The prognostic value of lymph node ratio and log odds of positive lymph nodes in patients with lung adenocarcinoma

Objective

To investigate whether lymph node ratio and log odds ratio can be used for predicting the prognosis of patients with lung adenocarcinoma.

Systematic analysis of nucleation-dependent polymerization reveals new insights into the mechanism of amyloid self-assembly

Self-assembly of misfolded proteins into ordered fibrillar aggregates known as amyloid results in numerous human diseases. Despite an increasing number of proteins and peptide fragments being recognised as amyloidogenic, how these amyloid aggregates assemble remains unclear. In particular, the identity of the nucleating species, an ephemeral entity that defines the rate of fibril formation, remains a key outstanding question. Here, we propose a new strategy for analyzing the self-assembly of amyloid fibrils involving global analysis of a large number of reaction progress curves and the subsequent systematic testing and ranking of a large number of possible assembly mechanisms. Using this approach, we have characterized the mechanism of the nucleation-dependent formation of beta(2)-microglobulin (beta(2)m) amyloid fibrils. We show, by defining nucleation in the context of both structural and thermodynamic aspects, that a model involving a structural nucleus size approximately the size of a hexamer is consistent with the relatively small concentration dependence of the rate of fibril formation, contrary to expectations based on simpler theories of nucleated assembly. We also demonstrate that fibril fragmentation is the dominant secondary process that produces higher apparent cooperatively in fibril formation than predicted by nucleated assembly theories alone. The model developed is able to explain and predict the behavior of beta(2)m fibril formation and provides a rationale for explaining generic properties observed in other amyloid systems, such as fibril growth acceleration and pathway shifts under agitation.     

Statistical Comparison of Survival Models for Analysis of Cancer Data

Background: The Cox Proportional Hazard model is the most popular technique to analysis the effects ofcovariates on survival time but under certain circumstances parametric models may offer advantages overCox’s model. In this study we use Cox regression and alternative parametric models such as: Weibull, Exponentialand Lognormal models to evaluate prognostic factors affecting survival of patients with stomach cancer.Comparisons were made to find the best model. Methods: To determine independent prognostic factors reducingsurvival time for stomach cancer, we compared parametric and semi-parametric methods applied to patientswho registered in one cancer registry center located in southern Iran using the Akaike Information Criterion.Results: Of a total of 442 patients, 266 (60.2%) died. The results of data analysis using Cox and parametricmodels were approximately similar. Patients with ages 60-75 and >75 years at diagnosis had an increased riskfor death followed by those with poor differentiated grade and presence of distant metastasis (P<0.05). Conclusion:Although the Hazard Ratio in Cox model and parametric ones are approximately similar, according to AkaikeInformation Criterion, the Weibull and Exponential models are the most favorable for survival analysis.     

Associations between grass and weed pollen and emergency department visits for asthma among children in Montreal

CONTEXT AND OBJECTIVE: Asthma among children is a major public health problem worldwide. There are increasing number of studies suggesting a possible association between allergenic pollen and exacerbations of asthma. In the context of global climate change, a number of future climate and air pollution scenarios predict increases in concentrations of pollen, an extension of the pollen season, and an increase in the allergenicity of pollen. The goal of the present study is to evaluate the short-term effects of exposure to grass and weed pollen on emergency department visits and readmissions for asthma among children aged 0-9 years living in Montreal between April and October, 1994-2004. METHODOLOGY AND RESULTS: Time-series analyses were carried out using parametric log-linear overdispersed Poisson models that were adjusted for temporal variations, daily weather conditions (temperature, atmospheric pressure), and gaseous air pollutants (ozone and nitrogen dioxide). We have found positive associations between emergency department visits and concentrations of grass pollen 3 days after exposure. The effect of grass pollen was higher on emergency department readmissions as compared to initial visits. Weak negative associations were found between weed pollen (including ragweed pollen) and emergency department visits 2 days after exposure. CONCLUSION: The data indicate that among children, emergency department visits increased with increasing concentrations of grass pollen.     

Early intraoperative iron-binding proteins are associated with acute kidney injury after cardiac surgery

Objectives

Iron regulation is an important modifier of renal ischemia–reperfusion injury, but the role of iron-binding proteins during cardiopulmonary bypass remains unclear. The goal was to characterize iron-binding proteins throughout ischemia–reperfusion injury to determine their association with acute kidney injury development.

One-month toxicokinetic study of SHENMAI injection in rats

Ethnopharmacological relevance

‘SHENMAI’ injection (SMI) has been widely used in cardioprotection and modulation of the immune system because of its great efficacy. SMI primarily comprises the saponins from Panax ginseng and Ophiopogon japonicas. The profiles of saponins in SMI during long-term toxicokinetics remain unclear. MiR-146a possesses excellent sensitivity as a bio-marker in the innate immunity modification effect of SMI.

Aim of the study

Is to monitor the exposure level of SMI during a one-month toxicokinetic experiment, an analytical method involving ESI–LC–MS/MS technology was developed to determine 20 (S)-protopanaxadiol-type ginsenoside (Rb1, Rb2, Rc, Rd), 20 (S)-protopanaxatriol-type ginsenoside (Rg1, Re, Rf), oleanolic acid-type ginsenoside (Ro), and ophiopogonin D in rats. The levels of AST, CK, ALT, SOD, GSH-pX, MDA, miR-146a, and ECG were measured to explore the effects of SMI in cardiologic function and immune activity.

Results

Results show that the levels of AST, CK, and MDA decreased upon the administration of SMI. The level of miR-146a increased upon the administration of SMI dosage. During the administration of SMI, increasing exposure levels of 20 (S)-protopanaxadiol-type ginsenosides were also observed.

Conclusion

The 20 (S)-protopanaxadiol-type ginsenosides were considered potential PK/TK markers because of their high exposure levels that continuously increased. Oxidative stress was slightly alleviated during the toxicokinetic study. Based on the level of miR-146a, negatively regulated innate immunity was observed. The regulation became more serious with increasing exposure levels of 20 (S)-protopanaxadiol-type ginsenosides. Negatively regulated innate immunity could be induced by long-term administration of SMI (>0.4 g/kg).     

运用单通道实验数据和仿真数据比较马尔可夫模型和分形模型

离子通道门控机制动力学的研究广泛地运用马尔可夫模型去讨论。马尔可夫模型假设离子通道动力学只含有少数几个离散的构象状态，并且状态之间的转移速率是常数、它不依赖于时间和先前的状态过程。Liebovitch和他的同事提出了运用分形模型去刻划离子通道门控机制动力学，他们认为：离子通道门控机制动力学具有连续的构象状态，状态之间的转移速率依赖于时间并且为时间t的函数。现在的焦点在于离子通道门控机制动力学马尔可夫模型或分形模型是否恰当地描述了其通道门控的分子事件，是否合理地解释其生理机理。在本研究中，我们采用实验记录的离子单通道数据和随机仿真的数据来比较马尔可夫模型和分形模型，实验记录的离子单通道数据来源于电压依赖性的钾离子单通道，随机仿真的数据来源于三个状态的马尔可夫模型。     

Development and validation of a nomogram for predicting survival on the base of modified lymph node ratio in breast cancer patients

BackgroundAxillary lymph node status is one of the most important prognostic factors in breast cancer and previous studies indicated that lymph node ratio (LNR) could better predict the outcome than the counting of positive lymph nodes. In the current study, we evaluated the prognostic effect of modified LNR in breast cancer patients.MethodsA total of 3339 breast cancer patients undergoing axillary lymph nodes dissection were enrolled and respectively analyzed. Seventy five percent of participants were randomly selected as training cohort and the remaining 25% were as validation cohort. Univariate and multivariate analyses were performed and the prognostic impact of mLNR was compared with pN staging. A prognostic nomogram was established and externally validated in the validation cohort.ResultIn multivariate analysis, both the mLNR and pN staging were independent prognostic factors for breast cancer patients, and the mLNR manifested superior discrimination power than the pN stages regardless of the total number of lymph nodes retrieved and the lymph node status. The nomogram was built including the identified independent prognostic factors and the calibration curves indicated optimal agreement between nomogram prediction and actual observation. The Concordance index (C-index) of the nomogram was statistically higher than that of the TNM system (0.747 vs. 0.711 in training cohort, 0.789 vs. 0.760 in validation cohort, both p < 0.05).ConclusionModified LNR is an important prognostic parameter and can predict survival more accurately than pN staging. The novel nomogram could provide individual prediction for breast cancer patients and help clinicians in treatment option making and prognosis evaluation.     

Correlation structure and variable selection in generalized estimating equations via composite likelihood information criteria

The method of generalized estimating equations (GEE) is popular in the biostatistics literature for analyzing longitudinal binary and count data. It assumes a generalized linear model for the outcome variable, and a working correlation among repeated measurements. In this paper, we introduce a viable competitor: the weighted scores method for generalized linear model margins. We weight the univariate score equations using a working discretized multivariate normal model that is a proper multivariate model. Because the weighted scores method is a parametric method based on likelihood, we propose composite likelihood information criteria as an intermediate step for model selection. The same criteria can be used for both correlation structure and variable selection. Simulations studies and the application example show that our method outperforms other existing model selection methods in GEE. From the example, it can be seen that our methods not only improve on GEE in terms of interpretability and efficiency but also can change the inferential conclusions with respect to GEE. Copyright © 2016 John Wiley & Sons, Ltd.     

Calu-3 cells grown under AIC and LCC conditions: Implications for dipeptide uptake and transepithelial transport of substances

The aim of the present study was to investigate whether Calu-3 cell culture conditions influence drug and nutrient transport known to occur via carriers or transporters. Calu-3 cell layers, an in vitro model of the lung epithelium, were cultured using air interfaced culture (AIC) or liquid covered culture (LCC) on either polycarbonate or polyester as filter support material. We found that the development of the Calu-3 cell layer barrier function did not depend on the filter material but rather on the culture conditions as follows: (i) the apical uptake of Gly-Sar was significantly larger for cells grown in AIC compared to LCC, (ii) the TEER values for cells grown in LCC were approximately three times larger than for cells grown in AIC, (iii) the transepithelial transport in both AIC and LCC Calu-3 cells was polarized in the apical-basolateral direction of proline, glycine, α-methyl-d-glucoside, glipizide, taurocholic acid and estrone-3-sulfate, whereas inulin, mannitol and Gly-Sar showed no polarized transport. Etoposide showed polarized efflux (basolateral to apical transport) in AIC and LCC Calu-3 layers. These findings provide information about nutrient and drug transport in Calu-3 cells, and this may have implications for selecting culture conditions for transport studies in this in vitro model of the lung epithelium.