bluuebunny/crossref_metadata_2025_split huggingface dataset:
The
ABCG8
G574R Variant, Serum Plant Sterol Levels, and Cardiovascular Disease Risk in the Old Order Amish
Authors: Horenstein Richard B. , Mitchell Braxton D. , Post Wendy S. , Lütjohann Dieter , von Bergmann Klaus , Ryan Kathleen A. , Terrin Michael , Shuldiner Alan R. , Steinle Nanette I. 
Published: December 2012

Objective—
To determine whether long-term exposure to moderate elevations in plasma plant sterol levels increases risk for atherosclerosis.

Methods and Results—

In Old Order Amish participants aged 18 to 85 years, with (n=110) and without (n=181) 1 copy of the
ABCG8
G574R variant, we compared mean plasma levels of plant sterols and cholesterol precursors and carotid intima-media wall thickness. Carriers of a single 574R allele had increased plant sterol levels (eg, 35%–37% higher plasma levels of sitosterol, campesterol, and stigmasterol) and increased plant sterol/cholesterol ratios (
P
<0.001 for all). 574R carriers had significantly decreased levels of lathosterol and lanosterol, precursors in a pathway for endogenous cholesterol synthesis, suggesting that plant sterols may alter regulation of genes involved in cholesterol synthesis. The G574R variant was not associated with high-density lipoprotein cholesterol or low-density lipoprotein cholesterol levels. Compared with noncarriers, 574R carriers had decreased carotid intima-media wall thickness (0.62 versus 0.66 mm; age- and sex-adjusted
P
=0.03). Adjustment for body weight, blood pressure, and standard lipid measures (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) did not alter this association.

Conclusion—
Although the G574R variant is associated with moderately elevated plant sterol levels, carriers of the 574R allele had modestly lower levels of carotid wall thickness compared with noncarriers.
Angiogenesis Mediated by Toll-Like Receptor 4 in Ischemic Neural Tissue
Authors: He Chang , Sun Yuying , Ren Xiangrong , Lin Qing , Hu Xiao , Huang Xi , Su Shao-Bo , Liu Yizhi , Liu Xialin 
Published: December 2012

Objective—
Activation of the immune system via toll-like receptors (TLRs) is implicated in atherosclerosis, microvascular complications, and angiogenesis. However, the involvement of TLRs in inflammation-associated angiogenesis in ischemic neural tissue has not been investigated. The goal of this study is to determine the role of TLR4 signaling in oxygen-induced neovascularization in retina, a neural tissue.

Methods and Results—

In oxygen-induced retinopathy model, we found that retinal neovascularization was significantly attenuated in TLR4
−/−
mice. The further study revealed that the absence of TLR4 led to downregulation of proinflammatory factors in association with the attenuated activation of glia in the ischemic retina, which was also associated with reduced expression of high-mobility group box-1, an endogenous ligand for TLR4. The application of high-mobility group box-1 to the ischemic retina promoted the production of proinflammatory factors in wild-type but not TLR4
−/−
mice. High-mobility group box-1 treatment in vitro also significantly promoted the production of proinflammatory factors in retinal glial cells from wild-type mice, but much less from TLR4
−/−
mice.

Conclusion—
Our results suggest that the release of high-mobility group box-1 in ischemic neural tissue initiates TLR4-dependent responses that contribute to neovascularization. These findings represented a previously unrecognized effect of TLR4 on angiogenesis in association with the activation of glia in ischemic neural tissue.
Cardiac MRI
Authors: Gerche Andre La , Claessen Guido , Van de Bruaene Alexander , Pattyn Nele , Van Cleemput Johan , Gewillig Marc , Bogaert Jan , Dymarkowski Steven , Claus Piet , Heidbuchel Hein 
Published: December 2012

Background—
Accurate measures are critical when attempting to distinguish normal from pathological changes in cardiac function during exercise, yet imaging modalities have seldom been assessed against invasive exercise standards. We sought to validate a novel method of biventricular volume quantification by cardiac MRI (CMR) during maximal exercise.

Methods and Results—

CMR was performed on 34 subjects during exercise and free-breathing with the use of an ungated real-time (RT-ungated) CMR sequence. ECG and respiratory movements were retrospectively synchronized, enabling compensation for cardiac cycle and respiratory phase. Feasibility of RT-ungated imaging was compared with standard exercise CMR imaging with ECG gating (gated); accuracy of RT-ungated CMR was assessed against an invasive standard (direct Fick); and reproducibility was determined after a second bout of maximal exercise. Ventricular volumes were analyzed more frequently during high-intensity exercise with RT-ungated compared with gated CMR (100% versus 47%;
P
<0.0001) and with better interobserver variability for RT-ungated (coefficient of variation=1.9% and 2.0% for left and right ventricular stroke volumes, respectively) than gated (coefficient of variation=15.2% and 13.6%;
P
<0.01). Cardiac output determined by RT-ungated CMR proved accurate against the direct Fick method with excellent agreement (intraclass correlation coefficient,
R
=0.96), which was highly reproducible during a second bout of maximal exercise (
R
=0.98).

Conclusions—
When RT-ungated CMR is combined with post hoc analysis incorporating compensation for respiratory motion, highly reproducible and accurate biventricular volumes can be measured during maximal exercise.
The Rapid Distraction of Attentional Resources toward the Source of Incongruent Stimulus Input during Multisensory Conflict
Authors: Donohue Sarah E. , Todisco Alexandra E. , Woldorff Marty G. 
Published: December 2012

Abstract
Neuroimaging work on multisensory conflict suggests that the relevant modality receives enhanced processing in the face of incongruency. However, the degree of stimulus processing in the irrelevant modality and the temporal cascade of the attentional modulations in either the relevant or irrelevant modalities are unknown. Here, we employed an audiovisual conflict paradigm with a sensory probe in the task-irrelevant modality (vision) to gauge the attentional allocation to that modality. ERPs were recorded as participants attended to and discriminated spoken auditory letters while ignoring simultaneous bilateral visual letter stimuli that were either fully congruent, fully incongruent, or partially incongruent (one side incongruent, one congruent) with the auditory stimulation. Half of the audiovisual letter stimuli were followed 500–700 msec later by a bilateral visual probe stimulus. As expected, ERPs to the audiovisual stimuli showed an incongruency ERP effect (fully incongruent versus fully congruent) of an enhanced, centrally distributed, negative-polarity wave starting ∼250 msec. More critically here, the sensory ERP components to the visual probes were larger when they followed fully incongruent versus fully congruent multisensory stimuli, with these enhancements greatest on fully incongruent trials with the slowest RTs. In addition, on the slowest-response partially incongruent trials, the P2 sensory component to the visual probes was larger contralateral to the preceding incongruent visual stimulus. These data suggest that, in response to conflicting multisensory stimulus input, the initial cognitive effect is a capture of attention by the incongruent irrelevant-modality input, pulling neural processing resources toward that modality, resulting in rapid enhancement, rather than rapid suppression, of that input.
Increased Facilitatory Connectivity from the Pre-SMA to the Left Dorsal Premotor Cortex during Pseudoword Repetition
Authors: Hartwigsen Gesa , Saur Dorothee , Price Cathy J. , Baumgaertner Annette , Ulmer Stephan , Siebner Hartwig R. 
Published: December 2012

AbstractPrevious studies have demonstrated that the repetition of pseudowords engages a network of premotor areas for articulatory planning and articulation. However, it remains unclear how these premotor areas interact and drive one another during speech production. We used fMRI with dynamic causal modeling to investigate effective connectivity between premotor areas during overt repetition of words and pseudowords presented in both the auditory and visual modalities. Regions involved in phonological aspects of language production were identified as those where regional increases in the BOLD signal were common to repetition in both modalities. We thus obtained three seed regions: the bilateral pre-SMA, left dorsal premotor cortex (PMd), and left ventral premotor cortex that were used to test 63 different models of effective connectivity in the premotor network for pseudoword relative to word repetition. The optimal model was identified with Bayesian model selection and reflected a network with driving input to pre-SMA and an increase in facilitatory drive from pre-SMA to PMd during repetition of pseudowords. The task-specific increase in effective connectivity from pre-SMA to left PMd suggests that the pre-SMA plays a supervisory role in the generation and subsequent sequencing of motor plans. Diffusion tensor imaging-based fiber tracking in another group of healthy volunteers showed that the functional connection between both regions is underpinned by a direct cortico-cortical anatomical connection.
Random Errors in Turbulence Measurements in the Atmospheric Surface Layer: Implications for Monin–Obukhov Similarity Theory
Authors: Salesky Scott T. , Chamecki Marcelo 
Published: December 2012

Abstract
An error propagation analysis is conducted to estimate random errors in the friction velocity u* and the Monin–Obukhov similarity theory (MOST) stability variable z/L from estimated random errors in the turbulent fluxes. Errors in the dimensionless mean wind shear φm and mean temperature gradient φh are also estimated. To the authors’ knowledge, this is the first time that errors in calculated values of z/L, φm, and φh have been systematically analyzed. Random errors in z/L are found to be large for unstable conditions, reaching values of 40% or greater. It is shown through statistical hypothesis tests that random errors cannot explain departures of calculated values of φm and φh from theory. The deviation of calculated values of φm from empirical curves is found to have a strong diurnal variation that increases with height; deviations of φh from theory are not found to have clear diurnal variation. These results support the findings of previous studies, which have suggested that additional dimensionless parameters representing additional physical processes need to be included in the set of governing parameters for surface layer similarity. Implications for atmospheric surface layer turbulence are also discussed.
Sensitivity of the Ocean State to the Vertical Distribution of Internal-Tide-Driven Mixing
Authors: Melet Angelique , Hallberg Robert , Legg Sonya , Polzin Kurt 
Published: December 2012

Abstract
The ocean interior stratification and meridional overturning circulation are largely sustained by diapycnal mixing. The breaking of internal tides is a major source of diapycnal mixing. Many recent climate models parameterize internal-tide breaking using the scheme of St. Laurent et al. While this parameterization dynamically accounts for internal-tide generation, the vertical distribution of the resultant mixing is ad hoc, prescribing energy dissipation to decay exponentially above the ocean bottom with a fixed-length scale. Recently, Polzin formulated a dynamically based parameterization, in which the vertical profile of dissipation decays algebraically with a varying decay scale, accounting for variable stratification using Wentzel–Kramers–Brillouin (WKB) stretching. This study compares two simulations using the St. Laurent and Polzin formulations in the Climate Model, version 2G (CM2G), ocean–ice–atmosphere coupled model, with the same formulation for internal-tide energy input. Focusing mainly on the Pacific Ocean, where the deep low-frequency variability is relatively small, the authors show that the ocean state shows modest but robust and significant sensitivity to the vertical profile of internal-tide-driven mixing. Therefore, not only the energy input to the internal tides matters, but also where in the vertical it is dissipated.
Embracing a Weight-of-Evidence Approach for Establishing NOAELs for Nanoparticle Inhalation Toxicity Studies
Authors: Warheit David B. , Reed Kenneth L. , DeLorme Michael P. 
Published: December 2012

The goal of this article is to evaluate a recently published subchronic inhalation study with carbon nanofibers in rats and discuss the importance of a weight-of-evidence (WOE) framework for determining no adverse effect levels (NOAELs). In this Organization for Economic Cooperation and Development (OECD) 413 guideline inhalation study with VGCF™-H carbon nanofibers (CNFs), rats were exposed to 0, 0.54, 2.5 or 25 mg/m3 CNF for 13 weeks. The standard toxicology experimental design was supplemented with bronchoalveolar lavage (BAL) and respiratory cell proliferation (CP) endpoints. BAL fluid (BALF) recovery of inflammatory cells and mediators (i.e., BALF– lactate dehydrogenase [LDH], microprotein [MTP], and alkaline phosphatase [ALKP] levels) were increased only at 25 mg/m3, 1 day after exposure. No differences versus control values in were measured at 0.54 or 2.5 mg/m3 exposure concentrations for any BAL fluid endpoints. Approximately 90% (2.5 and 25 mg/m3) of the BAL-recovered macrophages contained CNF. CP indices at 25 mg/m3 were increased in the airways, lung parenchyma, and subpleural regions, but no increases in CP versus controls were measured at 0.54 or 2.5 mg/m3. Based upon histopathology criteria, the NOAEL was set at 0.54 mg/m3, because at 2.5 mg/m3, “minimal cellular inflammation” of the airways/lung parenchyma was noted by the study pathologist; while the 25 mg/m3 exposure concentration produced slight inflammation and occasional interstitial thickening. In contrast, none of the more sensitive pulmonary biomarkers such as BAL fluid inflammation/cytotoxicity biomarkers or CP turnover results at 2.5 mg/m3 were different from air-exposed controls. Given the absence of convergence of the histopathological observations versus more quantitative measures at 2.5 mg/m3, it is recommended that more comprehensive guidance measures be implemented for setting adverse effect levels in (nano)particulate, subchronic inhalation studies including a WOE approach for establishing no adverse effect levels; and a suggestion that some findings should be viewed as normal physiological adaptations (e.g., normal macrophage phagocytic responses—minimal inflammation) to long-term particulate inhalation exposures.
New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation
Authors: Daikeler Thomas , Labopin Myriam , Ruggeri Annalisa , Crotta Alessandro , Abinun Mario , Hussein Ayad Ahmed , Carlson Kristina , Cornillon Jérôme , Diez-Martin Jose L. , Gandemer Virginie , Faraci Maura , Lindemans Caroline , O'Meara Anne , Mialou Valerie , Renard Marleen , Sedlacek Petr , Sirvent Anne , Socié Gérard , Sora Federica , Varotto Stefania , Sanz Jaime , Voswinkel Jan , Vora Ajay , Yesilipek M. Akif , Herr Andree-Laure , Gluckman Eliane , Farge Dominique , Rocha Vanderson 
Published: December 2012

Key Points
Autoimmune diseases do occur after CBT in approximately 5% of patients. Of these, AIHA or ITP were observed the most often and were treated with prednisone, CSA, and RTX.
Anti–IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection
Authors: Chi Chih-Yu , Chu Chen-Chung , Liu Jing-Pei , Lin Chia-Hao , Ho Mao-Wang , Lo Wen-Jyi , Lin Po-Chang , Chen Hung-Jen , Chou Chia-Huei , Feng Jia-Yih , Fung Chang-Phone , Sher Yuh-Pyng , Li Chi-Yuan , Wang Jen-Hsien , Ku Cheng-Lung 
Published: December 2012

Key Points
Anti–IFN-γ autoantibodies are associated with HLA-DRB1*16:02 and DQB1*05:02.
Willingness to use a rapid diagnostic test for malaria in a rural area of central Côte d’Ivoire
Authors: Comoé Colombe Coffie , Ouattara Allassane F , Raso Giovanna , Tanner Marcel , Utzinger Jürg , Koudou Benjamin G 
Published: December 2012

Abstract

Background
Malaria mortality is mainly a direct consequence of inadequate and/or delayed diagnosis and case management. Some important control interventions (e.g. long-lasting insecticidal nests) have contributed to reduce malaria morbidity and mortality in different parts of the world. Moreover, the development and effective use of rapid diagnostic tests (RDTs) hold promise to further enhance the control and elimination of malaria, particularly in areas where health services are deficient. The aim of this study was to determine knowledge, attitudes, practices and beliefs in relation to RDTs for malaria in rural Côte d’Ivoire.

Methods
One hundred individuals from Bozi and Yoho who sought care at the health centre in Bozi and were offered an RDT for malaria were interviewed in April 2010 using a pre-tested questionnaire on practice and perceptions in relation to RDTs for malaria. The relationships between acceptance of RDTs and factors related to opinions were identified, using generalized linear mixed models. Qualitative data from open-ended questions complemented the quantitative analysis.

Results
Only 34 out of 100 patients who were offered an RDT for malaria were willing to undergo the test. People who perceived blood as a sacred body fluid were less likely to comply with an RDT. The concurrent availability and use of RDTs for HIV and malaria was associated with an unwilling attitude towards RDTs for malaria (Fisher’s exact test, p <0.001). The initial willingness of patients to accept malaria testing with RDTs was significantly related to general fear and wanting to know malaria infection status. For further and regular use of RDTs, a strong relationship was observed between acceptance and the idea that an RDT is a pretext used by health worker to know HIV status (odds ratio (OR) = 16.61, 95% confidence interval (CI) = 1.03-268.5). Those thinking that blood samples were useful for medical diagnoses were 8.31-times (95% CI = 2.22-31.1) more likely to undergo an RDT compared to those rejecting blood sampling as a diagnostic strategy.

Conclusion
Socio-cultural factors might be barriers for accepting RDTs in general health services. There are social representations of malaria and HIV/AIDS, symbolic for blood or experiences in relation to blood taking and blood-related diseases in relation to the introduction and routine use of RDTs. Special attention should be given to these barriers as otherwise the promotion of RDTs for prompt and effective diagnosis and subsequent management of malaria is hampered.
Common sequence variants in CD36 gene and the levels of triglyceride and high-density lipoprotein cholesterol among ethnic Chinese in Taiwan
Authors: Chien Kuo-Liong , Hsu Hsiu-Ching , Liu Pi-Hua , Lin Hung-Ju , Chen Ming-Fong 
Published: December 2012

AbstractBackgroundEvidence of the genetic association betweenCD36candidate gene and the risk of metabolic syndrome and its components has been inconsistent. This case–control study assessed the haplotype-tagged SNPs fromCD36on the risk of metabolic syndrome and components.Methods and resultsWe recruited 1,000 cases and age, gender-matched controls were randomly selected from the participants with metabolic syndrome defined by International Diabetes Federation. Overall, the haplotype tagged SNPs of CD36 gene were not related to the risk of metabolic syndrome. For individuals with normal lipid levels, several SNPs were significantly associated with the triglycerides and HDL-cholesterol levels: Subjects with rs3211848 homozygote had a higher triglyceride level (99.16 ± 2.61 mg/dL), compared with non-carriers (89.27 ± 1.45 mg/dL,P = 0.001). In addition, compared with non-carriers, individuals with rs1054516 heterozygous and homozygous genotypes had a significantly lower HDL-cholesterol (46.6 ± 0.46 mg/dL for non-carrier, 44.6 ± 0.36 mg/dL for heterozygous, and 44.3 ± 0.56 mg/dL for homozygous,P = 0.0008).ConclusionTheCD36gene variants were significantly associated with triglycerides and HDL-cholesterol concentrations among ethnic Chinese in Taiwan.
Analysis of the tumor length and other prognosis factors in pT1-2 node-negative esophageal squamous cell carcinoma in a Chinese population
Authors: Song Zhengbo , Wang Jiwen , Lin Baochai , Zhang Yiping 
Published: December 2012

Abstract

Background
Tumor length is an important prognostic factor for many carcinomas, but its role in esophageal cancer remained undetermined. The aim of this study was to investigate the effect of tumor length on survival for patients with confined tumors (grade pT1-2) without lymph-node metastases in esophageal squamous cell carcinoma.

Methods
We enrolled 201 patients with esophageal squamous cell carcinoma (SCC) who had undergone surgical resection and been confirmed as pT1-2N0M0. The relationship of tumor length with overall survival was assessed and compared with other factors detailed in the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system published in 2009.

Results
The overall survival (OS) rates at 1, 3, and 5 years were 93.0%, 83.7%, and 69.2%, respectively. The tumor length adversely affected OS, with the 5-year rate being 93.5%, 82.0%, 68.6%, 67.9%, 55.3% and 41.1%, respectively for tumor lengths of less than 10 mm, 10 to 20 mm, 20 to 30 mm, 30 to 40 mm, 40 to 50 mm, and greater than 50 mm (P< 0.001). Multivariate analyses showed that the pathologic T classification and grade of tumor was significantly associated with OS. Tumor length of 30 mm or more remained an independent prognostic factor (P = 0.04), as did the other current TNM factors.

Conclusion
Tumor length appears to affect the OS of patients with early-stage esophageal squamous cell carcinoma. It may provide additional prognostic information for the current TNM staging system.
Prognosis significance of HER-2/neu overexpression/amplification in Chinese patients with curatively resected gastric cancer after the ToGA clinical trial
Authors: Zhou Fei , Li Ning , Jiang Weihua , Hua Zhaolai , Xia Lin , Wei Qingyi , Wang Liwei 
Published: December 2012

Abstract

Background
HER-2/neu-targeted therapy has been successfully used in advanced gastric cancer, but the role of HER-2/neu in the prognosis of gastric cancer is not yet clear. In this study, we investigated the correlation between HER-2/neu expression and amplification as well as their association with clinic outcomes in patients with curatively resected gastric cancer.

Methods
We constructed tissue microarray blocks containing >70% of gastric cancer tissue and matched adjacent normal gastric tissue for 227 patients. Expression of the HER-2/neu protein in these specimens was analyzed using immunohistochemical staining. Amplification of HER-2/neu was also analyzed for the same samples using fluorescence in situ hybridization. Data on clinicopathological features and relevant prognostic factors in these patients were analyzed.

Results
Of the 227 gastric cancer samples, 11.89% were positive for HER-2/neu overexpression/amplification under the new scoring system. HER-2/neu overexpression/amplification was closely correlated to the Lauren type, degree of differentiation, tumor size and lymph node metastasis. HER-2/neu overexpression/amplification predicted poor survival in univariate analysis but not in a Cox proportional hazards model.

Conclusion
HER-2/neu overexpression/amplification was not an independent predictor for survival in patients with curatively resected gastric cancer.