bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Study on Mixed Convection and Entropy Generation of a Nanofluid in a Lid-Driven Square Enclosure
Authors: Nayak R. K. , Bhattacharyya S. , Pop I.
Published: July 2015

A numerical investigation of mixed convection due to a copper–water nanofluid in an enclosure is presented. The mixed convection is governed by moving the upper lid of the enclosure and imposing a vertical temperature gradient. The transport equations for fluid and heat are modeled by using the Boussinesq approximation. A modified form of the control volume based SIMPLET algorithm is used for the solution of the transport equations. The fluid flow and heat transfer characteristics are studied for a wide range of Reynolds number and Grashof number so as to have the Richardson number greater or less than 1. The nanoparticle volume fraction is considered up to 20%. Heat flow patterns are analyzed through the energy flux vector. The rate of enhancement in heat transfer due to the addition of nanoparticles is analyzed. The entropy generation and Bejan number are evaluated to demonstrate the thermodynamic optimization of the mixed convection. We have obtained the enhancement rate in heat transfer and entropy generation in nanofluid for a wide range of parameter values.
A Simplified Model for Deposition and Removal of Soot Particles in an Exhaust Gas Recirculation Cooler
Authors: Reza Razmavar A. , Reza Malayeri M.
Published: July 2015

Nitrogen oxides (NOx) emissions from diesel engines can profoundly be suppressed if a portion of exhaust gases is cooled through a heat exchanger known as exhaust gas recirculation (EGR) cooler and returned to the intake of the combustion chamber. One major hurdle though for the efficient performance of EGR coolers is the deposition of various species, i.e., particulate matter (PM) on the surface of EGR coolers. In this study, a model is proposed for the deposition and removal of soot particles carried by the exhaust gases in a tubular cooler. The model takes thermophoresis into account as the primary deposition mechanism. Several removal mechanisms of incident particle impact, shear force, and rolling moment (RM) have rigorously been examined to obtain the critical velocity that is the maximum velocity at which the particulate fouling can profoundly be suppressed. The results show that the dominant removal mechanism changes from one to another based particle size and gas velocity. Based on particle mass and energy conservation equations, a model for the fouling resistance has also been developed which shows satisfactory agreement when compared with the fouling experimental results.
Investigation of Lean Premixed Swirl-Stabilized Hydrogen Burner With Axial Air Injection Using OH-PLIF Imaging
Authors: Reichel Thoralf G. , Goeckeler Katharina , Paschereit Oliver
Published: July 2015

In the context of lean premixed combustion, the prevention of upstream flame propagation in the premixing zone, referred to as flashback (FB), is a crucial challenge related to the application of hydrogen as a fuel for gas turbines. The location of flame anchoring and its impact on FB tendencies in a technically premixed, swirl-stabilized hydrogen burner are investigated experimentally at atmospheric pressure conditions using planar laser-induced fluorescence of hydroxyl radicals (OH-PLIF). The inlet conditions are systematically varied with respect to equivalence ratio (ϕ=0.2−1.0), bulk air velocity u0 = 30–90 m/s, and burner preheat temperature ranging from 300 K to 700 K. The burner is mounted in an atmospheric combustion test rig, firing at a power of up to 220 kW into a 105 mm diameter quartz cylinder, which provides optical access to the flame region. The experiments were performed using an in-house burner design that previously proved to be highly resistant against FB occurrence by applying the axial air injection strategy. Axial air injection constitutes a nonswirling air jet on the central axis of the radial swirl generator. While a high rate of axial air injection yields excellent FB resistance, reduced rates of air injection are utilized to trigger FB, which allowed to investigate the near FB flame behavior. Results show that both, fuel momentum of hydrogen and axial air injection, alter the isothermal flow field as they cause a downstream shift of vortex breakdown and, thus, the axial flame front location. Such a shift is proven beneficial for FB resistance from the recorded FB limits. This effect was quantified by applying an edge detection algorithm to the OH-PLIF images, in order to extract the location of maximum flame front probability xF. By these means, it was revealed that for hydrogen xF is shifted downstream with increasing equivalence ratio due to the added momentum of the fuel flow, superseding any parallel augmentation in the turbulent flame speed. The parameter xF is identified to be governed by J, the momentum ratio between fuel and air flow, over a wide range of inlet conditions. These results contribute to the understanding of the sensitivity of FB to changes in the flow field, stemming from geometry changes or specific fuel properties.
External validation of a publicly available computer assisted diagnostic tool for mammographic mass lesions with two high prevalence research datasets
Authors: Benndorf Matthias , Burnside Elizabeth S. , Herda Christoph , Langer Mathias , Kotter Elmar
Published: July 2015

Purpose:

Lesions detected at mammography are described with a highly standardized terminology: the breast imaging‐reporting and data system (BI‐RADS) lexicon. Up to now, no validated semantic computer assisted classification algorithm exists to interactively link combinations of morphological descriptors from the lexicon to a probabilistic risk estimate of malignancy. The authors therefore aim at the external validation of the mammographic mass diagnosis (MMassDx) algorithm. A classification algorithm like MMassDx must perform well in a variety of clinical circumstances and in datasets that were not used to generate the algorithm in order to ultimately become accepted in clinical routine.

Methods:

The MMassDx algorithm uses a naïve Bayes network and calculates post‐test probabilities of malignancy based on two distinct sets of variables, (a) BI‐RADS descriptors and age (“descriptor model”) and (b) BI‐RADS descriptors, age, and BI‐RADS assessment categories (“inclusive model”). The authors evaluate both the MMassDx (descriptor) and MMassDx (inclusive) models using two large publicly available datasets of mammographic mass lesions: the digital database for screening mammography (DDSM) dataset, which contains two subsets from the same examinations—a medio–lateral oblique (MLO) view and cranio–caudal (CC) view dataset—and the mammographic mass (MM) dataset. The DDSM contains 1220 mass lesions and the MM dataset contains 961 mass lesions. The authors evaluate discriminative performance using area under the receiver‐operating‐characteristic curve (AUC) and compare this to the BI‐RADS assessment categories alone (i.e., the clinical performance) using the DeLong method. The authors also evaluate whether assigned probabilistic risk estimates reflect the lesions’ true risk of malignancy using calibration curves.

Results:

The authors demonstrate that the MMassDx algorithms show good discriminatory performance. AUC for the MMassDx (descriptor) model in the DDSM data is 0.876/0.895 (MLO/CC view) and AUC for the MMassDx (inclusive) model in the DDSM data is 0.891/0.900 (MLO/CC view). AUC for the MMassDx (descriptor) model in the MM data is 0.862 and AUC for the MMassDx (inclusive) model in the MM data is 0.900. In all scenarios, MMassDx performs significantly better than clinical performance, P < 0.05 each. The authors furthermore demonstrate that the MMassDx algorithm systematically underestimates the risk of malignancy in the DDSM and MM datasets, especially when low probabilities of malignancy are assigned.

Conclusions:

The authors’ results reveal that the MMassDx algorithms have good discriminatory performance but less accurate calibration when tested on two independent validation datasets. Improvement in calibration and testing in a prospective clinical population will be important steps in the pursuit of translation of these algorithms to the clinic.
Transmission of innate immune signaling by packaging of cGAMP in viral particles
Authors: Gentili Matteo , Kowal Joanna , Tkach Mercedes , Satoh Takeshi , Lahaye Xavier , Conrad Cécile , Boyron Marilyn , Lombard Bérangère , Durand Sylvère , Kroemer Guido , Loew Damarys , Dalod Marc , Théry Clotilde , Manel Nicolas
Published: July 2015

Viruses pack antiviral mediators

Viruses often hijack host proteins for their own use, turning host cells into virion-spewing machines. However, Bridgeman
et al.
and Gentili
et al.
now report a sneaky way that the host can fight back (see the Perspective by Schoggins). Host cells that expressed the enzyme cGAS, an innate immune receptor that senses cytoplasmic DNA, packaged the cGAS-generated second messenger cGAMP into virions. Virions could then transfer cGAMP to neighboring cells, triggering an antiviral gene program in these newly infected cells. Such transfer of an antiviral mediator may help to speed up the immune response to put the brakes on viral spread.

Science
, this issue pp.
1228
and
1232
; see also p.
1166
Safeguarding gene drive experiments in the laboratory
Authors: Akbari Omar S. , Bellen Hugo J. , Bier Ethan , Bullock Simon L. , Burt Austin , Church George M. , Cook Kevin R. , Duchek Peter , Edwards Owain R. , Esvelt Kevin M. , Gantz Valentino M. , Golic Kent G. , Gratz Scott J. , Harrison Melissa M. , Hayes Keith R. , James Anthony A. , Kaufman Thomas C. , Knoblich Juergen , Malik Harmit S. , Matthews Kathy A. , O'Connor-Giles Kate M. , Parks Annette L. , Perrimon Norbert , Port Fillip , Russell Steven , Ueda Ryu , Wildonger Jill
Published: July 2015

Multiple stringent confinement strategies should be used whenever possible
Comparative Analysis of Whole-Genome Sequences of Influenza A(H1N1)pdm09 Viruses Isolated from Hospitalized and Nonhospitalized Patients Identifies Missense Mutations That Might Be Associated with Patient Hospital Admissions in Finland during 2009 to 2014
Authors: Mishel Polina , Ojala Teija , Benner Christian , Lakspere Triin , Bychkov Dmitrii , Jalovaara Petri , Kakkola Laura , Kallio-Kokko Hannimari , Kantele Anu , Kankainen Matti , Ikonen Niina , Ripatti Samuli , Julkunen Ilkka , Kainov Denis E.
Published: July 2015

Here, we report 40 new whole-genome sequences of influenza A(H1N1)pdm09 viruses isolated from Finnish patients during 2009 to 2014. A preliminary analysis of these and 186 other whole genomes of influenza A(H1N1)pdm09 viruses isolated from hospitalized and nonhospitalized patients during 2009 to 2014 in Finland revealed several viral mutations that might be associated with patient hospitalizations.
Draft Genome Sequence of
Lactobacillus
sp. Strain TCF032-E4, Isolated from Fermented Radish
Authors: Mao Yuejian , Chen Meng , Horvath Philippe
Published: July 2015

Here, we report the draft genome sequence of
Lactobacillus
sp. strain TCF032-E4 (= CCTCC AB2015090 = DSM 100358), isolated from a Chinese fermented radish. The total length of the 57 contigs is about 2.9 Mb, with a G+C content of 43.5 mol% and 2,797 predicted coding sequences (CDSs).
Mitochondrial Genome Sequence of the Glass Sponge
Oopsacas minuta
Authors: Jourda Cyril , Santini Sébastien , Rocher Caroline , Le Bivic André , Claverie Jean-Michel
Published: July 2015

We report the complete mitochondrial genome sequence of the Mediterranean glass sponge
Oopsacas minuta
. This 19-kb mitochondrial genome has 24 noncoding genes (22 tRNAs and 2 rRNAs) and 14 protein-encoding genes coding for 11 subunits of respiratory chain complexes and 3 ATP synthase subunits.
A novel approach to optimise glycaemic control in insulin users
Authors: Bashan Eran , Harper Roy , Bi Yixi , Hodish Israel
Published: July 2015

Insulin therapy has been available for almost a century. However, its success rate is still disappointing where the majority of users sustain harmfully elevated glycated haemoglobin (HbA1c) levels. The key element essential for effective and safe insulin therapy is frequent dosage titration to overcome constant variations in insulin requirements. In reality, dosage titration is done sporadically during clinic visits. A scalable solution to this problem is being reviewed. A diabetes nurses service improves glycaemic control without overburdening the health system. The service relies on a handheld device, which provides patients with an insulin dose recommendation for each injection while using the device to monitor glucose. Similar to the approach providers use during clinical encounters, the device analyses stored glucose trends and constantly titrates insulin dosage without care providers’ supervision. In this report, we describe the logic behind the technology by providing examples from users.
Clinicopathological significance of Melkersson-Rosenthal syndrome
Authors: Bohra Shruti , Kariya Pratik B , Bargale Seema Dinesh , Kiran Shital
Published: July 2015

Melkersson-Rosenthal syndrome (MRS) classically shows a triad of orofacial swelling, fissured tongue and facial palsy, more commonly the oligosymptomatic form. The orofacial swelling is characterised by swollen reddish-brown non-pruritic lips and facial oedema. In one-third to one half of patients, fissured tongue is seen, which also aids in diagnosis. The histological finding of MRS includes non-caseating, sarcoidal granulomas, but their absence does not exclude the diagnosis. All these findings together form a basis for a cautious search for confrontational reasons for the symptom complex of MRS.
On the Majorana neutrinos and neutrinoless double beta decays
Authors: Xing Zhi-Zhong , Zhou Ye-Ling
Published: July 2015

The neutrinoless double-beta [Formula: see text] decay is a lepton-number-violating process which is experimentally unique for identifying the Majorana nature of massive neutrinos. We give a brief overview of some theoretical aspects of this process. In particular, a novel “coupling-rod” diagram is introduced to describe the effective Majorana mass [Formula: see text] in the complex plane. Possible contributions of new physics to [Formula: see text] are also discussed.
Optimal Grip Points with Human Hand
Authors: Alò Roberta , Mantriota Giacomo
Published: July 2015

The aim of this work was to determine how an object of given shape should be grasped to maximize the grasping capacity of the human hand. To do that the model searches the optimal grip points on the object with the aim of maximizing the weight of the object lifted without slipping. The model solves both the equilibrium of the grasped object and the biomechanical constraints of the human hand, such as the stress limit of each muscle. To give some examples, grasps of three-dimensional (3D) objects of different shape and size were optimized. The results of the simulations done also allowed the identification of the parameters that further influence human grasping. Moreover, trials were done to prove the results given by the computational model.
Underreaction to News in the US Stock Market
Authors: Sinha Nitish Ranjan
Published: July 2015

Using a score that quantifies the tone of news articles, I construct a weekly measure of qualitative information that predicts returns over the next 13 weeks. A portfolio long stocks with past positive tone and short stocks with past negative tone has an average return of 16.54 basis points per week (8.60% per year). The findings suggest the market underreacts to the content of news articles. The underreaction is not constrained to small stocks, low analyst-coverage stocks, low institutional ownership, or loser stocks. The findings also suggest the tone of news articles is different from sentiment which is assumed to have no permanent impact on stock prices.
LavaSIM: its physical basis and applicability
Authors: Fujita Eisuke , Nagai Masashi
Published: July 2015

LavaSIM is a lava -flow simulator to carry out three-dimensional (3D) analysis of solid–liquid two-phase lava flows. Heat transfer between molten lava and solidified crust into the air, water and ground is calculated using radiation equations, so we can simulate not only the lava-flow distribution but also its physical characteristics: for instance, the internal convectional structure. Lava viscosity can be treated as a function of temperature, and is associated with the percentage of crystallization. The stop condition for the lava flow is determined by calculating the minimum spreading thickness, taking into consideration the yield strength. This paper also discusses whether LavaSIM, the deterministic lava-flow simulation, can be applied to basaltic lava flows and allow lava-flow characteristics, such as inundated area, temperature distribution, crust–melt distribution, velocity and pressure field, to be quantitatively evaluated.
The H2S-generating enzymes cystathionine β-synthase and cystathionine γ-lyase play a role in vascular development during normal lung alveolarization
Authors: Madurga Alicia , Golec Anita , Pozarska Agnieszka , Ishii Isao , Mižíková Ivana , Nardiello Claudio , Vadász István , Herold Susanne , Mayer Konstantin , Reichenberger Frank , Fehrenbach Heinz , Seeger Werner , Morty Rory E.
Published: July 2015

The gasotransmitter hydrogen sulfide (H2S) is emerging as a mediator of lung physiology and disease. Recent studies revealed that H2S administration limited perturbations to lung structure in experimental animal models of bronchopulmonary dysplasia (BPD), partially restoring alveolarization, limiting pulmonary hypertension, limiting inflammation, and promoting epithelial repair. No studies have addressed roles for endogenous H2S in lung development. H2S is endogenously generated by cystathionine β-synthase (Cbs) and cystathionine γ-lyase (Cth). We demonstrate here that the expression of Cbs and Cth in mouse lungs is dynamically regulated during lung alveolarization and that alveolarization is blunted in Cbs−/− and Cth−/− mouse pups, where a 50% reduction in the total number of alveoli was observed, without any impact on septal thickness. Laser-capture microdissection and immunofluorescence staining indicated that Cbs and Cth were expressed in the airway epithelium and lung vessels. Loss of Cbs and Cth led to a 100–500% increase in the muscularization of small- and medium-sized lung vessels, which was accompanied by increased vessel wall thickness, and an apparent decrease in lung vascular supply. Ablation of Cbs expression using small interfering RNA or pharmacological inhibition of Cth using propargylglycine in lung endothelial cells limited angiogenic capacity, causing a 30–40% decrease in tube length and a 50% decrease in number of tubes formed. In contrast, exogenous administration of H2S with GYY4137 promoted endothelial tube formation. These data confirm a key role for the H2S-generating enzymes Cbs and Cth in pulmonary vascular development and homeostasis and in lung alveolarization.
Sleep at high altitude: guesses and facts
Authors: Bloch Konrad E. , Buenzli Jana C. , Latshang Tsogyal D. , Ulrich Silvia
Published: July 2015

Lowlanders commonly report a poor sleep quality during the first few nights after arriving at high altitude. Polysomnographic studies reveal that reductions in slow wave sleep are the most consistent altitude-induced changes in sleep structure identified by visual scoring. Quantitative spectral analyses of the sleep electroencephalogram have confirmed an altitude-related reduction in the low-frequency power (0.8-4.6 Hz). Although some studies suggest an increase in arousals from sleep at high altitude, this is not a consistent finding. Whether sleep instability at high altitude is triggered by periodic breathing or vice versa is still uncertain. Overnight changes in slow wave-derived encephalographic measures of neuronal synchronization in healthy subjects were less pronounced at moderately high (2,590 m) compared with low altitude (490 m), and this was associated with a decline in sleep-related memory consolidation. Correspondingly, exacerbation of breathing and sleep disturbances experienced by lowlanders with obstructive sleep apnea during a stay at 2,590 m was associated with poor performance in driving simulator tests. These findings suggest that altitude-related alterations in sleep may adversely affect daytime performance. Despite recent advances in our understanding of sleep at altitude, further research is required to better establish the role of gender and age in alterations of sleep at different altitudes, to determine the influence of acclimatization and of altitude-related illness, and to uncover the characteristics of sleep in highlanders that may serve as a study paradigm of sleep in patients exposed to chronic hypoxia due to cardiorespiratory disease.
High-intensity interval training attenuates endothelial dysfunction in a Dahl salt-sensitive rat model of heart failure with preserved ejection fraction
Authors: Adams Volker , Alves Marcia , Fischer Tina , Rolim Natale , Werner Sarah , Schütt Nicole , Bowen T. Scott , Linke Axel , Schuler Gerhard , Wisloff Ulrik
Published: July 2015

Heart failure patients with preserved left ventricular ejection fraction (HFpEF) have endothelial dysfunction, but the underlying molecular mechanisms remain unknown. In addition, whether exercise training improves endothelial function in HFpEF is still controversial. The present study therefore aimed to determine the functional and molecular alterations in the endothelium associated with HFpEF, while further assessing the effects of high-intensity interval training (HIT). Female Dahl salt-sensitive rats were randomized for 28 wk into the following groups: 1) control: fed 0.3% NaCl; 2) HFpEF: fed 8% NaCl; and 3) HFpEF + HIT: animals fed 8% NaCl and HIT treadmill exercise. Echocardiography and invasive hemodynamic measurements were used to assess diastolic dysfunction. Endothelial function of the aorta was measured in vitro. Expression of endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate-oxidase [NAD(P)H oxidase], and advanced glycation end product (AGE)-modified proteins were quantified by Western blot, and zymography quantified matrix metalloproteinase (MMP) activity. In this model of HFpEF, endothelium-dependent and -independent vasodilation was impaired. However, this was prevented by HIT. In HFpEF protein expression of eNOS was reduced by 47%, but MMP-2 and MMP-9 activity was elevated by 186 and 68%. The expression of AGE-modified proteins was increased by 106%. All of these changes were prevented by HIT. Endothelial function was impaired in this model of HFpEF, which was associated with reduced expression of eNOS, increased MMP activity, and increased AGE-modified proteins. HIT was able to attenuate both these functional and molecular alterations. These findings therefore suggest HFpEF induces endothelial dysfunction, but this is reversible by HIT.
Prodding the Beast: Assessing the Impact of Treatment-Induced Metastasis
Authors: Ebos John M.L.
Published: July 2015

The arsenal of treatments for most cancers fit broadly into the categories of surgery, chemotherapy, radiation, and targeted therapy. All represent proven and successful strategies, yet each can trigger local (tumor) and systemic (host) processes that elicit unwanted, often opposing, influences on cancer growth. Under certain conditions, nearly all cancer treatments can facilitate metastatic spread, often in parallel (and sometimes in clear contrast) with tumor reducing benefits. The paradox of treatment-induced metastasis (TIM) is not new. Supporting preclinical studies span decades, but are often overlooked. With recent evidence of prometastatic effects following treatment with targeted agents blocking the tumor microenvironment, a closer inspection of this literature is warranted. The TIM phenomena may diminish the impact of effective therapies and play a critical role in eventual resistance. Alternatively, it may simply exemplify the gap between animal and human studies, and therefore have little impact for patient disease and treatment. This review will focus on the preclinical model systems used to evaluate TIM and explore the mechanisms that influence overall treatment efficacy. Understanding the role of TIM in established and emerging drug treatment strategies may help provide rationales for future drug combination approaches with antimetastatic agents to improve outcomes and reduce resistance. Cancer Res; 75(17); 3427–35. ©2015 AACR.
Association of HO-1 and BRCA1 Is Critical for the Maintenance of Cellular Homeostasis in Prostate Cancer
Authors: Labanca Estefanía , De Luca Paola , Gueron Geraldine , Paez Alejandra , Moiola Cristian P. , Massillo Cintia , Porretti Juliana , Giudice Jimena , Zalazar Florencia , Navone Nora , Vazquez Elba , De Siervi Adriana
Published: July 2015

Prostate cancer is the second leading cause of cancer-related death in men worldwide. Many factors that participate in the development of prostate cancer promote imbalance in the redox state of the cell. Accumulation of reactive oxygen species causes injury to cell structures, ultimately leading to cancer development. The antioxidant enzyme heme oxygenase 1 (HMOX1/HO-1) is responsible for the maintenance of the cellular homeostasis, playing a critical role in the oxidative stress and the regulation of prostate cancer development and progression. In the present study, the transcriptional regulation of HO-1 was investigated in prostate cancer. Interestingly, the tumor suppressor BRCA1 binds to the HO-1 promoter and modulates HO-1, inducing its protein levels through both the increment of its promoter activity and the induction of its transcriptional activation. In addition, in vitro and in vivo analyses show that BRCA1 also controls HO-1–negative targets: MMP9, uPA, and Cyclin D1. HO-1 transcriptional regulation is also modulated by oxidative and genotoxic agents. Induction of DNA damage by mitoxantrone and etoposide repressed HO-1 transcription, whereas hydrogen peroxide and doxorubicin induced its expression. Xenograft studies showed that HO-1 regulation by doxorubicin also occurs in vivo. Immunofluorescence analysis revealed that BRCA1 overexpression and/or doxorubicin exposure induced the cytoplasmic retention of HO-1. Finally, the transcription factor NRF2 cooperates with BRCA1 protein to activate HO-1 promoter activity. In summary, these results show that the activation of BRCA1–NRF2/HO-1 axis defines a new mechanism for the maintenance of the cellular homeostasis in prostate cancer.

Implications: Oxidative and genotoxic stress converge on HO-1 transcriptional activity through the combined actions of BRCA1 and NRF2. Mol Cancer Res; 13(11); 1455–64. ©2015 AACR.
Variation in the TAS1R2 Gene, Sweet Taste Perception and Intake of Sugars
Authors: Dias Andre G. , Eny Karen M. , Cockburn Moira , Chiu Winnie , Nielsen Daiva E. , Duizer Lisa , El-Sohemy Ahmed
Published: July 2015

Background/Aims: To determine whether variation in the TAS1R2 gene affects sucrose taste perception and sugar intake. Methods: Participants were men (n = 238) and women (n = 458) aged 20-29 years. A subset (n = 95) with body mass index (BMI) data available completed a sensory analysis study. A food frequency questionnaire assessed dietary intake, and eight polymorphisms were genotyped (rs12033832, rs12137730, rs35874116, rs3935570, rs4920564, rs4920566, rs7513755 and rs9701796). Sucrose taste thresholds were determined by staircase procedure (solutions: 9 × 10-6 to 0.5 mol/l). Suprathreshold sensitivity to 0.01-1.0 mol/l sucrose solutions was assessed using general Labeled Magnitude Scales. Results: A significant genotype-BMI interaction was observed for rs12033832 (G>A) for suprathreshold sensitivity (p = 0.01) and sugar intake (p = 0.003). Among participants with a BMI ≥25, G allele carriers had lower sensitivity ratings (mean incremental area under the taste sensitivity curve ± SE; GG/GA 54.4 ± 4.1 vs. AA 178.5 ± 66.6; p = 0.006), higher thresholds (GG/GA 9.3 ± 1.1 vs. AA 4.4 ± 4.3 mmol/l; p = 0.004) and consumed more sugars (GG/GA 130 ± 4 vs. AA 94 ± 13 g/day; p = 0.009). G allele carriers with a BMI <25 had lower thresholds (GG/GA 8.6 ± 0.5 vs. AA 16.7 ± 5.7 mmol/l; p = 0.02) and consumed less sugars (GG/GA 122 ± 2 vs. AA 145 ± 8 g/day; p = 0.004). Conclusion: The rs12033832 single nucleotide polymorphism in TAS1R2 is associated with sucrose taste and sugar intake, but the effect differs depending on BMI.
The Inhibition of Oxidised Low-Density Lipoprotein-Induced Apoptosis of Macrophages by Recombinant Human Brain Natriuretic Peptide and the Underlying Mechanism
Authors: Chang Chao , Yang Hua , Xin Shuan-li , Liu Ji-xiang , Zhao Xiu-feng , Liu Li-jun , Han Li-ying , Meng Li-min , Li Qin
Published: July 2015

Objective: Macrophage apoptosis plays a key role in atherosclerotic plaque rupture. This study investigated the effects of recombinant human brain natriuretic peptide (BNP) on oxidised low-density lipoprotein (ox-LDL)-induced macrophage apoptosis and explored the underlying mechanism. Methods: A model of ox-LDL-induced macrophage injury was established to evaluate the role of BNP. Flow cytometry was employed to detect apoptosis and changes in mitochondrial membrane potential (ΔΨm), and confocal microscopy was used to determine cellular reactive oxygen species (ROS) levels. Additionally, reverse transcription-polymerase chain reaction and colourimetry were used to detect the mRNA expression and activity, respectively, of superoxide dismutase (SOD) and malondialdehyde (MDA). Results: Ox-LDL induced macrophage apoptosis in a concentration-dependent manner, and maximum apoptosis occurred at 100 μg/ml ox-LDL (45.62 ± 2.76 vs. 6.84 ± 1.94%; p < 0.05). Conversely, BNP suppressed macrophage apoptosis, with a maximal effect at 10-9 mol/l (18.56 ± 1.79%; p < 0.05). Compared with the control group, intracellular ROS levels increased, ΔΨm decreased, SOD mRNA expression and activity decreased and MDA mRNA expression and content increased in the 100-μg/ml ox-LDL group (527.30 ± 36.20 vs. 100.00 ± 0.00%, 3.01 ± 0.52 vs. 9.67 ± 0.51%, 0.53 ± 0.18 vs. 1.00 ± 0.00, 256.6 ± 8.20 vs. 355.8 ± 9.58 U/ml, 1.59 ± 0.23 vs. 1.00 ± 0.00 and 29.4 ± 1.68 vs. 5.94 ± 0.51 nmol/ml; p < 0.05); these effects were significantly counteracted by 10-9 mol/l BNP (237.30 ± 30.62%, 6.55 ± 1.57%, 0.90 ± 0.07, 310.4 ± 2.97 U/ml, 1.14 ± 0.10, 20.54 ± 1.55 nmol/ml; p < 0.05). Conclusion: BNP attenuates ox-LDL-induced macrophage apoptosis by suppressing oxidative stress and preventing ΔΨm loss.
Health-Related Quality of Life in Children with Congenital Adrenal Hyperplasia
Authors: Yau Mabel , Vogiatzi Maria , Lewkowitz-Shpuntoff Ariana , Nimkarn Saroj , Lin-Su Karen
Published: July 2015

Background/Aims: Factors in congenital adrenal hyperplasia (CAH) that may affect quality of life (QOL) include the need for lifelong medication, the risk of adrenal crisis, and hyperandrogenic symptoms. The objectives were to evaluate health-related QOL (HRQOL) in children with CAH, and whether CAH poses an additional burden compared to other endocrine disorders. Methods: The validated PedsQL 4.0 generic core scales were administered to subjects (8-18 years) with CAH and hypothyroidism and their parents. The minimal clinically important difference (MCID) was determined for each scale score, allowing a comparison with the healthy population. A score of >1 standard deviation below the population mean was considered at risk for impaired HRQOL. Results: In CAH, the mean total HRQOL scores were >1 MCID below the population mean, and a higher percentage than expected had scores considered at risk. Conclusion: Compared to subjects with hypothyroidism, subjects with CAH self-reported lower school domain scores. CAH subjects more frequently reported peers not wanting to be friends.
Environmental Factors That Distinguish between Clinical and Healthy Samples with Childhood Experiences of Abuse and Neglect
Authors: Infurna Maria Rita , Giannone Francesca , Guarnaccia Cinzia , Lo Cascio Maria , Parzer Peter , Kaess Michael
Published: July 2015

Background: Childhood maltreatment is associated with a wide range of problems in adulthood. However, specific environmental factors (either positive or negative) influence mental health outcomes in maltreated children. The present study investigated the effect of environmental factors by comparing a group of clinical participants with experiences of abuse/neglect with a healthy group with similar patterns of experiences. Environmental factors selected were: separation from parents, financial hardship, parental psychiatric disorders, and low social involvement. Method: The study included 55 mixed clinical participants and 23 healthy participants. All participants were investigated using the Childhood Experience of Care and Abuse (CECA) interview. The two groups were specifically matched with regard to patterns of childhood maltreatment. Results: The findings indicated that psychopathological outcome was associated with a greater presence of negative environmental factors (p < 0.001). In particular, lack of social support seemed to be the only one predictor (OR = 27.86). Conclusion: This study is the first to investigate the influence of specific environmental factors in two groups with similar childhood experiences of abuse/neglect but different mental health outcomes. These findings suggest that efforts should be made to incorporate both familial and external sources of social support in promoting mental health for maltreated children.
Placental 11B-Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Intrauterine Growth Restriction versus Small-for-Gestational-Age Fetuses
Authors: Gómez-Roig M. Dolores , Mazarico Edurne , Cárdenas Daniela , Fernandez M. Teresa , Díaz Marta , Ruiz de Gauna Beatriz , Vela Antonio , Gratacós Eduard , Figueras Francesc
Published: July 2015

Introduction: The objective of this study was to evaluate placental 11B-hydroxysteroid dehydrogenase type 2 (11B-HSD-2) mRNA levels in intrauterine growth-restricted fetuses (IUGR) as compared with small-for-gestational-age (SGA) fetuses according to clinical criteria. Material and Methods: Placental levels of 11B-HSD-2 mRNA levels were measured in SGA (birth weight <10th centile) and gestational-age-matched, appropriate-for-gestational-age (AGA) births. SGA was classified as IUGR (birth weight <3rd centile or <10th percentile with abnormal uterine artery Doppler or cerebroplacental ratio) or non-IUGR SGA. After RNA extraction, mRNA levels were determined by reverse transcription and quantitative PCR. Results: A total of 38 placentas were analyzed (20 AGA and 18 SGA). Among the SGA pregnancies, 13 qualified as IUGR. The activity of 11B-HSD-2 in IUGR pregnancies [0.105 (SD 0.328)] was significantly reduced compared to non-IUGR SGA [0.304 (SD 0.261); p = 0.018] and AGA [0.294 (SD 0.328); p = 0.001]. These differences remained significant after adjusting for potential confounders (such as smoking or maternal cortisol levels). Activity levels did not significantly differ between non-IUGR SGA and AGA. Discussion: IUGR fetuses had reduced 11B-HSD-2 activity in comparison with SGA and normally grown fetuses. This finding provides opportunities to develop new placental biomarkers for the phenotypic characterization of fetal smallness.
Mediastinal Germ Cell Tumor Exhibiting a Discrepancy between Tumor Markers and Imaging: A Case Study
Authors: Takenaka Kei , Mukohara Toru , Hirai Chihoko , Funakoshi Yohei , Nakamura Yukiko , Chayahara Naoko , Toyoda Masanori , Kiyota Naomi , Itoh Tomoo , Yokozaki Hiroshi , Minami Hironobu
Published: July 2015

We report a mediastinal germ cell tumor (GCT) that exhibited a discrepancy between the time course of serum human chorionic gonadotropin (hCG) levels and clinical consequences. An otherwise healthy man, aged 34 years, was diagnosed with a nonseminomatous GCT, most likely embryonal carcinoma (EC), based on a mediastinal tumor biopsy. Standard chemotherapy resulted in an optimal decrease in serum hCG levels. However, multiple lesions in the liver continued to enlarge, which led to his death. Autopsy revealed few viable tumor cells in the liver, with the great majority of the tumor cells appearing to have undergone necrosis, suggesting that they responded to the chemotherapy. The residual tumor cells in the mediastinum and the liver were similar to syncytiotrophoblast cells, suggesting a choriocarcinoma (CC). On immunohistochemical analysis, the mediastinal tumor cells in the diagnostic biopsy specimen expressed both CD30 and hCG, whereas residual mediastinal and hepatic tumor cells in the autopsy specimen after chemotherapy also expressed hCG, but not CD30. These findings suggested that the patient suffered from a primary mixed GCT consisting of an EC and a CC. Both pre- and postchemotherapy tumors strongly expressed matrix metalloproteinase-2, supporting the aggressive and invasive features of the tumor phenotype. We speculate that the extremely invasive tumor destroyed normal liver structure, whereas chemotherapy and central necrosis reduced the number of viable cells themselves, causing a discordant decrease in serum hCG levels.
BMP9 Induces Cord Blood–Derived Endothelial Progenitor Cell Differentiation and Ischemic Neovascularization via ALK1
Authors: Kim Jihye , Kim Minhyung , Jeong Yoonjeong , Lee Wook-bin , Park Hyojin , Kwon Ja-Young , Kim Young-Myeong , Hwang Daehee , Kwon Young-Guen
Published: July 2015

Objective—

Modulating endothelial progenitor cells (EPCs) is essential for therapeutic angiogenesis, and thus various clinical trials involving EPCs are ongoing. However, the identification of environmental conditions and development of optimal methods are required to accelerate EPC-driven vasculogenesis.

Approach and Results—

We evaluated gene expression profiles of cord blood–derived EPCs and endothelial cells to identify the key factors in EPC→endothelial cell differentiation and to show that transforming growth factor-β family members contribute to EPC differentiation. The expression levels of activin receptor-like kinase 1 (ALK1) and its high-affinity ligand, bone morphogenetic protein 9 (BMP9) were markedly changed in EPC→endothelial cell differentiation. Interestingly, BMP9 induced EPC→endothelial cell differentiation and EPC incorporation into vessel-like structures by acting on ALK1 expressed on EPCs in vitro. BMP9 also induced neovascularization in mice with hindlimb ischemia by increasing vessel formation and the incorporation of EPCs into vessels. Conversely, neovascularization was impaired when ALK1 signaling was blocked. Furthermore, EPCs exposed to either short- or long-term BMP9 stimulation demonstrated these functions in EPC-mediated neovascularization.

Conclusions—

Collectively, our results indicated that BMP9/ALK1 augmented vasculogenesis and angiogenesis, and thereby enhanced neovascularization. Thus, we suggest that BMP9/ALK1 may improve the efficacy of EPC-based therapies for treating ischemic diseases.
The HARMONY Trial
Authors: Reiffel James A. , Camm A. John , Belardinelli Luiz , Zeng Dewan , Karwatowska-Prokopczuk Ewa , Olmsted Ann , Zareba Wojciech , Rosero Spencer , Kowey Peter
Published: July 2015

Background—

Atrial fibrillation (AF) requires arrhythmogenic changes in atrial ion channels/receptors and usually altered atrial structure. AF is commonly treated with antiarrhythmic drugs; the most effective block many ion channels/receptors. Modest efficacy, intolerance, and safety concerns limit current antiarrhythmic drugs. We hypothesized that combining agents with multiple anti-AF mechanisms at reduced individual drug doses might produce synergistic efficacy plus better tolerance/safety.

Methods and Results—

HARMONY tested midrange ranolazine (750 mg BID) combined with 2 reduced dronedarone doses (150 mg BID and 225 mg BID; chosen to reduce dronedarone’s negative inotropic effect—see text below) over 12 weeks in 134 patients with paroxysmal AF and implanted pacemakers where AF burden (AFB) could be continuously assessed. Patients were randomized double-blind to placebo, ranolazine alone (750 mg BID), dronedarone alone (225 mg BID), or one of the combinations. Neither placebo nor either drugs alone significantly reduced AFB. Conversely, ranolazine 750 mg BID/dronedarone 225 mg BID reduced AFB by 59% versus placebo (
P
=0.008), whereas ranolazine 750 mg BID/dronedarone 150 mg BID reduced AFB by 43% (
P
=0.072). Both combinations were well tolerated.

Conclusions—

HARMONY showed synergistic AFB reduction by moderate dose ranolazine plus reduced dose dronedarone, with good tolerance/safety, in the population enrolled.

Clinical Trial Registration—

ClinicalTrials.gov
; Unique identifier: NCT01522651.
Risk Factors of Ischemic Stroke and Subsequent Outcome in Patients Receiving Hemodialysis
Authors: Findlay Mark D. , Thomson Peter C. , Fulton Rachael L. , Solbu Marit D. , Jardine Alan G. , Patel Rajan K. , Stevens Kathryn K. , Geddes Colin C. , Dawson Jesse , Mark Patrick B.
Published: July 2015

Background and Purpose—

End-stage renal disease (ESRD) requiring hemodialysis carries up to a 10-fold greater risk of stroke than normal renal function. Knowledge on risk factors and management strategies derived from the general population may not be applicable to those with ESRD. We studied a large ESRD population to identify risk factors and outcomes for stroke.

Methods—

All adult patients receiving hemodialysis for ESRD from January 1, 2007, to December 31, 2012, were extracted from the electronic patient record. Variables associated with stroke were identified by survival analysis; demographic, clinical, imaging, and dialysis-related variables were assessed, and case-fatality was determined. Follow-up was until December 31, 2013.

Results—

A total of 1382 patients were identified (mean age, 60.5 years; 58.5% men). The prevalence of atrial fibrillation was 21.2%, and 59.4% were incident hemodialysis patients. One hundred and sixty patients (11.6%) experienced a stroke during 3471 patient-years of follow-up (95% ischemic). Stroke incidence was 41.5/1000 patient-years in prevalent and 50.1/1000 patient-years in incident hemodialysis patients. Factors associated with stroke on regression analysis were prior stroke, diabetes mellitus, and age at starting renal replacement therapy. Atrial fibrillation was not significantly associated with stroke, and warfarin did not affect stroke risk in warfarin-treated patients. Fatality was 18.8% at 7 days, 26.9% at 28 days, and 56.3% at 365 days after stroke.

Conclusions—

Incidence of stroke is high in patients with ESRD on hemodialysis with high case-fatality. Incident hemodialysis patients had the highest stroke incidence. Many, but not all, important risk factors commonly associated with stroke in the general population were not associated with stroke in patients receiving hemodialysis.
Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Asian Patients With Nonvalvular Atrial Fibrillation
Authors: Wang Kang-Ling , Lip Gregory Y.H. , Lin Shing-Jong , Chiang Chern-En
Published: July 2015

Background and Purpose—

The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants (NOACs) are safer alternatives. Here, we evaluate performance differences of NOACs between Asians and non-Asians.

Methods—

We compared efficacy and safety of NOACs between patients enrolled in Asian and non-Asian countries using aggregative data from phase III clinical trials. The odds ratios (ORs [95% confidence interval]) were calculated by a random effects model.

Results—

Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism (OR=0.65 [0.52–0.83] versus 0.85 [0.77–0.93],
P
interaction= 0.045) more in Asians than in non-Asians and were safer in Asians than in non-Asians about major bleeding (OR=0.57 [0.44–0.74] versus 0.89 [0.76–1.04],
P
interaction=0.004), hemorrhagic stroke (OR=0.32 [0.19–0.52] versus 0.56 [0.44–0.70],
P
interaction=0.046) in particular, whereas gastrointestinal bleeding was significantly increased in non-Asians (OR=0.79 [0.48–1.32] versus 1.44 [1.12–1.85],
P
interaction=0.041). Generally, low-dose NOACs were safer than VKAs without heterogeneity in efficacy and safety between Asians and non-Asians, except for ischemic stroke, major, and gastrointestinal bleeding.

Conclusions—

Our findings suggest that standard-dose NOACs were more effective and safer in Asians than in non-Asians, whereas low-dose NOACs performed similarly in both populations.
Increase in [18F]-Fluoroacetate Uptake in Patients With Chronic Hemodynamic Cerebral Ischemia
Authors: Yamauchi Hiroshi , Kagawa Shinya , Kishibe Yoshihiko , Takahashi Masaaki , Nishii Ryuichi , Mizuma Hiroshi , Takahashi Kazuhiro , Onoe Hirotaka , Higashi Tatsuya
Published: July 2015

Background and Purpose—

[18F]-fluoroacetate (
18
F-FACE) can be used for evaluating glial cell metabolism. Experimental studies have shown an increase in
18
F-FACE uptake in rodent models of cerebral ischemia. The aim of this study was to determine whether
18
F-FACE uptake is increased in the noninfarcted cerebral cortex in patients with hemodynamic ischemia owing to atherosclerotic internal carotid artery or middle cerebral artery disease.

Methods—

We evaluated 9 symptomatic patients with unilateral atherosclerotic internal carotid artery or middle cerebral artery disease and no cortical infarction using positron emission tomography with
18
F-FACE and
15
O-gases.
18
F-FACE uptake during 40 to 60 minutes after injection was compared with the cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, and cerebral blood volume in the middle cerebral artery distributions.

Results—

Significant decreases of cerebral blood flow and cerebral metabolic rate of oxygen and increases of oxygen extraction fraction and cerebral blood volume were found in the hemisphere ipsilateral to the arterial lesion, and
18
F-FACE uptake in this region was greater than that in the contralateral hemisphere. The relative
18
F-FACE uptake (ipsilateral/contralateral ratio) was negatively correlated with cerebral blood flow or cerebral metabolic rate of oxygen values and was positively correlated with oxygen extraction fraction values. Multivariate analysis showed that the ipsilateral/contralateral
18
F-FACE uptake ratio was independently correlated with the cerebral blood flow (or oxygen extraction fraction) and cerebral metabolic rate of oxygen values.

Conclusions—

In patients with atherosclerotic internal carotid artery or middle cerebral artery disease,
18
F-FACE uptake is increased in the noninfarcted cerebral cortex with chronic hemodynamic ischemia characterized by misery perfusion with decreased oxygen metabolism. Increased
18
F-FACE uptake may indicate the cortical regions that are at particular risk for ischemic damage.