bluuebunny/crossref_metadata_2025_split huggingface dataset:
New perspectives for the treatment of pulmonary hypertension
Authors: Baliga Reshma S , MacAllister Raymond J , Hobbs Adrian J 
Published: December 2010

Pulmonary hypertension (PH) is a debilitating disease with a poor prognosis. Therapeutic options remain limited despite the introduction of prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase 5 inhibitors within the last 15 years; these interventions address predominantly the endothelial and vascular dysfunctionS associated with the condition, but simply delay progression of the disease rather than offer a cure. In an attempt to improve efficacy, emerging approaches have focused on targeting the pro‐proliferative phenotype that underpins the pulmonary vascular remodelling in the lung and contributes to the impaired circulation and right heart failure. Many novel targets have been investigated and validated in animal models of PH, including modulation of guanylate cyclases, phosphodiesterases, tyrosine kinases, Rho kinase, bone morphogenetic proteins signalling, 5‐HT, peroxisome proliferator activator receptors and ion channels. In addition, there is hope that combinations of such treatments, harnessing and optimizing vasodilator and anti‐proliferative properties, will provide a further, possibly synergistic, increase in efficacy; therapies directed at the right heart may also offer an additional benefit. This overview highlights current therapeutic options, promising new therapies, and provides the rationale for a combination approach to treat the disease.LINKED ARTICLES This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐1
Pharmacological enhancement of fear reduction: preclinical models
Authors: Graham Bronwyn M , Langton Julia M , Richardson Rick 
Published: December 2010

Anxiety disorders have a high prevalence, and despite the substantial advances in the psychological treatment of anxiety, relapse is still a common problem. One approach to improving existing psychological treatments for anxiety has been to develop pharmacological agents that can be used to enhance the processes underlying exposure therapy, which is the most commonly used and empirically validated psychological treatment for anxiety during which individuals are taught to appropriately inhibit fear. Animal models of exposure therapy, particularly fear extinction, have proved to be a very useful way of examining the neural and molecular correlates of fear inhibition, which has in turn led to the identification of numerous drugs that enhance these processes in rats. Several of these drugs have subsequently been tested as novel pharmacological adjuncts to exposure therapy in humans with a range of anxiety disorders. The purpose of this review is to outline the key animal models of exposure therapy and to describe how these have been used to develop potential pharmacological adjuncts for anxiety disorders. Drugs that are currently in clinical use, as well as those currently in the preclinical stages of investigation, are described.LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐4
Quality assessment of 3D building data
Authors: Akca Devrim , Freeman Mark , Sargent Isabel , Gruen Armin 
Published: December 2010

Abstract Three‐dimensional building models are often now produced from lidar and photogrammetric data. The quality control of these models is a relevant issue both from the scientific and practical points of view. This work presents a method for the quality control of such models. The input model (3D building data) is co‐registered to the verification data using a 3D surface matching method. The 3D surface matching evaluates the Euclidean distances between the verification and input data‐sets. The Euclidean distances give appropriate metrics for the 3D model quality. This metric is independent of the method of data capture. The proposed method can favourably address the reference system accuracy, positional accuracy and completeness. Three practical examples of the method are provided for demonstration.
Survival Disparities within American and Israeli Dialysis Populations: Learning from Similarities and Distinctions across Race and Ethnicity
Authors: Kalantar‐Zadeh Kamyar , Golan Eliezer , Shohat Tamy , Streja Elani , Norris Keith C. , Kopple Joel D. 
Published: December 2010

AbstractThere are counterintuitive but consistent observations that African American maintenance dialysis patients have greater survival despite their less favorable socioeconomic status, high burden of cardiovascular risks including hypertension and diabetes, and excessively high chronic kidney disease prevalence. The fact that such individuals have a number of risk factors for lower survival and yet live longer when undergoing dialysis treatment is puzzling. Similar findings have been made among Israeli maintenance dialysis patients, in that those who are ethnically Arab have higher end‐stage renal disease but exhibit greater survival than Jewish Israelis. The juxtaposition of these two situations may provide valuable insights into racial/ethnic‐based mechanisms of survival in chronic diseases. Survival advantages of African American dialysis patients may be explained by differences in nutritional status, inflammatory profile, dietary intake habits, body composition, bone and mineral disorders, mental health and coping status, dialysis treatment differences, and genetic differences among other factors. Prospective studies are needed to examine similar models in other countries and to investigate the potential causes of these paradoxes in these societies. Better understanding the roots of racial/ethnic survival differences may help improve outcomes in both patients with chronic kidney disease and other individuals with chronic disease states.
Evaluation of Adult Kidney Transplant Candidates
Authors: Pham Phuong‐Thu , Pham Phuong‐Anh , Pham Phuong‐Chi , Parikh Sefali , Danovitch Gabriel 
Published: December 2010

AbstractImportant advances in immunosuppressive therapy and refinement in surgical techniques have allowed renal transplantation to become the treatment of choice for virtually all suitable candidates with end‐stage renal disease. Compared to dialysis, kidney transplantation improves both patient survival and quality of life and, over time, can reduce the total cost of medical care. It must be noted, however, that although the risk of death in the first year after transplantation is <5%, not all patients qualify for the surgery because of their unacceptable risks for complications. The transplant evaluation process requires a comprehensive assessment of each patient’s medical, surgical, and psychosocial histories. Selection of the suitable transplant candidate remains a challenge for transplant physicians owing, predominantly, to the presence of complex medical issues in the potential candidates and nonstandardized criteria for acceptance or rejection among transplant centers. Furthermore, with the ever‐increasing disparity between donor organ supply and demand and resultant increased wait‐list times, the transplant physicians must further consider the optimal management and re‐evaluation of wait‐list patients during the waiting period. This article describes a systematic approach for the evaluation of a potential renal transplant candidate. Various medical issues that arise during the evaluation process are discussed.
Lack of effect of unrefrigerated young whole blood transfusion on patient outcomes after massive transfusion in a civilian setting
Authors: Ho Kwok M. , Leonard Anton D. 
Published: December 2010

BACKGROUND: Warm fresh whole blood has been advocated for critical bleeding in the military setting. This study assessed whether unrefrigerated young whole blood transfusion, from donation to transfusion less than 24 hours, could reduce mortality of patients with critical bleeding in a civilian setting.STUDY DESIGN AND METHODS: A linked data cohort study was conducted on a total of 353 consecutive patients requiring massive transfusion, defined as 10 units or more of red blood cells or whole blood transfusion within 24 hours, in a quaternary health care center in Australia.RESULTS: Of the 353 patients with massive blood transfusion in the study, 77 received unrefrigerated young whole blood transfusion (mean, 4.0 units; interquartile range, 2‐6). The diagnosis, severity of acute illness, age, sex, and ABO blood group were not significantly different between the patients who received unrefrigerated young whole blood and those who did not. Unrefrigerated young whole blood transfusions were associated with a slightly improved coagulation profile (lowest fibrinogen concentrations 1.7 g/L vs. 1.4 g/L, p = 0.006; worst international normalization ratio, 2.4 vs. 2.8, p = 0.05) but did not reduce the total utilization of allogeneic blood products and subsequent use of recombinant Factor VIIa (27% vs. 22%, p = 0.358). Thirty‐day mortality and 8‐year survival after hospital discharge (hazard ratio, 1.05; 95% confidence interval, 0.41‐2.65; p = 0.93) were also not different after the use of unrefrigerated young whole blood transfusion.CONCLUSIONS: Unrefrigerated young whole blood transfusion was not associated with a reduced mortality of patients requiring massive transfusion in a civilian setting when other blood products were readily available.
Pregnancy planning in Sweden – a pilot study among 270 women attending antenatal clinics
Authors: TYDÉN TANJA , STERN JENNY , NYDAHL MARGARETHA , BERGLUND ANNA , LARSSON MARGARETA , ROSENBLAD ANDREAS , AARTS CLARA 
Published: December 2010

Abstract Objective. Health status and lifestyle before and at the time of conception could affect the health of both mother and child, but there is a lack of knowledge about the degree to which pregnancies are planned. The aim of this pilot study was to investigate whether and how women plan their pregnancies. Material and methods. The main outcome measures were use of timetables, ovulation tests and lifestyle changes. Women (n= 322) visiting four antenatal clinics were asked to fill out a questionnaire (participation rate = 83.9%, n= 270). Results. Three of four pregnancies (n= 202) were very or rather well planned, whereas 4.4% (n= 12) were totally unplanned. During the planning period, 37.1% (n= 100) made up a timetable for getting pregnant, 23% (n= 62) used ovulation tests, 20.7% (n= 56) took folic acid and 10.4% (n= 28) changed alcohol consumption. Conclusion. Although a majority of these women had planned pregnancies, only one in five had taken folic acid during the planning period.
Emergency cesarean sections can be predicted by markers for stress, worry and sleep disturbances in first‐time mothers
Authors: WANGEL ANNE‐MARIE , MOLIN JOHAN , ÖSTMAN MARGARETA , JERNSTRÖM HELENA 
Published: December 2010

Abstract Objective. To identify predictors as free‐text markers for mental ill‐health from an electronic perinatal record (EMR) system and the association with emergency cesarean section (CS) in nulliparous women. Material and methods. This was a population‐based study using an EMR system, set in the catchment area of Malmö University Hospital in Sweden. Of 10 662 nulliparous women presenting with a singleton cephalic baby for vaginal delivery between 2001 and 2006, 6 467 women with complete EMRs were selected. A free‐text search of markers for mental ill‐health was carried out, and results were analysed by multivariate logistic regression. Eleven markers for mental ill‐health were tested with Cohen's kappa for agreement and used as exposure variables. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for emergency CS, and adjusted for maternal age, diabetes, epidural anesthesia and gestational weeks <37 and >41 by a multivariate logistic regression model with vaginal delivery as the reference. Results. Three markers identified from the EMR system reached statistically significant associations with an increased risk for emergency CS in nulliparous women: stress, adjusted OR 1.66 (95% CI 1.34–2.06); sleep, adjusted OR 1.57 (95% CI 1.14–2.16); and worry, adjusted OR 1.41 (95% CI 1.10–1.79). Conclusion. Free‐text words in medical records that indicated stress, sleep disturbances or worry predicted increased adjusted OR for emergency CS in first‐time mothers. Recognizing pregnant women's reporting of their mental health status could have a predictive bearing on delivery outcomes.
Exposure to Phosphodiesterase Type 5 Inhibitors Stimulates Aromatase Expression in Human Adipocytes in vitro
Authors: Aversa Antonio , Caprio Massimiliano , Antelmi Antonella , Armani Andrea , Brama Marina , Greco Emanuela A. , Francomano Davide , Calanchini Matilde , Spera Giovanni , Luigi Luigi Di , Rosano Giuseppe M.C. , Lenzi Andrea , Migliaccio Silvia , Fabbri Andrea 
Published: December 2010

ABSTRACT

Introduction
Prolonged tadalafil administration in men with erectile dysfunction is associated with increased testosterone (T): estradiol (E2) ratio mainly related to reduction of E2 levels.

Aim
To investigate the presence of phosphodiesterase type 5 (PDE5) isoenzyme in primary human visceral adipocytes and whether different PDE5 inhibitors (PDE5i) could directly modulate aromatase (ARO) expression in differentiated human visceral adipocytes in culture.

Main Outcome Measures
PDE5 mRNA and protein expression in primary human visceral adipocytes as well as mRNA and protein expression of ARO, with functional activity after selective PDE5 blockade by tadalafil and sildenafil.

Methods
Purified primary human visceral pre-adipocytes were differentiated ex vivo and were exposed to tadalafil or sildenafil (1 µM) for different intervals of time (6-12-24-96 hours). ARO mRNA content and expression were measured by Western Blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. T and E2 in supernatants were measured by ELISA also in the presence of letrozole.

Results
Differentiated adipocytes were found to express detectable levels of PDE5 transcripts. Acute exposure (6 hours) to both PDE5i tadalafil and sildenafil increased ARO mRNA expression by 4.7- and 2.8-fold, respectively (P &lt; 0.001). ARO mRNA and protein levels were increased by the treatment with PDE5i in a time- and dose-dependent manner. Such effect was mimicked by 8-bromo-cGMP but was lost after 24 and 96 hours; differently, the PDE3B specific inhibitor milrinone (1 µM), displayed no effect. Accordingly, long-term exposure (24 and 96 hours) to PDE5i caused a significant increase in E2 concentrations in the supernatant (1.7 and 2 fold, respectively; P &lt; 0.001), with a parallel reduction of T (15% and 30%, respectively; P &lt; 0.001). Such effect was reversed by the co-incubation with the specific ARO-inhibitor letrozole.

Conclusions
Our results demonstrate that PDE5 is expressed in human visceral adipocytes and that acute exposure to PDE5i selectively stimulates ARO expression, which is related to a specific PDE5 blockade. We speculate that modulation of ARO activity by PDE5i could be one of the mechanisms responsible, at least in part, for the beneficial effects of PDE5i on endothelial and metabolic functions.
Alteration Geochemistry of Volcanic Rocks around Sarcheshmeh Porphyry Copper Deposit, Rafsanjan, Kerman, Iran: Implications for Regional Exploration
Authors: Aftabi Alijan , Atapour Habibeh 
Published: December 2010

AbstractTo discriminate the mineral potentiality of the trachybasalt around the Miocene Sarcheshmeh porphyry copper deposit, petrogeochemical characteristics of more than 45 samples of the volcanic rocks were studied. Sarcheshmeh is one of the world's largest Miocene porphyry copper deposits in a continental arc setting and contains about 1200 million tonnes of ores with an average grade of 1.2 percent copper, 0.03 percent molybdenum, 3.9 g/t Ag and 0.11 g/t Au. The biotized and sericitized trachybasalts around the Sarcheshmeh deposit are associated with chalcopyrite, pyrite and molybdenite and and are enriched in Cu (>3108 ppm), K2O (>4.2%), Rb (>155 ppm) and MgO (>2.9%), but depleted in yttrium (<11 ppm), MnO (<0.06%), CaO (<0.6%), Na2O (<0.33%), Sr (<107 ppm), and Ba (<181 ppm). The propylitized trachybasalts are enriched in CaO (>9.1%), Na2O (>3.2%), MnO (>0.24%), Y (>18.2 ppm), and Ba (>323 ppm). The results demonstrate that the diagrams of loss on ignition − Cu, Cu − Y, K2O/K2O + Na2O + CaO − Cu and Y − MnO may be used as an exploration guide for undiscovered porphyry copper mineralization in the Central Iranian volcano—plutonic copper belt.
Wakefieldite‐(Nd), a New Neodymium Vanadate Mineral in the Arase Stratiform Ferromanganese Deposit, Kochi Prefecture, Japan
Authors: Moriyama Takeru , Miyawaki Ritsuro , Yokoyama Kazumi , Matsubara Satoshi , Hirano Hideo , Murakami Hiroyasu , Watanabe Yasushi 
Published: December 2010

AbstractWakefieldite‐(Nd), NdVO4, is a new mineral found from the Arase stratiform ferromanganese deposit in Kochi Prefecture, Shikoku Island, Japan. It is the Nd‐dominant analogue of wakefieldite‐(Y) and wakefieldite‐(Ce). The ferromanganese ore specimen mainly consists of hematite and caryopilite, and wakefieldite‐(Nd) is typically enclosed in caryopilite. Wakefieldite‐(Nd) is tetragonal, I41/amd, a = 7.338(16) Å, c = 6.509(19) Å, V = 350.5(18) Å3, Z = 4. The four strongest lines in the X‐ray diffraction pattern [d(Å), I/I0, hkl] using a Gandolfi camera are (3.67, 100, 200); (2.74, 51, 112); (4.84, 27, 101) and (1.89, 25, 312). Chemical composition of wakefieldite‐(Nd) are V2O3 35.25, As2O3 0.93, SiO2 0.14, MnO 1.45, Fe2O3 0.41, Y2O3 2.87, La2O3 7.61, Ce2O3 7.37, Pr2O3 6.04, Nd2O3 26.79, Sm2O3 4.41, Eu2O3 1.36, Gd2O3 3.41, Tb2O3 0.22, Dy2O3 1.41, Er2O3 0.10, total 99.77 wt.%. The empirical formula is (Nd0.403La0.118Ce0.114Pr0.093Y0.064Sm0.064Mn0.052Gd0.048Eu0.020Dy0.019Fe0.013Tb0.003Er0.001)1.012(V0.981As0.020Si0.006)1.007O4 on the basis of O = 4. The calculated density is 4.782 g/cm3.Microtexture and co‐existing relationship between wakefieldite‐(Nd) and caryopilite suggest that recrystallization and dehydration of Fe‐ and Mn‐oxyhydroxide led to the generation of hematite, caryopilite, rhodochrosite and wakefieldite‐(Nd) by the metamorphism during the accretion of the host unit of the Arase deposit. Chondrite‐normalized REE pattern of the host ferromanganese ore, which is regarded as oceanic metalliferous sediment in origin, shows negative Ce anomaly. Chemical composition of wakefieldite‐(Nd) reflects Ce‐depleted bulk composition of REE‐enriched ferromanganese ore.
A proliferative melanoma cell phenotype is responsive to RAF/MEK inhibition independent of BRAF mutation status
Authors: Zipser Marie C. , Eichhoff Ossia M. , Widmer Daniel S. , Schlegel Natalie C. , Schoenewolf Nicola L. , Stuart Darrin , Liu Weihua , Gardner Humphrey , Smith Paul D. , Nuciforo Paolo , Dummer Reinhard , Hoek Keith S. 
Published: December 2010

SummaryOncogenic mutations within the MAPK pathway are frequent in melanoma, and targeting of MAPK signaling has yielded spectacular responses in a significant number of patients that last for several months before relapsing. We investigated the effects of two different inhibitors of MAPK signaling in proliferative and invasive melanoma cell cultures with various mutations in the MAPK pathway. Proliferative melanoma cells were more susceptible to pathway inhibition than invasive phenotype cells, irrespective of BRAF mutation status, while invasive phenotype cell response was dependent on BRAF mutation status. Critically, MAPK pathway inhibition of proliferative phenotype cells resulted in acquisition of invasive phenotype characteristics. These results show that melanoma cell phenotype is an important factor in MAPK pathway inhibition response. This suggests that while current therapeutic strategies target proliferative melanoma cells, future approaches should also account for the invasive phenotype population.
Sphingosine-1-phosphate decreases melanin synthesis via microphthalmia-associated transcription factor phosphorylation through the S1P3 receptor subtype
Authors: Kim Dong-Seok , Park Seo-Hyoung , Jeong Yun-Mi , Kwon Sun-Bang , Miller Arlo J , Fisher David E , Park Kyoung-Chan 
Published: December 2010

Abstract

Objectives
Previously, we reported that sphingosine-1-phosphate (S1P) reduced melanin synthesis. In this study we have investigated S1P receptor-mediated extracellular signal-regulated protein kinase (ERK) activation and microphthalmia-associated transcription factor (MITF) phosphorylation.

Methods
To examine S1P-induced signalling pathways, electron and confocal microscopic studies, reverse transcription-polymerase chain reaction and Western blot analysis were performed.

Key findings
S1P phosphorylated MITF at Ser73, which may have resulted in a MITF mobility shift. Furthermore, 90 kDa ribosomal S6 kinase-1 (RSK-1) phosphorylation was observed after S1P treatment. In addition, PD98059 abrogated the S1P-induced MITF mobility shift and RSK-1 activation. In experiments with MITF mutants, it was shown that dual phosphorylation at Ser73 and Ser409 was indispensable for MITF degradation. We investigated further the actions of S1P on its specific receptors. The results showed that pertussis toxin completely abolished the hypopigmentary effects and ERK pathway activation by S1P, suggesting that S1P regulated melanogenesis via its receptor. The use of specific receptor antagonists indicated that the S1P3 receptor was dominantly involved in S1P-induced ERK activation and hypopigmentation.

Conclusions
The results suggested that S1P reduced melanin synthesis via S1P3 receptor-mediated ERK and RSK-1 activation, and subsequent MITF dual phosphorylation and degradation.
Testosterone is involved in mediating the effects of prenatal stress in male guinea pig offspring
Authors: Kapoor Amita , Matthews Stephen G. 
Published: December 2010

Non‐technical summaryStudies in humans have demonstrated a link between stress during pregnancy and altered behaviour and stress reactivity in children. In guinea pigs, we have previously shown that a short period of maternal stress during gestation leads to increased anxiety, elevated basal cortisol levels and decreased testosterone levels in adult males. We hypothesized that restoring testosterone to normal levels in the adult males born to prenatally stressed mothers would reverse the changes in behaviours and endocrine function. We found differences in attention and anxiety‐related behaviours and basal stress endocrine activity between the prenatally stressed and control males. Administration of testosterone reversed the behavioural differences in the prenatally stressed offspring. There was, however, little effect of postnatal testosterone administration on stress‐related endocrine activity. This study provides new information to begin to address the mechanism underlying the interplay between prenatal stress, gonadal steroids and postnatal behaviours.
Gas Flow Simulations in Randomly Distributed Pebbles
Authors: Zhao Xiang , Montgomery Trent , Zhang Sijun 
Published: December 2010

Abstract
In this paper, computational fluid dynamics (CFD) gas flow simulations are carried out for the pebble bed reactor. In CFD calculations, geometry modeling and physical modeling are crucial to CFD results. The effects of the treatments of the interpebble contacts on gas flow fields and heat transfer are examined. A sensitivity analysis for the gap size is conducted with two spherical pebbles, in which the interpebble region is modeled by means of two types of interpebble gap and two kinds of direct contact. Both large eddy simulation and Reynolds-averaged Navier–Stokes models are employed to investigate the turbulent effects. It is found that the flow fields and relevant heat transfer are significantly dependent on the modeling of the interpebble region. The calculations indicate the complex flow structures present within the voids between the fuel pebbles.