bluuebunny/crossref_metadata_2025_split huggingface dataset:
Status of pediatric anesthesiology fellowship research education in the United States: a survey of fellowship program directors
Authors: Benzon Hubert A. , De Oliveira Gildasio S. , Hardy Courtney A. , Suresh Santhanam 
Published: December 2013

SummaryBackgroundCurrently, very little information is known regarding the research education of pediatric anesthesia fellows.ObjectiveThe main objective of the current investigation was to evaluate the status of research training in pediatric anesthesia fellowship programs in the United States.MethodsSurvey responses were solicited from forty‐six pediatric anesthesia fellowship directors. Questions evaluated department demographic information, the extent of faculty research activity, research resources and research funding in the department, the characteristics of fellow research education and fellow research productivity, departmental support for fellow research, and perceived barriers to fellow research education.ResultsThirty‐six of forty‐six fellowship directors responded to the survey, for a response rate of 78%. Eight of fourteen (57%) programs with a structured curriculum had more than 20% of graduating fellows publish a peer‐reviewed manuscript compared with only five of twenty‐two (23%) programs, which did not have a structured research curriculum (P = 0.03). While the majority of program directors (thirty of thirty‐six (83%)) did not think that fellows are adequately trained to pursue research activities, only a minority of program directors (7 of 36 (19%)) thought that an extra year of fellowship dedicated to research should become a requirement.ConclusionStructured research curriculum is associated with increased research productivity during pediatric anesthesia fellowship. Important barriers to fellows' research education include high clinical demands and lack of research time for faculty. Despite acknowledging the poor research education, a small minority of fellowship directors supports the addition of an extra year exclusively dedicated to research.
Expression of a single‐chain human leukocyte antigen‐DRA/DRB3*01:01 molecule and differential binding of a monoclonal antibody in the presence of specifically bound human platelet antigen‐1a peptide
Authors: Bouwmans Evelien E. , Smethurst Peter A. , Garner Stephen F. , Ouwehand Willem H. , Morley Sarah L. 
Published: December 2013

BackgroundStudies show that 1 in 1200 neonates have a low platelet (PLT) count due to alloimmunization against humanPLTantigen (HPA)‐1a (β3‐L33). This mainly occurs inHPA‐1a–negative mothers who are positive for the human leukocyte antigen (HLA)‐DRB3*01:01 allele, but only about one‐third of cases will mount an effective alloimmune response. The development of specific treatment modalities requires that the mechanisms driving the maternal alloimmune response against the fetalPLTsbe further explored. An antibody reagent that has a different binding affinity toHLA‐DRA/DRB3*01:01 with and without the β3‐L33 peptide would be a valuable reagent to study peptide presentation on maternal antigen‐presenting cells.Study Design and MethodsTo identify such antibodies,HLA‐DRA/DRB3*01:01 was recombinantly expressed inDrosophila S2 cells. To delineate the epitope of interesting antibodies, seven mutantHLA‐DRA/DRB3*01:01 molecules were generated by site‐directed mutagenesis introducing naturally occurring amino acid changes encoded byDRB3*02 andDRB3*03 alleles.ResultsThe murine monoclonal antibody (MoAb)DA2 showed robust binding by enzyme‐linked immunosorbent assay to recombinantHLA‐DRA/DRB3*01:01, but binding was reduced in the presence of β3‐L33 peptide. The binding affinity ofDA2 to the mutantHLA‐DRA/DRB3*0101 in which serine atPosition 60 of the β1‐chain was replaced by tyrosine was greatly enhanced. Interestingly the binding ofDA2 to the mutant was not reduced by the presence of β3‐L33 peptide.ConclusionThe results of this study generate a molecular model of the interaction of theHLA‐DRA/DRB3*01:01 molecule withMoAb DA2. This will inform functional studies with the recombinantClassIImolecules.
Complete Genome of Acinetobacter baumannii Podophage Petty
Authors: Mumm Ian P. , Wood Thammajun L. , Chamakura Karthik R. , Kuty Everett Gabriel F. 
Published: December 2013

ABSTRACT

Acinetobacter baumannii
is an emerging pathogen that was isolated from wounded soldiers in military treatment facilities in Iraq but has since become a problem in civilian hospitals. Here, we announce and describe the complete genome of the ϕKMV-like
A. baumannii
podophage Petty.
Complete Genome of Bacillus thuringiensis Myophage BigBertha
Authors: Ting Jose H. , Smyth Trinity B. , Chamakura Karthik R. , Kuty Everett Gabriel F. 
Published: December 2013

ABSTRACT

BigBertha is a myophage of
Bacillus thuringiensis
, a widely used biocontrol agent that is active against many insect pests of plants. Here, we present the complete annotated genome of BigBertha. The genome shares 85.9% sequence identity with
Bacillus cereus
phage B4.
Draft Genome Sequence of Veillonella parvula HSIVP1, Isolated from the Human Small Intestine
Authors: van den Bogert Bartholomeus , Boekhorst Jos , Smid Eddy J. , Zoetendal Erwin G. , Kleerebezem Michiel 
Published: December 2013

ABSTRACT

Veillonella
species are frequently encountered commensals in the human small intestine. Here, we report the draft genome sequence of the first cultured representative from this ecosystem,
Veillonella parvula
strain HSIVP1. The genome is predicted to encode all the necessary enzymes required for the pathway involved in the conversion of lactate to propanoate.
The Colony-Stimulating Factors and Cancer
Authors: Metcalf Donald 
Published: December 2013

AbstractThe colony-stimulating factors (CSF) are the master regulators of granulocyte and macrophage populations. There are four different aspects of the connection between the CSFs and cancer: (i) the CSFs can accelerate the regeneration of protective white cells damaged by chemotherapy; (ii) the CSFs can mobilize stem cells to the peripheral blood in convenient numbers for transplantation; (iii) the CSFs can enhance anticancer immune responses; and (iv) the CSFs are potentially involved in the genesis of the myeloid leukemias. Cancer Immunol Res; 1(6); 351–6. ©2013 AACR.
Aldosterone Promotes Vascular Remodeling by Direct Effects on Smooth Muscle Cell Mineralocorticoid Receptors
Authors: Pruthi Dafina , McCurley Amy , Aronovitz Mark , Galayda Carol , Karumanchi S. Ananth , Jaffe Iris Z. 
Published: December 2013

Objective—
Vascular remodeling occurs after endothelial injury, resulting in smooth muscle cell (SMC) proliferation and vascular fibrosis. We previously demonstrated that the blood pressure–regulating hormone aldosterone enhances vascular remodeling in mice at sites of endothelial injury in a placental growth factor–dependent manner. We now test the hypothesis that SMC mineralocorticoid receptors (MRs) directly mediate the remodeling effects of aldosterone and further explore the mechanism.

Approach and Results—
A wire-induced carotid injury model was performed in wild-type mice and mice with inducible SMC-specific deletion of the MR. Aldosterone did not affect re-endothelialization after injury in wild-type mice. Deletion of SMC-MR prevented the 79% increase in SMC proliferation induced by aldosterone after injury in MR-Intact littermates. Moreover, both injury-induced and aldosterone-enhanced vascular fibrosis were attenuated in SMC-specific MR knockout mice. Further exploration of the mechanism revealed that aldosterone-induced vascular remodeling is prevented by in vivo blockade of the placental growth factor–specific receptor, type 1 vascular endothelial growth factor receptor (VEGFR1), the receptor for placental growth factor. Immunohistochemistry of carotid vessels shows that the induction of VEGFR1 expression in SMC after vascular injury is attenuated by 72% in SMC-specific MR knockout mice. Moreover, aldosterone induction of vascular placental growth factor mRNA expression and protein release are also prevented in vessels lacking SMC-MR.

Conclusions—
These studies reveal that SMC-MR is necessary for aldosterone-induced vascular remodeling independent of renal effects on blood pressure. SMC-MR contributes to induction of SMC VEGFR1 in the area of vascular injury and to aldosterone-enhanced vascular placental growth factor expression and hence the detrimental effects of aldosterone are prevented by VEGFR1 blockade. This study supports exploring MR antagonists and VEGFR1 blockade to prevent pathological vascular remodeling induced by aldosterone.
Foraging behaviour of brown trout in wild populations: can population density cause behaviourally-mediated foraging specializations?
Authors: Sánchez-Hernández Javier , Cobo Fernando 
Published: December 2013

Brown trout is considered as a territorial fish, in which negative density effects on growth and survival rates can be mediated through competition mechanisms. Here, in order to examine whether competition mechanisms can affect the foraging behaviour of wildSalmo truttawith respect to active-bottom, benthic-drift or surface-drift foraging, three neighbouring populations under different levels of fish density (high, intermediate and low) were studied. We analysed the foraging behaviour of each population according to niche breadth, prey preferences, the modified Costello graphical method and prey trait analysis. The results revealed a remarkable similarity in the feeding behaviour among these feral fish populations, suggesting a foraging behaviour convergence in response to site-specific prey accessibility. A generalist foraging behaviour was the prevailing feeding strategy, independent of fish density. Hence, this study offered evidence for the occurrence of density-independent individual foraging behaviour when food is abundant and available; however, density-dependent foraging behaviour might occur when resource limitation exists. Studies under natural conditions like the present study are needed to increase ecological realism, and indeed this study opens promising research directions for future feeding studies in territorial fish species.
A Comparative Performance Analysis of TRMM 3B42 (TMPA) Versions 6 and 7 for Hydrological Applications over Andean–Amazon River Basins
Authors: Zulkafli Zed , Buytaert Wouter , Onof Christian , Manz Bastian , Tarnavsky Elena , Lavado Waldo , Guyot Jean-Loup 
Published: December 2013

Abstract
The Tropical Rainfall Measuring Mission 3B42 precipitation estimates are widely used in tropical regions for hydrometeorological research. Recently, version 7 of the product was released. Major revisions to the algorithm involve the radar reflectivity–rainfall rate relationship, surface clutter detection over high terrain, a new reference database for the passive microwave algorithm, and a higher-quality gauge analysis product for monthly bias correction. To assess the impacts of the improved algorithm, the authors compare the version 7 and the older version 6 products with data from 263 rain gauges in and around the northern Peruvian Andes. The region covers humid tropical rain forest, tropical mountains, and arid-to-humid coastal plains. The authors find that the version 7 product has a significantly lower bias and an improved representation of the rainfall distribution. They further evaluated the performance of the version 6 and 7 products as forcing data for hydrological modeling by comparing the simulated and observed daily streamflow in nine nested Amazon River basins. The authors find that the improvement in the precipitation estimation algorithm translates to an increase in the model Nash–Sutcliffe efficiency and a reduction in the relative bias between the observed and simulated flows by 30%–95%.
Improvement of Medium-Range Forecasts Using the Analog-Dynamical Method
Authors: Yu Haipeng , Huang Jianping , Chou Jifan 
Published: December 2013

AbstractThis study further develops the analog-dynamical method and applies it to medium-range weather forecasts. By regarding the forecast field as a small disturbance superimposed on historical analog fields, historical analog errors can be used to estimate and correct forecast errors. This method is applied to 10-day forecasts from the Global and Regional Assimilation and Prediction System (GRAPES). Both the distribution of atmospheric circulation and the pattern of sea surface temperature (SST) are considered in choosing the analog samples from a historical dataset for 2001–10 based on NCEP Final (FNL) data. The results demonstrate that the analog-dynamical method greatly reduces forecast errors and extends the period of validity of the global 500-hPa height field by 0.8 days, which is superior to results obtained using systematic correction. The correction effect at 500 hPa is increasingly significant when the lead time increases. Although the analogs are selected using 500-hPa height fields, the forecast skill at all vertical levels is improved. The average increase of the anomaly correlation coefficient (ACC) is 0.07, and the root-mean-square error (RMSE) is decreased by 10 gpm on average at a lead time of 10 days. The magnitude of errors for most forecast fields, such as height, temperature, and kinetic energy is decreased considerably by inverse correction. The model improvement is primarily a result of improvement for planetary-scale waves, while the correction for synoptic-scale waves does not affect model forecast skill. As this method is easy to operate and transport to other sophisticated models, it could be appropriate for operational use.
Prevalence of Self-Reported Nonmedical Use of Prescription Stimulants in North Carolina Doctor of Pharmacy Students
Authors: Volger Emily J. , McLendon Amber N. , Fuller Stephen H. , Herring Charles T. 
Published: December 2013

Objectives: To evaluate the prevalence, associated factors, and opinions regarding nonmedical use of prescription stimulants (NMUPS) in Doctor of Pharmacy (PharmD) students. Methods: An electronic survey was distributed to professional year 1 through 4 for students at 2 schools of pharmacy (public and private) in North Carolina. The survey was available for 3 weeks. Descriptive statistics (proportion of responders plus 95% confidence intervals [CIs]) were used to describe the primary objective. Results: Of the 1043 surveys distributed, 407 were completed giving a 39% response rate. The results indicated that 9% (95% CI: 6.44-11.93) of PharmD students acknowledge NMUPS at least once during their pharmacy education. Additionally, 3% (95% CI: 1.90-5.45) acknowledge NMUPS at least once during the current pharmacy school year (past 5 months). Nonmedical prescription stimulant users were 9 times more likely to participate in NMUPS prior to pharmacy school ( P < .0001) and 4.5 times more likely to use other illicit substances ( P = .0076). Conclusion: The study identified the PharmD student population as high risk of abuse of prescription drug stimulants, which requires further research and attention. Additionally, there was a clear upward trend in the prevalence of NMUPS, and this misuse was associated with other detrimental behaviors.
Pharmacogenomics of acute lymphoid leukemia: new insights into treatment toxicity and efficacy
Authors: Relling Mary V. , Ramsey Laura B. 
Published: December 2013

AbstractChildhood acute lymphoblastic leukemia (ALL) provides an outstanding model for pharmacogenomic research: it is a drug-responsive disseminated cancer that is cured with medications alone in ∼ 85% of patients, but relapse remains unacceptably high for some subgroups. Inherited genomic variation contributes to the risk of relapse and to the risk of short- and long-term serious adverse effects of therapy. Our goal is to identify the inherited genomic variants that contribute to interindividual differences in response in patients with ALL. We discuss results of whole-genome interrogations of germline DNA in ALL.
Therapeutic applications: natural killer cells in the clinic
Authors: Miller Jeffrey S. 
Published: December 2013

Abstract
Natural killer (NK) cells recognize targets stressed by malignant transformation or infection (particularly CMV). We now know that NK cells can be long-lived and remember past exposures. They become educated by interaction with MHC class I molecules to gain potent function to kill targets and produce cytokines. In the clinical setting, haploidentical NK cells can be transferred adoptively to treat cancer. Persistence and in vivo expansion of NK cells depends on lymphodepleting chemotherapy to make space for the release of endogenous IL-15. In vivo expansion is also enhanced by cytokine administration. IL-2 has been used at low doses to stimulate NK cells in vivo, but has the down side of stimulating CD25hi regulatory T cells. IL-15 is now being tested and has the advantage of avoiding inhibitory regulatory T cell stimulation. In refractory acute myeloid leukemia, leukemia clearance is correlated with the persistence and in vivo expansion of NK cells after adoptive transfer. Limitations to NK cell therapy include poor in vivo survival and lack of specificity. Monoclonal antibodies and bispecific or trispecific killer engagers to target CD16 on NK cells to enhance recognition of various tumor antigens and ADAM17 inhibition to prevent CD16 shedding after NK cell activation should promote enhanced killing of cancer with specificity. Future strategies to exploit favorable donor immunogenetics or to expand NK cells ex vivo from blood, progenitors, or pluripotent progenitors may overcome immune barriers of adoptive transfer and comparative clinical trials will be needed to test these approaches.
Inherited platelet disorders including Glanzmann thrombasthenia and Bernard-Soulier syndrome
Authors: Diz-Küçükkaya Reyhan 
Published: December 2013

AbstractInherited platelet disorders (IPDs) are a heterogeneous group of diseases affecting platelet production, morphology, and function. The degree of thrombocytopenia and functional abnormality of platelets determines the clinical manifestations. Although severe deficiencies may cause excessive bleeding beginning in early childhood, most of IPDs have mild bleeding tendencies and therefore are not always easy to distinguish from acquired platelet disorders. The diagnosis of IPD may require extensive laboratory investigation, because current routine laboratory tests are not satisfactory for differential diagnosis in some cases, and most of the specific tests are not readily available in many countries. This review summarizes the classification and clinical and molecular characteristics of known IPDs, including Bernard-Soulier syndrome and Glanzmann thrombasthenia, with a focus on current challenges in the laboratory diagnosis and management of bleeding in these patients.
Thrombotic thrombocytopenic purpura: basic pathophysiology and therapeutic strategies
Authors: Crawley James T. B. , Scully Marie A. 
Published: December 2013

Abstract
VWF is a multimeric plasma glycoprotein that specifically recruits platelets to sites of vessel injury. VWF multimeric size is central to this function, with larger multimers being more hemostatically active. Regulation of VWF multimeric size is mediated by the plasma metalloprotease ADAMTS13 (A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motifs, member 13). This enzyme can only recognize and cleave VWF when it is unraveled by rheological shear forces of the flowing blood. After the exposure of cryptic exosites, VWF recognition by ADAMTS13 involves multiple interactions that enable the protease to cleave VWF. Loss of VWF multimer size regulation caused by severe ADAMTS13 deficiency (either inherited or acquired) is associated with the microvascular thrombotic disorder thrombotic thrombocytopenic purpura (TTP). The sequelae associated with TTP are widely thought to be linked to hyperreactive circulating VWF that cause unwanted platelet aggregation in the high shear environment of the microvasculature. Diagnosis of TTP is primarily made through a combination of symptoms, analysis of plasma ADAMTS13 activity, and detection of inhibitory anti-ADAMTS13 antibodies. Current frontline treatments for TTP include plasma exchange, which serves to remove inhibitory antibodies (in acquired TTP) and provide a source of functional ADAMTS13, and steroids to treat the autoimmune component of acquired TTP. The use of anti-CD20 therapy has also exhibited encouraging results in the treatment of acquired TTP. Newer therapeutic strategies that are currently being explored or are in development include recombinant ADAMTS13, a hyperreactive ADAMTS13 variant, and anti-VWF therapy. This review discusses the basic biochemistry of VWF and ADAMTS13, their dysfunction in TTP, and therapeutic approaches for the amelioration of TTP.
Drug discovery in academic institutions
Authors: Frye Stephen V. 
Published: December 2013

Abstract
Although academic science has always provided a fundamental understanding of the biological and clinical basis of disease, the opportunity and imperative for academics to contribute more directly to the discovery of new medicines continues to grow. Embedding medicinal chemists with cancer biologists creates collaborative opportunities for drug discovery and the design and synthesis of chemical biology tool compounds (chemical probes) to better elucidate the role of specific proteins and pathways in biology and disease. Two case studies are presented here: (1) the discovery of inhibitors of mer kinase to treat acute lymphoblastic leukemia in children and (2) the discovery of chemical probes targeting epigenetic regulators. These case studies provide lessons in target selection strategies, the requirement for iterative optimization of lead compounds (useful drugs/probes rarely come directly from a screen), and the value of mutually dependent collaborations between medicinal chemists and cancer biologists.
Antibody-drug conjugates: the chemistry behind empowering antibodies to fight cancer
Authors: Drachman Jonathan G. , Senter Peter D. 
Published: December 2013

Abstract
For more than a century, the concept of a “magic bullet” to deliver cytotoxic therapy to the site of disease has been envisioned but only recently have technological advances enabled antibody-drug conjugates to fulfill that dream. The recent approvals of brentuximab vedotin and ado-trastuzumab emtansine and emerging data for many molecules in clinical trials highlight the potential for antibody-drug conjugates to offer new therapeutic options for patients. This chapter reviews the evolution, state of the art, and potential future improvements that are enabling rapid development of this important class of cancer therapeutics.
Allogeneic transplantation strategies including haploidentical transplantation in sickle cell disease
Authors: Gluckman Eliane 
Published: December 2013

Abstract
Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Despite antenatal counseling and neonatal screening programs implemented in higher income countries, SCD is still associated with multiple morbidities and early mortality. To date, the only curative approach to SCD is hematopoietic stem cell transplantation, but this therapy is not yet established worldwide. The registries of the European Blood and Marrow Transplant (EBMT) and the Centre for International Blood and Marrow Transplant Research (CIBMTR) account, respectively, for 611 and 627 patients receiving transplantations for SCD. Most of these patients were transplanted with grafts from an HLA-identical sibling donor. The main obstacles to increasing the number of transplantations are a lack of awareness on the part of physicians and families, the absence of reliable prognostic factors for severity, and the perceived risk that transplantation complications may outweigh the benefits of early transplantation. Results show that more than 90% of patients having undergone an HLA-identical sibling transplantation after myeloablative conditioning are cured, with very limited complications. Major improvement is expected from the use of new reduced-toxicity conditioning regimens and the use of alternative donors, including unrelated cord blood transplantations and related haploidentical bone marrow or peripheral blood stem cell transplantations.