bluuebunny/crossref_metadata_2025_split huggingface dataset:
ST9 MRSA strains carrying a variant of type IX SCCmec identified in the Thai community
Authors: Lulitanond Aroonlug , Ito Teruyo , Li Shanshuang , Han Xiao , Ma Xiao Xue , Engchanil Chulapan , Chanawong Aroonwadee , Wilailuckana Chotechana , Jiwakanon Netchanok , Hiramatsu Keiichi 
Published: May 2013

Abstract

Background
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in Thailand occur most frequently in healthcare facilities. However, reports of community-associated MRSA are limited.

Methods
We characterized 14 MRSA isolates from outpatients (O-1 to O-14) by phenotypic and genotypic methods and compared them with 5 isolates from inpatients (I-1 to I-5). Thai MRSA isolates from a healthcare worker (N-1) and a pig (P-1) were also included as ST9 MRSA strains from other sources.

Results
All MRSA isolates from the outpatients and inpatients were multidrug-resistant (resistant to ≥3 classes of antimicrobials). All of them except strains O-2 and I-3 carried type III SCCmec and belonged to agrI, coagulase IV, spa type t037 or t233, which related to ST239. The strain O-2 (JCSC6690) carried type IX SCCmec and belonged to agrII, coagulaseXIc, spa type t337 and ST9, whereas the strain I-3 carried a type III SCCmec and belonged to ST1429. Nucleotide sequence determination revealed that the type IX SCCmec element in strain O-2 was distinct from that in a Thai ST398 strain (JCSC6943) previously identified in 2011; nucleotide identities of ccrA and ccrB were 93 and 91%, respectively and several open reading frames (ORFs) at the joining regions were different. PCR experiments suggested that strain O-2 and N-1 carried similar SCCmec element, whereas that of strain P-1 was different, suggesting that distinct ST9-MRSA–IX clones might be spreading in this province.

Conclusions
The SCCmecIX-ST9 MRSA clones of distinct SCCmec subtypes might have emerged in the Thai community and might also have disseminated into the hospital.
Genetic association between selected cytokine genes and glioblastoma in the Han Chinese population
Authors: Jin Tianbo , Li Xiaolan , Zhang Jiayi , Wang Hong , Geng Tingting , Li Gang , Gao Guodong , Chen Chao 
Published: May 2013

Abstract

Background
Glioblastoma (GBM) is the most malignant brain tumor. Many abnormal secretion and expression of cytokines have been found in GBM, initially speculated that the occurrence of GBM may be involved in these abnormal secretion of cytokines. This study aims to detect the association of cytokine genes with GBM.

Methods
We selected seven tag single nucleotide polymorphisms (tSNPs) in six cytokine genes, which previously reported to be associated with brain tumors, and analyzed their association with GBM in a Han Chinese population using χ2 test and genetic model analysis.

Results
We found two risk tSNPs and one protective tSNP. By χ2 test, the rs1801275 in IL-4R showed an increased risk of GBM. In the genetic model analysis, the genotype “TC” of rs20541 in IL-13 gene showed an increased risk of GBM in over-dominant model (OR = 2.00; 95% CI, 1.13-3.54, p = 0.015); the genotype “CT” of rs1800871 in the IL-10 gene showed a decrease risk in the over-dominant model (OR = 0.57; 95% CI, 0.33 – 0.97; p = 0.037). The genotype “AG” of rs1801275 in the IL-4R gene showed an increase risk in over-dominant model (OR = 2.29; 95% CI, 1.20 - 4.35; p = 0.0081) We further analyzed whether the six cytokine genes have a different effect on the disease in gender specific population, and found that the allele “G” of rs2243248 in the IL-4 gene showed a decrease risk of GBM in female (OR = 0.35, 95% CI, 0.13 - 0.94, p = 0.0032), but the allele “T” showed a decrease risk in male (OR = 0.30, 95% CI, 0.17 - 0.53, p = 0.0032).

Conclusions
Our findings, combined with previously reported results, suggest that cytokine genes have potential role in GBM development, which may be useful to early prognostics for GBM in the Han Chinese population.
Equol enhances tamoxifen’s anti-tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells
Authors: Charalambous Christiana , Pitta Chara A , Constantinou Andreas I 
Published: May 2013

Abstract

Background
Soy phytoestrogens, such as daidzein and its metabolite equol, have been proposed to be responsible for the low breast cancer rate in Asian women. Since the majority of estrogen receptor positive breast cancer patients are treated with tamoxifen, the basic objective of this study is to determine whether equol enhances tamoxifen’s anti-tumor effect, and to identify the molecular mechanisms involved.

Methods
For this purpose, we examined the individual and combined effects of equol and tamoxifen on the estrogen-dependent MCF-7 breast cancer cells using viability assays, annexin-V/PI staining, cell cycle and western blot analysis.

Results
We found that equol (>50 μM) and 4-hydroxy-tamoxifen (4-OHT; >100 nM) significantly reduced the MCF-7 cell viability. Furthermore, the combination of equol (100 μM) and 4-OHT (10 μM) induced apoptosis more effectively than each compound alone. Subsequent treatment of MCF-7 cells with the pan-caspase inhibitor Z-VAD-FMK inhibited equol- and 4-OHT-mediated apoptosis, which was accompanied by PARP and α-fodrin cleavage, indicating that apoptosis is mainly caspase-mediated. These compounds also induced a marked reduction in the bcl-2:bax ratio, which was accompanied by caspase-9 and caspase-7 activation and cytochrome-c release to the cytosol. Taken together, these data support the notion that the combination of equol and tamoxifen activates the intrinsic apoptotic pathway more efficiently than each compound alone.

Conclusions
Consequently, equol may be used therapeutically in combination treatments and clinical studies to enhance tamoxifen’s effect by providing additional protection against estrogen-responsive breast cancers.
Alterations of the genes involved in the PI3K and estrogen-receptor pathways influence outcome in human epidermal growth factor receptor 2-positive and hormone receptor-positive breast cancer patients treated with trastuzumab-containing neoadjuvant chemotherapy
Authors: Takada Mamoru , Higuchi Toru , Tozuka Katsunori , Takei Hiroyuki , Haruta Masayuki , Watanabe Junko , Kasai Fumio , Inoue Kenichi , Kurosumi Masafumi , Miyazaki Masaru , Sato-Otsubo Aiko , Ogawa Seishi , Kaneko Yasuhiko 
Published: May 2013

Abstract

Background
Chemotherapy with trastuzumab is widely used for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but a significant number of patients with the tumor fail to respond, or relapse. The mechanisms of recurrence and biomarkers that indicate the response to the chemotherapy and outcome are not fully investigated.

Methods
Genomic alterations were analyzed using single-nucleotide polymorphism arrays in 46 HER2 immunohistochemistry (IHC) 3+ or 2+/fluorescent in situ hybridization (FISH)+ breast cancers that were treated with neoadjuvant chemotherapy with paclitaxel, cyclophosphamid, epirubicin, fluorouracil, and trastuzumab. Patients were classified into two groups based on presence or absence of alterations of 65 cancer-associated genes, and the two groups were further classified into four groups based on genomic HER2 copy numbers or hormone receptor status (HR+/−). Pathological complete response (pCR) and relapse-free survival (RFS) rates were compared between any two of the groups.

Results and discussion
The pCR rate was 54% in 37 patients, and the RFS rate at 3 years was 72% (95% CI, 0.55-0.89) in 42 patients. The analysis disclosed 8 tumors with nonamplified HER2 and 38 tumors with HER2 amplification, indicating the presence of discordance in tumors diagnosed using current HER2 testing. The 8 patients showed more difficulty in achieving pCR (P=0.019), more frequent relapse (P=0.018), and more frequent alterations of genes in the PI3K pathway (P=0.009) than the patients with HER2 amplification. The alterations of the PI3K and estrogen receptor (ER) pathway genes generally indicated worse RFS rates. The prognostic significance of the alterations was shown in patients with a HR+ tumor, but not in patients with a HR- tumor when divided. Alterations of the PI3K and ER pathway genes found in patients with a HR+ tumor with poor outcome suggested that crosstalk between the two pathways may be involved in resistance to the current chemotherapy with trastuzumab.

Conclusions
We recommend FISH analysis as a primary HER2 testing because patients with IHC 2+/3+ and nonamplified HER2 had poor outcome. We also support concurrent use of trastuzumab, lapatinib, and cytotoxic and anti-hormonal agents for patients having HR+ tumors with alterations of the PI3K and ER pathway genes.
Improved emollient use reduces atopic eczema symptoms and is cost neutral in infants: before-and-after evaluation of a multifaceted educational support programme
Authors: Mason James M , Carr Julie , Buckley Carolyn , Hewitt Steve , Berry Phillip , Taylor Josh , Cork Michael J 
Published: May 2013

AbstractBackgroundParents and carers of children with eczema often underuse emollient therapy, essential to repairing and protecting the defective skin barrier in atopic eczema. Educational interventions delivered by specialist dermatology nurses in hospital settings have been shown to improve emollient use and reduce symptoms of atopic eczema, but benefits of community-based interventions are uncertain. Support and information about appropriate care may often be inadequate for patients and carers in the community.MethodsA multifaceted educational support programme was evaluated as a method of increasing emollient use and reducing atopic eczema in children. Support provided for parents and carers included an educational DVD, online daily diary and telephone helpline. The before and after study included 136 British children and their parents, providing baseline and 12 week follow-up data while receiving the programme. Measures included emollient use, POEM and PEST scores, and cost of care.ResultsAverage emollient use increased by 87.6 g (95% CI: 81.9 to 119.5 g, p = 0.001) from baseline with the change being immediate and persistent. The POEM score reduced on average by 5.38 (95% CI: 4.36 to 6.41, p = 0.001), a 47% reduction from baseline. Similarly the PEST score reduced on average by 0.61 (95% CI: 0.47 to 0.75, p = 0.001), a 48% reduction from baseline. Sleep disturbance was reduced by 1.27 nights per week (95% CI: 0.85 to 1.68, p = 0.001) and parental feeling of control improved by 1.32 points (95% CI: 1.16 to 1.48, p = 0.001). From the NHS perspective, the programme was cost neutral overall within the study period.ConclusionA community-based multifaceted educational support programme greatly increased emollient use, reducing symptoms of atopic eczema and general practitioner contacts, without increasing cost. Significant benefits may accrue to the families and carers of children with atopic eczema due to improved sleep patterns and greater feeling of control. PEST, a new simple measure of acute and remitting atopic eczema severity designed to help parents and children to monitor and manage eczema, merits further evaluation.
Antibacterial, antidiarrhoeal, and cytotoxic activities of methanol extract and its fractions of Caesalpinia bonducella (L.) Roxb leaves
Authors: Billah Muhammad Mutassim , Islam Rafikul , Khatun Hajera , Parvin Shahnaj , Islam Ekramul , Islam SM Anisul , Mia Akbar Ali 
Published: May 2013

Abstract

Background

Caesalpinia bonducella is an important medicinal plant for its traditional uses against different types of diseases. Therefore, the present study investigated the antimicrobial, antidiarrhoeal, and cytotoxic activities of the methanol extract and ethyl acetate, chloroform, and petroleum ether (pet. ether) fractions of C. bonducella leaves.

Methods
The antibacterial potentialities of methanol extract and its fractions of C. bonducella leaves were investigated by the disc diffusion method against four gram-positive and five gram-negative bacteria at 300, 500 and 800 μg/disc. Kanamycin (30 μg/disc) was used as the standard drug. Antidiarrhoeal activities of leaf extracts were evaluated at two doses (200 and 400 mg/kg) and compared with loperamide in a castor oil-induced diarrhoeal model in rat. The fractions were subjected to a brine shrimp lethality test to evaluate their cytotoxicity.

Results
The methanol extract and other three fractions exhibited better activities at higher concentrations. Amongst, the chloroform fraction showed maximum activity at all three concentrations (300, 500, and 800 μg/disc) against almost all bacteria. S. aureus and P. aeruginosa showed better sensitivities to all extracts at all three concentrations excluding the pet. ether fraction. Bacillus megaterium and Klebsiella spp. were two bacteria amongst nine that showed lowest sensitivity to the extracts. Maximum zone of inhibition (25-mm) was obtained by the methanol extract at an 800 μg/disc concentration against S. aureus. In the antidiarrhoeal test, all fractions exhibited dose-dependent actions, which were statistically significant (p < 0.05). Ethyl acetate fraction exerted maximum inhibition (51.11%) against defecation, whereas 57.75% inhibition was obtained for loperamide. Moderate cytotoxicity was found for the methanol extract and its three fractions compared with the standard drug vincristine sulfate in the brine shrimp bioassay. In the present study, the LC50 values of the methanol crude extract and ethyl acetate, chloroform, pet. ether fractions and vincristine sulfate were 223.87, 281.84, 112.2, 199.53, and 12.59 μg/mL, respectively. Therefore, the ethyl acetate fraction showed maximum cytotoxicity, whereas minimum cytotoxicity was observed for the chloroform fraction.

Conclusion
The present study revealed that the ethyl acetate fraction of the C. bonducella leaves has significant antidiarrhoeal properties. The methanol extract and other three fractions of the C. bonducella leaves possess potent antibacterial activities along with moderate cytotoxicities that may lead to new drug development.
Interactions by 2D Gel Electrophoresis Overlap (iGEO): a novel high fidelity
approach to identify constituents of protein complexes
Authors: Yoshigi Masaaki , Pronovost Stephen M , Kadrmas Julie L 
Published: May 2013

Abstract

Background
Here we describe a novel approach used to identify the constituents of
protein complexes with high fidelity, using the integrin-associated
scaffolding protein PINCH as a test case. PINCH is comprised of five LIM
domains, zinc-finger protein interaction modules. In Drosophila
melanogaster, PINCH has two known high-affinity binding
partners—Integrin-linked kinase (ILK) that binds to LIM1 and Ras
Suppressor 1 (RSU1) that binds to LIM5—but has been postulated to bind
additional proteins as well.

Results
To purify PINCH complexes, in parallel we fused different affinity tags
(Protein A and Flag) to different locations within the PINCH sequence (N-
and C-terminus). We expressed these tagged versions of PINCH both in cell
culture (overexpressed in Drosophila S2 cell culture in the
presence of endogenous PINCH) and in vivo (at native levels in
Drosophila lacking endogenous PINCH). After affinity
purification, we analyzed PINCH complexes by a novel 2D-gel electrophoresis
analysis, iGEO (interactions by 2D Gel Electrophoresis Overlap), with mass
spectrometric identification of individual spots of interest. iGEO allowed
the identification of protein partners that associate with PINCH under two
independent purification strategies, providing confidence in the
significance of the interaction. Proteins identified by iGEO were validated
against a highly inclusive list of candidate PINCH interacting proteins
identified in previous analyses by MuDPIT mass spectrometry.

Conclusions
The iGEO strategy confirmed a core complex comprised of PINCH, RSU1, ILK, and
ILK binding partner Parvin. Our iGEO method also identified five novel
protein partners that specifically interacted with PINCH in
Drosophila S2 cell culture. Because of the improved
reproducibility of 2D-GE methodology and the increasing affordability of the
required labeling reagents, iGEO is a method that is accessible to most
moderately well-equipped biological laboratories. The biochemical
co-purifications inherent in iGEO allow for rapid and unambiguous
identification of the constituents of protein complexes, without the need
for extensive follow-up experiments.
Comparative analysis of cancer vaccine settings for the selection of an effective protocol in mice
Authors: Kalli Francesca , Machiorlatti Rodolfo , Battaglia Florinda , Parodi Alessia , Conteduca Giuseppina , Ferrera Francesca , Proietti Michele , Tardito Samuele , Sanguineti Marina , Millo Enrico , Fenoglio Daniela , De Palma Raffaele , Inghirami Giorgio , Filaci Gilberto 
Published: May 2013

Abstract

Background
Cancer vaccines are considered a promising therapeutic approach. However, their clinical results are not yet satisfactory. This may be due to the the difficulty of selection of an efficient tumor associated antigen (TAA) and immunization protocol. Indeed, the weak antigenicity of many TAA impairs the design of robust procedures, therefore a systematic analysis to identify the most efficient TAA is mandatory. Here, we performed a study to compare different gp100 vaccination strategies to identify the best strategy to provide a 100% protection against experimental melanoma in a reproducible manner.

Methods
C57BL/6J mice were challenged subcutaneously with B16F10 melanoma cells, after vaccination with: a) mouse or human gp10025-33 peptide plus CpG adjuvant; b) mouse or human gp100 gene; c) mouse or human gp10025-33 peptide-pulsed dendritic cells (DC). Alternatively, a neutralizing anti-IL-10 monoclonal antibody (mAb) was subcutaneously administered at the site of tumor challenge to counteract regulatory cells. Finally, combinatorial treatment was performed associating human gp10025-33 peptide-pulsed DC vaccination with administration of the anti-IL-10 mAb.

Results
Vaccination with human gp10025-33 peptide-pulsed DC was the most effective immunization protocol, although not achieving a full protection. Administration of the anti-IL-10 mAb showed also a remarkable protective effect, replicated in mice challenged with a different tumor, Anaplastic Large Cell Lymphoma. When immunization with gp10025-33 peptide-pulsed DC was associated with IL-10 counteraction, a 100% protective effect was consistently achieved. The analysis on the T-cell tumor infiltrates showed an increase of CD4+granzyme+ T-cells and a decreased number of CD4+CD25+Foxp3+ Treg elements from mice treated with either gp10025-33 peptide-pulsed DC vaccination or anti-IL-10 mAb administration. These data suggest that processes of intratumoral re-balance between effector and regulatory T cell subpopulations may play a critical protective role in immunotherapy protocols.

Conclusions
Here we demonstrate that, in the setting of a cancer vaccine strategy, a comparative analysis of different personalized approaches may favour the unveiling of the most effective protocol. Moreover, our findings suggest that counteraction of IL-10 activity may be critical to revert the intratumoral environment promoting Treg polarization, thus increasing the effects of a vaccination against selected TAA.
Depression as a non-causal variable risk marker in coronary heart disease
Authors: Meijer Anna , Zuidersma Marij , de Jonge Peter 
Published: May 2013

Abstract

Background
After decades of investigations, explanations for the prospective association between depression and coronary heart disease (CHD) are still incomplete.

Discussion
Depression is often suggested to be causally related to CHD. Based on the available literature, we would rather argue that depression can best be regarded as a variable risk marker, that is, a variable that fluctuates together with mechanisms leading to poor cardiovascular fitness. Despite numerous efforts, no evidence is found that manipulation of depression alters cardiovascular outcomes - a key premise for determining causality. To explain the concept of a variable risk marker, we discuss several studies on the heterogeneity of depression suggesting that depression is particularly harmful for the course of cardiovascular disease when it appears to be a physiological consequence of the cardiovascular disease itself.

Summary
We conclude that instead of depression being a causal risk factor for CHD, the association between depression and CHD is likely confounded, at least by the cardiac disease itself.
Using allometric procedures to substantiate the plastochrone method for eelgrass leaf growth assessments
Authors: Echavarría-Heras Héctor , Solana-Arellano Elena , Leal-Ramírez Cecilia , Castillo Oscar 
Published: May 2013

Abstract
Estimation of leaf productivity in eelgrass (Zostera marina L.) is crucial for evaluating the ecological role of this important seagrass species. Although leaf marking techniques are widely used to obtain estimates of leaf productivity, the accuracy of these assessments, has been questioned mainly because these fail to account for leaf growth bellow the reference mark and also because they apparently disregard the contribution of mature leaf tissues to the growth rate of leaves. On the other hand, the plastochrone method is a simpler technique that has been considered to effectively capture growth in a more realistic way, thereby providing more accurate assessments of both above- and below-ground productivities. But since the actual values of eelgrass growth rates are difficult to obtain, the worth of the plastochrone method has been largely vindicated because it produces assessments that overestimate productivity as compared to estimates obtained by leaf marking. Additionally, whenever eelgrass leaf biomass can be allometrically scaled in terms of matching leaf length in a consistent way, the associated leaf growth rates can be also projected allometrically. In this contribution, we used that approach to derive an authentication of the plastochrone method and formally demonstrate that, as has been claimed to occur for leaf marking approaches, the plastochrone method itself underestimates actual values of eelgrass leaf growth rates. We also show that this unavoidable bias is mainly due to the inadequacy of single-leaf biomass assessments in providing a proxy for the growth of all leaf tissue in a shoot over a given interval. Moreover, the derived formulae give conditions under which assessments of leaf growth rates using the plastochrone method would systematically underestimate matching values obtained by leaf marking procedures. And, assessments of leaf growth rates obtained by using the present data show that plastochrone method estimations underestimated corresponding proxies obtained allometrically (27%), or through leaf marking (35%). Allometric projection is recommended as a simpler and more effective procedure to reduce the bias in eelgrass leaf productivity estimations that associates to the use of plastochrone methods.