bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-Genome Sequences of Two Staphylococcus aureus ST398 Strains of Human Origin, S94 and S100
Authors: Corvaglia Anna-Rita , François Patrice , Bertrand Xavier , Quentin Roland , Hernandez David , van der Mee-Marquet Nathalie 
Published: August 2013

ABSTRACT

Sequence type 398 (ST398)
Staphylococcus aureus
was originally associated with animal infection. We announce the complete genome sequences of two ST398 methicillin-susceptible
S. aureus
strains of human origin, S94 and S100. The genome sequences assist in the characterization of interesting ST398 features related to host specificities
.
A Tumorigenic Factor Interactome Connected through Tumor Suppressor MicroRNA-198 in Human Pancreatic Cancer
Authors: Marin-Muller Christian , Li Dali , Bharadwaj Uddalak , Li Min , Chen Changyi , Hodges Sally E. , Fisher William E. , Mo Qianxing , Hung Mien-Chie , Yao Qizhi 
Published: August 2013

Abstract
Purpose: The majority of pancreatic cancers overexpress mesothelin (MSLN), which contributes to enhanced proliferation, invasion, and migration. However, the MSLN regulatory network is still unclear. Here, we investigated the regulation of a panel of tumorigenic factors and explored the potential of MSLN-regulated miR-198 treatment in vivo.
Experimental Design: The expression and functional regulation of the tumorigenic factors MSLN, NF-κB, and the homeobox transcription factors (TF) POU2F2 (OCT-2), Pre-B-cell leukemia homeobox factor 1 (PBX-1), valosin-containing protein (VCP), and miR-198 were studied in pancreatic cancer cell lines, patient tumor samples, and xenograft pancreatic cancer mouse models.
Results: We found that miR-198 is downregulated in pancreatic cancer and is involved in an intricate reciprocal regulatory loop with MSLN, which represses miR-198 through NF-κB–mediated OCT-2 induction. Furthermore, miR-198 repression leads to overexpression of PBX-1 and VCP. The dysregulated PBX-1/VCP axis leads to increased tumorigenicity. Reconstitution of miR-198 in pancreatic cancer cells results in reduced tumor growth, metastasis, and increased survival through direct targeting MSLN, PBX-1, and VCP. Most interestingly, reduced levels of miR-198 in human tissue samples are associated with upregulation of these tumorigenic factors (MSLN, OCT-2, PBX-1, VCP) and predict poor survival. Reduced miR-198 expression links this tumor network signature and prognosticates poor patient outcome. High miR-198 disrupts the network and predicts better prognosis and increased survival.
Conclusions: miR-198 acts as a central tumor suppressor and modulates the molecular makeup of a critical interactome in pancreatic cancer, indicating a potential prognostic marker signature and the therapeutic potential of attacking this tumorigenic network through a central vantage point. Clin Cancer Res; 19(21); 5901–13. ©2013 AACR.
Inhibition of Hedgehog and Androgen Receptor Signaling Pathways Produced Synergistic Suppression of Castration-Resistant Prostate Cancer Progression
Authors: Gowda Pramod S. , Deng Jianhong D. , Mishra Sweta , Bandyopadhyay Abhik , Liang Sitai , Lin Shu , Mahalingam Devalingam , Sun Lu-Zhe 
Published: August 2013

Abstract
Metastatic prostate cancer is initially treated with androgen ablation therapy, which causes regression of androgen-dependent tumors. However, these tumors eventually relapse resulting in recurrent castration-resistant prostate cancer (CRPC). Currently, there is no effective therapy for CRPC and the molecular mechanisms that lead to the development of CRPC are not well understood. Here, we evaluated the hypothesis that combined inhibition of Hedgehog (Hh) and androgen receptor (AR) signaling will synergistically attenuate the growth of CRPC in vitro and in vivo. Androgen deprivation induced full-length androgen receptor protein levels in CRPC cells, but decreased its nuclear localization and transcriptional activity. However, androgen deprivation also increased a truncated form of androgen receptor (lacking ligand-binding domain) that possessed transcriptional activity in CRPC cells. Androgen deprivation also promoted the expression of Hh signaling components in CRPC cells, xenograft tumors, and the prostate glands of castrated mice. Importantly, although inhibition of either Hh or androgen receptor signaling alone was only moderately effective in blocking CRPC cell growth, combination of an Hh pathway inhibitor and a noncompetitive androgen receptor inhibitor synergistically suppressed the growth of CRPC cells in vitro and in vivo. Finally, noncompetitive inhibition of androgen receptor, but not competitive inhibition, was effective at limiting the activity of truncated androgen receptor leading to the inhibition of CRPC.
Implications: Combined therapy using Hh inhibitors and a non-competitive AR inhibitor may limit CRPC growth. Mol Cancer Res; 11(11); 1448–61. ©2013 AACR.
Inverse Association between Programmed Death Ligand 1 and Genes in the VEGF Pathway in Primary Clear Cell Renal Cell Carcinoma
Authors: Joseph Richard W. , Parasramka Mansi , Eckel-Passow Jeanette E. , Serie Dan , Wu Kevin , Jiang Liuyan , Kalari Krishna , Thompson R. Houston , Huu Ho Thai , Castle Erik P. , Cheville John , Kwon Eugene D. , Thompson E. Aubrey , Parker Alexander 
Published: August 2013

Abstract
Increased angiogenesis and tumor-induced immune evasion are two mechanisms by which clear cell renal cell carcinoma (ccRCC) proliferate and metastasize; however, the relationship between these pathways in human ccRCC is poorly understood. We conducted a nested case–control study using 98 archived tumor samples from patients diagnosed with primary ccRCC between 1990 and 2006, half of which were identified by immunohistochemistry (IHC) as either programmed death ligand 1 (PDL-1)–positive or PDL-1–negative. RNAs were extracted from the formalin-fixed paraffin-embedded tumor slides and the expression of the VEGFA, VEGFR1, VEGFR2, and PDL-1 genes was quantified. We assessed the presence of tumor-infiltrating lymphocytes (TIL) by IHC for CD3, and then analyzed the relationship among VEGFA, VEGFR1, VEGFR2, CD3, and PDL-1. When analyzed as a continuous variable, PDL-1 protein expression by IHC inversely correlates with the expression of the three VEGF-related genes: VEGFA (r = −0.23; P = 0.01), VEGFR1 (r = −0.34; P &lt; 0.001), and VEGFR2 (r = −0.23; P = 0.01). When dichotomized, the PDL-1–positive cohort trended toward a lower expression of VEGFA (fold change = 0.72; P = 0.056) and VEGFR1 (fold change = 0.69; P = 0.057). In addition, there was a significant and positive relationship between the presence of TIL as assessed by IHC for CD3 and PDL-1 by IHC (r = 0.25; P = 0.015), and there was a trend toward an inverse relationship between TIL and VEGFA gene expression (r = −0.18; P = 0.089). In conclusion, this is the first demonstration of an inverse association between the angiogenesis and PDL-1 pathways in tumor samples from primary ccRCC, and this relationship may be related to the immunosuppressive effects of VEGF signaling. Cancer Immunol Res; 1(6); 378–85. ©2013 AACR.
Test Accuracy of Short Screening Tests for Diagnosis of Delirium or Cognitive Impairment in an Acute Stroke Unit Setting
Authors: Lees Rosalind , Corbet Sinead , Johnston Christina , Moffitt Emma , Shaw Grahame , Quinn Terence J. 
Published: August 2013

Background and Purpose—
Guidelines recommend cognitive screening in acute stroke. Various instruments are available, with no consensus on a preferred tool. We aimed to describe test accuracy of brief screening tools for diagnosis of cognitive impairment and delirium in acute stroke.

Methods—
We collected data on sequential stroke unit admission in a single center. Four assessors trained in cognitive testing independently performed screening and reference tests. Brief assessments comprised the following: 10- and 4-point Abbreviated Mental Test (AMT-10; AMT-4); 4-A Test (4AT); Clock Drawing Test (CDT); Cog-4; and Glasgow Coma Scale (GCS). We also recorded the multidisciplinary team’s informal review using single question (SQ). We compared against reference standards of Montreal Cognitive Assessment (MoCA) and Confusion Assessment Method for delirium using usual diagnostic cutpoints. For MoCA, we described effects of lowering the diagnostic threshold to MoCA <24 and MoCA <20. We described sensitivity, specificity, and positive and negative predictive values.

Results—
Over a 10-week period, 111 subjects had cognitive assessment data. Subjects were 50% male (n=55), and median age was 74 years (interquartile range, 64–85). AMT-4, AMT-10, and SQ all had excellent (1.00) specificity for detection of cognitive impairment, although sensitivity was poor (all <0.60). The 4AT had greatest sensitivity for detecting delirium (1.00 [confidence interval [CI], 0.74–1.00]) and reasonable specificity (0.82 [CI, 0.72–0.89]). Properties of 4AT for detection of cognitive impairment, at the traditional MoCA threshold, were also good (sensitivity, 0.86; specificity, 0.78). Using diagnostic thresholds of MoCA ≤26, <24, and <20 gave proportions with cognitive impairments of 86%, 61%, and 49%, respectively, with resulting changes in screening test properties. At lower MoCA thresholds, CDT had favorable sensitivity and specificity (MoCA <20: sensitivity, 0.93, specificity, 0.66; MoCA <24: sensitivity, 0.85, specificity, 0.77).

Conclusions—
Many brief screening assessments are specific but not sensitive for detection of cognitive impairment in acute stroke. Our primary analysis suggests that 4AT is a reasonable choice for delirium and cognitive screening in this setting. However, these data are based on standard MoCA diagnostic threshold and may not be suited for an acute stroke population.
Quantitative Analysis of Hypoperfusion in Acute Stroke
Authors: Nael Kambiz , Meshksar Arash , Liebeskind David S. , Coull Bruce M. , Krupinski Elizabeth A. , Villablanca J. Pablo 
Published: August 2013

Background and Purpose—
This study compares the concordance between arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) for the identification of regional hypoperfusion and diffusion-perfusion mismatch tissue classification using a quantitative method.

Methods—
The inclusion criteria for this retrospective study were as follows: patients with acute ischemic syndrome with symptom onset <24 hours and acquisition of both ASL and DSC MR perfusion. The volumes of infarction and hypoperfused lesions were calculated on ASL and DSC multi-parametric maps. Patients were classified into reperfused, matched, or mismatch groups using time to maximum >6 sec as the reference. In a subset of patients who were successfully recanalized, the identical analysis was performed and the infarction and hypoperfused lesion volumes were used for paired pre- and posttreatment comparisons.

Results—

Forty-one patients met our inclusion criteria. Twenty patients underwent successful endovascular revascularization (TICI>2a), resulting in a total of 61 ASL-DSC data pairs for comparison. The hypoperfusion volume on ASL-cerebral blood flow best approximated the DSC-time to peak volume (
r
=0.83) in pretreatment group and time to maximum (
r
=0.46) after recanalization. Both ASL-cerebral blood flow and DSC-TTP overestimated the hypoperfusion volume compared with time to maximum volume in pretreatment (
F
=27.41,
P
<0.0001) and recanalized patients (
F
=8.78,
P
<0.0001).

Conclusions—
ASL-cerebral blood flow overestimates the DSC time to maximum hypoperfusion volume and mismatch classification in patients with acute ischemic syndrome. Continued overestimation of hypoperfused volume after recanalization suggests flow pattern and velocity changes in addition to arterial transit delay can affects the performance of ASL.
Sports Diplomacy: The Chinese Experience and Perspective
Authors: Qingmin Zhang 
Published: August 2013

Summary
Sport is a political and diplomatic arena where politics parodies sport and vice versa. When relations between two nations are poor, sport can be employed as a tool to heighten confrontation or, if relations start to improve, sport can also create and accelerate diplomatic momentum. In both cases, sport is politicized, but in the Chinese perspective only the latter instance can be considered as sports diplomacy. Sport itself is neither sufficient for diplomatic breakthrough, nor sufficient for diplomatic breakdown. The increasing importance of sports diplomacy also validates the transformation of traditional to new diplomacy.
Ikaros limits basophil development by suppressing C/EBP-α expression
Authors: Rao Kavitha N. , Smuda Craig , Gregory Gregory D. , Min Booki , Brown Melissa A. 
Published: August 2013

Key PointsIk−/− mice overproduce basophils and their precursors in the absence of extrinsic inflammatory signals. Ikaros restrains development of basophils by regulating histone modifications at lineage-specifying genes, including Cebpa and Hes1.
Are concomitant treatments confounding factors in randomized controlled trials on intensive blood-glucose control in type 2 diabetes? a systematic review
Authors: Boussageon Rémy , Supper Irène , Erpeldinger Sylvie , Cucherat Michel , Bejan-Angoulvant Theodora , Kassai Behrouz , Cornu Catherine , Gueyffier François 
Published: August 2013

Abstract

Background
Open-label, randomized controlled trials (RCTs) are subject to observer bias. If patient management is conducted without blinding, a difference between groups may be explained by other factors than study treatment. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. In type 2 diabetes, some antihypertensive or lipid-lowering drugs are effective against diabetic complications. We wanted to determine if these concomitant treatments were correctly reported in articles of RCTs on type 2 diabetes and if they might have influenced the outcome.

Methods
We performed a systematic review using Medline, Embase, and the Cochrane Library (from January 1950 to July 2010). Open-label RCTs assessing the effectiveness of intensive blood-glucose control in type 2 diabetes were included. We chose five therapeutic classes with proven efficacy against diabetes complications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs), fibrates, statins, and aspirin. Differences between concomitant treatments were considered statistically significant when p < 0.05.

Results
A total of eight open-label RCTs were included, but only three (37.5%) of them published concomitant treatments. In two studies (ACCORD and ADVANCE), a statistically significant difference was observed between the two groups for aspirin (p = 0.02) and ACEIs (p = 0.02).

Conclusions
Few concomitant treatments were published in this sample of open-label RCTs. We cannot completely eliminate an observer bias for these studies. This bias probably influenced the results to an extent that has yet to be determined.
Geriatric assessment in undergraduate geriatric education – a structured interpretation guide improves the quantity and accuracy of the results: a cohort comparison
Authors: Igenbergs Elisabeth , Deutsch Tobias , Frese Thomas , Sandholzer Hagen 
Published: August 2013

Abstract

Background
With regard to the growing proportion of elderly multimorbid patients, a sound undergraduate geriatric education becomes more important. Therefore we included the execution and interpretation of a comprehensive geriatric assessment (CGA) into a mandatory two-week clerkship at a general practitioner's office. The present study examined the effect of a guide structuring the students’ considerations when interpreting a CGA on the quantity and accuracy of the documented findings and conclusions.

Methods
We compared random samples out of two cohorts of fourth-year medical students (interpreting the CGA with and without using the structured interpretation guide) completing their clerkship between April 2006 and March 2008 with regard to the content of the CGA interpretation and the grades the students achieved for their clerkship documentation, which were substantially determined by the quantity and accuracy of the documentation and interpretation of the CGA.

Results
The structured interpretation guide led to significantly more mentions of aspects that have to be considered in geriatric patient care and to a higher documentation rate of respective positive results. Furthermore, students who analysed the CGA by using the interpretation guide achieved significantly better grades.

Conclusions
An additional tool structuring medical students’ considerations when interpreting a CGA increases the quantity and the accuracy of the documented findings and conclusions. This may enhance the students’ learning gain.
Mahanine restores RASSF1A expression by down-regulating DNMT1 and DNMT3B in prostate cancer cells
Authors: Agarwal Soumik , Amin Karishma S , Jagadeesh Shankar , Baishay Gokul , Rao Paruchuri G , Barua Nabin C , Bhattacharya Samir , Banerjee Partha P 
Published: August 2013

Abstract

Background
Hypermethylation of the promoter of the tumor suppressor gene RASSF1A silences its expression and has been found to be associated with advanced grade prostatic tumors. The DNA methyltransferase (DNMT) family of enzymes are known to be involved in the epigenetic silencing of gene expression, including RASSF1A, and are often overexpressed in prostate cancer. The present study demonstrates how mahanine, a plant-derived carbazole alkaloid, restores RASSF1A expression by down-regulating specific members of the DNMT family of proteins in prostate cancer cells.

Results
Using methylation-specific PCR we establish that mahanine restores the expression of RASSF1A by inducing the demethylation of its promoter in prostate cancer cells. Furthermore, we show that mahanine treatment induces the degradation of DNMT1 and DNMT3B, but not DNMT3A, via the ubiquitin-proteasome pathway; an effect which is rescued in the presence of a proteasome inhibitor, MG132. The inactivation of Akt by wortmannin, a PI3K inhibitor, results in a similar down-regulation in the levels DNMT1 and DNMT3B. Mahanine treatment results in a decline in phospho-Akt levels and a disruption in the interaction of Akt with DNMT1 and DNMT3B. Conversely, the exogenous expression of constitutively active Akt inhibits the ability of mahanine to down-regulate these DNMTs, suggesting that the degradation of DNMT1 and DNMT3B by mahanine occurs via Akt inactivation.

Conclusions
Taken together, we show that mahanine treatment induces the proteasomal degradation of DNMT1 and DNMT3B via the inactivation of Akt, which facilitates the demethylation of the RASSF1A promoter and restores its expression in prostate cancer cells. Therefore, mahanine could be a potential therapeutic agent for advanced prostate cancer in men when RASSF1A expression is silenced.
Improving activity of minicellulosomes by integration of intra- and intermolecular synergies
Authors: Xu Qi , Ding Shi-You , Brunecky Roman , Bomble Yannick J , Himmel Michael E , Baker John O 
Published: August 2013

Abstract

Background
Complete hydrolysis of cellulose to glucose requires the synergistic action of three general types of glycoside hydrolases; endoglucanases, exoglucanases, and cellobiases. Cellulases that are found in Nature vary considerably in their modular diversity and architecture. They include: non-complexed enzymes with single catalytic domains, independent single peptide chains incorporating multiple catalytic modules, and complexed, scaffolded structures, such as the cellulosome. The discovery of the latter two enzyme architectures has led to a generally held hypothesis that these systems take advantage of intramolecular and intermolecular proximity synergies, respectively, to enhance cellulose degradation. We use domain engineering to exploit both of these concepts to improve cellulase activity relative to the activity of mixtures of the separate catalytic domains.

Results
We show that engineered minicellulosomes can achieve high levels of cellulose conversion on crystalline cellulose by taking advantage of three types of synergism; (1) a complementary synergy produced by interaction of endo- and exo-cellulases, (2) an intramolecular synergy of multiple catalytic modules in a single gene product (this type of synergism being introduced for the first time to minicellulosomes targeting crystalline cellulose), and (3) an intermolecular proximity synergy from the assembly of these cellulases into larger multi-molecular structures called minicellulosomes. The binary minicellulosome constructed in this study consists of an artificial multicatalytic cellulase (CBM4-Ig-GH9-X11-X12-GH8-Doc) and one cellulase with a single catalytic domain (a modified Cel48S with the structure CBM4-Ig-GH48-Doc), connected by a non-catalytic scaffoldin protein. The high level endo-exo synergy and intramolecular synergies within the artificial multifunctional cellulase have been combined with an additional proximity-dependent synergy produced by incorporation into a minicellulosome demonstrating high conversion of crystalline cellulose (Avicel). Our minicellulosome is the first engineered enzyme system confirmed by test to be capable of both operating at temperatures as high as 60°C and converting over 60% of crystalline cellulose to fermentable sugars.

Conclusion
When compared to previously reported minicellulosomes assembled from cellulases containing only one catalytic module each, our novel minicellulosome demonstrates a method for substantial reduction in the number of peptide chains required, permitting improved heterologous expression of minicellulosomes in microbial hosts. In addition, it has been shown to be capable of substantial conversion of actual crystalline cellulose, as well as of the less-well-ordered and more easily digestible fraction of nominally crystalline cellulose.
Beyond malignancy: the role of carbohydrate antigen 125 in heart failure
Authors: Hung Chung-Lieh , Hung Ta-Chuan , Lai Yau-Hui , Lu Chi-Sheng , Wu Yih-Jer , Yeh Hung-I 
Published: August 2013

Abstract
Carbohydrate antigen 125 (CA-125), traditionally a tumor marker for screening, diagnosis, and monitoring in ovarian malignancy, had recently been shown increasing evidence and more extensively recognized/explored as a novel surrogate of heart failure (HF). The exact mechanisms underlying the pathophysiologic link between elevated serum CA-125 concentration and HF may be multi-factorial, with both mechanical and inflammatory process including numerous potential cytokines involved. Accumulating data had consistently indicated its diagnostic and prognostic role in HF patients in various clinical settings, however, there is limited clinical information regarding the incremental value or head-to-head comparison of such marker to other well-established HF markers. In this brief review, we aimed to discuss the biosynthesis, and potential insights of underlying pathophysiologies associated with CA-125 secretion in the scenarios of cardiac structural/functional alterations and HF, and further explored its current usage and roles in several recent reports.
Measuring cell-type specific differential methylation in human brain tissue
Authors: Montaño Carolina M , Irizarry Rafael A , Kaufmann Walter E , Talbot Konrad , Gur Raquel E , Feinberg Andrew P , Taub Margaret A 
Published: August 2013

AbstractThe behavior of epigenetic mechanisms in the brain is obscured by tissue heterogeneity and disease-related histological changes. Not accounting for these confounders leads to biased results. We develop a statistical methodology that estimates and adjusts for celltype composition by decomposing neuronal and non-neuronal differential signal. This method provides a conceptual framework for deconvolving heterogeneous epigenetic data from postmortem brain studies. We apply it to find cell-specific differentially methylated regions between prefrontal cortex and hippocampus. We demonstrate the utility of the method on both Infinium 450k and CHARM data.