bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic transplantation for AML and MDS: GVL versus GVHD and disease recurrence
Authors: van Besien Koen 
Published: December 2013

Abstract
Allogeneic transplantation constitutes curative treatment for acute myeloid leukemia and myelodysplastic syndrome. Its therapeutic effects are to a large extent mediated by GVL effects, but partially offset by treatment-related mortality and loss of quality of life caused by acute and chronic GVHD. Although severe acute and chronic GVHD are associated with a reduction in relapse risk, they are not associated with improved survival. Recent efforts to modulate the GVL-GVH balance include novel methods of in vitro or in vivo T-cell depletion that are associated with a minimal impact on rates of disease recurrence and a dramatically decreased risk for GVHD. Donor selection algorithms may also have a significant impact on transplantation outcomes. Low-expression HLA alleles, particularly HLA-DP, should be incorporated in selection of adult unrelated donors. Evolving data suggest that KIR typing may also be important. High-resolution HLA typing and the importance of fetal-maternal interactions in umbilical cord blood transplantation are also briefly discussed. A combination of donor selection strategies and GVHD prophylaxis methods will favorably affect long-term outcomes and create an environment suitable for effective posttransplantation interventions.
The use of platelet-rich plasma in the nonsurgical management of sports injuries: hype or hope?
Authors: Harmon Kimberly G. , Rao Ashwin L. 
Published: December 2013

AbstractInterest in platelet-rich plasma (PRP) has skyrocketed over the last decade, with a growing body of research contributing to both excitement and skepticism regarding its use. Despite mixed opinions in the medical field, interest from the public has fueled increased utilization of PRP for musculoskeletal conditions, particularly those that are difficult to treat such as chronic, degenerative tendinopathy and osteoarthritis. PRP's reputation as a “natural healer” and stories in the lay press featuring the use of PRP by professional athletes and celebrities has created a lucrative market for PRP even absent insurance reimbursement, casting further doubt regarding motivation for use by some practitioners. Research of PRP is clouded by the fact that PRP is a heterogeneous term representing a variety of different platelet preparations and there are many variables in technique and postprocedure rehabilitation, all of which may have significant effects on outcome. This article discusses definitions and classification of PRP, reviews rationale and evidence for use of PRP in chronic tendon injuries and osteoarthritis, and looks at future directions.
Pharmacological methods to reduce disease recurrence
Authors: Craddock Charles 
Published: December 2013

Abstract
Allogeneic stem cell transplantation is an increasingly important treatment option in patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Although there has been substantial progress in reducing transplantation-related mortality (TRM), little progress has been made in reducing the risk of disease relapse, which continues to represent the major cause of treatment failure in patients allografted for AML and MDS. Experience with myeloablative conditioning regimens has demonstrated that, although intensification of the preparative regimen reduces relapse risk, any survival benefit is blunted by a concomitant increase in TRM. A similar inverse correlation between relapse risk and TRM is observed in patients allografted using a reduced-intensity conditioning regimen. However, the markedly lower toxicity of such regimens has permitted the design of novel conditioning strategies aimed at maximizing antitumor activity without excessive transplant toxicity. Coupled with recent advances in drug delivery and design, this has allowed the development of a spectrum of new conditioning regimens in patients with high-risk AML and MDS. At the same time, the optimization of a graft-versus-leukemia (GVL) effect by minimizing posttransplantation immunosuppression, with or without the infusion of donor lymphocytes, is essential if the risk of disease relapse is to be reduced. Recently, the delivery of adjunctive posttransplantation therapies has emerged as a promising method of augmenting antileukemic activity, either through a direct antitumor activity or consequent upon pharmacological manipulation of the alloreactive response. Taken together these advances present a realistic possibility of delivering improved outcome in patients allografted for high-risk AML or MDS.
Fresh versus old blood: are there differences and do they matter?
Authors: Zimring James C. 
Published: December 2013

Abstract
The medical effects of transfusing stored RBCs is an area of significant concern that has received substantial attention in recent years. Retrospective trials show all possible outcomes, including sequelae from transfusing older RBCs, no difference between older and fresher RBCs, and a benefit to older RBCs. Several prospective clinical trials are under way to further investigate potential untoward effects of stored RBCs. Thus far, the issue of potential sequelae from transfusing stored RBCs remains a highly controversial issue. However, what is not controversial is that RBC storage is an unnatural state during which a series of substantial changes take place to the stored RBCs. These changes result in the formation of cellular and chemical entities known to have biological activities in other settings, giving rise to several distinct hypotheses by which stored RBCs may alter recipient biology. Herein, the clinical background and basic science of RBC storage are reviewed, with a particular focus on factors that may complicate hypothesis testing and obfuscate underlying biologies. The complexity of the RBC storage lesion, donor-to-donor variation, and the diversity of recipient pathophysiologies remain a challenge to prospective trials assessing the safety of stored RBCs.
Resuscitation of trauma-induced coagulopathy
Authors: Hess John R. 
Published: December 2013

Abstract
For 30 years, the Advanced Trauma Life Support course of the American College of Surgeons taught that coagulopathy was a late consequence of resuscitation of injury. The recognition of trauma-induced coagulopathy overturns that medical myth and creates a rationale for procoagulant resuscitation. Analysis of the composition of currently available blood components allows prediction of the upper limits of achievable coagulation activity, keeping in mind that oxygen transport must be maintained simultaneously. RBCs, plasma, and platelets given in a 1:1:1 unit ratio results in a hematocrit of 29%, plasma concentration of 62%, and platelet count of 90 000 in the administered resuscitation fluid. Additional amounts of any 1 component dilute the other 2 and any other fluids given dilute all 3. In vivo recovery of stored RBCs is ∼ 90% and that of platelets ∼ 60% at the mean age at which such products are given to trauma patients. This means that useful concentrations of the administered products are a hematocrit of 26%, a plasma coagulation factor activity of 62% equivalent to an international normalized ratio of ∼ 1.2, and a platelet count of 54 000. This means there is essentially no good way to give blood products for resuscitation of trauma-induced coagulopathy other than 1:1:1. Because 50% of trauma patients admitted alive to an academic-level 1 trauma center who will die of uncontrolled hemorrhage will be dead in 2 hours, the trauma system must be prepared to deliver plasma- and platelet-based resuscitation at all times.
Heparin-induced thrombocytopenia
Authors: Lee Grace M. , Arepally Gowthami M. 
Published: December 2013

Abstract
Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 (PF4) and heparin. HIT is frequently considered in the differential diagnosis of thrombocytopenia occurring in patients on heparin therapy. HIT is a challenging diagnosis because of routine heparin use in hospitalized patients, the common occurrence of thrombocytopenia, and high rates of anti-PF4/heparin seroconversions in patients treated with heparin. Our diagnostic approach to HIT is presented here, underscoring critical elements of clinical and laboratory evaluation.
Should the presence of an antiphospholipid antibody affect the duration of anticoagulant treatment in patients with venous thromboembolism?
Authors: Garcia David A. , Lim Wendy 
Published: December 2013

Abstract
A 44-year-old otherwise healthy woman has completed 3 months of anticoagulation therapy for a first episode of unprovoked pulmonary embolism. At the time of diagnosis and before the initiation of anticoagulation, she was found to have an elevated IgG anticardiolipin antibody (ACLA), which was measured at 42 IgG phospholipid (GPL) units (reference range, < 15 GPL units) with negative lupus anticoagulant (LAC) testing. Should this laboratory finding affect the recommended duration of anticoagulant therapy?
Cancer-associated thrombosis
Authors: Connolly Gregory C. , Francis Charles W. 
Published: December 2013

AbstractCancer-associated thrombosis accounts for almost one-fifth of all cases of venous thromboembolism (VTE) and is a leading cause of death, morbidity, delays in care, and increased costs. Our understanding of risk factors for cancer-associated thrombosis has expanded in recent years, and investigators have begun to use biomarkers and clinical prediction models to identify those cancer patients at greatest risk for VTE. The Khorana Risk Model, which is based on easily obtained biomarkers and clinical factors, has now been validated in several studies. Recent clinical trials of prophylaxis and treatment of VTE in cancer patients are reviewed here. In addition, consensus guidelines and expert opinion regarding management of VTE in specific challenging situations are presented.
Older patients/older donors: choosing wisely
Authors: Artz Andrew S. 
Published: December 2013

Abstract
Two lingering problems regarding transplantation in older adults have been how to select patients appropriately and whether to use older sibling donors. Allogeneic hematopoietic cell transplantation (HCT) of older patients may result in long-term survival due to GVL, but the data remain observational and mostly restricted to those 50 to 69 years of age. Patients with excellent performance status and low comorbidity have the best long-term survival after HCT. Novel measures of health status such as self-report or performance-based functional measures allow “staging the age” and may inform candidacy for less robust patients. Older matched sibling donors should be preferred over matched unrelated donors (MUDs) because outcomes are equivalent to superior for matched sibling donors compared with MUD. However, MUDs also achieve acceptable outcomes and long-term disease control. An alternative donor can be considered based on institutional protocols and expertise. Very limited information is available in patients or related donors 70 years of age and older. Future efforts to more completely characterize patient health status before transplantation will allow better application of HCT in older adults.
Current concepts in the pathophysiology and treatment of aplastic anemia
Authors: Young Neal S. 
Published: December 2013

Abstract
Historically viewed in isolation as an odd, rare, and invariably fatal blood disease, aplastic anemia is now of substantial interest for its immune pathophysiology, its relationship to constitutional BM failure syndromes and leukemia, and the success of both stem cell transplantation and immunosuppressive therapies in dramatically improving survival of patients. Once relegated to a few presentations in the red cell and anemia sessions of the ASH, the Society now sponsors multiple simultaneous sessions and plenary and scientific committee presentations on these topics. This update emphasizes developments in our understanding of immune mechanisms and hematopoietic stem cell biology and new clinical approaches to stem cell stimulation as a therapy, alone and in combination with conventional suppression of the aberrant immune system.
Management of the refractory aplastic anemia patient: what are the options?
Authors: Marsh Judith C. W. , Kulasekararaj Austin G. 
Published: December 2013

Abstract
Refractory aplastic anemia (AA) is defined as a lack of response to first-line immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and is manifested as persistence of severe cytopenias at 6 months after IST. Although supportive care is critical for AA patients, it is of paramount importance for refractory disease in view of the longer duration of pancytopenia and susceptibility to life-threatening infections due to IST. Improvements in supportive care have largely contributed to better outcome over the past 2 decades, with 5-year overall survival reaching 57% during 2002 to 2008 for patients with AA unresponsive to initial IST. Exclusion of hypocellular myelodysplastic syndrome and constitutional BM failure masquerading as apparent idiopathic AA should be done in conjunction with centers of excellence. Hematopoietic stem cell transplantation is indicated if refractory AA patients are fit and have a suitably matched donor, either a sibling (> 40-50 years) or unrelated donor. Patients lacking a fully matched donor should be considered for a second course of antithymocyte globulin plus cyclosporin, although response in the refractory setting is only ∼ 30% to 35%. Response may also occur with alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA. The emerging data for alternate donor (cord or haploidentical) transplantation in AA has provided additional therapeutic choices to consider in refractory disease.
Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML
Authors: Laszlo George S. , Gudgeon Chelsea J. , Harrington Kimberly H. , Dell’Aringa Justine , Newhall Kathryn J. , Means Gary D. , Sinclair Angus M. , Kischel Roman , Frankel Stanley R. , Walter Roland B. 
Published: December 2013

Key Points
AMG 330 cytotoxicity against AML cells is proportional to the level of CD33 expression but is not affected by ABC transporter activity. AMG 330 cytotoxicity is amenable to modulation and augmentation by clinically available drugs such as histone deacetylase or DNA methyltransferase I inhibitors.
Genetic heterogeneity of asthma phenotypes identified by a clustering approach
Authors: Siroux Valérie , González Juan R. , Bouzigon Emmanuelle , Curjuric Ivan , Boudier Anne , Imboden Medea , Anto Josep Maria , Gut Ivo , Jarvis Deborah , Lathrop Mark , Omenaas Ernst Reidar , Pin Isabelle , Wjst Mathias , Demenais Florence , Probst-Hensch Nicole , Kogevinas Manolis , Kauffmann Francine 
Published: December 2013

The aim of the study was to identify genetic variants associated with refined asthma phenotypes enabling multiple features of the disease to be taken into account.Latent class analysis (LCA) was applied in 3001 adults ever having asthma recruited in the frame of three epidemiological surveys (the European Community Respiratory Health Survey (ECRHS), the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) and the Epidemiological Study on the Genetics and Environment of Asthma (EGEA)). 14 personal and phenotypic characteristics, gathered from questionnaires and clinical examination, were used. A genome-wide association study was conducted for each LCA-derived asthma phenotype, compared to subjects without asthma (n=3474).The LCA identified four adult asthma phenotypes, mainly characterised by disease activity, age of asthma onset and atopic status. Associations of genome-wide significance (p<1.25×10−7) were observed between “active adult-onset nonallergic asthma” and rs9851461 flankingCD200(3q13.2) and between “inactive/mild nonallergic asthma” and rs2579931 flankingGRIK2(6q16.3). Borderline significant results (2.5×10−7<p<8.2×10−7) were observed between three single nucleotide polymorphisms (SNPs) in theALCAMregion (3q13.11) and “active adult-onset nonallergic asthma”. These results were consistent across studies. 15 SNPs identified in previous genome-wide association studies of asthma have been replicated with at least one asthma phenotype, most of them with the “active allergic asthma” phenotype.Our results provide evidence that a better understanding of asthma phenotypic heterogeneity helps to disentangle the genetic heterogeneity of asthma.
A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis
Authors: Chang William Y.C. , Cane Jennifer L. , Kumaran Maruti , Lewis Sarah , Tattersfield Anne E. , Johnson Simon R. 
Published: December 2013

Lymphangioleiomyomatosis (LAM) is characterised by lung cysts and airflow obstruction. Matrix metalloproteinases have been implicated in lung destruction in LAM. We performed a randomised, double-blind trial, comparing the matrix metalloproteinases inhibitor doxycycline with placebo on the progression of LAM.23 females with LAM were randomised to doxycycline 100 mg daily for 3 months followed by 200 mg daily for 21 months, or matched placebo. Lung function, exercise capacity, quality of life and matrix metalloproteinases levels were measured.21 patients completed 6 months of treatment, 17 completed 1 year of treatment and 15 completed 2 years of treatment. Eight withdrew from the trial due, four due to a pneumothorax and four because of other reasons. The mean±sddecline in FEV1, the primary endpoint, did not differ between the groups being -90±154 mL·year−1in the placebo group and -123±246 mL·year−1in the doxycycline group (difference -32.5, 95% CI -213–148; p=0.35). Doxycycline had no effect upon vital capacity, gas transfer, shuttle walk distance or quality of life. Urine matrix metalloproteinases-9 measurements were lower with doxycycline treatment (p=0.03).Although with limited numbers we cannot completely exclude an effect of doxycycline, the lack of effect on any outcome makes it unlikely that doxycycline has a useful effect in LAM.
Arterial stiffness in patients with COPD: the role of systemic inflammation and the effects of pulmonary rehabilitation
Authors: Vanfleteren Lowie E.G.W. , Spruit Martijn A. , Groenen Miriam T.J. , Bruijnzeel Piet L.B. , Taib Ziad , Rutten Erica P.A. , Op ‘t Roodt Jos , Akkermans Marco A. , Wouters Emiel F.M. , Franssen Frits M.E. 
Published: December 2013

Clear evidence for an association between systemic inflammation and increased arterial stiffness in patients with chronic obstructive pulmonary disease (COPD) is lacking. Moreover, the effects of pulmonary rehabilitation on arterial stiffness are not well studied.We aimed to 1) confirm increased arterial stiffness in COPD; 2) evaluate its correlates including systemic inflammation; and 3) study whether or not it is influenced by pulmonary rehabilitation.Aortic pulse-wave velocity (APWV) was determined in 168 healthy volunteers, and APWV and inflammatory markers were determined in 162 COPD patients during baseline evaluation of a pulmonary rehabilitation programme. A complete post-pulmonary rehabilitation dataset was collected in 129 patients.It was found that APWV was increased in COPD patients when compared with controls, blood pressure and age predicted baseline APWV, and systemic inflammatory markers were not independently related to APWV. Although baseline APWV was predictive for the change in APWV after pulmonary rehabilitation (r= -0.77), on average APWV did not change (10.7±2.7versus10.9±2.5 m·s−1; p=0.339).Arterial stiffness in COPD is not related to systemic inflammation and does not respond to state-of-the-art pulmonary rehabilitation. These results emphasise the complexity of cardiovascular risk and its management in COPD.
On fixed point theorems involving altering distances in Menger probabilistic metric spaces
Authors: Došenović Tatjana , Kumam Poom , Gopal Dhananjay , Patel Deepesh Kumar , Takači Aleksandar 
Published: December 2013

Abstract
In this paper, we show by means of an example that the results of Babačev (Appl. Anal. Discrete Math. 6:257-264, 2012) do not hold for the class of t-norms

T
≤

T
p

. Further, we prove a fixed point theorem for quasi-type contraction involving altering distance functions which is weaker than that proposed by Babačev but for any continuous t-norm in a complete Menger space.

MSC:47H10, 54H25.
Sample size calculation based on exact test for assessing differential expression analysis in RNA-seq data
Authors: Li Chung-I , Su Pei-Fang , Shyr Yu 
Published: December 2013

AbstractBackgroundSample size calculation is an important issue in the experimental design of biomedical research. For RNA-seq experiments, the sample size calculation method based on the Poisson model has been proposed; however, when there are biological replicates, RNA-seq data could exhibit variation significantly greater than the mean (i.e. over-dispersion). The Poisson model cannot appropriately model the over-dispersion, and in such cases, the negative binomial model has been used as a natural extension of the Poisson model. Because the field currently lacks a sample size calculation method based on the negative binomial model for assessing differential expression analysis of RNA-seq data, we propose a method to calculate the sample size.ResultsWe propose a sample size calculation method based on the exact test for assessing differential expression analysis of RNA-seq data.ConclusionsThe proposed sample size calculation method is straightforward and not computationally intensive. Simulation studies to evaluate the performance of the proposed sample size method are presented; the results indicate our method works well, with achievement of desired power.