bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Physiological Correlates of Irritability in Depression: Results from the Netherlands Study of Depression and Anxiety
Authors: Verhoeven Floor E. A. , Booij Linda , Van der Wee Nic J. A. , Penninx Brenda W. H. J. , Van der Does A. J. Willem
Published: October 2011

Objective. Irritable and nonirritable depressed patients differ on demographic and clinical characteristics. We investigated whether this extends to psychological and physiological measures.Method. We compared irritable and nonirritable unipolar depressed patients on symptomatology, personality, and (psycho)physiological measures (cortisol, cholesterol, and heart rate variability). Symptomatology was reassessed after one year, and we also compared depressed patients who were irritable or non-irritable at both time points (Irr++ versus Irr−−).Results. Almost half (46%;N=420) of the sample was classified as irritable. These patients scored higher on depression severity, anxiety, hypomanic symptoms, and psychological variables. No differences were observed on physiological markers after correction for depression severity. The same pattern was found when comparing Irr++ and Irr−− groups.Conclusion. Irritable and non-irritable depressed patients differ on clinical and psychological variables, but not on the currently investigated physiological markers. The clinical relevance of the distinction and the significance of the hypomanic symptoms remain to be demonstrated.
Primary Carcinoid Tumor of the Ileal Efferent Limb of an Ileovesicostomy: A Case Report
Authors: Mellis Adamantios M. , Parker Daniel C. , Buethe David D. , Slobodov Gennady
Published: October 2011

We report on the evaluation and management of a 47-year-old white male found to have primary carcinoid tumor of the ileal segment of his diverting ileovesicostomy thirty-five months after initial creation. Subsequent to presentation with intermittent gross hematuria, CT urogram highlights an 8 mm enhancing lesion near the enterovesical junction of urinary diversion. Office cystoscopy confirms presence of a lesion that was later endoscopically resected and found to be a well-differentiated carcinoid tumor. Evaluation with serum markers, direct visualization utilizing endoscopy, and imaging was without finding of alternate primary or metastatic lesions. The patient ultimately had the proximal ileal portion of his ileovesicostomy excised and the distal portion converted into an ileal conduit. After briefly discussing the carcinoid tumor and the carcinoid syndrome it may cause, we review the literature on the incidence of carcinoid tumors in a population requiring the use of intestine in the urinary tract.
Contractile Strength during Variable Heart Duration Is Species and Preload Dependent
Authors: Torres Carlos A. A. , Janssen Paul M. L.
Published: October 2011

We investigate the effect of beat‐to‐beat variability on cardiac contractility. Cardiac trabeculae were isolated from the right ventricle of rabbits and beagle dogs and stimulated to isometrically contract, alternating between fixed steady state versus variable interbeat intervals. Trabeculae were stimulated at physiologically relevant frequencies for each species (dog 1 and 4 Hz; rabbit 2 and 4 Hz) intercalating fixed periods with 40% variability. A subset of the trabeculae (at 90% of optimal length) was stretched prior to stimulation between 5 and 13% and stimulated at the same frequencies with a fixed versus 40% variation. Fixed rate response at the same base frequency was measured before and after each variable period and the average force reported. In canine preparations no change in force was observed as a result of the imposed variability in beat‐to‐beat duration. In the rabbit, we observed a nonsignificant decrease in force between fixed and variable pacing at both 2 and 4 Hz (n = 8) when 40% variability was introduced. When a 5% and 13% stretch was applied, the correlation coefficient sharply increased, indicating a more prominent impact of the prebeat duration on the following cycle with higher preload.
Prevalence of Dyslipidemia in Patients Receiving Health Checkups: A Hospital-Based Study
Authors: Cheng Kao-Chi , Chen Yu-Lung , Lai Shih-Wei
Published: October 2011

We used the dataset from one medical center in Taiwan to explore the prevalence of dyslipidemia, which included 2695 subjects receiving private health checkups in 2003-2004. The overall prevalence of hypercholesterolemia was 53.3% in men and 48.2% in women (P=0.008). The overall prevalence of hypertriglyceridemia was 29.3% in men and 13.7% in women (P<0.001). The overall prevalence of elevated LDL level was 50.7% in men and 37.9% in women (P<0.001). The overall prevalence of low HDL level was 47.4% in men and 53% in women (P=0.004).
Performance Evaluation and Dimensioning of GIX/M/c/N Systems through Kernel Estimation
Authors: Gontijo G. M. , Atuncar G. S. , Cruz F. R. B. , Kerbache L.
Published: October 2011

We extend the analysis of queueing systems for real‐life situations, where the arrival pattern of customers is unknown. In real systems, we must understand how the choice of a method of estimation influences the configuration of the system. Using kernel smoothing, we evaluate algorithms to estimate performance measures of a GIX/M/c/N system, including the invariant probability distribution of the number of customers in the system, the blocking probability, the average queue size, and the average client queue time. We successfully apply the method to the arrivals to a call center to plan and improve the performance of these important queueing systems.
Voices That Care: Licensed Practical Nurses and the Emotional Labour Underpinning Their Collaborative Interactions with Registered Nurses
Authors: Huynh Truc , Alderson Marie , Nadon Michelle , Kershaw-Rousseau Sylvia
Published: October 2011

Recognizing the emotional labour underlying interprofessional collaborations (IPCs) could be considered a crucial step towards building a cohesive nursing team. Although IPCs between registered nurses (RNs) and licensed practical nurses (LPNs) have been linked to quality nursing care, little is known about the emotions experienced by LPNs during their interactions with RNs or those factors that influence IPCs. A questionnaire administered to 309 LPNs found that (1) the professional identity of LPNs has evolved into a that of a unique social group; (2) LPNs define IPC as an interpersonal process of exploring similar or dissimilar assessments of a patient's status with RNs and, together, establishing a course of nursing actions; (3) the primary organizational factor facilitating IPCs is inclusive nursing leadership; (4) the interpersonal factor promoting IPCs is the level of trust RNs extend to LPNs; and (5) an LPN's emotional labour (i.e., internal emotional regulation) is most tangible during uncollaborative interactions with RNs.
Impact of Biochar on Earthworm Populations: A Review
Authors: Weyers Sharon L. , Spokas Kurt A.
Published: October 2011

Despite the overwhelming importance of earthworm activity in the soil system, there are a limited number of studies that have examined the impact resulting from biochar addition to soil. Biochar is part of the black carbon continuum of chemo-thermal converted biomass. This review summarizes existing data pertaining to earthworms where biochar and other black carbon substances, including slash-and-burn charcoals and wood ash, have been applied. After analyzing existing studies on black carbon, we identified that these additions have a range from short-term negative impacts to long-term null effects on earthworm population density and total biomass. Documented cases of mortality were found with certain biochar-soil combinations; the cause is not fully understood, but hypothesized to be related to pH, whether the black carbon is premoistened, affects feeding behaviors, or other unknown factors. With wood ashes, negative impacts were overcome with addition of other carbon substrates. Given that field data is limited, soils amended with biochar did not appear to cause significant long-term impacts. However, this may indicate that the magnitude of short-term negative impacts on earthworm populations can be reduced with time.
Safety and Clinical Usage of Newcastle Disease Virus in Cancer Therapy
Authors: Lam Han Yuen , Yeap Swee Keong , Rasoli Mehdi , Omar Abdul Rahman , Yusoff Khatijah , Suraini Abd Aziz , Banu Alitheen Noorjahan
Published: October 2011

Newcastle disease virus (NDV) is an avian virus that causes deadly infection to over 250 species of birds, including domestic and wild‐type, thus resulting in substantial losses to the poultry industry worldwide. Many reports have demonstrated the oncolytic effect of NDV towards human tumor cells. The interesting aspect of NDV is its ability to selectively replicate in cancer cells. Some of the studies have undergone human clinical trials, and favorable results were obtained. Therefore, NDV strains can be the potential therapeutic agent in cancer therapy. However, investigation on the therapeutic perspectives of NDV, especially human immunological effects, is still ongoing. This paper provides an overview of the current studies on the cytotoxic and anticancer effect of NDV via direct oncolysis effects or immune stimulation. Safety of NDV strains applied for cancer immunotherapy is also discussed in this paper.
Is Ceftriaxone-Induced Biliary Pseudolithiasis Influenced by UDP-Glucuronosyltransferase 1A1 Gene Polymorphisms?
Authors: Fretzayas Andrew , Liapi Olga , Papadopoulou Anna , Nicolaidou Polyxeni , Stamoulakatou Alexandra
Published: October 2011

Ceftriaxone (cfx), a third-generation cephalosporin antibiotic, leads to transient cholelithiasis in some children, also known as pseudolithiasis. However, the underlying pathogenetic mechanism of this adverse effect has not yet been elucidated. We describe 3 children with ceftriaxone-induced pseudolithiasis, who were also carriers of the A(TA)7TAA polymorphism of theUGT1A1gene, implying that a cause and effect relation may exist.
Enterococcus faeciumWB2000 Inhibits Biofilm Formation by Oral Cariogenic Streptococci
Authors: Suzuki Nao , Yoneda Masahiro , Hatano Yuko , Iwamoto Tomoyuki , Masuo Yosuke , Hirofuji Takao
Published: October 2011

This study investigated the inhibitory effect of probioticEnterococcus faeciumWB2000 on biofilm formation by cariogenic streptococci. The ability ofE. faeciumWB2000 and JCM5804 andEnterococcus faecalisJCM5803 to inhibit biofilm formation by seven laboratory oral streptococcal strains and 13 clinical mutans streptococcal strains was assayed. TheEnterococcalstrains inhibited biofilm formation in dual cultures with the mutans streptococcal strainsStreptococcus mutansXc andStreptococcus sobrinusJCM5176 (P<0.05), but not with the noncariogenic streptococcal strains.Enterococcus faeciumWB2000 inhibited biofilm formation by 90.0% (9/10) of the clinicalS. mutansstrains and 100% (3/3) of the clinicalS. sobrinusstrains. After culturing, the pH did not differ between single and dual cultures. The viable counts of floating mutans streptococci were lower in dual cultures withE. faeciumWB2000 than in single cultures.Enterococcus faeciumWB2000 acted as a probiotic bacterial inhibitor of cariogenic streptococcal biofilm formation.
Regression Methods for Ophthalmic Glucose Sensing Using Metamaterials
Authors: Rapp Philipp , Mesch Martin , Giessen Harald , Tarín Cristina
Published: October 2011

We present a novel concept for in vivo sensing of glucose using metamaterials in combination with automatic learning systems. In detail, we use the plasmonic analogue of electromagnetically induced transparency (EIT) as sensor and evaluate the acquired data with support vector machines. The metamaterial can be integrated into a contact lens. This sensor changes its optical properties such as reflectivity upon the ambient glucose concentration, which allows for in situ measurements in the eye. We demonstrate that estimation errors below 2% at physiological concentrations are possible using simulations of the optical properties of the metamaterial in combination with an appropriate electrical circuitry and signal processing scheme. In the future, functionalization of our sensor with hydrogel will allow for a glucose-specific detection which is insensitive to other tear liquid substances providing both excellent selectivity and sensitivity.
Automatic Road Pavement Assessment with Image Processing: Review and Comparison
Authors: Chambon Sylvie , Moliard Jean-Marc
Published: October 2011

In the field of noninvasive sensing techniques for civil infrastructures monitoring, this paper addresses the problem of crack detection, in the surface of the French national roads, by automatic analysis of optical images. The first contribution is a state of the art of the image-processing tools applied to civil engineering. The second contribution is about fine-defect detection in pavement surface. The approach is based on a multi-scale extraction and a Markovian segmentation. Third, an evaluation and comparison protocol which has been designed for evaluating this difficult task—the road pavement crack detection—is introduced. Finally, the proposed method is validated, analysed, and compared to a detection approach based on morphological tools.
Instrument for Label-Free Detection of Noncoding RNAs
Authors: Noy Peter , Steiner Roger , Voelkle Joerg , Hegner Martin , Fattinger Christof
Published: October 2011

We set up a label-free direct binding assay for the detection of noncoding RNAs. The assay is based on nanomechanical cantilever arrays for the detection of surface stress induced by immobilized biomolecules and their interaction partners. We used various means to significantly reduce the drift of the cantilever readout that was a prominent feature in experiments with readout in stationary fluid before and after sample injection. Major improvements were achieved by focusing on a faster system equilibration (for instance temperature control and diffusion independence). Experimental protocols were improved to provide user-friendly and less time-consuming measurements. Further enhancements were achieved by, for example, using pre-gold-coated cantilever array wafers compared to individually prepared ones and a directly implemented data analysis tool as real-time feature of the measurement software. We have demonstrated picomolar specific biomarker target detection and can easily distinguish modified targets with single-nucleotide mismatches that hybridize with lower affinity.
Advances in Meniscal Tissue Engineering
Authors: Longo Umile Giuseppe , Loppini Mattia , Forriol Francisco , Romeo Giovanni , Maffulli Nicola , Denaro Vincenzo
Published: October 2011

Meniscal tears are the most common knee injuries and have a poor ability of healing. In the last few decades, several techniques have been increasingly used to optimize meniscal healing. Current research efforts of tissue engineering try to combine cell-based therapy, growth factors, gene therapy, and reabsorbable scaffolds to promote healing of meniscal defects. Preliminary studies did not allow to draw definitive conclusions on the use of these techniques for routine management of meniscal lesions. We performed a review of the available literature on current techniques of tissue engineering for the management of meniscal tears.
Potential Energy Surface of NO on Pt(997): Adsorbed States and Surface Diffusion
Authors: Tsukahara N. , Yoshinobu J.
Published: October 2011

The potential energy surface (PES) of NO on Pt(997) has been elucidated: the adsorption states and diffusion processes of NO on Pt(997) at low coverage were investigated by using infrared reflection absorption spectroscopy (IRAS) and scanning tunneling microscopy (STM). When NO molecules adsorb on a surface at a low temperature (11 K), each molecule transiently migrates on the surface from the first impact point to a possible adsorption site. We found that there are four stable adsorption sites for NO on Pt(997): a bridge site of the upper step, an fcc- (or hcp-) hollow site of the terrace, an on-top site of the terrace, and an fcc-hollow site of the lower step. At higher temperatures above 45 K, NO molecules start to migrate thermally to more stable adsorption sites on a terrace, and they are finally trapped at the bridge sites of the step, which are the most stable among the four sites.
Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance
Authors: Kim Mi-Young , Bae Jin-Sik , Kim Tae-Hyun , Park Joo-Man , Ahn Yong Ho
Published: October 2011

Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver not due to alcohol abuse. NAFLD is accompanied by variety of symptoms related to metabolic syndrome. Although the metabolic link between NAFLD and insulin resistance is not fully understood, it is clear that NAFLD is one of the main cause of insulin resistance. NAFLD is shown to affect the functions of other organs, including pancreas, adipose tissue, muscle and inflammatory systems. Currently efforts are being made to understand molecular mechanism of interrelationship between NAFLD and insulin resistance at the transcriptional level with specific focus on post-translational modification (PTM) of transcription factors. PTM of transcription factors plays a key role in controlling numerous biological events, including cellular energy metabolism, cell-cycle progression, and organ development. Cell type- and tissue-specific reversible modifications include lysine acetylation, methylation, ubiquitination, and SUMOylation. Moreover, phosphorylation and O-GlcNAcylation on serine and threonine residues have been shown to affect protein stability, subcellular distribution, DNA-binding affinity, and transcriptional activity. PTMs of transcription factors involved in insulin-sensitive tissues confer specific adaptive mechanisms in response to internal or external stimuli. Our understanding of the interplay between these modifications and their effects on transcriptional regulation is growing. Here, we summarize the diverse roles of PTMs in insulin-sensitive tissues and their involvement in the pathogenesis of insulin resistance.
Applications of the PhytomedicineEchinacea purpurea(Purple Coneflower) in Infectious Diseases
Authors: Hudson James B.
Published: October 2011

Extracts ofEchinacea purpurea(EP, purple coneflower) have been used traditionally in North America for the treatment of various types of infections and wounds, and they have become very popular herbal medicines globally. Recent studies have revealed that certain standardized preparations contain potent and selective antiviral and antimicrobial activities. In addition, they display multiple immune-modulatory activities, comprising stimulation of certain immune functions such as phagocytic activity of macrophages and suppression of the proinflammatory responses of epithelial cells to viruses and bacteria, which are manifested as alterations in secretion of various cytokines and chemokines. These immune modulations result from upregulation or downregulation of the relevant genes and their transcription factors. All these bioactivities can be demonstrated at noncytotoxic concentrations of extract and appear to be due to multiple components rather than the individual chemical compounds that characterizeEchinacea extracts. Potential applications of the bioactive extracts may go beyond their traditional uses.
A Review ofERCC1Gene in Bladder Cancer: Implications for Carcinogenesis and Resistance to Chemoradiotherapy
Authors: Kawashima Atsunari , Takayama Hitoshi , Tsujimura Akira
Published: October 2011

The excision repair cross-complementing group 1 (ERCC1) gene performs a critical incision step in DNA repair and is reported to be correlated with carcinogenesis and resistance to drug or ionizing radiation therapy. We reviewed the correlation between ERCC1 and bladder cancer. In carcinogenesis, several reports discussed the relation between ERCC1 single nucleotide polymorphisms and carcinogenesis in bladder cancer only in case-control studies. Regarding the relation between ERCC1 and resistance to chemoradiotherapy, in vitro and clinical studies indicate that ERCC1 might be related to resistance to radiation therapy rather than cisplatin therapy. It is controversial whether ERCC1 predicts prognosis of bladder cancer treated with cisplatin-based chemotherapy. Tyrosine kinase receptors or endothelial-mesenchymal transition are reported to regulate the expression of ERCC1, and further study is needed to clarify the mechanism of ERCC1 expression and resistance to chemoradiotherapy in vitro and to discover novel therapies for advanced and metastatic bladder cancer.
Regulation ofLYRM1Gene Expression by Free Fatty Acids, Adipokines, and Rosiglitazone in 3T3-L1 Adipocytes
Authors: Zhang Min , Zhao Hai-Ming , Qin Zhen-Ying , Qin Rui , Chen Xiao-Hui , Zhao Ya-Ping , Zhang Chun-Mei , Gao Chun-Lin , Zhu Chun , Ji Chen-Bo , Cao Xin-Guo , Guo Xi-Rong
Published: October 2011

LYR motif containing 1 (LYRM1) is a novel gene that is abundantly expressed in the adipose tissue of obese subjects and is involved in insulin resistance. In this study, free fatty acids (FFAs) and tumor necrosis factor-α(TNF-α) are shown to upregulateLYRM1mRNA expression in 3T3-L1 adipocytes. Conversely, resistin and rosiglitazone exert an inhibitory effect onLYRM1mRNA expression. These results suggest that the expression ofLYRM1mRNA is affected by a variety of factors that are related to insulin sensitivity.LYRM1may be an important mediator in the development of obesity-related insulin resistance.
The Challenge of Triaging Chest Pain Patients: The Bernese University Hospital Experience
Authors: Rohacek Martin , Bertolotti Amina , Grützmüller Nadine , Simmen Urs , Marty Hans , Zimmermann Heinz , Exadaktylos Aristomenis , Spyridon Arampatzis
Published: October 2011

Accurate diagnosis of the causes of chest pain and dyspnea remain challenging. In this preliminary observational study with a 5-year follow-up, we attempted to find a simplified approach to selecting patients with chest pain needing immediate care based on the initial evaluation in ED. During a 24-month period were randomly selected 301 patients and a conditional inference tree (CIT) was used as the basis of the prognostic rule. Common diagnoses were musculoskeletal chest pain (27%), ACS (19%) and panic attack (12%). Using variables of ACS symptoms we estimated the likelihood of ACS based on a CIT to be high at 91% (32), low at 4% (198) and intermediate at 20.5–40% in (71) patients. Coronary catheterization was performed within 24 hours in 91% of the patients with ACS. A culprit lesion was found in 79%. Follow-up (median 4.2 years) information was available for 70% of the patients. Of the 164 patients without ACS who were followed up, 5 were treated with revascularization for stable angina pectoris, 2 were treated with revascularization for myocardial infarction, and 25 died. Although a simple triage decision tree could theoretically help to efficient select patients needing immediate care we need also to be vigilant for those presenting with atypical symptoms.
p53-Responsive miR-194 Inhibits Thrombospondin-1 and Promotes Angiogenesis in Colon Cancers
Authors: Sundaram Prema , Hultine Stacy , Smith Lauren M. , Dews Michael , Fox Jamie L. , Biyashev Dauren , Schelter Janell M. , Huang Qihong , Cleary Michele A. , Volpert Olga V. , Thomas-Tikhonenko Andrei
Published: October 2011

Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis encoded by the THBS1 gene, whose promoter is activated by p53. In advanced colorectal cancers (CRC), its expression is sustained or even slightly increased despite frequent loss of p53. Here, we determined that in HCT116 CRC cells, p53 activates the THBS1 primary transcript, but fails to boost THBS1 mRNA or protein levels, implying posttranscriptional regulation by microRNAs (miRNA). In a global miRNA gain-of-function screen done in the Dicer-deficient HCT116 variant, several miRNAs negatively regulated THBS1 mRNA and protein levels, one of them being miR-194. Notably, in agreement with published data, p53 upregulated miR-194 expression in THBS1 retrovirus-transduced HCT116 cells, leading to decreased TSP-1 levels. This negative effect was mediated by a single miR-194 complementary site in the THBS1 3′-untranslated region, and its elimination resulted in TSP-1 reactivation, impaired angiogenesis in Matrigel plugs, and reduced growth of HCT116 xenografts. Conversely, transient overexpression of miR-194 in HCT116/THBS1 cells boosted Matrigel angiogenesis, and its stable overexpression in Ras-induced murine colon carcinomas increased microvascular densities and vessel sizes. Although the overall contribution of miR-194 to neoplastic growth is context dependent, p53-induced activation of this GI tract–specific miRNA during ischemia could promote angiogenesis and facilitate tissue repair. Cancer Res; 71(24); 7490–501. ©2011 AACR.
Dendritic Cell Internalization of α-Galactosylceramide from CD8 T Cells Induces Potent Antitumor CD8 T-cell Responses
Authors: Choi Dong Hoon , Kim Kwang Soon , Yang Se Hwan , Chung Doo Hyun , Song Boyeong , Sprent Jonathan , Cho Jae Ho , Sung Young Chul
Published: October 2011

Dendritic cells (DC) present α-galactosylceramide (αGalCer) to invariant T-cell receptor–expressing natural killer T cells (iNKT) activating these cells to secrete a variety of cytokines, which in turn results in DC maturation and activation of other cell types, including NK cells, B cells, and conventional T cells. In this study, we showed that αGalCer-pulsing of antigen-activated CD8 T cells before adoptive transfer to tumor-bearing mice caused a marked increase in donor T-cell proliferation, precursor frequency, and cytotoxic lymphocyte activity. This effect was interleukin (IL)-2 dependent and involved both natural killer T cells (NKT) and DCs, as mice lacking IL-2, NKTs, and DCs lacked any enhanced response to adoptively transferred αGalCer-loaded CD8 T cells. iNKT activation was mediated by transfer of αGalCer from the cell membrane of the donor CD8 T cells onto the αGalCer receptor CD1d which is present on host DCs. αGalCer transfer was increased by prior activation of the donor CD8 T cells and required AP-2–mediated endocytosis by host DCs. In addition, host iNKT cell activation led to strong IL-2 synthesis, thereby increasing expansion and differentiation of donor CD8 T cells. Transfer of these cells led to improved therapeutic efficacy against established solid tumors in mice. Thus, our findings illustrate how αGalCer loading of CD8 T cells after antigen activation in vitro may leverage the therapeutic potential of adoptive T-cell therapies. Cancer Res; 71(24); 7442–51. ©2011 AACR.
Dasatinib as a Single Agent in Triple-Negative Breast Cancer: Results of an Open-Label Phase 2 Study
Authors: Finn Richard S. , Bengala Carmelo , Ibrahim Nuhad , Roché Henri , Sparano Joseph , Strauss Lewis C. , Fairchild Justin , Sy Oumar , Goldstein Lori J.
Published: October 2011

Purpose: Dasatinib is a potent, oral SRC-family kinase inhibitor with preclinical antiproliferative, antimetastatic, and antiosteoclastic activity suggesting dasatinib sensitivity in triple-negative, or basal-like, breast cancer cell lines. This phase 2 trial assessed efficacy and safety of single-agent dasatinib in patients with advanced triple-negative breast cancer (TNBC).

Experimental Design: Female patients with measurable, locally advanced or metastatic TNBC initially received dasatinib 100 mg twice daily (BID); to improve tolerability, the protocol was amended and subsequent patients received 70 mg BID. Primary endpoint was Response Evaluation Criteria in Solid Tumors–defined objective response rate (ORR); secondary endpoints included progression-free survival (PFS), disease control rate (DCR), safety, and limited pharmacokinetics.

Results: Of the 44 treated patients, 43 were response evaluable. ORR was 4.7%: two patients had confirmed partial responses lasting 14 and 58 weeks, respectively. Of 11 patients with stable disease, two continued for more than 16 weeks, thus protocol-defined DCR was 9.3%. Median PFS was 8.3 weeks (95% CI: 7.3–15.3). Five patients discontinued before first tumor assessment. No grade 4 adverse events (AE) were reported; grade 3 AEs occurring in more than 5% of patients were fatigue (9.1%), diarrhea, pleural effusion, and dyspnea (all 6.8%). Laboratory abnormalities were uncommon. Dasatinib at 100 mg BID was not well tolerated; rates of treatment interruption, dose reduction, and serious AEs were lower with dasatinib 70 mg BID.

Conclusions: Single-agent dasatinib has limited activity in unselected patients with TNBC. Dasatinib 70 mg BID was better tolerated than 100 mg BID. Future studies will investigate dasatinib in other breast cancer settings, including chemotherapy combinations. Clin Cancer Res; 17(21); 6905–13. ©2011 AACR.
Identification of Docetaxel Resistance Genes in Castration-Resistant Prostate Cancer
Authors: Marín-Aguilera Mercedes , Codony-Servat Jordi , Kalko Susana G. , Fernández Pedro L. , Bermudo Raquel , Buxo Elvira , Ribal María José , Gascón Pedro , Mellado Begoña
Published: October 2011

Docetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer (CRPC). However, most patients eventually develop resistance to this treatment. In this study, we aimed to identify key molecular genes and networks associated with docetaxel resistance in two models of docetaxel-resistant CRPC cell lines and to test for the most differentially expressed genes in tumor samples from patients with CRPC. DU-145 and PC-3 cells were converted to docetaxel-resistant cells, DU-145R and PC-3R, respectively. Whole-genome arrays were used to compare global gene expression between these four cell lines. Results showed differential expression of 243 genes (P < 0.05, Bonferroni-adjusted P values and log ratio > 1.2) that were common to DU-145R and PC-3R cells. These genes were involved in cell processes like growth, development, death, proliferation, movement, and gene expression. Genes and networks commonly deregulated in both DU-145R and PC-3R cells were studied by Ingenuity Pathways Analysis. Exposing parental cells to TGFB1 increased their survival in the presence of docetaxel, suggesting a role of the TGF-β superfamily in conferring drug resistance. Changes in expression of 18 selected genes were validated by real-time quantitative reverse transcriptase PCR in all four cell lines and tested in a set of 11 FFPE and five optimal cutting temperature tumor samples. Analysis in patients showed a noteworthy downexpression of CDH1 and IFIH1, among others, in docetaxel-resistant tumors. This exploratory analysis provides information about potential gene and network involvement in docetaxel resistance in CRPC. Further clinical validation of these results is needed to develop targeted therapies in patients with CRPC that can circumvent such resistance to treatment. Mol Cancer Ther; 11(2); 329–39. ©2011 AACR.
Nicotine Does Not Enhance Tumorigenesis in MutantK-Ras–Driven Mouse Models of Lung Cancer
Authors: Maier Colleen R. , Hollander M. Christine , Hobbs Evthokia A. , Dogan Irem , Linnoila R. Ilona , Dennis Phillip A.
Published: October 2011

Smoking is the leading cause of preventable cancer deaths in the United States. Nicotine replacement therapies (NRT) have been developed to aid in smoking cessation, which decreases lung cancer incidence. However, the safety of NRT is controversial because numerous preclinical studies have shown that nicotine enhances tumor cell growth in vitro and in vivo. We modeled NRT in mice to determine the effects of physiologic levels of nicotine on lung tumor formation, tumor growth, or metastasis. Nicotine administered in drinking water did not enhance lung tumorigenesis after treatment with the tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Tumors that develop in this model have mutations in K-ras, which is commonly observed in smoking-related, human lung adenocarcinomas. In a transgenic model of mutant K-ras–driven lung cancer, nicotine did not increase tumor number or size and did not affect overall survival. Likewise, in a syngeneic model using lung cancer cell lines derived from NNK-treated mice, oral nicotine did not enhance tumor growth or metastasis. These data show that nicotine does not enhance lung tumorigenesis when given to achieve levels comparable with those of NRT, suggesting that nicotine has a dose threshold, below which it has no appreciable effect. These studies are consistent with epidemiologic data showing that NRT does not enhance lung cancer risk in former smokers. Cancer Prev Res; 4(11); 1743–51. ©2011 AACR.
Reduction of Oxidative Damage Reflects a Better Kidney Transplantation Outcome
Authors: La Manna Gaetano , Lanci Nicole , Della Bella Elena , Comai Giorgia , Cappuccilli Maria Laura , Nisi Katia , Todeschini Paola , Carretta Elisa , Scolari Maria Piera , Stefoni Sergio
Published: October 2011

Background/Aims: DNA fragmentation is one of the typical features of apoptosis, frequently induced by oxidative stress. Increased oxidative stress is known to be related to several pathological processes. In this study, we assessed oxidative damage in the early follow-up period after kidney transplantation measuring DNA oxidation and fragmentation of mononuclear cells and the circulating levels of inflammatory cytokines. Methods: Blood samples from 30 kidney transplant recipients were collected before transplantation and after 2 days, 1 month and 6 months. Oxidative DNA fragmentation was measured by Comet Assay, whereas DNA oxidation was evaluated measuring 8-OHdG leukocyte levels. Serum IL-1β, IL-4, IL-6, IL-8, IL-10, IFN-γ and TNF-α were assayed using a multiplex ELISA analysis. Results: At 6 months after transplantation, a significant reduction in DNA fragmentation and IL-6 plasma levels was observed; DNA oxidation was higher in patients with a worse outcome, with delayed graft function and low nutritional status. We also found a correlation of IL-6 and IL-10 levels with DNA fragmentation and of IL-10 levels with DNA oxidation. Conclusion: Low levels of oxidation and apoptosis at 6 months after transplantation correlate with a better recovery of renal function in kidney allografts. The measurement of cytokine levels confirmed a reduction of inflammatory parameters within 6 months of follow-up.
An Overview of Longitudinal Data Analysis Methods for Neurological Research
Authors: Locascio Joseph J. , Atri Alireza
Published: October 2011

The purpose of this article is to provide a concise, broad and readily accessible overview of longitudinal data analysis methods, aimed to be a practical guide for clinical investigators in neurology. In general, we advise that older, traditional methods, including (1) simple regression of the dependent variable on a time measure, (2) analyzing a single summary subject level number that indexes changes for each subject and (3) a general linear model approach with a fixed-subject effect, should be reserved for quick, simple or preliminary analyses. We advocate the general use of mixed-random and fixed-effect regression models for analyses of most longitudinal clinical studies. Under restrictive situations or to provide validation, we recommend: (1) repeated-measure analysis of covariance (ANCOVA), (2) ANCOVA for two time points, (3) generalized estimating equations and (4) latent growth curve/structural equation models.
Improvement of Non-Steroidal Anti-Inflammatory Drug-Induced Gastrointestinal Symptoms during Proton Pump Inhibitor Treatment: Are G-Protein β3 Subunit Genotype, Helicobacter pylori Status, and Environmental Factors Response Modifiers?
Authors: Holtmann G. , van Rensburg C. , Schwan T. , Sander P. , Siffert W.
Published: October 2011

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with significant upper and lower gastrointestinal (GI) morbidity. Aim: To determine the efficacy and safety of pantoprazole versus placebo in controlling GI symptoms during treatment with NSAIDs and to evaluate the influence of potential response modifiers. Methods: 800 patients with GI complaints during NSAID treatment were randomized to pantoprazole 20 mg once daily or placebo for 4 weeks in this double-blind, multicenter trial. Assessments included the difference in cumulated overall symptom load of any GI complaint during treatment (primary endpoint), proportion of days without GI symptoms, and influence of risk factors such as gender, age, alcohol consumption, smoking, Helicobacter pylori status, and GNB3 genotype SNP rs5443 (825C>T) on symptom load. Results: At 4 weeks, cumulated overall symptom load was significantly lower in pantoprazole than placebo recipients [p < 0.0001; intent-to-treat (ITT)]; the effect was statistically significant after 7 days’ treatment. Pantoprazole versus placebo recipients had 54 versus 29% of days without GI symptoms (p < 0.0001; ITT). Neither common risk factors nor GNB3 genotype were significantly associated with therapeutic response, while GNB3 825TT versus CT was associated with a significantly higher baseline symptom load (p < 0.05). Conclusion: In the population studied, treatment with the proton pump inhibitor pantoprazole significantly improves GI symptoms during NSAID therapy, irrespective of the risk factors investigated or GNB3 genotype.
Electrocardiographic Characteristics and
SCN5A
Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization
Authors: Watanabe Hiroshi , Nogami Akihiko , Ohkubo Kimie , Kawata Hiro , Hayashi Yuka , Ishikawa Taisuke , Makiyama Takeru , Nagao Satomi , Yagihara Nobue , Takehara Naofumi , Kawamura Yuichiro , Sato Akinori , Okamura Kazuki , Hosaka Yukio , Sato Masahito , Fukae Satoki , Chinushi Masaomi , Oda Hirotaka , Okabe Masaaki , Kimura Akinori , Maemura Koji , Watanabe Ichiro , Kamakura Shiro , Horie Minoru , Aizawa Yoshifusa , Shimizu Wataru , Makita Naomasa
Published: October 2011

Background—

Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear.

Methods and Results—

This study included 50 patients (44 men; age, 45±17 years) with idiopathic ventricular fibrillation associated with early repolarization, and 250 age- and sex-matched healthy controls. All of the patients had experienced arrhythmia events, and 8 (16%) had a family history of sudden death. Ventricular fibrillation was inducible by programmed electric stimulation in 15 of 29 patients (52%). The heart rate was slower and the PR interval and QRS duration were longer in patients with idiopathic ventricular fibrillation than in controls. We identified nonsynonymous variants in
SCN5A
(resulting in A226D, L846R, and R367H) in 3 unrelated patients. These variants occur at residues that are highly conserved across mammals. His-ventricular interval was prolonged in all of the patients carrying an
SCN5A
mutation. Sodium channel blocker challenge resulted in an augmentation of early repolarization or development of ventricular fibrillation in all of 3 patients, but none was diagnosed with Brugada syndrome. In heterologous expression studies, all of the mutant channels failed to generate any currents. Immunostaining revealed a trafficking defect in A226D channels and normal trafficking in R367H and L846R channels.

Conclusions—

We found reductions in heart rate and cardiac conduction and loss-of-function mutations in
SCN5A
in patients with idiopathic ventricular fibrillation associated with early repolarization. These findings support the hypothesis that decreased sodium current enhances ventricular fibrillation susceptibility.
SYNTAX Score Reproducibility and Variability Between Interventional Cardiologists, Core Laboratory Technicians, and Quantitative Coronary Measurements
Authors: Généreux Philippe , Palmerini Tullio , Caixeta Adriano , Cristea Ecaterina , Mehran Roxana , Sanchez Raquel , Lazar Dana , Jankovic Ivana , Corral Maria D. , Dressler Ovidiu , Fahy Martin P. , Parise Helen , Lansky Alexandra J. , Stone Gregg W.
Published: October 2011

Background—

In the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial, the SYNTAX score was useful in risk stratifying patients with complex coronary artery disease. The reproducibility of this score may affect its clinical utility. We therefore assessed SYNTAX score interobserver and intraobserver variability among a group of interventional cardiologists (ICs) and an experienced group of angiographic core laboratory (ACL) technicians.

Methods and Results—

After basic training from the SYNTAX score website, 3 ICs and 4 ACL technicians, each working independently, assessed the SYNTAX score of 30 multivessel disease angiograms. The ICs then underwent an intensive training session with ACL technicians, after which the SYNTAX score from 50 additional angiograms were assessed independently by both groups. Interobserver Fleiss κ statistic values were determined. A third assessment was performed using quantitative coronary angiography (QCA). The ACL technician interobserver strength of agreement from both periods was substantial or greater (k=0.82; 95% CI [0.72, 1.00] and 0.84 [0.76, 1.00]) and not different than QCA. The IC interobserver agreement was initially estimated to be at least slight (k=0.33 [0.18, 0.44]), improving to substantial or greater after advanced training (k=0.76 [0.64, 1.00]). Despite advanced training, ICs underscored the number of lesions, bifurcations, and small-vessel disease (
P
<0.001), resulting in a lower score than ACL technicians (mean difference=7.5,
P
<0.001).

Conclusions—

Highly reproducible SYNTAX score measurements were quickly achieved by experienced ACL technicians. In contrast, agreement among ICs after the basic tutorial was initially poor but improved considerably after further training with the ACL, although differences still remained in interpretation of several lesion types. These findings have important implications for adoption of SYNTAX score methodology in routine practice and future clinical trials.
Flagellin Enhances Saliva IgA Response and Protection of Anti-caries DNA Vaccine
Authors: Shi W. , Li Y.H. , Liu F. , Yang J.Y. , Zhou D.H. , Chen Y.Q. , Zhang Y. , Yang Y. , He B.X. , Han C. , Fan M.W. , Yan H.M.
Published: October 2011

We and others have shown that anti-caries DNA vaccines, including pGJA-P/VAX, are promising for preventing dental caries. However, challenges remain because of the low immunogenicity of DNA vaccines. In this study, we used recombinant flagellin protein derived from Salmonella (FliC) as a mucosal adjuvant for anti-caries DNA vaccine (pGJA-P/VAX) and analyzed the effects of FliC protein on the serum PAc-specific IgG and saliva PAc-specific IgA antibody responses, the colonization of Streptococcus mutans ( S. mutans) on rat teeth, and the formation of caries lesions. Our results showed that FliC promoted the production of PAc-specific IgG in serum and secretory IgA (S-IgA) in saliva of rats by intranasal immunization with pGJA-P/VAX plus FliC. Furthermore, we found that enhanced PAc-specific IgA responses in saliva were associated with the inhibition of S. mutans colonization of tooth surfaces and endowed better protection with significant fewer caries lesions. In conclusion, our study demonstrates that recombinant FliC could enhance specific IgA responses in saliva and protective ability of pGJA-P/VAX, providing an effective mucosal adjuvant candidate for intranasal immunization of an anti-caries DNA vaccine.
Evaluation of the perceived elasticity of sheepskin using a three-axis force sensor system
Authors: Kwon Euichul , Kamijo Masayoshi , Takatera Masayuki
Published: October 2011

Sheepskin refers to the hide taken from a sheep and is composed of a layer of skin and the attached hair. It has unique fabric handle properties, and sheepskin quality assessments generally depend on a subjective hand evaluation via sensory test. Therefore, it is necessary to measure the fabric handle of sheepskin mechanically. For this study, we focused on perceived elasticity, and attempted to clarify the relationship between the tactile sensation and the mechanical properties of sheepskin through the development of a new three-dimensional tactile sensation measurement system (3D-TSMS) to measure the compression properties in three axial directions. For compression testing, the compression parameters were calculated as follows: compression linearity ( LC), compressional energy ( WC), compressional resilience ( RC), compressional flexibility coefficient ( αmax), pressure relieving energy (Δ EPR), and continuous mean deviation ( CMD), etc. As a result of compression testing, the sheepskin samples which were highly rated for their perceived elasticity showed a convex curve during the initial compression process. In the statistical comparison analysis, LC, CMD, and Δ EPR showed a correlation to the perceived elasticity of sheepskin.
Study of the dynamics of rotor-spun composite yarn spinning process in forced vibration
Authors: Faraz Naeem , Khan Yasir
Published: October 2011

The non-linear force vibration oscillator is established for the rotor-spun composite yarn spinning process. The variational iteration method is used to calculate the approximate oscillating periods in the vertical and horizontal directions. Thecondition for resonance is obtained.
Thermal and mechanical properties of ultrasonically treated wool
Authors: Li Qing , Hurren Christopher J , Yu Hengxing , Ding Cailing , Wang Xungai
Published: October 2011

Wool fabrics, ultrasonically treated in various chemical conditions and for different time durations, were analysed for thermal properties by thermo-gravimetric analysis and differential scanning calorimeter, in comparison with the untreated fabric. Fabric mechanical properties, such as bending and tensile performance, and changes in fibre morphology were also evaluated before and after ultrasonic treatment.

It is found that wool treated with ultrasonics at the appropriate time, has less mass loss and a higher thermal degradation temperature than that without ultrasonic treatment or with prolonged ultrasonic treatment. Resistance to thermal degradation is reduced when wool is ultrasonically treated in the presence of alkali. Differential scanning calorimeter analysis shows that while ultrasonic treatment has little effect on fibre crystallinity, an appropriate treatment can provide wool with increased water absorption. Ultrasonic treatment stiffens wool fabric to some extent when the treatment time is prolonged. The addition of detergent alone to the ultrasonic bath has little effect on fabric tensile behaviour, whereas a treatment with both detergent and alkali produces severe fibre damage and significant loss of fabric tensile strength.
Antibacterial activity of capsaicin-coated wool fabric
Authors: Liu Xin , Lin Tong , Peng Bixian , Wang Xungai
Published: October 2011

Fabrics made from natural fibers, such as wool and cotton, are susceptible to attacks from micro-organisms, which may damage the fabrics and harm the human body. Antimicrobial finishing of natural textile products may involve harmful and non-environmentally friendly chemicals. In this study, a natural antibacterial agent, capsaicin, was coated on the surface of wool fabrics by a sol-gel process. The antibacterial properties of coated fabrics were evaluated against test bacteria Escherichia coli according to the American Association of Textile Chemists and Colorists (AATCC) method and standard American Society for Testing and Materials (ASTM) E2149-01. Compared with the control group (sol-gel coated fabric without capsaicin), the capsaicin-coated fabric inhibited bacterial growth markedly after 24 hours incubation at 37°C. The antibacterial efficiency after laundry washes was also investigated. Good durability to washing of capsaicin on fabric was achieved by the sol-gel coating technique.