bluuebunny/crossref_metadata_2025 huggingface dataset:
Rh-Matched Transfusion through Molecular Typing for β-Thalassemia Patients Is Required and Feasible in Chinese
Authors: Shao Chao-Peng , Zhao Cheng-Jiang , Wu Chang-Lin , Xu Hua , Wang Xue-Dong , Wu Xiao-Ying , Yi Ping , Dang Xin-Tang
Published: July 2018

Background: Molecular typing for RHCE blood group alleles has been established in many countries for patients and blood donors. In the Chinese literature nearly 80% of transfused patients with alloimmunization have antibodies specific for antigens of the Rh blood group system. We investigated if it is feasible to match packed red blood cells (RBCs) for Chinese β-thalassemia patients by RHCE genotyping. Methods: In this study, 481 patients with β-thalassemia were enrolled. They were genotyped for RHCE alleles by a simple PCR method with sequence-specific primers (PCR-SSP). Among these patients, 203 continuously received RBCs of the identical Rh subgroups according to the genotyping results for at least 3 months. Subsequently, their phenotypes were tested through a micro-column gel card method. For validation purposes, 400 donors were serologically typed with the same technology, of which 164 were genotyped too. Finally, the C, c, E, and e frequencies and the feasibility of the simple genotyping method were analyzed. Results: All patients showed mixed-field agglutination in the Rh subgroup gel cards before the same Rh subgroups in blood donors were selected for blood transfusion. The results, however, lacked mixed-field agglutination in all 203 cases after transfusion with RBC concentrates selected for the patient's C, c, E, and e antigens for at least 3 months. The genotyping results of 164 donors were all consistent with the serological results. Whole coding regions of RHCE were sequenced in 7 individuals with weak c, E, or e antigens. In only one sample we observed a 1059G>A nucleotide mutation coding for a truncated RhCE polypeptide (GenBank KT957625), in the other 6 samples no sequence variant was found. Both patients and donors were predominantly CcEe and CCee, with a prevalence of 55.3% and 24.9% for patients or 49.3% and 31.3% for donors, respectively. It revealed that about 80% of Chinese could receive Rh-matched RBCs easily. Conclusion: A simple RHCE genotyping technique is safe enough for Rh-matched transfusion of β-thalassemia patients in Chinese Han.
Egr-1 Maintains NSC Proliferation and Its Overexpression Counteracts Cell Cycle Exit Triggered by the Withdrawal of Epidermal Growth Factor
Authors: Cera Arcangela Anna , Cacci Emanuele , Toselli Camilla , Cardarelli Silvia , Bernardi Alessandra , Gioia Roberta , Giorgi Mauro , Poiana Giancarlo , Biagioni Stefano
Published: July 2018

In adult mammals, neural stem cells (NSCs) reside in specialized niches at the level of selected CNS regions, such as the subventricular zone (SVZ). The signaling pathways that reg­ulate NSC proliferation and differentiation remain poorly understood. Early growth response protein 1 (Egr-1) is an important transcription factor, widely studied in the adult mammalian brain, mediating the activation of target genes by a variety of extracellular stimuli. In our study, we aimed at testing how Egr-1 regulates adult NSCs derived from mouse SVZ and, in particular, the interplay between Egr-1 and the proliferative factor EGF. We demonstrate that Egr-1 expression in NSCs is induced by growth factor stimulation, and its level decreases after EGF deprivation or by using AG1478, an inhibitor of the EGF/EGFR signaling pathway. We also show that Egr-1 overexpression rescues the cell proliferation decrease observed either after EGF removal or upon treatment with AG1478, suggesting that Egr-1 works downstream of the EGF pathway. To better understand this mechanism, we investigated targets downstream of both the EGF pathway and Egr-1, and found that they regulate genes involved in NSC proliferation, such as cell cycle regulators, cyclins, and cyclin-dependent kinase inhibitors.
Clinical Characteristics and Surgical Treatment for Inguinal Endometriosis in Young Women of Reproductive Age
Authors: Niitsu Hiroaki , Tsumura Hiroaki , Kanehiro Tetsuya , Yamaoka Hiroaki , Taogoshi Hiroyuki , Murao Naoki
Published: July 2018

Aim: To study the characteristics and surgical treatment of inguinal endometriosis (IEM), which can occur in women of reproductive age. Methods: Patients who underwent groin surgery at the Hiroshima City Funairi Citizens Hospital between 2004 and 2017 were retrospectively examined. Patients with IEM were divided into 3 groups based on the site of occurrence as follows: at a hernia sac or hydrocele of Nuck’s canal (type I), round ligament (type II), or subcutaneous area (type III). Clinical characteristics were compared among groups. Results: Of 2,798 patients investigated, 28 were pathologically diagnosed as having IEM with 15, 10, and 3 classified as type I, II, and III respectively. All patients presented with a mass (median 20 mm) and/or bulge that mainly occurred at the right inguinal region. Sixteen patients presented with inguinal pain associated with menstruation. While the groups did not differ in terms of most clinical characteristics, the lack of a preoperative diagnosis of IEM occurred more frequently for type I than for types II and III. Conclusions: Because IEM-type I might be underdiagnosed preoperatively, complete resection of a hernia sac or hydrocele of Nuck’s canal with subsequent pathological examination is required for women of reproductive age with an inguinal disease.
Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: Practical Considerations on the Choice of Agent and Dosing
Authors: Farmakis Dimitrios , Davlouros Periklis , Giamouzis Gregory , Giannakoulas George , Pipilis Athanasios , Tsivgoulis Georgios , Parissis John 
Published: July 2018

Direct or new oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have recently revolutionized the field of antithrombotic therapy for stroke and systemic embolism prevention in nonvalvular atrial fibrillation (NVAF). Randomized controlled trials have shown that these agents have at least comparable efficacy with vitamin K antagonists along with superior safety, at least in what concerns intracranial hemorrhage. As a result, NOACs are indicated as first-line anticoagulation therapy for NVAF patients with at least one risk factor for stroke or systemic embolism. The rapid introduction, however, of NOACs in a field dominated for decades by vitamin antagonists and the variety of agents and dosing schemes may create difficulties in decision making. In the present article, we attempt to determine a practical approach to the choice of agent and dose in different clinical scenarios by considering not only the results of seminal randomized trials and post hoc analyses but also data from real-world patient populations as well as the recently available possibility of rapid NOAC reversal.
A Simple Method for Normalization of Aortic Contractility
Authors: Jin Lexiao , Lipinski Alexandra , Conklin Daniel J.
Published: July 2018

Vascular contractile function changes in proliferative vascular diseases, e.g. atherosclerosis, and is documented using isolated blood vessels; yet, many laboratories differ in their approach to quantification. Some use raw values (e.g., mg, mN); others use a “percentage of control agonist” approach; and others normalize by blood vessel characteristic, e.g. length, mass, etc. A lack of uniformity limits direct comparison of contractility outcomes. To address this limitation, we developed a simple 2-step normalization method: (1) measure blood vessel segment length (mm), area (mm2) and calculate volume (mm3); then, (2) normalize isometric contraction (mN) by segment length and volume. Normalized aortic contractions but not raw values were statistically different between normal chow and high-fat diet-fed mice, supporting the practical utility and general applicability of normalization. It is recommended that aortic contractions be normalized to segment length and/or volume to reduce variability, enhance efficiency, and to foster universal comparisons across isometric myography platforms, laboratories, and experimental settings.
Testicular Preservation in 46 XY Denys-Drash Syndrome: A Report of Two Cases
Authors: Hodhod Amr , Noureldin Yasser A. , El-Sherbiny Mohamed
Published: July 2018

Denys Drash Syndrome (DDS) is a rare combination of genital and urinary anomalies that are mostly associated with malignancy. We report 2 patients who presented with genital ambiguity and were diagnosed as 46-XY DDS. During the discussion of the management plan, parents preferred to keep the gonads to preserve its endocrinal function for future sexual development. However, both patients developed primary hypogonadism at puberty and required testosterone supplementation. Persevering gonads in such patients had no endocrinal benefits but put the patients at risk of malignant transformation.
Digital Image Analysis with Fully Connected Convolutional Neural Network to Facilitate Hysteroscopic Fibroid Resection
Authors: Török Péter , Harangi Balázs
Published: July 2018

Aims: The study aimed to determine the accuracy of deep neural network in identifying the plane between myoma and normal myometrium. Methods: On the images of surgery, different structures were signed and annotated for the training phase. After the appropriate training of the deep neural network with 4,688 images from that training set, 1,600 formerly unseen images were used for testing. Indication for surgery was heavy menstrual bleeding and hysteroscopic finding was submucous fibroid. Operative intervention was fibroid resection. Recorded videos of transcervical resection of myoma in 13 cases were used for the study. Different filters and procedures were applied by the fully convolutional neural network (FCNN) for identifying previously annotated structures. Results: Previously manually annotated images and the manually drawn bitmasks were used for training the applied FCNN and then this pre-trained network was used for automatic segmentation of normal myometrium in an unseen video frame. The segmentation pixel-wise accuracy achieved the 86.19% considering the Hausdorff metric. Conclusion: Using deep learning technique in analyzing process of endoscopic video frame could help in real-time identification of structures while performing endoscopic surgery.
Optimized Antigen-Matched in Sickle Cell Disease Patients: Chances and Challenges in Molecular Times - the Brazilian Way
Authors: Castilho Lilian , Dinardo Carla Luana
Published: July 2018

The development of red blood cell (RBC) alloantibodies and autoantibodies complicates transfusion therapy in sickle cell disease (SCD) patients. In an effort to reduce the risk of alloimmunization, some strategies have been used to provide antigen-matched RBC transfusions to patients with SCD in Brazil, including molecular matching in 3 levels: RH and K matching; extended matching (RH, KEL, FY, JK, MNS, DI), and extended matching including RHD and RHCE variant alleles. Molecular matching has shown clinical benefits to the patients with SCD, contributing significantly to reduce the rates of alloimmunization. Improvements in the clinical outcomes of the patients have also been observed as shown by an increase in their hemoglobin levels and reduction in their percentage of hemoglobin S as well as better in vivo RBC survival and diminished frequency of transfusions. However, prevention of RBC alloimmunization still remains a challenge in Brazil due to the difficulty to fulfill all transfusion requests of the patients with antigen-matching units, inaccuracy of RBC phenotyping, RBC transfusions outside the institution where the patient is treated, advanced age of some patients, the RBC antigen discrepancy between donors and recipients, and the presence of RH variants.
Genotyping in Sickle Cell Disease Patients: The French Strategy
Authors: Floch Aline , Tournamille Christophe , Chami Btissam , Pirenne France
Published: July 2018

This review presents the French strategy for blood group genotyping in high-responder and newly diagnosed sickle cell disease (SCD) patients. In addition to FY, JK, and MNS genotyping, the RH blood group system is now explored in SCD patients in France. Molecular typing has been used for the deduction of partial RH2 (C) antigens since 2010, and the gradual implementation of systematic RHD and RHCE genotyping nationwide was initiated in late 2014. In our laboratory, 962 RH:2 (C-positive) SCD patients have been tested since 2010, and 1,148 SCD patients of all RH phenotypes have been genotyped for clinically relevant alleles of RHD and RHCE since late 2014.
Survival Benefit of Germline BRCA Mutation is Associated with Residual Disease in Ovarian Cancer
Authors: Shi Tingyan , Wang Pan , Tang Wenbin , Jiang Rong , Yin Sheng , Shi Di , Wang Qing , Wei Qingyi , Zang Rongyu
Published: July 2018

Background/Aims: Prognostic value of germline BRCA1 or BRCA2 (gBRCA1/2) mutations in epithelial ovarian cancer (EOC) remains controversial, especially in the estimation of long-term survival. We previously reported the largest study of gBRCA1/2 mutation prevalence in Chinese EOC patients. The aim of this study is to further illustrate the correlation of residual disease and survival in BRCA-associated EOC in China. Methods: In the current cohort consisting of 615 cases from the Chinese EOC genome-wide association study, we evaluated the association between gBRCA1/2 mutation and clinical outcomes. Results: Overall, we did not find any significant difference between gBRCA1/2 mutation carriers and non-carriers in both progression-free survival (PFS) and overall survival (OS) (19.3 vs. 18.1 months and 77.2 vs. 73.2 months, P=0.528 and 0.147, HR 0.93 and 0.79, 95%CI 0.74-1.17 and 0.57-1.09, respectively). However, within three years after diagnosis, mutation carriers showed a longer OS than non-carriers (P=0.018, HR 0.53, 95%CI 0.31-0.90). Such a survival advantage decreased along with the extension of follow-up time. Quite interestingly, in the subgroup of patients with gross residual disease, mutation carriers had a longer survival than non-carriers (18.5 vs. 15.1 months and 68.5 vs. 54.3 months, P=0.046 and 0.038, HR 0.74 and 0.65, 95% CI 0.55-1.00 and 0.43-0.98, for PFS and OS respectively). Conclusions: Our findings provided the evidence that gBRCA1/2 mutation was not associated with survival in Chinese EOC patients, which possibly attributed to more than 37% of the patients without gross residual disease. Survival benefit of gBRCA1/2 mutation was prominent in ovarian cancer patients with gross residual disease.
Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5
Authors: Wei Yongchang , Liu Guohong , Wu Balu , Yuan Yufen , Pan Yunbao
Published: July 2018

Background/Aims: MicroRNAs (miRNAs) regulate the expressions of cancer-related genes, and are involved in the development and progression of various human cancers. Here, we performed further analyses to determine whether let-7d is functionally linked to Jab1 in breast cancer. Methods: In situ hybridization and immunohistochemical analyses were used to determine the level of let-7d and Jab1 in breast cancer clinical specimens and its correlation with clinicopathological data. Let-7d overexpressing breast cancer cell lines combined with mouse models bearing cell-derived xenografts were used to assess the functional role of let-7d both in vitro and in vivo. Results: In this study, we found that let-7d was downregulated in breast cancer tissues, coupled with the elevations of Jab1 protein expressions, compared with paired adjacent noncancerous breast tissues. Let-7d overexpression significantly suppressed the proliferation and invasion in MCF-7 and MDA-MB-231 cells. Dual luciferase reporter assay indicated that Jab1 was the direct target of let-7d. Stepwise studies from in vitro and in vivo experiments indicated that let-7d overexpression inhibited cell growth and decreased Jab1 expressions in breast cancer cells and nude mice tumor tissues. Statistical analyses demonstrated that breast cancer patients with low levels of let-7d or high levels of Jab1 had a significant correlation with worse prognosis. Conclusion: These findings provide novel insights into molecular mechanism of let-7d and Jab1 in tumor development and progression of breast cancer, and thus let-7d/Jab1 are novel potential therapeutic targets for breast cancer patients.
Decreased Hepatic Lactotransferrin Induces Hepatic Steatosis in Chronic Non-Alcoholic Fatty Liver Disease Model
Authors: Lee Sungmin , Son Beomseok , Jeon Jaewan , Park Gaeul , Kim Hyunwoo , Kang Hyunkoo , Youn HyeSook , Jo Sunmi , Song Jie-Young , Youn BuHyun
Published: July 2018

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is an emerging metabolic disease. Although it leads to severe hepatic diseases including steatohepatitis, cirrhosis, and hepatic cancer, little is known about therapy to prevent and cure hepatic steatosis, the first step of NAFLD. We conducted this investigation to unveil the mechanism of hepatic steatosis. Methods: We established a novel chronic NAFLD mouse model through whole body irradiation and verified the model through histological and biochemical analysis. To find molecular mechanism for hepatic steatosis, we analyzed hepatic transcriptomic profiles in this model and selected target molecule. To induce the expression of lactotransferrin (Ltf) and regulate the NAFLD, growth hormone (GH) and coumestrol was introduced to hepatocyte and mice. The universal effect of coumestrol was confirmed by administration of coumestrol to NAFLD mouse model induced by high-fructose, high-fat, and MCD diet. Results: It was observed that decreased hepatic Ltf expression led to excessive hepatic lipid accumulation in NAFLD mouse. Furthermore, we found that GH was decreased in irradiated mice and functioned as an upstream regulator of Ltf expression. It was observed that GH could stimulate Ltf expression and prevent uptake of dietary lipids in hepatocytes, leading to rescue of NAFLD. Finally, we suggested that coumestrol, a kind of isoflavonoid, could be used as an inducer of hepatic Ltf expression through cooperation with the GH signaling pathway both in vitro and in vivo. Conclusions: Hepatic Ltf prevents hepatic steatosis through inhibition of dietary lipid uptake in radiation-induced NAFLD mouse model. We also suggest coumestrol as a drug candidate for prevention of NAFLD.
Maquiavel: lições das Histórias Florentinas
Authors: Cardoso Sérgio
Published: July 2018

O presente artigo procura examinar — tendo como pano de fundo as controvérsias do campo do comentário — o tratamento dado por Maquiavel à questão do ‘conflito civil’ posta no cerne de suas Istorie Fiorentine. A partir da compreensão, empenhada na obra, da natureza da história como disciplina do saber e de sua finalidade prática, busca-se observar a dinâmica da ‘divisão civil’ e a oposição entre conflitos facciosos e os conflitos políticos nos episódios evocados. Considera-se ainda, no relato paradigmático da revolta dos Ciompi, no L. III, as motivações passionais e as aspirações republicanas da plebe, bem como as causas de sua reversão em desejo de poder, que reabre o caminho das lutas de facção e da corrupção das instituições da cidade.
Claude Lefort e a crítica de “A propósito da questão judaica” de Marx: dialética e ideologia
Authors: Fausto Ruy
Published: July 2018

Como o seu título indica, o texto tem como objeto as considerações críticas de Lefort — ver o ensaio “Droits de l’homme et politique”, incluído em L’Invention Démocratique, les limites de la domination totalitaire — contra a crítica dos direitos do homem, desenvolvida por Marx no seu artigo de juventude “A propósito da questão judaica”, publicado em 1843, nos Anais Franco-Alemães (revista que Marx fundara com o publicista Arnold Ruge). Depois de expor as razões de Marx e de Lefort, o presente escrito envereda por vários caminhos. Há primeiro uma tentativa de expor as duas séries de argumentos em forma, que se pretende, rigorosamente dialética. Segue-se uma apresentação mais histórico-estrutural, que introduz considerações sobre os chamados “dois liberalismos” (revolucionário e utilitarista). Explora-se, em seguida, a filosofia subjacente ao artigo de Marx nos Anais…, o que leva de novo um desenvolvimento teórico-dialético, e depois, histórico, sobre a questão do humanismo e do antihumanismo. Depois de analisar algumas objeções, de marxistas e de liberais, endereçadas à crítica lefortiana, o autor tenta uma avaliação crítica das posições de Lefort, o que conduz ao problema geral das relações democracia/ capitalismo, em Lefort, e para além dele.
Foucault: Les aveux de la chair e a genealogia do sujeito desejante
Authors: Noto Carolina De Souza
Published: July 2018

Resenha de:Michel Foucault, Histoire de la sexualité IV. Les aveux de la chair, Ed. Frédéric Gros, Paris: Gallimard, 2018.
Gut Microbiota–Dependent Trimethylamine
N
-Oxide Predicts Risk of Cardiovascular Events in Patients With Stroke and Is Related to Proinflammatory Monocytes
Authors: Haghikia Arash , Li Xinmin S. , Liman Thomas G. , Bledau Nils , Schmidt David , Zimmermann Friederike , Kränkel Nicolle , Widera Christian , Sonnenschein Kristina , Haghikia Aiden , Weissenborn Karin , Fraccarollo Daniela , Heimesaat Markus M. , Bauersachs Johann , Wang Zeneng , Zhu Weifei , Bavendiek Udo , Hazen Stanley L. , Endres Matthias , Landmesser Ulf
Published: July 2018

Objective—

Gut microbiota–dependent metabolites, in particular trimethylamine
N
-oxide (TMAO), have recently been reported to promote atherosclerosis and thrombosis. Here, we examined for the first time the relation of TMAO and the risk of incident cardiovascular events in patients with recent first-ever ischemic stroke in 2 independent prospective cohorts. Moreover, the link between TMAO and proinflammatory monocytes as a potential contributing factor for cardiovascular risk in stroke patients was studied.

Approach and Results—

In a first study (n=78), higher TMAO plasma levels were linked with an increased risk of incident cardiovascular events including myocardial infarction, recurrent stroke, and cardiovascular death (fourth quartile versus first quartile; hazard ratio, 2.31; 95% CI, 1.25–4.23;
P
<0.01). In the second independent validation cohort (n=593), high TMAO levels again heralded marked increased risk of adverse cardiovascular events (fourth quartile versus first quartile; hazard ratio, 5.0; 95% CI, 1.7–14.8;
P
<0.01), and also after adjustments for cardiovascular risk factors including hypertension, diabetes mellitus, LDL (low-density lipoprotein) cholesterol, and estimated glomerular filtration rate (hazard ratio, 3.3; 95% CI, 1.2–10.9;
P
=0.04). A significant correlation was also found between TMAO levels and percentage of proinflammatory intermediate CD14
++
CD16
+
monocytes (
r
=0.70;
P
<0.01). Moreover, in mice fed a diet enriched with choline to increase TMAO synthesis, levels of proinflammatory murine Ly6C
high
monocytes were higher than in the chow-fed control group (choline: 9.2±0.5×10
3
per mL versus control: 6.5±0.5×10
3
per mL;
P
<0.01). This increase was abolished in mice with depleted gut microbiota (choline+antibiotics: 5.4±0.7×10
3
per mL;
P
<0.001 versus choline).

Conclusions—

The present study demonstrates for the first time a graded relation between TMAO levels and the risk of subsequent cardiovascular events in patients with recent prior ischemic stroke. Our data support the notion that TMAO-related increase of proinflammatory monocytes may add to elevated cardiovascular risk of patients with increased TMAO levels.
Enhancement Strategies for Cardiac Regenerative Cell Therapy
Authors: Broughton Kathleen M. , Sussman Mark A.
Published: July 2018

The idiom heart of the matter refers to the focal point within a topic and, with regard to health and longevity, the heart is truly pivotal for quality of life. Societal trends worldwide continue toward increased percent body fat and decreased physical activity with coincident increases in chronic diseases including cardiovascular disease as the top global cause of death along with insulin resistance, accelerated aging, cancer. Although long-term survival rates for cardiovascular disease patients are grim, intense research efforts continue to improve both prevention and treatment options. Pharmacological interventions remain the predominant interventional strategy for mitigating progression and managing symptoms, but cellular therapies have the potential to cure or even mediate remission of cardiovascular disease. Adult stem cells are the most studied cellular therapy in both preclinical and clinical investigation. This review will focus on the advanced therapeutic strategies to augment products and methods of delivery, which many think heralds the future of clinical investigations. Advanced preclinical strategies using adult stem cells are examined to promote synergism between preclinical and clinical research, streamline implementation, and improve this imminent matter of the heart.
Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes as Models for Cardiac Channelopathies
Authors: Garg Priyanka , Garg Vivek , Shrestha Rajani , Sanguinetti Michael C. , Kamp Timothy J. , Wu Joseph C.
Published: July 2018

Life threatening ventricular arrhythmias leading to sudden cardiac death are a major cause of morbidity and mortality. In the absence of structural heart disease, these arrhythmias, especially in the younger population, are often an outcome of genetic defects in specialized membrane proteins called ion channels. In the heart, exceptionally well-orchestrated activity of a diversity of ion channels mediates the cardiac action potential. Alterations in either the function or expression of these channels can disrupt the configuration of the action potential, leading to abnormal electrical activity of the heart that can sometimes initiate an arrhythmia. Understanding the pathophysiology of inherited arrhythmias can be challenging because of the complexity of the disorder and lack of appropriate cellular and in vivo models. Recent advances in human induced pluripotent stem cell technology have provided remarkable progress in comprehending the underlying mechanisms of ion channel disorders or channelopathies by modeling these complex arrhythmia syndromes in vitro in a dish. To fully realize the potential of induced pluripotent stem cells in elucidating the mechanistic basis and complex pathophysiology of channelopathies, it is crucial to have a basic knowledge of cardiac myocyte electrophysiology. In this review, we will discuss the role of the various ion channels in cardiac electrophysiology and the molecular and cellular mechanisms of arrhythmias, highlighting the promise of human induced pluripotent stem cell-cardiomyocytes as a model for investigating inherited arrhythmia syndromes and testing antiarrhythmic strategies. Overall, this review aims to provide a basic understanding of the electrical activity of the heart and related channelopathies, especially to clinicians or research scientists in the cardiovascular field with limited electrophysiology background.
SMAD4 Prevents Flow Induced Arteriovenous Malformations by Inhibiting Casein Kinase 2
Authors: Ola Roxana , Künzel Sandrine H. , Zhang Feng , Genet Gael , Chakraborty Raja , Pibouin-Fragner Laurence , Martin Kathleen , Sessa William , Dubrac Alexandre , Eichmann Anne
Published: July 2018

Background:

Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder that causes arteriovenous malformations (AVMs). Mutations in the genes encoding Endoglin (
ENG
) and activin-receptor-like kinase 1 (
AVCRL1
encoding ALK1) cause HHT type 1 and 2, respectively. Mutations in the
SMAD4
gene are present in families with juvenile polyposis-HHT syndrome that involves AVMs. SMAD4 is a downstream effector of transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP) family ligands that signal via activin-like kinase receptors (ALKs). Ligand-neutralizing antibodies or inducible, endothelial-specific
Alk1
deletion induce AVMs in mouse models as a result of increased PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) signaling. Here we addressed if SMAD4 was required for BMP9-ALK1 effects on PI3K/AKT pathway activation.

Methods:

The authors generated tamoxifen-inducible, postnatal, endothelial-specific
Smad4
mutant mice (
Smad4
iΔEC
).

Results:

We found that loss of endothelial
Smad4
resulted in AVM formation and lethality. AVMs formed in regions with high blood flow in developing retinas and other tissues. Mechanistically, BMP9 signaling antagonized flow-induced AKT activation in an ALK1- and SMAD4-dependent manner.
Smad4
iΔEC
endothelial cells in AVMs displayed increased PI3K/AKT signaling, and pharmacological PI3K inhibitors or endothelial
Akt1
deletion both rescued AVM formation in
Smad4
iΔEC
mice. BMP9-induced SMAD4 inhibited casein kinase 2 (
CK2
) transcription, in turn limiting PTEN phosphorylation and AKT activation. Consequently, CK2 inhibition prevented AVM formation in
Smad4
iΔEC
mice.

Conclusions:

Our study reveals SMAD4 as an essential effector of BMP9-10/ALK1 signaling that affects AVM pathogenesis via regulation of
CK2
expression and PI3K/AKT1 activation.
Quantitative Lesion Water Uptake in Acute Stroke Computed Tomography Is a Predictor of Malignant Infarction
Authors: Broocks Gabriel , Flottmann Fabian , Scheibel Alexandra , Aigner Annette , Faizy Tobias D. , Hanning Uta , Leischner Hannes , Broocks Sabine I. , Fiehler Jens , Gellissen Susanne , Kemmling Andre
Published: July 2018

Background and Purpose—

Early selection of patients with acute middle cerebral artery infarction at risk for malignant edema is critical to initiate timely decompressive surgery. Net water uptake (NWU) per brain volume is a quantitative imaging biomarker of space-occupying ischemic edema which can be measured in computed tomography. We hypothesize that NWU in early infarct lesions can predict development of malignant edema. The aim was to compare NWU in acute brain infarct against other common predictors of malignant edema.

Methods—

After consecutive screening of single-center registry data, 153 patients with acute proximal middle cerebral artery occlusion fulfilled the inclusion criteria. A total of 29 (18.2%) patients developed malignant edema defined as end point in follow-up imaging leading to decompressive surgery and death as a direct implication of mass effect. Early infarct lesion volume and NWU were quantified in multimodal admission computed tomography; time from symptom onset to admission imaging was recorded.

Results—

Mean time from onset to admission imaging was equivalent between patients with and without malignant infarcts (mean±SD: 3.3±1.4 hours and 3.3±1.7 hours, respectively). Edematous tissue expansion by NWU within infarct lesions occurred across all patients in this cohort (NWU: 9.1%±6.8%; median, 7.9%; interquartile range, 8.8%; range, 0.1%–35.6%); 7.0% (±5.2) in nonmalignant and 18.0% (±5.7) in malignant infarcts. Based on univariate receiver operating characteristic curve analysis, NWU >12.7% or an edema rate >3.7% NWU/h identified malignant infarcts with high discriminative power (area under curve, 0.93±0.02). In multivariate binary logistic regression, the probability of malignant infarct was significantly associated with early infarct volume and NWU.

Conclusions—

Computed tomography–based quantitative NWU in early infarct lesions is an important surrogate marker for developing malignant edema. Besides volume of early infarct, the measurements of lesion water uptake may further support identifying patients at risk for malignant infarction.
[WITHDRAWN ARTICLE] A Study on the Performance of Solid Oxide Fuel Cells Based on Pr0.5Sr0.5Co0.8Cu0.2O3–δ-xSDC Composite Cathode
Authors: Wang Lizhong , Fu Xinmin , Liu Hongbo , Li Shumei
Published: July 2018

[WITHDRAWN ARTICLE] In this paper, because the new test equipment is used in the test, the debugging problems of the equipment are found in the recent experiments, resulting in the inaccurate test data, which can not reflect the actual results. We are afraid it will mislead the readers and can't explain the characteristics of the battery well. In order to maintain the seriousness of science, the authors of this article hereby apply to withdraw the manuscript and bear all consequences.
Applications of Aptamer-Conjugated Nanomaterials for Targeted Cancer Therapy
Authors: Xi Zhijiang , Zheng Bing
Published: July 2018

Aptamer is a new-type of specific recognition molecule and is emerging as a promising therapeutic agent. The greatest advantage of aptamers is their high binding affinity and specificity towards the target. The toxicity of anticancer drugs to surrounding healthy tissues limits their
clinical applications. However, nanomaterials for drug carriers can considerably improve drug efficacy while reducing toxicity, because they accumulate and release drugs at the lesion without affecting healthy tissues. As drug carriers, aptamer-conjugated nanomaterials can enhance active targeting
and then release the drug into the targeted cancer cells effectively. Therefore, aptamer-conjugated nanomaterials for targeted cancer therapy constitute an evolving treatment approach with considerable potential to enhance the efficacy of cancer therapy via the delivery of therapeutic agents
specific to and into the targeted tumor cells. In this paper, various aptamer-conjugated nanomaterials such as gold nanoparticles, magnetic nanoparticles, silica nanoparticles, carbon nanotubes, poly D,L-lactic-co-glycolic acid, and quantum dots for targeted cancer therapy, are reviewed and
their prospect as therapeutic agents is evaluated.
Influence of Grain and Grain Boundary Interfaces on Dielectric Relaxation of Ceria Nanocrystals Using Modulus Formalism Under Biased and Equilibrium Conditions
Authors: Chandrasekar P. , Begum S. N. Suraiya , Vishista K.
Published: July 2018

Dielectric relaxation of ceria nanocrystals under biased condition for different grain sizes was in this study evaluated in modulus formalism using impedance spectroscopy. Prior to the impedance measurements, the ceria sample was calcined at 200 °C for 30 min and pressed into cylindrical
pellets with 8 mm diameter and 1 mm thick by applying uniaxial four-ton pressure using a hydraulic press. This was then sintered at 300 °C, 450 °C, 600 °C and 900 °C for 30 min. Systematic analysis of modulus formalism data using commercial Z-view and Z-plot software's
permitted, reliable extraction of dielectric relaxation time (τ) of ceria nanocrystals. The observed dielectric relaxation time (τ) at equilibrium condition varied from 10–5 to 10–3 s when the grain size of ceria nanocrystals was increased
from 9 nm to 29 nm. But when the DC bias voltage was applied, the same dielectric relaxation time (τ) was tuned to ∼10–4 s for all the grain sizes of ceria nanocrystals, because of Schottky grain boundary potential barrier height (φb) suppression.
Properties of Ga–Zn–O Ultraviolet Phototransistors Using Radio-Frequency Magnetron Co-Sputtering Method
Authors: Yang C. P. , Chang S. P. , Chang S. J. , Chang T. H. , Chiu C. J. , Tsai Y. L. , Lin C. W. , Weng W. Y. , Liao T. Y.
Published: July 2018

In this paper, we report on the fabrication of Ga-doped zinc oxide (GZO) channel ultraviolet (UV) phototransistors. Under dark measurement conditions, it is found that the values of μFE, VT, SS, and ION/IOFF
of the fabricated device are 25.8 cm2/Vs, 0.35 V, 0.2 V/decade, and 1 × 105, respectively. Unpassivated devices have a negative VTH shift with positive bias stress, which results from the interactions of the moisture present in air with the GZO
channel during the fabrication procedure and/or storage. Furthermore, it is found that the deep-UV to visible-rejection ratio can reach 1.1 × 102 for the fabricated phototransistor. These electro-optical properties indicate that the fabricated devices not only present good
performance as thin-film transistors (TFTs), but are also useful for deep-UV light sensing applications.
Green Synthesis of Silver Nanoparticles Using Ginkgo biloba and Their Bactericidal and Larvicidal Effects
Authors: Balashanmugam Pannerselvam , Kim Hyung Joo , Singh Vijay , Kumaran Rangarajulu Senthil
Published: July 2018

The synthesis of metallic nanoparticles using plant extracts has attracted much attention. In this study, silver nanoparticles (AgNPs) were synthesized using the Ginkgo biloba plant-leaf extract and their antibacterial and larvicidal activities were investigated. AgNPs were characterized
using UV-visible, X-ray diffraction (XRD), Fourier transform infrared (FTIR), energy-dispersive X-ray (EDX) spectroscopy and field emission scanning electron microscope (FESEM) analysis. The UV-visible spectral analysis showed a surface plasmon resonance (SPR) peak at 430 nm, the FESEM analysis
revealed size of AgNPs between 25–45 nm and the XRD data confirmed the formation of the AgNPs using G. biloba-mediated green synthesis. AgNPs showed the highest antibacterial activities against Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtills,
Enterobacter aerogens, Salmonella paratyphi and Escherichia coli. Also, the AgNPs exerted a significant larvicidal effect on the Culex mosquito larvae.
Malus domestica Mediated Synthesis of Palladium Nanoparticles and Investigation of Their Catalytic Activity Towards the Suzuki Coupling Reactions
Authors: Qazi Farah , Hussain Zakir , Asghar Soneela , Abbas Ghayoor , Riaz Muhammad
Published: July 2018

Synthesis of nanoparticles through green methods is considered to be more eco-friendly and facile as compared to conventional physical and chemical methods. In this work, an environmental friendly method to synthesize palladium nanoparticles (Pd-NPs) by using a fruit extract has been
reported. This extract obtained from Malus domestica (apple); acted as a source of reducing agent and functioned as a capping agent as well. The Pd-NPs were monitored and characterized by ultraviolet-visible (UV-Vis) spectroscopy; powder X-rays diffraction (XRD), scanning electron microscopy
(SEM) and Fourier-transform infra-red (FT-IR) spectroscopy. FT-IR spectra revealed the presence of abundant amounts of ascorbic acid in the fruit extract which is assumed to reduce the Palladium chloride to Pd-NPs. XRD results confirmed the crystalline nature of Pd-NPs (JCPDS: No. 05-0681,
space group: Fm3m (225)). These nanoparticles were further investigated for their catalytic activity towards the Suzuki coupling reactions where by employing only 2 mol% of the catalyst loading these Pd-NPs demonstrated excellent catalytic activity. Progress and completion of reactions were
monitored by gas chromatography (GC) while products formed were characterized by gas chromatography-mass spectrometry (GC-MS), FT-IR as well as from their melting points data. Pd-NPs showed excellent catalytic activity; thereby suggesting their potential and scope for various other catalytic
transformations.
Comparison of Simulated Spatial Patterns Using Rain Gauge and Polarimetric-Radar-Based Precipitation Data in Catchment Hydrological Modeling
Authors: He Xin , Koch Julian , Zheng Chunmiao , Bøvith Thomas , Jensen Karsten H.
Published: July 2018

With the advance of the weather radar technology, dual-polarization (dual-pol) radar data are now available for hydrological studies, which go beyond the traditional rainfall products relying purely on rain gauge data. Previous studies have focused on the evaluation of rainfall products and their hydrological responses using point-based observational data; however, spatial patterns of simulated hydrological variables are equally important to be considered in order to fully address the distributed effect of the precipitation estimates. In the present study, we compare three rainfall estimations based on rain gauge, single-polarization, and dual-pol radar data. Special attention is given to the use of the two radar products and their corresponding hydrological simulations of both surface water and groundwater. Performance of the hydrological simulations is evaluated based first on traditional point-based observations of stream discharge and groundwater head, and second on remotely sensed land surface temperature data. For the latter, the empirical orthogonal function analysis, which quantifies spatial pattern similarities, is employed. The Skjern River catchment in western Denmark is selected as the study site, and the results show that all three models perform equally well in terms of the traditional aggregated evaluation criteria, such as Nash–Sutcliffe efficiency (NSE) and RMSE on time series data. It is found that the differences of simulated hydrological spatial patterns are sensitive to rainfall signal intensity, as well as the simulation scale in space (<100 km2) and time (subdaily). Our study suggests that the currently available observational data have limited capabilities to clearly differentiate the performance of the three applied models due to the low resolution.
Using Situation Awareness and Workload to Predict Performance in Submarine Track Management: A Multilevel Approach
Authors: Loft Shayne , Jooste Lisa , Li Yanqi Ryan , Ballard Timothy , Huf Samuel , Lipp Ottmar V. , Visser Troy A. W.
Published: July 2018

Objective:

Examine the extent to which subjective workload and situation awareness (SA) can predict variance in performance at the between- and within-person levels of analysis in a simulated submarine track management task.

Background:

SA and workload are crucial constructs in human factors that are conceptualized as states that change within individuals over time. Thus, a change in an individual’s subjective workload or SA over the course of performing a task should be predictive of their subsequent performance (within-person effects). However, there is little empirical evidence for this.

Method:

Participants monitored displays to track the behaviors of contacts in relationship to their own ship (Ownship) and landmarks. The Situational Awareness Global Assessment Technique measured SA, and the Air Traffic Workload Input Technique measured subjective workload.

Results:

When a participant’s subjective workload rating increased, their subsequent performance decreased, but there was no evidence for within-person effects of SA on performance. We replicated prior between-person level effects of SA; participants with higher SA performed better than those with lower SA.

Conclusion:

Change in an individual’s subjective workload rating (but not SA) was predictive of their subsequent performance. Because an increase in SA should increase the extent to which operators hold the knowledge required to perform subsequent tasks, further research is required to examine SA effects on performance at the within-person level.

Application:

Adapting automation is more likely to produce optimal outcomes if based on measurement of operator states that predict future task performance, such as workload.
The Dyadic Militarized Interstate Disputes (MIDs) Dataset Version 3.0: Logic, Characteristics, and Comparisons to Alternative Datasets
Authors: Maoz Zeev , Johnson Paul L. , Kaplan Jasper , Ogunkoya Fiona , Shreve Aaron P.
Published: July 2018

We introduce the new, substantially updated, and revised version of the Dyadic Militarized Interstate Disputes (MIDs) dataset. We discuss the underlying logic of constructing dyadic MIDs and demonstrate that these operations generate significant differences between the actual occurrence and properties of MID dyads and those extracted from machine-generated programs such as EUGene, or from the MID participant dataset. We provide some descriptive measures of dyadic MIDs over the period of 1816 to 2010 and compare some of the key dyadic results on the correlates of MIDs using different datasets. We discuss the theoretical and empirical implications of our results.
Ectopic Hedgehog Signaling Causes Cleft Palate and Defective Osteogenesis
Authors: Hammond N.L. , Brookes K.J. , Dixon M.J.
Published: July 2018

Cleft palate is a common birth defect that frequently occurs in human congenital malformations caused by mutations in components of the Sonic Hedgehog (S HH) signaling cascade. Shh is expressed in dynamic, spatiotemporal domains within epithelial rugae and plays a key role in driving epithelial-mesenchymal interactions that are central to development of the secondary palate. However, the gene regulatory networks downstream of Hedgehog (Hh) signaling are incompletely characterized. Here, we show that ectopic Hh signaling in the palatal mesenchyme disrupts oral-nasal patterning of the neural crest cell–derived ectomesenchyme of the palatal shelves, leading to defective palatine bone formation and fully penetrant cleft palate. We show that a series of Fox transcription factors, including the novel direct target Foxl1, function downstream of Hh signaling in the secondary palate. Furthermore, we demonstrate that Wnt/bone morphogenetic protein (BMP) antagonists, in particular Sostdc1, are positively regulated by Hh signaling, concomitant with downregulation of key regulators of osteogenesis and BMP signaling effectors. Our data demonstrate that ectopic Hh-Smo signaling downregulates Wnt/BMP pathways, at least in part by upregulating Sostdc1, resulting in cleft palate and defective osteogenesis.
Experimental Effects of Acute Exercise on Episodic Memory Function: Considerations for the Timing of Exercise
Authors: Haynes James T. , Frith Emily , Sng Eveleen , Loprinzi Paul D.
Published: July 2018

Our previous work employing a between-subject randomized controlled trial design suggests that exercising prior to memory encoding is more advantageous in enhancing retrospective episodic memory function when compared to exercise occurring during or after memory encoding. The present experiment evaluates this potential temporal effect of acute exercise on memory function while employing a within-subject, counterbalanced design. In a counterbalanced order (via Latin squares), 24 participants completed four visits including (1) exercising (moderate-intensity walking) prior to memory encoding, (2) exercising during memory encoding, (3) exercising after memory encoding, and (4) a control visit (no exercise). Retrospective memory function (short term and long term; 24-hour follow-up) was assessed from a multitrial word list. Prospective memory was assessed from a time-based task. Compared to all other visits, short-term memory was greater in the visit that involved exercising prior to memory encoding (F = 3.76; P = .01; η2 = .79). Similar results occurred for long-term memory, with no significant effects for prospective memory performance. We provide robust evidence demonstrating that acute moderate-intensity exercise prior to memory encoding is optimal in enhancing short-term and long-term memory function when compared to no exercise as well as exercising during and after memory encoding.
Finite-time stability control of an electric vehicle under tyre blowout
Authors: Meng Qinghua , Qian Chunjiang , Sun Zong-Yao
Published: July 2018

In this paper, the authors consider the problem of tyre blowout control via output feedback for an electric vehicle (EV) driven by four in-wheel motors to reduce fatal damage. First, an EV dynamic model in the case of a tyre blowout is established. The model considers the unmeasurable state, unknown added front wheel steering angle generated by a tyre blowout and uncertain external disturbances. Second, to address the difficulties in estimating the unmeasurable state, unknown parameters and disturbances for the EV, a finite-time observer is introduced. Then, by introducing a coordinate transformation, the state-space model of an EV with tyre blowout is converted into a simple form for which a state feedback control law is constructed by adding a power integrator method. Combining the finite-time observer with the finite-time control law, an output feedback controller is designed to stabilize the EV when a tyre bursts. A torque allocation method is also given to operate every wheel except the burst tyre to stabilize and stop the EV. Finally, computer simulations are given to validate the proposed finite-time output feedback controller for the EV tyre blowout control.