bluuebunny/crossref_metadata_2025 huggingface dataset:
Fault-Tolerant Control Strategy for Neutral-Point-Clamped Three-Level Inverter
Authors: Shen Yanxia , Miao Beibei , Wu Dinghui , Ali Ibrahim Kader
Published: February 2018

A fault-tolerant control technique is discussed for the Neutral-Point-Clamped (NPC) three-level inverter, which ensures that the NPC inverter operates normally even under device failures. A two-level leg is added to the NPC inverter; when the device open circuit fault occurs, the load of this faulty phase is connected to the neutral point of this two-level leg through the bidirectional thyristors. An improved Space Vector Pulse Width Modulation (SVPWM) strategy called “addition and subtraction substitution SVPWM” is proposed to effectively suppress fluctuation in capacitor neutral-point voltages by readjusting the sequence and action time of voltage vectors. The fault-tolerant topology in this paper has the advantages of fewer switching devices and lower circuit costs. Experimental results show that the proposed fault-tolerant system can operate in balance of capacitor neutral-point voltages at full output power and the reliability of the inverter is greatly enhanced.
Research Advances in the Correlation between Peroxisome Proliferator-Activated Receptor-γ and Digestive Cancers
Authors: Xu Shuqi , Xu Xuanfu
Published: February 2018

Peroxisome proliferator-activated receptor-γ (PPARγ) is a class of ligand-activated nuclear transcription factors, which is a member of type II nuclear receptor superfamily. Previous studies demonstrate that PPARγ is expressed in a variety of tumor tissues and is closely associated with the proliferation and prognosis of digestive system tumors by its roles in mediation of cell differentiation, induction of cell apoptosis, and inhibition of cell proliferation.
A Novel Polymorphism in the Promoter of theCYP4A11Gene Is Associated with Susceptibility to Coronary Artery Disease
Authors: Sirotina Svetlana , Ponomarenko Irina , Kharchenko Alexander , Bykanova Marina , Bocharova Anna , Vagaytseva Kseniya , Stepanov Vadim , Churnosov Mikhail , Solodilova Maria , Polonikov Alexey
Published: February 2018

Enzymes CYP4A11 and CYP4F2 are involved in biosynthesis of vasoactive 20-hydroxyeicosatetraenoic acid and may contribute to pathogenesis of coronary artery disease (CAD). We investigated whether polymorphisms of theCYP4A11andCYP4F2genes are associated with the risk of CAD in Russian population. DNA samples from 1323 unrelated subjects (637 angiographically confirmed CAD patients and 686 age- and sex-matched healthy individuals) were genotyped for polymorphisms rs3890011, rs9332978, and rs9333029 ofCYP4A11and rs3093098 and rs1558139 ofCYP4F2by using the Mass-ARRAY 4 system. SNPs rs3890011 and rs9332978 ofCYP4A11were associated with increased risk of CAD in women: OR = 1.26, 95% CI: 1.02–1.57,P=0.004, andQ=0.01and OR = 1.45, 95% CI: 1.13–1.87,P=0.004, andQ=0.01, respectively. Haplotype G-C-A ofCYP4A11was associated with increased risk of CAD (adjusted OR = 1.41, 95% CI: 1.12–1.78, andP=0.0036). Epistatic interactions were found between rs9332978 ofCYP4A11and rs1558139 ofCYP4F2(Pinteraction=0.025). In silico analysis allowed identifying that SNP rs9332978 is located at a binding site for multiple transcription factors; many of them are known to regulate the pathways involved in the pathogenesis of CAD. This is the first study in Europeans that reported association between polymorphism rs9332978 ofCYP4A11and susceptibility to coronary artery disease.
Portulaca Extract Attenuates Development of Dextran Sulfate Sodium Induced Colitis in Mice through Activation of PPARγ
Authors: Kong Rui , Luo Hui , Wang Nan , Li Jingjing , Xu Shizan , Chen Kan , Feng Jiao , Wu Liwei , Li Sainan , Liu Tong , Lu Xiya , Xia Yujing , Shi Yanhong , Zhou Yingqun , He Weigang , Dai Qi , Zheng Yuejuan , Lu Jie
Published: February 2018

Portulaca oleracea L. is a traditional Chinese medicine, which has been used as adjuvant therapy for inflammatory bowel disease (IBD). However, the mechanism of its activity in IBD still remains unclear. Since previous studies have documented the anti-inflammatory effect of peroxisome proliferator activated receptors-γ (PPAR-γ), Portulaca regulation of PPAR-γ in inflammation was examined in current study. Ulcerative colitis (UC) was generated by 5% dextran sulfate sodium (DSS) in mice and four groups were established as normal control, DSS alone, DSS plus mesalamine, and DSS plus Portulaca. Severity of UC was evaluated by body weight, stool blood form, and length of colorectum. Inflammation was examined by determination of inflammatory cytokines (TNF-a, IL-6, and IL-1a). Portulaca extract was able to attenuate development of UC in DSS model similar to the treatment of mesalazine. Moreover, Portulaca extract inhibited proinflammatory cytokines release and reduced the level of DSS-induced NF-κB phosphorylation. Furthermore, Portulaca extract restored PPAR-γ level, which was reduced by DSS. In addition, Portulaca extract protected DSS induced apoptosis in mice. In conclusion, Portulaca extract can alleviate colitis in mice through regulation of inflammatory reaction, apoptosis, and PPAR-γ level; therefore, Portulaca extract can be a potential candidate for the treatment of IBD.
Calibration of the Absolute Efficiency of Well-Type NaI(Tl) Scintillation Detector in 0.121–1.408 MeV Energy Range
Authors: Al Oraini Dalal
Published: February 2018

Well-type NaI(Tl) detectors are beneficial for low-level photon activity measurements because of the near 4π solid angle that can be gained with them. The detection efficiency can differ with the source-to-detector system geometries, the absorption of the photon in the detector material, and attenuation layers in front of the detector face. For these purposes, the absolute efficiency and the coincidence corrections of the well-type sodium iodide detector have been measured at 0.121–1.408 MeV energy range (obtained from 152Eu, 137Cs, and 60Co radioactive isotopes). The covenant between the experimental (present work) and the published theoretical values is good, with the high discrepancies being less than 1%.
Mathematical Modeling of the Adaptive Immune Responses in the Early Stage of the HBV Infection
Authors: Allali Karam , Meskaf Adil , Tridane Abdessamad
Published: February 2018

The aim of this paper is to study the early stage of HBV infection and impact delay in the infection process on the adaptive immune response, which includes cytotoxic T-lymphocytes and antibodies. In this stage, the growth of the healthy hepatocyte cells is logistic while the growth of the infected ones is linear. To investigate the role of the treatment at this stage, we also consider two types of treatment: interferon-α(IFN) and nucleoside analogues (NAs). To find the best strategy to use this treatment, an optimal control approach is developed to find the possibility of having a functional cure to HBV.
Acquired Elliptocytosis as a Manifestation of Myelodysplastic Syndrome Associated with Deletion of Chromosome 20q
Authors: Manthri Sukesh , Vasireddy Naresh K. , Bandaru Sindhura , Pathak Swati
Published: February 2018

Elliptocytosis is commonly seen as a hereditary condition. We present a case of myelodysplastic syndrome (MDS) del(q20) variant with concomitant acquired elliptocytosis. A 73-year-old male with a history of prostate cancer presented to the hospital for evaluation of bleeding gums. Initial evaluation showed Hgb of 9.3 gm/dl, hematocrit of 28%, platelet count of 36,000 K/cmm, and WBC of 1.8 K/cmm with an ANC of 0.8 K/cmm. A slightly elevated bilirubin of 1.2 mg/dl spurred a hemolytic workup. Peripheral smear showed frequent elliptocytes, teardrop cells, schistocytes, and occasional spherocytes. Bone marrow biopsy did not show significant fibrosis to explain the elliptocytosis. Cytogenetics showed 20q deletion, and later, he was started on therapy for intermediate risk MDS. Bone marrow biopsy after completion of 6 cycles showed complete cytogenetic remission with significant improvement in elliptocytosis. Elliptocytosis in the setting of MDS has rarely been reported, and association with 20q deletion is even rarer. Animal studies have shown that haploinsufficiency ofL3MBTL1contributes to some (20q−) myeloproliferative neoplasms and myelodysplastic syndromes by affecting erythroid differentiation. Our case report raises interesting questions: Does MDS with rarely reported elliptocytosis indicate a disease process that is different from the usual 20q deletion? Is haploinsufficiency ofL3MBTL1responsible for this manifestation?
Laparoscopic Management of Adhesions Developed after Peritoneal Nonclosure in Primary Cesarean Section Delivery
Authors: Seyam Emaduldin , Ibrahim Emad Moussa , Youseff Ayman Moheb , Khalifa Eissa M. , Hefzy Enas
Published: February 2018

Objective. The aim of the current study was to laparoscopically investigate the effects of peritoneal nonclosure on the sites, types, and degrees of adhesions developed after primary caesarean section (CS) in women complaining of secondary infertility after first CS delivery. Study Design. This was a cross-sectional study, where 250 women suffering from secondary infertility after their first CS had been recruited. They had been classified into group I (n = 89), where both the visceral and parietal peritoneum had been left opened; group II (n = 75), where only the parietal peritoneum had been closed; and group III (n = 86), where both peritoneal layers had been closed. Laparoscopy had been used to classify those adhesions according to the location, severity, and their adverse impact on the reproductive capacity. Results. Both adnexal and nonadnexal adhesions had been found significantly higher in group I, while adnexal types of adhesions were significantly higher after nonclosure of the visceral peritoneum in group II. Laparoscopic tubal surgery performed included tubo-ovariolysis, fimbrioplasty, and neosalpingostomy. Pregnancy rate was found correlating with the adnexal adhesion location and score. Conclusion. Nonclosure of the peritoneum in CS is associated with more adhesion formation, which might adversely affect the future women reproduction.
A Novel Covert Agent for Stealthy Attacks on Industrial Control Systems Using Least Squares Support Vector Regression
Authors: Li Weize , Xie Lun , Wang Zhiliang
Published: February 2018

Research on stealthiness has become an important topic in the field of data integrity (DI) attacks. To construct stealthy DI attacks, a common assumption in most related studies is that attackers have prior model knowledge of physical systems. In this paper, such assumption is relaxed and a covert agent is proposed based on the least squares support vector regression (LSSVR). By estimating a plant model from control and sensory data, the LSSVR-based covert agent can closely imitate the behavior of the physical plant. Then, the covert agent is used to construct a covert loop, which can keep the controller’s input and output both stealthy over a finite time window. Experiments have been carried out to show the effectiveness of the proposed method.
Efficient OCT Image Enhancement Based on Collaborative Shock Filtering
Authors: Liu Guohua , Wang Ziyu , Mu Guoying , Li Peijin
Published: February 2018

Efficient enhancement of noisy optical coherence tomography (OCT) images is a key task for interpreting them correctly. In this paper, to better enhance details and layered structures of a human retina image, we propose a collaborative shock filtering for OCT image denoising and enhancement. Noisy OCT image is first denoised by a collaborative filtering method with new similarity measure, and then the denoised image is sharpened by a shock-type filtering for edge and detail enhancement. For dim OCT images, in order to improve image contrast for the detection of tiny lesions, a gamma transformation is first used to enhance the images within proper gray levels. The proposed method integrating image smoothing and sharpening simultaneously obtains better visual results in experiments.
Simple and Selective HPLC-UV/Vis Bioanalytical Method to Determine Aluminum Phthalocyanine Chloride in Skin Permeation Studies
Authors: Reis Thaiene Avila , Jaculi Ana Elise , Alves Rubens da Costa , Gratieri Tais , Azevedo Ricardo Bentes , Joanitti Graziella Anselmo , Gelfuso Guilherme Martins , Cunha-Filho Marcilio
Published: February 2018

Considering the feasibility of the aluminum phthalocyanine chloride (AlPcCl) application in the topical photodynamic therapy of cutaneous tumors and the lack of HPLC methods capable of supporting skin permeation experiments using this compound, the aim of this study was to obtain a simple and selective chromatographic method for AlPcCl determination in skin matrices. A HPLC-UV/Vis method was developed using a normal-phase column operating at 30°C, an isocratic mobile phase of methanol : phosphoric acid (0.01 M) at 1.5 mL/min, and detection at 670 nm. The method exhibited (i) selectivity against various contaminants found in the different skin layers, (ii) high drug extraction capacity from the hair follicle (>70%) and remaining skin (>80%), and (iii) low limits of detection and of quantification (0.03 and 0.09 μg/mL, resp.). The method was also linear in the range from 0.1 to 5.0 µg/mL (r = 0.9994) and demonstrated robustness with regard to experimental chromatographic parameters according to a factorial design. Lastly, the developed method was successfully tested in in vitro skin permeation studies of AlPcCl, proving its effectiveness in the development of pharmaceutical delivery systems containing this drug for topical photodynamic therapy of skin cancers.
The Ferroelectric Domain Structures Induced by Electron Beam Scanning in Lithium Niobate
Authors: Vlasov Evgeny , Chezganov Dmitry , Chuvakova Maria , Shur Vladimir Ya.
Published: February 2018

Ferroelectric domain structure has been formed under the action of electron beam scanning in congruent lithium niobate single crystal covered by surface dielectric layer. The obtained types of the domain patterns have been considered as subsequent stages of domain structure evolution. The dependence on irradiated charge density of domain density, length, and period of domain rays and stripe domain width was used for characterization of the domain structure evolution. The threshold irradiated charge density necessary for the formation of solid stripe domain has been revealed. All obtained results have been discussed in terms of kinetic approach based on the analogy between domain structure evolution and first-order phase transition.
Retroperitoneal Lymph Node Dissection as Primary Treatment for Metastatic Seminoma
Authors: Hu Brian , Daneshmand Siamak
Published: February 2018

Reducing the long-term morbidity in testicular cancer survivors represents a major area of interest. External beam radiation therapy and systemic chemotherapy are established treatments for seminoma; however, they are associated with late toxicities such as cardiovascular disease, insulin resistance, and secondary malignancy. Retroperitoneal lymph node dissection (RPLND) is a standard treatment for nonseminomatous germ cell tumors (NSGCT) that has minimal long-term morbidity. Given the efficacy of RPLND in management of NSGCT, interest has developed in this surgery as a front-line treatment for seminoma with isolated lymph node metastasis to the retroperitoneum. Four retrospective studies have shown promising results when surgery is performed for seminomas with low-volume retroperitoneal metastases. To better determine if RPLND can be recommended as a primary treatment option, two prospective clinical trials (SEMS and PRIMETEST) are underway. This review will examine the literature, discuss the benefits/limitations of RPLND, and compare the methodologies of the two ongoing clinical trials.
Scaffolds for Pelvic Floor Prolapse: Logical Pathways
Authors: Bissoli Julio , Bruschini Homero
Published: February 2018

Pelvic organ prolapse (POP) has borrowed principles of treatment from hernia repair and in the last two decades we saw reinforcement materials to treat POP with good outcomes in terms of anatomy but with alarming complication rates. Polypropylene meshes to specifically treat POP have been withdrawn from market by manufactures and a blank space was left to be filled with new materials. Macroporous monofilament meshes are ideal candidates and electrospinning emerged as a reliable method capable of delivering production reproducibility and customization. In this review, we point out some pathways that seem logical to be followed but have been only researched in last couple of years.
Orlicz Mean Dual Affine Quermassintegrals
Authors: Zhao Chang-Jian , Cheung Wing-Sum
Published: February 2018

Our main aim is to generalize the mean dual affine quermassintegrals to the Orlicz space. Under the framework of dual Orlicz-Brunn-Minkowski theory, we introduce a new affine geometric quantity by calculating the first Orlicz variation of the mean dual affine quermassintegrals and call it the Orlicz mean dual affine quermassintegral. The fundamental notions and conclusions of the mean dual affine quermassintegrals and the Minkowski and Brunn-Minkowski inequalities for them are extended to an Orlicz setting. The related concepts and inequalities of dual Orlicz mixed volumes are also included in our conclusions. The new Orlicz isoperimetric inequalities in special case yield theLp-dual Minkowski inequality and Brunn-Minkowski inequality for the mean dual affine quermassintegrals, which also imply the dual Orlicz-Minkowski inequality and dual Orlicz-Brunn-Minkowski inequality.
Synthesis of a Cationic Polyacrylamide under UV Initiation and Its Flocculation in Estrone Removal
Authors: Sun Jiaoxia , Ma Xiqin , Li Xiang , Fan Jianxin , Chen Qingkong , Liu Xuelian , Pan Jin
Published: February 2018

A ternary cationic polyacrylamide (CPAM) with the hydrophobic characteristic was prepared through ultraviolet- (UV-) initiated polymerization technique for the estrone (E1) environmental estrogen separation and removal. The monomers of acrylamide (AM), acryloyloxyethyl-trimethyl ammonium chloride (DAC), and acryloyloxyethyl dimethylbenzyl ammonium chloride (AODBAC) were used to synthesize the ternary copolymer (PADA). Fourier transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance spectroscopy (1H NMR), thermogravimetry/differential scanning calorimetry (TG/DSC), and scanning electron microscopy (SEM) were employed to characterize the structure, thermal decomposition property, and morphology of the polymers, respectively. FT-IR and 1H NMR results indicated the successful formation of the polymers. Besides, with the introduction of hydrophobic groups (phenyl group), an irregular and porous surface morphology and a favorable thermal stability of the PADA were observed by SEM and TG/DSC analyses, respectively. At the optimal condition (pH = 7, flocculant dosage = 4.0 mg/L and E1 concentration = 0.75 mg/L), an excellent E1 flocculation performance (E1 removal rate: 90.1%, floc size: 18.3 μm, and flocculation kinetics: 22.69×10-4 s−1) was acquired by using the efficient flocculant PADA-3 (cationic degree = 40%, and intrinsic viscosity = 6.30 dL·g−1). The zeta potential and floc size analyses were used to analyze the possible flocculation mechanism for the E1 removal. Results indicated that the charge neutralization, adsorption, and birding effects were dominant in the E1 removal progress.
Surgical Management of a Giant Adrenal Pseudocyst: A Case Report and Review of the Literature in the Last Decade
Authors: Paramythiotis Daniel , Bangeas Petros , Karakatsanis Anestis , Goulas Patroklos , Nikolaou Irini , Rafailidis Vasileios , Kouskouras Konstantinos , Papadopoulos Vasileios , Lypiridou Sofia , Karayannopoulou Georgia , Michalopoulos Antonios
Published: February 2018

Adrenal pseudocysts are rare entities and occurred in the 5th and the 6th decades of life. They are discovered accidentally, while appearing with nonspecific clinical and imaging findings. We report a case of a 28-year-old woman presented in our Emergency Department complaining about upper abdomen pain. Computed tomography revealed a hypodense cystic lesion containing hyperdense material. The size of a mass was 11. 7 × 9.3 × 6.6 cm in diameter close to the pancreas, but the origin was from the left adrenal gland. The mass was excised with surgical laparotomy. Giant adrenal pseudocysts are rare entities. Final diagnosis usually confirmed with the pathology examination. Management of such adrenal lesions depends on the unique characteristics, the surgeon’s experience, and local resources.
Circuit Implementation, Synchronization of Multistability, and Image Encryption of a Four-Wing Memristive Chaotic System
Authors: Peng Guangya , Min Fuhong , Wang Enrong
Published: February 2018

The four-wing memristive chaotic system used in synchronization is applied to secure communication which can increase the difficulty of deciphering effectively and enhance the security of information. In this paper, a novel four-wing memristive chaotic system with an active cubic flux-controlled memristor is proposed based on a Lorenz-like circuit. Dynamical behaviors of the memristive system are illustrated in terms of Lyapunov exponents, bifurcation diagrams, coexistence Poincaré maps, coexistence phase diagrams, and attraction basins. Besides, the modular equivalent circuit of four-wing memristive system is designed and the corresponding results are observed to verify its accuracy and rationality. A nonlinear synchronization controller with exponential function is devised to realize synchronization of the coexistence of multiple attractors, and the synchronization control scheme is applied to image encryption to improve secret key space. More interestingly, considering different influence of multistability on encryption, the appropriate key is achieved to enhance the antideciphering ability.
Strategy Evaluation for Cavity Flooding during an ESBO Initiated Severe Accident
Authors: Jiang Nan , Peng Minjun , Wei Wei , Cong Tenglong
Published: February 2018

Intentional depressurization and cavity flooding are two important measures in current severe accident management guidelines (SAMGs). An extreme scenario of an extended station blackout (ESBO), when electric power is unavailable for more than 24 hours, actually occurred in the Fukushima Daiichi accident and attracted lots of attention. In an ESBO, the containment spray cannot be activated for condensation, and, thus, cavity flooding will generate a large amount of steam, which, ironically, overpressurizes the containment to failure before the reactor vessel is melted through. Therefore, consideration of these conflicting issues and the ways in which plants operate is crucial for strengthening the strategies outlined in SAMGs. In this paper, the effects of intentional depressurization and cavity flooding in an ESBO for a representative 900 MW second-generation pressurized water reactor (PWR) are simulated with MAAP4 code. Diverse scenarios with different starting times of depressurization and water injection are also compared to summarize the positive and negative impacts for accident mitigation. The phenomena associated with creep ruptures, hydrogen combustion, corium stratification, and cavity boiling are also analyzed in detail to strengthen our understanding of severe accident mechanisms. The results point out the facility limitations of second-generation PWRs which can improve existing SAMGs.
Global Sensitivity Analysis of High Speed Shaft Subsystem of a Wind Turbine Drive Train
Authors: Asadi Saeed , Berbyuk Viktor , Johansson Håkan
Published: February 2018

The wind turbine dynamics are complex and critical area of study for the wind industry. Quantification of the effective factors to wind turbine performance is valuable for making improvements to both power performance and turbine health. In this paper, the global sensitivity analysis of validated mathematical model for high speed shaft drive train test rig has been developed in order to evaluate the contribution of systems input parameters to the specified objective functions. The drive train in this study consists of a 3-phase induction motor, flexible shafts, shafts’ coupling, bearing housing, and disk with an eccentric mass. The governing equations were derived by using the Lagrangian formalism and were solved numerically by Newmark method. The variance based global sensitivity indices are introduced to evaluate the contribution of input structural parameters correlated to the objective functions. The conclusion from the current research provides informative beneficial data in terms of design and optimization of a drive train setup and also can provide better understanding of wind turbine drive train system dynamics with respect to different structural parameters, ultimately designing more efficient drive trains. Finally, the proposed global sensitivity analysis (GSA) methodology demonstrates the detectability of faults in different components.
microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer
Authors: Bhagirath Divya , Yang Thao Ly , Bucay Nathan , Sekhon Kirandeep , Majid Shahana , Shahryari Varahram , Dahiya Rajvir , Tanaka Yuichiro , Saini Sharanjot
Published: February 2018

Because of high heterogeneity, molecular characterization of prostate cancer based on biopsy sampling is often challenging. Hence, a minimally invasive method to determine the molecular imprints of a patient's tumor for risk stratification would be advantageous. In this study, we employ a novel, digital amplification-free quantification method using the nCounter technology (NanoString Technologies) to profile exosomal serum miRNAs (ex-miRNA) from aggressive prostate cancer cases, benign prostatic hyperplasia, and disease-free controls. We identified several dysregulated miRNAs, one of which was the tumor suppressor miR-1246. miR-1246 was downregulated in prostate cancer clinical tissues and cell lines and was selectively released into exosomes. Overexpression of miR-1246 in a prostate cancer cell line significantly inhibited xenograft tumor growth in vivo and increased apoptosis and decreased proliferation, invasiveness, and migration in vitro. miR-1246 inhibited N-cadherin and vimentin activities, thereby inhibiting epithelial–mesenchymal transition. Ex-miR-1246 expression correlated with increasing pathologic grade, positive metastasis, and poor prognosis. Our analyses suggest ex-miR-1246 as a promising prostate cancer biomarker with diagnostic potential that can predict disease aggressiveness.

Significance: Dysregulation of exosomal miRNAs in aggressive prostate cancer leads to alteration of key signaling pathways associated with metastatic prostate cancer. Cancer Res; 78(7); 1833–44. ©2018 AACR.
PBX3 Is Part of an EMT Regulatory Network and Indicates Poor Outcome in Colorectal Cancer
Authors: Lamprecht Sebastian , Kaller Markus , Schmidt Eva Marina , Blaj Cristina , Schiergens Tobias S. , Engel Jutta , Jung Andreas , Hermeking Heiko , Grünewald Thomas G.P. , Kirchner Thomas , Horst David
Published: February 2018

Purpose: Colorectal cancers are composed of phenotypically different tumor cell subpopulations within the same core genetic background. Here, we identify high expression of the TALE transcription factor PBX3 in tumor cells undergoing epithelial–mesenchymal transition (EMT), analyze PBX3 regulation, and determine clinical associations in colorectal cancer.

Experimental design: We used transcriptomic and in situ analyses to identify PBX3 expression in colorectal cancer and cell biology approaches to determine its regulation and function. Clinical associations were analyzed in independent tissue collections and gene expression datasets of colorectal cancers with recorded follow-up data.

Results: PBX3 was expressed in tumor cells with high WNT activity undergoing EMT at the leading tumor edge of colorectal cancers, whereas stromal cells were PBX3 negative. PBX3 expression was induced by WNT activation and by the EMT transcription factors SNAIL and ZEB1, whereas these effects were mediated indirectly through microRNA miR-200. PBX3 was required for a full EMT phenotype in colon cancer cells. On the protein level, PBX3 expression indicated poor cancer-specific and disease-free survival in a cohort of 244 UICC stage II colorectal cancers, and was associated with metastasis in a case–control collection consisting of 90 cases with or without distant metastasis. On the mRNA level, high PBX3 expression was strongly linked to poor disease-free survival.

Conclusions: PBX3 is a novel indicator of EMT in colorectal cancer, part of an EMT regulatory network, and a promising prognostic predictor that may aid in therapeutic decision making for patients with colorectal cancer. Clin Cancer Res; 24(8); 1974–86. ©2018 AACR.
Sevelamer-Induced Gastrointestinal Injury Presenting as Gastroenteritis
Authors: Magee Jared , Robles Matthew , Dunaway Peter
Published: February 2018

End-stage renal disease (ESRD) is a common disease encountered in clinical practice and is associated with increasing metabolic derangements through disease progression. Phosphate retention is one of the most common derangements and is associated with increased mortality. Hyperphosphatemia becomes increasingly prevalent as glomerular filtration rate decreases. Non-calcium phosphate-binding resins and dietary phosphate restriction are the mainstays for managing hyperphosphatemia in patients with ESRD. Sevelamer carbonate is the most frequently used non-calcium phosphate binder in the US due to ease of administration and an excellent safety profile. However, there is increasing recognition of gastrointestinal injury associated with medication use. Here we report a case of an 81-year-old male with biopsy-proven gastrointestinal mucosal injury secondary to sevelamer carbonate administration.
Adult Presentation of Noncirrhotic Portal Hypertension and Ascites following Treatment for Wilms’ Tumor in Childhood
Authors: Kievit Linda , Kræmer Pia , Hamilton-Dutoit Stephen , Grønbæk Henning
Published: February 2018

A 37-year-old male, who at the age of 8 years had been treated for right-sided Wilms’ tumor with nephrectomy, radiotherapy, and chemotherapy, presented with noncirrhotic portal hypertension (NCPH), grade 2 esophageal varices, and ascites. A CT scan demonstrated hypoplasia of liver segments 2 and 3. A liver biopsy showed portal tract fibrosis without cirrhosis, with histological features of NCPH. Liver vein catheterization showed a normal portal pressure gradient of 5 mm Hg while spleen to hepatic vein pressure was 29 mm Hg. NCPH after therapy for Wilms’ tumor is described in children within the first few years after treatment. This is the first case report in which the patient first presented symptoms as an adult, many years after cancer treatment.
Non-Melanoma Skin Cancers at Sites of Previous Frostbite: Case Report and Review
Authors: Imanbayev Khalel , Makishev Abay , Zhagiparov Murat , McLoone Pauline
Published: February 2018

The association between ultraviolet radiation exposure and skin cancer is well established. Limited studies have reported an association between frostbite and the development of non-melanoma skin cancer but evidence for a proven link is insufficient and possible carcinogenic mechanisms have not been fully explored. In this report, 3 cases of non-melanoma skin cancer (1 case of basal cell carcinoma and 2 cases of squamous cell carcinoma of the skin) which developed at a site of previous frostbite caused by exposure to extremely cold temperatures in Astana, the capital city of Kazakhstan, are described.
Intellectual Functioning in In-Patients with Substance Use Disorders: Preliminary Results from a Clinical Mediation Study of Factors Contributing to IQ Variance
Authors: Braatveit Kirsten J. , Torsheim Torbjørn , Hove Oddbjørn
Published: February 2018

Aims: To investigate the direct effect of different childhood difficulties on adult intelligence coefficient (IQ) and their possible indirect effect through the mediating pathways of education and severity substance use. Participants: Ninety in-patients aged 19–64. The participants had abstained from substance use for at least 6 weeks and had different substance use profiles. Measurements: Substance use disorder (SUD) and psychiatric illnesses were diagnosed according to the International Classification of Diseases 10th edition criteria. IQ was measured with the Wechsler Adult Intelligence Scale, 4th edition. Childhood difficulties, severity of substance use and level of education were assessed through a self-report questionnaire. Findings: Mean full scale IQ for the studied population was 87.3. Learning and attention deficit/hyperactivity difficulties in childhood were directly related to adult IQ. Education had a mediating effect between childhood learning difficulties/conduct problems and the verbal comprehension index. There was no significant difference in IQ due to the specific substance used or severity of substance use. Conclusion: IQ variance in in-treatment individuals with SUD was related to childhood functioning alone or through the mediator of education. Substance-related factors did not contribute to IQ variance. The results fit a normal theory of IQ development with commonly known risk factors and no disturbing effect of substance use.
Novel and Recurrent Mutations in the FGFR3 Gene and Double Heterozygosity Cases in a Cohort of Brazilian Patients with Skeletal Dysplasia
Authors: Gomes Maria E.S. , Kanazawa Thatiane Y. , Riba Fernanda R. , Pereira Natálya G. , Zuma Maria C.C. , Rabelo Natana C. , Sanseverino Maria T. , Horovitz Dafne D.G. , Llerena Jr. Juan C. , Cavalcanti Denise P. , Gonzalez Sayonara
Published: February 2018

Mutations in the fibroblast growth factor receptor 3 gene (FGFR3) cause achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia types I and II (TDI/TDII). In this study, we performed a genetic study of 123 Brazilian patients with these phenotypes. Mutation hotspots of the FGFR3 gene were PCR amplified and sequenced. All cases had recurrent mutations related to ACH, HCH, TDI or TDII, except for 2 patients. One of them had a classical TDI phenotype but a typical ACH mutation (c.1138G>A) in combination with a novel c.1130T>C mutation predicted as being pathogenic. The presence of the second c.1130T>C mutation likely explained the more severe phenotype. Another atypical patient presented with a compound phenotype that resulted from a combination of ACH and X-linked spondyloepiphyseal dysplasia tarda (OMIM 313400). Next-generation sequencing of this patient's DNA showed double heterozygosity for a typical de novo ACH c.1138G>A mutation and a maternally inherited TRAPPC2 c.6del mutation. All mutations were confirmed by Sanger sequencing. A pilot study using high-resolution melting (HRM) technique was also performed to confirm several mutations identified through sequencing. We concluded that for recurrent FGFR3 mutations, HRM can be used as a faster, reliable, and less expensive genotyping test than Sanger sequencing.
Correlation Between Baseline Osteoprotegerin Serum Levels and Prognosis of Advanced-Stage Colorectal Cancer Patients
Authors: De Toni Enrico , Nagel Dorothea , Philipp Alexander B. , Herbst Andreas , Thalhammer Isabel , Mayerle Julia , Török Helga-Paula , Brandl Lydia , Kolligs Frank T.
Published: February 2018

Background/Aims: Osteoprotegerin (OPG) is a soluble receptor of the pro-apoptotic cytokine TRAIL which is thought to contribute to tumour development by inhibiting apoptosis or affecting other aspects of tumour biology, including cell proliferation and immune response. Although immunohistochemical studies suggest that OPG correlates with survival in metastatic colorectal cancer (mCRC), only scarce data are available on serum OPG in CRC patients. Methods: In this pilot study, we assessed the prognostic significance of serum OPG and CEA (Carcinoembryonic antigen) in 81 patients with UICC (Union for International Cancer Control) stage-IV mCRC. OPG was additionally assessed by immunohistochemistry in primary tissue samples from 33 patients of the same cohort. Results: Baseline serum OPG correlated with CEA (r=0.36, p=0.0011), but independently predicted survival of mCRC patients. Life expectancy was poorer in patients with OPG levels above the median concentration of 51ng/ml (median overall survival [95% confidence interval] 1.8 years [1.3-3.0] vs. 1.0 [0.7-1.2] p=0.013). Patients with high levels of both OPG and CEA had an even poorer life expectancy vs. low-OPG/low-CEA patients (0.9 years [0.6-1.5] vs. 3 years [1.2-4.4], p=0.015), indicating that CEA and OPG have additive prognostic significance. Immunohistochemical analysis of OPG failed to show a correlation between OPG staining and survival (p=0.055) or OPG concentration from matched serum samples. Conclusions: This pilot study provides evidence of independent prognostic significance of serum OPG in patients with advanced mCRC and warrants its further prospective validation.
РОЛЬ МЕДИЧНОЇ СЕСТРИ У ПОПЕРЕДЖЕННІ ВПЛИВУ МЕТЕОРОЛОГІЧНИХ ФАКТОРІВ НА СТАН ПАЦІЄНТІВ З ГІПЕРТОНІЧНОЮ ХВОРОБОЮ
Authors: Mialiuk O. P. , Maruschak M. I. , Krynytska I. Y. , Rudenko O. V.
Published: February 2018

У статті проведено оцінку впливу природно-кліматичних та метеорологічних факторів на перебіг захворювання у пацієнтів із гіпертонічною хворобою та встановлено роль медичної сестри у профілактиці розвитку ускладнень.Встановлено, що на фоні коливання температури атмосферного повітря, динамічного зменшення кількості опадів відбувається зростання кількості стаціонарних пацієнтів кардіологічного профілю. Збільшення захворюваності та ускладнень гіпертонічної хвороби пов’язане з температурою атмосферного повітря, віку хворого і часу доби.Запропоновано план роботи середнього медичного персоналу для профілактики гіпертонічних кризів та інших ускладнень гіпертонічної хвороби: 1) формування групи ризику серед пацієнтів зони обслуговування зі значними коливаннями артеріального тиску, особливо в нічний період; 2) розробка журналу щоденної реєстрації загальножиттєвих показників (температура тіла, артеріальний тиск, пульс); 3) навчання та контроль за правильністю реєстрації загальножиттєвих показників; 4) проведення просвітницької роботи щодо факторів ризику та профілактики розвитку гіпертонічної хвороби та її ускладнень.
ОПИТУВАЛЬНИК SGRQ ЯК ОДИН З ІНСТРУМЕНТІВ ДОСЛІДЖЕННЯ ЯКОСТІ ЖИТТЯ ХВОРИХ ІЗ БРОНХООБСТРУКТИВНИМ СИНДРОМОМ РІЗНОГО ГЕНЕЗУ
Authors: Horodetskyy V. Ye. , Kvasha T. M.
Published: February 2018

У статті проаналізовано респіраторний опитувальник госпіталю Святого Георгія як один з інструментів дослідження якості життя хворих із бронхообструктивним синдромом різного генезу.
ОСОБЛИВОСТІ ОРГАНІЗАЦІЇ СЕСТРИНСЬКОЇ ДОПОМОГИ ОСОБАМ СТАРШОГО ВІКУ
Authors: Boguta Y. G. , Rudenko O. V. , Marushchak M. I. , Mialiuk O. P.
Published: February 2018

У статті наведено особливості організації сестринської допомоги особам старшого віку. Показано, що вирішити завдання зміцнення здоров’я населення, вдосконалення роботи установ вітчизняної охорони здоров’я в нових економічних умовах неможливо без підвищення ролі сестринського персоналу – найчисельнішої ланки медичних працівників. Неможливо також забезпечити потреби суспільства в якісній медичній допомозі без зміни статусу медсестри, розширення сфери її професійної діяльності, раціонального розподілу обов’язків між лікарями та медсестрами. Разом з тим перетворення в сестринській справі не можуть здійснюватися без аналізу сучасного стану сестринської допомоги, без чіткого визначення як сильних, так і слабких сторін діяльності медсестер. Отже, сучасна практика сестринського обслуговування перебуває в стадії системних перетворень та потребує наукового обґрунтування, оскільки незбалансованість медичних кадрів, малоефективне використання сестринського персоналу в практиці негативно впливає на якість медичної допомоги.
Estudio descriptivo de la Atención Especializada del Sistema Sanitario de España
Authors: Nombela-Monterroso Karen , González-Chordá Víctor M , Roman Pablo
Published: February 2018

OBJETIVO: Analizar la tendencia de los Indicadores Clave del Sistema Nacional de Salud de España y sus comunidades autónomas, relacionados con la Atención Especializada, desde la publicación de la Ley de Cohesión y Calidad. MÉTODOS: Estudio ecológico de series temporales de España y sus comunidades autónomas desde 2003 hasta 2014. Se analizaron 10 indicadores relacionados con Atención Especializada (porcentaje de gasto, profesionales, listas de espera, actividad quirúrgica, estancia media, infecciones y mortalidad) utilizando el método de auto-regresión de Prais-Winsten. Los datos se obtuvieron del sistema de información sanitaria del Ministerio de Sanidad, Servicios Sociales e Igualdad español. RESULTADOS: Existió una tendencia creciente del gasto en atención especializada (APC = 0,059; IC95% 0,041–0,074), número de profesionales de medicina (APC = 0,0006; IC95% 0,0003–0,0009) y enfermería (APC = 0,001; IC95% 0,0005–0,0016), infecciones hospitalarias (APC = 0,0003; IC95% 0,0002–0,0004) y mortalidad intrahospitalaria (APC = 0,0008; IC95% 0,0006–0,001) en España. La estancia media presentó una tendencia decreciente (APC = -0,0017; IC95% -0,002– -0,0014). La tendencia de las listas de espera (consulta especializada e intervenciones quirúrgicas no urgentes) fue estática. La tendencia de estos indicadores varió en las Comunidades Autónomas. CONCLUSIONES: Se observa un incumplimiento de los principios de equidad y calidad de las prestaciones ofrecidas. El aumento del envejecimiento, el desarrollo tecnológico y estrategias poco adecuadas tomadas para reducir los costes sanitarios pueden ser las principales causas.
Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability
Authors: Roberts Brian W. , Kilgannon J. Hope , Hunter Benton R. , Puskarich Michael A. , Pierce Lisa , Donnino Michael , Leary Marion , Kline Jeffrey A. , Jones Alan E. , Shapiro Nathan I. , Abella Benjamin S. , Trzeciak Stephen
Published: February 2018

Background:

Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome.

Methods:

This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (Pa
o
2
) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a Pa
o
2
>300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between Pa
o
2
and poor neurological outcome. To assess whether there was an association between other supranormal Pa
o
2
levels and poor neurological outcome, we used other Pa
o
2
cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg).

Results:

Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1–23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11–1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02–1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg.

Conclusions:

Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge.
Targeting Germinal Matrix Hemorrhage–Induced Overexpression of Sodium‐Coupled Bicarbonate Exchanger Reduces Posthemorrhagic Hydrocephalus Formation in Neonatal Rats
Authors: Li Qian , Ding Yan , Krafft Paul , Wan Weifeng , Yan Feng , Wu Guangyong , Zhang Yixin , Zhan Qunling , Zhang John H.
Published: February 2018

Background

Germinal matrix hemorrhage (
GMH
) is a leading cause of mortality and lifelong morbidity in preterm infants. Posthemorrhagic hydrocephalus (
PHH
) is a common complication of
GMH
. A sodium‐coupled bicarbonate exchanger (
NCBE
) encoded by solute carrier family 4 member 10 gene is expressed on the choroid plexus basolateral membrane and may play a role in cerebrospinal fluid production and the development of
PHH
. Following
GMH
, iron degraded from hemoglobin has been linked to
PHH
. Choroid plexus epithelial cells also contain iron‐responsive element‐binding proteins (
IRP
s),
IRP
1, and
IRP
2 that bind to
mRNA
iron‐responsive elements. The present study aims to resolve the following issues: (1) whether the expression of
NCBE
is regulated by
IRP
s; (2) whether
NCBE
regulates the formation of
GMH
‐induced hydrocephalus; and (3) whether inhibition of
NCBE
reduces
PHH
development.

Methods and Results

GMH
model was established in P7 rat pups by injecting bacterial collagenase into the right ganglionic eminence. Another group received iron trichloride injections instead of collagenase. Deferoxamine was administered intraperitoneally for 3 consecutive days after
GMH
/iron trichloride. Solute carrier family 4 member 10 small interfering RNA or scrambled small interfering RNA was administered by intracerebroventricular injection 24 hours before
GMH
and followed with an injection every 7 days over 21 days.
NCBE
expression increased while
IRP
2 expression decreased after
GMH
/iron trichloride. Deferoxamine ameliorated both the
GMH
‐induced and iron trichloride–induced decrease of
IRP
2 and decreased
NCBE
expressions. Deferoxamine and solute carrier family 4 member 10 small interfering RNA improved cognitive and motor functions at 21 to 28 days post
GMH
and reduced cerebrospinal fluid production as well as the degree of hydrocephalus at 28 days after
GMH
.

Conclusions

Targeting iron‐induced overexpression of
NCBE
may be a translatable therapeutic strategy for the treatment of
PHH
following
GMH
.
Absence of July Phenomenon in Acute Ischemic Stroke Care Quality and Outcomes
Authors: Gonzalez‐Castellon Marco , Ju Christine , Xian Ying , Hernandez Adrian , Fonarow Gregg C. , Schwamm Lee , Smith Eric E. , Bhatt Deepak L. , Reeves Matthew , Willey Joshua Z.
Published: February 2018

Background

Lower care quality and an increase in adverse outcomes as a result of new medical trainees is a concept well rooted in popular belief, termed the “July phenomenon.” Whether this phenomenon occurs in acute ischemic stroke has not been well studied.

Methods and Results

We analyzed data from patients admitted with ischemic stroke in 1625 hospitals participating in the Get With The Guidelines–Stroke program for the 5‐year period between January 2009 and December 2013. We compared acute stroke treatment processes and in‐hospitals outcomes among the 4 quarters (first quarter: July–September, last quarter: April–June) of the academic year. Multivariable logistic regression models were used to evaluate the relationship between academic year transition and processes measures. A total of 967 891 patients were included in the study. There was a statistically significant, but modest (<4 minutes or 5 percentage points) difference in distribution of or quality and clinical metrics including door‐to‐computerized tomography time, door‐to‐needle time, the proportion of patients with symptomatic intracranial hemorrhage within 36 hours of admission, and the proportion of patients who received defect‐free care in stroke performance measures among academic year quarters (
P
<0.0001). In multivariable analyses, there was no evidence that quarter 1 of the academic year was associated with lower quality of care or worse in‐hospital outcomes in teaching and nonteaching hospitals.

Conclusions

We found no evidence of the “July phenomenon” in patients with acute ischemic stroke among hospitals participating in the Get With The Guidelines–Stroke program.