bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Proteome Analysis in Patients with Rheumatoid Arthritis Receiving Therapy with Tocilizumab: An Anti-Interleukin-6 Receptor Antibody
Authors: Yanagida Mitsuaki , Kawasaki Mikiko , Fujishiro Maki , Miura Masako , Ikeda Keigo , Nozawa Kazuhisa , Kaneko Hiroshi , Morimoto Shinji , Takasaki Yoshinari , Ogawa Hideoki , Takamori Kenji , Sekigawa Iwao
Published: August 2013

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the synovial membrane that results in the destruction of bone and cartilage in affected joints. Tocilizumab is a biological agent and an anti-interleukin-6 (IL-6) receptor monoclonal antibody that blocks IL-6-mediated inflammatory processes in RA patients. In order to identify novel disease-related proteins and candidate biomarkers, we analyzed the changes in the serum proteome profiles of patients with RA who were treated with tocilizumab. Serum samples were collected from the RA patients before and after tocilizumab treatment. Following immunodepletion of major proteins, the proteins were digested and labeled with isobaric tag, iTRAQ reagent. The proteins were identified and quantified using liquid chromatography-tandem mass spectrometry. Among a total of 311 proteins identified, seven were decreased and 16 were increased by tocilizumab treatment. Although some of the proteins are known to be related to RA, several are currently unknown with respect to their relationship to RA and may be involved in the development of this disease. This study is the first to perform a comparative serum proteomic analysis of RA patients treated with tocilizumab. Our results may contribute to the identification of novel disease-related proteins and enhance the understanding of the pathogenesis of RA.
Study of the Nonlinear Dropping Shock Response of Expanded Foam Packaging System
Authors: Jiang Huan-xin , Zhu Yong , Lu Li-xin
Published: August 2013

The variational iteration method-2 (VIM-2) is applied to obtain approximate analytical solutions of EPS foam cushioning packaging system. The first-order frequency solution of the equation of motion was obtained and compared with the numerical simulation solution solved by the Runge-Kutta algorithm. The results showed the high accuracy of this VIM with convenient calculation.
A Nonlinear Shooting Method and Its Application to Nonlinear Rayleigh-Bénard Convection
Authors: Singh Jitender
Published: August 2013

The simple shooting method is revisited in order to solve nonlinear two-point BVP numerically. The BVP of the type is considered where components of are known at one of the boundaries and components of are specified at the other boundary. The map is assumed to be smooth and satisfies the Lipschitz condition. The two-point BVP is transformed into a system of nonlinear algebraic equations in several variables which, is solved numerically using the Newton method. Unlike the one-dimensional case, the Newton method does not always have quadratic convergence in general. However, we prove that the rate of convergence of the Newton iterative scheme associated with the BVPs of present type is at least quadratic. This indeed justifies and generalizes the shooting method of Ha (2001) to the BVPs arising in the higher order nonlinear ODEs. With at least quadratic convergence of Newton's method, an explicit application in solving nonlinear Rayleigh-Bénard convection in a horizontal fluid layer heated from the below is discussed where rapid convergence in nonlinear shooting essentially plays an important role.
How Noninvasive Haemoglobin Measurement with Pulse CO-Oximetry Can Change Your Practice: An Expert Review
Authors: Lindner Gregor , Exadaktylos Aristomenis K.
Published: August 2013

Trauma related haemorrhagic anaemia is rarely diagnosed by physical examination alone but typically includes measurement of blood haemoglobin, one of the most frequently ordered laboratory tests. Recently, noninvasive technologies have been developed that allow haemoglobin to be measured immediately without the need for intravenous access or having to take venous, arterial, or capillary blood. Moreover, with these technologies haemoglobin can be continuously measured in patients with active bleeding, to guide the start and stop of blood transfusions and to detect occult bleeding. Recent studies on the accuracy of the devices showed promising results in terms of accuracy of hemoglobin measurement compared to laboratory determination. The present review gives an overview on the technology itself and reviews the current literature on the subject.
Severe Intraperitoneal Haemorrhage following Suprapubic Catheter Insertion in a Patient Treated with Iloprost
Authors: Spence R. A. J. , Thwaini A. , O’Brien Aidan
Published: August 2013

Suprapubic catheter (SPC) insertion is a common urological procedure, performed both in the elective and emergency settings. The authors present an unusual case of severe intraperitoneal bleeding following the insertion of an SPC under direct vision, where the use of prostacyclin analogue may have been a contributing factor.
New Insights into Biology, Prognostic Factors, and Current Therapeutic Strategies in Chronic Lymphocytic Leukemia
Authors: Smolewski Piotr , Witkowska Magdalena , Korycka-Wołowiec Anna
Published: August 2013

Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation and accumulation of mature B lymphocytes. CLL cells show an antiapoptotic profile, suggesting the important role of apoptosis inhibition in the disease development. However, there is some population of proliferating CLL cells, which may also play a role in progression of the disease. There are several newer, biological prognostic factors in CLL. Currently, cytogenetic abnormalities with different prognostic values seem to be the most biologically relevant. During the last decades, the treatment of CLL has been significantly changed. Different strategies such as monotherapy with chlorambucil and purine nucleoside analogues (PNA) used alone or in combination with cyclophosphamide have been introduced. Most recently, immunochemotherapy with anti-CD20 monoclonal antibody, rituximab, combined with fludarabine and cyclophosphamide, became a gold standard of first-line treatment in eligible CLL patients. Currently, new treatment strategies including new monoclonal antibodies, bendamustine, lenalidomide, or inhibitors of several cell signaling pathways are under clinical studies in resistant/relapsed CLL patients. Moreover, allogeneic stem cell transplantation has to be considered, especially in younger high risk patients, for example, those who are resistant to PNA or those with 17p deletion. In this paper, we present the most important recent advances in CLL biology and treatment.
Increased Frequency of Antigen-Specific Polyfunctional T Cells in Tuberculosis Patients
Authors: Syed Ahamed Kabeer Basirudeen , Selvaraj Anbalagan , Raja Alamelu
Published: August 2013

This study assessed the polyfunctional T cells in healthy household contacts (HHCs) and TB patients. This study also assessed the memory subsets responsible for the secretion of IFN-γ during the short-term culture with Mycobacterium tuberculosis antigens. Frequencies of CD4+IFN-γ+TNF-α+ T cells and CD8+IFN-γ+TNF-α+ T cells specific to M. tuberculosis antigens were significantly higher in TB patients compared to HHC. IFN-γ-secreting T cells, during overnight stimulation with M. tuberculosis antigens, belonged to effector memory subset with a CD45RA−CD27− phenotype. However, the number of IFN-γ-secreting effector memory cells did not differ between HHC and TB patients.
Cross-Sectional and Longitudinal Associations between Body Mass Index and Cardiometabolic Risk Factors in Adolescents in a Country of the African Region
Authors: Lyngdoh Tanica , Viswanathan Bharathi , van Wijngaarden Edwin , Myers Gary J. , Bovet Pascal
Published: August 2013

We assessed the association between several cardiometabolic risk factors (CRFs) (blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, uric acid, and glucose) in 390 young adults aged 19-20 years in Seychelles (Indian Ocean, Africa) and body mass index (BMI) measured either at the same time (cross-sectional analysis) or at the age of 12–15 years (longitudinal analysis). BMI tracked markedly between age of 12–15 and age of 19-20. BMI was strongly associated with all considered CRFs in both cross-sectional and longitudinal analyses, with some exceptions. Comparing overweight participants with those having a BMI below the age-specific median, the odds ratios for high blood pressure were 5.4/4.7 (male/female) cross-sectionally and 2.5/3.9 longitudinally (P<0.05). Significant associations were also found for most other CRFs, with some exceptions. In linear regression analysis including both BMI at age of 12–15 and BMI at age of 19-20, only BMI at age of 19-20 remained significantly associated with most CRFs. We conclude that CRFs are predicted strongly by either current or past BMI levels in adolescents and young adults in this population. The observation that only current BMI remained associated with CRFs when including past and current levels together suggests that weight control at a later age may be effective in reducing CRFs in overweight children irrespective of past weight status.
The Role of Sport Involvement and General Self-Worth in the Interplay between Body Dissatisfaction, Worry, and School Disaffection in Preadolescent Boys and Girls
Authors: Raufelder Diana , Waak Sandra , Melchior Alice , Ittel Angela
Published: August 2013

While in recent years there has been increasing research on body dissatisfaction in preadolescence and a small body of research on worry in association with eating disorders, less is known about their effects on school disaffection. Therefore, the current study examined possible gender-specific relations between body dissatisfaction, worry, and school disaffection. To identify possible strategies of intervention and prevention, sport involvement and general self-worth were tested as mediators. Multigroup structural equation modeling (SEM) was used to test for the mediating role of sport involvement and general self-worth in the association between body dissatisfaction, worry, and school disaffection in a sample of 4th, 5th, and 6th grade students (; ) in elementary schools in Berlin, Germany. The results suggest that promoting feelings of general self-worth could be an effective starting point in decreasing the association between body dissatisfaction, worry, and school disaffection, in both boys and girls. Conversely, sport involvement was identified as a mediating factor for boys only.
The Preoperative Assessment of Hepatic Tumours: Evaluation of UK Regional Multidisciplinary Team Performance
Authors: Wiggans M. G. , Jackson S. A. , Fox B. M. T. , Mitchell J. D. , Aroori S. , Bowles M. J. , Armstrong E. M. , Shirley J. F. , Stell D. A.
Published: August 2013

Introduction. In the UK, patients where liver resection is contemplated are discussed at hepatobiliary multidisciplinary team (MDT) meetings. The aim was to assess MDT performance by identification of patients where radiological and pathological diagnoses differed. Materials and Methods. A retrospective review of a prospectively maintained database of all cases undergoing liver resection from March 2006 to January 2012 was performed. The presumed diagnosis as a result of radiological investigation and MDT discussion is recorded at the time of surgery. Imaging was reviewed by specialist gastrointestinal radiologists, and resultswereagreedonby consensus. Results. Four hundred and thirty-eight patients were studied. There was a significant increase in the use of preoperative imaging modalities () but no change in the rate of discrepant diagnosis over time. Forty-two individuals were identified whose final histological diagnosis was different to that following MDT discussion (9.6%). These included 30% of patients diagnosed preoperatively with hepatocellular carcinoma and 25% with cholangiocarcinoma of a major duct. Discussion. MDT assessment of patients preoperatively is accurate in terms of diagnosis. The highest rate of discrepancies occurred in patients with focal lesions without chronic liver disease or primary cancer, where hepatocellular carcinoma was overdiagnosed and peripheral cholangiocarcinoma underdiagnosed, where particular care should be taken. Additional care should be taken in these groups and preoperative multimodality imaging considered.
Integrin αvβ3 and Fibronectin Upregulate Slug in Cancer Cells to Promote Clot Invasion and Metastasis
Authors: Knowles Lynn M. , Gurski Lisa A. , Engel Charlotte , Gnarra James R. , Maranchie Jodi K. , Pilch Jan
Published: August 2013

The blood clotting cascade is selectively involved in lung metastasis, but the reason for this selectivity is unclear. Here, we show that tumor cells that metastasize predominantly to the lung, such as renal cell carcinoma (RCC) and soft tissue sarcoma (STS), have an inherent capacity to generate extensive invadopodia when embedded in a blood clot. Compared with other metastatic cancer cells tested, RCC and STS cells exhibited increased levels of expression of fibronectin and an activated form of the integrin αvβ3, which coordinately supported the generation of an elaborate fibronectin matrix and actin stress fibers in fibrin-embedded tumor cells. Together, fibronectin and αvβ3 induced upregulation of the transcription factor Slug, which mediates epithelial–mesenchymal transition as well as fibrin invasion and lung metastasis. This mechanism is clinically significant, because primary cancer cells from patients with metastatic RCC strongly invaded fibrin and this correlated with fibronectin matrix formation and Slug expression. In contrast, tumor cells from patients with localized RCC were largely noninvasive. Together, our findings establish that activated integrin αvβ3 and fibronectin promote lung metastasis by upregulating Slug, defining a mechanism through which cancer cells can colonize blood clots in the lung vasculature. Cancer Res; 73(20); 6175–84. ©2013 AACR.
Increased Proliferative Background in Healthy Women with BRCA1/2 Haploinsufficiency Is Associated with High Risk for Breast Cancer
Authors: Nisman Benjamin , Kadouri Luna , Allweis Tanir , Maly Bella , Hamburger Tamar , Gronowitz Simon , Peretz Tamar
Published: August 2013

Previous studies indicated that BRCA haploinsufficiency was associated with activation of the EGF receptor (EGFR) signaling pathway and increased proliferative activity in mammary epithelial cells of healthy women. We hypothesized that these processes might be reflected in the expression of serologic soluble EGFR (sEGFR) and thymidine kinase 1 (TK1) activity, which signal the initial and final steps of the proliferative pathway, respectively. We found that healthy carriers of BRCA1/2 mutations (n = 80) showed a significantly higher TK1 activity than age-matched controls (P = 0.0003), and TK1 activity was similar in women with BRCA1 and BRCA2 mutations (P = 0.74). The sEGFR concentration was significantly higher in women with BRCA1 than in controls and BRCA2 mutation (P = 0.013 and 0.002, respectively). During follow-up, four of 80 BRCA1/2 mutation carriers developed breast cancer. These women showed a significantly higher TK1 activity and somewhat higher sEGFR concentrations than the other 76 BRCA1/2 carriers (P = 0.04 and 0.09, respectively). All tumors were negative for ovarian hormone receptors, but showed a high EGFR expression. This study was limited by the short-term follow-up (mean, 27 months; range, 5–45), which resulted in a small sample size. Women with BRCA1 and BRCA2 mutations that had undergone risk-reducing bilateral salpingo-oophorectomy (BSO) showed significantly lower sEGFR compared with those without surgery (P = 0.007 and 0.038, respectively). Larger, prospective studies are warranted to investigate whether TK1 and sEGFR measurements may be useful for identifying healthy BRCA1/2 carriers with high risk of developing breast cancer; moreover, sEGFR measurements may serve as effective tools for assessing risk before and after BSO. Cancer Epidemiol Biomarkers Prev; 22(11); 2110–5. ©2013 AACR.
The Use of Metformin and Colorectal Cancer Incidence in Patients with Type II Diabetes Mellitus
Authors: Smiechowski Brielan , Azoulay Laurent , Yin Hui , Pollak Michael N. , Suissa Samy
Published: August 2013

Background: Experimental studies have suggested that metformin may decrease the incidence of colorectal cancer in patients with type II diabetes. However, previous observational studies have reported contradictory results, which are likely due to important methodologic limitations. Thus, the objective of this study was to assess whether the use of metformin is associated with the incidence of colorectal cancer in patients with type II diabetes.

Methods: A cohort study of patients newly treated with non-insulin antidiabetic agents was assembled using the United Kingdom Clinical Practice Research Datalink. A nested case–control analysis was conducted, where all incident cases of colorectal cancer occurring during follow-up were identified and randomly matched with up to 10 controls. Conditional logistic regression was used to estimate adjusted rate ratios (RR) of colorectal cancer associated with ever use, and cumulative duration of use of metformin. All models accounted for latency and were adjusted for relevant potential confounding factors.

Results: Overall, ever use of metformin was not associated with the incidence of colorectal cancer [RR: 0.93; 95% confidence interval (CI), 0.73–1.18]. Similarly, no dose–response relationship was observed in terms of cumulative duration of use.

Conclusions: The use of metformin was not associated with the incidence of colorectal cancer in patients with type II diabetes.

Impact: The results of this study do not support the launch of metformin randomized controlled trials for the chemoprevention of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 22(10); 1877–83. ©2013 AACR.
Phase II Trial of Bicalutamide in Patients with Androgen Receptor–Positive, Estrogen Receptor–Negative Metastatic Breast Cancer
Authors: Gucalp Ayca , Tolaney Sara , Isakoff Steven J. , Ingle James N. , Liu Minetta C. , Carey Lisa A. , Blackwell Kimberly , Rugo Hope , Nabell Lisle , Forero Andres , Stearns Vered , Doane Ashley S. , Danso Michael , Moynahan Mary Ellen , Momen Lamia F. , Gonzalez Joseph M. , Akhtar Arooj , Giri Dilip D. , Patil Sujata , Feigin Kimberly N. , Hudis Clifford A. , Traina Tiffany A.
Published: August 2013

Purpose: Patients with hormone receptor–negative breast cancer generally do not benefit from endocrine-targeted therapies. However, a subset with androgen receptor (AR) expression is predicted to respond to antiandrogen therapies. This phase II study explored bicalutamide in AR-positive, estrogen receptor (ER), and progesterone receptor (PgR)-negative metastatic breast cancer.

Experimental Design: Tumors from patients with ER/PgR-negative advanced breast cancer were tested centrally for AR [immunohistochemistry (IHC) > 10% nuclear staining considered positive]. If either the primary or a metastatic site was positive, patients were eligible to receive the AR antagonist bicalutamide at a dose of 150 mg daily. Clinical benefit rate (CBR), the primary endpoint, was defined as the total number of patients who show a complete response (CR), partial response (PR), or stable disease (SD) > 6 months; secondary endpoints included progression-free survival (PFS) and toxicity. Correlative studies included measurement of circulating endocrine markers and IHC surrogates for basal-like breast cancer.

Results: Of 424 patients with ER/PgR-negative breast cancer, 12% tested AR-positive. The 6-month CBR was 19% [95% confidence interval (CI), 7%–39%] for bicalutamide. The median PFS was 12 weeks (95% CI, 11–22 weeks). Bicalutamide was well-tolerated with no grade 4/5 treatment-related adverse events observed.

Conclusion: AR was expressed in 12% of patients with ER/PgR-negative breast cancer screened for this trial. The CBR of 19% observed with bicalutamide shows proof of principle for the efficacy of minimally toxic androgen blockade in a select group of patients with ER/PgR-negative, AR-positive breast cancer. Clin Cancer Res; 19(19); 5505–12. ©2013 AACR.
New Strategies in Neuroblastoma: Therapeutic Targeting of MYCN and ALK
Authors: Barone Giuseppe , Anderson John , Pearson Andrew D.J. , Petrie Kevin , Chesler Louis
Published: August 2013

Clinical outcome remains poor in patients with high-risk neuroblastoma, in which chemoresistant relapse is common following high-intensity conventional multimodal therapy. Novel treatment approaches are required. Although recent genomic profiling initiatives have not revealed a high frequency of mutations in any significant number of therapeutically targeted genes, two exceptions, amplification of the MYCN oncogene and somatically acquired tyrosine kinase domain point mutations in anaplastic lymphoma kinase (ALK), present exciting possibilities for targeted therapy. In contrast with the situation with ALK, in which a robust pipeline of pharmacologic agents is available from early clinical use in adult malignancy, therapeutic targeting of MYCN (and MYC oncoproteins in general) represents a significant medicinal chemistry challenge that has remained unsolved for two decades. We review the latest approaches envisioned for blockade of ALK activity in neuroblastoma, present a classification of potential approaches for therapeutic targeting of MYCN, and discuss how recent developments in targeting of MYC proteins seem to make therapeutic inhibition of MYCN a reality in the clinic. Clin Cancer Res; 19(21); 5814–21. ©2013 AACR.
Intratumoral Anti-CTLA-4 Therapy: Enhancing Efficacy While Avoiding Toxicity
Authors: Marabelle Aurélien , Kohrt Holbrook , Levy Ronald
Published: August 2013

Systemic administration of the checkpoint blockade antibody anti-CTLA4 results in severe autoimmune toxicity, limiting its clinical efficacy. Fransen and colleagues show here that peritumoral delivery of low doses of this immunomodulatory drug can trigger a systemic antitumor immune response while preventing the toxicity against other organs. Clin Cancer Res; 19(19); 5261–3. ©2013 AACR.
Synergistic Targeting of PI3K/AKT Pathway and Androgen Receptor Axis Significantly Delays Castration-Resistant Prostate Cancer ProgressionIn Vivo
Authors: Thomas Christian , Lamoureux Francois , Crafter Claire , Davies Barry R. , Beraldi Eliana , Fazli Ladan , Kim Soojin , Thaper Daksh , Gleave Martin E. , Zoubeidi Amina
Published: August 2013

The progression to castration-resistant prostate cancer (CRPC) correlates with gain-of-function of the androgen receptor (AR) and activation of AKT. However, as single agents, AR or AKT inhibitors result in a reciprocal feedback loop. Therefore, we hypothesized that combination of an AKT inhibitor with an antiandrogen might result in a more profound, long-lasting remission of CRPC. Here, we report that the AKT inhibitor AZD5363 potently inhibits proliferation and induces apoptosis in prostate cancer cell lines expressing the AR and has anticancer activity in vivo in androgen-sensitive and castration-resistant phases of the LNCaP xenograft model. However, we found that the effect of castration-resistant tumor growth inhibition and prostate-specific antigen (PSA) stabilization is transient and resistance occurs with increasing PSA after approximately 30 days of treatment. Mechanistically, we found that single agent AZD5363 induces increase of AR binding to androgen response element, AR transcriptional activity, and AR-dependent genes such as PSA and NKX3.1 expression. These effects were overcome by the combination of AZD5363 with the antiandrogen bicalutamide, resulting in synergistic inhibition of cell proliferation and induction of apoptosis in vitro, and prolongation of tumor growth inhibition and PSA stabilization in CRPC in vivo. This study provides a preclinical proof-of-concept that combination of an AKT inhibitor with antiandrogen results in prolonged disease stabilization in a model of CRPC. Mol Cancer Ther; 12(11); 2342–55. ©2013 AACR.
Hsp90 Inhibitors Promote p53-Dependent Apoptosis through PUMA and Bax
Authors: He Kan , Zheng Xingnan , Zhang Lin , Yu Jian
Published: August 2013

Hsp90 is widely overexpressed in cancer cells and believed to be essential for the maintenance of malignant phenotypes. Targeting Hsp90 by small molecules has shown promise in solid and hematologic malignancies, which likely involves degradation of client oncoproteins in a cell-type–specific manner. In this study, we found that structurally unrelated Hsp90 inhibitors induce DNA damage and apoptosis via p53-dependent induction of PUMA, which indirectly triggers Bax activation and mitochondrial dysfunction in colon cancer cells. Deficiency in PUMA, BAX, or p53, at lesser extent, abrogated 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced apoptosis and mitochondrial dysfunction, and enhanced clonogenic cell survival. Furthermore, suppression of p53-dependent p21 induction or enhanced p53 activation synergized with 17-AAG to induce PUMA-dependent apoptosis. Finally, PUMA was found to mediate apoptotic and therapeutic responses to the 17-AAG analog 17-DMAG in xenografts. These results show an important role of the p53/PUMA/Bax axis in Hsp90 inhibitor–induced killing of p53 wild-type cells, and have important implications for their clinical applications. Mol Cancer Ther; 12(11); 2559–68. ©2013 AACR.
RETRACTED: Combining PARP-1 Inhibition and Radiation in Ewing Sarcoma Results in Lethal DNA Damage
Authors: Lee Hae-June , Yoon Changhwan , Schmidt Benjamin , Park Do Joong , Zhang Alexia Y. , Erkizan Hayriye V. , Toretsky Jeffrey A. , Kirsch David G. , Yoon Sam S.
Published: August 2013

Ewing sarcomas (ES) harbor a chromosomal translocation that fuses the EWS gene to an ETS transcription factor, most commonly Friend leukemia integration 1 (FLI1). The EWS-FLI1 fusion protein acts in a positive feedback loop to maintain the expression of PARP-1, which is involved in repair of DNA damage. Here, we examine the effects of PARP-1 inhibition and radiation therapy on Ewing sarcomas. In proliferation assays, the Ewing sarcoma cell lines RD-ES and SK-N-MC were much more sensitive than non-Ewing sarcoma cell lines to the PARP-1 inhibitor olaparib (Ola; IC50 0.5–1 μmol/L vs. >5 μmol/L) and to radiation (IC50 2–4 Gy vs. >6 Gy). PARP-1 inhibition with short hairpin RNA (shRNA) or Ola sensitized Ewing sarcoma cells, but not non-Ewing sarcoma cells, to radiation therapy in both proliferation and colony formation assays. Using the Comet assay, radiation of Ewing sarcoma cells with Ola, compared to without Ola, resulted in more DNA damage at 1 hour (mean tail moment 36–54 vs. 26–28) and sustained DNA damage at 24 hours (24–29 vs. 6–8). This DNA damage led to a 2.9- to 4.0-fold increase in apoptosis and a 1.6- to 2.4-fold increase in cell death. The effect of PARP-1 inhibition and radiation therapy on Ewing sarcoma cells was lost when EWS-FLI1 was silenced by shRNA. A small dose of radiation therapy (4 Gy), when combined with PARP-1 inhibition, stopped the growth of SK-N-MC flank tumors xenografts. In conclusion, PARP-1 inhibition in Ewing sarcomas amplifies the level and duration of DNA damage caused by radiation therapy, leading to synergistic increases in apoptosis and cell death in a EWS-FLI1–dependent manner. Mol Cancer Ther; 12(11); 2591–600. ©2013 AACR.
Examining the Association between Oral Health and Oral HPV Infection
Authors: Bui Thanh Cong , Markham Christine M. , Ross Michael Wallis , Mullen Patricia Dolan
Published: August 2013

Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of oropharyngeal cancers; yet, no published study has examined the role of oral health in oral HPV infection, either independently or in conjunction with other risk factors. This study examined the relation between oral health and oral HPV infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years for whom data on oral HPV and oral health were available from the nationally representative 2009–2010 National Health and Nutrition Examination Survey. Results showed that higher unadjusted prevalence of oral HPV infection was associated with four measures of oral health, including self-rated oral health as poor-to-fair [prevalence ratio (PR) = 1.56; 95% confidence interval (CI), 1.25–1.95], indicated the possibility of gum disease (PR = 1.51; 95% CI, 1.13–2.01), reported use of mouthwash to treat dental problems in the past week (PR = 1.28; 95% CI, 1.07–1.52), and higher number of teeth lost (Ptrend = 0.035). In multivariable logistic regression models, oral HPV infection had a statistically significant association with self-rated overall oral health (OR = 1.55; 95% CI, 1.15–2.09), independent of smoking and oral sex. In conclusion, poor oral health was an independent risk factor of oral HPV infection, irrespective of smoking and oral sex practices. Public health interventions may aim to promote oral hygiene and oral health as an additional measure to prevent HPV-related oral cancers. Cancer Prev Res; 6(9); 917–24. ©2013 AACR.
Procoagulant reactivity to laboratory acute mental stress in Africans and Caucasians, and its relation to depressive symptoms: The SABPA Study
Authors: Hamer Mark , Malan Nico T. , Scheepers Kobus , Meiring Muriel , Malan Leonè , Känel Roland von
Published: August 2013

The risk of cardiovascular disease is dramatically increasing in Africans (black). The prothrombotic stress response contributes to atherothrombotic disease and is modulated by depressive symptoms. We examined coagulation reactivity to acute mental stress and its relation to psychological well-being in Africans relative to Caucasians (white). A total of 102 African and 165 Caucasian school teachers underwent the Stroop Color-Word Conflict test. Circulating levels of von Willebrand factor (VWF) antigen, fibrinogen, and D-dimer were measured before and after the Stroop. Cardiovascular reactivity measures were also obtained. All participants completed the Patient Health Questionnaire-9 and the General Health Questionnaire-28 for the assessment of depressive symptoms and total psychological distress, respectively. After controlling for covariates, resting levels of VWF, fibrinogen, and D-dimer were higher in Africans than in Caucasians (all p-values ≤0.006). Depressive symptoms and psychological distress were not significantly associated with resting coagulation measures. Stress reactivity in VWF (p<0.001) and fibrinogen (p=0.016), but not in D-dimer (p=0.27), were decreased in Africans relative to Caucasians with Africans showing greater reactivity of total peripheral resistance (p=0.017). Depressive symptoms, but not general psychological distress, were associated with greater VWF increase (p=0.029) and greater fibrinogen decrease (p=0.030) in Africans relative to Caucasians. In conclusion, Africans showed greater hypercoagulability at rest but diminished procoagulant reactivity to acute mental stress when compared with Caucasians. Ethnic differences in the vascular adrenergic stress response might partially explain this finding. Depressive symptoms were associated with exaggerated VWF reactivity in Africans relative to Caucasians. The clinical implications of these findings for Africans need further study.
Use of Hydralazine‐Isosorbide Dinitrate Combination in African American and Other Race/Ethnic Group Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction
Authors: Golwala Harsh B. , Thadani Udho , Liang Li , Stavrakis Stavros , Butler Javed , Yancy Clyde W. , Bhatt Deepak L. , Hernandez Adrian F. , Fonarow Gregg C.
Published: August 2013

Background

Hydralazine‐isosorbide dinitrate (H‐
ISDN
) therapy is recommended for
A
frican
A
merican patients with moderate to severe heart failure with reduced ejection fraction (<40%) (
HF
r
EF
), but use, temporal trends, and clinical characteristics associated with H‐
ISDN therapy
in clinical practice are unknown.

Methods and Results

An observational analysis of 54 622 patients admitted with
HF
r
EF
and discharged home from 207 hospitals participating in the Get With The Guidelines–
H
eart
F
ailure registry from April 2008 to March 2012 was conducted to assess prescription, trends, and predictors of use of H‐
ISDN
among eligible patients. Among 11 185
A
frican
A
merican patients eligible for H‐
ISDN
therapy, only 2500 (22.4%) received H‐
ISDN
therapy at discharge. In the overall eligible population, 5115 of 43 498 (12.6%) received H‐
ISDN
at discharge. Treatment rates increased over the study period from 16% to 24% among
A
frican
A
mericans and from 10% to 13% among the entire
HF
r
EF
population. In a multivariable model, factors associated with H‐
ISDN
use among the entire cohort included younger age; male sex;
A
frican
A
merican/Hispanic ethnicity; and history of diabetes, hypertension, anemia, renal insufficiency, higher systolic blood pressure, and lower heart rate. In
A
frican
A
merican patients, these factors were similar; in addition, being uninsured was associated with lower use.

Conclusions

Overall, few potentially eligible patients with
HF
r
EF
are treated with H‐
ISDN
, and among
A
frican‐
A
mericans fewer than one‐fourth of eligible patients received guideline‐recommended H‐
ISDN
therapy. Improved ways to facilitate use of H‐
ISDN
therapy in
A
frican
A
merican patients with
HF
r
EF
are needed.
Princelings and Paupers? State Employment and the Distribution of Human Capital Investments Among Households in Viet Nam
Authors: Coxhead Ian , Phan Diep
Published: August 2013

Inequality in access to education is known to be a key driver of income inequality in developing countries. Viet Nam, a transitional economy, exhibits significant segmentation in the market for skilled labor based on more remunerative employment in government and state firms. We ask whether this segmentation is also reflected in human capital investments at the household level. We find that households whose heads hold state jobs keep their children in school longer, spend more on education, and are more likely to enroll their children in tertiary institutions relative to households whose heads hold nonstate jobs. The estimates are robust to a wide range of household and individual controls. Over time, disparities in educational investments based on differential access to jobs that reward skills and/or credentials help widen existing income and earnings gaps between well-connected “princelings” and the rest of the labor market. Capital market policies that create segmentation in the market for skills also crowd out investment in private sector firms, further reducing incentives for human capital deepening.
Political Connection and Firm Value
Authors: Ang James S. , Ding David K. , Thong Tiong Yang
Published: August 2013

We study the effect of political connection (PC) on company value in an environment where low PC is due to better institutions and not confounded by favorable social/cultural factors. We find that in Singapore, the only country that fits this description, PC in general adds little to the value of a company. However, in industries that are subject to more stringent government regulations, PC appears to be somewhat important. Robustness checks show that alternative PC variables give rise to similar results, and the addition of control variables do not drastically change the findings. Politically connected firms have higher managerial ownership and tend to be smaller than non-PC firms, rendering them more susceptible to poorer governance practices. We show that the presence of politically connected directors somewhat neutralizes such potential negative effects. PC firms are associated with good governance practices such as nonduality in their chairman and chief executive officer positions and fewer executive directors.
Social Performance Studies: Discipline vs. Freedom
Authors: Fei Faye C. , Sun William H.
Published: August 2013

Social performance studies is a new brand of performance studies with Chinese characteristics, focusing on actions performed outside of the theatre, and especially on professional activities meant to have definite effects on particular recipients and spectators.
The Fire and the Frying Pan: Censorship and Performance in Egypt
Authors: Selaiha Nehad
Published: August 2013

Censorship in Egypt, both official and societal, has its roots in a repressive cultural heritage. There are clear signs of further repression under the new Islamist regime.
Imaginaries of Exile and Emergence in Israeli Jewish and Palestinian Hip Hop
Authors: McDonald David A.
Published: August 2013

The landscape of hip hop among Jewish and Palestinian communities in Israel may be understood as the performative interplay of two discursive strategies: exile and emergence. The shift from exile to emergence, embodied in the work of several contemporary hip hop artists, offers a unique reimagining of the Israeli nation-state and provides opportunities for interrogating the dynamics of power and performance in Israel/Palestine.
Be About It: Graffiteras Performing Feminist Community
Authors: Pabón Jessica N.
Published: August 2013

What is the future of feminist movement? What can we learn about that future by looking to the performance of feminism in purportedly “nonfeminist” approaches to women's empowerment and community-building efforts? As participants in a male-dominated, transnational subculture heavily informed by patriarchal ideologies, female graffiti artists are making their presence known in major metropolitan centers across the globe—even as many disidentify with feminist identities.
Death Dressed As a Dancer: The Grotesque, Violence, and the Argentine Tango
Authors: Taylor Julie
Published: August 2013

Tango dancers in Buenos Aires milongas (dance clubs) create a mise-en-scène where intimacy and anonymity clash. Their tango and the rules of etiquette they practice share dissonant experiences of violence, exclusion, and trauma with an Argentine grotesque, the grotesco criollo.
Orgasms and Oppositions: Dani Ploeger's ELECTRODE
Authors: Clarke Alissa
Published: August 2013

In his performance installation, ELECTRODE (2011), Dani Ploeger repeatedly “fakes” orgasms. Using medical devices, digital sound synthesis, and graphs, Ploeger rigorously and specifically labors to replicate the sphincter muscle contraction pattern registered by an anonymous male subject during masturbation and orgasm. In so doing, Ploeger critically explores gender and abjection and creates a heightened, embodied presence.
Perifrasi aspettuali in greco e in latino, Origini e grammaticalizzazioni
Authors: Bentein Klaas
Published: August 2013

I present here a detailed appraisal of Luisa Amenta's Perifrasi aspettuali in greco e in latino, Origini e grammaticalizzazioni (2003). Amenta's study on verbal periphrases is a revised version of her Ph. D. thesis (1999), completed at the Università degli Studi di Roma Tre under the supervision of Prof. Dr. Marco Mancini. It off ers a diachronic and typological confrontation of periphrastic constructions in both Greek and Latin. I outline the contents of the book and give some critical remarks and suggestions for further research, concentrating on periphrases in Greek.
Reconsidering the 'Modal Particles' in Modern Greek
Authors: Tsangalidis Anastasios , Roussou Anna
Published: August 2013

In the present paper we consider the elements na, a and as, which combine with the finite verb and give rise to a variety of modal readings, such as future, subjunctive, etc. On the basis of their distributional similarities and differences, we argue that the elements under consideration are situated in the left periphery and fall into two categories: a and as have a verbal property, while na has a locative one which also underlies its deictic use. This approach allows us to get a better understanding of their current syntactic status, and also has certain implications regarding their diachronic development (e.g. 'grammaticalization'). Our analysis is consistent with the view that there is no syntactic category 'particle' (Zwicky 1985).
Closing in on Story Openings and Closings: Evidence from Conversational Stories in Greek
Authors: Georgakopoulou Alexandra
Published: August 2013

My aim in this paper is to show the benefits of incorporating a conversation-analytic perspective in the analysis of Greek storytelling data with regard to the endpoints of a telling, that is, the opening and the closing. I specifically explore the types of story openings and closings occurring in a data set that comprises the conversations of a group of female adolescents in a small town in Greece. I also discuss the salience of economic openings (Jefferson 1978) realized by certain conventionalized devices and the importance and local design of what I call counter stories in the stories' closing. I juxtapose counter stories to second stories (Sacks 1992), which have been found within CA to be frequent after a story's closing and I assess the frequency of second stories told by the same teller and not by a story recipient in my data. Overall, I argue that these systematic openings and closings in my data are interrelated with the types of stories told and the participants' roles and relations. Finally, I ponder the implications of this close connection for CA work on stories as talk-in-interaction.
A Word-Association Study in Greek and the Concept of the Syntagmatic-Paradigmatic Shift
Authors: Mattheoudakis Marina
Published: August 2013

This paper examines the developmental shift of response type through a qualitative study of word associations in Greek. In particular, it tests whether the associations produced by Greek speakers confirm findings of similar studies in other languages with respect to the syntagmatic-paradigmatic shift. To this aim, a translated version of the Kent-Rosanoff test was administered to both adults and children who were native speakers of Greek. The findings of this study do not provide support for the concept of the syntagmatic-paradigmatic shift, as they indicate a predominance of paradigmatic associations in children's responses and a majority of syntagmatic associations in adults' responses. The paper discusses the concept of the syntagmatic-paradigmatic shift and suggests the need for further research in word associations in Greek but also in other languages.
Switches between Direct and Indirect Speech in Ancient Greek
Authors: Maier Emar
Published: August 2013

I propose a uni ied semantic analysis of two phenomena characteristic of ancient Greek speech reporting, (i) the unmarked switching between direct and indirect discourse, and (ii) the use of οτι ('that') as a quotation introduction. I accommodate these phenomena in a formal semantic framework, where both can be modeled uniformly as instances of mixed quotation.
Greek Anaphora in Cross-Linguistic Perspective
Authors: Kiparsky Paul
Published: August 2013

The Homeric and Classical Greek systems of referentially dependent pronouns support an approach to binding and anaphoric reference which characterizes pronouns by two cross-classifying features, which specify the maximal domain in which their antecedent must be located, and whether they can overlap in reference with a coargument (Kiparsky 2002). By treating reflexivity as a special case of referential dependency, this approach predicts a class of referentially dependent non-reflexive anaphors, or discourse anaphors, whose characteristic is that they need not have a structural antecedent but can serve as reflexives in contexts where a dedicated reflexive is unavailable. This class is instantiated in the Greek clitic anaphors ε&ogr;, ε, &ogr;ι, μιν. It also predicts a class of reflexive pronouns which must be disjoint in reference from a coargument, attested in Homeric Greek as the bare reflexive ε-. Greek also gives some support to the Blocking principle, which dictates the use of the most restricted pronoun available in a given context. The proposal is compared to the well-known theory of Reinhart & Reuland (1993) on the basis of Greek as well as Germanic (Swedish, German, Dutch, Frisian, Old English), and is shown to provide a better answer to the challenge raised by Evans & Levinson (2009).
NN Combinations in Greek
Authors: Gavriilidou Zoe
Published: August 2013

In this paper, multiword NN combinations in Greek are explored within the framework of construction morphology (Booij 2009, 2010a, 2010b). I understand NN combinations as multiword sequences constructed by two inflected words, such as: arxitéktonas-arxeolóγos ‘architect-archeologist’; taksíδi-astrapí lit. ‘trip-lightning’, thus ‘very fast and sudden trip’; sáltsa manitárja lit. ‘sauce mushrooms’, thus ‘mushroom sauce’. I use the classification of Gavriilidou (1997) in order to account for possible different subtypes of NN combinations. I claim that all three types of NN combinations (coordinate, attributive and complementation NN combinations) are visible to syntactic operations, they exhibit, however, various degrees of tightness which are due to whether they exhibit a naming function or not.
oti, na and Negative Markers in the L1 Production of Greek wh-Questions
Authors: Asproudi Evangelia K.
Published: August 2013

The present paper investigates the use of oti, na and negation in wh-question production in L1 Greek. Children’s preference is explored for use of oti and na, and for use of the negation markers ðen and min. These elements have been extensively studied from a theoretical perspective, yet they remain poorly investigated from an acquisition perspective, hence the present study. In long-distance wh-questions na is predicted to be preferred over oti due to its stronger entrenchment as clause-introducing element and as mood marker; in short-distance questions, however, na is predicted to be less preferred than the indicative due to the enriched modal semantics it carries in matrix clause environments. In negative matrix questions ðen is expected to be the preferred choice, since min occurs with na, which carries an extra semantic/pragmatic load. To test these predictions, a group of ninety four-to-seven-year-old Greek children participated in elicited production tasks designed mainly along the methodological principles of Crain and Thornton (1998). The results were generally in line with initial expectations. Children resorted mostly to na in long-distance contexts and to the semantically simpler indicative questions in short-distance contexts. With negative questions, higher accurate use rates were attested for target ðen than for target min, reflecting the simpler semantics associated with the former. Overall, these findings provide evidence that children opt for economy, with semantic factors contributing to their economy-based choices.
Redefining Constructio Praegnans: On the Variation between Allative and Locative Expressions in Ancient Greek
Authors: Nikitina Tatiana , Maslov Boris
Published: August 2013

In traditional Ancient Greek grammar, the term constructio praegnans refers to an apparent syntactic anomaly whereby the idea of motion is missing from either the verb or the prepositional phrase: a verb that does not express motion is combined with a directional prepositional phrase (e.g., ‘slaughter into a container’) or a motion verb combines with a static prepositional phrase describing a goal of motion (e.g., ‘throw in the fire’). This study explores such usages in the period from Archaic to Classical Greek and argues against treating constructio praegnans as a unitary phenomenon. The seemingly aberrant combinations of the verb’s meaning and the type of prepositional phrase are shown to be motivated by four independent factors: 1) lexical (some individual non-motion verbs select for a directional argument); 2) aspectual (static encoding of endpoints is allowed with perfect participles); 3) the encoding of results with change of state verbs; and 4) the archaic use of static prepositional phrases in directional contexts (the goal argument of a motion verb is described by a static prepositional phrase). The four types of “pregnant” use are paralleled by different phenomena in other languages. Based on statistical analysis, they are also argued to undergo different kinds of diachronic development. Some of these developments, nevertheless, fall into a more general pattern: Ancient Greek gradually moves toward a more consistent use of specialized directional expressions to mark goals of motion, conforming increasingly to the “satellite-framed” type of motion encoding.