bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing maximal oxygen uptake in young people during a ramp cycle test to exhaustion
Authors: Barker A R , Williams C A , Jones A M , Armstrong N 
Published: August 2009

ObjectivesThis study tested the hypotheses that (1) secondary criteria (respiratory exchange ratio (RER), heart rate, blood [lactate]) traditionally used to verify the determination of maximum oxygen uptake (V̇O2max) in children can result in the acceptance of a ‘submaximal’ V̇O2maxor falsely reject a ‘true’ V̇O2maxand (2) the V̇O2peakrecorded during a ramp test in children is comparable to the V̇O2peakachieved during supramaximal testing.MethodsThirteen children (9–10 years) completed a ramp cycle test to exhaustion to determine their V̇O2peak. After 15 min of recovery, the participants performed a supramaximal cycle test to exhaustion at 105% of their ramp test peak power.ResultsCompared with the V̇O2peakduring the ramp test, a significantly lower V̇O2was recorded at a RER of 1.00 (1.293 litre/min (SD 0.265) vs 1.681 litre/min (SD 0.295), p<0.001, n=12), at a heart rate of 195 beats/min (1.556 litre/min (SD 0.265) vs 1.721 litre/min (SD 0.318), p<0.001, n=10) and at 85% of age-predicted maximum (1.345 litre/min (SD 0.228) vs 1.690 litre/min (SD 0.284), p<0.001, n=13). Supramaximal testing yielded a V̇O2peakthat was not significantly different from the ramp test (1.615 litre/min (SD 0.307) vs 1.690 litre/min (SD 0.284), p=0.090, respectively).ConclusionsThe use of secondary criteria to verify a maximal effort in young people during ramp cycling exercise may result in the acceptance of a submaximal V̇O2max. As supramaximal testing elicits a V̇O2peaksimilar to the ramp protocol, thus satisfying the plateau criterion, the use of such tests is recommended as the appropriate method of confirming a ‘true’ V̇O2maxwith children.KeywordsChildren, Aerobic Fitness, Fitness Testing, Supramaximal Exercise.
Hepatocyte nuclear factor 4α attenuates hepatic fibrosis in rats
Authors: Yue H-Y , Yin C , Hou J-L , Zeng X , Chen Y-X , Zhong W , Hu P-F , Deng X , Tan Y-X , Zhang J-P , Ning B-F , Shi J , Zhang X , Wang H-Y , Lin Y , Xie W-F 
Published: August 2009

Background and aimsHepatocyte nuclear factor 4α (HNF4α) is a central transcriptional regulator of hepatocyte differentiation and function. The aim of this study was to evaluate the effect of HNF4α on attenuation of hepatic fibrosis.MethodsThe adenoviruses carrying HNF4α gene or containing siRNA targeting HNF4α were injected through tail vein on two distinct hepatic fibrosis models either induced by dimethylnitrosamine or by bile duct ligation in rats. Moreover, HNF4α, epithelial–mesenchymal transition (EMT)-related and fibrotic markers in hepatocytes, hepatic stellate cells (HSCs) and liver tissues were detected by real time PCR, immunofluorescence or immunohistochemistry.ResultsWe demonstrated that decreased expression of HNF4α and epithelial markers accompanied by enhanced expression of mesenchymal markers occurred in fibrotic liver. More importantly, forced expression of HNF4α remarkably alleviated hepatic fibrosis and improved liver function with suppression of EMT in both fibrosis models. In contrast, downregulation of HNF4α by siRNA aggravated hepatic fibrosis and decreased the expression of E-cadherin in association with the enhanced expression of vimentin and fibroblast-specific protein-1. In vitro study revealed that HNF4α could suppress the EMT process of hepatocytes induced by transforming growth factor-β1 and increase the expression of liver-specific genes. A similar phenomenon of the EMT process was observed during the activation of HSCs, which was abrogated by HNF4α. Additionally, HNF4α deactivated the myofibroblasts through inducing the mesenchymal-to-epithelial transition and inhibited their proliferation.ConclusionsOur study suggests that HNF4α is critical for hepatic fibrogenesis and upregulation of HNF4α might present as an ideal option for the treatment of hepatic fibrosis.
Biomass fuel use and indoor air pollution in homes in Malawi
Authors: Fullerton D G , Semple S , Kalambo F , Suseno A , Malamba R , Henderson G , Ayres J G , Gordon S B 
Published: August 2009

Background:Air pollution from biomass fuels in Africa is a significant cause of mortality and morbidity both in adults and children. The work describes the nature and quantity of smoke exposure from biomass fuel in Malawian homes.Methods:Markers of indoor air quality were measured in 62 homes (31 rural and 31 urban) over a typical 24 h period. Four different devices were used (one gravimetric device, two photometric devices and a carbon monoxide (HOBO) monitor. Gravimetric samples were analysed for transition metal content. Data on cooking and lighting fuel type together with information on indicators of socioeconomic status were collected by questionnaire.Results:Respirable dust levels in both the urban and rural environment were high with the mean (SD) 24 h average levels being 226 μg/m3(206 μg/m3). Data from real-time instruments indicated respirable dust concentrations were >250 μg/m3for >1 h per day in 52% of rural homes and 17% of urban homes. Average carbon monoxide levels were significantly higher in urban compared with rural homes (6.14 ppm vs 1.87 ppm; p<0.001). The transition metal content of the smoke was low, with no significant difference found between urban and rural homes.Conclusions:Indoor air pollution levels in Malawian homes are high. Further investigation is justified because the levels that we have demonstrated are hazardous and are likely to be damaging to health. Interventions should be sought to reduce exposure to concentrations less harmful to health.
Does the availability of single cigarettes promote or inhibit cigarette consumption? Perceptions, prevalence and correlates of single cigarette use among adult Mexican smokers
Authors: Thrasher J F , Villalobos V , Dorantes-Alonso A , Arillo-Santillán E , Cummings K Michael , O’Connor R , Fong G T 
Published: August 2009

Background:Single cigarette use and its implications have rarely been studied among adults.Objective:To assess perceptions, prevalence and correlates of single cigarette purchase behaviour and its relation to harm reduction.Design:Focus group transcripts and cross-sectional data were analysed.Setting and participants:Focus groups among convenience samples of adult smokers in two Mexican cities and a population-based sample of 1079 adult smokers from the International Tobacco Control Policy Evaluation Project in four Mexican cities.Main outcome measures:Purchase of single cigarettes last time cigarettes were bought, frequency of purchasing single cigarettes in the previous month and intention to quit in the next 6 months.Results:Focus group data indicated that smokers bought single cigarettes as a harm reduction strategy. Survey data indicated that 38% of participants purchased single cigarettes in the last month and 10% purchased them the last time they bought cigarettes, with more frequent consumption among young adults and those with lower income. Purchasing single cigarettes was independently associated with the frequency of using single cigarettes to reduce consumption and, less consistently, with the frequency of being cued to smoke after seeing single cigarettes for sale. Using single cigarettes to reduce consumption was positively associated with quit intention, whereas being cued to smoke by single cigarettes was negatively associated with quit intention.Conclusions:Study results suggest that some adult Mexican smokers purchase single cigarettes as a method to limit, cut down on and even quit smoking. Nevertheless, promotion of the availability of single cigarettes as a harm reduction strategy could provide additional smoking cues that undermine quit attempts and promote youth smoking.
Smoking restrictions in the home and secondhand smoke exposure among primary schoolchildren before and after introduction of the Scottish smoke-free legislation
Authors: Akhtar P C , Haw S J , Currie D B , Zachary R , Currie C E 
Published: August 2009

Objective:To examine change in home smoking restrictions one year after introduction of Scottish smoke-free legislation, and whether type of restriction impacts upon secondhand smoke (SHS) exposure among children.Design:Comparison of nationally representative, cross-sectional, class-based surveys carried out in the same schools before and after legislation.Participants:2527 primary schoolchildren (aged around 11 years) surveyed in January 2006 and 2379 in January 2007.Outcome measures:Self-reported home smoking restrictions, salivary cotinine concentrations.Results:Children surveyed after implementation of legislation were more likely than those surveyed before its introduction to report complete home smoking restrictions as opposed to partial (relative risk ratio (partial vs complete) 0.75 (95% CI 0.63 to 0.89) or no restrictions (RR (no restrictions vs complete) 0.50 (0.40 to 0.63). Children living with smokers were less likely to have stringent restrictions in place compared with children living with non-smokers (for both vs neither parents smoke: RR (partial vs complete) 18.29 (13.26 to 25.22) and RR (no restrictions vs complete) 104.73 (70.61 to 155.33). Among smoking households, restriction type varied according to the number and gender of parents who smoke. In both smoking and non-smoking households, children’s SHS exposure was directly related to type of home smoking restriction, with lowest exposures among those reporting complete restrictions.Conclusion:This study has shown an increase in the proportion of children reporting a complete ban on smoking in their household after the introduction of smoke-free legislation and supports growing evidence of the wider impact smoke-free legislation can have on smoker behaviour. However, quitting smoking combined with complete home smoking bans will still afford children the best protection from SHS exposure.
Risk factors associated with smoking behaviour in recreational venues: findings from the International Tobacco Control (ITC) China Survey
Authors: Li X , Li Q , Dong L , Sun B , Chen J , Jiang Y , Yang Y , Zhou B , Fong G T 
Published: August 2009

ObjectiveTo explore the determinants of smoking behaviour in recreational venues and to provide scientific bases for establishing smoke-free measures applying to these locations.MethodsThe International Tobacco Control (ITC) China Survey—a face-to-face cross-sectional survey of representative adult smokers from six cities (Shenyang, Beijing, Shanghai, Guangzhou, Changsha and Yinchuan) was conducted between April and August 2006. A total of 4815 smokers were selected using multistage sampling methods, and final analyses were conducted on 2875 smokers who reported patronising recreational venues at least once in the last six months. Multivariate logistic regression models were used to identify factors influencing the smoking behaviour within recreational settings.Outcome measureWhether a smoker reported smoking in recreational venues during the last 6 months.Results84% subjects reported smoking in recreational venues. Analyses showed that smoke-free laws had been exempted, 32.0% of the patrons reporting bans on smoking in these locations. The following factors were significant predictors of smoking in recreational venues: absence of bans on smoking, support for non-bans, being aged 18–24 years, positive smoking-related attitudes, low number of health effects reported and not living in Beijing.ConclusionsThe findings point to the importance of informing Chinese smokers about the active smoking and passive smoking harmfulness in both building support for smoke-free laws and in reducing smokers’ desire to smoke within recreational venues. They also point to the importance of good enforcement of smoke-free laws when implemented. Such strategies could also serve to de-normalise smoking in China, a key strategy for reducing smoking in general.
The "Equation missing" Solutions of the Series-Like Iterative Equation with Variable Coefficients
Authors: Mi Yuzhen , Li Xiaopei , Ma Ling 
Published: August 2009

AbstractBy constructing a structure operator quite different from that ofZhang and Baker (2000) and using the Schauder fixed point theory, the existence and uniqueness of the "Equation missing" solutions of the series-like iterative equations with variable coefficients are discussed.
Fixed Point Theorems for Random Lowersemi-continuous Mappings
Authors: Fierro Raúl , Martínez Carlos , Morales Claudio H. 
Published: August 2009

AbstractWe prove a general principle in Random Fixed Point Theory by introducing a condition named ("Equation missing") which was inspired by some of Petryshyn's work, and then we apply our result to prove some random fixed points theorems, including generalizations of some Bharucha-Reid theorems.
Novel Mechanism of Lapatinib Resistance in HER2-Positive Breast Tumor Cells: Activation of AXL
Authors: Liu Li , Greger James , Shi Hong , Liu Yuan , Greshock Joel , Annan Roland , Halsey Wendy , Sathe Ganesh M. , Martin Anne-Marie , Gilmer Tona M. 
Published: August 2009

Abstract
HER2-directed therapies, such as trastuzumab and lapatinib, are important treatments for breast cancer. However, some tumors do not respond or develop resistance to these agents. We isolated and characterized multiple lapatinib-resistant, HER2-positive, estrogen receptor (ER)–positive breast cancer clones derived from lapatinib-sensitive BT474 cells by chronic exposure to lapatinib. We show overexpression of AXL as a novel mechanism of acquired resistance to HER2-targeted agents in these models. GSK1363089 (foretinib), a multikinase inhibitor of AXL, MET, and vascular endothelial growth factor receptor currently in phase II clinical trials, restores lapatinib and trastuzumab sensitivity in these resistant cells that exhibit increased AXL expression. Furthermore, small interfering RNA to AXL, estrogen deprivation, or fulvestrant, an ER antagonist, decreases AXL expression and restores sensitivity to lapatinib in these cells. Taken together, these data provide scientific evidence to assess the expression of AXL in HER2-positive, ER-positive patients who have progressed on either lapatinib or trastuzumab and to test the combination of HER2-targeted agents and GSK1363089 in the clinic. [Cancer Res 2009;69(17):6871–8]
Kisspeptin-10, a KISS1-Derived Decapeptide, Inhibits Tumor Angiogenesis by Suppressing Sp1-Mediated VEGF Expression and FAK/Rho GTPase Activation
Authors: Cho Sung-Gook , Yi Zhengfang , Pang Xiufeng , Yi Tingfang , Wang Ying , Luo Jian , Wu Zirong , Li Dali , Liu Mingyao 
Published: August 2009

Abstract
Kisspeptin-10 (Kp-10), a decapeptide derived from the primary translation product of KISS1 gene, has been reported previously to be a key hormone for puberty and an inhibitor for tumor metastasis via the activation of G protein–coupled receptor 54. However, whether Kp-10 inhibits angiogenesis, which is critical for tumor growth and metastasis and other human diseases, is still unknown. Here we show that Kp-10 significantly inhibits human umbilical vein endothelial cell (HUVEC) migration, invasion, and tube formation, key processes in angiogenesis. Using chicken chorioallantoic membrane assay and vascular endothelial growth factor (VEGF)–induced mouse corneal micropocket assay, we show that Kp-10 inhibits angiogenesis in vivo. Furthermore, Kp-10 inhibits tumor growth in severe combined immunodeficient mice xenografted with human prostate cancer cells (PC-3) through inhibiting tumor angiogenesis, whereas Kp-10 has little effect on the proliferation of HUVECs and human prostate cancer cells. In deciphering the underlying molecular mechanisms, we show that Kp-10 suppresses VEGF expression by inhibiting the binding of specificity protein 1 to VEGF promoter and by blocking the activation of c-Src/focal adhesion kinase and Rac/Cdc42 signaling pathways in HUVECs, leading to the inhibition of tumor angiogenesis. [Cancer Res 2009;69(17):7062–70]
Paclitaxel Directly Binds to Bcl-2 and Functionally Mimics Activity of Nur77
Authors: Ferlini Cristiano , Cicchillitti Lucia , Raspaglio Giuseppina , Bartollino Silvia , Cimitan Samanta , Bertucci Carlo , Mozzetti Simona , Gallo Daniela , Persico Marco , Fattorusso Caterina , Campiani Giuseppe , Scambia Giovanni 
Published: August 2009

AbstractWe reported previously that Bcl-2 is paradoxically down-regulated in paclitaxel-resistant cancer cells. We reveal here that paclitaxel directly targets Bcl-2 in the loop domain, thereby facilitating the initiation of apoptosis. Molecular modeling revealed an extraordinary similarity between the paclitaxel binding sites in Bcl-2 and β-tubulin, leading us to speculate that paclitaxel could be mimetic of an endogenous peptide ligand, which binds both proteins. We tested the hypothesis that paclitaxel mimics Nur77, which, like paclitaxel, changes the function of Bcl-2. This premise was confirmed by Nur77 interacting with both paclitaxel targets (Bcl-2 and β-tubulin) and a peptide sequence mimicking the Nur77 structural region, thus reproducing the paclitaxel-like effects of tubulin polymerization and opening the permeability transition pore channel in mitochondria. This discovery could help in the development of novel anticancer agents with nontaxane skeleton as well as in identifying the clinical subsets responsive to paclitaxel-based therapy. [Cancer Res 2009;69(17):6906–14]
Epigenetic Deregulation of DNA Repair and Its Potential for Therapy
Authors: Hegi Monika E. , Sciuscio Davide , Murat Anastasia , Levivier Marc , Stupp Roger 
Published: August 2009

Abstract
Epigenetic silencing of essential components of DNA repair pathways is a common event in many tumor types, and comprise O6-methylguanine-DNA methyltransferase (MGMT), human mut L homolog 1 (hMLH1), Werner syndrome gene (WRN), breast cancer susceptibility gene 1 (BRCA1), and genes of the Fanconi anemia pathway. Most interestingly, some of these alterations become the Achilles heel of the affected tumors upon treatment with certain classes of anticancer agents. That is, patients whose tumors carry such defects can be stratified for respective therapy rendering some classic DNA damaging agents, such as alkylators or DNA crosslinking agents, into “targeted therapies.” Here we review some of the affected repair pathways that, when inactivated, sensitize the tumors to specific drugs and are thus exploitable for individualized therapy. (Clin Cancer Res 2009;15(16):5026–31)
miR-200 Expression Regulates Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Reverses Resistance to Epidermal Growth Factor Receptor Therapy
Authors: Adam Liana , Zhong Meng , Choi Woonyoung , Qi Wei , Nicoloso Milena , Arora Ameeta , Calin George , Wang Hua , Siefker-Radtke Arlene , McConkey David , Bar-Eli Menashe , Dinney Colin 
Published: August 2009

Abstract
Purpose: The epithelial-to-mesenchymal transition (EMT) is a cell development-regulated process in which noncoding RNAs act as crucial modulators. Recent studies have implied that EMT may contribute to resistance to epidermal growth factor receptor (EGFR)–directed therapy. The aims of this study were to determine the potential role of microRNAs (miRNA) in controlling EMT and the role of EMT in inducing the sensitivity of human bladder cancer cells to the inhibitory effects of the anti-EGFR therapy.
Experimental Design: miRNA array screening and real-time reverse transcription-PCR were used to identify and validate the differential expression of miRNAs involved in EMT in nine bladder cancer cell lines. A list of potential miR-200 direct targets was identified through the TargetScan database. The precursor of miR-200b and miR-200c was expressed in UMUC3 and T24 cells using a retrovirus or a lentivirus construct, respectively. Protein expression and signaling pathway modulation, as well as intracellular distribution of EGFR and ERRFI-1, were validated through Western blot analysis and confocal microscopy, whereas ERRFI-1 direct target of miR-200 members was validated by using the wild-type and mutant 3′-untranslated region/ERRFI-1/luciferse reporters.
Results: We identified a tight association between the expression of miRNAs of the miR-200 family, epithelial phenotype, and sensitivity to EGFR inhibitors–induced growth inhibition in bladder carcinoma cell lines. Stable expression of miR-200 in mesenchymal UMUC3 cells increased E-cadherin levels, decreased expression of ZEB1, ZEB2, ERRFI-1, and cell migration, and increased sensitivity to EGFR-blocking agents. The changes in EGFR sensitivity by silencing or forced expression of ERRFI-1 or by miR-200 expression have also been validated in additional cell lines, UMUC5 and T24. Finally, luciferase assays using 3′-untranslated region/ERRFI-1/luciferase and miR-200 cotransfections showed that the direct down-regulation of ERRFI-1 was miR-200-dependent because mutations in the two putative miR-200-binding sites have rescued the inhibitory effect.
Conclusions: Members of the miR-200 family appear to control the EMT process and sensitivity to EGFR therapy in bladder cancer cells and the expression of miR-200 is sufficient to restore EGFR dependency at least in some of the mesenchymal bladder cancer cells. The targets of miR-200 include ERRFI-1, which is a novel regulator of EGFR-independent growth. (Clin Cancer Res 2009;15(16):5060–72)
A Three-Gene Signature for Outcome in Soft Tissue Sarcoma
Authors: Hoffmann Andreas-Claudius , Danenberg Kathleen D. , Taubert Helge , Danenberg Peter V. , Wuerl Peter 
Published: August 2009

AbstractPurpose: Finding markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens in soft tissue sarcomas is necessary. In this study, we investigated the prognostic values of hypoxia-inducible factor 1a (HIF1a), heparin-binding epidermal growth factor–like growth factor (HB-EGF), vascular endothelial growth factor (VEGF), and other angiogenesis-related gene expressions, as well as their interrelationships.Experimental Design: Formalin-fixed paraffin-embedded tissue samples were obtained from 45 patients with soft tissue sarcoma (median age 57 years, range 16–85 years). After laser capture microdissection direct quantitative real-time reverse transcription-PCR (TaqMan) assays were done in triplicates to determine HIF1a, HB-EGF, VEGF, and other gene expression levels.Results: Multivariate Cox regression analysis revealed significant independent associations of HB-EGF, HIF1a, and VEGF-C gene expression to the overall survival (P &lt; 0.0001). A combined factor of these three genes showed a relative risk for shorter survival of 5.5, more than twice higher as in an increasing International Union against Cancer Stage. Receiver operating characteristic curve analysis showed a significant sensitivity of 73% and specificity of 82% of this factor for the diagnosis of short (&lt;3 years) versus long (3-9 years) survival (P = 0.0002). VEGF-A showed significant gender differences in the association to survival.Conclusions: Measuring HIF1a, HB-EGF, and VEGF-C expression may contribute to a better understanding of the prognosis of patients with soft tissue sarcoma and may even play a crucial role for the distribution of patients to multimodal therapeutic regimens. Prospective studies investigating the response to different adjuvant or palliative therapies seem to be warranted. (Clin Cancer Res 2009;15(16):5191–8)