bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of toe spreader in people with overactive toe flexors post stroke: a randomized controlled pilot study
Authors: Chiong Yi , Tay San-San , Lim Peter AC , Tan Dawn ML 
Published: May 2012

Objectives: To investigate the long-term effects of the toe spreader on gait characteristics, pain, activity level and balance in individuals with chronic stroke who exhibited tonic toe flexion reflex. The secondary objectives were to determine the sample size for future studies and to assess compliance to the use of the toe spreader. Design: Single-blind, randomized controlled pilot trial. Setting: Outpatient clinic of a tertiary hospital in Singapore. Subjects: Nine ambulatory participants with tonic toe flexion reflex more than six months post stroke. Intervention: Control or customized toe spreader groups for six months. The toe spreader was made of Rolyan Ezemix elastomer putty and worn with sport sandals during ambulation. Main measures: Gait speed and plantar surface contact area, pain visual analogue scale (VAS), Berg Balance Scale, Modified Ashworth Scale, activity level measured on pedometer and compliance via logbook. Results: There were no significant differences between the groups. Both groups showed non-significant improvements in gait speed (toe spreader 0.34 (0.26) versus 0.37 (0.29) m/s; control 0.40 (0.27) versus 0.50 (0.17) m/s), activity level, step length of the hemiplegic leg and stride length at six months. All participants in the intervention group used the toe spreader less than 50% of the days, indicating suboptimal compliance. Conclusion: The use of the toe spreader did not result in significant improvements in any outcomes. Studies with sample sizes of at least 56 participants and strategies to increase compliance to the use of the toe spreader are recommended.
Positive effect of eplerenone treatment on endothelial progenitor cells in patients with chronic heart failure
Authors: Jung Christian , Florvaag Anna , Oberle Volker , Fritzenwanger Michael , Kretschmar Daniel , Kuethe Friedhelm , Betge Stefan , Goebel Bjoern , Franz Marcus , Barz Dagmar , Ferrari Markus , Figulla Hans R 
Published: May 2012

Background: Endothelial progenitor cells (EPCs) are known to play a significant role in reendothelialization and vascular repair. Recently, a mineralocorticoid receptor was demonstrated to be expressed by EPCs. The study aimed to evaluate a potential influence of eplerenone treatment on the total number of EPCs in patients with chronic heart failure. Methods: Eighty-seven male patients with chronic heart failure were included (age: 23–83 years; body mass index 29.1 ± 5.1 kg/m2; New York Heart failure classification (NYHA) I: 29 patients, NYHA II: 32 patients, NYHA III: 26 patients). Numbers of circulating EPCs were quantified immediately using flow cytometry. Twenty-eight patients received therapy with eplerenone. Patients were further characterized by echocardiography, spirometry and laboratory markers. Results: Patients with ongoing eplerenone administration showed higher levels of circulating cells expressing CD34+ ( p<0.05) and CD34+KDR+ ( p<0.05) and CD34+CD133+KDR+ cells ( p<0.05). The effects of eplerenone treatment could be shown to be independent of NYHA status, genesis of the underlying cardiovascular morbidity, left ventricular function and co-medication. Conclusion: Patients with chronic heart failure treated with eplerenone show higher numbers of EPCs. The clinical benefit for treatment with eplerenone has been demonstrated even for patients with mild heart failure and might be partially mediated by EPCs.
APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair
Authors: Nowarski Roni , Wilner Ofer I. , Cheshin Ori , Shahar Or D. , Kenig Edan , Baraz Leah , Britan-Rosich Elena , Nagler Arnon , Harris Reuben S. , Goldberg Michal , Willner Itamar , Kotler Moshe 
Published: May 2012

AbstractAPOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.
Survivin is highly expressed in CD34+38− leukemic stem/progenitor cells and predicts poor clinical outcomes in AML
Authors: Carter Bing Z. , Qiu Yihua , Huang Xuelin , Diao Lixia , Zhang Nianxiang , Coombes Kevin R. , Mak Duncan H. , Konopleva Marina , Cortes Jorge , Kantarjian Hagop M. , Mills Gordon B. , Andreeff Michael , Kornblau Steven M. 
Published: May 2012

Abstract
Survivin, a member of the inhibitors of apoptosis protein family, plays important roles in cell proliferation and survival and is highly expressed in various malignancies, including leukemias. To better understand its role in acute myeloid leukemia (AML), we profiled survivin expression in samples obtained from 511 newly diagnosed AML patients and in CD34+38− AML stem/progenitor cells using a validated reverse-phase protein array; we correlated its levels with clinical outcomes and with levels of other proteins in the same sample set. We found that survivin levels were higher in bone marrow than in paired peripheral blood leukemic cells (n = 140, P = .0001) and that higher survivin levels significantly predicted shorter overall (P = .016) and event-free (P = .023) survival in multivariate Cox model analysis. Importantly, survivin levels were significantly higher in CD34+38− AML stem/progenitor cells than in bulk blasts and total CD34+ AML cells (P < .05). Survivin expression correlated with the expressions of multiple proteins involved with cell proliferation and survival. Particularly, its expression strongly correlated with HIF1α in the stem/progenitor cell compartment. These results suggest that survivin is a prognostic biomarker in AML and that survivin, which is overexpressed in AML stem/progenitor cells, remains a potentially important target for leukemia therapy.
Proteasome inhibitors in multiple myeloma: 10 years later
Authors: Moreau Philippe , Richardson Paul G. , Cavo Michele , Orlowski Robert Z. , San Miguel Jesús F. , Palumbo Antonio , Harousseau Jean-Luc 
Published: May 2012

Abstract
Proteasome inhibition has emerged as an important therapeutic strategy in multiple myeloma (MM). Since the publication of the first phase 1 trials of bortezomib 10 years ago, this first-in-class proteasome inhibitor (PI) has contributed substantially to the observed improvement in survival in MM patients over the past decade. Although first approved as a single agent in the relapsed setting, bortezomib is now predominantly used in combination regimens. Furthermore, the standard twice-weekly schedule may be replaced by weekly infusion, especially when bortezomib is used as part of combination regimens in frontline therapy. Indeed, bortezomib is an established component of induction therapy for patients eligible or ineligible for autologous stem cell transplantation. Bortezomib has also been incorporated into conditioning regimens before autologous stem cell transplantation, as well as into post-ASCT consolidation therapy, and in the maintenance setting. In addition, a new route of bortezomib administration, subcutaneous infusion, has recently been approved. Recently, several new agents have been introduced into the clinic, including carfilzomib, marizomib, and MLN9708, and trials investigating these “second-generation” PIs in patients with relapsed/refractory MMs have demonstrated positive results. This review provides an overview of the role of PIs in the treatment of MM, focusing on developments over the past decade.
miR-107: a Toll-like receptor-regulated miRNA dysregulated in obesity and type II diabetes
Authors: Foley Niamh H , OˈNeill Luke A 
Published: May 2012

Abstract
Review on the link between miR-107 dyregulation and TLR4 inflammation in type 2 diabetes.
miRNAs are small noncoding RNAs that act as regulators of gene expression. Dysregulation of miRNAs has been shown to contribute to multiple disease processes. It has become apparent that miRNAs play a key role in the innate immune response, whereby a large number of miRNAs have been demonstrated to be regulated by TLRs, key initiators of the innate immune response to infection. Recently, the LPS receptor, TLR4, has been shown to down-regulate miR-107 in macrophages. In addition, miR-107 has been demonstrated to be dysregulated in murine and rodent models of obesity and insulin resistance, respectively, with miR-107 contributing to both conditions. With obesity and inflammation being so intrinsically associated, the link between the miR-107 expression levels, inflammation, and insulin resistance may be of particular importance in metabolic diseases. The decrease in miR-107 in response to TLR4 may be an attempt to limit insulin resistance, a feature of obesity-related inflammation. If this process is impaired, disease, such as T2D, might persist. This review aims to discuss a possible link between the molecular phenomena of obesity and inflammation and the role that miR-107 may contribute to these processes.
Influence of age on the association of GIRK4 with metabolic syndrome
Authors: Li Nanfang , Zhang Delian , Zhang Juhong , Guo Yanying , Yan Zhitao , Wang Hongmei , Zhou Ling , Hong Jing , Wang Xinling , A Zufeiya 
Published: May 2012

Background G protein-coupled inward rectifier K+ channel 4 (GIRK4) gene expressions have been implicated in the development of obesity, a key feature of metabolic syndrome (MetS). We investigated whether sequence variants of GIRK4 may represent metabolic risk factors for the Uygur Chinese population. Methods The entire GIRK4 gene, including all exons, the promoter and untranslated regions from 48 MetS individuals, was studied in order to identify genetic variations associated with the disorder. Targeted genotyping of four common single nucleotide polymorphisms (SNPs: rs11221497, rs6590357, rs4937391 and rs2604204) and one novel missense mutation (M210I) was performed using the TaqMan polymerase chain reaction method for 443 MetS and 786 non-MetS subjects. Results When all MetS cases were compared against all non-MetS controls, no significant association was found between the three SNPs (rs2604204, rs4937391 and rs6590357) and MetS status or metabolic traits. After adjustment, rs11221497 was associated with MetS (odds ratio (OR) [95% CI] = 0.731 [0.551–0.968], P= 0.029). Interestingly, when the MetS group was stratified into subclasses by age, an association was found for the three SNPs (rs2604204, rs4937391 and rs6590357) having estimated false discovery rates <0.001 and age of <50 y. After adjustment, the SNPs rs2604204, rs4937391 and rs6590357 were also associated with MetS in younger subjects: ORs [95% CI]: 1.678 [1.149–2.450], 1.839 [1.204–2.809] and 0.602 [0.379–0.958], respectively. All of the four SNPs showed a trend towards lower or higher metabolic traits ( P< 0.05) in younger subjects. In addition, a newly identified missense mutation (M210I) was not specifically related with MetS. Conclusions GIRK4 sequence variants appear to associate with MetS in the Uygurian population, and this association may be influenced by age.
Levels of cytokines in umbilical cord blood in relation to spontaneous term labor
Authors: Tutdibi Erol , Hunecke Angela , Lindner Ulrike , Monz Dominik , Gortner Ludwig 
Published: May 2012

Abstract

Objective: Inflammatory mechanisms are thought to play an important role in the process of labor, both in preterm and spontaneous term delivery. We aimed to determine whether normal spontaneous vaginal delivery (SVD) at term was associated with an inflammatory activation compared with elective cesarean section (ECS) without previous onset of labor.

Methods: Cytokine concentrations were measured in venous cord blood obtained from 60 term newborns (ECS, n=35; SVD, n=25) born to mothers with clinically uneventful pregnancy and without signs of infection.

Results: Both study groups showed no differences in birth weight, umbilical artery pH, Apgar at 5 min, and gender distribution. Infants delivered by ECS had lower gestational age: mean, 38.5 weeks (range, 37.0–39.6 weeks) vs. mean, 39.8 weeks (range, 37.9–42.4 weeks) (P<0.001). Concentrations of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-17, IL-1 receptor antagonist, soluble IL-2 receptor α, granulocyte-macrophage colony-stimulating factor, interferon (IFN)-α2, IFN-γ, tumor necrosis factor (TNF)-α, TNF-β, and interferon inducible protein 10 were not different between ECS and SVD. Newborns after SVD displayed increased levels of transforming growth factor β1 (TGF-β1): mean, 8580 pg/mL (95% CI, 5554–11,606) vs. mean, 4864 pg/mL (95% CI, 2471–7257) (P<0.0012).

Conclusions: Our findings suggest that, in healthy, term neonates, the exposition to normal spontaneous delivery and labor is not associated with systemic activation of different inflammatory mediators compared with ECS except for TGF-β1. Further studies are needed to evaluate the immunomodulatory role of labor-associated TGF-β1 increase in fetal cord blood.
Thyreotropin levels in diabetic patients on metformin treatment
Authors: Cappelli Carlo , Rotondi Mario , Pirola Ilenia , Agosti Barbara , Formenti Annamaria , Zarra Emanuela , Valentini Umberto , Leporati Paola , Chiovato Luca , Castellano Maurizio 
Published: May 2012

ObjectiveA retrospective study to evaluate the changes in TSH concentrations in diabetic patients treated or not treated with metformin and/or l-thyroxine (l-T4).MethodsThree hundred and ninety three euthyroid diabetic patients were divided into three groups on the basis of metformin and/or l-T4 treatment: Group (M−/L−), 119 subjects never treated with metformin and l-T4; Group (M+/L−), 203 subjects who started metformin treatment at recruitment; and Group (M+/L+), 71 patients on l-T4 who started metformin recruitment.ResultsThe effect of metformin on serum TSH concentrations was analyzed in relation to the basal value of TSH (below 2.5 mIU/l (Q1) or between 2.51 and 4.5 mIU/l (Q2)). In patients of group M+/L+, TSH significantly decreased independently from the basal level (Q1, from 1.45±0.53 to 1.01±1.12 mU/l (P=0.037); Q2, from 3.60±0.53 to 1.91±0.89 mU/l (P<0.0001)). In M+/L− group, the decrease in TSH was significant only in those patients with a basal high-normal serum TSH (Q2: from 3.24±0.51 to 2.27±1.28 mU/l (P=0.004)); in M−/L− patients, no significant changes in TSH levels were observed. In patients of group M+/L− showing high-normal basal TSH levels, a significant decrease in TSH was observed independently from the presence or absence of thyroid peroxidase antibodies (AbTPO; Q2 AbTPO +: from 3.38±0.48 to 1.87±1.08 mU/l (P<0.001); Q2 AbTPO −: from 3.21±0.52 to 2.34±1.31 mU/l (P<0.001)).ConclusionsThese data strengthen the known TSH-lowering effect of metformin in diabetic patients on l-T4 treatment and shows a significant reduction of TSH also in euthyroid patients with higher baseline TSH levels independently from the presence of AbTPO.
Cancer Risk Associated with Use of Metformin and Sulfonylurea in Type 2 Diabetes: A Meta-Analysis
Authors: Soranna Davide , Scotti Lorenza , Zambon Antonella , Bosetti Cristina , Grassi Guido , Catapano Alberico , La Vecchia Carlo , Mancia Giuseppe , Corrao Giovanni 
Published: May 2012

Abstract

Objective.
Oral antidiabetic drugs (including metformin and sulfonylurea) may play a role in the relationship between type 2 diabetes and cancer. To quantify the association between metformin and sulfonylurea and the risk of cancer, we performed a meta-analysis of available studies on the issue.

Materials and Methods.
We performed a MEDLINE search for observational studies that investigated the risk of all cancers and specific cancer sites in relation to use of metformin and/or sulfonylurea among patients with type 2 diabetes mellitus. Fixed- and random-effect models were fitted to estimate the summary relative risk (RR). Between-study heterogeneity was tested using χ2 statistics and measured with the I2 statistic. Publication bias was evaluated using funnel plot and Egger's regression asymmetry test.

Results.
Seventeen studies satisfying inclusion criteria and including 37,632 cancers were evaluated after reviewing 401 citations. Use of metformin was associated with significantly decreased RR of all cancers (summary RR 0.61, 95% confidence interval [CI] 0.54–0.70), colorectal cancer (0.64, 95% CI 0.54–0.76), and pancreatic cancer (0.38, 95% CI 0.14–0.91). With the exception of colorectal cancer, significant between-study heterogeneity was observed. Evidence of publication bias for metformin-cancer association was also observed. There was no evidence that metformin affects the risk of breast and prostate cancers, nor that sulfonylurea affects the risk of cancer at any site.

Conclusions.
Metformin, but not sulfonylurea, appears to reduce subsequent cancer risk. This has relevant implications in light of the exploding global epidemic of diabetes.
Predicting the distribution of out‐of‐reach biotopes with decision trees in a Swedish marine protected area
Authors: Gonzalez-Mirelis Genoveva , Lindegarth Mats 
Published: May 2012

Through spatially explicit predictive models, knowledge of spatial patterns of biota can be generated for out‐of‐reach environments, where there is a paucity of survey data. This knowledge is invaluable for conservation decisions. We used distribution modeling to predict the occurrence of benthic biotopes, or megafaunal communities of the seabed, to support the spatial planning of a marine national park. Nine biotope classes were obtained prior to modeling from multivariate species data derived from point source, underwater imagery. Five map layers relating to depth and terrain were used as predictor variables. Biotope type was predicted on a pixel‐by‐pixel basis, where pixel size was 15 × 15 m and total modeled area was 455 km2.To choose a suitable modeling technique we compared the performance of five common models based on recursive partitioning: two types of classification and regression trees ([1] pruned by 10‐fold cross‐validation and [2] pruned by minimizing complexity), random forests, conditional inference (CI) trees, and CI forests. The selected model was a CI forest (an ensemble of CI trees), a machine‐learning technique whose discriminatory power (class‐by‐class area under the curve [AUC] ranged from 0.75 to 0.86) and classification accuracy (72%) surpassed those of the other methods tested. Conditional inference trees are virtually new to the field of ecology. The final model's overall prediction error was 28%. Model predictions were also checked against a custom‐built measure of dubiousness, calculated at the polygon level. Key factors other than the choice of modeling technique include: the use of a multinomial response, accounting for the heterogeneity of observations, and spatial autocorrelation. To illustrate how the model results can be implemented in spatial planning, representation of biodiversity in the national park was described and quantified.Given a goal of maximizing classification accuracy, we conclude that conditional inference trees are a promising tool to map biota. Species distribution modeling is presented as an ecological tool that can handle a wide variety of systems (e.g., the benthic system).
Dual Chelant Mechanism for the Deployment of Scale Inhibitors in Controlled Solubility/Precipitation Treatments
Authors: Todd M. J. , Savin A. J. , Sorbie K. S. 
Published: May 2012

Abstract
In scale inhibitor squeeze treatments, precipitation of the inhibitor within the formation can lead to extended squeeze lifetimes. However, such processes also have the potential to cause formation damage unless they are carefully designed and controlled. The formation of a partially soluble inhibitor/metal complex within a reservoir is the objective for almost all precipitation squeeze packages. However, historically there are numerous ways this is achieved almost all of which require a limited operational window to be deployed successfully. In this paper, we describe the development of a novel dual chelant system which provides a method for controlling both the "wanted" and "unwanted" precipitation of the scale inhibitor package within the formation. The highly tunable nature of the system allows for ease of pumping at more extreme conditions (higher and low temperatures, calcium levels etc.) than have previously been possible. By using the dual chelant mechanism described in this paper, a package can be tuned to precipitate within a certain time frame both at low and high temperatures in brines with varying degrees of salinity and hardness. The scale inhibitor (SI) itself is a chelant or ligand for divalent ions present (mainly Ca2+) and this is denoted L2 and the second chelant, L1, is added to the system at certain design concentrations, as explained in the paper.
In many situations, the high divalent metal ion content of a produced brine, or formation water can limit the successful pumping of a scale inhibitor due to high levels of calcium, for example. Under these conditions the dual chelant mechanism can also be deployed to prevent scale inhibitor phase separation.
This paper discloses the theory of how the dual chelant mechanism works using computer modeling and the subsequent confirmation of the simulations by laboratory testing. The importance of the pKa of the SI (L2) and the added chelant, L1, and the relative metal binding constant interactions between L1/ L2 and Ca2+ are explained and investigated. The comparison of the dual chelant mechanism versus conventional packages is demonstrated by core flood experiments. The dual chelant mechanism gives a clear improvement in squeeze lifetime and controllability and provides a platform for the development of many types of controlled solubility scale inhibitor treatment.