bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Low‐Frequency Variant in
MAPK14
Provides Mechanistic Evidence of a Link With Myeloperoxidase: A Prognostic Cardiovascular Risk Marker
Authors: Waterworth Dawn M. , Li Li , Scott Robert , Warren Liling , Gillson Christopher , Aponte Jennifer , Sarov‐Blat Lea , Sprecher Dennis , Dupuis Josée , Reiner Alex , Psaty Bruce M. , Tracy Russell P. , Lin Honghuang , McPherson Ruth , Chissoe Stephanie , Wareham Nick , Ehm Margaret G. 
Published: August 2014

Background

Genetics can be used to predict drug effects and generate hypotheses around alternative indications. To support Losmapimod, a p38 mitogen‐activated protein kinase inhibitor in development for acute coronary syndrome, we characterized gene variation in

MAPK
11/14

genes by exome sequencing and follow‐up genotyping or imputation in participants well‐phenotyped for cardiovascular and metabolic traits.

Methods and Results

Investigation of genetic variation in

MAPK
11

and

MAPK
14

genes using additive genetic models in linear or logistic regression with cardiovascular, metabolic, and biomarker phenotypes highlighted an association of
RS
2859144 in

MAPK
14

with myeloperoxidase in a dyslipidemic population (Genetic Epidemiology of Metabolic Syndrome Study),
P
=2.3×10
−6
). This variant (or proxy) was consistently associated with myeloperoxidase in the Framingham Heart Study and Cardiovascular Health Study studies (replication meta‐
P
=0.003), leading to a meta‐
P
value of 9.96×10
−7
in the 3 dyslipidemic groups. The variant or its proxy was then profiled in additional population‐based cohorts (up to a total of 58 930 subjects) including Cohorte Lausannoise, Ely, Fenland, European Prospective Investigation of Cancer, London Life Sciences Prospective Population Study, and the Genetics of Obesity Associations study obesity case–control for up to 40 cardiovascular and metabolic traits. Overall analysis identified the same single nucleotide polymorphisms to be nominally associated consistently with glomerular filtration rate (
P
=0.002) and risk of obesity (body mass index ≥30 kg/m
2
,
P
=0.004).

Conclusions

As myeloperoxidase is a prognostic marker of coronary events, the

MAPK
14

variant may provide a mechanistic link between p38 map kinase and these events, providing information consistent with current indication of Losmapimod for acute coronary syndrome. If replicated, the association with glomerular filtration rate, along with previous biological findings, also provides support for kidney diseases as alternative indications.
The Minotaur’s Labyrinth: Third State Intervention before the International Court of Justice
Authors: Uchkunova Inna 
Published: August 2014

The procedure for intervention before the International Court of Justice has been little explored in literature, which may be explained by the uncertainties that inhabit it.
In fact, this is the reason why States have had little recourse to it – and worse yet – only a few applications for intervention have been successful. The present article seeks to throw light on the most problematic aspects of third State intervention, with a view to finding the thread which will guide a way out of the labyrinth of uncertainty.
Impact of early molecular response in children with chronic myeloid leukemia treated in the French Glivec phase 4 study
Authors: Millot Frédéric , Guilhot Joelle , Baruchel André , Petit Arnaud , Bertrand Yves , Mazingue Françoise , Lutz Patrick , Vérité Cecile , Berthou Christian , Galambrun Claire , Sirvent Nicolas , Yakouben Karima , Schmitt Claudine , Gandemer Virginie , Reguerre Yves , Couillault Gérard , Mechinaud Françoise , Cayuela Jean-Michel 
Published: August 2014

Key Points
Early molecular response at 3 months can predict outcome in children treated with imatinib for CML. Children with CML may be less likely to achieve an early molecular response to imatinib than adults with CML.
Potentiating antilymphoma efficacy of chemotherapy using a liposome for integration of CD20 targeting, ultra-violet irradiation polymerizing, and controlled drug delivery
Authors: Wu Cong , Li Huafei , Zhao He , Zhang Weiwei , Chen Yan , Yue Zhanyi , Lu Qiong , Wan Yuxiang , Tian Xiaoyu , Deng Anmei 
Published: August 2014

Abstract
Unlike most malignancies, chemotherapy but not surgery plays the most important role in treating non-Hodgkin lymphoma (NHL). Currently, liposomes have been widely used to encapsulate chemotherapeutic drugs in treating solid tumors. However, higher in vivo stability owns a much more important position for excellent antitumor efficacy in treating hematological malignancies. In this study, we finely fabricated a rituximab Fab fragment-decorated liposome based on 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC), which can form intermolecular cross-linking through the diacetylenic group by ultra-violet (UV) irradiation. Our experimental results demonstrated that after the UV irradiation, the liposomes exhibit better serum stability and slower drug release with a decreased mean diameter of approximately 285 nm. The cellular uptake of adriamycin (ADR) by this Fab-navigated liposome was about four times of free drugs. Cytotoxicity assays against CD20+ lymphoma cells showed that the half maximal (50%) inhibitory concentration (IC50) of ADR-loaded immunoliposome was only one fourth of free ADR at the same condition. In vivo studies were evaluated in lymphoma-bearing SCID mice. With the high serum stability, finely regulated structure, active targeting strategy via antigen-antibody reaction and passive targeting strategy via enhanced permeability and retention (EPR) effect, our liposome exhibits durable and potent antitumor activities both in the disseminated and localized human NHL xeno-transplant models.
Food allergy training event for restaurant staff; a pilot evaluation
Authors: Bailey Samuel , Billmeier Kindratt Tiffany , Smith Helen , Reading David 
Published: August 2014

AbstractA previous cross‐sectional survey highlighted that restaurant staff in Brighton had gaps in their knowledge of food allergy, which could lead to the provision of unsafe meals to food‐allergic customers. A food allergy training event was developed by a multi‐disciplinary team (health service researcher, clinician, teacher and patient group representative) to equip restaurant staff with the knowledge and skills necessary to safely serve food‐allergic customers. This evaluation summarises the training event's impact on participants’ knowledge of food allergy and their satisfaction with the event.No attendee had previously attended any formal training on food allergy. The percentage of participants who answered all true‐false questions correctly increased from 82% before the training event to 91% afterwards. The percentage of participants who were able to name at least three common allergens increased from 9% to 64%. Both quantitative and qualitative feedback was positive.Restaurant staff require a good understanding of food allergy to ensure that food‐allergic customers are kept safe, and their restaurants operate within the law. This food allergy training event improved participants’ absolute knowledge of food allergy, and attendees changed practice. Recommendations are made which could improve the impact and uptake of future food allergy training events.
DNA copy number evolution in Drosophila cell lines
Authors: Lee Hangnoh , McManus C Joel , Cho Dong-Yeon , Eaton Matthew , Renda Fioranna , Somma Maria Patrizia , Cherbas Lucy , May Gemma , Powell Sara , Zhang Dayu , Zhan Lijun , Resch Alissa , Andrews Justen , Celniker Susan E , Cherbas Peter , Przytycka Teresa M , Gatti Maurizio , Oliver Brian , Graveley Brenton , MacAlpine David 
Published: August 2014

Abstract
Background
Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at the organismal level, but are common in immortalized cell lines and tumors, where they may be an advantage to cells. In order to explore the biological consequences of copy number changes in the Drosophila genome, we resequenced the genomes of 19 tissue-culture cell lines and generated RNA-Seq profiles.

Results
Our work revealed dramatic duplications and deletions in all cell lines. We found three lines of evidence indicating that copy number changes were due to selection during tissue culture. First, we found that copy numbers correlated to maintain stoichiometric balance in protein complexes and biochemical pathways, consistent with the gene balance hypothesis. Second, while most copy number changes were cell line-specific, we identified some copy number changes shared by many of the independent cell lines. These included dramatic recurrence of increased copy number of the PDGF/VEGF receptor, which is also over-expressed in many cancer cells, and of bantam, an anti-apoptosis miRNA. Third, even when copy number changes seemed distinct between lines, there was strong evidence that they supported a common phenotypic outcome. For example, we found that proto-oncogenes were over-represented in one cell line (S2-DRSC), whereas tumor suppressor genes were under-represented in another (Kc167).

Conclusion
Our study illustrates how genome structure changes may contribute to selection of cell lines in vitro. This has implications for other cell-level natural selection progressions, including tumorigenesis.
Generation of transgenic rice with reduced content of major and novel high molecular weight allergens
Authors: Ogo Yuko , Wakasa Yuhya , Hirano Kana , Urisu Atsuo , Matsuda Tsukasa , Takaiwa Fumio 
Published: August 2014

AbstractBackgroundRice seed proteins contain antigens that provoke allergic responses in some individuals with food allergy, particularly in those with cereal allergy, and these antigens can elicit clinical symptoms such as eczema and dermatitis. We previously generated transgenic rice with reduced accumulation of the three major allergens, which dramatically reduced the level of IgE binding from patients’ sera. However, the transgenic rice still possesses allergenic reactivity. Recently, two globulin-like proteins were identified as candidates of novel high molecular weight (HMW) IgE-binding proteins that cause rice allergy.ResultsWe identified a glucosidase family encoded by four genes as novel HMW rice allergens based on IgE antibody reactivity from individuals with allergy to rice. To further reduce allergenicity, we generated transgenic rice with reduced accumulation of these HMW allergens. We crossed the rice with reduced HMW allergens and with reduced major allergens, and all major and HMW allergens were substantially reduced in the progeny of the crossed rice. Allergen suppression did not significantly alter accumulation patterns of seed storage proteins and protein folding enzymes. The sera of a portion of patients showed low IgE-binding to the crossed line, suggesting that the crossed line is effective for a portion of patients who are allergic to proteins other than major allergens.ConclusionsThe transgenic rice with reduced levels of all major and HMW allergens is thought to be an option for a portion of allergy patients with hypersensitive responses to various kinds of rice allergens.
Estimated cerebral oxyhemoglobin as a useful indicator of neuroprotection in patients with post-cardiac arrest syndrome: a prospective, multicenter observational study
Authors: Hayashida Kei , Nishiyama Kei , Suzuki Masaru , Abe Takayuki , Orita Tomohiko , Ito Noritoshi , Hori Shingo ,   J-POP Registry Investigators
Published: August 2014

Abstract
Introduction
Little is known about oxyhemoglobin (oxy-Hb) levels in the cerebral tissue during the development of anoxic and ischemic brain injury. We hypothesized that the estimated cerebral oxy-Hb level, a product of Hb and regional cerebral oxygen saturation (rSO2), determined at hospital arrival may reflect the level of neuroprotection in patients with post-cardiac arrest syndrome (PCAS).

Methods
The Japan Prediction of neurological Outcomes in patients with Post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurologic outcomes after out-of-hospital cardiac arrest (OHCA). This study assessed a subgroup of consecutive patients who fulfilled the J-POP registry criteria and successfully achieved return of spontaneous circulation (ROSC) from OHCA. The primary outcome measure was the neurologic status at 90 days.

Results
We analyzed data from 495 consecutive comatose survivors who were successfully resuscitated from OHCA, including 119 comatose patients with prehospital return of spontaneous circulation (ROSC; 24.0%) and 376 cardiac arrests at hospital arrival. In total, 75 patients (15.1%) presented with good neurologic outcomes. Univariate analysis revealed that the cerebral oxy-Hb levels were significantly higher in patients with good outcomes. Multivariate logistic regression using the backward-elimination method confirmed that the oxy-Hb level was a significant predictor of good neurologic outcomes (adjusted odds ratio, 1.27; 95% confidence interval (CI), 1.11 to 1.46). Analysis of the area under the receiver operating characteristic curve (AUC) revealed that an oxy-Hb cut-off of 5.5 provided optimal sensitivity and specificity for predicting good neurologic outcomes (AUC, 0.87; 95% CI, 0.83 to 0.91; sensitivity, 77.3%; specificity, 85.6%). The oxy-Hb level appeared to be an excellent prognostic indicator with significant advantages over rSO2 and base excess, according to AUC analysis. The significant trend for good neurologic outcomes was consistent, even in the subgroup of patients who achieved return of spontaneous circulation on hospital arrival (1st quartile, 0; 2nd quartile, 16.7%; 3rd quartile, 29.4%; 4th quartile, 53.3%; P < 0.05).

Conclusions
The cerebral oxy-Hb level may predict neurologic outcomes and is a simple and excellent indicator of neuroprotection in patients with PCAS.

Trial registration
UMIN Clinical Trials Registry UMIN000005065. Registered 1 April 2011.
Imago Mundi, Imago AD, Imago ADNI
Authors: Villemagne Victor L , Kim Seong Yoon , Rowe Christopher C , Iwatsubo Takeshi 
Published: August 2014

AbstractSince the launch in 2003 of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in the USA, ever growing, similarly oriented consortia have been organized and assembled around the world. The various accomplishments of ADNI have contributed substantially to a better understanding of the underlying physiopathology of aging and Alzheimer’s disease (AD). These accomplishments are basically predicated in the trinity of multimodality, standardization and sharing. This multimodality approach can now better identify those subjects with AD-specific traits that are more likely to present cognitive decline in the near future and that might represent the best candidates for smaller but more efficient therapeutic trials - trials that, through gained and shared knowledge, can be more focused on a specific target or a specific stage of the disease process. In summary, data generated from ADNI have helped elucidate some of the pathophysiological mechanisms underpinning aging and AD pathology, while contributing to the international effort in setting the groundwork for biomarker discovery and establishing standards for early diagnosis of AD.
Poly-β-hydroxybutyrate production and management of cardboard industry effluent by new Bacillus sp. NA10
Authors: Bhuwal Anish Kumari , Singh Gulab , Aggarwal Neeraj Kumar , Goyal Varsha , Yadav Anita 
Published: August 2014

Abstract

Background
In the present study, we aim to utilize the ecological diversity of soil for the isolation and screening for poly β-hydroxybutyrate (PHB)-accumulating bacteria and production of cost-effective bioplastic using cardboard industry effluent.

Results
A total of 120 isolates were isolated from different soil samples and a total of 62 isolates showed positive results with Nile blue A staining, a specific dye for PHB granules and 27 isolates produced PHB using cardboard industry effluent. The selected isolate NA10 was identified as Bacillus sp. NA10 by studying its morphological, biochemical, and molecular characteristics. The growth pattern for the microorganism was studied by logistic model and exactly fitted in the model. A maximum cell dry weight (CDW) of 7.8 g l−1 with a PHB concentration of 5.202 g l−1 was obtained when batch cultivation was conducted at 37°C for 72 h, and the PHB content was up to 66.6% and productivity was 0.072 g l−1 h−1 in 2.0 L fermentor. Chemical characterization of the extracted PHB was done by H1NMR, Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), Gas chromatography–mass spectrometry (GC-MS) analysis to determine the structure, melting point, and molecular mass of the purified PHB. The polymer sheet of extracted polymer was prepared by blending the polymer with starch for packaging applications.

Conclusions
The isolate NA10 can be a good candidate for industrial production of PHB from cardboard industry waste water cost-effectively and ecofriendly.
The Neuroendocrinology of Chronic Fatigue Syndrome
Authors: Cleare Anthony J. 
Published: August 2014

AbstractChronic fatigue syndrome (CFS) is a common and disabling problem; although most likely of biopsychosocial origin, the nature of the pathophysiological components remains unclear. There has been a wealth of interest in the endocrinology of this condition, which will be reviewed in this article. Most studied has been the hypothalamic-pituitary-adrenal (HPA) axis; although the quality of many studies is poor, the overall balance of evidence points to reduced cortisol output in at least some patients, with some evidence that this is linked to symptom production or persistence. There is evidence for heightened negative feedback and glucocorticoid receptor function and for impaired ACTH and cortisol responses to a variety of challenges. However, there is no evidence for a specific or uniform dysfunction of the HPA axis. Given the many factors that may impinge on the HPA axis in CFS, such as inactivity, sleep disturbance, psychiatric comorbidity, medication, and ongoing stress, it seems likely that HPA axis disturbance is heterogeneous and of multifactorial etiology in CFS. Studies assessing GH, dehydroepiandrostenedione and its sulfate, melatonin, leptin, and neuroendocrine-monoamine interactions are also reviewed. There is some evidence from these studies to suggest alterations of dehydroepiandrostenedione sulfate function and abnormal serotonin function in CFS, but whether these changes are of functional importance remains unclear. To obtain a clearer assessment of the etiological and pathophysiological relevance of endocrine changes in CFS, it is suggested that more prospective cohort studies be undertaken in groups at high risk for CFS, that patients with CFS are followed up into recovery, and that multidimensional assessments are undertaken to unravel the influence of the various confounding factors on the observed endocrine changes in CFS.
Fabrication of Ceria Nanoparticles Incorporated in Porous Coordination Polymer
Authors: Kim Cho Rong , Uemura Takashi , Kitagawa Susumu 
Published: August 2014

Abstract
Nanosized ceria was fabricated in the channels of a porous coordination polymer (PCP) by the sol–gel polycondensation of cerium tetraisopropoxide. The resulting composite was characterized by IR, UV–vis, XRD, and XPS measurements, and the obtained ceria was found to be composed of a higher concentration of Ce3+ as compared to that of bulk synthesized ceria. Gas sorption of the composite showed the presence of ceria nanoparticles inside the channels of the PCP, which gave oxygen affinity for the PCP.
N-Alkylation of α-Iminophosphonates and Application to Horner–Wadsworth–Emmons Reaction
Authors: Shimizu Makoto , Tateishi Masasato , Mizota Isao 
Published: August 2014

Abstract
N-Alkylation of α-iminophosphonates with Grignard reagents gives α-N-alkylaminophosphonates. A subsequent Horner–Wadsworth–Emmons reaction of the intermediary α-metalated phosphonate takes place with aldehydes to give enamines. The enamine thus prepared reacts with MVK to give a four-component coupling product.
Nomenclature and typification of the name Crinum balfourii Mast. (Amaryllidaceae)
Authors: Choo Thereis Y.S. , Trias-Blasi Anna , Reveal James L. 
Published: August 2014

AbstractThe bibliographic citation of Crinum balfourii is revised. The species authority has traditionally been attributed to J.G. Baker who described the species in honour of its discoverer, I.B. Balfour, from a flowering specimen cultivated at the Royal Botanic Gardens, Kew, England. However, the species name and a brief diagnostic description were published earlier in the horticultural periodical, The Gardeners' Chronicle, edited by M.T. Masters. Determination of Masters's original type material is open to interpretation and the various possibilities are discussed. In light of current evidence, we herein designate a neotype for the species, rendering Baker's name an isonym.
A multi–step comparison of short–read full plastome sequence assembly methods in grasses
Authors: Wysocki William P. , Clark Lynn G. , Kelchner Scot A. , Burke Sean V. , Pires J. Chris , Edger Patrick P. , Mayfield Dustin R. , Triplett Jimmy K. , Columbus J. Travis , Ingram Amanda L. , Duvall Melvin R. 
Published: August 2014

AbstractTechnological advances have allowed phylogenomic studies of plants, such as full chloroplast genome (plastome) analysis, to become increasingly popular and economically feasible. Although next–generation short–read sequencing allows for full plastomes to be sequenced relatively rapidly, it requires additional attention using software to assemble these reads into comprehensive sequences. Here we compare the use of three de novo assemblers combined with three contig assembly methods. Seven plastome sequences were analyzed. Three of these were Sanger–sequenced. The other four were assembled from short, single–end read files generated from next–generation libraries. These plastomes represented a total of six grass species (Poaceae), one of which was sequenced in duplicate by the two methods to allow direct comparisons for accuracy. Enumeration of missing sequence and ambiguities allowed for assessments of completeness and efficiency. All methods that used de Bruijn–based de novo assemblers were shown to produce assemblies comparable to the Sanger–sequenced plastomes but were not equally efficient. Contig assembly methods that utilized automatable and repeatable processes were generally more efficient and advantageous when applied to larger scale projects with many full plastomes. However, contig assembly methods that were less automatable and required more manual attention did show utility in determining plastomes with lower read depth that were not able to be assembled when automatable procedures were implemented. Although the methods here were used exclusively to generate grass plastomes, these could be applied to other taxonomic groups if previously sequenced plastomes were available. In addition to comparing sequencing methods, a supplemental guide for short–read plastome assembly and applicable scripts were generated for this study.