bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of Glomerular Filtration Rate in Elderly Chronic Kidney Disease Patients: Comparison of Three Novel Sophisticated Equations and Simple Cystatin C Equation
Authors: Bevc Sebastjan , Hojs Nina , Hojs Radovan , Ekart Robert , Gorenjak Maksimiljan , Puklavec Ludvik 
Published: March 2017

AbstractEstimating glomerular filtration rate (GFR) in elderly patients is a problem, since they are poorly represented in studies developing GFR equations. Serum cystatin C is a better indicator of GFR than serum creatinine in elderly patients. Therefore the aim of our study was to compare frequently used serum cystatin C based GFR equations with a gold standard (51CrEDTA clearance) in elderly chronic kidney disease (CKD) patients. 106 adult Caucasian patients, older than 65 years (58 women, 48 men; mean age 72.5 years), were included. In each patient 51CrEDTA clearance, serum creatinine (IDMS traceable method) and serum cystatin C (immunonephelometric method) were determined. GFR was estimated using the Simple cystatin C, CKD‐EPI cystatin C, CKD‐EPI creatinine‐cystatin C and BIS2 equation. Mean serum creatinine of our patients was 141.4 ± 41.5 μmol/L, mean serum cystatin C 1.79 ± 0.6 mg/L, mean 51CrEDTA clearance was 52.2 ± 15.9 mL/min per 1.73 m2. Statistically significant correlations between 51CrEDTA clearance and all formulas were found (P < 0.0001). In the receiver operating characteristic (ROC) curve analysis (cut‐off for GFR 45 mL/min per 1.73 m2) no significant differences in diagnostic accuracy between all the before mentioned equations were found. Bland‐Altman analysis for the same cut‐off showed that CKD‐EPI creatinine‐cystatin C and BIS2 equation underestimated and CKD‐EPI cystatin C and Simple cystatin C equation overestimated measured GFR. All equations lacked precision. Analysis of ability to correctly predict patient's GFR below or above 45 mL/min per 1.73 m2 showed similar ability for all equations (P = 0.24–0.89). All equations are equally accurate for estimating GFR in elderly Caucasian CKD patients. For daily practice Simple cystatin C equation is most practical.
MicroRNA‐1254 inhibits the migration of colon adenocarcinoma cells by targeting PSMD10
Authors: Chu Yi Min , Peng Hai Xia , Xu Ying , Yang Da Ming , Zhou Feng Li , Li Ji , Kuai Rong , Lin Yong 
Published: March 2017

OBJECTIVEMicroRNA‐1254 (miR‐1254) has not been studied in colorectal cancer (CRC) to date. This study aimed to investigate the inhibitory mechanism of miR‐1254 in CRC tumorigenesis.METHODSMiR‐1254 expression was examined using real‐time polymerase chain reaction in CRC and adjacent non‐tumorous tissues. The correlation between miR‐1254 expressions and proliferation and migration of cancer cells was determined using the CCK‐8 and transwell assays. RNA sequencing was used to identify differentially expressed genes downstream from miR‐1254. A luciferase reporter assay was used to confirm the direct interaction between miR‐1254 and its predicted target gene, PSMD10. Moreover, PSMD10 was either overexpressed or silenced in colon carcinoma cells overexpressing miR‐1254 to determine whether their interaction contributed to CRC migration and epithelial‐mesenchymal transition (EMT).RESULTSSignificantly lower miR‐1254 expressions were observed in CRC tissues than in adjacent non‐tumorous tissues. Exogenous miR‐1254 expression suppressed the migration of colon carcinoma cell lines SW1116 and HCT116. RNA sequencing and luciferase assays revealed that miR‐1254 directly binded to the 3′‐untranslated region of PSMD10, an important regulator of EMT and cell migration. PSMD10 knockdown inhibited EMT and colon cancer cell migration, whereas PSMD10 overexpression reversed the inhibition of EMT and cell migration caused by miR‐1254.CONCLUSIONMiR‐1254 may act as a tumor suppressor in CRC and may inhibit CRC migration by directly targeting PSMD10 to suppress the EMT process.
Anxiety, Anxiety Sensitivity, and Perceived Stress as Predictors of Recent Drinking, Alcohol Craving, and Social Stress Response in Heavy Drinkers
Authors: McCaul Mary E. , Hutton Heidi E. , Stephens Mary Ann C. , Xu Xiaoqiang , Wand Gary S. 
Published: March 2017

BackgroundStress and anxiety are widely considered to be causally related to alcohol craving and consumption, as well as development and maintenance of alcohol use disorder (AUD). However, numerous preclinical and human studies examining effects of stress or anxiety on alcohol use and alcohol‐related problems have been equivocal. This study examined relationships between scores on self‐report anxiety, anxiety sensitivity, and stress measures and frequency and intensity of recent drinking, alcohol craving during early withdrawal, as well as laboratory measures of alcohol craving and stress reactivity among heavy drinkers with AUD.MethodsMedia‐recruited, heavy drinkers with AUD (N = 87) were assessed for recent alcohol consumption. Anxiety and stress levels were characterized using paper‐and‐pencil measures, including the Beck Anxiety Inventory (BAI), the Anxiety Sensitivity Index‐3 (ASI‐3), and the Perceived Stress Scale (PSS). Eligible subjects (N = 30) underwent alcohol abstinence on the Clinical Research Unit; twice daily measures of alcohol craving were collected. On day 4, subjects participated in the Trier Social Stress Test; measures of cortisol and alcohol craving were collected.ResultsIn multivariate analyses, higher BAI scores were associated with lower drinking frequency and reduced drinks/drinking day; in contrast, higher ASI‐3 scores were associated with higher drinking frequency. BAI anxiety symptom and ASI‐3 scores also were positively related to Alcohol Use Disorders Identification Test total scores and AUD symptom and problem subscale measures. Higher BAI and ASI‐3 scores but not PSS scores were related to greater self‐reported alcohol craving during early alcohol abstinence. Finally, BAI scores were positively related to laboratory stress‐induced cortisol and alcohol craving. In contrast, the PSS showed no relationship with most measures of alcohol craving or stress reactivity.ConclusionsOverall, clinically oriented measures of anxiety compared with perceived stress were more strongly associated with a variety of alcohol‐related measures in current heavy drinkers with AUD.
Hypomania Checklist‐32 – cross‐validation of shorter versions screening for bipolar disorders in an epidemiological study
Authors: Meyer T. D. , Castelao E. , Gholamrezaee M. , Angst J. , Preisig M. 
Published: March 2017

ObjectiveSelf‐reports such as Hypomania Checklist (HCL‐32) can be used to enhance recognition of bipolar disorders, but they are often too long and only validated in clinical samples. The objectives of this study are therefore to test whether (i) the HCL‐32 can be used for screening in the community and (ii) whether two previously suggested shorter versions would do as well.MethodData stemmed from the CoLaus|PsyColaus, a prospective cohort study which included randomly selected residents aged 35–66 years from an urban area. Participants underwent semistructured interviews to assess DSM‐IV disorders and 1712 of them completed the HCL‐32.ResultsForty individuals (2.3%) were diagnosed as having BD. Compared to others, participants with BD scored significantly higher on the HCL‐32. The HCL‐32 had a sensitivity of 0.78 and specificity of 0.68. Very similar figures were found for two previously proposed shorter versions with 16 and 20 items. The results of confirmatory factor analysis and item response theory (IRT) models supported the postulated two‐factor structure for the three HCL versions.ConclusionDespite the low base rate of BD in this sample, the screening properties of the HCL‐32 remained almost as good. Importantly, two previously proposed shorter versions performed as well, suggesting that those could be used without losing essential information.
Identification of the interaction between bta‐miR‐370 and OLR1 gene in bovine adipocyte
Authors: Li H. F. , Wang S. H. , Guo Y. , Zhao H. B. , Li X. Y. , Wang X. 
Published: March 2017

SummaryIt has been shown that the oxidized low density lipoprotein receptor 1 (OLR1) gene plays an important role in the degradation of oxidized low density lipoprotein. Previous studies found a SNP in the 3′‐untranslated region (3′‐UTR) of the OLR1 gene associated with milk production traits in different dairy cattle populations and with loin eye area and marbling depth in beef cattle. MicroRNAs can regulate gene expression by binding the 3′‐UTR of target genes to degrade or to repress the translation of target genes. Bioinformatics have shown that there is a binding site of bta‐miR‐370 in the 3′‐UTR of the OLR1 gene, and a previous luciferase reporter assay system showed that the A/C mutation occurring in the 3′‐UTR of this gene caused the binding sites of bta‐miR‐370 to disappear in HEK293 cells. To further validate whether OLR1 was the target gene of bta‐miR‐370, the over‐expression and interference expression of bta‐miR‐370 were determined by transfecting bta‐miR‐370 mimics and inhibitor supplementations into bovine adipocyte. The qRT‐PCR result showed that the relative expression of OLR1 gene significantly decreased in the mimics group compared to the control, whereas the expression level in inhibitor group was higher than its control group. The above results were further verified by a Western blot at the protein level. In addition, lipid formation analysis of bovine adipocytes was performed via oil red O staining, and we found that cytoplasm lipid droplets in the inhibitor group showed a tendency to increase compared to the control group, whereas in the mimics group, we observed an obvious decrease of cytoplasm lipid droplets compared to the control and inhibitor groups. Taken together, our data here suggest that bta‐miR‐370 has a negative regulation role for OLR1 both at the gene expression and protein levels and bovine adipocytes cytoplasm lipid droplets formation, which provides a reference for illustrating how the OLR1 gene affects milk production and beef quality traits in cattle.
Children with atopic dermatitis and frequent emollient use have increased urinary levels of low‐molecular‐weight phthalate metabolites and parabens
Authors: Overgaard L. E. K. , Main K. M. , Frederiksen H. , Stender S. , Szecsi P. B. , Williams H. C. , Thyssen J. P. 
Published: March 2017

AbstractBackgroundParabens may be added to cosmetic and personal care products for preservation purposes. Low‐molecular weight (LMW) phthalate diesters function as plasticizers, fixatives or solvents in such products, but may also be found in small quantities as contaminants from plastic containers.ObjectiveTo evaluate the association between emollient use, atopic dermatitis and FLG mutations, respectively, with urinary concentrations of phthalate metabolites and parabens in Danish children.MethodsEight hundred and forty‐five Danish children 4‐9 years of age were studied. Urinary concentrations of phthalate metabolites and parabens were determined, and children were genotyped for common FLG loss‐of‐function mutations. Information about atopic dermatitis and use of emollients was obtained from questionnaires completed by parents.ResultsThe prevalence of atopic dermatitis was 16.1%. Phthalate metabolite and paraben levels were generally higher in children with frequent use of emollients compared to uncommon users, reaching statistical significance for some LMW phthalates and parabens. While there was no association with common FLG mutations, children with atopic dermatitis had significantly higher urinary levels of one LMW phthalate and two parabens, respectively, when compared to children without atopic dermatitis.ConclusionEmollient use and atopic dermatitis were associated with modestly increased internal LMW phthalate and paraben exposure in 4‐9 year old children. It is unknown whether the difference is explained by increased use of the specific emollients that are used to treat pruritic and inflamed skin, and/or whether the impaired skin barrier allows chemicals to penetrate more easily. Moreover, the putative toxicological burden is unknown.
An investigation of the potential effect of sperm nuclear vacuoles in human spermatozoa on DNA fragmentation using a neutral and alkaline Comet assay
Authors: Pastuszek E. , Kiewisz J. , Skowronska P. , Liss J. , Lukaszuk M. , Bruszczynska A. , Jakiel G. , Lukaszuk K. 
Published: March 2017

SummaryPresence of vacuoles and degree of sperm DNA damage are considered to be the basic factors used for the assessment of sperm fertilization capacity. We aimed to investigate the link between these two parameters. According to our knowledge, this is the first study where the Comet assay was used to assess the degree of DNA fragmentation of sperm categorized by Motile Sperm Organelle Morphology Examination (MSOME) Grades. Semen samples from 10 patients were assessed. Spermatozoa were graded into four MSOME groups according to the Vanderzwalmen's criteria. A total of 3930 motile spermatozoa were selected one‐by‐one using an inverted microscope and transferred onto two different slides. The degree of DNA fragmentation was analyzed by alkaline and neutral Comet assay. Results of the neutral Comet assay showed that Grade I spermatozoa (absence of vacuoles) presented significantly lower dsDNA fragmentation level (mean: 3.13 ± 1.17%) than Grade II (maximum of two small vacuoles; mean: 10.34 ± 2.65%), Grade III (more than two small vacuoles or at least one large vacuole; mean: 23.88 ± 8.37%), and Grade IV (large vacuoles associated with abnormal head shapes or other abnormalities; mean: 36.94 ± 7.78%; p < 0.05). Results of the alkaline Comet assay showed that Grade I spermatozoa had significantly lower DNA (ssDNA + dsDNA) fragmentation level (mean: 8.33 ± 3.62%) than Grade III (mean: 25.64 ± 9.15%) and Grade IV (mean: 40.10 ± 9.10%, p < 0.05), but not significantly lower than Grade II (mean: 12.73 ± 5.06%; p > 0.05). Probably, the vacuoles may be responsible for double strand DNA breaks rather than single strand DNA breaks (only 2.39% spermatozoa in MSOME Grade II, 1.76% in III, and 3.16% in IV has single strand breaks). The results demonstrate that lower MSOME grading correlates with lower sperm DNA fragmentation. Therefore, the observation of sperm nuclear vacuoles using real‐time optical microscopy without precise DNA fragmentation examination is not sufficient for optimal sperm selection for intracytoplasmic sperm injection.
DNA methylation imprinting errors in spermatogenic cells from maturation arrest azoospermic patients
Authors: Marques P. I. , Fernandes S. , Carvalho F. , Barros A. , Sousa M. , Marques C. J. 
Published: March 2017

SummaryImprinting errors have been described in spermatozoa from infertile patients with oligozoospermia and azoospermia. However, little is known about methylation of imprinted genes in other spermatogenic cells from azoospermic patients. Therefore, we aimed to evaluate the methylation status of single CpGs located in the differentially methylated regions (DMRs) of two imprinted genes, one paternally (H19) and one maternally (MEST) methylated, in primary spermatocytes of azoospermic patients presenting complete (MAc, n = 7) and incomplete (MAi, n = 8) maturation arrest, as well as in other spermatogenic cells from MAi patients that presented focus of complete spermatogenesis in some seminiferous tubules. We observed H19 imprinting errors in primary spermatocytes from one MAi patient and MEST imprinting errors in one MAi and two MAc patients. Additionally, H19 imprinting errors were observed in elongated spermatids/spermatozoa from one MAi patient. Nevertheless, no statistical differences were found for H19 and MEST global methylation levels (percentage of methylated and unmethylated CpGs, respectively) between patients with complete and incomplete MA and also between MA groups and a control group. These results provide further evidence that imprinting errors occur in spermatogenic cells from patients presenting impaired spermatogenesis, as we and others have previously described in ejaculated and testicular spermatozoa. As paternal imprinting errors can be transmitted to the embryo by the sperm cell, they can provide a possible explanation for poor embryo development and/or low pregnancy rates as correct expression of imprinted genes is crucial for embryo and placental development and function. Therefore, in cases with male factor infertility where unsuccessful in vitro fertilization (IVF) treatments are recurrent, analysis of imprinting marks in spermatozoa might be a useful diagnostic tool.
Effect of endocrine disruptors on male reproduction in humans: why the evidence is still lacking?
Authors: Bliatka D. , Lymperi S. , Mastorakos G. , Goulis D. G. 
Published: March 2017

SummaryThe so‐called “endocrine disruption hypothesis” suggests that exposures to endocrine disruption (EDs) during fetal, neonatal and adult life may interfere with the development of reproductive organs and alter semen quality and reproductive hormone production. Even though animal studies provide substantial evidence of adverse effects of EDs on male reproductive system, epidemiological studies in humans arrive at conflicting results. The aim of the present study was to systematically review the literature to locate methodological characteristics of the studies that struggle the formation of an association between EDs and human male reproduction. Such characteristics include: (i) definition of the exposed and the non‐exposed population, (ii) age, (iii) insufficient control for confounders, (iv) ED assay and threshold, (v) time parameters of ED exposure, and (vi) study outcomes. Additional issues are: (i) the late effect of an early exposure, (ii) the multiple exposure effect, and (iii) the fact the same ED may exhibit different modes of action. Unfortunately, the nature of the field precludes the conduction of randomized‐controlled trials, which could result to etiological associations between EDs and human male reproduction. Consequently, there is a great need to conduct well‐designed studies of case–control or cohort type to evaluate EDs effects on human male reproductive health, and apply possible measures that could limit dangerous exposures.
Hypothesis Testing in Functional Linear Models
Authors: Su Yu-Ru , Di Chong-Zhi , Hsu Li 
Published: March 2017

SummaryFunctional data arise frequently in biomedical studies, where it is often of interest to investigate the association between functional predictors and a scalar response variable. While functional linear models (FLM) are widely used to address these questions, hypothesis testing for the functional association in the FLM framework remains challenging. A popular approach to testing the functional effects is through dimension reduction by functional principal component (PC) analysis. However, its power performance depends on the choice of the number of PCs, and is not systematically studied. In this article, we first investigate the power performance of the Wald-type test with varying thresholds in selecting the number of PCs for the functional covariates, and show that the power is sensitive to the choice of thresholds. To circumvent the issue, we propose a new method of ordering and selecting principal components to construct test statistics. The proposed method takes into account both the association with the response and the variation along each eigenfunction. We establish its theoretical properties and assess the finite sample properties through simulations. Our simulation results show that the proposed test is more robust against the choice of threshold while being as powerful as, and often more powerful than, the existing method. We then apply the proposed method to the cerebral white matter tracts data obtained from a diffusion tensor imaging tractography study.
Learning Gene Regulatory Networks from Next Generation Sequencing Data
Authors: Jia Bochao , Xu Suwa , Xiao Guanghua , Lamba Vishal , Liang Faming 
Published: March 2017

SummaryIn recent years, next generation sequencing (NGS) has gradually replaced microarray as the major platform in measuring gene expressions. Compared to microarray, NGS has many advantages, such as less noise and higher throughput. However, the discreteness of NGS data also challenges the existing statistical methodology. In particular, there still lacks an appropriate statistical method for reconstructing gene regulatory networks using NGS data in the literature. The existing local Poisson graphical model method is not consistent and can only infer certain local structures of the network. In this article, we propose a random effect model-based transformation to continuize NGS data and then we transform the continuized data to Gaussian via a semiparametric transformation and apply an equivalent partial correlation selection method to reconstruct gene regulatory networks. The proposed method is consistent. The numerical results indicate that the proposed method can lead to much more accurate inference of gene regulatory networks than the local Poisson graphical model and other existing methods. The proposed data-continuized transformation fills the theoretical gap for how to transform discrete data to continuous data and facilitates NGS data analysis. The proposed data-continuized transformation also makes it feasible to integrate different types of data, such as microarray and RNA-seq data, in reconstruction of gene regulatory networks.
Augmented Estimation for t-Year Survival with Censored Regression Models
Authors: Zheng Yu , Cai Tianxi 
Published: March 2017

Summary
Reliable and accurate risk prediction is fundamental for successful management of clinical conditions. Estimating comprehensive risk prediction models precisely, however, is a difficult task, especially when the outcome of interest is time to a rare event and the number of candidate predictors, p, is not very small. Another challenge in developing accurate risk models arises from potential model misspecification. Time-specific generalized linear models estimated with inverse censoring probability weighting are robust to model misspecification, but may be inefficient in the rare event setting. To improve the efficiency of such robust estimation procedures, various augmentation methods have been proposed in the literature. These procedures can also leverage auxiliary variables such as intermediate outcomes that are predictive of event risk. However, most existing methods do not perform well in the rare event setting, especially when p is not small. In this article, we propose a two-step, imputation-based augmentation procedure that can improve estimation efficiency and that is robust to model misspecification. We also develop regularized augmentation procedures for settings where p is not small, along with procedures to improve the estimation of individualized treatment effect in risk reduction. Numerical studies suggest that our proposed methods substantially outperform existing methods in efficiency gains. The proposed methods are applied to an AIDS clinical trial for treating HIV-infected patients.