bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of rigorous study design in the research of autologous bone marrow-derived mononuclear cell transfer in patients with acute myocardial infarction
Authors: Jeong Hyunsuk , Yim Hyeon Woo , Cho Youngseung , Park Hun Jun , Jeong Sona , Kim Hyun-bin , Hong Wonhee , Kim Heejung 
Published: July 2013

Abstract
Introduction
Although blinding is a methodologic safeguard to ensure obtaining comparability of groups in a clinical trial, it is very difficult to maintain blinding from the beginning to the end of a study. The aim of the study was to see how proper blinding of both participants and treatment providers from the planning phase of the study to during the study affected the study outcomes.

Methods
We searched Medline, EMBASE, and Cochrane databases from inception to November 2011. The studies included in this review were randomized controlled trials, with acute myocardial infarction (AMI) patients who received percutaneous coronary intervention (PCI), intracoronary (IC) infusion of autologous bone marrow stem cells (BMSCs), unselected BMSCs, 108 or more cell dose, and up to 6-month follow-up periods.

Results
The initial search identified 881 references, of which 17 references were eligible for inclusion. Six of 17 trials isolated cells directly from bone marrow by aspiration in the control group as well as in the BMSC group. Nine of 17 trials underwent both cardiac catheterization and an identical injection procedure on the control group as well as the BMSC group.
Compared with the control group, BMSC transplantation improved left ventricular ejection fraction (LVEF) by 2.51 (95% CI, 1.20 to 3.83; P = 0.0002; I
2
= 75%) at 6 months. In the present results, the studies that did not perform bone marrow aspiration in the control group showed significant improvement in LVEF by 3.81% (95% CI, 2.44 to 5.17), whereas no significant treatment effect was found in the studies in which the control group underwent bone marrow aspiration, as indicated the LVEF change of −1.29% (95% CI, 4.15 to 1.58). The trials that did not conduct catheterization on control subjects showed significant LVEF changes (4.45%; 95% CI, 2.48 to 6.43); however, those with cardiac catheterization as a sham procedure on the control group did not show significant changes in LVEF at 6 months (0.92%; 95% CI, -0.61 to 2.44).

Conclusions
Unblinding might be overestimating the treatment effect. These findings suggest that randomized controlled trials testing the efficacy of BMSC therapy should be appropriately designed and rigorously applied to avoid bias.
Emerging role for the voltage-dependent K+ channel Kv1.5 in B-lymphocyte physiology: expression associated with human lymphoma malignancy
Authors: Vallejo-Gracia Albert , Bielanska Joanna , Hernández-Losa Javier , Castellví Josep , Ruiz-Marcellan M Carmen , Ramón y Cajal Santiago , Condom Enric , Manils Joan , Soler Concepció , Comes Núria , Ferreres Joan Carles , Felipe Antonio 
Published: July 2013

ABSTRACTKv, which play a role in the immune system, are remodeled during carcinogenesis. Leukocytes present a limited Kv repertoire, with Kv1.3 and Kv1.5 as isoforms that are involved in neoplastic processes, such as proliferation and migration. In this study, we identified Kv1.5 in B-lymphocytes, characterized its role in proliferation and migration, and analyzed Kv1.3 and Kv1.5 expression in human non-Hodgkin lymphomas. DLBCL, F, MCL, ALCL, and T, along with control N specimens, were analyzed. Kv1.3 and Kv1.5 were found to be remodeled differentially; whereas Kv1.3 expression did not correlate with the state of dedifferentiation or the nature of lymphomatous cells, Kv1.5 abundance correlated inversely with clinical aggressiveness. Whereas indolent F expressed noticeable levels of Kv1.5, aggressive DLBCL showed low Kv1.5 levels. In addition, control LNs expressed heterogeneous high levels of Kv1.3, which could indicate some reactivity, whereas Kv1.5 abundance was low and quite homogeneous. Our data show that Kv1.5 is a determinant of human B cell proliferation and migration, thereby identifying this channel as a new target for immunomodulation. Our work also provides new insights into the use of Kv1.3 and Kv1.5 as potential targets during tumorigenesis.
N6-isopentenyladenosine, an endogenous isoprenoid end product, directly affects cytotoxic and regulatory functions of human NK cells through FDPS modulation
Authors: Ciaglia Elena , Pisanti Simona , Picardi Paola , Laezza Chiara , Malfitano Anna Maria , D'Alessandro Alba , Gazzerro Patrizia , Vitale Mario , Carbone Ennio , Bifulco Maurizio 
Published: July 2013

ABSTRACTiPA is a naturally occurring nucleoside with an isopentenyl moiety derived from the mevalonate pathway and a well-established anti-tumor activity. In analogy to the unique specificity for phosphoantigens, such as IPP, shown by human Vγ9Vδ2 T cells, here, we report for the first time the ability of iPA to selectively expand and directly target human NK cells. Interestingly, submicromolar doses of iPA stimulate resting human NK cells and synergize with IL-2 to induce a robust activation ex vivo with significant secretion of CCL5 and CCL3 and a large increase in TNF-α and IFN-γ production when compared with IL-2 single cytokine treatment. Moreover, iPA promotes NK cell proliferation and up-regulates the expression of specific NK cell-activating receptors, as well as CD69 and CD107a expression. Accordingly, this phenotype correlates with significantly greater cytotoxicity against tumor targets. At the molecular level, iPA leads to a selective, potent activation of MAPK signaling intermediaries downstream of the IL-2R. The effect results, at least in part, from the fine modulation of the FDPS activity, the same enzyme implicated in the stimulation of the human γδ T cells. The iPA-driven modulation of FDPS can cause an enhancement of post-translational prenylation essential for the biological activity of key proteins in NK signaling and effector functions, such as Ras. These unanticipated properties of iPA provide an additional piece of evidence of the immunoregulatory role of the intermediates of the mevalonate pathway and open novel therapeutic perspectives for this molecule as an immune-modulatory drug.
Molecular and functional properties of densely and sparsely granulated GH-producing pituitary adenomas
Authors: Mayr Bernhard , Buslei Rolf , Theodoropoulou Marily , Stalla Günter K , Buchfelder Michael , Schöfl Christof 
Published: July 2013

ObjectiveGH-producing pituitary adenomas display two distinct morphological patterns of cytoplasmic GH-containing secretory granules, namely the densely and sparsely granulated somatotroph adenoma subtype. It is unknown whether these morphological variants reflect distinct pathophysiological entities at the molecular level.MethodsIn 28 GH-producing adenoma tissues from a consecutive set of patients undergoing pituitary surgery for acromegaly, we studied the GH granulation pattern, the expression of somatostatin receptor subtypes (SSTR) as well as the calcium, cAMP and ZAC1 pathways in primary adenoma cell cultures.ResultsThe expression ofGSPoncogene was similar between densely and sparsely granulated somatotroph adenoma cells. There were no differences in the calcium, cAMP and ZAC1 pathways as well as in their regulation by SSTR agonists. SSTR2 was exclusively expressed in densely but not in sparsely granulated tumours (membrane expression 86 vs 0%; cytoplasmic expression 67 vs 0%). By contrast, expression of SSTR5 was only found in sparsely but not in densely granulated somatotroph adenomas (membrane expression 29 vs 0%; cytoplasmic expression 57 vs 0%).ConclusionsOur results indicate that different granulation patterns in GH-producing adenomas do not reflect differences in pathways and factors pivotal for somatotroph differentiation and function.In vitro, the vast majority of both densely and sparsely granulated tumour cells were responsive to SSTR activation at the molecular level. Sparsely granulated adenomas lacking SSTR2, but expressing SSTR5, might be responsive to novel SSTR agonists with increased affinity to SSTR5.
Physiological Dynamics of Maize Nitrogen Uptake and Partitioning in Response to Plant Density and N Stress Factors: I. Vegetative Phase
Authors: Ciampitti Ignacio A. , Murrell Scott T. , Camberato J.J. , Tuinstra Mitch , Xia Yanbing , Friedemann Peter , Vyn Tony J. 
Published: July 2013

ABSTRACTFrom a physiological perspective, field studies that quantify the influence of plant density (PD) and N rate on biomass (BM) and N uptake are needed to build more functional partitioning models for maize (Zea mays L.). The overall goal was to quantify the effects of maize hybrid (two genotypes), PD (low = 54,000; medium = 79,000 and high = 104,000 pl ha‐1), and N rate (low = 0, medium = 112 and high = 224 kg N ha‐1) on the organ‐specific dry mass and N allocation, and on the resource capture (ratio of leaf area index [LAI] to BM), and resource use efficiency (ratio of N uptake to LAI) parameters, during the vegetative phase at four site‐years. Allometric analyses revealed that the resource capture was primarily affected by the PD, and the resource use efficiency by the N rate. The stoichiometry between leaf and stem dry mass was unaffected by the treatment factors, but no isometry was documented (greater BM to the stem than leaf). The N rate primarily modified the leaf and stem N concentrations (0N vs. 112–224N). With respect to resource use efficiency, modifications in the leaf N content per unit of LAI were joint outcomes of changes in leaf mass and %N (N concentration). In contrast, physiological changes in the stem N content per unit of LAI were more dependent on changes in the stem %N (greater N storage capacity) rather than in the stem mass. Intensifying competition with neighboring plants reduced per‐plant mass similarly in both leaf and stem structures, and improving N supply was proportionately more beneficial in maintaining plant mass and stem %N at high PD during vegetative growth.
Genotype × Storage Environment Interaction and Stability of Potato Chip Color: Implications in Breeding for Cold Storage Chip Quality
Authors: Rak Kyle , Navarro Felix M. , Palta Jiwan P. 
Published: July 2013

ABSTRACTPotato (Solanum tuberosum L.) genotypes exhibit significant variation for chip color across different storage regimes. Lines that maintain light chip color after long postharvest storage durations and low storage temperatures are desirable to the potato industry. Since storage regimes vary among growers and processors, lines that exhibit stable chip performance across various storage regimes have a high probability of commercial success. The objective was to test if treating storage regimes as “environments,” analyzing genotype × storage environment interactions, and applying stability statistics can help identify desirable chip processing lines. To examine this, chip color of 47 breeding clones and six standard varieties was evaluated across eight storage environments. Chip color data was analyzed using stability metrics as well as stability‐adjusted selection indices. The effects of genotype, storage environment, and genotype × environment on chip color were significant, explaining 47, 24, and 17% of total variance, respectively. Types I, II, and III stable lines were identified through stability analyses. Type I stability was significantly correlated with mean chip color. The most desirable lines were identified under long and cold storage environments. Using Type I stability and stability‐adjusted indices, this study identified breeding clones for advancement, including W5840‐4, W6484‐5, and W6929‐1, which outperformed standard chipping varieties for chip quality and stability.
Creation of Hexaploid and Octaploid Zoysiagrass Using Colchicine and Breeding
Authors: Schwartz Brian M. , Harris‐Shultz Karen R. , Contreras Ryan N. , Hans Christian S. , Jackson Scott A. 
Published: July 2013

ABSTRACTZoysiagrasses (Zoysia Willd.) are a slow‐growing, tetraploid (2n = 4x = 40) turfgrass that can be successfully managed with less input than many other warm‐season grasses. Despite extensive genetic and morphological variation, genotypes with the ability to recuperate quickly from damage are rare. Therefore, a long‐term effort to increase vegetative growth rates was initiated during 2009 by first studying the effectiveness of six colchicine seed treatments and breeding for manipulating the ploidy level of ‘Zenith’ zoysiagrass. Colchicine‐treated seedlings were screened using flow cytometry for genome size changes. Four putative octaploids and one cytochimera were identified. Average stomata length of the four colchicine‐induced putative octaploids were 28% larger than that of Zenith, but the cytochimera's stomata length was not altered. Pollen diameter of the four putative octaploids was larger than that of Zenith and the cytochimera. Pollen stainability was relatively unchanged by the colchicine treatments. Further self‐ and cross‐pollination of 09‐TZ‐103 (putative M0 octaploid) led to the development and verification of M1 octaploid and M1 hexaploid genotypes. These results support that DNA content of the L‐I (epidermis), L‐II (germ line), and L‐III (adventitious roots) histogenic layers of Zoysia can be manipulated with colchicine and breeding. Future evaluation of the turfgrass performance of these polyploids is the next step in determining the value of this breeding procedure for improvement of zoysiagrass.
Renal Survival in Proteinase 3 and Myeloperoxidase ANCA-Associated Systemic Vasculitis
Authors: de Joode Anoek A.E. , Sanders Jan Stephan F. , Stegeman Coen A. 
Published: July 2013

Summary

Background and objectives
This study evaluated predictors for patient and renal survival in patients with ANCA-associated vasculitis (AAV) with and without renal involvement.

Design, setting, participants, & measurements
There were 273 consecutive AAV patients from January 1990 until December 2007 who were followed until death, loss to follow-up, or December 2010. Based on organ involvement, patients were divided into renal (n=212) and nonrenal groups (n=61). The primary end point was ESRD requiring renal replacement therapy (RRT) or renal transplantation or death.

Results
Patient survival was significantly better in the nonrenal group compared with the renal group (hazard ratio, 0.55; 95% confidence interval, 0.33 to 0.92; P=0.02). In the renal group, renal survival was significantly worse in MPO-ANCA–positive patients (n=65) compared with PR3-ANCA–positive patients (n=138) (hazard ratio, 2.1; 95% confidence interval, 1.11 to 3.8; P=0.01). Of 48 patients who needed RRT at diagnosis, 11 patients (23%) died within 6 months and 14 patients (29%) did not regain renal function. Of all 23 patients who regained renal function after RRT, 7 patients (30%) were temporarily dialysis independent and needed dialysis later (range, 13–63 months). Five patients had a renal relapse in the 6 months before restart of RRT. Of all 203 PR3-ANCA–positive and MPO-ANCA–positive patients with renal involvement, 12 patients (6%) developed ESRD during follow-up. These patients were classified as CKD stage 4 or 5 after initial treatment and eight patients had a renal relapse before becoming dialysis dependent.

Conclusions
AAV patients with renal involvement who needed RRT had the worst survival probability. In multivariate analysis, the only major determinants for long-term renal survival were renal function at 6 months and renal relapses.
Benchmarking Is Associated With Improved Quality of Care in Type 2 Diabetes
Authors: Hermans Michel P. , Elisaf Moses , Michel Georges , Muls Erik , Nobels Frank , Vandenberghe Hans , Brotons Carlos ,   for the OPTIMISE (OPtimal Type 2 dIabetes Management Including benchmarking and Standard trEatment) International Steering Committee
Published: July 2013

OBJECTIVE
To assess prospectively the effect of benchmarking on quality of primary care for patients with type 2 diabetes by using three major modifiable cardiovascular risk factors as critical quality indicators.

RESEARCH DESIGN AND METHODS
Primary care physicians treating patients with type 2 diabetes in six European countries were randomized to give standard care (control group) or standard care with feedback benchmarked against other centers in each country (benchmarking group). In both groups, laboratory tests were performed every 4 months. The primary end point was the percentage of patients achieving preset targets of the critical quality indicators HbA1c, LDL cholesterol, and systolic blood pressure (SBP) after 12 months of follow-up.

RESULTS
Of 4,027 patients enrolled, 3,996 patients were evaluable and 3,487 completed 12 months of follow-up. Primary end point of HbA1c target was achieved in the benchmarking group by 58.9 vs. 62.1% in the control group (P = 0.398) after 12 months; 40.0 vs. 30.1% patients met the SBP target (P &lt; 0.001); 54.3 vs. 49.7% met the LDL cholesterol target (P = 0.006). Percentages of patients meeting all three targets increased during the study in both groups, with a statistically significant increase observed in the benchmarking group. The percentage of patients achieving all three targets at month 12 was significantly larger in the benchmarking group than in the control group (12.5 vs. 8.1%; P &lt; 0.001).

CONCLUSIONS
In this prospective, randomized, controlled study, benchmarking was shown to be an effective tool for increasing achievement of critical quality indicators and potentially reducing patient cardiovascular residual risk profile.
Temporal Relationship Between Insulin Sensitivity and the Pubertal Decline in Physical Activity in Peripubertal Hispanic and African American Females
Authors: Spruijt-Metz Donna , Belcher Britni R. , Hsu Ya-Wen , McClain Arianna D. , Chou Chih-Ping , Nguyen-Rodriguez Selena , Weigensberg Marc J. , Goran Michael I. 
Published: July 2013

OBJECTIVE
Little attention has been paid to possible intrinsic biological mechanisms for the decline in physical activity that occurs during puberty. This longitudinal observational study examined the association between baseline insulin sensitivity (SI) and declines in physical activity and increases in sedentary behavior in peripubertal minority females over a year.

RESEARCH DESIGN AND METHODS
Participants were Hispanic and African American girls (n = 55; 76% Hispanic; mean age 9.4 years; 36% obese). SI and other insulin indices were measured at baseline using the frequently sampled intravenous glucose tolerance test. Physical activity was measured on a quarterly basis by accelerometry and self-report.

RESULTS
Physical activity declined by 25% and time spent in sedentary behaviors increased by ∼13% over 1 year. Lower baseline SI predicted the decline in physical activity measured by accelerometry, whereas higher baseline acute insulin response to glucose predicted the decline in physical activity measured by self-report. Time spent in sedentary behavior increased by ~13% over 1 year, and this was predicted by lower baseline SI. All models controlled for adiposity, age, pubertal stage, and ethnicity.

CONCLUSIONS
When evaluated using a longitudinal design with strong outcome measures, this study suggests that lower baseline SI predicts a greater decline in physical activity in peripubertal minority females.
Etching a Fiber Post Surface with High-concentration Bleaching Agents
Authors: Menezes MS , Faria-e-Silva AL , Silva FP , Reis GR , Soares CJ , Stape THS , Martins LR 
Published: July 2013

Summary

Introduction
Commonly, resin composites/cements fail to achieve proper bonding to fiber posts when their surfaces have not been previously etched. This study evaluated the effect of the concentration and application mode of hydrogen peroxide on the surface topography and bond strength of resin composite to glass-fiber posts.

Methods and Materials
Fiber posts were immersed in 24% or 35% solutions (a high-concentration bleaching agent) of hydrogen peroxide (H2O2), or these solutions were applied over the post surface using a microbrush (n=10). Posts without any treatment were used as a control. After etching, the posts were silanated and an adhesive was applied. The posts were positioned in a mold, and a resin composite was incrementally inserted and light-cured. The post/resin assembly was serially sectioned into several beams that were subjected to a tensile bond strength test. The data were subjected to the two-way analysis of variance and Tukey test (α=0.05). The Dunnet's test was used to compare the experimental conditions to the control. The surface topography was analyzed using scanning electronic microscopy.

Results
The non-etched post presented a relatively smooth surface without fiber exposure. Except for the application of 24% H2O2, the other experimental conditions increased the number of exposed fibers and bond strength in relation to the control. Although immersion resulted in higher values for the 24% H2O2 application, the mode of application did not alter bond strength when 35% H2O2 was used.

Conclusions
The effect of the mode of application of H2O2 depended on its level of concentration. A high-concentration bleaching agent improved the bond strength of the resin composite to the post surface, regardless of which mode was used.
Enamel Wear Opposing Polished and Aged Zirconia
Authors: Burgess JO , Janyavula S , Lawson NC , Lucas TJ , Cakir D 
Published: July 2013

SUMMARYAging of dental zirconia roughens its surface through low temperature degradation. We hypothesized that age-related roughening of zirconia crowns may cause detrimental wear to the enamel of an opposing tooth. To test our hypothesis, we subjected artificially aged zirconia and reference specimens to simulated mastication in a wear device and measured the wear of an opposing enamel cusp. Additionally, the roughness of the pretest surfaces was measured. The zirconia specimens, artificially aged by autoclave, showed no significant increase in roughness compared to the nonaged specimens. Furthermore, no significant difference in material or opposing enamel wear between the aged and nonaged zirconia was seen. All zirconia specimens showed less material and opposing enamel wear than the enamel to enamel control or veneering porcelain specimens. Scanning electron micrographs showed relatively smooth surfaces of aged and nonaged zirconia following wear testing. The micrographs of the veneering ceramic showed sharp fractured edges and fragments of wear debris. Zirconia may be considered a wear-friendly material for restorations opposing enamel, even after simulated aging.
End-to-side neurorrhaphy in brachial plexus reconstruction
Authors: Haninec Pavel , Mencl Libor , Kaiser Radek 
Published: July 2013

Object
Although a number of theoretical and experimental studies dealing with end-to-side neurorrhaphy (ETSN) have been published to date, there is still a considerable lack of clinical trials investigating this technique. Here, the authors describe their experience with ETSN in axillary and musculocutaneous nerve reconstruction in patients with brachial plexus palsy.

Methods
From 1999 to 2007, out of 791 reconstructed nerves in 441 patients treated for brachial plexus injury, the authors performed 21 axillary and 2 musculocutaneous nerve sutures onto the median, ulnar, or radial nerves. This technique was only performed in patients whose donor nerves, such as the thoracodorsal and medial pectoral nerves, which the authors generally use for repair of axillary and musculocutaneous nerves, respectively, were not available. In all patients, a perineurial suture was carried out after the creation of a perineurial window.

Results
The overall success rate of the ETSN was 43.5%. Reinnervation of the deltoid muscle with axillary nerve suture was successful in 47.6% of the patients, but reinnervation of the biceps muscle was unsuccessful in the 2 patients undergoing musculocutaneous nerve repair.

Conclusions
The authors conclude that ETSN should be performed in axillary nerve reconstruction but only when commonly used donor nerves are not available.