bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of qnr gene in Escherichia coli and Klebsiella pneumoniae resistant to ciprofloxacin isolated from pediatric patients in China
Authors: Wang Aihua , Yang Yonghong , Lu Quan , Wang Yi , Chen Yuan , Deng Li , Ding Hui , Deng Qiulian , Zhang Hong , Wang Chuanqing , Liu Lan , Xu Xiwei , Wang Li , Shen Xuzhuang 
Published: May 2008

Abstract

Background
Quinolone resistance in Enterobacteriaceae results mainly from mutations in type II DNA topoisomerase genes and/or changes in the expression of outer membrane and efflux pumps. Several recent studies have indicated that plasmid-mediated resistance mechanisms also play a significant role in fluoroquinolone resistance, and its prevalence is increasing worldwide. In China, the presence of the qnr gene in the clinical isolates of Enterobacteriaceae has been reported, but this transmissible quinolone resistance gene has not been detected in strains isolated singly from pediatric patients. Because quinolones associated with a variety of adverse side effects on children, they are not authorized for pediatric use. This study therefore aimed to investigate the presence of the qnr gene in clinical isolates of E. coli and K. pneumoniae from pediatric patients in China.

Methods
A total 213 of non-repetitive clinical isolates resistant to ciprofloxacin from E. coli and K. pneumoniae were collected from hospitalized patients at five children's hospital in Beijing, Shanghai, Guangzhou, and Chongqing. The isolates were screened for the plasmid-mediated quinolone resistance genes of qnrA, qnrB, and qnrS by PCR. Transferability was examined by conjugation with the sodium azide-resistant E. coli J53. All qnr-positive were analyzed for clonality by enterobacterial repetitive intergenic consensus (ERIC)-PCR.

Results
The study found that 19 ciprofloxacin-resistant clinical isolates of E. coli and K. pneumoniae were positive for the qnr gene, and most of the qnr positive strains were ESBL producers. Conjugation experiments showed that quinolone resitance could be transferred to recipients. Apart from this, different DNA banding patterns were obtained by ERIC-PCR from positive strains, which means that most of them were not clonally related.

Conclusion
This report on transferable fluoroquinolone resistance due to the qnr gene among E. coli and K. pneumoniae strains indicated that plasmid-mediated quinolone resistance has emerged in pediatric patients in China.
A novel de novo mutation in the serine-threonine kinase STK11 gene in a Korean patient with Peutz-Jeghers syndrome
Authors: Yoo Jong-Ha , Yoo Jee-Hyoung , Choi Yoon-Jung , Kang Jung-Gu , Sun Young-Kyu , Ki Chang-Seok , Lee Kyung-A , Choi Jong-Rak 
Published: May 2008

Abstract

Background
Peutz-Jeghers syndrome (PJS) is an unusual autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple gastrointestinal hamartomatous polyps. Patients with PJS are at an increased risk of developing multi-organ cancer, most frequently those involving the gastrointestinal tract. Germline mutation of the STK11 gene, which encodes a serine-threonine kinase, is responsible for PJS.

Methods
Using DNA samples obtained from the patient and his family members, we sequenced nine exons and flanking intron regions of the STK11 gene using polymerase chain reaction (PCR) and direct sequencing.

Results
Sequencing of the STK11 gene in the proband of the family revealed a novel 1-base pair deletion of guanine (G) in exon 6 (c.826delG; Gly276AlafsX11). This mutation resulted in a premature termination at codon 286, predicting a partial loss of the kinase domain and complete loss of the C-terminal domain. We did not observe this mutation in both parents of the PJS patient. Therefore, it is considered a novel de novo mutation.

Conclusion
The results presented herein enlarge the spectrum of mutations of the STK11 gene by identifying a novel de novo mutation in a PJS patient and further support the hypothesis that STK11 mutations are disease-causing mutations for PJS with or without a positive family history.
The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies
Authors: Cauchi Stéphane , Nead Kevin T , Choquet Hélène , Horber Fritz , Potoczna Natascha , Balkau Beverley , Marre Michel , Charpentier Guillaume , Froguel Philippe , Meyre David 
Published: May 2008

Abstract

Background
Considering that a portion of the heterogeneity amongst previous replication studies may be due to a variable proportion of obese subjects in case-control designs, we assessed the association of genetic variants with type 2 diabetes (T2D) in large groups of obese and non-obese subjects.

Methods
We genotyped RETN, KCNJ11, HNF4A, HNF1A, GCK, SLC30A8, ENPP1, ADIPOQ, PPARG, and TCF7L2 polymorphisms in 1,283 normoglycemic (NG) and 1,581 T2D obese individuals as well as in 3,189 NG and 1,244 T2D non-obese subjects of European descent, allowing us to examine T2D risk over a wide range of BMI.

Results
Amongst non-obese individuals, we observed significant T2D associations with HNF1A I27L [odds ratio (OR) = 1.14, P = 0.04], GCK -30G>A (OR = 1.23, P = 0.01), SLC30A8 R325W (OR = 0.87, P = 0.04), and TCF7L2 rs7903146 (OR = 1.89, P = 4.5 × 10-23), and non-significant associations with PPARG Pro12Ala (OR = 0.85, P = 0.14), ADIPOQ -11,377C>G (OR = 1.00, P = 0.97) and ENPP1 K121Q (OR = 0.99, P = 0.94). In obese subjects, associations with T2D were detected with PPARG Pro12Ala (OR = 0.73, P = 0.004), ADIPOQ -11,377C>G (OR = 1.26, P = 0.02), ENPP1 K121Q (OR = 1.30, P = 0.003) and TCF7L2 rs7903146 (OR = 1.30, P = 1.1 × 10-4), and non-significant associations with HNF1A I27L (OR = 0.96, P = 0.53), GCK -30G>A (OR = 1.15, P = 0.12) and SLC30A8 R325W (OR = 0.95, P = 0.44). However, a genotypic heterogeneity was only found for TCF7L2 rs7903146 (P = 3.2 × 10-5) and ENPP1 K121Q (P = 0.02). No association with T2D was found for KCNJ11, RETN, and HNF4A polymorphisms in non-obese or in obese individuals.

Conclusion
Genetic variants modulating insulin action may have an increased effect on T2D susceptibility in the presence of obesity, whereas genetic variants acting on insulin secretion may have a greater impact on T2D susceptibility in non-obese individuals.
An economic analysis of email-based telemedicine: A cost minimisation study of two service models
Authors: Caffery Liam , Smith Anthony C , Scuffham Paul A 
Published: May 2008

Abstract

Background
Email-based telemedicine has been reported to be an efficient method of delivering online health services to patients at a distance and is often described as a low-cost form of telemedicine. The service may be low-cost if the healthcare organisation utilise their existing email infrastructure to provide their telemedicine service. Many healthcare organisations use commercial-off-the-shelf (COTS) email applications. COTS email applications are designed for peer-to-peer communication; hence, in situations where multiple clinicians need to be involved, COTS applications may be deficient in delivering telemedicine. Larger services often rely on different staff disciplines to run their service and telemedicine tools for supervisors, clinicians and administrative staff are not available in COTS applications. Hence, some organisations may choose to develop a purpose-written email application to support telemedicine. We have conducted a cost-minimisation analysis of two different service models for establishing and operating an email service. The first service model used a COTS email application and the second used a purpose-written telemedicine application.

Methods
The actual costs used in the analysis were from two organisations that originally ran their counselling service with a COTS email application and later implemented a purpose-written application. The purpose-written application automated a number of the tasks associated with running an email-based service. We calculated a threshold at which the higher initial costs for software development were offset by efficiency gains from automation. We also performed a sensitivity analysis to determine the effect of individual costs on the threshold.

Results
The cost of providing an email service at 1000 consultations per annum was $19,930 using a COTS email application and $31,925 using a purpose-written application. At 10,000 consultations per annum the cost of providing the service using COTS email software was $293,341 compared to $272,749 for the purpose-written application. The threshold was calculated at a workload of 5216 consultations per annum. When more than 5216 email consultations per annum are undertaken, the purpose-written application was cheaper than the COTS service model. The sensitivity analysis showed the threshold was most sensitive to changes in administrative staff salaries.

Conclusion
In the context of telemedicine, we have compared two different service models for email-based communication – purpose-written and COTS applications. Under the circumstances described in the paper, when workload exceeded 5216 email consultations per annum, there were savings made when a purpose-written email application was used. This analysis provides a useful economic model for organisations contemplating the use of an email-based telemedicine system.
Interactions between dendritic cells and CD4+ T cells during Plasmodium infection
Authors: Ocaña-Morgner Carlos , Wong Kurt A , Rodriguez Ana 
Published: May 2008

AbstractBackgroundDuring infection, dendritic cells (DCs) encounter pathogenic microorganisms that can modulate their function and shape the T cell responses generated. During the process of T cell activation, DCs establish strong, long-lasting interactions with naïve T cells.MethodsUsing a mouse malaria model, the interactions of DCs and naïve CD4+T cells have been analysed.ResultsDCs, either incubatedin vitrowith infected erythrocytes or isolated from infected mice, are able to present exogenous antigens by MHC-II, but are not able to establish prolonged effective interactions with naïve CD4+T cells and do not induce T cell activation. It was also found that effective T cell activation of naïve CD4+T cells is impaired during latePlasmodium yoeliiinfection.ConclusionThese data may provide a mechanism for the lack of effective adaptive immune responses induced by the Plasmodium parasite.
The potential impact of climate change on annual and seasonal mortality for three cities in Québec, Canada
Authors: Doyon Bernard , Bélanger Diane , Gosselin Pierre 
Published: May 2008

Abstract

Background
The impact of climate change and particularly increasing temperature on mortality has been examined for three cities in the province of Québec, Canada.

Methods
Generalized linear Poisson regression has been fitted to the total daily mortality for each city. Smooth parametric cubic splines of temperature and humidity have been used to do nonlinear modeling of these parameters. The model, to control for day of the week and for non-temperature seasonal factors, used a smooth function of time, including delayed effects. The model was then used to assess variation in mortality for simulated future temperatures obtained from an atmospheric General Circulation Model coupled with downscaling regression techniques. Two CO2 emission scenarios are considered (scenarios A2 and B2). Projections are made for future periods around year 2020 (2010–2039), 2050 (2040–2069) and 2080 (2070–2099).

Results
A significant association between mortality and current temperature has been found for the three cities. Under CO2 emission scenarios A2 and B2, the mortality model predicts a significant increase in mortality in the summertime, and a smaller, but significant decrease in the fall season. The slight variations in projected mortality for future winter and spring seasons were found to be not statistically significant. The variations in projected annual mortality are dominated by an increase in mortality in the summer, which is not balanced by the decrease in mortality in the fall and winter seasons. The summer increase and the annual mortality range respectively from about 2% and 0.5% for the 2020 period, to 10% and 3% for the years around 2080. The difference between the mortality variations projected with the A2 or B2 scenarios was not statistically significant.

Conclusion
For the three cities, the two CO2 emission scenarios considered led to an increase in annual mortality, which contrasts with most European countries, where the projected increase in summer mortality with respect to climate change is overbalanced by the decrease in winter mortality. This highlights the importance of place in such analyses. The method proposed here to establish these estimates is general and can also be applied to small cities, where mortality rates are relatively low (ex. two deaths/day).
DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk
Authors: Bernard-Gallon Dominique , Bosviel Rémy , Delort Laetitia , Fontana Luc , Chamoux Alain , Rabiau Nadège , Kwiatkowski Fabrice , Chalabi Nasséra , Satih Samir , Bignon Yves-Jean 
Published: May 2008

AbstractBreast and ovarian cancers increased in the last decades. Except rare cases with a genetic predisposition and high penetrance, these pathologies are viewed as a polygenic disease. In this concept, association studies look for genetic variations such as polymorphisms in low penetrance genes,i.e. genes in interaction with environmental factors. DNA repair systems that protect the genome from deleterious endogenous and exogenous damages have been shown to have significantly reduced. In particular, enzymes of the nucleotide excision repair pathway are suspected to be implicated in cancer. In this study, 2 functional polymorphisms in a DNA repair geneERCC2were analyzed. The population included 911 breast cancer cases, 51 ovarian cancer cases and 1000 controls. The genotyping of 2 SNP (Single Nucleotide Polymorphism) was carried out on the population with the MGB (Minor Groove Binder) probe technique which consists of the use of the allelic discrimination with the Taqman®method. This study enabled us to show an increase in risk of breast cancer with no oral contraceptive users and with women exhibiting a waist-to-hip ratio (WHR) > 0.85 for Asn homozygous forERCC2 312.
Epigenetic changes within the promoter region of the HLA-G gene in ovarian tumors
Authors: Menendez Laura , Walker L DeEtte , Matyunina Lilya V , Totten Kimberly A , Benigno Benedict B , McDonald John F 
Published: May 2008

Abstract

Background
Previous findings have suggested that epigenetic-mediated HLA-G expression in tumor cells may be associated with resistance to host immunosurveillance. To explore the potential role of DNA methylation on HLA-G expression in ovarian cancer, we correlated differences in HLA-G expression with methylation changes within the HLA-G regulatory region in an ovarian cancer cell line treated with 5-aza-deoxycytidine (5-aza-dC) and in malignant and benign ovarian tumor samples and ovarian surface epithelial cells (OSE) isolated from patients with normal ovaries.

Results
A region containing an intact hypoxia response element (HRE) remained completely methylated in the cell line after treatment with 5-aza-dC and was completely methylated in all of the ovarian tumor (malignant and benign) samples examined, but only variably methylated in normal OSE samples. HLA-G expression was significantly increased in the 5-aza-dC treated cell line but no significant difference was detected between the tumor and OSE samples examined.

Conclusion
Since HRE is the binding site of a known repressor of HLA-G expression (HIF-1), we hypothesize that methylation of the region surrounding the HRE may help maintain the potential for expression of HLA-G in ovarian tumors. The fact that no correlation exists between methylation and HLA-G gene expression between ovarian tumor samples and OSE, suggests that changes in methylation may be necessary but not sufficient for HLA-G expression in ovarian cancer.
RETRACTED ARTICLE: Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability
Authors: Verdina Alessandra , Cardillo Irene , Nebbioso Angela , Galati Rossella , Menegozzo Simona , Altucci Lucia , Sacchi Ada , Baldi Alfonso 
Published: May 2008

AbstractNonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma.
Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR
Authors: Van Duyne Rachel , Easley Rebecca , Wu Weilin , Berro Reem , Pedati Caitlin , Klase Zachary , Kehn-Hall Kylene , Flynn Elizabeth K , Symer David E , Kashanchi Fatah 
Published: May 2008

Abstract

Background
The rate of transcription of the HIV-1 viral genome is mediated by the interaction of the viral protein Tat with the LTR and other transcriptional machinery. These specific interactions can be affected by the state of post-translational modifications on Tat. Previously, we have shown that Tat can be phosphorylated and acetylated in vivo resulting in an increase in the rate of transcription. In the present study, we investigated whether Tat could be methylated on lysine residues, specifically on lysine 50 and 51, and whether this modification resulted in a decrease of viral transcription from the LTR.

Results
We analyzed the association of Tat with histone methyltransferases of the SUV39-family of SET domain containing proteins in vitro. Tat was found to associate with both SETDB1 and SETDB2, two enzymes which exhibit methyltransferase activity. siRNA against SETDB1 transfected into cell systems with both transient and integrated LTR reporter genes resulted in an increase in transcription of the HIV-LTR in the presence of suboptimal levels of Tat. In vitro methylation assays with Tat peptides containing point mutations at lysines 50 and 51 showed an increased incorporation of methyl groups on lysine 51, however, both residues indicated susceptibility for methylation.

Conclusion
The association of Tat with histone methyltransferases and the ability for Tat to be methylated suggests an interesting mechanism of transcriptional regulation through the recruitment of chromatin remodeling proteins to the HIV-1 promoter.
The host protein Staufen1 interacts with the Pr55Gagzinc fingers and regulates HIV-1 assembly via its N-terminus
Authors: Chatel-Chaix Laurent , Boulay Karine , Mouland Andrew J , DesGroseillers Luc 
Published: May 2008

Abstract

Background
The formation of new infectious human immunodeficiency type 1 virus (HIV-1) mainly relies on the homo-multimerization of the viral structural polyprotein Pr55Gag and on the recruitment of host factors. We have previously shown that the double-stranded RNA-binding protein Staufen 1 (Stau1), likely through an interaction between its third double-stranded RNA-binding domain (dsRBD3) and the nucleocapsid (NC) domain of Pr55Gag, participates in HIV-1 assembly by influencing Pr55Gag multimerization.

Results
We now report the fine mapping of Stau1/Pr55Gag association using co-immunoprecipitation and live cell bioluminescence resonance energy transfer (BRET) assays. On the one hand, our results show that the Stau1-Pr55Gag interaction requires the integrity of at least one of the two zinc fingers in the NC domain of Pr55Gag but not that of the NC N-terminal basic region. Disruption of both zinc fingers dramatically impeded Pr55Gag multimerization and virus particle release. In parallel, we tested several Stau1 deletion mutants for their capacity to influence Pr55Gag multimerization using the Pr55Gag/Pr55Gag BRET assay in live cells. Our results revealed that a molecular determinant of 12 amino acids at the N-terminal end of Stau1 is necessary to increase Pr55Gag multimerization and particle release. However, this region is not required for Stau1 interaction with the viral polyprotein Pr55Gag.

Conclusion
These data highlight that Stau1 is a modular protein and that Stau1 influences Pr55Gag multimerization via 1) an interaction between its dsRBD3 and Pr55Gag zinc fingers and 2) a regulatory domain within the N-terminus that could recruit host machineries that are critical for the completion of new HIV-1 capsids.
A haptic-robotic platform for upper-limb reaching stroke therapy: Preliminary design and evaluation results
Authors: Lam Paul , Hebert Debbie , Boger Jennifer , Lacheray Hervé , Gardner Don , Apkarian Jacob , Mihailidis Alex 
Published: May 2008

Abstract

Background
It has been shown that intense training can significantly improve post-stroke upper-limb functionality. However, opportunities for stroke survivors to practice rehabilitation exercises can be limited because of the finite availability of therapists and equipment. This paper presents a haptic-enabled exercise platform intended to assist therapists and moderate-level stroke survivors perform upper-limb reaching motion therapy. This work extends on existing knowledge by presenting: 1) an anthropometrically-inspired design that maximizes elbow and shoulder range of motions during exercise; 2) an unobtrusive upper body postural sensing system; and 3) a vibratory elbow stimulation device to encourage muscle movement.

Methods
A multi-disciplinary team of professionals were involved in identifying the rehabilitation needs of stroke survivors incorporating these into a prototype device. The prototype system consisted of an exercise device, postural sensors, and a elbow stimulation to encourage the reaching movement. Eight experienced physical and occupational therapists participated in a pilot study exploring the usability of the prototype. Each therapist attended two sessions of one hour each to test and evaluate the proposed system. Feedback about the device was obtained through an administered questionnaire and combined with quantitative data.

Results
Seven of the nine questions regarding the haptic exercise device scored higher than 3.0 (somewhat good) out of 4.0 (good). The postural sensors detected 93 of 96 (97%) therapist-simulated abnormal postures and correctly ignored 90 of 96 (94%) of normal postures. The elbow stimulation device had a score lower than 2.5 (neutral) for all aspects that were surveyed, however the therapists felt the rehabilitation system was sufficient for use without the elbow stimulation device.

Conclusion
All eight therapists felt the exercise platform could be a good tool to use in upper-limb rehabilitation as the prototype was considered to be generally well designed and capable of delivering reaching task therapy. The next stage of this project is to proceed to clinical trials with stroke patients.