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Fengting Wang,1,* Limin Rong,1,* Linlin Luo,2 Fuqin Mu,1 Liju Qian,3 Yandan Qian,4 Xinyao Zhang,1 Yuying Lang,1 Weijia Wang,1 Yan Liu,5,6 Ying Zhang,7 Jianli Wang1,8 1School of Mental Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Hematology, Tai’an Central Hospital, Tai’an, Shandong, People’s Republic of China; 3Shandong Daizhuang Hospital, Jining, Shandong, People’s Republic of China; 4The Third People’s Hospital of Jiashan County, Jiashan, Zhejiang, People’s Republic of China; 5School of Public Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 6Center of Evidence-Based Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China; 7School of Public Health, University of Sydney, Sydney, NSW, Australia; 8Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada*These authors contributed equally to this workCorrespondence: Fengting Wang, School of Mental Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email wft.0810@163.com Yan Liu, School of Public Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email hakunaly@163.comBackground: Youth and young adults have a high prevalence of major depressive disorder (MDD). Limited longitudinal research has explored the relationship between different dimensions of psychological stress and MDD. This study aimed to estimate the effect of psychological stress on the risk of first onset MDD in a sample of Chinese freshmen.Methods: Using a longitudinal design, 8079 Chinese first-year students were recruited at baseline, and 6985 were followed up one year later. The Psychological Stress Scale for College Students was utilized to evaluate the levels of psychological stress. MDD was evaluated using the Chinese version of the Composite International Diagnostic Interview (CIDI-3.0). Logistic regression modeling was utilized to estimate the associations between dimensions of psychological stress and the risk of MDD.Results: Two dimensions of psychological stress, namely learning stress (OR=1.05, 95% CI:1.01– 1.09, P=0.017) and economic stress (OR=1.11, 95% CI:1.04– 1.19, P=0.001), were significantly associated with the risk of MDD. Other dimensions of psychological stress (specify family stress, interpersonal stress, intimate relationship stress, employment stress and appearance stress) were not associated with MDD.Conclusion: Psychological stress, especially learning and economic stresses, could increase the risk of MDD in university students. These factors should be incorporated into mental health prevention and intervention programs at universities to reduce the risks of MDD.Keywords: major depressive disorder, psychological stress, longitudinal study, freshmen

Donna D Carstens,1 Diego J Maselli,2 Erin E Cook,3 Fan Mu,3 Jingyi Chen,3 Danni Yang,3 Jessica Karacz DeMartino,1 Yen Chung1 1Respiratory & Immunology, AstraZeneca, Wilmington, DE, USA; 2Division of Pulmonary Diseases & Critical Care, University of Texas Health, San Antonio, TX, USA; 3Health Economic and Outcomes Research, Analysis Group, Boston, MA, USACorrespondence: Jessica Karacz DeMartino, AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE, 19897, USA, Tel +1 302-897-0843, Email jessica.demartino@astrazeneca.com

Fengchun Mu,1,2,&ast; Bingjie Fan,1,&ast; Butuo Li,1 Wenru Qin,1 Haoqian Li,1,2 Chunni Wang,1 Bing Zou,1 Shijiang Wang,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 2Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 271016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626142, Fax +86-531-67626141, Email wanglinlinatjn@163.comPurpose: The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with advanced lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT).Patients and Methods: Patients with advanced lung adenocarcinoma simultaneously treated with 1G/2G/3G EGFR-TKIs and TRT between 2015– 2021 at Shandong Cancer Hospital and Institute were screened. The incidence rate of clinical and imaging RP was compared between the three groups.Results: A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups were 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP were 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥ 3 in the three groups were 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥ 3 in the three groups were 11%, 32%, and 10% (p=0.002), respectively. The incidence of clinical RP was higher in the CFRT group than in the SBRT group, with an overall clinical grade of 38% vs 10% (p< 0.001) and imaging grade of 46% vs 10% (p< 0.001), respectively. In the multivariate analysis, only GTV volume was an independent predictive factor for all risks of clinical and imaging RP. V20 and grouping of 1G/2G/3G EGFR-TKIs were other independent predictive factors for the risk factors of RP for imaging grades.Conclusion: Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP.Keywords: EGFR-TKI, molecular targeted therapy, radiation pneumonitis, thoracic radiotherapy, lung adenocarcinoma

Based on the CICE sea ice model and the PDAF parallel data assimilation framework, this paper uses the local error subspace transform Kalman filter method (LESTKF) to assimilate the sea ice concentration, sea ice thickness and sea ice freeboard data into the model, and designs experiments to study the improvement of multi-parameter assimilation on the simulation of Arctic sea ice concentration and range. The results show that data assimilation has a good improvement effect on the simulation of Arctic sea ice concentration and range. The average deviation, root mean square error and mean absolute error of the assimilation experiment are significantly reduced compared with the control experiment. The assimilation experiment improves the simulation of sea ice concentration and range most obviously in summer. Multi-parameter assimilation can improve the prediction accuracy and reliability of Arctic sea ice change.

With the large-scale integration of distributed renewable energy into low-voltage distribution station areas, rapidly growing services put forward new requirements on transparent monitoring. In order to accurately and objectively quantify the transparency of various distribution station areas and measure the impact of different dimensional indexes on the transparency evaluation of distribution station areas, this paper proposes a confidence relative off-target distance-based multi-dimensional transparency evaluation method. First, a multi-dimensional transparency evaluation index system with electrical and communication integration is constructed. Second, an improved gray target model combining both positive and negative target vectors is established to realize bi-directional quantitative analysis. Then, the relative off-target distance is calculated based on the endowment coefficient by leveraging both subjective and objective weights. Finally, the confidence of the relative off-target distance is calculated based on fuzzy entropy to improve the reliability of transparency evaluation. The simulation results show that this method can effectively distinguish the transparency gap between different distribution station areas, identify the single dimensional index with the greatest contribution or potential, and verify the effectiveness of the proposed method applied to the transparency evaluation of distribution station areas.

The global football market has grown in the past three decades, and football clubs' sustainable financial operations have gradually gained attention. This study aims to construct a financial risk assessment model applicable to the football industry, explore globally listed football clubs' overall financial operating characteristics, and analyse the leading causes of the club's financial crisis. We selected a sample of 24 currently listed football clubs worldwide and an exploratory factor analysis (EFA) model to construct the model of financial risk assessment for football clubs. The model identified and classified the financial risk components for listed football clubs, thus facilitating risk warning and prevention for modern professional clubs. This study found that football clubs are at higher financial risk overall, with the following general characteristics: (1) small amount of listed capital; (2) high asset-liability ratio; (3) low net profits and a large proportion of clubs make losses; and (4) weak asset liquidity. Finally, the study discussed the leading causes of the financial crises of football clubs in both external and internal dimensions, providing a reference for the self-sustainability of clubs and football authorities.

In the past 30 years, the global influence of the FIFA World Cup has continued to grow. According to statistics, the final match of the 2022 World Cup in Qatar attracted an audience of over 3 billion. Nowadays, nations (and regions) emphasize the correlation between overall social progress, football tradition, and national sporting prowess. This study aims to comprehend the dynamics of international football development and secure a competitive edge in the global arena. The study collected panel data from 68 countries (regions) participating in the final stage of the World Cup from 1994 to 2022. It modelled them using a generalized linear mixed model (GLMM) to reveal the macro determinants of success and winning patterns in international football performance. The findings show that (1) football tradition's “characteristic values” (e.g. World Cup host, the experience of hosting the World Cup and the number of all-time World Cup winners) and national comprehensive sporting strength (as represented by the Olympic Games results) have significantly contributed to the national team's World Cup performance; (2) the country's Human Development Index (HDI) has a significant negative impact on World Cup performance; (3) the history of football participation (e.g. the number of years of membership in the Intercontinental Football Association (IFA), history of professional leagues) will have little impact on World Cup performance; (4) two interactive variables: population scale × national comprehensive sporting strength (GPOP × CSOGMedals) and economic level × football tradition (lnGDP × PLHistory), have a negative and positive combined effect on World Cup performance, respectively.

ABSTRACTFlexoelectric effect can be used to design actuators to control engineering structures including beams, plates, and shells. Multiple flexoelectric actuators method has the advantage of less stress concentration and better control effect, but the mode-dependent optimal actuator locations could influence the flexoelectric actuation effect significantly. In this work, a neural network model is established to study the optimal combinations of multiple flexoelectric actuators on a rectangular plate. In the physical model, an atomic force microscope (AFM) probe was employed to generate an electric field gradient in the flexoelectric patch, so that flexoelectric control force and moment can be obtained. Multiple flexoelectric actuators on the plate was considered. Case studies showed that the flexoelectricity induced stress mainly concentrate near the probe, the size and shape of the flexoelectric patch have limited effect on the actuation, hence, only the actuator positions were choosing as the input of the ANN model. Using the prediction of the neural network model, the driving effect of a large number of actuators at different positions can be quickly obtained, and the optimal position of the actuator can be analyzed more accurately.

Existing object pose estimation methods cannot provide estimated poses with inter-frame stability.As a result,when the results are directly used in visualization scenarios such as augmented reality,it will cause screen jitter,so it's not suitable enough for application scenarios such as human-machine collaboration.This paper proposes an object pose estimation optimization method that includes multiple methods.By improving the loss function of the original pose estimation method and using causal filtering to optimize the pose estimation result,a stable estimated pose can be obtained.In addition,in order to consummate the eva-luation system of the degree of stability of the pose estimation method,this paper proposes three evaluation indicators:the direct deviation distance DBD,the direction reversal rate DRR and the average displacement angle ADA,which can evaluate the object pose estimation method from multiple viewpoints.Finally,the YCB-STB dataset is used to test,and the method is compared with the original method without optimization.The results show that the proposed method can improve the inter-frame stability of the existing object pose estimation methods without introducing additional resources,and has a small impact on the accuracy of the original method,which satisfies the requirement of object attitude estimation in human-machine collaborative scene.

Abstract A mouse model of human Familial Adenomatous Polyposis responds favorably to pharmacological inhibition of 5′-methylthioadenosine phosphorylase (MTAP). Methylthio-DADMe-Immucillin-A (MTDIA) is an orally available, transition state analogue inhibitor of MTAP. 5′-Methylthioadenosine (MTA), the substrate for MTAP, is formed in polyamine synthesis and is recycled by MTAP to S-adenosyl-l-methionine (SAM) via salvage pathways. MTDIA treatment causes accumulation of MTA, which inhibits growth of human head and neck (FaDu) and lung (H359, A549) cancers in immunocompromised mouse models. We investigated the efficacy of oral MTDIA as an anti-cancer therapeutic for intestinal adenomas in immunocompetent APCMin/+ mice, a murine model of human Familial Adenomatous Polyposis. Tumors in APCMin/+ mice were decreased in size by MTDIA treatment, resulting in markedly improved anemia and doubling of mouse lifespan. Metabolomic analysis of treated mice showed no changes in polyamine, methionine, SAM or ATP levels when compared with control mice but indicated an increase in MTA, the MTAP substrate. Generation of an MTDIA-resistant cell line in culture showed a four-fold amplification of the methionine adenosyl transferase (MAT2A) locus and expression of this enzyme. MAT2A is downstream of MTAP action and catalyzes synthesis of the SAM necessary for methylation reactions. Immunohistochemical analysis of treated mouse intestinal tissue demonstrated a decrease in symmetric dimethylarginine, a PRMT5-catalyzed modification. The anti-cancer effects of MTDIA indicate that increased cellular MTA inhibits PRMT5-mediated methylations resulting in attenuated tumor growth. Oral dosing of MTDIA as monotherapy has potential for delaying the onset and progression of colorectal cancers in Familial Adenomatous Polyposis (FAP) as well as residual duodenal tumors in FAP patients following colectomy. MTDIA causes a physiologic inactivation of MTAP and may also have efficacy in combination with inhibitors of MAT2A or PRMT5, known synthetic-lethal interactions in MTAP −/− cancer cell lines.

Purpose: To explore the efficacy of nimodipine, nifedipine, and edaravone (EDA) combined with Nao-Xue-Shu in patients with hypertensive intracerebral hemorrhage (HICH) and to determine the best western medicine combined with Nao-Xue-Shu for treating HICH patients using a ranking method.Methods: After a comprehensive search of the China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP information database, Chinese Biomedical Database (CBM), PubMed, Embase, and Cochrane Library database from the database establishment 31 December 2021, data extraction and quality assessment were conducted for the included articles. The primary outcome measure was the effectiveness after treatment. Secondary outcome measures were after-treatment the National Institutes of Health Stroke Scale (NIHSS) scores, hematoma volume, perihematoma edema volume, and inflammatory factor expression levels. Statistical analyses were performed using Stata 16.0 and RevMan 5.3.0 software.Results: We included 19 randomized controlled trials (RCTs) and six non-RCTs. The effective rate after treatment was ranked from the best to the worst as follows: routine cure measure (RCM) + nifedipine + Nao-Xue-Shu, RCM + EDA + Nao-Xue-Shu, RCM + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + EDA, and RCM. The post-treatment NHISS scores from lowest to highest were as follows: RCM + EDA + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + EDA, RCM + nimodipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, RCM + Nao-Xue-Kang, and RCM. The post-treatment hematoma volume from minimum to maximum was as follows: RCM + EDA + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, RCM + Nao-Xue-Kang, and RCM. The post-treatment perihematoma edema volume from minimum to maximum was as follows: RCM + EDA + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, and RCM. For inflammatory factor expression levels after treatment, IL-6 concentration levels after treatment from lowest to highest wasas follows: RCM + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + EDA + Nao-Xue-Shu, and RCM. TNF-α concentration levels after treatment from lowest to highest was as follow: RCM + nimodipine + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, and RCM.Conclusion: Nao-Xue-Shu combined with nifedipine showed better effectiveness after treatment in HICH patients compared with the other combinations. Nao-Xue-Shu combined with EDA was more effective for improving neurological function and reducing both hematoma and edema volumes around the hematoma compared with the other combinations. However, Nao-Xue-Shu alone or Nao-Xue-Shu combined with nimodipine may be more effective for reducing proinflammatory factor expression.

Abstract Background In the absence of effective drugs, controlling SARS relies on the rapid identification of cases and appropriate management of the close contacts, or effective vaccines for SARS. Therefore, developing specific and sensitive laboratory tests for SARS as well as effective vaccines are necessary for national authorities. Results Genes encoding truncated nucleocapsid (N) and spike (S) proteins of SARSCoV were cloned into the expression vector pQE30 and fusionally expressed in Escherichia coli M15. The fusion protein was analyzed for reactivity with SARS patients' sera and with anti-sera against the two human coronaviruses HCoV 229E and HCoV OC43 by ELISA, IFA and immunoblot assays. Furthermore, to evaluate the antigen-specific humoral antibody and T-cell responses in mice, the fusion protein was injected into 6-week-old BALB/c mice and a neutralization test as well as a T-cell analysis was performed. To evaluate the antiviral efficacy of immunization, BALB/c mice were challenged intranasally with SARSCoV at day 33 post injection and viral loads were determined by fluorescent quantitative RT-PCR. Serological results showed that the diagnostic sensitivity and specificity of the truncated S-N fusion protein derived the SARS virus were > 99% (457/460) and 100.00% (650/650), respectively. Furthermore there was no cross-reactivity with other two human coronaviruses. High titers of antibodies to SRASCoV appeared in the immunized mice and the neutralization test showed that antibodies to the fusion protein could inhibit SARSCoV. The T cell proliferation showed that the fusion protein could induce an antigen-specific T-cell response. Fluorescent quantitative RT-PCR showed that BALB/c mice challenged intranasally with SARSCoV at day 33 post injection were completely protected from virus replication. Conclusion The truncated S-N fusion protein is a suitable immunodiagnostic antigen and vaccine candidate.