bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of red blood cell glutathione status in insulin resistance
Authors: Galgani Jose E. , Vasquez Karla , Leonelli Giannella , Espinosa Alejandra , Araya Hector , Perez-Bravo Francisco 
Published: August 2012

The aim of this study was to assess red blood cell glutathione from insulin-sensitive and insulin-resistant individuals before and after an oral glucose dose. Fifteen healthy, young (24 ± 5 years), nonobese (23 ± 2 kg·m–2), insulin-sensitive (ISI composite = 6.0 ± 1.2) individuals and 14 healthy, young (22 ± 2 years), nonobese (24 ± 2 kg·m–2), insulin-resistant (ISI composite = 2.7 ± 1.1) individuals received a 75 g oral glucose dose. Blood samples were drawn before and for 2 h after glucose ingestion for red blood cell glutathione and serum glucose and insulin concentrations. Glycemia before and after glucose ingestion was similar between groups (p = 0.17), which suggest that hyperinsulinemia compensated impaired insulin sensitivity. Red blood cell total (p = 0.81), reduced (p = 0.79), and oxidized (p = 0.88) glutathione concentrations were similar between groups under fasting and postprandial conditions. However, in response to glucose, increases in total and reduced glutathione concentrations were found at the end of the 2 h assessment period in both groups (p < 0.05). Direct associations between postprandial glucose response and red blood cell total (r = 0.52; p < 0.05) and oxidized (r = 0.61; p = 0.02) glutathione concentrations were observed only in insulin-sensitive subjects. In conclusion, healthy individuals differing in their degree of insulin resistance showed similar red blood cell glutathione concentrations under non-glucose- and glucose-stimulated conditions.
A New Nonestrogenic Steroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type I Blocks the Estrogen-Dependent Breast Cancer Tumor Growth Induced by Estrone
Authors: Ayan Diana , Maltais René , Roy Jenny , Poirier Donald 
Published: August 2012

Abstract
17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) converts estrone (E1) into estradiol (E2) and is expressed in many steroidogenic tissues and breast cancer cell lines. Because the potent estrogen E2 stimulates the growth and development of hormone-dependent diseases, inhibition of the final step of E2 synthesis is considered a promising strategy for the treatment of breast cancer. On the basis of our previous study identifying 16β-(m-carbamoylbenzyl)-E2 (CC-156) as a lead compound for the inhibition of 17β-HSD1, we conducted a number of structural modifications to reduce its undesired residual estrogenic activity. The steroid derivative PBRM [3-(2-bromoethyl)-16β-(m-carbamoylbenzyl)-17β-hydroxy-1,3,5(10)-estratriene] emerged as a potent inhibitor of 17β-HSD1 with an IC50 value of 68 nmol/L for the transformation of E1 into E2. When tested in the estrogen-sensitive breast cancer cell line T-47D and in mice, PBRM showed no estrogenic activity in the range of concentrations tested. Furthermore, with the purpose of evaluating the bioavailability of PBRM and CC-156 injected subcutaneously (2.3 mg/kg), we measured their plasmatic concentrations as a function of time, calculated the area under the curve (AUC0–12h) and showed a significant improvement for PBRM (772 ng*h/mL) compared with CC-156 (445 ng*h/mL). We next tested the in vivo efficiency of PBRM on the T-47D xenograft tumor model in female ovariectomized athymic nude mice. After a treatment with PBRM, tumor sizes in mice stimulated with exogenous E1 were completely reduced at the control group level (without E1 treatment). As a conclusion, PBRM is a promising nonestrogenic inhibitor of 17β-HSD1 for the treatment of estrogen-dependent diseases such as breast cancer. Mol Cancer Ther; 11(10); 2096–104. ©2012 AACR.
How Does the Eye Warm? Part I: A Potential Temperature Budget Analysis of an Idealized Tropical Cyclone
Authors: Stern Daniel P. , Zhang Fuqing 
Published: August 2012

Abstract
In this first part of a two-part study, the mechanisms that accomplish the warming in the eye of tropical cyclones are investigated through a potential temperature budget analysis of an idealized simulation. The spatial structure of warming varies substantially with time. During rapid intensification (RI), the warming is maximized at midlevels, and as a consequence, the perturbation temperature is always maximized in this region.
At the start of RI, total advection of potential temperature is the only significant term contributing to warming the eye. However, for a substantial portion of RI, the region of most rapid warming actually undergoes mean ascent. The net advective warming is shown to be a result of eddy radial advection of potential temperature, dominated by a wavenumber-1 feature that is likely due to a dynamic instability. At a sufficient intensity, mean vertical advective warming becomes concentrated in a narrow zone just inward of the eyewall. In agreement with prior studies, this advective tendency is largely canceled by diabatic cooling. Subgrid-scale horizontal diffusion of potential temperature plays a surprisingly large role in the maintenance of the warm-core structure, and when the storm is intense, yields a negative tendency that can be of the same magnitude as advective warming.
The Cessation of Continuous Turbulence as Precursor of the Very Stable Nocturnal Boundary Layer
Authors: Van de Wiel B. J. H. , Moene A. F. , Jonker H. J. J. 
Published: August 2012

AbstractThe mechanism behind the collapse of turbulence in the evening as a precursor to the onset of the very stable boundary layer is investigated. To this end a cooled, pressure-driven flow is investigated by means of a local similarity model. Simulations reveal a temporary collapse of turbulence whenever the surface heat extraction, expressed in its nondimensional form h/L, exceeds a critical value. As any temporary reduction of turbulent friction is followed by flow acceleration, the long-term state is unconditionally turbulent. In contrast, the temporary cessation of turbulence, which may actually last for several hours in the nocturnal boundary layer, can be understood from the fact that the time scale for boundary layer diffusion is much smaller than the time scale for flow acceleration. This limits the available momentum that can be used for downward heat transport. In case the surface heat extraction exceeds the so-called maximum sustainable heat flux (MSHF), the near-surface inversion rapidly increases. Finally, turbulent activity is largely suppressed by the intense density stratification that supports the emergence of a different, calmer boundary layer regime.
Improving Reliability of Coupled Model Forecasts of Australian Seasonal Rainfall
Authors: Langford Sally , Hendon Harry H. 
Published: August 2012

Abstract
Seasonal rainfall predictions for Australia from the Predictive Ocean Atmosphere Model for Australia (POAMA), version P15b, coupled model seasonal forecast system, which has been run operationally at the Australian Bureau of Meteorology since 2002, are overconfident (too low spread) and only moderately reliable even when forecast accuracy is highest in the austral spring season. The lack of reliability is a major impediment to operational uptake of the coupled model forecasts. Considerable progress has been made to reduce reliability errors with the new version of POAMA2, which makes use of a larger ensemble from three different versions of the model. Although POAMA2 can be considered to be multimodel, its individual models and forecasts are similar as a result of using the same perturbed initial conditions and the same model lineage. Reliability of the POAMA2 forecasts, although improved, remains relatively low. Hence, the authors explore the additional benefit that can be attained using more independent models available in the European Union Ensemble-Based Predictions of Climate Changes and their Impacts (ENSEMBLES) project.
Although forecast skill and reliability of seasonal predictions of Australian rainfall are similar for POAMA2 and the ENSEMBLES models, forming a multimodel ensemble using POAMA2 and the ENSEMBLES models is shown to markedly improve reliability of Australian seasonal rainfall forecasts. The benefit of including POAMA2 into this multimodel ensemble is due to the additional information and skill of the independent model, and not just due to an increase in the number of ensemble members. The increased reliability, as well as improved accuracy, of regional rainfall forecasts from this multimodel ensemble system suggests it could be a useful operational prediction system.
A murine model to characterize the antithrombotic effect of molecules targeting human von Willebrand factor
Authors: Navarrete Ana-Maria , Casari Caterina , Legendre Paulette , Marx Isabelle , Hu Jiun-Ruey , Lenting Peter J. , Christophe Olivier D. , Denis Cécile V. 
Published: August 2012

Abstractvon Willebrand factor (VWF) is a promising target for developing antithrombotic drugs. The absence of accessible animal models impedes the study of specific human VWF (huVWF) targeting molecules in thrombosis. huVWF is not functional in the mouse because of a lack of interaction between huVWF and murine glycoprotein Ib. Using site-directed mutagenesis, we have replaced single or multiple amino acids in huVWF with their murine counterparts to eliminate species incompatibility. Using hydrodynamic injection, we have expressed the different chimeric VWF constructs into VWF−/− mice. Only huVWF with a complete murine A1 domain insertion was able to correct bleeding in vivo and form occlusive thrombi in mesenteric vessels after FeCl3 treatment. Using this model, we tested the antithrombotic effect of monoclonal antibodies against huVWF, blocking its interaction with collagens (mAbs 203 and 505) or with glycoprotein IIbIIIa (mAb 9). The 3 mAbs inhibited the thrombotic process in arterioles of VWF−/− mice expressing huVWFmuA1. Inhibiting VWF-interaction with collagens was more potent, emphasizing the potential of such a target as an antithrombotic tool. Our results validate our murine model as a simple in vivo tool to evaluate anti-huVWF agents.
A support vector machine based test for incongruence between sets of trees in tree space
Authors: Haws David C , Huggins Peter , O’Neill Eric M , Weisrock David W , Yoshida Ruriko 
Published: August 2012

Abstract

Background
The increased use of multi-locus data sets for phylogenetic reconstruction has increased the need to determine whether a set of gene trees significantly deviate from the phylogenetic patterns of other genes. Such unusual gene trees may have been influenced by other evolutionary processes such as selection, gene duplication, or horizontal gene transfer.

Results
Motivated by this problem we propose a nonparametric goodness-of-fit test for two empirical distributions of gene trees, and we developed the software to estimate a p-value for the test. Our approach maps trees into a multi-dimensional vector space and then applies support vector machines (SVMs) to measure the separation between two sets of pre-defined trees. We use a permutation test to assess the significance of the SVM separation. To demonstrate the performance of , we applied it to the comparison of gene trees simulated within different species trees across a range of species tree depths. Applied directly to sets of simulated gene trees with large sample sizes, was able to detect very small differences between two set of gene trees generated under different species trees. Our statistical test can also include tree reconstruction into its test framework through a variety of phylogenetic optimality criteria. When applied to DNA sequence data simulated from different sets of gene trees, results in the form of receiver operating characteristic (ROC) curves indicated that performed well in the detection of differences between sets of trees with different distributions in a multi-dimensional space. Furthermore, it controlled false positive and false negative rates very well, indicating a high degree of accuracy.

Conclusions
The non-parametric nature of our statistical test provides fast and efficient analyses, and makes it an applicable test for any scenario where evolutionary or other factors can lead to trees with different multi-dimensional distributions. The software is freely available under the GNU public license.
A prospective study of health care resource utilisation and selected costs of schizophrenia in France
Authors: Sarlon Emmanuelle , Heider Dirk , Millier Aurélie , Azorin Jean-Michel , König Hans-Helmut , Hansen Karina , Angermeyer Matthias C , Aballéa Samuel , Toumi Mondher 
Published: August 2012

Abstract

Background
Schizophrenia is among the most burdensome and costly illnesses worldwide. To estimate the cost of schizophrenia in France, a longitudinal study was carried out between 1998 and 2002. The main objective of this study was to describe and update the cost of schizophrenia in a longitudinal, representative sample of French patients. The second objective was to identify cost drivers in the treatment of schizophrenia.

Methods
Based on a cohort of 288 French schizophrenic patients during 2 years of prospective follow-up, this study collected clinical, patient reported outcomes, quality of life, functioning, patient management, care giver involvement and resource utilisation data every 6 months. For each service, information was collected on the type of service, the frequency of attendance and type of intervention provided to the patient. Unit costs were based on available French databases. Mean service use and costs over the five time points were estimated using between-effects regression models.

Results
In the total sample of 288 patients aged 18-64 years, the mean total cost (€ 3 534) was mainly accounted for by the cost of inpatient treatment (€ 1 390) and day care (€ 1 331). The estimate of the annual cost for direct medical health care for all French schizophrenic patients was € 1 581 million, including € 621 million for inpatient treatment and € 595 million for day care (77%). The costs for medication accounted for 16.1% of total annual costs. The remaining costs (6.9%) included visits to psychiatrists, general practitioners, other physicians and psychologists. The direct resource allocation showed inpatient treatment as the main direct cost. Unemployment was identified as a major indirect cost of schizophrenia treatment. Positive and depressive schizophrenia symptoms at baseline and relapse occurrence during the follow-up period were associated with a higher cost of treatment. Health satisfaction or negative symptoms of schizophrenia at baseline were associated with lower costs.

Conclusion
Several cost drivers were identified. Based on the results obtained in France, we suggest further analysis of mechanisms that influence the service-specific costs for schizophrenia in other areas of the world.
The baseline distribution of malaria in the initial phase of elimination in Sabang Municipality, Aceh Province, Indonesia
Authors: Asih Puji BS , Rozi Ismail E , Herdiana  , Pratama Nandha R , Hidayati Anggi PN , Marantina Sylvia S , Kosasih Sully , Chand Krisin , Wangsamuda Suradi , Rusdjy Faisal A , Sumiwi Maria E , Imran Ali , Yuniarti Titik , Sianturi Tahi , Nur Jamilah , Asnita  , Bukhari  , Barussanah Cut , Yani Muhammad , Ainun Cut , Jamil Kurnia , Mariam Cut , Sengkerij Simon P , Laihad Ferdinand J , Hawley William , Syafruddin Din 
Published: August 2012

Abstract

Background
Sabang Municipality, in Aceh Province, Indonesia, plans to initiate a malaria elimination programme in 2013. A baseline survey of the distribution of malaria in the municipality was conducted to lay the foundations for an evidence-based programme and to assess the island’s readiness to begin the elimination process.

Methods
The entire population of the municipality was screened for malaria infection and G6PD deficiency. Specimens collected included blood slides, blots and tubes for selected households.

Results and Discussion
Samples were collected from 16,229 residents. Microscopic examination of the blood smears revealed 12 malaria infections; 10 with Plasmodium falciparum and 2 with Plasmodium vivax. To confirm the parasite prevalence, polymerase chain reaction (PCR) diagnosis was performed on the entire positive cases by microscopy and randomized 10% of the microscopically negative blood samples. PCR revealed an additional 11 subjects with malaria; one P. falciparum infection from the village of Paya Keunekai, and nine P. vivax infections and one mixed P. falciparum/P. vivax infection from the village of Batee Shok. The overall slide positivity rate was 0.074% (CI 95%: 0.070 – 0.078) and PCR corrected prevalence 0,590% (CI 95%: 0.582 – 0.597). Analysis of 937 blood samples for G6PD deficiency revealed two subjects (0.2%) of deficient G6PD. Analysis of several genes of the parasite, such as Pfdhfr, Pfdhps, Pfmdr1, Pfcrt, Pfmsp1, Pfmsp2, Pvdhfr, Pvdhps, Pvmdr1 and host gene, such as G6PD gene revealed that both P. falciparum and P. vivax carried the mutation associated with chloroquine resistance.

Conclusion
Malariometric and host genetic analysis indicated that there is a low prevalence of both malaria and G6PD deficiency in the population of Sabang Municipality. Nevertheless, malaria cases were clustered in three rural villages and efforts for malaria elimination in Sabang should be particularly focused on those three villages.
Human amniotic fluid stem cell injection therapy for urethral sphincter regeneration in an animal model
Authors: Kim Bum Soo , Chun So Young , Lee Jong Kil , Lim Hyun Ju , Bae Jae-sung , Chung Ho-Yun , Atala Anthony , Soker Shay , Yoo James J , Kwon Tae Gyun 
Published: August 2012

Abstract

Background
Stem cell injection therapies have been proposed to overcome the limited efficacy and adverse reactions of bulking agents. However, most have significant limitations, including painful procurement, requirement for anesthesia, donor site infection and a frequently low cell yield. Recently, human amniotic fluid stem cells (hAFSCs) have been proposed as an ideal cell therapy source. In this study, we investigated whether periurethral injection of hAFSCs can restore urethral sphincter competency in a mouse model.

Methods
Amniotic fluids were collected and harvested cells were analyzed for stem cell characteristics and in vitro myogenic differentiation potency. Mice underwent bilateral pudendal nerve transection to generate a stress urinary incontinence (SUI) model and received either periurethral injection of hAFSCs, periurethral injection of Plasma-Lyte (control group), or underwent a sham (normal control group).
For in vivo cell tracking, cells were labeled with silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate (MNPs@SiO2 (RITC)) and were injected into the urethral sphincter region (n = 9). Signals were detected by optical imaging. Leak point pressure and closing pressure were recorded serially after injection.
Tumorigenicity of hAFSCs was evaluated by implanting hAFSCs into the subcapsular space of the kidney, followed two weeks later by retrieval and histologic analysis.

Results
Flow activated cell sorting showed that hAFSCs expressed mesenchymal stem cell (MSC) markers, but no hematopoietic stem cell markers. Induction of myogenic differentiation in the hAFSCs resulted in expression of PAX7 and MYOD at Day 3, and DYSTROPHIN at Day 7. The nanoparticle-labeled hAFSCs could be tracked in vivo with optical imaging for up to 10 days after injection. Four weeks after injection, the mean LPP and CP were significantly increased in the hAFSC-injected group compared with the control group. Nerve regeneration and neuromuscular junction formation of injected hAFSCs in vivo was confirmed with expression of neuronal markers and acetylcholine receptor. Injection of hAFSCs caused no in vivo host CD8 lymphocyte aggregation or tumor formation.

Conclusions
hAFSCs displayed MSC characteristics and could differentiate into cells of myogenic lineage. Periurethral injection of hAFSCs into an SUI animal model restored the urethral sphincter to apparently normal histology and function, in absence of immunogenicity and tumorigenicity.
IL-1β reactivity and the development of severe fatigue after military deployment: a longitudinal study
Authors: van Zuiden Mirjam , Kavelaars Annemieke , Amarouchi Karima , Maas Mirjam , Vermetten Eric , Geuze Elbert , Heijnen Cobi J 
Published: August 2012

Abstract

Background
It has been suggested that pro-inflammatory cytokine signaling to the brain may contribute to severe fatigue. We propose that not only the level of circulating cytokines, but also increased reactivity of target cells to cytokines contributes to the effect of cytokines on behavior. Based on this concept, we assessed the reactivity of peripheral blood cells to IL-1β in vitro as a novel approach to investigate whether severe fatigue is associated with increased pro-inflammatory signaling.

Methods
We included 504 soldiers before deployment to a combat-zone. We examined fatigue severity and the response to in vitro stimulation with IL-1β prior to deployment (T0), and 1 (T1) and 6 months (T2) after deployment. IL-8 production was used as read-out. As a control we determined LPS-induced IL-8 production. The presence of severe fatigue was assessed with the Checklist Individual Strength (CIS-20R). Differences in dose–response and the longitudinal course of IL-1β and LPS-induced IL-8 production and fatigue severity were investigated using repeated measures ANOVA.

Results
At T2, the group who had developed severe fatigue (n = 65) had significantly higher IL-1β-induced IL-8 production than the non-fatigued group (n = 439). This group difference was not present at T0, but developed over time. Longitudinal analysis revealed that in the non-fatigued group, IL-1β-induced IL-8 production decreased over time, while IL-1β-induced IL-8 production in the fatigued group had not decreased. To determine whether the observed group difference was specific for IL-1β reactivity, we also analyzed longitudinal LPS-induced IL-8 production. We did not observe a group difference in LPS-induced IL-8 production.

Conclusions
Collectively, our findings indicate that severe fatigue is associated with a higher reactivity to IL-1β. We propose that assessment of the reactivity of the immune system to IL-1β may represent a promising novel method to investigate the association between behavioral abnormalities and pro-inflammatory cytokine signaling.