bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Histone Deacetylation Potentiates the Evolution of Acquired Temozolomide Resistance Linked to MGMT Upregulation in Glioblastoma Xenografts
Authors: Kitange Gaspar J. , Mladek Ann C. , Carlson Brett L. , Schroeder Mark A. , Pokorny Jenny L. , Cen Ling , Decker Paul A. , Wu Wenting , Lomberk Gwen A. , Gupta Shiv K. , Urrutia Raul A. , Sarkaria Jann N. 
Published: June 2012

Abstract
Purpose: The therapeutic benefit of temozolomide in glioblastoma multiforme (GBM) is limited by resistance. The goal of this study was to elucidate mechanisms of temozolomide resistance in GBM.
Experimental Design: We developed an in vivo GBM model of temozolomide resistance and used paired parental and temozolomide-resistant tumors to define the mechanisms underlying the development of resistance and the influence of histone deacetylation (HDAC) inhibition.
Results: Analysis of paired parental and resistant lines showed upregulation of O6-methylguanine-DNA methyltransferase (MGMT) expression in 3 of the 5 resistant xenografts. While no significant change was detected in MGMT promoter methylation between parental and derivative-resistant samples, chromatin immunoprecipitation showed an association between MGMT upregulation and elevated acetylation of lysine 9 of histone H3 (H3K9-ac) and decreased dimethylation (H3K9-me2) in GBM12 and GBM14. In contrast, temozolomide resistance development in GBM22 was not linked to MGMT expression, and both parental and resistant lines had low H3K9-ac and high H3K9-me2 within the MGMT promoter. In the GBM12TMZ-resistant line, MGMT reexpression was accompanied by increased recruitment of SP1, C-JUN, NF-κB, and p300 within the MGMT promoter. Interestingly, combined treatment of GBM12 flank xenografts with temozolomide and the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) favored the evolution of temozolomide resistance by MGMT overexpression as compared with treatment with temozolomide alone.
Conclusion: This study shows, for the first time, a unique mechanism of temozolomide resistance development driven by chromatin-mediated MGMT upregulation and highlights the potential for epigenetically directed therapies to influence the mechanisms of resistance development in GBM. Clin Cancer Res; 18(15); 4070–9. ©2012 AACR.
Pretreatment EBV-DNA Copy Number Is Predictive of Response and Toxicities to SMILE Chemotherapy for Extranodal NK/T-cell Lymphoma, Nasal Type
Authors: Ito Yoshinori , Kimura Hiroshi , Maeda Yoshinobu , Hashimoto Chizuko , Ishida Fumihiro , Izutsu Koji , Fukushima Noriyasu , Isobe Yasushi , Takizawa Jun , Hasegawa Yuichi , Kobayashi Hajime , Okamura Seiichi , Kobayashi Hikaru , Yamaguchi Motoko , Suzumiya Junji , Hyo Rie , Nakamura Shigeo , Kawa Keisei , Oshimi Kazuo , Suzuki Ritsuro 
Published: June 2012

Abstract
Purpose: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is an Epstein–Barr virus (EBV)–associated lymphoma for which a new chemotherapeutic regimen called SMILE (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) recently showed promising results.
Experimental Design: The amount of EBV-DNA was prospectively measured in whole-blood and plasma samples by real-time quantitative PCR from 26 patients registered in the SMILE phase II study.
Results: Before treatment, the EBV-DNA was detected in 22 samples of whole blood with a median number of 3,691 copies/mL (range: 0–1.14 × 107), but 15 samples of plasma with a median of 867 copies/mL (range: 0–1.27 × 107). Results of these 2 measurements of EBV-DNA well correlated (R2 = 0.994, P &lt; 0.001). The overall response rate to SMILE was significantly higher in patients with less than 105 copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P = 0.007) and in patients with less than 104 copies/mL of EBV-DNA in plasma (95% vs. 29%, P = 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 105 copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P = 0.007) than that of others and in patients with 104 copies/mL or more in plasma (86% vs. 26%, P = 0.002).
Conclusions: These findings suggest that whole blood is more sensitive for clinical use than plasma. The EBV-DNA amount in whole blood was useful for predicting tumor response, toxicity, and prognosis after SMILE chemotherapy for ENKL. Clin Cancer Res; 18(15); 4183–90. ©2012 AACR.
Coarctation of the Aorta and Coronary Artery Disease
Authors: Roifman Idan , Therrien Judith , Ionescu-Ittu Raluca , Pilote Louise , Guo Liming , Kotowycz Mark A. , Martucci Giuseppe , Marelli Ariane J. 
Published: June 2012

Background—
Aortic coarctation (CoA) is reported to predispose to coronary artery disease (CAD). However, our clinical observations do not support this premise. Our objectives were to describe the prevalence of CAD among adults with CoA and to determine whether CoA is an independent predictor of CAD or premature CAD.

Methods and Results—

The study population was derived from the Quebec Congenital Heart Disease Database. We compared patients with CoA and those with a ventricular septal defect, who are not known to be at increased risk of CAD. The prevalence of CAD in patients with CoA compared with those with ventricular septal defect was determined. We then used a nested case-control design to determine whether CoA independently predicted for the development of CAD. Of 756 patients with CoA who were alive in 2005, 37 had a history of CAD compared with 224 of 6481 patients with ventricular septal defect (4.9% versus 3.5%;
P
=0.04). Male sex (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.62–2.80), hypertension (OR, 1.95; 95% CI, 1.44–2.64), diabetes mellitus (OR, 1.68; 95% CI, 1.09–2.58), age (OR per 10-year increase, 2.28; 95% CI, 2.09–2.48), and hyperlipidemia (OR, 11.58; 95% CI, 5.75–23.3) all independently predicted for the development of CAD. CoA did not independently predict for the development of CAD (OR, 1.04; 95% CI, 0.68–1.57) or premature CAD (OR for CoA versus ventricular septal defect, 1.44; 95% CI, 0.79–2.64) after adjustment for other factors.

Conclusions—
Although traditional cardiovascular risk factors independently predicted for the development of CAD, the diagnosis of CoA alone did not. Our findings suggest that cardiovascular outcomes of these patients may be improved with tight risk factor control.
Ambivalence and fluidity in the teenage smoking and quitting experience: Lessons from a qualitative study at an English secondary school
Authors: Buswell Marina , Duncan Peter 
Published: June 2012

Objective: To evaluate a school-based stop smoking pilot project and to understand the teenage experience of smoking and quitting within that context. Design: Flexible design methods. Setting: A Kent (United Kingdom [UK]) secondary school. Methods: Semi-structured interviews analyzed following a grounded theory approach. Results: The main themes that emerged were ambivalence and fluidity. Young people can have mixed feelings towards their smoking behaviour. They experience ambivalence at the societal level in the messages they get about starting and stopping smoking and at the individual level in how they feel about other people smoking. Ambivalence in the quitting process is intensified by the phenomenon of addiction. Fluidity characterizes their way of life; things are not fixed and arrangements open to change. This was reflected in the way they approached coming to appointments. Conclusion: This research contributes a new perspective on the teenage smoking and quitting experience which others working in the field may find useful in characterizing their experience of working with young people. This ambivalence and fluidity suggests that a flexible approach in interventions with young people may be a key to success.
Indigenista Dreams Meet Sober Realities
Authors: Lewis Stephen E. 
Published: June 2012

In 1951, Mexico’s National Indigenist Institute (Instituto Nacional Indigenista—INI) opened its pilot coordinating center in highland Chiapas. For several years, Mexico’s top indigenistas directed the center and tested several innovative projects aimed at promoting economic development, modernization, and cultural assimilation among the Tzeltal and Tzotzil Maya. They also tried to protect the indigenous from their worst non-Indian exploiters. After a period of initial fanfare, this important center slid into decline, hampered by inadequate budgets, compromised programs in education, health, and agriculture, and a demoralized staff. Its decadence had implications for the dozens of centers built by the INI in subsequent years. Crippled by local opposition, an outdated theoretical underpinning, and tepid political support, this coordinating center—and the INI in general—also suffered from close association with the Ministry of Public Education and other institutions of Mexico’s corporatist state. En 1951, el Instituto Nacional Indigenista (INI), en México, abrió su coordinadora piloto en los altos de Chiapas. Durante muchos años, los mayores indigenistas de México dirigieron el centro y probaron varios proyectos innovadores dedicados al fomento del desarrollo económico, modernización, y asimilación cultural entre Mayas Tzeltales y Tzotziles. También intentaban proteger a los indígenas de sus mayores explotadores no-indígenas. Luego de un periodo de fanfarria inicial, este centro importante se deslizó al decline, obstaculizado por presupuestos inadecuados, programas transigidos en la educación, salubridad, y agricultura, y un equipo desmoralizado. Su decadencia tuvo implicaciones para docenas de centros que construyera el INI en años posteriores.
Functional Connectivity during Modulation of Tinnitus with Orofacial Maneuvers
Authors: Lee Megan H. , Solowski Nancy , Wineland Andre , Okuyemi Oluwafunmilola , Nicklaus Joyce , Kallogjeri Dorina , Piccirillo Jay F. , Burton Harold 
Published: June 2012

ObjectiveTo determine changes in cortical neural networks as defined by resting‐state functional connectivity magnetic resonance imaging during voluntary modulation of tinnitus with orofacial maneuvers.Study DesignCross‐sectional study.SettingAcademic medical center.Subjects and MethodsParticipants were scanned during the maneuver and also at baseline to serve as their own control. The authors chose, a priori, 58 seed regions to evaluate previously described cortical neural networks by computing temporal correlations between all seed region pairs. Seed regions whose correlations significantly differed between rest and maneuver (P <. 05, uncorrected) entered into a second‐stage analysis of computing the correlation coefficient between the seed region and time courses in each of the remaining brain voxels. A threshold‐free cluster enhancement permutation analysis evaluated the distribution of these correlation coefficients after transformation to Fisher z scores and registration to a surface‐based reconstruction using Freesurfer.ResultsThe median age for the 16 subjects was 54 years (range, 27‐72 years), and all had subjective, unilateral or bilateral, nonpulsatile tinnitus for 6 months or longer. In 9 subjects who could voluntarily increase the loudness of their tinnitus, there were no significant differences in functional connectivity in any cortical networks. A separate analysis evaluated results from 3 patients who decreased the loudness of their tinnitus. Four subjects were excluded because of excessive motion in the scanner.ConclusionThe absence of significant differences in functional connectivity due to voluntary orofacial maneuvers that increased tinnitus loudness failed to confirm prior reports of altered cerebral blood flows during somatomotor behaviors.
Antioxidant status in MgO nanoparticle-exposed rats
Authors: Kiranmai G , Reddy A Rama Narsimha 
Published: June 2012

In this present study, antioxidant status was evaluated in rat serum following exposure to magnesium oxide (MgO) nanoparticles. The lungs of rats were intratracheally instilled with (single dose) phosphate-buffered saline (PBS) + 1% of Tween 80 (solvent control) or MgO or carbonyl iron (negative control) or quartz particles (positive control) at a dose of 1 and 5 mg/kg of body weight. The blood samples were collected at 1, 7, and 30 days of postinstillation of nanoparticles after their exposure, and different parameters were estimated to assess the oxidative stress induced by the instillation of MgO. Exposure of rats to MgO produced a significant ( p < 0.05) dose-dependent reduction in blood total antioxidant capacity, superoxide dismutase, and catalase activity levels than PBS + 1% Tween 80 control group. This reduction in the antioxidant capacity in MgO nanoparticle-exposed rats indicates the reduction in antioxidant defense mechanisms due to the instillation of MgO. These results indicate that exposure to MgO nanoparticles induces oxidative stress by reducing the total antioxidant capacity in rats. The findings suggest possible occupational health hazard in chronic exposures.
Breastfeeding Support in Neonatal Intensive Care
Authors: Maastrup Ragnhild , Bojesen Susanne Norby , Kronborg Hanne , Hallström Inger 
Published: June 2012

Background: The incidence of breastfeeding of preterm infants is affected by the support provided at the hospital and in the neonatal intensive care unit (NICU). However, policies and guidelines promoting breastfeeding vary both nationally and internationally. Objectives: The aim of this survey was to describe breastfeeding support in Danish NICUs, where approximately 98% of mothers initiate lactation. Methods: A national survey of all 19 Danish NICUs was conducted in 2009. Four NICUs were at designated Baby-Friendly hospitals, and 5 had a lactation consultant. In all NICUs, it was possible for some parents to stay overnight; 2 units had short restrictions on parents’ presence. Five NICUs had integrated postpartum care for mothers. Breastfeeding policies, written guidelines, and systematic breastfeeding training for the staff were common in most NICUs. Seventeen NICUs recommended starting breast milk expression within 6 hours after birth, and mothers were encouraged to double pump. Most NICUs aimed to initiate skin-to-skin contact the first time the parents were in the NICU, and daily skin-to-skin contact was estimated to last for 2-4 hours in 63% and 4-8 hours in 37% of the units. The use of bottle-feeding was restricted. Conclusions: The Danish NICUs described the support of breastfeeding as a high priority, which was reflected in the recommended policies for breast milk pumping, skin-to-skin contact, and the parents’ presence in the NICU, as well as in the restricted use of bottle-feeding. However, support varied between units, and not all units supported optimal breastfeeding.
Expansion of the Ten Steps to Successful Breastfeeding into Neonatal Intensive Care
Authors: Nyqvist Kerstin Hedberg , Häggkvist Anna-Pia , Hansen Mette Ness , Kylberg Elisabeth , Frandsen Annemi Lyng , Maastrup Ragnhild , Ezeonodo Aino , Hannula Leena , Koskinen Katja , Haiek Laura N. 
Published: June 2012

The World Health Organization/United Nations Children’s Fund Baby-Friendly Hospital Initiative: Revised, Updated, and Expanded for Integrated Care (2009) identifies the need for expanding the guidelines originally developed for maternity units to include neonatal intensive care. For this purpose, an expert group from the Nordic countries and Quebec, Canada, prepared a draft proposal, which was discussed at an international workshop in Uppsala, Sweden, in September 2011. The expert group suggests the addition of 3 “Guiding Principles” to the Ten Steps to support this vulnerable population of mothers and infants: 1. The staff attitude to the mother must focus on the individual mother and her situation. 2. The facility must provide family-centered care, supported by the environment. 3. The health care system must ensure continuity of care, that is, continuity of pre-, peri-, and postnatal care and post-discharge care. The goal of the expert group is to create a final document, the Baby Friendly Hospital Initiative for Neonatal Units, including standards and criteria for each of the 3 Guiding Principles, Ten Steps, and the Code; to develop tools for self-appraisal and monitoring compliance with the guidelines; and for external assessment to decide whether neonatal intensive/intermediate care units meet the conditions required to be designated as Baby-Friendly. The documents will be finalized after consultation with the World Health Organization/United Nations Children’s Fund, and the goal is to offer these documents to international health care, professional, and other nongovernmental organizations involved in lactation and breastfeeding support for mothers of infants who require special neonatal care.
Hospital Practices and Breastfeeding Rates before and after the UNICEF/WHO 20-Hour Course for Maternity Staff
Authors: Zakarija-Grković Irena , Šegvić Olga , Božinović Toni , Ćuže Anamarija , Lozančić Toni , Vučković Ana , Burmaz Tea 
Published: June 2012

Background: The Baby-Friendly Hospital Initiative (BFHI) is the most widely promoted program for increasing breastfeeding rates. Objective: To evaluate the impact of BFHI training on hospital practices and breastfeeding rates during the first 12 months of life. Methods: Eighty percent of maternity medical and nursing staff at the University Hospital in Split, Croatia, completed the updated and expanded United Nations Children’s Fund/World Health Organization 20-hour course. Seven hundred seventy-three mothers (388 in the pre- and 385 in the post-training group) were included in a birth cohort and interviewed at discharge and at 3, 6, and 12 months postpartum to evaluate hospital practices and infant feeding. Six out of 10 Baby-Friendly practices were assessed using standard BFHI forms. Results: Three months after training was completed, 3 of the Baby-Friendly practices assessed (Step 4, “Initiate breastfeeding within a half-hour of birth”; Step 7, “Rooming-in”; and Step 8, “Feeding on demand”) had significantly improved. The proportion of newborns exclusively breastfed during the first 48 hours increased from 6.0% to 11.7% ( P < .005). There was no difference in breastfeeding rates at discharge or at 3, 6, or 12 months between the pre- and post-training groups. Conclusion: Training of health professionals, based on the BFHI, was associated with significant improvement in some Baby-Friendly hospital practices and initial exclusive breastfeeding rates. A high rate of in-hospital supplementation may partly explain the lack of improvement in breastfeeding exclusivity and duration after discharge. Strong institutional support and commitment is needed to enable full implementation of recommended Baby-Friendly practices.
Modeling and prediction of subject accrual and event times in clinical trials: a systematic review
Authors: Zhang Xiaoxi , Long Qi 
Published: June 2012

Background Modeling and prediction of subject accrual and event times in clinical trials has been a topic of considerable interest for important practical reasons. It has implications not only at the initial planning stage of a trial but also on its ongoing monitoring. Purpose To provide a systematic view of the recent research in the field of modeling and prediction of subject accrual and event times in clinical trials. Methods Two classes of methods for modeling and prediction of subject accrual are reviewed, namely, one that uses the Brownian motion and the other uses the Poisson process. Extensions of the accrual models in multicenter clinical trials are also discussed. Trials with survival endpoints require proper joint modeling of subject accrual and event/lost-to-follow-up (LTFU) times, the latter of which can be modeled either parametrically (e.g., exponential and Weibull) or nonparametrically. Results Flexible stochastic models are better suited when modeling real trials that does not follow constant underlying enrollment rate. The accrual model generally improves as center-specific information is accounted for in multicenter trials. The choice between parametric and nonparametric event models can depend on confidence on the underlying event rates. Limitations All methods reviewed in event modeling assume noninformative censoring, which cannot be tested. Conclusions We recommend using proper stochastic accrual models, in combination with flexible event time models when applicable, for modeling and prediction of subject enrollment and event times in clinical trials.
Mll partial tandem duplication and Flt3 internal tandem duplication in a double knock-in mouse recapitulates features of counterpart human acute myeloid leukemias
Authors: Zorko Nicholas A. , Bernot Kelsie M. , Whitman Susan P. , Siebenaler Ronald F. , Ahmed Elshafa H. , Marcucci Gabriele G. , Yanes Daniel A. , McConnell Kathleen K. , Mao Charlene , Kalu Chidimma , Zhang Xiaoli , Jarjoura David , Dorrance Adrienne M. , Heerema Nyla A. , Lee Benjamin H. , Huang Gang , Marcucci Guido , Caligiuri Michael A. 
Published: June 2012

Abstract
The MLL-partial tandem duplication (PTD) associates with high-risk cytogenetically normal acute myeloid leukemia (AML). Concurrent presence of FLT3-internal tandem duplication (ITD) is observed in 25% of patients with MLL-PTD AML. However, mice expressing either Mll-PTD or Flt3-ITD do not develop AML, suggesting that 2 mutations are necessary for the AML phenotype. Thus, we generated a mouse expressing both Mll-PTD and Flt3-ITD. MllPTD/WT:Flt3ITD/WT mice developed acute leukemia with 100% penetrance, at a median of 49 weeks. As in human MLL-PTD and/or the FLT3-ITD AML, mouse blasts exhibited normal cytogenetics, decreased Mll-WT-to-Mll-PTD ratio, loss of the Flt3-WT allele, and increased total Flt3. Highlighting the adverse impact of FLT3-ITD dosage on patient survival, mice with homozygous Flt3-ITD alleles, MllPTD/WT:Flt3ITD/ITD, demonstrated a nearly 30-week reduction in latency to overt AML. Here we demonstrate, for the first time, that Mll-PTD contributes to leukemogenesis as a gain-of-function mutation and describe a novel murine model closely recapitulating human AML.