bluuebunny/crossref_metadata_2025 huggingface dataset:
The Exact Absorbing Conditions Method in the Analysis of Open Electrodynamic Structures: Circular and Coaxial Waveguides
Authors: Sautbekov Seil S. , Sirenko Yuriy K. , Velychko Lyudmyla G. , Vertiy Alexey A.
Published: April 2014

The exact absorbing conditions (EAC) have been constructed and used for truncating an unbounded domain of computation in open initial boundary value problems, which describe space-time transformations of electromagnetic waves in axially symmetrical waveguides. The equivalence theorem is proved that gives grounds for rigorous theoretical justification of the EAC-method.
Predictive Function Optimization Control for a Class of Hydraulic Servo Vibration Systems
Authors: Feng Xugang , Zhang Jiayan , Wang Jing , Xiong Shaokang , Wu Qiling , Fei Yetai
Published: April 2014

This paper is concerned with the problem of predictive function control (PFC) for a class of hydraulic vibration servo control systems. Our aim is to design a new advanced control strategy such that the control system can track trajectory in a fast and accurate way. For this end, the mathematical model of the hydraulic vibration servo control system is firstly studied. By analyzing the nonlinear, time-varying, and model structure uncertainty features of the objects, the desired control strategy is presented based on PFC. Finally, the simulation results show that our proposed method is effective and can be used to improve the tracking speed, accuracy, and robustness.
Improvement of Energy Density in Single Stator Interior Permanent Magnet Using Double Stator Topology
Authors: Nor Firdaus Raja , Misron Norhisam , Aravind Vaithilingam Chockalingam , Nirei Masami , Wakiwaka Hiroyuki
Published: April 2014

The paper presents the energy density improvement using magnetic circuit analysis of the interior permanent magnet motor. The leakage flux from the conventional structure is improved with modified magnetic circuit to improve the energy and thereby the torque value. This is approached with a double stator structure design. The proposed structure is investigated with two design variations, namely, the double stator with thin pole shoe and the double stator with thick pole shoe motors. Variations in the mechanical parameters of the all the developed models are analyzed through the finite element analysis tool. In all investigations the magnetic source is fixed in both the permanent magnet volume and coil magnetomotive force, respectively, as 400 mm3 per each pole and 480 Ampere turns per pole. From the analysis the best fit magnetic structure based on the torque characteristics is derived and is fabricated for the same volume as that of the conventional structure for performance evaluations. It is found out that there is improvement on the motor constant square density for the proposed improved magnetic circuit through the best fit double stator with thick pole shoe by about 83.66% greater than that of the conventional structure.
Average and Small Signal Modeling of Negative‐Output KY Boost Converter in CCM Operation
Authors: Wang Faqiang , Li Jing , Ma Xikui
Published: April 2014

Negative‐output KY Boost converter, which can obtain the negative output voltage and could be driven easily, is a good topology to overcome traditional Boost and Buck‐Boost converters and it is believed that this converter will be widely used in engineering applications in the future. In this study, by using the averaging method and geometrical technique, the average and small signal model of the negative‐output KY Boost converter are established. The DC equilibrium point and transfer functions of the system are derived and analyzed. Finally, the effectiveness of the established model and the correctness of the theoretical analysis are confirmed by the circuit experiment.
Investigation of Gamma and Neutron Shielding Parameters for Borate Glasses Containing NiO and PbO
Authors: Singh Vishwanath P. , Badiger N. M.
Published: April 2014

The mass attenuation coefficients, μ/ρ, half-value layer, HVL, tenth-value layer, TVL, effective atomic numbers, ZPIeff, and effective electron densities, Ne,eff, of borate glass sample systems of (100-x-y) Na2B4O7 : xPbO : yNiO (where x and y=0, 2, 4, 6, 8, and 10 weight percentage) containing PbO and NiO, with potential gamma ray and neutron shielding applications, have been investigated. The gamma ray interaction parameters, μ/ρ, HVL, TVL, ZPIeff, and Ne,eff, were computed for photon energy range 1 keV–100 GeV. The macroscopic fast neutron removal cross-sections (ΣR) have also been calculated. Appreciable variations were noted for all the interaction parameters by varying the photon energy and the chemical composition of the glass samples. The better shielding properties of borate glass samples containing PbO were found. These results indicated that borate glass samples are a good radiation shielding material.
Recent Updates in the Treatment of Neurodegenerative Disorders Using Natural Compounds
Authors: Rasool Mahmood , Malik Arif , Qureshi Muhammad Saeed , Manan Abdul , Pushparaj Peter Natesan , Asif Muhammad , Qazi Mahmood Husain , Qazi Aamer Mahmood , Kamal Mohammad Amjad , Gan Siew Hua , Sheikh Ishfaq Ahmed
Published: April 2014

Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS). Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in the CNS also leads to various CNS‐related diseases. Even though synthetic drugs are used for the management of Alzheimer’s disease, Parkinson’s disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti‐inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.
Comparative Oncogenomics Identifies PSMB4 and SHMT2 as Potential Cancer Driver Genes
Authors: Lee Genee Y. , Haverty Peter M. , Li Li , Kljavin Noelyn M. , Bourgon Richard , Lee James , Stern Howard , Modrusan Zora , Seshagiri Somasekar , Zhang Zemin , Davis David , Stokoe David , Settleman Jeffrey , de Sauvage Frederic J. , Neve Richard M.
Published: April 2014

Cancer genomes maintain a complex array of somatic alterations required for maintenance and progression of the disease, posing a challenge to identify driver genes among this genetic disorder. Toward this end, we mapped regions of recurrent amplification in a large collection (n = 392) of primary human cancers and selected 620 genes whose expression is elevated in tumors. An RNAi loss-of-function screen targeting these genes across a panel of 32 cancer cell lines identified potential driver genes. Subsequent functional assays identified SHMT2, a key enzyme in the serine/glycine synthesis pathway, as necessary for tumor cell survival but insufficient for transformation. The 26S proteasomal subunit, PSMB4, was identified as the first proteasomal subunit with oncogenic properties promoting cancer cell survival and tumor growth in vivo. Elevated expression of SHMT2 and PSMB4 was found to be associated with poor prognosis in human cancer, supporting the development of molecular therapies targeting these genes or components of their pathways. Cancer Res; 74(11); 3114–26. ©2014 AACR.
Influence of Drug Formulation on OATP1B-Mediated Transport of Paclitaxel
Authors: Nieuweboer Annemieke J.M. , Hu Shuiying , Gui Chunshan , Hagenbuch Bruno , Ghobadi Moghaddam-Helmantel Inge M. , Gibson Alice A. , de Bruijn Peter , Mathijssen Ron H.J. , Sparreboom Alex
Published: April 2014

Taxane antineoplastic agents are extensively taken up into hepatocytes by OATP1B-type transporters before metabolism and excretion. Because the biodistributional properties imposed upon these agents by different solubilizers drive clinically important pharmacodynamic endpoints, we tested the hypothesis that the in vitro and in vivo interaction of taxanes with OATP1B transporters is affected by the choice of drug delivery system. Transport of paclitaxel, docetaxel, and cabazitaxel was studied in vitro using various cell lines transfected with OATP1B1, OATP1B3, or the rodent equivalent OATP1B2. Pharmacokinetic studies were done in wild-type and OATP1B2-knockout mice in the presence or absence of polysorbate 80 (PS80) or Kolliphor EL (formerly Cremophor EL; CrEL). Paclitaxel and docetaxel, but not cabazitaxel, were transported substrates of OATP1B1, OATP1B3, and OATP1B2, and these in vitro transport processes were strongly reduced in the presence of clinically relevant concentrations of PS80 and CrEL. When paclitaxel was administered without any solubilizers, deficiency of OATP1B2 in mice was associated with a significantly decreased systemic clearance because of a liver distribution defect (P = 0.000484). However, this genotype dependence of paclitaxel clearance was masked in the presence of PS80 or CrEL because of significant inhibition of OATP1B2-mediated hepatocellular uptake of the drug (P < 0.05). Our findings confirm the importance of OATP1B-type transporters in the hepatic elimination of taxanes and indicate that this process can be inhibited by PS80 and CrEL. These results suggest that the likelihood of drug–drug interactions mediated by these transporters is strongly dependent on the selected taxane solubilizer. Cancer Res; 74(11); 3137–45. ©2014 AACR.
Molecular Pathways: Niches in Metastatic Dormancy
Authors: Yumoto Kenji , Eber Matthew R. , Berry Janice E. , Taichman Russell S. , Shiozawa Yusuke
Published: April 2014

Despite the best available treatments for primary tumors, cancer can return, even after a long disease-free interval. During this period, cancer cells are believed to lie dormant in either primary sites, metastatic sites, or independent sites like bone marrow, effectively escaping adjuvant cytotoxic treatments. To date, little is known about how these cells transition to dormancy, or how they are reactivated if cancer recurs. Recent studies have revealed the effects of tumor microenvironment or niche on the regulation of tumor dormancy via the signaling pathways of growth arrest–specific 6, bone morphogenetic protein 7, and TGFβ1, and that the balance between activation of p38 MAPK and ERK MAPK plays a pivotal role in tumor dormancy. In this review, we discuss tumor dormancy from the perspective of the niche and consider potential therapeutic targets. Greater understanding of the mechanisms involved will help guide innovation in the care of patients with advanced cancer. Clin Cancer Res; 20(13); 3384–9. ©2014 AACR.
Generation of a Canine Anti-EGFR (ErbB-1) Antibody for Passive Immunotherapy in Dog Cancer Patients
Authors: Singer Josef , Fazekas Judit , Wang Wei , Weichselbaumer Marlene , Matz Miroslawa , Mader Alexander , Steinfellner Willibald , Meitz Sarah , Mechtcheriakova Diana , Sobanov Yuri , Willmann Michael , Stockner Thomas , Spillner Edzard , Kunert Renate , Jensen-Jarolim Erika
Published: April 2014

Passive immunotherapy with monoclonal antibodies represents a cornerstone of human anticancer therapies, but has not been established in veterinary medicine yet. As the tumor-associated antigen EGFR (ErbB-1) is highly conserved between humans and dogs, and considering the effectiveness of the anti-EGFR antibody cetuximab in human clinical oncology, we present here a “caninized” version of this antibody, can225IgG, for comparative oncology studies. Variable region genes of 225, the murine precursor of cetuximab, were fused with canine constant heavy gamma and kappa chain genes, respectively, and transfected into Chinese hamster ovary (CHO) DUKX-B11 cells. Of note, 480 clones were screened and the best clones were selected according to productivity and highest specificity in EGFR-coated ELISA. Upon purification with Protein G, the recombinant cetuximab-like canine IgG was tested for integrity, correct assembly, and functionality. Specific binding to the surface of EGFR-overexpressing cells was assessed by flow cytometry and immunofluorescence; moreover, binding to canine mammary tissue was demonstrated by immunohistochemistry. In cell viability and proliferation assays, incubation with can225IgG led to significant tumor cell growth inhibition. Moreover, this antibody mediated significant tumor cell killing via phagocytosis in vitro. We thus present here, for the first time, the generation of a canine IgG antibody and its hypothetical structure. On the basis of its cetuximab-like binding site, on the one hand, and the expression of a 91% homologous EGFR molecule in canine cancer, on the other hand, this antibody may be a promising research compound to establish passive immunotherapy in dog patients with cancer. Mol Cancer Ther; 13(7); 1777–90. ©2014 AACR.
Metronomic Docetaxel in PRINT Nanoparticles and EZH2 Silencing Have Synergistic Antitumor Effect in Ovarian Cancer
Authors: Gharpure Kshipra M. , Chu Kevin S. , Bowerman Charles J. , Miyake Takahito , Pradeep Sunila , Mangala Selanere L. , Han Hee-Dong , Rupaimoole Rajesha , Armaiz-Pena Guillermo N. , Rahhal Tojan B. , Wu Sherry Y. , Luft J. Christopher , Napier Mary E. , Lopez-Berestein Gabriel , DeSimone Joseph M. , Sood Anil K.
Published: April 2014

The purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic experiments were conducted in well-established orthotopic mouse models of epithelial ovarian cancer. Antitumor effects were determined on the basis of reduction in mean tumor weight and number of metastatic tumor nodules in the animals. The tumor tissues from these in vivo studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase 3), and microvessel density (CD31). The lowest dose of metronomic regimen (0.5 mg/kg) resulted in significant reduction in tumor growth. The combination of PLGA-PRINT-docetaxel and CH-mEZH2 siRNA showed significant antitumor effects in the HeyA8 and SKOV3ip1 tumor models (P < 0.05). Individual as well as combination therapies showed significant antiangiogenic, antiproliferative, and proapoptotic effects, and combination therapy had additive effects. Metronomic delivery of PLGA-PRINT-docetaxel combined with CH-mEZH2 siRNA has significant antitumor activity in preclinical models of ovarian cancer. Mol Cancer Ther; 13(7); 1750–7. ©2014 AACR.
Short- and Long-term Lung Cancer Risk Associated with Noncalcified Nodules Observed on Low-Dose CT
Authors: Pinsky Paul F. , Nath P. Hrudaya , Gierada David S. , Sonavane Sushil , Szabo Eva
Published: April 2014

Chemoprevention is an important potential tool in reducing lung cancer incidence. Noncalcified nodules (NCN) observed on low-dose computed tomography (LDCT) have been proposed as intermediate endpoints in chemoprevention trials, but whether NCNs represent cancer precursors is unclear. We analyzed data from subjects in the LDCT arm of the National Lung Screening Trial (NLST) to examine short- and long-term lung cancer risks associated with NCNs and to elucidate whether some NCNs may be cancer precursors. NLST subjects received a baseline and two additional LDCT screens and were followed for a median of 6.5 years. We examined lung cancer incidence over three distinct periods from baseline—0–23 months (short-term), 24–59 months (medium-term), and 60–84 months (long-term)—in relation to baseline NCN characteristics. Spatially, lung cancer incidence was analyzed at the person, lung, and lobe levels relative to NCN location. A total of 26,272 subjects received the baseline LDCT screen, with 468, 413, and 190 lung cancers observed in the three periods. The presence of an NCN gave significantly elevated long-term lung cancer risk ratios (RR) of 1.8, 2.4, and 3.5 at the person, lung, and lobe levels; corresponding short-term RRs were 10.3, 16.8, and 38.0. Ground-glass attenuation was positively associated with long-term lung cancer risk but inversely associated with short-term risk; NCN size was positively associated with short-term risk but not significantly associated with long-term risk. That NCNs convey significantly elevated excess long-term of lung cancer lends evidence to the hypothesis that some NCNs may be cancer precursors. Cancer Prev Res; 7(12); 1179–85. ©2014 AACR.
Subcortical and Deep Cortical Atrophy in Frontotemporal Dementia due to Granulin Mutations
Authors: Premi Enrico , Garibotto Valentina , Gazzina Stefano , Formenti Anna , Archetti Silvana , Gasparotti Roberto , Padovani Alessandro , Borroni Barbara
Published: April 2014

Background/Aims: Parkinsonism is often associated with symptoms of frontotemporal dementia (FTD), but its pathogenesis has been largely neglected. In genetic inherited FTD-related granulin (GRN) mutations, parkinsonism is an early sign, and it is more common than in sporadic disorders. Our aim was to study grey matter (GM) volume changes in subcortical and deep cortical regions in GRN-related FTD. Methods: A total of 33 FTD patients (13 carriers of the GRN mutation, GRN+, and 20 non-carriers, GRN-) and 12 healthy controls (HC) were included in the study. Each subject underwent an MRI examination (1) for voxel-based morphometry to study GM differences in cortical and subcortical regions, and (2) for a region of interest approach using a probabilistic atlas of subcortical regions (caudate nucleus, putamen, thalamus and amygdala) to assess the regional differences. Results: The GRN+ group showed greater damage in frontotemporal regions than the GRN- group. The FTD patients had greater GM atrophy in the caudate nucleus and in the thalamus bilaterally than the HC. Damage to these subcortical and deep cortical regions was greater in the GRN+ than in the GRN- patients. Discussion: Subcortical and deep cortical involvement is a key feature of FTD, and more pronounced in GRN-related disease. Damage to the caudate region in GRN+ patients may explain the parkinsonism frequently associated since the early stages of the disease.
Autoimmune Aspects of Type 2 Diabetes Mellitus - A Mini-Review
Authors: Itariu Bianca K. , Stulnig Thomas M.
Published: April 2014

Autoimmunity is a well-known pathogenic component in type 1 diabetes (T1DM). The assumption that the pathogenesis of type 2 diabetes (T2DM) also encompasses autoimmune aspects is recognized increasingly, based on the presence of circulating autoantibodies against β cells, self-reactive T cells, but also on the glucose-lowering efficacy of some immunomodulatory therapies in T2DM. The identification of these autoantibodies in elderly patients with slowly progressive manifestation of diabetes led to the introduction of a distinct clinical entity termed latent autoimmune diabetes of the adult (LADA), which combines features of both T1DM and T2DM. The autoantibody cluster differs in patients with LADA from patients with T1DM, but their presence indicates steady progression towards β-cell death and subsequent need for initiation of insulin treatment in a shorter period of time compared to autoantibody-negative T2DM patients. Autoimmune aspects in T2DM are not solely restricted to autoantibodies and thus LADA. They include the self-reactive T cells or defects in regulatory T cells (Tregs), which have been detected in autoantibody-negative T2DM patients as well. One contributor to the autoimmune activation in T2DM seems to be the chronic inflammatory state, characteristic of this disease. Upon inflammation-induced tissue destruction, cryptic ‘self' antigens can trigger an autoimmune response, which in turn accelerates β-cell death. Both innate and adaptive immune system components, specifically macrophages and self-reactive T cells, contribute to an increased secretion of inflammatory cytokines involved in inflammatory and autoimmune processes. However, the extent to which inflammation overlaps with autoimmunity is not known. Our review focuses on autoimmune involvement in T2DM, with an emphasis on LADA and the humoral immune response, on the involvement of chronic inflammation in autoimmunity, and specifically the role of B and T cells as links between inflammatory and autoimmune reactions. We will further stress the consequences of autoimmune activation for T2DM patients and present novel therapeutic approaches for T2DM management that rely on immune modulation.
Epigenetic Involvement in Hutchinson-Gilford Progeria Syndrome: A Mini-Review
Authors: Arancio Walter , Pizzolanti Giuseppe , Genovese Swonild I. , Pitrone Maria , Giordano Carla
Published: April 2014

Hutchinson-Gilford progeria syndrome (HGPS) is a rare human genetic disease that leads to a severe premature ageing phenotype, caused by mutations in the LMNA gene. The LMNA gene codes for lamin-A and lamin-C proteins, which are structural components of the nuclear lamina. HGPS is usually caused by a de novo C1824T mutation that leads to the accumulation of a dominant negative form of lamin-A called progerin. Progerin also accumulates physiologically in normal ageing cells as a rare splicing form of lamin-A transcripts. From this perspective, HGPS cells seem to be good candidates for the study of the physiological mechanisms of ageing. Progerin accumulation leads to faster cellular senescence, stem cell depletion and the progeroid phenotype. Tissues of mesodermic origin are especially affected by HGPS. HGPS patients usually have a bad quality of life and, with current treatments, their life expectancy does not exceed their second decade at best. Though progerin can be expressed in almost any tissue, when death occurs, it is usually due to cardiovascular complications. In HGPS, severe epigenetic alterations have been reported. Histone-covalent modifications are radically different from control specimens, with the tendency to lose the bipartition into euchromatin and heterochromatin. This is reflected in an altered spatial compartmentalization and conformation of chromatin within the nucleus. Moreover, it seems that microRNAs and microRNA biosynthesis might play a role in HGPS. Exemplary in this connection is the suggested protective effect of miR-9 on the central nervous system of affected individuals. This mini-review will report on the state of the art of HGPS epigenetics, and there will be a discussion of how epigenetic alterations in HGPS cells can alter the cellular metabolism and lead to the systemic syndrome.
Ultrasonographic Assessment of the Diaphragm in Chronic Obstructive Pulmonary Disease Patients: Relationships with Pulmonary Function and the Influence of Body Composition - A Pilot Study
Authors: Smargiassi Andrea , Inchingolo Riccardo , Tagliaboschi Linda , Di Marco Berardino Alessandro , Valente Salvatore , Corbo Giuseppe Maria
Published: April 2014

Background: Skeletal muscle weakness with loss of fat-free mass (FFM) is one of the main systemic effects of chronic obstructive pulmonary disease (COPD). The diaphragm is also involved, leading to disadvantageous conditions and poor contractile capacities. Objectives: We measured the thickness of the diaphragm (TD) by ultrasonography to evaluate the relationships between echographic measurements, parameters of respiratory function and body composition data. Methods: Thirty-two patients (23 males) underwent (1) pulmonary function tests, (2) echographic assessment of TD in the zone of apposition at various lung volumes, i.e. TD at residual volume (TDRV), TD at functional residual capacity (TDFRC) and TD at total lung capacity (TDTLC), and (3) bioelectrical body impedance analysis. The BMI and the BODE (BMI-Obstruction-Dyspnea-Exercise) index values were reported. Results: TDRV, TDFRC and TDTLC measured 3.3, 3.6 and 6 mm, respectively, with good intraobserver reproducibility (0.97, 0.97 and 0.96, respectively). All the TDs were found to be related to FFM, with the relationship being greater for TDFRC (r2 = 0.39 and p = 0.0002). With regard to lung volumes, inspiratory capacity (IC) was found to be closely related to TDTLC (r2 = 0.42 and p = 0.0001). The difference between TDTLC and TDRV, as a thickening value (TDTLCRV), was closely related to FVC (r2 = 0.34 and p = 0.0004) and to air-trapping indices (RV/TLC, FRC/TLC and IC/TLC): the degree of lung hyperinflation was greater and the TDTLCRV was less. Finally, we found a progressive reduction of both thicknesses and thickenings as the severity of IC/TLC increased, with a significant p value for the trend in both analyses (p = 0.02). Conclusions: Ultrasonographic assessment of the diaphragm could be a useful tool for studying disease progression in COPD patients, in terms of lung hyperinflation and the loss of FFM.
The Identification of Regions of Significance in the Effect of Multimorbidity on Depressive Symptoms Using Longitudinal Data: An Application of the Johnson-Neyman Technique
Authors: Rast Philippe , Rush Jonathan , Piccinin Andrea , Hofer Scott M.
Published: April 2014

Background: The investigation of multimorbidity and aging is complex and highly intertwined with aging-related changes in physical and cognitive capabilities, and mental health and is known to affect psychological distress and quality of life. Under these circumstances it is important to understand how the effects of chronic conditions evolve over time relative to aging-related and end-of-life changes. The identification of periods in time where multimorbidity impacts particular outcomes such as depressive symptoms, versus periods of time where this is not the case, reduces the complexity of the phenomenon. Objective: We present the Johnson-Neyman (J-N) technique in the context of a curvilinear longitudinal model with higher-order terms to probe moderators and to identify regions of statistical significance. In essence, the J-N technique allows one to identify conditions under which moderators impact an outcome from conditions where these effects are not significant. Methods: To illustrate the use of the J-N technique in a longitudinal sample, we used data from the Health and Retirement Study. Analyses were based on time-to-death models including participants who died within the study duration of 12 years. Results: Multimorbidity differentially affects rates of change in depression. For some periods in time the effects are statistically significant while in other periods the same effects are not statistically different from zero. Conclusion: The J-N technique is useful to continuously probe moderating effects and to identify particular interactions with the model for time when certain effects are or are not statistically significant. In the context of multimorbidity this method is particularly useful for interpreting the complex interactions with differential change over time.
A Multicenter Case-Control Study on Screening of Single Nucleotide Polymorphisms in Estrogen-Metabolizing Enzymes and Susceptibility to Uterine Leiomyoma in Han Chinese
Authors: Shen Yang , Ren Mu-Lan , Xu Jie , Xu Qian , Ding Yi-Qian , Wu Zhi-Cong , Zhang Hai-Bao , Huang Xian-Xia , Cai Yun-Lang
Published: April 2014

Uterine leiomyoma (UL) is an estrogen-responsive benign tumor in the female reproductive system and the main risk of hysterectomy for women. However, gene polymorphism of estrogen-metabolizing enzymes may lead to the different susceptibility to UL. We detected 10 single mucleotide polymorphisms in three key estrogen metabolite enzymes (COMT, CYP1A1, CYP1B1) in a Chinese Han population consisting of 800 patients and 800 healthy women from five different medical centers. The genetic polymorphism of rs3087869 (IVS1+2329C>T) (OR 3.200, 95% CI 1.614-6.345) and rs4680 (Val158Met) (OR 5.675, 95% CI 2.696-11.942) loci on COMT, rs1048943 (Ile462Val) (OR 4.629, 95% CI 2.216-9.672) and rs4646422 (Gly45Asp) (OR 3.240, 95% CI 1.624-6.461) loci on CYP1A1 and rs1065827 (Ala119Ser) (OR 5.635, 95% CI 2.990-10.619) locus on CYP1B1 were the risk factors to UL development and rs1056836 (Leu432Val) (OR 0.188, 95% CI 0.061-0.575) locus on CYB1B1 may be the protective factor to UL. The results provide a theoretical basis for genetic screening and early intervention to UL-susceptible populations.
Determinants of Neurological Functional Recovery Potential after Stroke in Young Adults
Authors: Haselbach Daniel , Renggli Anastasia , Carda Stefano , Croquelois Alexandre
Published: April 2014

Background/Objectives: Despite recent progress in stroke prevention and acute treatment, neurorehabilitation remains one of the main methods of treatment in the management of stroke patients. The aim of this study is to point out some important predicting factors of in-hospital neurorehabilitation outcomes. Methods: A rehabilitation registry including all patients who had undergone a standardized program of neurorehabilitation at the neurorehabilitation unit of the Lausanne University Hospital, Lausanne, Switzerland, was created. Patients aged <65 years and having experienced a first ever nontraumatic stroke from 2005 to 2010 were admitted. Using logistical regression models, predicting factors for each patient were compared to the exit Functional Independence Measure (FIM) score. Results: Age >55 years, gender, aphasia, hemilateral spatial neglect, spasticity, complications, length of stay >70 days, entry FIM >100 and relative possible FIM gain/week of >10% were considered to be significant and independent predicting factors of the neurorehabilitation outcome. Discussion/Conclusion: Some factors of the in-hospital rehabilitation period have been identified before (spasticity, complications, length of stay, relative possible FIM gain/week) and should be considered for a better management of the neurorehabilitation therapy. In addition, a personalized rehabilitation strategy based on the patient's individual needs should be aimed at. The question of resource allocation can also be addressed with regard to the present findings.
Culture Qualitatively but Not Quantitatively Influences Performance in the Boston Naming Test in a Chinese-Speaking Population
Authors: Chen Ting-Bin , Lin Chi-Ying , Lin Ker-Neng , Yeh Yen-Chi , Chen Wei-Ta , Wang Kuo-Shu , Wang Pei-Ning
Published: April 2014

Background/Aims: The Boston Naming Test (BNT) is the most frequently administered confrontational naming test, but the cultural background of the patients may influence their performance in the BNT. The aim of this study was to identify differences in performance in the BNT between a Chinese population in Taiwan, Chinese populations in other areas and a Caucasian population. Methods: A total of 264 native, Chinese-speaking, cognitively normal elders aged >60 years were enrolled in our study and conducted the 30-item Chinese version of the BNT. Another 10 BNT studies were categorized, analyzed and compared with the present study. Results: Higher education was associated with higher scores, whereas age and gender had no effect on performance in the BNT. The score of the Chinese-speaking population was equivalent to the English-speaking population. A disparity in difficulties with items was not only apparent between the Taiwanese and Caucasian populations, but also between the Chinese-speaking populations in the different geographic areas. Conclusion: For the most part, the impact of culture on performance in the BNT may not be quantitative but qualitative. Attention should be paid to a potential effect of culture on difficulties with items when administering the BNT to non-English-speaking populations. Understanding differences in performance in the BNT in distinct cultural settings improves the clinical application of the BNT.
Effect of KTP Laser Cochleostomy on Morphology in the Guinea Pig Inner Ear
Authors: Kamalski Digna M.A. , Peters Jeroen P.M. , de Boorder Tjeerd , Trabalzini Franco , Klis Sjaak F.L. , Grolman Wilko
Published: April 2014

Background: The main advantage of using the KTP (potassium-titanyl-phosphate) laser for stapedotomy instead of the conventional micropick instrument is the smaller risk for mechanical damage. However, the KTP laser could theoretically inflict damage to inner ear structures. We hypothesize that KTP laser light [wavelength (λ) = 532 nm] is hardly absorbed in perilymph but well absorbed in solid structures. The aim of this pilot study was to assess if damage occurred after KTP laser cochleostomy in an animal model and, if so, to what extent and at which settings. Materials and Methods: In six guinea pigs, a KTP laser cochleostomy at the basal turn was created. Laser settings of 1, 3 and 5 W and 100 ms pulse time (n = 2 each) were used. Histological preparations were studied for damage to neuroendothelial cells and intrascalar blood. Results: No damage to inner ear neuroendothelial cells was observed, even at the highest power. Blood clots in the scala tympani from vessels in the cochlear wall were seen. The effects were minimal in the lowest, currently clinically used settings. Conclusion: KTP laser cochleostomy gives no damage to inner ear neuroendothelial cells but may cause intrascalar hemorrhages.
Progression of Coronary Artery Calcification in Living Kidney Donors: A Follow-Up Study
Authors: Alagoz Selma , Cebi Deniz , Akman Canan , Altiparmak Mehmet R. , Serdengecti Kamil , Seyahi Nurhan
Published: April 2014

Background: Data on the long-term mortality and morbidity of living kidney donors are scarce. In the general population, coronary artery calcification (CAC) and progression of CAC are predictors of future cardiac risk. We conducted a study to determine the progression of CAC in renal transplant donors. Methods: We used multidetector computed tomography to examine CAC in 75 former renal transplant donors. A baseline and a follow-up scan were performed and changes in CAC scores were evaluated in each subject individually to calculate the incidence of CAC progression. Results: Baseline CAC prevalence was 16% and the mean CAC score was 5.3 ± 25.8. At the follow-up scan that was performed after an average of 4.8 ± 0.3 years, CAC prevalence increased to 72% and the mean CAC score to 12.5 ± 23.4. Progression of the individual CAC score was found between 18.7 and 26.7%, depending on the method used to define progression. In patients with baseline CAC, the mean annualized rate of CAC progression was 2.1. Presence of hypertension, high systolic blood pressure and an increase in BMI were the determinants of CAC progression. Conclusions: The rate of CAC progression does not seem to be high in carefully selected donors.
Sporotrichosis with Bone Involvement: An Alert to an Occupational Disease
Authors: Aguinaga Felipe de Carvalho , Trope Beatriz Moritz , Fernandes Nurimar Conceição , Engel Delia Celser , Ramos-e-Silva Marcia
Published: April 2014

Sporotrichosis is a subacute or chronic mycosis caused by a fungus of the genus Sporothrix, which is found in soil. It can be acquired by trauma to the skin. Bone and joint lesions are very rare. The city of Rio de Janeiro is undergoing an epidemic transmitted by cats, and this should be an alert for the risk to professionals in contact with these animals. The patient was a veterinarian who developed occupational sporotrichosis with osteoarticular involvement transmitted by a cat during a consultation.
Validity of Deterministic Record Linkage Using Multiple Indirect Personal Identifiers
Authors: Setoguchi Soko , Zhu Ying , Jalbert Jessica J. , Williams Lauren A. , Chen Chih-Ying
Published: April 2014

Background—

Linking patient registries with administrative databases can enhance the utility of the databases for epidemiological and comparative effectiveness research. However, registries often lack direct personal identifiers, and the validity of record linkage using multiple indirect personal identifiers is not well understood.

Methods and Results—

Using a large contemporary national cardiovascular device registry and 100% Medicare inpatient data, we linked hospitalization-level records. The main outcomes were the validity measures of several deterministic linkage rules using multiple indirect personal identifiers compared with rules using both direct and indirect personal identifiers. Linkage rules using 2 or 3 indirect, patient-level identifiers (ie, date of birth, sex, admission date) and hospital ID produced linkages with sensitivity of 95% and specificity of 98% compared with a gold standard linkage rule using a combination of both direct and indirect identifiers.

Conclusions—

Ours is the first large-scale study to validate the performance of deterministic linkage rules without direct personal identifiers. When linking hospitalization-level records in the absence of direct personal identifiers, provider information is necessary for successful linkage.
Notch Pathway Targets Proangiogenic Regulator Sox17 to Restrict Angiogenesis
Authors: Lee Seung-Hun , Lee Sungsu , Yang Hanseul , Song Sukhyun , Kim Kangsan , Saunders Thomas L. , Yoon Jeong K. , Koh Gou Young , Kim Injune
Published: April 2014

Rationale
:

The Notch pathway stabilizes sprouting angiogenesis by favoring stalk cells over tip cells at the vascular front. Because tip and stalk cells have different properties in morphology and function, their transcriptional regulation remains to be distinguished. Transcription factor Sox17 is specifically expressed in endothelial cells, but its expression and role at the vascular front remain largely unknown.

Objective
:

To specify the role of Sox17 and its relationship with the Notch pathway in sprouting angiogenesis.

Methods and Results
:

Endothelial-specific
Sox17
deletion reduces sprouting angiogenesis in mouse embryonic and postnatal vascular development, whereas
Sox17
overexpression increases it. Sox17 promotes endothelial migration by destabilizing endothelial junctions and rearranging cytoskeletal structure and upregulates expression of several genes preferentially expressed in tip cells. Interestingly, Sox17 expression is suppressed in stalk cells in which Notch signaling is relatively high. Notch activation by overexpressing Notch intracellular domain reduces Sox17 expression both in primary endothelial cells and in retinal angiogenesis, whereas Notch inhibition by delta-like ligand 4 (Dll4) blockade increases it. The Notch pathway regulates Sox17 expression mainly at the post-transcriptional level. Furthermore, endothelial
Sox17
ablation rescues vascular network from excessive tip cell formation and hyperbranching under Notch inhibition in developmental and tumor angiogenesis.

Conclusions
:

Our findings demonstrate that the Notch pathway restricts sprouting angiogenesis by reducing the expression of proangiogenic regulator Sox17.
The Learning Curve for Transradial Percutaneous Coronary Intervention Among Operators in the United States
Authors: Hess Connie N. , Peterson Eric D. , Neely Megan L. , Dai David , Hillegass William B. , Krucoff Mitchell W. , Kutcher Michael A. , Messenger John C. , Pancholy Samir , Piana Robert N. , Rao Sunil V.
Published: April 2014

Background—

Adoption of transradial percutaneous coronary intervention (TRI) in the United States is low and may be related to challenges learning the technique. We examined the relationships between operator TRI volume and procedural metrics and outcomes.

Methods and Results—

We used CathPCI Registry data from July 2009 to December 2012 to identify new radial operators, defined by an exclusively femoral percutaneous coronary intervention approach for 6 months after their first percutaneous coronary intervention in the database and ≥15 total TRIs thereafter. Primary outcomes of fluoroscopy time, contrast volume, and procedure success were chosen as markers of technical proficiency. Secondary outcomes included in-hospital mortality, bleeding, and vascular complications. Adjusted outcomes were analyzed by using operator TRI experience as a continuous variable with generalized linear mixed models. Among 54 561 TRI procedures performed at 704 sites, 942 operators performed 1 to 10 procedures, 942 operators performed 11 to 50 procedures, 375 operators performed 51 to 100 procedures, and 148 operators performed 101 to 200 procedures. As radial caseload increased, more TRIs were performed in women, in patients presenting with ST-segment elevation myocardial infarction, and for emergency indications. Decreased fluoroscopy time and contrast use were nonlinearly associated with greater operator TRI experience, with faster reductions observed for newer (<30–50 cases) compared with more experienced (>30–50 cases) operators. Procedure success was high, whereas mortality, bleeding, and vascular complications remained low across TRI volumes.

Conclusions—

As operator TRI volume increases, higher-risk patients are chosen for TRI. Despite this, operator proficiency improves with greater TRI experience, and safety is maintained. The threshold to overcome the learning curve appears to be approximately 30 to 50 cases.
Bisphenol A Increases Atherosclerosis in Pregnane X Receptor‐Humanized ApoE Deficient Mice
Authors: Sui Yipeng , Park Se‐Hyung , Helsley Robert N. , Sunkara Manjula , Gonzalez Frank J. , Morris Andrew J. , Zhou Changcheng
Published: April 2014

Background

Bisphenol A (
BPA
) is a base chemical used extensively in many consumer products.
BPA
has recently been associated with increased risk of cardiovascular disease (
CVD
) in multiple large‐scale human population studies, but the underlying mechanisms remain elusive. We previously reported that
BPA
activates the pregnane X receptor (
PXR
), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro‐atherogenic effects in animal models upon activation. Interestingly,
BPA
is a potent agonist of human
PXR
but does not activate mouse or rat
PXR
signaling, which confounds the use of rodent models to evaluate mechanisms of
BPA
‐mediated
CVD
risk. This study aimed to investigate the atherogenic mechanism of
BPA
using a
PXR
‐humanized mouse model.

Methods and Results

A
PXR
‐humanized ApoE deficient (hu
PXR
•ApoE
−/−
) mouse line was generated that respond to human
PXR
ligands and feeding studies were performed to determine the effects of
BPA
exposure on atherosclerosis development. Exposure to
BPA
significantly increased atherosclerotic lesion area in the aortic root and brachiocephalic artery of hu
PXR
•ApoE
−/−
mice by 104% (
P
<0.001) and 120% (
P
<0.05), respectively. By contrast,
BPA
did not affect atherosclerosis development in the control littermates without human
PXR
.
BPA
exposure did not affect plasma lipid levels but increased
CD
36 expression and lipid accumulation in macrophages of hu
PXR
•ApoE
−/−
mice.

Conclusion

These findings identify a molecular mechanism that could link
BPA
exposure to increased risk of
CVD
in exposed individuals.
PXR
is therefore a relevant target for future risk assessment of
BPA
and related environmental chemicals in humans.
CD3 Antibody and IL‐2 Complex Combination Therapy Inhibits Atherosclerosis by Augmenting a Regulatory Immune Response
Authors: Kasahara Kazuyuki , Sasaki Naoto , Yamashita Tomoya , Kita Tomoyuki , Yodoi Keiko , Sasaki Yoshihiro , Takeda Masafumi , Hirata Ken‐ichi
Published: April 2014

Background

Accumulating evidence suggests that the balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for controlling atherosclerotic disease. We hypothesized that a combination therapy with anti‐
CD
3 antibody (
CD
3‐Ab) and
IL
‐2/anti‐
IL
‐2 monoclonal antibody complex (
IL
‐2 complex) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice.

Methods and Results

We treated apolipoprotein E‐deficient mice fed a high‐cholesterol diet with vehicle,
CD
3‐Ab,
IL
‐2 complex, or their combination. Mice receiving the combination therapy had markedly reduced atherosclerotic lesions than mice treated with
CD
3‐Ab or
IL
‐2 complex alone. In addition, a striking increase in the Treg/Teff ratio of lymphoid organs and atherosclerotic lesions, along with plaque stabilization characterized by decreased macrophage content and increased collagen content was observed. The combination treatment also markedly reduced splenic Ly6C
high
inflammatory monocytes and might induce a favorable macrophage phenotype change in atherosclerotic lesions.

Conclusions

Our results indicate that in addition to suppressing Teff responses, enhancing Treg‐mediated immune responses is more efficacious in preventing atherosclerosis, suggesting a novel therapeutic approach for atherosclerosis.
Delayed Hyperbaric Oxygen Therapy Promotes Neurogenesis Through Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/β-Catenin Pathway in Middle Cerebral Artery Occlusion Rats
Authors: Hu Qin , Liang Xiping , Chen Di , Chen Yujie , Doycheva Desislava , Tang Junjia , Tang Jiping , Zhang John H.
Published: April 2014

Background and Purpose—

Hyperbaric oxygen (HBO) has been reported to be neuroprotective and to improve neurofunctional outcomes in acute stroke. However, it is not clear whether delayed HBO enhances endogenous neurogenesis and promotes neurofunctional recovery. The aim of this study is to evaluate the effects of delayed HBO therapy on neurogenesis and its potential mechanisms.

Methods—

One hundred eleven male Sprague–Dawley rats that survived for 7 days from 2 hours of middle cerebral artery occlusion and reperfusion were used. Delayed and multiple HBO were administrated beginning at 7 days after middle cerebral artery occlusion and lasting for 42 days with 3 HBO-free intervals (5 days each). Motor sensory deficits were measured by foot-fault test, and learning and memory abilities were evaluated by Morris water maze. Neurogenesis was examined by double immunostaining of bromodeoxyuridine and doublecortin, bromodeoxyuridine and neuronal nuclei at day 42. For mechanism studies, inhibitors for reactive oxygen species (ROS), hypoxia-inducible factor (HIF)-1α, and β-catenin were administrated, and the levels of ROS, HIF-1α, β-catenin, lymphoid enhancer–binding factor-1, T-cell factor-1, neurogenin-1, doublecortin, and synapsin-1 were assessed by ELISA or Western blot at day 14.

Results—

Delayed HBO treatment promoted neurogenesis and improved neurofunctional recovery at day 42, and the improvements were reversed by inhibition of ROS and HIF-1α. Delayed HBO significantly increased ROS and HIF-1α, and upregulated the expression of neurogenin-1, doublecortin, and synapsin-1. Inhibition of ROS and HIF-1α removed the effects of delayed HBO.

Conclusions—

Delayed HBO enhanced endogenous neurogenesis and improved neurofunctional recovery in the late-chronic phase of stroke possibly mediated by ROS/HIF-1α/β-catenin pathway. Delayed HBO may serve as an alternative treatment to improve long-term recovery of stroke survivors.
Nomenclatural changes in Bulbophyllum (Orchidaceae; Epidendroideae)
Authors: VERMEULEN JAAP J. , SCHUITEMAN ANDRÉ , DE VOGEL EDUARD F.
Published: April 2014

New combinations in Bulbophyllum (Orchidaceae) are made to correspond to the revised classification of the genus in Genera orchidacearum, vol. 6. Several new sections introduced in that publication are formally described and validated here.
Begonia intermedia, a new species of Begoniaceae from Hainan, China
Authors: TIAN DAI-KE , LI CHUN , YAN YUE-HONG , LI XIANG-PENG , MENG JING
Published: April 2014

Begonia intermedia D.K. Tian & Y.H. Yan, a new species in Begonia sect. Diploclinium (Wright) A. DC (Begoniaceae) from Hainan, China, is described and illustrated. It differs from the morphologically similar B. fimbristipula Hance by its orchid-root-like rhizomes, later flowering and distinctive hairy bracts. Also, based on a molecular phylogenetic analysis, B. intermedia is distinct from B. fimbristipula.