetes, and the number has tripled over the last two decades. Here, we describe the global epidemiology of diabetes in 2019 and forecast the trends to 2030 and 2045 in China, India, USA, and the globally. The gut microbiota plays a major role in metabolic diseases, especially diabetes. In this review, we describe the interaction between diabetes and gut microbiota in three aspects: probiotics, antidiabetic medication, and diet. Recent findings indicate that probiotics, antidiabetic medications, or dietary interventions treat diabetes by shifting the gut microbiome, particularly by raising beneficial bacteria and reducing harmful bacteria. We conclude that targeting the gut microbiota is becoming a novel therapeutic strategy for diabetes.

In the effect of periodically varying wind speeds, a wind turbine in an external field environment often works under stall conditions. This paper explores the factors that average wind speed, wind speed amplitude, and oscillation frequency resulted in the changes in blade torque by dynamic stall. According to the blade surface flow field during the dynamic change of wind speed, the law of surface pressure change of the blade in the period of periodic stall is analyzed, and the power changes of the wind turbine blade in the stages of no stall, light stall, and deep stall are studied. As a result, as the oscillation frequency increases, the amount of torque change also increases, and the maximum torque also increases. When the average wind speed increases, the torque experienced by the blades decreases stepwise. As the wind speed amplitude increases, the area of the closed-loop curve where the torque varies with the wind speed continues to expand. Accurately understanding the impact of dynamic stalls and stall delays on wind turbines can further improve the efficiency of wind turbines.

Background The proto-oncogene c-MET (mesenchymal-epithelial transition factor gene) plays a critical role in cellular proliferation, survival, migration, and invasion in cancers. The aim of this study is to explore the relationship between c-MET expression and the clinicopathological characteristics of colorectal cancer (CRC) patients. Methods A total of 337 enrolled patients were collected in present study. Here, the c-MET and EGFR expression were detected by immunohistochemistry (IHC). The mutational statuses of KRAS in exons 2, 3, and 4, NRAS in exons 2, 3, and 4, and BRAF in exon 15 from formalin-fixed sections were detected by direct DNA sequencing. Results Our results showed that high c-MET expression was significantly associated with tumor perineural invasion (P=0.007) and gender (P=0.016). High level c-MET expression (c-MET-high) in the primary tumors was observed in 68.2% of patients. In the 337 enrolled patients, 43.2% of patients had KRAS mutations, 3.3% of patients had NRAS mutations, and 4.7% of patients had BRAF mutations. However, KRAS, NRAS, and BRAF gene mutations had no association with c-MET protein levels in primary tumors. Additionally, c-MET protein expression had a strong correlation with EGFR expression (P=0.002). The survival time was not significantly longer for patients with c-MET-high primary tumors than for those with c-MET-low primary tumors. Conclusions c-MET immunohistochemistry was significantly higher in primary tumors with perineural invasion, female gender, and EGFR high expression. However, c-MET-high in the primary tumors was not significantly associated with longer survival compared with c-MET-low tumors. Further studies are required to investigate c-MET as potential molecular marker of progression and to test the possibility of its incorporation as a new therapeutic target.

Background: The influencing factors of diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM) were explored to develop and validate a DKD diagnostic tool based on nomogram approach for patients with T2DM.Methods: A total of 2,163 in-hospital patients with diabetes diagnosed from March 2015 to March 2017 were enrolled. Specified logistic regression models were used to screen the factors and establish four different diagnostic tools based on nomogram according to the final included variables. Discrimination and calibration were used to assess the performance of screening tools.Results: Among the 2,163 participants with diabetes (1,227 men and 949 women), 313 patients (194 men and 120 women) were diagnosed with DKD. Four different screening equations (full model, laboratory-based model 1 [LBM1], laboratory-based model 2 [LBM2], and simplified model) showed good discriminations and calibrations. The C-indexes were 0.8450 (95% confidence interval [CI], 0.8202 to 0.8690) for full model, 0.8149 (95% CI, 0.7892 to 0.8405) for LBM1, 0.8171 (95% CI, 0.7912 to 0.8430) for LBM2, and 0.8083 (95% CI, 0.7824 to 0.8342) for simplified model. According to Hosmer-Lemeshow goodness-of-fit test, good agreement between the predicted and observed DKD events in patients with diabetes was observed for full model (χ2=3.2756, P=0.9159), LBM1 (χ2=7.749, P=0.4584), LBM2 (χ2=10.023, P=0.2634), and simplified model (χ2=12.294, P=0.1387).Conclusion: LBM1, LBM2, and simplified model exhibited excellent predictive performance and availability and could be recommended for screening DKD cases among Chinese patients with diabetes.

The formulation and implementation of Low-Carbon City Policy (LCCP) is an essential initiative for China to build its low-carbon society. Based on the panel data of 282 prefecture-level cities in China from 2003 to 2016, this study evaluates the effects of LCCP implementation on pilot cities’ carbon emission performance using difference-in-differences method, and then the mechanism has also been examined with a mediating effect model. The results show that: first, the LCCP implementation has increased the carbon emission performance of the pilot cities significantly, indicating that it is an effective way to promote the low-carbon transformation of Chinese cities. Second, the positive effects in CO2 performance resulting from LCCP demonstrate significant heterogeneity: in general, the cities in east China, with higher economic development level and in a larger size, achieve more significant CO2 emission reduction than their respective counterparts. The results on the mechanism test imply that the LCCP helps improve pilot cities’ carbon emission performance in three ways, including reducing energy consumption, updating the industrial structure, and promoting technological progress. Finally, some useful policy recommendations are put forward to promote China’s low-carbon city construction.

Objective:. Venlafaxine is a common antidepressant and its therapeutic effect varies among people with different genetic backgrounds. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the SLC17A7 gene are associated with the treatment outcome of venlafaxine in a Chinese Han population with major depressive disorder. Methods:. This prospective pharmacogenetic case-control study that involved genotyping of four SNPs of SLC17A7 was conducted on 175 major depressive disorder patients of Chinese Han origin, aged 18 to 65 years, participated in the study from April 2005 to September 2006. Comparisons of allele and genotype frequencies of all SNPs were performed between the responder/remission group and the nonresponder/nonremission group. This study was approved by the Institutional Ethics Committee of Sichuan University (approval No. 20151112-265). Results:. The allele and genotype frequencies of the four candidate SNPs in SCL17A7 showed no significant difference between responders and nonresponders. Meanwhile, no significant difference was detected in the four investigated SLC17A7 SNPs between patients who did and did not exhibit remission. Although one of the investigated SLC17A7 variants (rs1578944) demonstrated a significant association (P = 0.022) with a response to venlafaxine after 6 weeks of treatment in the survival analysis, the association was unclear after a Bonferroni multiple comparisons test was conducted. Conclusion:. No significant association exists between the four candidate SNPs (rs1043558, rs1320301, rs1578944, and rs74174284) in SLC17A7 and venlafaxine treatment in the Chinese Han population.

In order to study the stability of tunnels under static-dynamic load, a new large-scale static-dynamic model test system was developed. The system was composed of a static loading unit, a dynamic loading unit, a data acquisition unit and a test bench, which were specially designed to overcome the technical problems of large-scale static-dynamic model test, such as dynamic loading and control, high-rate strain measurement and easy operation. The system used a model of 3600 × 3600 × 2500 mm in size to study a larger load disturbance area than static tests. It can accurately apply three-dimensional gradient static stress and dynamic load with adjustable amplitude (or magnitude), frequency and waveform to simulate the true geo-stress field and disturbance field, and accurately and rapidly collect displacement, stress, strain, velocity, acceleration and other important parameters of the model. In addition, it was convenient to adjust the scale of the model, remove and retain the test model. The system was used to carry out a static load model test and a static-dynamic load model test with a tunnel as a prototype. The results of the tests were consistent with the numerical results by FLAC-3D, which proved the reliability and accuracy of the system.

Fangfang Duan,&ast; Chenge Song,&ast; Yuyu Ma, Kuikui Jiang, Fei Xu, Xiwen Bi, Jiajia Huang, Ruoxi Hong, Zhangzan Huang, Qianyi Lu, Zhongyu Yuan, Shusen Wang, Wen Xia Departments of Medical Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen XiaDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of ChinaEmail xiawen@sysucc.org.cnBackground: There are no clinically available prognostic models for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer treated with everolimus. We aimed to develop a tool to predict the progression-free survival (PFS) and overall survival (OS) of these patients and to identify optimal candidates who would benefit from everolimus-based treatment in this heterogeneous patient population.Methods: The clinical data of patients with HR+, HER2- metastatic breast cancer receiving everolimus between May 2012 and January 2018 at Sun Yat-sen University Cancer Center were retrospectively retrieved. Based on potential prognostic factors derived from multivariate Cox analysis, we established predictive nomogram models for PFS and OS and evaluated their predictive values by means of the concordance index (C-index). Calibration curves were used to estimate the consistency between the actual observations and the nomogram-predicted probabilities.Results: A total of 116 patients with HR+, HER2- metastatic breast cancer were enrolled in this study. Three independent prognostic factors, including the line of everolimus in the metastatic setting, everolimus clinical benefit rate and number of liver metastatic lesions, were identified from the multivariate Cox analysis. Prognostic models for individual survival prediction were established and graphically presented as nomograms. The C-index was 0.738 (95% confidence interval [CI]: 0.710– 0.767) for the PFS nomogram and 0.752 (95% CI: 0.717– 0.788) for the OS nomogram, which showed favourable discrimination. The calibration curves for the probabilities of 6-, 9-, and 12-month PFS and 1-, 2-, and 3-year OS suggested satisfactory consistency between the actual observations and the predicted probabilities.Conclusion: We constructed convenient nomogram models for patients with HR+, HER2- metastatic breast cancer to individually predict their potential benefits from everolimus in the metastatic setting. The models showed good performance in terms of accuracy, discrimination capacity and clinical application value.Keywords: prognostic nomogram, metastatic breast cancer, everolimus, progression-free survival, overall survival

The aim of the study was to investigate the effects of 4-week small-sided games (SSG) and high-intensity interval training with changes of direction (HIT-COD) on physical performance and specific technical skills in female collegiate basketball players. Nineteen players were divided into SSG (n = 9) and HIT-COD (n = 10) groups, that performed either SSG or HIT-COD three times per week for 4 weeks during the pre-season. Players’ heart rate (HR) and perceived exertion responses (RPE) were assessed during the intervention. Before and after the intervention period, performances were assessed with 30-15 intermittent fitness test (30-15IFT), repeated sprint ability (RSA) test, modified agility T-test (MAT), countermovement jump (CMJ), 20-m sprint, shooting accuracy test, 1 min shooting test, passing test, defensive movement test and control dribble test. Both training interventions led to similar physiological and perceived exertion responses, showing no significant differences in HR ( P = .49, d = 0.2) and RPE ( P = .77, d = 0.1) between groups. Significant improvements were observed in 30-15IFT (SSG: 4.1%, d = 1.5; HIT-COD: 4.2%, d = 1.7), RSAmean (SSG: −2.2%, d = 1.0; HIT-COD: −1.9%, d = 1.0), RSAbest (SSG: −2.0%, d = 0.9; HIT-COD: −2.1%, d = 1.1), MAT (SSG: −7.2%, d = 1.7; HIT-COD: 5.7%, d = 1.5), defensive movement test (SSG: −5.1%, d = 2.1; HIT-COD: −5.8%, d = 1.8) and control dribble test (SSG: −3.4%, d = 1.0; HIT-COD: −2.6%, d = 1.0). The only significant group × time interaction was found ( P = .032, [Formula: see text] = 0.24), with SSG improving 1 min shooting (22.4%, d = 1.0) and HIT-COD performing slightly worse (−2.6%, d = 0.1) after a 4-week intervention. The current study suggests that using SSG is more effective than HIT-COD for female collegiate basketball players in pre-season, since SSG improves physical performance and basketball-specific movements as well as shooting abilities after a 4-week intervention.

Background:. Chronic obstructive pulmonary disease (COPD) is a common public health problem worldwide. Recent studies have reported that socioeconomic status (SES) is related to the incidence of COPD. This study aimed to investigate the association between SES and COPD among adults in Jiangsu province, China, and to determine the possible direct and indirect effects of SES on the morbidity of COPD. Methods:. A cross-sectional study was conducted among adults aged 40 years and above between May and December of 2015 in Jiangsu province, China. Participants were selected using a multistage sampling approach. COPD, the outcome variable, was diagnosed by physicians based on spirometry, respiratory symptoms, and risk factors. Education, occupation, and monthly family average income (FAI) were used to separately indicate SES as the explanatory variable. Mixed-effects logistic regression models were introduced to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for examining the SES-COPD relationship. A pathway analysis was conducted to further explore the pulmonary function impairment of patients with different SES. Results:. The mean age of the 2421 participants was 56.63 ± 9.62 years. The prevalence of COPD was 11.8% (95% CI: 10.5%–13.1%) among the overall sample population. After adjustment for age, gender, residence, outdoor and indoor air pollution, body weight status, cigarette smoking, and potential study area-level clustering effects, educational attainment was negatively associated with COPD prevalence in men; white collars were at lower risk (OR: 0.60, 95% CI: 0.43–0.83) of experiencing COPD than blue collars; compared with those within the lower FAI subgroup, participants in the upper (OR: 0.68, 95% CI: 0.49–0.97) tertiles were less likely to experience COPD. Such negative associations between all these three SES indicators and COPD were significant among men only. Education, FAI, and occupation had direct or indirect effects on pulmonary function including post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), FEV1, FVC, and FEV1 percentage of predicted. Education, FAI, and occupation had indirect effects on pulmonary function indices of all participants mainly through smoking status, indoor air pollution, and outdoor air pollution. We also found that occupation could affect post-bronchodilator FEV1/FVC through body mass index. Conclusions:. Education, occupation, and FAI had an adverse relationship with COPD prevalence in Jiangsu province, China. SES has both direct and indirect associations with pulmonary function impairment. SES is of great significance for COPD morbidity. It is important that population-based COPD prevention strategies should be tailored for people with different SES.

Identification of geographical origin is of great importance for protecting the authenticity of valuable agri-food products with designated origins. In this study, a robust and accurate analytical method that could authenticate the geographical origin of Geographical Indication (GI) products was developed. The method was based on elemental profiling using inductively coupled plasma mass spectrometry (ICP-MS) in combination with machine learning techniques for model building and feature selection. The method successfully predicted and classified six varieties of Chinese GI rice. The elemental profiles of 131 rice samples were determined, and two machine learning algorithms were implemented, support vector machines (SVM) and random forest (RF), together with the feature selection algorithm Relief. Prediction accuracy of 100% was achieved by both Relief-SVM and Relief-RF models, using only four elements (Al, B, Rb, and Na). The methodology and knowledge from this study could be used to develop reliable methods for tracing geographical origins and controlling fraudulent labeling of diverse high-value agri-food products.

Background: While racial–ethnic disparities in cesarean delivery rates among nulliparous women delivering a term singleton in the vertex position (NTSV) exist, it remains unclear the extent to whic...

The large deformation of deep soft rock roadways and the corresponding support technology are important to the coal mining industry. This study investigated the large deformation mechanism and the concrete-filled steel tubular support technology of a ventilation shaft roadway (VSR) on the basis of a well-documented engineering case. The mechanical parameters of the rock surrounding the VSR were evaluated in accordance with the geological strength index, and the failure modes of the VSR were summarized and analyzed on the basis of geological background and field survey results. The VSR exhibited asymmetrical deformation and the fracture of the 29U-shaped steel support at the side and vault. The deformation, stress, and plastic zone of the VSR without support and with the original support scheme were investigated using the Three-Dimensional Distinct Element Code, and the depth of the plastic zone was verified in accordance with the equivalent radius theory. Dramatic and multiple disturbances, the low strength of the surrounding rock, and the insufficient strength of the support caused the deformation of the VSR. The bottom of the two side walls of the original roadway was prone to inward deformation. Thus, the shape of the original roadway section was optimized by converting it from a straight wall with a semi-circular arch into an inclined wall with a semi-circular arch. A composite concrete-filled steel tubular support scheme is proposed and can be divided into active and passive support. The composite support scheme was verified through numerical simulation and a field application. The monitoring results obtained from the numerical simulation and on-site analysis reveal that the composite support scheme can control the large deformation of the VSR.

Lung cancer is one of the most prevalent and lethal cancers worldwide (1). The traditional treatments include surgery, chemotherapy, radiotherapy and interventional therapy. The survival of lung cancer patients has dramatically been prolonged in recent years with the availability of targeted therapies, antiangiogenic agents and immune checkpoint inhibitors (ICIs). Meanwhile, technologies for the molecular detection of lung cancer have also advanced rapidly: the detection of single driver genes has evolved to cover combined multi-gene analysis, and whole exome sequencing (WES) has increasingly been applied in the clinical setting. In addition, life support technologies, including ventilators, artificial liver, and artificial kidney as well as extracorporeal membrane oxygenation (ECMO), have further matured, providing powerful forms of life support for patients with various acute and critical diseases. However, most clinical studies have only enrolled patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores from 0 to 1, with few patients having PS scores of 2; patients with a PS score of 3 or 4 have been typically excluded. Therefore, due to the lack of high-quality evidence, supportive care is recommended for patients with a PS score of 3 to 4 in the current guidelines. In the real-world, however, approximately 25% of lung cancer patients present with PS score of 3 or 4 (2) or attain scores between 3 and 4 during the course of treatment. Certain patients with high PS scores can benefit from individualized anti-tumor treatment plus appropriate life-support techniques. In 2017, the Lung Cancer Research Team at the First Affiliated Hospital of Guangzhou Medical College & Institute of Respiratory Diseases for the first time pioneered the concept of “advanced severe lung cancer” (3) and argued that standardized therapy for chronic obstructive pulmonary disease (COPD) plus anti-tumor therapy can improve both quality of life and prognosis in patients with lung cancer combined with COPD. The authors also found that the early detection of lung cancer driver genes and timely targeted therapy can be successful in treating patients with advanced severe lung adenocarcinoma with a PS score of 4 (4). In 2019, the concept of advanced severe lung cancer was further developed in a featured article (5) that indicated “Advanced severe lung cancer: does not refer to end-stage lung cancer but rather to stage IIIB, IIIC and IV lung cancers with a PS score of 2–4, which can result from a variety of factors related to the disease itself or anti-tumor drugs and which are highly likely to benefit from the currently available systemic anti-tumor therapies”. In recent years, with the advances in lung cancer diagnosis and treatment techniques and life support technologies, more clinical studies have enrolled patients with a PS score of 2, and some real-world studies have enrolled patients with PS scores of 3–4. Even for patients with early-stage lung cancer, studies have shown that patients with poor PS scores and co-morbidities have a reduced chance of undergoing surgery and an increased mortality rate (6); nevertheless, survival benefit may still be obtained through surgical modifications combined with individualized and multidisciplinary treatment (7). Therefore, the concept of severe lung cancer should not be limited to advanced lung cancer, but applied to all lung cancer patients. In particular, due to the increase in treatment options as well as substantially prolonged survival, the majority of patients may have a PS score between 2 and 4 for a certain period of time due to a variety of reasons. How to provide timely and reasonable treatment for these lung cancer patients has become a critically important real-world research topic. Therefore, we invited lung cancer experts at home and abroad to consider this issue, and this group has reached the following consensus.

Objective Leptomeningeal metastases (LM) occur in up to 5% of non–small cell lung cancer (NSCLC) patients and often develop after previous systemic treatments. In this article, we explored whether immune checkpoint inhibitors (ICIs) enhanced the dismal survival of patients with LM. Materials and methods Data on NSCLC patients with LM prescribed ICIs were collected at the Guangdong Lung Cancer Institute. Furthermore, relevant literature was reviewed. Results A total of 255 NSCLC patients diagnosed with LM were screened from January 2015 to March 2020 at our institute. Cases reported by literature were also included. Finally, 32 NSCLC patients received ICIs after LM diagnosis; their median age was 55 years. Druggable genes were detected in 37.5% of all patients. The ICI regimens included nivolumab (n = 21), pembrolizumab (n = 9), and atezolizumab (n = 2). Ultimately, 62.5% of patients evidenced neurological symptom controlled. Two patients exhibited both intracranial and extracranial complete tumour response; one patient showed both intracranial and extracranial partial response (PR), one patient indicated intracranial PR and a systemic PR, and one patient showed central nervous system PR without extracranial response reported. The median progression-free survival (PFS) in the single-agent subgroup was 2.1 months (95% confidence interval [CI]: 1.4–2.9 months), and the median overall survival (OS) was 4.0 months (95% CI: 0.1–13.3 months). In the combined subgroup, the median PFS and OS were 3.0 months (95% CI: 1.1–4.9 months) and 5.4 months (95% CI: 0.5–10.3 months), respectively. Three patients exhibited remarkable PFS of over 20 months: all patients had ICI single agent, received cranial radiotherapy before ICI prescription, and took ICIs as second-line therapy, and two patients were EGFR/ALK wild type. Multivariate analysis showed that a better Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score was associated with prolonged PFS (P = 0.04). No difference in survival was seen between monotherapy and combination therapy groups. Conclusion NSCLC patients with LM may benefit from ICIs of both monotherapy and combination with other therapies, especially those with good ECOG-PS scores. Further work in this regard is required.

Fasudil has the potential to prevent liver fibrosis by activating natural killer cells and inhibiting the proliferation of hepatic stellate cells. Fasudil may be a promising clinical therapeutic drug for the prevention and treatment of liver fibrosis.

Background The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma (HCC) used placebo or sorafenib as comparators, and there are limited data providing a cross comparison of treatments in this setting, especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments. Aim To systematically review and compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma. Methods We searched PubMed, Science Direct, the Cochrane Database, Excerpta Medica Database, and abstracts from the American Society of Clinical Oncology 2020 annual congress. Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC. Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials. A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments. P value, a frequentist analog to the surface under the cumulative ranking curve, was used to rank treatments. Results In total, 1398 articles were screened and 27 included. Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and three other combination therapies. For overall response rate, lenvatinib ranked 1/19, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival (PFS), atezolizumab + bevacizumab was ranked 1/15, followed by lenvatinib. With the exception of atezolizumab + bevacizumab [hazard ratios (HR)PFS = 0.90; 95% confidence interval (CI): 0.64-1.25], the estimated HRs for PFS for all included treatments vs lenvatinib were > 1; however, the associated 95%CI passed through unity for bevacizumab plus erlotinib, linifanib, and FOLFOX4. For overall survival, atezolizumab plus bevacizumab was ranked 1/25, followed by vandetanib 100 mg/d and donafinib, with lenvatinib ranked 6/25. Atezolizumab + bevacizumab was associated with a lower risk of death vs lenvatinib (HRos = 0.63; 95%CI: 0.44-0.89), while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity. Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13, respectively, for the lowest incidence of treatment terminations due to adverse events, followed by sorafenib (5/13), lenvatinib (10/13), and atezolizumab + bevacizumab (13/13). Conclusion There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements. Therefore, first-line systemic treatment should be selected based on individualized treatment goals.

Background Asthma is a heterogeneous chronic inflammatory disease of the airway, involving reversible airflow limitation and airway remodeling. T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. However, there is limited understanding of the signaling pathways controlling Th17 cell differentiation in asthma. The aim of this study was to investigate if the Yes-associated protein (YAP)/hypoxia inducible factor-1α (HIF-1α)/microRNA-182 (miR-182)/early growth response 2 (EGR2) axis is involved in mediating Th17 cell differentiation and disease severity in asthma. Methods The study included 29 pediatric patients with asthma, 22 healthy volunteers, ovalbumin-induced murine asthma models, and mouse naive CD4+ T cells. The subpopulation of Th17 cells was examined by flow cytometry. The levels of interleukin-17A were determined by enzyme linked immunosorbent assay. Chromatin immunoprecipitation-quantitative polymerase chain reaction assays and dual-luciferase reporter gene assays were performed to examine interactions between HIF-1α and miR-182, and between miR-182 and EGR2. Results YAP, HIF-1α, and miR-182 were upregulated but EGR2 was downregulated in human and mouse peripheral blood mononuclear cells from the asthma group. Abundant expression of YAP and HIF-1α promoted miR-182 expression and then inhibited EGR2, a target of miR-182, thus enhancing Th17 differentiation and deteriorating asthma and lipid metabolism dysfunction. In addition, in vivo overexpression of EGR2 countered the promoting effect of the YAP/HIF-1α/miR-182 axis on asthma and lipid metabolism dysfunction. Conclusion These results indicate that activation of the YAP/HIF-1α/miR-182/EGR2 axis may promote Th17 cell differentiation, exacerbate asthma development, and aggravate lipid metabolism dysfunction, thus suggesting a potential therapeutic target for asthma.

Background Programmed death protein (ligand) 1 [PD-(L)1] inhibitors have provided new therapeutic options for advanced lung cancer. However, patients with hepatitis B virus (HBV) infection have been traditionally excluded from most registered trials of this form of treatment. Methods We performed a retrospective analysis of patients with HBV and advanced lung cancer who received anti-PD-1 immunotherapy from September 2018 to May 2020 in our department. Treatment-related hepatotoxicity was evaluated and recorded. Overall response rate and progression free survival were also assessed in the patients using iRECIST. Results Seventeen patients were evaluated in this analysis. Of these, six (35.3%) experienced hepatic transaminase elevation during immunotherapy. Three of these patients developed Grade 3 hepatic immune-related adverse events and received systemic corticosteroids, following which aminotransferase levels recovered to normal in all patients and no adverse events were observed in subsequent treatment. No patient experienced HBV reactivation or flare. One patient developed active pulmonary tuberculosis (TB). Other adverse events were mild, well tolerated and short term. The objective response rate (ORR) of the cohort was 62.5%, and the median progression-free survival (PFS) was 3 months. Conclusions Lung cancer patients can be treated safely with anti-PD-1 inhibitors in the context of HBV infection. Close monitoring for hepatotoxicity and prophylactic antiviral therapy is advised. Further studies on the use of anti-PD-1 inhibitors in HBV-infected patients are needed.

The effects of low-price element Al doping and Cu deficiency on the thermoelectric performance of Bacchus are studied in the paper. Bi1−xAlxCu1−xSeO (x = 0, 0.025, 0.05, 0.075, 0.1, 0.125) were prepared by high-energy ball-milling, high-temperature solid-state reaction and hot-press sintering. Due to the massive substitutions of Bi3+ with Al2+, the Al in Bacchus exceeds the solution limit and the thermal conductivity decreases significantly. The structure of the thermoelectric materials is lamellar and tetragonal, and Al doping and Cu deficiency can refine the grains. The deficiency of Cu can reduce the generation of Al4Cu9, which guarantees the stability of the sample at high temperature and leads to the formation of a large number of holes. Moreover, the hole carrier again becomes the main carrier of the sample. Therefore, all the samples belong to p-type semiconductors at room temperature. In the results, the combination of optimized conductivity and thermal conductivity is helpful to improve the ZT value; the maximum the ZT value is 0.90 of Bi0.875Al0.125Cu0.875SeO at 873 K, which is 2.46 times higher than that of Bacchus.

Distributed deep neural network (DDNN) training becomes increasingly compelling as the DNN model gets complex and the dataset grows large. Through an in-depth analysis of the latest Microsoft GPU cluster trace, we show that the co-located Parameter Server (PS) configuration is not uncommon in production DDNN training clusters, which inevitably causes intense network resource contention among the co-located PS and worker tasks. Our motivation experiments on Amazon EC2 further show that such network resource contention brings severe performance variation to DDNN training jobs. While existing works largely mitigate the inter-job network resource contention, the intra-job (i.e., task-level) network resource contention among the co-located PS and worker tasks has received comparably little attention. To tackle such performance issues, in this paper, we design and implement Nebula, a Network bandwidth resource allocation strategy for DDNN training tasks, in order to mitigate the network resource contention and alleviate the performance variation of DDNN training jobs. Nebula monitors the weights of co-located PS and workers and rations the network bandwidth resources for the two tasks by comparing the corresponding task weights. We implement a prototype of Nebula and conduct extensive prototype experiments with representative DNN models trained on Amazon EC2. Our experiment results demonstrate that Nebula can reduce the iteration time of a DDNN training job by up to 25% and improve the cluster resource utilization by up to 30% in comparison to MXNet, yet with practically acceptable runtime overhead.

Background The outbreak of COVID-19 pandemic in China has greatly impacted the radiotherapy (RT) strategy for breast cancer (BC) patients, which might lead to an increased distressing psychological symptom. Thus, we perform a multi-center cross-section survey aiming to investigate the prevalence of fears of cancer recurrence (FCR) and explore predictors for FCR in BC patients referred for RT during pandemic. Methods: 542 BC patients who referred for RT between 24th Jan and 30th April 2020 during pandemic were consecutively enrolled from 14 hospitals around China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients’ sociodemographic, treatment information as well as psychological characteristics were collected using an information sheet, Fear of progression questionnaire-short form (FoP-Q-SF), Hospital Anxiety and Depression Scale (HADS) and EORTC QLQ-C30. The influence of pandemic on RT schedule was divided into four categories: “delay” was defined as >12 weeks from surgery to RT in patients without chemotherapy or >8 weeks from last time of anti-tumor therapy (including chemotherapy and surgery) to RT in patients with chemotherapy; “Special normal” was defined that patients themselves believed to have delayed RT initiation but actually not; “Interruption” was defined as any unplanned gaps in original RT regime and all other would be classified into “normal”. Another type of influence on RT strategy was that patients had to shift planned RT hospital from Grade-A tertiary hospital to local hospitals. Univariable analyses of FCR were performed in a one-way analysis of variance (ANOVA) or student t-test or Pearson correlation analyses and candidate variables with P Citation Format: Jinrong Xie, Weixiang Qi, Lu Cao, Yuting Tan, Jin Huang, Xiaodong Gu, Bingguang Chen, Peipei Shen, Ying Zhang, Qingwen Zhao, Hecheng Huang, Yubin Wang, Haicheng Fang, Zhenjun Jin, Hui Li, Xuehong Zhao, Xiaofang Qian, Feifei Xu, Dan Ou, Shubei Wang, Cheng Xu, Min Li, Zefei Jiang, Yu Wang, Xiaobo Huang, Jiayi Chen. Predictors for fear of cancer recurrence in breast cancer patients referred for radiation therapy during the COVID-19 pandemic: A multi-center cross-section survey [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS2-07.

Background Subclinical hypothyroidism (SCH) is characterized by an elevated thyroid-stimulating hormone and normal free thyroxine. This study aimed to evaluate the influence of SCH on the recovery of patients after coronary artery bypass grafting (CABG). Methods From January 2015 to December 2018, 548 SCH patients and 6718 euthyroid patients who underwent CABG were identified. Propensity score matching was used to create two cohorts with similar baseline characteristics (n = 545 in each group). The early postoperative outcomes were compared. Results After CABG, there was no difference in the incidence of postoperative atrial fibrillation between the two groups (20.4% in the SCH group and 20.6% in the euthyroidism group; odds ratio: 0.99; 95% confidence interval: 0.74-1.33; p = 0.94). Subgroup analyses did not indicate an effect in any category of patients. The proportions of the use of dopamine and noradrenaline in the SCH group were higher than those in the euthyroid patients (76.7% vs. 68.6%, p = 0.003; 56.5% vs. 49.0%, p = 0.01, respectively). The total duration of inotropic support in the SCH group was longer than that in the euthyroid patients (median duration: 4 vs. 3 days, p = 0.002). The incidence of impaired wound healing was higher in the SCH group than in the euthyroid group (3.7% vs. 1.1%, p = 0.005). Conclusions Compared with euthyroidism, SCH is not associated with an increased risk of atrial fibrillation in patients undergoing CABG. It is associated with an increased risk of several minor perioperative problems, which should be anticipated and preemptively managed.

Background The introductions of anti‐ human epidermal growth factor receptor‐2 (HER2) agents have significantly improved the treatment outcome of patients with HER2‐positive breast cancer. BAT8001 is a novel antibody‐drug conjugate targeting human epidermal growth factor receptor‐2 (HER2)‐expressing cells composed of a trastuzumab biosimilar linked to the drug‐linker Batansine. This dose‐escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti‐tumor activity of BAT8001 in patients with HER2‐positive locally advanced or metastatic breast cancer. Methods This trial was conducted in subjects with histologically confirmed HER2‐positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21‐day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective. Results Between March 2017 to May 2018, 29 HER2‐positive breast cancer patients were enrolled. The observed dose‐limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ‐glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%‐61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%‐94.2%) patients. Conclusions BAT8001 demonstrated favorable safety profiles, with promising anti‐tumor activity in patients with HER2‐positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2‐positive breast cancer., BAT8001 demonstrated favorable safety and tolerability profiles, with promising anti‐tumour activity in patients with HER2‐positive advanced or recurrent solid tumours. BAT8001 has the potential to provide a new therapeutic option in heavily pretreated patients with metastatic Her2‐positive breast cancer.

Based on the magnetic field recorded with a magnetic sensor deployed at 130-m distance from the channel base, we remotely measured the return stroke current waveform in classical rocket-triggering lightning flashes, including 40 M-components and 48 return strokes (RSs) in eight triggered flashes observed during the summer of 2019. The current waveform retrieved from the close magnetic field is in excellent agreement with the coaxial shunt measurement. For return strokes, the amplitude error of the peak current is less than 1 kA. The error of the 30%–90% risetime is less than 0.1 μ s. The error of the half-peak width is less than 1 μ s. The error of charge transfer within 0.1 ms of the return strokes is less than 0.1 C. For M-components, the amplitude error of the peak current is about less than 0.3 kA. The error of the 30%–90% risetime is generally less than 4%. The error of the half-peak width is approximately less than 3%. The error of charge transfer within 0.1 ms of M-components is less than 0.02 C. The magnetic sensor is likely applicable to measure lightning current without direct current measurement at near range in rocket-triggered lightning or natural lightning flashes.

Scarf repair method which can get uniform stress distributions and smooth surfaces has emerged as an adequate technique to repair damaged aerospace composite components. However, a prominent proble...

SUMMARY: This study estimates causality of physical activity (PA) on bone mineral density (BMD) by conducting multivariable Mendelian randomization (MR). The findings suggest that habitual vigorous PA increases lumbar spine BMD, and higher overall acceleration average would improve forearm BMD. The results could promote PA intervention targeting individuals with optimized type. INTRODUCTION: Evidence from epidemiologic studies showed type, frequency, and duration of PA influenced BMD. However, these observational studies may be confounded by many factors, resulting in spurious associations. We aimed to conduct multivariable MR to estimate the causal effect of self-reported and device-measured PA on osteoporosis. METHODS: Three self-reported and two device-measured PA-related traits were selected as exposures. Outcomes were BMD at different skeletal sites: femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD). Exposure datasets were obtained from UK Biobank with total 377,234 subjects. Outcome datasets were obtained from GEFOS consortium with 53,236 subjects. Standard MR analysis and multivariable MR were conducted to assess the total and direct causal effect of PA on BMD. RESULTS: For self-reported PA, inverse-normalized moderate-to-vigorous had a direct causal effect on FN BMD independently (β = − 1.116 (95% confidence interval, 95%CI: − 2.210, − 0.023), P = 0.045); vigorous PA showed a direct effect (β = 3.592 (95%CI: 0.310, 6.874), P = 0.032) on LS BMD independently. While overall acceleration average and fraction of accelerations both had a direct causal effect on FA BMD independently. CONCLUSIONS: Habitual vigorous PA could increase LS BMD. Individuals with higher overall acceleration average would have a higher FA BMD.

Background: Ischemia-reperfusion (I/R) injury is the main cause of acute kidney injury (AKI), and its incidence and mortality increase year by year in the population. Dexmedetomidine (DEX) can improve AKI by regulating inflammation and oxidative stress, but its mechanism is still unclear. Methods: A hypoxia/reoxygenation (H/R) model of HK-2 cells and a kidney I/R model of C57BL/6J mice were established. In the experiment, cells were transfected with sh-PGC-1α to inhibit PGC-1α expression. The changes of ROS level and mitochondrial membrane potential (MMP) were analyzed. HE staining was used to assess kidney damage in mice. Concentration of kidney injury markers serum creatinine and blood urea nitrogen and expression of inflammatory factors were detected by ELISA. qPCR analysis was used to detect mRNA levels of related proteins in cells and mouse kidney tissues. The protein intracellular content and phosphorylation levels were determined by Western blotting. Result: The production of inflammatory factors and ROS was increased in HK-2 cells treated with H/R, while MMP, cell viability, and mitochondrial-related protein levels were decreased. DEX attenuated pathological changes induced by H/R, while knockdown of PGC-1α eliminated the mitigation effect. DEX inhibited the damage of I/R to the kidneys of mice and increased the expression of mitochondrial-related proteins and PGC-1α in the kidneys, while inhibiting the phosphorylation of STAT1 and the expression of IRF-1. Conclusions: DEX appears to inhibit mitochondrial damage and cellular inflammation by upregulating PGC-1α to affect STAT1 phosphorylation level and IRF-1 expression, thereby preventing AKI.

Compositional characteristics of maceral and extractable organic matter (EOM) of the No. 10 coal from the Yueliangtian mine, Guizhou, Southwestern China, were analyzed by optical microscopy, gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS). The depositional conditions, thermodynamic effect, type and maturity of organic matter, and possible health hazards were evaluated. The random vitrinite reflectance (R o) is 1.01%, and the macerals are dominated by collodetrinite, inertodetrinite, collotelinite, and fusinite. The coal seam is a terrestrial sedimentary environment of the lower delta plain through the analysis of coal facies. Additionally, the extracted yield of EOM is 1.01%. The low ratio of saturated to aromatic fraction and the distribution of n-alkanes indicate that the coal-forming plants are primarily terrestrial higher plants. Typical isoprenoid biomarker parameters, including pristane/phytane (Pr/Ph), Pr/n-C17, and Ph/n-C18, reflect a weak oxidizing environment of coal. The hopanoid biomarkers, odd-even predominance index (OEP), and carbon preference index (CPI) reveal that the organic matter was mature. More than one hundred polycyclic aromatic compounds (PACs) were eluted and identified, and the phenanthrenes and naphthalenes account for a higher proportion. Thermodynamic stabilities play an essential role in the conversion of molecular structures, which support the relatively high contents of 2-methylnaphthalene, 2- and 3-methylphenanthrenes, and 2,6- and 2,7-dimethylphenanthrenes compared to their respective isomers. The oxygen-containing and sulfur-containing aromatic compounds also indicate the weak oxidization of the coal-formation environment, which is consistent with the results of isoprenoid biomarkers. Because of the carcinogenicity and mutagenicity of PACs, the distribution and toxic equivalency of PACs are briefly summarized.

Social relation, as the basic relation in our daily life, is vital for social action analysis. However, how to learn the social feature between people is still not tackled. In this work, we propose a gaze-aware graph convolutional network (GA-GCN) for social relation recognition, which targets discovering the context-aware social relation inference with gaze-aware attention. To predict the gaze direction, we apply a convolutional network trained with gaze direction loss. Then, we build a graph convolutional inference module, which is a two-stream graph inference with both gaze-aware attention and distance-aware attention. The attention can pick up relevant context objects for context-aware representation. We further introduce additional scene features and construct a multiple feature fusion module, which can adaptively learn social relation representation from both scene feature and context-aware feature. Extensive experiments on the PISC and the PIPA datasets demonstrate that our GA-GCN can find interesting contextual objects and achieves state-of-the-art performances.

Recently, microfiber-optic sensors with high sensitivity, fast response times, and a compact size have become an area of interest that integrates fiber optics and nanotechnology. Distinct advantages of optical microfiber, such as large accessible evanescent fields and convenient configurability, provide attractive benefits for micro- and nano-scale optical sensing. Here, we review the basic principles of microfiber-optic sensors based on a broad range of microstructures, nanostructures, and functional materials. We also introduce the recent progress and state-of-the-art in this field and discuss the limitations and opportunities for future development.

Nano (or) microfiber structures made from biodegradable polymers offer many benefits for biomedical applications, including the tissue engineering system. In this study, a mixture of poly (lactic acid) (PLA)/gelatin (GEL) conjugated epidermal growth factor (EGF) electrospun nanofiber scaffolds, which may have potential applications for nursing care of diabetic wound healing. The amount of EGF conjugation on the PLA/GEL nanofibers was quantitated by X-ray photoelectron spectroscopy. A morphological examination of the electrospun nanofibers was performed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), which has bead-free morphology nanofibers. After characterizing, the PLA/GEL and PLA/GEL/EGF scaffolds were selected for further investigation based on their superior mechanical properties, including tensile strength, maximum elongation, and tensile modulus. We evaluated the antibacterial activity, cell proliferation and the efficiency of diabetic wound healing in vivo. The antibacterial effect of EGF present in the PLA/GEL nanofibers was assessed using the zone inhibition test against S. aureus and E. coli. In vitro cell proliferation activity was well maintained after the PLA/GEL conjugation and was compared to that of EGF with L929 fibroblast cells. The nanofiber PLA/GEL conjugated with EGF exerted greater curative activities in vivo compared to the control groups or EGF solutions. This study showed that the nanofiber PLA/GEL in combination with EGF could potentially be used as a novel material for nursing care of wound healing by antibacterial, increasing inflammatory cell, and re-epithelialization.

Lessons Learned Fulvestrant 500 mg maintenance therapy showed a clinical benefit rate of 76% and median progression-free survival of 16.1 months in patients who achieved objective responses or disease control after first-line chemotherapy. Adverse events with fulvestrant maintenance therapy were consistent with the known safety profile of the drug. Background Evidence for maintenance hormonal therapy after chemotherapy for estrogen receptor (ER)–positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer is scarce. This study aimed to evaluate the efficacy of fulvestrant 500 mg maintenance therapy in patients after first-line chemotherapy. Methods We enrolled postmenopausal women with ER-positive/HER2-negative advanced breast cancer who attained tumor responses or disease control with four to eight cycles of chemotherapy as first-line treatment. Fulvestrant 500 mg was injected on days 1, 15, and 29 and every 28 (±3) days thereafter. The primary endpoint was the clinical benefit rate (CBR); the secondary endpoints included the objective response rate (ORR), progression-free survival (PFS), and safety. Results We included 58 patients; the median follow-up duration was 32.6 months. The CBR since commencing fulvestrant maintenance therapy was 76% (95% confidence interval [CI], 63%–86%), and ORR was 14% (95% CI, 6%–25%); eight patients achieved partial response. The median PFS for fulvestrant maintenance therapy was 16.1 months (95% CI, 10.3–21.0 months). Thirty-nine patients (67%) reported at least one adverse event, of which most were grade 1/2, whereas three patients (5%) reported grade 3 adverse events. Conclusion Fulvestrant 500 mg is a feasible and promising hormonal maintenance strategy in patients with ER-positive/HER2-negative advanced breast cancer who have no disease progression after first-line chemotherapy.

Background Nearly 30% of stage IA non-small-cell lung cancer patients eventually die of recurrence or metastasis. This study aimed to predict stage IA lung adenocarcinoma (LADC) patients who underwent radical resection with a high risk of recurrence or metastasis. Methods Information on clinicopathological, genetic and therapeutic features and recurrence status was collected in this retrospective and two-center study. A nomogram based on multivariate analysis was established to predict disease-free survival. Further stratification was performed to identify populations with a high risk of relapse. Results A total of 1584 patients with pathological stage IA LADC who underwent radical surgery between 2011 and 2015 were enrolled from two medical institutions in this study. The nomogram including tumor differentiation and EGFR mutation had a higher C-index of 0.880 (95% CI 0.833-0.926) compared to 0.598 (95% CI 0.486-0.711) for the AJCC 8th TNM staging system. Furthermore, the C-index for the validation cohort was 0.798 (95% CI 0.738-0.857). In addition, the 3-year cumulative nonrecurrence rate in the high-risk group stratified by this model was 21.8% compared to 98.1% in the low-risk group. Conclusion This study proposed a new nomogram including tumor differentiation and EGFR mutation to predict recurrence or metastatic probability in stage IA LADC patients who underwent radical surgery. This nomogram could identify patients in the high-risk group and help guide adjuvant treatment in the future.