bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary energy density and adiposity: Employing bias adjustments in a meta-analysis of prospective studies
Authors: Wilks Désirée C , Mander Adrian P , Jebb Susan A , Thompson Simon G , Sharp Stephen J , Turner Rebecca M , Lindroos Anna Karin 
Published: January 2011

Abstract

Background
Dietary studies differ in design and quality making it difficult to compare results. This study quantifies the prospective association between dietary energy density (DED) and adiposity in children using a meta-analysis method that adjusts for differences in design and quality through eliciting and incorporating expert opinion on the biases and their uncertainty.

Method
Six prospective studies identified by a previous systematic literature search were included. Differences in study quality and design were considered respectively as internal and external biases and captured in bias checklists. Study results were converted to correlation coefficients; biases were considered either additive or proportional on this scale. The extent and uncertainty of the internal and external biases in each study were elicited in a formal process by five quantitatively-trained assessors and five subject-matter specialists. Biases for each study were combined across assessors using median pooling and results combined across studies by random-effects meta-analysis.

Results
The unadjusted combined correlation between DED and adiposity change was 0.06 (95%CI 0.01, 0.11; p = 0.013), but with considerable heterogeneity (I2 = 52%). After bias-adjustment the pooled correlation was 0.17 (95%CI - 0.11, 0.45; p = 0.24), and the studies were apparently compatible (I2 = 0%).

Conclusions
This method allowed quantitative synthesis of the prospective association between DED and adiposity change in children, which is important for the development of evidence-informed policy. Bias adjustment increased the magnitude of the positive association but the widening confidence interval reflects the uncertainty of the assessed biases and implies that higher quality studies are required.
Endoscopic treatment of vesicoureteral reflux using calcium hydroxyl apatite in dogs
Authors: Bakhtiari Jalal , Kajbafzadeh Abdol Mohammad , Marjani Mahdi , Veshkini Abbas , Tavakoli Azin , Gharagozlou Mohammad Javad , Niasari-Naslaji Amir 
Published: January 2011

Abstract

Background
Injection of biomaterial to suburetral region, using minimally invasive procedure, has become an interesting topic for urologists to treat vesicoureteral reflux. The objective of this study was to evaluate the feasibility of injecting newly introduced calcium hydroxyl apatite to suburetral region, for treating an experimentally induced vesicoureteral reflux in dogs.

Findings
Bilateral vesicoureteral refluxed (VUR) mixed breed dogs (n = 12; 10-15 kg live weight, 3-6 months of age) were selected for this study. The presence and grade of the reflux were determined using cystography. Accordingly, 6 dogs displayed grade 1 & 2 and the other 6 showed grade 3 & 4 bilateral VUR. Every single dog, with bilateral VUR, underwent endoscopic treatment and received an injection of calcium hydroxyl apatite (an Iranian made product) into the left (treated side) and an injection of the similar volume of normal saline in to the right (control side) subureteric space. One week, 3 and 6 months after treatment, cystography was performed. On each occasion, 4 dogs were euthanized by gas inhalation and biopsy samples were collected for histopathological study from ureter, bladder, kidney, lung and spleen in order to investigate the biomaterial migration into different organs. Data were analyzed using Chi-squared test. In control sides, radiographs confirmed the same grade of VUR, found at the initiation of the study. VUR was resolved in 100% (6/6) of Grade 1 & 2 and 83.33% (5/6) of Grade 3 & 4 in treated side. Therefore, the total success rate of this study was 91.67% (11/12). Macroscopic examination of the vesicouretral region of the treated side revealed a firm and consistent biomaterial mass at the site of injection. Histological findings confirmed inflammation at treated side. In contrast, there was no tissue reaction on control side. There was no evidence for biomaterial migration in macroscopic and microscopic observations in this study.

Conclusion
In the present study, a new biocompatible material produced a firm, consist and sustainable biomaterial mass in the suburetral region for treating vesicouretral reflux without any evidence of biomaterial migration.
Molecular mechanism of the schedule-dependent synergistic interaction in EGFR-mutant non-small cell lung cancer cell lines treated with paclitaxel and gefitinib
Authors: Cheng Hua , An She-Juan , Dong Song , Zhang Yi-Fang , Zhang Xu-Chao , Chen Zhi-Hong , Jian-Su  , Wu Yi-Long 
Published: January 2011

AbstractBackgroundChemotherapy combined concurrently with TKIs produced a negative interaction and failed to improve survival when compared with chemotherapy or TKIs alone in the treatment of non-small cell lung cancer (NSCLC). The present study investigated the sequence-dependent interaction between paclitaxel and gefitinib and clarified the underlying mechanism.MethodsThe effects on cell proliferation, EGFR signaling pathway, and TGFα expression were evaluated in a panel of human NSCLC cell lines harboring EGFR mutations with three different combination sequences: sequential treatment with paclitaxel followed by gefitinib (T→G), sequential treatment with gefitinib followed by paclitaxel (G→T), or concomitant treatment (T + G).ResultsThe sequence-dependent anti-proliferative effects differed between EGFR-TKI-sensitive and -resistant cell lines carryingEGFRmutations. A synergistic anti-proliferative activity was obtained with paclitaxel treatment followed by gefitinib in all cell lines, with mean CI values of 0.63 in Hcc827, 0.54 in PC-9, 0.81 in PC-9/GR, and 0.77 in H1650 cells for the T→G sequence. The mean CI values for the G→T sequence were 1.29 in Hcc827, 1.16 in PC-9, 1.52 in PC-9/GR, and 1.5 in H1650 cells. The mean CI values for T+G concomitant treatment were 0.88 in Hcc827, 0.91 in PC-9, 1.05 in PC-9/GR, and 1.18 in H1650 cells. Paclitaxel produced a dose-dependent increase in EGFR phosphorylation. Paclitaxel significantly increased EGFR phosphorylation compared with that in untreated controls (mean differences: +50% in Hcc827, + 56% in PC-9, + 39% in PC-9/GR, and + 69% in H1650 cells;p< 0.05). The T→G sequence produced significantly greater inhibition of EGFR phosphorylation compared with the opposite sequence (mean differences: -58% in Hcc827, -38% in PC-9, -35% in PC-9/GR, and -30% in H1650 cells;p< 0.05). Addition of a neutralizing anti-TGFα antibody abolished paclitaxel-induced activation of the EGFR pathway in PC-9 and H1650 cells. Sequence-dependent TGFα expression and release are responsible for the sequence-dependent EGFR pathway modulation.ConclusionThe data suggest that the sequence of paclitaxel followed by gefitinib is an appropriate treatment combination for NSCLC cell lines harboring EGFR mutations. Our results provide molecular evidence to support clinical treatment strategies for patients with lung cancer.
Enhanced RAD21 cohesin expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers
Authors: Xu Huiling , Yan Max , Patra Jennifer , Natrajan Rachael , Yan Yuqian , Swagemakers Sigrid , Tomaszewski Jonathan M , Verschoor Sandra , Millar Ewan KA , van der Spek Peter , Reis-Filho Jorge S , Ramsay Robert G , O'Toole Sandra A , McNeil Catriona M , Sutherland Robert L , McKay Michael J , Fox Stephen B 
Published: January 2011

Abstract
Introduction
RAD21 is a component of the cohesin complex, which is essential for chromosome segregation and error-free DNA repair. We assessed its prognostic and predictive power in a cohort of in situ and invasive breast cancers, and its effect on chemosensitivity in vitro.

Methods
RAD21 immunohistochemistry was performed on 345 invasive and 60 pure in situ carcinomas. Integrated genomic and transcriptomic analyses were performed on a further 48 grade 3 invasive cancers. Chemosensitivity was assessed in breast cancer cell lines with an engineered spectrum of RAD21 expression.

Results
RAD21 expression correlated with early relapse in all patients (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.06 to 2.86, P = 0.029). This was due to the effect of grade 3 tumors (but not grade 1 or 2) in which RAD21 expression correlated with early relapse in luminal (P = 0.040), basal (P = 0.018) and HER2 (P = 0.039) groups. In patients treated with chemotherapy, RAD21 expression was associated with shorter overall survival (P = 0.020). RAD21 mRNA expression correlated with DNA copy number, with amplification present in 32% (7/22) of luminal, 31% (4/13) of basal and 22% (2/9) of HER2 grade 3 cancers. Variations in RAD21 mRNA expression in the clinical samples were reflected in the gene expression data from 36 breast cancer cell lines. Knockdown of RAD21 in the MDA-MB-231 breast cancer cell line significantly enhanced sensitivity to cyclophosphamide, 5-fluorouracil and etoposide. The findings for the former two drugs recapitulated the clinical findings.

Conclusions
RAD21 expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers. RAD21 may be a novel therapeutic target.
Aberrations in Pseudoautosomal Regions (PARs) Found in Infertile Men with Y-Chromosome Microdeletions
Authors: Jorgez Carolina J. , Weedin John W. , Sahin Aysegul , Tannour-Louet Mounia , Han Shuo , Bournat Juan C. , Mielnik Anna , Cheung Sau Wai , Nangia Ajay K. , Schlegel Peter N. , Lipshultz Larry I. , Lamb Dolores J. 
Published: January 2011

AbstractContext:The pseudoautosomal regions (PARs) of the Y-chromosome undergo meiotic recombination with the X-chromosome. PAR mutations are associated with infertility and mental and stature disorders.Objective:The aim of the study was to determine whether men with Y-chromosome microdeletions have structural defects in PARs.Design and Participants:Eighty-seven infertile men with Y-chromosome microdeletions and 35 controls were evaluated for chromosomal rearrangements using commercial or custom (X- and Y-chromosome) array comparative genomic hybridization or by quantitative PCR of selected PAR genes. Multisoftware-defined chromosomal gains or losses were validated by quantitative PCR and FISH.Results:Array comparative genomic hybridization confirmed the AZF deletions identified by multiplex PCR. All men with Y-chromosome microdeletions and an abnormal karyotype displayed PAR abnormalities, as did 10% of men with Y-chromosome microdeletions and a normal karyotype. None of the control subjects or infertile men without Y-chromosome microdeletions had PAR duplications or deletions. SHOX aberrations occurred in 14 men (nine gains and five losses); four were short in stature (&lt;10th percentile), and one was tall (&gt;95th percentile). In contrast, the height of 23 men with Y-chromosome microdeletions and normal PARs was average at 176.8 cm (50th percentile).Conclusions:Y-chromosome microdeletions can include PAR defects causing genomic disorders such as SHOX, which may be transmitted to offspring. Previously unrecognized PAR gains and losses in men with Y-chromosome microdeletions may have consequences for offspring.
Plasma Cholesteryl Ester Transfer, But Not Cholesterol Esterification, Is Related to Lipoprotein-Associated Phospholipase A2: Possible Contribution to an Atherogenic Lipoprotein Profile
Authors: Dullaart Robin P. F. , Constantinides Alexander , Perton Frank G. , van Leeuwen Jeroen J. J. , van Pelt Joost L. , de Vries Rindert , van Tol Arie 
Published: January 2011

AbstractContext:Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) predicts incident cardiovascular disease and is associated preferentially with negatively charged apolipoprotein B-containing lipoproteins. The plasma cholesteryl ester transfer (CET) process, which contributes to low high-density lipoprotein cholesterol and small, dense low-density lipoproteins, is affected by the composition and concentration of apolipoprotein B-containing cholesteryl ester acceptor lipoproteins.Objective:We tested relationships of CET with Lp-PLA2 in subjects with and without metabolic syndrome (MetS).Design and Setting:In 68 subjects with MetS and 74 subjects without MetS, plasma Lp-PLA2 mass, cholesterol esterification (EST), lecithin:cholesterol acyltransferase (LCAT) activity level, CET, CET protein (CETP) mass, and lipoproteins were measured.Results:EST, LCAT activity, CET (P &lt; 0.001 for all), and CETP (P = 0.030) were increased, and Lp-PLA2 was decreased (P = 0.043) in MetS. CET was correlated positively with Lp-PLA2 in subjects with and without MetS (P &lt; 0.05 for both). EST and LCAT activity were unrelated to Lp-PLA2, despite a positive correlation between EST and CET (P &lt; 0.001). After controlling for age, sex, and diabetes status, CET was determined by Lp-PLA2 in the whole group (β = 0.245; P &lt; 0.001), and in subjects with (β = 0.304; P = 0.001) and without MetS (β = 0.244; P = 0.006) separately, independently of triglycerides and CETP.Conclusions:Plasma CET is related to Lp-PLA2 in subjects with and without MetS. The process of CET, but not EST, may be influenced by Lp-PLA2. These findings provide a rationale to evaluate whether maneuvers that inhibit Lp-PLA2 will reduce CET, and vice versa to document effects of CETP inhibition on Lp-PLA2.
Interrelationship between Fatty Liver and Insulin Resistance in the Development of Type 2 Diabetes
Authors: Sung Ki-Chul , Kim Sun H. 
Published: January 2011

Abstract

Context:
Although fatty liver and insulin resistance are known to be associated, the relationship between the two in the development of type 2 diabetes mellitus (T2DM) is unclear.

Objective:
We investigated the 5-yr risk of developing T2DM in individuals diagnosed with fatty liver using ultrasound and stratified by insulin sensitivity using quartiles of fasting insulin concentration.

Design and Methods:
We examined the clinical and laboratory data of 11,091 Koreans who had a medical evaluation including fasting insulin concentration and abdominal ultrasound at baseline and had a follow-up after 5 yr.

Results:
At baseline, 27% of the population had fatty liver. Almost half (47%) of the individuals with fatty liver had baseline insulin concentration in the highest quartile compared with 17% in those without fatty liver (P &lt; 0.001). Regardless of baseline insulin concentration, individuals with fatty liver had significantly (P &lt; 0.001) more baseline clinical and metabolic abnormalities, including higher glucose and triglyceride concentration and lower high-density lipoprotein cholesterol concentration. In addition, regardless of baseline insulin concentration, individuals with fatty liver had a significantly increased risk for incident T2DM compared with those without fatty liver [crude odds ratio, 5.05 (95% confidence interval, 2.08–12.29) in the lowest insulin quartile and 6.34 (3.58–11.21) in the highest quartile]. In individuals in the highest insulin quartile, the odds ratio for developing T2DM remained significant even after multivariate adjustment including baseline glucose concentration [2.42 (1.23–4.75)].

Conclusion:
Although associated with insulin resistance, fatty liver diagnosed by ultrasound appears to independently increase the risk of T2DM.
Organizing Contests for Status: The Matthew Effect vs. the Mark Effect
Authors: Bothner Matthew S. , Podolny Joel M. , Smith Edward Bishop 
Published: January 2011

What is the best way to design tournaments for status, in which individuals labor primarily for the esteem of their peers? What process, in other words, should organizers of status-based contests impose upon those who covet peer recognition? We propose a formal model of status-based competition that contrasts two competing alternatives. The first, following Merton, is the “Matthew Effect,” according to which a tournament's architect directs slack resources to elite actors and thus widens the distribution of rewards by favoring cumulative advantage. The second is the “Mark Effect,” under which a tournament's designer instead pushes slack resources to marginal actors and thus tightens the distribution of rewards. Our results suggest that although the Mark Effect is better for the social welfare of most tournaments, the Matthew Effect is preferable in two distinct contexts: in small tournaments where variation in underlying ability translates into acute advantages for the most capable contestants; and in large tournaments whose contestants face constant, rather than rising, marginal costs—a condition we relate to contestants' perception of their work as intrinsically valuable. Our contributions are twofold: We find, counter to the thrust of Merton's work, that cumulative advantage is not invariably optimal for the functioning of status contests; and we identify circumstances in which the production of superstars is likely to make contests for status better off in aggregate. Implications for future research on status and management are discussed. This paper was accepted by Olav Sorenson, organizations and social networks.
The relationship between testosterone deficiency and frailty in elderly men
Authors: Saad Farid 
Published: January 2011

Abstract
The vulnerable health status usually preceding the onset of overt disability is often referred to as frailty. A stringent definition is elusive but it can be viewed as a physiological syndrome, characterized by decreased reserve and diminished resistance to stressors, resulting from a cumulative decline across multiple physiological systems and causing vulnerability to adverse outcomes. Elements of frailty are related to the neurological system, metabolism, joints, bones, and muscles. Sarcopenia seems to be the major determinant of frailty. Several components of the frailty syndrome are related to loss of physiological actions of testosterone (T). T and/or its aromatized metabolite, estradiol, are necessary for maintenance of bone mineral density. Furthermore, T stimulates erythrocyte formation. T has a profound effect on body composition. Androgens promote differentiation of mesenchymal pluripotent cells into the myogenic lineage and inhibit differentiation into the adipogenic lineage. Skeletal muscles of older men are as responsive to the anabolic effects of T as of younger men. Thus, although frailty is obviously a complex syndrome, some elements are androgen-associated and these can improve in men with subnormal T levels when treated with T. Evidence suggests that T treatment in frail elderly men with low T improves body composition, quality of life, and physical function, including increased axial bone mineral density and body composition. The data available to date strongly suggest a relationship between T-deficiency and frailty and warrant further basic and clinical investigations to extend these observations to the management of elderly men with frailty.
Ti–Al–Si–C–N Hard Coatings Synthesized by Hybrid Arc-Enhanced Magnetron Sputtering
Authors: Wu Guizhi , Liu Sitao , Ma Shengli , Xu Kewei , Ji Vincent , Chu Paul K. 
Published: January 2011

Abstract
Ti–Al–Si–C–N coatings are deposited by hybrid arc-enhanced magnetron sputtering and characterized by various micro and macro-tools. X-ray diffraction, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy reveal that the coatings are probably nanocomposites consisting of nanocrystallites and amorphous phases. They are generally in the form of nc-(Ti,Al)(C,N)/a-SiN/a-C, depending on the composition of the coatings. With increasing Al concentrations, the X-ray diffraction peaks shift to a lower angle and the measured hardness diminishes, implying a reduced contribution of the self-organized stable nanostructure. The dry friction coefficients of the Ti–Al–Si–C–N coatings are about 0.3, which is lower than that of conventional Ti–Si–N coatings. These coatings can find potential applications requiring heavy contact loading subject to high temperature.
High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly
Authors: Wassenaar M J E , Biermasz N R , Hamdy N A T , Zillikens M C , van Meurs J B J , Rivadeneira F , Hofman A , Uitterlinden A G , Stokkel M P M , Roelfsema F , Kloppenburg M , Kroon H M , Romijn J A , Pereira A M 
Published: January 2011

ObjectiveTo establish the prevalence of osteoporosis, vertebral fractures (VFs), and non-VFs in acromegaly patients with long-term controlled disease and factors potentially influencing fracture risk.DesignCase–control study.Patients and measurementsEighty-nine patients (46% male, mean age: 58 years) were included. We studied VFs and non-VFs, bone mineral density (BMD), and markers of bone turnover. In 48 patients, BMD assessment was also obtained 7 years prior to the current study. To compare VF prevalence, data from a sample of the Dutch population (n=3469) were used.ResultsVF prevalence was 59% (men 64% and women 54%), significantly increased when compared with controls (odds ratio up to 6.5), and independent of the duration of disease control, BMD, markers of bone turnover, and acromegalic disease characteristics. Mean number of VFs per patient was 3.4±0.3 (range 1–8). There was no relationship between the number and severity of fractures, parameters of bone turnover, and follow-up BMD measurements. BMD did not change during prolongation of follow-up by 7 years of controlled acromegaly.ConclusionThere is a very high prevalence of VFs in acromegaly patients with long-term controlled disease, independently of BMD. In view of the significant morbidity and mortality associated with VFs in general and the inability of BMD to predict fracture risk in acromegalic patients, we propose to include VF assessment, for example by lateral conventional radiographs of the spine in the screening of patients with acromegaly, both at diagnosis and during follow-up after establishment of disease control.