bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced expression of the DNA glycosylase gene MUTYH is associated with an increased number of somatic mutations via a reduction in the DNA repair capacity in prostate adenocarcinoma
Authors: Shinmura Kazuya , Kato Hisami , Kawanishi Yuichi , Yoshimura Kimio , Igarashi Hisaki , Goto Masanori , Tao Hong , Inoue Yusuke , Sugiyama Takayuki , Furuse Hiroshi , Ozono Seiichiro , Sugimura Haruhiko
Published: June 2016

8‐Hydroxyguanine (8OHG), a major oxidative DNA lesion, is known to accumulate in prostate cancer; however, the status of one of its repair enzymes, MUTYH, in prostate cancer remains to be elucidated. In this study, we showed that the expression levels of MUTYH mRNA and protein were significantly lower in prostate cancer than in non‐cancerous prostatic tissue by examining two independent, publicly available databases and by performing an immunohistochemical analysis of prostate cancer specimens obtained at our hospital, respectively. About two‐thirds of the prostate cancers exhibited a reduced MUTYH expression. When the effect of reduced MUTYH expression in prostate adenocarcinoma on the somatic mutation load was examined using data from the Cancer Genome Atlas (TCGA) database, the numbers of total somatic mutations and somatic G:C to T:A mutations were significantly higher in the reduced MUTYH expression group than in the other group (P < 0.0001 and P = 0.0013, respectively). To determine the reason why reduced MUTYH expression leads to somatic mutation loads in prostate adenocarcinoma, we compared the DNA repair capacities between PC‐3 prostatic cell line derived clones with different MUTYH expression levels. Both the capacities to cleave DNA containing adenine:8OHG mispairs and to suppress mutations caused by 8OHG were significantly lower in prostatic cell lines with lower MUTYH expression than in prostatic cell lines with higher MUTYH expression. These results suggested that reduced MUTYH expression is associated with somatic mutation loads via a reduction in DNA repair capacity in prostate adenocarcinoma. © 2016 Wiley Periodicals, Inc.
Loss of tyrosine phosphorylation at Y406 abrogates the tumor suppressor functions of the thyroid hormone receptor β
Authors: Park Jeong Won , Zhao Li , Willingham Mark C. , Cheng Sheue‐yann
Published: June 2016

We have recently identified that phosphorylation at tyrosine (Y)406 is critical for the tumor suppressor functions of the thyroid hormone receptor β1 (TRβ) in a breast cancer line. However, still unclear is whether the critical tumor suppressor role of phosphorylated Y406 of TRβ is limited to only breast cancer cells or could be extended to other cell types. In the present studies, we addressed this question by stably expressing TRβ, a mutated TRβ oncogene (PV), or a TRβ mutated at Y406 (TRβY406F) in rat PCCL3 thyroid follicular cells and evaluated their tumor characteristics in athymic mice with elevated thyroid stimulating hormone. PCCL3 cells stably expressing PV (PCCL3‐PV), TRβY406F (PCCL3‐TRβY406F), or vector only (PCCL3‐Neo) developed tumors with sizes in the rank order of TRβY406F>PV = Neo, whereas PCCL3 cells expressing TRβ (PCCL3‐TRβ) barely developed tumors. As evidenced by markedly elevated Ki67, cyclin D1, and p‐Rb protein abundance, proliferative activity was high in PV and TRβY406F tumors, but low in TRβ tumors. These results indicate that TRβ acted as a tumor suppressor in PCCL3 cells, whereas TRβY406F and PV had lost tumor suppressor activity. Interestingly, TRβY406F tumors had very low necrotic areas with decreased TNFα‐NFκB signaling to lower apoptotic activity. In contrast, PV tumors had prominent large necrotic areas, with no apparent changes in TNFα‐NFκB signaling, indicating distinct oncogenic activities of mutant PV and TRβY406F. Thus, the present studies uncovered a novel mechanism by which TRβ could function as a tumor suppressor through modulation of the TNFα‐NFκB signaling. © 2016 Wiley Periodicals, Inc.
Estimation of Apparent Kinetic Constants of Individual Site Types for the Polymerization of Ethylene and α‐olefins with Ziegler–Natta Catalysts
Authors: Chen Keran , Mehdiabadi Saeid , Liu Boping , Soares João B. P.
Published: June 2016

This article proposes a method to quantify the polymerization kinetics of ethylene and α‐olefins with commercial TiCl4/MgCl2 Ziegler–Natta catalysts. The method determines the leading apparent polymerization kinetic constants for each active site in a Ziegler–Natta catalyst by simultaneously fitting the instantaneous polymerization rate, cumulative polymer yield, and polymer molecular weight distribution measured at different times during a series of semi‐batch polymerization experiments. This approach quantifies the behavior of olefin polymerization with multisite catalysts using the least number of adjustable parameters needed to consistently model polymerization kinetics and polymer microstructural data.

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Heterogeneous characteristics of MRI changes of thigh muscles in patients with dysferlinopathy
Authors: Jin Suqin , Du Jing , Wang Zhaoxia , Zhang Wei , Lv He , Meng Lingchao , Xiao Jiangxi , Yuan Yun
Published: June 2016

Introduction: The aim of this study was to evaluate the pattern of thigh muscle MRI changes in a large cohort of patients with dysferlinopathy. Methods: MRI of the thigh was performed in 60 patients. We correlated the scale of muscle involvement on MRI with the modified Gardner‐Medwin and Walton (GM‐W) scale and disease duration. We also analyzed the relationship between muscle changes and genetic mutations. Results: Fatty infiltration and edema were observed in 95.50% and 86.67% of patients, respectively. The hamstring muscles had the highest frequency and mean score of fatty infiltration, although a posterior‐dominant pattern was found in only 56%. Edema most commonly and severely affected the quadriceps and adductor magnus muscles. Fatty infiltration score correlated positively with disease duration and GM‐W scale. Conclusions: The pattern of fatty infiltration was heterogeneous in dysferlinopathy patients. Muscle edema was common. Fatty infiltration can be used to assess disease progression. Muscle Nerve 54: 1072–1079, 2016
Dual Decentralization and Fragmented Authoritarianism in Governance: Crowding Out among Social Programmes in China
Authors: Qian Jiwei , Mok Ka Ho
Published: June 2016

In this paper, we use city‐level datasets of social assistance programmes over 280 cities between year 2003 and 2011 to verify the existence of the crowding out between social assistance programmes and unemployment insurance in China. In other words, the expansion of social assistance programmes is associated with a reduction in the enrolment of unemployment insurance. With verifying the existence of the crowding out, this article argues that the crowding out is a result of an ineffective coordination across government departments. In the process of ‘dual decentralization,’ in which the central government has delegated welfare provision responsibility to local governments, the misalignment of incentive and institutions between central and local governments explains the ineffective coordination. Different from many studies in the literature, this paper presents an adverse consequence of China's bureaucratic incentive system in social policy implementation. Also, while the conceptual framework ‘fragmented authoritarianism’ has highlighted the policy ineffectiveness in the economic policy area, this paper contributes to this literature by illustrating the policy ineffectiveness in the social policy areas. Copyright © 2016 John Wiley & Sons, Ltd.
Effects of different plasma treatments of short fibers on the mechanical properties of polypropylene‐wood composites
Authors: Cavalcante Cordeiro Rafael , Villela Pacheco Laura , Schierl Stefan , Víana Hamílton , Antoun Simão Renata
Published: June 2016

In this work, a custom‐made reactor was developed to treat batches of short wood fibers with plasma. Three different plasma gases were tested: air, methane (CH4) and sulfur hexafluoride (SF6). The latter showed very promising results and was therefore used to prepare additional samples to determine the effects of plasma treatment and conditions on the wood fiber surface properties as well as the adhesion in a polypropylene matrix. As a result, composites made out of fibers plasma treated for 40 min at 60 W demonstrated an increase in the elastic modulus of more than 25%. Scanning electron microscope micrographs of the composites’ fracture surfaces indicated stronger interactions between treated fibers and the matrix. The incorporation of fluorine on treated fiber surfaces, mostly in covalent bonds with carbon, was clearly observed and analyzed by X‐ray photoelectron spectroscopy. The water contact angle on wood specimens treated under similar conditions displayed hydrophobic to superhydrophobic behavior, with contact angles exceeding 130°. POLYM. COMPOS., 39:1468–1479, 2018. © 2016 Society of Plastics Engineers
Absolute protein quantification of the yeast chaperome under conditions of heat shock
Authors: Mackenzie Rebecca J. , Lawless Craig , Holman Stephen W. , Lanthaler Karin , Beynon Robert J. , Grant Chris M. , Hubbard Simon J. , Eyers Claire E.
Published: June 2016

Chaperones are fundamental to regulating the heat shock response, mediating protein recovery from thermal‐induced misfolding and aggregation. Using the QconCAT strategy and selected reaction monitoring (SRM) for absolute protein quantification, we have determined copy per cell values for 49 key chaperones in Saccharomyces cerevisiae under conditions of normal growth and heat shock. This work extends a previous chemostat quantification study by including up to five Q‐peptides per protein to improve confidence in protein quantification. In contrast to the global proteome profile of S. cerevisiae in response to heat shock, which remains largely unchanged as determined by label‐free quantification, many of the chaperones are upregulated with an average two‐fold increase in protein abundance. Interestingly, eight of the significantly upregulated chaperones are direct gene targets of heat shock transcription factor‐1. By performing absolute quantification of chaperones under heat stress for the first time, we were able to evaluate the individual protein‐level response. Furthermore, this SRM data was used to calibrate label‐free quantification values for the proteome in absolute terms, thus improving relative quantification between the two conditions. This study significantly enhances the largely transcriptomic data available in the field and illustrates a more nuanced response at the protein level.
High‐Rate Deposition of Stoichiometric Compounds by Reactive Magnetron Sputtering at Oblique Angles
Authors: Alvarez Rafael , Garcia‐Valenzuela Aurelio , Lopez‐Santos Carmen , Ferrer Francisco J. , Rico Victor , Guillen Elena , Alcon‐Camas Mercedes , Escobar‐Galindo Ramon , Gonzalez‐Elipe Agustin R. , Palmero Alberto
Published: June 2016

Target poisoning in reactive magnetron sputtering deposition of thin films is an undesired phenomenon, well known for causing a drastic fall of the process efficiency. We demonstrate that when this technique is operated at oblique angles, films with composition raging from pure metallic to stoichiometric compound can be grown in non‐poisoned conditions, thus avoiding most of the associated drawbacks. We have employed amorphous TiOx, although the presented results can be easily extrapolated to other materials and conditions. It is found that the proposed method improves 400% the growth rate of TiO2 thin films.
Characterization of P(BAMO/AMMO) ETPE Prepared Using Different Diisocyanates
Authors: Wang Gang , Luo Yunjun
Published: June 2016

Poly(3,3‐bisazidomethyl oxetane/3‐azidomethyl‐3‐methyl oxetane) energetic thermoplastic elastomers (P(BAMO/AMMO) ETPEs) is one of the most valuable ETPEs in the field of energetic binders. P(BAMO/AMMO) ETPEs were prepared using different diisocyanates (TDI, HMDI, IPDI, and HDI) to investigate the influence of the diisocyanate on the performance of P(BAMO/AMMO) ETPEs. Mechanical properties and heats of formation were investigated. FT‐IR spectroscopy results showed that TDI‐based ETPE has the highest degree of hydrogen bonding with a value of 69.00 %. Mechanical test results showed that the TDI‐based ETPE has better mechanical property with maximum stress at 5.24 MPa and breaking elongation at 390 %. The order for degree of hydrogen bonding and mechanical property of different diisocyanate‐based ETPEs was TDI>HMDI>IPDI>HDI. The heats of formation were calculated by the group additivity method and by the heat of combustion method. The values of heats of formation for TDI‐based ETPE were 3.44 kJ g−1 and 3.75 kJ g−1 according to the two methods. Additionally, TDI‐based ETPE has a lager heat of formation than the other ETPEs.
Graphene growth on silicon carbide: A review
Authors: Mishra Neeraj , Boeckl John , Motta Nunzio , Iacopi Francesca
Published: June 2016

Graphene has been widely heralded over the last decade as one of the most promising nanomaterials for integrated, miniaturized applications spanning from nanoelectronics, interconnections, thermal management, sensing, to optoelectronics. Graphene grown on silicon carbide is currently the most likely candidate to fulfill this promise. As a matter of fact, the capability to synthesize high‐quality graphene over large areas using processes and substrates compatible as much as possible with the well‐established semiconductor manufacturing technologies is one crucial requirement. We review here, the enormous scientific and technological advances achieved in terms of epitaxial growth of graphene from thermal decomposition of bulk silicon carbide and the fine control of the graphene electronic properties through intercalation. Finally, we discuss perspectives on epitaxial graphene growth from silicon carbide on silicon, a particularly challenging area that could result in maximum benefit for the integration of graphene with silicon technologies.
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.
Self‐Assembly of Hierarchical Chiral Nanostructures Based on Metal–Benzimidazole Interactions: Chiral Nanofibers, Nanotubes, and Microtubular Flowers
Authors: Zhou Xiaoqin , Jin Qingxian , Zhang Li , Shen Zhaocun , Jiang Long , Liu Minghua
Published: June 2016

Controlled hierarchical self‐assembly of synthetic molecules into chiral nanoarchitectures to mimic those biological chiral structures is of great importance. Here, a low‐molecular‐weight organogelator containing a benzimidazole moiety conjugated with an amphiphilic l‐glutamic amide has been designed and its self‐assembly into various hierarchical chiral nanostructures is investigated. Upon gel formation in organic solvents, 1D chiral nanostructure such as nanofiber and nanotube are obtained depending on the solvents. In the presence of transition and rare earth metal ions, hierarchical chiral nanostructures are formed. Specifically, the addition of TbCl3, EuCl3, and AgNO3 leads to nanofiber structures, while the addition of Cu(NO3)2, Tb(NO3)3, or Eu(NO3)3 provides the microflower structures and microtubular flower structures, respectively. While Eu(III) and Tb(III)‐containing microtubular flowers keep the chirality, the Cu(II)‐coordinated microflowers lose chirality. More interestingly, the nanofibers formed by the gelator coordinated with Eu(III) or Tb(III) ions show not only the supramolecular chirality but also the circularly polarized luminescence.
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

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.1368

This 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

Five 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

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

Cabbage 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.
New versus Frequent Donors: Exploring the Behaviour of the Most Desirable Donors
Authors: Faulkner Margaret , Romaniuk Jenni , Stern Philip
Published: June 2016

While there is no shortage of worthy recipients for prosocial behaviour, there is a constant battle to attract and keep donors. This research examines both money and blood donor behaviour for two key groups, new donors, (to grow the donor base), and frequent donors (to secure current support streams). We draw on over 1.2 million records from a U.S. health related charity for a three-year timeframe; and records of all Australian blood donors (1.1 million) for a five-year timeframe. We show the law-like patterns that underpin brand growth in other markets also apply in the non-profit sector. The vast majority of new donors give just once or twice a year with few giving at higher frequency levels. The stability of donation churn across blood and money suggests a structural norm in behaviour over time rather than an outcome of marketing activity. We discuss implications for resource allocation and marketing strategies.
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

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

Background

Anticoagulation 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.

Methods

We 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).

Results

The 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.

Conclusion

NOACs 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

The 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

A 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.
P047: Frailty assessment to help predict patients at risk of ED-induced delirium
Authors: Giroux M. , Boucher V. , Émond M. , Sirois M. , Daoust R. , Gouin E. , Pelletier M. , Berthelot S. , Voyer P. , Moore L. , Lemire S. , Lamontagne M. , Lee J.S.
Published: June 2016

Introduction: Delirium is a frequent complication among seniors in the emergency department (ED). This condition is often underdiagnosed by ED professionals even though it is associated with functional & cognitive decline, longer hospital length of stay, institutionalization and death. Frailty is increasingly recognized as an independent predictor of adverse events in seniors and screening for frailty in EDs has recently been recommended. The aim of this study was to assess if screening seniors for frailty in EDs could help identify those at risk of ED-induced delirium. Methods: This study is part of the Incidence and Impact measurement of Delirium Induced by ED-Stay study, an ongoing multicenter prospective cohort study in 5 Quebec EDs. Patients were recruited after 8 hours in the ED exposure & followed up to 24h after ward admission. Frailty was assessed at ED admission using the Canadian Study of Health and Aging-Clinical Frailty Scale (CSHA-CFS) which classified seniors from robust (1/7) to severely frail (7/7). Seniors with CSHA-CFS ≥ 5/7 were considered frail. Delirium was assessed using the Confusion assessment method and Delirium Index. Results: Of the 380 patients recruited, mean age was 76.5 (±8.9). Male were 50%. Mean stay in the ED was 1.4 day (±0.82). Preliminary data show an incidence of ED-induced delirium of 8.4%. Average frailty score at baseline was 3.5/7. 72 patients were considered frail, while 289 were considered robust. Among the frail seniors, there were 48.4% (30-66%) patients with ED-induced delirium vs 17.9% (13.7-22.0] in the non-frail ones (p<0.0001). Conclusion: Increased frailty appears to be associated with increased ED-induced delirium. Screening for frailty at emergency triage could help ED professionals identify seniors at higher risk of ED-induced delirium. Further studies are required to confirm the importance of the association between frailty and ED-induced delirium
PL004: A population-based analysis of outcomes in patients with a primary diagnosis of hypertension in the emergency department, using linked datasets
Authors: Masood S. , Atzema C.L. , Austin P.
Published: June 2016

Introduction: Patients seen primarily for hypertension are common in the emergency department. The outcomes of these patients have not been described at a population level. In this study we describe the characteristics and outcomes of the patients making these visits, as well as changes over time. Methods: This retrospective cohort study used linked health databases from the province of Ontario, Canada, to assess emergency department visits made between April 1, 2002 and March 31, 2012 with a primary diagnosis of hypertension. We determined the annual number of visits as well as the age and sex standardized rates. We examined visit disposition and assessed mortality outcomes and potential hypertensive complications at 7, 30, 90, 365 days and 2 years subsequent to the ED visit. Results: There were 206,147 qualifying ED visits from 180 sites. Visits increased by 64% between 2002 and 2012, from 15793 to 25950 annual visits, respectively. The age- and sex-standardized rate increased from 170/100,000 persons to 228/100,000 persons over the same time period, a 34% increase. Eight percent of visits ended in hospitalization, but this proportion decreased from 9.9% to 7.1% over the study period. Mortality was very low, at less than 1% within 90 days, 2.5% within 1 year, and 4.1% within 2 years. Among subsequent hospitalizations for potential hypertensive complications, stroke was the most frequent admitting diagnosis, but the frequency was still <1% within 1 year. Together hospitalizations for stroke, heart failure, acute myocardial infarction, atrial fibrillation, renal failure, hypertensive encephalopathy and dissection were <1% at 30 days. Conclusion: The number of visits made primarily for hypertension has increased dramatically over the last decade. While some of the increase is due to aging of the population, other forces are contributing to the increase. Subsequent mortality and complication rates are low and have declined. With current practice patterns, the feared complications of hypertension are extremely infrequent.
LO018: The utility of ECG characteristics as prognostic markers in pulseless electrical activity arrests: a retrospective observational cohort study
Authors: Ho M. , Gatien M. , Vaillancourt C. , Whitham V. , Stiell I.G.
Published: June 2016

Introduction: Compared to pseudo-pulseless electrical activity (PEA with myocardial contractions present), true PEA is hypothesized to carry a poorer prognosis and to show bradycardia and a wide QRS complex on ECG. Our objective was to study the predictive potential of ECG characteristics on survival to hospital discharge (SHD) for out-of-hospital cardiac arrest (OHCA) patients with PEA initial rhythm. Methods: We studied a cohort of OHCA patients prospectively enrolled between Sept. 2007 and Oct. 2009 at the Ottawa/OPALS site (13 cities, 7 EMS, and 6 Fire services) of the ROC PRIMED study. We included adult (≥ 18) non-traumatic OHCA with PEA initial rhythm where resuscitation was attempted, and for which ECG characteristics were available. We measured mean heart rate (HR), mean QRS interval, and presence of P waves (each with kappa agreement) using the first six QRS complex available. We report patient and system characteristics using descriptive statistics and determined the impact of ECG characteristics (HR, QRS width, P waves) on return of spontaneous circulation (ROSC) and SHD using multivariate regression analysis. Results: Demographics of 332 included cases were: mean age 71.7; male 58.4%; home residence 76.5%; bystander witnessed 56.3%; bystander CPR 28.5%; interval from dispatch to paramedic arrival 6min:24sec; ROSC at ED arrival 26.5%; SHD 5.4%. Survivors had higher mean HR (66.1 vs. 52.0 bpm, p=0.83; kappa=0.69) and shorter mean QRS intervals (108.3 vs. 129.6 ms, p=0.01; kappa=0.74) compared to non-survivors. Presence of p waves could not reliably be ascertained (kappa=0.35). Predictors of ROSC were: ALS paramedic on scene (AdjOR=8.90, 95%CI 1.11-71.41; p=0.04), successful intubation (AdjOR=3.35, 1.75-6.39; p=0.0002), and use of atropine (AdjOR=0.27, 0.14 - 0.50; p<0.0001). Predictors of survival were: location of arrest (AdjOR=1.49, 1.11 - 1.99; p=0.007), and use of atropine (AdjOR=0.06, 0.02-0.22; p<0.0001). Despite various cutoff explorations, ECG characteristics were not predictive of ROSC or survival in multivariate analyses. Survivors had HR as low as 6 bpm and QRS as wide as 357 ms. Conclusion: Early ECG characteristics could not predict ROSC or SHD in a population of OHCA PEA victims, and should not be used to terminate resuscitation efforts. Atropine administration was consistently associated with decreased likelihood of ROSC and survival.
LO057: Association between metoclopramide treatment in the ED for concussion and persistent post-concussion headaches: a propensity score matching analysis
Authors: Bresee N. , Aglipay M. , Barrowman N. , Momoli F. , Dubrovsky A. , Zemek R.
Published: June 2016

Introduction: There is a paucity of pediatric literature regarding effective treatment for post-concussion headache. The objective of this study was to assess whether metoclopramide treatment in the Emergency Department (ED) within 48 hours of injury was associated with reduced persistent headache symptoms post-concussion at 1-week and 1-month post-injury. Methods: Children aged 8-18 years with acute concussion were enrolled across 9 EDs of the Pediatric Emergency Research Canada network in a prospective cohort study [Predicting and Preventing Post-concussive Problems in Paediatrics (5P)] from August 2013 to June 2015. Treatments administered in ED (including metoclopramide) were collected using standardized forms. Self-report symptom questionnaires were rated at baseline, at 7 and 28 days follow-up using the validated Post-Concussion Symptom Inventory (PCSI). Propensity scores for treatment with metoclopramide were calculated using a multivariate logistic regression model including confounders. Intervention and control groups were matched 1:4 on the logit of the propensity scores using a greedy algorithm and nearest-neighbour approach. The primary outcome was headache persistence at one-month. Results: 2095 patients met inclusion criteria and completed baseline assessment. At 1 and 4 weeks respectively, 54% (963/1808) and 26% (456/1780) of participants completing follow-up had persistent headache symptoms. 50 metoclopramide treated participants were propensity score matched to 234 controls (1:4 matching). At 4 weeks, no statistically significant difference in persistent headache symptoms was observed between the treatment and propensity score matched control groups (OR: 0.67; 95% CI: 0.33-1.36, p=0.26). There was also no statistically significant difference between the groups at 1-week post-concussion (OR 0.58; 95% CI: 0.32-1.05, p=0.07). Conclusion: This secondary analysis was unable to detect a statistically significant association between acute ED treatment with metoclopramide and reduced medium and long-term headache symptoms post-concussion. Nevertheless, the 1-week results hold promise, but require a well-powered RCT to fully address confounding issues to determine the benefit of metoclopramide post-concussion.
New singularities for Stokes waves
Authors: Crew Samuel C. , Trinh Philippe H.
Published: May 2016

In 1880, Stokes famously demonstrated that the singularity that occurs at the crest of the steepest possible water wave in infinite depth must correspond to a corner of $120^{\circ }$. Here, the complex velocity scales like $f^{1/3}$ where $f$ is the complex potential. Later in 1973, Grant showed that for any wave away from the steepest configuration, the singularity $f=f^{\ast }$ moves into the complex plane, and is of order $(f-f^{\ast })^{1/2}$ (Grant J. Fluid Mech., vol. 59, 1973, pp. 257–262). Grant conjectured that as the highest wave is approached, other singularities must coalesce at the crest so as to cancel the square-root behaviour. Despite recent advances, the complete singularity structure of the Stokes wave is still not well understood. In this work, we develop numerical methods for constructing the Riemann surface that represents the extension of the water wave into the complex plane. We show that a countably infinite number of distinct singularities exist on other branches of the solution, and that these singularities coalesce as Stokes’ highest wave is approached.
Open/Closed List and Party Choice: Experimental Evidence from the UK
Authors: Blumenau Jack , Eggers Andrew C. , Hangartner Dominik , Hix Simon
Published: June 2016

Which parties benefit from open-list (as opposed to closed-list) proportional representation elections? This article shows that a move from closed-list to open-list competition is likely to be more favorable to parties with more internal disagreement on salient issues; this is because voters who might have voted for a unified party under closed lists may be drawn to specific candidates within internally divided parties under open lists. The study provides experimental evidence of this phenomenon in a hypothetical European Parliament election in the UK, in which using an open-list ballot would shift support from UKIP (the Eurosceptic party) to Eurosceptic candidates of the Conservative Party. The findings suggest that open-list ballots could restrict support for parties that primarily mobilize on a single issue.
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

Recent 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

The 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

The 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

Principal 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.