bluuebunny/crossref_metadata_2025 huggingface dataset:
Malignant Germ Cell Tumors Display Common MicroRNA Profiles Resulting in Global Changes in Expression of Messenger RNA Targets
Authors: Palmer Roger D. , Murray Matthew J. , Saini Harpreet K. , van Dongen Stijn , Abreu-Goodger Cei , Muralidhar Balaji , Pett Mark R. , Thornton Claire M. , Nicholson James C. , Enright Anton J. , Coleman Nicholas ,   on behalf of the Children's Cancer and Leukaemia Group
Published: March 2010

Despite their extensive clinical and pathologic heterogeneity, all malignant germ cell tumors (GCT) are thought to originate from primordial germ cells. However, no common biological abnormalities have been identified to date. We profiled 615 microRNAs (miRNA) in pediatric malignant GCTs, controls, and GCT cell lines (48 samples in total) and re-analyzed available miRNA expression data in adult gonadal malignant GCTs. We applied the bioinformatic algorithm Sylamer to identify miRNAs that are of biological importance by inducing global shifts in mRNA levels. The most significant differentially expressed miRNAs in malignant GCTs were all from the miR-371–373 and miR-302 clusters (adjusted P < 0.00005), which were overexpressed regardless of histologic subtype [yolk sac tumor (YST)/seminoma/embryonal carcinoma (EC)], site (gonadal/extragonadal), or patient age (pediatric/adult). Sylamer revealed that the hexamer GCACTT, complementary to the 2- to 7-nucleotide miRNA seed AAGUGC shared by six members of the miR-371–373 and miR-302 clusters, was the only sequence significantly enriched in the 3′-untranslated region of mRNAs downregulated in pediatric malignant GCTs (as a group), YSTs and ECs, and in adult YSTs (all versus nonmalignant tissue controls; P < 0.05). For the pediatric samples, downregulated genes containing the 3′-untranslated region GCACTT showed significant overrepresentation of Gene Ontology terms related to cancer-associated processes, whereas for downregulated genes lacking GCACTT, Gene Ontology terms generally represented metabolic processes only, with few genes per term (adjusted P < 0.05). We conclude that the miR-371–373 and miR-302 clusters are universally overexpressed in malignant GCTs and coordinately downregulate mRNAs involved in biologically significant pathways. Cancer Res; 70(7); 2911–23
Kallikrein-Related Peptidase 7 Promotes Multicellular Aggregation via the α5β1 Integrin Pathway and Paclitaxel Chemoresistance in Serous Epithelial Ovarian Carcinoma
Authors: Dong Ying , Tan Olivia L. , Loessner Daniela , Stephens Carson , Walpole Carina , Boyle Glen M. , Parsons Peter G. , Clements Judith A.
Published: March 2010

Kallikrein-related peptidase 7 (KLK7) is upregulated in epithelial ovarian carcinoma (EOC) with high levels correlated with poor prognosis. However, the mechanisms underlying this relationship and the role of KLK7 in EOC progression are unknown. We report that two different KLK7 transcripts, KLK7-253 and KLK7-181, are simultaneously expressed in high-grade serous EOC. Multicellular aggregates (MCA), which promote cell survival and chemoresistance, were observed in SKOV-3 cells stably overexpressing KLK7-253 in particular. Importantly, these MCAs invade into a monolayer of mesothelial cells and form cancer cell foci. Blocking MCA using antibodies against KLK7 and α5β1 and β1 integrins confirmed the involvement of KLK7 and integrin-regulated cell adhesion. Increased levels of α5/β1 integrins and enhanced attachment to fibronectin and vitronectin, which was blocked with an anti–β1 integrin antibody, were also observed. Finally, Western blot and immunohistochemistry showed higher KLK7 and α5/β1 integrin levels in serous EOC cells from ascites and tumor samples from chemotherapy nonresponders with short postsurvival times. Additionally, both KLK7-253 and KLK7-181 clones were more resistant to paclitaxel treatment in vitro. These findings suggest a mechanism for the association of high KLK7 levels with chemoresistance and poor prognosis for serous EOC patients by promotion of peritoneal dissemination and reinvasion via increased MCA and α5β1 integrin–dependent cell adhesion. Cancer Res; 70(7); 2624–33
A Role for HPV16 E5 in Cervical Carcinogenesis
Authors: Maufort John P. , Shai Anny , Pitot Henry C. , Lambert Paul F.
Published: March 2010

A subset of the mucosotropic human papillomaviruses (HPV), including HPV16, are etiologic agents for the vast majority of cervical cancers, other anogenital cancers, and a subset of head and neck squamous cell carcinomas. HPV16 encodes three oncogenes: E5, E6, and E7. Although E6 and E7 have been well-studied and clearly shown to be important contributors to these cancers, less is known about E5. In this study, we used E5 transgenic mice to investigate the role of E5 in cervical cancer. When treated for 6 months with estrogen, a cofactor for cervical carcinogenesis, E5 transgenic mice developed more severe neoplastic cervical disease than similarly treated nontransgenic mice, although no frank cancers were detected. In addition, E5 when combined with either E6 or E7 induced more severe neoplastic disease than seen in mice expressing only one viral oncogene. Prolonged treatment of E5 transgenic mice with exogenous estrogen uncovered an ability of E5 to cause frank cancer. These data indicate that E5 acts as an oncogene in the reproductive tracts of female mice. Cancer Res; 70(7); 2924–31
Kinome Profiling of Clinical Cancer Specimens
Authors: Parikh Kaushal , Peppelenbosch Maikel P.
Published: March 2010

Over the past years novel technologies have emerged to enable the determination of the transcriptome and proteome of clinical samples. These data sets will prove to be of significant value to our elucidation of the mechanisms that govern pathophysiology and may provide biological markers for future guidance in personalized medicine. However, an equally important goal is to define those proteins that participate in signaling pathways during the disease manifestation itself or those pathways that are made active during successful clinical treatment of the disease: the main challenge now is the generation of large-scale data sets that will allow us to define kinome profiles with predictive properties on the outcome-of-disease and to obtain insight into tissue-specific analysis of kinase activity. This review describes the current techniques available to generate kinome profiles of clinical tissue samples and discusses the future strategies necessary to achieve new insights into disease mechanisms and treatment targets. Cancer Res; 70(7); 2575–8
Regulation of Minichromosome Maintenance Gene Family by MicroRNA-1296 and Genistein in Prostate Cancer
Authors: Majid Shahana , Dar Altaf A. , Saini Sharanjot , Chen Yi , Shahryari Varahram , Liu Jan , Zaman Mohd Saif , Hirata Hiroshi , Yamamura Soichiro , Ueno Koji , Tanaka Yuichiro , Dahiya Rajvir
Published: March 2010

The minichromosome maintenance (MCM) gene family is essential for DNA replication and is frequently upregulated in various cancers. Here, we examined the role of MCM2 in prostate cancer and the effect of microRNA-1296 (miR-1296), genistein, and trichostatin A (TSA) on the MCM complex. Profiling results showed that expression of MCM genes was higher in tumor samples. Genistein and TSA significantly downregulated the expression of all MCM genes. Genistein, TSA, and small interfering RNA duplexes caused a significant decrease in the S phase of the cell cycle. There was also downregulation of CDT1, CDC7, and CDK2 genes, which govern loading of the MCM complex on chromatin. We also found that miR-1296 was significantly downregulated in prostate cancer samples. In PC3 cells, inhibition of miR-1296 upregulated both MCM2 mRNA and protein, whereas overexpression caused a significant decrease in MCM2 mRNA, protein, and the S phase of the cell cycle. MCM genes are excellent anticancer drug targets because they are essential DNA replication factors that are highly expressed in cancer cells. This is the first report showing anti-MCM effect by miR-1296, genistein, and TSA. TSA is undergoing clinical trials as a prostate cancer treatment but has high toxicity. Genistein, a natural, nontoxic dietary isoflavone, may be an advantageous therapeutic agent for treating prostate cancer. The use of RNA interference is currently being implemented as a gene-specific approach for molecular medicine. The specific downregulation of oncogenes by miR may contribute to novel therapeutic approaches in the treatment of prostate cancer. Cancer Res; 70(7); 2809–18
Vascular Endothelial Growth Factor Secreted by Activated Stroma Enhances Angiogenesis and Hormone-Independent Growth of Estrogen Receptor–Positive Breast Cancer
Authors: Pinto Mauricio P. , Badtke Melanie M. , Dudevoir Michelle L. , Harrell J. Chuck , Jacobsen Britta M. , Horwitz Kathryn B.
Published: March 2010

“Reactive” or activated stroma characterizes many malignancies including breast cancers. Recently, we isolated a reactive mouse mammary gland stromal cell line called BJ3Z. These cells express α-smooth muscle actin and stromal cell–derived factor 1 (SDF-1) and are tumorigenic when injected into mice. Here we show that, in vivo, BJ3Z cells influence the angiogenesis and proliferation of xenografted estrogen receptor (ER)–positive MCF-7 human breast cancer cell–derived solid tumors. The growth-promoting effects of BJ3Z cells are equivalent to those of estradiol (E2). BJ3Z cells also increase the proliferation of normal mouse mammary luminal cells adjacent to tumors. In vitro, BJ3Z cells reorganize and increase the proliferation of cocultured malignant MCF-7 and normal human breast MCF10A cells grown as organoids in three-dimensional culture. The effects of BJ3Z cells on MCF-7 cells are equivalent to those of E2. In contrast, BJ3Z cells do not alter the growth of highly aggressive ER-negative MDA-MB-231 human breast cancer cells. We show that BJ3Z cells secrete vascular endothelial growth factor (VEGF). The growth of MCF-7 organoids induced by BJ3Z can be inhibited by antagonists of VEGF and SDF-1. Conversely, recombinant VEGF stimulates the proliferation of MCF-7, but not MDA-MB-231, organoids. We conclude that, in addition to angiogenesis, VEGF released by activated stroma increases the growth of ER-positive malignant epithelial cells and of adjacent normal epithelium. Because activated stroma can substitute for E2 and fosters hormone-independent growth of ER-positive tumors, we suggest that breast cancers exhibiting intrinsic hormone resistance may respond to antiangiogenic therapies. Cancer Res; 70(7); 2655–64
MLL-Rearranged B Lymphoblastic Leukemias Selectively Express the Immunoregulatory Carbohydrate-Binding Protein Galectin-1
Authors: Juszczynski Przemyslaw , Rodig Scott J. , Ouyang Jing , O'Donnell Evan , Takeyama Kunihiko , Mlynarski Wojciech , Mycko Katarzyna , Szczepanski Tomasz , Gaworczyk Anna , Krivtsov Andrei , Faber Joerg , Sinha Amit U. , Rabinovich Gabriel A. , Armstrong Scott A. , Kutok Jeffery L. , Shipp Margaret A.
Published: March 2010

Purpose: Patients with mixed lineage leukemia (MLL)–rearranged B-lymphoblastic leukemias (B-ALL) have an unfavorable prognosis and require intensified treatment. Multiple MLL fusion partners have been identified, complicating the diagnostic evaluation of MLL rearrangements. We analyzed molecular markers of MLL rearrangement for use in rapid diagnostic assays and found the immunomodulatory protein, Galectin-1 (Gal-1), to be selectively expressed in MLL-rearranged B-ALL.

Experimental Design: Transcriptional profiling of ALL subtypes revealed selective overexpression of Gal-1 in MLL-rearranged ALLs. For this reason, we analyzed Gal-1 protein expression in MLL-germline and MLL-rearranged adult and infant pediatric B-ALLs and cell lines by immunoblotting, immunohistochemistry, and intracellular flow cytometry of viable tumor cell suspensions. Because deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of the MLL fusion protein complex, we also analyzed histone H3 lysine 79 (H3K79) dimethylation in the LGALS1 promoter region using chromatin immunoprecipitation.

Results: Gal-1 transcripts were significantly more abundant in MLL-rearranged B-ALLs. All 32 primary MLL-rearranged B-ALLs exhibited abundant Gal-1 immunostaining, regardless of the translocation partner, whereas only 2 of 81 germline-MLL B-ALLs expressed Gal-1. In addition, Gal-1 was selectively detected in newly diagnosed MLL-rearranged B-ALLs by intracellular flow cytometry. The LGALS1 promoter H3K79 was significantly hypermethylated in MLL-rearranged B-ALLs compared with MLL-germline B-ALLs and normal pre-B cells.

Conclusion: In B-ALL, Gal-1 is a highly sensitive and specific biomarker of MLL rearrangement that is likely induced by a MLL-dependent epigenetic modification. Clin Cancer Res; 16(7); 2122–30. ©2010 AACR.
Relaxin Enhances S100A4 and Promotes Growth of Human Thyroid Carcinoma Cell Xenografts
Authors: Radestock Yvonne , Willing Cornelia , Kehlen Astrid , Hoang-Vu Cuong , Hombach-Klonisch Sabine
Published: March 2010

Relaxin increases cell motility and in vitro invasiveness in human thyroid carcinoma cells but the underlying molecular mechanisms of this action are largely unknown. In the present study, we show that relaxin transcriptionally upregulates the calcium-binding protein S100A4 (metastasin) and increases the cytosolic 10-kDa monomer and the 20-kDa dimer form of S100A4 in human thyroid carcinoma cells. The relaxin-induced increase in cell motility was blocked completely when S100A4 expression was diminished using an S100A4 small interfering RNA knockdown approach. We have shown previously the expression of the insulin-like family member relaxin in human thyroid carcinoma tissues but not in benign thyroid tissues. Human thyroid carcinoma tissues expressing relaxin also stained positive for S100A4. In nude mouse experiments, human thyroid carcinoma cell transfectants with constitutive expression of relaxin generated large and fast-growing tumors with significantly increased numbers of proliferating cells. We provide evidence in our cell model that the relaxin target protein S100A4 secreted by the thyroid carcinoma transfectants may not only enhance tumor cell motility but also promote xenograft angiogenesis as determined by the higher density of tumor microvessels and the angiogenic potential of S100A4 in in vitro tube formation assays. In conclusion, we have identified S100A4 as a major mediator of the actions of relaxin in thyroid carcinoma cell motility and in vivo thyroid tumor angiogenesis. Mol Cancer Res; 8(4); 494–506. ©2010 AACR.
Transcription Factor Egr-1 Is Essential for Maximal Matrix Metalloproteinase-9 Transcription by Tumor Necrosis Factor α
Authors: Shin Soon Young , Kim Ji Ho , Baker Andrew , Lim Yoongho , Lee Young Han
Published: March 2010

Matrix metalloproteinase-9 (MMP-9) is involved in a wide range of normal and pathologic conditions, including inflammation, tissue repair, tumor invasion, and metastasis. Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine that plays crucial roles in tumor progression, including tumor invasion and metastasis in the tumor microenvironment. Egr-1 is a member of the zinc-finger transcription factor family induced by diverse stimuli, including TNFα. However, the role of Egr-1 in MMP-9 expression was previously unknown. This study shows that Egr-1 directly binds to the MMP-9 promoter and plays an essential role for TNFα induction of MMP-9 transcription. Furthermore, Egr-1 together with NF-κB can synergistically activate both basal and TNFα-induced MMP-9 promoter activities in the presence of p300. We found that Egr-1 mediates extracellular signal–regulated kinase and c-jun NH2-terminal kinase mitogen-activated protein kinase–dependent MMP-9 transcription on TNFα stimulation. The requirement for Egr-1 in MMP-9 expression is further supported by the fact that HeLa cells expressing Egr-1 siRNA and Egr-1–null mouse embryonic fibroblasts were refractory to TNFα-induced MMP-9 expression. This report establishes that Egr-1 is essential for MMP-9 transcription in response to TNFα within the tumor microenvironment. Mol Cancer Res; 8(4); 507–19. ©2010 AACR.
Nano-Bio-Chip Sensor Platform for Examination of Oral Exfoliative Cytology
Authors: Weigum Shannon E. , Floriano Pierre N. , Redding Spencer W. , Yeh Chih-Ko , Westbrook Stephen D. , McGuff H. Stan , Lin Alan , Miller Frank R. , Villarreal Fred , Rowan Stephanie D. , Vigneswaran Nadarajah , Williams Michelle D. , McDevitt John T.
Published: March 2010

Oral cancer is a deadly and disfiguring disease that could greatly benefit from new diagnostic approaches enabling early detection. In this pilot study, we describe a nano-bio-chip (NBC) sensor technique for analysis of oral cancer biomarkers in exfoliative cytology specimens, targeting both biochemical and morphologic changes associated with early oral tumorigenesis. Here, oral lesions from 41 dental patients, along with normal epithelium from 11 healthy volunteers, were sampled using a noninvasive brush biopsy technique. Specimens were enriched, immunolabeled, and imaged in the NBC sensor according to previously established assays for the epidermal growth factor receptor (EGFR) biomarker and cytomorphometry. A total of 51 measurement parameters were extracted using custom image analysis macros, including EGFR labeling intensity, cell and nuclear size, and the nuclear-to-cytoplasmic ratio. Four key parameters were significantly elevated in both dysplastic and malignant lesions relative to healthy oral epithelium, including the nuclear area and diameter (P < 0.0001), the nuclear-to-cytoplasmic ratio (P < 0.0001), and EGFR biomarker expression (P < 0.03). Further examination using logistic regression and receiver operating characteristic curve analyses identified morphologic features as the best predictors of disease (area under the curve ≤0.93) individually, whereas a combination of all features further enhanced discrimination of oral cancer and precancerous conditions (area under the curve, 0.94) with high sensitivity and specificity. Further clinical trials are necessary to validate the regression model and evaluate other potential biomarkers, but this pilot study supports the NBC sensor technique as a promising new diagnostic tool for early detection of oral cancer, which could enhance patient care and survival. Cancer Prev Res; 3(4); 518–28. ©2010 AACR.
The Detection of Chromosomal Aneusomy by Fluorescence In situ Hybridization in Sputum Predicts Lung Cancer Incidence
Authors: Varella-Garcia Marileila , Schulte Aline P. , Wolf Holly J. , Feser William J. , Zeng Chan , Braudrick Sarah , Yin Xiang , Hirsch Fred R. , Kennedy Timothy C. , Keith Robert L. , Barón Anna E. , Belinsky Steven A. , Miller York E. , Byers Tim , Franklin Wilbur A.
Published: March 2010

Lung cancer usually is disseminated (advanced) and has a poor prognosis at diagnosis. Current and former smokers are at a high risk for lung cancer and are candidates for prevention and early detection strategies. Sputum is a potential source of biomarkers that might determine either lung cancer risk or the presence of early lung cancer, but no current sputum test is sufficiently sensitive and specific for effective screening. We used fluorescence in situ hybridization (FISH) to measure chromosomal aneusomy (CA) in sputum samples collected prospectively from 100 incident lung cancer cases and 96 controls (matched on age, gender, and date of collection) nested within an ongoing high-risk cohort. The CA-FISH assay was aimed at four DNA targets: epidermal growth factor receptor, MYC, 5p15, and CEP 6. The sensitivity of a positive CA-FISH assay (abnormal for two or more of the four markers) for lung cancer was substantially higher for samples collected within 18 months (76% sensitivity) than for samples collected more than 18 months (31%) before lung cancer diagnosis. Sensitivity was higher for squamous cell cancers (94%) than for other histologic types (69%). CA-FISH specificity based on samples collected within 18 months before diagnosis was 88%. The adjusted odds ratio (OR) of lung cancer for specimens collected within 18 months before a cancer diagnosis was higher for the CA-FISH assay [OR, 29.9; 95% confidence interval (95% CI), 9.5-94.1] than for previously studied ORs of cytologic atypia (OR, 1.8; 95% CI, 1.3-2.6) and gene promoter methylation (OR, 6.5; 95% CI, 1.2-35.5). Whether CA-FISH is an indicator of extreme risk for incident lung cancer or detects exfoliated cancer cells is unknown. The apparent promise of CA-FISH in sputum for assessing lung cancer risk and/or for lung cancer early detection now needs to be validated in a clinical screening trial. Cancer Prev Res; 3(4); 447–53. ©2010 AACR.
Vaccine against MUC1 Antigen Expressed in Inflammatory Bowel Disease and Cancer Lessens Colonic Inflammation and Prevents Progression to Colitis-Associated Colon Cancer
Authors: Beatty Pamela L. , Narayanan Sowmya , Gariépy Jean , Ranganathan Sarangarajan , Finn Olivera J.
Published: March 2010

Association of chronic inflammation with an increased risk of cancer is well established, but the contributions of innate versus adaptive immunity are not fully delineated. There has furthermore been little consideration of the role played by chronic inflammation–associated antigens, including cancer antigens, and the possibility of using them as vaccines to lower the cancer risk. We studied the human tumor antigen MUC1 which is abnormally expressed in colon cancers and also in inflammatory bowel disease (IBD) that gives rise to colitis-associated colon cancer (CACC). Using our new mouse model of MUC1+ IBD that progresses to CACC, interleukin-10 knockout mice crossed with MUC1 transgenic mice, we show that vaccination against MUC1 delays IBD and prevents progression to CACC. One mechanism is the induction of MUC1-specific adaptive immunity (anti-MUC1 IgG and anti-MUC1 CTL), which seems to eliminate abnormal MUC1+ cells in IBD colons. The other mechanism is the change in the local and the systemic microenvironments. Compared with IBD in vaccinated mice, IBD in control mice is dominated by larger numbers of neutrophils in the colon and myeloid-derived suppressor cells in the spleen, which can compromise adaptive immunity and facilitate tumor growth. This suggests that the tumor-promoting microenvironment of chronic inflammation can be converted to a tumor-inhibiting environment by increasing adaptive immunity against a disease-associated antigen. Cancer Prev Res; 3(4); 438–46. ©2010 AACR.
The Ultimate in Cancer Chemoprevention: Cancer Vaccines
Authors: Disis Mary L.
Published: March 2010

This perspective on Beatty et al. (beginning on page 438 in this issue of the journal) discusses the role of the immune system as nature's ultimate chemoprevention agent. A successful immune response to vaccination results in immunologic memory. In the case of a successful cancer-related response, antigen-specific T cells will be poised to destroy an aberrantly expressed protein even if the host is not exposed until years after the end of immunizations. After the abnormal cell is eradicated, T cells will lie in wait for the next exposure. The ability to develop effective cancer vaccines for prevention is fast becoming a reality as immunogenic aberrant proteins that drive malignant transformation are identified. Cancer Prev Res; 3(4); 406–9. ©2010 AACR.
Inactivation of the Tumor Suppressor Genes Causing the Hereditary Syndromes Predisposing to Head and Neck Cancer via Promoter Hypermethylation in Sporadic Head and Neck Cancers
Authors: Smith Ian M. , Mithani Suhail K. , Mydlarz Wojciech K. , Chang Steven S. , Califano Joseph A.
Published: March 2010

Fanconi anemia (FA) and dyskeratosis congenita (DC) are rare inherited syndromes that cause head and neck squamous cell cancer (HNSCC). Prior studies of inherited forms of cancer have been extremely important in elucidating tumor suppressor genes inactivated in sporadic tumors. Here, we studied whether sporadic tumors have epigenetic silencing of the genes causing the inherited forms of HNSCC. Using bisulfite sequencing, we investigated the incidence of promoter hypermethylation of the 17 Fanconi- and DC-associated genes in sporadic HNSCC. Genes that only showed methylation in the tumor patients were chosen for quantitative methylation-specific PCR (qMSP) in a set of 45 tumor and 16 normal patients. Three gene promoters showed differences in methylation: FancB (FAAP95, FA core complex), FancJ (BRIP1, DNA Helicase/ATPase), and DKC1 (dyskeratin). Bisulfite sequencing revealed that only FancB and DKC1 showed no methylation in normal patients, yet the presence of promoter hypermethylation in tumor patients. On qMSP, 1/16 (6.25%) of the normal mucosal samples from non-cancer patients and 14/45 (31.1%) of the tumor patients demonstrated hypermethylation of the FancB locus (p < 0.05). These results suggest that inactivation of FancB may play a role in the pathogenesis of sporadic HNSCC.
Low-Temperature Bipolar Radiofrequency Ablation (Coblation) of the Tongue Base for Supine-Position-Associated Obstructive Sleep Apnea
Authors: Babademez Mehmet Ali , Ciftci Bulent , Acar Baran , Yurekli Muge Fethiye , Karabulut Hayriye , Yilmaz Aydin , Karasen Rıza Murat
Published: March 2010

Objective: To assess the effectiveness of low-temperature bipolar radiofrequency ablation for Coblation of the tongue base in the multilevel management of supine-position-associated obstructive sleep apnea syndrome (OSAS). Study Design and Setting: A retrospective analysis of the data of 16 subjects undergoing uvulopalatopharyngoplasty and tongue base Coblation. The efficacy of the procedure was investigated on the basis of polysomnographic results. Results: The success rate was 62.5% in 16 patients who underwent surgery for OSAS, with decreases in the mean Apnea Hypopnea Index of 20.1–8.9. The success rate was separately evaluated according to the subjects’ posture. A rate of 87.5% was found for the supine position, while the rate was 56.6% in non-supine positions. The minimum postoperative O2 saturation was significantly increased for REM and non-REM stage 3 sleep rates. Conclusion: It is important to evaluate the relation of the disease to the body position in sleep apnea subjects. Coblation of the tongue base is an applicable method of therapy for patients who have sleep apnea that is more marked in the supine position.
Reversible Record Breaking and Variability: Temperature Distributions across the Globe
Authors: Anderson Amalia , Kostinski Alexander
Published: March 2010

Based on counts of record highs and lows, and employing reversibility in time, an approach to examining natural variability is proposed. The focus is on intrinsic variability; that is, variance separated from the trend in the mean. A variability index α is suggested and studied for an ensemble of monthly temperature time series around the globe. Deviation of 〈α〉 (mean α) from zero, for an ensemble of time series, signifies a variance trend in a distribution-independent manner. For 15 635 monthly temperature time series from different geographical locations (Global Historical Climatology Network), each time series about a century-long, 〈α〉 = −1.0, indicating decreasing variability. This value is an order of magnitude greater than the 3σ value of stationary simulations. Using the conventional best-fit Gaussian temperature distribution, the trend is associated with a change of about −0.2°C (106 yr)−1 in the standard deviation of interannual monthly mean temperature distributions (about 10%).
Composite Structure of Monsoon Low Pressure Systems and Its Relation to Indian Rainfall
Authors: Krishnamurthy V. , Ajayamohan R. S.
Published: March 2010

The tropical disturbances formed in the Bay of Bengal and the Arabian Sea and over land points in central India, known as low pressure systems (LPSs), are shown to contribute significantly to the seasonal monsoon rainfall over India. Analyses of daily rainfall over India and statistics of the LPSs for the period of 1901–2003 show that the rainfall pattern when the LPSs are present captures the most dominant daily rainfall pattern that represents the active monsoon phase. The rainfall pattern when the LPSs are absent is similar to the pattern representing the break monsoon phase. The location, number, and duration of the LPSs are found to be closely related to the phases and propagation of the dominant intraseasonal modes of the Indian rainfall. The LPSs are also associated with the strengthening of the monsoon trough and low-level monsoon winds. The number of LPSs and their total duration and the corresponding rainfall during July and August exceed those in June and September. The LPS tracks reach up to northwest India during flood years, whereas they are confined to central India during drought years. However, the contribution of rainfall during the LPSs to the total seasonal rainfall is same during flood or drought years. Although the LPSs seem to play an important role in the monsoon rainfall, they alone may not determine the interannual variability of the seasonal mean monsoon rainfall.
Activation of GABAergic Neurons following Tooth Pulp Stimulation
Authors: Wu L.-A. , Huang J. , Wang W. , Wang W. , Li Y.Q. , Wang X.J. , Wu S.X.
Published: March 2010

The functional impact of GABA (γ-aminobutyric acid)ergic neurons in nociceptive transmission of the spinal trigeminal nucleus is not fully established. Using both the glutamic acid decarboxylase (GAD)67-green fluorescence protein (GFP) knock-in mouse and the tooth pulp stimulation model, we performed double-immunofluorescent histochemistry to determine the characteristics of GABAergic neuron activation in the spinal trigeminal nucleus. The number of Fos-positive GABAergic neuronal profiles was significantly increased 2 hrs after tooth pulp stimulation. The Fos/GFP double-labeled neurons were mainly present in superficial laminae of the spinal trigeminal subnucleus interpolaris-caudalis transition (Vi/Vc) and subnucleus caudalis (Vc) on the side ipsilateral to the stimulation. Subsequently, the number of double-labeled neurons decreased gradually and became comparable with that of the controls by 48 hrs. Our results provide direct morphological evidence that a subset of GABAergic neurons in the spinal trigeminal system was activated during tooth pulp stimulation.
Cytotoxicity of Titanium and Titanium Alloying Elements
Authors: Li Y. , Wong C. , Xiong J. , Hodgson P. , Wen C.
Published: March 2010

It is commonly accepted that titanium and the titanium alloying elements of tantalum, niobium, zirconium, molybdenum, tin, and silicon are biocompatible. However, our research in the development of new titanium alloys for biomedical applications indicated that some titanium alloys containing molybdenum, niobium, and silicon produced by powder metallurgy show a certain degree of cytotoxicity. We hypothesized that the cytotoxicity is linked to the ion release from the metals. To prove this hypothesis, we assessed the cytotoxicity of titanium and titanium alloying elements in both forms of powder and bulk, using osteoblast-like SaOS2 cells. Results indicated that the metal powders of titanium, niobium, molybdenum, and silicon are cytotoxic, and the bulk metals of silicon and molybdenum also showed cytotoxicity. Meanwhile, we established that the safe ion concentrations (below which the ion concentration is non-toxic) are 8.5, 15.5, 172.0, and 37,000.0 µg/L for molybdenum, titanium, niobium, and silicon, respectively.
Use of Three-dimensional Angle-interlock Woven Fabric for Seamless Female Body Armor: Part II: Mathematical Modeling
Authors: Xiaogang Chen  , Dan Yang
Published: March 2010

Angle-interlock woven fabric off the potential to make female body armor as it can form integrally the required dome shape without cutting or molding because of its extraordinary moldability. In Part I of this paper, ballistic impact testing proved that the angle interlock fabrics provide no less ballistic performance than other commercially used fabrics according to the National Institute of Justice (NIJ) standard. Based on the extraordinary moldability and the satisfactory ballistic performance, Part II presents a mathematical model to determine the pattern geometry for the front panel of female body armor. The raised bust area was divided into seven different parts for the modeling, using the simplest surfaces possible. This mathematical model takes the body size and bra size as the input, and the output is the profile of the front pattern of the female body armor. This work enables the speedy creation of the front pattern of female body armor, and more importantly a novel approach for making seamless female body armor with satisfactory ballistic performance.
Investigation of the Effect of Titanium Dioxide on Optical Aspects and Physical and Mechanical Characteristics of ABS Polymer
Authors: Asiaban Saeed , Taghinejad Soheil Farshbaf
Published: March 2010

Acrylonitryl-butadiene-styrene (ABS) is an engineering polymer with intrinsic yellowness and translucency due to blue wavelength absorption and partial light transmission, respectively. Generally, using titanium dioxide pigment helps to whiten ABS polymer and reduce its intrinsic yellowness. Also, it can impart opacity to polymeric parts. However, it must be considered that this pigment may cause some unfavorable effects in ABS parts. In this article, effects of surface treatment type and content of TiO2 pigment on optical aspects of a general purpose ABS have been investigated. In addition, physical and mechanical characteristics including tensile strength, izod impact strength and Rockwell hardness of the polymer have been studied. By adding titanium dioxide pigment opacity and whitening index increased and yellowness index decreased. It is important to note that surface treatment type of titanium dioxide pigment had no considerable effect on optical properties of titanium dioxide pigmented ABS polymer. The results showed that arising content of organic and inorganic surface treated TiO2 pigments up to 0.5% and 1.5%, respectively, causes to increase impact strength and decrease yield stress and maximum strain of pigmented ABS samples. Above these percentages, impact strength decreased due to agglomeration and decreasing inter-particle spacing. Also hardness of all the ABS samples reduced in the presence of inorganic and organic treated titanium dioxide pigments.
Perceived Access to Contraception Among Adolescents With Diabetes
Authors: Schwarz Eleanor B. , Sobota Mindy , Charron-Prochownik Denise
Published: March 2010

Purpose

The purpose of this study was to assess beliefs, perceived access to, and practices regarding contraception among adolescent women with type 1 diabetes.

Methods

Eighty-nine females with type 1 diabetes between the ages of 13 and 19 years, who were recruited from 2 endocrinology practices as part of a larger study, completed a battery of questionnaires designed to assess variables relevant to discussions of sexuality, preconception counseling, contraception, and pregnancy. In addition, items were designed to explore adolescents’ relationship with their health care provider and comfort requesting birth control. Baseline data were analyzed using descriptive statistics.

Results

Half of the sexually active adolescents in this sample reported having had sex without birth control at a time they were trying to avoid pregnancy. A third (36%) of subjects felt that women with diabetes have very limited choices of birth control, and 43% incorrectly believe that all birth control methods are less effective when used by women with diabetes. Less than half (47%) reported that they had discussed birth control with a health care professional, and 29% of subjects reported they had not received formal instruction on birth control in any setting. Perhaps of greatest concern, only 69% stated they would feel comfortable asking a professional for birth control.

Conclusion

Many adolescent women with diabetes are at risk of unintended pregnancy and do not feel comfortable asking a health professional for birth control. Diabetes educators who initiate preconception counseling at puberty and discuss contraceptive options with adolescent women with diabetes may improve pregnancy outcomes.
Racial Disparities in Men’s Health and the Transition to Marriage Among Unmarried Fathers
Authors: Haldane Eva C. , Mincy Ronald B. , Miller Daniel P.
Published: March 2010

This article uses data from the Fragile Families and Child Well-being Survey to examine the association between transitioning to marriage and general health status or serious health problems among low-income men. Beginning with a sample of 3,631 unmarried fathers, the study observes the relationship between their transitions to marriage within 3 years after the birth of their child and their health status 5 years postbirth. The authors also explore if unmarried fathers benefit from marrying mothers who have health insurance. Results indicate that transitions to marriage and transitions to marriage with mothers who have health insurance, are associated with fewer serious health problems. The authors did not observe a significant relationship between transitioning to marriage and general health, likely because the sample comprised men who were young (average age was 26 years) and in very good health.
Marriage and End-Stage Renal Disease: Implications for African Americans
Authors: Shortridge Emily F. , James Cara V.
Published: March 2010

African Americans are disproportionately represented among patients with end-stage renal disease (ESRD). ESRD is managed with a strict routine that might include regular dialysis as well as dietary, fluid intake, and other lifestyle changes. In a disease such as this, with such disruptive treatment modalities, marriage, specifically, and its ties to well-being have the potential to significantly affect adherence to medical treatment and lifestyle recommendations as well as downstream health outcomes such as disease progression and mortality. The authors used data from the Dialysis Morbidity and Mortality Study, Wave 2, of the U.S. Renal Data System Database, a prospective study of 4,000 ESRD patients selected from a random sample of 25% U.S. dialysis facilities, to investigate these research questions. They found that married African American ESRD patients had marginally better outcomes on several clinical and psychosocial measures, which they hypothesize may be attributable to the instrumental and emotional support conferred by marriage.
Red Lines
Authors: Cammarata Manlio
Published: March 2010

Comparison with the terrorism of the 1970s is being used as a pretext for online censorship in Italy, says Manlio Cammarata
Secret Histories
Authors: Freely Maureen
Published: March 2010

As Turkey grapples with an unprecedented string of military scandals, a new book re-examines the legacy of the Armenian genocide, reports Maureen Freely
No Hiding Place
Authors: Hosein Gus
Published: March 2010

Privacy is a political right and governments must not be allowed to forget it, says Gus Hosein
Power to the People
Authors: Valadbaygi Saeed
Published: March 2010

The Iranian state is working hard to crush grass-roots dissent and its ability to organise itself through the internet. It will ultimately fail, says Saeed Valadbaygi
Gate to Freedom
Authors: Khaled Mohamed
Published: March 2010

The Egyptian government continues to harass bloggers, but they’ve become a vital source of information even for the state media, says Mohamed Khaled
Google Rules
Authors: MacKinnon Rebecca
Published: March 2010

Rebecca MacKinnon talks to David Drummond about privacy, censorship and China
Positive Effect of an Autologous Platelet Concentrate in Lateral Epicondylitis in a Double-Blind Randomized Controlled Trial
Authors: Peerbooms Joost C. , Sluimer Jordi , Bruijn Daniël J. , Gosens Taco
Published: March 2010

Background

Platelet-rich plasma (PRP) has shown to be a general stimulation for repair.

Purpose

To determine the effectiveness of PRP compared with corticosteroid injections in patients with chronic lateral epicondylitis.

Study Design

Randomized controlled trial; Level of evidence, 1.

Patients

The trial was conducted in 2 teaching hospitals in the Netherlands. One hundred patients with chronic lateral epicondylitis were randomly assigned in the PRP group (n = 51) or the corticosteroid group (n = 49). A central computer system carried out randomization and allocation to the trial group. Patients were randomized to receive either a corticosteroid injection or an autologous platelet concentrate injection through a peppering technique. The primary analysis included visual analog scores and DASH Outcome Measure scores (DASH: Disabilities of the Arm, Shoulder, and Hand).

Results

Successful treatment was defined as more than a 25% reduction in visual analog score or DASH score without a reintervention after 1 year. The results showed that, according to the visual analog scores, 24 of the 49 patients (49%) in the corticosteroid group and 37 of the 51 patients (73%) in the PRP group were successful, which was significantly different (P < .001). Furthermore, according to the DASH scores, 25 of the 49 patients (51%) in the corticosteroid group and 37 of the 51 patients (73%) in the PRP group were successful, which was also significantly different (P = .005). The corticosteroid group was better initially and then declined, whereas the PRP group progressively improved.

Conclusion

Treatment of patients with chronic lateral epicondylitis with PRP reduces pain and significantly increases function, exceeding the effect of corticosteroid injection. Future decisions for application of the PRP for lateral epicondylitis should be confirmed by further follow-up from this trial and should take into account possible costs and harms as well as benefits.
The Triad That Matters: Palliative Medicine, Code Status, and Health Care Costs
Authors: Celso Brian G. , Meenrajan Senthil
Published: March 2010

Introduction: Delayed discussion of a patient’s code status can lead to shortsighted care plans that increase hospital length of stay (LOS) and costs. Methods: Retrospective study compared intensive care unit (ICU) patients who accepted verses rejected palliation and examined the relationships between 5 predictor variables with the outcome variables ICU LOS and total hospital LOS, and total direct and variable hospital cost. Results: A significant number of patients who accepted palliative care agreed to a hospice referral or expired in the hospital. The relationships between days until a family conference, do-not-resuscitate (DNR) order, and the number of invasive procedures were significant. Conclusions: The amount of time that expires until the issue of code status was settled to clearly related to utilization of hospital resources.
Judicial Politicization, Ideology, and Activism at the High Courts of the United States, Canada, and Australia
Authors: Weiden David L.
Published: March 2010

This article proposes a new cross-national thesis for judicial decision making. The judicial politicization theory posits that judges on highly politicized high courts will be more likely to decide cases using ideological and attitudinal factors than judges at less politicized courts. The theory holds that informal norms regarding judicial appointment by the executive are more important than the formal selection mechanism in determining whether a judiciary is highly or less politicized. The results show significant attitudinal judicial voting at each high court and strong support for the contention that judges on highly politicized courts are more likely to decide cases ideologically.
Cost savings from dose rounding of biologic anticancer agents in adults
Authors: Winger Brenda J , Clements Elizabeth A , DeYoung Jaculin L , O'Rourke Timothy J , Claypool Deborah L , Vachon Steve , VanDyke Thomas H , Zimmer-Young Jennifer , Kintzel Polly E
Published: March 2010

Purpose: The purpose of this project was to determine the cost savings related to a dose-rounding process for adult biologic anticancer agents.

Methods: Biologic anticancer agents prepared by the inpatient pharmacy were identified retrospectively through completed chemotherapy preparation checklists and medication orders on file in the pharmacy or by the clinical pharmacist for adult oncology from the medical records of patients in her practice. The specific products screened for evaluation were aldesleukin, bevacizumab, cetuximab, denileukin diftitox, gemtuzumab, rituximab, and trastuzumab. Data collected included drug name, ordered dose, rounded dose, and product vials not wasted. Specific drug costs were provided by the department’s purchasing office. The project was reviewed and approved by the institutional review board to allow retrospective data collection from patient records. Cost savings were evaluated retrospectively for the time period of January 1, 2005 through March 31, 2005.

Results: One hundred and twenty-six orders for biologic anticancer agents were processed by the pharmacy department during the 3-month time period of data collection. Dose rounding could reduce drug wastage for 42% of these orders. Potential cost savings from dose rounding was $24,434 for the 3-month interval evaluated. However, nonadherence to dose rounding for 29 rituximab orders decreased the actual cost savings to $15,922. Individual staff education was reinforced to address nonadherence.

Conclusion: Routine dose rounding of biologic anticancer agents to an amount within 10% of the ordered dose achieved cost savings through reduction of drug wastage at our institution.
Predictors of ADHD Persistence in Girls at 5-Year Follow-Up
Authors: Mick Eric , Byrne Deirdre , Fried Ronna , Monuteaux Michael , Faraone Stephen V. , Biederman Joseph
Published: March 2010

Objective: The main aim of this study was to examine the age-dependent remission from ADHD in girls transitioning through childhood into adolescence and early adulthood. Method: We conducted a 5-year prospective follow-up study of 123 girls with ADHD and 106 non-ADHD control girls aged between 6 and 17 years at ascertainment. ADHD was considered persistent at follow-up if participants met full diagnostic criteria for DSM-IV ADHD or met residual criteria for DSM-IV ADHD with associated impairment (Global Age Forum [GAF] score < 60). Results: By age 16 years, ADHD was persistent in 71% (95% CI = 61-79%) of girls with ADHD. Participants with persistent ADHD at follow-up had more psychiatric comorbidity, behavior problems, and functional impairment than girls with ADHD in remission. Remitted ADHD, however, continued to be associated with functional impairment relative to non-ADHD controls. Persistence at 5 years was predicted by increased behavioral impairment at baseline. Conclusion: This 5-year follow-up suggests that many girls with ADHD experience persistent symptoms and/or functional impairment through late adolescence and into early adulthood. (J. of Att. Dis. 2011; 15(3) 183-192)
Cannabinoid Receptor Agonist WIN-55,212-2 Protects Differentiated PC12 Cells From Organophosphorus- Induced Apoptosis
Authors: Sadri Soheil , Bahrami Farideh , Khazaei Mozafar , Hashemi Mansoureh , Asgari Alireza
Published: March 2010

Cannabinoid neuroprotection is usually greater in vivo than in neuronal cell culture systems. To the authors' knowledge, a good in vitro culture model for the neuroprotective effects of cannabinoids does not exist. Therefore, a 3-dimensional (3D) culture system was developed to investigate the neuroprotective effects of the cannabinoid receptor agonist WIN-55,212-2 on apoptosis of differentiated PC12 cells, caused by the organophosphorus compounds paraoxon and diazinon. Cells pretreated with WIN-55,212-2 were exposed to a proapoptotic concentration of paraoxon and diazinon. TUNEL was used to detect apoptosis, and neurite length was assessed by morphometry. Both paraoxon and diazinon induced apoptosis, although the latter was more potent. WIN-55,212-2 also protected cells from neurite retraction and DNA fragmentation induced by the OPs. The results suggest that WIN-55,212-2 protects PC12 cells cultured under 3D conditions from organophosphorus-induced apoptosis. This 3D culture system may prove to be a useful tool for investigating the neuroprotective effects of cannabinoids.