bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress Signaling Pathways for the Pathogenicity of Cryptococcus
Authors: Bahn Yong-Sun , Jung Kwang-Woo 
Published: September 2013

ABSTRACT

Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. This ability is also essential for
Cryptococcus neoformans
and its sibling species
Cryptococcus gattii
, as these pathogens have saprobic and parasitic life cycles in natural and animal host environments. The ability of
Cryptococcus
to cause fatal meningoencephalitis is highly related to its capability to remodel and optimize its metabolic and physiological status according to external cues. These cues act through multiple stress signaling pathways through a panoply of signaling components, including receptors/sensors, small GTPases, secondary messengers, kinases, transcription factors, and other miscellaneous adaptors or regulators. In this minireview, we summarize and highlight the importance of several stress signaling pathways that influence the pathogenicity of
Cryptococcus
and discuss future challenges in these areas.
ICE
Slu
van, a 94-Kilobase Mosaic Integrative Conjugative Element Conferring Interspecies Transfer of VanB-Type Glycopeptide Resistance, a Novel Bacitracin Resistance Locus, and a Toxin-Antitoxin Stabilization System
Authors: Bjørkeng Eva K. , Hjerde Erik , Pedersen Torunn , Sundsfjord Arnfinn , Hegstad Kristin 
Published: September 2013

ABSTRACT

A 94-kb integrative conjugative element (ICE
Slu
van) transferable to
Enterococcus faecium
and
Enterococcus faecalis
from an animal isolate of
Streptococcus lutetiensis
consists of a mosaic of genetic fragments from different Gram-positive bacteria. A variant of ICE
Slu
van was confirmed in
S. lutetiensis
from a patient. A complete Tn
5382
/Tn
1549
with a
vanB2
operon is integrated into a streptococcal ICE
Sde
3396-like region harboring a putative bacteriophage exclusion system, a putative agglutinin receptor precursor, and key components of a type IV secretion system. Moreover, ICE
Slu
van encodes a putative MobC family mobilization protein and a relaxase and, thus, in total has all genetic components essential for conjugative transfer. A 9-kb element within Tn
5382
/Tn
1549
encodes, among others, putative proteins similar to the TnpX site-specific recombinase in
Faecalibacterium
and VanZ in
Paenibacillus
, which may contribute to the detected low-level teicoplanin resistance. Furthermore, ICE
Slu
van encodes a novel bacitracin resistance locus that is associated with reduced susceptibility to bacitracin when transferred to
E. faecium
. The expression of a streptococcal
pezAT
toxin-antitoxin-encoding operon of ICE
Slu
van in
S. lutetiensis
,
E. faecium
, and
E. faecalis
was confirmed by reverse transcription (RT)-PCR, indicating an active toxin-antitoxin system which may contribute to stabilizing ICE
Slu
van within new hosts. Junction PCR and DNA sequencing confirmed that ICE
Slu
van excised to form a circular intermediate in
S. lutetiensis
,
E. faecalis
, and
E. faecium
. Transfer between
E. faecalis
cells was observed in the presence of helper plasmid pIP964. Sequence analysis of the original
S. lutetiensis
donor and enterococcal transconjugants showed that ICE
Slu
van integrates in a site-specific manner into the C-terminal end of the chromosomal tRNA methyltransferase gene
rumA
.
Advertising, Expectations and Informed Consent: The Contents and Functions of Acupuncture Leaflets
Authors: Bishop Felicity L , Salmon Cathy 
Published: September 2013

Objective To evaluate the content of patient information leaflets about acupuncture. Methods 401 patient information leaflets were obtained from practising UK acupuncturists and subjected to content and thematic analysis. Results 59% of included leaflets were from NHS physiotherapists. Almost all the leaflets defined acupuncture and the majority explained how it might work, described the treatment process and placed it in a historical context. Most described possible benefits and risks of acupuncture and discussed contraindications and safety. Just under a third of leaflets (120, 30%) suggested conditions that might be helped by acupuncture, most commonly musculoskeletal pain, arthritis and injuries. By emphasising differences between individuals in acupuncture treatments and responsiveness, the leaflets fostered hope for positive effects without making any guarantees. Conclusions Information leaflets are broadly consistent with the evidence for acupuncture, but some claims are inconsistent with official advice from advertising regulators. An ethically sound, scientifically grounded and psychologically effective leaflet should accurately convey both benefits and risks of treatment, optimise patients’ expectations and allay concerns about needling. This study suggests that acupuncture leaflets might achieve these multiple functions but care should be taken to ensure adequate coverage of risks.
Endovascular treatment of fusiform intracranial vertebral artery aneurysms using reconstructive techniques
Authors: Dabus Guilherme , Lin Eugene , Linfante Italo 
Published: September 2013

ObjectiveTo report our single center experience in the treatment of fusiform aneurysms involving the intracranial vertebral arteries using reconstructive endovascular techniques.Patients and methodsThe neurointerventional database of our institution was retrospectively reviewed from June 2010 to February 2013. Patients who underwent endovascular treatment of fusiform intracranial vertebral artery aneurysms using reconstructive techniques were included in the analysis. Clinical presentation, size, reconstructive technique used, procedural complication, and clinical and angiographic follow-ups were included in the analysis.ResultsNine patients, aged 41–76 years (mean 54.8 years), were included. Mean angiographic diameter of unruptured aneurysms was 8.4 mm (range 4–14) while ruptured aneurysms averaged 6 mm (range 5–7 ). Two patients (two women) presented with acute subarachnoid hemorrhage (SAH). One patient with a large partially thrombosed aneurysm was treated with stent reconstruction requiring deployment of two stents (no coiling). There was one asymptomatic procedural complication (non-flow limiting cervical vertebral dissection). All patients had good clinical outcomes (modified Rankin Scale score of 0 or ≤1) including the two patients that presented with SAH (Hunt and Hess grades 2 and 3). There were no late hemorrhages at a mean clinical follow-up of 12 months (6–24 months). Eight patients had angiographic follow-up (6–18 months, mean 10.5 months) and six demonstrated aneurysm occlusion with complete vessel reconstruction at the angiographic follow-up.ConclusionsThe use of reconstructive techniques in the endovascular treatment of unruptured fusiform intracranial vertebral artery aneurysms is feasible, safe, and effective in the mid term. In patients presenting with SAH, however, the safety and effectiveness of these techniques remain unclear.
Levels of advertised unprotected vaginal and oral sex by independent indoor female sex workers in West Yorkshire, UK
Authors: Eccles Claire , Clarke Janette 
Published: September 2013

ObjectivesTo assess the proportion of independent indoor female sex workers (FSW) in West Yorkshire, UK who advertise unprotected sex, and to investigate any association with cost, location and provision of anal sex.MethodsData on whether independent indoor FSW (defined as those not advertising via an escort agency or through a parlour) advertised unprotected sexual services, along with demographic data, were collected from 462 advertisement profiles of FSW in West Yorkshire from the websitehttp://www.adultwork.com. Independent t test and χ2statistics were used to test the association between advertised unprotected vaginal and oral sex, and FSW age, cost of services, location and whether they advertised anal sex.ResultsUnprotected vaginal sex was advertised by 8% of FSW, and unprotected oral sex by 74% of FSW. FSW advertising unprotected vaginal sex were more likely to live in Wakefield and Bradford than in Leeds, had significantly lower hourly rates, and were more likely to advertise anal sex.ConclusionsAdvertised condom use for vaginal and oral sex by independent indoor FSW in West Yorkshire was significantly lower than reported rates of protected sex found in previous studies based in London and the south of England. The advertisement of unprotected vaginal sex is associated with factors such as lower hourly rates and the advertisement of higher risk anal sex, which may signify greater economic need. FSW offering unprotected sex therefore represent an at-risk target group for health promotion.
A DNA Methylation Prognostic Signature of Glioblastoma: Identification of NPTX2-PTEN-NF-κB Nexus
Authors: Shukla Sudhanshu , Pia Patric Irene Rosita , Thinagararjan Sivaarumugam , Srinivasan Sujaya , Mondal Baisakhi , Hegde Alangar S. , Chandramouli Bangalore A. , Santosh Vani , Arivazhagan Arimappamagan , Somasundaram Kumaravel 
Published: September 2013

Abstract
Glioblastoma (GBM) is the most common, malignant adult primary tumor with dismal patient survival, yet the molecular determinants of patient survival are poorly characterized. Global methylation profile of GBM samples (our cohort; n = 44) using high-resolution methylation microarrays was carried out. Cox regression analysis identified a 9-gene methylation signature that predicted survival in GBM patients. A risk-score derived from methylation signature predicted survival in univariate analysis in our and The Cancer Genome Atlas (TCGA) cohort. Multivariate analysis identified methylation risk score as an independent survival predictor in TCGA cohort. Methylation risk score stratified the patients into low-risk and high-risk groups with significant survival difference. Network analysis revealed an activated NF-κB pathway association with high-risk group. NF-κB inhibition reversed glioma chemoresistance, and RNA interference studies identified interleukin-6 and intercellular adhesion molecule-1 as key NF-κB targets in imparting chemoresistance. Promoter hypermethylation of neuronal pentraxin II (NPTX2), a risky methylated gene, was confirmed by bisulfite sequencing in GBMs. GBMs and glioma cell lines had low levels of NPTX2 transcripts, which could be reversed upon methylation inhibitor treatment. NPTX2 overexpression induced apoptosis, inhibited proliferation and anchorage-independent growth, and rendered glioma cells chemosensitive. Furthermore, NPTX2 repressed NF-κB activity by inhibiting AKT through a p53-PTEN-dependent pathway, thus explaining the hypermethylation and downregulation of NPTX2 in NF-κB-activated high-risk GBMs. Taken together, a 9-gene methylation signature was identified as an independent GBM prognosticator and could be used for GBM risk stratification. Prosurvival NF-κB pathway activation characterized high-risk patients with poor prognosis, indicating it to be a therapeutic target. Cancer Res; 73(22); 6563–73. ©2013 AACR.
New Strategies in Radiation Therapy: Exploiting the Full Potential of Protons
Authors: Mohan Radhe , Mahajan Anita , Minsky Bruce D. 
Published: September 2013

Abstract
Protons provide significant dosimetric advantages compared with photons because of their unique depth–dose distribution characteristics. However, they are more sensitive to the effects of intra- and intertreatment fraction anatomic variations and uncertainties in treatment setup. Furthermore, in the current practice of proton therapy, the biologic effectiveness of protons relative to photons is assumed to have a generic fixed value of 1.1. However, this is a simplification, and it is likely higher in different portions of the proton beam. Current clinical practice and trials have not fully exploited the unique physical and biologic properties of protons. Intensity-modulated proton therapy, with its ability to manipulate energies (in addition to intensities), provides an entirely new dimension, which, with ongoing research, has considerable potential to increase the therapeutic ratio. Clin Cancer Res; 19(23); 6338–43. ©2013 AACR.
Associations between Single-Nucleotide Polymorphisms in the PI3K–PTEN–AKT–mTOR Pathway and Increased Risk of Brain Metastasis in Patients with Non–Small Cell Lung Cancer
Authors: Li Qianxia , Yang Ju , Yu Qianqian , Wu Huanlei , Liu Bo , Xiong Huihua , Hu Guangyuan , Zhao Jing , Yuan Xianglin , Liao Zhongxing 
Published: September 2013

Abstract
Purpose: Non–small cell lung cancer (NSCLC) metastasizes fairly often to the brain, but identifying which patients will develop brain metastases is problematic. The phosphoinositide 3-kinase (PI3K)–AKT–mTOR signaling pathway is important in the control of cell growth, tumorigenesis, and cell invasion. We hypothesized that genotype variants in this pathway could predict brain metastasis in patients with NSCLC.
Methods: We genotyped 16 single-nucleotide polymorphisms (SNP) in five core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) by using DNA from blood samples of 317 patients with NSCLC, and evaluated potential associations with the subsequent development of brain metastasis, the cumulative incidence of which was estimated with Kaplan–Meier analysis. Multivariate Cox regression analysis was used to analyze correlations between genotype variants and the occurrence of brain metastasis.
Results: In analysis of individual SNPs, the GT/GG genotype of AKT1: rs2498804, CT/TT genotype of AKT1: rs2494732, and AG/AA genotype of PIK3CA: rs2699887 were associated with higher risk of brain metastasis at 24-month follow-up [respective HRs, 1.860, 95% confidence interval (CI) 1.199–2.885, P = 0.006; HR 1.902, 95% CI 1.259–2.875, P = 0.002; and HR 1.933, 95% CI 1.168–3.200, P = 0.010]. We further found that these SNPs had a cumulative effect on brain metastasis risk, with that risk being highest for patients carrying both of these unfavorable genotypes (P = 0.003).
Conclusions: Confirmation of our findings, the first to indicate that genetic variations in PI3K–AKT–mTOR can predict brain metastasis, in prospective studies would facilitate stratification of patients for brain metastasis prevention trials. Clin Cancer Res; 19(22); 6252–60. ©2013 AACR.
Promoter Hypomethylation of EpCAM-Regulated Bone Morphogenetic Protein Gene Family in Recurrent Endometrial Cancer
Authors: Hsu Ya-Ting , Gu Fei , Huang Yi-Wen , Liu Joseph , Ruan Jianhua , Huang Rui-Lan , Wang Chiou-Miin , Chen Chun-Liang , Jadhav Rohit R. , Lai Hung-Cheng , Mutch David G. , Goodfellow Paul J. , Thompson Ian M. , Kirma Nameer B. , Huang Tim Hui-Ming 
Published: September 2013

Abstract
Purpose: Epigenetic regulation by promoter methylation plays a key role in tumorigenesis. Our goal was to investigate whether altered DNA methylation signatures associated with oncogenic signaling delineate biomarkers predictive of endometrial cancer recurrence.
Experimental Design: Methyl-CpG-capture sequencing was used for global screening of aberrant DNA methylation in our endometrial cancer cohort, followed by validation in an independent The Cancer Genome Atlas (TCGA) cohort. Bioinformatics as well as functional analyses in vitro, using RNA interference (RNAi) knockdown, were performed to examine regulatory mechanisms of candidate gene expression and contribution to aggressive phenotype, such as epithelial–mesenchymal transition (EMT).
Results: We identified 2,302 hypermethylated loci in endometrial tumors compared with control samples. Bone morphogenetic protein (BMP) family genes, including BMP1, 2, 3, 4, and 7, were among the frequently hypermethylated loci. Interestingly, BMP2, 3, 4, and 7 were less methylated in primary tumors with subsequent recurrence and in patients with shorter disease-free interval compared with nonrecurrent tumors, which was validated and associated with poor survival in the TCGA cohort (BMP4, P = 0.009; BMP7, P = 0.007). Stimulation of endometrial cancer cells with epidermal growth factor (EGF) induced EMT and transcriptional activation of these genes, which was mediated by the epithelial cell adhesion molecule (EpCAM). EGF signaling was implicated in maintaining the promoters of candidate BMP genes in an active chromatin configuration and thus subject to transcriptional activation.
Conclusions: Hypomethylation signatures of candidate BMP genes associated with EpCAM-mediated expression present putative biomarkers predictive of poor survival in endometrial cancer. Clin Cancer Res; 19(22); 6272–85. ©2013 AACR.
Another Surprise from Metformin: Novel Mechanism of Action via K-Ras Influences Endometrial Cancer Response to Therapy
Authors: Iglesias David A. , Yates Melinda S. , van der Hoeven Dharini , Rodkey Travis L. , Zhang Qian , Co Ngai Na , Burzawa Jennifer , Chigurupati Sravanthi , Celestino Joseph , Bowser Jessica , Broaddus Russell , Hancock John F. , Schmandt Rosemarie , Lu Karen H. 
Published: September 2013

Abstract
Metformin is an oral biguanide commonly used for the treatment of type II diabetes and has recently been demonstrated to possess antiproliferative properties that can be exploited for the prevention and treatment of a variety of cancers. The mechanisms underlying this effect have not been fully elucidated. Using both in vitro and in vivo models, we examined the effects of metformin on endometrial tumors with defined aberrations in the PI3K/PTEN/mTOR and MAPK signaling pathways to understand metformin mechanism of action and identify clinically useful predictors of response to this agent. In vitro assays of proliferation, cytotoxicity, and apoptosis were used to quantify the effects of metformin on endometrial cancer cell lines with mutations in the PI3K/PTEN/mTOR and MAPK signaling pathways. The in vivo effects of oral metformin on tumor progression were further examined using xenograft mouse models of endometrial cancer. K-Ras localization was analyzed by confocal microscopy using GFP-labeled oncogenic K-Ras and by immunoblot following subcellular fractionation. Metformin inhibited cell proliferation, induced apoptosis, and decreased tumor growth in preclinical endometrial cancer models, with the greatest response observed in cells harboring activating mutations in K-Ras. Furthermore, metformin displaces constitutively active K-Ras from the cell membrane, causing uncoupling of the MAPK signaling pathway. These studies provide a rationale for clinical trials using metformin in combination with PI3K-targeted agents for tumors harboring activating K-Ras mutations, and reveal a novel mechanism of action for metformin. Mol Cancer Ther; 12(12); 2847–56. ©2013 AACR.
Association of Low-Grade Albuminuria With Adverse Cardiac Mechanics
Authors: Katz Daniel H. , Selvaraj Senthil , Aguilar Frank G. , Martinez Eva E. , Beussink Lauren , Kim Kwang-Youn A. , Peng Jie , Sha Jin , Irvin Marguerite R. , Eckfeldt John H. , Turner Stephen T. , Freedman Barry I. , Arnett Donna K. , Shah Sanjiv J. 
Published: September 2013

Background—
Albuminuria is a marker of endothelial dysfunction and has been associated with adverse cardiovascular outcomes. The reasons for this association are unclear but may be attributable to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction.

Methods and Results—

In the Hypertension Genetic Epidemiology Network (HyperGEN) Study, a population- and family-based study of hypertension, we examined the relationship between urine albumin-to-creatinine ratio (UACR) and cardiac mechanics (n=1894, all of whom had normal left ventricular ejection fraction and wall motion). We performed speckle-tracking echocardiographic analysis to quantify global longitudinal, circumferential, and radial strain, and early diastolic (e′) tissue velocities. We used E/e′ ratio as a marker of increased left ventricular filling pressures. We used multivariable-adjusted linear mixed effect models to determine independent associations between UACR and cardiac mechanics. The mean age was 50±14 years, 59% were female, and 46% were black. Comorbidities were increasingly prevalent among higher UACR quartiles. Albuminuria was associated with global longitudinal strain, global circumferential strain, global radial strain, e′ velocity, and E/e′ ratio on unadjusted analyses. After adjustment for covariates, UACR was independently associated with lower absolute global longitudinal strain (multivariable-adjusted mean global longitudinal strain [95% confidence interval] for UACR Quartile 1 = 15.3 [15.0–15.5]% versus UACR Q4 = 14.6 [14.3–14.9]%,
P
for trend <0.001) and increased E/e′ ratio (Q1 = 25.3 [23.5–27.1] versus Q4 = 29.0 [27.0–31.0],
P
=0.003). The association between UACR and global longitudinal strain was present even in participants with UACR < 30 mg/g (
P
<0.001 after multivariable adjustment).

Conclusions—
Albuminuria, even at low levels, is associated with adverse cardiac mechanics and higher E/e′ ratio.
Continuously moving table aorto-iliofemoral run-off contrast-enhanced magnetic resonance angiography: image quality analysis in comparison to the multistep acquisition
Authors: Asbach Patrick , Meade Michael D , Sattenberg Ronald J , Klessen Christian , Huppertz Alexander , Heidenreich Jens O 
Published: September 2013

Background Optimal vessel contrast is a prerequisite for vascular imaging. Consecutive stationary imaging of multiple fields of view is contrary to the continuous contrast material passage through the vascular tree. A continuous acquisition of a magnetic resonance (MR) sequence might overcome this limitation. Purpose To investigate the image quality of a continuously moving table (CMT) acquisition compared with the established multistep approach for contrast-enhanced magnetic resonance angiography (CE-MRA) of the aorto-iliofemoral run-off. Material and Methods Institutional review board approved this retrospective interindividual study of 60 consecutive patients referred to CE-MRA for peripheral arterial disease. Thirty patients underwent CE-MRA using the routine multistep acquisition and 30 patients were scanned using the CMT technique at 1.5 Tesla. All patients received a fixed contrast dose of 25 mL gadoterate meglumine. A quantitative analysis was performed to assess the relative contrast of 10 vascular segments from the proximal abdominal aorta to the distal calf arteries. A qualitative evaluation of three separate vascular regions (abdomen and pelvis, thighs, and calves) was performed. Two radiologists graded independently arterial vessel conspicuity, venous contamination, presence of artifacts, and diagnostic confidence on a 4-point scale. Overall scan time, including all localizer scans, was recorded. Statistical differences were tested using the Wilcoxon signed-rank test with Bonferroni correction. Results No significant differences were found between the continuously moving table acquisition and the multistep acquisition with regard to the relative vascular contrast and the qualitative image criteria. The agreement between both readers was significant (Kendall tau rank correlation coefficient, 0.373). The absolute reader agreement was 71.4%. The mean overall scan time was 12 min 44 s for the CMT protocol and 21 min 41 s for the multistep protocol. Conclusion Aorto-iliofemoral run-off CE-MRA acquired with CMT technique provides a high image quality equivalent to a multistep technique at an overall scan time reduction of 41.3%.