bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic Cancer–Specific Cell Death Induced In Vivo by Cytoplasmic-Delivered Polyinosine–Polycytidylic Acid
Authors: Bhoopathi Praveen , Quinn Bridget A. , Gui Qin , Shen Xue-Ning , Grossman Steven R. , Das Swadesh K. , Sarkar Devanand , Fisher Paul B. , Emdad Luni 
Published: September 2014

Abstract
Polyinosine–polycytidylic acid [pIC] is a synthetic dsRNA that acts as an immune agonist of TLR3 and RLR to activate dendritic and natural killer cells that can kill tumor cells. pIC can also trigger apoptosis in pancreatic ductal adenocarcinoma cells (PDAC) but its mechanism of action is obscure. In this study, we investigated the potential therapeutic activity of a formulation of pIC with polyethylenimine ([pIC]PEI) in PDAC and investigated its mechanism of action. [pIC]PEI stimulated apoptosis in PDAC cells without affecting normal pancreatic epithelial cells. Mechanistically, [pIC]PEI repressed XIAP and survivin expression and activated an immune response by inducing MDA-5, RIG-I, and NOXA. Phosphorylation of AKT was inhibited by [pIC]PEI in PDAC, and this event was critical for stimulating apoptosis through XIAP and survivin degradation. In vivo administration of [pIC]PEI inhibited tumor growth via AKT-mediated XIAP degradation in both subcutaneous and quasi-orthotopic models of PDAC. Taken together, these results offer a preclinical proof-of-concept for the evaluation of [pIC]PEI as an immunochemotherapy to treat pancreatic cancer. Cancer Res; 74(21); 6224–35. ©2014 AACR.
Reducing CD73 Expression by IL1β-Programmed Th17 Cells Improves Immunotherapeutic Control of Tumors
Authors: Chatterjee Shilpak , Thyagarajan Krishnamurthy , Kesarwani Pravin , Song Jin H. , Soloshchenko Myroslawa , Fu Jianing , Bailey Stefanie R. , Vasu Chenthamarkshan , Kraft Andrew S. , Paulos Chrystal M. , Yu Xue-Zhong , Mehrotra Shikhar 
Published: September 2014

Abstract
T cells of the T helper (Th)17 subset offer promise in adoptive T-cell therapy for cancer. However, current protocols for ex vivo programming of Th17 cells, which include TGFβ exposure, increase the expression of CD39 and CD73, two cell surface ATP ectonucleotidases that reduce T-cell effector functions and promote immunosuppression. Here, we report that ATP-mediated suppression of IFNγ production by Th17 cells can be overcome by genetic ablation of CD73 or by using IL1β instead of TGFβ to program Th17 cells ex vivo. Th17 cells cultured in IL1β were also highly polyfunctional, expressing high levels of effector molecules and exhibiting superior short-term control of melanoma in mice, despite reduced stem cell-like properties. TGFβ addition at low doses that did not upregulate CD73 expression but induced stemness properties drastically improved the antitumor effects of IL1β-cultured Th17 cells. Effector properties of IL1β-dependent Th17 cells were likely related to their high glycolytic capacity, since ex vivo programming in pyruvate impaired glycolysis and antitumor effects. Overall, we show that including TGFβ in ex vivo cultures used to program Th17 cells blunts their immunotherapeutic potential and demonstrate how this potential can be more fully realized for adoptive T-cell therapy. Cancer Res; 74(21); 6048–59. ©2014 AACR.
Cisplatin-Induced Antitumor Immunomodulation: A Review of Preclinical and Clinical Evidence
Authors: de Biasi Andreas R. , Villena-Vargas Jonathan , Adusumilli Prasad S. 
Published: September 2014

Abstract
Contrary to the long held belief that chemotherapy is immunosuppressive, emerging evidence indicates that the anticancer activity of cisplatin is not limited to its ability to inhibit mitosis, but that cisplatin also has important immunomodulatory effects. We therefore methodically examined the relevant preclinical literature and identified four main mechanisms of cisplatin-induced antitumor immunomodulation: (i) MHC class I expression upregulation; (ii) recruitment and proliferation of effector cells; (iii) upregulation of the lytic activity of cytotoxic effectors; and (iv) downregulation of the immunosuppressive microenvironment. Cisplatin-based combination chemotherapy's antitumor immunomodulatory effects are also beginning to be harnessed in the clinic; we therefore additionally reviewed the applicable clinical literature and discussed how monitoring various components of the immune system (and their responses to cisplatin) can add new levels of sophistication to disease monitoring and prognostication. In summation, this growing body of literature on cisplatin-induced antitumor immunomodulation ultimately highlights the therapeutic potential of synergistic strategies that combine traditional chemotherapy with immunotherapy. Clin Cancer Res; 20(21); 5384–91. ©2014 AACR.
miR200c Attenuates P-gp–Mediated MDR and Metastasis by Targeting JNK2/c-Jun Signaling Pathway in Colorectal Cancer
Authors: Sui Hua , Cai Guo-Xiang , Pan Shu-Fang , Deng Wan-Li , Wang Yu-Wei , Chen Zhe-Sheng , Cai San-Jun , Zhu Hui-Rong , Li Qi 
Published: September 2014

Abstract
MicroRNA-200c (miR200c) recently emerged as an important regulator of tumorigenicity and cancer metastasis; however, its role in regulating multidrug resistance (MDR) remains unknown. In the current study, we found that the expression levels of miR200c in recurrent and metastatic colorectal cancers were significantly lower, whereas the JNK2 expression was higher compared with primary tumors. We showed that in MDR colorectal cancer cells, miR200c targeted the 3′ untranslated region of the JNK2 gene. Overexpression of miR200c attenuated the levels of p-JNK, p-c-Jun, P-gp, and MMP-2/-9, the downstream factors of the JNK signaling pathway, resulting in increased sensitivity to chemotherapeutic drugs, which was accompanied by heightened apoptosis and decreased cell invasion and migration. Moreover, in an orthotopic MDR colorectal cancer mouse model, we demonstrated that overexpression of miR200c effectively inhibited the tumor growth and metastasis. At last, in the tumor samples from patients with locally advanced colorectal cancer with routine postsurgical chemotherapy, we observed an inverse correlation between the levels of mRNA expression of miR200c and JNK2, ABCB1, and MMP-9, thus predicting patient therapeutic outcomes. In summary, we found that miR200c negatively regulated the expression of JNK2 gene and increased the sensitivity of MDR colorectal cancer cells to chemotherapeutic drugs, via inhibiting the JNK2/p-JNK/p-c-Jun/ABCB1 signaling. Restoration of miR200c expression in MDR colorectal cancer may serve as a promising therapeutic approach in MDR-induced metastasis. Mol Cancer Ther; 13(12); 3137–51. ©2014 AACR.
Inhibition of Mitochondrial P53 Abolishes the Detrimental Effects of Social Isolation on Ischemic Brain Injury
Authors: Venna Venugopal Reddy , Verma Rajkumar , O’Keefe Lena M. , Xu Yan , Crapser Joshua , Friedler Brett , McCullough Louise D. 
Published: September 2014

Background and Purpose—
Social isolation (SI) increases stroke incidence and delays poststroke recovery. Women may be at greater risk from the negative consequences of SI, but few studies have examined both sexes in experimental models, and none have evaluated the effects of isolation initiated after stroke. The effects of poststroke SI in men and women were examined, and the role of mitochondrial P53 was evaluated.

Methods—
C57Bl6 mice were pair-housed (PH; male and ovariectomized female) for 2 weeks, subjected to stroke and then assigned to a housing condition (isolated or PH). The effects of housing on infarct volume and recovery were examined. Changes in Bcl-2 and mitochondrial p53 were assessed by Western blot. A mitochondrial p53 inhibitor (pifithrin-μ) was given to mice of both sexes.

Results—
Compared with pair-housed mice, poststroke SI significantly increased infarct size in both sexes; SI mice also had worse neurological deficits. The detrimental effects of SI paralleled increases in mitochondrial p53 levels. Pharmacological inhibition of mitochondrial p53 using pifithrin-μ abolished the detrimental effects of SI and reduced cell death.

Conclusions—
Poststroke SI results in increased ischemic injury in both sexes. The effect of housing on infarct was more pronounced in women. Targeting the mitochondrial P53 pathway could minimize the detrimental effects of isolation after stroke.
An Orthotopic Mouse Model of Laryngeal Squamous Cell Carcinoma
Authors: Cohen Jacob T. , Gil Ziv , Binenbaum Yoav , Na’ara Shorook , Amit Moran 
Published: September 2014

Objective: This study aimed to create a reliable and reproducible orthotopic mouse model of laryngeal malignancy that recapitulates its biologic behavior, local invasiveness, and spread as seen in patients. Methods: Via direct laryngoscopy, human squamous cell carcinoma line FaDu (ATCC HTB-43) was implanted in the larynx (supraglottis and glottis) in nu/nu mice (n = 31). Animals were monitored with direct laryngoscopy and ultrasound for tumor growth and survival. Specimens of larynxes, neck lymphatics, livers, and lungs were removed for histopathologic evaluation to assess tumor extension, thyroid cartilage invasion, and nodal spread. Results: Thirty-one successful direct laryngoscopies were performed. Supraglottic and glottic tumor uptake was 100% and 25%, respectively. Median survival for the animals with supraglottic tumors was 35 days. Histopathologic evaluation revealed pre-epiglottic extension, paraglottic extension, thyroid cartilage invasion, and lymph node metastasis. Conclusion: We describe the first orthotopic model for laryngeal cancer. Our model faithfully recapitulates the phenotype and malignant behavior that reproduces its natural biologic behavior as seen in laryngeal cancer patients. This model offers an opportunity to identify and specifically target therapy for larynx squamous cell carcinoma.
Prognosis and Patterns of Failure for the Extubation of Patients Who Remain Intubated After Head and Neck Surgery
Authors: Graboyes Evan M. , Bradley Joseph P. , Kallogjeri Dorina , Cavallone Laura F. , Nussenbaum Brian 
Published: September 2014

Objective: This study aimed to analyze the rate of failure, patterns of failure, and prognostic factors for patients who remain intubated after head and neck surgery and then undergo delayed extubation. Methods: Retrospective chart review of all otolaryngology patients who remained intubated after head and neck surgery and then underwent delayed extubation between 2006 and 2013. The incidence and patterns of extubation failure were analyzed. Univariable logistic regression analysis was performed to identify risk factors for postextubation failure. Results: Fifteen of the 129 patients (12%) who remained intubated after head and neck surgery and underwent delayed extubation subsequently failed and required either repeat intubation or an emergency surgical airway. The most common reasons for failure were hemorrhage (47%) and upper airway edema (33%). Failure typically occurred within 6 hours of extubation. Twenty-seven percent of the patients who failed extubation (4/15) required an emergency surgical airway. On univariable logistic regression analysis, ligation of a major neck vessel predicted extubation failure (odds ratio = 5.20; 95% confidence interval, 1.48-18.23). Conclusion: Postextubation failure in carefully selected patients undergoing delayed extubation after head and neck surgery is infrequent and most commonly due to postoperative bleeding. Prospective data are required to facilitate safe and quality care for these patients.
Between modern and traditional values: Informal mental health help-seeking attitudes according to Israeli Arab women, primary care patients and their providers
Authors: Ayalon Liat , Karkabi Khaled , Bleichman Igor , Fleischmann Silvia , Goldfracht Margalit 
Published: September 2014

Background: Israeli Arab women under-utilize mental health services. Objectives: The present study evaluated the use of alternative services for dealing with depression and anxiety among Israeli Arab women and primary care providers. Material: Four focus groups with primary care patients and two focus groups with primary care providers were conducted. Constant comparisons were employed in order to identify major themes related to informal help-seeking behaviors. Discussion: Three informal help-seeking behaviors were identified: (a) social support, divided into extended family and neighbors versus nuclear family and close friends; (b) religiosity, divided into inner, direct practices and beliefs versus externally mediated ones; and (c) self-help techniques, such as engagement in activities and distancing oneself from the situation. Both social support and religiosity were viewed with ambivalence by primary care patients and providers. Conclusion: The findings suggest that the Arab population in Israel might be lacking informal sources of support at times of mental health needs.
Ensuring political responsiveness: politicization mechanisms in ministerial bureaucracies
Authors: Hustedt Thurid , Salomonsen Heidi Houlberg 
Published: September 2014

Although politicization is a perennial research topic in public administration to investigate relationships between ministers and civil servants, the concept still lacks clarification. This article contributes to this literature by systematically identifying different conceptualizations of politicization and suggests a typology including three politicization mechanisms to strengthen the political responsiveness of the ministerial bureaucracy: formal, functional and administrative politicization. The typology is empirically validated through a comparative case analysis of politicization mechanisms in Germany, Belgium, the UK and Denmark. The empirical analysis further refines the general idea of Western democracies becoming ‘simply’ more politicized, by illustrating how some politicization mechanisms do not continue to increase, but stabilize – at least for the time being. Points for practitioners The claim of increasing politicization of the interaction between ministers and civil servants is often made in research and government practice. As the completely neutral bureaucracy is a myth rather than empirical reality, all democracies have to balance demands for both neutral expertise and political responsiveness. The latter often involves the introduction of politicization mechanisms. Politicization comes in a variety of forms, and the article develops a typology covering formal, functional and administrative politicization. Further it empirically demonstrates how politicization mechanisms not only increase, but how they develop and interact, altering balances of neutrality and responsiveness in potentially conflicting ways.
Citizen participation as a contributor to sustainable democracy in South Africa
Authors: Lues Liezel 
Published: September 2014

Academe has argued that democracy cannot be effective on its own, but is reliant on the government and citizens to sustain it. For the South African democracy to be sustained, the roles of the government and the citizens need to be integrated to ensure accountability, transparency, effectiveness and good quality provision of public services to the citizens. The aim of this study is to establish what students view as the role of the government, and of citizens, in strengthening South African democracy. To this effect, information was collected by means of a survey targeting students enrolled for modules in Public Administration and Management at a South African university. It emerged that the respondents deemed it important to educate themselves about democracy as well as the monitoring of politicians' behaviour. The findings further indicated that the respondents considered issues such as education, health, public order and safety, and job creation to a lesser extent, to be key roles of government. The article concludes by contemplating the importance of educating citizens in strengthening the South African democracy with special reference to the South African Medium Term Strategic Framework, and its 12 outcomes. Points for practitioners This article evaluates current South African democracy with reference to the different roles of both government and citizens, respectively. The study revealed the perceptions of students enrolled for modules in Public Administration and Management at a South African university regarding the role of government and citizens in the creation of a sustainable democracy. Furthermore, background information is given on the South African growth path towards democracy and equality.
Clinical and Radiological Long-term Outcomes After Matrix-Induced Autologous Chondrocyte Transplantation
Authors: Aldrian Silke , Zak Lukas , Wondrasch Barbara , Albrecht Christian , Stelzeneder Beate , Binder Harald , Kovar Florian , Trattnig Siegfried , Marlovits Stefan 
Published: September 2014

Background: It is unclear whether matrix-associated autologous chondrocyte transplantation (MACT) results in objective and subjective clinical improvements at 10 years after surgery. Hypothesis: Matrix-associated autologous chondrocyte transplantation will result in clinical and radiological improvements in patients with symptomatic, traumatic chondral defects of the knee joint. Study Design: Case series; Level of evidence, 4. Methods: A total of 16 patients with chondral defects of the knee were treated with MACT between November 2000 and April 2002 and evaluated for up to 10 years after the intervention. The International Knee Documentation Committee (IKDC) form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner activity score, Brittberg score, Noyes sports activity rating scale, and visual analog scale (VAS) for pain as well as 3-T magnetic resonance imaging (MRI) using the magnetic resonance observation of cartilage repair tissue (MOCART) score and functional evaluation by the limb symmetry index (LSI) formed the basis of this study. The Friedman test and the Wilcoxon signed-rank test were performed for a comparison between all time points and 2 separate time points, respectively. If significant differences were revealed, a Bonferroni adjustment to the α level was applied so that P values <.007 (<.05/7) were regarded as significant in the paired comparisons. Results: Significant improvements ( P < .05) from baseline to 120 months postoperatively were observed for the IKDC score (mean, 44.1 ± 26.9 to 59.0 ± 27.4), Noyes sports activity rating score (mean, 37.7 ± 30.1 to 62.1 ± 31.3), and KOOS Quality of Life and Pain subscores, whereas no statistically significant improvement was detected for the Brittberg score, Tegner activity score, or VAS score. After 5 years, a slight downward tendency of all clinical scores was evident. After 10 years, the mean MOCART score was 70.4 ± 16.1. Complete filling of the defect was observed in 73.9% of cases, and osteophytes were present in 78.3%. In 65.2% of the cases, a subchondral bone edema <1 cm was visible, whereas in 21.7% of the cases, a subchondral bone edema >1 cm was seen. The mean LSI for the single-legged hop test was 95.6% ± 16.2% and for the triple hop test for distance was 91.3% ± 12.2%. The mean VAS score for self-perceived stability was 60.2 ± 3.5 (range, 0-9.5) for the injured and 60.7 ± 3.8 (range, 0-10) for the uninjured leg. No adhesions or effusions were seen regarding the clinical and radiological outcomes. Conclusion: The significantly improved results on 3 outcome measures after 10 years suggest that MACT represents a suitable option in the treatment of local cartilage defects in the knee.
An Opening Door
Authors: Le Clézio JMG 
Published: September 2014

AbstractThe author of this paper, a Nobel Laureate in Literature (2008), develops here a plea in favour of the practice of interculturality. He takes the case of its family's historic birthplace, the Island of Mauritius, as an example of intercultural human coexistence, and analyses its achievements, challenges, and possible developments in today's world.
The application of smart cards in hotels
Authors: Friel Martin 
Published: September 2014

At the moment there is limited use of smart cards in hotels although the industry has begun to recognise their potential and more implementations are in the pipeline. Certain features of the smart card are examined in the light of their relevance for, and potential impact on, hotel marketing activities. The smart card is adjudged to enhance the speed, accuracy and economy with which an array of hotel marketing activities can be carried out, in particular customer profiling, promotions, distribution and loyalty schemes with an eventual impact on quality of service. The smart card, however, is not a panacea and indeed the swipe card already performs many of the same functions, albeit more laborioursly.
Gait and Apathy as Relevant Symptoms of Subcortical Vascular Dementia
Authors: Moretti Rita , Cavressi Monica , Tomietto Paola 
Published: September 2014

Background: Subcortical vascular dementia relates to small-vessel disease and hypoperfusion, resulting in focal and diffuse ischemic white matter lesions. The main target of the disease are the frontal subcortical neural networks. There is no clinical standard definition of the pathology, on the contrary, everyday clinical practice suggests dominant behavioral alterations and dysexecutive syndrome. Methods: The aim of this study was to investigate gait disorders, behavioral alteration, and drug intake of a subcortical population with dementia (n = 1155). A complete neuropsychological examination was conducted at baseline and every 6 months, and the results were compared. Results: Our data suggest that there is a significant increment in apathy levels and a dramatic decrease in gait and equilibrium control in the patients examined during follow-up. Conclusion: Subcortical vascular dementia may be associated with gait and balance alteration and apathy per se; we suggest to implement clinical data with these major aspects.
Performance of standard procedures in detection of EGFR mutations in daily practice in advanced NSCLC patients selected according to the ESMO guideline: a large Caucasian cohort study
Authors: Hantson Inge , Dooms Christophe , Verbeken Eric , Vandenberghe Peter , Vliegen Liesbet , Roskams Tania , Borght Sara Vander , Nackaerts Kris , Wauters Isabelle , Vansteenkiste Johan 
Published: September 2014

Abstract

Background
ESMO consensus recommends EGFR mutation testing in never/former light smokers (<15 pack-years) or patients with non-squamous NSCLC. The aim of this work was to determine the frequency and clinical predictors of EGFR mutations, and the role of specimen sampling tests, in Caucasian standard practice setting.

Methods
We screened 297 patients according to this consensus. Mutational analysis of EGFR was performed using the Therascreen EGFR RGQ PCR mutation kit. Clinical and pathological correlative data were collected.

Results
An EGFR activating mutation was found in 32 patients (11%), twelve exon 19 deletions, two exon 18 and eighteen exon 21 point mutations. Most were in females, but half were in smokers. Negative TTF-1 staining had a very strong negative predictive value (all except one patient had TTF-1 positive adenocarcinoma). Both biopsies as well as cytology specimens (mainly EBUS-TBNA) did well: 24 mutations in 213 biopsy samples (11.2%) and 8 in 84 cytology samples (9.5%), respectively. The Therascreen acted as a sensitive test in all types of samples: 7 activating mutations were found in samples rated to have <5% of tumour cells, and there were only 4 test failures in the whole series.

Conclusion
In this Caucasian standard practice NSCLC cohort, tested according to the ESMO consensus, activating EGFR mutation occurred in 11% of the patients. Half of these were in former/current smokers. With our sampling technique and use of the Therascreen kit, EBUS-TBNA cell blocks performed as good as biopsies.