bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new concordance measure for risk prediction models in external validation settings
Authors: van Klaveren David , Gönen Mithat , Steyerberg Ewout W. , Vergouwe Yvonne 
Published: June 2016

Concordance measures are frequently used for assessing the discriminative ability of risk prediction models. The interpretation of estimated concordance at external validation is difficult if the case‐mix differs from the model development setting. We aimed to develop a concordance measure that provides insight into the influence of case‐mix heterogeneity and is robust to censoring of time‐to‐event data.We first derived a model‐based concordance (mbc) measure that allows for quantification of the influence of case‐mix heterogeneity on discriminative ability of proportional hazards and logistic regression models. This mbc can also be calculated including a regression slope that calibrates the predictions at external validation (c‐mbc), hence assessing the influence of overall regression coefficient validity on discriminative ability. We derived variance formulas for both mbc and c‐mbc. We compared the mbc and the c‐mbc with commonly used concordance measures in a simulation study and in two external validation settings.The mbc was asymptotically equivalent to a previously proposed resampling‐based case‐mix corrected c‐index. The c‐mbc remained stable at the true value with increasing proportions of censoring, while Harrell's c‐index and to a lesser extent Uno's concordance measure increased unfavorably. Variance estimates of mbc and c‐mbc were well in agreement with the simulated empirical variances.We conclude that the mbc is an attractive closed‐form measure that allows for a straightforward quantification of the expected change in a model's discriminative ability due to case‐mix heterogeneity. The c‐mbc also reflects regression coefficient validity and is a censoring‐robust alternative for the c‐index when the proportional hazards assumption holds. Copyright © 2016 John Wiley & Sons, Ltd.
Stromal Tissue Rigidity Promotes Mesenchymal Stem Cell-Mediated Corneal Wound Healing Through the Transforming Growth Factor β Signaling Pathway
Authors: Yang Yun-Hsiang , Hsieh Ting-Lieh , Ji Andrea Tung-Qian , Hsu Wei-Tse , Liu Chia-Yu , Lee Oscar Kuang-Sheng , Ho Jennifer Hui-Chun 
Published: June 2016

Abstract
The healing of a corneal epithelial defect is essential for preventing infectious corneal ulcers and subsequent blindness. We previously demonstrated that mesenchymal stem cells (MSCs) in the corneal stroma, through a paracrine mechanism, yield a more favorable therapeutic benefit for corneal wound re-epithelialization than do MSCs in the corneal epithelium. In this study, MSCs were grown on a matrix with the rigidity of the physiological human vitreous (1 kPa), corneal epithelium (8 kPa), or corneal stroma (25 kPa) for investigating the role of corneal tissue rigidity in MSC functions regarding re-epithelialization promotion. MSC growth on a 25-kPa dish significantly promoted the wound healing of human corneal epithelial (HCE-T) cells. Among growth factors contributing to corneal epithelial wound healing, corneal stromal rigidity selectively enhanced transforming growth factor-beta (TGF-β) secretion from MSCs. Inhibitors of TGF-β pan receptor, TGF-β receptor 1, and Smad2 dose dependently abrogated MSC-mediated HCE-T wound healing. Furthermore, MSCs growth on a matrix with corneal stromal rigidity enhanced the ability of themselves to promote corneal re-epithelialization by activating matrix metalloproteinase (MMP) expression and integrin β1 production in HCE-T cells through TGF-β signaling pathway activation. Smad2 activation resulted in the upregulation of MMP-2 and −13 expression in HCE-T cells, whereas integrin β1 production favored a Smad2-independent TGF-β pathway. Altogether, we conclude that corneal stromal rigidity is a critical factor for MSC-induced promotion of corneal re-epithelialization. The activation of the TGF-β signaling pathway, which maintains the balance between integrin and MMP expression, in HCE-T cells is the major pathway responsible for MSC-mediated wound healing.
Hallmarks of cancer and AU‐rich elements
Authors: Khabar Khalid S. A. 
Published: June 2016

Post‐transcriptional control of gene expression is aberrant in cancer cells. Sustained stabilization and enhanced translation of specific mRNAs are features of tumor cells. AU‐rich elements (AREs), cis‐acting mRNA decay determinants, play a major role in the posttranscriptional regulation of many genes involved in cancer processes. This review discusses the role of aberrant ARE‐mediated posttranscriptional processes in each of the hallmarks of cancer, including sustained cellular growth, resistance to apoptosis, angiogenesis, invasion, and metastasis. WIREs RNA 2017, 8:e1368. doi: 10.1002/wrna.1368This article is categorized under:

RNA Turnover and Surveillance > Regulation of RNA Stability
RNA in Disease and Development > RNA in Disease
Lanthanide‐Coordination Polymers with Pyridinedicarboxylic Acids: Syntheses, Structures, and Luminescent Properties
Authors: Song Yuqi , Wang Xiaoling , Zhang Sheng , Wang Jiwu , Gao Shengli , Chen Sanping 
Published: June 2016

AbstractFive lanthanide coordination polymers (Ln‐CPs) based on pyridine‐dicarboxylate and lanthanide metal ions were synthesized and characterized, namely [Sm(pydc)(Hpydc)(H2O)5]·4H2O (1) (H2pydc = 2, 5‐pyridine‐dicarboxylic acid), [Ho(pydc)(Hpydc)(H2O)3]n·4nH2O (2), [Ce(pydc)(bdc)(H2O)]n (3) (H2bdc = 1, 4‐benzenedicarboxylic acid), [Nd2(dipic)3(H2O)3]n (4), and [Pr2Ag2(dipic)4(H2O)5]n·5nH2O (5) (H2dipic = 3, 5‐pyridine‐dicarboxylic acid). Complexes 1 and 2 display mononuclear structure and 1D zigzag chains, respectively. In complex 3, the CeIII ions are connected through pydc2– and bdc2– ligands to generate an intricate 3D architecture. Complex 4 is constructed through dinuclear {Nd2} SBUs and oxygen bridging from carboxyl groups of dipic2– to generate a 3D framework. In 5, PrIII ions and AgI ions are assembled into a 2D heterometallic layer, in which the rare Ag···Ag weak interactions are observed. Furthermore, the solid state luminescent properties of 1–4 were measured and discussed.
Isolation and structure determination of a new lantibiotic cinnamycin B from Actinomadura atramentaria based on genome mining
Authors: Kodani Shinya , Komaki Hisayuki , Ishimura Sho , Hemmi Hikaru , Ohnishi-Kameyama Mayumi 
Published: June 2016

Abstract
New lantibiotic cinnamycin B was isolated from the extract of Actinomadura atramentaria NBRC 14695T, based on genome mining and chemical investigation. The partial structure of cinnamycin B was established by 2D NMR experiments, which indicated that cinnamycin B had same methyl lanthionine bridging pattern with cinnamycin. The reduction with NaBH4-NiCl2 afforded the reduced cinnamycin B, and MS/MS experiment indicated the presence of hydroxy asparatic acid in the molecule. Cinnamycin B showed an antibacterial activity against Streptomyces antibioticus with dosage of 5 μg (0.5μL, 10 mg/mL solution) at spot-on-lawn testing method. The gene cluster of cinnamycin B on the genome of A. atramentaria was identified and discussed in comparison with that of cinnamycin.
Antibiosis resistance against larval cabbage root fly, Delia radicum, in wild Brassica-species
Authors: Shuhang Wang , Voorrips Roeland E. , Steenhuis-Broers Greet , Vosman Ben , van Loon Joop J. A. 
Published: June 2016

AbstractCabbage root flies (Delia radicum) are a major threat to cabbage production in Western Europe and North America. Host plant resistance is the most promising option in controlling cabbage root fly damage. In a no-choice field test, we evaluated 94 accessions belonging to 16Brassica-species for antibiosis resistance against the larvae. Thirteen accessions were selected as putatively resistant, which were subsequently re-tested in the greenhouse. The proportion of eclosed flies was introduced as the main parameter to assess antibiosis in the greenhouse, together with other insect and plant parameters. High levels of antibiosis resistance were identified inB. fruticulosaPI663081 andB. spinescensBRA2994, with significantly lower proportions of eclosed flies (1 % of the number of eggs used for infestation) compared to other accessions. Both species are difficult to cross withB. oleracea. Plants with a high level of antibiosis and medium to high tolerance were found in several accessions of otherBrassicaspecies (B. villosaBRA2922,B. montanaBRA2950,B. hilarionisHRIGU12483,B. macrocarpaBRA2944) which are more amenable for crossing withB. oleracea. Selection of the most resistant plants belonging to these accessions may yield promising candidates for breeding cabbages resistant toDelia radicum.
Journey to Zero Central Line-Associated Bloodstream Infections: An Intensive Care Unit's Story of Sustained Success and Quality Improvement
Authors: Jock Leighann , Emery Laurie , Jameson Lorri , Woods Phyllis A. 
Published: June 2016

Abstract
Background: Patients who have a central line (CL) are at increased risk for developing a CL-associated bloodstream infection (CLABSI), which increases morbidity, length of stay, and cost. Our goal is zero CLABSI infections.
Methodology: In 2009 our organization implemented a CL bundle to prevent CLABSIs, and staff education was introduced in 2012. In 2013 a 2% chlorhexidine gluconate (CHG) wipe was introduced and used to clean around CL dressings. In 2014 a new CL dressing was adopted and during 2015 the organization began using a 3.15% CHG/70% alcohol swab for disinfection of needleless connectors. A final intervention was put into place in 2015 called “nose to toes” in which a patient is bathed from nose to toes (excluding the face) using 2% CHG wipes.
Results: Before implementation of the above methods, our intensive care unit had an average infection rate of 1.9/1000 CL-days in 2009. Incidence of CLABSIs continued to decrease as the organization implemented the additional products and practices. In the 15 months following implementation, the ICU has been able to consistently maintain a zero CLABSI rate.
Conclusions: The implementation of these changes in practice along with bringing in new products has made it possible to achieve the goal of reaching and maintaining zero infections. Due to the successful results in our intensive care unit, we have implemented these changes to all patient care areas in the hospital for use on all CLs.
Non‐vitamin K antagonist oral anticoagulants versus warfarin for cardioversion of atrial fibrillation in clinical practice: A single‐center experience
Authors: Shibata Naoki , Morishima Itsuro , Okumura Kenji , Morita Yasuhiro , Takagi Kensuke , Yoshida Ruka , Nagai Hiroaki , Tomomatsu Toshiro , Ikai Yoshihiro , Terada Kazushi , Tsuzuki Kazuhito , Tsuboi Hideyuki , Sone Takahito , Murohara Toyoaki 
Published: June 2016

AbstractBackgroundAnticoagulation therapy with the vitamin K antagonist (VKA) warfarin has been demonstrated to reduce thromboembolic risk after electrical cardioversion (ECV). However, data concerning ECV with non‐VKA oral anticoagulants (NOACs) is limited. The objective of this study was to determine the efficacy and safety of NOACs in patients undergoing ECV in a real‐world clinical practice at a single center in Japan.MethodsWe retrospectively analyzed the data of 406 consecutive patients who underwent ECV for atrial fibrillation (AF) or flutter under anticoagulation with one of the three NOACs (n=149) or with a VKA (n=257).ResultsThe CHADS2 and HAS‐BLED scores were significantly higher in the VKA group, whereas the NOACs group had a tendency toward greater spontaneous echo contrast grades. After ECV, ischemic stroke occurred in three patients of the VKA group and one patient in the NOAC group, all of whom had persistent AF, indicating no significant difference in the thromboembolic event rate within 30 days following ECV. No other thromboembolic events, major bleeding, or death occurred in either group. Among the NOAC and VKA patients in whom we newly introduced an oral anticoagulant to perform ECV, the number of days leading to ECV was significantly lesser for the NOAC patients.ConclusionNOACs may be used as an alternative to VKAs for ECV and may allow prompt ECV in clinical practices.
Successful intermuscular implantation of subcutaneous implantable cardioverter defibrillator in a Japanese patient with pectus excavatum
Authors: Kondo Yusuke , Ueda Marehiko , Winter Joachim , Nakano Miyo , Nakano Masahiro , Ishimura Masayuki , Miyazawa Kazuo , Tateno Kaoru , Kobayashi Yoshio 
Published: June 2016

AbstractThe entirely subcutaneous implantable cardioverter‐defibrillator (ICD) system was developed to provide a life‐saving defibrillation therapy that does not affect the heart and vasculature. The subcutaneous ICD is preferred over the transvenous ICD for patients with a history of recurrent infection presenting major life‐threatening rhythms. In this case report, we describe the first successful intermuscular implantation of a completely subcutaneous ICD in a Japanese patient with pectus excavatum. There were no associated complications with the device implantation or lead positioning. Further, the defibrillation threshold testing did not pose any problem with the abnormal anatomy of the patient.
Successful percutaneous epicardial catheter ablation of ventricular tachycardia arising from the crux of the heart in a patient with prior coronary artery bypass grafting
Authors: Yoshida Naoki , Yamada Takumi 
Published: June 2016

AbstractA 63‐year‐old man with a history of remote inferior myocardial infarction and coronary artery bypass grafting (CABG) underwent catheter ablation of ventricular tachycardia (VT). Epicardial catheter ablation of the VT was successful at the crux of the heart despite limited mapping within the pericardial space due to pericardial adhesion. Percutaneous subxiphoidal pericardial approach is usually impossible in patients with a history of open heart surgery due to pericardial adhesions. This report suggested that epicardial VT arising from the crux of the heart could be successfully treated by catheter ablation via subxiphoidal pericardial approach despite pericardial adhesions complicated by prior CABG.
Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model
Authors: Gomez-Cadena A , Urueña C , Prieto K , Martinez-Usatorre A , Donda A , Barreto A , Romero P , Fiorentino S 
Published: June 2016

AbstractRecent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma. Here, we report that P2Et treatment results in activation of caspase 3 and 9, mobilization of cytochrome c and externalization of annexin V in tumor cells, thus suggesting the induction of apoptosis. This was preceded by the onset of autophagy and the expression of immunogenic cell death markers. We further demonstrate that P2Et-treated tumor cells are highly immunogenic in vaccinated mice and induce immune system activation, clearly shown by the generation of interferon gamma (IFN-γ) producing tyrosine-related protein 2 antigen-specific CD8+ T cells. Moreover, the tumor protective effects of P2Et treatment were abolished in immunodeficient mice, and partially lost after CD4 and CD8 depletion, indicating that P2Et’s anti-tumor activity is highly dependent on immune system and at least in part of T cells. Altogether, these results support the hypothesis that the gallotannin-rich fraction P2Et’s anti-tumor effects are mediated to a great extent by the endogenous immune response following to the exposure to immunogenic dying tumor cells.
Lifespan-regulating genes in C. elegans
Authors: Uno Masaharu , Nishida Eisuke 
Published: June 2016

AbstractThe molecular mechanisms underlying the aging process have garnered much attention in recent decades because aging is the most significant risk factor for many chronic diseases such as type 2 diabetes and cancer. Until recently, the aging process was not considered to be an actively regulated process; therefore, discovering that the insulin/insulin-like growth factor-1 signaling pathway is a lifespan-regulating genetic pathway in Caenorhabditis elegans was a major breakthrough that changed our understanding of the aging process. Currently, it is thought that animal lifespans are influenced by genetic and environmental factors. The genes involved in lifespan regulation are often associated with major signaling pathways that link the rate of aging to environmental factors. Although many of the major mechanisms governing the aging process have been identified from studies in short-lived model organisms such as yeasts, worms and flies, the same mechanisms are frequently observed in mammals, indicating that the genes and signaling pathways that regulate lifespan are highly conserved among different species. This review summarizes the lifespan-regulating genes, with a specific focus on studies in C. elegans.
Surgical Outcomes of Synchronous Multiple Primary Non-Small Cell Lung Cancers
Authors: Zhang Zhirong , Gao Shugeng , Mao Yousheng , Mu Juwei , Xue Qi , Feng Xiaoli , He Jie 
Published: June 2016

AbstractThe prognostic indicators for synchronous multiple primary non-small cell lung cancer (NSCLC) vary across reports. In present study, the prognostic factors for the patients with synchronous multiple primary NSCLC were analyzed in a large cohort. A total of 285 patients with synchronous multiple primary NSCLC who underwent radical surgical resection and with complete follow-up information were included in this study. The Kaplan-Meier method were used for survival analysis, Cox proportional hazards regression models were used for risk factors evaluation. Among them, 94 (33.0%) patients had bilateral tumors and 51 (17.9%) had multiple (≥3) tumors. The 5-year disease-free survival (DFS) and overall survival (OS) rate was 58.7% and 77.6%, respectively. Univariate analysis identified parameters conferring shorter OS including male gender, symptomatic disease, negative family history, large maximal tumor size, not all adenocarcinomas, advanced highest T stage and lymph node involvement. Multivariate analysis showed that male gender (p = 0.020), symptomatic disease (p = 0.017) and lymph node involvement (p < 0.001) were independent adverse prognosticators. For patients with multiple adenocarcinomas, the 5-year DFS and OS rate was 59.6% and 82.4%, respectively. The subtypes other than lepidic predominant (p < 0.001) and lymph node involvement (p = 0.002) were the independent unfavorable prognosticators. In conclusion, we identified independent prognosticators which will provide the valuable clues for postoperative management of patients with synchronous multiple primary NSCLC.
Principal components analysis and the reported low intrinsic dimensionality of gene expression microarray data
Authors: Lenz Michael , Müller Franz-Josef , Zenke Martin , Schuppert Andreas 
Published: June 2016

AbstractPrincipal components analysis (PCA) is a common unsupervised method for the analysis of gene expression microarray data, providing information on the overall structure of the analyzed dataset. In the recent years, it has been applied to very large datasets involving many different tissues and cell types, in order to create a low dimensional global map of human gene expression. Here, we reevaluate this approach and show that the linear intrinsic dimensionality of this global map is higher than previously reported. Furthermore, we analyze in which cases PCA fails to detect biologically relevant information and point the reader to methods that overcome these limitations. Our results refine the current understanding of the overall structure of gene expression spaces and show that PCA critically depends on the effect size of the biological signal as well as on the fraction of samples containing this signal.
Tracing the locality of prisoners and workers at the Mausoleum of Qin Shi Huang: First Emperor of China (259-210 BC)
Authors: Ma Ying , Fuller Benjamin T. , Sun Weigang , Hu Songmei , Chen Liang , Hu Yaowu , Richards Michael P. 
Published: June 2016

AbstractThe mausoleum complex of the First Emperor of China, Qin Shi Huang (259-210 BC), is one of the most famous and important archaeological sites in China, yet questions remain as to how it was constructed and by whom. Here we present isotopic results of individuals from the Liyi (n = 146) and Shanren sites (n = 14), both associated with the mausoleum complex. Those buried at Liyi represent the local workers/inhabitants of the Qin population, and the δ13C (−8.7 ± 1.5%) and δ15N (10.3 ± 0.7%) values indicate that they consumed predominately millet and/or domestic animals fed millet. In contrast, the Shanren individuals were prisoners forced to construct the mausoleum (found buried haphazardly in a mass grave and some in iron leg shackles), and their δ13C (−15.4 ± 2.9%) and δ15N (8.0 ± 0.6%) results indicate a more mixed C3/C4 diet, with possibly less domestic animals and more wild game protein consumed. This pattern of decreased millet consumption is also characteristic of archaeological sites from southern China, and possible evidence the Shanren prisoners originated from this region (possibly the ancient Chu state located in modern day Hubei Province and parts of Hunan and Anhui Provinces). Further, this finding is in agreement with historical sources and is supported by previous ancient DNA evidence that the mausoleum workers had diverse origins, with many genetically related to southern Chinese groups.
RNA-Seq reveals 10 novel promising candidate genes affecting milk protein concentration in the Chinese Holstein population
Authors: Li Cong , Cai Wentao , Zhou Chenghao , Yin Hongwei , Zhang Ziqi , Loor Juan J. , Sun Dongxiao , Zhang Qin , Liu Jianfeng , Zhang Shengli 
Published: June 2016

AbstractPaired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non-lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we detected 157 at peak lactation and 497 in the non-lactating period with a highly significant correlation with milk protein concentration. Integrated interpretation of differential gene expression indicated that SERPINA1, CLU, CNTFR, ERBB2, NEDD4L, ANG, GALE, HSPA8, LPAR6 and CD14 are the most promising candidate genes affecting milk protein concentration. Similarly, LTF, FCGR3A, MEGF10, RRM2 and UBE2C are the most promising candidates that in the non-lactating period could help the mammary tissue prevent issues with inflammation and udder disorders. Putative genes will be valuable resources for designing better breeding strategies to optimize the content of milk protein and also to provide new insights into regulation of lactogenesis.