bluuebunny/crossref_metadata_2025 huggingface dataset:
The Rising Burden of Diabetes and Hypertension in Southeast Asian and African Regions: Need for Effective Strategies for Prevention and Control in Primary Health Care Settings
Authors: Mohan Viswanathan , Seedat Yackoob K. , Pradeepa Rajendra
Published: March 2013

Aim. To review the available literature on burden of diabetes mellitus (DM) and hypertension (HTN) and its coexistence in Southeast Asian (SEA) and the African (AFR) regions and to suggest strategies to improve DM and HTN prevention and control in primary health care (PHC) in the two regions.Methods. A systematic review of the papers published on DM, HTN, and prevention/control of chronic diseases in SEA and AFR regions between 1980 and December 2012 was included.Results. In the year 2011, SEA region had the second largest number of people with DM (71.4 million), while the AFR region had the smallest number (14.7 million). Screening studies identified high proportions (>50%) of individuals with previously undiagnosed HTN and DM in both of the SEA and AFR regions. Studies from both regions have shown that DM and HTN coexist in type 2 DM ranging from 20.6% in India to 78.4% in Thailand in the SEA region and ranging from 9.7% in Nigeria to 70.4% in Morocco in the AFR region. There is evidence that by lifestyle modification both DM and HTN can be prevented.Conclusion. To meet the twin challenge of DM and HTN in developing countries, PHCs will have to be strengthened with a concerted and multipronged effort to provide promotive, preventive, curative, and rehabilitative services.
Investigation and Estimation of Structure of Web from Electrospun Nanofibres
Authors: Malašauskienė Jolanta , Milašius Rimvydas
Published: March 2013

During the electrospinning process the web of nanofibres is manufactured by means of electrostatic forces between two electrodes. The diameters of nanofibres usually differ and they depend on various parameters. The different fineness of fibres influences the structure of the web and herewith the end‐use properties of such kind of nanomaterial. Analysis of nanofibres diameters distribution also shows big differences; even more, the distributions are not spread along the normal distribution. Understanding the influence of electrospinning parameters and the reason why the shapes of distributions are so sophisticated is very important. The goal of this paper is to analyse the distribution of diameter and to propose the new criterion for nanofibres diameter comparison and web of nanofibres estimation. In this paper the influence of covering time of support material on structure of PA6.6 nanofibre web has been investigated. It was estimated that this parameter does not have a significant influence on the average diameter of nanofibres, and only the structure of web has been influenced by the changes in covering time. According to the results provided the phenomena of nanofibres sticking on the support material at the time of electrospinning can be proved and explained.
Actin Colocalization with Metaphase Chromosomes of the Second Meiosis in Ovulated Mouse Oocytes
Authors: Bogolyubova Natalie , Ginzburg Alexander
Published: March 2013

Functional interrelation of nuclear actin with transcriptional active chromatin in the interphase nucleus was reliably established in numerous experiments, but the relationship between actin and transcriptional silent chromatin is still unclear. We examined localization area of the second meiotic division metaphase plate in ovulated mouse oocytes with the aim to study the possibility of actin-chromatin colocalization and uncovering the distribution patterns of different functional forms of actin near the metaphase chromosomes. Confocal microscopy and probes for actin that are distinguished from each other by the mechanism of actin binding (TRITC-phalloidin, fluorescent DNase-I, and antibodies against fragment of C-terminal and fragment of N-terminal domain of actin) were used for actin visualization. Despite the fact that TRITC-phalloidin could not detect F-actin in the area of metaphase plate, oocytes staining with antibody against fragment of the actin N-terminal domain demonstrates the presence near the metaphase chromosomes of some spindle-like structure composed of actin filaments. Among all used probes for actin, only the antibody against fragment of the C-terminal domain detected accurate actin colocalization with metaphase chromosomes. We conclude that this antibody labeled noncanonical form of the nuclear actin existing in long-term association with highly condensed chromatin.
An Empirical Likelihood Method for Semiparametric Linear Regression with Right Censored Data
Authors: Fang Kai-Tai , Li Gang , Lu Xuyang , Qin Hong
Published: March 2013

This paper develops a new empirical likelihood method for semiparametric linear regression with a completely unknown error distribution and right censored survival data. The method is based on the Buckley-James (1979) estimating equation. It inherits some appealing properties of the complete data empirical likelihood method. For example, it does not require variance estimation which is problematic for the Buckley-James estimator. We also extend our method to incorporate auxiliary information. We compare our method with the synthetic data empirical likelihood of Li and Wang (2003) using simulations. We also illustrate our method using Stanford heart transplantation data.
A Study Involving the Completion of a Quasi-2-Normed Space
Authors: Kır Mehmet , Acikgoz Mehmet
Published: March 2013

The fundamental aim of this paper is to introduce and investigate a new property of a quasi-2-normed space based on a question given by Park (2006) for the completion quasi-2-normed space. Finally, we also find an answer for Park's question.
Metabolic Profiles Distinguish Non-Dampness-Phlegm and Dampness-Phlegm Patterns among Korean Patients with Acute Cerebral Infarction
Authors: Cha Min Ho , Jones A. Daniel , Ko Mi Mi , Zhang Chen , Lee Myeong Soo
Published: March 2013

Traditional Korean Medicine classifies stroke into four subtype patterns according to symptomatic pattern identification: Qi deficiency (QD), Yin deficiency (YD), Dampness-phlegm (DP), and Fire and Heat (FH). This study investigated the difference in metabolic profiles of plasma comparing subjects displaying non-DP and DP patterns. A total of 141 patients with cerebral infarction enrolled in this study were distributed as non-DP (N=68) and DP (N=73). Anthropometric parameters and symptom/sign index were measured. Metabolic profiling was performed using ultrahigh-performance liquid chromatography-mass spectrometry. The Ratio of subjects with slippery pulse was higher in DP pattern, but fine pulse was lower than that in non-DP pattern. As a result of metabolomics analysis, twenty-one metabolites displayed different levels between non-DP and DP patterns. Two were identified as lysophosphatidylcholines (LPCs), LPC(18:2), and LPC(20:3) having an unsaturated acyl chain and showed lower levels in DP pattern than in non-DP pattern (P=0.015, 0.034, resp.). However, the saturated LPCs, LPC(18:0) and LPC(16:0), exhibited slight but statistically insignificant elevation in DP pattern. Our results demonstrated that plasma LPCs with polyunsaturated fatty acid groups were associated with DP pattern and suggest that variation of plasma lipid profiles may serve as potential biomarker for diagnosis of DP pattern.
Docking Studies of Binding of Ethambutol to the C‐Terminal Domain of the Arabinosyltransferase from Mycobacterium tuberculosis
Authors: Salgado-Moran Guillermo , Ramirez-Tagle Rodrigo , Glossman-Mitnik Daniel , Ruiz-Nieto Samuel , Kishore-Deb Pran , Bunster Marta , Lobos-Gonzalez Francisco
Published: March 2013

The binding of ethambutol to the C‐terminal domain of the arabinosyltransferase from Mycobacterium tuberculosis was studied. The analysis was performed using an in silico approach in order to find out, by docking calculations and energy descriptors, the conformer of Ethambutol that forms the most stable complex with the C‐terminal domain of arabinosyltransferase. The complex shows that location of the Ethambutol coincides with the cocrystallization ligand position and that amino acid residues ASH1051, ASN740, ASP1052, and ARG1055 should be critical in the binding of Ethambutol to C‐terminal domain EmbC.
Amiodarone-Induced Cirrhosis of Liver: What Predicts Mortality?
Authors: Hussain Nasir , Bhattacharyya Anirban , Prueksaritanond Suartcha
Published: March 2013

Introduction. Amiodarone has been used for more than 5 decades for the treatment of various tachyarrhythmias and previously for the treatment of refractory angina. There are multiple well-established side effects of amiodarone. However, amiodarone-induced cirrhosis (AIC) of liver is an underrecognized complication.Methods. A systematic search of Medline from January 1970 to November 2012 by using the following terms, amiodarone and cirrhosis, identified 37 reported cases of which 30 were used in this analysis. Patients were divided into 2 subsets, survivors versus nonsurvivors, at 5 months.Results. Aspartate aminotransferase was significantly lower (P=0.03) in patients who survived at 5-months (mean 103.33 IU/L) compared to nonsurvivors (mean 216.88 IU/L). There was no statistical difference in the levels of prothrombin time, total bilirubin, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, cumulative dose, and latency period between the two groups. The prevalence of DM, HTN, HLD, CAD, and CHF was similar in the two groups. None of the above-mentioned variables could be identified as a predictor of survival at 5 months.Conclusion. AIC carries a mortality risk of 60% at 5 months once the diagnosis is established. Further prospective studies are needed to identify predictors of AIC and of mortality or survival in cases of AIC.
Anxiety due to Dental Treatment and Procedures among University Students and Its Correlation with Their Gender and Field of Study
Authors: Sghaireen Mohd G. , Zwiri Abdalwhab M. A. , Alzoubi Ibrahim A. , Qodceih Sadeq M. , AL-Omiri Mahmoud K.
Published: March 2013

Aim of Study. To investigate dental anxiety levels among university students and its relation with their specialty and gender.Materials and Methods. 850 undergraduate university students were recruited into the study. The Modified Corah Dental Anxiety Scale (MDAS) was used to measure the levels of their dental anxiety. 700 questionnaires were returned, 390 females and 310 males (response rate of 0.92% among females, 0.73% among males). The MDAS score ranged from 5 to 25. Patients were considered to suffer from high dental anxiety if they scored 13 to 20 points. Statistical analysis significance was set atP≤0.05.Results. Seven hundred students participated in this study including 13% of medical students, 10% of dental students, 58% of arts students, and 18% of computer science students. Medical and dental students were less anxious than arts and computer science students (P<0.05). Local anesthesia injection was the most fearful dental procedure (P<0.05). Females were more anxious than males (P<0.05).Conclusion. Male students were less anxious than female students. Students from medical background faculties were less anxious than students from nonmedical faculties. Lack of adequate dental health education may result in a higher level of dental anxiety among nonmedical students in Saudi Arabia.
Paramonostomum bubaki n. sp. (Digenea: Notocotylidae) from the Black Coot, Fulica atra (Gruiformes: Rallidae), in South Central Pakistan
Authors: Birmani Nadir Ali , Dharejo Ali Murtaza , Naz Shagufta , Khan Muhammad Munif , Shaikh Abdul Manan
Published: March 2013

During a helminthological survey of black coot, Fulica atra (Gruiformes: Rallidae), in Sindh Province of Pakistan, eight specimens of undescribed species of trematode belonging to genus Paramonostomum Lühe, 1909 were recovered from large intestine of the single host bird. Paramonostomum bubaki n. sp. differs from its congeners except P. macrovesiculum Dharejo et al., 2006 by having less attenuated anterior end, a pharynx, a bifurcal genital pore, a longer posttesticular space, a Y-shaped excretory vesicle, number of uterine loops (16), and large size of filamentous eggs. P. bubaki n. sp. resembles P. macrovesiculum Dharejo et al., 2006 collected from Fulica atra from Pakistan by having a pharynx but differs in larger body, smaller esophagus, a bifurcal genital pore, shape of cirrus sac, seminal vesicle and gonads, ceca reaching posterior extremity, and a longer posttesticular space.
Pediatric Transepiphyseal Seperation and Dislocation of the Femoral Head
Authors: Elmadag Mehmet , Ceylan Hasan H. , Erdem Ahmet Can , Bilsel Kerem , Uzer Gokcer , Acar Mehmet Ali
Published: March 2013

Pediatric hip fractures and dislocations are rare in practice and are related to high-energy trauma. The incidence of postoperative avascular necrosis is increasing, especially in the case of transepiphyseal fractures. Surgery is the most common form of treatment, and its timing is important for prognosis of the fracture. Patients and their families should be informed about the possibility of avascular necrosis and further complications related to the fracture.
Nonlinear Conjugate Gradient Methods with Wolfe Type Line Search
Authors: Chen Yuan-Yuan , Du Shou-Qiang
Published: March 2013

Nonlinear conjugate gradient method is one of the useful methods for unconstrained optimization problems. In this paper, we consider three kinds of nonlinear conjugate gradient methods with Wolfe type line search for unstrained optimization problems. Under some mild assumptions, the global convergence results of the given methods are proposed. The numerical results show that the nonlinear conjugate gradient methods with Wolfe type line search are efficient for some unconstrained optimization problems.
Beneficial Effects of an 8-Week, Very Low Carbohydrate Diet Intervention on Obese Subjects
Authors: Gu Yunjuan , Yu Haoyong , Li Yuehua , Ma Xiaojing , Lu Junxi , Yu Weihui , Xiao Yunfeng , Bao Yuqian , Jia Weiping
Published: March 2013

Aim. To investigate the effects of weight loss during an 8-week very low carbohydrate diet (VLCD) on improvement of metabolic parameters, adipose distribution and body composition, and insulin resistance and sensitivity in Chinese obese subjects.Methods. Fifty-three healthy obese volunteers were given an 8-week VLCD. The outcomes were changes in anthropometry, body composition, metabolic profile, abdominal fat distribution, liver fat percent (LFP), and insulin resistance and sensitivity.Results. A total of 46 (86.8%) obese subjects completed the study. The VLCD caused a weight loss of−8.7±0.6 kg (mean ± standard error (SE),P<0.0001) combined with a significant improvement of metabolic profile. In both male and female, nonesterified fatty acid (NEFA) significantly decreased (−166.2±47.6 μmol/L,P=0.001) andβ-hydroxybutyric acid (BHA) increased (0.15±0.06 mmol/L,P=0.004) after eight weeks of VLCD intervention. The significant reductions in subcutaneous fat area (SFA), visceral fat area (VFA), and LFP were−66.5±7.9 cm2,−35.3±3.9 cm2, and−16.4±2.4%, respectively (allPvaluesP<0.0001). HOMA IR and HOMAβsignificantly decreased while whole body insulin sensitivity index (WBISI) increased (allPvaluesP<0.001).Conclusion. Eight weeks of VLCD was an effective intervention in obese subjects. These beneficial effects may be associated with enhanced hepatic and whole-body lipolysis and oxidation.
Cardiovascular Changes in Animal Models of Metabolic Syndrome
Authors: Lehnen Alexandre M. , Rodrigues Bruno , Irigoyen Maria Cláudia , De Angelis Kátia , Schaan Beatriz D’Agord
Published: March 2013

Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans.
A Game Theoretic Sensor Resource Allocation Using Fuzzy Logic
Authors: Stubberud Stephen C. , Kramer Kathleen A.
Published: March 2013

A sensor resource management system that employs fuzzy logic to provide the utility functions to a game theoretic approach is developed. The application looks at a virtual fence problem where several unattended ground sensors are placed in remote locations to act as virtual sentries. The goal of the approach is to maximize the battery life while tracking targets of interest. This research also considers the incorporation of uncertainty into the fuzzy membership functions. Both type-2 fuzzy logic and the use of conditional fuzzy membership function are employed. The type-2 fuzzy logic is employed in the case of acoustical sensor tracking accuracy degradation, while the condition-based membership functions are used to adapt to different conditions, such as environmental conditions and sensor performance degradation, over time. The resource management process uses fuzzy logic to determine which of the sensor systems on a sensor pod is used to provide initial classification of the target and which sensor or sensors are to be used in tracking and better classifying the target if it is determined to be of value to the mission. The three different approaches are compared to determine when the best times for the more complex approaches are warranted.
Isolated Uterine Metastasis of Invasive Ductal Carcinoma
Authors: Arslan Deniz , Tural Deniz , Tatlı Ali Murat , Akar Emre , Uysal Mükremin , Erdoğan Gülgün
Published: March 2013

Introduction. Most common metastasis sites of breast cancer are the lungs, bones, liver, and brain, whereas uterine involvement by metastatic breast disease is rare. Metastatic carcinoma of the uterus usually originates from other genital sites, most commonly being from the ovaries. Invasive lobular carcinoma spreads to gynecologic organs more frequently than invasive ductal carcinoma.Case Report. A 57-year-old postmenopausal woman was diagnosed with breast carcinoma 2 years ago and modified radical mastectomy was performed. Pathological examination of tumor revealed invasive ductal carcinoma, stage IIIc. She presented with abdominal pain and distension. Diagnostic workup and gynecologic examination revealed lesions that caused diffuse thickening of the uterus wall. Endometrial sampling was performed for confirmation of the diagnosis. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically.Conclusion. We herein report the first case of isolated uterine patient who had invasive ductal carcinoma of breast.
Heat Shock Proteins and Regulatory T Cells
Authors: Brenu E. W. , Staines D. R. , Tajouri L. , Huth T. , Ashton K. J. , Marshall-Gradisnik S. M.
Published: March 2013

Heat shock proteins (HSPs) are important molecules required for ideal protein function. Extensive research on the functional properties of HSPs indicates that HSPs may be implicated in a wide range of physiological functions including immune function. In the immune system, HSPs are involved in cell proliferation, differentiation, cytokine release, and apoptosis. Therefore, the ability of the immune system, in particular immune cells, to function optimally and in unison with other physiological systems is in part dependent on signaling transduction processes, including bidirectional communication with HSPs. Regulatory T cells (Tregs) are important T cells with suppressive functions and impairments in their function have been associated with a number of autoimmune disorders. The purpose of this paper is to examine the relationship between HSPs and Tregs. The interrelationship between cells and proteins may be important in cellular functions necessary for cell survival and expansion during diseased state.
Protumor Activities of the Immune Response: Insights in the Mechanisms of Immunological Shift, Oncotraining, and Oncopromotion
Authors: Chimal-Ramírez G. K. , Espinoza-Sánchez N. A. , Fuentes-Pananá E. M.
Published: March 2013

Experimental and clinical studies indicate that cells of the innate and adaptive immune system have both anti- and pro-tumor activities. This dual role of the immune system has led to a conceptual shift in the role of the immune system’s regulation of cancer, in which immune-tumor cell interactions are understood as a dynamic process that comprises at least five phases: immunosurveillance, immunoselection, immunoescape, oncotraining, and oncopromotion. The tumor microenvironment shifts immune cells to perform functions more in tune with the tumor needs (oncotraining); these functions are related to chronic inflammation and tissue remodeling activities. Among them are increased proliferation and survival, increased angiogenesis and vessel permeability, protease secretion, acquisition of migratory mesenchymal characteristics, and self-renewal properties that altogether promote tumor growth and metastasis (oncopromotion). Important populations in all these pro-tumor processes are M2 macrophages, N2 neutrophils, regulatory T cells, and myeloid derived suppressor cells; the main effectors molecules are CSF-1, IL-6, metalloproteases, VEGF, PGE-2, TGF-β, and IL-10. Cancer prognosis correlates with densities and concentrations of protumoral populations and molecules, providing ideal targets for the intelligent design of directed preventive or anticancer therapies.
“Color-Tripole Ice” as a Conceptual Generalization of “Spin Ice”
Authors: Hu Chia-Ren
Published: March 2013

“Spin Ice” is an exotic type of frustrated magnet realized in “pyrochlore” materials Ho2Ti2O7, Dy2Ti2O7, Ho2Sn2O7, and so forth, in which magnetic atoms (spins) reside on a sublattice made of the vertices of corner-sharing tetrahedra. Each spin is Ising-like with respect to a local axis which connects the centers of two tetrahedra sharing the vertex occupied by the spin. The macroscopically degenerate ground states of these magnets obey the “two-in two-out” “ice rule” within each tetrahedron. Magnetic monopoles and antimonopoles emerge as elementary excitations, “fractionalizing” the constituent magnetic dipoles. This system is also a novel type of statistical mechanical system. Here we introduce a conceptual generalization of “spin ice” to what we shall call “color-tripole ice,” in which three types of “color charges” can emerge as elementary excitations, which are Abelian approximations of the color charges introduced in high energy physics. Two two-dimensional (2D) models are introduced first, where the color charges are found to be 1D and constrained 2D, respectively. Generalizations of these two models to 3D are then briefly discussed. In the second one the color charges are likely 3D. Pauling-type estimates of the “residual (or zero-point) entropy” are also made for
these models.
Stronger Correlation between Interleukin 18 and Soluble Fas in Lupus Nephritis Compared with Mild Lupus
Authors: Hatef Mohammad Reza , Sahebari Maryam , Rezaieyazdi Zahra , Nakhjavani Mohammad Reza , Mahmoudi Mahmoud
Published: March 2013

Lupus nephritis (LN) is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Several cytokines and apoptotic markers such as IL-18 and soluble Fas (sFas) have been assumed to play a role in the pathogenesis of LN. Previous studies confirmed that serum concentrations of sFas and IL-18 are increased in SLE. However, only a few studies have suggested a possible correlation between IL-18 and sFas. This study was planned to continue our previous study on the correlation between those markers to evaluate this correlation in LN. Thirty-two patients with only LN and 46 patients without any major organ involvement participated in this study. SLEDAI score (except for scores related to nephritis) was the same in these two groups. In both groups, patients with any other major organ involvement were excluded. We found a significant rise in the serum concentrations of sFas (P=0.03) and IL-18 (P=0.02) in patients with proteinuria compared to those without it. This study showed that the correlation between sFas and IL-18 in LN (P<0.001, rp=0.5) is significantly stronger than it is in mild SLE (P<0.001, rp=0.4) with similar nonrenal SLEDAI score (P=0.032, z=1.85). Between these two serum markers, sFas is the only predictor of proteinuria.
Foxp3+Regulatory T Cells in Mouse Models of Type 1 Diabetes
Authors: Petzold Cathleen , Riewaldt Julia , Watts Deepika , Sparwasser Tim , Schallenberg Sonja , Kretschmer Karsten
Published: March 2013

Studies on human type 1 diabetes (T1D) are facilitated by the availability of animal models such as nonobese diabetic (NOD) mice that spontaneously develop autoimmune diabetes, as well as a variety of genetically engineered mouse models with reduced genetic and pathogenic complexity, as compared to the spontaneous NOD model. In recent years, increasing evidence has implicated CD4+CD25+regulatory T (Treg) cells expressing the transcription factor Foxp3 in both the breakdown of self-tolerance and the restoration of immune homeostasis in T1D. In this paper, we provide an overview of currently available mouse models to study the role of Foxp3+Treg cells in the control of destructiveβcell autoimmunity, including a novel NOD model that allows specific and temporally controlled deletion of Foxp3+Treg cells.
Effective Resistance of Gas Flow in Microchannels
Authors: Shan Xiao-Dong , Wang Moran
Published: March 2013

The resistance of gas flow in microchannels is higher because of the relatively more importance of interfacial effects at microscale. We studied the effective resistance of gas from the wall interactions, the ends effect, and the rarefication effect quantitatively using the three-dimensional (3D) direct simulation Monte Carlo (DSMC) method. The effective resistance is enhanced by the wall interactions, increasing exponentially as the concerned walls distance decreases. For short microchannels, the ends effects from both inlet and outlet also raise the effective resistance of gas flow in microchannels following a reciprocal exponential relationship with the aspect ratio of length to height. The gas rarefication strengthens the effective resistance enhancement by either the wall interaction effects or the ends effects. This work turns a complicated micromechanical problem into simple available formulae for designs and optimization of microengineering.
Dachshund Binds p53 to Block the Growth of Lung Adenocarcinoma Cells
Authors: Chen Ke , Wu Kongming , Cai Shaoxin , Zhang Wei , Zhou Jie , Wang Jing , Ertel Adam , Li Zhiping , Rui Hallgeir , Quong Andrew , Lisanti Michael P. , Tozeren Aydin , Tanes Ceylan , Addya Sankar , Gormley Michael , Wang Chenguang , McMahon Steven B. , Pestell Richard G.
Published: March 2013

Hyperactive EGF receptor (EGFR) and mutant p53 are common genetic abnormalities driving the progression of non–small cell lung cancer (NSCLC), the leading cause of cancer deaths in the world. The Drosophila gene Dachshund (Dac) was originally cloned as an inhibitor of hyperactive EGFR alleles. Given the importance of EGFR signaling in lung cancer etiology, we examined the role of DACH1 expression in lung cancer development. DACH1 protein and mRNA expression was reduced in human NSCLC. Reexpression of DACH1 reduced NSCLC colony formation and tumor growth in vivo via p53. Endogenous DACH1 colocalized with p53 in a nuclear, extranucleolar location, and shared occupancy of −15% of p53-bound genes in ChIP sequencing. The C-terminus of DACH1 was necessary for direct p53 binding, contributing to the inhibition of colony formation and cell-cycle arrest. Expression of the stem cell factor SOX2 was repressed by DACH1, and SOX2 expression was inversely correlated with DACH1 in NSCLC. We conclude that DACH1 binds p53 to inhibit NSCLC cellular growth. Cancer Res; 73(11); 3262–74. ©2013 AACR.
Sequential Binary Gene Ratio Tests Define a Novel Molecular Diagnostic Strategy for Malignant Pleural Mesothelioma
Authors: De Rienzo Assunta , Richards William G. , Yeap Beow Y. , Coleman Melissa H. , Sugarbaker Peter E. , Chirieac Lucian R. , Wang Yaoyu E. , Quackenbush John , Jensen Roderick V. , Bueno Raphael
Published: March 2013

Purpose: To develop a standardized approach for molecular diagnostics, we used the gene expression ratio bioinformatic technique to design a molecular signature to diagnose malignant pleural mesothelioma (MPM) from among other potentially confounding diagnoses and differentiate the epithelioid from the sarcomatoid histologic subtype of MPM. In addition, we searched for pathways relevant in MPM in comparison with other related cancers to identify unique molecular features in MPM.

Experimental Design: We conducted microarray analysis on 113 specimens including MPMs and a spectrum of tumors and benign tissues comprising the differential diagnosis of MPM. We generated a sequential combination of binary gene expression ratio tests able to discriminate MPM from other thoracic malignancies. We compared this method with other bioinformatic tools and validated this signature in an independent set of 170 samples. Functional enrichment analysis was conducted to identify differentially expressed probes.

Results: A sequential combination of gene expression ratio tests was the best molecular approach to distinguish MPM from all the other samples. Bioinformatic and molecular validations showed that the sequential gene ratio tests were able to identify the MPM samples with high sensitivity and specificity. In addition, the gene ratio technique was able to differentiate the epithelioid from the sarcomatoid type of MPM. Novel genes and pathways specifically activated in MPM were identified.

Conclusions: New clinically relevant molecular tests have been generated using a small number of genes to accurately distinguish MPMs from other thoracic samples, supporting our hypothesis that the gene expression ratio approach could be a useful tool in the differential diagnosis of cancers. Clin Cancer Res; 19(9); 2493–502. ©2013 AACR.
Targeted Delivery of microRNA-29b by Transferrin-Conjugated Anionic Lipopolyplex Nanoparticles: A Novel Therapeutic Strategy in Acute Myeloid Leukemia
Authors: Huang Xiaomeng , Schwind Sebastian , Yu Bo , Santhanam Ramasamy , Wang Hongyan , Hoellerbauer Pia , Mims Alice , Klisovic Rebecca , Walker Alison R. , Chan Kenneth K. , Blum William , Perrotti Danilo , Byrd John C. , Bloomfield Clara D. , Caligiuri Michael A. , Lee Robert J. , Garzon Ramiro , Muthusamy Natarajan , Lee Ly James , Marcucci Guido
Published: March 2013

Purpose: miR-29b directly or indirectly targets genes involved in acute myeloid leukemia (AML), namely, DNMTs, CDK6, SP1, KIT, and FLT3. Higher miR-29b pretreatment expression is associated with improved response to decitabine and better outcome in AML. Thus, designing a strategy to increase miR-29b levels in AML blasts may be of therapeutic value. However, free synthetic miRs are easily degraded in bio-fluids and have limited cellular uptake. To overcome these limitations, we developed a novel transferrin-conjugated nanoparticle delivery system for synthetic miR-29b (Tf-NP-miR-29b).

Experimental Design: Delivery efficiency was investigated by flow cytometry, confocal microscopy, and quantitative PCR. The expression of miR-29b targets was measured by immunoblotting. The antileukemic activity of Tf-NP-miR-29b was evaluated by measuring cell proliferation and colony formation ability and in a leukemia mouse model.

Results: Tf-NP-miR-29b treatment resulted in more than 200-fold increase of mature miR-29b compared with free miR-29b and was approximately twice as efficient as treatment with non-transferrin–conjugated NP-miR-29b. Tf-NP-miR-29b treatment significantly downregulated DNMTs, CDK6, SP1, KIT, and FLT3 and decreased AML cell growth by 30% to 50% and impaired colony formation by approximately 50%. Mice engrafted with AML cells and then treated with Tf-NP-miR-29b had significantly longer survival compared with Tf-NP-scramble (P = 0.015) or free miR-29b (P = 0.003). Furthermore, priming AML cell with Tf-NP-miR-29b before treatment with decitabine resulted in marked decrease in cell viability in vitro and showed improved antileukemic activity compared with decitabine alone (P = 0.001) in vivo.

Conclusions: Tf-NP effectively delivered functional miR-29b, resulting in target downregulation and antileukemic activity and warrants further investigation as a novel therapeutic approach in AML. Clin Cancer Res; 19(9); 2355–67. ©2013 AACR.
Association between Loss-of-Function Mutations in the Filaggrin Gene and Self-Reported Food Allergy and Alcohol Sensitivity
Authors: Linneberg Allan , Fenger Runa V. , Husemoen Lise-Lotte N. , Thuesen Betina H. , Skaaby Tea , Gonzalez-Quintela Arturo , Vidal Carmen , Carlsen Berit C. , Johansen Jeanne D. , Menné Torkil , Stender Steen , Melgaard Michael , Szecsi Pal B. , Berg Nikolaj D. , Thyssen Jacob P.
Published: March 2013

Background: Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy. Objective: We investigated the association of FLG mutations with self-reported food allergy, symptoms of oral allergy syndrome (OAS), and alcohol sensitivity. Methods: A total of 3,471 adults from the general population participated in a health examination. Information on food allergies, OAS and alcohol sensitivity was obtained by questionnaire. FLG mutation carriers were defined as having at least one null mutation allele of R501X or 2282del4. Primary lactose intolerance (PLI) was defined as the C/C genotype of the rs4988235 polymorphism. Results: FLG mutations were associated with a higher risk of self-reported allergy to eggs (OR 3.22 and 95% CI 1.46-7.11), milk (OR 2.10 and 95% CI 1.12-3.92), fish (OR 4.54 and 95% CI 1.88-10.96) and wheat (OR 3.59 and 95% CI 1.61-8.02), but not with symptoms of OAS (OR 1.05 and 95% CI 0.73-1.51). Serum-specific IgE was measured in a subsample and confirmed the association between FLG and IgE to milk. A significant gene-by-gene interaction between FLG and PLI was observed in relation to self-reported allergy to milk. Furthermore, FLG mutations were associated with a higher risk of alcohol sensitivity. Conclusions: We found that loss-of-function mutations in the FLG gene were significantly associated with self-reported food allergy and alcohol sensitivity, but not with OAS. These findings, if confirmed, support the idea that skin barrier functions may be involved in the pathogenesis of food allergy.
Oral Challenges with Four Apple Cultivars Result in Significant Differences in Oral Allergy Symptoms
Authors: Nybom Hilde , Cervin-Hoberg Charlotte , Andersson Morgan
Published: March 2013

Background: We analyzed the hypoallergenic potential of a recently bred apple selection with unusually low content of Mal d 1, using an oral challenge model with three additional apple cultivars for comparison. Methods: Sixty-six birch pollen-allergic individuals with a history of oral allergy syndrome after apple intake were subjected to a double-blind oral provocation with two apple cultivars (B:0654 and ‘Discovery'). Thirteen also tested two other apple cultivars (‘Ingrid Marie' and ‘Gloster'). Three doses were given consecutively, 30 min apart: 10 g without peel, and 10 and 50 g with peel. A final assessment was conducted 30 min after the last intake. Oral symptoms were graded from 0 to 5. Total oral symptom score (TOS) included all scores for each cultivar at all time points. Results: B:0654 induced significantly higher TOS than ‘Discovery' when tested by 66 individuals, in spite of its lower Mal d 1 content. TOS values were higher in females and increased with increasing age of the individuals when challenged with ‘Discovery'. Among the 13 individuals who tested all four cultivars, B:0654 produced a higher score after the second dose compared to ‘Ingrid Marie'. This was also the case after the third dose compared to ‘Ingrid Marie' and ‘Gloster', and again 30 min after the last intake compared to each of the other three cultivars, as well as a higher TOS compared to each of the other three cultivars (all p < 0.01). Conclusions: Our test was safe and well tolerated, and produced significant differences among the apple cultivars. Contrary to expectations, B:0654 was less well tolerated than the other three cultivars.
Allergen Chip Diagnosis for Soy-Allergic Patients: Gly m 4 as a Marker for Severe Food-Allergic Reactions to Soy
Authors: Berneder M. , Bublin M. , Hoffmann-Sommergruber K. , Hawranek T. , Lang R.
Published: March 2013

Background: Gly m 5 and Gly m 6 are known to induce severe reactions in soy-allergic patients. For birch pollen (BP)-allergic patients, the Bet v 1 homologous allergen Gly m 4 is also a potential trigger of generalized severe reactions upon soy consumption. Therefore, reliable component-resolved diagnosis of soy allergy is needed. Methods: IgE reactivity from sera of 20 patients from a BP environment with reported soy allergy was assessed. Skin prick tests (SPT) with BP and soy drink were performed. Specific IgE for BP, soy, Bet v 1 and Gly m 4 was analyzed by ImmunoCAP. In addition, ISAC microarray profiling was performed. Results: Nineteen of 20 patients were BP allergic (positive SPT and/or CAP results for BP extract and Bet v 1). Eighteen soy-allergic patients were tested positive with soy drink in SPT. Soy CAP results were negative in the majority of tests (15/20), whereas 19/20 sera had specific IgE to Gly m 4. In the microarray approach, 14/20 sera displayed Gly m 4-specific IgE, the additional 6 sera had IgE levels below 0.3 ISAC standardized units. The BP-negative serum had Gly m 5- and Gly m 6-specific IgE which correlated with positive soy ImmunoCAP. Conclusions: Soy sensitization detected by SPT and Gly m 4 ImmunoCAP were in good qualitative agreement with ISAC results. Soy ImmunoCAP was only specific for Gly m 5 and Gly m 6 sensitization. Gly m 4 ImmunoCAP has a higher sensitivity than ImmunoCAP ISAC. In this patient cohort, Gly m 4 sensitization was linked to the development of severe and generalized allergic reactions upon soy consumption.
Rice Allergy Demonstrated by Double-Blind Placebo-Controlled Food Challenge in Peach-Allergic Patients Is Related to Lipid Transfer Protein Reactivity
Authors: Pastorello Elide Anna , Scibilia Joseph , Farioli Laura , Primavesi Laura , Giuffrida Maria Gabriella , Mascheri Ambra , Piantanida Marta , Mirone Corrado , Stafylaraki Chrysi , Violetta Marta Riva , Nichelatti Michele , Preziosi Donatella , Losappio Laura , Pravettoni Valerio
Published: March 2013

Background: The risk factors for sensitisation to rice and the involved allergens are still partially unknown. In this study we evaluated the clinically relevant aspects of rice allergy in DBPCF-positive patients, the major rice allergens, the severity of peach- and rice-induced symptoms in respect to Pru p 3 sensitisation and the role of anti-rPru p 3 IgE levels as a risk factor for rice allergy. Methods: In 148 peach-allergic subjects, patients with allergic reactions to rice and rice-positive serum IgE were selected. Symptoms were verified by double-blind placebo-controlled food challenges (DBPCFCs), performed at a maximum dosage of 25 g. Rice allergens, identified by IgE immunoblotting, were characterised by N-terminal amino acid sequencing. The relationship between anti-rPru p 3, 1 and 4 IgE levels and rice symptoms were statistically analysed. Results: Eight out of 10 recruited rice-allergic patients had positive DBPCFCs, while 2 patients were not challenged due to their previously documented severe reactions. All patients with rice-induced symptoms were Pru p 3 positive and presented with higher anti-rPru p 3 levels than the rice-sensitised but tolerant patients. A 9-kDa lipid transfer protein, which was highly homologous to Pru p 3, was identified as the major rice allergen and elicited a positive response in all of the patients. Five patients reacted to a putative 15- to 17-kDa rice allergenic protein, and 3 patients reacted to an [alpha]-amylase/subtilisin inhibitor that was approximately 20 kDa. Conclusion: Rarely, allergic reactions to rice can arise in patients with peach allergies who are sensitised to Pru p 3, particularly in patients with high anti-rPru p 3 IgE levels.
Factors Associated with the Risk of Adenoma Recurrence in Distal and Proximal Colon
Authors: Laiyemo Adeyinka O. , Doubeni Chyke , Pinsky Paul F. , Doria-Rose V. Paul , Marcus Pamela M. , Schoen Robert E. , Lanza Elaine , Cross Amanda J.
Published: March 2013

Background/Aims: Colonoscopy may be less effective in preventing cancer in the proximal colon. We evaluated whether risk factors for adenoma recurrence exhibit differential effect on adenoma recurrence by colon subsite. Methods: We examined the association of age, sex, body mass index, smoking status and use of nonsteroidal anti-inflammatory drugs (NSAIDs) on proximal and distal adenoma recurrence among 1,864 participants in the Polyp Prevention Trial. We used multinomial logistic regression models to calculate the relative risk ratios (RRR) and 95% CI. Results: 733 (39.3%) participants had adenoma recurrence (228 distal only, 369 proximal only and 136 synchronous proximal and distal adenoma). When compared to participants without adenoma recurrence, no factor was associated with an increased risk of distal only adenoma recurrence. Age 65-69 years (RRR = 1.47, 95% CI 1.00-2.16), age ≥70 years (RRR = 2.24, 95% CI 1.57-3.20), and male sex (RRR = 1.73, 95% CI 1.32-2.27) were positively associated with proximal only adenoma recurrence. NSAIDs use was associated with a reduced risk of adenoma recurrence by similar magnitude in distal (RRR = 0.78, 95% CI 0.58-1.07) and proximal colon (RRR = 0.77, 95% CI 0.60-1.00). Conclusions: We did not find any modifiable risk factor that differentially increases proximal as compared to distal adenoma recurrence to be clinically useful for targeted intervention.
Efficacy of Recombinant Allergens for Diagnosis of Cockroach Allergy in Patients with Asthma and/or Rhinitis
Authors: Barbosa Michelle C.R. , Santos Ana Beatriz R. , Ferriani Virginia P.L. , Pomés Anna , Chapman Martin D. , Arruda L.Karla
Published: March 2013

Background: Immunoglobulin E (IgE) reactivity to individual allergens among cockroach-allergic patients has revealed wide variability. The aim of this study was to assess the effectiveness of recombinant cockroach allergens for skin testing, and to determine sensitization profiles among cockroach-allergic patients living in Brazil. Methods: Fifty-seven cockroach-allergic patients with asthma and/or rhinitis were recruited. Skin testing with recombinant (r) allergens from Periplaneta americana (rPer a 1 and rPer a 7) and Blattella germanica (rBla g 2, rBla g 4 and rBla g 5) were performed at 10 μg/ml and 5 μg/ml (rPer a 1). IgE antibodies to rPer a 7 and rPer a 1 were quantitated by ELISA. Results: Of 57 patients tested, 3 (5.3%), 24 (42.1%), 4 (7%), 3 (5.3%) and 4 (7%) showed positive reactions to rPer a 1, rPer a 7, rBla g 2, rBla g 4 and rBla g 5, respectively. Twenty-eight patients (49.1%) had positive tests to at least one allergen. In keeping with skin test results, 31/57 patients (54.4%) and 5/55 patients (9%) had detectable IgE to rPer a 7 and rPer a 1, respectively. Levels of IgE to rPer a 7 were higher in patients with positive tests to rPer a 7 than those with negative tests (geometric mean 13.2 and 1.8 IU/ml, p < 0.05). There was good concordance of results of skin tests and measurements of serum IgE to rPer a 7. Conclusion: IgE reactivity to rPer a 7 (P. americana tropomyosin) was dominant among patients in Brazil. However, 50% of the patients did not present reactivity to any of the recombinant allergens tested.
Sublingual Immunotherapy for Experimental Allergic Conjunctivitis in a Murine Model Induced by Dermatophagoides farinae Allergen
Authors: Liu Li-lin , Guo Dan-dan , Liang Qiao-xia , Ding Shan , Chen Jing-ya , Wu Bing , Li Qin
Published: March 2013

Background: Sublingual immunotherapy (SLIT) is a clinically effective treatment in allergic conjunctivitis (AC); however, the mechanism of the underlying pharmacodynamics remains unclear. Here, we investigate the efficacy and the mechanism of a sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine AC model. Methods: A murine model of AC caused by Der f extract was developed in BALB/c mice by repeated application of allergen. Sensitized mice were SLIT treated by Der f drops and subsequently analyzed for AC symptoms, histopathological and immunological parameters. Results: In this study, Der f extract successfully induced the symptoms of AC in BALB/c mice. In these sensitized mice, clinical symptoms (scratching behavior, lacrimation, conjunctival hyperemia and edema), immunological and histopathological findings (inflammatory cell infiltration) were very similar to those in human AC. SLIT treatment of sensitized mice markedly reduced the clinical and histopathological symptoms and decreased the expression levels of total immunoglobulin E (IgE), Der f-specific IgE and T helper cell 2 (Th2) cytokine interleukin-4, with a significant increase in Der f-specific IgG4 and Th1 cytokine interferon-γ. Conclusions: SLIT with Der f drops is a potentially effective means of immunotherapy for Der f-induced AC by modulating the Th2-biased allergic immune response.
Non-Natriuretic Doses of Furosemide: Potential Use for Decreasing the Workload of the Renal Outer Medulla with Minimal Magnesium Wasting in the Rat
Authors: Kim Namhee , Cheema-Dhadli Surinder , Hare Gregory M.T. , Chong Chee Kiong , Halperin Mitchell L. , Kamel Kamel S. , Mazer C. David
Published: March 2013

Background/Aims: Since furosemide (FS) inhibits active Na+ reabsorption by medullary thick ascending limb (mTAL) in the renal outer medulla, it may decrease its work during periods of low O2 supply to deep in the renal outer medulla. This study was designed to demonstrate that there may be a dose of FS would reduce its metabolic work while preventing the excessive loss of magnesium (Mg2+). Mg2+ is important because the ATP needed to perform work must have bound Mg2+ to it. Methods: Rats were injected intraperitoneally with a range of doses of FS. The measured outcomes were urine flow rate and parameters of functions of the mTAL (i.e. urine and renal papillary osmolality and urinary excretion of Na+, Cl-, K+ and Mg2+, and concentrations of Mg2+ in serum). Results: The urine flow rate increased significantly starting at 2.4 mg FS/kg. The renal papillary osmolality decreased at ≥0.4 mg FS/kg, and the large detectable natriuresis started at 1.6 mg FS/kg. At this latter dose, the urinary excretion of Mg2+ rose significantly. Conclusion: In rats, the non-natriuretic dose of FS may reduce the work of the mTAL. The earliest indicator of reduced work in the mTAL appears to be a decrease in urine osmolality rather than a rise in urine flow rate. Higher doses of FS should be avoided, as they induce high rates of Mg2+ excretion, which can deplete the body of this essential electrolyte.