bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel clinical trials for pediatric leukemias: lessons learned from genomic analyses
Authors: Biondi Andrea , Cazzaniga Giovanni 
Published: December 2013

Abstract
Acute lymphoblastic leukemia in childhood has shown remarkable improvements in outcome over the past decades. This achievement was the result of better patient risk assessment, intensification of treatment, appropriate use of BM transplantation, and improved supportive therapies. Among risk factors, early response (originally morphologic and today minimal residual disease) has acquired a prominent role. The predictive value of minimal residual disease evaluation as a measurement of in vivo drug resistance opened new perspectives for its use in clinical evaluation to determine a risk-based treatment and as a potential surrogate end point for efficacy. More recently, detailed genomic analyses of childhood acute lymphoblastic leukemia have increased our knowledge in this disease. It is likely that this will lead to further improvement of risk assessment and stratification to targeted therapies. Leukemic subsets defined on the basis of biological mechanisms and driver mutations will be ever smaller. To facilitate continued progress, this new scenario will raise methodological issues in study design and the need for collaboration across large, well-characterized patient populations.
Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon's perspective
Authors: Holcomb John B. , Pati Shibani 
Published: December 2013

AbstractOver the past century, blood banking and transfusion practices have moved from whole blood therapy to components. In trauma patients, the shift to component therapy was achieved without clinically validating which patients needed which blood products. Over the past 4 decades, this lack of clinical validation has led to uncertainty on how to optimally use blood products and has likely resulted in both overuse and underuse in injured patients. However, recent data from both US military operations and civilian trauma centers have shown a survival advantage with a balanced transfusion ratio of RBCs, plasma, and platelets. This has been extended to include the prehospital arena, where thawed plasma, RBCs, and antifibrinolytics are becoming more widely used. The Texas Trauma Institute in Houston has followed this progression by putting RBCs and thawed plasma in the emergency department and liquid plasma and RBCs on helicopters, transfusing platelets earlier, and using thromboelastogram-guided approaches. These changes have not only resulted in improved outcomes, but have also decreased inflammatory complications, operations, and overall use of blood products. In addition, studies have shown that resuscitating with plasma (instead of crystalloid) repairs the “endotheliopathy of trauma,” or the systemic endothelial injury and dysfunction that lead to coagulation disturbances and inflammation. Data from the Trauma Outcomes Group, the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, and the ongoing Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial represent a decade-long effort to programmatically determine optimal resuscitation practices, balancing risk versus benefits. With injury as the leading cause of death in patients age 1 to 44 years and hemorrhage the leading cause of potentially preventable death in this group, high-quality data must be obtained to provide superior care to the civilian and combat injured.
Antiphospholipid syndrome
Authors: Lim Wendy 
Published: December 2013

Abstract
The antiphospholipid syndrome (APS) is defined by venous or arterial thrombosis and/or pregnancy morbidity in patients with persistent presence of antiphospholipid antibodies (aPLs). Catastrophic APS is the most severe form of APS, which is associated with rapid development of microvascular thrombosis resulting in multiorgan failure in patients with aPLs. Patients with APS and catastrophic APS are recognized to have a high risk of recurrent thrombosis that can occur despite anticoagulant therapy. Although antithrombotic therapy remains the mainstay of treatment, bleeding manifestations can complicate management and contribute to increased morbidity. Patients with persistently elevated aPL levels, particularly those who exhibit positive testing for lupus anticoagulant, anticardiolipin antibodies, and anti-β2GPI antibodies (triple positivity), appear to be at increased risk for thrombosis and pregnancy complications, whereas isolated positivity for aPLs appears to be associated with low risk. Recognizing that patients with APS have different thrombotic risk profiles may assist clinicians in assessing the risks and benefits of anticoagulation. The optimal type, intensity, and duration of anticoagulation in the treatment of APS remain controversial, particularly for arterial thrombosis and recurrent thrombosis. Future studies that delineate thrombotic risk in APS and evaluate current and novel anticoagulants as well as nonanticoagulant therapies are required.
The ASH Choosing Wisely® campaign: five hematologic tests and treatments to question
Authors: Hicks Lisa K. , Bering Harriet , Carson Kenneth R. , Kleinerman Judith , Kukreti Vishal , Ma Alice , Mueller Brigitta U. , O'Brien Sarah H. , Pasquini Marcelo , Sarode Ravindra , Solberg Lawrence , Haynes Adam E. , Crowther Mark A. 
Published: December 2013

Abstract
Choosing Wisely® is a medical stewardship and quality improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The ASH is an active participant in the Choosing Wisely® project. Using an iterative process and an evidence-based method, ASH has identified 5 tests and treatments that in some circumstances are not well supported by evidence and which in certain cases involve a risk of adverse events and financial costs with low likelihood of benefit. The ASH Choosing Wisely® recommendations focus on avoiding liberal RBC transfusion, avoiding thrombophilia testing in adults in the setting of transient major thrombosis risk factors, avoiding inferior vena cava filter usage except in specified circumstances, avoiding the use of plasma or prothrombin complex concentrate in the nonemergent reversal of vitamin K antagonists, and limiting routine computed tomography surveillance after curative-intent treatment of non-Hodgkin lymphoma. We recommend that clinicians carefully consider anticipated benefits of the identified tests and treatments before performing them.
Bruton’s tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL)
Authors: Woyach Jennifer A. , Bojnik Engin , Ruppert Amy S. , Stefanovski Matthew R. , Goettl Virginia M. , Smucker Kelly A. , Smith Lisa L. , Dubovsky Jason A. , Towns William H. , MacMurray Jessica , Harrington Bonnie K. , Davis Melanie E. , Gobessi Stefania , Laurenti Luca , Chang Betty Y. , Buggy Joseph J. , Efremov Dimitar G. , Byrd John C. , Johnson Amy J. 
Published: December 2013

Key PointsKinase-functional BTK is important in the development and expansion of CLL. Both targeted genetic inactivation of BTK and inhibition of BTK by ibrutinib inhibit the development of CLL in the TCL1 mouse model.
6-minute walk distance is an independent predictor of mortality in patients with idiopathic pulmonary fibrosis
Authors: du Bois Roland M. , Albera Carlo , Bradford Williamson Z. , Costabel Ulrich , Leff Jonathan A. , Noble Paul W. , Sahn Steven A. , Valeyre Dominique , Weycker Derek , King Talmadge E. 
Published: December 2013

6-min walk distance (6MWD) has recently been shown to be associated with the risk of mortality in patients with idiopathic pulmonary fibrosis (IPF); however, the independent contribution of 6MWD to the prediction of mortality risk has not been evaluated in a large, well-defined population of patients with IPF.A Cox proportional hazards model was used to characterise the relationship between risk factors of interest and all-cause mortality in IPF patients who completed a week 24 study visit in a clinical trial evaluating interferon γ-1b (n=748). Risk factors of interest included the independent predictors of mortality in the previously published clinical prediction model together with 6MWD and 24-week change in 6MWD.Baseline 6MWD <250 m was associated with a two-fold increase in the risk of mortality (hazard ratio 2.12, 95% CI 1.15–3.92) and a 24-week decline in 6MWD >50 m was associated with a nearly three-fold increase in mortality risk (hazard ratio 2.73; 95% CI 1.60–4.66). Inclusion of 6MWD data improved model discrimination compared with the original model (C-statistic 0.80 (95% CI 0.76–0.85)versus0.75 (0.71–0.79)).Both 6MWD and change in 6MWD are independent predictors of mortality in patients with IPF. The addition of 6MWD to the clinical prediction model improves model discrimination compared with the original model.
Caspase 3 involves in neuroplasticity, microglial activation and neurogenesis in the mice hippocampus after intracerebral injection of kainic acid
Authors: Tzeng Tsai-Teng , Tsay Huey-Jen , Chang Luping , Hsu Chia-Lin , Lai Tzu-Hsuan , Huang Fong-Lee , Shiao Young-Ji 
Published: December 2013

Abstract

Background
The roles of caspase 3 on the kainic acid-mediated neurodegeneration, dendritic plasticity alteration, neurogenesis, microglial activation and gliosis are not fully understood. Here, we investigate hippocampal changes using a mouse model that receive a single kainic acid-intracerebral ventricle injection. The effects of caspase 3 inhibition on these changes were detected during a period of 1 to 7 days post kainic acid injection.

Result
Neurodegeneration was assessed by Fluoro-Jade B staining and neuronal nuclei protein (NeuN) immunostaining. Neurogenesis, gliosis, neuritic plasticity alteration and caspase 3 activation were examined using immunohistochemistry. Dendritic plasticity, cleavvage-dependent activation of calcineurin A and glial fibrillary acidic protein cleavage were analyzed by immunoblotting. We found that kainic acid not only induced neurodegeneration but also arouse several caspase 3-mediated molecular and cellular changes including dendritic plasticity, neurogenesis, and gliosis. The acute caspase 3 activation occurred in pyramidal neurons as well as in hilar interneurons. The delayed caspase 3 activation occurred in astrocytes. The co-injection of caspase 3 inhibitor did not rescue kainic acid-mediated neurodegeneration but seriously and reversibly disturb the structural integrity of axon and dendrite. The kainic acid-induced events include microglia activation, the proliferation of radial glial cells, neurogenesis, and calcineurin A cleavage were significantly inhibited by the co-injection of caspase 3 inhibitor, suggesting the direct involvement of caspase 3 in these events. Alternatively, the kainic acid-mediated astrogliosis is not caspase 3-dependent, although caspase 3 cleavage of glial fibrillary acidic protein occurred.

Conclusions
Our results provide the first direct evidence of a causal role of caspase 3 activation in the cellular changes during kainic acid-mediated excitotoxicity. These findings may highlight novel pharmacological strategies to arrest disease progression and control seizures that are refractory to classical anticonvulsant treatment.
Comparison of sample characteristics in two pregnancy cohorts: community-based versus population-based recruitment methods
Authors: Leung Brenda MY , McDonald Sheila W , Kaplan Bonnie J , Giesbrecht Gerald F , Tough Suzanne C 
Published: December 2013

Abstract

Background
One of the biggest challenges for population health studies is the recruitment of participants. Questions that investigators have asked are “who volunteers for studies?” and “does recruitment method influence characteristics of the samples?” The purpose of this paper was to compare sample characteristics of two unrelated pregnancy cohort studies taking place in the same city, in the same time period, that employed different recruitment strategies, as well as to compare the characteristics of both cohorts to provincial and national statistics derived from the Maternity Experiences Survey (MES).

Methods
One pregnancy cohort used community-based recruitment (e.g. posters, pamphlets, interviews with community media and face-to-face recruitment in maternity clinics); the second pregnancy cohort used both community-based and population-based (a centralized system identifying pregnant women undergoing routine laboratory testing) strategies.

Results
The pregnancy cohorts differed in education, income, ethnicity, and foreign-born status (p < 0.01), but were similar for maternal age, BMI, and marital status. Compared to the MES, the lowest age, education, and income groups were under-represented, and the cohorts were more likely to be primiparous.

Conclusions
The findings suggest that non-stratified strategies for recruitment of participants will not necessarily result in samples that reflect the general population, but can reflect the target population of interest. Attracting and retaining young, low resource women into urban studies about pregnancy may require alternate and innovative approaches.
A nationwide population-based study of the inflammatory bowel diseases between 1998 and 2008 in Taiwan
Authors: Wei Shu-Chen , Lin Meng-Hung , Tung Chien-Chih , Weng Meng-Tzu , Kuo Jen-Shin , Shieh Ming-Jium , Wang Cheng-Yi , Ho Wen-Chao , Wong Jau-Min , Chen Pau-Chung 
Published: December 2013

Abstract

Background
The incidence of the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), has been increasing in Asia. We probed the nationwide registered database to assess the incidence, prevalence, gender distribution, age of diagnosis and the survival status of IBD patients in Taiwan.

Methods
A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Department of Health, Taiwan, from January 1998 through December 2008.

Results
A total of 1591 IBD patients were registered from 1998 to 2008 in Taiwan (CD: 385; UC: 1206). The incidence of CD increased from 0.19/100,000 in 1998 to 0.24/100,000 in 2008. The incidence of UC increased from 0.61/100,000 in 1998 to 0.94/100,000 in 2008. The prevalence of CD increased from 0.19/100,000 in 1998 to 1.78/100,000 in 2008. The prevalence of UC increased from 0.61/100,000 in 1998 to 7.62/100,000 in 2008. Male to female ratio for CD was 2.22 and 1.64 for UC. Age of registered for CD was predominantly between 20 to 39, and for UC between 30 to 49 years of age. The standardized mortality ratio (95% CI) was 4.97 (3.72–6.63) for CD and 1.78 (1.46–2.17) for UC, from 1998 to 2008 in Taiwan.

Conclusions
Using the Taiwan nationwide database for IBD, the incidence and prevalence of IBD in Taiwan significantly increased from 1998 to 2008. The mortality rate was higher for CD patients than UC patients, and both were higher than the general population.
The influence of ACE ID and ACTN3 R577X polymorphisms on lower-extremity function in older women in response to high-speed power training
Authors: Pereira Ana , Costa Aldo M , Leitão José C , Monteiro António M , Izquierdo Mikel , Silva António J , Bastos Estela , Marques Mário C 
Published: December 2013

Abstract

Background
We studied the influence of the ACE I/D and ACTN3 R577X polymorphisms (single or combined) on lower-extremity function in older women in response to high-speed power training.

Methods
One hundred and thirty-nine healthy older Caucasian women participated in this study (age: 65.5 ± 8.2 years, body mass: 67.0 ± 10.0 kg and height: 1.57 ± 0.06 m). Walking speed (S10) performance and functional capacity assessed by the “get-up and go” (GUG) mobility test were measured at baseline (T1) and after a consecutive 12-week period of high-speed power training (40-75% of one repetition maximum in arm and leg extensor exercises; 3 sets 4–12 reps, and two power exercises for upper and lower extremity). Genomic DNA was extracted from blood samples, and genotyping analyses were performed by PCR methods. Genotype distributions between groups were compared by Chi-Square test and the gains in physical performance were analyzed by two-way, repeated-measures ANOVA.

Results
There were no significant differences between genotype groups in men or women for adjusted baseline phenotypes (P > 0.05). ACE I/D and ACTN3 polymorphisms showed a significant interaction genotype-training only in S10 (P = 0.012 and P = 0.044, respectively) and not in the GUG test (P = 0.311 and P = 0.477, respectively). Analyses of the combined effects between genotypes showed no other significant differences in all phenotypes (P < 0.05) at baseline. However, in response to high-speed power training, a significant interaction on walking speed (P = 0.048) was observed between the “power” (ACTN3 RR + RX & ACE DD) versus “non-power” muscularity-oriented genotypes (ACTN3 XX & ACE II + ID)].

Conclusions
Thus, ACE I/D and ACTN3 R577X polymorphisms are likely candidates in the modulation of exercise-related gait speed phenotype in older women but not a significant influence in mobility traits.
Diffusion and interaction in PEG-DA hydrogels
Authors: Hagel Valentin , Haraszti Tamás , Boehm Heike 
Published: December 2013

Abstract
Polyethylenglycol (PEG) hydrogels are widely used as tuneable substrates for biological and technical applications due to their good biocompatibility and their high hydrophilicity. Here we compare the mesh size and diffusion characteristics of PEG hydrogels by analyzing the diffusion of solutes with different, well-defined sizes over long and short time scales. Interestingly, one can tune the mesh size and the density of the gel simply by changing the inital concentrations of the PEG-diacrylate (PEG-DA) polymer, which also enhances the solute uptake in equilibrium through the interaction with the PEG chains. This increased uptake can be characterized by an enhancement factor determined by partition ratio analysis. It increases linearly with the polymer volume fraction, but is not caused by immobilization inside the hydrogel as evident from FRAP measurements, thus rendering these hydrogels ideal materials for i.e. drug delivery applications.
An epidemiological investigation into the association between biomarkers and growth performance in nursery pigs
Authors: Slifierz Mackenzie J , Friendship Robert , de Lange Cornelius FM , Rudar Marko , Farzan Abdolvahab 
Published: December 2013

Abstract

Background
Biomarkers are useful tools in research and clinical practice where they are often used to detect and monitor differences in the physiological state of an animal. The proteins IGF-1, IGFBP-3, GHR, CRP, SAA, Hp, IFN-α, IFN-γ, TNF-α, IL-1β, IL-6, IL-10, and IL-18 have been proposed as potential biomarkers for monitoring growth in livestock. The objective of this study was to determine whether hepatic gene expression of these proposed biomarkers is associated with growth performance in nursery pigs. Herd information and growth parameters were collected for 168 piglets from 8 commercial farms in southern Ontario. From these pigs, a subset of liver tissue samples (n = 74) was used for gene expression analysis of the proposed biomarkers. Multivariable linear regression methods were used to determine whether genetic expression of the proposed biomarkers was associated with growth performance in the nursery.

Results
Modelling the herd information and individual piglet traits in relation to growth performance revealed that the weight at weaning and the age at weaning are significantly associated with nursery performance. Average daily gain (ADG) was significantly associated with hepatic IGFBP-3 and GHR expression in the liver (P < 0.05), and tended to be associated with hepatic IGF-1 expression (P = 0.071). Similarly, 9-week body weight was significantly associated with hepatic expression of IGFBP-3 and GHR expression (P < 0.05), and tended to be associated with hepatic expression of IGF-1 (P = 0.055).

Conclusion
The age and weight at which pigs are weaned is an important determinant for nursery performance. Hepatic gene expression of IGF-1, IGFBP-3, and GHR can be useful biomarkers for monitoring growth performance in nursery pigs.
Least-squares reverse time migration of multiples
Authors: Zhang Dongliang , Schuster Gerard T. 
Published: December 2013

The theory of least-squares reverse time migration of multiples (RTMM) is presented. In this method, least squares migration (LSM) is used to image free-surface multiples where the recorded traces are used as the time histories of the virtual sources at the hydrophones and the surface-related multiples are the observed data. For a single source, the entire free-surface becomes an extended virtual source where the downgoing free-surface multiples more fully illuminate the subsurface compared to the primaries. Since each recorded trace is treated as the time history of a virtual source, knowledge of the source wavelet is not required and the ringy time series for each source is automatically deconvolved. If the multiples can be perfectly separated from the primaries, numerical tests on synthetic data for the Sigsbee2B and Marmousi2 models show that least-squares reverse time migration of multiples (LSRTMM) can significantly improve the image quality compared to RTMM or standard reverse time migration (RTM) of primaries. However, if there is imperfect separation and the multiples are strongly interfering with the primaries then LSRTMM images show no significant advantage over the primary migration images. In some cases, they can be of worse quality. Applying LSRTMM to Gulf of Mexico data shows higher signal-to-noise imaging of the salt bottom and top compared to standard RTM images. This is likely attributed to the fact that the target body is just below the sea bed so that the deep water multiples do not have strong interference with the primaries. Migrating a sparsely sampled version of the Marmousi2 ocean bottom seismic data shows that LSM of primaries and LSRTMM provides significantly better imaging than standard RTM. A potential liability of LSRTMM is that multiples require several round trips between the reflector and the free surface, so that high frequencies in the multiples suffer greater attenuation compared to the primary reflections. This can lead to lower resolution in the migration image compared to that computed from primaries. Another liability is that the multiple migration image is more down-dip limited than the standard primaries migration image. Finally, if the surface-related multiple elimination method is imperfect and there are strong multiples interfering with the primaries, then the resulting LSRTMM image can be significantly degraded. We conclude that LSRTMM can be a useful complement, not a replacement, for RTM of primary reflections.