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Cytoskeletal reorganization and epithelial-to-mesenchymal transition (EMT) are key processes and typical characteristics of metastatic cancer cells. Rho GTPase‑activating protein 35 (ARHGAP35) is a GTPase-activating protein, which has a significant effect on cell motility. However, the particular function of ARHGAP35 in gastric cancer (GC) remains unknown. In the present study, the role of ARHGAP35 in GC was investigated by

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. In science and engineering, multi-objective optimization problems usually contain multiple complex constraints, which poses a significant challenge in obtaining the optimal solution. This paper aims to solve the challenges brought by multiple complex constraints. First, this paper analyzes the relationship between single constrained Pareto Front (SCPF) and their common Pareto Front sub-constrained Pareto Front (SubCPF). Next, we discussed the SCPF, SubCPF, and Unconstrainti Pareto Front (UPF)’s help to solve constraining Pareto Front (CPF). Then further discusses what kind of cooperation should be used between multiple populations constrained multi-objective optimization algorithm (CMOEA) to better deal with multi-constrained multi-objective optimization problems (mCMOPs). At the same time, based on the discussion in this paper, we propose a new multi-population CMOEA called MCCMO, which uses a new cooperation mechanism. MCCMO uses C+2 (C is the number of constraints) populations to find the UPF, SCPF, and SubCPF at an appropriate time. Furthermore, MCCMO uses the newly proposed Activation Dormancy Detection (ADD) to accelerate the optimization process and uses the proposed Combine Occasion Detection (COD) to find the appropriate time to find the SubCPF. The performance on 32 mCMOPs and real-world mCMOPs shows that our algorithm can obtain competitive solutions on MOPs with multiple constraints.

1-3 piezoelectric composite has been widely used in underwater acoustic high frequency transducer because of its excellent high frequency characteristics. Resonance frequency, transmitting voltage ...

Background and aimsCurrent treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier.MethodsFive hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32–79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion.ResultsA new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi’an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi’an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients’ capacity of Xi’an criterion was confirmed in both early and late-stage PBC.ConclusionsXi’an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi’an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Background and aims There is no data regarding the efficacy and safety of fibrates in patients with decompensated liver disease associated with PBC, as published studies have systematically excluded this population. This study aims to evaluate the efficacy and safety of UDCA in combination with fenofibrate in patients with decompensated liver disease related to UDCA-refractory PBC. Methods We conducted a retrospective analysis comparing the clinical results of additional fenofibrate (FF) therapy and continued UDCA monotherapy in decompensated patients refractory to UDCA. Results Total of 63 patients included: 32 cases underwent UDCA monotherapy and 31 cases underwent UDCA combined with FF therapy. Among UDCA-refractory patients with decompensated cirrhosis, FF add-on therapy for 60 months significantly improved the Mayo risk score, the Globe risk score and the alkaline phosphatase (ALP) normalization rate. Parallel changes in liver transplant-free survival, the UK-PBC risk score and surrogate serum indices of liver fibrosis were consistent with this effect. During follow-up, serum ALP, aminotransferase and gamma-glutamyl transpeptidase decreased significantly, while total bilirubin, albumin, serum creatinine, blood urea, estimated glomerular filtration rate, APRI index, FIB-4 index and Forns index remained stable in FF-treated cases. Only the Globe risk score, not ALP normalization, was independently and negatively associated with improved outcomes on multivariable analysis (odds ratio, 2.934; confidence interval, 1.046-8.235; p = 0.041). No significant adverse effects associated with FF-related symptoms or nephrotoxicity were observed in our cohort. However, decompensated cirrhosis with deteriorated cholestasis should be considered as potential limiting factors for FF therapy. Conclusions Additional FF therapy clearly improves the Mayo risk score, the Globe risk score and the ALP normalization rate in patients with decompensated liver disease related to UDCA-refractory PBC. However, the survival rate was not significantly different between the groups. Decompensated cirrhosis with deteriorated cholestasis should be considered as potential limiting factors for FF therapy.

Drawing upon a social media perspective, this study explores the phenomenon of opportunistic behaviour in supply chain finance (SCF). Based on research into the factors that drive opportunistic beh...

Research around sport-related concussion (SRC) has made great advances during the twenty-first century. However, few studies have systematically analyzed the published SRC research.A bibliometric analysis was conducted of data from articles from the Web of Science Core Collection database. Descriptive statistics were used to analyze publication trends, most productive countries, institutions, authors, journals, research fields, and references with the highest citation number. VOSviewer software was used to perform network visualization and keywords co-occurrence analysis. CiteSpace software was used to perform reference co-citation analysis.1) The number of publications and number of citations of research in SRC progressively increased between 2000 and 2021; 2) the United States was the leading country in research in SRC; 3) extensive cooperation among countries, institutions, and investigators was prevalent in SRC research; 4) P. McCrory, M. McCrea, and K.M. Guskiewicz were the 3 most prolific and influential authors; 5) research in SRC involved multidisciplinary perspectives and approaches; 6) research in SRC mainly covered aspects of primary prevention, diagnosis, and management, and the latter two have gained more attention in recent years; and 7) specific questions about "education," "predictors," "youth," "exercise," "reliability," "validity," and "baseline" were the research frontiers of SRC.Attention to research in SRC has rapidly increased in recent years. Our work is a holistic overview that summarizes the hotspots, frontiers, and prospects of SRC, thus providing valuable information and guidance concerning research directions for those who are interested in or are dedicated to SRC research.

To investigate the pathogenic gene of a patient with nonsyndromic oligodontia, and analyze its possible pathogenic mechanism.The variant was detected by whole exome sequencing (WES) and Sanger sequencing in a family with oligodontia. Bioinformatic and structural analyses were used to analyze variant. Functional studies including western blotting and immunofluorescent analyses and luciferase reporter assay were conducted to explore the functional effects.We identified a novel frameshift variant of PAX9 (c.491-510delGCCCT-ATCACGGCGGCGGCC, p.P165Qfs*145) outside the DNA-binding domain causing an autosomal-dominant nonsyndromic oligodontia in a Chinese family. Bioinformatic and structural analyses revealed that the variant is pathogenic and conserved evolutionarily, and the changes might affect protein stability or folding. Functional studies demonstrate dramatically reduced ability in activating transcription activity of BMP4 promoter and a marked decrease in protein production, as evaluated by western blotting and immunofluorescent analyses.We found a novel frameshift variant of PAX9 causing nonsyndromic oligodontia in a Chinese family. Our findings indicate that frameshift variants cause loss of function of PAX9 protein during the patterning of the dentition and the subsequent tooth agenesis, providing new molecular insights into the role of frameshift variant of PAX9 and broaden the pathogenic spectrum of PAX9 variants.

Purpose In recent years, the rapid growth of big data has presented immense potential for business applications as well as raised great interest from academia. In response to this emerging phenomenon, the purpose of this paper is to provide a comprehensive literature review of big data. Design/methodology/approach A bibliometric method was used to analyze the articles obtained from the Scopus database published between 2013 and 2018. A sample size of 4,070 articles was evaluated using SciVal metrics. Findings The analysis revealed an array of interesting findings as follows: the number of publications related to big data increased steadily over the past six years, though the rate of increase has slowed since 2014; the scope of big data research is quite broad in regards to both research domains and countries; despite a large volume of publications, the overall performance of big data research is not well presented as measured by the field-weighted citation impact metric; collaboration between different institutions, particularly in the form of international collaboration and academic–corporate collaboration, has played an important role in improving the performance of big data research. Originality/value To the best of the authors’ knowledge, this is the first study to provide a holistic view of the big data research. The insights obtained from the analysis are instrumental for both academics and practitioners.

Background: Vagus nerve stimulation (VNS) functions through neuromodulatory mechanisms to provide quality of life improvements to those with drug-resistant epilepsy. Responsive VNS (rVNS) generators are designed to further reduce seizure burden by detecting ictal tachycardia and aborting seizures soon after their onset. Methods: Electronic medical records were accessed from January 2015 to December 2018 to identify patients with epilepsy managed with rVNS generators. Data were collected on seizure burden before and after rVNS implantation. Seizure burden was compared using t-tests, and monthly seizure reductions were gauged with the McHugh scale. Twenty-seven individuals met inclusion criteria; 10 were eliminated due to prior VNS implantation or undocumented seizure frequencies. Results: The average seizure burden prior to rVNS implantation was 24.78 seizures/month. Following generator placement, the mean seizure frequencies at three months, six months, 12 months, and 18 months were 6.81, 16.57, 5.65, and 5.78 seizures/month, respectively. However, despite documented reductions in the average monthly seizure frequency, we found no statistically significant differences in seizure frequency relative to baseline. Conclusion: While many participants showed individual reductions in seizure burden, this study was unable to definitively conclude that rVNS therapy leads to statistically significant reduction in seizure burden.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. It is challenging to solve constrained multi-objective optimization problems (CMOPs). Different from the traditional multi-objective optimization problem, the feasibility, convergence, and diversity of the population must be considered in the optimization process of a CMOP. How these factors are balanced will affect the performance of the constrained multi-objective optimization algorithm. To solve this problem, we propose a dual-population multi-objective optimization evolutionary algorithm. The proposed algorithm can make good use of its secondary population and alternative between evolution and degeneration according to the state of the secondary population to provide better information for the main population. The test results of three benchmark constrained multi-objective optimization problem suites, and four real-world constrained multi-objective optimization problems show that the algorithm is better than existing dual-population multi-objective optimization, especially when there is a distance between the unconstrained PF and the constrained PF.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. There are usually multiple constraints in constrained multi-objective optimization. Those constraints reduce the feasible area of the constrained multi-objective optimization problems (CMOPs) and make it difficult for current multi-objective optimization algorithms (CMOEAs) to obtain satisfactory feasible solutions. In order to solve this problem, this paper studies the relationship between constraints, then obtains the priority between constraints according to the relationship between the Pareto Front (PF) of the single constraint and their common PF. Meanwhile, this paper proposes a multi-stage CMOEA and applies this priority, which can save computing resources while helping the algorithm converge. The proposed algorithm completely abandons the feasibility in the early stage to better explore the objective space, and obtains the priority of constraints according to the relationship; Then the algorithm evaluates a single constraint in the medium stage to further explore the objective space according to this priority, and abandons the evaluation of some less-important constraints according to the relationship to save the evaluation times; At the end stage of the algorithm, the feasibility will be fully considered to improve the quality of the solutions obtained in the first two stages, and finally get the solutions with good convergence, feasibility, and diversity. The results on five CMOP suites and three real-world CMOPs show that the algorithm proposed in this paper can have strong competitiveness in existing constrained multi-objective optimization.

We report a rare case of ecchordosis physaliphora presenting with headache, nausea, and diplopia. On neurological examination, the patient was found to have left abducens nerve palsy. CT of the head without contrast was unremarkable. Brain MRI demonstrated a non-enhancing retroclival mass with a mass effect upon the ventral pons. The mass had increased signal intensity on T2 and decreased signal intensity on T1-weighted sequences. Lumbar puncture revealed an opening pressure of 37 cm H2O. The patient underwent an endoscopic endonasal approach for retroclival mass resection three weeks later. The tissue analysis of the mass was consistent with ecchordosis physaliphora. This could have been misdiagnosed as idiopathic intracranial hypertension had the MRI of the brain not been performed.

In order to boost the electromechanical coupling factor and decrease the characteristic impedance, a 1-3 piezoelectric composite with a 3-tier polymer structure was designed and fabricated, in which epoxy resin constitutes the middle layer and silicone rubber is used to clamp the epoxy. The effective parameters of the composite, such as resonant frequency, electromechanical coupling factor, and characteristic impedance, were studied by the finite element method and experiment. The experimental results indicate that the electromechanical coupling factor of the composite is enhanced by 8.4% and the characteristic impedance is decreased by 52.8%, compared with the traditional 1-3 ceramic/epoxy composite.