bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIK3CA-mediated PI3-kinase signalling is essential for HPV-induced transformation in vitro
Authors: Henken Florianne E , Banerjee N Sanjib , Snijders Peter JF , Meijer Chris JLM , De-Castro Arce Johanna , Rösl Frank , Broker Thomas R , Chow Louise T , Steenbergen Renske DM 
Published: June 2011

Abstract

Background
High-risk human papillomavirus (hrHPV) infections are causally related to cervical cancer development. The additional (epi)genetic alterations driving malignant transformation of hrHPV-infected cells however, are not yet fully elucidated. In this study we experimentally assessed the role of the PI3-kinase pathway and its regulator PIK3CA, which is frequently altered in cervical cancer, in HPV-induced transformation.

Methods
Cervical carcinomas and ectocervical controls were assessed for PIK3CA mRNA and protein expression by quantitative RT-PCR and immunohistochemical staining, respectively. A longitudinal in vitro model system of hrHPV-transfected keratinocytes, representing the immortal and anchorage independent phenotype, was assayed for PI3-kinase activation and function using chemical pathway inhibition i.e. LY294002 treatment, and PIK3CA RNA interference. Phenotypes examined included cellular viability, migration, anchorage independent growth and differentiation. mRNA expression of hTERT and HPV16 E6E7 were studied using quantitative RT-PCR and Northern blotting.

Results
Cervical carcinomas showed significant overexpression of PIK3CA compared to controls. During HPV-induced transformation in vitro, expression of the catalytic subunit PIK3CA as well as activation of downstream effector PKB/AKT progressively increased in parallel. Inhibition of PI3-kinase signalling in HPV16-transfected keratinocytes by chemical interference or siRNA-mediated silencing of PIK3CA resulted in a decreased phosphorylation of PKB/AKT. Moreover, blockage of PI3-kinase resulted in reduced cellular viability, migration, and anchorage independent growth. These properties were accompanied with a downregulation of HPV16E7 and hTERT mRNA expression. In organotypic raft cultures of HPV16- and HPV18-immortalized cells, phosphorylated PKB/AKT was primarily seen in differentiated cells staining positive for cytokeratin 10 (CK10). Upon PI3-kinase signalling inhibition, there was a severe impairment in epithelial tissue development as well as a dramatic reduction in p-PKB/AKT and CK10.

Conclusion
The present data indicate that activation of the PI3-kinase/PKB/AKT pathway through PIK3CA regulates various transformed phenotypes as well as growth and differentiation of HPV-immortalized cells and may therefore play a pivotal role in HPV-induced carcinogenesis.
The function of 7D-cadherins: a mathematical model predicts physiological importance for water transport through simple epithelia
Authors: Ahl Mareike , Weth Agnes , Walcher Sebastian , Baumgartner Werner 
Published: June 2011

Abstract

Background
7D-cadherins like LI-cadherin are cell adhesion molecules and represent exceptional members of the cadherin superfamily. Although LI-cadherin was shown to act as a functional Ca2+-dependent adhesion molecule, linking neighboring cells together, and to be dysregulated in a variety of diseases, the physiological role is still enigmatic. Interestingly 7D-cadherins occur only in the lateral plasma membranes of cells from epithelia of water transporting tissues like the gut, the liver or the kidney. Furthermore LI-cadherin was shown to exhibit a highly cooperative Ca2+-dependency of the binding activity. Thus it is tempting to assume that LI-cadherin regulates the water transport through the epithelium in a passive fashion by changing its binding activity in dependence on the extracellular Ca2+.

Results
We developed a simple mathematical model describing the epithelial lining of a lumen with a content of variable osmolarity covering an interstitium of constant osmolarity. The width of the lateral intercellular cleft was found to influence the water transport significantly. In the case of hypertonic luminal content a narrow cleft is necessary to further increase concentration of the luminal content. If the cleft is too wide, the water flux will change direction and water is transported into the lumen. Electron microscopic images show that in fact areas of the gut can be found where the lateral intercellular cleft is narrow throughout the lateral cell border whereas in other areas the lateral intercellular cleft is widened.

Conclusions
Our simple model clearly predicts that changes of the width of the lateral intercellular cleft can regulate the direction and efficiency of water transport through a simple epithelium. In a narrow cleft the cells can increase the concentration of osmotic active substances easily by active transport whereas if the cleft is wide, friction is reduced but the cells can hardly build up high osmotic gradients. It is now tempting to speculate that 7D-cadherins, owing to their location and their Ca2+-dependence, will adapt their binding activity and thereby the width of the lateral intercellular cleft automatically as the Ca2+-concentration is coupled to the overall electrolyte concentration in the lateral intercellular cleft. This could provide a way to regulate the water resorption in a passive manner adapting to different osmotic conditions.
Evaluation of wet-cupping therapy for persistent non-specific low back pain: a randomised, waiting-list controlled, open-label, parallel-group pilot trial
Authors: Kim Jong-In , Kim Tae-Hun , Lee Myeong Soo , Kang Jung Won , Kim Kun Hyung , Choi Jun-Yong , Kang Kyung-Won , Kim Ae-Ran , Shin Mi-Suk , Jung So-Young , Choi Sun-mi 
Published: June 2011

Abstract

Background
Persistent non-specific low back pain (PNSLBP) is one of the most frequently experienced types of back pain around the world. Wet-cupping is a common intervention for various pain conditions, especially in Korea. In this context, we conducted a pilot study to determine the effectiveness and safety of wet-cupping treatment for PNSLBP.

Methods
We recruited 32 participants (21 in the wet-cupping group and 11 in the waiting-list group) who had been having PNSLBP for at least 3 months. The participants were recruited at the clinical research centre of the Korea Institute of Oriental Medicine, Korea. Eligible participants were randomly allocated to wet-cupping and waiting-list groups. Following the practice of traditional Korean medicine, the treatment group was provided with wet-cupping treatment at two acupuncture points among the BL23, BL24 and BL25 6 times within 2 weeks. Usual care, including providing brochures for exercise, general advice for PNSLBP and acetaminophen, was allowed in both groups. Separate assessors participated in the outcome assessment. We used the 0 to100 numerical rating scale (NRS) for pain, the McGill Pain Questionnaire for pain intensity (PPI) and the Oswestry Disability Questionnaire (ODQ), and we assessed acetaminophen use and safety issues.

Results
The results showed that the NRS score for pain decreased (-16.0 [95% CI: -24.4 to -7.7] in the wet-cupping group and -9.1 [-18.1 to -0.1] in the waiting-list group), but there was no statistical difference between the groups (p = 0.52). However, the PPI scores showed significant differences between the two groups (-1.2 [-1.6 to -0.8] for the wet-cupping group and -0.2 [-0.8 to 0.4] for the waiting-list group, p < 0.01). In addition, less acetaminophen was used in the wet-cupping group during 4 weeks (p = 0.09). The ODQ score did not show significant differences between the two groups (-5.60 [-8.90 to -2.30] in the wet-cupping group and -1.8 [-5.8 to 2.2] in the waiting-list group, p = 0.14). There was no report of adverse events due to wet-cupping.

Conclusion
This pilot study may provide preliminary data on the effectiveness and safety of wet-cupping treatments for PNSLBP. Future full-scale randomised controlled trials will be needed to provide firm evidence of the effectiveness of this intervention.

Trial Registration
ClinicalTrials.gov: (Identifier: NCT00925951)
Date of trial registration: June 19th, 2009
The date when the first patient was randomised: July 15th, 2009
The date when the study was completed: November 27th, 2009
Screening for tuberculosis and prediction of disease in Portuguese healthcare workers
Authors: Torres Costa José , Silva Rui , Ringshausen Felix C , Nienhaus Albert 
Published: June 2011

Abstract

Introduction
Results of systematic screening of healthcare workers (HCWs) for tuberculosis (TB) with the tuberculin skin test (TST) and interferon-γ release assays (IGRA) in a Portuguese hospital from 2007 to 2010 are reported.

Methods
All HCWs are offered screening for TB. Screening is repeated depending on risk assessment. TST and QuantiFERON Gold In-Tube (QFT) are used simultaneously. X-ray is performed when TST is > 10 mm, IGRA is positive or typical symptoms exist.

Results
The cohort comprises 2,889 HCWs. TST and IGRA were positive in 29.5%, TST-positive but IGRA-negative results were apparent in 43.4%. Active TB was diagnosed in twelve HCWs - eight cases were detected during screening and four cases were predicted by IGRA as well as by TST. However, the progression rate in IGRA-positive was higher than in TST-positive HCWs (0.4% vs. 0.2%, p-value 0.06).

Conclusions
The TB burden in this cohort was high (129.8 per 100,000 HCWs). However, the progression to active TB after a positive TST or positive IGRA was considerably lower than that reported in literature for close contacts in low-incidence countries. This may indicate that old LTBI prevails in these HCWs.
A rapid, simple method for the genetic discrimination of intact Arabidopsis thaliana mutant seeds using metabolic profiling by direct analysis in real-time mass spectrometry
Authors: Kim Suk Weon , Kim Hye Jin , Kim Jong Hyun , Kwon Yong Kook , Ahn Myung Suk , Jang Young Pyo , Liu Jang R 
Published: June 2011

Abstract

Background
Efficient high throughput screening systems of useful mutants are prerequisite for study of plant functional genomics and lots of application fields. Advance in such screening tools, thanks to the development of analytic instruments. Direct analysis in real-time (DART)-mass spectrometry (MS) by ionization of complex materials at atmospheric pressure is a rapid, simple, high-resolution analytical technique. Here we describe a rapid, simple method for the genetic discrimination of intact Arabidopsis thaliana mutant seeds using metabolic profiling by DART-MS.

Results
To determine whether this DART-MS combined by multivariate analysis can perform genetic discrimination based on global metabolic profiling, intact Arabidopsis thaliana mutant seeds were subjected to DART-MS without any sample preparation. Partial least squares-discriminant analysis (PLS-DA) of DART-MS spectral data from intact seeds classified 14 different lines of seeds into two distinct groups: Columbia (Col-0) and Landsberg erecta (Ler) ecotype backgrounds. A hierarchical dendrogram based on partial least squares-discriminant analysis (PLS-DA) subdivided the Col-0 ecotype into two groups: mutant lines harboring defects in the phenylpropanoid biosynthetic pathway and mutants without these defects. These results indicated that metabolic profiling with DART-MS could discriminate intact Arabidopsis seeds at least ecotype level and metabolic pathway level within same ecotype.

Conclusion
The described DART-MS combined by multivariate analysis allows for rapid screening and metabolic characterization of lots of Arabidopsis mutant seeds without complex metabolic preparation steps. Moreover, potential novel metabolic markers can be detected and used to clarify the genetic relationship between Arabidopsis cultivars. Furthermore this technique can be applied to predict the novel gene function of metabolic mutants regardless of morphological phenotypes.
Detecting differential allelic expression using high-resolution melting curve analysis: application to the breast cancer susceptibility gene CHEK2
Authors: Nguyen-Dumont Tú , Jordheim Lars P , Michelon Jocelyne , Forey Nathalie , McKay-Chopin Sandrine ,   Kathleen Cuningham Foundation Consortium for Research into Familial Aspects of Breast Cancer (kConFab), Sinilnikova Olga , Le Calvez-Kelm Florence , Southey Melissa C , Tavtigian Sean V , Lesueur Fabienne 
Published: June 2011

AbstractBackgroundThe geneCHEK2encodes a checkpoint kinase playing a key role in the DNA damage pathway. ThoughCHEK2has been identified as an intermediate breast cancer susceptibility gene, only a small proportion of high-risk families have been explained by genetic variants located in its coding region. Alteration in gene expression regulation provides a potential mechanism for generating disease susceptibility. The detection of differential allelic expression (DAE) represents a sensitive assay to direct the search for a functional sequence variant within the transcriptional regulatory elements of a candidate gene. We aimed to assess whetherCHEK2was subject to DAE in lymphoblastoid cell lines (LCLs) from high-risk breast cancer patients for whom no mutation inBRCA1orBRCA2had been identified.MethodsWe implemented an assay based on high-resolution melting (HRM) curve analysis and developed an analysis tool for DAE assessment.ResultsWe observed allelic expression imbalance in 4 of the 41 LCLs examined. All four were carriers of the truncating mutation 1100delC. We confirmed previous findings that this mutation induces non-sense mediated mRNA decay. In our series, we ruled out the possibility of a functional sequence variant located in the promoter region or in a regulatory element ofCHEK2that would lead to DAE in the transcriptional regulatory milieu of freely proliferating LCLs.ConclusionsOur results support that HRM is a sensitive and accurate method for DAE assessment. This approach would be of great interest for high-throughput mutation screening projects aiming to identify genes carrying functional regulatory polymorphisms.
Genetic characterization, species differentiation and detection of Fasciola spp. by molecular approaches
Authors: Ai Lin , Chen Mu-Xin , Alasaad Samer , Elsheikha Hany M , Li Juan , Li Hai-Long , Lin Rui-Qing , Zou Feng-Cai , Zhu Xing-Quan , Chen Jia-Xu 
Published: June 2011

AbstractLiver flukes belonging to the genusFasciolaare among the causes of foodborne diseases of parasitic etiology. These parasites cause significant public health problems and substantial economic losses to the livestock industry. Therefore, it is important to definitively characterize theFasciolaspecies. Current phenotypic techniques fail to reflect the full extent of the diversity ofFasciolaspp. In this respect, the use of molecular techniques to identify and differentiateFasciolaspp. offer considerable advantages. The advent of a variety of molecular genetic techniques also provides a powerful method to elucidate many aspects ofFasciolabiology, epidemiology, and genetics. However, the discriminatory power of these molecular methods varies, as does the speed and ease of performance and cost. There is a need for the development of new methods to identify the mechanisms underpinning the origin and maintenance of genetic variation within and amongFasciolapopulations. The increasing application of the current and new methods will yield a much improved understanding ofFasciolaepidemiology and evolution as well as more effective means of parasite control. Herein, we provide an overview of the molecular techniques that are being used for the genetic characterization, detection and genotyping ofFasciolaspp..
Production of polyhydroxyalkanoates from waste frying oil by Cupriavidus necator
Authors: Verlinden Rob AJ , Hill David J , Kenward Melvin A , Williams Craig D , Piotrowska-Seget Zofia , Radecka Iza K 
Published: June 2011

Abstract
Polyhydroxyalkanoates (PHAs) are biopolymers, which can replace petrochemical plastics in many applications. However, these bioplastics are currently far more expensive than petrochemical plastics. Many researchers are investigating the use of inexpensive substrates derived from waste streams. Waste frying oil is abundant and can be used in PHA production without filtration.

Cupriavidus
necator (formerly known as Ralstonia eutropha) is a versatile organism for the production of PHAs. Small-scale batch fermentation studies have been set up, using different concentrations of pure vegetable oil, heated vegetable oil and waste frying oil. These oils are all rapeseed oils.
It has been shown that Cupriavidus necator produced the homopolymer polyhydroxybutyrate (PHB) from the rapeseed oils. The achieved PHB concentration from waste frying oil was 1.2 g/l, which is similar to a concentration that can be obtained from glucose. The PHB harvest from pure oil and heated oil was 0.62 g/l and 0.9 g/l respectively. A feed of waste frying oil could thus achieve more biopolymer than pure vegetable oil. While the use of a waste product is beneficial from a life-cycle perspective, PHB is not the only product that can be made from waste oil. The collection of waste frying oil is becoming more widespread, making waste oil a good alternative to purified oil or glucose for PHB production.
High-sensitivity versus conventional troponin in the emergency department for the diagnosis of acute myocardial infarction
Authors: Freund Yonathan , Chenevier-Gobeaux Camille , Bonnet Pascale , Claessens Yann-Erick , Allo Jean-Christophe , Doumenc Benoit , Leumani François , Cosson Claudine , Riou Bruno , Ray Patrick 
Published: June 2011

Abstract
Introduction
Recently, newer assays for cardiac troponin (cTn) have been developed which are able to detect changes in concentration of the biomarker at or below the 99th percentile for a normal population. The objective of this study was to compare the diagnostic performance of a new high-sensitivity troponin T (HsTnT) assay to that of conventional cTnI for the diagnosis of acute myocardial infarction (AMI) according to pretest probability (PTP).

Methods
In consecutive patients who presented to our emergency departments with chest pain suggestive of AMI, levels of HsTnT were measured at presentation, blinded to the emergency physicians, who were asked to estimate the empirical PTP of AMI. The discharge diagnosis was adjudicated by two independent experts on the basis of all available data.

Results
A total of 317 patients were included, comprising 149 (47%) who were considered to have low PTP, 109 (34%) who were considered to have moderate PTP and 59 (19%) who were considered to have high PTP. AMI was confirmed in 45 patients (14%), 22 (9%) of whom were considered to have low to moderate PTP and 23 (39%) of whom were considered to have high PTP (P < 0.001). In the low to moderate PTP group, HsTnT levels ≥ 0.014 μg/L identified AMI with a higher sensitivity than cTnI (91%, 95% confidence interval (95% CI) 79 to 100, vs. 77% (95% CI 60 to 95); P = 0.001), but the negative predictive value was not different (99% (95% CI 98 to 100) vs. 98% (95% CI 96 to 100)). There was no difference in area under the receiver operating characteristic (ROC) curve between HsTnT and cTnI (0.93 (95% CI 0.90 to 0.98) vs. 0.94 (95% CI 0.88 to 0.97), respectively).

Conclusions
In patients with low to moderate PTP of AMI, HsTnT is slightly more useful than cTnI. Our results confirm that the use of HsTnT has a higher sensitivity than conventional cTnI.
A Retrospective Comparison of Varenicline Monotherapy Versus the Combination of Varenicline and Bupropion or Bupropion and Nicotine Patches in a VA Tobacco Cessation Clinic
Authors: Shiltz Dane , Paniagua Angie , Hastings James E. 
Published: June 2011

AbstractPurpose:To determine whether the combination of bupropion SR and varenicline offers improved smoking cessation outcomes compared to varenicline monotherapy or to combination of bupro-pion SR and nicotine patch.Methods:This retrospective chart review included 489 volunteer enrolees in a Veterans Affairs (VA) tobacco cessation clinic who received one of the three treatments upon clinic enrolment. The study endpoints were smoking cessation and clinic completion rates, changes in the number of cigarettes smoked, carbon monoxide (CO) levels, urges to smoke, self-confidence to quit and medication-attributed adverse effects.Results:The relative smoking cessation rates were 33%, 32%, and 40% for bupropion SR and nicotine patch, bupropion SR and varenicline, and varenicline groups, respectively. The 0.21 p value established that no significant cessation rate differences existed between any of the groups. Varenicline alone or in combination was as well tolerated as the combination of bupropion SR and nicotine patch.Conclusions:The combination of bupropion SR and varenicline did not demonstrate any smoking cessation advantage over varenicline monotherapy or the combination of bupropion SR and nicotine patch and therefore do not support the use of bupro-pion SR and varenicline over varenicline monotherapy.
The Association Between Household Smoking Restrictions and Smoking Abstinence: Does Age Matter?
Authors: Edjoc Rojiemiahd 
Published: June 2011

AbstractAim: The purpose of this study is to explore how effective household smoking restrictions (HSRs) are in different age groups in predicting smoking abstinence. Methods: The study analysed the Canadian Community Health Survey (CCHS) cycle, 3.1. Smoking abstinence was defined as individuals who reported to not have smoked greater than 100 cigarettes (n = 1 024 578) and were selected for this analysis. Important covariates include sex, age, education and immigrant status. Logistic regression was used to assess the association between smoking household restrictions and smoking abstinence when taking covariates into consideration. Results: Individuals who implemented HSRs reported to be abstinent from smoking at 12% compared to those with no HSRs at 0.7%. When adjusted for covariates of interest, the odds ratio (OR) for smoking abstinence was 1.43 (95% confidence interval (CI): 1.04, 1.97; P < .026). It was found that age was a strong predictor of smoking abstinence particularly in youths at 3.11 (95% CI: 1.65, 5.84; P < .001) and young adults at 1.92 (95% CI: 1.44, 1.92; P < .001). Conclusion: It is suggested that HSRs is an important anti-tobacco socialisation tool in youths and young adults. Individuals living in a home with HSRs may internalise behavioural norms against the initiation or continuation of smoking.
Gender Differences in Smoking Behaviour and Cessation
Authors: Torchalla Iris , Okoli Chizimuzo T.C. , Hemsing Natalie , Greaves Lorraine 
Published: June 2011

AbstractThis article reviews the literature to compare differential outcomes among men and women after smoking cessation, assess barriers they may face during cessation and provide recommendation to address gender-specific challenges in smoking cessation interventions. There is some evidence that women achieve lower abstinence rates than men after a quit attempt with nicotine replacement therapy, as well as without pharmacotherapy, and several underlying mechanisms were discussed to account for these findings. These include: (a) women have specific genetic variants that affect pharmacokinetics and pharmacodynamics of the medication, (b) hormonal influences increase nicotine metabolism and withdrawal symptoms, (c) women are more responsive to nonpharmacological aspects of smoking than men, (d) women are more vulnerable to depression and negative mood than men, (e) weight concerns are greater barriers for women than for men and (g) women receive less effective social support than men during a quit attempt. Gender-specific counselling that accounts for these factors and addresses the different needs of men and women may be a promising approach to improve long-term abstinence rates. However, more research is required to identify gender-related underlying mechanisms of differential smoking cessation outcomes, develop tailored interventions that account for gender differences and study the implementation and outcomes of gender-responsive treatment approaches.