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Trastuzumab has been approved for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric and gastroesophageal junction cancers (GC and GJC) in combination with chemotherapy. The aim of this HER2 early/advanced gastric epidemiology (HER-EAGLE) study was to evaluate the frequency of HER2 over-expression and to evaluate agreement on HER2 status assessment in GC and GJC patients in local laboratories versus a central laboratory in China. Tumor samples from 734 GC or GJC patients who were enrolled at 11 different hospitals in China were examined. HER2 status was assessed by immunohistochemistry (IHC), and followed by dual-color silver-enhanced in Situ hybridization (DSISH) in IHC 2+ cases. Clinicopathologic characteristics were collected from all of the patients. HER2-positive tumors were identified in 12.0% (88/734) of the GC and GJC cases. There were significantly higher rates of HER2 positivity in patients with GJC (GJC: 18.1%, GC: 9.7%, P=0.002), and intestinal-type cancers using the Lauren classification (intestinal: 23.6%, diffuse/mixed: 4.3%, P

The hydraulic accumulator is widely used for storing energy in hydraulic system, but it is a passive device; the flowrate and volume of hydraulic oil adjusted by the accumulator are not well adapted to working-condition changes or payload disturbances. A novel semiactive power-assisted unit (PAU), which is a flow valve-controlled accumulator virtually, is proposed. The flowrate and volume of the accumulator can be regulated by adjusting the spool-opening of the flow valve. The mathematical model of the semiactive PAU is deduced. Then the static characteristic and dynamic characteristic of the PAU are presented. The simulations of the proposed PAU applied in variable-speed electrohydraulic drive system are implemented. The results show the influences of PAU's main parameters on its performance.

BACKGROUND: Glomerulosclerosis correlates with reduction in podocyte number that occurs through mechanisms which include apoptosis. Podocyte injury or podocyte loss in the renal glomerulus has been proposed as the crucial mechanism in the development of glomerulosclerosis. However, the mechanism by which podocytes respond to injury is poorly understood. TNF and TNF receptor superfamilies are important in the pathogenesis of podocyte injury and apoptosis. The ligand of receptor activator of NF-kappaB (RANKL) and receptor activator of NF-kappaB (RANK) are members of the TNF and receptor superfamilies. We investigated whether RANK-RANKL is a receptor-ligand complex for podocytes responding to injury. METHODOLOGY/PRINCIPAL FINDINGS: In this study, RANKL and RANK were examined in human podocyte diseases and a rat model of puromycin aminonucleoside nephrosis (PAN). Compared with controls, RANK and RANKL were increased in both human podocyte diseases and the rat PAN model; double immunofluorescence staining revealed that RANK protein expression was mainly attributed to podocytes. Immunoelectron microscopy showed that RANK was localized predominantly at the top of the foot process membrane and the cytoplasm of rat podocyte. In addition, RANK was upregulated in mouse podocytes in vitro after injury induced by puromycin aminonucleoside (PA). Knockdown of RANK expression by small interference RNA (siRNA) exacerbated podocyte apoptosis induced by PA. However, RANKL inhibited significantly the apoptosis of podocytes induced by PA. CONCLUSIONS/SIGNIFICANCE: These findings suggest the increase in RANK-RANKL expression is a response to podocyte injury, and RANK-RANKL may be a novel receptor-ligand complex for the survival response during podocyte injury.

Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary physiological signals.

BACKGROUND: To evaluate the risk of the recurrence and the efficiency of the vaccination, we followed-up antibody responses in patients with the 2009 pandemic H1N1 influenza and persons who received the pandemic H1N1 vaccine in Guangzhou China. METHODS: We collected serum samples from 129 patients and 86 vaccinated persons at day 0, 15, 30, 180 after the disease onset or the vaccination, respectively. Antibody titers in these serum samples were determined by haemagglutination inhibition (HI) assay using a local isolated virus strain A/Guangdong Liwan/SWL1538/2009(H1N1). RESULTS: HI antibody positive rate of the patients increased significantly from 0% to 60% at day 15 (χ(2) = 78, P

Quantification of nonlinear interactions between two nonstationary signals presents a computational challenge in different research fields, especially for assessments of physiological systems. Traditional approaches that are based on theories of stationary signals cannot resolve nonstationarity-related issues and, thus, cannot reliably assess nonlinear interactions in physiological systems. In this review we discuss a new technique called multimodal pressure flow (MMPF) method that utilizes Hilbert-Huang transformation to quantify interaction between nonstationary cerebral blood flow velocity (BFV) and blood pressure (BP) for the assessment of dynamic cerebral autoregulation (CA). CA is an important mechanism responsible for controlling cerebral blood flow in responses to fluctuations in systemic BP within a few heart-beats. The MMPF analysis decomposes BP and BFV signals into multiple empirical modes adaptively so that the fluctuations caused by a specific physiologic process can be represented in a corresponding empirical mode. Using this technique, we showed that dynamic CA can be characterized by specific phase delays between the decomposed BP and BFV oscillations, and that the phase shifts are significantly reduced in hypertensive, diabetics and stroke subjects with impaired CA. Additionally, the new technique can reliably assess CA using both induced BP/BFV oscillations during clinical tests and spontaneous BP/BFV fluctuations during resting conditions.

Background: This study aimed to identify prognostic factors for survival and develop a prognostic nomogram to predict the survival probability of elderly patients with lower-grade gliomas (LGGs). Methods: Elderly patients with histologically confirmed LGG were recruited from the Surveillance, Epidemiology, and End Results (SEER) database. These individuals were randomly allocated to the training and validation cohorts at a 2:1 ratio. First, Kaplan-Meier survival analysis and subgroup analysis were performed. Second, variable screening of all 13 variables and a comparison of predictive models based on full Cox regression and LASSO-Cox regression analyses were performed, and the key variables in the optimal model were selected to construct prognostic nomograms for OS and CSS. Finally, a risk stratification system and a web-based dynamic nomogram were constructed. Results: A total of 2307 elderly patients included 1220 males and 1087 females, with a median age of 72 years and a mean age of 73.30 ± 6.22 years. Among them, 520 patients (22.5%) had Grade 2 gliomas, and 1787 (77.5%) had Grade 3 gliomas. Multivariate Cox regression analysis revealed four independent prognostic factors (age, WHO grade, surgery, and chemotherapy) that were used to construct the full Cox model. In addition, LASSO-Cox regression analysis revealed five prognostic factors (age, WHO grade, surgery, radiotherapy, and chemotherapy), and a LASSO model was constructed. A comparison of the two models revealed that the LASSO model with five variables had better predictive performance than the full Cox model with four variables. Ultimately, five key variables based on LASSO-Cox regression were utilized to develop prognostic nomograms for predicting the 1-, 2-, and 5-year OS and CSS rates. The nomograms exhibited relatively good predictive ability and clinical utility. Moreover, the risk stratification system based on the nomograms effectively divided patients into low-risk and high-risk subgroups. Conclusion: Variable screening based on LASSO-Cox regression was used to determine the optimal prediction model in this study. Prognostic nomograms could serve as practical tools for predicting survival probabilities, categorizing these patients into different mortality risk subgroups, and developing personalized decision-making strategies for elderly patients with LGGs. Moreover, the webbased dynamic nomogram could facilitate its use in the clinic. [ABSTRACT FROM AUTHOR]

Calculating impact forces in asymmetrical lateral structures has been a complex challenge that spans decades in engineering. Traditional models often fall short due to the inherent complexity of asymmetrical members and the need for significant computational resources or a vast pool of training data. This paper develops an approximate formula for accurately calculating the impact force of asymmetrical lateral-impact members under lateral impact. Existing methods for assessing impact forces have been limited in their application due to the inherent complexity of asymmetrical members and the significant computational resources or extensive training data they often require. Our approach employs the residuals margin method, and Laplace transforms to derive an efficient and accurate formula for impact force calculation. The paper rigorously validates this Formula through experimental testing, demonstrating high precision with an error margin of less than 5%. Further validation against diverse impact data from multiple studies on different materials and loadings under static and dynamic conditions confirmed the Formula's consistency. Despite simplifying assumptions, this research contributes a novel and computationally efficient approach for calculating impact forces. The formula offers engineers a practical tool while advancing a fundamental understanding of asymmetric impact dynamics. Rigid experimentation verified its significant accuracy, establishing the formula as a valuable structural impact analysis and design resource. This research presents an analytical formula for calculating impact forces on structures like buildings, bridges, and vehicles experiencing asymmetrical lateral impacts. Such impacts commonly occur due to falling debris, vehicle collisions, seismic pounding, and derailed train strikes. However, existing design formulas often oversimplify impact mechanics or require complex simulations. The proposed method provides engineers with a simple spreadsheet-compatible equation relating impact force directly to tangible mechanical quantities like momentum. This enables rapid impact load assessments essential for performance-based design against accidental hazards. The formula was validated through laboratory impact tests on reinforced concrete slabs, demonstrating precision within 5% of measured forces. Additional validations against published experimental and simulation data on different construction materials confirmed accuracy. The proposed formula equips structural engineers and safety analysts with a practical impact analysis tool by offering a computationally efficient approach with proven reliability. It facilitates assessing design performance for asymmetrical impact load scenarios, helping improve resilience for critical facilities subjected to hazardous lateral impacts. [ABSTRACT FROM AUTHOR]

This study provides a comprehensive analysis of collision and impact problems' numerical solutions, focusing on geometric, contact, and material nonlinearities, all essential in solving large deformation problems during a collision. The initial discussion revolves around the stress and strain of large deformation during a collision, followed by explanations of the fundamental finite element solution method for addressing such issues. The hourglass mode's control methods, such as single-point reduced integration and contact-collision algorithms are detailed and implemented within the finite element framework. The paper further investigates the dynamic response and failure modes of Reinforced Concrete (RC) members under asymmetrical impact using a 3D discrete model in ABAQUS that treats steel bars and concrete connections as bond slips. The model's validity was confirmed through comparisons with the node-sharing algorithm and system energy relations. Experimental parameters were varied, including the rigid hammer's mass and initial velocity, concrete strength, and longitudinal and stirrup reinforcement ratios. Findings indicated that increased hammer mass and velocity escalated RC member damage, while increased reinforcement ratios improved impact resistance. Contrarily, increased concrete strength did not significantly reduce lateral displacement when considering strain rate effects. The study also explores material nonlinearity, examining different materials' responses to collision-induced forces and stresses, demonstrated through an elastic rod impact case study. The paper proposes a damage criterion based on the residual axial load-bearing capacity for assessing damage under the asymmetrical impact, showing a correlation between damage degree hammer mass and initial velocity. The results, validated through comparison with theoretical and analytical solutions, verify the ABAQUS program's accuracy and reliability in analyzing impact problems, offering valuable insights into collision and impact problems' nonlinearities and practical strategies for enhancing RC structures' resilience under dynamic stress. [ABSTRACT FROM AUTHOR]