bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Wilms’ tumor gene (WT1) regulates E-cadherin expression and migration of prostate cancer cells
Authors: Brett Adina , Pandey Sony , Fraizer Gail 
Published: January 2013

Abstract

Background
One key step in the development of prostate cancer (PCa) metastasis is the loss of E-cadherin expression associated with increased cellular motility and tumor invasion. This loss of E-cadherin expression is also required during normal embryogenesis and similar transcriptional repressors have been identified in both processes. We have previously reported the presence of one such transcription factor, WT1 in high Gleason grade prostate tumor tissues, and its absence in non-neoplastic or benign prostatic hyperplasia tissues.

Results
To better understand the effect of WT1 on E-cadherin expression and migration of PCa cells we quantified WT1 and E-cadherin mRNA levels in normal prostate epithelial and PCa cell lines with varying migratory potential. In WT1 transfected cells E-cadherin transcript levels were decreased, while they were increased in siWT1-RNA transfected PCa cells, suggesting that elevated WT1 expression was sufficient to dampen E-cadherin levels and potentially enhance migratory ability. To delineate the mechanism of WT1-mediated repression of E-cadherin, potential WT1 binding sites were tested in vitro and in vivo binding of WT1 to the E-cadherin promoter in the chromatin of LNCaP and PC3 cells was assessed by Chromatin Immunoprecipitation. The effect of WT1 binding was measured in reporter assays; in PC3 and DU145 cells WT1 decreased the activity of the proximal E-cadherin promoter. Using site-directed mutagenesis, a newly identified WT1 binding site located 146 bp from the transcription start site was shown to be required for this repression by WT1. Transwell migration and wound healing assays revealed that in LNCaP cells with low migratory potential, over-expression of WT1 was sufficient to enhance migration, conversely, in the highly migratory PC3 cells silencing of WT1 decreased migration.

Conclusions
These findings suggested that WT1 expression in high grade prostate cancer may contribute to migration and metastasis. Thus, in prostate cancer WT1 may function as a novel oncogene facilitating development of the lethal metastatic phenotype.
Editorial: can China master the guideline challenge?
Authors: Yang Kehu , Chen Yaolong , Li Youping , Schünemann Holger J ,   Members of the Lanzhou International Guideline Symposium
Published: January 2013

Abstract
China is experiencing increased health care use and expenditures, without sufficient controls to ensure quality and value. Transparent, cost-conscious and patient-centered guidelines based on the best available evidence could help establishing these quality and practice measures.
We examined how guidelines could support the Chinese health reform. Specifically, we summarized the current state of the art and related challenges in guideline development and explored possible solutions in the context of the Chinese health reform.
China currently lacks capacity for evidence-based guideline development and coordination by a central agency. Most Chinese guideline users rely on recommendations developed by professional groups that lack demonstration of transparency (including conflict of interest management and evidence synthesis) and quality. These deficiencies appear larger than in other regions of the world. In addition, misperceptions about the role of guidelines in assisting practitioners as opposed to providing rules requiring adherence, and a perception that traditional Chinese medicine (TCM) cannot be appropriately incorporated in guidelines are present.
China’s capacity could be strengthened by a central guideline agency to provide or coordinate evidence synthesis for guideline development and to oversee the work of guideline developers. China can build on what is known and work with the international community to develop methods to meet the challenges of evidence-based guideline development.
Simple projection algorithm for a countable family of weak relatively nonexpansive mappings and applications
Authors: Zhang Jingling , Su Yongfu , Cheng Qingqing 
Published: January 2013

Abstract
Let E be a uniformly convex and uniformly smooth Banach space, let C be a nonempty closed convex subset of E, let

{

T
n

}
:
C
→
C

be a countable family of weak relatively nonexpansive mappings such that

F
=

⋂

n
=
1

∞

F
(

T
n

)
≠
∅

. For any given gauss

x
0

∈
C

, define a sequence

{

x
n

}

in C by the following algorithm:

{

C
0

=
C
,

C

n
+
1

=
{
z
∈

C
n

:
ϕ
(
z
,

T
n

x
n

)
=
ϕ
(
z
,

x
n

)
}
,

n
=
0
,
1
,
2
,
3
,
…
,

x

n
+
1

=

Π

C

n
+
1

x
0

.

Then

{

x
n

}

converges strongly to

q
=

Π
F

x
0

.

MSC:47H05, 47H09, 47H10.
Bovine herpesvirus 4 glycoprotein B is indispensable for lytic replication and irreplaceable by VSVg
Authors: Franceschi Valentina , Capocefalo Antonio , Cavirani Sandro , Donofrio Gaetano 
Published: January 2013

Abstract

Background
Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus, belonging to Rhadinovirus genus, with no clear association with disease. However, there is increasing evidence of its secondary pathogenic role in cases of post-partum metritis in cattle. BoHV-4 Open Reading Frame 8 (ORF8) codifies for glycoprotein B (gB) that shows a heterodimeric structure, composed of two subunits and covalently linked by disulfide bonds and responsible for host cell adhesion through binding to heparan sulfates associated with cellular proteoglycans. Here we describe the generation of several tagged soluble forms of gB ectodomain, in order to test their ability to neutralize BoHV-4 infection.

Results
The results show, however, that none of these soluble forms are able to block viral infectivity. To better understand the role of gB during BoHV-4 lytic replication, a recombinant BoHV-4 was generated by homologous recombination from a BoHV-4 cloned as a Bacterial artificial chromosome (BAC) (pBAC-BoHV-4-A), in which most of the BoHV-4 gB ORF was substituted by the insertion of a DNA stuffer selectable cassette. The resulting recombinant BoHV-4 genome (pBAC-BoHV-4-AΔgB-KanaGalK) was completely unable to reconstitute infectious replicating viral particles (Infectious Replicating Viral Particles, IRVPs) and to replicate when transfected in permissive cell lines in comparison to its revertant clone (pBAC-BoHV-4-ΔgB-Rev) or pBAC-BoHV-4-A parental clone.

Conclusion
This demonstrates that the BoHV-4 replicating cycle is dependent on gB. Moreover, when gB was deleted from a recombinant BoHV-4 genome delivering an heterologous glycoprotein, Vesicular Stomatitis Virus Glycoprotein (VSVg), VSVg was unable to complement gB. This study provides direct evidence that gB is necessary for BoHV-4 lytic replication.
Additional circular intercostal space created by bifurcation of the left 3rd rib and its costal cartilage: a case report
Authors: Kumar Naveen , Guru Anitha , Patil Jyothsna , Ravindra Swamy , Badagabettu Satheesha Nayak 
Published: January 2013

Abstract

Introduction
In the thorax there are normally 11 pairs of intercostal spaces: the spaces between adjacent ribs. The intercostal spaces contain intercostal muscles, intercostal nerves and vessels.

Case presentation
During a routine dissection for undergraduate medical students, we observed a variation involving the left 3rd rib and 3rd costal cartilage in the cadaver of a man of Indian ethnicity aged about 65 years. The left 3rd rib and its costal cartilage were bifurcated at their costochondral junction enclosing a small circular additional intercostal space. Muscle tissue covered by deep fascia was present in this circular intercostal space. The muscle in the circular intercostal space received its nerve supply from a branch of the 2nd intercostal nerve.

Conclusions
Knowledge of such variations is helpful to surgeons operating on the anterior thoracic wall involving ribs and intercostal spaces. Knowing the possibility of the presence of an additional space between normal intercostal spaces can guide a surgeon through to a successful surgery.
Changes in Timing and kinematics of goal directed eye-hand movements in early-stage Parkinson’s disease
Authors: Muilwijk Danya , Verheij Simone , Pel Johan JM , Boon Agnita JW , van der Steen Johannes 
Published: January 2013

Abstract

Objective
Many daily activities involve intrinsic or extrinsic goal-directed eye and hand movements. An extensive visuomotor coordination network including nigro-striatal pathways is required for efficient timing and positioning of eyes and hands. The aim of this study was to investigate how Parkinson’s disease (PD) affects eye-hand coordination in tasks with different cognitive complexity.

Methods
We used a touch screen, an eye-tracking device and a motion capturing system to quantify changes in eye-hand coordination in early-stage PD patients (H&Y < 2.5) and age-matched controls. Timing and kinematics of eye and hand were quantified in four eye-hand coordination tasks (pro-tapping, dual planning, anti-tapping and spatial memory task).

Results
In the pro-tapping task, saccade initiation towards extrinsic goals was not impaired. However, in the dual planning and anti-tapping task initiation of saccades towards intrinsic goals was faster in PD patients. Hand movements were differently affected: initiation of the hand movement was only delayed in the pro-tapping and dual planning task. Overall, hand movements in PD patients were slower executed compared to controls.

Interpretation
Whereas initiation of saccades in an extrinsic goal-directed task (pro-tapping task) is not affected, early stage PD patients have difficulty in suppressing reflexive saccades towards extrinsic goals in tasks where the endpoint is an intrinsic goal (e.g. dual planning and anti-tapping task). This is specific for eye movements, as hand movements have delayed responses in the pro-tapping and dual planning task. This suggests that reported impairment of the dorsolateral prefrontal cortex in early-stage PD patients affects only inhibition of eye movements. We conclude that timing and kinematics of eye and hand movements in visuomotor tasks are affected in PD patients. This result may have clinical significance by providing a behavioral marker for the early diagnosis of PD.
Selecting age-related functional characteristics in the human gut microbiome
Authors: Lan Yemin , Kriete Andres , Rosen Gail L 
Published: January 2013

Abstract

Background
Human gut microbial functions are often associated with various diseases and host physiologies. Aging, a less explored factor, is also suspected to affect or be affected by microbiome alterations. By combining functional feature selection with supervised classification, we aim to facilitate identification of age-related functional characteristics in metagenomes from several human gut microbiome studies (MetaHIT, MicroAge, MicroObes, Kurokawa et al.’s and Gill et al.’s dataset).

Results
We apply two feature selection methods, term frequency-inverse document frequency (TF-iDF) and minimum-redundancy maximum-relevancy (mRMR), to identify functional signatures that differentiate metagenomes by age. After features are reduced, we use a support vector machine (SVM) to predict host age of new metagenomes. Functional features are from protein families (Pfams), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, KEGG ontologies and the Gene Ontology (GO) database. Initial investigations demonstrate that ordination of the functional principal components shows great overlap between different age groups. However, when feature selection is applied, mRMR tightens the ordination cluster for each age group, and TF-iDF offers better linear separation. Both TF-iDF and mRMR were used in conjunction with a SVM classifier and achieved areas under receiver operating characteristic curves (AUCs) 10 to 15% above chance to classify individuals above/below mid-ages (about 38 to 43 years old) using Pfams. Better performance around mid-ages is also observed when using other functional categories and age-balanced dataset. We also identified some age-related Pfams that improved age discrimination at age 65 with another feature selection method called LEfSe, on an age-balanced dataset. The selected functional characteristics identify a broad range of age-relevant metabolisms, such as reduced vitamin B12 synthesis, reduced activity of reductases, increased DNA damage, occurrences of stress responses and immune system compromise, and upregulated glycosyltransferases in the aging population.

Conclusions
Feature selection can yield biologically meaningful results when used in conjunction with classification, and makes age classification of new human gut metagenomes feasible. While we demonstrate the promise of this approach, the data-dependent prediction performance could be further improved. We hypothesize that while the Qin et al. dataset is the most comprehensive to date, even deeper sampling is needed to better characterize and predict the microbiomes’ functional content.
Giant prolactinoma: case report and review of literature
Authors: Rahmanian Masoud , Meybodi Hamidreza Aghaei , Larijani Bagher , Mohajeri-Tehrani Mohammad-reza 
Published: January 2013

Abstract“Invasive giant prolactinoma” is a large prolactinoma (>4 cm in dimension) presenting with serum prolactin levels of >1000 ng/dL and mass related clinical symptoms. Here we report a patient with a giant prolactinoma presented with central hypogonadism, suppressed adrenal and thyroid function, supra sellar extension, visual field impairment and high prolactin level.The patient was treated with cabergoline, levothyroxin and prednisolone. After 18 months, tumor size markedly reduced, associated with adrenal function and visual field improvement, but central hypogonadism and secondary hypothyroidism persisted.Previous studies showed normalization of thyrotropin secretion after treatment but it remained low in our patient even after 18 months follow up.
The anti-inflammatory effect of the synthetic antimicrobial peptide 19-2.5 in a murine sepsis model: a prospective randomized study
Authors: Schuerholz Tobias , Doemming Sabine , Hornef Mathias , Martin Lukas , Simon Tim-Philipp , Heinbockel Lena , Brandenburg Klaus , Marx Gernot 
Published: January 2013

Abstract
Introduction
Increasing rates of multi-resistant bacteria are a major problem in the treatment of critically ill patients. Furthermore, conventional antibiotics lead to the release of bacterial derived membrane parts initiating pro-inflammatory cascades with potential harm to the patient. Antimicrobial peptides (AMP) may kill bacteria without releasing pro-inflammatory factors. Thus, we compared three newly developed synthetic anti-lipopolysaccharide peptides (SALPs) with a broader range of efficacy to suppress cytokine release in plasma and CD14 mRNA expression in organ tissue in a murine, polymicrobial sepsis model.

Methods
A randomized, experimental trial was conducted in an animal research facility. Male NMRI mice (n = 90; 8- to 12-weeks old) were randomized to the following six groups: (i) sham operation and parenteral vehicle (NaCl 0.9%) administration (sham); (ii) cecal ligation and puncture (CLP) and vehicle infusion (sepsis-control), (iii) CLP and polymyxin B infusion (polyB), or (iv to vi) CLP and infusion of three different synthetic antimicrobial peptides Peptide 19-2.5 (Pep2.5), Peptide 19-4 (Pep4) or Peptide 19-8 (Pep8). All animals underwent arterial and venous catheterization for hemodynamic monitoring 48 hours prior to CLP or sham-operation. Physical appearance and behavior (activity), plasma cytokine levels, and CD14 mRNA expression in heart, lung, liver, spleen and kidney tissue were determined 24 hours after CLP or sham operation.

Results
Only Pep2.5 significantly enhanced the activity after CLP, whereas none of the therapeutic regimens elevated the mean arterial pressure or heart rate. The strongly elevated IL-6, IL-10 and monocyte chemoattractant protein serum levels in septic animals were significantly reduced after Pep2.5 administration (P < 0.001, P < 0.001, and P < 0.001, respectively). Similarly, Pep2.5 significantly reduced the sepsis-induced CD14 mRNA expression in heart (P = 0.003), lung (P = 0.008), and spleen tissue (P = 0.009) but not in kidney and liver.

Conclusions
Structurally variable SALPs exhibit major differences in their anti-inflammatory effect in vivo. Continuous parenteral administration of Pep2.5 is able to reduce sepsis-induced cytokine release and tissue inflammation.
Control of Dividends, Capital Subscriptions, and Physical Inventories
Authors: Li Lode , Shubik Martin , Sobel Matthew J. 
Published: January 2013

Manufacturers manage interrelated flows of material and cash. Material needs capital, and sales contribute cash. Therefore, it may be beneficial to coordinate operational and financial decisions. We study a dynamic model of coordination in an equity-financed firm in which inventory and financial decisions interact in the presence of demand uncertainty, financial constraints, and a risk of default. The criterion is to maximize the expected present value of dividends net of capital subscriptions. The optimal target inventory level and financial decision variables are nondecreasing functions of the levels of inventory and retained earnings. Some important attributes of an optimal policy remain the same regardless of whether default precipitates Chapter 7 or Chapter 11 bankruptcy. The optimal policy is myopic, and if pertinent cost functions are piecewise linear, it is characterized with simple formulas. We show that the methods of inventory theory are useful in analyzing models of operational and financial coordination. This paper was accepted by Yossi Aviv, operations management.
The Fragility of Commitment
Authors: Morgan John , Várdy Felix 
Published: January 2013

We show that the value of commitment is fragile in many standard games. When the follower faces a small cost to observe the leader's action, equilibrium payoffs are identical to the case where the leader's actions are unobservable. Applications of our result include standard Stackelberg–Cournot and differentiated product Bertrand games, as well as forms of indirect commitment, highlighted in Bulow et al. [Bulow J, Geanakoplos J, Klemperer P (1985) Multimarket oligopoly: Strategic substitutes and strategic complements. J. Political Econom. 93:488–511]. Weakening full rationality in favor of boundedly rational solution concepts such as quantal-response equilibrium restores the value of commitment. This paper was accepted by Peter Wakker, decision analysis.
Total Cost Control in Project Management via Satisficing
Authors: Goh Joel , Hall Nicholas G. 
Published: January 2013

We consider projects with uncertain activity times and the possibility of expediting, or crashing, them. Activity times come from a partially specified distribution within a family of distributions. This family is described by one or more of the following details about the uncertainties: support, mean, and covariance. We allow correlation between past and future activity time performance across activities. Our objective considers total completion time penalty plus crashing and overhead costs. We develop a robust optimization model that uses a conditional value-at-risk satisficing measure. We develop linear and piecewise-linear decision rules for activity start time and crashing decisions. These rules are designed to perform robustly against all possible scenarios of activity time uncertainty, when implemented in either static or rolling horizon mode. We compare our procedures against the previously available Program Evaluation and Review Technique and Monte Carlo simulation procedures. Our computational studies show that, relative to previous approaches, our crashing policies provide both a higher level of performance, i.e., higher success rates and lower budget overruns, and substantial robustness to activity time distributions. The relative advantages and information requirements of the static and rolling horizon implementations are discussed. This paper was accepted by Dimitris Bertsimas, optimization.
Stability Study of EBC/TBC Hybrid System on Si-based Ceramics in Gas Turbines
Authors: Xu JiaPeng , Sarin Vinod , Basu Soumendra 
Published: January 2013

ABSTRACTCurrently, ceramics are being used under increasingly demanding environments. These materials have to exhibit phase stability and resist chemical attack during service. This research involves the study of the high-temperature stability of ceramic materials in gas turbines. SiC/SiC ceramic matrix composites (CMCs) are being increasingly used in the hot-sections of gas turbines, especially for aerospace applications. These CMCs are prone to recession of their surface if exposed to a flow of high-velocity water vapor, and to hot-corrosion when exposed to molten alkali salts. The objective of this investigation was the development of a hybrid system containing an environmental barrier coating (EBC) for protection of the CMC from chemical attack and a thermal barrier coating (TBC) that allows a steep temperature gradient across it to lower the temperature of the CMC for increased lifetimes. The EBC used was a functionally graded mullite (3Al2O3∙2SiO2) coating deposited by chemical vapor deposition (CVD), while the TBC layer was yttria-stabilized zirconia (YSZ) deposited by air plasma spray (APS). The stability of this system was investigated, via adhesion between the two coating layers and the substrate, the physical and chemical stability of each layer at high temperature, and the performance under severe thermal shock and exposure to hot corrosion.
CF102 for the Treatment of Hepatocellular Carcinoma: A Phase I/II, Open-Label, Dose-Escalation Study
Authors: Stemmer Salomon M. , Benjaminov Ofer , Medalia Gal , Ciuraru Noab B. , Silverman Michael H. , Bar-Yehuda Sara , Fishman Sari , Harpaz Zivit , Farbstein Motti , Cohen Shira , Patoka Renana , Singer Barak , Kerns William D. , Fishman Pnina 
Published: January 2013

Abstract

Background.
The A3 adenosine receptor (A3AR) is overexpressed in the tumor and in the peripheral blood mononuclear cells of patients with hepatocellular carcinoma (HCC). The orally active drug candidate CF102, an A3AR agonist, induces apoptosis of HCC cells via deregulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC.

Methods.
The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally (1, 5, and 25 mg BID) in 28-day cycles. Evaluation of anti-tumor effects and the utilization of A3AR as a biological predictive marker of response to CF102 were the secondary objectives.

Results.
Eighteen patients received CF102—six at each dose level. No serious drug-related adverse events or dose-limiting toxicities were observed. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom had received prior sorafenib, was 7.8 months, and for Child Pugh B patients (28%) it was 8.1 months. Stable disease by RECIST was observed in four patients for at least 4 months. CF102 maintained liver function over a 6-month period. A correlation between receptor overexpression levels at baseline and patients' overall survival was found. One of the patients who presented with skin nodules that were biopsy-proven to be HCC metastases prior to the trial showed complete metastasis regression during three months of treatment with CF102.

Conclusions.
CF102 is safe and well-tolerated, showing favorable PK characteristics in Child Pugh A and B HCC patients, justifying further clinical development.