bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Alanine Aminotransferase and Periodontitis: A Cross-Sectional Analysis—NHANES 2009–2012
Authors: Wiener R. Constance , Sambamoorthi Usha , Jurevic Richard J.
Published: February 2016

Objective. Alanine Aminotransferase is an enzyme associated with not only liver diseases, liver conditions, and metabolic syndrome, but also inflammation. Periodontitis is associated with increased cytokines and other markers of inflammation. The purpose of this study is to determine if an independent association between Alanine Aminotransferase and periodontitis exists.Methods. Data from the 2009-2010 and 2011-2012 National Health and Nutrition Surveys (NHANES) were combined. Data concerning periodontitis and Alanine Aminotransferase were extracted and analyzed with Rao Scott Chi-square and logistic regressions. Serum Alanine Aminotransferase was dichotomized at 40 units/liter, and periodontitis was dichotomized to the presence or absence of periodontitis.Results. In bivariate Chi-square analyses, periodontitis and Alanine Aminotransferase were associated (p=0.0360) and remained significant in unadjusted logistic regression (OR = 1.30 [95% CI: 1.02, 1.65]). However, when other known risk factors of periodontitis were included in the analyses, the relationship attenuated and failed to reach significance (adjusted OR = 1.17 [95% CI: 0.85, 1.60]).Conclusion. Our study adds to the literature a positive but attenuated association of serum Alanine Aminotransferase with periodontitis which failed to reach significance when other known, strong risk factors of periodontitis were included in the analysis.
High Dielectric Constant Study of TiO2-Polypyrrole Composites with Low Contents of Filler Prepared byIn SituPolymerization
Authors: Ahmed Khalil , Kanwal Farah , Ramay Shahid M. , Mahmood Asif , Atiq Shahid , Al-Zaghayer Yousef S.
Published: February 2016

TiO2/polypyrrole composites with high dielectric constant have been synthesized byin situpolymerization of pyrrole in an aqueous dispersion of low concentration of TiO2, in the presence of small amount of HCl. Structural, optical, surface morphological, and thermal properties of the composites were investigated by X-ray diffractometer, Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, and thermogravimetric analysis, respectively. The data obtained from diffractometer and thermal gravimetric analysis confirmed the crystalline nature and thermal stability of the prepared composites. The dielectric constant of 5 wt% TiO2increased with filler content up to 4.3 × 103at 1 kHz and then decreased to 1.25 × 103at 10 kHz.
A Woman with Rheumatoid Arthritis and a Bilateral Fracture of the Proximal Tibia
Authors: Hooghof J. Th. (Arjan) , Mellema Joris J. , Posthumus Marcel D. , van Raaij Jos J. A. M.
Published: February 2016

A 52-year-old woman presented herself with pain on the medial sides of the proximal tibia after a minimal trauma. Conventional X-rays did not show any pathology. However, the MRI showed a bilateral fracture of the proximal tibia. Since the patient was treated with methotrexate due to rheumatoid arthritis, methotrexate osteopathy was considered. Long term treatment with low doses of methotrexate proved to inhibit osteoblast proliferation and may eventually lead to decreased bone formation and osteopenia. On the other hand, immobilization, joint deformities, and steroid treatment are associated with rheumatoid arthritis and are also known risk factors for fractures. The clinical relevance of methotrexate osteopathy still has to be established. However, if a patient treated with methotrexate localizes pain in the tibia, methotrexate osteopathy should be considered. Withdrawal of the drug may improve symptoms.
Gesture-Controlled Interface for Contactless Control of Various Computer Programs with a Hooking-Based Keyboard and Mouse-Mapping Technique in the Operating Room
Authors: Park Ben Joonyeon , Jang Taekjin , Choi Jong Woo , Kim Namkug
Published: February 2016

We developed a contactless interface that exploits hand gestures to effectively control medical images in the operating room. We developed an in-house program called GestureHook that exploits message hooking techniques to convert gestures into specific functions. For quantitative evaluation of this program, we used gestures to control images of a dynamic biliary CT study and compared the results with those of a mouse (8.54±1.77 s to5.29±1.00 s;p<0.001) and measured the recognition rates of specific gestures and the success rates of tasks based on clinical scenarios. For clinical applications, this program was set up in the operating room to browse images for plastic surgery. A surgeon browsed images from three different programs: CT images from a PACS program, volume-rendered images from a 3D PACS program, and surgical planning photographs from a basic image viewing program. All programs could be seamlessly controlled by gestures and motions. This approach can control all operating room programs without source code modification and provide surgeons with a new way to safely browse through images and easily switch applications during surgical procedures.
Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells from Decidua Basalis of Human Term Placenta
Authors: Abomaray F. M. , Al Jumah M. A. , Alsaad K. O. , Jawdat D. , Al Khaldi A. , AlAskar A. S. , Al Harthy S. , Al Subayyil A. M. , Khatlani T. , Alawad A. O. , Alkushi A. , Kalionis B. , Abumaree M. H.
Published: February 2016

Mesenchymal stem cell (MSC) therapies for the treatment of diseases associated with inflammation and oxidative stress employ primarily bone marrow MSCs (BMMSCs) and other MSC types such as MSC from the chorionic villi of human term placentae (pMSCs). These MSCs are not derived from microenvironments associated with inflammation and oxidative stress, unlike MSCs from the decidua basalis of the human term placenta (DBMSCs). DBMSCs were isolated and then extensively characterized. Differentiation of DBMSCs into three mesenchymal lineages (adipocytes, osteocytes, and chondrocytes) was performed. Real‐time polymerase chain reaction (PCR) and flow cytometry techniques were also used to characterize the gene and protein expression profiles of DBMSCs, respectively. In addition, sandwich enzyme‐linked immunosorbent assay (ELISA) was performed to detect proteins secreted by DBMSCs. Finally, the migration and proliferation abilities of DBMSCs were also determined. DBMSCs were positive for MSC markers and HLA‐ABC. DBMSCs were negative for hematopoietic and endothelial markers, costimulatory molecules, and HLA‐DR. Functionally, DBMSCs differentiated into three mesenchymal lineages, proliferated, and migrated in response to a number of stimuli. Most importantly, these cells express and secrete a distinct combination of cytokines, growth factors, and immune molecules that reflect their unique microenvironment. Therefore, DBMSCs could be attractive, alternative candidates for MSC‐based therapies that treat diseases associated with inflammation and oxidative stress.
Environmental Influences on Growth and Reproduction of InvasiveCommelina benghalensis
Authors: Riar Mandeep K. , Carley Danesha S. , Zhang Chenxi , Schroeder-Moreno Michelle S. , Jordan David L. , Webster Theodore M. , Rufty Thomas W.
Published: February 2016

Commelina benghalensis(Benghal dayflower) is a noxious weed that is invading agricultural systems in the southeastern United States. We investigated the influences of nutrition, light, and photoperiod on growth and reproductive output ofC. benghalensis. In the first experimental series, plants were grown under high or low soil nutrition combined with either full light or simulated shade. Lowered nutrition strongly inhibited vegetative growth and aboveground spathe production. Similar but smaller effects were exerted by a 50% reduction in light, simulating conditions within a developing canopy. In the second series of experiments,C. benghalensisplants were exposed to different photoperiod conditions that produced short- and long-day plants growing in similar photosynthetic periods. A short-day photoperiod decreased time to flowering by several days and led to a 40 to 60% reduction in vegetative growth, but reproduction above and below ground was unchanged. Collectively, the results indicate that (1) fertility management in highly weathered soils may strongly constrain competitiveness ofC. benghalensis; (2) shorter photoperiods will limit vegetative competitiveness later in the growing seasons of most crops; and (3) the high degree of reproductive plasticity and output possessed byC. benghalensiswill likely cause continual persistence problems in agricultural fields.
Glioma Stem Cells and Their Microenvironments: Providers of Challenging Therapeutic Targets
Authors: Codrici Elena , Enciu Ana-Maria , Popescu Ionela-Daniela , Mihai Simona , Tanase Cristiana
Published: February 2016

Malignant gliomas are aggressive brain tumors with limited therapeutic options, possibly because of highly tumorigenic subpopulations of glioma stem cells. These cells require specific microenvironments to maintain their “stemness,” described as perivascular and hypoxic niches. Each of those niches induces particular signatures in glioma stem cells (e.g., activation of Notch signaling, secretion of VEGF, bFGF, SDF1 for the vascular niche, activation of HIF2α, and metabolic reprogramming for hypoxic niche). Recently, accumulated knowledge on tumor‐associated macrophages, possibly delineating a third niche, has underlined the role of immune cells in glioma progression, via specific chemoattractant factors and cytokines, such as macrophage‐colony stimulation factor (M‐CSF). The local or myeloid origin of this new component of glioma stem cells niche is yet to be determined. Such niches are being increasingly recognized as key regulators involved in multiple stages of disease progression, therapy resistance, immune‐escaping, and distant metastasis, thereby substantially impacting the future development of frontline interventions in clinical oncology. This review focuses on the microenvironment impact on the glioma stem cell biology, emphasizing GSCs cross talk with hypoxic, perivascular, and immune niches and their potential use as targeted therapy.
Fate and Effect of Intravenously Infused Mesenchymal Stem Cells in a Mouse Model of Hepatic Ischemia Reperfusion Injury and Resection
Authors: Saat T. C. , van den Engel S. , Bijman-Lachger W. , Korevaar S. S. , Hoogduijn M. J. , IJzermans J. N. M. , de Bruin R. W. F.
Published: February 2016

Liver ischemia reperfusion injury (IRI) is inevitable during transplantation and resection and is characterized by hepatocellular injury. Therapeutic strategies to reduce IRI and accelerate regeneration could offer major benefits. Mesenchymal stem cells (MSC) are reported to have anti‐inflammatory and regeneration promoting properties. We investigated the effect of MSC in a model of combined IRI and partial resection in the mouse. Hepatic IRI was induced by occlusion of 70% of the blood flow during 60 minutes, followed by 30% hepatectomy. 2 × 105 MSC or PBS were infused 2 hours before or 1 hour after IRI. Six, 48, and 120 hours postoperatively mice were sacrificed. Liver damage was evaluated by liver enzymes, histology, and inflammatory markers. Regeneration was determined by liver/body weight ratio, proliferating hepatocytes, and TGF‐β levels. Fate of MSC was visualized with 3D cryoimaging. Infusion of 2 × 105 MSC 2 hours before or 1 hour after IRI and resection showed no beneficial effects. Tracking revealed that MSC were trapped in the lungs and did not migrate to the site of injury and many cells had already disappeared 2 hours after infusion. Based on these findings we conclude that intravenously infused MSC disappear rapidly and were unable to induce beneficial effects in a clinically relevant model of IRI and resection.
A Homemade Snare: An Alternative Method for Mechanical Removal ofDirofilaria immitisin Dogs
Authors: Alho Ana Margarida , Fiarresga António , Landum Miguel , Lima Clara , Gamboa Óscar , Meireles José , Sales Luís José , Madeira de Carvalho Luís
Published: February 2016

Canine dirofilariosis is a life-threatening parasitic disease that is increasingly reported worldwide. Once diagnosed the main treatment goals are to improve the animal’s clinical condition and to eliminate all life stages of the parasite with minimal posttreatment side effects. This can be achieved through mechanical, surgical, or chemotherapeutical approaches. Currently, manual extraction is the preferred method to remove adult heartworms due to its diminished invasiveness, reduced damage to the vascular endothelium, and shortened anaesthesia duration. However, it remains an expensive technique that can be highly traumatic. To address this issue, a nontraumatic homemade catheter-guided snare was developed for heartworm removal by adapting and folding a 0.014-inch coronary wire (BMW, Abbott Vascular). Transvenous heartworm extraction was performed on a dog severely infected with adult heartworms by inserting the modified snare into a 6-F Judkins right coronary guiding catheter BMW (Cordis) and advancing it into the right ventricle under fluoroscopic guidance. Fifteen adult specimens ofDirofilaria immitiswere successfully extracted from the pulmonary artery and right ventricle without complications. To assure the death of both larvae and adults, postoperative treatment was successfully managed using ivermectin, doxycycline, and melarsomine, with no recurrence after surgery.
Routine Head Computed Tomography for Patients in the Emergency Room with Trauma Requires Both Thick- and Thin-Slice Images
Authors: Maetani Kazuhide , Namiki Jun , Matsumoto Shokei , Matsunami Katsutoshi , Narumi Atsushi , Tsuneyoshi Toshimi , Kishikawa Masanobu
Published: February 2016

Background. Images of head CT for the supratentorial compartment are sometimes recommended to be reconstructed with a thickness of 8–10 mm to achieve lesion conspicuity. However, additional images of a thin slice may not be routinely provided for patients with trauma in the emergency room (ER). We investigated the diagnostic sensitivity of a head CT, where axial images were 10 mm thick slices, in cases of linear skull fractures.Methods. Two trauma surgeons retrospectively reviewed head CT with 10 mm slices and skull X-rays of patients admitted to the ER that were diagnosed with a linear skull fracture. All patients had undergone both head CT and skull X-rays (n=410).Result. The diagnostic sensitivity of head CT with a thickness of sequential 10 mm was 89% for all linear skull fractures but only 56% for horizontal fractures. This CT technique with 10 mm slices missed 6% of patients with linear skull fractures. False-negative diagnoses were significantly more frequent for older (≥55 years) than for young (<15 years) individuals (p=0.048).Conclusions. A routine head CT of the supratentorial region for patients in the ER with head injuries requires both thick-slice images to visualize cerebral hemispheres and thin-slice images to detect skull fractures of the cranial vault.
Role of Viral miRNAs and Epigenetic Modifications in Epstein‐Barr Virus‐Associated Gastric Carcinogenesis
Authors: Giudice Aldo , D’Arena Giovanni , Crispo Anna , Tecce Mario Felice , Nocerino Flavia , Grimaldi Maria , Rotondo Emanuela , D’Ursi Anna Maria , Scrima Mario , Galdiero Massimiliano , Ciliberto Gennaro , Capunzo Mario , Franci Gianluigi , Barbieri Antonio , Bimonte Sabrina , Montella Maurizio
Published: February 2016

MicroRNAs are short (21–23 nucleotides), noncoding RNAs that typically silence posttranscriptional gene expression through interaction with target messenger RNAs. Currently, miRNAs have been identified in almost all studied multicellular eukaryotes in the plant and animal kingdoms. Additionally, recent studies reported that miRNAs can also be encoded by certain single‐cell eukaryotes and by viruses. The vast majority of viral miRNAs are encoded by the herpesviruses family. These DNA viruses including Epstein‐Barr virus encode their own miRNAs and/or manipulate the expression of cellular miRNAs to facilitate respective infection cycles. Modulation of the control pathways of miRNAs expression is often involved in the promotion of tumorigenesis through a specific cascade of transduction signals. Notably, latent infection with Epstein‐Barr virus is considered liable of causing several types of malignancies, including the majority of gastric carcinoma cases detected worldwide. In this review, we describe the role of the Epstein‐Barr virus in gastric carcinogenesis, summarizing the functions of the Epstein‐Barr virus‐encoded viral proteins and related epigenetic alterations as well as the roles of Epstein‐Barr virus‐encoded and virally modulated cellular miRNAs.
Molecular Typing Characteristic and Drug Susceptibility Analysis ofMycobacterium tuberculosisIsolates from Zigong, China
Authors: Liu Hai-Can , Deng Jian-Ping , Dong Hai-Yan , Xiao Ti-Quan , Zhao Xiu-Qin , Zhang Zheng-Dong , Jiang Yi , Liu Zhi-Guang , Li Qun , Wan Kang-Lin
Published: February 2016

China is one of the 22 countries with high TB burden worldwide, and Sichuan contained the second-largest number of TB cases among all of the Chinese provinces. But the characteristics ofMycobacterium tuberculosiscirculated in Zigong, Sichuan, were still unknown. To investigate the character and drug resistance profile, 265 clinical isolates were cultured from tuberculosis patient’s sputum samples in the year of 2010, of which the genetic profile was determined by using Spoligotyping and MIRU-VNTR typing methods, and the drug sensibility testing to the four first-line and four second-line antituberculosis (anti-TB) drugs was performed by using proportion method on Lowenstein-Jensen (L-J) media. The major Spoligotype was Beijing family (143/265, 53.96%), followed by T (80/265, 30.19%) and H (9/265, 3.40%) genotypes; the total Hunter-Gaston discrimination index (HGDI) of the 24 loci MIRU-VNTR was 0.9995. About 27.17% (72/265) of the isolates were resistant to at least one of the eight tested anti-TB drugs, and for Beijing and non-Beijing family isolates the proportion of drug resistance was 28.47% (41/144) and 25.62% (31/121), respectively. That is, the most prevalent genotype here was Beijing family, and the 24 loci VNTR analysis could supply a high resolution for genotyping, and Beijing and non-Beijing isolates had no difference (p>0.05) for drug resistance.
Mechanisms and Clinical Management of Ventricular Arrhythmias following Blunt Chest Trauma
Authors: Wolbrom Daniel H. , Rahman Aleef , Tschabrunn Cory M.
Published: February 2016

Nonpenetrating, blunt chest trauma is a serious medical condition with varied clinical presentations and implications. This can be the result of a dense projectile during competitive and recreational sports but may also include other etiologies such as motor vehicle accidents or traumatic falls. In this setting, the manifestation of ventricular arrhythmias has been observed both acutely and chronically. This is based on two entirely separate mechanisms and etiologies requiring different treatments. Ventricular fibrillation can occur immediately after chest wall injury (commotio cordis) and requires rapid defibrillation. Monomorphic ventricular tachycardia can develop in the chronic stage due to underlying structural heart disease long after blunt chest injury. The associated arrhythmogenic tissue may be complex and provides the necessary substrate to form a reentrant VT circuit. Ventricular tachycardia in the absence of overt structural heart disease appears to be focal in nature with rapid termination during ablation. Regardless of the VT mechanism, patients with recurrent episodes, despite antiarrhythmic medication in the chronic stage following blunt chest injury, are likely to require ablation to achieve VT control. This review article will describe the mechanisms, pathophysiology, and treatment of ventricular arrhythmias that occur in both the acute and chronic stages following blunt chest trauma.
Herd Behavior and Financial Crashes: An Interacting Particle System Approach
Authors: Crescimanna Vincenzo , Di Persio Luca
Published: February 2016

We provide an approach based on a modification of the Ising model to describe the dynamics of stock markets. Our model incorporates three different factors: imitation, the impact of external news, and private information; moreover, it is characterized by coupling coefficients, static in time, but not identical for each agent. By analogy with physical models, we consider thetemperatureparameter of the system, assuming that it evolves with memory of the past, hence considering how former news influences realized market returns. We show that a standard Ising potential assumption is not sufficient to reproduce the stylized facts characterizing financial markets; this is because it assigns low probabilities to rare events. Hence, we study a variation of the previous setting providing, also by concrete computations, new insights and improvements.
Fixed Point Theorems for Cyclic Contractions inC⁎-Algebra-Valuedb-Metric Spaces
Authors: Klin-eam Chakkrid , Kaskasem Prondanai
Published: February 2016

We study fundamental properties ofC⁎-algebra-valuedb-metric space which was introduced by Ma and Jiang (2015) and give some fixed point theorems for cyclic mapping with contractive and expansive condition on such space analogous to the results presented in Ma and Jiang, 2015.
Impacts of Québec Primary Healthcare Reforms on Patients’ Experience of Care, Unmet Needs, and Use of Services
Authors: Pineault Raynald , Borgès Da Silva Roxane , Provost Sylvie , Breton Mylaine , Tousignant Pierre , Fournier Michel , Prud’homme Alexandre , Levesque Jean-Frédéric
Published: February 2016

Introduction. Healthcare reforms launched in the early 2000s in Québec, Canada, involved the implementation of new forms of primary healthcare (PHC) organizations: Family Medicine Groups (FMGs) and Network Clinics (NCs). The objective of this paper is to assess how the organizational changes associated with these reforms have impact on patients’ experience of care, use of services, and unmet needs.Methods. We conducted population and organization surveys in 2005 and 2010 in two regions of the province of Québec. The design was a before-and-after natural experiment. Changes over time between new models and other practices were assessed using difference-in-differences statistical procedures.Results. Accessibility decreased between 2003 and 2010, but less so in the treatment than in the comparison group. Continuity of care generally improved, but the increase was less for patients in the treatment group. Responsiveness also increased during the period and more so in the treatment group. There was no other significant difference between the two groups.Conclusion. PHC reform in Québec has brought about major organizational changes that have translated into slight improvements in accessibility of care and responsiveness. However, the reform does not seem to have had an impact on continuity, comprehensiveness, perceived care outcomes, use of services, and unmet needs.
A Model for Sorting Activities to Be Outsourced in Civil Construction Based on ROR-UTADIS
Authors: Palha Rachel Perez , de Almeida Adiel Teixeira , Alencar Luciana Hazin
Published: February 2016

The subcontractor’s selection problem is currently treated as a supply chain problem with a prequalification procedure to balance the main objectives of the client: cost, quality, and time. Unfortunately, most of the selection processes are analysed under the same methodology without considering that variations in project, type of activity, and other attributes should affect the chosen method. To provide a novel form of treating subcontractor’s selection, we proposed an additive sorting method to categorize activities to be outsourced in civil construction based on ROR-UTADIS method, which is a modification of the UTADIS method that includes new forms of supplying preference information. It was applied in the construction of a brewery in Brazil. It was perceived that the method is applicable and intuitive for decision makers, even though there are quite a few points to be taken, analysed to avoid misclassification.
Fortifying the Treatment of Prostate Cancer with Physical Activity
Authors: Champ Colin E. , Francis Lanie , Klement Rainer J. , Dickerman Roger , Smith Ryan P.
Published: February 2016

Over the past decade, significant data have shown that obese men experience a survival detriment after treatment for prostate cancer. While methods to combat obesity are of utmost importance for the prostate cancer patient, newer data reveal the overall metabolic improvements that accompany increased activity levels and intense exercise beyond weight loss. Along these lines, a plethora of data have shown improvement in prostate cancer-specific outcomes after treatment accompanied with these activity levels. This review discusses the metabolic mechanisms in which increased activity levels and exercise can help improve both outcomes for men treated for prostate cancer while lowering the side effects of treatment.
A Context-Aware Adaptive Streaming Media Distribution System in a Heterogeneous Network with Multiple Terminals
Authors: Ni Yepeng , Shuai Qianjun , Yang Cheng , Liu Jianbo
Published: February 2016

We consider the problem of streaming media transmission in a heterogeneous network from a multisource server to home multiple terminals. In wired network, the transmission performance is limited by network state (e.g., the bandwidth variation, jitter, and packet loss). In wireless network, the multiple user terminals can cause bandwidth competition. Thus, the streaming media distribution in a heterogeneous network becomes a severe challenge which is critical for QoS guarantee. In this paper, we propose a context-aware adaptive streaming media distribution system (CAASS), which implements the context-aware module to perceive the environment parameters and use the strategy analysis (SA) module to deduce the most suitable service level. This approach is able to improve the video quality for guarantying streaming QoS. We formulate the optimization problem of QoS relationship with the environment parameters based on the QoS testing algorithm for IPTV in ITU-T G.1070. We evaluate the performance of the proposed CAASS through 12 types of experimental environments using a prototype system. Experimental results show that CAASS can dynamically adjust the service level according to the environment variation (e.g., network state and terminal performances) and outperforms the existing streaming approaches in adaptive streaming media distribution according to peak signal-to-noise ratio (PSNR).
Parallel Digital Watermarking Process on Ultrasound Medical Images in Multicores Environment
Authors: Khor Hui Liang , Liew Siau-Chuin , Zain Jasni Mohd.
Published: February 2016

With the advancement of technology in communication network, it facilitated digital medical images transmitted to healthcare professionals via internal network or public network (e.g., Internet), but it also exposes the transmitted digital medical images to the security threats, such as images tampering or inserting false data in the images, which may cause an inaccurate diagnosis and treatment. Medical image distortion is not to be tolerated for diagnosis purposes; thus a digital watermarking on medical image is introduced. So far most of the watermarking research has been done on single frame medical image which is impractical in the real environment. In this paper, a digital watermarking on multiframes medical images is proposed. In order to speed up multiframes watermarking processing time, a parallel watermarking processing on medical images processing by utilizing multicores technology is introduced. An experiment result has shown that elapsed time on parallel watermarking processing is much shorter than sequential watermarking processing.
CD44+ Cells in Head and Neck Squamous Cell Carcinoma Suppress T-Cell–Mediated Immunity by Selective Constitutive and Inducible Expression of PD-L1
Authors: Lee Yunqin , Shin June Ho , Longmire Michelle , Wang Hua , Kohrt Holbrook E. , Chang Howard Y. , Sunwoo John B.
Published: February 2016

Purpose: Human tumors consist of heterogeneous populations of cells with distinct marker expression and functional properties. In squamous cell carcinoma of the head and neck (SCCHN), CD44 is a well-characterized marker of a resilient subpopulation of cells associated with increased tumorigenesis, radioresistance, and chemoresistance. Evidence indicates that these cells have an immunosuppressive phenotype; however, mechanisms have been elusive.

Experimental Design: Using primary human SCCHN tumor samples and patient-derived xenografts, we examined the phenotypes of subsets of tumor cells and investigated mechanisms regulating their immunogenicity.

Results: CD44+ cells in primary human SCCHN were found to have an epithelial-to-mesenchymal (EMT) phenotype and were less immunogenic than CD44− cells when cultured with autologous CD8+ tumor-infiltrating T cells. Selective expression of the programmed death-ligand 1 (PD-L1) was observed on CD44+ cells compared with CD44− cells and was associated with constitutive phosphorylation of STAT3 on CD44+ cells. Importantly, inhibition of STAT3 decreased expression of PD-L1 on CD44+ cells. IFNγ treatment preferentially induced even further PD-L1 expression on CD44+ cells and was associated with enhanced IFNγ receptor expression and phosphorylation of STAT1. Finally, the decreased immunogenicity of CD44+ cells was partially reversed by antibody blockade of the programmed death 1 (PD-1) receptor, indicating that the differences in PD-L1 expression between CD44+ and CD44− cells are biologically and clinically relevant.

Conclusions: Our findings provide a mechanism by which long-lived CD44+ tumor-initiating cells can selectively evade host immune responses and provide rationale for targeting the PD-1 pathway in the adjuvant therapy setting of SCCHN. Clin Cancer Res; 22(14); 3571–81. ©2016 AACR.
Severe Hyperinsulinaemic Hypoglycaemia in Beckwith-Wiedemann Syndrome due to Paternal Uniparental Disomy of 11p15.5 Managed with Sirolimus Therapy
Authors: Güemes Maria , Shah Pratik , Roženková Klára , Gilbert Clare , Morgan Kate , Hussain Khalid
Published: February 2016

Background: Almost half of the children with Beckwith-Wiedemann syndrome (BWS) will develop hyperinsulinaemic hypoglycaemia (HH). In the majority of BWS cases, HH will be transient; however, approximately in 5% of them, HH will be severe and often medically-unresponsive. Children with BWS due to paternal uniparental disomy (UPD) of chromosome 11p15 belong to this severe category and have traditionally required near-total pancreatectomy. The use of mTOR inhibitors had not been reported yet in this type of patients. Case: A 1-month-old female with genetically confirmed BWS due to UPD of chromosome 11p15 was admitted for management of severe HH. Blood glucose concentrations were stabilised with high intravenous dextrose concentration, glucagon and octreotide infusions as she was proven to be diazoxide unresponsive. To avoid a subtotal pancreatectomy, an mTOR inhibitor - sirolimus - was introduced. The dose of sirolimus was optimised progressively and she was able to come off intravenous fluids and glucagon therapy. She has not presented any side effects and her growth is normal after 19 months of therapy. Conclusion: This is the first case reported of BWS due to UPD of chromosome 11p15 where sirolimus treatment has been effective in stabilising the blood glucose concentrations and avoiding a near-total pancreatectomy without major side effects detected.
Robot-Assisted Bladder Diverticulectomy with Concurrent Management of Bladder Outlet Obstruction
Authors: Tufek Ilter , Mourmouris Panagiotis , Argun Omer Burak , Öbek Can , Keskin Mehmet Selcuk , Akpinar Haluk , Atug Fatih , Kural Ali Riza
Published: February 2016

Introduction: Robot-assisted bladder diverticulectomy (RABD) through a technique for easier identification of diverticulum along with concomitant management of bladder outlet obstruction (BOO) utilizing a combination of transurethral prostatectomy (TUR-P) and photoselective vaporization of prostate (PVP) is presented. Materials and Methods: Between 2008 and 2015, 9 patients underwent RABD with concurrent treatment of BOO. Diverticula were identified by a technique of catheterizing the diverticulum and the bladder simultaneously and individually. Results: Mean patient age was 62 ± 9.8 and prostate volume was 70 ± 26 ml. Mean time for endourological procedure was 77 ± 35, mean console and total operative times were 108 ± 38 and 186 ± 56 min, respectively. Mean estimated blood loss was 71 ± 37 ml. All diverticula were excised and BOO treated successfully. Bladder irrigation was not necessary in any patient. Mean hospitalization and catheter removal time was 5 ± 3 and 8 ± 3 days, respectively. No complications were observed. Conclusions: BOO is the main cause of acquired bladder diverticula and is largely due to benign prostatic hyperplasia. Concomitant performance of TUR-P and PVP along with RABD is feasible and safe. Individual catheterization of the diverticulum and bladder facilitates the identification of diverticulum even in the presence of multiple diverticula.
Late Presentation of Fulminant Necrotizing Enterocolitis in a Child with Hyperinsulinism on Octreotide Therapy
Authors: Hawkes Colin Patrick , Adzick N. Scott , Palladino Andrew A. , De León Diva D.
Published: February 2016

Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infants and children. In cases of diazoxide-unresponsive HI, alternative medical and surgical approaches may be required to reduce the risk of hypoglycemia. Octreotide, a somatostatin analog, often has a role in the management of these children, but a dose-dependent reduction in splanchnic blood flow is a recognized complication. Necrotizing enterocolitis (NEC) has been reported within the first few weeks of initiating predominantly high doses of octreotide. We describe the case of an infant with Beckwith-Wiedemann syndrome and diazoxide-unresponsive HI, who had persistent hypoglycemia after two pancreatectomy surgeries. She developed NEC 2 months after beginning octreotide therapy at a relatively low dose of 8 µg/kg/day. This complication has occurred later, and at a lower dose, than has previously been described. We review the case and identify the known and suspected multifactorial risk factors for NEC that may contribute to the development of this complication in patients with HI.
Etiology and Prevention of Gastric Cancer
Authors: Cheng Xiao Jiao , Lin Jia Cheng , Tu Shui Ping
Published: February 2016

Background: Gastric cancer is a heterogeneous malignant disease associated with environmental and genetic predisposing factors. While gastric cancer incidence and mortality fell greatly globally over the past decades, it remains the fourth cause of cancer-related death worldwide. Thus, prevention of gastric cancer is still a major strategy for improvement of gastric cancer prognosis. Summary:Helicobacter pylori infection has been demonstrated to be a major risk factor for the development of gastric cancer. Unhealthy diet and lifestyle, including high-salt food, smoking and drinking, are able to induce genotypic and phenotypic transformation of gastric epithelial cells. Gene mutations (such as E-cadherin) in stomach epithelial cells are major genetic causes for gastric cancer. The eradication of H. pylori has been demonstrated to be an effective approach for primary prevention of gastric cancer. Increased intake of a diet rich in vegetables and fresh fruits as well as smoking cessation have been shown to reduce the incidence of gastric cancer. The secondary prevention strategy is to screen premalignant gastric lesions by endoscopy. Biomarker tests are also reliable methods to identify gastric precancerous lesions. Endoscopy screening is still the gold standard for diagnosis of gastric cancer. Key Message:H. pylori infection, a diet rich in salted and/or smoked food and red meat, as well as gene mutations are major risk factors for the development of gastric cancer. Practical Implications: The eradication of H. pylori is a major primary preventive strategy of gastric cancer. A healthy lifestyle, including increased intake of a diet rich in fruit and vegetables, reduced intake of salted and smoked food and red meat, a reduction of alcohol intake as well as smoking cessation will be effective approaches for the prevention of gastric cancer.
MRI Assessment of Ischemic Lesion Evolution within White and Gray Matter
Authors: Berner Lise-Prune , Cho Tae-Hee , Haesebaert Julie , Bouvier Julien , Wiart Marlène , Hjort Niels , Klærke Mikkelsen Irene , Derex Laurent , Thomalla Götz , Pedraza Salvador , Østergaard Leif , Baron Jean-Claude , Nighoghossian Norbert , Berthezène Yves
Published: February 2016

Background: In acute ischemic stroke (AIS), gray matter (GM) and white matter (WM) have different vulnerabilities to ischemia. Thus, we compared the evolution of ischemic lesions within WM and GM using MRI. Methods: From a European multicenter prospective database (I-KNOW), available T1-weighted images were identified for 50 patients presenting with an anterior AIS and a perfusion weighted imaging (PWI)/diffusion weighted imaging (DWI) mismatch ratio of 1.2 or more. Six lesion compartments were outlined: initial DWI (b = 1,000 s/mm2) lesion, initial PWI-DWI mismatch (Tmax >4 s and DWI-negative), final infarct mapped on 1-month fluid-attenuated inversion recovery (FLAIR) imaging, lesion growth between acute DWI and 1-month FLAIR, DWI lesion reversal at 1 month and salvaged mismatch. The WM and GM were segmented on T1-weighted images, and all images were co-registered within subjects to the baseline MRI. WM and GM proportions were calculated for each compartment. Results: Fifty patients were eligible for the study. Median delay between symptom onset and baseline MRI was 140 min. The percentage of WM was significantly greater in the following compartments: initial mismatch (52.5 vs. 47.5%, p = 0.003), final infarct (56.7 vs. 43.3%, p < 0.001) and lesion growth (58.9 vs. 41.2%, p < 0.001). No significant difference was found between GM and WM percentages within the initial DWI lesion, DWI reversal and salvaged mismatch compartments. Conclusions: Ischemic lesions may extend preferentially within the WM. Specific therapeutic strategies targeting WM ischemic processes may deserve further investigation.
Intralenticular Sustained-Release Dexamethasone Implant: Is It Still Effective on Macular Edema
Authors: Sekeroglu Mehmet Ali , Anayol Mustafa Alpaslan , Koc Fatih , Tirhis Hakan , Ozkan Seyhan Sonar , Yilmazbas Pelin
Published: February 2016

Purpose: To report the therapeutic efficacy of an accidentally injected intralenticular sustained-release dexamethasone implant in a patient with macular edema secondary to branch retinal vein occlusion and shortly discuss the management strategy of this rare complication. Methods: Complete ophthalmological examination and optical coherence tomography imaging were performed at each visit. Results: The implant accidentally caused a posterior capsular tear during the procedure and was injected into the crystalline lens because of an involuntary head movement of the patient. Since the anterior segment was normal, and the resultant cataract and implant itself did not obscure the visual axis, the decision was made to observe the patient with intralenticular implant, preserve the therapeutic effect and avoid reinjection. The macular edema resolved within time, while visual acuity did not show significant improvement due to an increase in lens opacification. The patient underwent phacoemulsification surgery at 7 months after the injection with implantation of posterior chamber IOL into the capsular bag. Conclusion: Inadvertent injection of sustained-release intravitreal dexamethasone implant into the crystalline lens is an uncommon but possible complication that is mostly caused by surgeon inexperience, improper technique and uncontrolled head movement during the procedure. Once this complication occurs, early phacoemulsification and repositioning of the implant into the vitreous is the frequently preferred management strategy. However, remarkable decrease in macular edema and visual acuity improvement can also be achieved without an immediate surgical intervention.
Short-Term High-Fat Diet Feeding Provides Hypothalamic but Not Hippocampal Protection against Acute Infection in Male Mice
Authors: Astiz Mariana , Pernía Olga , Barrios Vicente , Garcia-Segura Luis Miguel , Diz-Chaves Yolanda
Published: February 2016

Obesity is associated with increased fever and sickness behavior in response to infection. The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the reaction to immune stimuli. Bacterial infection, or bacterial lipopolysaccharide (LPS), induces the expression of peripheral cytokines that stimulate the hypothalamus and the hippocampus and activate the HPA axis. In this study, we explored whether the hypothalamic and hippocampal responses to infection are altered during the development of diet-induced obesity. Male mice were exposed to a high-fat diet (HFD) or a low-fat diet (LFD) for 15 days. They were then administered a single intraperitoneal injection of bacterial LPS or vehicle and sacrificed 24 h later. LPS increased circulating levels of insulin and leptin, but only in LFD animals. LPS induced a significant decrease in hypothalamic corticotrophin-releasing hormone and glucocorticoid receptor mRNA levels in LFD animals but exerted the opposite effect in HFD-fed mice. LPS increased the hypothalamic expression of molecules involved in the leptin signaling pathway (SOCS3 and STAT3), nuclear factor-κB pathway members, inflammatory mediators (tumor necrosis factor-α and interleukin-6) and glial proliferation markers (Emr1 and CD68) in LFD animals. These effects were dampened in HFD-fed mice. In contrast, the hippocampal responses to LPS were largely insensitive to HFD. These results suggest that HFD feeding reduced the inflammatory response induced by LPS in the hypothalamus but not in the hippocampus.
United They Fall: Why the International Community Should Not Promote Military Integration after Civil War
Authors: Krebs Ronald R. , Licklider Roy
Published: February 2016

Preventing the recurrence of civil war has become a critical problem for both scholarship and policy. Conventional wisdom urges the creation of capable, legitimate, and inclusive postwar states to reduce the risk of relapse into civil war, and international peacebuilders have often encouraged the formation of a new national army that would include members of the war's opposing sides. However, both the theoretical logics and the empirical record identifying military integration as a significant contributor to durable post–civil war peace are weak. An analysis of eleven cases finds little evidence that military integration played a substantial causal role in preventing the return to civil war. Military integration does not usually send a costly signal of the parties’ commitment to peace, provide communal security, employ many possible spoilers, or act as a powerful symbol of a unified nation. It is therefore both unwise and unethical for the international community to press military integration on reluctant local forces.
Are naïve birds attracted to herbivore-induced plant defences?
Authors: Amo Luisa , Dicke Marcel , Visser Marcel E.
Published: February 2016

Arthropod herbivory induces the emission of plant volatiles that can be used by natural enemies of the herbivores to find their prey. Recently it has been shown that insectivorous birds also use these volatiles to locate their prey. Results of a previous study showed that birds with experience in foraging for caterpillars in trees were able to discriminate between caterpillar-infested and uninfested trees, even in the absence of caterpillars or their damage on leaves. Here, we tested whether the attraction to caterpillar-infested trees is exhibited in birds naïve with respect to finding caterpillars on trees. Results show that naïve great tits (Parus major) were not attracted to infested trees, when they could not see the larvae or their feeding damage. Naïve birds cannot discriminate between caterpillar-infested and uninfested trees. Therefore, the attraction to caterpillar-infested trees does not seem to be innate in great tits, and may be acquired through learning.
Printing and Instrument Making in the Early Modern Atlantic, 1520–1600
Authors: Gulizia Stefano
Published: February 2016

This essay addresses printing and instrument making as crucial features in the accumulation and dissemination of cosmographical knowledge; as a corollary, it also frames the avalanche of data from the New World as a problem of ‘information management’. In this respect, while standard treatments of the topic emphasize the epistemological gathering directed by royal institutions, I maintain that armchair erudition and discovery were still coessential, if not overlapping. My discussion pursues a specific case study – the use of Pedro de Medina’s nautical tract in Seville, Venice and Antwerp – aiming to rewrite some aspects of network theory in terms of translation. Simultaneously, it tracks epistemological changes taking place within the cognitive jurisdictions of the printing house, and examines descriptions of instruments, woodcuts, and diagrams, to visualize how historical actors used to communicate with patrons, mathematicians, and craftsmen.
From Europe to Latin American
Authors: Jobim José Luís , Castro Rocha João Cezar de
Published: February 2016

In this paper, we will first present two precursors of World Literature as a transnational project: Hugo Meltzl (1846–1908) and Machado de Assis (1839–1908), authors whose paths never crossed, but who both produced arguments against the grain of the nationalist wave sweeping the West in the nineteenth century. Having done so, we will provide a concise examination of historical ways of looking at the relationship between Europe and America, and finally of ideas of imitation/emulation in the literature and culture of Latin America.
Grand Challenges! Great Literature?
Authors: Thomsen Mads Rosendahl
Published: February 2016

A changing world has always fed great literature with the dual ambition to thrive on the conflict between old and new worlds while bringing into play all the creativity of literature to frame, redefine, comprehend and criticize with a view to understanding changes in the human condition in its widest sense. Migration, digitalization, climate change and the possible end of humanity as we know it are each in their own way grand challenges to the world. Competing with more media than ever, literature will have to arm itself with expressions that are unique for literature; and fortunately literature’s capacity to mix concrete stories and general reflections, to cross time more effortlessly than any other media, and to be rooted in the most distinctive human feature (language) bodes well for this.
Canon and World Literature
Authors: Zhang Longxi
Published: February 2016

Canon or the classic refers to the best and most representative works in a literary or cultural tradition, and the rise of world literature now provides an opportunity for scholars of different literary traditions, particularly non-Western and the less well-known and insufficiently studied “minor” traditions, to introduce and present the canonical works they know best to form a canon of world literatures. World literature is not just all the works that happen to circulate beyond their culture of origin, but the collective body of the best canonical works from various literary traditions that circulate to constitute what we call world literature.