bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Quantum Encryption Algorithm Based on Multiqubit Quantum Shift Register and Hill Cipher
Authors: Khalaf Rifaat Zaidan , Abdullah Alharith Abdulkareem
Published: November 2014

Based on a quantum shift register, a novel quantum block cryptographic algorithm that can be used to encrypt classical messages is proposed. The message is encoded and decoded by using a code generated by the quantum shift register. The security of this algorithm is analysed in detail. It is shown that, in the quantum block cryptographic algorithm, two keys can be used. One of them is the classical key that is used in the Hill cipher algorithm where Alice and Bob use the authenticated Diffie Hellman key exchange algorithm using the concept of digital signature for the authentication of the two communicating parties and so eliminate the man-in-the-middle attack. The other key is generated by the quantum shift register and used for the coding of the encryption message, where Alice and Bob share the key by using theBB84 protocol. The novel algorithm can prevent a quantum attack strategy as well as a classical attack strategy. The problem of key management is discussed and circuits for the encryption and the decryption are suggested.
Abdominoplasty Improves Quality of Life, Psychological Distress, and Eating Disorder Symptoms: A Prospective Study
Authors: Saariniemi Kai M. M. , Salmi Asko M. , Peltoniemi Hilkka H. , Helle Marjo H. , Charpentier Pia , Kuokkanen Hannu O. M.
Published: November 2014

Background. Only some studies provide sufficient data regarding the effects of nonpostbariatric (aesthetic) abdominoplasty on various aspects of quality of life. Nevertheless, when considering the effects on eating habits, publications are lacking. Therefore we decided to assess the effects of nonpostbariatric abdominoplasty on eating disorder symptoms, psychological distress, and quality of life. Materials and Methods. 64 consecutive women underwent nonpostbariatric abdominoplasty. Three outcome measures were completed: the Eating Disorder Inventory (EDI), Raitasalo’s modification of the Beck Depression Inventory (RBDI), and the 15D general quality of life questionnaire. Results. The mean age at baseline was 42 years and the mean body mass index (BMI) 26.4. Fifty-three (83%) women completed all the outcome measures with a mean follow-up time of 5 months. A significant improvement from baseline to follow-up was noted in women’s overall quality of life, body satisfaction, effectiveness, sexual functioning, and self-esteem. The women were significantly less depressive and had significantly less drive for thinness as well as bulimia, and their overall risk of developing an eating disorder also decreased significantly. Conclusions. Abdominoplasty results in significantly improved quality of life, body satisfaction, effectiveness, sexual functioning, self-esteem, and mental health. The risk of developing an eating disorder is decreased significantly. This trial is registered with Clinicaltrials.gov NCT02151799.
An Uncommon, Life-Threatening, Traumatic Hematoma in the Neck Area
Authors: Peroulis Michalis , Lianos Georgios D. , Nousias Vasilios , Anastasiadi Zoi , Lianou Aikaterini , Katsios Christos , Matsagkas Miltiadis
Published: November 2014

It is well known that blunt neck trauma, when compared to a penetrating injury in the same anatomical area, is very rare. We report a case of an 81-year-old Caucasian woman with a blunt life-threatening neck trauma due to a bully goat. Although rare, direct evaluation should always be done in these cases because any misinterpretation may result in unfavorable outcomes. We have to highlight that close medical attention and prompt surgical treatment should be always considered in order to avoid dramatic consequences.
Benzene Uptake in Hookah Smokers and Non-smokers Attending Hookah Social Events: Regulatory Implications
Authors: Kassem Nada O.F. , Kassem Noura O. , Jackson Sheila R. , Liles Sandy , Daffa Reem M. , Zarth Adam T. , Younis Maram A. , Carmella Steven G. , Hofstetter C. Richard , Chatfield Dale A. , Matt Georg E. , Hecht Stephen S. , Hovell Melbourne F.
Published: November 2014

Background: Benzene is a human hematotoxicant and a leukemogen that causes lymphohematopoietic cancers, especially acute myelogenous leukemia. We investigated uptake of benzene in hookah smokers and non-smokers attending hookah social events in naturalistic settings where hookah tobacco was smoked exclusively.

Methods: We quantified S-phenylmercapturic acid (SPMA), a metabolite of benzene, in the urine of 105 hookah smokers and 103 non-smokers. Participants provided spot urine samples the morning of and the morning after attending an indoor hookah-only smoking social event at a hookah lounge or in a private home.

Results: Urinary SPMA levels in hookah smokers increased significantly following a hookah social event (P < 0.001). This increase was 4.2 times higher after hookah lounge events (P < 0.001) and 1.9 times higher after home events (P = 0.003). In non-smokers, urinary SPMA levels increased 2.6 times after hookah lounge events (P = 0.055); however, similar urinary SPMA levels were detected before and after home events, possibly indicating chronic exposure to benzene (P = 0.933).

Conclusions: Our data provide the first evidence for uptake of benzene in hookah smokers and non-smokers exposed to hookah tobacco secondhand smoke at social events in private homes compared with their counterparts in hookah lounges. Hookah tobacco smoke is a source of benzene exposure, a risk factor for leukemia.

Impact: Because there is no safe level of exposure to benzene, our results call for interventions to reduce or prevent hookah tobacco use, regulatory actions to limit hookah-related exposure to toxicants including benzene, initiate labeling of hookah-related products, and include hookah smoking in clean indoor air legislation. Cancer Epidemiol Biomarkers Prev; 23(12); 2793–809. ©2014 AACR.
HPV Type Attribution in High-Grade Cervical Lesions: Assessing the Potential Benefits of Vaccines in a Population-Based Evaluation in the United States
Authors: Hariri Susan , Unger Elizabeth R. , Schafer Sean , Niccolai Linda M. , Park Ina U. , Bloch Karen C. , Bennett Nancy M. , Steinau Martin , Johnson Michelle L. , Markowitz Lauri E.
Published: November 2014

Background: Two currently available vaccines targeting human papillomavirus (HPV) types 16 and 18 could prevent 70% of cervical cancers and 50% of high-grade cervical lesions. Next-generation vaccines against additional types, such as a candidate 9-valent vaccine against HPV6/11/16/18/31/33/45/52/58, could further reduce HPV-associated disease burden.

Methods: HPV was typed in archived tissues from women ages 21 to 39 years residing in five catchment areas in the United States with cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ (CIN2+) using L1 consensus PCR and type-specific hybridization. Type attribution was estimated using weights to account for lesions with multiple types detected.

Results: From 2008 to 2011, 5,498 of 6,306 (87.2%) specimens obtained from 8,469 women with CIN2+ had valid typing results; HPV DNA was detected in 97.3%. Overall, 50.1% of lesions were attributable to HPV16/18, ranging from 50.3% to 52.4% among those ages 21 to 34 years, and significantly declined in 35 to 39 year-olds (43.5%). HPV16/18 attribution was higher in non-Hispanic whites (56.4%) versus racial/ethnic minorities (range, 41.8%–45.9%; P < 0.001). HPV31/33/45/52/58 attribution was 25.0% overall and increased with age (P < 0.001). A higher proportion of CIN2+ was attributable to HPV31/33/45/52/58 in non-Hispanic black (29.9%), Hispanic (29.2%), and Asian (33.1%) women compared with non-Hispanic whites (22.8%; P < 0.001).

Conclusions: Overall, 75% of lesions were attributable to 7 oncogenic HPV types: 50% to HPV16/18 and 25% to HPV31/33/45/52/58. HPV16/18 had the largest attributable fraction in CIN2+ across all subpopulations, although to a lesser extent in older women and racial/ethnic minorities.

Impact: Vaccines targeting additional oncogenic HPV types could prevent more high-grade cervical lesions, especially among racial/ethnic minorities. Cancer Epidemiol Biomarkers Prev; 24(2); 393–9. ©2014 AACR.
Depressive Symptoms and Short Telomere Length Are Associated with Increased Mortality in Bladder Cancer Patients
Authors: Lin Jie , Blalock Janice A. , Chen Meng , Ye Yuanqing , Gu Jian , Cohen Lorenzo , Cinciripini Paul M. , Wu Xifeng
Published: November 2014

Background: Depression is associated with an increased risk of mortality in patients with cancer; it has been hypothesized that depression-associated alterations in cell aging mechanisms, in particular, the telomere/telomerase maintenance system, may underlie this increased risk. We evaluated the association of depressive symptoms and telomere length to mortality and recurrence/progression in 464 patients with bladder cancer.

Methods: We used the Center for Epidemiologic Studies Depression Scale (CES-D) and Structured Clinical Interview for DSM-IV Disorder (SCID) to assess current depressive symptoms and lifetime major depressive disorder (MDD), respectively, and telomere length was assessed from peripheral blood lymphocytes. Multivariate Cox regression was used to assess the association of depression and telomere length to outcomes and the joint effect of both. Kaplan–Meier plots and log-rank tests were used to compare survival time of subgroups by depression variables and telomere length.

Results: Patients with depressive symptoms (CES-D ≥ 16) had a 1.83-fold [95% confidence interval (CI), 1.08–3.08; P = 0.024] increased risk of mortality compared with patients without depressive symptoms (CES-D < 16) and shorter disease-free survival time (P = 0.004). Patients with both depressive symptoms and lifetime history of MDD were at 4.88-fold (95% CI, 1.40–16.99; P = 0.013) increased risk compared with patients with neither condition. Compared to patients without depressive symptoms and long telomere length, patients with depressive symptoms and short telomeres exhibited a 4-fold increased risk of mortality (HR, 3.96; 95% CI, 1.86–8.41; P = 0.0003) and significantly shorter disease-free survival time (P < 0.001).

Conclusion: Short telomere length and depressive symptoms are associated with bladder cancer mortality individually and jointly.

Impact: Further investigation of interventions that impact depression and telomere length may be warranted in patients with cancer. Cancer Epidemiol Biomarkers Prev; 24(2); 336–43. ©2014 AACR.
Biochemical Estimation of Noncompliance with Smoking of Very Low Nicotine Content Cigarettes
Authors: Benowitz Neal L. , Nardone Natalie , Hatsukami Dorothy K. , Donny Eric C.
Published: November 2014

Background: The reduction of the nicotine content of cigarettes to nonaddicting levels is a potential federal regulatory intervention to reduce the prevalence of cigarette smoking and related disease. Many clinical trials on the effects and safety of nicotine reduction are ongoing. An important methodologic concern is noncompliance with reduced nicotine content cigarettes in the context of freely available conventional cigarettes. We propose two approaches using biomarkers to estimate noncompliance in smokers of very low nicotine content (VLNC) cigarettes in a clinical trial.

Methods: Data from 50 subjects in a study of gradual nicotine reduction were analyzed. Using plasma cotinine concentrations measured at baseline and while smoking VLNC cigarettes, we compared within-subject ratios of plasma cotinine comparing usual brand to VLNC in relation to nicotine content of these cigarettes. In another approach, we used nicotine pharmacokinetic data to estimate absolute plasma cotinine/cigarettes per day (CPD) threshold values for compliance based on the nicotine content of VLNC.

Results: The two approaches showed concordance, indicating at least 60% noncompliance with smoking VLNC. In a sensitivity analysis assuming extreme compensation and extreme values for nicotine metabolic parameters, noncompliance was still at least 40%, much higher than self-reported noncompliance.

Conclusion: Biomarker analysis demonstrates a high degree of noncompliance with smoking VLNC cigarettes, indicating that smokers are supplementing these with conventional cigarettes.

Impact: We propose a practical approach to assessing compliance with smoking VLNC in clinical trials of nicotine reduction. Cancer Epidemiol Biomarkers Prev; 24(2); 331–5. ©2014 AACR.
Immunotherapy Targeting Folate Receptor Induces Cell Death Associated with Autophagy in Ovarian Cancer
Authors: Wen Yunfei , Graybill Whitney S. , Previs Rebecca A. , Hu Wei , Ivan Cristina , Mangala Lingegowda S. , Zand Behrouz , Nick Alpa M. , Jennings Nicholas B. , Dalton Heather J. , Sehgal Vasudha , Ram Prahlad , Lee Ju-Seog , Vivas-Mejia Pablo E. , Coleman Robert L. , Sood Anil K.
Published: November 2014

Purpose: Cancer cells are highly dependent on folate metabolism, making them susceptible to drugs that inhibit folate receptor activities. Targeting overexpressed folate receptor alpha (FRα) in cancer cells offers a therapeutic opportunity. We investigated the functional mechanisms of MORAB-003 (farletuzumab), a humanized mAb against FRα, in ovarian cancer models.

Experimental Design: We first examined FRα expression in an array of human ovarian cancer cell lines and then assessed the in vivo effect of MORAB-003 on tumor growth and progression in several orthotopic mouse models of ovarian cancer derived from these cell lines. Molecular mechanisms of tumor cell death induced by MORAB-003 were investigated by cDNA and protein expression profiling analysis. Mechanistic studies were performed to determine the role of autophagy in MORAB-003–induced cell death.

Results: MORAB-003 significantly decreased tumor growth in the high-FRα IGROV1 and SKOV3ip1 models but not in the low-FRα A2780 model. MORAB-003 reduced proliferation, but had no significant effect on apoptosis. Protein expression and cDNA microarray analyses showed that MORAB-003 regulated an array of autophagy-related genes. It also significantly increased expression of LC3 isoform II and enriched autophagic vacuolization. Blocking autophagy with hydroxychloroquine or bafilomycin A1 reversed the growth inhibition induced by MORAB-003. In addition, alteration of FOLR1 gene copy number significantly correlated with shorter disease-free survival in patients with ovarian serous cancer.

Conclusions: MORAB-003 displays prominent antitumor activity in ovarian cancer models expressing FRα at high levels. Blockade of folate receptor by MORAB-003 induced sustained autophagy and suppressed cell proliferation. Clin Cancer Res; 21(2); 448–59. ©2014 AACR.
Mechanisms of Resistance to Cabazitaxel
Authors: Duran George E. , Wang Yan C. , Francisco E. Brian , Rose John C. , Martinez Francisco J. , Coller John , Brassard Diana , Vrignaud Patricia , Sikic Branimir I.
Published: November 2014

We studied mechanisms of resistance to the novel taxane cabazitaxel in established cellular models of taxane resistance. We also developed cabazitaxel-resistant variants from MCF-7 breast cancer cells by stepwise selection in drug alone (MCF-7/CTAX) or drug plus the transport inhibitor PSC-833 (MCF-7/CTAX-P). Among multidrug-resistant (MDR) variants, cabazitaxel was relatively less cross-resistant than paclitaxel and docetaxel (15- vs. 200-fold in MES-SA/Dx5 and 9- vs. 60-fold in MCF-7/TxT50, respectively). MCF-7/TxTP50 cells that were negative for MDR but had 9-fold resistance to paclitaxel were also 9-fold resistant to cabazitaxel. Selection with cabazitaxel alone (MCF-7/CTAX) yielded 33-fold resistance to cabazitaxel, 52-fold resistance to paclitaxel, activation of ABCB1, and 3-fold residual resistance to cabazitaxel with MDR inhibition. The MCF-7/CTAX-P variant did not express ABCB1, nor did it efflux rhodamine-123, BODIPY-labeled paclitaxel, and [3H]-docetaxel. These cells are hypersensitive to depolymerizing agents (vinca alkaloids and colchicine), have reduced baseline levels of stabilized microtubules, and impaired tubulin polymerization in response to taxanes (cabazitaxel or docetaxel) relative to MCF-7 parental cells. Class III β-tubulin (TUBB3) RNA and protein were elevated in both MCF-7/CTAX and MCF-7/CTAX-P. Decreased BRCA1 and altered epithelial–mesenchymal transition (EMT) markers are also associated with cabazitaxel resistance in these MCF-7 variants, and may serve as predictive biomarkers for its activity in the clinical setting. In summary, cabazitaxel resistance mechanisms include MDR (although at a lower level than paclitaxel and docetaxel), and alterations in microtubule dynamicity, as manifested by higher expression of TUBB3, decreased BRCA1, and by the induction of EMT. Mol Cancer Ther; 14(1); 193–201. ©2014 AACR.
TAS-116, a Highly Selective Inhibitor of Heat Shock Protein 90α and β, Demonstrates Potent Antitumor Activity and Minimal Ocular Toxicity in Preclinical Models
Authors: Ohkubo Shuichi , Kodama Yasuo , Muraoka Hiromi , Hitotsumachi Hiroko , Yoshimura Chihoko , Kitade Makoto , Hashimoto Akihiro , Ito Kenjiro , Gomori Akira , Takahashi Koichi , Shibata Yoshihiro , Kanoh Akira , Yonekura Kazuhiko
Published: November 2014

The molecular chaperone HSP90 plays a crucial role in cancer cell growth and survival by stabilizing cancer-related proteins. A number of HSP90 inhibitors have been developed clinically for cancer therapy; however, potential off-target and/or HSP90-related toxicities have proved problematic. The 4-(1H-pyrazolo[3,4-b]pyridine-1-yl)benzamide TAS-116 is a selective inhibitor of cytosolic HSP90α and β that does not inhibit HSP90 paralogs such as endoplasmic reticulum GRP94 or mitochondrial TRAP1. Oral administration of TAS-116 led to tumor shrinkage in human tumor xenograft mouse models accompanied by depletion of multiple HSP90 clients, demonstrating that the inhibition of HSP90α and β alone was sufficient to exert antitumor activity in certain tumor models. One of the most notable HSP90-related adverse events universally observed to differing degrees in the clinical setting is visual disturbance. A two-week administration of the isoxazole resorcinol NVP-AUY922, an HSP90 inhibitor, caused marked degeneration and disarrangement of the outer nuclear layer of the retina and induced photoreceptor cell death in rats. In contrast, TAS-116 did not produce detectable photoreceptor injury in rats, probably due to its lower distribution in retinal tissue. Importantly, in a rat model, the antitumor activity of TAS-116 was accompanied by a higher distribution of the compound in subcutaneously xenografted NCI-H1975 non–small cell lung carcinoma tumors than in retina. Moreover, TAS-116 showed activity against orthotopically transplanted NCI-H1975 lung tumors. Together, these data suggest that TAS-116 has a potential to maximize antitumor activity while minimizing adverse effects such as visual disturbances that are observed with other compounds of this class. Mol Cancer Ther; 14(1); 14–22. ©2014 AACR.
Near Infrared Photoimmunotherapy in the Treatment of Disseminated Peritoneal Ovarian Cancer
Authors: Sato Kazuhide , Hanaoka Hirofumi , Watanabe Rira , Nakajima Takahito , Choyke Peter L. , Kobayashi Hisataka
Published: November 2014

Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of disseminated peritoneal ovarian cancer. In vitro and in vivo experiments were conducted with a HER2-expressing, luciferase-expressing, ovarian cancer cell line (SKOV-luc). An antibody–photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized (tra-IR700) and cells or tumors were exposed to NIR light. In vitro PIT cytotoxicity was assessed with dead staining and luciferase activity in freely growing cells and in a three-dimensional (3D) spheroid model. In vivo NIR-PIT was performed in mice with tumors implanted in the peritoneum and in the flank and these were assessed by tumor volume and/or bioluminescence. In vitro NIR-PIT–induced cytotoxicity was light dose dependent. Repeated light exposures induced complete tumor cell killing in the 3D spheroid model. In vivo the antitumor effects of NIR-PIT were confirmed by significant reductions in both tumor volume and luciferase activity in the flank model (NIR-PIT vs. control in tumor volume changes at day 10, P = 0.0001; NIR-PIT vs. control in luciferase activity at day 4, P = 0.0237), and the peritoneal model (NIR-PIT vs. control in luciferase activity at day 7, P = 0.0037). NIR-PIT provided effective cell killing in this HER2-positive model of disseminated peritoneal ovarian cancer. Thus, NIR-PIT is a promising new therapy for the treatment of disseminated peritoneal tumors. Mol Cancer Ther; 14(1); 141–50. ©2014 AACR.
Combined Use of Vitamin D3 and Metformin Exhibits Synergistic Chemopreventive Effects on Colorectal Neoplasia in Rats and Mice
Authors: Li Wan , Wang Qi-Long , Liu Xia , Dong Shu-Hong , Li Hong-Xia , Li Chun-Yang , Guo Li-Shu , Gao Jing-Miao , Berger Nathan A. , Li Li , Ma Lan , Wu Yong-Jie
Published: November 2014

Vitamin D3 and metformin are widely used in humans for regulating mineral metabolism and as an antidiabetic drug, respectively; and both of them have been shown to have chemopreventive effects against various tumors. This study was designed to investigate the potential synergistic chemopreventive effects of vitamin D3 and metformin against the development of early colon neoplasia in two models. The first model was a 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colon cancer rat model and the second, a DMH-dextran sodium sulfate (DSS)-induced colitis-associated colon neoplasia mouse model. Compared with either vitamin D3 or metformin alone, combined use of vitamin D3 and metformin showed more pronounced effect in reducing the numbers of aberrant crypt foci (ACF) and tumor in the colon. The most prominent inhibitory effects were observed in the vitamin D3 medium dose (100 IU/kg/d) and metformin medium dose (120 mg/kg/d) combination group. Furthermore, our results showed that enhancement of metformin's chemopreventive effects by vitamin D3 was associated with downregulation of S6P expression, via the AMPK (IGFI)/mTOR pathway. In addition, enhancement of vitamin D3′s chemopreventive effects by metformin was associated with inhibition of the protein expressions of c-Myc and Cyclin D1, via the vitamin D receptor/β-catenin pathway. These findings show that the combined use of vitamin D3 and metformin exhibits synergistic effects against the development of early colon neoplasia. They suggest that the combined use of vitamin D3 and metformin may represent a novel strategy for chemoprevention of colorectal cancer. Cancer Prev Res; 8(2); 139–48. ©2014 AACR.
Urinary Protein Biomarkers in the Early Detection of Lung Cancer
Authors: Nolen Brian M. , Lomakin Aleksey , Marrangoni Adele , Velikokhatnaya Liudmila , Prosser Denise , Lokshin Anna E.
Published: November 2014

The early detection of lung cancer has the potential to greatly impact disease burden through the timely identification and treatment of affected individuals at a manageable stage of development. The insufficient specificity demonstrated by currently used screening and diagnostic techniques has led to intense investigation into biomarkers as diagnostic tools. Urine may represent a noninvasive alternative matrix for diagnostic biomarker development. We performed an analysis of 242 biomarkers in urines obtained from 83 patients with non–small cell lung carcinomas (NSCLC), 74 patients diagnosed with benign pulmonary conditions, and 77 healthy donors. A large number of significant alterations were observed between the NSCLC and control groups. A multivariate analysis identified a three-biomarker panel consisting of IGFBP-1, sIL-1Ra, CEACAM-1, which discriminated NSCLC from healthy controls with a sensitivity/specificity of 84/95 in an initial training set and 72/100 in an independent validation set. This panel performed well among multiple subtypes of NSCLC and early-stage disease but demonstrated only limited efficacy for the discrimination of NSCLC from benign controls and limited specificity for patients with several other cancers and tuberculosis. These findings demonstrate that urine biomarkers may provide screening and diagnostic properties which exceed those reported for serum biomarkers and approach a level necessary for further clinical development. Cancer Prev Res; 8(2); 111–9. ©2014 AACR.
Enhanced Antitumor Effects of Novel Intracellular Delivery of an Active Form of Menaquinone-4, Menahydroquinone-4, into Hepatocellular Carcinoma
Authors: Setoguchi Shuichi , Watase Daisuke , Matsunaga Kazuhisa , Matsubara Misa , Kubo Yohei , Kusuda Mariko , Nagata-Akaho Nami , Enjoji Munechika , Nakashima Manabu , Takeshita Morishige , Karube Yoshiharu , Takata Jiro
Published: November 2014

Reduced cellular uptake of menaquinone-4 (MK-4), a vitamin K2 homolog, in human hepatocellular carcinoma (HCC) limits its usefulness as a safe long-term antitumor agent for recurrent HCC and produces des-γ-carboxy prothrombin (DCP). We hypothesized that effective delivery of menahydroquinone-4 (MKH), the active form of MK-4 for γ-glutamyl carboxylation, into HCC cells is critical for regulating HCC growth, and may enable it to be applied as a safe antitumor agent. In this study, we verified this hypothesis using menahydroquinone-4 1,4-bis-N,N-dimethylglycinate hydrochloride (MKH-DMG), a prodrug of MKH, and demonstrated its effectiveness. Intracellular delivery of MKH and subsequent growth inhibition of PLC/PRF/5 and Hep3B (DCP-positive) and SK-Hep-1 (DCP-negative) cells after MKH-DMG administration were determined and compared with MK-4. The activity of MKH-DMG against tumor progression in the liver alongside DCP formation was determined in a spleen–liver metastasis mouse model. MKH-DMG exhibited greater intracellular delivery of MKH in vitro (AUC0–72 hour of MKH) and increased growth-inhibitory activity against both DCP-positive and DCP-negative HCC cell lines. The phenomena of MKH delivery into cells in parallel with simultaneous growth inhibition suggested that MKH is the active form for growth inhibition of HCC cells. Cell-cycle arrest was determined to be involved in the growth inhibition mechanisms of MKH-DMG. Furthermore, MKH-DMG showed significant inhibition of tumor progression in the liver, and a substantial decrease in plasma DCP levels in the spleen–liver metastasis mouse model. Our results suggest that MKH-DMG is a promising new candidate antitumor agent for safe long-term treatment of HCC. Cancer Prev Res; 8(2); 129–38. ©2014 AACR.
Physical Inactivity and Low Fitness Deserve More Attention to Alter Cancer Risk and Prognosis
Authors: Sanchis-Gomar Fabian , Lucia Alejandro , Yvert Thomas , Ruiz-Casado Ana , Pareja-Galeano Helios , Santos-Lozano Alejandro , Fiuza-Luces Carmen , Garatachea Nuria , Lippi Giuseppe , Bouchard Claude , Berger Nathan A.
Published: November 2014

Sedentary lifestyle is associated with elevated cancer risk whereas regular physical activity (PA) and high cardiorespiratory fitness (CRF) have the opposite effect, with several biologic mechanisms mediating such associations. There is a need for lifestyle interventions aimed at increasing the PA levels and CRF of the general population and particularly cancer survivors. Furthermore, provocative data suggest a dose-dependent benefit of increasing levels of PA and/or CRF against cancer risk or mortality. Thus, current PA guidelines (≥150 min/wk of moderate-to-vigorous PA) may not be sufficiently rigorous for preventing cancer nor for extending cancer survivorship. Research targeting this issue is urgently needed. Promoting regular PA along with monitoring indicators of CRF and adiposity may provide powerful strategies to prevent cancer in populations, help patients with cancer more effectively deal with their disease and enhance secondary prevention programs in those who are affected by cancer. Cancer Prev Res; 8(2); 105–10. ©2014 AACR.
Left Septal Atrial Tachycardia After Open-Heart Surgery
Authors: Adachi Toru , Yoshida Kentaro , Takeyasu Noriyuki , Masuda Keita , Sekiguchi Yukio , Sato Akira , Tada Hiroshi , Nogami Akihiko , Aonuma Kazutaka
Published: November 2014

Background—

Septal atrial tachycardia (AT) can occur in patients without structural heart disease and in patients with previous catheter ablation of atrial fibrillation. We aimed to assess septal AT that occurs after open-heart surgery.

Methods and Results—

This study comprised 20 consecutive patients undergoing catheter ablation of macroreentrant AT after open-heart surgery. Relevance to surgical approach, mechanisms, anatomic and electrophysiological characteristics, and outcomes were assessed. Septal AT was identified in 7 patients who had all undergone mitral valve surgery. All septal ATs were localized in the left atrial septum, whereas 10 of 13 nonseptal ATs originated from the right atrium. Patients with left septal AT had a thicker fossa ovalis (median, 4.0; 25th–75th percentile, 3.6–4.2 versus 2.3; 1.6–2.6 mm;
P
=0.006) and broader area of low voltage (<0.3 mV) in the septum than patients with nonseptal AT (82; 76–89 versus 31; 28%–36%;
P
=0.02). Repeated gradual prolongations of the tachycardia cycle length without change of the septal circuit were observed in all patients with septal AT (70; 63–100 versus 15; 10–40 ms;
P
=0.0008). Although ablation terminated all ATs, recurrence of targeted ATs was more frequent in patients with left septal AT during 30-month follow-up (71 versus 0%;
P
=0.001).

Conclusions—

Left septal AT after open-heart surgery was characterized by a thicker septum, more scar burden in the septum, and repeated prolongations of the tachycardia cycle length during ablation. Such an arrhythmogenic substrate may interfere with transmural lesion formation by ablation and may account for higher likelihood of recurrence of left septal AT.
Stoichiometry of Gata4, Mef2c, and Tbx5 Influences the Efficiency and Quality of Induced Cardiac Myocyte Reprogramming
Authors: Wang Li , Liu Ziqing , Yin Chaoying , Asfour Huda , Chen Olivia , Li Yanzhen , Bursac Nenad , Liu Jiandong , Qian Li
Published: November 2014

Rationale:

Generation of induced cardiac myocytes (iCMs) directly from fibroblasts offers great opportunities for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate of fibroblasts to fully reprogrammed iCMs, which could in part be attributed to unbalanced expression of reprogramming factors Gata4 (G), Mef2c (M), and Tbx5 (T) using the current gene delivery approach.

Objective:

We aimed to establish a system to express distinct ratios of G, M, T proteins in fibroblasts and determine the effect of G, M, T stoichiometry on iCM reprogramming.

Methods and Results:

We took advantage of the inherent feature of the polycistronic system and generated all possible combinations of G, M, T with identical 2A sequences in a single transgene. We demonstrated that each splicing order of G, M, T gave rise to distinct G, M, T protein expression levels. Combinations that resulted in higher protein level of Mef2c with lower levels of Gata4 and Tbx5 significantly enhanced reprogramming efficiency compared with separate G, M, T transduction. Importantly, after further optimization, the MGT vector resulted in more than 10-fold increase in the number of mature beating iCM loci. Molecular characterization revealed that more optimal G, M, T stoichiometry correlated with higher expression of mature cardiac myocyte markers.

Conclusions:

Our results demonstrate that stoichiometry of G, M, T protein expression influences the efficiency and quality of iCM reprogramming. The established optimal G, M, T expression condition will provide a valuable platform for future iCM studies.
Components of Hemodynamic Load and Cardiovascular Events
Authors: Cooper Leroy L. , Rong Jian , Benjamin Emelia J. , Larson Martin G. , Levy Daniel , Vita Joseph A. , Hamburg Naomi M. , Vasan Ramachandran S. , Mitchell Gary F.
Published: November 2014

Background—

Elevated blood pressure is the leading modifiable risk factor for cardiovascular disease (CVD) and premature death. The blood pressure waveform consists of discrete hemodynamic components, derived from measured central pressure and flow, which may contribute separately to risk for an adverse outcome. However, pressure-flow measures have not been studied in a large, community-based sample.

Methods and Results—

We used proportional hazards models to examine the association of incident CVD with forward pressure wave amplitude, mean arterial pressure, and global reflection coefficient derived from wave separation analysis and echocardiography in 2492 participants (mean age 66±9 years, 56% women) in the Framingham Heart Study. During follow-up (0.04–6.8 years), 149 participants (6%) had a CVD event. In multivariable models adjusting for age, sex, antihypertensive therapy, body mass index, heart rate, total and high-density lipoprotein cholesterol concentrations, smoking, and the presence of diabetes mellitus, forward pressure wave amplitude (hazard ratio, 1.40; 95% confidence interval, 1.16–1.67;
P
=0.0003) was associated with incident CVD, whereas mean arterial pressure (hazard ratio, 1.10; 95% confidence interval, 0.94–1.29;
P
=0.25) and global wave reflection (hazard ratio, 0.93; 95% confidence interval, 0.78–1.12;
P
=0.58) were not. After adding systolic blood pressure and carotid-femoral pulse wave velocity to the model, forward pressure wave amplitude persisted as a correlate of events (hazard ratio, 1.33; 95% confidence interval, 1.05–1.68;
P
=0.02).

Conclusions—

Higher forward pressure wave amplitude (a measure of proximal aortic geometry and stiffness) was associated with increased risk for incident CVD, whereas mean arterial pressure and relative wave reflection (correlates of resistance vessel structure and function) were not associated with increased risk for incident CVD.
Electrocardiographic Deep Terminal Negativity of the P Wave in V
1
and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Tereshchenko Larisa G. , Henrikson Charles A. , Sotoodehnia Nona , Arking Dan E. , Agarwal Sunil K. , Siscovick David S. , Post Wendy S. , Solomon Scott D. , Coresh Josef , Josephson Mark E. , Soliman Elsayed Z.
Published: November 2014

Background

Identifying individuals at risk for sudden cardiac death (
SCD
) is of critical importance. Electrocardiographic (
ECG
) deep terminal negativity of P wave in V
1
(
DTNPV
1), a marker of left atrial abnormality, has been associated with increased risk of all‐cause and cardiovascular mortality. We hypothesized that
DTNPV
1 is associated with increased risk of sudden cardiac death (
SCD
).

Methods and Results

This analysis included 15 375 participants (54.1±5.8 years, 45% men, 73% whites) from the Atherosclerosis Risk in Communities (
ARIC
) study.
DTNPV
1 was defined from the resting 12‐lead
ECG
as presence of biphasic P wave (positive/negative) in V
1
with the amplitude of the terminal negative phase >100 μV, or one small box on
ECG
scale. After a median of 14 years of follow‐up, 311 cases of
SCD
occurred. In unadjusted Cox regression,
DTNPV
1 was associated with an 8‐fold increased risk of
SCD
(
HR
8.21; [95%
CI
5.27 to 12.79]). Stratified by race and study center, and adjusted for age, sex, coronary heart disease (
CHD
), and
ECG
risk factors, as well as atrial fibrillation (
AF
), stroke,
CHD
, and heart failure (
HF
) as time‐updated variables, the risk of
SCD
associated with
DTNPV
1 remained significant (2.49, [1.51–4.10]).
DTNPV
1 improved reclassification: additional 3.4% of individuals were appropriately reclassified into a higher
SCD
risk group, as compared with traditional
CHD
risk factors alone. In fully adjusted models
DTNPV
1 was associated with increased risk of non‐fatal events:
AF
(5.02[3.23–7.80]),
CHD
(2.24[1.43–3.53]),
HF
(1.90[1.19–3.04]), and trended towards increased risk of stroke (1.88[0.99–3.57]).

Conclusion

DTNPV
1 is predictive of
SCD
suggesting its potential utility in risk stratification in the general population.
Sensing Informal Networks in Organizations
Authors: Orbach Maya , Demko Maegen , Doyle Jeremy , Waber Benjamin N. , Pentland Alex (Sandy)
Published: November 2014

We present an examination of informal network structure within the sales division of a global manufacturing organization. Sociometric Badges were used to collect data on face-to-face interactions over a total of 8 weeks, the latter half of which was spent in a redesigned workspace. These data were supplemented by employees’ e-mail and instant messaging log activity. The allocation of an individual’s communication among colleagues reflected the company’s structure as a post-bureaucratic organization. The observed interteam communication patterns differed from those expected to arise based on the various functions performed by each team throughout the sales cycle, suggesting that the communication needs of each team were not wholly provided for by the available media. A subset of workers who were encouraged to utilize flexible seating arrangements in a remodeled space had a higher proportion of face-to-face interactions with colleagues outside of their team, while employees seated far away from each other were less likely to exchange e-mail. This research has implications for companies hoping to understand the structure of informal networks within their organization as well as those considering workplace redesign as a method of stimulating communication within these networks.
Therapeutic Action and the Analyst’s Responsibility
Authors: Greenberg Jay
Published: November 2014

Models of the psychoanalytic situation can usefully be thought of as fictions. Viewed this way, the models can be understood as narrative structures that shape what we are able to see and how we are able to think about what happens between us and our analysands. Theories of therapeutic action are elements of what can be called a “controlling fiction,” mediating between these theories and our very real responsibilities, both to our preferred method and to a suffering patient. This venture into comparative psychoanalysis is illustrated by a discussion of published case material.
Prevertebral Space Invasion in Head and Neck Cancer
Authors: Imre Abdulkadir , Pinar Ercan , Erdoğan Nezahat , Ece Ahmet Ata , Olgun Yuksel , Aladag Ibrahim , Ozturkcan Sedat
Published: November 2014

Objective:

This study evaluated the diagnostic value of magnetic resonance imaging (MRI) and computed tomography (CT) in prevertebral space invasion in patients with head and neck squamous cell carcinomas (HNSCC).

Subjects and Methods:

This study retrospectively reviewed 197 patients with advanced primary laryngeal or hypopharyngeal carcinoma who underwent laryngectomy and neck dissection at our institution. The MRI and CT findings were compared with the surgical findings and postoperative pathology.

Results:

In 191 patients, the macro- and microscopic margins of the surgical specimens were tumor-free. In the remaining 6 patients, prevertebral space involvement was observed intraoperatively. MRI predicted the absence of prevertebral fascia invasion in 40 of 42 patients with a negative predictive value of 100% and specificity of 95.2%, while the negative predictive value and specificity of CT were 99.2% and 88.2%, respectively.

Conclusion:

Preservation of the retropharyngeal fat plane on MRI reliably predicts the absence of prevertebral space fixation in patients with advanced HNSCC.
The Effect of Voice Rest on the Outcome of Phonosurgery for Benign Laryngeal Lesions
Authors: Kiagiadaki Devora , Remacle Marc , Lawson George , Bachy Vincent , Van der Vorst Sebastien
Published: November 2014

Objectives:

According to the literature, voice rest following phonosurgery, as recommended in clinical practice, varies between 3 and 7 days. However, up until now, no randomized trials have been published comparing voice rest of short versus long duration.

Methods:

This is an ongoing prospective randomized study, comparing strict voice rest of 5 versus 10 days on the voice following phonosurgery. Thirty-one elective patients operated on for benign laryngeal lesions were randomized. They completed pre- and postoperative assessments, including perceptual voice quality (Grade, Roughness, Breathiness, Asthenia, Strain, Instability scale), Voice Handicap Index total score, and voice analysis with both acoustic and aerodynamic measurements. Additional factors such as smoking, vocal abuse, reflux, and preoperative speech therapy were also taken into account.

Results:

Sixteen patients were randomized to follow 5 days’ voice rest and 15 patients were randomized to 10 days’ voice rest. Statistical analysis showed no significant differences in pre- or postoperative measurements between the 2 groups. However, multilinear regression analysis for the effect of voice rest duration on postoperative values showed a significant improvement in maximum phonation time (MPT) with 10 days’ voice rest.

Conclusions:

Preliminary results show a benefit of prolonged voice rest (10 days’ duration) on MPT.
Diurnal variation and short-term pre-analytical stability of serum soluble α-klotho in healthy volunteers: a pilot study
Authors: Tan Sven-Jean , Smith Edward R , Hewitson Tim D , Holt Stephen G , Toussaint Nigel D
Published: November 2014

Aim

To investigate the diurnal variability and pre-analytical stability of soluble α-klotho in serum.

Background

Recent evidence suggests that the cleaved extracellular domain of the α-klotho receptor, soluble α-klotho, affects phosphate homeostasis, ion channel regulation and antifibrotic/antioxidant pathways. However, soluble α-klotho measurements have yielded inconsistent results when related to renal function, markers of mineral metabolism and patient outcomes. Pre-analytical factors such as biological variation and analyte stability may affect the interpretation of soluble α-klotho results but are yet to be formally assessed.

Methods

Clotted blood samples were collected from 10 healthy adult volunteers at three time-points during the day to assess diurnal change. Additional samples were collected and allowed to stand at room temperature for 30, 60 and 120 min, prior to centrifugation and analysis to evaluate analyte stability. Serum soluble α-klotho was measured using a validated commercial enzyme-linked immunosorbent assay.

Results

Delayed processing of samples had no significant effect on serum soluble α-klotho concentrations over a 2-h period. Serum soluble α-klotho concentrations remained stable over morning, midday and afternoon time-points in this pilot study.

Conclusion

Serum soluble α-klotho demonstrates short-term pre-analytical stability and minimal diurnal variability in this pilot study. Larger studies are warranted to confirm these findings.
Essays on International Non-Market Strategy and the Political Economy of Environmental Regulation
Authors: Patnaik Sanjay
Published: November 2014

This article contains an abstract of Dr. Sanjay Patnaik’s dissertation as well as a commentary essay on the research process in the appendix. In his dissertation, Dr. Patnaik examines the importance of the non-market environment for firm strategy and performance within the context of newly introduced regulations for greenhouse gases in Europe. The dissertation abstract contains a description of each dissertation chapter, including research questions, methodologies, and results. The commentary essay describes the author’s perspective on conducting research as an emerging scholar.
Social Issues in Management Division Award Competition for 2013
Authors: Muethel Miriam
Published: November 2014

In 2013, the Social Issues in Management (SIM) Division of the Academy of Management awarded the best dissertation in the field of SIM research at the AOM’s annual conference in Orlando, Florida. This essay, written by the best dissertation committee chair, describes the procedures behind the dissertation award and the criteria used to identify the winner. Furthermore, it reflects on the finalists’ unique contributions and the takeaways for future best dissertation awards.
Real-Time Electronic Medical Record Alerts Increase High Blood Pressure Recognition in Children
Authors: Brady Tammy M. , Neu Alicia M. , Miller Edgar R. , Appel Lawrence J. , Siberry George K. , Solomon Barry S.
Published: November 2014

Objective. Pediatric hypertension remains largely unrecognized. We hypothesized that an electronic medical record (EMR) alert would increase elevated blood pressure (BP) recognition in a pediatric primary care setting. Study Design. Pre–post evaluation of a real-time EMR alert and one-time provider educational session. A total of 1305 encounters of children 3 to 21 years with elevated intake BP and no prior hypertension diagnosis were included. Elevated BP recognition and relationship of recognition with cardiovascular disease (CVD) risk factors during the intervention was compared with an historical control. Results. Recognition increased from 12.5% to 42% ( P < .001). Recognition increased soon after alert implementation and was sustained without evidence of “alert fatigue.” During both periods, presence of CVD risk factors was associated with recognition. However, the magnitude was lesser in the intervention period. Conclusions. Real-time EMR alerts substantially increase elevated BP recognition in children. However, underrecognition of elevated BP persisted, highlighting the need for additional strategies to improve provider recognition.
The African Union’s Call for Global Pan-Africanism and the Ghana-Diaspora Relations in the 21st Century
Authors: Bolaji Mohammed Hadi Abdul-Ganiy
Published: November 2014

One of the most outstanding initiatives that the African Union (AU) has taken that distinguishes it from its predecessor (the Organization of African Unity) is the adoption of the African diaspora as its sixth region. This article has two principal sections. First, by establishing the reasons for adopting the African diaspora as its sixth region from development perspectives, it explores how the African diaspora can engineer development processes in Africa and the challenges that the AU must address if the African diasporas are expected to play this role. In the second section, the article explores how Ghana provided a political base for Pan-Africanism and how Nkrumah laid an intellectual foundation for the movement. It also examines how Rawlings and Kufuor built on Nkrumah’s Pan-Africanist legacy by creating incentives for the returnees/repatriates from the diaspora. While probing the character of the returnees/repatriates phenomenon and politics in Ghana, the second section also explores the controversies that center on dual citizenship, the right of return and abode, and voting rights of Ghanaians Living Abroad (GLA). Finally, the section investigates the receptivity of the traditional political system to the returnee/repatriate phenomenon in Ghana. The article concludes by making recommendations on how the Ghana-diaspora relations can be strengthened.