bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2-Driven Breast Tumorigenesis Relies upon Interactions of the Estrogen Receptor with Coactivator MED1
Authors: Yang Yongguang , Leonard Marissa , Zhang Yijuan , Zhao Dan , Mahmoud Charif , Khan Shugufta , Wang Jiang , Lower Elyse E. , Zhang Xiaoting 
Published: November 2017

Abstract
Studies of the estrogen receptor (ER) coactivator protein Mediator subunit 1 (MED1) have revealed its specific roles in pubertal mammary gland development and potential contributions to breast tumorigenesis, based on coamplification of MED1 and HER2 in certain breast cancers. In this study, we generated a mouse model of mammary tumorigenesis harboring the MMTV-HER2 oncogene and mutation of MED1 to evaluate its role in HER2-driven tumorigenesis. MED1 mutation in its ER-interacting LxxLL motifs was sufficient to delay tumor onset and to impair tumor growth, metastasis, and cancer stem-like cell formation in this model. Mechanistic investigations revealed that MED1 acted directly to regulate ER signaling through the downstream IGF1 pathway but not the AREG pathway. Our findings show that MED1 is critical for HER2-driven breast tumorigenesis, suggesting its candidacy as a disease-selective therapeutic target.
Significance: These findings identify an estrogen receptor-binding protein as a critical mediator of HER2-driven breast tumorigenesis, suggesting its candidacy as a disease-selective therapeutic target. Cancer Res; 78(2); 422–35. ©2017 AACR.
Photodynamic Priming Mitigates Chemotherapeutic Selection Pressures and Improves Drug Delivery
Authors: Huang Huang-Chiao , Rizvi Imran , Liu Joyce , Anbil Sriram , Kalra Ashish , Lee Helen , Baglo Yan , Paz Nancy , Hayden Douglas , Pereira Steve , Pogue Brian W. , Fitzgerald Jonathan , Hasan Tayyaba 
Published: November 2017

Abstract
Physiologic barriers to drug delivery and selection for drug resistance limit survival outcomes in cancer patients. In this study, we present preclinical evidence that a subtumoricidal photodynamic priming (PDP) strategy can relieve drug delivery barriers in the tumor microenvironment to safely widen the therapeutic window of a nanoformulated cytotoxic drug. In orthotopic xenograft models of pancreatic cancer, combining PDP with nanoliposomal irinotecan (nal-IRI) prevented tumor relapse, reduced metastasis, and increased both progression-free survival and 1-year disease-free survival. PDP enabled these durable improvements by targeting multiple tumor compartments to (i) increase intratumoral drug accumulation by &gt;10-fold, (ii) increase the duration of drug exposure above a critical therapeutic threshold, and (iii) attenuate surges in CD44 and CXCR4 expression, which mediate chemoresistance often observed after multicycle chemotherapy. Overall, our results offer preclinical proof of concept for the effectiveness of PDP to minimize risks of tumor relapse, progression, and drug resistance and to extend patient survival.
Significance: A biophysical priming approach overcomes key treatment barriers, significantly reduces metastases, and prolongs survival in orthotopic models of human pancreatic cancer. Cancer Res; 78(2); 558–71. ©2017 AACR.
Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
Authors: Kraft Ira L. , Akshintala Srivandana , Zhu Yuelin , Lei Haiyan , Derse-Anthony Claudia , Dombi Eva , Steinberg Seth M. , Lodish Maya , Waguespack Steven G. , Kapustina Oxana , Fox Elizabeth , Balis Frank M. , Merino Maria J. , Meltzer Paul S. , Glod John W. , Shern Jack F. , Widemann Brigitte C. 
Published: November 2017

AbstractPurpose: Vandetanib is well-tolerated in patients with advanced medullary thyroid carcinoma (MTC). Long-term outcomes and mechanisms of MTC progression have not been reported previously.Experimental Design: We monitored toxicities and disease status in patients taking vandetanib for hereditary, advanced MTC. Tumor samples were analyzed for molecular mechanisms of disease progression.Results: Seventeen patients [8 male, age 13 (9–17)* years] enrolled; 16 had a RET p.Met918Thr germline mutation. The duration of vandetanib therapy was 6.1 (0.1–9.7+)* years with treatment ongoing in 9 patients. Best response was partial response in 10, stable disease in 6, and progressive disease in one patient. Duration of response was 7.4 (0.6–8.7+)* and 4.9 (0.6–7.8+)* years in patients with PR and SD, respectively. Six patients died 2.0 (0.4–5.7)* years after progression. Median progression-free survival (PFS) was 6.7 years [95% confidence interval (CI): 2.3 years–undefined] and 5-year overall survival (OS) was 88.2% (95% CI: 60.6%–96.9%). Of 16 patients with a RET p.Met918Thr mutation, progression-free survival was 6.7 years (95% CI: 3.1–undefined) and 5-year overall survival was 93.8% (95% CI: 63.2%–99.1%). No patients terminated treatment because of toxicity. DNA sequencing of tissue samples (n = 11) identified an increase in copy number alterations across the genome as a potential mechanism of drug resistance [*median (range)].Conclusions: This study demonstrates that vandetanib is safe and results in sustained responses in children and adolescents with hereditary MTC. Our preliminary molecular data suggest that an increase in copy number abnormalities may be associated with tumor progression in hereditary MTC patients treated with vandetanib. Clin Cancer Res; 24(4); 753–65. ©2017 AACR.
Assessment of Homocysteine as a Diagnostic and Early Prognostic Biomarker for Patients with Acute Lacunar Infarction
Authors: Fan Huimin , Yang Shuna , Li Yue , Yin Jiangmei , Qin Wei , Yang Lei , Yuan Junliang , Hu Wenli 
Published: November 2017

<b><i>Background:</i></b> Although increasing evidence has demonstrated that elevated homocysteine (Hcy) levels may be an important contributor for the development of cerebral infarction, rare studies focused on its diagnostic and early prognostic roles in acute lacunar infarction. <b><i>Methods:</i></b> A total of 197 patients with acute lacunar infarction and 192 to form the control group were prospectively recruited between January 2013 and February 2017. Early neurological deterioration was defined as an increase of ≥2 points in National Institutes of Health Stroke Scale or the decrease in Barthel index (BI) score at discharge. <b><i>Results:</i></b> Univariate and multivariate logistic regression analyses revealed that higher levels of fibrinogen and Hcy were independently clinical predictors associated with lacunar infarction. Receiver operating characteristic curves analysis demonstrated that the diagnosis value of Hcy was superior to fibrinogen, with the area under the curve of 0.881 and 0.688 respectively. Using the optimal cutoff value of 15.5 μmol/L of Hcy, a sensitivity of 65% and a specificity of 100% were achieved for predicting lacunar infarction. Hcy was only significantly related with BI reduction in the males (30.5 [15.5–65.5] vs. 18 [15–24], <i>p</i> = 0.034) in the univariate analysis but not in the females and the multivariate analysis. <b><i>Conclusions:</i></b> Serum Hcy may be an independent diagnostic and not an early prognostic biomarker for patients with acute lacunar infarction.
Phylogeography and postglacial colonization of Central Europe by Anguis fragilis and Anguis colchica
Authors: Jablonski Daniel , Najbar Bartłomiej , Grochowalska Renata , Gvoždík Václav , Strzała Tomasz 
Published: November 2017

Five slow-worm species are distributed in the Palearctic region. Two species, Anguis fragilis and A. colchica, are native to Central Europe, where only limited information on the phylogeography of the genus exists. Here, we examined the situation in Poland and surrounding regions, where a mitochondrial contact zone between the species is expected. We used new mitochondrial DNA sequences and available published data from Central Europe and the northern Balkans. Haplotypes of both species were recorded in the study area. Anguis fragilis is represented by a single haplogroup, while A. colchica by three haplogroups. This suggests four independent sources/refugia for postglacial colonization of northern Central Europe. The mitochondrial contact zone seems to mirror the borders between lowlands of the North European Plain and East European Plain, and the south-eastern Poland uplands, while the Vistula River does not constitute a barrier. The presence of both species, A. fragilis and A. colchica, in Poland should also be considered for protection by the Polish conservation legislation.
The EU-FP7 ERA-CLIM2 Project Contribution to Advancing Science and Production of Earth System Climate Reanalyses
Authors: Buizza Roberto , Brönnimann Stefan , Haimberger Leopold , Laloyaux Patrick , Martin Matthew J. , Fuentes Manuel , Alonso-Balmaseda Magdalena , Becker Andreas , Blaschek Michael , Dahlgren Per , de Boisseson Eric , Dee Dick , Doutriaux-Boucher Marie , Feng Xiangbo , John Viju O. , Haines Keith , Jourdain Sylvie , Kosaka Yuki , Lea Daniel , Lemarié Florian , Mayer Michael , Messina Palmira , Perruche Coralie , Peylin Philippe , Pullainen Jounie , Rayner Nick , Rustemeier Elke , Schepers Dinand , Saunders Roger , Schulz Jörg , Sterin Alexander , Stichelberger Sebastian , Storto Andrea , Testut Charles-Emmanuel , Valente Maria-Antóonia , Vidard Arthur , Vuichard Nicolas , Weaver Anthony , While James , Ziese Markus 
Published: November 2017

AbstractThe European Reanalysis of Global Climate Observations 2 (ERA-CLIM2) is a European Union Seventh Framework Project started in January 2014 and due to be completed in December 2017. It aims to produce coupled reanalyses, which are physically consistent datasets describing the evolution of the global atmosphere, ocean, land surface, cryosphere, and the carbon cycle. ERA-CLIM2 has contributed to advancing the capacity for producing state-of-the-art climate reanalyses that extend back to the early twentieth century. ERA-CLIM2 has led to the generation of the first European ensemble of coupled ocean, sea ice, land, and atmosphere reanalyses of the twentieth century. The project has funded work to rescue and prepare observations and to advance the data-assimilation systems required to generate operational reanalyses, such as the ones planned by the European Union Copernicus Climate Change Service. This paper summarizes the main goals of the project, discusses some of its main areas of activities, and presents some of its key results.
Relationships between Electrification and Storm-Scale Properties Based on Idealized Simulations of an Intensifying Hurricane-Like Vortex
Authors: Fierro Alexandre O. , Mansell Edward R. 
Published: November 2017

AbstractThis study investigates relationships between storm-scale properties and the electrification and lightning of two simulations of an intensifying idealized tropical cyclone (TC) using the cloud-resolving Collaborative Model for Multiscale Atmospheric Simulation (COMMAS). To produce an intensifying storm, an initial weak TC is subjected to a linear increase in sea surface temperature.As the TC intensifies, lightning flash rates increase in both the inner core (r ≤ 100 km) and outer region (100 &lt; r ≤ 300 km). As time progresses, lightning in the outer region gradually decreases, while the inner-core lightning remains relatively steady. Bootstrapped correlation statistics using 1000 random samples between the pressure trace and time series of lightning rates shows a statistically significant negative correlation between inner-core lightning and TC intensification. Lightning rates in the outer bands were found to lag minimum surface pressure by 12 h.The increases in lightning in both the inner core and outer region coincided well with increases in 0.5 g kg−1 graupel and 5 m s−1 updraft volumes in each respective region. Correlation statistics with selected kinematic and microphysical variables known to be associated with lightning in thunderstorms, such as the ice water path, integrated updraft volume, and graupel volume, revealed that their increase in the inner core indicated an ongoing deepening, similar to the lightning. Trends in these proxy variables in the outer bands were also found to lag TC intensification by 12 h.Overall, the best linear relationships with lightning in either the inner core or the outer region were obtained with the 0.5 g kg−1 graupel volume and total graupel mass.
Internalized stigma in people with severe mental illness in rural China
Authors: Ran Mao-Sheng , Zhang Tian-Ming , Wong Irene Yin-Ling , Yang Xin , Liu Chang-Cheng , Liu Bo , Luo Wei , Kuang Wei-Hong , Thornicroft Graham , Chan Cecilia Lai-Wan ,   CMHP Study Group
Published: November 2017

Background: It is unknown whether there are differences in self-stigma among persons with different types of severe mental illness (SMI) in rural communities. Aim: This study was to examine the differences of self-stigma and its correlates in persons with schizophrenia, major depressive disorder or bipolar disorder in a rural community in China. Methods: A total of 453 persons with schizophrenia, major depressive disorder or bipolar disorder in a rural community participated in the study. The Internalized Stigma of Mental Illness (ISMI) was used to measure self-stigma. The t-test and analyses of variance (ANOVA) were used to examine the differences in mean scores of ISMI and subscales among the three diagnoses. Logistic regression was used to explore the contributing factors to the level of self-stigma among the three groups. Results: Self-stigma was moderate and severe with 94.7% of the total sample. Persons with schizophrenia had significantly higher mean scores of total ISMI, alienation and discrimination experience than those with bipolar disorders. Lower family income was significantly associated with higher levels of self-stigma in persons with schizophrenia and major depressive disorder. Factors predicting the level of self-stigma among the three groups were various. Conclusion: Self-stigma is common and severe in persons with schizophrenia, major depressive disorder and bipolar disorder, especially those with lower income status in rural community in China. Persons with schizophrenia may have higher levels of self-stigma than those with bipolar disorder. Individual-level interventions should be developed to reduce self-stigma among persons with SMI in Chinese rural communities.
“It looks kind of cool when cool people smoke, but…” Norwegian adolescents’ decoding of smoking scenes in films
Authors: Sæbø Gunnar , Scheffels Janne , Tokle Rikke 
Published: November 2017

Aims: Exposure to smoking scenes in films is seen as contributing to smoking initiation among young people. This has triggered calls to include depictions of smoking as a criterion in film ratings. All the same time, little is known about how adolescents interpret different smoking scenes. This study analyses how young people decode smoking scenes by contextualising identification with, and evaluation of, various characters who smoke, as well as the significance of film genres. Design: In order to explore how adolescents conceptualize smoking scenes in different film genres, we conducted eight focus-group interviews with adolescents aged 13–17 years ( n = 54), using purposive sampling. The discussions were semi-structured with a standard guide, and we used clips from eight films containing various positive and negative moods and character types as stimuli for the discussions. To analyse interpretations qualitatively, thematic coding was applied. Results: The adolescents acknowledged that smoking is a narrative ingredient designed to illustrate and amplify character traits and situational moods. Characters who smoked were usually interpreted in terms of smoking stereotypes: stress relief, romantic seduction, social interaction between equals, habitual smoking, and as a symbol of “bad guys”. The adolescents identified more strongly with elegant, positive, and self-assured smoking characters than with negative, anxious, or ambiguous characters. Conclusions: Adolescents interpret smoking scenes in accordance with encoded meanings: they tend to get the messages inscribed by the filmmakers. As positive and glamorous representations are more likely to stimulate smoking experimentation and initiation among adolescents than negative representations, future research should distinguish more clearly between exposure to positive and to negative representations.
Metastasectomy for Tumor-Infiltrating Lymphocytes: An Emerging Operative Indication in Surgical Oncology
Authors: Crompton Joseph G. , Klemen Nicholas , Kammula Udai S. 
Published: November 2017

AbstractAdoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) is an emerging immunotherapy for metastatic cancer. Surgeons play a central role in ACT treatments by performing resection of tumors from which TILs are isolated. It is important that surgeons have familiarity with this emerging treatment method because it is increasingly performed for an expanding variety of solid tumors at institutions around the world. This report offers a brief introduction to ACT for cancer, highlights historical milestones in its development, and provides patient selection and operative considerations for surgeons called upon to perform metastasectomy for the purpose of isolating TILs.
Polypharmacy in Alzheimer's disease patients in Brazil: Guidance for pharmaceutical assistance
Authors: Vaz Felipe Nathanael Coelho , Bortoluzzi Trombim Luana , de Freitas Guilherme Barroso L. , Haskel Maria Vaitsa Loch , dos Santos Giovana , Wouk Jéssica , Mendes Dayanna Hartmann Cambruzzi , Fermino Barbara Luisa , Ivanski Flávia , Bonini Juliana Sartori 
Published: November 2017

Background: Elderly patients frequently have concomitant diseases, triggering the necessity of utilizing several different medications, which can cause adverse events associated with therapy, called polypharmacy. This study aimed to evaluate the main concomitant diseases with Alzheimer's disease (AD) and discuss possible interactions between drugs utilized to treat dementia and its comorbidities, and indicate safe medicines for patients with AD. Methods: 41 individuals with AD who withdraw medicines for dementia from the Brazilian public health system (SUS) participated in this study. Data collection was performed using three questionnaires: 1) Clinical Dementia Rating, to verify disease stage; 2) Mini–mental state examination, to measure cognitive impairment; and 3) Sociodemographic analysis, to evaluate concomitant diseases, utilized drugs, drug-drug interactions, among other demographic variables. Statistical analyses were performed using SPSS and data was presented as relative frequency. Results: The results of this study showed that the most frequent concomitant diseases with AD are: systemic arterial hypertension, depression, diabetes mellitus, and hypercholesterolemia. Polypharmacy was observed in 95.12% of patients. The pharmacologic classes that presented interactions with AD medications were anxiolytics, antidepressants, antipsychotics, antihypertensives, and antidiabetics. Conclusion: In the present study, polypharmacy in patients with AD and other concomitant diseases has been characterized. The average number of drugs that these patients ingested was seven per day, and this leads to drug interactions, which are potentially damaging to the body. Consequently, we have tried to reduce these interactions, by suggesting drugs that are safer, for example furosemide instead of amlodipine to treat hypertension.
Psychometric evaluation of the Major Depression Inventory among young people living in Coastal Kenya
Authors: Otiende Mark , Abubakar Amina , Mochamah George , Walumbe David , Nyundo Christopher , Doyle Aoife M , Ross David A , Newton Charles R , Bauni Evasius 
Published: November 2017

Background: The lack of reliable, valid and adequately standardized measures of mental illnesses in sub-Saharan Africa is a key challenge for epidemiological studies on mental health. We evaluated the psychometric properties and feasibility of using a computerized version of the Major Depression Inventory (MDI) in an epidemiological study in rural Kenya. Methods: We surveyed 1496 participants aged 13-24 years in Kilifi County, on the Kenyan coast. The MDI was administered using a computer-assisted system, available in three languages. Internal consistency was evaluated using both Cronbach’s alpha and the Omega Coefficient. Confirmatory factor analysis was performed to evaluate the factorial structure of the MDI. Results: Internal consistency using both Cronbach’s Alpha (α= 0.83) and the Omega Coefficient (0.82; 95% confidence interval 0.81- 0.83) was above acceptable thresholds. Confirmatory factor analysis indicated a good fit of the data to a unidimensional model of MDI (χ2 (33, N = 1409) = 178.52 p < 0.001, TLI = 0.947, CFI = 0.961, and Root Mean Square Error of Approximation, RMSEA = .056), and this was confirmed using Item Response Models (Loevinger’s H coefficient 0.38) that proved the MDI was a unidimensional scale. Equivalence evaluation indicated invariance across sex and age groups. In our population, 3.6% of the youth presented with scores suggesting major depression using the ICD-10 scoring algorithm, and 8.7% presented with total scores indicating presence of depression (mild, moderate or severe). Females and older youth were at the highest risk of depression. Conclusions: The MDI has good psychometric properties. Given its brevity, relative ease of usage and ability to identify at-risk youth, it may be useful for epidemiological studies of depression in Africa. Studies to establish clinical thresholds for depression are recommended. The high prevalence of depressive symptoms suggests that depression may be an important public health problem in this population group.
Generating Value Through Open Source: Software Service Market Regulation and Licensing Policy
Authors: August Terrence , Shin Hyoduk , Tunca Tunay I. 
Published: November 2017

In the software industry, commercial open-source software vendors have recognized that providing services to help businesses derive greater value in the implementation of open source–based systems can be a profitable business model. Moreover, society may greatly benefit when software originators choose an open-source development strategy as their products become widely available, readily customizable, and open to community contributions. In this study, we present an economic model to study how software licensing attributes affect a software originator’s decisions, aiming to provide policy makers with insights into how welfare-improving, open-source outcomes can be incentivized. We show that when a competing contributor is apt at reaping the benefits of software development investment, a less restrictive open source license (e.g., Berkeley Software Distribution, or BSD style) can improve welfare. On the other hand, when the originator is better at leveraging investment and service costs are high, a more restrictive license (e.g., General Public License, or GPL style) can be best for social welfare even when a contributor can cost-efficiently develop the software. The online appendix is available at https://doi.org/10.1287/isre.2017.0726 .