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Background: Mutation processes leave different signatures in genes. For single-base substitutions, previous studies have suggested that mutation signatures are not only reflected in mutation bases but also in neighboring bases. However, because of the lack of a method to identify features of long sequences next to mutation bases, the understanding of how flanking sequences influence mutation signatures is limited.Methods: We constructed a long short-term memory – self organizing map (LSTM-SOM) unsupervised neural network. By extracting mutated sequence features via LSTM and clustering similar features with the SOM, single-base substitutions in The Cancer Genome Atlas database were clustered according to both their mutation site and flanking sequences. The relationship between mutation sequence signatures and clinical features was then analyzed. Finally, we clustered patients into different classes according to the composition of the mutation sequence signatures by the K-means method and then studied the differences in clinical features and survival between classes.Results: Ten classes of mutant sequence signatures (mutation blots, MBs) were obtained from 2,141,527 single-base substitutions via LSTM-SOM machine learning approach. Different features in mutation bases and flanking sequences were revealed among MBs. MBs reflect both the site and pathological features of cancers. MBs were related to clinical features, including age, gender, and cancer stage. The class of an MB in a given gene was associated with survival. Finally, patients were clustered into 7 classes according to the MB composition. Significant differences in survival and clinical features were observed among different patient classes.Conclusions: We provided a method for analyzing the characteristics of mutant sequences. Result of this study showed that flanking sequences, together with mutation bases, shape the signatures of SBSs. MBs were shown related to clinical features and survival of cancer patients. Composition of MBs is a feasible predictive factor of clinical prognosis. Further study of the mechanism of MBs related to cancer characteristics is suggested.

BACKGROUND Lymph node metastasis (LNM) affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma (ESCC). However, reports of the risk factors for LNM have been controversial. AIM To evaluate risk factors for LNM in T1 ESCC. METHODS We searched Embase, PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC. Included studies were divided into LNM and non-LNM groups. We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features. Odds ratio (OR), mean differences and 95% confidence interval (CI) were assessed using a fixed-effects or random-effects model. RESULTS Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria. After excluding studies with heterogeneity based on influence analysis, tumor size (OR = 1.93, 95%CI = 1.49-2.50, P < 0.001), tumor location (OR = 1.46, 95%CI = 1.17-1.82, P < 0.001), macroscopic type (OR = 3.17, 95%CI = 2.33-4.31, P < 0.001), T1 substage (OR = 6.28, 95%CI = 4.93-8.00, P < 0.001), differentiation (OR = 2.11, 95%CI = 1.64-2.72, P < 0.001) and lymphovascular invasion (OR = 5.86, 95%CI = 4.60-7.48, P < 0.001) were found to be significantly associated with LNM. Conversely, sex, age and infiltrative growth pattern were not identified as risk factors for LNM. CONCLUSION A tumor size > 2 cm, lower location, nonflat macroscopic type, T1b stage, poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.

Mutation processes leave different signatures in genes. Previous studies suggested that both the mutated and flanking bases influence somatic mutation characteristics. However, the understanding of how flanking sequences influence somatic mutation characteristics is limited. Here, we constructed A long short-term memory – self organizing map (LSTM-SOM) unsupervised neural network. By extracting mutated sequence features via LSTM and clustering similar features with SOM, we obtained 10 classes of mutant sequences (named mutation blots, MBs) from 2,141,527 somatic mutations in The Cancer Genome Atlas (TCGA) database. Differences features were revealed among MBs. MBs were related to clinical features, including age, sex, and cancer stage. Different kinds of MBs for specific genes may affect patient survival. Finally, we clustered the patients into 7 classes by MB composition. Significant differences in survival and clinical features were observed among different patient classes. This study provides a novel method for understanding mutant sequences and revealing the extensive relationships among mutant sequences, clinical features, and cancer patient survival.

The objectives of this study were to evaluate the effects of different salinity levels on tissue histology, blood biochemistry, and genes transcription of the GH/IGF system in juvenile golden trout (Oncorhynchus mykiss). Five experimental salinity levels (0, 8, 16, 24, and 32‰) were selected to domesticate juvenile O. mykiss for 7 days. Histological characteristics changed with salinity, including higher ionocites area and epithelium thickness in gills, narrow lumen of collecting tubules in kidneys, and high numbers of goblet cells in the intestines. Similarly, increments in slits, degenerate hepatocytes, and individualization of hepatocytes have been shown in fish reared in the 32‰ salinity group. The lowest triglyceride (TG) and the highest level of total protein (TP) were detected in fish reared at the 32‰ group. The genes transcription of the GH/IGF system altered in response to the increase of salinity. The present results add to the understanding of the physiological responses of O. mykiss on salinity stress and would be helpful in formulating strategies to optimize the aquaculture of this species in environments with fluctuating patterns of salinity.

To investigate the expression and clinical significance of mitogen-activated protein kinase (MAPK) and epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC), a total of 300 TNBC and 120 paired paracancerous tissues were examined. Immunohistochemistry was conducted to determine the expression levels of MAPK and EGFR, and the correlation between MAPK and EGFR expression was evaluated using Cramer's V test. The association between MAPK and EGFR expression, and various clinicopathological variables (such as lymph node metastasis, clinical stage, recurrence and metastasis) was also evaluated, using the χ2 test. MAPK and EGFR expression levels in TNBC tissues were significantly higher than in the paired paracancerous tissues. Moreover, MAPK expression was associated with that of EGFR in TNBC tissues. The positive expression rates of MAPK and EGFR in patients with lymph node metastasis, advanced clinical stage, tumor recurrence and metastasis were higher than those without. Patients with positive expression of MAPK and EGFR in TNBC tissues had poorer prognoses and lower overall survival times than those without expression. In summary, the expression of MAPK and EGFR is closely associated with tumor invasion and the metastasis of TNBC, and may therefore be used as an indicator of poor prognosis in patients with TNBC.

Objective: This study aims to investigate the feasibility of combined application of indocyanine green (ICG) and methylene blue (MB) for sentinel lymph node biopsy (SLNB) in patients with early breast cancer. Methods: A total of 415 patients who underwent SLNB and axillary lymph node dissection were enrolled. Sentinel lymph node (SLN) was assessed in 197 patients with ICG and MB combination method, while, the other 218 patients were detected by MB method alone. During surgery, all SLNs were harvested for pathological examination. Then the detection rate and false negative rate of SLNs were comparatively analyzed between the 2 groups. Results: In the combined ICG and MB group, the detection rate of SLNs was 96.9%, significantly higher than that of MB group, which was 89.7% (P

Roll-forging process is widely used to fabricate the automobile front axle beams. The reasonable selection of the process parameters is significant to ensure the quality and improve the property of the automobile front axle beam owing to the complexity and importance of the preliminary roll-forging process. This paper developed a 3D Finite element (FE) model of the preliminary roll-forging process of the AISI-1045 automobile front axle beam under the Deform-3D platform. A corresponding experiment is subsequently conducted. Good agreement between the experimental and simulative results validates the employed model. Based on this dependable FE model, the influences of initial temperature of billet T0, rotational speed of rolls n and friction factor m on the geometric dimension, temperature inhomogeneity, deformation inhomogeneity, and roll-forging load are investigated comprehensively. The results can provide reliable guidelines for the selection of process parameters.

ObjectiveThis article reviewed research conducted on economic evaluations of clinical pharmacy services (CPS) in China. We aimed to identify the types of CPS and the possible economic effects of these services and to hopefully provide some suggestions for designing future economic evaluations of pharmacy interventions in the region.DesignSystematic review.Data sourcesSeveral English databases (PubMed, Embase, The Cochrane Library, National Health Service Economic Evaluation Database), Chinese databases (China National Knowledge Infrastructure, VIP, Chinese Biomedical Literature Database and WanFang Data) and search engines (Google Scholar and BaiDu Scholar) were searched through December 2017.Eligibility criteria for selecting studiesStudies with an economic assessment of CPSs in China were included.Data extraction and synthesisTwo reviewers independently screened the studies, extracted the data, assessed the quality of the included studies and then qualitatively analysed the results.ResultsForty articles were included in the final analysis. Most studies were performed in hospitals and the intervention populations mainly included adults. The types of pharmaceutical services included antimicrobial management, chronic disease state management and multidimensional clinical pharmaceutical services. A positive economic benefit associated with CPS was noted in 80% (n=32) of these articles, showing that CPS were associated with cost savings and improved patient outcomes. However, only three studies were full economic evaluations, using the method of cost-effectiveness analysis.ConclusionCPS was associated with cost savings and generated positive economic value. With the expanding role of pharmacists in the healthcare sector, it is suggested that new pharmaceutical services be used in future studies and that high-quality full economic evaluations capturing both expenses and cost savings be conducted.

Background. Seawater-immersed open abdominal injury is a special injury during marine activities. Effective warmed peritoneal lavage in the field early after injury is the key to treatment. This pilot study aimed at exploring the treatment effects of a self-developed portable peritoneal lavage device compared with conventional treatment model. Material and Methods. Beagle dogs were used to develop models of seawater-immersed open abdominal injury. A conventional lavage method or a novel peritoneal lavage device was used for lavage and rewarming. The vital signs, electrolyte, serum inflammatory cytokine expression levels, histological changes of mucosa, and microstructure variety of different groups were observed and compared before and after immersion and 2 h, 1 d, 3 d, and 5 d after lavage. Results. The levels of TNF-α, IL-1β, IL-8, IFN-γ, VEGF, and TGF-β in the blood and the damage of tissues and cells in three groups were increased after immersion and decreased at the later points of time after lavage. The concentration of Na+, K+, Cl-, lactate, and lactate dehydrogenase in the plasma was significantly higher than that before immersion (P<0.05), and the concentration of Ca2+ and HCO3- and plasma pH decreased slightly (P<0.05). The degree of tissue inflammation and mucosal injury in the delayed control group and device group was lower than the control group. Conclusions. Timely lavage and rewarming using a portable peritoneal lavage device reduced the inflammatory response of seawater-immersed open abdominal injury dogs and reduced the damage of multiple organs. The dogs recovered better and faster than the conventional treatment group.

The objective of the present study was to investigate and analyze the epithelial-cadherin (E-cadherin) expression in invasive ductal carcinoma of the breast, and to analyze the associations between the expression and clinicopathological characteristics of lymph node metastasis and the prognosis of breast cancer. The immunohistochemical streptavidin-peroxidase method was used to detect the E-cadherin expression in 30 cases of breast fibroadenoma and in 450 cases of invasive breast cancer, and then the χ2test and Kaplan-Meier method were used to analyze the data. The 30 cases of breast fibroadenoma showed positive expression of E-cadherin. Specifically, results found that E-cadherin was highly expressed in 49.04% (77/157) of patients with non-metastatic breast cancer, while low expression was found in 50.96% (80/157). Additionally, E-cadherin was highly expressed in 29.69% (87/293) of patients with lymph node metastasis of breast cancer, with low expression in 70.31% (206/293); these differences were significantly different (χ2=16.53; P

The aim of this article is to investigate the expression of E-cadherin (E-cad) and vascular endothelial growth factor (VEGF) in triple-negative breast cancer (TNBC) of Han and Uygur women patients in western China, and their relationship with clinical features of TNBC. Totally, 172 cases of Han TNBC patients and 79 cases of Uighur TNBC patients were enrolled. The expressions of E-cad and VEGF were detected with immunohistochemistry. The correlation of E-cad and VEGF expression with lymph node metastasis, TNM stage, and histological grade were analyzed. The 5-year disease-free survival rate of the 2 groups was also evaluated. There was no significant difference in the 5-year disease-free survival rate (P > .05) and the expression of E-cad between the 2 groups. The positive rate of VEGF in Han was significantly lower than that in Uygur (P

Roll-forging process, an innovative local plastic deformation process, is very suitable for forming the automotive front axle beam. Due to the complicated geometry of automotive front axle beam and the complicated roll-forging process, it is difficult to develop an accurate FE model of roll-forging of automotive front axle beam. In this paper, an experiment of roll-forging of automotive front axle beam is carried out. By comparing the simulation results with the experimental ones, the reasonable friction factors between the dies and roll-forged pieces are determined, so that an accurate 3D FE model of roll-forging of automotive front axle beam is developed under the Deform-3D platform. Based on this accurate 3D FE model, the forming laws of roll-forging of automotive front axle beam are illustrated, which includes the geometry development, effective strain distribution and evolution, temperature distribution and evolution, roll-forging load evolution, and metal flowing velocity distribution and evolution. The research results have important significance for comprehensively revealing the macro-deformation laws of roll-forging of automotive front axle beam.

The methodology used for large commercial aircraft impact assessment is introduced. This paper mainly forcus on the topics of physical damage. The vibration damage and fire damage are also briefly introduced. The challenging topics discussed in this paper are: 1) How to choose the type of commercial plane and the impact velocity (or the load curve). 2) Two different kinds of impact effect analysis method, “Impact Force Time History Method” and “Missile-Target Interaction Analysis Method”, are introduced. They are both accepted by regulations, but lead to greatly different results. 3) Experiment benchmarking for analysis methods. 4) Rationality demonstration of the analysis. 5) Target screening and NI arrangement. 6) Methodology of vibration and fire effect assessment.

Due to low automation of hot-pressing machine and low precision of parameter control at present, a automatic control system for hot-pressing machine combined upper computer with lower computer is proposed in this paper, a system that Programmable Logic Controller (PLC) acts as its control core and Kingview (Kingview 6.53) acts as its monitoring core. PLC is responsible for controlling equipment and instrumentations on the site. Kingview 6.53 provides a good man-machine interface, and it is responsible for monitoring equipment and instrumentations on the site. Because of large reduction of the number of components and strict control of the hot-pressing machine, temperature and time of hot-pressing machine, this system can improve the level of automation of hot-pressing machine and reduce the labor intensity.

The prognosis of patients with high grade gliomas (HGG) is quite poor, in spite of the standard combination of surgery, radiotherapy and chemotherapy. Recently, many clinical researchers have been focusing their efforts on the safety, feasibility and efficiency of dendritic cells (DCs) based vaccine against HGG. According to the literature search, 23 phase I/II clinic studies were picked and systemically reviewed to assess the application, the effect, and the future of DC vaccine for HGG. DC vaccine appears to have potential to increase overall survival with minimal complications. However, there still remains to be many challenges during vaccination, such as targeting specific/associated antigens, adjuvants, clinical status, and the evaluation of the response.

Surface roughness plays an important role in product quality. This paper focuses on developing an empirical model for the prediction of surface roughness in finish turning. The model considers the following working parameters: workpiece hardness (material); feed; cutting tool point angle; depth of cut; spindle speed; and cutting time. One of the most important data mining techniques, nonlinear regression analysis with logarithmic data transformation, is applied in developing the empirical model. The values of surface roughness predicted by this model are then verified with extra experiments and compared with those from some of the representative models in the literature. Metal cutting experiments and statistical tests demonstrate that the model developed in this work produces smaller errors than those from some of the existing models and have a satisfactory goodness in both model construction and verification. Finally, further research directions are presented.

CAP1400 is a new type nuclear plant designed by SNERDI. As a 3rd generation nuclear plant, it should survive after a large commercial plane crash on its shield building. A large wide-body commercial plane is chosen as the impact aircraft and these phenomena will be modeled by LS-DYNA. This paper will demonstrate the results of these impact simulations and how to check the rationality of these analyses.

Urban sewage pipeline project often using the pipe jacking technology, the existing communications cables had an obstacle in the construction process, affecting the progress of the project. This paper introduced the principle of the radar method to detect underground pipeline. Combined with project examples, it described the application of determining the location of the original communication cable before the pipe jacking process begins, it had a positive guidance to the right to solve the problem of similar projects.

This paper presents a drastically different approach to testing the Heckscher-Ohlin Theorem (HO Theorem) of factor endowment theory by explicitly recognizing the underlying assumptions of the theory and designing a testing strategy that is capable of controlling most of the influencing forces implied by the assumptions. The testing strategy abandoned the methods of estimating and comparing product factor contents of imports and exports, or factor contents of net exports base on the input-output tables that to date has been default approaches in testing the HO Theorem. Instead, attention is focused on the industry factor intensity and its relationship with the export capability of the industry based on our restatement of the HO Theorem. Utilizing 1989-2008 Chinese industry data provided by the National Bureau of Statistics of China (NBSC) and US import data by the United States International Trade Commission (USITC), the authors constructed a data set consists of 30 industry groups for the 1989-1992 and 32 for the 1993-2008 periods that covers more than 80% of total US commodity imports from China, with proxies for industry factor intensity, industry competition intensity, average firm scale, and industry export capability. In testing the HO Theorem, both simple and multiple regressions are performed for each and every individual year, and the results invariably lend strong support for the factor endowment theory.

OBJECTIVEThe authors previously described a graded approach to skull base repair following endonasal microscopic or endoscope-assisted tumor surgery. In this paper they review their experience with skull base reconstruction in the endoscopic era.METHODSA retrospective review of a single-institution endonasal endoscopic patient database (April 2010–April 2017) was undertaken. Intraoperative CSF leaks were graded based on size (grade 0 [no leak], 1, 2, or 3), and repair technique was documented across grades. The series was divided into 2 epochs based on implementation of a strict perioperative antibiotic protocol and more liberal use of permanent and/or temporary buttresses; repair failure rates and postoperative meningitis rates were assessed for the 2 epochs and compared.RESULTSIn total, 551 operations were performed in 509 patients for parasellar pathology, including pituitary adenoma (66%), Rathke’s cleft cyst (7%), meningioma (6%), craniopharyngioma (4%), and other (17%). Extended approaches were used in 41% of cases. There were 9 postoperative CSF leaks (1.6%) and 6 cases of meningitis (1.1%). Postoperative leak rates for all 551 operations by grade 0, 1, 2, and 3 were 0%, 1.9%, 3.1%, and 4.8%, respectively. Fat grafts were used in 33%, 84%, 97%, and 100% of grade 0, 1, 2, and 3 leaks, respectively. Pedicled mucosal flaps (78 total) were used in 2.6% of grade 0–2 leaks (combined) and 79.5% of grade 3 leaks (60 nasoseptal and 6 middle turbinate flaps). Nasoseptal flap usage was highest for craniopharyngioma operations (80%) and lowest for pituitary adenoma operations (2%). Two (3%) nasoseptal flaps failed. Contributing factors for the 9 repair failures were BMI ≥ 30 (7/9), lack of buttress (4/9), grade 3 leak (4/9), and postoperative vomiting (4/9). Comparison of the epochs showed that grade 1–3 repair failures decreased from 6/143 (4.1%) to 3/141 (2.1%) and grade 1–3 meningitis rates decreased from 5 (3.5%) to 1 (0.7%) (p = 0.08). Prophylactic lumbar CSF drainage was used in only 4 cases (< 1%), was associated with a higher meningitis rate in grades 1–3 (25% vs 2%), and was discontinued in 2012. Comparison of the 2 epochs showed increase buttress use in the second, with use of a permanent buttress in grade 1 and 3 leaks increasing from 13% to 55% and 32% to 76%, respectively (p < 0.001), and use of autologous septal/keel bone as a permanent buttress in grade 1, 2, and 3 leaks increasing from 15% to 51% (p < 0.001).CONCLUSIONSA graded approach to skull base repair after endonasal surgery remains valid in the endoscopic era. However, the technique has evolved significantly, with further reduction of postoperative CSF leak rates. These data suggest that buttresses are beneficial for repair of most grade 1 and 2 leaks and all grade 3 leaks. Similarly, pedicled flaps appear advantageous for grade 3 leaks, while CSF diversion may be unnecessary and a risk factor for meningitis. High BMI should prompt an aggressive multilayered repair strategy. Achieving repair failure and meningitis rates lower than 1% is a reasonable goal in endoscopic skull base tumor surgery.