bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in spatial and temporal incidence of the crustacean pathogen Hematodinium perezi in environmental samples from Atlantic Coastal Bays
Authors: Hanif Ammar W , Dyson Whitney D , Bowers Holly A , Pitula Joseph S , Messick Gretchen A , Jagus Rosemary , Schott Eric J 
Published: May 2013

Abstract

Background

Hematodinium perezi, a parasitic dinoflagellate, infects and kills blue crabs, Callinectes sapidus, along the Atlantic and Gulf coasts of the United States. The parasite proliferates within host hemolymph and tissues, and also produces free-swimming biflagellated dinospores that emerge from infected crabs. Infections in C. sapidus recur annually, and it is not known if biotic or environmental reservoirs contribute to reinfection and outbreaks. To address this data gap, a quantitative PCR assay based on the internal transcribed spacer 2 (ITS2) region of H. perezi rRNA genes was developed to asses the temporal and spatial incidence of the parasite in Delaware and Maryland coastal bays.

Results
A previously-used PCR assay for H. perezi, based on the small subunit rRNA gene sequence, was found to lack adequate species specificity to discriminate non-Hematodinium sp. dinoflagellate species in environmental samples. A new ITS2-targeted assay was developed and validated to detect H. perezi DNA in sediment and water samples using E. coli carrying the H. perezi rDNA genes. Application of the method to environmental samples identified potential hotspots in sediment in Indian River Inlet, DE and Chincoteague Bay, MD and VA. H. perezi DNA was not detected in co-occurring shrimp or snails, even during an outbreak of the parasite in C. sapidus.

Conclusions

H. perezi is present in water and sediment samples in Maryland and Delaware coastal bays from April through November with a wide spatial and temporal variability in incidence. Sampling sites with high levels of H. perezi DNA in both bays share characteristics of silty, organic sediments and low tidal currents. The environmental detection of H. perezi in spring, ahead of peak prevalence in crabs, points to gaps in our understanding of the parasite’s life history prior to infection in crabs as well as the mode of environmental transmission. To better understand the H. perezi life cycle will require further monitoring of the parasite in habitats as well as hosts. Improved understanding of potential environmental transmission to crabs will facilitate the development of disease forecasting.
Alternative Splice Variants of the Rainbow Trout Leptin Receptor Encode Multiple Circulating Leptin-Binding Proteins
Authors: Gong Ningping , Einarsdottir Ingibjörg E. , Johansson Marcus , Björnsson Björn Thrandur 
Published: May 2013

Abstract
In mammals, leptin (Lep) binding proteins (LepBPs) derived from Lep receptor (LepR) gene or protein bind most of the circulating Lep, but to date, information on LepBPs in nonmammalian vertebrate classes is lacking. This study details the characterization of multiple LepBPs in rainbow trout (Oncorhynchus mykiss), an early poikilothermic vertebrate, and presents the complete coding sequences for 3 of them. Size-exclusion chromatography and cross-linking assay identified plasma proteins bound to Lep ranging from 70 to 100 kDa. LepBPs were isolated from plasma by affinity chromatography, and their binding specificity was assessed by a competitive binding assay. A RIA for LepBPs indicates that plasma LepBP levels decline after fasting for 3 weeks. Immunoblotting of LepBPs using antibodies against different LepR epitopes shows that the LepBPs are indeed LepR isoforms. The alternatively spliced LepR transcripts (LepRS1–3) that include only the extracellular segment transcribe the 90-kDa LepBP1, the 80-kDa LepBP2, and the 70-kDa LepBP3, respectively. LepRS1 generally has lower expression than the long-form LepR in most tissues. LepRS2 is primarily expressed in adipose tissue, whereas LepRS3 is expressed abundantly in brain and spleen, and moderately in liver and gills. The mRNA levels of hepatic LepRS3 increase after 2 weeks of fasting. This study demonstrates a mechanism in fish for the generation of LepBPs that differs from that seen in mammals and indicates that the physiologic action of Lep in these poikilothermic vertebrates can be modulated, both centrally and peripherally, by the differentiated, tissue-specific expression of multiple LepBPs.
Amylin Acts in the Central Nervous System to Increase Sympathetic Nerve Activity
Authors: Fernandes-Santos Caroline , Zhang Zhongming , Morgan Donald A. , Guo Deng-Fu , Russo Andrew F. , Rahmouni Kamal 
Published: May 2013

Abstract
The pancreatic hormone amylin acts in the central nervous system (CNS) to decrease food intake and body weight. We hypothesized that amylin action in the CNS promotes energy expenditure by increasing the activity of the sympathetic nervous system. In mice, ip administration of amylin significantly increased c-Fos immunoreactivity in hypothalamic and brainstem nuclei. In addition, mice treated with intracerebroventricular (icv) amylin (0.1 and 0.2 nmol) exhibited a dose-related decrease in food intake and body weight, measured 4 and 24 hours after treatment. The icv injection of amylin also increased body temperature in mice. Using direct multifiber sympathetic nerve recording, we found that icv amylin elicited a significant and dose-dependent increase in sympathetic nerve activity (SNA) subserving thermogenic brown adipose tissue (BAT). Of note, icv injection of amylin also evoked a significant and dose-related increase in lumbar and renal SNA. Importantly, icv pretreatment with the amylin receptor antagonist AC187 (20 nmol) abolished the BAT SNA response induced by icv amylin, indicating that the sympathetic effects of amylin are receptor-mediated. Conversely, icv amylin-induced BAT SNA response was enhanced in mice overexpressing the amylin receptor subunit, RAMP1 (receptor-activity modifying protein 1), in the CNS. Our data demonstrate that CNS action of amylin regulates sympathetic nerve outflow to peripheral tissues involved in energy balance and cardiovascular function.
Heat storage in Asian elephants during submaximal exercise: behavioral regulation of thermoregulatory constraints on activity in endothermic gigantotherms
Authors: Rowe M. F. , Bakken G. S. , Ratliff J. J. , Langman V. A. 
Published: May 2013

SUMMARY
Gigantic size presents both opportunities and challenges in thermoregulation. Allometric scaling relationships suggest that gigantic animals have difficulty dissipating metabolic heat. Large body size permits the maintenance of fairly constant core body temperatures in ectothermic animals by means of gigantothermy. Conversely, gigantothermy combined with endothermic metabolic rate and activity likely results in heat production rates that exceed heat loss rates. In tropical environments, it has been suggested that a substantial rate of heat storage might result in a potentially lethal rise in core body temperature in both elephants and endothermic dinosaurs. However, the behavioral choice of nocturnal activity might reduce heat storage. We sought to test the hypothesis that there is a functionally significant relationship between heat storage and locomotion in Asian elephants (Elephas maximus), and model the thermoregulatory constraints on activity in elephants and a similarly sized migratory dinosaur, Edmontosaurus. Pre- and post-exercise (N=37 trials) measurements of core body temperature and skin temperature, using thermography were made in two adult female Asian elephants at the Audubon Zoo in New Orleans, LA, USA. Over ambient air temperatures ranging from 8 to 34.5°C, when elephants exercised in full sun, ~56 to 100% of active metabolic heat production was stored in core body tissues. We estimate that during nocturnal activity, in the absence of solar radiation, between 5 and 64% of metabolic heat production would be stored in core tissues. Potentially lethal rates of heat storage in active elephants and Edmontosaurus could be behaviorally regulated by nocturnal activity.
One-pot Synthesis of Shape-controlled Fe3O4 Nanocrystals with Alkylsulfonylacetic Acid
Authors: Shen Kaihua , Wang Yanshai , Li Yang 
Published: May 2013

Abstract
A simple, generalized method to prepare magnetite Fe3O4 nanocrystals based on the thermal decarboxylation of an admixture of iron(II) and iron(III) cetylsulfonylacetate is reported. This one-pot process exhibits well shape-controlled magnetite Fe3O4 nanocrystals—from nanoparticles to nanorods—by controlling the reaction temperature in the thermo-decarboxylation procedure.
Complex Biological Pattern of Fertility Hormones in Children and Adolescents: A Study of Healthy Children from the CALIPER Cohort and Establishment of Pediatric Reference Intervals
Authors: Konforte Danijela , Shea Jennifer L , Kyriakopoulou Lianna , Colantonio David , Cohen Ashley H , Shaw Julie , Bailey Dana , Chan Man Khun , Armbruster David , Adeli Khosrow 
Published: May 2013

BACKGROUNDPediatric endocrinopathies are commonly diagnosed and monitored by measuring hormones of the hypothalamic-pituitary-gonadal axis. Because growth and development can markedly influence normal circulating concentrations of fertility hormones, accurate reference intervals established on the basis of a healthy, nonhospitalized pediatric population and that reflect age-, gender-, and pubertal stage–specific changes are essential for test result interpretation.METHODSHealthy children and adolescents (n = 1234) were recruited from a multiethnic population as part of the CALIPER study. After written informed parental consent was obtained, participants filled out a questionnaire including demographic and pubertal development information (assessed by self-reported Tanner stage) and provided a blood sample. We measured 7 fertility hormones including estradiol, testosterone (second generation), progesterone, sex hormone–binding globulin, prolactin, follicle-stimulating hormone, and luteinizing hormone by use of the Abbott Architect i2000 analyzer. We then used these data to calculate age-, gender-, and Tanner stage–specific reference intervals according to Clinical Laboratory Standards Institute C28-A3 guidelines.RESULTSWe observed a complex pattern of change in each analyte concentration from the neonatal period to adolescence. Consequently, many age and sex partitions were required to cover the changes in most fertility hormones over this period. An exception to this was prolactin, for which no sex partition and only 3 age partitions were necessary.CONCLUSIONSThis comprehensive database of pediatric reference intervals for fertility hormones will be of global benefit and should lead to improved diagnosis of pediatric endocrinopathies. The new database will need to be validated in local populations and for other immunoassay platforms as recommended by the Clinical Laboratory Standards Institute.
Rare Variant Association Testing Under Low-Coverage Sequencing
Authors: Navon Oron , Sul Jae Hoon , Han Buhm , Conde Lucia , Bracci Paige M , Riby Jacques , Skibola Christine F , Eskin Eleazar , Halperin Eran 
Published: May 2013

AbstractDeep sequencing technologies enable the study of the effects of rare variants in disease risk. While methods have been developed to increase statistical power for detection of such effects, detecting subtle associations requires studies with hundreds or thousands of individuals, which is prohibitively costly. Recently, low-coverage sequencing has been shown to effectively reduce the cost of genome-wide association studies, using current sequencing technologies. However, current methods for disease association testing on rare variants cannot be applied directly to low-coverage sequencing data, as they require individual genotype data, which may not be called correctly due to low-coverage and inherent sequencing errors. In this article, we propose two novel methods for detecting association of rare variants with disease risk, using low coverage, error-prone sequencing. We show by simulation that our methods outperform previous methods under both low- and high-coverage sequencing and under different disease architectures. We use real data and simulation studies to demonstrate that to maximize the power to detect associations for a fixed budget, it is desirable to include more samples while lowering coverage and to perform an analysis using our suggested methods.
The Aurora B Kinase Promotes Inner and Outer Kinetochore Interactions in Budding Yeast
Authors: Akiyoshi Bungo , Nelson Christian R , Biggins Sue 
Published: May 2013

Abstract
The kinetochore is the macromolecular protein complex that mediates chromosome segregation. The Dsn1 component is crucial for kinetochore assembly and is phosphorylated by the Aurora B kinase. We found that Aurora B phosphorylation of Dsn1 promotes the interaction between outer and inner kinetochore proteins in budding yeast.
Priors in Whole-Genome Regression: The Bayesian Alphabet Returns
Authors: Gianola Daniel 
Published: May 2013

AbstractWhole-genome enabled prediction of complex traits has received enormous attention in animal and plant breeding and is making inroads into human and even Drosophila genetics. The term “Bayesian alphabet” denotes a growing number of letters of the alphabet used to denote various Bayesian linear regressions that differ in the priors adopted, while sharing the same sampling model. We explore the role of the prior distribution in whole-genome regression models for dissecting complex traits in what is now a standard situation with genomic data where the number of unknown parameters (p) typically exceeds sample size (n). Members of the alphabet aim to confront this overparameterization in various manners, but it is shown here that the prior is always influential, unless n ≫ p. This happens because parameters are not likelihood identified, so Bayesian learning is imperfect. Since inferences are not devoid of the influence of the prior, claims about genetic architecture from these methods should be taken with caution. However, all such procedures may deliver reasonable predictions of complex traits, provided that some parameters (“tuning knobs”) are assessed via a properly conducted cross-validation. It is concluded that members of the alphabet have a room in whole-genome prediction of phenotypes, but have somewhat doubtful inferential value, at least when sample size is such that n ≪ p.
Prospective Head and Neck Cancer Research: A Four-Decade Bibliometric Perspective
Authors: Sun Gordon H. , Houlton Jeffrey J. , Moloci Nicholas M. , MacEachern Mark P. , Bradford Carol R. , Prince Mark E. , Jagsi Reshma 
Published: May 2013

Learning Objectives
Outline trends in the gender and continent of origin of first and corresponding authors of prospective head and neck cancer treatment research. Identify trends in the presence of pharmacotherapy, radiotherapy, and surgery in prospective head and neck cancer treatment research.
Real-World Effectiveness of Systemic Agents Approved for Advanced Non-Small Cell Lung Cancer: A SEER–Medicare Analysis
Authors: Owonikoko Taofeek K. , Ragin Camille , Chen Zhengjia , Kim Sungjin , Behera Madhusmita , Brandes Johann C. , Saba Nabil F. , Pentz Rebecca , Ramalingam Suresh S. , Khuri Fadlo R. 
Published: May 2013

Abstract

Objectives.
Disparity exists between patients with lung cancer enrolled in clinical trials and patients treated in the community setting. This study assessed the real-world effectiveness of cytotoxic agents that became available for the treatment of non-small cell lung cancer (NSCLC) in the last 2 decades.

Methods.
We employed the linked Surveillance, Epidemiology, and End Results (SEER)–Medicare database for patients diagnosed with stage IIIB/IV NSCLC between 1988 and 2005 to assess the effectiveness of newly approved agents. Effectiveness of specific agents was assessed at time periods immediately following the approval of the agent for NSCLC: baseline, 1988–1994; platinum, 1995–1999; docetaxel, 1999–2003; pemetrexed and bevacizumab, 2004–2005. Significant associations between specific drug treatment and survival improvement were determined using the Kaplan-Meier method, Cox proportional hazard model, and propensity score analyses. Significant differences were established by log-rank test.

Results.
This analysis employed data from 143,548 patients by sex (58% male, 42% female), cancer stage (35% stage IIIB, 65% stage IV), and age (12% 20–64 years, 22% 65–69 years, 45% 70–79 years, 22% 80 years and older). There was temporal improvement in survival for patients treated with newly approved chemotherapy (1-year survival rates: 32.41% in 1988–1994, 32.95% in 1995–1998, 37.40% in 1999–2003, and 39.55% in 2004–2005). Patients treated with a newly approved drug during the relevant treatment era had a significant reduction in the risk of death when compared with patients treated with chemotherapy other than the newly approved agent (hazard ratios [95% confidence interval] were 0.76 [0.71–0.81] for platinum, 0.73 [0.70–0.75] for docetaxel, 0.40 [0.37–0.44] for pemetrexed, and 0.33 [0.27–0.40] for bevacizumab; p &lt; .001). Propensity score adjustment did not significantly alter these results.

Conclusions.
Currently approved drugs for the treatment of advanced NSCLC are associated with improved survival in the U.S. Medicare patient population. Our findings support the effectiveness of these agents in the real-world oncology practice.
Creating Portfolio Insights by a Practical Multimethod Optimization Approach
Authors: Willigers B.J.A.. J.A. , Weis F.. , Majou F.. 
Published: May 2013

Summary
This study demonstrates how portfolio insights can be created by combining well-known optimization methods that are generally used individually—genetic algorithm (GA), linear programming (LP), and portfolio filtering (PF). An integrated optimization approach combines the advantages of individual methods while mitigating their shortcomings.
Effective portfolio management requires a comprehensive understanding of the tradeoffs between different portfolio choices. Given a set of constraints, portfolio-optimization techniques based on LP and GAs can be applied to identify an optimal portfolio. However, this optimal portfolio might not be the preferred portfolio. Decision makers have to understand the tradeoffs between generally conflicting objectives and constraints before one portfolio can be identified as the preferred option. Such assessment of the overall search space is not made with LP and GAs when used to identify a single best solution, and many portfolio options will have been eliminated before an understanding of these alternatives has been developed.
Markowitz's mean-variance (M-V) approach and the traditional “rank and cut” approach are used typically to establish a relationship between a portfolio's value and its variance or associated development cost. Although these methods enable decision makers to compare and contrast different options, the optimization is limited to the portfolio value measure and a single other metric. This latter limitation is overcome by the more recently developed PF approach. This method is practical and transparent and allows for a quick development of strategic portfolio alternatives while considering a large number of portfolio attributes. Its main drawback is that the analyzed set of portfolios generally represents a subset of the total search space. Thus, as the number of feasible portfolio options increases, so does the chance that the optimal portfolio is not present in the population of sampled portfolios.
Randomized Trial of Continuous Subcutaneous Delivery of Exenatide by ITCA 650 Versus Twice-Daily Exenatide Injections in Metformin-Treated Type 2 Diabetes
Authors: Henry Robert R. , Rosenstock Julio , Logan Douglas K. , Alessi Thomas R. , Luskey Kenneth , Baron Michelle A. 
Published: May 2013

OBJECTIVE
To evaluate ITCA 650, a continuous subcutaneous miniature osmotic pump delivery system of exenatide versus twice-daily exenatide injections (Ex-BID) in subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS
We conducted a randomized, two-stage, 24-week, open-label, phase 2 study in type 2 diabetes inadequately controlled with metformin. Stage I: 155 subjects were randomized to 20 or 40 μg/day of ITCA 650 or Ex-BID 5→10 μg. Stage II: 131 subjects were rerandomized to 20, 40, 60, or 80 μg/day of ITCA 650. Change from baseline for HbA1c, weight, and fasting plasma glucose were evaluated at weeks 12 and 24.

RESULTS
HbA1c was significantly lower in all groups after 12 and 24 weeks. Stage I: mean change in HbA1c from a mean baseline of 7.9–8.0% was −0.98, −0.95, and −0.72% for the 20 and 40 μg/day ITCA 650 and Ex-BID groups, respectively, with 63, 65, and 50% of subjects achieving HbA1c levels ≤7% (P &lt; 0.05). Stage II: significant (P &lt; 0.05) reductions in HbA1c (∼1.4% from baseline) were achieved with 60 and 80 μg/day ITCA 650, and 86 and 78% of subjects achieved HbA1c ≤7% at 24 weeks; respectively. Weight was reduced by 2.8–3.7 kg (P &lt; 0.05) at 24 weeks in all except the 20→20 μg/day group. ITCA 650 was well tolerated; nausea was lower and transient with 20 μg/day relative to Ex-BID; and 60 μg/day had the best profile of tolerability and HbA1c lowering.

CONCLUSIONS
ITCA 650 significantly reduced HbA1c and weight and was well tolerated. The 20→60 μg/day regimen was considered the best dose for further examination in phase 3.
A Critical Analysis of the Clinical Use of Incretin-Based Therapies
Authors: Nauck Michael A. 
Published: May 2013

There is no question that incretin-based glucose-lowering medications have proven to be effective glucose-lowering agents. Glucagon-like peptide 1 (GLP-1) receptor agonists demonstrate an efficacy comparable to insulin treatment and appear to do so with significant effects to promote weight loss with minimal hypoglycemia. In addition, there are significant data with dipeptidyl peptidase 4 (DPP-4) inhibitors showing efficacy comparable to sulfonylureas but with weight neutral effects and reduced risk for hypoglycemia. However, over the recent past there have been concerns regarding the long-term consequences of using such therapies, and the issues raised are in regard to the potential of both classes to promote acute pancreatitis, to initiate histological changes suggesting chronic pancreatitis including associated preneoplastic lesions, and potentially, in the long run, pancreatic cancer. Other issues relate to an increase in thyroid cancer. There are clearly conflicting data that have been presented in preclinical studies and in epidemiologic studies. To provide an understanding of both sides of the argument, we provide a discussion of this topic as part of this two-part point-counterpoint narrative. In the point narrative preceding the counterpoint narrative below, Dr. Butler and colleagues provide their opinion and review of the data to date and that we need to reconsider use of incretin-based therapies because of the growing concern of potential risk and based on a clearer understanding of the mechanism of action. In the counterpoint narrative provided below, Dr. Nauck provides a defense of incretin-based therapies and that benefits clearly outweigh any concern of risk.
—William T. Cefalu, MD Editor in Chief, Diabetes Care