bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of nicotine replacement therapy for temporary abstinence in the home to protect children from environmental tobacco smoke exposure: a qualitative study with disadvantaged smokers
Authors: Atkinson Olesya , Coleman Tim , McNeill Ann , Lewis Sarah , Jones Laura L 
Published: March 2013

Abstract

Background
Nicotine replacement therapy (NRT) has recently been licensed to help smokers to abstain from smoking for short time periods and recent studies have shown that 8-14% of smokers are regularly using NRT to cope when they cannot or are not allowed to smoke. These data suggest that, potentially, NRT for temporary abstinence might be an acceptable method to help smoking caregivers, who are not able to stop smoking completely, to avoid smoking whilst inside their home in order to protect their children from the harms of environmental tobacco smoke (ETS). The aim of this study was therefore to explore the concept of using NRT for temporary abstinence in the home, to protect children from exposure to ETS.

Methods
Qualitative in-depth interviews were conducted with thirty six disadvantaged smoking parents who were currently, or had recently stopped smoking in the home with at least one child under the age of five. Parents were recruited from Children’s Centres and Health Visitor Clinics in Nottingham, UK. Interviews were audio recorded and transcribed verbatim. Data were coded and analysed thematically to identify emergent main and subthemes.

Results
Overall, participants responded negatively to the concept of attempting temporary abstinence in the home in general and more specifically to the use of NRT whilst at home to reduce children’s exposure to ETS. Many parents would prefer to either attempt cutting down or quitting completely to make a substantial effort to change their smoking behaviour. There was limited interest in the use of NRT for temporary abstinence in the home as a first step to quitting, although some parents did express a willingness to use NRT to cut down as a first step to quitting.

Conclusion
Disadvantaged smoking parents were reluctant to initiate and maintain temporary abstinence with or without NRT as a way of making their homes smoke free to protect their children’s health. More education about the specific risks of ETS to their children and the utility of NRT for use in the home might be needed to have a public health impact on children’s health.
Gaps in detailed knowledge of human papillomavirus (HPV) and the HPV vaccine among medical students in Scotland
Authors: McCusker Sarah M , Macqueen Ishbel , Lough Graham , MacDonald Alasdair I , Campbell Christine , Graham Sheila V 
Published: March 2013

Abstract

Background
A vaccination programme targeted against human papillomavirus (HPV) types16 and 18 was introduced in the UK in 2008, with the aim of decreasing incidence of cervical disease. Vaccine roll out to 12–13 year old girls with a catch-up programme for girls aged up to 17 years and 364 days was accompanied by a very comprehensive public health information (PHI) campaign which described the role of HPV in the development of cervical cancer.

Methods
A brief questionnaire, designed to assess acquisition of knowledge of HPV infection and its association to cervical cancer, was administered to two different cohorts of male and female 1st year medical students (school leavers: 83% in age range 17–20) at a UK university. The study was timed so that the first survey in 2008 immediately followed a summer's intensive PHI campaign and very shortly after vaccine roll-out (150 students). The second survey was exactly one year later over which time there was a sustained PHI campaign (213 students).

Results
We addressed three research questions: knowledge about three specific details of HPV infection that could be acquired from PHI, whether length of the PHI campaign and/or vaccination of females had any bearing on HPV knowledge, and knowledge differences between men and women regarding HPV. No female student in the 2008 cohort had completed the three-dose vaccine schedule compared to 58.4% of female students in 2009. Overall, participants’ knowledge regarding the sexually transmitted nature of HPV and its association with cervical cancer was high in both year groups. However, in both years, less than 50% of students correctly identified that HPV causes over 90% of cases of cervical cancer. Males gave fewer correct answers for these two details in 2009. In 2008 only around 50% of students recognised that the current vaccine protects against a limited subset of cervical cancer-causing HPV sub-types, although there was a significant increase in correct response among female students in the 2009 cohort compared to the 2008 cohort.

Conclusions
This study highlights a lack of understanding regarding the extent of protection against cervical cancer conferred by the HPV vaccine, even among an educated population in the UK who could have a vested interest in acquiring such knowledge. The intensive PHI campaign accompanying the first year of HPV vaccination seemed to have little effect on knowledge over time. This is one of the first studies to assess detailed knowledge of HPV in both males and females. There is scope for continued improvements to PHI regarding the link between HPV infection and cervical cancer.
Treatment for sleep apnea by continuous positive airway pressure improves levels of inflammatory markers - a meta-analysis
Authors: Baessler Aaron , Nadeem Rashid , Harvey Michael , Madbouly Essam , Younus Amna , Sajid Hassan , Naseem Jawed , Asif Asma , Bawaadam Hasnain 
Published: March 2013

Abstract

Background
Obstructive sleep apnea (OSA) is associated with coronary artery disease (CAD). Intermittent hypoxia associated with OSA increases sympathetic activity and may cause systemic inflammation, which may contribute to CAD in patients with OSA. Treatment with continuous positive airway pressure (CPAP) has been shown to change levels of inflammatory markers. We analyzed data from published studies by a systematic meta-analysis.

Objective
To asses if treatment for sleep apnea by CPAP will affect levels of inflammatory markers.

Data resources
PubMed, Embase and Cochrane library.

Methods
Study eligibility criteria full text English studies of adult, human subjects, addressing values of at least one of the inflammatory markers before and after CPAP treatment. We used the definition of OSA as an apnea-hypopnea index (AHI) of ≥ 5/h, reported values in mean and standard deviation or median with range.

Participants
Adult, human.

Interventions
CPAP treatment for OSA.

Study appraisal and synthesis method
A total of 3835 studies were reviewed for inclusion, while 23 studies pooled for analysis. A total of 14 studies with 771 patients were pooled for C-reactive protein (CRP); 9 studies with 209 patients were pooled for tumor necrosis factor-alpha (TNF-α); and 8 studies with 165 patients were pooled for interleukin-6 (IL-6).

Endpoint definitions
The following inflammatory markers were chosen: CRP, TNF-α, and IL-6.

Results
C-reactive protein: Study level means ranged from 0.18 to 0.85 mg/dl before CPAP treatment and 0.10 to 0.72 mg/dl after CPAP treatment. Mean differences, at a study level, ranged from −0.05 to 0.50. The pooled mean difference was 0.14 [95% confidence interval 0.08 to 0.20, p < 0.00001]. There was heterogeneity in this endpoint (df = 13, p < 0.00001, I2 = 95%).
Tumor necrosis factor-α: Study level means ranged from 1.40 to 50.24 pg/ml before CPAP treatment and 1.80 to 28.63 pg/ml after CPAP treatment. Mean differences, at a study level, ranged from −1.23 to 21.61. The pooled mean difference was 1.14 [95% confidence interval 0.12 to 2.15, p = 0.03]. There was heterogeneity in this endpoint (df = 8, p < 0.00001, I2 = 89%).
Interleukin-6: Study level means ranged from 1.2 to 131.66 pg/ml before CPAP treatment and 0.45 to 66.04 pg/ml after CPAP treatment. Mean differences, at a study level, ranged from −0.40 to 65.62. The pooled mean difference was 1.01 [95% confidence interval −0.00 to 2.03, p = 0.05]. There was heterogeneity in this endpoint (df = 7, p < 0.00001, I2 = 95%).

Limitations
Only published data. Studies pooled were mainly small, non-randomized trials.

Conclusion
Sleep apnea treatment with CPAP improves levels of inflammatory markers.
Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism
Authors: Valles Soraya L , Benlloch María , Rodriguez María L , Mena Salvador , Pellicer José A , Asensi Miguel , Obrador Elena , Estrela José M 
Published: March 2013

Abstract

Background
Interleukin (IL)-6 (mainly of tumor origin) activates glutathione (GSH) release from hepatocytes and its interorgan transport to B16-F10 melanoma metastatic foci. We studied if this capacity to overproduce IL-6 is regulated by cancer cell-independent mechanisms.

Methods
Murine B16-F10 melanoma cells were cultured, transfected with red fluorescent protein, injected i.v. into syngenic C57BL/6J mice to generate lung and liver metastases, and isolated from metastatic foci using high-performance cell sorting. Stress hormones and IL-6 levels were measured by ELISA, and CRH expression in the brain by in situ hybridization. DNA binding activity of NF-κB, CREB, AP-1, and NF-IL-6 was measured using specific transcription factor assay kits. IL-6 expression was measured by RT-PCR, and silencing was achieved by transfection of anti-IL-6 small interfering RNA. GSH was determined by HPLC. Cell death analysis was distinguished using fluorescence microscopy, TUNEL labeling, and flow cytometry techniques. Statistical analyses were performed using Student’s t test.

Results
Plasma levels of stress-related hormones (adrenocorticotropin hormone, corticosterone, and noradrenaline) increased, following a circadian pattern and as compared to non-tumor controls, in mice bearing B16-F10 lung or liver metastases. Corticosterone and noradrenaline, at pathophysiological levels, increased expression and secretion of IL-6 in B16-F10 cells in vitro. Corticosterone- and noradrenaline-induced transcriptional up-regulation of IL-6 gene involves changes in the DNA binding activity of nuclear factor-κB, cAMP response element-binding protein, activator protein-1, and nuclear factor for IL-6. In vivo inoculation of B16-F10 cells transfected with anti-IL-6-siRNA, treatment with a glucocorticoid receptor blocker (RU-486) or with a β-adrenoceptor blocker (propranolol), increased hepatic GSH whereas decreased plasma IL-6 levels and metastatic growth. Corticosterone, but not NORA, also induced apoptotic cell death in metastatic cells with low GSH content.

Conclusions
Our results describe an interorgan system where stress-related hormones, IL-6, and GSH coordinately regulate metastases growth.
A three-gene signature as potential predictive biomarker for irinotecan sensitivity in gastric cancer
Authors: Shen Jie , Wei Jia , Wang Hao , Yue Guofeng , Yu Lixia , Yang Yang , Xie Li , Zou Zhengyun , Qian Xiaoping , Ding Yitao , Guan Wenxian , Liu Baorui 
Published: March 2013

Abstract

Objective
Personalized chemotherapy based on molecular biomarkers can maximize anticancer efficiency. We aim to investigate predictive biomarkers capable of predicting response to irinotecan-based treatment in gastric cancer.

Methods
We examined gene expression of APTX, BRCA1, ERCC1, ISG15, Topo1 and methylation of SULF2 in formalin-fixed paraffin-embedded gastric cancer tissues from 175 patients and evaluated the association between gene expression levels or methylation status and in vitro sensitivity to irinotecan. We used multiple linear regression analysis to develop a gene-expression model to predict irinotecan sensitivity in gastric cancer and validated this model in vitro and vivo.

Results
Gene expression levels of APTX, BRCA1 and ERCC1 were significantly lower in irinotecan-sensitive gastric cancer samples than those irinotecan-resistant samples (P < 0.001 for all genes), while ISG15 (P = 0.047) and Topo1 (P = 0.002) were significantly higher. Based on those genes, a three-gene signature were established, which was calculated as follows: Index =0.488 - 0.020× expression level of APTX + 0.015× expression level of Topo1 - 0.011 × expression level of BRCA1. The three-gene signature was significantly associated with irinotecan sensitivity (rho = 0.71, P < 0.001). The sensitivity and specificity for the prediction of irinotecan sensitivity based on the three-gene signature reached 73% and 86%, respectively. In another independent testing set, the irinotecan inhibition rates in gastric samples with sensitive-signature were much higher than those with resistant-signature (65% vs. 22%, P < 0.001). Irinotecan therapy with 20 mg/kg per week to immunodeficient mice carrying xenografts with sensitive-signature dramatically arrested the growth of tumors (P < 0.001), but had no effect on mice carrying xenografts with resistant-signature.

Conclusions
The three-gene signature established herein is a potential predictive biomarker for irinotecan sensitivity in gastric cancer.
In silico approaches for designing highly effective cell penetrating peptides
Authors: Gautam Ankur , Chaudhary Kumardeep , Kumar Rahul , Sharma Arun , Kapoor Pallavi , Tyagi Atul ,   Open source drug discovery consortium, Raghava Gajendra P S 
Published: March 2013

Abstract

Background
Cell penetrating peptides have gained much recognition as a versatile transport vehicle for the intracellular delivery of wide range of cargoes (i.e. oligonucelotides, small molecules, proteins, etc.), that otherwise lack bioavailability, thus offering great potential as future therapeutics. Keeping in mind the therapeutic importance of these peptides, we have developed in silico methods for the prediction of cell penetrating peptides, which can be used for rapid screening of such peptides prior to their synthesis.

Methods
In the present study, support vector machine (SVM)-based models have been developed for predicting and designing highly effective cell penetrating peptides. Various features like amino acid composition, dipeptide composition, binary profile of patterns, and physicochemical properties have been used as input features. The main dataset used in this study consists of 708 peptides. In addition, we have identified various motifs in cell penetrating peptides, and used these motifs for developing a hybrid prediction model. Performance of our method was evaluated on an independent dataset and also compared with that of the existing methods.

Results
In cell penetrating peptides, certain residues (e.g. Arg, Lys, Pro, Trp, Leu, and Ala) are preferred at specific locations. Thus, it was possible to discriminate cell-penetrating peptides from non-cell penetrating peptides based on amino acid composition. All models were evaluated using five-fold cross-validation technique. We have achieved a maximum accuracy of 97.40% using the hybrid model that combines motif information and binary profile of the peptides. On independent dataset, we achieved maximum accuracy of 81.31% with MCC of 0.63.

Conclusion
The present study demonstrates that features like amino acid composition, binary profile of patterns and motifs, can be used to train an SVM classifier that can predict cell penetrating peptides with higher accuracy. The hybrid model described in this study achieved more accuracy than the previous methods and thus may complement the existing methods. Based on the above study, a user- friendly web server CellPPD has been developed to help the biologists, where a user can predict and design CPPs with much ease. CellPPD web server is freely accessible at http://crdd.osdd.net/raghava/cellppd/.
Strong plasmon-exciton coupling in a hybrid system of gold nanostars and J-aggregates
Authors: Melnikau Dzmitry , Savateeva Diana , Susha Andrey , Rogach Andrey L , Rakovich Yury P 
Published: March 2013

Abstract
Hybrid materials formed by plasmonic nanostructures and J-aggregates provide a unique combination of highly localized and enhanced electromagnetic field in metal constituent with large oscillator strength and extremely narrow exciton band of the organic component. The coherent coupling of localized plasmons of the multispiked gold nanoparticles (nanostars) and excitons of JC1 dye J-aggregates results in a Rabi splitting reaching 260 meV. Importantly, broad absorption features of nanostars extending over a visible and near-infrared spectral range allowed us to demonstrate double Rabi splitting resulting from the simultaneous coherent coupling between plasmons of the nanostars and excitons of J-aggregates of two different cyanine dyes.
Genetic characterization of a Coxsackie A9 virus associated with aseptic meningitis in Alberta, Canada in 2010
Authors: Pabbaraju Kanti , Wong Sallene , Chan Eve N Y , Tellier Raymond 
Published: March 2013

AbstractBackgroundAn unusually high incidence of aseptic meningitis caused by enteroviruses was noted in Alberta, Canada between March and October 2010. Sequence based typing was performed on the enterovirus positive samples to gain a better understanding of the molecular characteristics of the Coxsackie A9 (CVA-9) strain responsible for most cases in this outbreak.MethodsMolecular typing was performed by amplification and sequencing of the VP2 region. The genomic sequence of one of the 2010 outbreak isolates was compared to a CVA-9 isolate from 2003 and the prototype sequence to study genetic drift and recombination.ResultsOf the 4323 samples tested, 213 were positive for enteroviruses (4.93%). The majority of the positives were detected in CSF samples (n = 157, 73.71%) and 81.94% of the sequenced isolates were typed as CVA-9. The sequenced CVA-9 positives were predominantly (94.16%) detected in patients ranging in age from 15 to 29 years and the peak months for detection were between March and October. Full genome sequence comparisons revealed that the CVA-9 viruses isolated in Alberta in 2003 and 2010 were highly homologous to the prototype CVA-9 in the structural VP1, VP2 and VP3 regions but divergent in the VP4, non-structural and non-coding regions.ConclusionThe increase in cases of aseptic meningitis was associated with enterovirus CVA-9. Sequence divergence between the prototype strain of CVA-9 and the Alberta isolates suggests genetic drifting and/or recombination events, however the sequence was conserved in the antigenic regions determined by the VP1, VP2 and VP3 genes. These results suggest that the increase in CVA-9 cases likely did not result from the emergence of a radically different immune escape mutant.
Invariance and optimality in the regulation of an enzyme
Authors: Reznik Ed , Yohe Stefan , Segrè Daniel 
Published: March 2013

Abstract

Background
The Michaelis-Menten equation, proposed a century ago, describes the kinetics of enzyme-catalyzed biochemical reactions. Since then, this equation has been used in countless, increasingly complex models of cellular metabolism, often including time-dependent enzyme levels. However, even for a single reaction, there remains a fundamental disconnect between our understanding of the reaction kinetics, and the regulation of that reaction through changes in the abundance of active enzyme.

Results
We revisit the Michaelis-Menten equation under the assumption of a time-dependent enzyme concentration. We show that all temporal enzyme profiles with the same average enzyme level yield identical substrate degradation– a simple analytical conclusion that can be thought of as an invariance principle, and which we validate experimentally using a β-galactosidase assay. The ensemble of all time-dependent enzyme trajectories with the same average concentration constitutes a space of functions. We develop a simple model of biological fitness which assigns a cost to each of these trajectories (in the form of a function of functions, i.e. a functional). We then show how one can use variational calculus to analytically infer temporal enzyme profiles that minimize the overall enzyme cost. In particular, by separately treating the static costs of amino acid sequestration and the dynamic costs of protein production, we identify a fundamental cellular tradeoff.

Conclusions
The overall metabolic outcome of a reaction described by Michaelis-Menten kinetics is ultimately determined by the average concentration of the enzyme during a given time interval. This invariance in analogy to path-independent phenomena in physics, suggests a new way in which variational calculus can be employed to address biological questions. Together, our results point to possible avenues for a unified approach to studying metabolism and its regulation.

Reviewers
This article was reviewed by Sergei Maslov, William Hlavacek and Daniel Kahn.
Effect of lateral meniscectomy and osteochondral grafting of a lateral femoral condylar defect on contact mechanics: a cadaveric study in dogs
Authors: Choate Christina J , Kim Stanley E , Hudson Caleb C , Spreng David , Pozzi Antonio 
Published: March 2013

AbstractBackgroundOsteochondral autograft transfer (OAT) aims at restoring normal articular cartilage surface geometry and articular contact mechanics. To date, no studies have evaluated the contact mechanics of the canine stifle following OAT. Additionally, there are no studies that evaluated the role of the meniscus in contact mechanics following OAT in human or canine femorotibial joints. The objective of this study was to measure the changes in femorotibial contact areas (CA), mean contact pressure (MCP) and peak contact pressure (PCP) before and after osteochondral autograft transplantation (OAT) of a simulated lateral femoral condylar cartilage defect with an intact lateral meniscus and following lateral meniscectomy.ResultsWith an intact lateral meniscus, creation of an osteochondral defect caused a decrease in MCP and PCP by 11% and 30%, respectively, compared to the intact stifle (p < 0.01). With an intact meniscus, implanting an osteochondral graft restored MCP and PCP to 96% (p = 0.56) and 92% (p = 0.41) of the control values. Lateral meniscectomy with grafting decreased CA by 54% and increased PCP by 79% compared to the intact stifle (p < 0.01).ConclusionsOAT restored contact pressures in stifles with a simulated lateral condylar defect when the meniscus was intact. The lateral meniscus has a significant role in maintaining normal contact pressures in both stifles with a defect or following OAT. Meniscectomy should be avoided when a femoral condylar defect is present and when performing OAT.