bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review of sensorimotor function during adolescence: a developmental stage of increased motor awkwardness?
Authors: Quatman-Yates Catherine C , Quatman Carmen E , Meszaros Andrew J , Paterno Mark V , Hewett Timothy E 
Published: April 2011

BackgroundAlthough adolescent motor awkwardness and increased injury susceptibility have often been speculated and researched, studies regarding adolescent regressions in motor control have yielded inconsistent conclusions. Thus, the relationship between adolescent maturation and injury risk remains unclear. The purpose of this study was to systematically review the literature relative to two questions: (1) Which sensorimotor mechanisms are not fully mature by the time children reach adolescence? and (2) Is adolescence a period when children exhibit delays or regressions in sensorimotor mechanisms?MethodsSystematic searches for keywords were performed in February 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982) and SPORTDiscus (from 1985) databases. Articles were reviewed relative to predetermined criteria, and the methodological quality of each included study was assessed.ResultsThe search identified 2304 studies, of which 33 studies met the inclusion criteria. All 33 identified studies provided results associated with Question 1, 6 of which also yielded results pertaining to Question 2. The search results indicated that many aspects of sensorimotor function continue to mature throughout adolescence, and at least some children experience delays or regressions in at least some sensorimotor mechanisms. The results also exposed several significant weaknesses in our knowledge base.ConclusionThe identified knowledge gaps are critical barriers because they hinder methods for identifying children at high risk and diminish the efficacy of targeted prevention programmes. Implications regarding research on adolescent injury risk are discussed and recommendations for future research such as improved methodological designs and integration of non-linear analyses are provided.
An Empirical Study of the Impact of Intellectual Capital on Business Performance
Authors: Chu Samuel Kai Wah , Chan Kin Hang , Yu Ka Yin , Ng Hing Tai , Wong Wai Kwan 
Published: April 2011

This empirical study examines the intellectual capital (IC) performance of Hong Kong companies and its association with business performance. Data were collected from constituent companies of the Hang Seng Index listed on the Hong Kong Stock Exchange (2005–2008). An IC measurement, Value Added Intellectual Coefficient (VAICTM), was utilised to evaluate the IC investment of the companies. Four accounting ratios: market-to-book value (MB), return on assets (ROA), asset turnover (ATO) and return on equity (ROE) were used as the indicators of business performance. Regression analyses were conducted to test the ability of IC and its components in order to explain the variance in business performance measures. No conclusive evidence was found to support the associations between VAICTM as an aggregate measure and the four financial indicators. However, components of VAICTM were found to predict a substantial variance in business performance. Capital Employed Efficiency (CEE) was found to be a key factor in predicting business financial performance. Structural Capital Efficiency (SCE) was found to have a significant effect on businesses' market valuation, as measured by MB, and on profitability, as measured by ROE. Negative correlations were found between Human Capital Efficiency (HCE) and the financial indicators. The findings indicate a gap between the traditional accounting perspective and the value creation perspective, which is central to the VAICTM methodology in measuring IC. It is believed that the findings of this research provide insights for business stakeholders of Hong Kong companies in utilising IC, particularly the noted impact of structural capital. While our findings indicate the importance of IC for corporations, as shown by the significant effect of SCE on ROE, physical and financial assets may still be considered as the key resources in delivering business success.
Does the Hepatitis B Antigen HBx Promote the Appearance of Liver Cancer Stem Cells?
Authors: Arzumanyan Alla , Friedman Tiffany , Ng Irene O.L. , Clayton Marcia M. , Lian Zhaorui , Feitelson Mark A. 
Published: April 2011

Abstract
Hepatitis B virus (HBV) is a major etiologic agent of chronic liver disease and hepatocellular carcinoma (HCC). HBV-encoded X antigen, HBx, and pathways implicated in the self-renewal of stem cells contribute to HCC, but it is not clear whether HBx expression promotes “stemness.” Thus, experiments were designed to test the hypothesis that HBx triggers malignant transformation by promoting properties that are characteristic of cancer stem cells (CSC). To test this hypothesis, HepG2 cells were stably transduced with HBx and then assayed for phenotypic and molecular characteristics of “stemness.” The relationship between HBx and “stemness”-associated markers was also evaluated by immunohistochemical staining of liver and tumor tissue sections from HBV-infected patients. The results showed that Oct-4, Nanog, Klf-4, β-catenin, and epithelial cell adhesion molecule (EpCAM) were activated by HBx in vitro and in vivo. EpCAM was detected in the nuclei of human HCC cells from infected patients. HBx promotes “stemness” by activating β-catenin and epigenetic upregulation of miR-181, both of which target EpCAM. HBx expression was also associated with depressed levels of E-cadherin. Moreover, HBx stimulated cell migration, growth in soft agar, and spheroid formation. This work is the first to propose that HBV promotes “stemness” in the pathogenesis of HCC. HBx-associated upregulated expression of multiple “stemness” markers supports the hypothesis that HBx contributes to hepatocarcinogenesis, at least in part, by promoting changes in gene expression that are characteristics of CSCs. Cancer Res; 71(10); 3701–8. ©2011 AACR.
MYC in Chronic Myeloid Leukemia: Induction of Aberrant DNA Synthesis and Association with Poor Response to Imatinib
Authors: Albajar Marta , Gómez-Casares M. Teresa , Llorca Javier , Mauleon Itsaso , Vaqué Jose P. , Acosta Juan C. , Bermúdez Arancha , Donato Nicholas , Delgado M. Dolores , León Javier 
Published: April 2011

Abstract
Untreated chronic myeloid leukemia (CML) progresses from chronic phase to blastic crisis (BC). Increased genomic instability, deregulated proliferation, and loss of differentiation appear associated to BC, but the molecular alterations underlying the progression of CML are poorly characterized. MYC oncogene is frequently deregulated in human cancer, often associated with tumor progression. Genomic instability and induction of aberrant DNA replication are described as effects of MYC. In this report, we studied MYC activities in CML cell lines with conditional MYC expression with and without exposure to imatinib, the front-line drug in CML therapy. In cells with conditional MYC expression, MYC did not rescue the proliferation arrest mediated by imatinib but provoked aberrant DNA synthesis and accumulation of cells with 4C content. We studied MYC mRNA expression in 66 CML patients at different phases of the disease, and we found that MYC expression was higher in CML patients at diagnosis than control bone marrows or in patients responding to imatinib. Further, high MYC levels at diagnosis correlated with a poor response to imatinib. MYC expression did not directly correlate with BCR-ABL levels in patients treated with imatinib. Overall our study suggests that, as in other tumor models, MYC-induced aberrant DNA synthesis in CML cells is consistent with MYC overexpression in untreated CML patients and nonresponding patients and supports a role for MYC in CML progression, possibly through promotion of genomic instability. Mol Cancer Res; 9(5); 564–76. ©2011 AACR.
Expression Regulation of the Metastasis-Promoting Protein InsP3-Kinase-A in Tumor Cells
Authors: Chang Lydia , Schwarzenbach Heidi , Meyer-Staeckling Sönke , Brandt Burkard , Mayr Georg W. , Weitzel Joachim M. , Windhorst Sabine 
Published: April 2011

Abstract
Under physiologic conditions, the inositol-1,4,5-trisphosphate (InsP3)-metabolizing, F-actin–bundling InsP3-kinase-A (ITPKA) is expressed only in neurons. Tumor cells that have gained the ability to express ITPKA show an increased metastatic potential due to the migration-promoting properties of ITPKA. Here we investigated the mechanism how tumor cells have gained the ability to reexpress ITPKA by using a breast cancer cell line (T47D) with no expression and a lung carcinoma cell line (H1299) with ectopic ITPKA expression. Cloning of a 1,250-bp ITPKA promoter fragment revealed that methylation of CpG islands was reduced in H1299 as compared with T47D cells, but DNA demethylation did not alter the expression of ITPKA. Instead, we showed that the repressor-element-1–silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), which suppresses expression of neuronal genes in nonneuronal tissues, regulates expression of ITPKA. Knockdown of REST/NRSF induced expression of ITPKA in T47D cells, whereas its overexpression in H1299 cells strongly reduced the level of ITPKA. In T47D cells, REST/NRSF was bound to the RE-1 site of the ITPKA promoter and strongly reduced its activity. In H1299 cells, in contrast, expressing comparable REST/NRSF levels as T47D cells, REST/NRSF only slightly reduced ITPKA promoter activity. This reduced suppressor activity most likely results from expression of a dominant-negative isoform of REST/NRSF, REST4, which impairs binding of REST/NRSF to the RE-1 site. Thus, ITPKA may belong to the neuronal metastasis-promoting proteins whose ectopic reexpression in tumor cells is associated with impaired REST/NRSF activity. Mol Cancer Res; 9(4); 497–506. ©2011 AACR.
Vinculin Activators Target Integrins from Within the Cell to Increase Melanoma Sensitivity to Chemotherapy
Authors: Nelson Elke S. , Folkmann Andrew W. , Henry Michael D. , DeMali Kris A. 
Published: April 2011

Abstract
Metastatic melanoma is an aggressive skin disease for which there are no effective therapies. Emerging evidence indicates that melanomas can be sensitized to chemotherapy by increasing integrin function. Current integrin therapies work by targeting the extracellular domain, resulting in complete gains or losses of integrin function that lead to mechanism-based toxicities. An attractive alternative approach is to target proteins, such as vinculin, that associate with the integrin cytoplasmic domains and regulate its ligand-binding properties. Here, we report that a novel reagent, denoted vinculin-activating peptide or VAP, increases integrin activity from within the cell, as measured by elevated (i) numbers of active integrins, (ii) adhesion of cells to extracellular matrix ligands, (iii) numbers of cell–matrix adhesions, and (iv) downstream signaling. These effects are dependent on both integrins and a key regulatory residue A50 in the vinculin head domain. We further show that VAP dramatically increases the sensitivity of melanomas to chemotherapy in clonal growth assays and in vivo mouse models of melanoma. Finally, we show that the increase in chemosensitivity results from increases in DNA damage–induced apoptosis in a p53-dependent manner. Collectively, these findings show that integrin function can be manipulated from within the cell and validate integrins as a new therapeutic target for the treatment of chemoresistant melanomas. Mol Cancer Res; 9(6); 712–23. ©2011 AACR.
Nkx2-5 Represses
Gata1
Gene Expression and Modulates the Cellular Fate of Cardiac Progenitors During Embryogenesis
Authors: Caprioli Arianna , Koyano-Nakagawa Naoko , Iacovino Michelina , Shi Xiaozhong , Ferdous Anwarul , Harvey Richard P. , Olson Eric N. , Kyba Michael , Garry Daniel J. 
Published: April 2011

Background—
Recent studies suggest that the hematopoietic and cardiac lineages have close ontogenic origins, and that an early mesodermal cell population has the potential to differentiate into both lineages. Studies also suggest that specification of these lineages is inversely regulated. However, the transcriptional networks that govern the cell fate specification of these progenitors are incompletely defined.

Methods and Results—

Here, we show that Nkx2-5 regulates the hematopoietic/erythroid fate of the mesoderm precursors early during cardiac morphogenesis. Using transgenic technologies to isolate Nkx2-5 expressing cells, we observed an induction of the erythroid molecular program, including
Gata1
, in the
Nkx2-5
–null embryos. We further observed that overexpression of Nkx2-5 with an Nkx2-5–inducible embryonic stem cell system significantly repressed
Gata1
gene expression and suppressed the hematopoietic/erythroid potential, but not the endothelial potential, of the embryonic stem cells. This suppression was cell-autonomous, and was partially rescued by overexpressing Gata1. In addition, we demonstrated that Nkx2-5 binds to the
Gata1
gene enhancer and represses the transcriptional activity of the
Gata1
gene.

Conclusions—

Our results demonstrate that the hematopoietic/erythroid cell fate is suppressed via Nkx2-5 during mesodermal fate determination, and that the
Gata1
gene is one of the targets that are suppressed by Nkx2-5.
Meta-Analysis
Authors: Kronish Ian M. , Woodward Mark , Sergie Ziad , Ogedegbe Gbenga , Falzon Louise , Mann Devin M. 
Published: April 2011

Background—
Observational studies suggest that there are differences in adherence to antihypertensive medications in different classes. Our objective was to quantify the association between antihypertensive drug class and adherence in clinical settings.

Methods and Results—
Studies were identified through a systematic search of English-language articles published from the inception of computerized databases until February 1, 2009. Studies were included if they measured adherence to antihypertensives using medication refill data and contained sufficient data to calculate a measure of relative risk of adherence and its variance. An inverse-variance–weighted random-effects model was used to pool results. Hazard ratios (HRs) and odds ratios were pooled separately, and HRs were selected as the primary outcome. Seventeen studies met inclusion criteria. The pooled mean adherence by drug class ranged from 28% for β-blockers to 65% for angiotensin II receptor blockers. There was better adherence to angiotensin II receptor blockers compared with angiotensin-converting enzyme inhibitors (HR, 1.33; 95% confidence interval, 1.13 to 1.57), calcium channel blockers (HR, 1.57; 95% confidence interval, 1.38 to 1.79), diuretics (HR, 1.95; 95% confidence interval, 1.73 to 2.20), and β-blockers (HR, 2.09; 95% confidence interval, 1.14 to 3.85). Conversely, there was lower adherence to diuretics compared with the other drug classes. The same pattern was present when studies that used odds ratios were pooled. After publication bias was accounted for, there were no longer significant differences in adherence between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors or between diuretics and β-blockers.

Conclusion—
In clinical settings, there are important differences in adherence to antihypertensives in separate classes, with lowest adherence to diuretics and β-blockers and highest adherence to angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. However, adherence was suboptimal regardless of drug class.
The Effects of Arousing Negative and Neutral Picture Stimuli on Target Detection in a Vigilance Task
Authors: Helton William S. , Russell Paul N. 
Published: April 2011

Objectives: The present study was designed to explore whether target detection in a vigilance task is influenced by task-irrelevant negative emotional and neutral picture stimuli and to test predictions derived from the boredom-mindlessness versus resource depletion accounts of vigilance performance. Background: Previous research indicates that emotional stimuli can capture spatial attention. Research on the effect of negative emotional and neutral visual stimuli on temporal aspects of attention has not, however, been researched in detail. Method: For this study, 51 participants (15 men and 36 women) were assigned at random to one of three vigilance conditions: a visual vigil with task-irrelevant negative-arousing pictures, a visual vigil with task-irrelevant neutral pictures, or a no-picture visual vigil control. Vigilance performance was assessed in all conditions. Results: Overall performance efficiency was negatively influenced by the negative-arousing pictures and was interpreted to favor resource depletion to boredom-mindlessness accounts of vigilance performance. Conclusion: Task-unrelated negative emotional stimuli appear to impair absolute levels of target detections in a vigilance task. Application: In monitoring settings where negative emotional stimuli are present, the intrusion of negative emotional stimuli should be mitigated via alterations in the system design, or if this is implausible, the monitors may need additional stress coping and emotional resilience training.
Induction of Spontaneous Hyaline Cartilage Regeneration Using a Double-Network Gel
Authors: Kitamura Nobuto , Yasuda Kazunori , Ogawa Munehiro , Arakaki Kazunobu , Kai Shuken , Onodera Shin , Kurokawa Takayuki , Gong Jian Ping 
Published: April 2011

Background: A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N′-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. Purpose: To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Study Design: Controlled laboratory study. Methods: A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O’Driscoll et al. Results: The DN gel–implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel–implanted defects compared with the untreated control at each period ( P < .0001). The mean relative values of type 2 collagen mRNAs in the regenerated tissue were obviously higher in the DN gel–implanted defect than in the untreated control at each period. The mean surface roughness of the untreated control was significantly higher than the normal cartilage at 12 weeks ( P = .0106), while there was no statistical difference between the DN gel–implanted and normal knees. Conclusion: This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. Clinical Relevance: This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.
Sharp increase in the incidence and prevalence of multiple sclerosis in Isfahan, Iran
Authors: Etemadifar Masoud , Maghzi Amir-Hadi 
Published: April 2011

Background: The epidemiology of multiple sclerosis (MS) has changed in recent decades. Objectives: This study aimed to give an update on the prevalence and incidence of MS in Isfahan, Iran. Methods: The study population was all residents of Isfahan province during the period from April 2003 to July 2010. In April 2003, a registry of MS patients was created at the Isfahan MS Society (IMSS), which is the only referral center for MS patients in the province. Nearly all MS patients in Isfahan province are now registered with IMSS and were included in the analysis. Results: Among the 3522 registered patients, 2716 were female and 806 were male (sex ratio: 3.37 : 1), and 431 were diagnosed in 2009. This results in a prevalence figure of 73.3 (95% CI: 70.9–75.8) and an incidence of 9.1 (95% CI: 8.3–10.0) per 100,000. Conclusion: The reported prevalence and incidence figures in our study were higher than in our previous report of 2007, in which the prevalence and incidence of MS were reported to be 43.8 and 3.64 per 100,000, respectively. This dramatic increase in the prevalence of MS puts Isfahan amongst the regions with the highest prevalence of MS in Asia and Oceania and is mostly due to changing environmental factors, amongst which vitamin D deficiency seems an important factor in our population.
Genetic and pharmacologic inactivation of cannabinoid CB1 receptor inhibits angiogenesis
Authors: Pisanti Simona , Picardi Paola , Prota Lucia , Proto Maria Chiara , Laezza Chiara , McGuire Paul G. , Morbidelli Lucia , Gazzerro Patrizia , Ziche Marina , Das Arup , Bifulco Maurizio 
Published: April 2011

Abstract
In this study we investigated the role of CB1 receptor signaling in angiogenesis and the therapeutic exploitation of CB1 inactivation as an antiangiogenic strategy. We started from the observation that CB1 receptor expression is induced during angiogenesis and that the endocannabinoid anandamide stimulated bFGF-induced angiogenesis in the nanomolar physiologic range. To define the functional involvement of CB1 receptor signaling during angiogenesis, 2 different strategies have been carried out: siRNA-mediated knockdown and pharmacologic antagonism of CB1 receptors. CB1 receptors inactivation resulted in the inhibition of bFGF-induced endothelial proliferation, migration, and capillary-like tube formation, through prosurvival and migratory pathways involving ERK, Akt, FAK, JNK, Rho, and MMP-2. To corroborate the potential therapeutic exploitation of CB1 blockade as an antiangiogenic strategy, we performed in vivo assays founding that CB1 blockade was able to inhibit bFGF-induced neovascular growth in the rabbit cornea assay. A relevant finding was the ability to reduce ocular pathologic neo-vascularization in mouse oxygen-induced retinopathy. These results demonstrate that CB1 signaling participates to the proliferative response elicited by proangiogenic growth factors in angiogenesis and that for this reason CB1 receptor could represent a novel target for the treatment of diseases where excessive neoangiogenesis is the underlying pathology.