bluuebunny/crossref_metadata_2025_split huggingface dataset:
High mammographic breast density and its implications for the early detection of breast cancer
Authors: van Gils C.H. , Otten J.D.M. , Hendriks J.H.C.L. , Holland R. , Straatman H. , Verbeek A.L.M. 
Published: May 2013

Objectives Women with high mammographic breast density are at increased risk of breast cancer. This study explores whether these women should receive intensified screening (more frequent screening or screening with alternative techniques that increase the length of the preclinical detectable phase) to reduce further breast cancer mortality. Methods Mathematical models were used to estimate the effects of intensified screening in women with high breast density. The effects were expressed as a reduction in the number of interval cancers. Results If women with >25% breast density (comprising about one fifth of all women) are screened annually instead of biennially, an 18% reduction in the total number of interval cancers can be expected. Screening these women with alternative screening techniques biennially may produce the same reduction, provided that these techniques double the mean lead time. Conclusions By screening women with dense breasts more intensively, many more breast cancers can theoretically be detected at an early stage. The results provide an early indication of what may be expected from screening strategies. Next, cost-benefit analyses are needed.
Cancer Research Advocacy: Past, Present, and Future
Authors: Perlmutter Jane , Bell Shannon K. , Darien Gwen 
Published: May 2013

AbstractIn this article, we present a brief history of cancer advocacy and discuss the variety of ways advocates have become involved in cancer research and subsequently present principles that establish a framework for successful research advocacy based on a review of many early initiatives coupled with our knowledge as long-time cancer advocates. Challenges to effective advocacy are described, and recommendations for increasing meaningful contributions by research advocates are proposed. The purpose of this article is to discuss the exciting field of research advocacy and to help shape a more productive future for advocates and their scientific collaborators. Cancer Res; 73(15); 4611–5. ©2013 AACR.
O-GlcNAc Transferase Integrates Metabolic Pathways to Regulate the Stability of c-MYC in Human Prostate Cancer Cells
Authors: Itkonen Harri M. , Minner Sarah , Guldvik Ingrid J. , Sandmann Mareike Julia , Tsourlakis Maria Christina , Berge Viktor , Svindland Aud , Schlomm Thorsten , Mills Ian G. 
Published: May 2013

Abstract
Metabolic disruptions that occur widely in cancers offer an attractive focus for generalized treatment strategies. The hexosamine biosynthetic pathway (HBP) senses metabolic status and produces an essential substrate for O-linked β-N-acetylglucosamine transferase (OGT), which glycosylates and thereby modulates the function of its target proteins. Here, we report that the HBP is activated in prostate cancer cells and that OGT is a central regulator of c-Myc stability in this setting. HBP genes were overexpressed in human prostate cancers and androgen regulated in cultured human cancer cell lines. Immunohistochemical analysis of human specimens (n = 1987) established that OGT is upregulated at the protein level and that its expression correlates with high Gleason score, pT and pN stages, and biochemical recurrence. RNA interference–mediated siliencing or pharmacologic inhibition of OGT was sufficient to decrease prostate cancer cell growth. Microarray profiling showed that the principal effects of OGT inhibition in prostate cancer cells were related to cell-cycle progression and DNA replication. In particular, c-MYC was identified as a candidate upstream regulator of OGT target genes and OGT inhibition elicited a dose-dependent decrease in the levels of c-MYC protein but not c-MYC mRNA in cell lines. Supporting this relationship, expression of c-MYC and OGT was tightly correlated in human prostate cancer samples (n = 1306). Our findings identify HBP as a modulator of prostate cancer growth and c-MYC as a key target of OGT function in prostate cancer cells. Cancer Res; 73(16); 5277–87. ©2013 AACR.
Molecular Pathways: ROS1 Fusion Proteins in Cancer
Authors: Davies Kurtis D. , Doebele Robert C. 
Published: May 2013

Abstract
Genetic alterations that lead to constitutive activation of kinases are frequently observed in cancer. In many cases, the growth and survival of tumor cells rely upon an activated kinase such that inhibition of its activity is an effective anticancer therapy. ROS1 is a receptor tyrosine kinase that has recently been shown to undergo genetic rearrangements in a variety of human cancers, including glioblastoma, non–small cell lung cancer (NSCLC), cholangiocarcinoma, ovarian cancer, gastric adenocarcinoma, colorectal cancer, inflammatory myofibroblastic tumor, angiosarcoma, and epithelioid hemangioendothelioma. These rearrangements create fusion proteins in which the kinase domain of ROS1 becomes constitutively active and drives cellular proliferation. Targeting ROS1 fusion proteins with the small-molecule inhibitor crizotinib is showing promise as an effective therapy in patients with NSCLC whose tumors are positive for these genetic abnormalities. This review discusses the recent preclinical and clinical findings on ROS1 gene fusions in cancer. Clin Cancer Res; 19(15); 4040–5. ©2013 AACR.
Evaluation of Midkine as a Diagnostic Serum Biomarker in Hepatocellular Carcinoma
Authors: Zhu Wen-Wei , Guo Jia-Jian , Guo Lei , Jia Hu-Liang , Zhu Ming , Zhang Ju-Bo , Loffredo Christopher A. , Forgues Marshonna , Huang Hua , Xing Xu-Jian , Ren Ning , Dong Qiong-Zhu , Zhou Hai-Jun , Ren Zheng-Gang , Zhao Nai-Qing , Wang Xin Wei , Tang Zhao-You , Qin Lun-Xiu , Ye Qing-Hai 
Published: May 2013

Abstract
Purpose: To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage.
Experimental Design: MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.
Results: MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.
Conclusions: Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas. Clin Cancer Res; 19(14); 3944–54. ©2013 AACR.
Nanoparticles Engineered with Rituximab and Loaded with Nutlin-3 Show Promising Therapeutic Activity in B-Leukemic Xenografts
Authors: Voltan Rebecca , Secchiero Paola , Ruozi Barbara , Forni Flavio , Agostinis Chiara , Caruso Lorenzo , Vandelli Maria Angela , Zauli Giorgio 
Published: May 2013

Abstract
Purpose: Because the nongenotoxic inhibitor of the p53/MDM2 interactions Nutlin-3 has shown promising in vitro therapeutic activity against a variety of p53wild-type cancer cells, in this study we evaluated an innovative strategy able to specifically target Nutlin-3 toward CD20+ malignant cells.
Experimental Design: The cytotoxic effects of Nutlin-3 encapsulated into poly(lactide-co-glycolide) nanoparticles (NP-Nut) and into rituximab (anti-CD20 antibody)-engineered NP (NP-Rt-Nut) as well as of NPs engineered with rituximab alone (NP-Rt) were initially analyzed in vitro in JVM-2 B-leukemic cells, by assessing both the functional activation of the p53 pathway (by Nutlin-3) and/or the activation of the complement cascade (by rituximab). Moreover, the potential therapeutic efficacy of NP-Nut, NP-Rt, and NP-Rt-Nut were comparatively assessed in vivo in CD20+ JVM-2 leukemic xenograft SCID mice.
Results: Functional in vitro assays showed that NP-Nut and NP-Rt-Nut exhibited a comparable ability to activate the p53 pathway in the p53wild-type JVM-2 leukemic cells. On the other hand, NP-Rt and NP-Rt-Nut, but not NP nor NP-Nut, were able to promote activation of the complement cascade. Of note, the in vivo intratumoral injection in JVM-2 B-leukemic/xenograft mice showed that NP-Rt-Nut displayed the maximal therapeutic activity promoting a survival rate significantly higher not only with respect to control animals, treated either with vehicle or with empty NP, but also with respect to animals treated with NP-Nut or NP-Rt.
Conclusions: Our data show for the first time the potential antileukemic activity of rituximab-engineered Nutlin-3–loaded NPs in xenograft SCID mice. Clin Cancer Res; 19(14); 3871–80. ©2013 AACR.
Biomarker Modulation following Short-Term Vorinostat in Women with Newly Diagnosed Primary Breast Cancer
Authors: Stearns Vered , Jacobs Lisa K. , Fackler MaryJo , Tsangaris Theodore N. , Rudek Michelle A. , Higgins Michaela , Lange Julie , Cheng Zandra , Slater Shannon A. , Jeter Stacie C. , Powers Penny , Briest Susanne , Chao Calvin , Yoshizawa Carl , Sugar Elizabeth , Espinoza-Delgado Igor , Sukumar Saraswati , Gabrielson Edward , Davidson Nancy E. 
Published: May 2013

Abstract
Purpose: Agents that target the epigenome show activity in breast cancer models. In preclinical studies, the histone deacetylase inhibitor vorinostat induces cell-cycle arrest, apoptosis, and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women with newly diagnosed invasive disease who received vorinostat and those who did not.
Experimental Design: Tumor specimens were collected from 25 women who received up to 6 doses of oral vorinostat 300 mg twice daily and from 25 untreated controls in a nonrandomized study. Candidate gene expression was analyzed by reverse transcription PCR (RT-PCR) using the Oncotype DX 21-gene assay, and by immunohistochemistry for Ki-67 and cleaved caspase-3. Matched samples from treated women were analyzed for gene methylation by quantitative multiplex methylation-specific PCR (QM-MSP). Wilcoxon nonparametric tests were used to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated controls, and changes in gene methylation between pre- and post-vorinostat samples.
Results: Vorinostat was well tolerated and there were no study-related delays in treatment. Compared with untreated controls, there were statistically significant decreases in the expression of proliferation-associated genes Ki-67 (P = 0.003), STK15 (P = 0.005), and Cyclin B1 (P = 0.03) following vorinostat, but not in other genes by the Oncotype DX assay, or in expression of Ki-67 or cleaved caspase-3 by immunohistochemistry. Changes in methylation were not observed.
Conclusions: Short-term vorinostat administration is associated with a significant decrease in expression of proliferation-associated genes in untreated breast cancers. This demonstration of biologic activity supports investigation of vorinostat in combination with other agents for the management of breast cancer. Clin Cancer Res; 19(14); 4008–16. ©2013 AACR.
A Spatially Distributed Model to Simulate Water, Energy, and Vegetation Dynamics Using Information from Regional Climate Models
Authors: Maneta M. P. , Silverman N. L. 
Published: May 2013

Abstract
Studies seeking to understand the impacts of climate variability and change on the hydrology of a region need to take into account the dynamics of vegetation and its interaction with the hydrologic and energy cycles. Yet, most of the hydrologic models used for these kinds of studies assume that vegetation is static. This paper presents a dynamic, spatially explicit model that couples a vertical energy balance scheme (surface and canopy layer) to a hydrologic model and a forest growth component to capture the dynamic interactions between energy, vegetation, and hydrology at hourly to daily time scales. The model is designed to be forced with outputs from regional climate models. Lateral water transfers are simulated using a 1D kinematic wave model. Infiltration is simulated using the Green and Ampt approximation to Richard's equation. The dynamics of soil moisture and energy drives carbon assimilation and forest growth, which in turn affect the distribution of energy and water through leaf dynamics by altering light interception, shading, and enhanced transpiration. The model is demonstrated in two case studies simulating energy, water, and vegetation dynamics at two different spatial and temporal scales.
The cost of healthcare for children with mental health difficulties
Authors: Lucas Nina , Bayer Jordana K , Gold Lisa , Mensah Fiona K , Canterford Louise , Wake Melissa , Westrupp Elizabeth M , Nicholson Jan M 
Published: May 2013

Objective: Childhood mental health difficulties affect one in every seven children in Australia, posing a potential financial burden to society. This paper reports on the early lifetime individual and population non-hospital healthcare costs to the Australian Federal Government for children experiencing mental health difficulties. It also reports on the use and cost of particular categories of service use, including the Medicare Benefits Schedule (MBS) mental health items introduced in 2006. Method: Data from the Longitudinal Study of Australian Children (LSAC) were used to calculate total Medicare costs (government subsidised healthcare attendances and prescription medications) from birth to the 8th birthday associated with childhood mental health difficulties measured to 8–9 years of age. Results: Costs were higher among children with mental health difficulties than those without difficulties. While individual costs increased with the persistence of difficulties, population-level costs were highest for those with transient mental health difficulties. Although attenuated, these patterns persisted after child, parent and family characteristics were taken into account. Use of the MBS-reimbursed mental health services among children with a mental health difficulty was very low (around 2%). Conclusions: Australian healthcare costs for young children with mental health difficulties are substantial and provide further justification for early intervention and prevention. The current provision of Medicare-rebated mental health services does not appear to be reaching young children with mental health difficulties.
Factors influencing mortality among alcohol and drug treatment clients in Victoria, Australia: The role of demographic and substance use characteristics
Authors: Lloyd Belinda , Barratt Monica J , Ferris Jason , Best David , Lubman Dan I 
Published: May 2013

Objective: Clinical studies consistently identify alcohol- and drug-related treatment populations as more likely to die prematurely compared with an age-matched general population. However, demographic characteristics and primary drug of concern as predictors of mortality risk following treatment have not been adequately explored. This paper examines relationships between substance use, demographic factors and mortality among alcohol and drug treatment clients. Method: A retrospective cohort incorporating 7 years of data was utilised to examine mortality outcomes in the 2 years following treatment among Victorian clients recorded on the Alcohol and Drug Information Service (ADIS) database by linking partial client identifiers with the National Death Index (NDI). A cohort of 18,686 clients engaged in at least one course of treatment over a 12-month period was included. Analysis was of crude and standardised mortality rates across client groups in terms of the presenting drug of concern for treatment and demographic characteristics. Results: A higher risk of premature death was associated with older age, being male, not being employed, living alone, medical and psychiatric comorbidity, recent injecting, and a history of intensive drug treatment access. Alcohol treatment clients had the worst prognosis. After adjustment for client characteristics, alcohol treatment clients experienced a significantly higher rate of death compared with other clients. Conclusions: Findings from these previously unexplored data highlight the need to increase awareness of the range and magnitude of risks associated with harmful alcohol use, and to identify approaches to enhance treatment effectiveness to reduce negative outcomes following treatment for populations at elevated risk of harm.
Glucocorticoids in adult cardiac surgery; old drugs revisited
Authors: Zakkar M , Kanagasabay R 
Published: May 2013

Glucocorticoids can play a pivotal role in modulating different immune responses. The role of glucocorticoids in cardiac surgery is still controversial as many surgeons are concerned about the potential side effects. In this review, we looked at the role of glucocorticoid administration in modulating postoperative inflammatory responses, atrial fibrillation (AF) and intimal hyperplasia and whether glucocorticoid use is associated with a significant increase in undesirable postoperative complication.
Headache yesterday in China: A new approach to estimating the burden of headache, applied in a general-population survey in China
Authors: Yu Shengyuan , He Mianwang , Liu Ruozhuo , Feng Jiachun , Qiao Xiangyang , Yang Xiaosu , Cao Xiutang , Zhao Gang , Fang Yannan , Steiner Timothy J 
Published: May 2013

Background In order to minimize recall bias in burden estimation, questions about headache yesterday were included in a population-based survey initiated by Lifting The Burden: The Global Campaign against Headache. Methods Throughout China, nonrelated respondents aged 18–65 years were randomly sampled from the general population by a door-to-door survey. A validated structured questionnaire included inquiry into occurrence and burden of headache on the preceding day (“headache yesterday”). Results The participation rate was 94.1%. Of 5041 participants, 286 (5.7%) (male 3.6%, female 7.9%) reported headache yesterday. Age-weighted prevalence of headache yesterday was 4.8% (male 3.0%, female 6.6%). Headache yesterday lasted all day in 36.8%, <1 hour in 14.3% and for a mean of 3.7 ± 3.3 hours in 48.9%. Headache yesterday was moderate to severe in 79.9%; disability such that they could do less than half of what they had expected was reported by 19.9% and such that they could do nothing by a further 7.5% (total 27.4%). Almost three-quarters (71.5%) with headache yesterday took medication to treat it. Conclusions Of the adult Chinese population, 1.8% have headache at any one time that is of moderate to severe intensity in 1.4%, and 1.3% lose the equivalent of a whole day to headache-attributed disability every day. In China this means 12.3 million people.
Successful treatment of post-dural-puncture headache with surgical dura repair two years after spinal anesthesia
Authors: Pouskoulas Christos D , Taub Ethan , Ruppen Wilhelm 
Published: May 2013

Background Post-dural-puncture headache (PDPH) can be a highly disturbing complication of elective spinal anesthesia. The incidence of PDPH when small needles are used is estimated to be 0%–14.5%. PDPH usually resolves spontaneously within a few days, but there are rare cases that persist in spite of conventional and epidural blood patch therapy. Case A 59-year-old man suffered from persistent postural headache for more than two years after an otherwise uneventful spinal anesthesia. Conventional and minimally invasive treatments were unsuccessful. Intervention/outcome A neurosurgical procedure was performed, during which a dural leak was identified and repaired. The patient was immediately pain free after surgery and has remained so for the duration of follow-up (more than one year).
Migraine attacks after transcatheter closure of atrial septal defect
Authors: Kato Yuji , Kobayashi Toshiki , Ishido Hirotaka , Hayashi Takeshi , Furuya Daisuke , Tanahashi Norio 
Published: May 2013

Objective The purpose of our study was to evaluate the effect of atrial septal defect (ASD) closure on migraine headache attacks (MHA). Methods A total of 247 patients who underwent percutaneous ASD closure at our facilities were sent a structured questionnaire. We diagnosed MHA according to the criteria of the International Headache Society. Results A total of 207 patients were included in the study. New-onset MHA occurred in 23 patients and persisted in 15 at a mean follow-up of 45 months. Of the 29 patients who had MHA prior to ASD closure, 11 reported exacerbation of MHA, 11 reported no change and seven reported improvement within three months after ASD closure. Compared with the patients who had no MHA, patients with de novo MHA were younger and patients with MHA improvement tended to be older. Switching from aspirin to ticlopidine or clopidogrel rapidly aborted frequent MHA in nine patients who had severe symptoms after ASD closure. Conclusions These results indicate that Amplatzer device implantation can act as a permanent trigger of MHA in not a few patients, and that age may be an important predictive factor of the influence of ASD closure on MHA.