QUADRATIC MODEL TO ESTIMATE THE DOSES CAUSING THE HIGHEST CHOLESTEROL CONCENTRATION AND THE SAME CHOLESTEROL CONCENTRATION AS CONTROL GROUP

High plasma cholesterol (particularly high LDL-cholesterol) is a high risk factor for coronary heart disease (CHD), which causes a high CHD morbidity and mortality. Besides clinical drugs, more and more interest is focused on finding natural components in the diet that may have hypocholesterolemic effects. Plant sterols are natural components in human diets and found to have cholesterol-lowering effects in humans. Sheanut oil has a relatively high amolmt of plant sterols. Therefore, the two experiments were designed to investigate the hypocholesterolemic effect of sheanut oil in hamsters. The response was not monotonic. Low doses increased plasma cholesterol, but high doses decreased plasma cholesterol. Because there was partial dose repetition between the two experiments, the two were combined together to estimate the dose leading to the highest cholesterol concentration and the dose leading to the same cholesterol concentration as the control group. A quadratic model was selected to fit the combined data after appropriate transformation of exploratory and response variable. Nonparametric smoothing method was used to justify the quadratic model. The results of point estimation and confidence interval were compared by Delta, Fieller\u27s and bootstrapping methods

Comparison of methods for analysis of selective genotyping survival data

Survival traits and selective genotyping datasets are typically not normally distributed, thus common models used to identify QTL may not be statistically appropriate for their analysis. The objective of the present study was to compare models for identification of QTL associated with survival traits, in particular when combined with selective genotyping. Data were simulated to model the survival distribution of a population of chickens challenged with Marek disease virus. Cox proportional hazards (CPH), linear regression (LR), and Weibull models were compared for their appropriateness to analyze the data, ability to identify associations of marker alleles with survival, and estimation of effects when all individuals were genotyped (full genotyping) and when selective genotyping was used. Little difference in power was found between the CPH and the LR model for low censoring cases for both full and selective genotyping. The simulated data were not transformed to follow a Weibull distribution and, as a result, the Weibull model generally resulted in less power than the other two models and overestimated effects. Effect estimates from LR and CPH were unbiased when all individuals were genotyped, but overestimated when selective genotyping was used. Thus, LR is preferred for analyzing survival data when the amount of censoring is low because of ease of implementation and interpretation. Including phenotypic data of non-genotyped individuals in selective genotyping analysis increased power, but resulted in LR having an inflated false positive rate, and therefore the CPH model is preferred for this scenario, although transformation of the data may also make the Weibull model appropriate for this case. The results from the research presented herein are directly applicable to interval mapping analyses

Inonotus sanghuang Polyphenols Attenuate Inflammatory Response Via Modulating the Crosstalk Between Macrophages and Adipocytes

Aims: Obesity is characterized as a chronic state of low-grade inflammation with progressive immune cell infiltration into adipose tissue. Adipose tissue macrophages play a critical role in the establishment of chronic inflammatory states and metabolic dysfunctions. Inonotus (I.) sanghuang and its extract polyphenols exhibit anti-carcinogenesis, anti-inflammatory, and anti-oxidant activities. However, the action of I. sanghuang polyphenols in obesity-related inflammation has not been reported. The aim of this study was to explore the anti-inflammatory action of polyphenols from I. sanghuang extract (ISE) in macrophages and the interaction between macrophages and adipocytes.Materials and Methods: RAW264.7 macrophages were stimulated with LPS or conditioned medium of hypertrophied 3T3-L1 adipocytes or cocultured with differentiated adipocytes in the presence of different doses of ISE. The inflammatory cytokines were evaluated by ELISA, the MAPK, NF-κB, and IL-6/STAT3 signals were determined by immunoblotting, and the migrated function of macrophages was determined by migration assay.Results: ISE suppressed the inflammatory mediators including NO, TNF-α, IL-6, and MCP-1 induced by either LPS or conditioned medium derived from 3T3-L1 adipocytes. ISE also decreased the production of these inflammatory mediators in cocultures of 3T3-L1 adipocytes and RAW264.7 macrophages. Furthermore, ISE blocked RAW264.7 macrophages migration toward 3T3-L1 adipocytes in cocultures. Finally, this effect of ISE might be mediated via inhibiting ERK, p38, and STAT3 activation.Conclusions: Our findings indicate the possibility that ISE suppresses the interaction between macrophages and adipocytes, attenuates chronic inflammation in adipose tissue and improves obesity-related insulin resistance and complication, suggesting that ISE might be a valuable medicinal food effective in improving insulin resistance and metabolic syndrome

Biological N fixation but not mineral N fertilization enhances the accumulation of N in peanut soil in maize/peanut intercropping system

Legume/cereal intercropping has the potential to maximize the use of resources to raise yields due to enhanced nitrogen (N) fixation by legume root nodules, while high N fertilization may inhibit the nodulation of legume. However, whether legume/cereal intercropping can promote the accumulation of soil N storage with N fertilization and its underlying mechanism are less clear. Here, we evaluated the long-term (5 years) effects of maize/peanut intercropping and mineral N fertilization on peanut soil total N content and soil N cycling functional genes. The experiment includes two planting patterns (peanut maize intercropping and peanut monocropping) with three N fertilization rates (0, 150, and 300 kg N ha−1). Intercropping increased soil total N content (STN) by average 18.2%, and the positive effect of intercropping on STN decreased with N application rate. Highest N application decreased the nodule fresh weight (NFW) by 64.3% and 46.0% in intercropping and monocropping system, respectively. However, intercropping has no effect on NFW. Intercropping increased the nifH gene abundance by average 26.5%. SEM analysis indicated that NFW and nifH gene abundance combined can explain 46% of the variance of STN. Our results indicate that biological N fixation but not mineral N fertilization enhances the accumulation of N in soil planted with peanut in maize/peanut intercropping system.info:eu-repo/semantics/publishedVersio

Randomised study of PF-06410293, an adalimumab (ADL) biosimilar, compared with reference ADL for the treatment of active rheumatoid arthritis: results from weeks 26–52, including a treatment switch from reference ADL to PF-06410293

Objective To investigate the efficacy, safety, immunogenicity and pharmacokinetics of biosimilar adalimumab (ADL) PF-06410293 (ADL-PF; adalimumab-afzb) versus EU-sourced reference ADL (ADL-EU) in patients with active rheumatoid arthritis (RA) on longer-term treatment and after being switched from ADL-EU to ADL-PF.Methods In this multinational, double-blind study, patients with active RA were initially randomised to ADL-PF or ADL-EU for 26 weeks (treatment period (TP) 1). At the start of TP2 (weeks 26–52), patients in the ADL-EU arm were blindly re-randomised 1:1 to remain on ADL-EU (ADL-EU/ADL-EU; n=135) or switched to ADL-PF (ADL-EU/ADL-PF; n=134); patients receiving ADL-PF continued blinded treatment (ADL-PF/ADL-PF; n=283).Results The American College of Rheumatology 20% improvement (ACR20) response rates were comparable between treatment groups at all visits during TP2. At week 52, ACR20 response rates were 82.7% (ADL-PF/ADL-PF), 79.3% (ADL-EU/ADL-EU) and 84.3% (ADL-EU/ADL-PF). Other measures of deep response (ACR50/70, ACR/EULAR-defined remission, EULAR good response, and Disease Activity Score in 28 Joints Based on High-Sensitivity C-Reactive Protein <2.6) and Health Assessment Questionnaire−Disability Index were maintained over TP2 and comparable between groups. Treatment-emergent adverse events were reported in 43.5% (ADL-PF/ADL-PF), 44.4% (ADL-EU/ADL-EU) and 38.3% (ADL-EU/ADL-PF) of patients; there were no clinically meaningful differences in the safety profiles between groups. The percentage of patients who were antidrug antibody positive was comparable overall among ADL-PF/ADL-PF (47.3%), ADL-EU/ADL-EU (54.1%) and ADL-EU/ADL-PF (45.9%).Conclusions The similar efficacy, safety, immunogenicity and pharmacokinetics of ADL-PF and ADL-EU, maintained up to week 52, were unaffected by blinded treatment switch from ADL-EU to ADL-PF at week 26.Trial registration number ClinicalTrials.gov identifier: NCT02480153; EudraCT number: 2014-000352-29

Comparison of methods for analysis of selective genotyping survival data

Survival traits and selective genotyping datasets are typically not normally distributed, thus common models used to identify QTL may not be statistically appropriate for their analysis. The objective of the present study was to compare models for identification of QTL associated with survival traits, in particular when combined with selective genotyping. Data were simulated to model the survival distribution of a population of chickens challenged with Marek disease virus. Cox proportional hazards (CPH), linear regression (LR), and Weibull models were compared for their appropriateness to analyze the data, ability to identify associations of marker alleles with survival, and estimation of effects when all individuals were genotyped (full genotyping) and when selective genotyping was used. Little difference in power was found between the CPH and the LR model for low censoring cases for both full and selective genotyping. The simulated data were not transformed to follow a Weibull distribution and, as a result, the Weibull model generally resulted in less power than the other two models and overestimated effects. Effect estimates from LR and CPH were unbiased when all individuals were genotyped, but overestimated when selective genotyping was used. Thus, LR is preferred for analyzing survival data when the amount of censoring is low because of ease of implementation and interpretation. Including phenotypic data of non-genotyped individuals in selective genotyping analysis increased power, but resulted in LR having an inflated false positive rate, and therefore the CPH model is preferred for this scenario, although transformation of the data may also make the Weibull model appropriate for this case. The results from the research presented herein are directly applicable to interval mapping analyses.This article is published as McElroy, Joseph P., Wuyan Zhang, Kenneth J. Koehler, Susan J. Lamont, and Jack CM Dekkers. "Comparison of methods for analysis of selective genotyping survival data." Genetics Selection Evolution 38, no. 6 (2006): 637. DOI: 10.1186/1297-9686-38-6-637. Posted with permission.</p

Investigating the Spatial Heterogeneity and Influencing Factors of Urban Multi-Dimensional Network Using Multi-Source Big Data in Hangzhou Metropolitan Circle, Eastern China

Exploring the spatial heterogeneity of urban multi-dimensional networks and influencing factors are of great significance for the integrated development of metropolitan circle. This study took Hangzhou metropolitan circle as an example, using multi-source geospatial big data to obtain urban population, transportation, goods, capital, and information flow information among sub-cities. Then, spatial visualization analysis, social network analysis, and geographical detector were applied to analyze the differences in spatial structure of multiple urban networks and influencing factors in Hangzhou metropolitan circle, respectively. The results showed that (1) the network connections of population, traffic, goods, and capital flows transcended geographical proximity except that of information flow, and population and traffic flow networks were found to be more flattened in Hangzhou metropolitan circle than in other urban networks; (2) the comprehensive urban network of Hangzhou metropolitan circle was imbalanced across sub-cities, presenting hierarchical and unipolar characteristics; and (3) the influence of traffic distance on the network spatial structure of Hangzhou metropolitan was stronger than the geographical distance, and the interactions between traffic distance and socioeconomic factors would further enhance the regional differentiation of the network spatial structure. This study could provide scientific reference for constructing a coordinated and integrated development pattern in a metropolitan circle