bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies
Authors: Seidel Petra , Alkhouri Hatem , Lalor Daniel J , Burgess Janette K , Armour Carol L , Hughes J Margaret 
Published: October 2012

Abstract

Background
Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro.

Methods
Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test.

Results
Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production.

Conclusions
Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.
LRpath analysis reveals common pathways dysregulated via DNA methylation across cancer types
Authors: Kim Jung H , Karnovsky Alla , Mahavisno Vasudeva , Weymouth Terry , Pande Manjusha , Dolinoy Dana C , Rozek Laura S , Sartor Maureen A 
Published: October 2012

Abstract

Background
The relative contribution of epigenetic mechanisms to carcinogenesis is not well understood, including the extent to which epigenetic dysregulation and somatic mutations target similar genes and pathways. We hypothesize that during carcinogenesis, certain pathways or biological gene sets are commonly dysregulated via DNA methylation across cancer types. The ability of our logistic regression-based gene set enrichment method to implicate important biological pathways in high-throughput data is well established.

Results
We developed a web-based gene set enrichment application called LRpath with clustering functionality that allows for identification and comparison of pathway signatures across multiple studies. Here, we employed LRpath analysis to unravel the commonly altered pathways and other gene sets across ten cancer studies employing DNA methylation data profiled with the Illumina HumanMethylation27 BeadChip. We observed a surprising level of concordance in differential methylation across multiple cancer types. For example, among commonly hypomethylated groups, we identified immune-related functions, peptidase activity, and epidermis/keratinocyte development and differentiation. Commonly hypermethylated groups included homeobox and other DNA-binding genes, nervous system and embryonic development, and voltage-gated potassium channels. For many gene sets, we observed significant overlap in the specific subset of differentially methylated genes. Interestingly, fewer DNA repair genes were differentially methylated than expected by chance.

Conclusions
Clustering analysis performed with LRpath revealed tightly clustered concepts enriched for differential methylation. Several well-known cancer-related pathways were significantly affected, while others were depleted in differential methylation. We conclude that DNA methylation changes in cancer tend to target a subset of the known cancer pathways affected by genetic aberrations.
Cardiac structure and function in relation to cardiovascular risk factors in Chinese
Authors: Zhang Yi , Li Yan , Liu Ming , Sheng Chang-Sheng , Huang Qi-Fang , Wang Ji-Guang 
Published: October 2012

Abstract

Background
Cardiac structure and function are well-studied in Western countries. However, epidemiological data is still scarce in China.

Methods
Our study was conducted in the framework of cardiovascular health examinations for the current and retired employees of a factory and their family members. According to the American Society of Echocardiography recommendations, we performed echocardiography to evaluate cardiac structure and function, including left atrial volume, left ventricular hypertrophy and diastolic dysfunction.

Results
The 843 participants (43.0 years) included 288 (34.2%) women, and 191 (22.7%) hypertensive patients, of whom 82 (42.9%) took antihypertensive drugs. The prevalence of left atrial enlargement, left ventricular hypertrophy and concentric remodeling was 2.4%, 5.0% and 12.7%, respectively. The prevalence of mild and moderate-to-severe left ventricular diastolic dysfunction was 14.2% and 3.3%, respectively. The prevalence of these cardiac abnormalities significantly (P ≤ 0.002) increased with age, except for the moderate-to-severe left ventricular diastolic dysfunction. After adjustment for age, gender, body height and body weight, left atrial enlargement was associated with plasma glucose (P = 0.009), and left ventricular hypertrophy and diastolic dysfunction were significantly associated with systolic and diastolic blood pressure (P ≤ 0.03), respectively.

Conclusions
The prevalence of cardiac structural and functional abnormalities increased with age in this Chinese population. Current drinking and plasma glucose had an impact on left atrial enlargement, whereas systolic and diastolic blood pressures were major correlates for left ventricular hypertrophy and diastolic dysfunction, respectively.
Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes
Authors: Hsieh Ming-Ju , Lan Kuang-Ping , Liu Hao-Yu , Zhang Xiao-Zong , Lin Yaw-Feng , Chen Tzy-Yen , Chiou Hui-Ling 
Published: October 2012

Abstract

Background
Hepatitis C virus (HCV) infection may cause liver diseases of various severities ranging from primary acute infection to life-threatening diseases, such as cirrhosis or hepatocellular carcinoma with poor prognosis. According to clinical findings, HCV infection may also lead to some extra-hepatic symptoms, including type 2 diabetes mellitus (DM). Since insulin resistance is the major etiology for type 2 DM and numerous evidences showed that HCV infection associated with insulin resistance, the involvement of E2 in the pathogenesis of type 2 DM and underlying mechanisms were investigated in this study.

Methods
Reverse transcription and real-time PCR, Western blot assay, Immunoprecipitation, Glucose uptake assay and analysis of cellular glycogen content.

Results
Results showed that E2 influenced on protein levels of insulin receptor substrate-1 (IRS-1) and impaired insulin-induced Ser308 phosphorylation of Akt/PKB and Ser9 phosphorylation of GSK3β in Huh7 cells, leading to an inhibition of glucose uptake and glycogen synthesis, respectively, and eventually insulin resistance.

Conclusions
Therefore, HCV E2 protein indeed involved in the pathogenesis of type 2 DM by inducing insulin resistance.
Body composition, dietary composition, and components of metabolic syndrome in overweight and obese adults after a 12-week trial on dietary treatments focused on portion control, energy density, or glycemic index
Authors: Melanson Kathleen J , Summers Amber , Nguyen Von , Brosnahan Jen , Lowndes Joshua , Angelopoulos Theodore J , Rippe James M 
Published: October 2012

AbstractBackgroundGiven the rise in obesity and associated chronic diseases, it is critical to determine optimal weight management approaches that will also improve dietary composition and chronic disease risk factors. Few studies have examined all these weight, diet, and disease risk variables in subjects participating in recommended multi-disciplinary weight loss programs using different dietary strategies.MethodsThis study compared effects of three dietary approaches to weight loss on body composition, dietary composition and risk factors for metabolic syndrome (MetS). In a 12-week trial,sedentary but otherwise healthy overweight and obese adults (19 M & 138 F; 38.7 ± 6.7 y; BMI 31.8 ± 2.2) who were attending weekly group sessions for weight loss followed either portion control, low energy density, or low glycemic index diet plans. At baseline and 12 weeks, measures included anthropometrics, body composition, 3-day food diaries, blood pressure, total lipid profile, HOMA, C-reactive protein, and fasting blood glucose and insulin. Data were analyzed by repeated measures analysis of variance.ResultsAll groups significantly reduced body weight and showed significant improvements in body composition (p < 0.001), and components of metabolic syndrome (p < 0.027 to 0.002), although HDL decreased (p < 0.001). Dietary energy, %fat and %saturated fat decreased while protein intake increased significantly (p < 0.001). There were no significant differences among the three groups in any variable related to body composition, dietary composition, or MetS components.ConclusionDifferent dietary approaches based on portion control, low energy density, or low glycemic index produced similar, significant short-term improvements in body composition, diet compositin, and MetS components in overweight and obese adults undergoing weekly weight loss meetings. This may allow for flexibility in options for dietary counseling based on patient preference.
Prognostic significance of solitary lymph node metastasis in patients with squamous cell carcinoma of middle thoracic esophagus
Authors: Wu Jie , Chen Qi-Xun , Zhou Xing-Ming , Mao Wei-Ming , Krasna Mark J. , Teng Li-Song 
Published: October 2012

Abstract

Background
The aim of this study is to compare clinical outcomes between patients with solitary lymph node metastasis and node-negative (N0) patients in squamous cell carcinoma of the middle thoracic esophagus.

Methods
A series of 135 patients with squamous cell carcinoma of the middle thoracic esophagus were retrospectively investigated. There were 33 patients with solitary lymph node metastasis and 102 N0 patients. Skip metastasis in 33 patients with solitary lymph node metastasis was defined according to three criteria: Japanese Society for Esophageal Disease (JSED), American Joint Commission on Cancer (AJCC), and the anatomical compartment.

Results
In 33 patients with solitary lymph node metastasis, skip metastasis was shown in 13, 23, and 8 patients according JSED, AJCC and anatomical compartment respectively. The 5-year survival rates for N0 patients and patients with solitary lymph node metastasis were 58% and 32% respectively (
P
=0.008). Multivariate analysis revealed that skip metastasis was not an independent prognostic factor.

Conclusions
For patients with middle thoracic esophageal squamous cell carcinoma, solitary lymph node metastasis has a negative impact on survival compared with N0 disease; skip metastasis, however, is comparable to N0 diseases in predicting prognosis.
Evaluation of age-related changes in translocator protein (TSPO) in human brain using 11C-[R]-PK11195 PET
Authors: Kumar Ajay , Muzik Otto , Shandal Varun , Chugani Diane , Chakraborty Pulak , Chugani Harry T 
Published: October 2012

Abstract

Background
We studied the distribution and expression of translocator protein in the human brain using 11C-[R]-PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes.

Methods
A dynamic PK11195 PET scan was performed in 15 normal healthy adults (mean age: 29 ±8.5 years (range: 20 to 49); 7 males) and 10 children (mean age: 8.8 ±5.2 years (range: 1.2 to 17); 5 males), who were studied for potential neuroinflammation but showed no focally increased PK11195 binding. The PET images were evaluated by calculating standard uptake values and regional binding potential, based on a simplified reference region model, as well as with a voxel-wise analysis using statistical parametric mapping.

Results
PK11195 uptake in the brain is relatively low, compared with the subcortical structures, and symmetrical. The overall pattern of PK11195 distribution in the brain does not change with age. PK11195 uptake was lowest in the frontal-parietal-temporal cortex and highest in the pituitary gland, midbrain, thalamus, basal ganglia, occipital cortex, hippocampus and cerebellum, in descending order. White matter showed negligible PK11195 uptake. Overall, brain PK11195 uptake increased with age, with midbrain and thalamus showing relatively higher increases with age compared with other brain regions.

Conclusions
The brain shows low PK11195 uptake, which is lower in the cortex and cerebellum compared with subcortical structures, suggesting a low level of translocator protein expression. There is no hemispheric asymmetry in PK11195 uptake and the overall pattern of PK11195 distribution in the brain does not change with age. However, brain PK11195 uptake increases with age, with the thalamus and midbrain showing relatively higher increases compared with other brain regions. This increase in uptake suggests an age-related increase in translocator protein expression or the number of cells expressing these receptors or both.
Upper extremity rehabilitation of stroke: Facilitation of corticospinal excitability using virtual mirror paradigm
Authors: Kang Youn Joo , Park Hae Kyung , Kim Hyun Jung , Lim Taeo , Ku Jeonghun , Cho Sangwoo , Kim Sun I , Park Eun Sook 
Published: October 2012

Abstract

Background
Several experimental studies in stroke patients suggest that mirror therapy and various virtual reality programs facilitate motor rehabilitation. However, the underlying mechanisms for these therapeutic effects have not been previously described.

Objectives
We attempted to delineate the changes in corticospinal excitability when individuals were asked to exercise their upper extremity using a real mirror and virtual mirror. Moreover, we attempted to delineate the role of visual modulation within the virtual environment that affected corticospinal excitability in healthy subjects and stroke patients.

Methods
A total of 18 healthy subjects and 18 hemiplegic patients were enrolled into the study. Motor evoked potential (MEP)s from transcranial magnetic stimulation were recorded in the flexor carpi radialis of the non-dominant or affected upper extremity using three different conditions: (A) relaxation; (B) real mirror; and (C) virtual mirror. Moreover, we compared the MEPs from the virtual mirror paradigm using continuous visual feedback or intermittent visual feedback.

Results
The rates of amplitude increment and latency decrement of MEPs in both groups were higher during the virtual mirror task than during the real mirror. In healthy subjects and stroke patients, the virtual mirror task with intermittent visual feedback significantly facilitated corticospinal excitability of MEPs compared with continuous visual feedback.

Conclusion
Corticospinal excitability was facilitated to a greater extent in the virtual mirror paradigm than in the real mirror and in intermittent visual feedback than in the continuous visual feedback, in both groups. This provides neurophysiological evidence supporting the application of the virtual mirror paradigm using various visual modulation technologies to upper extremity rehabilitation in stroke patients.
PAM50 Breast Cancer Subtyping by RT-qPCR and Concordance with Standard Clinical Molecular Markers
Authors: Bastien Roy RL , Rodríguez-Lescure Álvaro , Ebbert Mark TW , Prat Aleix , Munárriz Blanca , Rowe Leslie , Miller Patricia , Ruiz-Borrego Manuel , Anderson Daniel , Lyons Bradley , Álvarez Isabel , Dowell Tracy , Wall David , Seguí Miguel Ángel , Barley Lee , Boucher Kenneth M , Alba Emilio , Pappas Lisa , Davis Carole A , Aranda Ignacio , Fauron Christiane , Stijleman Inge J , Palacios José , Antón Antonio , Carrasco Eva , Caballero Rosalía , Ellis Matthew J , Nielsen Torsten O , Perou Charles M , Astill Mark , Bernard Philip S , Martín Miguel 
Published: October 2012

Abstract

Background
Many methodologies have been used in research to identify the “intrinsic” subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E) and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC) markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions.

Methods
We used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu (HER2) protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH). Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and “intrinsic” subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments.

Results

ESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC) ≥ 0.9). Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B) subtypes (92%), but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74%) and Luminal A tumors were less likely to have high proliferation (11% vs 77%). Seventy-seven percent (30/39) of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57%) and HER2-E (30%) subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as shown in a multivariate analysis.

Conclusions
The standard immunohistochemical panel for breast cancer (ER, PR, and HER2) does not adequately identify the PAM50 gene expression subtypes. Although there is high agreement between biomarker scoring by protein immunohistochemistry and gene expression, the gene expression determinations for ESR1 and ERBB2 status was more prognostic.
Screening for foot problems in children: is this practice justifiable?
Authors: Evans Angela Margaret 
Published: October 2012

AbstractPodiatry screening of children is a common practice, which occurs largely without adequate data to support the need for such activity. Such programs may be either formalised, or more ad hoc in nature, depending upon the use of guidelines or existing models. Although often not used, the well‐established criteria for assessing the merits of screening programs can greatly increase the understanding as to whether such practices are actually worthwhile. This review examines the purpose of community health screening in the Australian context, as occurs for tuberculosis, breast, cervical and prostate cancers, and then examines podiatry screening practices for children with reference to the criteria of the World Health Organisation (WHO). Topically, the issue of paediatric foot posture forms the focus of this review, as it presents with great frequency to a range of clinicians. Comparison is made with developmental dysplasia of the hip, in which instance the WHO criteria are well met. Considering that the burden of the condition being screened for must be demonstrable, and that early identification must be found to be beneficial, in order to justify a screening program, there is no sound support for either continuing or establishing podiatry screenings for children.
Synthesis, in vitro antifungal evaluation and in silico study of 3-azolyl-4-chromanone phenylhydrazones
Authors: Ayati Adile , Falahati Mehraban , Irannejad Hamid , Emami Saeed 
Published: October 2012

Abstract

Background
The currently available antifungal drugs suffer from toxicity, greatest potential drug interactions with other drugs, insufficient pharmacokinetics properties, and development of resistance. Thus, development of new antifungal agents with optimum pharmacokinetics and less toxicity is urgent task. In the search for new azole antifungals, we have been previously described azolylchromanone oxime ethers as rigid analogs of oxiconazole. In continuation of our work, we incorporated phenylhydrazone moiety instead of oxime ether fragment in azolylchromanone derivatives.

Methods
The 3-azolyl-4-chromanone phenylhydrazones were synthesized via ring closure of 2-azolyl-2'-hydroxyacetophenones and subsequent reaction with phenylhydrazine. The biological activity of title compounds was evaluated against different pathogenic fungi including Candida albicans, Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum. Docking study, in silico toxicity risks and drug-likeness predictions were used to better define of title compounds as antifungal agents.

Results
The in vitro antifungal activity of compounds based on MIC values revealed that all compounds showed good antifungal activity against C. albicans, S. cerevisiae and M. gypseum at concentrations less than 16 μg/mL. Among the test compounds, 2-methyl-3-imidazolyl derivative 3b showed the highest values of drug-likeness and drug-score.

Conclusion
The 3-azolyl-4-chromanone phenylhydrazones considered as analogs of 3-azolyl-4-chromanone oxime ethers basically designed as antifungal agents. The antifungal activity of title compounds was comparable to that of standard drug fluconazole. The drug-likeness data of synthesized compounds make them promising leads for future development of antifungal agents.
Chondrocalcinosis is common in the absence of knee involvement
Authors: Abhishek Abhishek , Doherty Sally , Maciewicz Rose , Muir Kenneth , Zhang Weiya , Doherty Michael 
Published: October 2012

Abstract
Introduction
We aimed to describe the distribution of radiographic chondrocalcinosis (CC) and to examine whether metacarpophalangeal joint (MCPJ) calcification and CC at other joints occurs in the absence of knee involvement.

Methods
This was a cross-sectional study embedded in the Genetics of Osteoarthritis and Lifestyle study (GOAL). All participants (n = 3,170) had radiographs of the knees, hands, and pelvis. These were scored for radiographic changes of osteoarthritis (OA), for CC at knees, hips, symphysis pubis, and wrists, and for MCPJ calcification. The prevalence of MCPJ calcification and CC overall, at each joint, and in the presence or absence of knee involvement, was calculated.

Results
The knee was the commonest site of CC, followed by wrists, hips, and symphysis pubis. CC was more likely to be bilateral at knees and wrists but unilateral at hips. MCPJ calcification was usually bilateral, and less common than CC at knees, hips, wrists, and symphysis pubis. Unlike that previously reported, CC commonly occurred without any knee involvement; 44.4% of wrist CC, 45.9% of hip CC, 45.5% of symphysis pubis CC, and 31.3% of MCPJ calcification occurred in patients without knee CC. Those with meniscal or hyaline articular cartilage CC had comparable ages (P = 0.21), and neither preferentially associated with fibrocartilage CC at distant joints.

Conclusions
CC visualized on a plain radiograph commonly occurs at other joints in the absence of radiographic knee CC. Therefore, knee radiographs alone are an insufficient screening test for CC. This has significant implications for clinical practice, for epidemiologic and genetic studies of CC, and for the definition of OA patients with coexistent crystal deposition.