bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome‐wide association studies and prediction of 17 traits related to phenology, biomass and cell wall composition in the energy grass Miscanthus sinensis
Authors: Slavov Gancho T. , Nipper Rick , Robson Paul , Farrar Kerrie , Allison Gordon G. , Bosch Maurice , Clifton‐Brown John C. , Donnison Iain S. , Jensen Elaine 
Published: December 2013

Summary

Increasing demands for food and energy require a step change in the effectiveness, speed and flexibility of crop breeding. Therefore, the aim of this study was to assess the potential of genome‐wide association studies (GWASs) and genomic selection (i.e. phenotype prediction from a genome‐wide set of markers) to guide fundamental plant science and to accelerate breeding in the energy grass Miscanthus.

We generated over 100 000 single‐nucleotide variants (SNVs) by sequencing restriction site‐associated DNA (RAD) tags in 138 Micanthus sinensis genotypes, and related SNVs to phenotypic data for 17 traits measured in a field trial.

Confounding by population structure and relatedness was severe in naïve GWAS analyses, but mixed‐linear models robustly controlled for these effects and allowed us to detect multiple associations that reached genome‐wide significance. Genome‐wide prediction accuracies tended to be moderate to high (average of 0.57), but varied dramatically across traits. As expected, predictive abilities increased linearly with the size of the mapping population, but reached a plateau when the number of markers used for prediction exceeded 10 000–20 000, and tended to decline, but remain significant, when cross‐validations were performed across subpopulations.

Our results suggest that the immediate implementation of genomic selection in Miscanthus breeding programs may be feasible.
Electrophysiological evidence for early perceptual facilitation and efficient categorization of self‐related stimuli during an Implicit Association Test measuring neuroticism
Authors: Fleischhauer Monika , Strobel Alexander , Diers Kersten , Enge Sören 
Published: December 2013

AbstractThe Implicit Association Test (IAT) is a widely used latency‐based categorization task that indirectly measures the strength of automatic associations between target and attribute concepts. So far, little is known about the perceptual and cognitive processes underlying personality IATs. Thus, the present study examined event‐related potential indices during the execution of an IAT measuring neuroticism (N = 70). The IAT effect was strongly modulated by the P1 component indicating early facilitation of relevant visual input and by a P3b‐like late positive component reflecting the efficacy of stimulus categorization. Both components covaried, and larger amplitudes led to faster responses. The results suggest a relationship between early perceptual and semantic processes operating at a more automatic, implicit level and later decision‐related categorization of self‐relevant stimuli contributing to the IAT effect.
Draft Genome Sequences of Elizabethkingia anophelis Strains R26
T
and Ag1 from the Midgut of the Malaria Mosquito Anopheles gambiae
Authors: Kukutla Phanidhar , Lindberg Bo G. , Pei Dong , Rayl Melanie , Yu Wanqin , Steritz Matthew , Faye Ingrid , Xu Jiannong 
Published: December 2013

ABSTRACT

Elizabethkingia anophelis
is a species in the family
Flavobacteriaceae
. It is a dominant resident in the mosquito gut and also a human pathogen. We present the draft genome sequences of two strains of
E. anophelis
, R26
T
and Ag1, which were isolated from the midgut of the malaria mosquito
Anopheles gambiae
.
Detection of angiographically occult, ruptured cerebral aneurysms: case series and literature review
Authors: Chen Michael 
Published: December 2013

BackgroundRuptured and thrombosed cerebral aneurysms pose a risk for rebleeding that may go undetected because they are angiographically occult. The presence of multiple aneurysms may further complicate efforts in accurately identifying the true source because their treatment may circumvent further necessary investigations.MethodsThis case series and literature review illustrates the background and clinical features of ruptured thrombosed cerebral aneurysms.ResultsThrombosed ruptured cerebral aneurysms have several common anatomic and physiologic mechanisms for their occurrence. They may evade detection if not considered part of a diligent thorough approach that includes careful analysis of the pattern of initial bleeding on non-contrast head CT scan.ConclusionsDespite negative angiographic studies, and even when multiple cerebral aneurysms are present, diffuse subrachnoid hemorrhage may still warrant further investigation.
Deletion of Cysteine-Cysteine Receptor 7 Promotes Fibrotic Injury in Experimental Post-Thrombotic Vein Wall Remodeling
Authors: Laser Adriana , Elfline Megan , Luke Cathy , Slack Dallas , Shah Anuj , Sood Vikram , Deatrick Barry , McEvoy Brendan , Ostra Carson , Comerota Anthony , Kunkel Steven , Hogaboam Cory , Henke Peter K. 
Published: December 2013

Objective—
Deep vein thrombosis (VT) can result in vein wall injury, which clinically manifests as post-thrombotic syndrome. Postinjury fibrosis may be modulated in part through cellular cysteine-cysteine receptor 7 (CCR7)–mediated events. We tested the hypothesis that late vein wall fibrotic remodeling is dependent on CCR7.

Approach and Results—

CCR7
−/−
and C57BL/6 wild-type mice had inferior vena cava VT induced by nonstasis or stasis mechanisms. In both models, VT size was largest at day 1 and trended down by day 21, and CCR7
+
cells peaked at day 8 in wild-type mice. No significant differences in VT resolution were found in CCR7
−/−
as compared with wild type in either model. In the nonstasis VT model, vein wall changes consistent with fibrotic injury were evidenced by significant increases in collagen I, III, matrix metalloproteinase 2, and transforming growth factor-β gene expression, increases in α-smooth muscle actin and fibroblast specific protein-1 antigen, and total collagen at 8 days. Correspondingly, SM22α and fibroblast specific protein-1, but not DDR2
+
cells, were increased at 8 days. Early wild-type thrombus exposure inhibited profibrotic gene expression in CCR7
−/−
in ex vivo vein wall culture. Bone marrow chimera experiments further showed that circulating CCR7
+
leukocytes partially rescued midterm profibrotic changes in CCR7
−/−
mice. In human histological sections of chronic thrombosed femoral veins, CCR7
+
cells were present in the fibrotic areas.

Conclusions—

Post-thrombotic vein wall remodeling is impaired in CCR7
−/−
mice, with a profibrotic phenotype, is dependent on the thrombotic mechanism, and is mediated by circulating CCR7
+
cells. Unlike other postinjury fibrotic responses, CCR7
+
signaling may be important for positive vein wall remodeling after VT.
Postprocessing of Ensemble Weather Forecasts Using a Stochastic Weather Generator
Authors: Chen Jie , Brissette François P. , Li Zhi 
Published: December 2013

Abstract
This study proposes a new statistical method for postprocessing ensemble weather forecasts using a stochastic weather generator. Key parameters of the weather generator were linked to the ensemble forecast means for both precipitation and temperature, allowing the generation of an infinite number of daily times series that are fully coherent with the ensemble weather forecast. This method was verified through postprocessing reforecast datasets derived from the Global Forecast System (GFS) for forecast leads ranging between 1 and 7 days over two Canadian watersheds in the Province of Quebec. The calibration of the ensemble weather forecasts was based on a cross-validation approach that leaves one year out for validation and uses the remaining years for training the model. The proposed method was compared with a simple bias correction method for ensemble precipitation and temperature forecasts using a set of deterministic and probabilistic metrics. The results show underdispersion and biases for the raw GFS ensemble weather forecasts, which indicated that they were poorly calibrated. The proposed method significantly increased the predictive power of ensemble weather forecasts for forecast leads ranging between 1 and 7 days, and was consistently better than the bias correction method. The ability to generate discrete, autocorrelated daily time series leads to ensemble weather forecasts’ straightforward use in forecasting models commonly used in the fields of hydrology or agriculture. This study further indicates that the calibration of ensemble forecasts for a period up to one week is reasonable for precipitation, and for temperature it could be reasonable for another week.
Iron and hepcidin: a story of recycling and balance
Authors: Camaschella Clara 
Published: December 2013

Abstract
To avoid iron deficiency and overload, iron availability is tightly regulated at both the cellular and systemic levels. The liver peptide hepcidin controls iron flux to plasma from enterocytes and macrophages through degradation of the cellular iron exporter ferroportin. The hepcidin-ferroportin axis is essential to maintaining iron homeostasis. Genetic inactivation of proteins of the hepcidin-activating pathway causes iron overload of varying severity in human and mice. Hepcidin insufficiency and increased iron absorption are also characteristic of anemia due to ineffective erythropoiesis in which, despite high total body iron, hepcidin is suppressed by the high erythropoietic activity, worsening both iron overload and anemia in a vicious cycle. Hepcidin excess resulting from genetic inactivation of a hepcidin inhibitor, the transmembrane protease serine 6 (TMPRSS6) leads to a form of iron deficiency refractory to oral iron. Increased hepcidin explains the iron sequestration and iron-restricted erythropoiesis of anemia associated with chronic inflammatory diseases. In mice, deletion of TMPRSS6 in vivo has profound effects on the iron phenotype of hemochromatosis and beta-thalassemia. Hepcidin manipulation to restrict iron is a successful strategy to improve erythropoiesis in thalassemia, as shown clearly in preclinical studies targeting TMPRSS6; attempts to control anemia of chronic diseases by antagonizing the hepcidin effect are ongoing. Finally, the metabolic pathways identified from iron disorders are now being explored in other human pathologic conditions, including cancer.
New immune strategies for the treatment of acute lymphoblastic leukemia: antibodies and chimeric antigen receptors
Authors: Advani Anjali S. 
Published: December 2013

AbstractThe prognosis of adult acute lymphoblastic leukemia (ALL) remains poor and novel treatment strategies are needed. Antibody-based therapies represent such an approach. ALL cells express various surface antigens that are targets for monoclonal antibodies. This review focuses on 4 major classes of antibody therapy: (1) naked antibodies, (2) T-cell-engaging bispecific single-chain antibodies, (3) immunoconjugates/immunotoxins, and (4) chimeric antigen receptors. Preclinical and clinical data are reviewed. This area of research represents an exciting new approach to help improve the outcome of this disease. Several clinical trials are currently incorporating this therapy in the treatment of newly diagnosed and relapsed adult ALL patients.
Signaling the end of chronic lymphocytic leukemia: new frontline treatment strategies
Authors: Hallek Michael 
Published: December 2013

AbstractThe management of chronic lymphocytic leukemia (CLL) is undergoing profound changes. Several new drugs have been approved for CLL treatment (fludarabine, bendamustine, and the monoclonal antibodies alemtuzumab, rituximab, and ofatumumab) and many more drugs are in advanced clinical development to be approved for this disease. In addition, the extreme heterogeneity of the clinical course and our improved ability to foresee the prognosis of this leukemia by the use of clinical, biological, and genetic parameters now allow us to characterize patients with a very mild onset and course, an intermediate prognosis, or a very aggressive course with high-risk leukemia. Therefore, it becomes increasingly challenging to select the right treatment strategy for each condition. This article summarizes the currently available diagnostic and therapeutic tools and gives an integrated recommendation of how to manage CLL in 2013. Moreover, I propose a strategy how we might integrate the novel agents for CLL therapy into sequential treatment approaches in the near future.
Immunotherapeutic strategies including transplantation: eradication of disease
Authors: Gribben John G. , Riches John C. 
Published: December 2013

Abstract
Although there have been recent advances with targeted therapies in chronic lymphocytic leukemia (CLL), chemoimmunotherapy remains the treatment of choice; however, this approach is not curative. A key feature of CLL is that it induces a state of immunosuppression, causing increased susceptibility to infections and failure of an antitumor immune response, often worsened by the immunosuppressive effect of treatment. Because of its improved specificity, immunotherapy potentially offers a way out of this dilemma. Allogeneic stem cell transplantation remains the only curative option, but is hampered by the toxicity of GVHD. After many years of promise but little reward, many other immunotherapeutic approaches are now in transition to the clinical setting. Clinical trials including CLL vaccines, CXCR4 antagonists, and adoptive cellular immunotherapies such as chimeric antigen receptor–modified T cells, CD40 ligand gene therapy, and the immunomodulatory drug lenalidomide are ongoing. Results to date suggest that immunotherapeutic approaches for the treatment of CLL might finally be fulfilling their promise.
Update on current monitoring recommendations in chronic myeloid leukemia: practical points for clinical practice
Authors: Oehler Vivian G. 
Published: December 2013

Abstract
Excellent therapeutic options exist for the treatment of chronic-phase chronic myeloid leukemia (CML) patients. Therefore, managing CML patients has become a more common practice for many physicians. Most chronic-phase CML patients achieve durable cytogenetic and molecular responses on first-line tyrosine kinase inhibitor therapy. However, careful monitoring and assessment of adherence are essential for successful outcomes and to identify patients at risk for failing therapy. The European LeukemiaNet and National Comprehensive Cancer Network provide guidance and strategies for monitoring and managing patients treated with TKIs. These recommendations continue to evolve as approved treatment options expand to include second- and third-generation tyrosine kinase inhibitors. How measurements of response are defined and data supporting recent recommended changes to monitoring are reviewed here. These changes include increasing recognition of the importance of early response. The relevance of achieving deep molecular responses will also be addressed.
Drug discovery in rare indications: opportunities and challenges
Authors: Richon Victoria M. 
Published: December 2013

Abstract
Over the past decade, the number of new therapies developed for the treatment of rare diseases continues to increase. The most rapid growth has been in the development of new drugs for oncology indications. One focus in drug discovery for oncology indications is the development of targeted therapies for select patient subgroups characterized by genetic alterations. The identification of these patient subgroups has increased in the past decade and has resulted in a corresponding increase in the development of new drugs for genetically defined patient subgroups. As an example of the development of new therapeutics for rare indications, I describe here the drug discovery efforts leading to the development of DOT1L inhibitors for the treatment of MLL-rearranged leukemia.
Core-binding factor acute myeloid leukemia: can we improve on HiDAC consolidation?
Authors: Paschka Peter , Döhner Konstanze 
Published: December 2013

AbstractAcute myeloid leukemia (AML) with t(8;21) or inv(16) is commonly referred to as core-binding factor AML (CBF-AML). The incorporation of high-dose cytarabine for postremission therapy has substantially improved the outcome of CBF-AML patients, especially when administered in the setting of repetitive cycles. For many years, high-dose cytarabine was the standard treatment in CBF-AML resulting in favorable long-term outcome in approximately half of the patients. Therefore, CBF-AML patients are generally considered to be a favorable AML group. However, a substantial proportion of patients cannot be cured by the current treatment. Additional genetic alterations discovered in CBF-AML help in our understanding of the process of leukemogenesis and some of them may refine the risk assessment in CBF-AML and, importantly, also serve as targets for novel therapeutic approaches. We discuss the clinical and genetic heterogeneity of CBF-AML, with a particular focus on the role of KIT mutations as a prognosticator, and also discuss recent efforts to target the KIT kinase in the context of existing therapeutic regimens.
T-cell therapy for viral infections
Authors: Heslop Helen E. , Leen Ann M. 
Published: December 2013

Abstract
Viral infections remain a major cause of morbidity in patients with immunodeficiency, such as recipients of hemopoietic stem cell transplantation. Adoptive transfer of donor-derived virus-specific cytotoxic T lymphocytes is a strategy to restore virus-specific immunity to prevent or treat viral diseases and has been tested in the clinical setting for more than 20 years. Several different groups have used expanded virus-specific T-cell products specific for one or multiple viruses to both reconstitute antiviral immunity after transplantation and to treat active viral infections. Response rates are encouraging, although resistance has been seen when the infused cell population has had restricted specificity or has targeted antigens expressed in donor-infected but not virally infected recipient cells. The goal of current trials is to make this approach more broadly applicable using more rapidly available products from the donor, such as directly selected or briefly expanded cells or closely matched banked cells.
T-cell adoptive immunotherapy for acute lymphoblastic leukemia
Authors: Fry Terry J. , Mackall Crystal L. 
Published: December 2013

AbstractSubstantial progress has been made in the treatment of precursor B-cell acute lymphoblastic leukemia (B-ALL), but recurrent disease remains a leading cause of death in children due to cancer and outcomes for adults with B-ALL remain poor. Recently, complete clinical responses have been observed in small numbers of patients with B-ALL treated with adoptive immunotherapy using T cells genetically engineered to express chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule present in essentially all cases of B-ALL. Preclinical data suggest that CARs targeting CD22, another antigen present in the majority of B-ALL cases, are similarly potent. Several clinical studies already under way will soon more clearly define the rate of response to this novel therapy in B-ALL. Further work is needed to identify optimal platforms for CAR-based adoptive immunotherapy for leukemia, to establish guidelines for managing toxicity, and to determine whether the remissions induced by this approach can be rendered durable.
Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies
Authors: Manwani Deepa , Frenette Paul S. 
Published: December 2013

AbstractRecurrent and unpredictable episodes of vaso-occlusion are the hallmark of sickle cell disease. Symptomatic management and prevention of these events using the fetal hemoglobin–reactivating agent hydroxyurea are currently the mainstay of treatment. Discoveries over the past 2 decades have highlighted the important contributions of various cellular and soluble participants in the vaso-occlusive cascade. The role of these elements and the opportunities for therapeutic intervention are summarized in this review.
Long-lasting recombinant factor VIII proteins for hemophilia A
Authors: Shapiro Amy D. 
Published: December 2013

Abstract
In the past 50 years, the lifespan of an individual affected with severe hemophilia A has increased from a mere 20 years to near that of the general unaffected population. These advances are the result of and parallel advances in the development and manufacture of replacement therapies. We are now poised to witness further technologic leaps with the development of longer-lasting replacement therapies, some of which are likely to be approved for market shortly. Prophylactic therapy is currently the standard of care for young children with severe hemophilia A, yet requires frequent infusion to achieve optimal results. Longer-lasting products will transform our ability to deliver prophylaxis, especially in very young children. Longer-lasting replacement therapies will require changes to our current treatment plans including those for acute bleeding, prophylaxis, surgical interventions, and even perhaps immunotolerance induction. Ongoing observation will be required to determine the full clinical impact of this new class of products.
Management of early-stage Hodgkin lymphoma: is there still a role for radiation?
Authors: Johnson Peter W. M. 
Published: December 2013

Abstract
Although radiotherapy is highly effective for the treatment of Hodgkin lymphoma, the realization of its potential long-term toxicity and the demonstration of excellent results from combination chemotherapy have led to a retreat from its use in early-stage disease. Recent trials using functional imaging may allow better identification of those patients for whom radiotherapy may be safely omitted without compromising cure rates and this review examines the evidence for this.
Treatment of fungal disease in the setting of neutropenia
Authors: Walsh Thomas J. , Gamaletsou Maria N. 
Published: December 2013

Abstract
Invasive fungal infections are important causes of morbidity and attributable mortality in neutropenic patients with hematological malignancies, myelodysplasia, and aplastic anemia. Successful risk-based strategies can be implemented for prophylaxis, empirical therapy, and preemptive therapy for the prevention and early treatment of invasive fungal infections in neutropenic hosts. The use of echinocandins for invasive candidiasis and voriconazole for invasive aspergillosis has significantly improved outcome. Recent studies demonstrate, however, that resistant fungal pathogens may emerge during the course of these antifungal interventions. Although triazole-resistant Candida spp. have been well described as causes of breakthrough candidemia, other organisms now pose a similar threat. Such organisms include echinocandin-resistant Candida glabrata and Candida parapsilosis species complex. The Mucorales, Fusarium spp., and Scedosporium spp. may emerge in the setting of voriconazole prophylaxis. The challenges of these emerging pathogens underscore the need for the development of new antifungal agents and strategies.