bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidental Finding of Inferior Vena Cava Atresia Presenting with Deep Venous Thrombosis following Physical Exertion
Authors: Koppisetty Shalini , Smith Alton G. , Dhillon Ravneet K.
Published: November 2015

Inferior vena cava atresia (IVCA) is a rare but well described vascular anomaly. It is a rare risk factor for deep venous thrombosis (DVT), found in approximately 5% of cases of unprovoked lower extremity (LE) DVT in patients <30 years of age. Affected population is in the early thirties, predominantly male, often with a history of major physical exertion and presents with extensive or bilateral DVTs. Patients with IVC anomalies usually develop compensatory circulation through the collateral veins with enlarged azygous/hemizygous veins. Despite the compensatory circulation, the venous drainage of the lower limbs is often insufficient leading to venous stasis and thrombosis. We describe a case of extensive and bilateral deep venous thrombosis following physical exertion in a thirty-six-year-old male patient with incidental finding of IVCA on imaging.
Child Health in the Peruvian Amazon: Prevalence and Factors Associated with Referred Morbidity and Health Care Access in the City of Iñapari
Authors: Guimarães Maria Gabriela Silva , Braña Athos Muniz , Oliart-Guzmán Humberto , Branco Fernando Luiz Cunha Castelo , Delfino Breno Matos , Pereira Thasciany Moraes , Mantovani Saulo Augusto Silva , Martins Antonio Camargo , Santos Ana Paula , Filgueira-Júnior José Alcântara , Ramalho Alanderson Alves , Guimarães Andreia da Silva , Oliveira Cristieli Sérgio de Menezes , Araújo Thiago Santos de , Estrada Carlos Hermógenes Manrique de Lara , Arróspide Nancy , da Silva-Nunes Mônica
Published: November 2015

Introduction. Children under 5 years of age are more susceptible to developing morbidities such as diarrhea, respiratory infections, anemia, and malnutrition. The objective of the study is to evaluate the prevalence of reported morbidities in this age group in the city of Iñapari (Peru) and the access to health services in this municipality.Methods. Data collection using interviews that assessed socioeconomic and demographic conditions, child morbidity, and access to health services was performed in 2011. Statistical analysis was performed using SPSS 13.0.Results. Regarding morbidities that occurred during lifetime, 39.8% reported previous anemia and intestinal parasite infection. About 53.7% of the children reported any type of morbidities in the last 15 days before interview, being most frequent respiratory symptoms (38.9%), diarrhea (23,4%), and fever (23,1%). Only 63.1% of those reporting recent morbidities sought health care. These morbidities were associated with precarious sanitation and lack of infrastructure, the presence of other comorbidities, and poor access to health services.Conclusion. The main referred morbidities in Amazonian Peruvian children were diarrhea, respiratory symptoms, anemia, and vomiting. Incentives and improvements in the health and sanitation conditions would be important measures to improve the quality of life of the Amazonian child population.
The Mind and Heart of the Social Child: Developing the Empathy and Theory of Mind Scale
Authors: Wang Zhenlin , Wang Lamei
Published: November 2015

Empathy and theory of mind (ToM) are distinctive psychological constructs in predicting children’s social functioning. This study provided evidence of the independent nature of these constructs and developed a parent questionnaire for measuring individual differences in children’s empathy and ToM. In Study 1, exploratory factor analysis and confirmatory factor analysis based on responses of 116 parents of Hong Kong children established a three-factor structure of the Empathy and Theory of Mind Scale (EToMS), that is, Empathy, Nice ToM, and Nasty ToM. An additional 189 parents of Study 2 confirmed this three-factor model. A subsample of 93 children (M=4.97, SD = .84, 47 boys) from Study 2 took part in child measures of helping and lying behaviors as well as false belief understanding. The results supported the reliability and validity of the EToMS, making it a useful assessment of children’s social predispositions.
Analysis of a Functional IL-6 Gene Polymorphism in HLAB27 Associated and Intermediate Uveitis Gives New Insight in Disease Pathogenesis and Commonality with Other Autoimmune Diseases
Authors: Ewald Lindner , Beate Langner-Wegscheider , Stephanie Sarny , Wilfried Renner , Yosuf El-Shabrawi
Published: November 2015

Purpose. Interleukin 6 (IL-6) plays a crucial role in both adaptive and innate immunity. The rs1800795 gene polymorphism of IL-6 is associated with various autoimmune diseases, like multiple sclerosis.Methods. 134 patients with HLAB27 positive iridocyclitis, 84 patients with intermediate uveitis, 132 controls, and 65 HLAB27 positive controls were recruited for the present case-control study. Main outcome measures were genotype distribution and allelic frequencies determined by polymerase chain reaction.Results. The frequency of carriers of the minor allele for rs1800795 was significantly higher in patients with intermediate uveitis compared to controls (p=0.04; OR: 1.46; CI: 1.02–2.11). Frequencies of the minor allele for rs1800795 did not differ significantly in patients with HLAB27 associated uveitis when compared to controls (p>0.05).Conclusion. These findings further deepen our understanding of the commonality between multiple sclerosis and intermediate uveitis. Given the functionality of the investigated polymorphism, new pathophysiological insights are gained that help to evaluate possible therapeutic targets.
Bifid Median Nerve in the Bulgarian Population: An Anatomical and Clinical Study
Authors: Georgiev Georgi P. , Slavchev Svetoslav A. , Dimitrova Iva N. , Landzhov Boycho
Published: November 2015

High division of the median nerve proximal to the carpal tunnel, also known as a bifid median nerve, is a rare anatomical variant with an incidence between 1 and 3%. In order to study the incidence of this anatomical variation in the Bulgarian population, we examined the upper limbs of 51 formol-carbol fixed human cadavers and also 154 upper limbs undergoing carpal tunnel decompression. We detected one case of bifid median nerve during anatomical dissections and two cases in patients with carpal tunnel syndrome. In one of the clinical cases, the anatomical variation was detected preoperatively by MRI. We discuss different variations of this nerve and emphasize their potential clinical implications.
Possible Mechanism of Action of the Antiallergic Effect of an Aqueous Extract of Heliotropium indicum L. in Ovalbumin-Induced Allergic Conjunctivitis
Authors: Kyei Samuel , Koffuor George Asumeng , Ramkissoon Paul , Abokyi Samuel , Owusu-Afriyie Osei , Wiredu Eric Addo
Published: November 2015

Heliotropium indicum is used traditionally as a remedy for conjunctivitis in Ghana. This study therefore evaluated the antiallergic potential of an aqueous whole plant extract of Heliotropium indicum (HIE) in ovalbumin-induced allergic conjunctivitis and attempted to predict its mode of action. Clinical scores for allergic conjunctivitis induced by intraperitoneal ovalbumin sensitization (100 : 10 μg OVA/Al(OH)3 in phosphate-buffered saline [PBS]) and topical conjunctival challenge (1.5 mg OVA in 10 μL PBS) in Dunkin-Hartley guinea pigs were estimated after a week’s daily treatment with 30–300 mg kg−1 HIE, 30 mg kg−1 prednisolone, 10 mg kg−1 chlorpheniramine, or 10 mL kg−1 PBS. Ovalbumin-specific IgG and IgE and total IgE in serum were estimated using Enzyme-Linked Immunosorbent Assay. Histopathological assessment of the exenterated conjunctivae was also performed. The 30 and 300 mg kg−1 HIE treatment resulted in a significantly (p≤0.001) low clinical score of allergic conjunctivitis. Ovalbumin-specific IgG and IgE as well as total serum IgE also decreased significantly (p≤0.01–0.001). The conjunctival tissue in HIE treated guinea pigs had mild mononuclear infiltration compared to the PBS-treated ones, which had intense conjunctival tissue inflammatory infiltration. HIE exhibited antiallergic effect possibly by immunomodulation or immunosuppression.
Senescence-Associated Changes in Proteome andO-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells
Authors: Herzog Rebecca , Tarantino Silvia , Rudolf András , Aufricht Christoph , Kratochwill Klaus , Witowski Janusz
Published: November 2015

Introduction. Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins withO-linked N-acetylglucosamine (O-GlcNAcylation).Methods. A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis.O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decreaseO-GlcNAcylation orO-(2-acetamido-2-deoxy-D-glucopyranosylidene) aminoN-phenyl carbamate (PUGNAc) to increaseO-GlcNAcylation.Results. Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasomeβ-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5′(3′)-deoxyribonucleotidase. Although the global level ofO-GlcNAcylation was comparable, senescent cells were not sensitive to modulation by PUGNAc.Discussion. This study identified changes of the proteome and altered dynamics ofO-GlcNAc regulation in senescent mesothelial cells. Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis.
The Vertex Version of Weighted Wiener Number for Bicyclic Molecular Structures
Authors: Gao Wei , Wang Weifan
Published: November 2015

Graphs are used to model chemical compounds and drugs. In the graphs, each vertex represents an atom of molecule and edges between the corresponding vertices are used to represent covalent bounds between atoms. We call such a graph, which is derived from a chemical compound, a molecular graph. Evidence shows that the vertex-weighted Wiener number, which is defined over this molecular graph, is strongly correlated to both the melting point and boiling point of the compounds. In this paper, we report the extremal vertex-weighted Wiener number of bicyclic molecular graph in terms of molecular structural analysis and graph transformations. The promising prospects of the application for the chemical and pharmacy engineering are illustrated by theoretical results achieved in this paper.
Impacts of Climate Change and Human Activities on Runoff and Sediment Load of the Xiliugou Basin in the Upper Yellow River
Authors: Yao Haifang , Shi Changxing , Shao Wenwei , Bai Jianbin , Yang Hui
Published: November 2015

Using data of temperature, wind, precipitation, water discharge, and sediment load, the changes in runoff and sediment load of the Xiliugou basin in the upper Yellow River were investigated and the contributions of climate change and human activities to these changes were quantitatively estimated. Results show that the runoff and sediment load of the stream declined gradually in 1960–2012. According to the abrupt change point detected, the runoff and sediment series were divided into two periods: 1960–1998 and 1999–2012. The reductions of runoff and sediment load in 1999–2012 were found to be related to climate change and human activities, and the latter played a dominant role with a contribution of about 68% and 75%, respectively. The effects of rainfall intensity should be considered to avoid overestimating or underestimating the contributions of rainfall changes to the variations of runoff and sediment load in the semiarid region. An inspection of changes in water discharge and sediment regime indicated that the frequency of discharge between 0 and 5 m3/s increased while that between 5 and 1000 m3/s decreased in 2006–2012. This phenomenon can be attributed principally to the soil and water conservation practices.
Comparison of Body, Auricular, and Abdominal Acupuncture Treatments for Insomnia Differentiated as Internal Harassment of Phlegm-Heat Syndrome: An Orthogonal Design
Authors: Jiao Yue , Han Ying , Li Xin , Fang Yi-gong , Liu Zhao-hui , Zhou Wen-na , Zhou Jin-cao , Wu Zhong-chao , Yang Jin-hong , Li Shao-yuan , Meng Fan-ying , Xu Wei-wei
Published: November 2015

Objective.To identify the optimum treatment protocol for insomnia among auricular, body, and abdominal needling methods.Methods.A three-factor (3 needling protocols) and three-level experimental scheme was designed based on orthogonal method. 54 patients of insomnia differentiated as internal harassment of phlegm-heat syndrome were given two courses of acupuncture treatment (each with 20 times of acupuncture). The therapeutic effects were evaluated by comparing the Pittsburgh sleep quality index (PSQI), Hamilton Depression Scale (HAMD) scores, and Hamilton Anxiety Scale (HAMA) scores of patients before treatment, after one course of treatment, and after two courses of treatment as well as one month after treatment.Results.Body, auricular, and abdominal acupuncture treatments all alleviated symptoms of insomnia, depression, and anxiety, but body and auricular acupuncture had stronger therapeutic effects.Conclusions.Body acupuncture at basic points shall be given priority in protocol selection for insomnia. The second-best choice is auricular acupuncture with basic points combined with points based on Traditional Chinese Medicine (TCM) theories. Abdominal needling with very quick effect can be an alternative protocol with basic points combined with syndrome differentiation points.
Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?
Authors: Khedr Mohamed Ahmed , Sira Ahmad Mohamed , Saber Magdy Anwar , Raia Gamal Yousef
Published: November 2015

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important.Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls.Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p<0.0001,p=0.071, andp=0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p<0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders,p<0.0001andp=0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p=0.044).Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.
Distal Insertional Footprint of the Brachialis Muscle: 3D Morphometric Study
Authors: Kamineni Srinath , Bachoura Abdo , Behrens William , Kamineni Ellora , Deane Andrew
Published: November 2015

Objective. The purpose of this study is to describe the three-dimensional morphometry of the brachialis muscle at its distal attachment to the ulna. Methods. Fifty cadaveric elbows were dissected and the brachialis distal insertion was isolated on the ulna bone and probed with a three-dimensional digitizer, to create a three-dimensional model of the footprint. Measurements and analysis of each footprint shape were recorded and compared based on gender and size. Results. There was significant gender difference in the surface length (P= 0.002) and projected length (P= 0.001) of the brachialis footprint. The shapes of the footprint also differed among the specimens. Conclusion. The shape of the brachialis muscle insertion differed among all the specimens without significant variation in gender or sides. There was also a significant difference in muscle length between males and females with little difference in the width and surface area. Significance. The information obtained from this study is important for kinematic understanding and surgical procedures around the elbow joint as well as the understanding of the natural age related anatomy of the brachialis footprint morphology.
Assessment of the First Commercial ELISA Kit for the Diagnosis ofTheileria annulata
Authors: Al-Hosary Amira A. T. , Ahmed Jabbar , Nordengrahn Ann , Merza Malik
Published: November 2015

The present study assesses the efficacy of SVANOVIRTheileria annulata-Ab, the first commercial ELISA kit for the diagnosis ofTheileria annulatainfection in cattle based on a recombinant protein known asT. annulatasurface protein (TaSp). As a reference test, a polymerase chain reaction (PCR) assay depending onT. annulatamerozoite surface antigen (Tams-1) was applied. A total of 468 blood samples as well as serum samples were randomly collected from cattle and tested in the PCR as well as in the ELISA developed in this study. Moreover, all samples were also analyzed by conventional Giemsa-stained blood smear. The results of this study revealed a good correlation between the results obtained by PCR and the ELISA, whereas all PCR positive samples scored correctly positive in the ELISA and 73 of the 125 PCR negative samples scored correctly negative. Taken together, a sensitivity of 91.25% and a specificity of 78.4% were recorded, when compared to the PCR data. In conclusion, the SVANOVIRTheileria annulata-Ab is a suitable diagnostic assay for use in the diagnosis and epidemiological surveys ofTheileria annulatainfection in chronic and carrier animals.
Enhanced DET-Based Fault Signature Analysis for Reliable Diagnosis of Single and Multiple-Combined Bearing Defects
Authors: Jeong In-Kyu , Kang Myeongsu , Kim Jaeyoung , Kim Jong-Myon , Ha Jeong-Min , Choi Byeong-Keun
Published: November 2015

To early identify cylindrical roller bearing failures, this paper proposes a comprehensive bearing fault diagnosis method, which consists of spectral kurtosis analysis for finding the most informative subband signal well representing abnormal symptoms about the bearing failures, fault signature calculation using this subband signal, enhanced distance evaluation technique- (EDET-) based fault signature analysis that outputs the most discriminative fault features for accurate diagnosis, and identification of various single and multiple-combined cylindrical roller bearing defects using the simplified fuzzy adaptive resonance map (SFAM). The proposed comprehensive bearing fault diagnosis methodology is effective for accurate bearing fault diagnosis, yielding an average classification accuracy of 90.35%. In this paper, the proposed EDET specifically addresses shortcomings in the conventional distance evaluation technique (DET) by accurately estimating the sensitivity of each fault signature for each class. To verify the efficacy of the EDET-based fault signature analysis for accurate diagnosis, a diagnostic performance comparison is carried between the proposed EDET and the conventional DET in terms of average classification accuracy. In fact, the proposed EDET achieves up to 106.85% performance improvement over the conventional DET in average classification accuracy.
A New Transmissibility Based Indicator of Local Variation in Structure and Its Application for Damage Detection
Authors: Li X. Z. , Peng Z. K. , Dong X. J. , Zhang W. M. , Meng G.
Published: November 2015

The presence of damage in engineering structures could usually cause local variation in stiffness or damping, and therefore it is meaningful to detect the variation as early as possible for protecting the engineering structure from serious damage. In the study, a novel method is developed to detect and locate the local variation in stiffness and damping for structures based on transmissibility. Some important properties of transmissibility are first analytically revealed and, further, a variation detection indicator is proposed to locate the variation. The effectiveness of the proposed method is verified by numerical studies and the usefulness of it is demonstrated by application for detecting crack position in beam structures. The results show that the proposed new method has better performance than the three conventional transmissibility based methods when considering different frequency bands and noise.
DistributedH∞Consensus Control of Networked Control Systems with Time-Triggered Protocol
Authors: Xie Ronghua , Fan Weihua , Chen Qingwei
Published: November 2015

The analysis and design of traditional networked control systems focused on single closed-loop scenario. This paper introduces a distributed control approach for the networked control systems (NCSs) with multiple subsystems based on a time-triggered network protocol. Firstly, some basic ideas of the time-triggered protocol are introduced and a time schedule scheme is employed for the NCS. Then, a novel model is proposed to the NCS regarding the network-induced delay. The resulting closed-loop system is time-delay linear system considering a distributed control law. A sufficient condition toH∞consensus control is present based on the Lyapunov-Krasovskii function. Also, the controller design approach towards the givenH∞performance index is given by a cone complement linearization and iterative algorithm. Finally, numerical examples are given to validate the approach.
Efficient Deep Neural Network for Digital Image Compression Employing Rectified Linear Neurons
Authors: Hussain Farhan , Jeong Jechang
Published: November 2015

A compression technique for still digital images is proposed with deep neural networks (DNNs) employing rectified linear units (ReLUs). We tend to exploit the DNNs capabilities to find a reasonable estimate of the underlying compression/decompression relationships. We aim for a DNN for image compression purpose that has better generalization property and reduced training time and support real time operation. The use of ReLUs which map more plausibly to biological neurons, makes the training of our DNN significantly faster, shortens the encoding/decoding time, and improves its generalization ability. The introduction of the ReLUs establishes an efficient gradient propagation, induces sparsity in the proposed network, and is efficient in terms of computations making these networks suitable for real time compression systems. Experiments performed on standard real world images show that using ReLUs instead of logistic sigmoid units speeds up the training of the DNN by converging markedly faster. The evaluation of objective and subjective quality of reconstructed images also proves that our DNN achieves better generalization as most of the images are never seen by the network before.
Airborne Polarimetric Remote Sensing for Atmospheric Correction
Authors: Liang Tianquan , Sun Xiaobing , Wang Han , Ti Rufang , Shu Cunming
Published: November 2015

The problem, whose targets can not be effectively identified for airborne remote sensing images, is mainly due to the atmospheric scattering effect. This problem is necessary to be overcome. According to the statistical evaluations method and the different characteristics of polarization between the objects radiance and atmospheric path radiation, a new atmospheric correction method for airborne remote sensing images was proposed. Using this new method on the airborne remote sensing images which acquired on the north coast areas of China during the haze weather, we achieved a high quality corrected atmosphere-free image. The results demonstrate the power of the method on the harbor area. The results show that the algorithm, improving image contrast and image information entropy, can effectively identify the targets after atmospheric correction. The image information entropy was enhanced from 5.59 to 6.62. The research provides a new and effective atmospheric correction technical approach for the airborne remote sensing images.
Land Use Transformation Rule Analysis in Beijing-Tianjin-Tangshan Region Using Remote Sensing and GIS Technology
Authors: Zhao Shang-min , Cheng Wei-ming , Liu Hai-jiang , Xia Yao , Chai Hui-xia , Song Yang , Zhang Wen-jie , You Tian
Published: November 2015

Based on land use classification system, this paper acquires the land use distribution status at 2000, 2005, and 2010 in Beijing-Tianjin-Tangshan Region using remote sensing images, field survey data, images in Google Earth, and visual interpretation methods. Then, the land use transformation rules from 2000 to 2010 are achieved using GIS (geographic information system) technology. The research results shows the following: (1) as to the distribution area of the land use types, dry field has the largest area, followed by forest land, building land, paddy field, water area, grassland, and unused land; (2) from 2000 to 2010, the area of building land has the largest increase, which is mainly transformed from cropland and sea reclamation area; the largest decreased land use type is paddy field, which mainly transforms to dry field and building land; (3) the high increase of building land and decrease of cropland suggest the land use transformation in the quick development process of economy; meanwhile, the total area of forestland and grassland changes little, so the ecological environment does not have apparent deterioration in the 1st decade of the new century.
Toll‐Like Receptor 4 Reduces Oxidative Injury via Glutathione Activity in Sheep
Authors: Deng Shoulong , Yu Kun , Wu Qian , Li Yan , Zhang Xiaosheng , Zhang Baolu , Liu Guoshi , Liu Yixun , Lian Zhengxing
Published: November 2015

Toll‐like receptor 4 (TLR4) is an important sensor of Gram‐negative bacteria and can trigger activation of the innate immune system. Increased activation of TLR4 can lead to the induction of oxidative stress. Herein, the pathway whereby TLR4 affects antioxidant activity was studied. In TLR4‐overexpressing sheep, TLR4 expression was found to be related to the integration copy number when monocytes were challenged with lipopolysaccharide (LPS). Consequently, production of malondialdehyde (MDA) was increased, which could increase the activation of prooxidative stress enzymes. Meanwhile, activation of an antioxidative enzyme, glutathione peroxidase (GSH‐Px), was increased. Real‐time PCR showed that expression of activating protein‐1 (AP‐1) and the antioxidative‐related genes was increased. By contrast, the expression levels of superoxide dismutase 1 (SOD1) and catalase (CAT) were reduced. In transgenic sheep, glutathione (GSH) levels were dramatically reduced. Furthermore, transgenic sheep were intradermally injected with LPS in each ear. The amounts of inflammatory infiltrates were correlated with the number of TLR4 copies that were integrated in the genome. Additionally, the translation of γ‐glutamylcysteine synthetase (γ‐GCS) was increased. Our findings indicated that overexpression of TLR4 in sheep could ameliorate oxidative injury through GSH secretion that was induced by LPS stimulation. Furthermore, TLR4 promoted γ‐GCS translation through the AP‐1 pathway, which was essential for GSH synthesis.
Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy
Authors: Picaud Sarah , Fedorov Oleg , Thanasopoulou Angeliki , Leonards Katharina , Jones Katherine , Meier Julia , Olzscha Heidi , Monteiro Octovia , Martin Sarah , Philpott Martin , Tumber Anthony , Filippakopoulos Panagis , Yapp Clarence , Wells Christopher , Che Ka Hing , Bannister Andrew , Robson Samuel , Kumar Umesh , Parr Nigel , Lee Kevin , Lugo Dave , Jeffrey Philip , Taylor Simon , Vecellio Matteo L. , Bountra Chas , Brennan Paul E. , O'Mahony Alison , Velichko Sharlene , Müller Susanne , Hay Duncan , Daniels Danette L. , Urh Marjeta , La Thangue Nicholas B. , Kouzarides Tony , Prinjha Rab , Schwaller Jürg , Knapp Stefan
Published: November 2015

The histone acetyltransferases CBP/p300 are involved in recurrent leukemia-associated chromosomal translocations and are key regulators of cell growth. Therefore, efforts to generate inhibitors of CBP/p300 are of clinical value. We developed a specific and potent acetyl-lysine competitive protein–protein interaction inhibitor, I-CBP112, that targets the CBP/p300 bromodomains. Exposure of human and mouse leukemic cell lines to I-CBP112 resulted in substantially impaired colony formation and induced cellular differentiation without significant cytotoxicity. I-CBP112 significantly reduced the leukemia-initiating potential of MLL-AF9+ acute myeloid leukemia cells in a dose-dependent manner in vitro and in vivo. Interestingly, I-CBP112 increased the cytotoxic activity of BET bromodomain inhibitor JQ1 as well as doxorubicin. Collectively, we report the development and preclinical evaluation of a novel, potent inhibitor targeting CBP/p300 bromodomains that impairs aberrant self-renewal of leukemic cells. The synergistic effects of I-CBP112 and current standard therapy (doxorubicin) as well as emerging treatment strategies (BET inhibition) provide new opportunities for combinatorial treatment of leukemia and potentially other cancers. Cancer Res; 75(23); 5106–19. ©2015 AACR.
Crosstalk of Various Biomarkers That Might Provide Prompt Identification of Acute or Chronic Cardiorenal Syndromes
Authors: Tasić Danijela , Radenkovic Sonja , Stojanovic Dijana , Milojkovic Maja , Stojanovic Miodrag , Deljanin Ilic Marina , Kocic Gordana
Published: November 2015

Introduction: Pathophysiological interaction between the heart and kidneys represents the basis for clinical entities called cardiorenal syndromes. The purpose of the study was to assess the relations between acute and chronic cardiorenal syndromes and biomarkers [advanced oxidation protein products, brain natriuretic peptide, malondialdehyde, xanthine oxidoreductase (XOD), xanthine oxidase, xanthine dehydrogenase, interleukin 8, cystatin C, plasminogen activator inhibitor-1, high-sensitive troponin T, C-reactive protein and glomerular filtration rate, measured by the Modification of Diet in Renal Disease (MDRD) formula], to hypothesize biomarkers that might provide a prompt identification of acute or chronic cardiorenal syndromes, and to distinguish acute versus chronic types of these syndromes. Methods: A total of 114 participants were enrolled in this study, i.e. 79 patients divided into subgroups of acute and chronic cardiorenal syndromes and 35 volunteers. Results: Nonadjusted odds ratio (OR) showed that there was a significant risk for acute cardiorenal syndrome with increased XOD activity (p = 0.037), elevated cystatin C concentration (p = 0.038) and MDRD (p = 0.028). Multivariable adjusted OR, on the other hand, revealed that only glomerular filtration rate measured by the MDRD formula had a significance for acute cardiorenal syndrome (p = 0.046). Nonadjusted OR showed a significant risk for chronic cardiorenal syndrome only in elderly (p = 0.002). Multivariable adjusted OR exhibited that age was the only risk factor for chronic cardiorenal syndrome (p = 0.012). Conclusion: Cystatin C, glomerular filtration rate measured by the MDRD equation and XOD were independent risk factors for acute cardiorenal syndrome, while age remained an independent risk factor for chronic cardiorenal syndrome. When comparing ORs of evaluated parameters, the highest significance for acute cardiorenal syndrome was plasma concentration of cystatin C.
Metamorphopsia: An Overlooked Visual Symptom
Authors: Midena Edoardo , Vujosevic Stela
Published: November 2015

Metamorphopsia is a common symptom in different macular disorders. Micropsia and macropsia are special types of metamorphopsia. Recent theories suggest that both retinal and cortical mechanisms are involved in the development and changes of metamorphopsia. Different functional tests have been proposed for the evaluation of metamorphopsia: from the Amsler grid to the hand-held mobile devices for home monitoring. This review addresses some new insights into the pathophysiology of metamorphopsia and different available tests for the evaluation of this symptom in most common macular disorders. The importance of quantification of metamorphopsia in macular diseases is confirmed by the most recent therapeutic approaches.
Genetic Testing Awareness and Attitudes among Latinos: Exploring Shared Perceptions and Gender-Based Differences
Authors: Hamilton Jada G. , Shuk Elyse , Arniella Guedy , González C. Javier , Gold Geoffrey S. , Gany Francesca , Robson Mark E. , Hay Jennifer L.
Published: November 2015

Background: Latinos, whose views are infrequently examined in genomic research, may be at risk of missing out on the benefits of genomic medicine. Aims: To explore this possibility, we conducted a qualitative study of awareness and attitudes about genetic testing among Latinos with lower acculturation in New York City. Methods: We conducted four focus groups (7 English-speaking men, 5 Spanish-speaking men, 13 English-speaking women and 13 Spanish-speaking women) to explore factors that influence the adoption of new innovations through the discussion of genetic testing in general, and a hypothetical vignette describing a genetic test for skin cancer risk, in particular. Results: Through inductive thematic text analysis of focus group transcripts, our multidisciplinary team identified themes within knowledge and attitudes, communication and sources of information, anticipated responses, factors that may increase adoption, and barriers to adoption of genetic testing. Specifically, a majority of participants expressed some degree of uncertainty regarding the purpose of genetic tests and information these tests provide, rarely discussed genetic testing with others in their social networks, and expressed concerns about the misuse of and possible adverse emotional responses to genetic information. However, participants also expressed high levels of interest in receiving a skin cancer genetic test in response to the vignette and believed that receiving actionable health information was a primary reason to consider testing. Gender-based differences in perceived barriers to testing emerged. Conclusions: The results highlight beliefs and barriers that future interventions could target to help ensure that Latinos have adequate understanding of and access to genomic medicine advances.
Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box?
Authors: Lawler Mark , Sullivan Richard
Published: November 2015

Cancer clinical trials have been one of the key foundations for significant advances in oncology. However, there is a clear recognition within the academic, care delivery and pharmaceutical/biotech communities that our current model of clinical trial discovery and development is no longer fit for purpose. Delivering transformative cancer care should increasingly be our mantra, rather than maintaining the status quo of, at best, the often miniscule incremental benefits that are observed with many current clinical trials. As we enter the era of precision medicine for personalised cancer care (precision and personalised medicine), it is important that we capture and utilise our greater understanding of the biology of disease to drive innovative approaches in clinical trial design and implementation that can lead to a step change in cancer care delivery. A number of advances have been practice changing (e.g. imatinib mesylate in chronic myeloid leukaemia, Herceptin in erb-B2-positive breast cancer), and increasingly we are seeing the promise of a number of newer approaches, particularly in diseases like lung cancer and melanoma. Targeting immune checkpoints has recently yielded some highly promising results. New algorithms that maximise the effectiveness of clinical trials, through for example a multi-stage, multi-arm type design are increasingly gaining traction. However, our enthusiasm for the undoubted advances that have been achieved are being tempered by a realisation that these new approaches may have significant cost implications. This article will address these competing issues, mainly from a European perspective, highlight the problems and challenges to healthcare systems and suggest potential solutions that will ensure that the cost/value rubicon is addressed in a way that allows stakeholders to work together to deliver optimal cost-effective cancer care, the benefits of which can be transferred directly to our patients.
Hemodynamic, Functional, and Clinical Responses to Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension of Different Causes
Authors: Chen Shao-Liang , Zhang Hang , Xie Du-Jiang , Zhang Juan , Zhou Ling , Rothman Alexander M.K. , Stone Gregg W.
Published: November 2015

Background—

The mechanisms underlying pulmonary arterial hypertension (PAH) are multifactorial. The efficacy of pulmonary artery denervation (PADN) for idiopathic PAH treatment has been evaluated. This study aimed to analyze the hemodynamic, functional, and clinical responses to PADN in patients with PAH of different causes.

Methods and Results—

Between April 2012 and April 2014, 66 consecutive patients with a resting mean pulmonary arterial pressure ≥25 mm Hg treated with PADN were prospectively followed up. Target drugs were discontinued after the PADN procedure. Hemodynamic response and 6-minute walk distance were repeatedly measured within the 1 year post PADN follow-up. The clinical end point was the occurrence of PAH-related events at the 1-year follow-up. There were no PADN-related complications. Hemodynamic success (defined as the reduction in mean pulmonary arterial pressure by a minimal 10% post PADN) was achieved in 94% of all patients, with a mean absolute reduction in systolic pulmonary arterial pressure and mean pulmonary arterial pressure within 24 hours of −10 mm Hg and −7 mm Hg, respectively. The average increment in 6-minute walk distance after PADN was 94 m. Worse PAH-related events occurred in 10 patients (15%), mostly driven by the worsening of PAH (12%). There were 8 (12%) all-cause deaths, with 6 (9%) PAH-related deaths.

Conclusions—

PADN was safe and feasible for the treatment of PAH. The PADN procedure was associated with significant improvements in hemodynamic function, exercise capacity, and cardiac function and with less frequent PAH-related events and death at 1 year after PADN treatment. Further randomized studies are required to confirm the efficacy of PADN for PAH.

Clinical Trial Registration—

URL:
http://www.chictr.trc.com.cn
. Unique identifier: chiCTR-ONC-12002085.
Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome
Authors: Eisenberg Mark J. , Windle Sarah B. , Roy Nathalie , Old Wayne , Grondin François R. , Bata Iqbal , Iskander Ayman , Lauzon Claude , Srivastava Nalin , Clarke Adam , Cassavar Daniel , Dion Danielle , Haught Herbert , Mehta Shamir R. , Baril Jean-François , Lambert Charles , Madan Mina , Abramson Beth L. , Dehghani Payam
Published: November 2015

Background—

Less than one-third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS.

Methods and Results—

We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline or placebo for 12 weeks. All patients received low-intensity counseling. The primary end point was point-prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. A total of 302 patients were randomized (mean age 55±9 years; 75% male; 56% ST-segment elevation myocardial infarction; 38% non-ST-segment elevation myocardial infarction; 6% unstable angina). Patients smoked a mean of 21±11 cigarettes/d at the time of hospitalization and had been smoking for a mean of 36±12 years. At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. Point-prevalence abstinence rates were 47.3% in the varenicline group and 32.5% in the placebo group (
P
=0.012; number needed to treat=6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively (
P
=0.081; number needed to treat=10.0), and rates of reduction ≥50% in daily cigarette consumption were 67.4% and 55.6%, respectively (
P
=0.05; number needed to treat=8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.9%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%).

Conclusions—

Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation. Future studies are needed to establish safety in these patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00794573.
Association of Left Ventricular Hypertrophy With a Faster Rate of Renal Function Decline in Elderly Patients With Non‐End‐Stage Renal Disease
Authors: Shi Hong‐tao , Wang Xiao‐jing , Li Jun , Song Gui‐fang , Huang Zhe‐yong , Guo Xiang‐yu , Guo Jun‐jie , Lv Zhi‐yang , Li Hong‐wei , Ge Jun‐bo , Cui Jie , Qi Guan‐ming
Published: November 2015

Background

Several studies have indicated that chronic kidney disease is independently associated with the presence of left ventricular hypertrophy (
LVH
). However, little clinical data are currently available regarding the detailed correlation between
LVH
and renal function in elderly patients with non–end‐stage renal disease.

Methods and Results

A total of 300 in‐ and outpatients (more than 60 years of age, non‐end‐stage renal disease), 251 with
LVH
and 49 without
LVH
, seen at Beijing Friendship Hospital from January 2000 to December 2010 were included in this retrospective study. One observation period of 12 months was used to detect rapid kidney function decline. The evaluations of cardiac structure and function were performed via echocardiography. The multivariable logistic analysis showed patients with
LVH
had a much higher risk of rapid kidney function decline than those without
LVH
. Additionally, the baseline left ventricular mass index was 140 (125–160) g/m
2
in the non–chronic kidney disease group, 152 (130–175) g/m
2
in the mild chronic kidney disease group (estimated glomerular filtration rate (eGFR)≥60 ml/min/1.73 m
2
), and 153 (133–183) g/m
2
in the severe chronic kidney disease group (eGFR<60 ml/min/1.73 m
2
), with a significant difference (
P
=0.009).

Conclusions

Our data demonstrate that a high rate of renal function decline contributes to pathological
LVH
in non–end‐stage renal disease elderly patients and that
LVH
is positively associated with renal function decline followed by an increased risk of rapid kidney function decline.
Neoalloionema tricaudatum gen. n., sp. n. (Nematoda: Alloionematidae) associated with a cyclophorid snail in Cuc Phuong Natural Park, Vietnam
Authors: Ivanova Elena , Luc Pham Van , Spiridonov Sergei
Published: November 2015

A new nematode genus and species associated with terrestrial gastropods from Vietnam is described and illustrated. Partial SSU and ITS rDNA sequences were obtained and subjected to phylogenetic analysis. Both morphologically and molecularly,Neoalloionema tricaudatumgen. n., sp. n. is closest toAlloionemaappendiculatum, another gastropod associate. It is differentiated fromA. appendiculatumby the presence of an outstretchedvsreflexed testis and the absence of denticles in the stoma, by the parasitic juveniles inhabiting the pallial cavityvsthe foot of the host and having sixvstwo lips and large sucker-like phasmidsvspore-like. The most peculiar feature ofN. tricaudatumgen. n., sp. n. is the presence of paired, solid appendages located at the mid-tail region of juveniles from the pallial cavity of the host. The nature of the association betweenN. tricaudatumgen. n., sp. n. and its gastropod host is discussed.
From Antithesis to Synthesis
Authors: Sutanto Nathaniel Gray
Published: November 2015

Recent scholarship further substantiates the observation that Cornelius Van Til depends on Herman Bavinck for his own constructive efforts. This observation creates a stimulus for comparative studies on the two theologians. In this essay I offer one such comparison by tracing an antithesis-synthesis strategy present in both Bavinck and Van Til. Though they share a motivation from the doctrine of common grace, the two theologians apply the strategy in distinct (though related) ways: Bavinck applies it for theological construction in a manner symbiotic with his organic ontology, while Van Til develops it into a self-consciously transcendental mode of reasoning and apologetics. This observation gives us insights as to why both theologians have been received (and misinterpreted) in similar ways, and that Van Til, though deeply dependent and influenced by Bavinck, developed Bavinck’s synthetic tendencies in ways that Bavinck did not do.
The Reformed Stance
Authors: van den Brink Gijsbert , Smits Johan
Published: November 2015

This article attempts to answer the question what makes a particular theology “Reformed”. First of all, three fairly common ways to answer this question are criticized as being reductionist. Over against such attempts, the authors emphasize the plurality of Reformed theology. Next, however, drawing on a concept introduced by philosopher of science Bas van Fraassen, they argue that Reformed theology can still be described as a distinct phenomenon when it is approached as a stance, i.e. as a particular outlook characterized by specific commitments and concerns, rather than as a unique set of propositional beliefs. Finally, it is argued that many of the concerns and commitments that are typical of Reformed theology can be loosely derived from the traditional Reformed adage ecclesia reformata quia semper reformanda secundum verbum Dei.
Lecanicillium sabanense sp. nov. (Cordycipitaceae) a new fungal entomopathogen of coccids
Authors: Chiriví-Salomón Juan S , Danies Giovanna , Restrepo Silvia , Sanjuan Tatiana
Published: November 2015

A new species of Lecanicillium was found associated with the soft scale insect Pulvinaria caballeroramosae (Coccidae), an important pest of Ficus soatensis (Moraceae) in Bogotá, Colombia. Lecanicillium sabanense sp. nov. differs from similar Lecanicillium spp. mainly in the size of the conidia, in the vertical arrangement of phialides on the host, and in the tomentose mycelium that sparsely covers the cuticle of the host. Phylogenetic analyses using ITS, SSU, LSU, TEF, RPB1, and RPB2 also confirmed the distinctness of this new species. Fungal epizootics were found on female soft scale insects, which may have implications for biological control in the forestry program of the city. The ecology of the fungus as well as its potential use as a biological control agent are further discussed.