bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of feeding management and time of day on the occurrence of self‐suckling in dairy goats
Authors: Martínez‐de la Puente J. , Moreno‐Indias I. , Morales‐Delanuez A. , Ruiz‐Díaz M. D. , Hernández‐Castellano L. E. , Castro N. , Argüello A. 
Published: March 2011

The occurrence of self‐suckling was recorded in 21 dairy goats during periods of 20 minutes at three different times per day (immediately after milking and the first feed, immediately after the second feed and in the afternoon) for 27 days (divided into three experimental periods of nine days). As expected, negative associations between milk yield and the frequency of self‐suckling were observed (P<0.05). Goats suckled on their own right teat more frequently than on the left teat. The width of the right teat (measured at the middle of the teat) was positively associated with the frequency of self‐suckling after controlling for the width of the left teat. A higher self‐suckling frequency was observed immediately after milking than in the other two periods of the day. The frequency of self‐suckling by each goat was reduced when animals were supplemented ad libitum with wheat straw in addition to their ordinary feed.
Role for Stromal Heterogeneity in Prostate Tumorigenesis
Authors: Kiskowski Maria A. , Jackson Roger S. , Banerjee Jheelam , Li Xiaohong , Kang Minchul , Iturregui Juan M. , Franco Omar E. , Hayward Simon W. , Bhowmick Neil A. 
Published: March 2011

Abstract
Prostate cancer develops through a stochastic mechanism whereby precancerous lesions on occasion progress to multifocal adenocarcinoma. Analysis of human benign and cancer prostate tissues revealed heterogeneous loss of TGF-β signaling in the cancer-associated stromal fibroblastic cell compartment. To test the hypothesis that prostate cancer progression is dependent on the heterogeneous TGF-β responsive microenvironment, a tissue recombination experiment was designed in which the ratio of TGF-β responsive and nonresponsive stromal cells was varied. Although 100% TGF-β responsive stromal cells supported benign prostate growth and 100% TGF-β nonresponsive stromal cells resulted in precancerous lesions, only the mixture of TGF-β responsive and nonresponsive stromal cells resulted in adenocarcinoma. A computational model was used to resolve a mechanism of tumorigenic progression in which proliferation and invasion occur in two independent steps mediated by distinct stromally derived paracrine signals produced by TGF-β nonresponsive and responsive stromal cells. Complex spatial relationships of stromal and epithelial cells were incorporated into the model on the basis of experimental data. Informed by incorporation of experimentally derived spatial parameters for complex stromal–epithelial relationships, the computational model indicated ranges for the relative production of paracrine factors by each cell type and provided bounds for the diffusive range of the molecules. Because SDF-1 satisfied model predictions for an invasion-promoting paracrine factor, a more focused computational model was subsequently used to investigate whether SDF-1 was the invasion signal. Simulations replicating SDF-1 expression data revealed the requirement for cooperative SDF-1 expression, a prediction supported biologically by heterotypic stromal interleukin-1β signaling between fibroblastic cell populations. The cancer stromal field effect supports a functional role for the unaltered fibroblasts as a cooperative mediator of cancer progression. Cancer Res; 71(10); 3459–70. ©2011 AACR.
STAT3 Mediates Resistance to MEK Inhibitor through MicroRNA miR-17
Authors: Dai Bingbing , Meng Jieru , Peyton Michael , Girard Luc , Bornmann William G. , Ji Lin , Minna John D. , Fang Bingliang , Roth Jack A. 
Published: March 2011

Abstract
AZD6244 is a small molecule inhibitor of the MEK (MAP/ERK kinase) pathway currently in clinical trials. However, the mechanisms mediating intrinsic resistance to MEK inhibition are not fully characterized. To define molecular mechanisms of MEK inhibitor resistance, we analyzed responses of 38 lung cancer cell lines following AZD6244 treatment and their genome-wide gene expression profiles and identified a panel of genes correlated with sensitivity or resistance to AZD6244 treatment. In particular, ingenuity pathway analysis revealed that activation of the STAT3 pathway was associated with MEK inhibitor resistance. Inhibition of this pathway by JSI-124, a STAT3-specific small molecule inhibitor, or with STAT3-specific siRNA sensitized lung cancer cells to AZD6244 and induced apoptosis. Moreover, combining a STAT3 inhibitor with AZD6244 induced expression of BIM and PARP cleavage, whereas activation of the STAT3 pathway inhibited BIM expression and elicited resistance to MEK inhibitors. We found that the STAT3-regulated microRNA miR-17 played a critical role in MEK inhibitor resistance, such that miR-17 inhibition sensitized resistant cells to AZD6244 by inducing BIM and PARP cleavage. Together, these results indicated that STAT3-mediated overexpression of miR-17 blocked BIM expression and caused resistance to AZD6244. Our findings suggest novel approaches to overcome resistance to MEK inhibitors by combining AZD6244 with STAT3 or miR-17 inhibitors. Cancer Res; 71(10); 3658–68. ©2011 AACR.
Differential Expression of S6K2 Dictates Tissue-Specific Requirement for S6K1 in Mediating Aberrant mTORC1 Signaling and Tumorigenesis
Authors: Nardella Caterina , Lunardi Andrea , Fedele Giuseppe , Clohessy John G. , Alimonti Andrea , Kozma Sara C. , Thomas George , Loda Massimo , Pandolfi Pier Paolo 
Published: March 2011

Abstract
The S6K1 and S6K2 kinases are considered important mTOR signaling effectors, yet their contribution to tumorigenesis remains unclear. Aberrant mTOR activation is a frequent event in cancer that commonly results from heterozygous loss of PTEN. Here, we show for the first time a differential protein expression between S6K1 and S6K2 in both mouse and human tissues. Additionally, the inactivation of S6k1 in the context of Pten heterozygosity (Pten+/−) suggests a differential requirement for this protein across multiple tissues. This tissue specificity appears to be governed by the relative protein expression of S6k2. Accordingly, we find that deletion of S6k1 markedly impairs Pten+/− mediated adrenal tumorigenesis, specifically due to low expression of S6k2. Concomitant observation of low S6K2 levels in the human adrenal gland supports the development of S6K1 inhibitors for treatment of PTEN loss–driven pheochromocytoma. Cancer Res; 71(10); 3669–75. ©2011 AACR.
Tumor-Evoked Regulatory B Cells Promote Breast Cancer Metastasis by Converting Resting CD4+ T Cells to T-Regulatory Cells
Authors: Olkhanud Purevdorj B. , Damdinsuren Bazarragchaa , Bodogai Monica , Gress Ronald E. , Sen Ranjan , Wejksza Katarzyna , Malchinkhuu Enkhzol , Wersto Robert P. , Biragyn Arya 
Published: March 2011

AbstractPulmonary metastasis of breast cancer requires recruitment and expansion of T-regulatory cells (Treg) that promote escape from host protective immune cells. However, it remains unclear precisely how tumors recruit Tregs to support metastatic growth. Here we report the mechanistic involvement of a unique and previously undescribed subset of regulatory B cells. These cells, designated tumor-evoked Bregs (tBreg), phenotypically resemble activated but poorly proliferative mature B2 cells (CD19+ CD25High CD69High) that express constitutively active Stat3 and B7-H1High CD81High CD86High CD62LLow IgMInt. Our studies with the mouse 4T1 model of breast cancer indicate that the primary role of tBregs in lung metastases is to induce TGF-β–dependent conversion of FoxP3+ Tregs from resting CD4+ T cells. In the absence of tBregs, 4T1 tumors cannot metastasize into the lungs efficiently due to poor Treg conversion. Our findings have important clinical implications, as they suggest that tBregs must be controlled to interrupt the initiation of a key cancer-induced immunosuppressive event that is critical to support cancer metastasis. Cancer Res; 71(10); 3505–15. ©2011 AACR.
Following Cytochrome c Release, Autophagy Is Inhibited during Chemotherapy-Induced Apoptosis by Caspase 8–Mediated Cleavage of Beclin 1
Authors: Li Hua , Wang Peng , Sun Quanhong , Ding Wen-Xing , Yin Xiao-Ming , Sobol Robert W. , Stolz Donna B. , Yu Jian , Zhang Lin 
Published: March 2011

Abstract
Autophagy is an evolutionarily conserved stress response mechanism that often occurs in apoptosis-defective cancer cells and can protect against cell death. In this study, we investigated how apoptosis and autophagy affect each other in cancer cells in response to chemotherapeutic treatment. We found that specific ablation of the proapoptotic function of cytochrome c, a key regulator of mitochondria-mediated apoptosis, enhanced autophagy following chemotherapeutic treatment. Induction of autophagy required Beclin 1 and was associated with blockage of Beclin 1 cleavage by caspase 8 at two sites. To investigate the role of Beclin 1 cleavage in the suppression of autophagy and cell survival, a caspase-resistant mutant of Beclin 1 was knocked into HCT116 colon cancer cells. Beclin 1 mutant knockin resulted in markedly increased autophagy and improved long-term cell survival after chemotherapeutic treatment but without affecting apoptosis and caspase activation. Furthermore, Beclin 1 mutant tumors were significantly less responsive to chemotherapeutic treatment than were wild-type tumors. These results show that chemotherapy-induced apoptosis inhibits autophagy at the execution stage subsequent to cytochrome c release through caspase 8–mediated cleavage of Beclin 1. If apoptosis fails to execute, autophagy is unleashed due to lack of Beclin 1 cleavage by caspases and can contribute to cancer cell survival and therapeutic resistance. Therefore, Beclin 1 may be a useful target for inhibiting autophagy to sensitize chemotherapy. Cancer Res; 71(10); 3625–34. ©2011 AACR.
Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy
Authors: Wu Chih-Hsiung , Lee Chia-Hwa , Ho Yuan-Soon 
Published: March 2011

AbstractThe nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and α-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that α9-nAChR is important for breast cancer formation, and in many in vivo studies, α9-nAChR–specific antagonists (e.g., α-ImI, α-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine- and estrogen-induced breast cancer cell proliferation through inhibition of the α9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation. Clin Cancer Res; 17(11); 3533–41. ©2011 AACR.
Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis
Authors: Jamieson Nigel B. , Carter C. Ross , McKay Colin J. , Oien Karin A. 
Published: March 2011

Abstract
Purpose: The management of pancreatic ductal adenocarcinoma (PDAC) continues to present a great challenge particularly with regard to prediction of outcome following pancreaticoduodenectomy. Molecular markers have been extensively investigated by numerous groups with the aim of enhancing prognostication; however, despite hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the clinical course following resection of PDAC, at this time, no molecular marker assay forms part of recommended clinical practice.
Experimental Design: We conducted a systematic review and meta-analysis of the published literature for immunohistochemistry-based biomarkers of PDAC outcome. A dual search strategy was applied to the PubMed database on January 6, 2010, to identify cohort studies that reported associations between immunohistochemical biomarker expression and survival outcomes in PDAC, and conformed to the REMARK (REporting recommendations for tumor MARKer prognostic studies) criteria.
Results: A total of 103 distinct proteins met all inclusion criteria. Promising markers that emerged for the prediction of overall survival included BAX (HR = 0.31, 95% CI: 0.71–0.56), Bcl-2 (HR = 0.41, 95% CI: 0.27–0.63), survivin (HR = 0.46, 95% CI: 0.29–0.73), Ki-67: (HR = 2.42, 95% CI: 1.87–3.14), COX-2 (HR = 1.39, 95% CI: 1.13–1.71), E-cadherin (HR = 1.80, 95% CI: 1.33–2.42), and S100 calcium-binding proteins, in particular S100A2 (HR = 3.23, 95% CI: 1.58–6.62).
Conclusions: We noted that that there was incomplete adherence to the REMARK guidelines with inadequate methodology reporting as well as failure to perform multivariate analysis. Addressing the persistent incomplete adoption of these criteria may eventually result in the incorporation of molecular marker assessment within PDAC management algorithms. Clin Cancer Res; 17(10); 3316–31. ©2011 AACR.
Effects of Optimal Medical Treatment With or Without Coronary Revascularization on Angina and Subsequent Revascularizations in Patients With Type 2 Diabetes Mellitus and Stable Ischemic Heart Disease
Authors: Dagenais Gilles R. , Lu Jiang , Faxon David P. , Kent Kenneth , Lago Rodrigo M. , Lezama Carlos , Hueb Whady , Weiss Melvin , Slater James , Frye Robert L. ,   the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Study Group
Published: March 2011

Background—
In the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, an initial strategy of coronary revascularization and optimal medical treatment (REV) compared with an initial optimal medical treatment with the option of subsequent revascularization (MED) did not reduce all-cause mortality or the composite of cardiovascular death, myocardial infarction, and stroke in patients with type 2 diabetes mellitus and stable ischemic heart disease. In the same population, we tested whether the REV strategy was superior to the MED strategy in preventing worsening and new angina and subsequent coronary revascularizations.

Methods and Results—

Among the 2364 men and women (mean age, 62.4 years) with type 2 diabetes mellitus, documented coronary artery disease, and myocardial ischemia, 1191 were randomized to the MED and 1173 to the REV strategy preselected in the percutaneous coronary intervention (796) and coronary artery bypass graft (377) strata. Compared with the MED strategy, the REV strategy at the 3-year follow-up had a lower rate of worsening angina (8% versus 13%;
P
<0.001), new angina (37% versus 51%;
P
=0.001), and subsequent coronary revascularizations (18% versus 33%;
P
<0.001) and a higher rate of angina-free status (66% versus 58%;
P
=0.003). The coronary artery bypass graft stratum patients were at higher risk than those in the percutaneous coronary intervention stratum, and had the greatest benefits from REV.

Conclusions—
In these patients, the REV strategy reduced the occurrence of worsening angina, new angina, and subsequent coronary revascularizations more than the MED strategy. The symptomatic benefits were observed particularly for high-risk patients.

Clinical Trial Registration—

URL:
http://www.ClinicalTrials.gov
. Unique identifier: NCT00006305.
Endothelial Function in Resistance and Conduit Arteries and 5-Year Risk of Cardiovascular Disease
Authors: Lind Lars , Berglund Lars , Larsson Anders , Sundström Johan 
Published: March 2011

Background—
Impaired endothelial function has been implicated as a cause of cardiovascular disease. Little is known of the relations of measures of endothelial function in resistance and conduit arteries to incident cardiovascular disease in the general population, and available techniques have not been compared.

Methods and Results—

In 1016 participants (70 years of age) of the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (52% women), we measured endothelium-dependent vasodilation using the invasive forearm technique with acetylcholine given in the brachial artery, the brachial artery ultrasound technique with measurement of flow-mediated dilatation, and the pulse-wave analysis–based method with β-2-agonist terbutaline provocation. During 5 years of follow-up, 101 participants experienced a composite end point of myocardial infarction, stroke, or death, excluding the 85 persons with a history of myocardial infarction or stroke at baseline. In logistic regression models adjusted for several established and novel cardiovascular disease risk factors and medications, endothelium-dependent vasodilation by the invasive forearm technique with acetylcholine was associated with risk of the end point (odds ratio, 0.72 per SD; 95% confidence interval, 0.56 to 0.93;
P
=0.01). Endothelial function by the other 2 methods was not related to risk of the end point. Addition of endothelium-dependent vasodilation to the Framingham risk score improved discrimination of risk of the end point.

Conclusions—
Endothelium-dependent vasodilation in resistance arteries, but not in the brachial conduit artery (flow-mediated dilatation), was associated with 5-year risk of a composite end point of death, myocardial infarction, or stroke independently of major cardiovascular disease risk factors. This vascular measurement improved risk discrimination when added to an established risk score in an elderly population.
The effect of an education program utilising PRECEDE model on the Quality of Life in patients with type 2 diabetes
Authors: Taghdisi MH , Borhani M , Solhi M , Afkari ME , Hosseini F 
Published: March 2011

Background and objective: The problems caused by diabetes have direct and indirect impacts on the quality of life of diabetic patients. An increase of these problems means a decrease in a patient’s quality of life. This study was conducted to assess the effect of the educational programme based on the precede model in promoting quality of life of patients with type 2 diabetes. Design and methods: This pre- and post-intervention quasi-experimental study was conducted on 78 patients with type 2 diabetes who were referred to a diabetes clinic in Minoodasht, Iran. The educational programme was based on the precede model and patients’ educational needs were included in the design. The data were collected using two questionnaires, including The World Health Organization Quality of Life (WHOQOL) questionnaire and the precede model-based educational questionnaire. The subjects were followed for one month after intervention to identify the role of educational intervention them. The data were analyzed by paired sample t-test, variance of analysis test and bivariate correlation test using SPSS version 15. Results: After the intervention, the mean score of quality of life increased from 80.39 ± 11.35 to 81.35 ± 8.31. No significant difference existed in the total score of quality of life after intervention, but there were significant differences in physical health ( p < 0.05), self-evaluation of quality of life by patients ( p < 0.01), and self-assessment of health by patients after educational intervention. In addition, no significant differences were observed between demographic parameters and quality of life, except in the number of children. Conclusion: The educational programme based on the precede model was effective in improving the quality of life of patients with regard to physical health and self-assessment of their health status.
Biomechanical in Vitro Validation of Intramedullary Cortical Button Fixation for Distal Biceps Tendon Repair
Authors: Siebenlist Sebastian , Lenich Andreas , Buchholz Arne , Martetschläger Frank , Eichhorn Stefan , Heinrich Petra , Fingerle Alexander , Doebele Stefan , Sandmann Gunther H. , Millett Peter J. , Stöckle Ulrich , Elser Florian 
Published: March 2011

Background Extramedullary cortical button–based fixation for distal biceps tendon ruptures exhibits maximum load to failure in vitro but cannot restore the anatomic footprint and has the potential risk for injury to the posterior interosseous nerve. Hypothesis Double intramedullary cortical button fixation repair provides superior fixation strength to the bone when compared with single extramedullary cortical button–based repair. Study Design Controlled laboratory study. Methods The technique of intramedullary cortical button fixation with 1 or 2 buttons was compared with single extramedullary cortical button–based repair using 12 paired human cadaveric elbows. All specimens underwent computed tomography analysis to determine intramedullary dimensions of the radial tuberosity as well as the thickness of the anterior and posterior cortices before biomechanical testing. Maximum load to failure and failure modes were recorded. For baseline measurements, the native tendon was tested for maximum load to failure. Results The intramedullary area of the radial tuberosity provides sufficient space for single or double intramedullary cortical button implantation. The mean thickness of the anterior cortex was 1.13 ± 0.15 mm, and for the posterior cortex it was 1.97 ± 0.48 mm ( P < .001). We found the highest loads to failure for double intramedullary cortical button fixation with a mean load to failure of 455 ± 103 N, versus 275 ± 44 N for single intramedullary cortical button fixation ( P < .001) and 305 ± 27 N for single extramedullary cortical button–based technique ( P = .003). There were no statistically significant differences between single intramedullary and single extramedullary button fixation repair ( P = .081). The mean load to failure for the native tendon was 379 ± 87 N. Conclusion Double intramedullary cortical button fixation provides the highest load to failure in the specimens tested. Clinical Relevance Double intramedullary cortical button fixation provides reliable fixation strength to the bone for distal biceps tendon repair and potentially minimizes the risk of posterior interosseous nerve injury. Further, based on a 2-point-fixation, this method may offer a wider, more anatomic restoration of the distal biceps tendon to its anatomic footprint.
Goodwin or Kalecki in Demand? Functional Income Distribution and Aggregate Demand in the Short Run
Authors: Stockhammer Engelbert , Stehrer Robert 
Published: March 2011

In a seminal paper on Marxian business cycle theory, Goodwin (1967) presented a model which assumed that a higher wage share leads to lower investment and thus a general economic slowdown. In contrast Kalecki (1971) was arguing that a higher wage share would have an expansionary effect because the consumption propensity out of wage income is higher than that out of profit income. Based on a general model that allows for wage-led as well as profit-led demand regimes, this paper estimates the effects of a change in the wage share on aggregate private domestic demand with quarterly data for 12 OECD countries. JEL classification: E11, E12, E20, E22, E25
Evaluation and Management of Posterior Shoulder Instability
Authors: Tannenbaum Eric , Sekiya Jon K. 
Published: March 2011

Context: Posterior shoulder instability is a commonly misdiagnosed disorder in many competitive athletes. Type of Study: Clinical review. Evidence Acquisition: Relevant studies on posterior shoulder instability from 1950 to 2010 in PubMed and Cochrane databases were reviewed. Results: A total of 107 studies were reviewed. Conclusion: Patients who have undergone at least 6 months of physical therapy and still experience instability symptoms should be considered for surgical stabilization directed at their underlying pathology.