bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIRT2 Deacetylates and Inhibits the Peroxidase Activity of Peroxiredoxin-1 to Sensitize Breast Cancer Cells to Oxidant Stress-Inducing Agents
Authors: Fiskus Warren , Coothankandaswamy Veena , Chen Jianguang , Ma Hongwei , Ha Kyungsoo , Saenz Dyana T. , Krieger Stephanie S. , Mill Christopher P. , Sun Baohua , Huang Peng , Mumm Jeffrey S. , Melnick Ari M. , Bhalla Kapil N. 
Published: August 2016

Abstract
SIRT2 is a protein deacetylase with tumor suppressor activity in breast and liver tumors where it is mutated; however, the critical substrates mediating its antitumor activity are not fully defined. Here we demonstrate that SIRT2 binds, deacetylates, and inhibits the peroxidase activity of the antioxidant protein peroxiredoxin (Prdx-1) in breast cancer cells. Ectopic overexpression of SIRT2, but not its catalytically dead mutant, increased intracellular levels of reactive oxygen species (ROS) induced by hydrogen peroxide, which led to increased levels of an overoxidized and multimeric form of Prdx-1 with activity as a molecular chaperone. Elevated levels of SIRT2 sensitized breast cancer cells to intracellular DNA damage and cell death induced by oxidative stress, as associated with increased levels of nuclear FOXO3A and the proapoptotic BIM protein. In addition, elevated levels of SIRT2 sensitized breast cancer cells to arsenic trioxide, an approved therapeutic agent, along with other intracellular ROS-inducing agents. Conversely, antisense RNA-mediated attenuation of SIRT2 reversed ROS-induced toxicity as demonstrated in a zebrafish embryo model system. Collectively, our findings suggest that the tumor suppressor activity of SIRT2 requires its ability to restrict the antioxidant activity of Prdx-1, thereby sensitizing breast cancer cells to ROS-induced DNA damage and cell cytotoxicity. Cancer Res; 76(18); 5467–78. ©2016 AACR.
Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis
Authors: Alba-Castellón Lorena , Olivera-Salguero Rubén , Mestre-Farrera Aida , Peña Raúl , Herrera Mercedes , Bonilla Félix , Casal J. Ignacio , Baulida Josep , Peña Cristina , García de Herreros Antonio 
Published: August 2016

Abstract
Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here an EMT-independent action of Snail1 on tumor invasion, as it is required for the activation of cancer-associated fibroblasts (CAF). Snail1 expression in fibroblasts requires signals derived from tumor cells, such as TGFβ; reciprocally, in fibroblasts, Snail1 organizes a complex program that stimulates invasion of epithelial cells independent of the expression of Snail1 in these cells. Epithelial cell invasion is stimulated by the secretion by fibroblast of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine CAFs to promote tumor invasion is dependent on Snail1 expression. Inducible Snail1 depletion in mice decreases the invasion of breast tumors; moreover, epithelial tumor cells coxenografted with Snail1-depleted fibroblasts originated tumors with lower invasion than those transplanted with control fibroblasts. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to EMT, but it is also dependent on its activity in stromal fibroblasts, where it orchestrates the cross-talk with epithelial tumor cells. Cancer Res; 76(21); 6205–17. ©2016 AACR.
Chromatin-Remodeling Complex SWI/SNF Controls Multidrug Resistance by Transcriptionally Regulating the Drug Efflux Pump ABCB1
Authors: Dubey Ramin , Lebensohn Andres M. , Bahrami-Nejad Zahra , Marceau Caleb , Champion Magali , Gevaert Olivier , Sikic Branimir I. , Carette Jan E. , Rohatgi Rajat 
Published: August 2016

Abstract
Anthracyclines are among the most effective yet most toxic drugs used in the oncology clinic. The nucleosome-remodeling SWI/SNF complex, a potent tumor suppressor, is thought to promote sensitivity to anthracyclines by recruiting topoisomerase IIa (TOP2A) to DNA and increasing double-strand breaks. In this study, we discovered a novel mechanism through which SWI/SNF influences resistance to the widely used anthracycline doxorubicin based on the use of a forward genetic screen in haploid human cells, followed by a rigorous single and double-mutant epistasis analysis using CRISPR/Cas9-mediated engineering. Doxorubicin resistance conferred by loss of the SMARCB1 subunit of the SWI/SNF complex was caused by transcriptional upregulation of a single gene, encoding the multidrug resistance pump ABCB1. Remarkably, both ABCB1 upregulation and doxorubicin resistance caused by SMARCB1 loss were dependent on the function of SMARCA4, a catalytic subunit of the SWI/SNF complex. We propose that residual SWI/SNF complexes lacking SMARCB1 are vital determinants of drug sensitivity, not just to TOP2A-targeted agents, but to the much broader range of cancer drugs effluxed by ABCB1. Cancer Res; 76(19); 5810–21. ©2016 AACR.
Anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of the Presence of Cardiovascular Comorbidities in Cancer Survivors
Authors: Jordan Jennifer H. , Vasu Sujethra , Morgan Timothy M. , D’Agostino Ralph B. , Meléndez Giselle C. , Hamilton Craig A. , Arai Andrew E. , Liu Songtao , Liu Chia-Ying , Lima João A.C. , Bluemke David A. , Burke Gregory L. , Hundley W. Gregory 
Published: August 2016

Background—
Cardiovascular magnetic resonance T1 mapping characteristics are elevated in adult cancer survivors; however, it remains unknown whether these elevations are related to age or presence of coincident cardiovascular comorbidities.

Methods and Results—

We performed blinded cardiovascular magnetic resonance analyses of left ventricular T1 and extracellular volume (ECV) fraction in 327 individuals (65% women, aged 64±12 years). Thirty-seven individuals had breast cancer or a hematologic malignancy but had not yet initiated their treatment, and 54 cancer survivors who received either anthracycline-based (n=37) or nonanthracycline-based (n=17) chemotherapy 2.8±1.3 years earlier were compared with 236 cancer-free participants. Multivariable analyses were performed to determine the association between T1/ECV measures and variables associated with myocardial fibrosis. Age-adjusted native T1 was elevated pre- (1058±7 ms) and post- (1040±7 ms) receipt of anthracycline chemotherapy versus comparators (965±3 ms;
P
<0.0001 for both). Age-adjusted ECV, a marker of myocardial fibrosis, was elevated in anthracycline-treated cancer participants (30.4±0.7%) compared with either pretreatment cancer (27.8±0.7%;
P
<0.01) or cancer-free comparators (26.9±0.2%;
P
<0.0001). T1 and ECV of nonanthracycline survivors were no different than pretreatment survivors (
P
=0.17 and
P
=0.16, respectively). Native T1 and ECV remained elevated in cancer survivors after accounting for demographics (including age), myocardial fibrosis risk factors, and left ventricular ejection fraction or myocardial mass index (
P
<0.0001 for all).

Conclusions—
Three years after anthracycline-based chemotherapy, elevations in myocardial T1 and ECV occur independent of underlying cancer or cardiovascular comorbidities, suggesting that imaging biomarkers of interstitial fibrosis in cancer survivors are related to prior receipt of a potentially cardiotoxic cancer treatment regimen.
The Combined Use of Losartan and Muscle-Derived Stem Cells Significantly Improves the Functional Recovery of Muscle in a Young Mouse Model of Contusion Injuries
Authors: Kobayashi Makoto , Ota Shusuke , Terada Satoshi , Kawakami Yohei , Otsuka Takanobu , Fu Freddie H. , Huard Johnny 
Published: August 2016

Background: Although muscle injuries tend to heal uneventfully in most cases, incomplete functional recovery commonly occurs as a result of scar tissue formation at the site of injury, even after treatment with muscle-derived stem cells (MDSCs). Hypothesis: The transplantation of MDSCs in the presence of a transforming growth factor β1 (TGF-β1) antagonist (losartan) would result in decreased scar tissue formation and enhance muscle regeneration after contusion injuries in a mouse model. Study Design: Controlled laboratory study. Methods: An animal model of muscle contusion was developed using the tibialis anterior muscle in 48 healthy mice at 8 to 10 weeks of age. After sustaining muscle contusion injuries, the mice were divided into 4 groups: (1) saline injection group (control group; n = 15), (2) MDSC transplantation group (MDSC group; n = 15), (3) MDSC transplantation plus oral losartan group (MDSC/losartan group; n = 15), and (4) healthy uninjured group (healthy group; n = 3). Losartan was administrated systemically beginning 3 days after injury and continued until the designated endpoint (1, 2, or 4 weeks after injury). MDSCs were transplanted 4 days after injury. Muscle regeneration and fibrotic scar formation were evaluated by histology, and the expression of follistatin, MyoD, Smad7, and Smad2/3 were analyzed by immunohistochemistry and reverse transcription polymerase chain reaction analysis. Functional recovery was measured via electrical stimulation of the peroneal nerve. Results: When compared with MDSC transplantation alone, MDSC/losartan treatment resulted in significantly decreased scar formation, an increase in the number of regenerating myofibers, and improved functional recovery after muscle contusions. In support of these findings, the expression levels of Smad7 and MyoD were significantly increased in the group treated with both MDSCs and losartan. Conclusion: When compared with MDSCs alone, the simultaneous treatment of muscle contusions with MDSCs and losartan significantly reduced scar formation, increased the number of regenerating myofibers, and improved the functional recovery of muscle; these effects were caused, at least in part, by the losartan-mediated upregulation of Smad7 and MyoD. Increased levels of Smad7 and MyoD together reduced the deposition of scar tissue (via the inhibition of TGF-β1 by Smad7) and committed the transplanted MDSCs toward a myogenic lineage (via Smad7-regulated MyoD expression). Clinical Relevance: The study findings contribute to the development of biological treatments to accelerate and improve the quality of muscle healing after injury.
Lower Limb Length Discrepancy After High Tibial Osteotomy
Authors: Kim Joong Il , Kim Bo Hyun , Lee Ki Woung , Lee Osung , Han Hyuk Soo , Lee Sahnghoon , Lee Myung Chul 
Published: August 2016

Background: High tibial osteotomy (HTO) produces valgus limb alignment, and this change can affect lower limb length. Purpose: To compare the change in lower limb length and the discrepancy compared with the contralateral limb after unilateral lateral closing wedge HTO (CWHTO) and medial opening wedge HTO (OWHTO). Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In this study, 30 knees undergoing unilateral CWHTO and 30 knees undergoing unilateral OWHTO for medial compartmental osteoarthritis were analyzed with 1-year follow-up. The tibial length, lower limb length, and lower limb length discrepancy were measured preoperatively and 1 year postoperatively. The patients’ subjective sensation of, and discomfort due to, the lower limb length discrepancy were recorded 1 year postoperatively. Univariate and multivariate linear regression analyses were conducted to identify predictors related to the change in lower limb length. Results: The mean lengths of the tibia and lower limb increased significantly after OWHTO (5.2 ± 3.7 and 7.6 ± 2.1 mm, respectively; P < .001). The mean tibial length decreased significantly after CWHTO (−6.0 ± 2.1 mm; P < .001); however, the mean lower limb length change was not significant (−0.8 ± 2.5 mm; P = .073). The mean lower limb length discrepancy increased significantly after OWHTO (−0.5 ± 0.7 to 7.2 ± 2.1 mm; P < .001) but not after CWHTO (−0.7 ± 0.6 to −1.0 ± 2.5 mm; P = .539). A significantly greater proportion of patients in the OWHTO group were aware of (70% vs 20%, respectively; P = .002), and uncomfortable because of (37% vs 7%, respectively; P = .010), the lower limb length discrepancy compared with those in the CWHTO group. The strongest predictor of a change in lower limb length was the wedge length in the OWHTO group and the preoperative hip-knee-ankle angle in the CWHTO group. Conclusion: The lower limb length change and discrepancy were significant after unilateral OWHTO, whereas they were negligible after unilateral CWHTO. CWHTO was more beneficial in cases of unilateral HTO to minimize the discrepancy of lower limb length rather than OWHTO, particularly in knees requiring a large correction. Registration: Clinical Trials Registry Platform (protocol number KCT00001684).
The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and Septic Shock
Authors: Theerawit Pongdhep , Na Petvicharn Chalermpon , Tangsujaritvijit Viratch , Sutherasan Yuda 
Published: August 2016

Background: Applying peripheral venous lactate instead of arterial lactate in clinical practice is questionable because of deviation between both values. We aimed to find the relationship between the arterial lactate and the peripheral venous lactate before reasoned that the venous lactate could be used in substitution to the arterial lactate in sepsis. Methods: We conducted a prospective, cross-sectional study at a university hospital. The patients with sepsis in ICU who required lactate level monitoring were enrolled in this research. The correlation and agreement between arterial lactate (A-LACT) and peripheral venous lactate (V-LACT) were the primary outcomes. Results: A total of 63 paired samples were collected. The A-LACT and V-LACT were strongly correlated ( r = .934, P < .0001, r2 = .873). The regression equation was A-LACT = (0.934 × V-LACT) − 0.236. The mean difference between V-LACT and A-LACT was 0.66 ± 1.53 mmol/L. The 95% limits of agreement were between −3.66 and 2.33 mmol/L. The V-LACT ≥ 4 mmol/L can predict A-LACT level ≥ 4 mmol/L with 87.5% sensitivity and 91.5% specificity, and the area under receiver operating characteristic curve was 0.948. Conclusion: The present study demonstrated a strong correlation between A-LACT and V-LACT, but an agreement between both parameters was poor. We suggest not to use the V-LACT in substitution to the A-LACT in sepsis regarding the absolute value and clearance rate, but the V-LACT ≥ 4.5 mmol/L may be used for predicting the A-LACT ≥ 4 mmol/L.
Association Between Monetary Deposits and Weight Loss in Online Commitment Contracts
Authors: Lesser Lenard I. , Thompson Caroline A. , Luft Harold S. 
Published: August 2016

Purpose: To examine the characteristics of voluntary online commitment contracts that may be associated with greater weight loss. Design: Retrospective analysis of weight loss commitment contracts derived from a company that provides web-based support for personal commitment contracts. Using regression, we analyzed whether percentage weight loss differed between participants who incentivized their contract using monetary deposits and those who did not. Setting: Online. Participants: Users (N = 3857) who voluntarily signed up online in 2013 for a weight loss contract. Intervention: Participants specified their own weight loss goal, time period, and self-reported weekly weight. Deposits were available in the following 3 categories: charity, anticharity (a nonprofit one does not like), or donations made to a friend. Measures: Percentage weight loss per week. Analysis: Multivariable linear regressions. Results: Controlling for several participant and contract characteristics, contracts with anticharity, charity, and friend deposits had greater reported weight loss than nonincentivized contracts. Weight change per week relative to those without deposits was −0.33%, −0.28%, and −0.25% for anti-charity, charity, and friend, respectively ( P < 0.001). Contracts without a weight verification method claimed more weight loss than those with verification. Conclusion: Voluntary use of commitment contracts may be an effective tool to assist weight loss. Those who choose to use monetary incentives report more weight loss. It is not clear whether this is due to the incentives or higher motivation.
Application of quantitative techniques in decision making by healthcare managers and administrators in Nigerian public tertiary health institutions
Authors: Esan Oluwaseun T , Akanbi Charles T , Esan Oluwadare , Fajobi Olusola , Ikenebomeh Primus I 
Published: August 2016

Introduction The study was aimed at comparing the applicability of quantitative techniques and its relevance in decision making by clinical and non-clinical healthcare managers and administrators. Methods A comparative cross-sectional study in design conducted at the Obafemi Awolowo University Teaching Hospital, Ile-Ife amongst 52 clinical and 50 non-clinically related healthcare managers and administrators. Data collection tool was a semi-structured self-administered questionnaire. Data were analysed using descriptive and inferential statistics of SPSS version 20 with statistical significance determined at p < 0.05. Results A higher proportion of the non-clinical healthcare managers and administrators were familiar and had used more quantitative techniques than their clinical counterparts. Experience ranked highest as the current method employed by both groups for most decision needing scenarios presented. There was no statistically significant difference in their perceived effectiveness of the current methods guiding decision making. However, a statistically significant difference was found in the methods preferred by both study population only for ‘reducing waiting lines, p = 0.015’ and in ‘maximising the use of human resources, p = 0.017’. Conclusions Approach to decision making in the Nigerian health sector is still largely experiential and more of a personalised bargaining process. Acknowledgement of the relevance of quantitative techniques by clinical and non-clinically related health managers and administrators as found in this study is hoped to accelerate the adoption of these techniques. It is believed that its application will lead to improved health service delivery and health outcomes.
Domestic Violence and Poverty
Authors: Slabbert Ilze 
Published: August 2016

Purpose: Domestic violence poses a major challenge to social workers. Low-income families are significantly more likely to have to contend with domestic violence, as poverty can act as a fuelling factor in this type of conflict. The objective of this study was to explore and describe the experiences of low-income abused women. Method: A qualitative research approach was followed to explore and describe the phenomenon of low-income abused women. Purposive and snowball sampling were used to obtain 20 participants. Data were collected by means of semi-structured interviews. The data were categorized into four themes. Results: Domestic violence and poverty are issues that some women might experience. Low-income abused women are especially more vulnerable to domestic violence and poverty limits choices and resources. Conclusion: Domestic violence and poverty should be seen in a serious light. Social workers should recognise the complexity and correlation between domestic violence and poverty.
Influence of alterations in heart rate on left ventricular echocardiographic measurements in healthy cats
Authors: Sugimoto Keisuke , Fujii Yoko , Ogura Yuto , Sunahara Hiroshi , Aoki Takuma 
Published: August 2016

Objectives The purpose of this study was to evaluate the effect of sudden alterations in heart rate (HR) on left ventricular (LV) wall thickness and dimensions determined by echocardiography in healthy cats. Methods Six experimental cats were used. All cats were anaesthetised and HR was controlled with right atrial pacing. The interventricular septum and left ventricular free wall thickness at end diastole (IVSd and LVFWd, respectively), left ventricular end-diastolic and end-systolic diameter (LVIDd and LVIDs, respectively) and shortening fraction (FS) of each cat were assessed using echocardiography at pacing rates of 120, 130, 140, 150, 160, 170 and 180 ppm. Results There were significant relationships between HR and IVSd, LVFWd, LVIDd, LVIDs and FS. As the HR increased, LV wall thickness increased and chamber dimensions got smaller in a linear fashion. The maximum and minimum differences in wall thickness between 120 ppm and 180 ppm were 2.0 mm and 0.7 mm in single measurements, respectively. Conclusions and relevance LV wall thickness and dimensions were significantly influenced by alterations in HR.
Adaptive Radiotherapy for Head and Neck Cancer
Authors: Surucu Murat , Shah Karan K. , Roeske John C. , Choi Mehee , Small William , Emami Bahman 
Published: August 2016

Objective: To investigate the effects of adaptive radiotherapy on dosimetric, clinical, and toxicity outcomes for patients with head and neck cancer undergoing chemoradiotherapy with intensity-modulated radiotherapy. Methods: Fifty-one patients with advanced head and neck cancer underwent definitive chemoradiotherapy with the original plan optimized to deliver 70.2 Gy. All patients were resimulated at a median dose of 37.8 Gy (range, 27.0-48.6 Gy) due to changes in tumor volume and/or patient weight loss (>15% from baseline). Thirty-four patients underwent adaptive replanning for their boost planning (21.6 Gy). The dosimetric effects of the adaptive plan were compared to the original plan and the original plan copied on rescan computed tomography. Acute and late toxicities and tumor local control were assessed. Gross tumor volume reduction rate was calculated. Results: With adaptive replanning, the maximum dose to the spinal cord, brain stem, mean ipsilateral, and contralateral parotid had a median reduction of −4.5%, −3.0%, −6.2%, and −2.5%, respectively (median of 34 patients). Median gross tumor volume and boost planning target volume coverage improved by 0.8% and 0.5%, respectively. With a median follow-up time of 17.6 months, median disease-free survival and overall survival was 14.8 and 21.1 months, respectively. Median tumor volume reduction rate was 35.2%. For patients with tumor volume reduction rate ≤35.2%, median disease-free survival was 8.7 months, whereas it was 16.9 months for tumor volume reduction rate >35.2%. Four patients had residual disease after chemoradiotherapy, whereas 64.7% (20 of 34) of patients achieved locoregional control. Conclusion: Implementation of adaptive radiotherapy in head and neck cancer offers benefits including improvement in tumor coverage and decrease in dose to organs at risk. The tumor volume reduction rate during treatment was significantly correlated with disease-free survival and overall survival.