bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonsurgical Korean Integrative Treatments for Symptomatic Lumbar Spinal Stenosis: A Three‐Armed Randomized Controlled Pilot Trial Protocol
Authors: Kim Kiok , Shin Kyung-Min , Lee Jun-Hwan , Seo Bok-Nam , Jung So-Young , Youn Yousuk , Lee Sang Ho , Kim Jaehong , Qu Wenchun , Kim Tae-Hun
Published: January 2016

This is a study protocol for a pilot three‐armed randomized controlled trial on nonsurgical integrative Korean medicinal treatment for symptomatic lumbar spinal stenosis (LSS). Thirty‐six participants who have been diagnosed with (LSS) and recommended for spinal surgery by neurosurgeons or orthopedics and have had spinal symptoms such as severe low back pain and neurological claudication regardless of at least three months of conservative treatments will be recruited. Participants will be randomly assigned to be one of the three intervention groups, including the Mokhuri treatment program group 1 or 2 or usual care group. All treatments will be administered in inpatient units over a period of 4 weeks. The primary outcomes are 0 to 100 Visual Analogue Scales for low back pain and leg pain and the secondary outcomes are Oswestry Disability Index; EQ‐5D; Roland‐Morris Disability Questionnaire; Oxford Claudication Score; physical function test, including treadmill test, walking duration, and distance assessment for free leg pain; radiologic testing; and adverse events which will be assessed during the 4‐week treatment period as well as after 3 and 6 months of follow‐up. Then, we will assess the feasibility of the clinical trial design as well as a nonsurgical integrative treatment program. This trial is registered with CRIS registration number: KCT0001218.
Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats
Authors: Elshama Said Said , EL-Kenawy Ayman El-Meghawry , Osman Hosam-Eldin Hussein
Published: January 2016

Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40 mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose.
Protective Effect ofDiospyros kakiagainst Glucose-Oxygen-Serum Deprivation-Induced PC12 Cells Injury
Authors: Forouzanfar Fatemeh , Torabi Shaghayegh , Askari Vahid R. , Asadpour Elham , Sadeghnia Hamid R.
Published: January 2016

Ischemic cerebrovascular disease is one of the most common causes of death in the world. Recent interests have been focused on natural antioxidants and anti-inflammatory agents as potentially useful neuroprotective agents.Diospyros kaki(persimmon) has been shown to exert anti-inflammatory, antioxidant, and antineoplastic effects. However, its effects on ischemic damage have not been evaluated. Here, we used anin vitromodel of cerebral ischemia and studied the effects of hydroalcoholic extract of peel (PeHE) and fruit pulp (PuHE) of persimmon on cell viability and markers of oxidative damage mainly intracellular reactive oxygen species (ROS) induced by glucose-oxygen-serum deprivation (GOSD) in PC12 cells. GOSD for 6 h produced significant cell death which was accompanied by increased levels of ROS. Pretreatment with different concentrations of PeHE and PuHE (0–500 μg/mL) for 2 and 24 h markedly restored these changes only at high concentrations. However, no significant differences were seen in the protection against ischemic insult between different extracts and the time of exposure. The experimental results suggest that persimmon protects the PC12 cells from GOSD-induced injury via antioxidant mechanisms. Our findings might raise the possibility of potential therapeutic application of persimmon for managing cerebral ischemic and other neurodegenerative disorders.
CP-ABE with Hidden Policy from Waters Efficient Construction
Authors: Wang Zhiwei , He Mingjun
Published: January 2016

ABE provides a good way for access controlling in cloud computing. However, in many application scenarios, access policies for encryption also should be protected since they may directly contain sensitive information. For example, in smart grid, the access policies may contain the private information about underlying data, data owner or the data recipients, and disclosing some sensitive access policies could result in negative publicity, or loss of market revenue. In this paper, we present a CP-ABE scheme with hidden policy from Waters efficient construction. In our scheme, the access policy is hidden by using the composite order bilinear groups and can be expressed with LSSS. Our scheme is proved CPA secure under four statics assumptions.
Do We Pay Enough Attention to Culture Conditions in Context of Perinatal Outcome after In Vitro Fertilization? Up-to-Date Literature Review
Authors: Marianowski Piotr , Dąbrowski Filip A. , Zyguła Aleksandra , Wielgoś Mirosław , Szymusik Iwona
Published: January 2016

Adverse perinatal outcomes in singleton IVF pregnancies have been most often explained by parental underlying diseases and so far laboratory conditions during embryo culture are still not explored well. The following review discusses the current state of knowledge on the influence of IVF laboratory procedures on the possible perinatal outcome. The role of improved media for human embryo culture is unquestionable. Addition of certain components to culture media and their effect on embryo survival and implantation rates have been taken into consideration recently and studied on animal model. Impact of media on perinatal outcome in IVF offspring has also been studied. It has been discovered that epigenetic changes and neonatal birth weight are probably associated with the use of specific culture media, as is the relation between placental size and its influence on perinatal outcome. There are still questions in the discussion about duration of embryo culture (cleavage stage versus blastocyst transfer). Some of the IVF methods, such as in vitro maturation of oocytes and freezing/thawing procedures, also require well-powered randomized controlled trials in order to define their exact impact on perinatal outcome. Constant further research is needed to assess the impact of laboratory environment on fetal and postnatal development.
Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study
Authors: Basak Silpi , Singh Priyanka , Rajurkar Monali
Published: January 2016

Background and Objective. Antimicrobial resistance is now a major challenge to clinicians for treating patients. Hence, this short term study was undertaken to detect the incidence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacterial isolates in a tertiary care hospital.Material and Methods. The clinical samples were cultured and bacterial strains were identified in the department of microbiology. The antibiotic susceptibility profile of different bacterial isolates was studied to detect MDR, XDR, and PDR bacteria.Results. The antibiotic susceptibility profile of 1060 bacterial strains was studied. 393 (37.1%) bacterial strains were MDR, 146 (13.8%) strains were XDR, and no PDR was isolated. All (100%) Gram negative bacterial strains were sensitive to colistin whereas all (100%) Gram positive bacterial strains were sensitive to vancomycin.Conclusion. Close monitoring of MDR, XDR, or even PDR must be done by all clinical microbiology laboratories to implement effective measures to reduce the menace of antimicrobial resistance.
Assessment of Optical Quality at Different Contrast Levels in Pseudophakic Eyes
Authors: Park Chang Won , Kim Hyojin , Joo Choun-Ki
Published: January 2016

Purpose. To assess visual function using Optical Quality Analysis System (OQAS) at varying levels of contrast in pseudophakic eyes.Methods. The study included patients admitted to Seoul St. Mary’s Hospital between January and February 2012: 143 pseudophakic eyes with one of five intraocular lens types, examined 2–6 months after cataract surgery, and 93 normal eyes (enhanced visual acuity (VA) < 0.1 logMAR) in age-matched controls. Subjects were examined at three contrast levels using the OQAS.Results. At 100%, 20%, and 9% contrast, simulated mean VA was0.16±0.18 logMAR,0.30±0.18 logMAR, and0.52±0.17 logMAR, in normal eyes, and0.16±0.12 logMAR,0.33±0.20 logMAR, and0.56±0.21 logMAR, respectively, in pseudophakic eyes. Simulated VA decreased significantly when contrast was reduced, regardless of ocular status, age group, and lens type (p<0.05). There were no significant differences between normal and pseudophakic eyes among subjects aged 50–69 (p>0.05). Among subjects aged 70–79, pseudophakic eyes showed improved simulated VA (p=0.000) and objective scattering index values (p=0.008).Conclusions. Patients with intraocular lenses have similar or superior visual function when compared to those with normal eyes at 2–6 months after cataract surgery, even under low-contrast conditions.
Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications
Authors: Passos Giordani Rodrigues Dos , Sato Douglas Kazutoshi , Becker Jefferson , Fujihara Kazuo
Published: January 2016

Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders.
Postobstructive Pulmonary Edema following Tonsillectomy/Adenoidectomy in a 2-Year-Old with Poland-Moebius Syndrome
Authors: Powell Tanisha , Sharma Nirupma , McKie Kathleen T.
Published: January 2016

A 2-year-old male with Poland-Moebius syndrome was transferred from a local hospital to the Pediatric ICU at Children’s Hospital of Georgia for suspected postobstructive pulmonary edema (POPE) after tonsillectomy/adenoidectomy (T&A). The patient’s respiratory status ultimately declined and he developed respiratory failure. Imaging suggested pulmonary edema as well as a left-sided pneumonia. Echocardiogram showed pulmonary hypertension and airway exam via direct fiberoptic bronchoscopy revealed tracheomalacia and bronchomalacia. He developed acute respiratory distress syndrome (ARDS) and remained intubated for ten days. This case highlights the association between congenital upper body abnormalities with cranial nerve dysfunction and the development of POPE with delayed resolution of symptoms. Patients with upper body abnormalities as above are at great risk of postoperative complications and should therefore be managed in a tertiary-care facility.
Dual-Energy CT for Evaluation of Intra- and Extracapsular Silicone Implant Rupture
Authors: Glazebrook Katrina N. , Leng Shuai , Jacobson Steven R. , McCollough Cynthia M.
Published: January 2016

Silicone implants are commonly used for both breast augmentation and breast reconstruction. With aging of the implant, the silicone envelope may become weak or may rupture. The technique of choice for evaluation of implant integrity is breast MRI; however this may be contraindicated in some patients or the cost may be prohibitive. Dual-energy CT allows determination of density and atomic number of tissue and can provide material composition information. We present a case of extracapsular implant rupture with MRI and dual-energy CT imaging and surgical correlation.
International Appraisal of Nursing Culture and Curricula: A Qualitative Study of Erasmus Students
Authors: Siles Gonzalez Jose , Solano Ruiz Carmen , Gaban Gutierrez Angela
Published: January 2016

Introduction. Globalization of knowledge has emphasized the need to promote the adoption of international exchange programs in nursing. Nevertheless, the differences in cultural, educational, and structural schemes have challenged the mutual appraisal and understanding of the nursing curricula between countries. Research on nursing curricula should allow performing an analysis of different cultural idiosyncrasies in which educational and health institutions are found. These studies would contribute valuable information to the educative and organizational systems and their cultural variability.Objective. To examine the experiences of nursing students on international exchange programs.Methods. Comparative Education was taken as theoretical background. The clinical practice diaries of seven Spanish Nursing Erasmus students (a European international exchange program) were used as field journals. These students undertook their placements in the United Kingdom. A content analysis was carried out to find major themes.Results. Data extracted from the students clinical practice diaries indicated cultural, educational, and structural differences between countries. Most students reflected the hidden curriculum in their diaries, writing about affective, ideological, personal, and social elements and beliefs.Conclusions. The students’ experiences on international exchange programs were found to be sources of interest to clarify the ideological and cultural connections that underlie educational and health systems.
Does IL-17 Respond to the Disordered Lung Microbiome and Contribute to the Neutrophilic Phenotype in Asthma?
Authors: Yang Xu , Jiang Yunqiu , Wang Changzheng
Published: January 2016

Th17/IL-17 plays an important role in host defense and hyperimmune responses against pathogenic bacteria accompanied by the recruitment of neutrophils. Th17-associated immune response is also involved in the pathogenesis of asthma, which is known as a noninfectious allergic airway disease and has been shown to be heterogeneous. Th17-associated inflammation usually contributes to the neutrophilic phenotype, which is often characterized by greater severity, airflow obstruction, and steroid resistance. Concurrently, advanced culture-independent molecular techniques have increased our understanding of the lung microbiome and demonstrated that disorders of the lung microbiome, including changes of the total burden, diversity, and community composition, may contribute to severe, treatment-resistant neutrophilic asthma, although the precise mechanism is still unclear. Because Th17/IL-17 plays a role in bacteria-mediated immune responses and is involved in neutrophilic asthma, there may be a link between them. We review the effects of Th17/IL-17 on bacteria and asthma, showing the possibility that Th17/IL-17 may be a key player in neutrophilic asthma which may be characterized as severe or treatment-resistant by responding to the disordered lung microbiome.
Quality Assurance Competition Strategy under B2C Platform
Authors: Gui Yunmiao , Gong Bengang
Published: January 2016

This paper examines the platform competition strategy in offering quality assurance policy based on two-sided B2C markets with buyers and sellers who trade through the B2C platform. We model this as a strategy decision whether control rights of quality assurance level are better held by the seller or by the platform. Whether the seller or the platform that provides quality assurance policy is preferred depends on their influence on network effects. We show that the seller and the platform have no strong intention to improve the quality assurance level in the monopoly markets. When all buyers multihome and all sellers single-home, sellers who hold the control rights of quality assurance are better than platforms. However, platforms that hold quality assurance drive more profits than sellers in the B2C markets where all buyers and all sellers multihome. Our findings connect platform competitive strategies to market and microfoundation of quality, which applies directly to managerial decisions in the B2C two-sided platform.
A Novel Structurally Stable Multiepitope Protein for Detection of HCV
Authors: Galdino Alexsandro S. , Santos José C. , Souza Marilen Q. , Nóbrega Yanna K. M. , Xavier Mary-Ann E. , Felipe Maria S. S. , Freitas Sonia M. , Torres Fernando A. G.
Published: January 2016

Hepatitis C virus (HCV) has emerged as the major pathogen of liver diseases in recent years leading to worldwide blood-transmitted chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Accurate diagnosis for differentiation of hepatitis C from other viruses is thus of pivotal importance for proper treatment. In this work we developed a recombinant multiepitope protein (rMEHCV) for hepatitis C diagnostic purposes based on conserved and immunodominant epitopes from core, NS3, NS4A, NS4B, and NS5 regions of the virus polyprotein of genotypes 1a, 1b, and 3a, the most prevalent genotypes in South America (especially in Brazil). A synthetic gene was designed to encode eight epitopes in tandem separated by a flexible linker and bearing a his-tag at the C-terminal end. The recombinant protein was produced in Escherichia coli and purified in a single affinity chromatographic step with >95% purity. Purified rMEHCV was used to perform an ELISA which showed that the recombinant protein was recognized by IgG and IgM from human serum samples. The structural data obtained by circular dichroism (CD) spectroscopy showed that rMEHCV is a highly thermal stable protein at neutral and alkaline conditions. Together, these results show that rMEHCV should be considered an alternative antigen for hepatitis C diagnosis.
Consensus of High-Order Linear Multiagent Systems with Multitype Switching Topologies Based on the Dynamic Dwell Time Approach
Authors: Zhang Yaxiao , Chen Yangzhou , Qu Xiaojun
Published: January 2016

This paper investigates the consensus problem of high-order continuous-time linear multiagent systems (LMASs) with multitype switching topologies which include both consensusable and unconsensusable communication topologies. A linear transformation is introduced, which equivalently transforms the consensus problem into the stability problem of a corresponding switched system, along with a necessary and sufficient condition to analyze the consensus problem. This paper is aimed at studying the impact of a switching rule on communication topologies for consensus of LMASs. Based on the dynamic dwell time method, a sufficient condition is derived for consensus of LMASs. It is shown that, with switching signals that satisfy this switching rule, LMASs can achieve consensus under directed switching communication topologies. A numerical example is provided to illustrate the effectiveness of the theoretical results.
Cellular Barriers after Extravasation: Leukocyte Interactions with Polarized Epithelia in the Inflamed Tissue
Authors: Reglero-Real Natalia , García-Weber Diego , Millán Jaime
Published: January 2016

During the inflammatory response, immune cells egress from the circulation and follow a chemotactic and haptotactic gradient within the tissue, interacting with matrix components in the stroma and with parenchymal cells, which guide them towards the sites of inflammation. Polarized epithelial cells compartmentalize tissue cavities and are often exposed to inflammatory challenges such as toxics or infections in non-lymphoid tissues. Apicobasal polarity is critical to the specialized functions of these epithelia. Indeed, a common feature of epithelial dysfunction is the loss of polarity. Here we review evidence showing that apicobasal polarity regulates the inflammatory response: various polarized epithelia asymmetrically secrete chemotactic mediators and polarize adhesion receptors that dictate the route of leukocyte migration within the parenchyma. We also discuss recent findings showing that the loss of apicobasal polarity increases leukocyte adhesion to epithelial cells and the consequences that this could have for the inflammatory response towards damaged, infected or transformed epithelial cells.
Caregiver Stigma and Burden in Memory Disorders: An Evaluation of the Effects of Caregiver Type and Gender
Authors: Kahn Phoebe V. , Wishart Heather A. , Randolph Jennifer S. , Santulli Robert B.
Published: January 2016

Despite considerable gains in public awareness of dementia, dementia patients and their caregivers continue to be stigmatized. Previous work has explored stigma and burden among adult children of persons with dementia in Israel, but no similar data exist for spousal caregivers or caregivers in general in the United States. This study examines the differences in stigma and burden experienced by spousal and adult child caregivers and male and female caregivers of persons with dementia. Eighty-two caregivers were given the Zarit Burden Inventory Short Form (ZBI) and the Caregiver Section of the Family Stigma in Alzheimer’s Disease Scale (FS-ADS-C). Scores on the FS-ADS-C and ZBI were positively correlated (rs=.51,p<.001). Female caregivers reported experiencing more stigma on the FS-ADS-C (t(80)= −4.37,p<.001) and more burden on the ZBI (t(80)= −2.68,p=.009) compared to male caregivers, and adult child caregivers reported experiencing more stigma on the FS-ADS-C (t(30.8)= −2.22,p=.034) and more burden on the ZBI (t(80)= −2.65,p=.010) than spousal caregivers. These results reinforce the importance of support for caregivers, particularly adult child and female caregivers who may experience higher levels of stigma and burden.
Serous Retinal Detachment Associated with Dome-Shaped Macula and Staphyloma Edge in Myopic Patients before and after Treatment with Spironolactone
Authors: Fernández-Vega Sanz Álvaro , Rangel Carlos Mario , Villota Deleu Eva , Fernández-Vega Sanz Beatriz , Sánchez-Ávila Ronald Mauricio
Published: January 2016

Objective. Serous retinal detachment (SRD) is a common anatomical complication associated with dome-shaped macula (DSM) and staphyloma margin in myopic patients. Here we described the anatomical and functional outcomes obtained with the use of oral spironolactone, a mineralocorticoid antagonist, in the management of myopic patients with SRD associated with DSM and staphyloma margin.Methods. We evaluated both eyes of twelve myopic patients with long-standing SRD associated with DSM or staphyloma margin. The patients were treated daily for six months with oral spironolactone 50 mg. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT), determined by optical coherence tomography, were evaluated on the first day and on monthly follow-up visits.Results. Pretreatment BCVA (mean ± standard deviation) was 0.406 ± 0.324 LogMAR, and posttreatment BCVA was 0.421 ± 0.354 LogMAR (P=0.489). Pretreatment CRT was 323.9 ± 78.6 μm, and after six months of treatment it was significantly lower, 291.2 ± 74.5 μm (P=0.010). There were no treatment-related complications.Conclusions.We evaluated a novel treatment for SRD associated with DSM and staphyloma margin in myopic patients. After six months of treatment with the mineralocorticoid antagonist spironolactone, the subretinal fluid and CRT were significantly reduced; however, there was no improvement in BCVA.
Visualizing Changes in Strategy Use across Attempts via State Diagrams: A Case Study
Authors: Kerr Deirdre
Published: January 2016

Game log data have great potential to provide actionable information about the in-game behavior of players. However, these low-level behavioral data are notoriously difficult to analyze due to the challenges associated with extracting meaning from sparse data stored at such a small grain size. This paper describes a three-step solution that uses cluster analysis to determine which strategies players use to solve levels in the game, sequence mining to identify changes in strategy across multiple attempts at the same level, and state transition diagrams to visualize the strategy sequences identified by the sequence mining. In the educational video game used in this case study, cluster analysis successfully identified 15 different in-game strategies. The sequence mining found an average of 40 different sequences of strategy use per level, which the state transition diagrams successfully displayed in an interpretable way.
Study of Thermal Properties of Mixed (PP/EPR)/ABS with Five Model Compatibilizers
Authors: Noah Pierre Marcel Anicet , Ayina Ohandja Louis-Max , Eba Medjo Rolant , Chabira Salem , Betene Ebanda Fabien , Anyouzoa Ondoua Patrick
Published: January 2016

The influences of incorporating compatibilizers E-EA-MAH, E-MA-GMA, E-AM, SEBS KRATON G, or PP-g-MAH on the thermal properties of mixed (polypropylene/ethylene propylene rubber)/acrylonitrile butadiene styrene (PP/EPR)/ABS have been investigated. DSC investigations have revealed that the incorporation of 5% of ABS in the copolymer (PP/EPR) does not fundamentally affect the thermal properties of the basic copolymer; additionally, the addition of 1.5% of each of the compatibilizers in the basic mixture does not significantly alter the crystallization temperature values and the melting of the -P- sequences. There is a variation of melting enthalpy values of the -P- sequences of 18.23% using SEBS KRATON G and of 10.38% using E-AM-GMA. When the rate of each of the compatibilizers increases to 5%, overall crystallization enthalpies of -P- sequences are almost kept unchanged, except for the case of using the compatibilizer E-AM-GMA with a variation of 8.42%. There is a minor variation of the melting enthalpy of -P- sequences with higher levels of compatibilizer. The incorporation of 5% ABS copolymer in the PP/EPR does not significantly alter the thermal properties of the basic structure of (PP/EPR)/ABS.
Review of Sensing Methodologies for Estimation of Combustion Metrics
Authors: Jia Libin , Naber Jeffrey D. , Blough Jason R.
Published: January 2016

For reduction of engine-out emissions and improvement of fuel economy, closed-loop control of the combustion process has been explored and documented by many researchers. In the closed-loop control, the engine control parameters are optimized according to the estimated instantaneous combustion metrics provided by the combustion sensing process. Combustion sensing process is primarily composed of two aspects: combustion response signal acquisition and response signal processing. As a number of different signals have been employed as the response signal and the signal processing techniques can be different, this paper did a review work concerning the two aspects: combustion response signals and signal processing techniques. In-cylinder pressure signal was not investigated as one of the response signals in this paper since it has been studied and documented in many publications and also due to its high cost and inconvenience in the application.
Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-κB Pathway in Cultured Human Uveal Melanoma Cells
Authors: Bi Ming-Chao , Hose Nicole , Xu Cai-Lian , Zhang Chen , Sassoon Jodi , Song E.
Published: January 2016

Zeaxanthin at nonlethal dosages (3–10 μM) significantly inhibited the cell migration of cultured uveal melanoma cells (C918 cell line) as determined by wound healing assay and Boyden chamber assay. Matrigel invasion assay showed that cell invasion of uveal melanoma cells could be significantly inhibited by zeaxanthin. Secretion of MMP-2 by melanoma cells was significantly inhibited by zeaxanthin in a dose-dependent manner as measured by ELISA kit. Zeaxanthin also significantly inhibited the NF-κB levels in nuclear extracts of the UM cells, which is the upstream of the MMP-2 secretion. These results suggest that zeaxanthin might be a potentially therapeutic approach in the prevention of metastasis in uveal melanoma.
Pancreatic Cancer Epidemiology, Detection, and Management
Authors: Zhang Qiubo , Zeng Linjuan , Chen Yinting , Lian Guoda , Qian Chenchen , Chen Shaojie , Li Jiajia , Huang Kaihong
Published: January 2016

PC (pancreatic cancer) is the fourth most common cause of death due to cancer worldwide. The incidence and mortality rates have been increasing year by year worldwide, and this review has analyzed the most recent incidence and mortality data for pancreatic cancer occurrence in China. Several possible risk factors have been discussed here, involving known established risk factors and novel possible risk factors. The development of this cancer is a stepwise progression through intraepithelial neoplasia to carcinoma. Though early and accurate diagnosis is promising based on a combination of recent techniques including tumor markers and imaging modalities, lacking early clinical symptoms makes the diagnosis late. Correct staging is critical because treatment is generally based on this parameter. Treatment options have improved throughout the last decades. However, surgical excision remains the primary therapy and efficacy of conventional chemoradiotherapy for PC is limited. Recently, some novel new therapies have been developed and will be applied in clinics soon. This review will provide an overview of pancreatic cancer, including an understanding of the developments and controversies.
An Update on Oxidative Damage to Spermatozoa and Oocytes
Authors: Opuwari Chinyerum S. , Henkel Ralf R.
Published: January 2016

On the one hand, reactive oxygen species (ROS) are mandatory mediators for essential cellular functions including the function of germ cells (oocytes and spermatozoa) and thereby the fertilization process. However, the exposure of these cells to excessive levels of oxidative stress by too high levels of ROS or too low levels of antioxidative protection will render these cells dysfunctional thereby failing the fertilization process and causing couples to be infertile. Numerous causes are responsible for the delicate bodily redox system being out of balance and causing disease and infertility. Many of these causes are modifiable such as lifestyle factors like obesity, poor nutrition, heat stress, smoking, or alcohol abuse. Possible correctable measures include foremost lifestyle changes, but also supplementation with antioxidants to scavenge excessive ROS. However, this should only be done after careful examination of the patient and establishment of the individual bodily antioxidant needs. In addition, other corrective measures include sperm separation for assisted reproductive techniques. However, these techniques have to be carried out very carefully as they, if applied wrongly, bear risks of generating ROS damaging the germ cells and preventing fertilization.
Particle Swarm and Bacterial Foraging Inspired Hybrid Artificial Bee Colony Algorithm for Numerical Function Optimization
Authors: Mao Li , Mao Yu , Zhou Changxi , Li Chaofeng , Wei Xiao , Yang Hong
Published: January 2016

Artificial bee colony (ABC) algorithm has good performance in discovering the optimal solutions to difficult optimization problems, but it has weak local search ability and easily plunges into local optimum. In this paper, we introduce the chemotactic behavior of Bacterial Foraging Optimization into employed bees and adopt the principle of moving the particles toward the best solutions in the particle swarm optimization to improve the global search ability of onlooker bees and gain a hybrid artificial bee colony (HABC) algorithm. To obtain a global optimal solution efficiently, we make HABC algorithm converge rapidly in the early stages of the search process, and the search range contracts dynamically during the late stages. Our experimental results on 16 benchmark functions of CEC 2014 show that HABC achieves significant improvement at accuracy and convergence rate, compared with the standard ABC, best-so-far ABC, directed ABC, Gaussian ABC, improved ABC, and memetic ABC algorithms.
Fibroblast-Mediated Collagen Remodeling Within the Tumor Microenvironment Facilitates Progression of Thyroid Cancers Driven by BrafV600E and Pten Loss
Authors: Jolly Lee Ann , Novitskiy Sergey , Owens Phillip , Massoll Nicole , Cheng Nikki , Fang Wei , Moses Harold L. , Franco Aime T.
Published: January 2016

Contributions of the tumor microenvironment (TME) to progression in thyroid cancer are largely unexplored and may illuminate a basis for understanding rarer aggressive cases of this disease. In this study, we investigated the relationship between the TME and thyroid cancer progression in a mouse model where thyroid-specific expression of oncogenic BRAF and loss of Pten (BrafV600E/Pten−/−/TPO-Cre) leads to papillary thyroid cancers (PTC) that rapidly progress to poorly differentiated thyroid cancer (PDTC). We found that fibroblasts were recruited to the TME of BrafV600E/Pten−/−/TPO-Cre thyroid tumors. Conditioned media from cell lines established from these tumors, but not tumors driven by mutant H-ras, induced fibroblast migration and proliferation in vitro. Notably, the extracellular matrix of BrafV600E/Pten−/−/TPO-Cre tumors was enriched with stromal-derived fibrillar collagen, compared with wild-type or Hras-driven tumors. Further, type I collagen enhanced the motility of BrafV600E/Pten−/−/TPO-Cre tumor cells in vitro. In clinical specimens, we found COL1A1 and LOX to be upregulated in PTC and expressed at highest levels in PDTC and anaplastic thyroid cancer. Additionally, increased expression levels of COL1A1 and LOX were associated with decreased survival in thyroid cancer patients. Overall, our results identified fibroblast recruitment and remodeling of the extracellular matrix as pivotal features of the TME in promoting thyroid cancer progression, illuminating candidate therapeutic targets and biomarkers in advanced forms of this malignancy. Cancer Res; 76(7); 1804–13. ©2016 AACR.
What Predicts an Advanced-Stage Diagnosis of Breast Cancer? Sorting Out the Influence of Method of Detection, Access to Care, and Biologic Factors
Authors: Lipscomb Joseph , Fleming Steven T. , Trentham-Dietz Amy , Kimmick Gretchen , Wu Xiao-Cheng , Morris Cyllene R. , Zhang Kun , Smith Robert A. , Anderson Roger T. , Sabatino Susan A.
Published: January 2016

Background: Multiple studies have yielded important findings regarding the determinants of an advanced-stage diagnosis of breast cancer. We seek to advance this line of inquiry through a broadened conceptual framework and accompanying statistical modeling strategy that recognize the dual importance of access-to-care and biologic factors on stage.

Methods: The Centers for Disease Control and Prevention–sponsored Breast and Prostate Cancer Data Quality and Patterns of Care Study yielded a seven-state, cancer registry–derived population-based sample of 9,142 women diagnosed with a first primary in situ or invasive breast cancer in 2004. The likelihood of advanced-stage cancer (American Joint Committee on Cancer IIIB, IIIC, or IV) was investigated through multivariable regression modeling, with base-case analyses using the method of instrumental variables (IV) to detect and correct for possible selection bias. The robustness of base-case findings was examined through extensive sensitivity analyses.

Results: Advanced-stage disease was negatively associated with detection by mammography (P < 0.001) and with age < 50 (P < 0.001), and positively related to black race (P = 0.07), not being privately insured [Medicaid (P = 0.01), Medicare (P = 0.04), uninsured (P = 0.07)], being single (P = 0.06), body mass index > 40 (P = 0.001), a HER2 type tumor (P < 0.001), and tumor grade not well differentiated (P < 0.001). This IV model detected and adjusted for significant selection effects associated with method of detection (P = 0.02). Sensitivity analyses generally supported these base-case results.

Conclusions: Through our comprehensive modeling strategy and sensitivity analyses, we provide new estimates of the magnitude and robustness of the determinants of advanced-stage breast cancer.

Impact: Statistical approaches frequently used to address observational data biases in treatment-outcome studies can be applied similarly in analyses of the determinants of stage at diagnosis. Cancer Epidemiol Biomarkers Prev; 25(4); 613–23. ©2016 AACR.
The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma
Authors: Ruella Marco , Kenderian Saad S. , Shestova Olga , Fraietta Joseph A. , Qayyum Sohail , Zhang Qian , Maus Marcela V. , Liu Xiaobin , Nunez-Cruz Selene , Klichinsky Michael , Kawalekar Omkar U. , Milone Michael , Lacey Simon F. , Mato Anthony , Schuster Stephen J. , Kalos Michael , June Carl H. , Gill Saar , Wasik Mariusz A.
Published: January 2016

Purpose: Responses to therapy with chimeric antigen receptor T cells recognizing CD19 (CART19, CTL019) may vary by histology. Mantle cell lymphoma (MCL) represents a B-cell malignancy that remains incurable despite novel therapies such as the BTK inhibitor ibrutinib, and where data from CTL019 therapy are scant. Using MCL as a model, we sought to build upon the outcomes from CTL019 and from ibrutinib therapy by combining these in a rational manner.

Experimental Design: MCL cell lines and primary MCL samples were combined with autologous or normal donor-derived anti-CD19 CAR T cells along with ibrutinib. The effect of the combination was studied in vitro and in mouse xenograft models.

Results: MCL cells strongly activated multiple CTL019 effector functions, and MCL killing by CTL019 was further enhanced in the presence of ibrutinib. In a xenograft MCL model, we showed superior disease control in the CTL019- as compared with ibrutinib-treated mice (median survival not reached vs. 95 days, P < 0.005) but most mice receiving CTL019 monotherapy eventually relapsed. Therefore, we added ibrutinib to CTL019 and showed that 80% to 100% of mice in the CTL019 + ibrutinib arm and 0% to 20% of mice in the CTL019 arm, respectively, remained in long-term remission (P < 0.05).

Conclusions: Combining CTL019 with ibrutinib represents a rational way to incorporate two of the most recent therapies in MCL. Our findings pave the way to a two-pronged therapeutic strategy in patients with MCL and other types of B-cell lymphoma. Clin Cancer Res; 22(11); 2684–96. ©2016 AACR.
Nucleosome Assembly Protein 1-Like 1 (Nap1l1) Regulates the Proliferation of Murine Induced Pluripotent Stem Cells
Authors: Yan Yuan , Yin Peipei , Gong Hui , Xue Yuanyuan , Zhang Guoping , Fang Bo , Chen Zhidan , Li Yang , Yang Chunjie , Huang Zheyong , Yang Xiangdong , Ge Junbo , Zou Yunzeng
Published: January 2016

Background/Aims: To investigate whether nucleosome assembly protein 1-like 1 (Nap1l1) regulates the proliferation of induced pluripotent stem cells (iPSC) and the potential mechanisms. Methods: Nap1l1-knockdown-iPSC and Nap1l1-overexpression-iPSC were constructed by transfection of lentiviral particles. The proliferation of iPSC was detected by MTT analysis, and cell cycle was analyzed by flow cytometry. Results: Nap1l1 overexpression promoted iPSC proliferation and induced G2/M transition compared to their control iPSC while Nap1l1-knockdown-iPSC dramatically displayed the reduced proliferation and accumulated G2/M phase cells. Further analysis showed that Nap1l1 overexpression in iPSC increased the expression of cyclin B1, downregulated the expression of p21 and p27, while knockdown of Nap1l1 showed the opposite effects. In addition, overexpression of Nap1l1 promoted the phosphorylation of AKT and ERK in iPSC, while knockdown of Nap1l1 inhibited the effects. However, these effects displayed in Nap1l1-overexpression-iPSC were greatly suppressed by the inhibition of AKT or ERK signaling. Conclusions: The results indicate that Nap1l1 promotes the proliferation of iPSC attributable to G2/M transition caused by downregulation of p27 and p21, and upregulation of cyclin B1, the activation of AKT or ERK is involved in the process. The present study has revealed a novel molecular mechanism involved in the proliferation of iPSC.
Nocodazole Induced Suicidal Death of Human Erythrocytes
Authors: Signoretto Elena , Honisch Sabina , Briglia Marilena , Faggio Caterina , Castagna Michela , Lang Florian
Published: January 2016

Background: The microtubule assembly inhibitor nocodazole has been shown to trigger caspase-independent mitotic death and caspase dependent apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress and ceramide. The present study explored, whether and how nocodazole induces eryptosis. Methods: Flow cytometry was employed to determine phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, the abundance of reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein (DCF) diacetate dependent fluorescence as well as ceramide surface abundance utilizing specific antibodies. Tubulin abundance was quantified by TubulinTracker™ Green reagent and visualized by confocal microscopy. Results: A 48 hours exposure of human erythrocytes to nocodazole (≥ 30 µg/ml) significantly increased the percentage of annexin-V-binding cells without significantly modifying average forward scatter. Nocodazole significantly increased Fluo3-fluorescence, significantly increased DCF fluorescence and significantly increased ceramide surface abundance. The effect of nocodazole on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+ and was not modified in the presence of Caspase 3 inhibitor zVAD (1 µM). Nocodazole treatment reduced the content of total tubulin. Conclusions: Nocodazole triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of Ca2+ entry, oxidative stress and ceramide.
Pttg1 Promotes Growth of Breast Cancer through P27 Nuclear Exclusion
Authors: Xiea Yishan , Wangb Rui
Published: January 2016

Background/Aims: A role of Pituitary Tumor Transforming Gene 1 (Pttg1) in the carcinogenesis has been shown in some cancers, but not in BC (BC). Methods: We compared the levels of Pttg1 in the resected BC tissue with the adjacent normal breast tissue from the same patient. We modified Pttg1 levels in a BC cell line, MCF7, by either a Pttg1 transgene, or a Pttg1 shRNA. The cell growth was measured in an MTT assay. The cell apoptosis was measured by apoptosis assay. The nuclear protein of cell-cycle-related genes was examined in Pttg1-modifed BC cells. Co-immunoprecipitation was performed to examine the association of Pttg1 and p27. Results: We detected significantly higher levels of Pttg1 in the resected BC tissue, compared to the adjacent normal breast tissue from the same patient. Overexpression or depletion of Pttg1 in MCF7 significantly increased or inhibited cell growth, respectively. Changes in Pttg1 levels, however, did not alter cell apoptosis, suggesting that Pttg1 increases cell growth through augmented cell proliferation, rather than decreased cell apoptosis. Among all examined cell-cycle-related proteins in Pttg1-modifed BC cells, only nuclear p27 levels were significantly affected. Further, co-immunoprecipitation showed that Pttg1 directly associated with p27. Conclusion: Pttg1 may increase BC cell growth through nuclear exclusion of p27, which highlights a novel molecular regulatory machinery in tumorigenesis of BC.
The Impact of Lowering Haemoglobin Targets on Patterns of Erythropoiesis-Stimulating Agent Use in Patients on Haemodialysis
Authors: Hazara Adil M. , Owen Samantha J. , Bhandari Sunil
Published: January 2016

Background/Aims: Haemoglobin (Hb) targets have been reduced in patients receiving haemodialysis (HD). We have investigated the impact of new guidance on current practices and costs. Methods: Anaemia management in all patients undergoing thrice-weekly HD was retrospectively reviewed. Hb targets were compared against Kidney Disease: Improving Global Outcomes 2012 recommendations. The impact of new guidance was assessed by comparing anaemia parameters pre- and post-guideline publication. Results: Two hundred and ninety two patients, with a mean age of 64 years were included. The Hb target range was achieved in 44% patients and was above target in 51%. In a sub-group of 230 patients, the mean Hb did not differ during Q4-2011 and Q4-2012. A reduction in erythropoiesis-stimulating agent (ESA) use was observed. ESA efficiency (Hb/ESA) increased in the later period (6.08 vs. 6.41 g/l/μg) and was associated with a 3% cost reduction. Conclusion: Introduction of guidelines lowering Hb targets in HD patients led to more efficient ESA usage and cost-savings. Anaemia treatment, however, remains unnecessarily aggressive in some patients. Further reductions in Hb and ESA dose are achievable.
The Real-World Routine Use of Caffeine Citrate in Preterm Infants: A European Postauthorization Safety Study
Authors: Lista Gianluca , Fabbri Laura , Polackova Renáta , Kiechl-Kohlendorfer Ursula , Papagaroufalis Konstantinos , Saenz Pilar , Ferrari Fania , Lasagna Giovanna , Carnielli Virgilio P. ,   for the Peyona® PASS Group
Published: January 2016

Background: Caffeine citrate is the treatment of choice for apnea of prematurity (AOP). Regulatory agencies have requested real-world data on drug utilization and safety, a postauthorization safety study, of a pharmaceutical-grade caffeine citrate, Peyona®, to confirm its benefit for preterm infants. Objectives: To investigate the clinical use, outcomes, and safety profile of this pharmaceutical-grade caffeine citrate in the routine treatment of preterm infants with a gestational age (GA) <37 weeks. Methods: We conducted a multicenter, noninterventional, prospective study in five European countries. Patients eligible for study enrollment were <37-week GA neonates who received treatment with the pharmaceutical-grade caffeine citrate and whose parents had given informed consent. Results: A total of 506 preterm infants were enrolled from 21 institutions. The pharmaceutical-grade caffeine citrate doses were administered intravenously, orally, or via both routes. The main indication of use was AOP treatment (58%) followed by AOP prophylaxis (37%). Median treatment duration was 21 days. The primary cause of study termination was AOP resolution (n = 407; 80%). Hundred and six patients (21%) required supplemental oxygen on day 28; 48 patients (9.5%) had bronchopulmonary dysplasia at 36 weeks' postmenstrual age. Twenty-three adverse drug reactions were observed in 21 neonates (4.2%); the most frequent was tachycardia (2.3%) and only one (seizures) was considered serious. Thirty-one patients (8.1%) had hepatic or renal functional impairment; the side effects were manageable, and these patients also benefitted from treatment. Conclusions: The use of this caffeine citrate is safe for the management of AOP in a real-world setting.