bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulated IL-19 in Breast Cancer Promotes Tumor Progression and Affects Clinical Outcome
Authors: Hsing Chung-Hsi , Cheng Hung-Chi , Hsu Yu-Hsiang , Chan Chien-Hui , Yeh Ching-Hua , Li Chien-Feng , Chang Ming-Shi 
Published: December 2011

Abstract
Purpose: Interleukin (IL)-19 was expressed in invasive ductal carcinoma (IDC) of the breast tissue but not in healthy breast tissue. We explored the effects of IL-19 on the pathogenesis of breast cancer and its clinical outcome.
Experimental Design: Tumor expression of IL-19 was assessed by immunohistochemistry and/or real-time quantitative PCR between two groups of patients with breast IDC (n = 60 and 143, respectively) with available clinical and survival data. We examined the effects of IL-19 on cytokine and chemokine production as well as proliferation and migration in breast cancer cells. Mice were injected with IL-19–overexpressing or vector control 67NR cells and the tumor growth and lung metastatic micronodules were measured.
Results: Of the IDC specimens, high IL-19 expression was associated with advanced tumor stage, high tumor metastasis, and worse survival. In vitro, IL-19 induced transcripts of IL-1β, IL-6, TGF-β, matrix metalloproteinase (MMP)2, MMP9, and CXCR4 in 4T1 breast cancer cells; induced fibronectin expression and assembly; and promoted cancer cell proliferation and migration, which were inhibited by anti-IL-19 monoclonal antibody (mAb). Endogenous fibronectin expression and cancer cell migration were lower in IL-19 knockdown 4T1 cells. In 4T1 cells, hypoxia induced IL-19 and CXCR4 expression, which was inhibited by anti-IL-19 mAb. IL-19 overexpression in noninvasive 67NR cancer cells increased cell proliferation and migration. In vivo, mice injected with IL-19–overexpressing 67NR cell clones showed larger tumors and more metastatic micronodules in the lung.
Conclusions: High IL-19 expression in breast cancer tissue is associated with a poor clinical outcome. IL-19 is pivotal in the pathogenesis of breast cancer. Clin Cancer Res; 18(3); 713–25. ©2011 AACR.
MiR-1 Downregulation Cooperates with MACC1 in Promoting MET Overexpression in Human Colon Cancer
Authors: Migliore Cristina , Martin Valentina , Leoni Vera P. , Restivo Angelo , Atzori Luigi , Petrelli Annalisa , Isella Claudio , Zorcolo Luigi , Sarotto Ivana , Casula Giuseppe , Comoglio Paolo M. , Columbano Amedeo , Giordano Silvia 
Published: December 2011

Abstract
Purpose: MET, the tyrosine kinase receptor for hepatocyte growth factor, is frequently overexpressed in colon cancers with high metastatic tendency. We aimed to evaluate the role of its negative regulators, miR-1 and miR-199a*, and its transcriptional activator, the metastasis-associated in colon cancer 1 (MACC1), in controlling MET expression in human colon cancer samples.
Experimental Design: The expression of MET, miR-1, miR-199a*, and MACC1 was evaluated by real-time PCR in 52 matched pairs of colorectal cancers and nontumoral surrounding tissues. The biological role of miR-1 in controlling MET expression and biological activity was assessed in colon cancer cells either by its forced expression or by AntagomiR-mediated inhibition.
Results: MiR-1 was downregulated in 84.6% of the tumors and its decrease significantly correlated with MET overexpression, particularly in metastatic tumors. We found that concurrent MACC1 upregulation and miR-1 downregulation are required to elicit the highest increase of MET expression. Consistent with a suppressive role of miR-1, its forced in vitro expression in colon cancer cells reduced MET levels and impaired MET-induced invasive growth. Finally, we identified a feedback loop between miR-1 and MET, resulting in their mutual regulation.
Conclusions: This study identifies an oncosuppressive role of miR-1 in colorectal cancer in which it acts by controlling MET expression through a feedback loop. Concomitant downregulation of miR-1 and increase of MACC1 can thus contribute to MET overexpression and to the metastatic behavior of colon cancer cells. Clin Cancer Res; 18(3); 737–47. ©2011 AACR.
Dovitinib Induces Apoptosis and Overcomes Sorafenib Resistance in Hepatocellular Carcinoma through SHP-1–Mediated Inhibition of STAT3
Authors: Tai Wei-Tien , Cheng Ann-Lii , Shiau Chung-Wai , Liu Chun-Yu , Ko Ching-Huai , Lin Mai-Wei , Chen Pei-Jer , Chen Kuen-Feng 
Published: December 2011

Abstract
The multiple kinase inhibitor dovitinib is currently under clinical investigation for hepatocellular carcinoma (HCC). Here, we investigated the mechanistic basis for the effects of dovitinib in HCCs. Dovitinib showed significant antitumor activity in HCC cell lines PLC5, Hep3B, Sk-Hep1, and Huh-7. Dovitinib downregulated phospho-STAT3 (p-STAT3) at tyrosine 705 and subsequently reduced the levels of expression of STAT3-related proteins Mcl-1, survivin, and cyclin D1 in a time-dependent manner. Ectopic expression of STAT3 abolished the apoptotic effect of dovitinib, indicating that STAT3 is indispensable in mediating the effect of dovitinib in HCC. SHP-1 inhibitor reversed downregulation of p-STAT3 and apoptosis induced by dovitinib, and silencing of SHP-1 by RNA interference abolished the effects of dovitinib on p-STAT3, indicating that SHP-1, a protein tyrosine phosphatase, mediates the effects of dovitinib. Notably, dovitinib increased SHP-1 activity in HCC cells. Incubation of dovitinib with pure SHP-1 protein enhanced its phosphatase activity, indicating that dovitinib upregulates the activity of SHP-1 via direct interactions. In addition, dovitinib induced apoptosis in two sorafenib-resistant cell lines through inhibition of STAT3, and sorafenib-resistant cells showed significant activation of STAT3, suggesting that targeting STAT3 may be a useful approach to overcome drug resistance in HCC. Finally, in vivo, dovitinib significantly suppressed growth of both Huh-7 and PLC5 xenograft tumors and downregulated p-STAT3 by increasing SHP-1 activity. In conclusion, dovitinib induces significant apoptosis in HCC cells and sorafenib-resistant cells via SHP-1–mediated inhibition of STAT3. Mol Cancer Ther; 11(2); 452–63. ©2011 AACR.
βII-Tubulin and βIII-Tubulin Mediate Sensitivity to Peloruside A and Laulimalide, but not Paclitaxel or Vinblastine, in Human Ovarian Carcinoma Cells
Authors: Kanakkanthara Arun , Northcote Peter T. , Miller John H. 
Published: December 2011

Abstract
Increased abundance of βII- and βIII-tubulin isotypes in cancer cells confers resistance to vinca and taxoid site drugs; however, the role of these isotypes in the acquired resistance of cancer cells to non-vinca or non-taxoid site binding agents has not been described. Peloruside A (PLA) and laulimalide are the only known non-taxoid site microtubule-stabilizing agents. A human ovarian cancer cell line, 1A9-L4 (L4), previously selected in high concentrations of laulimalide, has both a single point mutation in βI-tubulin and overexpression of βII- and βIII-tubulin. The cells are highly resistant to PLA as well as laulimalide but show no cross-resistance to taxoid site drugs or drugs that bind to the vinca site on β-tubulin. To understand the functional significance of the βII- and βIII-tubulin changes in this resistant cell line, isotype-specific short interfering RNA was used to knock down the expression of the βII and βIII isotypes, and the cellular effects of PLA and laulimalide were examined before and after silencing. It was found that inhibition of βII- and βIII-tubulin partially sensitized L4 cells to PLA and laulimalide, as seen by increased potency of PLA and laulimalide for inducing growth inhibition, cellular tubulin polymerization, microtubule aberrations, and G2-M arrest in the resistant cells. The sensitivity to paclitaxel, vinblastine, ixabepilone, and cisplatin was unaffected by the inhibition of isotype expression. It was concluded that the increased βII- and βIII-tubulin contributed significantly to the resistance phenotype, along with the tubulin structural mutation, and that the altered isotype effect was binding site specific. Mol Cancer Ther; 11(2); 393–404. ©2011 AACR.
Use of aspirin in Chinese after recovery from primary intracranial haemorrhage
Authors: Chong Boon-Hor , Chan Koon-Ho , Pong Vincent , Lau Kui-Kai , Chan Yap-Hang , Zuo Ming-Liang , Lui Wai-Man , Leung Gilberto , Lau Chu-Pak , Tse Hung-Fat , Pu Jenny , Siu Chung-Wah 
Published: December 2011

SummaryIntracranial haemorrhage (ICH) accounts for ~35% of all strokes in Chinese. Anti-platelet agent is often avoided after an index event due to the possibility of recurrent ICH. This single-centered observational study included 440 consecutive Chinese patients with a first spontaneous ICH surviving the first month performed during 1996–2010. The subjects were identified, and their clinical characteristics, anti-platelet therapy after ICH, and outcomes including recurrent ICH, ischaemic stroke, and acute coronary syndrome were checked from hospital records. Of these 440 patients, 56 patients (12.7%) were prescribed aspirin (312 patient-aspirin years). After a follow-up of 62.2 ± 1.8 months, 47 patients had recurrent ICH (10.7%, 20.6 per 1,000 patient years). Patients prescribed aspirin did not have a higher risk of recurrent ICH compared with those not prescribed aspirin (22.7 per 1,000 patient-aspirin years vs. 22.4 per 1,000 patient years, p=0.70). Multivariate analysis identified age > 60 years (hazard ratio [HR]: 2.0, 95% confidence interval [CI]: 1.07–3.85, p=0.03) and hypertension (HR: 2.0, 95% CI: 1.06–3.75, p=0.03) as independent predictors for recurrent ICH. In a subgroup analysis including 127 patients with standard indications for aspirin of whom 56 were prescribed aspirin, the incidence of combined vascular events including recurrent ICH, ischaemic stroke, and acute coronary syndrome was statistically lower in patients prescribed aspirin than those not prescribed aspirin (52.4 per 1,000 patient-aspirin years, vs. 112.8 per 1,000 patient-years, p=0.04). In conclusion, we observed in a cohort of Chinese post-ICH patients that aspirin use was not associated with an increased risk for a recurrent ICH.
Prevalence of Cardiomyopathy in Italian Asymptomatic Children With Electrocardiographic T-Wave Inversion at Preparticipation Screening
Authors: Migliore Federico , Zorzi Alessandro , Michieli Pierantonio , Perazzolo Marra Martina , Siciliano Mariachiara , Rigato Ilaria , Bauce Barbara , Basso Cristina , Toazza Daniela , Schiavon Maurizio , Iliceto Sabino , Thiene Gaetano , Corrado Domenico 
Published: December 2011

Background—
T-wave inversion on a 12-lead ECG is usually dismissed in young people as normal persistence of the juvenile pattern of repolarization. However, T-wave inversion is a common ECG abnormality of cardiomyopathies such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, which are leading causes of sudden cardiac death in athletes. We prospectively assessed the prevalence, age relation, and underlying cardiomyopathy of T-wave inversion in children undergoing preparticipation screening.

Methods and Results—

The study population included 2765 consecutive Italian children (1914 male participants; mean age, 13.9±2.2 years; range 8–18 years) undergoing preparticipation screening including an ECG. Of 229 children (8%) who underwent further evaluation because of positive findings at initial preparticipation screening, 33 (1.2%) were diagnosed with cardiovascular disease. T-wave inversion was recorded in 158 children (5.7%) and was localized in the right precordial leads in 131 (4.7%). The prevalence of right precordial T-wave inversion decreased significantly with increasing age (8.4% in children <14 years of age versus 1.7% in those ≥14 years;
P
<0.001), pubertal development (9.5% of children with incomplete versus 1.6% with complete development;
P
<0.001), and body mass index below the 10th percentile (
P
<0.001). Incomplete pubertal development was the only independent predictor for right precordial T-wave inversion (odds ratio, 3.6; 95% confidence interval, 1.9–6.8;
P
<0.001). Of 158 children with T-wave inversion, 4 (2.5%) had a diagnosis of cardiomyopathy, including arrhythmogenic right ventricular cardiomyopathy (n=3) and hypertrophic cardiomyopathy (n=1).

Conclusions—
The prevalence of T-wave inversion decreases significantly after puberty. Echocardiographic investigation of children with postpubertal persistence of T-wave inversion at preparticipation screening is warranted because it may lead to presymptomatic diagnosis of a cardiomyopathy that could lead to sudden cardiac death during sports.
Rainfall Regime of a Mountainous Mediterranean Region: Statistical Analysis at Short Time Steps
Authors: Molinié Gilles , Ceresetti Davide , Anquetin Sandrine , Creutin Jean Dominique , Boudevillain Brice 
Published: December 2011

AbstractThis paper presents an analysis of the rainfall regime of a Mediterranean mountainous region of southeastern France. The rainfall regime is studied on temporal scales from hourly to yearly using daily and hourly rain gauge data of 43 and 16 years, respectively. The domain is 200 × 200 km2 with spatial resolution of hourly and daily rain gauges of about 8 and 5 km, respectively. On average, yearly rainfall increases from about 0.5 m yr−1 in the large river plain close to the Mediterranean Sea to up to 2 m yr−1 over the surrounding mountain ridges. The seasonal distribution is also uneven: one-third of the cumulative rainfall occurs during the autumn season and one-fourth during the spring. At finer time scales, rainfall is studied in terms of rain–no-rain intermittency and nonzero intensity. The monthly intermittency (proportion of dry days per month) and the daily intermittency (proportion of dry hours per day) is fairly well correlated with the relief. The higher the rain gauges are, the lower the monthly and daily intermittencies are. The hourly and daily rainfall intensities are analyzed in terms of seasonal variability, diurnal cycle, and spatial pattern. The difference between regular and heavy-rainfall event is depicted by using both central parameters and maximum values of intensity distributions. The relationship between rain gauge altitudes and rainfall intensity is grossly inverted relative to intermittency and is also far more complex. The spatial and temporal rainfall patterns depicted from rain gauge data are discussed in the light of known meteorological processes affecting the study region.
Searching for Well-Being
Authors: Fachin Dina 
Published: December 2011

A Zapotec community from the Valle Central of Oaxaca, Mexico, has recently employed video technology as a tool to disseminate knowledge about local projects of economic development and to foster cultural awareness among community members. A study drawing on the literature on the sociopolitical relevance of community video making in the context of the globalization of cultures sheds light on the way traditional practices, pedagogical values, and local notions of time and place inform the Zapotec documentary Ben rguil guialznak/Buscando bienestar/Searching for Wellbeing. This video shows that the accommodation of different cultural contributions continues to be a strategy of survival for indigenous peoples. Una comunidad zapoteca del Valle Central de Oaxaca, en México, recientemente empleó el vídeo como herramienta para difundir información sobre proyectos de desarrollo económico locales y fomentar una consciencia cultural entre los miembros de la comunidad. Este estudio, con base en teorías sobre la relevancia socio-política del vídeo comunitario en el contexto de la globalización cultural, explora las formas en las que se expresan prácticas tradicionales, valores pedagógicos, y nociones locales de tiempo y lugar en el documental zapoteco Ben rguil guialznak/Buscando bienestar/Searching for Wellbeing. Este vídeo muestra que el acomodo de distintos aportes culturales sigue siendo una estrategia de supervivencia para los pueblos indígenas.
Using observation as a data collection method to help understand patient and professional roles and actions in palliative care settings
Authors: Walshe Catherine , Ewing Gail , Griffiths Jane 
Published: December 2011

Background: Observational research methods are important for understanding people’s actions, roles and behaviour. However, these techniques are underused generally in healthcare research, including research in the palliative care field. Aim: The aim in this paper is to place qualitative observational data collection methods in their methodological context and provide an overview of issues to consider when using observation as a method of data collection. This paper discusses practical considerations when conducting palliative care research using observation. Findings: Observational data collection methods span research paradigms, and qualitative approaches contribute by their focus on ‘natural’ settings which allow the explanation of social processes and phenomena. In particular, they can facilitate understanding of what people do and how these can alter in response to situations and over time, especially where people find their own practice difficult to articulate. Observational studies can be challenging to carry out: we focus on the potentially problematic areas of sampling, consent and ethics, data collection and recording, data management and analysis. Conclusion: Qualitative observational data collection methods can contribute to theoretical and conceptual development and the explanation of social processes in palliative care. In particular this contribution to understanding care structures and processes should improve understanding of patients’ experiences of their care journey and thus impact on care outcomes.
Experiences of persons with early-onset dementia in everyday life: A qualitative study
Authors: Johannessen Aud , Möller Anders 
Published: December 2011

Background: The small number of existing studies confirms that people with early-onset dementia (EOD) need special assistance from the beginning and as the disease progresses. There is a need to develop services to respond to the specific needs of persons with EOD. Aim: To find out how people experience living with early-onset dementia, and to assess the implications for practice and the development of further services. Method: Grounded theory, a qualitative method, with interviews of 20 informants (aged 54–67 years; 12 of them men) during 2010–2011. Findings: One category, the process toward a dementia diagnosis, covered two subcategories; describing changes and being diagnosed. Another category fighting for dignity describes how the informants try to maintain their quality of life, covering two subcategories; intrapsychic challenges and s ocial challenges. Conclusion: Health services should give persons with EOD the ability to maintain contact with society and their voices should not be overlooked.
Networking to Leadership in Higher Education
Authors: Baltodano Josefina Castillo , Carlson Susan , Jackson Leah Witcher , Mitchell Wanda 
Published: December 2011

The Problem. Women continue to be underrepresented in the leadership of higher education, a particularly pressing problem given the aging of college presidents and growing numbers of women students. The Solution. The American Council on Education and its Office of Women in Higher Education (OWHE) provide leadership training and support to thousands of women interested in leadership in higher education through a state-based, volunteer network; women of color summits and training; and national and regional leadership forums. The primary purpose of this article is to highlight the structure of these OWHE-supported leadership development programs and networks. The Stakeholders. These leadership development programs provide solutions for higher education institutions seeking to provide leadership training for their women leaders. The programs, structures, and strategies highlighted offer a model for consideration by HRD and leadership development professionals charged with diversifying leadership in other professions, business, and industry.
Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function
Authors: Foley Bree , Cooley Sarah , Verneris Michael R. , Pitt Michelle , Curtsinger Julie , Luo Xianghua , Lopez-Vergès Sandra , Lanier Lewis L. , Weisdorf Daniel , Miller Jeffrey S. 
Published: December 2011

AbstractDuring mouse cytomegalovirus (CMV) infection, a population of Ly49H+ natural killer (NK) cells expands and is responsible for disease clearance through the induction of a “memory NK-cell response.” Whether similar events occur in human CMV infection is unknown. In the present study, we characterized the kinetics of the NK-cell response to CMV reactivation in human recipients after hematopoietic cell transplantation. During acute infection, NKG2C+ NK cells expanded and were potent producers of IFNγ. NKG2C+ NK cells predominately expressed killer cell immunoglobulin–like receptor, and self-killer cell immunoglobulin–like receptors were required for robust IFNγ production. During the first year after transplantation, CMV reactivation induced a more mature phenotype characterized by an increase in CD56dim NK cells. Strikingly, increased frequencies of NKG2C+ NK cells persisted and continued to increase in recipients who reactivated CMV, whereas these cells remained at low frequency in recipients without CMV reactivation. Persisting NKG2C+ NK cells lacked NKG2A, expressed CD158b, preferentially acquired CD57, and were potent producers of IFNγ during the first year after transplantation. Recipients who reactivated CMV also expressed higher amounts of IFNγ, T-bet, and IL-15Rα mRNA transcripts. Our findings support the emerging concept that CMV-induced innate memory-cell populations may contribute to malignant disease relapse protection and infectious disease control long after transplantation.
Thigh-length versus below-knee compression elastic stockings for prevention of the postthrombotic syndrome in patients with proximal-venous thrombosis: a randomized trial
Authors: Prandoni Paolo , Noventa Franco , Quintavalla Roberto , Bova Carlo , Cosmi Benilde , Siragusa Sergio , Bucherini Eugenio , Astorri Francesco , Cuppini Stefano , Dalla Valle Fabio , Lensing Anthonie W. A. , Prins Martin H. , Villalta Sabina 
Published: December 2011

Abstract
Although below-knee compression elastic stockings (CES) are effective for the prevention of the postthrombotic syndrome (PTS), a substantial number of patients with deep venous thrombosis still develop PTS. In the present open-label, randomized clinical trial, we compared thigh-length with below-knee CES for the prevention of PTS. A total of 267 patients with the first episode of proximal deep venous thrombosis were randomized to wear either thigh-length or below-knee CES for 2 years. After 3, 6, 12, 18, 24, and 36 months, they were assessed for PTS manifestations according to the Villalta scale. PTS developed in 44 (32.6%) of the 135 patients randomized to thigh-length CES and in 47 (35.6%) of the 132 allocated to below-knee CES, for an adjusted hazard ratio of 0.93 (95% confidence interval, 0.62-1.41). Severe PTS developed in 3 patients in each group. CES-related side effects developed in 55 (40.7%) of the 135 patients allocated to thigh-length CES and in 36 (27.3%) of those randomized to the below-knee group (P = .017), and led to premature discontinuation of their use in 29 (21.5%) and 18 (13.6%) patients, respectively. We conclude that thigh-length CES do not offer a better protection against PTS than below-knee CES and are less well tolerated. This study is registered as Clinical Trial number NCT00426075.