bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulatory effects of gentisic acid against genotoxicity and hepatotoxicity induced by cyclophosphamide in Swiss albino mice
Authors: Nafees Sana , Ahmad Shiekh Tanveer , Arjumand Wani , Rashid Summya , Ali Nemat , Sultana Sarwat 
Published: December 2011

Abstract

Objectives
This study evaluated the protective effects of gentisic acid (GA) against genotoxicity and hepatotoxicity induced by cyclophosphamide (CP) in Swiss albino mice.

Methods
Mice were pretreated with GA orally at doses of 50 and 100 mg/kg for 14 consecutive days before the administration of a single intraperitoneal dose of 50 mg/kg CP. The ameliorative effect of GA on genotoxicity was studied using the in-vivo bone marrow micronuclei induction test, DNA integrity and alkaline unwinding assay. The activity of various oxidative stress enzymes were estimated in hepatic tissue.

Key findings
A single intraperitoneal administration of CP in mice increased the malondialdehyde level, depleted the glutathione content and antioxidant enzyme activity (glutathione peroxidase, glutathione reductase, catalase and quinone reductase), and induced DNA strand breaks and micronuclei induction. Oral pretreatment with GA at both doses caused a significant reduction in malondialdehyde and glutathione levels, restoration of antioxidant enzyme activity, reduction in micronuclei formation and DNA fragmentation. Serum toxicity marker enzymes such as aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were increased after CP treatment but restored in GA pretreated groups.

Conclusion
The results support the protective effect of GA against CP induced genotoxicity and hepatotoxicity.
Publication trends in newspapers and scientific journals for SSRIs and suicidality: a systematic longitudinal study
Authors: Hernandez J F , Mantel-Teeuwisse A K , van Thiel G J M W , Belitser S V , Raaijmakers J A M , Pieters T 
Published: December 2011

BackgroundIn the period 2003–2008, the regulatory authorities issued several warnings restricting the use of selective serotonin re-uptake inhibitors (SSRIs) in paediatrics, in reaction to safety concerns regarding the risk of suicidality. In this study, the SSRIs and suicidality controversy serves as a template to analyse the long-term publication trends regarding the benefit/risk profile of medications. The aim is to ascertain differences (in terms of numbers, categories and timing) between negative and positive newspaper and journal articles on SSRIs and suicidality and to ascertain correlations between changes in the reports and regulatory warnings.MethodsA systematic review of scientific articles (Embase) and the Netherlands (NL) and the UK newspapers (LexisNexis) was performed between 2000 and 2010. Categorisation was done by ‘effect’ (related treatment effect), ‘type of article’ and ‘age group’. The articles' positive-to-negative effect ratio was determined. Differences in distribution of effect categories were analysed across sources, type of article and age group using the Mann–Whitney (two subgroups) or Kruskal–Wallis test (three or more).FindingsIn total, 1141 articles were categorised: 352 scientific, 224 Dutch and 565 British newspaper articles. Scientific articles were predominantly on research and were positive, whereas newspaper articles were negative (ratios=3.50—scientific, 0.69—NL and 0.94—UK; p<0.001). Articles on paediatrics were less positive in scientific journals and more negative in newspapers (ratios=2.29—scientific, 0.26—NL and 0.20—UK; p<0.001), while articles on adults were positive overall (ratios=10.0—scientific, 1.06—NL and 1.70—UK; p<0.001). In addition, negative-effect reporting trends were exacerbated following regulatory warnings and were generally opinion articles, both in scientific journals and in newspapers (2003/2004 and after 2007).InterpretationThe authors found a positive publication tendency inherent in journal research articles. This apparent positive publication bias present in scientific journals, however, does not seem to prevent the dissemination of ‘bad’ news about medications. The negative tendency present in Dutch and British newspapers was perceivable in the paediatrics group and during the warnings, indicating that national news media have informed the public about this international drug safety controversy on time.
Validating the acute heart failure index for patients presenting to the emergency department with decompensated heart failure
Authors: Hsiao James , Motta Michelle , Wyer Peter 
Published: December 2011

BackgroundThe acute heart failure index (AHFI) is a previously derived prediction rule to identify patients presenting to emergency departments (ED) with decompensated heart failure (DHF) at low risk of early life-threatening events.Study objectivesTo validate the AHFI prospectively.MethodsUsing a prospective cohort study, adult patients presenting to an urban university hospital ED with DHF were included. Data on 21 variables were gathered to calculate the AHFI. Primary endpoints included inpatient death and non-fatal serious outcomes (myocardial infarction, ventricular fibrillation, cardiogenic shock, cardiac arrest, intubation, or cardiac reperfusion). Secondary endpoints included death from any cause or readmission for heart failure within 30 days. Primary and secondary endpoint rates were calculated with 95% CI for the low and higher-risk subgroups.Results259 patients were enrolled. 245/259 (95%) were admitted. 60/259 (23%) met low-risk criteria, of whom 1/60 (1.7%, CI 0.04 to 8.9) was discharged after sustaining pulseless electrical activity arrest. The comparable primary outcome rate in the derivation study was 1.4% (CI 1.1 to 1.7). 17/199 (8.5%, CI 5.1 to 13.3) higher-risk patients experienced an endpoint, compared with 13.3% (CI 12.9 to 13.7) in the derivation cohort. One low-risk patient (1.7%, CI 0.04 to 8.9) died within 30 days, and five (8.3%, CI 2.8 to 18.4) were readmitted. Corresponding rates in the derivation study were 2% and 5%, respectively.ConclusionThe results are consistent with those previously reported for the low-risk subgroup of the AHFI. Further research is needed to determine the impact, safety and full range of generalisability of the AHFI as an adjunct to decision making.
Migrating husbands and changing cardiovascular risk factors in the wife: a cross sectional study in Asian Indian women
Authors: Gupta Rajeev , Gupta Rajiv , Agrawal Aachu , Misra Anoop , Guptha Soneil , Pandey Ravindra M , Misra Puneet , Vikram Naval K , Dey Sanjit , Rao Shobha , Menon V Usha , Kamalamma N , Revathi K , Mathur Beena , Sharma Vinita 
Published: December 2011

ObjectiveThe authors studied the influence of migration of husband on cardiovascular risk factors in Asian Indian women.MethodsPopulation-based studies in women aged 35–70 years were performed in four urban and five rural locations. 4608 (rural 2604 and urban 2004) of the targeted 8000 (57%) were enrolled. Demographic details, lifestyle factors, anthropometry, fasting glucose and cholesterol were measured. Multivariate logistic and quadratic regression was performed to compare influence of migration and its duration on prevalence of risk factors.ResultsDetails of migration were available in 4573 women (rural 2267, rural–urban migrants 455, urban 1552 and urban–rural migrants 299). Majority were married, and illiteracy was high. Median (interquartile) duration of residence in urban locations among rural–urban migrants was 9 (4–18) years and in rural areas for urban–rural migrants 23 (18–30) years. In rural, rural–urban migrants, urban and urban–rural migrants, age-adjusted prevalence (%) of risk factors was tobacco use 41.9, 22.7, 18.8 and 38.1; sedentary lifestyle 69.7, 82.0, 79.9 and 74.6; high-fat diet 33.3, 54.2, 66.1 and 61.1; overweight 21.3, 42.7, 46.3 and 29.7; large waist 8.5, 38.5, 29.2 and 29.2; hypertension 30.4, 49.4, 47.7 and 38.4; hypercholesterolaemia 14.4, 31.3, 26.6 and 9.1 and diabetes 3.9, 15.8, 14.9 and 8.4, respectively (p<0.001). In rural–urban migrants, there was a significant correlation of duration of migration with waist size, waist-to-hip ratio and systolic blood pressure (quadratic regression, p<0.001). Association of risk factors with migration remained significant, though attenuated, after adjustment for socioeconomic, lifestyle and obesity variables (logistic regression, p<0.01).ConclusionsCompared with rural women, rural–urban migrants and urban have significantly greater cardiometabolic risk factors. Prevalence is lower in urban–rural migrants. There is significant correlation of duration of migration with obesity and blood pressure. Differences are attenuated after adjusting for social and lifestyle variables.
EVALUATION OF THE MAGNITUDE OF PISTONING MOTION OF THE BELOW KNEE PROSTHESES
Authors: KARIMI MOHAMMAD TAGHI , ABTAHI FAHIMOSSADAT 
Published: December 2011

The incidence of amputation varies between 2.8 and 43.9 per 100,000 of population. Nearly 43% of the lower limb amputations are below knee amputee. One of the prosthesis which has being used for transtibial is patellar-tendon-bearing prosthesis (PTB) developed in the Biomechanics laboratory of California University. It is made of socket, foot and suspension system. The main role of the suspension system is to minimize the motion occurring between residual limb and prosthesis. Any failures in the function of the suspension system increase the interface motion between stump and socket and lead to troubling issues for the prosthesis users. It is not clearly defined which types of suspension systems of this prosthesis have better performance to decrease the pistoning motions. Therefore, the aim of this research was to evaluate the effects of using different kinds of suspension systems on the magnitude of pistoning motion and also on the functional performance of the below knee prosthesis.Method: A group of 51 below knee amputee participated in this study. The main criteria for selecting the patients were having no contraindications for standing and walking with prosthesis and using the current prosthesis for at least one year. In order to evaluate the efficiency of suspension system on pistoning movement, the distance between some fixed markers on the prosthesis was measured under various weight bearing conditions.Results: The correlation between the amount of pistoning movement and the type of suspension system was not significant. However, the function of the supracondylar strap and PTB total contact was better than other systems. The amount of pistoning movement differed between left and right sides.Conclusion: The magnitude of pistoning motion of the stump is not influenced by the type of selected suspension system and the stump length.
Dysregulation of Ezrin Phosphorylation Prevents Metastasis and Alters Cellular Metabolism in Osteosarcoma
Authors: Ren Ling , Hong Sung-Hyeok , Chen Qing-Rong , Briggs Joseph , Cassavaugh Jessica , Srinivasan Satish , Lizardo Michael M. , Mendoza Arnulfo , Xia Ashley Y. , Avadhani Narayan , Khan Javed , Khanna Chand 
Published: December 2011

Abstract
Ezrin links the plasma membrane to the actin cytoskeleton where it plays a pivotal role in the metastatic progression of several human cancers; however, the precise mechanistic basis for its role remains unknown. Here, we define transitions between active (phosphorylated open) and inactive (dephosphorylated closed) forms of Ezrin that occur during metastatic progression in osteosarcoma. In our evaluation of these conformations we expressed C-terminal mutant forms of Ezrin that are open (phosphomimetic T567D) or closed (phosphodeficient T567A) and compared their biologic characteristics to full-length wild-type Ezrin in osteosarcoma cells. Unexpectedly, cells expressing open, active Ezrin could form neither primary orthotopic tumors nor lung metastases. In contrast, cells expressing closed, inactive Ezrin were also deficient in metastasis but were unaffected in their capacity for primary tumor growth. By imaging single metastatic cells in the lung, we found that cells expressing either open or closed Ezrin displayed increased levels of apoptosis early after their arrival in the lung. Gene expression analysis suggested dysregulation of genes that are functionally linked to carbohydrate and amino acid metabolism. In particular, cells expressing closed, inactive Ezrin exhibited reduced lactate production and basal or ATP-dependent oxygen consumption. Collectively, our results suggest that dynamic regulation of Ezrin phosphorylation at amino acid T567 that controls structural transitions of this protein plays a pivotal role in tumor progression and metastasis, possibly in part by altering cellular metabolism. Cancer Res; 72(4); 1001–12. ©2011 AACR.
Identification of Molecular Vulnerabilities in Human Multiple Myeloma Cells by RNA Interference Lethality Screening of the Druggable Genome
Authors: Tiedemann Rodger E. , Zhu Yuan Xao , Schmidt Jessica , Shi Chang Xin , Sereduk Chris , Yin Hongwei , Mousses Spyro , Stewart A. Keith 
Published: December 2011

Abstract
Despite recent advances in targeted treatments for multiple myeloma, optimal molecular therapeutic targets have yet to be identified. To functionally identify critical molecular targets, we conducted a genome-scale lethality study in multiple myeloma cells using siRNAs. We validated the top 160 lethal hits with four siRNAs per gene in three multiple myeloma cell lines and two non-myeloma cell lines, cataloging a total of 57 potent multiple myeloma survival genes. We identified the Bcl2 family member MCL1 and several 26S proteasome subunits among the most important and selective multiple myeloma survival genes. These results provided biologic validation of our screening strategy. Other essential targets included genes involved in RNA splicing, ubiquitination, transcription, translation, and mitosis. Several of the multiple myeloma survival genes, especially MCL1, TNK2, CDK11, and WBSCR22, exhibited differential expression in primary plasma cells compared with other human primary somatic tissues. Overall, the most striking differential functional vulnerabilities between multiple myeloma and non–multiple myeloma cells were found to occur within the 20S proteasome subunits, MCL1, RRM1, USP8, and CKAP5. We propose that these genes should be investigated further as potential therapeutic targets in multiple myeloma. Cancer Res; 72(3); 757–68. ©2011 AACR.
Measured Body Mass Index in Adolescence and the Incidence of Colorectal Cancer in a Cohort of 1.1 Million Males
Authors: Levi Zohar , Kark Jeremy D. , Barchana Micha , Liphshitz Irena , Zavdy Ofir , Tzur Dorit , Derazne Estela , Furman Moshe , Niv Yaron , Gordon Barak , Afek Arnon , Shamiss Ari 
Published: December 2011

Abstract
Background and Aims: The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with colorectal cancer incidence in a large cohort of males.
Methods: Body mass index (BMI) was measured in 1.1 million Jewish Israeli males who underwent a general health examination at ages 16 to 19 between 1967 and 2005. Overweight was defined as BMI ≥ 85th percentile of the standard U.S. distribution in adolescence. Colorectal cancer was identified by linkage with the Israel National Cancer Registry up to 2006. The mean follow-up period was 17.6 ± 10.9 years, reflecting 19.5 million person-years. Cox proportional hazards modeling was used.
Results: The prevalence of adolescent overweight increased from 9.9% to 16.8% in the first 10 and last 10 annual examination cohorts. Colon (n = 445) and rectal cancer (n = 193) cases were detected. Overweight predicted an increased risk of colon cancer [HR = 1.53; 95% confidence interval (CI), 1.17–2.02, P = 0.002] but not of rectal cancer (HR = 1.09; 95% CI, 0.38–1.73, P = 0.72). The risk was greatest for nonmucinous adenocarcinoma of the colon (HR = 1.68, 95% CI, 1.26–2.23, P = 0.001). The association of BMI ≥ 85th percentile with colon cancer was even more pronounced in analyses that were restricted to men followed until at least 40 years of age [N = 367,478; HR = 1.75 (95% CI, 1.33–2.3, P &lt; 0.001)].
Conclusions: Adolescent overweight is substantially associated with colon cancer incidence in young to middle-aged adults.
Impact: These long-term sequelae add to the urgency to seriously address increasing childhood and adolescent obesity with its attendant increasing population impact. Cancer Epidemiol Biomarkers Prev; 20(12); 2524–31. ©2011 AACR.
Cancer Risk Associated with Long-term Use of Acetaminophen in the Prospective VITamins and Lifestyle (VITAL) Study
Authors: Walter Roland B. , Brasky Theodore M. , White Emily 
Published: December 2011

Abstract
Background: Acetaminophen (paracetamol) is a widely used over-the-counter drug, but concerns of genotoxic effects have been raised. After we recently found an almost two-fold increased risk of hematologic malignancies associated with high use of acetaminophen in the prospective VITamins And Lifestyle (VITAL) study, we herein further examined the association between acetaminophen use and cancer risk in the VITAL cohort.
Methods: A total of 62,841 men and women aged 50 to 76 years were recruited from 2000 to 2002, and incident malignancies other than nonmelanoma skin cancer (n = 5,750) were identified through December 2008 via linkage to the Surveillance, Epidemiology, and End Results cancer registry. HRs associated with acetaminophen use for incidence of total cancers and nonhematologic cancer subcategories were estimated with Cox proportional hazards models that were adjusted for age, demographics, cancer risk factors, and medical conditions that may be indications for acetaminophen use.
Results: Use of acetaminophen was not associated with total cancer risk. We also observed no associations for most major nonhematologic cancer sites, including cancers of the gastrointestinal system, lung, urinary tract, skin, prostate, or female organs.
Conclusion: This study failed to provide evidence of an association between acetaminophen use and total cancer risk or incidence of nonhematologic malignancies.
Impact: Together with our previous findings, the analyses from the VITAL study suggest a particular sensitivity of the hematopoietic system to the mutagenic effects of acetaminophen. Cancer Epidemiol Biomarkers Prev; 20(12); 2637–41. ©2011 AACR.
Endogenous Sex Steroids and Risk of Cervical Carcinoma: Results from the EPIC Study
Authors: Rinaldi Sabina , Plummer Martyn , Biessy Carine , Castellsagué Xavier , Overvad Kim , Krüger Kjær Susanne , Tjønneland Anne , Clavel-Chapelon Françoise , Chabbert-Buffet Nathalie , Mesrine Sylvie , Lukanova Annekatrin , Kaaks Rudolf , Weikert Cornelia , Boeing Heiner , Trichopoulou Antonia , Lagiou Pagona , Trichopoulos Dimitrios , Palli Domenico , Agnoli Claudia , Tumino Rosario , Vineis Paolo , Panico Salvatore , Bueno-de-Mesquita Bas , van Kranen Henk J. , Peeters Petra HM. , Bakken Kjersti , Lund Eiliv , Gram Inger Torhild , Rodríguez Laudina , Bosch F Xavier , Sánchez Maria-José , Dorronsoro Miren , Navarro Carmen , Gurrea Aurelio Barricarte , Kjellberg Lennart , Dillner Joakim , Manjer Jonas , Butt Salma , Khaw Kay-Tee , Wareham Nicholas , Allen Naomi E. , Travis Ruth , Romieu Isabelle , Ferrari Pietro , Riboli Elio , Franceschi Silvia 
Published: December 2011

Abstract
Background: Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC).
Methods: Ninety-nine ICC cases, 121 cervical intraepithelial neoplasia grade 3 (CIN3) cases and 2 control women matched with each case for center, age, menopausal status and blood collection–related variables, were identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Circulating levels of testosterone (T) and estradiol (E2); dehydroepiandrosterone sulfate (DHEAS); progesterone (premenopausal women); and sex hormone–binding globulin (SHBG) were measured using immunoassays. Levels of free (f) T and E2 were calculated from absolute concentrations of T, E2, and SHBG. Odds ratios (ORs) and 95% confidence intervals (CI) were computed using regularized conditional logistic regression.
Results: Among premenopausal women, associations with ICC were observed for fT (OR for highest vs. lowest tertile = 5.16, 95% CI, 1.50–20.1). SHBG level was associated with a significant downward trend in ICC risk. T, E2, fE2, and DHEAS showed nonsignificant positive association with ICC. Progesterone was uninfluential. Among postmenopausal women, associations with ICC were found for T (OR = 3.14; 95% CI, 1.21–9.37), whereas E2 and fT showed nonsignificant positive association. SHBG level was unrelated to ICC risk in postmenopausal women. No associations between any hormone and CIN3 were detected in either pre- or postmenopausal women.
Conclusions: Our findings suggest for the first time that T and possibly E2 may be involved in the etiology of ICC.
Impact: The responsiveness of cervical tumors to hormone modulators is worth exploring. Cancer Epidemiol Biomarkers Prev; 20(12); 2532–40. ©2011 AACR.
HIV Infection, Immunodeficiency, Viral Replication, and the Risk of Cancer
Authors: Silverberg Michael J. , Chao Chun , Leyden Wendy A. , Xu Lanfang , Horberg Michael A. , Klein Daniel , Towner William J. , Dubrow Robert , Quesenberry Charles P. , Neugebauer Romain S. , Abrams Donald I. 
Published: December 2011

Abstract
Background: Few studies have compared cancer risk between HIV-infected individuals and a demographically similar HIV-uninfected internal comparison group, adjusting for cancer risk factors.
Methods: We followed 20,775 HIV-infected and 215,158 HIV-uninfected individuals enrolled in Kaiser Permanente (KP) California for incident cancer from 1996 to 2008. Rate ratios (RR) were obtained from Poisson models comparing HIV-infected (overall and stratified by recent CD4 count and HIV RNA) with HIV-uninfected individuals, adjusted for age, sex, race/ethnicity, calendar period, KP region, smoking, alcohol/drug abuse, and overweight/obesity.
Results: We observed elevated RRs for Kaposi sarcoma (KS; RR = 199; P &lt; 0.001), non-Hodgkin lymphoma (NHL; RR = 15; P &lt; 0.001), anal cancer (RR = 55; P &lt; 0.001), Hodgkin lymphoma (HL; RR = 19; P &lt; 0.001), melanoma (RR = 1.8; P = 0.001), and liver cancer (RR = 1.8; P = 0.013), a reduced RR for prostate cancer (RR = 0.8; P = 0.012), and no increased risk for oral cavity/pharynx (RR = 1.4; P = 0.14), lung (RR = 1.2; P = 0.15), or colorectal (RR = 0.9; P = 0.34) cancers. Lung and oral cavity/pharynx cancers were elevated for HIV-infected subjects in models adjusted only for demographics. KS, NHL, anal cancer, HL, and colorectal cancer had significant (P &lt; 0.05) trends for increasing RRs with decreasing recent CD4. The RRs for lung and oral cavity/pharynx cancer were significantly elevated with CD4 &lt; 200 cells/μL and for melanoma and liver cancer with CD4 &lt; 500 cells/μL. Only KS and NHL were associated with HIV RNA.
Conclusion: Immunodeficiency was positively associated with all cancers examined except prostate cancer among HIV-infected compared with HIV-uninfected individuals, after adjustment for several cancer risk factors.
Impact: Earlier antiretroviral therapy initiation to maintain high CD4 levels might reduce the burden of cancer in this population. Cancer Epidemiol Biomarkers Prev; 20(12); 2551–9. ©2011 AACR.