bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ulinastatin as a neuroprotective and anti‐inflammatory agent in infant piglets model undergoing surgery on hypothermic low‐flow cardiopulmonary bypass
Authors: Wang Xiaocou , Xue Qinghua , Yan Fuxia , Li Lihuan , Liu Jinping , Li Shoujun , Hu Shengshou 
Published: February 2013

SummaryObjectiveInfants are potentially more susceptible to brain injury mediated via cell death attributed to cardiopulmonary bypass (CPB) especially with prolonged hypothermic low flow (HLF). We hypothesized that a human urinary protease inhibitor (ulinastatin), by its anti‐inflammatory effect, would reduce central nervous system (CNS) injury during HLF.MethodsFifteen general‐type infant piglets were randomized to ulinastatin group (Group U, n = 5), control group (Group C, n = 5), and sham operation group (Group S, n = 5). Routine CPB was established after median thoracotomy in Group U and C under anesthesia. When the temperature of infant piglets dropped down to 25°C, low‐flow CPB (50 ml·kg−1·min−1) was instituted. After 120 min of aortic cross‐clamping and 20‐ to 30‐min rewarming, the aortic cross‐clamp was removed and finally the piglet was weaned from CPB. Five thousand units per killogram of ulinastatin and equivalently normal saline were, respectively, given at the beginning of and at aortic declamping in Group U and Group C. Group S just received sham median thoracotomy. Venous blood samples were taken immediately after anesthesia induction in all three groups, 5‐ and 120‐min post CPB in both Group U and C, respectively; plasma markers of inflammation and CNS injury were compared. Pathology results of hippocampus were observed by light microscopy.ResultsStatistically significant differences between Group C and U were noted in the expression of inflammatory markers such as IL‐10, TNF‐α and neuron‐specific enolase at 120‐min post CPB. Brain injuries were observed in both groups (index cases and controls) and were milder in Group U.ConclusionsIn our study, HLF CPB on infant piglets resulted in brain injury, and ulinastatin might reduce the extent of such injury.
Controversies in Implicit Race Bias Research
Authors: Tinkler Justine E. 
Published: February 2013

AbstractAdvances in measurement have allowed researchers to empirically distinguish between explicit attitudes, which are conscious and controllable, and implicit attitudes, which are activated automatically without cognitive effort or even awareness. Researchers using these methods have shown that although survey data reveal unprecedented declines in Americans’ expressions of overtly racist attitudes, most Americans continue to harbor an implicit pro‐White bias relative to other racial minority groups. This research has generated a great deal of controversy. The primary focus of the controversy has been on the findings that have come out of studies using the Implicit Association Test or IAT – a response‐time computer software program that records the speed with which positive and negative evaluations of different racial groups come to mind. This paper addresses the following questions that continue to divide researchers: (1) What does the IAT measure? (2) How do implicit attitudes as measured by the IAT relate to people’s race‐related judgments and behaviors? (3) What are the political and legal implications of being able to measure implicit racial bias?
Assessing Television’s ‘Political Dramas’
Authors: Richardson Kay , Corner John 
Published: February 2013

AbstractBecause drama is so important to the television schedules, and because television remains a ubiquitous and pervasive medium, TV drama is a constant cultural presence. Some of its stories are about politics, featuring the work of government, the contestation of elections, party rivalry and negotiation, and so on, with a cast of characters including leaders, advisors, journalists, celebrities and citizens: they echo, refract, replay, model and feed into narratives about real‐world politics in a variety of ways. Dramatic stories of this kind are important for the sake of their potential contribution to what citizens believe ‐ and feel ‐ about politics itself. Dramatised political stories and characters appear in a wide range of genres, from factually based docudramas to situation comedy and soap opera, and have become the focus of international academic attention for a number of scholars in politics departments as well as those working from within media and cultural studies. This article looks at a range of approaches to studying political drama on television, raising questions about generic variety, the ideas and the kinds of analysis that have been applied and the varying assessments that have been put forward.
The Co‐evolution of Residential Segregation and the Built Environment at the Turn of the 20th Century: A Schelling Model
Authors: Spielman Seth , Harrison Patrick 
Published: February 2013

AbstractTo what degree does the built environment of cities shape the social environment? In this article we use a Schelling‐like agent‐based model to consider how changes to the built environment of cities relate to changes in residential segregation by income and ethnicity. To develop this model we exploit insights from a high resolution historical GIS which maps 100% of the population of Newark, NJ in 1880. Newark in 1880 had a complex social landscape characterized by areas of significant social and economic segregation and areas of relative integration. We develop a Schelling model capable of reproducing these residential patterns. We use this model to explore the decentralization of housing, a specific phenomenon associated with the demise of the walking city in the late 19th century. Holding agent preferences constant, but allowing the landscape of the Schelling model to evolve in ways that reflect historical changes to the built environment, produces changes to the social landscape that are also consistent with history. Our work suggests that changes in residential segregation do not necessarily imply changes to individual attitudes and preferences. Changes in residential segregation can be generated by changes to the built environment, specifically the geographic distribution of housing.
Arabidopsis COBRA‐LIKE 10, a GPI‐anchored protein, mediates directional growth of pollen tubes
Authors: Li Sha , Ge Fu‐Rong , Xu Ming , Zhao Xin‐Ying , Huang Guo‐Qiang , Zhou Liang‐Zi , Wang Jia‐Gang , Kombrink Anja , McCormick Sheila , Zhang Xian Sheng , Zhang Yan 
Published: February 2013

SummarySuccessful reproduction of flowering plants requires constant communication between female tissues and growing pollen tubes. Female cells secrete molecules and peptides as nutrients or guidance cues for fast and directional tube growth, which is executed by dynamic changes of intracellular activities within pollen tubes. Compared with the extensive interest in female cues and intracellular activities of pollen tubes, how female cues are sensed and interpreted intracellularly in pollen is poorly understood. We show here that COBL10, a glycosylphosphatidylinositol (GPI)‐anchored protein, is one component of this pollen tube internal machinery. Mutations in COBL10 caused gametophytic male sterility due to reduced pollen tube growth and compromised directional sensing in the female transmitting tract. Deposition of the apical pectin cap and cellulose microfibrils was disrupted in cobl10 pollen tubes. Pollen tube localization of COBL10 at the apical plasma membrane is critical for its function and relies on proper GPI processing and its C‐terminal hydrophobic residues. GPI‐anchored proteins are widespread cell sensors in mammals, especially during egg‐sperm communication. Our results that COBL10 is critical for directional growth of pollen tubes suggest that they play critical roles in cell‐cell communications in plants.
Novel alginate three‐dimensional static and rotating culture systems for effective ex vivo amplification of human cord blood hematopoietic stem cells and in vivo functional analysis of amplified cells in NOD/SCID mice
Authors: Yuan Yan , Sin Wai‐Yee , Xue Bofu , Ke Yan , Tse Kai‐Tai , Chen Zi , Xie Yi , Xie Yong 
Published: February 2013

BackgroundAutologous and allogeneic hematopoietic stem cell (HSC) transplantations serve as effective therapy for a variety of hematologic and other diseases. Umbilical cord blood (UCB) is an important source of HSCs. However, it is difficult to obtain a sufficient number of HSCs with complete self‐renewal capability derived from a single unit of UCB for use in adult transplantation. In this study, we investigated two novel three‐dimensional (3D) culture systems (static and rotating) for ex vivo expansion of HSCs from UCB.Study Design and MethodsWe encapsulated the human cord blood mononuclear cells (CBMCs) in alginate 3D static and rotating culture systems, compared the cell number amplification, the proportion of CD34+ cells, and the colony‐forming capacity of these systems to those of the conventional two‐dimensional (2D) system. The amplified cells were transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice to confirm the hematopoiesis reconstruction capacity of the cells.ResultsThe increase in the cell number and the proportion of CD34+ cells in the CBMCs was more effective in these 3D alginate culture systems than in the conventional 2D culture system under the same conditions (p < 0.05). The stem cell maintenance capability was confirmed by flow cytometry and colony‐forming assay ex vivo and NOD/SCID mice xenogeneic transplantation model in vivo.ConclusionOur results demonstrated that these 3D alginate culture systems are an efficient way to amplify cord blood HSCs for extended periods without having them lose their self‐renewal capacity in vivo. These novel 3D alginate culture systems are promising for the amplification of UCB‐derived HSCs for clinical application in the future.
Diagnosing Mild Cognitive Impairment (MCI) in clinical trials: a systematic review
Authors: Christa Maree Stephan Blossom , Minett Thais , Pagett Emma , Siervo Mario , Brayne Carol , McKeith Ian G 
Published: February 2013

ObjectiveTo describe how criteria for amnestic Mild Cognitive Impairment (aMCI) have been operationalised in randomised controlled clinical trials (RCTs).DesignSystematic review.Information sourcesEMBASE, PubMed and PSYCHInfo were searched from their inception to February 2012. Electronic clinical trial registries were also searched (February 2012).Study selectionRCTs were included where participant selection was made using Petersenet al-defined aMCI. There was no restriction on intervention type or the outcome tested.Data extractionFor each trial, we extracted information on study design, demographics, exclusion criteria and the operationalisation strategy for the five aMCI diagnostic criteria including: (1) memory complaint, (2) normal general cognitive function, (3) memory impairment, (4) no functional impairment and (5) no dementia.Results223 articles and 278 registered trials were reviewed, of which 22 met inclusion criteria. Various methods were applied for operationalising aMCI criteria resulting in variability in participant selection. Memory complaint and assessment of general cognitive function were the most consistently measured criteria. There was large heterogeneity in the neuropsychological methods used to determine memory impairment. It was not possible to assess the impact of these differences on case selection accuracy for dementia prediction. Further limitations include selective and unclear reporting of how each of the criteria was measured.ConclusionsThe results highlight the urgent need for a standardised approach to map aMCI. Lack of uniformity in clinical diagnosis, however, is not exclusively a problem for MCI but also for other clinical states such as dementia including Alzheimer's disease, Lewy Body, frontotemporal or vascular dementia. Defining a uniform approach to MCI classification, or indeed for any classification concept within the field of dementia, should be a priority if further trials are to be undertaken in the older aged population based on these concepts.
A service-based approach to nurse training in sexual and reproductive health care
Authors: Shawe Jill , Cox Sarah , Penny Nikki , White Alison , Wilkinson Christopher 
Published: February 2013

AimsTo develop and pilot a reproducible curriculum for nurses with limited or no sexual and reproductive health care (SRH) experience to become competent dual-trained practitioners. The model used supernumerary training posts and clinical training and assessment adapted from that used to train doctors for the Diploma of the Faculty of Sexual & Reproductive Healthcare in the UK.BackgroundThere is currently no standard SRH nurse training in the UK. Nurses undertake various university-based qualifications supported by clinical sessions, and employers can be reluctant to sponsor these because of the cost and the time required.MethodsTwo nurses were employed on a 6-month programme consisting of five parts: (1) the Faculty of Sexual & Reproductive Healthcare (FSRH) e-learning programme, in conjunction with e-Learning for Healthcare; (2) the FSRH ‘Course of 5’; (3) structured clinical training; (4) visits to other relevant services; and (5) clinical supervision and mentoring. Assessment was by a portfolio of evidence; signed competences; reflections from clinical sessions; and outcomes of visits to services. The project was evaluated by means of questionnaires and interviews with trainees and staff.ConclusionsThe project demonstrated that by using a model similar to that used for basic SRH medical training it is possible to train nurses in core holistic SRH care within the workplace. Many SRH services are reporting severe difficulties in the recruitment of nurses trained in SRH, and this practice-based training would allow services and providers to invest in training to build up the workforce they require.
miR-7 Suppresses Brain Metastasis of Breast Cancer Stem-Like Cells By Modulating KLF4
Authors: Okuda Hiroshi , Xing Fei , Pandey Puspa R. , Sharma Sambad , Watabe Misako , Pai Sudha K. , Mo Yin-Yuan , Iiizumi-Gairani Megumi , Hirota Shigeru , Liu Yin , Wu Kerui , Pochampally Radhika , Watabe Kounosuke 
Published: February 2013

Abstract
Despite significant improvement in survival rates of patients with breast cancer, prognosis of metastatic disease is still dismal. Cancer stem-like cells (CSC) are considered to play a role in metastatic progression of breast cancer; however, the exact pathologic role of CSCs is yet to be elucidated. In this report, we found that CSCs (CD24−/CD44+/ESA+) isolated from metastatic breast cell lines are significantly more metastatic than non-CSC populations in an organ-specific manner. The results of our microRNA (miRNA) profile analysis for these cells revealed that CSCs that are highly metastatic to bone and brain expressed significantly lower level of miR-7 and that this miRNA was capable of modulating one of the essential genes for induced pluripotent stem cell, KLF4. Interestingly, high expression of KLF4 was significantly and inversely correlated to brain but not bone metastasis-free survival of patients with breast cancer, and we indeed found that the expression of miR-7 significantly suppressed the ability of CSCs to metastasize to brain but not to bone in our animal model. We also examined the expression of miR-7 and KLF4 in brain-metastatic lesions and found that these genes were significantly down- or upregulated, respectively, in the tumor cells in brain. Furthermore, the results of our in vitro experiments indicate that miR-7 attenuates the abilities of invasion and self-renewal of CSCs by modulating KLF4 expression. These results suggest that miR-7 and KLF4 may serve as biomarkers or therapeutic targets for brain metastasis of breast cancer. Cancer Res; 73(4); 1434–44. ©2012 AACR.
Hepatocyte Growth Factor Sensitizes Brain Tumors to c-MET Kinase Inhibition
Authors: Zhang Ying , Farenholtz Kaitlyn E. , Yang Yanzhi , Guessous Fadila , diPierro Charles G. , Calvert Valerie S. , Deng Jianghong , Schiff David , Xin Wenjun , Lee Jae K. , Purow Benjamin , Christensen James , Petricoin Emanuel , Abounader Roger 
Published: February 2013

Abstract
Purpose: The receptor tyrosine kinase (RTK) c-MET and its ligand hepatocyte growth factor (HGF) are deregulated and promote malignancy in cancer and brain tumors. Consequently, clinically applicable c-MET inhibitors have been developed. The purpose of this study was to investigate the not-well-known molecular determinants that predict responsiveness to c-MET inhibitors and to explore new strategies for improving inhibitor efficacy in brain tumors.
Experimental Design: We investigated the molecular factors and pathway activation signatures that determine sensitivity to c-MET inhibitors in a panel of glioblastoma and medulloblastoma cells, glioblastoma stem cells, and established cell line–derived xenografts using functional assays, reverse protein microarrays, and in vivo tumor volume measurements, but validation with animal survival analyses remains to be done. We also explored new approaches for improving the efficacy of the inhibitors in vitro and in vivo.
Results: We found that HGF coexpression is a key predictor of response to c-MET inhibition among the examined factors and identified an ERK/JAK/p53 pathway activation signature that differentiates c-MET inhibition in responsive and nonresponsive cells. Surprisingly, we also found that short pretreatment of cells and tumors with exogenous HGF moderately but statistically significantly enhanced the antitumor effects of c-MET inhibition. We observed a similar ligand-induced sensitization effect to an EGF receptor small-molecule kinase inhibitor.
Conclusions: These findings allow the identification of a subset of patients that will be responsive to c-MET inhibition and propose ligand pretreatment as a potential new strategy for improving the anticancer efficacy of RTK inhibitors. Clin Cancer Res; 19(6); 1433–44. ©2013 AACR.
CHFR Protein Expression Predicts Outcomes to Taxane-Based First Line Therapy in Metastatic NSCLC
Authors: Pillai Rathi N. , Brodie Seth A. , Sica Gabriel L. , Shaojin You , Li Ge , Nickleach Dana C. , Yuan Liu , Varma Vijay A. , Bonta Dacian , Herman James G. , Brock Malcom V. , Ribeiro Maria J.A. , Ramalingam Suresh S. , Owonikoko Taofeek K. , Khuri Fadlo R. , Brandes Johann C. 
Published: February 2013

Abstract
Purpose: Currently, there is no clinically validated test for the prediction of response to tubulin-targeting agents in non–small cell lung cancer (NSCLC). Here, we investigated the significance of nuclear expression of the mitotic checkpoint gene checkpoint with forkhead and ringfinger domains (CHFR) as predictor of response and overall survival with taxane-based first-line chemotherapy in advanced stage NSCLC.
Methods: We studied a cohort of 41 patients (median age 63 years) with advanced NSCLC treated at the Atlanta VAMC between 1999 and 2010. CHFR expression by immunohistochemistry (score 0–4) was correlated with clinical outcome using chi-square test and Cox proportional models. A cutoff score of “3” was determined by receiver operator characteristics analysis for “low” CHFR expression. Results were validated in an additional 20 patients who received taxane-based chemotherapy at Emory University Hospital and the Atlanta VAMC.
Results: High expression (score = 4) of CHFR is strongly associated with adverse outcomes: the risk for progressive disease after first-line chemotherapy with carboplatin–paclitaxel was 52% in patients with CHFR-high versus only 19% in those with CHFR-low tumors (P = 0.033). Median overall survival was strongly correlated with CHFR expression status (CHFR low: 9.9 months; CHFR high: 6.2 months; P = 0.002). After multivariate adjustment, reduced CHFR expression remained a powerful predictor of improved overall survival (HR = 0.24; 95% CI, 0.1–0.58%; P = 0.002). In the validation set, low CHFR expression was associated with higher likelihood of clinical benefit (P = 0.03) and improved overall survival (P = 0.038).
Conclusions: CHFR expression is a novel predictive marker of response and overall survival in NSCLC patients treated with taxane-containing chemotherapy. Clin Cancer Res; 19(6); 1603–11. ©2013 AACR.
Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy
Authors: Kothari Vishal , Wei Iris , Shankar Sunita , Kalyana-Sundaram Shanker , Wang Lidong , Ma Linda W. , Vats Pankaj , Grasso Catherine S. , Robinson Dan R. , Wu Yi-Mi , Cao Xuhong , Simeone Diane M. , Chinnaiyan Arul M. , Kumar-Sinha Chandan 
Published: February 2013

Abstract
Protein kinases represent the most effective class of therapeutic targets in cancer; therefore, determination of kinase aberrations is a major focus of cancer genomic studies. Here, we analyzed transcriptome sequencing data from a compendium of 482 cancer and benign samples from 25 different tissue types, and defined distinct “outlier kinases” in individual breast and pancreatic cancer samples, based on highest levels of absolute and differential expression. Frequent outlier kinases in breast cancer included therapeutic targets like ERBB2 and FGFR4, distinct from MET, AKT2, and PLK2 in pancreatic cancer. Outlier kinases imparted sample-specific dependencies in various cell lines, as tested by siRNA knockdown and/or pharmacologic inhibition. Outlier expression of polo-like kinases was observed in a subset of KRAS-dependent pancreatic cancer cell lines, and conferred increased sensitivity to the pan-PLK inhibitor BI-6727. Our results suggest that outlier kinases represent effective precision therapeutic targets that are readily identifiable through RNA sequencing of tumors.
Significance: Various breast and pancreatic cancer cell lines display sensitivity to knockdown or pharmacologic inhibition of sample-specific outlier kinases identified by high-throughput transcriptome sequencing. Outlier kinases represent personalized therapeutic targets that could improve combinatorial therapy options. Cancer Discov; 3(3); 280–93. ©2013 AACR.
See related commentary by Yegnasubramanian and Maitra, p. 252
This article is highlighted in the In This Issue feature, p. 239
A Multisensor Observational Depiction of the Transition from Light to Heavy Rainfall on Subdaily Time Scales
Authors: Elsaesser Gregory S. , Kummerow Christian D. 
Published: February 2013

AbstractUtilizing data from the Quick Scatterometer (QuikSCAT), a new observational parameter related to mesoscale cold pool activity [termed cold pool kinetic energy (CPKE)] is developed and investigated. CPKE and the Climate Prediction Center (CPC) morphing technique (CMORPH) rainfall product (both scaled to 2.25°) are geolocated to 25 tropical island radiosonde sites. CPKE and radiosonde-derived nondilute CAPE, entraining CAPE (ECAPE), saturation fraction, and a new measure of convective inhibition (that takes into account stable layers above the LFC) are investigated with respect to rainfall time tendencies. Over the life cycle of rainfall, the composite temporal evolutions of CPKE and convective inhibition are quantitatively similar, but slightly out of phase. The maximum in CPKE precedes the maximum in convective inhibition by 3–6 h, thus allowing for an oscillation in the ratio of convective inhibition to CPKE relative to maximum rainfall. This ratio falls below unity at the time rainfall begins increasing and averages to near unity over the entire life cycle. These results imply a lagged, coupled relationship between CPKE and convective inhibition during rainfall. The rapid increase in rainfall occurs when saturation fraction and ECAPE exceed approximately 70% and 280 J kg−1, respectively, consistent with previously noted thresholds for deep convection transition. However, since similar thermodynamic conditions are found before the increase in rainfall, observations support a hypothesis that the onset time for transition from light to heavy rainfall occurs when triggering energy (as captured in CPKE) approaches and exceeds convective inhibition. The observed onset and time scale for CAPE depletion by convection is nearly equivalent to the initial temporal appearance and time duration (6–12 h) that CPKE exceeds convective inhibition.