bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin-Free Tetraspanin CD151 Can Inhibit Tumor Cell Motility upon Clustering and Is a Clinical Indicator of Prostate Cancer Progression
Authors: Palmer Trenis D. , Martínez Carlos H. , Vasquez Catalina , Hebron Katie E. , Jones-Paris Celestial , Arnold Shanna A. , Chan Susanne M. , Chalasani Venu , Gomez-Lemus Jose A. , Williams Andrew K. , Chin Joseph L. , Giannico Giovanna A. , Ketova Tatiana , Lewis John D. , Zijlstra Andries 
Published: November 2013

Abstract
Normal physiology relies on the organization of transmembrane proteins by molecular scaffolds, such as tetraspanins. Oncogenesis frequently involves changes in their organization or expression. The tetraspanin CD151 is thought to contribute to cancer progression through direct interaction with the laminin-binding integrins α3β1 and α6β1. However, this interaction cannot explain the ability of CD151 to control migration in the absence of these integrins or on non-laminin substrates. We demonstrate that CD151 can regulate tumor cell migration without direct integrin binding and that integrin-free CD151 (CD151free) correlates clinically with tumor progression and metastasis. Clustering CD151free through its integrin-binding domain promotes accumulation in areas of cell–cell contact, leading to enhanced adhesion and inhibition of tumor cell motility in vitro and in vivo. CD151free clustering is a strong regulator of motility even in the absence of α3 expression but requires PKCα, suggesting that CD151 can control migration independent of its integrin associations. The histologic detection of CD151free in prostate cancer correlates with poor patient outcome. When CD151free is present, patients are more likely to recur after radical prostatectomy and progression to metastatic disease is accelerated. Multivariable analysis identifies CD151free as an independent predictor of survival. Moreover, the detection of CD151free can stratify survival among patients with elevated prostate-specific antigen levels. Cumulatively, these studies demonstrate that a subpopulation of CD151 exists on the surface of tumor cells that can regulate migration independent of its integrin partner. The clinical correlation of CD151free with prostate cancer progression suggests that it may contribute to the disease and predict cancer progression. Cancer Res; 74(1); 173–87. ©2013 AACR.
The Detection of Hepatocellular Carcinoma Using a Prospectively Developed and Validated Model Based on Serological Biomarkers
Authors: Johnson Philip J. , Pirrie Sarah J. , Cox Trevor F. , Berhane Sarah , Teng Mabel , Palmer Daniel , Morse Janet , Hull Diana , Patman Gillian , Kagebayashi Chiaki , Hussain Syed , Graham Janine , Reeves Helen , Satomura Shinji 
Published: November 2013

Abstract
Background: Hepatocellular carcinoma is a common complication of chronic liver disease (CLD), and is conventionally diagnosed by radiological means. We aimed to build a statistical model that could determine the risk of hepatocellular carcinoma in individual patients with CLD using objective measures, particularly serological tumor markers.
Methods: A total of 670 patients with either CLD alone or hepatocellular carcinoma were recruited from a single UK center into a case–control study. Sera were collected prospectively and specifically for this study. A logistic regression analysis was used to determine independent factors associated with hepatocellular carcinoma and a model built and assessed in terms of sensitivity, specificity, and proportion of correct diagnoses.
Results: The final model involving gender, age, AFP-L3, α fetoprotein (AFP), and des-carboxy-prothrombin (“GALAD”) was developed in a “discovery” data set and validated in independent data sets both from the same institution and from an external institution. When optimized for sensitivity and specificity, the model gave values of more than 0.88 irrespective of the disease stage.
Conclusions: The presence of hepatocellular carcinoma can be detected in patients with CLD on the basis of a model involving objective clinical and serological factors. It is now necessary to test the model's performance in a prospective manner and in a routine clinical practice setting, to determine if it may replace or, more likely, enhance current radiological approaches.
Impact: Our data provide evidence that an entirely objective serum biomarker–based model may facilitate the detection and diagnosis of hepatocellular carcinoma and form the basis for a prospective study comparing this approach with the standard radiological approaches. Cancer Epidemiol Biomarkers Prev; 23(1); 144–53. ©2013 AACR.
Targeting Fibroblast Activation Protein in Tumor Stroma with Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth and Augment Host Immunity without Severe Toxicity
Authors: Wang Liang-Chuan S. , Lo Albert , Scholler John , Sun Jing , Majumdar Rajrupa S. , Kapoor Veena , Antzis Michael , Cotner Cody E. , Johnson Laura A. , Durham Amy C. , Solomides Charalambos C. , June Carl H. , Puré Ellen , Albelda Steven M. 
Published: November 2013

Abstract
The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAPhi stromal cells and inhibited the growth of multiple types of subcutaneously transplanted tumors in wild-type, but not FAP-null immune-competent syngeneic mice. The antitumor effects could be augmented by multiple injections of the CAR T cells, by using CAR T cells with a deficiency in diacylglycerol kinase, or by combination with a vaccine. A major mechanism of action of the muFAP-CAR T cells was the augmentation of the endogenous CD8+ T-cell antitumor responses. Off-tumor toxicity in our models was minimal following muFAP-CAR T-cell therapy. In summary, inhibiting tumor growth by targeting tumor stroma with adoptively transferred CAR T cells directed to FAP can be safe and effective, suggesting that further clinical development of anti-human FAP-CAR is warranted. Cancer Immunol Res; 2(2); 154–66. ©2013 AACR.
Regional Climate Modeling over the Maritime Continent. Part II: New Parameterization for Autoconversion of Convective Rainfall
Authors: Gianotti Rebecca L. , Eltahir Elfatih A. B. 
Published: November 2013

Abstract
This paper describes a new method for parameterizing the conversion of convective cloud liquid water to rainfall (“autoconversion”) that can be used within large-scale climate models, and evaluates the new method using the Regional Climate Model, version 3 (RegCM3), coupled to the land surface scheme Integrated Biosphere Simulator (IBIS). The new method is derived from observed distributions of cloud water content and is constrained by observations of cloud droplet characteristics and climatological rainfall intensity. This new method explicitly accounts for subgrid variability with respect to cloud water density and is independent of model resolution, making it generally applicable for large-scale climate models. This work builds on the development of a new parameterization method for convective cloud fraction, which was described in Part I.
Simulations over the Maritime Continent using the Emanuel convection scheme show significant improvement in model performance, not only with respect to convective rainfall but also in shortwave radiation, net radiation, and turbulent surface fluxes of latent and sensible heat, without any additional modifications made to the simulation of those variables. Model improvements are demonstrated over a 19-yr validation period as well as a shorter 4-yr evaluation. Model performance with the Grell convection scheme is not similarly improved and reasons for this outcome are discussed. This work illustrates the importance of representing observed subgrid-scale variability in diurnally varying convective processes for simulations of the Maritime Continent region.
Management of Combined Anterior Cruciate Ligament–Posterolateral Corner Tears
Authors: Bonanzinga Tommaso , Zaffagnini Stefano , Grassi Alberto , Marcheggiani Muccioli Giulio Maria , Neri Maria Pia , Marcacci Maurilio 
Published: November 2013

Background: A consensus on the treatment of combined anterior cruciate ligament (ACL) and posterolateral corner (PLC) injuries is still lacking. Purpose: To review the available literature on the management of these combined lesions to investigate the influence that injuries of knee posterolateral structures play in the outcome of an ACL lesion. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive search was performed on PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases using various combinations of the following keywords: “posterolateral corner,” “plc,” “posterolateral instability,” “posterolateral injury,” “anterior cruciate ligament,” and “acl.” Results: A total of 6 studies involving 95 patients were included. For those with PLC lesions, 14 patients were treated nonoperatively, 9 underwent an early anatomic repair, while the remaining 72 underwent a reconstruction. In all 95 patients, an ACL reconstruction was performed. Sixty-seven of the 72 patients who underwent a PLC reconstruction were assessed for anteroposterior laxity, with a mean side-to-side difference of 1.5 ± 1.1 mm. Evaluated by the objective International Knee Documentation Committee (IKDC) Knee Form, 88% of the patients who underwent a PLC reconstruction were graded as good/excellent (A/B). The 9 patients who underwent an early surgical repair of the PLC lesion were evaluated by means of the objective IKDC score, with 3 patients (33%) graded as good/excellent (A/B), and by means of a clinical evaluation, with 5 of 9 patients (56%) graded as 1+ for varus laxity. For the 14 patients who were managed nonoperatively for PLC injuries, the only clinical score available was the subjective IKDC score, with a mean value of 80.5 (87.8 for the 6 patients with type A PLC injuries and 75.0 for type B PLC injuries). Conclusion: There is a paucity of literature focused on the management of combined ACL and PLC injuries. Combined ACL and PLC reconstruction seems to be the most effective approach to these combined lesions. However, future work is needed to explore the long-term outcome of the different treatment options.
Stem Cell Therapies for Knee Cartilage Repair
Authors: Anderson John A. , Little Dianne , Toth Alison P. , Moorman Claude T. , Tucker Bradford S. , Ciccotti Michael G. , Guilak Farshid 
Published: November 2013

Background: Articular cartilage damage of the knee is common, causing significant morbidity worldwide. Many adult tissues contain cells that are able to differentiate into multiple cell types, including chondrocytes. These stem cells have gained significant attention over the past decade and may become frontline management for cartilage defects in the very near future. Purpose: The role of stem cells in the treatment of knee osteochondral defects was reviewed. Recent animal and clinical studies were reviewed to determine the benefits and potential outcomes of using stem cells for cartilage defects. Study Design: Literature review. Methods: A PubMed search was undertaken. The key phrase “stem cells and knee” was used. The search included reviews and original articles over an unlimited time period. From this search, articles outlining animal and clinical trials were selected. A search of current clinical trials in progress was performed on the clinicaltrials.gov website, and “stem cells and knee” was used as the search phrase. Results: Stem cells have been used in many recent in vitro and animal studies. A number of cell-based approaches for cartilage repair have progressed from preclinical animal studies into clinical trials. Conclusion: The use of stem cells for the treatment of cartilage defects is increasing in animal and clinical studies. Methods of delivery of stem cells to the knee’s cartilage vary from direct injection to implantation with scaffolds. While these approaches are highly promising, there is currently limited evidence of a direct clinical benefit, and further research is required to assess the overall outcome of stem cell therapies for knee cartilage repair.
Proliferative changes of renal arteriolar walls induced by administration of angiotensin II receptor blocker are frequent in juvenile rats
Authors: Nagai Yohko , Nakanishi Kazushige , Akimoto Tatsuo , Yamanaka Nobuaki 
Published: November 2013

Introduction: Our previous study of angiotensin II receptor blocker (ARB) administration in rats induced unusual proliferative changes of smooth muscle cells in renal arteriolar walls. The present study examined if the incidence of the changes depended on the rats’ age, and how long it would take to find changes. Materials and methods: Six-week-old (juvenile spontaneous hypertensive rats (SHRs)+ARB group, n=15) and 20-week-old (adult SHRs+ARB group, n=10) male SHRs were fed a standard diet (0.4% NaCl) containing valsartan (10 mg/kg/day; Novartis Co.). Fifteen age-matched SHRs were studied as controls. After 4, 8, and 12 weeks, the rat kidneys were examined under light and electron microscopes and through immunohistochemical studies. Results: Extremely concentric proliferative changes in afferent arteriolar walls were frequently observed in the juvenile SHR+ARB group compared to the adult SHR+ARB group (48.7±6.8% vs 19.3±6.9%; p=0.0307) at the 12th week. Increased renin expression and arteriolar changes were found from the 4th week in the juvenile SHR+ARB group. Conclusion: This study indicates that ARB administration induces unusual proliferative changes and a marked renin-producing cell increase in afferent arterioles more frequently in juveniles than adult rats. It is suggested that the treatment of ARB in juveniles might have a higher risk of changes in renal afferent arterioles.
Genome-wide survey and expression profiles of the AP2/ERF family in castor bean (Ricinus communis L.)
Authors: Xu Wei , Li Fei , Ling Lizhen , Liu Aizhong 
Published: November 2013

AbstractBackgroundThe AP2/ERF transcription factor, one of the largest gene families in plants, plays a crucial role in the regulation of growth and development, metabolism, and responses to biotic and abiotic stresses. Castor bean (Ricinus communisL., Euphobiaceae) is one of most important non-edible oilseed crops and its seed oil is broadly used for industrial applications. The available genome provides a great chance to identify and characterize the global information on AP2/ERF transcription factors in castor bean, which might provide insights in understanding the molecular basis of the AP2/ERF family in castor bean.ResultsA total of 114 AP2/ERF transcription factors were identified based on the genome in castor bean. According to the number of the AP2/ERF domain, the conserved amino acid residues within AP2/ERF domain, the conserved motifs and gene organization in structure, and phylogenetical analysis, the identified 114 AP2/ERF transcription factors were characterized. Global expression profiles among different tissues using high-throughput sequencing of digital gene expression profiles (DGEs) displayed diverse expression patterns that may provide basic information in understanding the function of the AP2/ERF gene family in castor bean.ConclusionsThe current study is the first report on identification and characterization of the AP2/ERF transcription factors based on the genome of castor bean in the family Euphobiaceae. Results obtained from this study provide valuable information in understanding the molecular basis of the AP2/ERF family in castor bean.
Lipopolysaccharide (LPS)-induced autophagy is involved in the restriction of Escherichia coliin peritoneal mesothelial cells
Authors: Wang Juan , Feng Xiaoran , Zeng Youjia , Fan Jinjin , Wu Juan , Li Zhijian , Liu Xinhui , Huang Rong , Huang Fengxian , Yu Xueqing , Yang Xiao 
Published: November 2013

Abstract

Background
Host cell autophagy is implicated in the control of intracellular pathogen. Escherichia coli (E.coli) is the most common organism caused single-germ enterobacterial peritonitis during peritoneal dialysis. In this study, we investigated autophagy of peritoneal mesothelial cells and its role in defense against E.coli.

Results
Autophagy in human peritoneal mesothelial cell line (HMrSV5) was induced by lipopolysaccharide (LPS) in a dose-dependent and time-dependent way, which was demonstrated by increased expression of Beclin-1 and light chain 3 (LC3)-II, the accumulation of punctate green fluorescent protein-LC3, and a higher number of monodansylcadaverine-labeled autophagic vacuoles. After incubation of HMrSV5 cells with E.coli following LPS stimulation, both the intracellular bactericidal activity and the co-localization of E.coli (K12-strain) with autophagosomes were enhanced. Conversely, blockade of autophagy with 3-methyladenine, wortmannin or Beclin-1 small-interfering RNA (siRNA) led to a significant reduction in autophagy-associated protein expression, attenuation of intracellular bactericidal activity, and reduced co-localization of E.coli with monodansylcadaverine-labeled autophagosomes. In addition, treatment of HMrSV5 cells with LPS caused a dose-dependent and time-dependent increase in Toll-like receptor 4 (TLR4) expression. Both knockdown of TLR4 with siRNA and pharmacological inhibition of TLR4 with Polymyxin B significantly decreased LPS-induced autophagy. Furthermore, TLR4 siRNA attenuated remarkably LPS-induced intracellular bactericidal activity.

Conclusions
Our findings demonstrated for the first time that LPS-induced autophagy in peritoneal mesothelial cells could enhance the intracellular bactericidal activity and the co-localization of E.coli with autophagosomes. The activation of TLR4 signaling was involved in this process. These results indicate that LPS-induced autophagy may be a cell-autonomous defense mechanism triggered in peritoneal mesothelial cells in response to E.coli infection.
Hospital process orientation from an operations management perspective: development of a measurement tool and practical testing in three ophthalmic practices
Authors: Gonçalves Pedro D , Hagenbeek Marie Louise , Vissers Jan M H 
Published: November 2013

Abstract

Background
Although research interest in hospital process orientation (HPO) is growing, the development of a measurement tool to assess process orientation (PO) has not been very successful yet. To view a hospital as a series of processes organized around patients with a similar demand seems to be an attractive proposition, but it is hard to operationalize this idea in a measurement tool that can actually measure the level of PO. This research contributes to HPO from an operations management (OM) perspective by addressing the alignment, integration and coordination of activities within patient care processes. The objective of this study was to develop and practically test a new measurement tool for assessing the degree of PO within hospitals using existing tools.

Methods
Through a literature search we identified a number of constructs to measure PO in hospital settings. These constructs were further operationalized, using an OM perspective. Based on five dimensions of an existing questionnaire a new HPO-measurement tool was developed to measure the degree of PO within hospitals on the basis of respondents’ perception. The HPO-measurement tool was pre-tested in a non-participating hospital and discussed with experts in a focus group. The multicentre exploratory case study was conducted in the ophthalmic practices of three different types of Dutch hospitals. In total 26 employees from three disciplines participated. After filling in the questionnaire an interview was held with each participant to check the validity and the reliability of the measurement tool.

Results
The application of the HPO-measurement tool, analysis of the scores and interviews with the participants resulted in the possibility to identify differences of PO performance and the areas of improvement – from a PO point of view – within each hospital. The result of refinement of the items of the measurement tool after practical testing is a set of 41 items to assess the degree of PO from an OM perspective within hospitals.

Conclusions
The development and practically testing of a new HPO-measurement tool improves the understanding and application of PO in hospitals and the reliability of the measurement tool. The study shows that PO is a complex concept and appears still hard to objectify.
Researching male circumcision for HIV prevention in Papua New Guinea: a process that incorporates science, faith and culture
Authors: Tommbe Rachael , MacLaren David J , Redman-MacLaren Michelle L , Mafile’o Tracie A , Asugeni Lester , McBride William John H 
Published: November 2013

AbstractBackgroundUndertaking HIV research in the culturally diverse Pacific nation of Papua New Guinea (PNG) requires careful consideration of social, cultural and religious beliefs and practices. Here, we share a detailed description of culturally informed research processes and lessons learned from the first ever study undertaken on male circumcision for HIV prevention at a faith-based university in PNG.MethodsMale and female staff and students at Pacific Adventist University were invited to complete an anonymous self-administered questionnaire, and/or participate in a semi-structured interview or focus group discussion. Male participants were invited for clinical examination. Results were collated and disseminated to the university community in gender segregated sessions. The study deliberately partnered with student leaders and centralised social, cultural, and religious paradigms. Student leaders were interviewed about their experience of partnering in sensitive health research.ResultsThe student leaders reported that pre-existing relationships, cultural ties, gendered sensitivity and regular communication reinforced trust between researchers, student leaders and participants, and helped the success of the study. The amount of time, complex logistics and social and cultural relationships between single and married staff and students were highlighted as challenges.ConclusionsPartnering with regional student leaders to plan and implement the study gave a legitimate and immediate mechanism for involving PNG staff and students in this sensitive health research. Gendered research processes utilised established social and cultural structures and ensured the safety of participants; all of these factors contributed to the acceptability of the study. Capacity was strengthened in PNG and Australian researchers to undertake sensitive HIV research in PNG. The study demonstrated that it is possible to conduct sensitive sexual health research at a faith-based university in PNG.