bluuebunny/crossref_metadata_2025_split huggingface dataset:
Otolith-derived estimates of marine temperature use by West Greenland Atlantic salmon (Salmo salar)
Authors: Minke-Martin Vanessa , Brian Dempson J. , Sheehan Timothy F. , Power Michael 
Published: March 2015

AbstractOtolith-derived estimates of mean marine temperatures used by West Greenland 1SW Atlantic salmon (Salmo salar) of North American origin were determined for fish collected in 2009 and 2010. Otolith material corresponding to the second summer at sea was subsampled, via micro-milling, and analysed by mass spectrometry to produce stable oxygen isotope (δ18O) values from which temperature use estimates were obtained from a salmonid-based fractionation equation. Mean temperature estimates did not differ significantly by period (early vs. late summer), or capture year. The mean and variation estimates were also consistent with temperature use values previously published in the literature or derived from the limited number of data storage tags that have been retrieved for Atlantic salmon, with 80% of all individuals occupying temperatures in the 3.9–9.7°C range. Among-individual differences in temperature use did not correlate with measured otolith growth zone widths. Given the temporal, spatial and methodological variation associated with the derivation of marine temperature use estimates for Atlantic salmon, the data were interpreted to define a range of preferred temperatures within which among-individual differences in growth were driven by the interaction of feeding and temperature use, possibly as a result of the opportunistic feeding behaviour known to predominate among Atlantic salmon.
A novel tetravalent formulation combining the four aggregated domain III-capsid proteins from dengue viruses induces a functional immune response in mice and monkeys
Authors: Suzarte Edith , Gil Lázaro , Valdés Iris , Marcos Ernesto , Lazo Laura , Izquierdo Alienys , García Angélica , López Lázaro , Álvarez Maylin , Pérez Yusleydis , Castro Jorge , Romero Yaremis , Guzmán María G. , Guillén Gerardo , Hermida Lisset 
Published: March 2015

Abstract
Our group developed a subunit vaccine candidate against dengue virus based on two different viral regions: the domain III of the envelope protein and the capsid protein. The novel chimeric protein from dengue-2 virus [domain III-capsid (DIIIC-2)], when presented as aggregated incorporating oligodeoxynucleotides, induced anti-viral and neutralizing antibodies, a cellular immune response and conferred significant protection to mice and monkeys. The remaining constructs were already obtained and properly characterized. Based on this evidence, this work was aimed at assessing the immune response in mice of the chimeric proteins DIIIC of each serotype, as monovalent and tetravalent formulations. Here, we demonstrated the immunogenicity of each protein in terms of humoral and cell-mediated immunity, without antigen competition on the mixture forming the formulation tetra DIIIC. Accordingly, significant protection was afforded as measured by the limited viral load in the mouse encephalitis model. The assessment of the tetravalent formulation in non-human primates was also conducted. In this animal model, it was demonstrated that the formulation induced neutralizing antibodies and memory cell-mediated immune response with IFN-γ-secreting and cytotoxic capacity, regardless the route of immunization used. Taken together, we can assert that the tetravalent formulation of DIIIC proteins constitutes a promising vaccine candidate against dengue virus, and propose it for further efficacy experiments in monkeys or in the dengue human infection model, as it has been recently proposed.
Investigation of a possible outbreak of carbapenem-resistant Acinetobacter baumannii in Odense, Denmark using PFGE, MLST and whole-genome-based SNPs
Authors: Hammerum Anette M. , Hansen Frank , Skov Marianne N. , Stegger Marc , Andersen Paal S. , Holm Anette , Jakobsen Lotte , Justesen Ulrik S. 
Published: March 2015

Abstract

Objectives
The objectives were to study a possible outbreak of carbapenem-resistant Acinetobacter baumannii by comparing three different typing methods (PFGE, MLST and whole-genome SNPs) and to compare the resistance gene profiles of the isolates.

Methods
From December 2012 to October 2013, eight carbapenem-resistant A. baumannii were detected at Odense University Hospital, Odense, Denmark. These isolates were typed by PFGE, with ApaI and SmaI, respectively, and subjected to WGS. The WGS data were used for in silico extraction of MLST types using two different schemes, resistance genes and SNPs, to which 31 publicly available A. baumannii genomes were added.

Results
Using ApaI, the eight isolates had four different PFGE profiles, which were further differentiated using SmaI, separating one of the profiles into two distinct PFGE types. Five ST2 (Pasteur MLST) OXA-23-producing isolates, two ST1 OXA-72-producing isolates and one ST158 OXA-23-producing isolate were detected. The five ST2 isolates were subdivided into ST195, ST208 and ST218 using the Oxford MLST scheme. The phylogenetic analysis based on the core genome showed that six of the eight Danish A. baumannii isolates were located in three distinct clusters. The two remaining isolates did not cluster with other Danish or international isolates included in the study. Isolates that clustered using PFGE, Oxford MLST and phylogenetic analysis also shared similar resistance gene profiles.

Conclusions
The SNP profile, Oxford MLST, PFGE and resistance gene profiles clearly indicated spread of three different A. baumannii strains.
Does Iron Increase the Risk of Malaria in Pregnancy?
Authors: Moya-Alvarez Violeta , Cottrell Gilles , Ouédraogo Smaila , Accrombessi Manfred , Massougbodgi Achille , Cot Michel 
Published: March 2015

Abstract
Background.  Pregnancy-associated malaria (PAM) remains a significant health concern in sub-Saharan Africa. Cross-sectional studies report that iron might be associated with increased malaria morbidity, raising fears that current iron supplementation policies will cause harm in the present context of increasing resistance against intermittent preventive treatment in pregnancy (IPTp). Therefore, it is necessary to assess the relation of iron levels with malaria risk during the entire pregnancy.
Methods.  To investigate the association of maternal iron levels on malaria risk in the context of an IPTp clinical trial, 1005 human immunodeficiency virus-negative, pregnant Beninese women were monitored throughout their pregnancy between January 2010 and May 2011. Multilevel models with random intercept at the individual levels and random slope for gestational age were used to analyze the factors associated with increased risk of a positive blood smear and increased Plasmodium falciparum density.
Results.  During the follow-up, 29% of the women had at least 1 episode of malaria. On average, women had 0.52 positive smears (95% confidence interval [CI], 0.44–0.60). High iron levels (measured by the log10 of ferritin corrected on inflammation) were significantly associated with increased risk of a positive blood smear (adjusted odds ratio = 1.75; 95% CI, 1.46–2.11; P &lt; .001) and high P falciparum density (beta estimate = 0.22; 95% CI, 0.18–0.27; P &lt; .001) during the follow-up period adjusted on pregnancy parameters, comorbidities, environmental and socioeconomic indicators, and IPTp regime. Furthermore, iron-deficient women were significantly less likely to have a positive blood smear and high P falciparum density (P &lt; .001 in both cases).
Conclusions.  Iron levels were positively associated with increased PAM during pregnancy in the context of IPTp. Supplementary interventional studies are needed to determine the benefits and risks of differently dosed iron and folate supplements in malaria-endemic regions.
A Human Immunodeficiency Virus Controller With a Large Population of CD4+CD8+ Double-Positive T Cells
Authors: Durand Christine M. , Buckheit Robert W. , Salgado Maria , Pohlmeyer Christopher W. , Walker-Sperling Victoria E. , Hegarty Robert W. , Ambinder Richard F. , Blankson Joel N. 
Published: March 2015

Abstract
Human immunodeficiency virus (HIV) controllers are patients who control viral replication without antiretroviral therapy. We present the case of an HIV controller who had CD4 and CD8 coexpressed on 40% of his T cells. Although a recent study found that double-positive T cells had superior antiviral capacity in HIV-1 controllers, in this case, the CD4+CD8+ T cells did not have strong antiviral activity.
Bio4j: a high-performance cloud-enabled graph-based data platform
Authors: Pareja-Tobes Pablo , Tobes Raquel , Manrique Marina , Pareja Eduardo , Pareja-Tobes Eduardo 
Published: March 2015

AbstractBackgroundNext Generation Sequencing and other high-throughput technologies have brought a revolution to the bioinformatics landscape, by offering sheer amounts of data about previously unaccessible domains in a cheap and scalable way. However, fast, reproducible, and cost-effective data analysis at such scale remains elusive. A key need for achieving it is being able to access and query the vast amount of publicly available data, specially so in the case of knowledge-intensive, semantically rich data: incredibly valuable information about proteins and their functions, genes, pathways, or all sort of biological knowledge encoded in ontologies remains scattered, semantically and physically fragmented.Methods and ResultsGuided by this, we have designed and developed Bio4j. It aims to offer a platform for the integration of semantically rich biological data using typed graph models. We have modeled and integrated most publicly available data linked with proteins into a set of interdependent graphs. Data querying is possible through a data model aware Domain Specific Language implemented in Java, letting the user write typed graph traversals over the integrated data. A ready to use cloud-based data distribution, based on the Titan graph database engine is provided; generic data import code can also be used for in-house deployment.ConclusionBio4j represents a unique resource for the current Bioinformatician, providing at once a solution for several key problems: data integration; expressive, high performance data access; and a cost-effective scalable cloud deployment model.
Repeatability of evolution on epistatic landscapes
Authors: Bauer Benedikt , Gokhale Chaitanya S. 
Published: March 2015

AbstractEvolution is a dynamic process. The two classical forces of evolution are mutation and selection. Assuming small mutation rates, evolution can be predicted based solely on the fitness differences between phenotypes. Predicting an evolutionary process under varying mutation rates as well as varying fitness is still an open question. Experimental procedures, however, do include these complexities along with fluctuating population sizes and stochastic events such as extinctions. We investigate the mutational path probabilities of systems having epistatic effects on both fitness and mutation rates using a theoretical and computational framework. In contrast to previous models, we do not limit ourselves to the typicalstrong selection, weak mutation (SSWM)-regime or to fixed population sizes. Rather we allow epistatic interactions to also affect mutation rates. This can lead to qualitatively non-trivial dynamics. Pathways, that are negligible in the SSWM-regime, can overcome fitness valleys and become accessible. This finding has the potential to extend the traditional predictions based on the SSWM foundation and bring us closer to what is observed in experimental systems.
Breaking through evolutionary constraint by environmental fluctuations
Authors: de Vos Marjon GJ , Dawid Alexandre , Sunderlikova Vanda , Tans Sander J 
Published: March 2015

AbstractEpistatic interactions can frustrate and shape evolutionary change1, 23–7. Indeed, phenotypes may fail to evolve because essential mutations can only be selected positively if fixed simultaneously5,8,9. How environmental variability affects such constraints is poorly understood. Here we studied genetic constraints in fixed and fluctuating environments, using theEscherichia coli lacoperon as a model system for genotype-environment interactions. The data indicated an apparent paradox: in different fixed environments, mutational trajectories became trapped at sub-optima where no further improvements were possible, while repeated switching between these same environments allowed unconstrained adaptation by continuous improvements. Pervasive cross-environmental trade-offs transformed peaks into valleys upon environmental change, thus enabling escape from entrapment. This study shows that environmental variability can lift genetic constraint, and that trade-offs not only impede but can also facilitate adaptive evolution.
CSN and CAVA: variant annotation tools for rapid, robust next-generation sequencing analysis in the clinic
Authors: Münz Márton , Ruark Elise , Renwick Anthony , Ramsay Emma , Clarke Matthew , Mahamdallie Shazia , Cloke Victoria , Seal Sheila , Strydom Ann , Lunter Gerton , Rahman Nazneen 
Published: March 2015

ABSTRACTBackgroundNext-generation sequencing (NGS) offers unprecedented opportunities to expand clinical genomics. It also presents challenges with respect to integration with data from other sequencing methods and historical data. Provision of consistent, clinically applicable variant annotation of NGS data has proved difficult, particularly of indels, an important variant class in clinical genomics. Annotation in relation to a reference genome sequence, the DNA strand of coding transcripts and potential alternative variant representations has not been well addressed. Here we present tools that address these challenges to provide rapid, standardized, clinically appropriate annotation of NGS data in line with existing clinical standards.MethodsWe developed a clinical sequencing nomenclature (CSN), a fixed variant annotation consistent with the principles of the Human Genome Variation Society (HGVS) guidelines, optimized for automated variant annotation of NGS data. To deliver high-throughput CSN annotation we created CAVA (Clinical Annotation of VAriants), a fast, lightweight tool designed for easy incorporation into NGS pipelines. CAVA allows transcript specification, appropriately accommodates the strand of a gene transcript and flags variants with alternative annotations to facilitate clinical interpretation and comparison with other datasets. We evaluated CAVA in exome data and a clinicalBRCA1/BRCA2gene testing pipeline.ResultsCAVA generated CSN calls for 10,313,034 variants in the ExAC database in 13.44 hours, and annotated the ICR1000 exome series in 6.5 hours. Evaluation of 731 different indels from a single individual revealed 92% had alternative representations in left aligned and right aligned data. Annotation of left aligned data, as performed by many annotation tools, would thus give clinically discrepant annotation for the 339 (46%) indels in genes transcribed from the forward DNA strand. By contrast, CAVA provides the correct clinical annotation for all indels. CAVA also flagged the 370 indels with alternative representations of a different functional class, which may profoundly influence clinical interpretation. CAVA annotation of 50BRCA1/BRCA2gene mutations from a clinical pipeline gave 100% concordance with Sanger data; only 8/25BRCA2mutations were correctly clinically annotated by other tools.ConclusionsCAVA is a freely available tool that provides rapid, robust, high-throughput clinical annotation of NGS data, using a standardized Clinical Sequencing Nomenclature.
Effect of Coenzyme Q10 on Th1/Th2 Paradigm in Females with Idiopathic Recurrent Pregnancy Loss
Authors: Talukdar Ayantika , Sharma Kandala Aparna , Rai Reeta , Deka Dipika , Rao Donthamsetty Nageshwara 
Published: March 2015

ProblemRecurrent pregnancy loss is characterized by predominant Th1‐type immunity and increased reactive oxygen species. Low levels of Coenzyme Q10 are found in the plasma of RPL as compared to healthy pregnant females. Our aim was to investigate whether in vitro supplementation of PBMCs from such females with CoQ10 could change the observed Th1 bias.Method of studyPBMCs were isolated from 20 RPL pregnant and non‐pregnant females and 16 healthy pregnant females and incubated with CoQ10 in in vitro conditions. Phenotyping of Th1, Th2, and Th17 cells was performed by flow cytometry. Cytokine levels were determined by ELISA.ResultsPBMCs treated with CoQ10 showed significantly decreased percentage of Th1 cells (P < 0.005) in pregnant females with history of RPL than in the untreated ones. Also, levels of IFN‐γ and TNF‐α were significantly decreased in the culture supernatant of treated PBMCs from RPL. DCFDA staining showed significantly reduced production of ROS in the treated PBMCs in RPL females.ConclusionCoQ10 was effective in maintaining the immune homeostasis by reducing the proportion of IFN‐γ‐producing T cells and proinflammatory cytokine levels in the RPL pregnant females. This property could be attributed to the capability of CoQ10 in reducing oxidative stress by decreasing ROS production.
Primary synovial epithelioid sarcoma of the knee: distinctly unusual location leading to its confusion with pigmented villonodular synovitis
Authors: Chow Louis Tsun Cheung 
Published: March 2015

Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor occurring in the distal extremities of young adults and is characterized histologically by nodules of epithelioid cells showing central necrosis. Intra‐articular ES is extremely rare; only four cases have been reported, but their radiologic and histologic documentation of intra‐articular origin have been imprecise. We report the first radiologically and histologically well‐documented case of primary synovial ES. A 59‐year‐old woman presented with pain followed by swelling of her right knee for 6 months. MRI revealed an entirely intra‐articular nodular synovial mass in the lateral part of the right knee joint in a background of diffusely thickened synovium. Synovectomy was performed under the clinical impression of pigmented villonodular synovitis (PVNS), a diagnosis erroneously confirmed by the reporting pathologist. The tumor rapidly recurred 3 months afterward and the diagnosis of primary synovial ES was made. Despite above‐knee amputation, the tumor continued to spread proximally to the retroperitoneum. She developed multiple lung metastases and died 20 months after initial presentation. The nodular aggregates of tumor cells with central necrosis resulted in diffuse polypoid synovial thickening mimicking tuberculous synovitis and PVNS. The tumor cells showed positive staining for EMA, CK19, CD34, and complete loss of INI1 staining, establishing the diagnosis of primary synovial ES. The ES spread from the synovium to and along the joint capsule, and then extra‐articularly into the soft tissue surrounding the knee joint, with lymphovascular permeation. Such pattern of spread calls for radical surgical excision as the treatment of choice.
Peripheral blood monocyte and T‐lymphocyte activation levels at diagnosis predict long‐term survival in head and neck squamous cell carcinoma patients
Authors: Aarstad Hans Jørgen , Vintermyr Olav K. , Ulvestad Elling , Aarstad Helene H. , Kross Kenneth W. , Heimdal John. H. 
Published: March 2015

This study was performed to determine whether peripheral blood (PB) monocyte and/or lymphocyte activation at diagnosis were associated with long‐term prognosis in patients with head and neck squamous cell carcinoma (HNSCC), and to what extent such prognostic properties relate to human papilloma virus (HPV)‐associated tumor infection of the included patients. This was a long‐term prospective study describing patient survival in relation to PB T lymphocyte and monocyte activation in patients observed for up to 14 years following diagnosis. Sixty‐four patients from a consecutive cohort of newly diagnosed HNSCC patients along with 16 non‐cancer control patients were included over a period of almost 2 years. Monocyte responsiveness was assessed at diagnosis (N = 56 HNSCC/16 non‐cancer controls) by measuring net levels of spontaneous vs lipopolysaccharide‐induced monocyte chemotactic protein (MCP)‐1 secretion in vitro. PB T lymphocyte activation was determined (N = 58 HNSCC/16 controls) by measuring the percentage of T cells expressing CD69 by flow cytometry. Whether HPV infection or not was determined by PCR analysis on formalin fixed paraffin‐embedded tumor tissue. Tumor HPV‐positive patients had better prognosis than HPV‐negative patients. A low net MCP‐1 response in monocytes predicted increased survival (Relative risk (RR) = 2.1; Confidence interval (CI): 1.1–4.0; p < 0.05). A low percentage of CD69 positive T lymphocytes also predicted better prognosis (RR = 2.6; CI: 1.3–5.0; p = 0.005). The predictive power of MCP‐1 monocyte and CD69 T lymphocyte measures were retained when adjusted for age and gender of the patients and shown to be independent of each other (N = 50 HNSCC/16 controls). The results were similar in HPV tumor‐positive and ‐negative patients. Patients with high monocyte‐ and/or T lymphocyte activation status had low survival with 8% 5 year overall survival (OS) compared to 65% 5 year OS for patients with dual low activation levels (RR = 0.27; CI: 0.14–0.56; p < 0.001), mostly secondary to disease‐specific survival. Both tumor HPV‐positive and ‐negative HNSCC patients with high percentage of CD69 positive T lymphocytes and/or high monocyte MCP‐1 secretion had low long‐term survival. The data suggest that the general inflammatory and adaptive immune systems are independently linked to the clinical aggressiveness of both tumor HPV‐negative and ‐positive HNSCC patients.
Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients
Authors: Taniguchi Hiroya , Yamazaki Kentaro , Yoshino Takayuki , Muro Kei , Yatabe Yasushi , Watanabe Toshiaki , Ebi Hiromichi , Ochiai Atsushi , Baba Eishi , Tsuchihara Katsuya 
Published: March 2015

The Japanese guidelines for the testing of KRAS mutations in colorectal cancer have been used for the past 5 years. However, new findings of RAS (KRAS/NRAS) mutations that can further predict the therapeutic effects of anti‐epidermal growth factor receptor (EGFR) antibody therapy necessitated a revision of the guidelines. The revised guidelines included the following five basic requirements for RAS mutation testing to highlight a patient group in which anti‐EGFR antibody therapy may be ineffective: First, anti‐EGFR antibody therapy may not offer survival benefit and/or tumor shrinkage to patients with expanded RAS mutations. Thus, current methods to detect KRAS exon 2 (codons 12 and 13) mutations are insufficient for selecting appropriate candidates for this therapy. Additional testing of extended KRAS/NRAS mutations is recommended. Second, repeated tests are not required for the detection; tissue materials of either primary or metastatic lesions are applicable for RAS mutation testing. Evaluating RAS mutations prior to anti‐EGFR antibody therapy is recommended. Third, direct sequencing with manual dissection or allele‐specific PCR‐based methods is currently applicable for RAS mutation testing. Fourth, thinly sliced sections of formalin‐fixed, paraffin‐embedded tissue blocks are applicable for RAS mutation testing. One section stained with H&E should be provided to histologically determine whether the tissue contains sufficient amount of tumor cells for testing. Finally, RAS mutation testing must be performed in laboratories with appropriate testing procedures and specimen management practices.
802. DACTYLORHIZA VIRIDIS
Authors: Fay Michael F. , Sayers Brendan , Taylor Ian 
Published: March 2015

SummaryDactylorhiza viridis(L.)R.M.Bateman,Pridgeon &M.W.Chase, the frog orchid, is described and illustrated. Details of its distribution, relationships, pollination, patterns of hybridization and its conservation status inBritain andIreland are provided. Notes on propagation and cultivation are also included.