bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS26 Prevalence and Associations of Limited Health Literacy in Chronic Kidney Disease: A Systematic Review
Authors: Fraser SDS , Roderick PJ , Casey M , Taal MW , Yuen HM , Nutbeam D 
Published: September 2012

BackgroundChronic kidney disease (CKD) is a prevalent and growing problem, strongly associated with obesity, diabetes, hypertension, and cardiovascular disease. Health inequalities are recognised throughout the CKD pathway, including prevalence of risk factors, prevalence of CKD, progression, and renal replacement therapy. There is evidence that an adequate level of health literacy (defined as ‘the cognitive and social skills which determine the motivation and ability of individuals to gain access to, understand, and use information in ways that promote and maintain good health’) contributes to improved disease management, and that inadequate health literacy is a potentially modifiable determinant of poor health outcomes and health inequalities in people with chronic disease. The aim of this review was to synthesise and critically appraise the literature evidence on the prevalence and associations of limited health literacy in CKD.MethodsSeven databases were searched using terms for CKD and health literacy (HL). Cross sectional studies, and baseline data from cohort and randomised controlled trials were included where they assessed and presented the prevalence of limited HL using a validated tool in adults with CKD of any stage. The primary outcome was an objectively measured prevalence of limited HL in a population with CKD. The secondary outcome was associations of limited HL. Study quality was assessed by two reviewers using standardised criteria. Prevalence values were combined using a random effect model to give overall prevalence.Results82 studies were identified from searching, of which six met the inclusion criteria. The total number of people with CKD in all studies was 1,405. Five studies were in dialysis or transplant populations, and all were from the US. There was significant heterogeneity in the prevalence of limited HL (9% to 32% (median 25%, inter-quartile range 16%)). The pooled prevalence of limited HL in all studies was 22.7% (95% CI 20.6%, 24.8%). The review identified associations between limited HL and socioeconomic factors (lower education attainment, lower income), and certain process and outcome measures (lower likelihood of referral for transplant, higher mortality). Overall study quality was poor, with particular weaknesses of sampling and non-response.ConclusionLimited health literacy is common among people with CKD and independently associated with socioeconomic factors and health outcomes. It may represent an important determinant of inequality of outcomes in CKD. There is a need for further investigation of limited health literacy in people with pre-end stage CKD, and in UK CKD populations.
PS35 The Role of Time Preference in Smoking Cessation: A Longitudinal Analysis of Data from the Household Income and Labour Dynamics of Australia Survey, 2001-08
Authors: Adams J , Brown H 
Published: September 2012

Background‘Time preference’ is an economic concept that describes the trade-offs that individuals make between costs and benefits occurring at different points of time. Related psychological concepts include time perspective, impulsivity and delay of gratification. Present orientated people prefer immediate over future gains and place more value on these. Differences in how much value different individuals place on future outcomes are likely to play some role in present day behavioural decisions.There is substantial cross-sectional evidence that smokers tend to have shorter term time preferences than non-smokers. However, few studies have explored the longitudinal relationship between time preference and smoking cessation.We explored the relationship between time preference and smoking cessation in a general adult cohort using data from a large Australian longitudinal panel study: the Household Income and Labour Dynamics of Australia (HILDA) survey.MethodsHILDA is a longitudinal, nationally representative, household survey which began in 2001. The focus of the survey is on economic and subjective well-being, and labour market and family dynamics. Data is collected by annual interview and self-complete questionnaire.Members of the HILDA panel, aged 15–64, who responded to at least four waves of data collection between 2001 and 2008, and reported any level of tobacco consumption at any wave were included in the analyses.Smoking cessation was measured using self-report questions. Time preference was measured using self-reported time period for financial planning. A range of sociodemographic (age, number of children, various markers of socio-economic position) and smoking-related (previous quit attempts, years smoked) co-variates were controlled for.Results1,817 individuals (representing 7,913 unique observations) were included in the analyses. In univariable analyses, both men and women who reported quitting smoking were more likely to have a longer term time preference in the data collection period immediately prior to quitting than those who did not quit (men: t(4,126)=4.59, p<0.001; women: t(3,783)=7.18, p<0.001). These relationships persisted after control for socio-demographic and smoking-related covariates (hazard ratio of quitting in those with longer vs shorter term time preference (95% confidence intervals) = 1.27 (1.03 – 1.57) in men; 1.31 (1.05 – 1.63) in women).ConclusionAdult smokers with a longer term time preference are more likely to quit smoking. This does not exclude the possibility that quitting smoking simultaneously leads to development of longer term time preference. Interventions that encourage development of longer term time preference may enable smoking cessation.
PS40 Profiles of Polydrug Use at a Local and a National Level: Risk Factors and Associations with Mental Health and Functioning
Authors: Clark JL , Frissa S , Hatch S , Hotopf M 
Published: September 2012

BackgroundPolydrug use is an understudied phenomenon with potential implications for individual functioning and health. Its frequency within the general public and its individual costs thus need to be documented. This study’s aims were to compare the types of polydrug users in the general public at a national and a local level, and to examine how risk factors and impairments differed between them.MethodsUsing comparable datasets from a local community in South East London during 2008–2010 (n=1,698) and from England in 2007 (n=7,403), latent class analysis was used to construct profiles of polydrug users. Eight binary indices reporting drug use in the last year for cannabis, amphetamine, cocaine, ecstasy, LSD, tranquilisers, crack, heroin, and two items for hazardous alcohol drinking and current cigarette smoking, were regressed on a latent variable of polydrug use with age and sex covariates. The latent class solution from each dataset was then used in a multinomial logistic regression comparing risk factors from socio-demographic, neighbourhood, social support, and mental health domains.ResultsBoth datasets produced three class solutions with comparable proportions: in London, 61.6% were in the “Nondrug user” group, 30.5% in the “Moderate user group” (characterised by hazardous drinking, cigarettes and some cannabis use) and 7.9% in the “High Drug User” group (characterised by drug use across all substances); in the national dataset the proportions were 57.4%, 37.9 %, and 4.6% respectively. In a logistic regression comparing both polydrug user groups to the nonuser group, both samples reported higher odds for polydrug use and common mental disorder, suicidal ideation, and functional limitation; higher levels of education, stressful life events and a never-married status were also associated with polydrug use. Differences between the local and national samples for polydrug use were found on factors such as ethnicity, social support, and employment status. Further analysis revealed no difference between the “Moderate” and “High Drug” groups in the local sample for these risk factors and mental health indicators, whereas several dose-response relationships between these groups were found nationally.ConclusionApproximately a third of the general public both nationally and locally exhibit a pattern of moderate polydrug use associated with mental health and daily functioning impairments. Furthermore, local services and policy makers should note that higher education is a risk factor for polydrug use, and that factors related to employment and social support may be differentially linked to substance use depending on geographical residence.
Impact of operator and site experience on outcomes after angioplasty and stenting in the SAMMPRIS trial
Authors: Derdeyn Colin P , Fiorella David , Lynn Michael J , Barnwell Stanley L , Zaidat Osama O , Meyers Philip M , Gobin Y Pierre , Dion Jacques , Lane Bethany F , Turan Tanya N , Janis L Scott , Chimowitz Marc I ,   for the SAMMPRIS Trial Investigators
Published: September 2012

Background and purposeTo investigate the relationship between physician and site experience and the risk of 30 day hemorrhagic and ischemic strokes in the stenting arm of the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial.MethodsStudy records and an investigator survey were examined for physician and site related factors, including: number of Wingspan and aneurysm stents submitted for credentialing, number of study procedures performed in SAMMPRIS, years in practice after training, primary specialty, and site enrollment. Bivariate and multivariate analyses were performed to determine if these factors were associated with the 30 day rate of cerebrovascular events after angioplasty and stenting.Results213 patients underwent angioplasty alone (n=5) or angioplasty and stenting (n=208) with study devices by 63 interventionists at 48 sites. For credentialing, the median number of Wingspan and similar aneurysm stent cases submitted by study interventionists were 10 and 6, respectively. Interventionists with higher numbers (>10) of Wingspan cases submitted for credentialing tended to have higher rates of 30 day events (19.0% vs 9.9%) than those with <10 cases. High enrolling sites in the trial tended to have lower rates of hemorrhagic stroke (9.8% at sites enrolling <12 patients vs 2.7% at sites enrolling>12 patients).ConclusionsInterventionists credentialed with less Wingspan experience were not responsible for the high rate of periprocedural stroke in SAMMPRIS. Hemorrhagic stroke may be related to low enrollment in the trial but not previous Wingspan experience.
Distinct Patterns of Dysregulated Expression of Enzymes Involved in Androgen Synthesis and Metabolism in Metastatic Prostate Cancer Tumors
Authors: Mitsiades Nicholas , Sung Clifford C. , Schultz Nikolaus , Danila Daniel C. , He Bin , Eedunuri Vijay Kumar , Fleisher Martin , Sander Chris , Sawyers Charles L. , Scher Howard I. 
Published: September 2012

AbstractAndrogen receptor (AR) signaling persists in castration-resistant prostate carcinomas (CRPC), because of several mechanisms that include increased AR expression and intratumoral androgen metabolism. We investigated the mechanisms underlying aberrant expression of transcripts involved in androgen metabolism in CRPC. We compared gene expression profiles and DNA copy number alteration (CNA) data from 29 normal prostate tissue samples, 127 primary prostate carcinomas (PCa), and 19 metastatic PCas. Steroidogenic enzyme transcripts were evaluated by quantitative reverse transcriptase PCR in PCa cell lines and circulating tumor cells (CTC) from CRPC patients. Metastatic PCas expressed higher transcript levels for AR and several steroidogenic enzymes, including SRD5A1, SRD5A3, and AKR1C3, whereas expression of SRD5A2, CYP3A4, CYP3A5, and CYP3A7 was decreased. This aberrant expression was rarely associated with CNAs. Instead, our data suggest distinct patterns of coordinated aberrant enzyme expression. Inhibition of AR activity by itself stimulated AKR1C3 expression. The aberrant expression of the steroidogenic enzyme transcripts was detected in CTCs from CRPC patients. In conclusion, our findings identify substantial interpatient heterogeneity and distinct patterns of dysregulated expression of enzymes involved in intratumoral androgen metabolism in PCa. These steroidogenic enzymes represent targets for complete suppression of systemic and intratumoral androgen levels, an objective that is supported by the clinical efficacy of the CYP17 inhibitor abiraterone. A comprehensive AR axis–targeting approach via simultaneous, frontline enzymatic blockade, and/or transcriptional repression of several steroidogenic enzymes, in combination with GnRH analogs and potent antiandrogens, would represent a powerful future strategy for PCa management. Cancer Res; 72(23); 6142–52. ©2012 AACR.
FoxM1 Inhibition Sensitizes Resistant Glioblastoma Cells to Temozolomide by Downregulating the Expression of DNA-Repair Gene Rad51
Authors: Zhang Nu , Wu Xinjian , Yang Lixuan , Xiao Feizhe , Zhang Heng , Zhou Aidong , Huang Zhengsong , Huang Suyun 
Published: September 2012

Abstract
Purpose: Recurrent glioblastoma multiforme (GBM) is characterized by resistance to radiotherapy and chemotherapy and a poor clinical prognosis. In this study, we investigated the role of the oncogenic transcription factor FoxM1 in GBM cells' resistance to alkylator temozolomide (TMZ) and its potential molecular mechanism.
Experimental Design: FoxM1 expression levels were measured by immunohistochemical analysis in 38 pairs of primary and recurrent GBM tumor samples. Expression levels were also measured in primary recurrent GBM cell lines, and their responses to TMZ were characterized. In a mechanistic study, an siRNA array was used to identify downstream genes, and a chromatin immunoprecipitation assay was used to confirm transcriptional regulation.
Results: Recurrent tumors that were TMZ resistant expressed higher levels of FoxM1 than did primary tumors. Recurrent GBM cell lines expressed higher levels of FoxM1 and the DNA damage repair gene Rad51 and were resistant to TMZ. TMZ treatment led to increased FoxM1 and Rad51 expression. FoxM1 knockdown inhibited Rad51 expression and sensitized recurrent GBM cells to TMZ cytotoxicity. FoxM1 directly regulated Rad51 expression through 2 FoxM1-specific binding sites in its promoter. Rad51 reexpression partially rescued TMZ resistance in FoxM1-knockdown recurrent GBM cells. A direct correlation between FoxM1 expression and Rad51 expression was evident in recurrent GBM tumor samples.
Conclusion: Targeting the FoxM1-Rad51 axis may be an effective method to reverse TMZ resistance in recurrent GBM. Clin Cancer Res; 18(21); 5961–71. ©2012 AACR.
Overexpression of Ecdysoneless in Pancreatic Cancer and Its Role in Oncogenesis by Regulating Glycolysis
Authors: Dey Parama , Rachagani Satyanarayana , Chakraborty Subhankar , Singh Pankaj K. , Zhao Xiangshan , Gurumurthy Channabasavaiah Basavaraju , Anderson Judy M. , Lele Subodh , Hollingsworth Michael A. , Band Vimla , Batra Surinder K. 
Published: September 2012

Abstract
Purpose: To study the expression and function of a novel cell-cycle regulatory protein, human ecdysoneless (Ecd), during pancreatic cancer pathogenesis.
Experimental Design: Immunohistochemical expression profiling of Ecd was done in nonneoplastic normal pancreatic tissues and pancreatic ductal adenocarcinoma lesions (from tissue microarray and Rapid Autopsy program) as well as precancerous PanIN lesions and metastatic organs. To analyze the biological significance of Ecd in pancreatic cancer progression, Ecd was stably knocked down in pancreatic cancer cell line followed by in vitro and in vivo functional assays.
Results: Normal pancreatic ducts showed very weak to no Ecd expression compared to significant positive expression in pancreatic cancer tissues (mean ± SE composite score: 0.3 ± 0.2 and 3.8 ± 0.2 respectively, P &lt; 0.0001) as well as in PanIN precursor lesions with a progressive increase in Ecd expression with increasing dysplasia (PanIN-1–PanIN-3). Analysis of matched primary tumors and metastases from patients with pancreatic cancer revealed that Ecd is highly expressed in both primary pancreatic tumor and in distant metastatic sites. Furthermore, knockdown of Ecd suppressed cell proliferation in vitro and tumorigenicity of pancreatic cancer cells in mice orthotopic tumors. Microarray study revealed that Ecd regulates expression of glucose transporter GLUT4 in pancreatic cancer cells and was subsequently shown to modulate glucose uptake, lactate production, and ATP generation by pancreatic cancer cells. Finally, knockdown of Ecd also reduced level of pAkt, key signaling molecule known to regulate aerobic glycolysis in cancer cells.
Conclusion: Ecd is a novel tumor-promoting factor that is differentially expressed in pancreatic cancer and potentially regulates glucose metabolism within cancer cells. Clin Cancer Res; 18(22); 6188–98. ©2012 AACR.
Proliferation in the Normal FTE Is a Hallmark of the Follicular Phase, Not BRCA Mutation Status
Authors: George Sophia H.L. , Milea Anca , Shaw Patricia A. 
Published: September 2012

Abstract
Purpose: Women who have inherited germline mutations of BRCA1/BRCA2 are at increased risk of developing high-grade serous carcinoma, and many of these cancers arise in the distal fimbriated end of the fallopian tube. We have previously shown that the fallopian tube epithelia of BRCA1 mutation carriers (FTE-BRCA) have altered signaling pathways compared to nonmutation carriers. In this study, we sought to determine whether these differences result in a proliferative advantage to the epithelia in this high-risk patient population and to investigate whether the postovulation environment of the FTE-BRCA compared to FTE from nonmutation carriers experiences a differential abundance of immune cells.
Method: Immunohistochemistry for Ki67, CD3, CD8, CD20, and CD68 was performed on histologically normal tubal epithelium (ampulla, n = 83), fimbria (n = 18) with known ovarian cycle status and germline mutation status and for Ki67 on fimbrial epithelium from women (n = 144) with and without BRCA1 or BRCA2 mutations who underwent risk-reducing salpingo-oophorectomy (RRSO). Serous tubal intraepithelial carcinomas (STIC) with concomitant cancer (n = 15) were also analyzed for presence of immune infiltrates. All slides were digitized and analyzed using automated image analysis software.
Results: There was no significant difference in the proliferative index in histologically normal FTE between BRCA1/BRCA2 and non-BRCA, in 144 fimbriae and 83 ampullae. The FTE-BRCA1 epithelia did not exhibit a differential presence of lymphocytes or macrophages, however more macrophages were present in the luteal phase compared to the follicular phase epithelia. In STICs macrophages were more abundant than lymphocytes with an incremental increase noted with disease progression.
Conclusions: BRCA1/2 mutation carriers exhibited no significant increase in proliferation in the fallopian tube epithelial cells either in the ampulla or fimbriated ends of the tube. Rather, a significant proliferative increase was defined in the cases determined to be in the follicular, or proliferative, preovulatory phase of the ovarian cycle. Finally, we also show an incremental increase in leukocytes invading the STICs and HGSC, implicating a possible role of the leukocytes early in the progression or inhibition of tumor formation, which is independent of ovarian cycle status. Clin Cancer Res; 18(22); 6199–207. ©2012 AACR.
Epithelial–Mesenchymal Transition and Stem Cell Markers in Patients with HER2-Positive Metastatic Breast Cancer
Authors: Giordano Antonio , Gao Hui , Anfossi Simone , Cohen Evan , Mego Michal , Lee Bang-Ning , Tin Sanda , De Laurentiis Michele , Parker Charla A. , Alvarez Ricardo H. , Valero Vicente , Ueno Naoto T. , De Placido Sabino , Mani Sendurai A. , Esteva Francisco J. , Cristofanilli Massimo , Reuben James M. 
Published: September 2012

Abstract
Currently, there is extensive information about circulating tumor cells (CTC) and their prognostic value; however, little is known about other characteristics of these cells. In this prospective study, we assessed the gene transcripts of epithelial-to-mesenchymal transition—inducing transcription factors (EMT-TF) and cancer stem cell (CSC) features in patients with HER2+ metastatic breast cancer (MBC). Epithelial cells were enriched from peripheral blood mononuclear cells (PBMC) using antibody-coated anti-CD326 antibody (CD326+) magnetic beads, and the residual CD326− PBMCs were further depleted of leukocytes using anti-CD45 antibody-coated magnetic beads (CD326−CD45−). RNA was extracted from all cell fractions, reverse transcribed to cDNA, and subjected to quantitative reverse transcription PCR to detect EMT-TFs (TWIST1, SNAIL1, ZEB1, and TG2) as a measure of CTCs undergoing EMT (EMT-CTCs). In addition, PBMCs were analyzed using multiparameter flow cytometry for ALDH activity and CSCs that express CD24, CD44, and CD133. Twenty-eight patients were included in this study. At least one EMT-TF mRNA was elevated in the CTCs of 88.2% of patients and in the CD326−CD45− cell fraction of 60.7% of patients. The CD326−CD45− fraction of patients with elevated SNAIL1 and ZEB1 transcripts also had a higher percentage of ALDH+/CD133+ cells in their blood than did patients with normal SNAIL1 and ZEB1 expression (P = 0.038). Our data indicate that patients with HER2+ MBCs have EMT-CTCs. Moreover, an enrichment of CSCs was found in CD326−CD45− cells. Additional studies are needed to determine whether EMT-CTCs and CSCs have prognostic value in patients with HER2+ MBCs treated with trastuzumab-based therapy. Mol Cancer Ther; 11(11); 2526–34. ©2012 AACR.
Multiple Reaction Monitoring to Identify Site-Specific Troponin I Phosphorylated Residues in the Failing Human Heart
Authors: Zhang Pingbo , Kirk Jonathan A. , Ji Weihua , dos Remedios Cristobal G. , Kass David A. , Van Eyk Jennifer E. , Murphy Anne M. 
Published: September 2012

Background—
Human cardiac troponin I is known to be phosphorylated at multiple amino acid residues by several kinases. Advances in mass spectrometry allow sensitive detection of known and novel phosphorylation sites and measurement of the level of phosphorylation simultaneously at each site in myocardial samples.

Methods and Results—
On the basis of in silico prediction and liquid chromatography/mass spectrometry data, 14 phosphorylation sites on cardiac troponin I, including 6 novel residues (S4, S5, Y25, T50, T180, S198), were assessed in explanted hearts from end-stage heart failure transplantation patients with ischemic heart disease or idiopathic dilated cardiomyopathy and compared with samples obtained from nonfailing donor hearts (n=10 per group). Thirty mass spectrometry–based multiple reaction monitoring quantitative tryptic peptide assays were developed for each phosphorylatable and corresponding nonphosphorylated site. The results show that in heart failure there is a decrease in the extent of phosphorylation of the known protein kinase A sites (S22, S23) and other newly discovered phosphorylation sites located in the N-terminal extension of cardiac troponin I (S4, S5, Y25), an increase in phosphorylation of the protein kinase C sites (S41, S43, T142), and an increase in phosphorylation of the IT-arm domain residues (S76, T77) and C-terminal domain novel phosphorylation sites of cardiac troponin I (S165, T180, S198). In a canine dyssynchronous heart failure model, enhanced phosphorylation at 3 novel sites was found to decline toward control after resynchronization therapy.

Conclusions—
Selective, functionally significant phosphorylation alterations occurred on individual residues of cardiac troponin I in heart failure, likely reflecting an imbalance in kinase/phosphatase activity. Such changes can be reversed by cardiac resynchronization.