bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excess Weight Gain Accelerates 1-Methyl-1-Nitrosourea–Induced Mammary Carcinogenesis in a Rat Model of Premenopausal Breast Cancer
Authors: Matthews Shawna B. , Zhu Zongjian , Jiang Weiqin , McGinley John N. , Neil Elizabeth S. , Thompson Henry J. 
Published: January 2014

Abstract
In contrast to the null effects generally reported, high-risk premenopausal women (Gail score ≥1.66) enrolled in the Breast Cancer Prevention P-1 Trial were recently reported to be at increased risk for breast cancer when overweight (HR = 1.59) or obese (HR = 1.70). To investigate this clinical observation in a preclinical setting, ovary-intact female rats were intraperitoneally injected with 50 mg/kg 1-methyl-1-nitrosourea at 21 days of age to simulate premenopausal women with increased risk. Two commercially available strains of Sprague–Dawley rat (Taconic Farms) were used, which are dietary resistant (DR) or dietary susceptible (DS) to excess weight gain when fed a purified diet containing 32% kcal from fat, similar to levels consumed by the typical American woman. DS rats were approximately 15.5% heavier than DR rats at study termination and plasma leptin indicated a marked difference in adiposity. DS rats had higher incidence (26% increase), multiplicity (2.5-fold increase), and burden (5.4-fold increase) of mammary carcinomas with a concomitant reduction in cancer latency (16% earlier detection) compared with DR rats (P &lt; 0.001 for all analyses), and displayed a higher proportion of hormone receptor negative tumors compared with DR rats [OR = 1.78; 95% confidence interval (CI), 0.83–3.81]. Circulating levels of several breast cancer–risk factors, including leptin, adiponectin:leptin ratio, insulin, insulin-like growth factor (IGF)-1, IGF-1:IGF-1 binding protein-3 ratio, and calculated insulin resistance (HOMA-IR) were negatively impacted in DS rats (P &lt; 0.05 for all analyses). These findings support further investigation of the effects of excess weight in high-risk premenopausal women and demonstrate a useful preclinical model for rapid evaluation of mechanistic hypotheses. Cancer Prev Res; 7(3); 310–8. ©2014 AACR.
Requirement and Epigenetics Reprogramming of Nrf2 in Suppression of Tumor Promoter TPA-Induced Mouse Skin Cell Transformation by Sulforaphane
Authors: Su Zheng-Yuan , Zhang Chengyue , Lee Jong Hun , Shu Limin , Wu Tien-Yuan , Khor Tin Oo , Conney Allan H. , Lu Yao-Ping , Kong Ah-Ng Tony 
Published: January 2014

AbstractNrf2 is a transcription factor that plays critical roles in regulating the expression of cellular defensive antioxidants and detoxification enzymes. However, the role of Nrf2 and Nrf2's epigenetics reprogramming in skin tumor transformation is unknown. In this study, we investigated the inhibitory role and epigenetics of Nrf2 on tumor transformation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin epidermal JB6 (JB6 P+) cells and the anticancer effect of sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables. After five days of treatment, SFN significantly inhibited TPA-induced JB6 cellular transformation and SFN enhanced the nuclear translocation of Nrf2 and increased the mRNA and protein levels of the Nrf2 target genes HO-1, NQO1 and UGT1A1. Knockdown of Nrf2 attenuated the induction of Nrf2, HO-1 and NQO1 by SFN, enhanced TPA-induced colony formation and dampened the inhibitory effect of SFN on TPA-induced JB6 transformation. Epigenetics investigation using bisulfite genomic sequencing showed that SFN decreased the methylation ratio of the first 15 CpGs of the Nrf2 gene promoter, which was corroborated by increased Nrf2 mRNA expression. Furthermore, SFN strongly reduced the protein expression of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b). SFN also inhibited the total histone deacetylase (HDAC) activity and decreased the protein expression of HDAC1, HDAC2, HDAC3 and HDAC4. Collectively, these results suggest that the anti-cancer effect of SFN against TPA-induced neoplastic transformation of mouse skin could involve the epigenetic reprogramming of anti-cancer genes such as Nrf2, leading to the epigenetic reactivation of Nrf2 and the subsequent induction of downstream target genes involved in cellular protection. Cancer Prev Res; 7(3); 319–29. ©2014 AACR.
Adherence to Endocrine Therapy in Breast Cancer Adjuvant and Prevention Settings
Authors: Chlebowski Rowan T. , Kim Jisang , Haque Reina 
Published: January 2014

Abstract
Adherence to oral endocrine therapy in adjuvant breast cancer settings is a substantial clinical problem. To provide current perspective on adherence to oral endocrine therapies, a comprehensive literature review was conducted. In adjuvant trials, endocrine therapy adherence is relatively high with greater adherence for aromatase inhibitors compared with tamoxifen. In contrast, adherence to adjuvant therapy in clinical practice is relatively poor, with only about 50% of women successfully completing 5-year therapy. Importantly, good adherence (&gt;80% use) has been associated with lower recurrence risk. Endocrine therapy adherence in primary breast cancer prevention trials parallels that seen in adjuvant trials. Factors associated with nonadherence include low recurrence risk perception, side effects, age extremes, medication cost, suboptimal patient–physician communication, and lack of social support. Few prospective studies have evaluated interventions designed to improve adherence. Interventions currently proposed reflect inferences from clinical trial procedures in which clinical contacts are commonly greater than in usual practice settings. In conclusion, for optimal breast cancer outcome, adherence to endocrine therapy must improve. Although general recommendations likely to improve adherence can be made based on clinical trial results and preliminary prospective trial findings, research specifically targeting this issue is needed to establish effective intervention strategies. Cancer Prev Res; 7(4); 378–87. ©2014 AACR.
Radiogenomics: Using Genetics to Identify Cancer Patients at Risk for Development of Adverse Effects Following Radiotherapy
Authors: Kerns Sarah L. , Ostrer Harry , Rosenstein Barry S. 
Published: January 2014

Abstract
Normal-tissue adverse effects following radiotherapy are common and significantly affect quality of life. These effects cannot be accounted for by dosimetric, treatment, or demographic factors alone, and evidence suggests that common genetic variants are associated with radiotherapy adverse effects. The field of radiogenomics has evolved to identify such genetic risk factors. Radiogenomics has two goals: (i) to develop an assay to predict which patients with cancer are most likely to develop radiation injuries resulting from radiotherapy, and (ii) to obtain information about the molecular pathways responsible for radiation-induced normal-tissue toxicities. This review summarizes the history of the field and current research.
Significance: A single-nucleotide polymorphism–based predictive assay could be used, along with clinical and treatment factors, to estimate the risk that a patient with cancer will develop adverse effects from radiotherapy. Such an assay could be used to personalize therapy and improve quality of life for patients with cancer. Cancer Discov; 4(2); 155–65. ©2014 AACR.
Apoptosis-Regulated Low-Avidity Cancer-Specific CD8+ T Cells Can Be Rescued to Eliminate HER2/neu–Expressing Tumors by Costimulatory Agonists in Tolerized Mice
Authors: Black Chelsea M. , Armstrong Todd D. , Jaffee Elizabeth M. 
Published: January 2014

AbstractA major barrier to vaccines in cancer treatment is their failure to activate and maintain a complete cancer-specific CD8+ effector T-cell repertoire. Low-avidity T cells are more likely to escape clonal deletion in the thymus when compared with high-avidity T cells, and therefore comprise the major population of effector T cells available for activation in patients with cancer. However, low-avidity T cells fail to traffic into the tumor microenvironment and function in eradicating tumor under optimal vaccination conditions as opposed to high-avidity T cells that escape clonal deletion and function in tumor killing. We used high- and low-avidity T-cell receptor transgenic CD8+ T cells specific for the immunodominant epitope HER2/neu (RNEU420–429) to identify signaling pathways responsible for the inferior activity of the low-avidity T cells. Adoptive transfer of these cells into tumor-bearing vaccinated mice identified the members of apoptosis pathways that are upregulated in low-avidity T cells. The increased expression of proapoptotic proteins by low-avidity T cells promoted their own cell death and also that of other tumor-specific CD8+ T cells within their local environment. Importantly, we show that this proapoptotic effect can be overcome by using a strong costimulatory signal that prevents the activation-induced cell death and enables the low-avidity T cells to traffic into the tumor and assist in tumor clearance. These findings identify new therapeutic opportunities for activating the most potent anticancer T-cell responses. Cancer Immunol Res; 2(4); 307–19. ©2014 AACR.
MEK Inhibition, Alone or in Combination with BRAF Inhibition, Affects Multiple Functions of Isolated Normal Human Lymphocytes and Dendritic Cells
Authors: Vella Laura J. , Pasam Anupama , Dimopoulos Nektaria , Andrews Miles , Knights Ashley , Puaux Anne-Laure , Louahed Jamila , Chen Weisan , Woods Katherine , Cebon Jonathan S. 
Published: January 2014

AbstractCombination therapy with BRAF and MEK inhibition is currently in clinical development for the treatment of BRAF-mutated malignant melanoma. BRAF inhibitors are associated with enhanced antigen-specific T-lymphocyte recognition in vivo. Consequently, BRAF inhibition has been proposed as proimmunogenic and there has been considerable enthusiasm for combining BRAF inhibition with immunotherapy. MEK inhibitors inhibit ERK phosphorylation regardless of BRAF mutational status and have been reported to impair T-lymphocyte and modulate dendritic cell function. In this study, we investigate the effects on isolated T lymphocytes and monocyte-derived dendritic cells (moDC) of a MEK (trametinib) and BRAF (dabrafenib) inhibitor combination currently being evaluated in a randomized controlled clinical trial. The effects of dabrafenib and trametinib, alone and in combination, were studied on isolated normal T lymphocytes and moDCs. Lymphocyte viability, together with functional assays including proliferation, cytokine production, and antigen-specific expansion, were assessed. MoDC phenotype in response to lipopolysaccharide stimulation was evaluated by flow cytometry, as were effects on antigen cross-presentation. Dabrafenib did not have an impact on T lymphocytes or moDCs, whereas trametinib alone or in combination with dabrafenib suppressed T-lymphocyte proliferation, cytokine production, and antigen-specific expansion. However, no significant decrease in CD4+ or CD8+ T-lymphocyte viability was observed following kinase inhibition. MoDC cross-presentation was suppressed in association with enhanced maturation following combined inhibition of MEK and BRAF. The results of this study demonstrate that MEK inhibition, alone or in combination with BRAF inhibition, can modulate immune cell function, and further studies in vivo will be required to evaluate the potential clinical impact of these findings. Cancer Immunol Res; 2(4); 351–60. ©2014 AACR.
Outcomes of Patients With Peripartum Cardiomyopathy Who Received Mechanical Circulatory Support
Authors: Loyaga-Rendon Renzo Y. , Pamboukian Salpy V. , Tallaj Jose A. , Acharya Deepak , Cantor Ryan , Starling Randall C. , Naftel David , Kirklin James 
Published: January 2014

Background—
We describe the characteristics and outcomes of peripartum cardiomyopathy (PPCMP) patients who received durable mechanical circulatory support and compared it with other etiologies of advanced heart failure.

Methods and Results—

We analyzed 1258 women who were registered in Interagency Registry for Mechanically Assisted Circulatory Support between June 2006 and March 2012. Baseline characteristics, implant strategies, hemodynamics, echocardiographic data, and outcomes were compared. Ninety-nine women had PPCMP and 1159 had non-PPCMP as primary diagnosis. PPCMP women were younger (
P
<0.001), more likely to be blacks, and had less comorbidities than non-PPCMP patients. PPCMP women had better survival than non-PPCMP women (
P
=0.01) with a 2-year survival of 83%. Multivariable risk factor adjustment analysis showed that the improved survival was likely because of younger age and fewer comorbidities. At 36 months, a proportion of 48% PPCMP received heart transplantation. Recovery occurred at a frequency of 6% and 2% in the PPCMP and non-PPCMP groups (
P
=0.1). Adverse event rates were similar in PPCMP and non-PPCMP patients except for higher cardiac arrhythmias and respiratory failure in the non-PPCMP in the first 3 months post implant.

Conclusions—
PPCMP women who receive durable mechanical circulatory support have a better survival than women with non-PPCPM. The improved survival observed in PPCMP is likely related to their fewer comorbidities and younger age. Myocardial recovery was uncommon and less than half of women with end-stage PPCPM received heart transplantation after 3 years of mechanical support.
Effects of Conversation on Situation Awareness and Working Memory in Simulated Driving
Authors: Heenan Adam , Herdman Chris M. , Brown Matthew S. , Robert Nicole 
Published: January 2014

Objective: In the present research, we investigated the hypothesis that working memory mediates conversation-induced impairment of situation awareness (SA) while driving. Background: Although there is empirical evidence that conversation impairs driving performance, the cognitive mechanisms that mediate this relationship remain underspecified. Researchers have reported that a phonological working memory task decreased drivers’ SA for vehicles located behind them whereas a visuospatial working memory task impaired SA for vehicles ahead. Conversation, therefore, might impair SA for vehicles behind the driver by preferentially taxing the phonological loop. Method: A 20-questions task was used as a proxy for natural conversation. In Experiment 1, driving performance was measured across three within-subjects conversation conditions (i.e., no conversation, driver asks questions, driver answers questions) with the use of a driving simulator. In Experiment 2, participants drove in the same simulator while either conversing (20-questions task) or not. Participants estimated the positions of other vehicles after the screens were blanked at the end of each trial. Results: Speed monitoring and responses to visual probes were impaired by the 20-questions conversation task (Experiment 1). As predicted, conversation impaired SA for the location of other vehicles more for vehicles located behind the driver than for those in front (Experiment 2). Conclusion: Conversation impairs drivers’ SA of vehicles behind them by taxing working memory’s phonological loop and impairs SA generally by taxing working memory’s central executive. Application: Provides a theoretical framework that links driver SA to working memory and a mechanism for understanding why conversation impairs driving performance.
Positive Effects of Basic Training on Cognitive Performance and Mood of Adult Females
Authors: Lieberman Harris R. , Karl J. Philip , Niro Philip J. , Williams Kelly W. , Farina Emily K. , Cable Sonya J. , McClung James P. 
Published: January 2014

Objective: This study investigated whether a stressful military training program, the 9- to 10-week U.S. Army basic combat training (BCT) course, alters the cognitive performance and mood of healthy young adult females. Background: Structured training programs including adolescent boot camps, sports training camps, learning enrichment programs, and military basic training are accepted methods for improving academic and social functioning. However, limited research is available on the behavioral effects of structured training programs in regard to cognitive performance and mood. Method: Two separate, within-subject studies were conducted with different BCT classes; in total 212 female volunteers were assessed before and after BCT. In Study 1, Four-Choice Reaction Time, Match-to-Sample, and Grammatical Reasoning tests were administered. The Psychomotor Vigilance Test (PVT) was administered in Study 2. The Profile of Mood States (POMS) was administered in both studies. Results: In Study 1, reaction time to correct responses on all three of the performance tests improved from pre- to post-BCT. In Study 2, PVT reaction time significantly improved. All POMS subscales improved over time in the second study, whereas POMS subscales in the first study failed to meet criteria for statistically significant differences over time. Conclusion: Cognition and mood substantially improved over military basic training. These changes may be a result of structured physical and mental training experienced during basic training or other factors not as yet identified. Application: Properly structured training may have extensive, beneficial effects on cognitive performance and mood; however, additional research is needed to determine what factors are responsible for such changes.
Role of diffusion-weighted MRI in acute pyelonephritis: a prospective study
Authors: Rathod Santosh B , Kumbhar Sachin S , Nanivadekar Avinash , Aman Kumar 
Published: January 2014

BackgroundImaging is vital in diagnosis of complicated pyelonephritis and has been traditionally performed by computed tomography (CT). However, CT with contrast agents cannot be performed in patients with renal failure. Diffusion-weighted (DW) magnetic resonance imaging (MRI) has the potential to overcome this disadvantage.PurposeTo prospectively evaluate the accuracy of quantitative apparent diffusion coefficient (ADC) values to differentiate nephritis from renal abscesses in patients with pyelonephritis.Material and MethodsForty-two patients with clinical and laboratory diagnosis of pyelonephritis underwent CT and DW MRI examinations. Diffusion images were obtained by using a non-breath-hold, single-shot echo-planar sequence with b values of 0, 600, and 1000 s/mm2. Circular regions of interest were places on areas of nephritis, normal renal parenchyma, and renal abscesses as localized by CT and DW MRI images to obtain the ADC values of each of these regions. The ADC values of these three different tissue types were statistically compared using the one-way analysis of variance test for statistical significance. A P value <0.05 was considered to be statistically significant.ResultsFor the diagnosis of pyelonephritis, DW MRI had a higher sensitivity of 95.3% as compared to that of non-contrast CT (66.7%) and contrast-enhanced CT (88.1%). Areas of nephritis had significantly lower ADC values ( P < 0.001) than the normal renal cortical parenchyma. Also, renal abscesses had significantly lower ADC values ( P < 0.001) than areas of nephritis. However, CT is more useful for the diagnosis of renal calculi and emphysematous pyelonephritis.ConclusionADC values derived from the diffusion sequence have significantly lower values in renal abscesses than in areas of nephritis.
Effect of Cup Feeding and Bottle Feeding on Breastfeeding in Late Preterm Infants
Authors: Yilmaz Gonca , Caylan Nilgun , Karacan Can Demir , Bodur İlknur , Gokcay Gulbin 
Published: January 2014

Background: Cup feeding has been used as an alternative feeding method for preterm infants. Objective: The purpose of this study was to determine the effect of bottle and cup feeding on exclusive breastfeeding rates at hospital discharge and 3 and 6 months post-discharge in late preterm infants. Methods: Included in the study were preterm infants of 32 to 35 weeks’ gestation fed only by intermittent gastric tube at the time of recruitment; 522 infants were randomly assigned to 2 groups: the cup-fed group (n = 254) and bottle-fed group (n = 268). Main outcomes were prevalence of exclusive breastfeeding at discharge and 3 and 6 months after discharge, and length of hospital stay. Results: Infants randomized to cup versus bottle feeding were more likely to be exclusively breastfed at discharge home (relative risk [RR], 1.58; 95% confidence interval [CI], 1.36-1.83), 3 months after discharge (RR, 1.64; 95% CI, 1.42-1.89), and 6 months after discharge (RR, 1.36; 95% CI, 1.14-1.63). There was no significant difference between groups for length of hospital stay. The mean hospital stay was 25.96 ± 2.20 days in the bottle-fed group and 25.68 ± 2.22 days in the cup-fed group. There was no significant difference between groups for time spent feeding, feeding problems, or weight gain in hospital. Conclusion: Cup feeding significantly increased the likelihood of late preterm infants being exclusively breastfed at discharge and 3 and 6 months after discharge, and cup feeding did not increase the length of hospital stay. Overall, we recommend cup feeding as a transitional method prior to breastfeeding for late preterm infants during hospitalization.
Prospective Study of Hammertoe Correction With an Intramedullary Implant
Authors: Catena Fernanda , Doty Jesse F. , Jastifer James , Coughlin Michael J. , Stevens Faustin 
Published: January 2014

Background: Operative correction of a hammertoe deformity is often accomplished by excision of the articular surface of the proximal interphalangeal joint (PIP) and fixation across the joint. This study aimed to prospectively evaluate clinical and radiographic outcomes of hammertoe operative correction utilizing an internal implant and assess its ability to maintain postoperative alignment. Methods: Twenty-nine patients (53 toes) with a painful rigid hammertoe deformity were prospectively enrolled and operatively treated with resection arthroplasty of the PIP joint and fixation with an implant. Five patients were lost to follow-up, and 24 patients (42 toes) returned at an average of 12 months for final clinical and radiographic evaluation. All patients were evaluated pre- and postoperatively by AOFAS and Visual Analog Pain Scale (VAS) scores. On physical exam, the location and magnitude of the deformity, callosities, and digit circumference were recorded. Radiological parameters evaluated were digital alignment, successful union, implant position, and bone reaction. Results: All patients reported satisfaction at final follow-up, with an average improvement of AOFAS score from 52 (range, 24-87 points) to 71 (range, 42-95 points) points. The mean VAS pain score improved from 5 points (range, 2 to 10) preoperatively to 1 point (range, 0 to 5) postoperatively. Of patients, 87% reported an ability to return to their preoperative activities without limitations. Regarding digital alignment, there were no recurrent deformities or transverse plane deformities; 1 toe presented with a minor digital rotational deformity at final follow-up. Postoperative radiographs indicated 100% of proximal interphalangeal (PIP) joints with good alignment, and 81% demonstrated bony union. Conclusion: Our results suggest that utilization of an internal implant for hammertoe correction was safe and provided acceptable alignment, pain reduction, and improved function at final follow-up. Level of Evidence: Level IV, case series.