bluuebunny/crossref_metadata_2025 huggingface dataset:
Observation of a Long Primo Vessel in a Lymph Vessel from the Inguinal Node of a Rabbit
Authors: Noh Young-Il , Yoo Yeong-Min , Kim Ran-Hyang , Hong Ye-Ji , Lee Hye-Rie , Rho Min-Suk , Lee Sang-Suk
Published: June 2013

Though primo vessels are frequently found in the lymph near the abdominal aorta of rabbit by Alcian blue dye, the reproductions are still difficult to require considerable skills and technical know-how at dissected tissue of animal species. However, in the inguinal lymph node of a rabbit we found a long-type primo vascular system (LTP) dyed with Alcian blue, from an abdominal lymph vessel to an inguinal lymph node. The length of LTP was over an average length of 9.1 cm. The average diameters of the primo and the lymph vessels were about 23.9 μm and 242 μm, respectively. The primo vessels were not floating but adhered to lymph vessels with fascial connective tissue. These primo vessels might be a functional integration in the lymph system.
User Demand Aware Grid Scheduling Model with Hierarchical Load Balancing
Authors: Suresh P. , Balasubramanie P.
Published: June 2013

Grid computing is a collection of computational and data resources, providing the means to support both computational intensive applications and data intensive applications. In order to improve the overall performance and efficient utilization of the resources, an efficient load balanced scheduling algorithm has to be implemented. The scheduling approach also needs to consider user demand to improve user satisfaction. This paper proposes a dynamic hierarchical load balancing approach which considers load of each resource and performs load balancing. It minimizes the response time of the jobs and improves the utilization of the resources in grid environment. By considering the user demand of the jobs, the scheduling algorithm also improves the user satisfaction. The experimental results show the improvement of the proposed load balancing method.
A Behcet’s Disease Patient with Right Ventricular Thrombus, Pulmonary Artery Aneurysms, and Deep Vein Thrombosis Complicating Recurrent Pulmonary Thromboembolism
Authors: Aşker Selvi , Aşker Müntecep , Gürsu Özgür , Mercan Rıdvan , Timuçin Özgür Bülent
Published: June 2013

Intracardiac thrombus, pulmonary artery aneurysms, deep vein thrombosis, and pulmonary thromboembolism are rarely seen symptoms of Behcet’s disease. A 20-year-old female patient was admitted for complaints of cough, fever, palpitations, and chest pain. On the dynamic thorax computed tomograms (CT) obtained because of significantly enlarged hilar structures seen on chest radiograms, aneurysmal dilatation of the pulmonary artery segments bilaterally, chronic thrombus with collapse, and consolidation substances compatible with pulmonary embolism involving both lower lobes have been observed. It is learned that, four years ago, the patient had been diagnosed with Behcet’s disease and received colchicine treatment but not regularly. The patient was hospitalized. On the transthoracic echocardiogram, a thrombosis with a dimension of 4.2 × 1.6 cm was recognized in the right ventricle. On abdomen CT, aneurysmal iliac veins and deep vein thrombus on Doppler ultrasonograms were diagnosed. At the controls after three months of immunosuppressive and anticoagulant therapies, some clinical and radiological improvements were recognized. The patient suspended the treatment for a month and the thrombus recurred. We present our case in order to show the effectiveness of immunosuppressive and anticoagulant therapies and rarely seen pulmonary thromboembolism in recurrent Behcet’s disease.
High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δAgonism
Authors: Benetti Elisa , Mastrocola Raffaella , Rogazzo Mara , Chiazza Fausto , Aragno Manuela , Fantozzi Roberto , Collino Massimo , Minetto Marco A.
Published: June 2013

Peroxisome Proliferator Activated Receptor (PPAR)-δagonists may serve for treating metabolic diseases. However, the effects of PPAR-δagonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways activated in the gastrocnemius muscle by chronic administration of the selective PPAR-δagonist, GW0742 (1 mg/kg/day for 16 weeks), in male C57Bl6/J mice treated for 30 weeks with high-fructose corn syrup (HFCS), the major sweetener in foods and soft-drinks (15% wt/vol in drinking water). Mice fed with the HFCS diet exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP-activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5 expression and membrane translocation. GW0742 administration induced PPAR-δupregulation and improvement in glucose and lipid metabolism. Diet-induced activation of nuclear factor-κB and expression of inducible-nitric-oxide-synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment. These effects were accompanied by reduction in the serum concentration of interleukin-6 and increase in muscular expression of fibroblast growth factor-21. Overall, here we show that PPAR-δactivation protects the skeletal muscle against the metabolic abnormalities caused by chronic HFCS exposure by affecting multiple levels of the insulin and inflammatory cascades.
The Experimental Study on Concrete Permeability of Wireless Communication Module Embedded in Reinforced Concrete Structures
Authors: Jo Byung-Wan , Park Jung-Hoon , Yoon Kwang-Won
Published: June 2013

Recently, as the information industry and mobile communication technology develop, their study is conducted on the new concept of intelligent structures and maintenance techniques that apply wireless sensor network, USN (Ubiquitous Sensor Network), to social infrastructures such as civil and architectural structures on the basis of the concept of Ubiquitous Computing, which invisibly provides human life with computing, along with mutually cooperating, compromising, and connecting networks to each other by having computers within all objects around us. The purpose of this study is to investigate the capability of wireless communication of sensor node embedded in reinforced concrete structure with a basic experiment on electric wave permeability of sensor node by fabricating molding with variables of concrete thickness and steel bars that are mostly used in constructing structures to determine the feasibility of application to constructing structures with USN. By installing wireless communication module inside the structures, it is possible to communicate to measure the pitch of steel bars and permeability of concrete, by measuring in both directions horizontally and vertically. The magnitude of an electric wave in the range of used frequencies was measured by using Spectrum Analyzer. This electric wave was numerically analyzed and the effective wavelength of frequencies was analyzed by the properties of a frequency band area. As a result of constructing structures with wireless sensors, Plain concrete showed 45 cm for depth of permeability. Reinforced concretes that has pitches of 5 cm showed 37 cm and pitches of 15 cm showed 45 cm for the depth of permeability. This suggests that if the pitch of steel bars was more than 15 cm, it would not affect wireless communication.
Autonomic Involvement in Subacute and Chronic Immune-Mediated Neuropathies
Authors: Mazzeo Anna , Stancanelli Claudia , Di Leo Rita , Vita Giuseppe
Published: June 2013

Autonomic function can be impaired in many disorders in which sympathetic, parasympathetic, and enteric arms of the autonomic nervous system are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Availability of noninvasive, sensitive, and reproducible tests can help to recognize these disorders and to better understand specific mechanisms of some, potentially treatable, immune-mediated autonomic neuropathies. This paper describes autonomic involvement in immune-mediated neuropathies with a subacute or chronic course.
Some Characteristic Properties of Parallelz-Equidistant Ruled Surfaces
Authors: As Engin , Şenyurt Süleyman
Published: June 2013

Some characteristic properties of two ruled surfaces whose principal normal vectors are parallel along their striction curves inE3are examined by assuming that the distance between two central planes at suitable points is constant,E3. In case of which two ruled surfaces are close, the relationship between the integral invariants of this ruled surfaces is computed.
Improving the Efficiency of Medical Services Systems: A New Integrated Mathematical Modeling Approach
Authors: Shishebori Davood , Jabalameli Mohammad Saeed
Published: June 2013

Nowadays, the efficient design of medical service systems plays a critical role in improving the performance and efficiency of medical services provided by governments. Accordingly, health care planners in countries especially with a system based on a National Health Service (NHS) try to make decisions on where to locate and how to organize medical services regarding several conditions in different residence areas, so as to improve the geographic equity of comfortable access in the delivery of medical services while accounting for efficiency and cost issues especially in crucial situations. Therefore, optimally locating of such services and also suitable allocating demands them, can help to enhance the performance and responsiveness of medical services system. In this paper, a multiobjective mixed integer nonlinear programming model is proposed to decide locations of new medical system centers, link roads that should be constructed or improved, and also urban residence centers covered by these medical service centers and link roads under investment budget constraint in order to both minimize the total transportation cost of the overall system and minimize the total failure cost (i.e., maximize the system reliability) of medical service centers under unforeseen situations. Then, the proposed model is linearized by suitable techniques. Moreover, a practical case study is presented in detail to illustrate the application of the proposed mathematical model. Finally, a sensitivity analysis is done to provide an insight into the behavior of the proposed model in response to changes of key parameters of the problem.
A Service Model for 6LoWPAN Wireless Sensor Networks
Authors: Wang Xiaonan , Huang Haili
Published: June 2013

This paper proposes a 6LoWPAN service model based on the IPv6-based k-Anycast communication model. This model is extended into 6LoWPAN service model so that the data-centric services of WSN can be achieved efficiently in the address-centric 6LoWPAN. In the proposed service model, an IPv6 node can obtain multiple network services through one request-response interaction where multiple sensor nodes cooperate to complete all requested network services and they provide their respective network services at the same time. As a result, the delay time is shortened. In addition, the proposed service model avoids the service failure caused by dormant sensor nodes. Since users can only request the network services they are interested in, the redundant data transmission is avoided. The performance parameters of the proposed service model are analyzed, and the data results show that the performance of the proposed service model is better.
Efficacy of Fish Oil on Serum of TNFα, IL-1β, and IL-6 Oxidative Stress Markers in Multiple Sclerosis Treated with Interferon Beta-1b
Authors: Ramirez-Ramirez V. , Macias-Islas M. A. , Ortiz G. G. , Pacheco-Moises F. , Torres-Sanchez E. D. , Sorto-Gomez T. E. , Cruz-Ramos J. A. , Orozco-Aviña G. , Celis de la Rosa A. J.
Published: June 2013

Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system. Oxidative stress is also thought to promote tissue damage in multiple sclerosis. Current research findings suggest that omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil may have anti-inflammatory, antioxidant, and neuroprotective effects. The aim of the present work was to evaluate the efficacy of fish oil supplementation on serum proinflammatory cytokine levels, oxidative stress markers, and disease progression in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. The primary outcome was serum TNFαlevels; secondary outcomes were IL-1β1b, IL-6, nitric oxide catabolites, lipoperoxides, progression on the expanded disability status scale (EDSS), and annualized relapses rate (ARR). Fish oil treatment decreased the serum levels of TNFα, IL-1β, IL-6, and nitric oxide metabolites compared with placebo group (P≤0.001). There was no significant difference in serum lipoperoxide levels during the study. No differences in EDSS and ARR were found.Conclusion.Fish oil supplementation is highly effective in reducing the levels of cytokines and nitric oxide catabolites in patients with relapsing-remitting MS.
Chrononutrition against Oxidative Stress in Aging
Authors: Garrido M. , Terrón M. P. , Rodríguez A. B.
Published: June 2013

Free radicals and oxidative stress have been recognized as important factors in the biology of aging and in many age-associated degenerative diseases. Antioxidant systems deteriorate during aging. It is, thus, considered that one way to reduce the rate of aging and the risk of chronic disease is to avoid the formation of free radicals and reduce oxidative stress by strengthening antioxidant defences. Phytochemicals present in fruits, vegetables, grains, and other foodstuffs have been linked to reducing the risk of major oxidative stress-induced diseases. Some dietary components of foods possess biological activities which influence circadian rhythms in humans. Chrononutrition studies have shown that not only the content of food, but also the time of ingestion contributes to the natural functioning of the circadian system. Dietary interventions with antioxidant-enriched foods taking into account the principles of chrononutrition are of particular interest for the elderly since they may help amplify the already powerful benefits of phytochemicals as natural instruments with which to prevent or delay the onset of common age-related diseases.
Biological and Chemical Diversity of Biogenic Volatile Organic Emissions into the Atmosphere
Authors: Guenther Alex
Published: June 2013

Biogenic volatile organic compounds (BVOC) emitted by terrestrial ecosystems into the atmosphere play an important role in determining atmospheric constituents including the oxidants and aerosols that control air quality and climate. Accurate quantitative estimates of BVOC emissions are needed to understand the processes controlling the earth system and to develop effective air quality and climate management strategies. The large uncertainties associated with BVOC emission estimates must be reduced, but this is challenging due to the large number of compounds and biological sources. The information on the immense biological and chemical diversity of BVOC is reviewed with a focus on observations that have been incorporated into the MEGAN2.1 BVOC emission model. Strategies for improving current BVOC emission modeling approaches by better representations of this diversity are presented. The current gaps in the available data for parameterizing emission models and the priorities for future measurements are discussed.
Reduction of Orbital Inflammation following Decompression for Thyroid-Related Orbitopathy
Authors: Oh Sang-Rog , Tung Jonathan D. , Priel Ayelet , Levi Leah , Granet David B. , Korn Bobby S. , Kikkawa Don O.
Published: June 2013

Purpose. Thyroid-related orbitopathy (TRO) is associated with inflammation, expansion of orbital fat, enlargement of extraocular muscles, and optic neuropathy (ON). We examined the effects of orbital decompression on the inflammatory and congestive signs of TRO in patients who underwent emergent orbital decompression.Methods. This retrospective, consecutive study included patients with ON from TRO who underwent orbital decompression. Pre- and postoperative orbital inflammatory signs in the operated and nonoperated, contralateral eyes were graded with the 10-item clinical activity score (CAS).Results. Thirty-one orbits were included. Postoperatively, 22 patients and 29 orbits had resolution of ON while the remaining 2 patients had improvement in visual acuity. Mean preoperative CAS was 9.5 ± 0.4. At 12 months, postoperative CAS was 2.1 ± 0.6 (P<0.01) in the operated eye and 3.2 ± 0.5 (P<0.05) in the nonoperated, contralateral eye.Conclusion. In our series, 94% of orbits had resolution of ON. There was also a statistically significant postoperative reduction in the CAS in both the operated and nonoperated, contralateral eyes. This phenomenon may be due to lowered venous congestion, decreased intraorbital pressure, and diminution in inflammatory factors.
Mucosal Leishmaniasis: An Underestimated Presentation of a Neglected Disease
Authors: Strazzulla Alessio , Cocuzza Salvatore , Pinzone Marilia Rita , Postorino Maria Concetta , Cosentino Stefano , Serra Agostino , Cacopardo Bruno , Nunnari Giuseppe
Published: June 2013

We present a review of current knowledge about mucosal leishmaniasis (ML). Although involvement of mucous membranes is classically admitted in New World leishmaniasis, particularly occurring in infection byLeishmania (L.) braziliensisspecies complex, ML is also a possible presentation of Old World leishmaniasis, in eitherL. donovaniorL. majorspecies complex infections. Thus, ML has to be considered not only as a Latin American disease but as an Old and New World disease. We describe ML epidemiology, pathogenesis, clinics, diagnosis, and therapy. Considering both its highly disfiguring lesions and its possible lethal outcome, ML should not be underestimated by physicians. Moreover, leishmaniasis is expected to increase its burden in many countries as sandfly vector distribution is widespreading towards non-endemic areas. Finally, the lack of clear understanding of ML pathogenesis and the absence of effective human vaccines strongly claim for more research.
Investigation of the Effects of Length to Depth Ratio on Open Supersonic Cavities Using CFD and Proper Orthogonal Decomposition
Authors: Yilmaz Ibrahim , Ayli Ece , Aradag Selin
Published: June 2013

Simulations of supersonic turbulent flow over an open rectangular cavity are performed to observe the effects of length to depth ratio (L/D) of the cavity on the flow structure. Two‐dimensional compressible time‐dependent Reynolds‐averaged Navier‐Stokes equations with k‐ω turbulence model are solved. A reduced order modeling approach, Proper Orthogonal Decomposition (POD) method, is used to further analyze the flow. Results are obtained for cavities with several L/D ratios at a Mach number of 1.5. Mostly, sound pressure levels (SPL) are used for comparison. After a reduced order modeling approach, the number of modes necessary to represent the systems is observed for each case. The necessary minimum number of modes to define the system increases as the flow becomes more complex with the increase in the L/D ratio. This study provides a basis for the control of flow over supersonic open cavities by providing a reduced order model for flow control, and it also gives an insight to cavity flow physics by comparing several simulation results with different length to depth ratios.
Ethnobotanical Studies of Port Harcourt Metropolis, Nigeria
Authors: Nwauzoma A. B. , Dappa Magdalene S.
Published: June 2013

The objective of this study was to show the different ways medicinal herbs are used by the indigenous people in Port Harcourt metropolis (07 °3′ E, 04° 51′ N) in the Niger Delta region, Nigeria. One hundred and fifty structured questionnaires were administered, including oral interviews to herbal practitioners and users located at different parts of the city. Also, three popularly known herbal companies—Emiola naturalist care, Yem-Kem international herbal center, and Abiola medical herbal center—were included as they are healthcare providers, especially the medium income group. The results showed that a total of 83 plant species were recorded and classified according to their family, botanical, common, and local names. Also, the plant part used, mode of preparation, and type of ailment cured were included. The most frequently used plant parts were leaves followed by barks, roots, and fruits and with malaria fever as the most treated ailment. Deforestation, agricultural expansion, and fire were noted as the most important factors threatening the availability of these plants. The authors are of the opinion that paying special attention to the medicinal plants found in the area through conservation may help to amplify their role in the healthcare system, poverty alleviation, and environmental protection.
Effect of Glu‐B3 Allelic Variation on Sodium Dodecyl Sulfate Sedimentation Volume in Common Wheat (Triticum aestivum L.)
Authors: Si Hongqi , Zhao Manli , He Fuxia , Ma Chuanxi
Published: June 2013

Sodium dodecyl sulfate (SDS) sedimentation volume has long been used to characterize wheat flours and meals with the aim of predicting processing and end‐product qualities. In order to survey the influence of low‐molecular‐weight glutenin subunits (LMW‐GSs) at Glu‐B3 locus on wheat SDS sedimentation volume, a total of 283 wheat (Triticum aestivum L.) varieties including landraces and improved and introduced cultivars were analyzed using 10 allele‐specific PCR markers at the Glu‐B3 locus. The highest allele frequency observed in the tested varieties was Glu‐B3i with 21.9% in all varieties, 21.1% in landraces, 25.5% in improved cultivars, and 12% in introduced cultivars. Glu‐B3 locus represented 8.6% of the variance in wheat SDS sedimentation volume, and Glu‐B3b, Glu‐B3g, and Glu‐B3h significantly heightened the SDS sedimentation volume, but Glu‐B3a, Glu‐B3c, and Glu‐B3j significantly lowered the SDS sedimentation volume. For the bread‐making quality, the most desirable alleles Glu‐B3b and Glu‐B3g become more and more popular and the least desirable alleles Glu‐B3a and Glu‐B3c got less and less in modern improved cultivars, suggesting that wheat grain quality in China has been significantly improved through breeding effort.
Why Are Seizures Rare in Rapid Eye Movement Sleep? Review of the Frequency of Seizures in Different Sleep Stages
Authors: Ng Marcus , Pavlova Milena
Published: June 2013

Since the formal characterization of sleep stages, there have been reports that seizures may preferentially occur in certain phases of sleep. Through ascending cholinergic connections from the brainstem, rapid eye movement (REM) sleep is physiologically characterized by low voltage fast activity on the electroencephalogram, REMs, and muscle atonia. Multiple independent studies confirm that, in REM sleep, there is a strikingly low proportion of seizures (~1% or less). We review a total of 42 distinct conventional and intracranial studies in the literature which comprised a net of 1458 patients. Indexed to duration, we found that REM sleep was the most protective stage of sleep against focal seizures, generalized seizures, focal interictal discharges, and two particular epilepsy syndromes. REM sleep had an additional protective effect compared to wakefulness with an average 7.83 times fewer focal seizures, 3.25 times fewer generalized seizures, and 1.11 times fewer focal interictal discharges. In further studies REM sleep has also demonstrated utility in localizing epileptogenic foci with potential translation into postsurgical seizure freedom. Based on emerging connectivity data in sleep, we hypothesize that the influence of REM sleep on seizures is due to a desynchronized EEG pattern which reflects important connectivity differences unique to this sleep stage.
The Health Profile of Populations Living in Contaminated Sites: Sentieri Approach
Authors: Pirastu Roberta , Pasetto Roberto , Zona Amerigo , Ancona Carla , Iavarone Ivano , Martuzzi Marco , Comba Pietro
Published: June 2013

SENTIERI project (Epidemiological Study of Residents in Italian Contaminated Sites) studied mortality in the sites of national interest for environmental remediation (National Priority Contaminated Sites—NPCSs). SENTIERI described mortality of residents in NPCSSs, and it specifically focused on causes of death for which environmental exposure is suspected or ascertained to play an etiologic role. The epidemiological evidence of the causal association was classifieda prioriinto one of these three categories: Sufficient (S), Limited (L), and Inadequate (I). Mortality in the period 1995−2002 was studied for 63 single or grouped causes at the municipal level by computing: crude rate, standardized rate, standardized mortality ratios (SMR), and SMR adjusted for anad hocdeprivation index. Regional populations were used as references for SMR calculations and 90% CI accompanied SMR values. The deprivation index was constructed using 2001 national census variables for the following socioeconomic domains: education, unemployment, dwelling ownership, and overcrowding. SENTIERI results will allow the priorities setting in remediation intervention so as to prevent adverse health effects from environmental exposure. This paper’s objective is to present the rationale, methods, advantages, and limitations underlying SENTIERI project and to describe data and resources required to apply a similar approach in other countries.
Expression Level of IL-6 Secreted by Bone Marrow Stromal Cells in Mice with Aplastic Anemia
Authors: Chen Yong Feng , Wu Zhong Min , Xie Cong , Bai Shi , Zhao Li Dong
Published: June 2013

Parasecretion of the hematopoietic cytokines is considered as one of the mechanisms account for bone marrow hematopoiesis disorder. In this study, the level of IL-6 secreted by bone marrow stromal cells from a mouse model of aplastic anemia was analyzed. The aplastic anemia mouse model was established with cyclophosphamide in combination with chloramphenicol and 60Coγ radiation. The impairment of bone marrow hematopoiesis induced by irradiation and chemotherapeutic drugs was subsequently characterized by peripheral blood cell count, pathomorphological changes, and apoptosis rate. Furthermore, the in vitro proliferation of bone marrow stromal cells (BMSC) and the IL-6 secretion levels of BMSC were analyzed. In our model of aplastic anemia, the number of peripheral blood cells and bone marrow cells (BMC) were notably decreased, and the apoptosis rate of BMC increased. Furthermore, the proliferation of BMSC was obviously impeded while the IL-6 secretion levels of BMSC significantly increased. The findings of our study suggested that the IL-6 secretion level may be enhanced to some extent by the induction of aplastic anemia caused by irradiation and chemotherapeutic drugs and that the abnormal level of IL-6 might probably interfere with the stability of the bone marrow hematopoietic microenvironment.
Clinical Applications of Omics Technologies on ZHENG Differentiation Research in Traditional Chinese Medicine
Authors: Song Ya-Nan , Zhang Gui-Biao , Zhang Yong-Yu , Su Shi-Bing
Published: June 2013

Traditional Chinese medicine (TCM) ZHENG is the basic concept of TCM theory. The effectiveness of TCM treatment depends on the accuracy of ZHENG differentiation. ZHENG differentiation, using the “four diagnostic methods,” has the drawbacks of subjectivity and variability. Following development of omics technologies, which study the functional activities of human body from a system-wide perspective, it has been more and more applied in study of objectivity differentiating TCM ZHENG and understanding its biological mechanisms. This paper reviewed the literatures of clinical TCM ZHENG differentiation researches, underlying omics technologies, and indicated the increased trends of related articles with four kinds of omics technologies, including genomics, transcriptomics, proteomics and metabolomics, and the correlations between ZHENG differentiation and findings in omics studies. Moreover, the paper summarized the typical omics application in common studied diseases and TCM ZHENGs and discussed the main problems and countermeasure of ZHENG differentiation researches. The work here may provide a reference for further research of TCM ZHENG differentiation using omics technologies.
Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression
Authors: Fischer Silvia , Gesierich Sabine , Griemert Barbara , Schänzer Anne , Acker Till , Augustin Hellmut G. , Olsson Anna-Karin , Preissner Klaus T.
Published: June 2013

Extracellular RNA (eRNA) released from injured cells promotes tissue permeability, thrombosis, and inflammation in vitro and in vivo, and RNase1 pretreatment can reduce all these effects. In this study, we investigated the role of the eRNA/RNase1 system in tumor progression and metastasis. Under quiescent and stimulatory conditions, tumor cells released much higher levels of endogenous extracellular RNA (eRNA) than nontumor cells. In glioblastomas, eRNA was detected at higher levels in tumors than nontumor tissue. eRNA induced tumor cells to adhere to and migrate through human cerebral microvascular endothelial cells (HCMEC/D3), in a manner requiring activation of VEGF signaling. In addition, eRNA liberated TNF-α from macrophages in a manner requiring activation of the TNF-α–converting enzyme TACE. Accordingly, supernatants derived from eRNA-treated macrophages enhanced tumor cell adhesion to HCMEC/D3. TNF-α release evoked by eRNA relied upon signaling activation of mitogen-activated protein kinases and the NF-κB pathway. In subcutaneous xenograft models of human cancer, administration of RNase1 but not DNase decreased tumor volume and weight. Taken together, these results suggest that eRNA released from tumor cells has the capacity to promote tumor cell invasion through endothelial barriers by both direct and indirect mechanisms, including through a mechanism involving TNF-α release from tumor-infiltrating monocytes/macrophages. Our findings establish a crucial role for eRNA in driving tumor progression, and they suggest applications for extracellular RNase1 as an antiinvasive regimen for cancer treatment. Cancer Res; 73(16); 5080–9. ©2013 AACR.
RHPN2 Drives Mesenchymal Transformation in Malignant Glioma by Triggering RhoA Activation
Authors: Danussi Carla , Akavia Uri David , Niola Francesco , Jovic Andreja , Lasorella Anna , Pe'er Dana , Iavarone Antonio
Published: June 2013

Mesenchymal transformation is a hallmark of aggressive glioblastoma (GBM). Here, we report the development of an unbiased method for computational integration of copy number variation, expression, and mutation data from large datasets. Using this method, we identified rhophilin 2 (RHPN2) as a central genetic determinant of the mesenchymal phenotype of human GBM. Notably, amplification of the human RHPN2 gene on chromosome 19 correlates with a dramatic decrease in the survival of patients with glioma. Ectopic expression of RHPN2 in neural stem cells and astrocytes triggered the expression of mesenchymal genes and promoted an invasive phenotype without impacting cell proliferation. Mechanistically, these effects were implemented through RHPN2-mediated activation of RhoA, a master regulator of cell migration and invasion. Our results define RHPN2 amplification as a central genetic determinant of a highly aggressive phenotype that directs the worst clinical outcomes in patients with GBM. Cancer Res; 73(16); 5140–50. ©2013 AACR.
Targeting Epigenetics for Cancer Prevention By Dietary Cancer Preventive Compounds—The Case of miRNA
Authors: Kong Ah-Ng Tony , Zhang Chengyue , Su Zheng-Yuan
Published: June 2013

In cancer, genetic mutations have long been considered to be the only driver of neoplasia. However, there is increasing evidence that epigenetic alterations could also play a major role in carcinogenesis and cancer. A number of experimental and epidemiologic studies have shown that many classes of dietary phytochemicals possess cancer-preventive and epigenetic-modifying properties. The report by Derry and colleagues in this issue of the journal shows that grape seed extract (GSE) prevents azoxymethane (AOM)-induced colon colitis via epigenetic microRNA (miRNA) regulation. Although the precise mechanism underlying the control of miRNA expression is not well understood currently, epigenetic changes could play a major role. This report, along with increasing evidence showing the impact of dietary phytochemicals on epigenetic activities, offers new perspectives on miRNA and epigenetic regulation in cancer prevention. Cancer Prev Res; 6(7); 622–4. ©2013 AACR.
Conservative Treatment of Chronic Pancreatitis
Authors: Löhr J.-Matthias , Haas Stephen L. , Lindgren Fredrik , Enochsson Lars , Hedström Aleksandra , Swahn Fredrik , Segersvärd Ralf , Arnelo Urban
Published: June 2013

Background: Chronic pancreatitis is a progressive inflammatory disease giving rise to several complications that need to be treated accordingly. Because pancreatic surgery has significant morbidity and mortality, less invasive therapy seems to be an attractive option. Aim: This paper reviews current state-of-the-art strategies to treat chronic pancreatitis without surgery and the current guidelines for the medical therapy of chronic pancreatitis. Results: Endoscopic therapy of complications of chronic pancreatitis such as pain, main pancreatic duct strictures and stones as well as pseudocysts is technically feasible and safe. The long-term outcome, however, is inferior to definitive surgical procedures such as resection or drainage. On the other hand, the medical therapy of pancreatic endocrine and exocrine insufficiency is well established and evidence based. Conclusions: Endoscopic therapy may be an option to bridge for surgery and in children/young adolescents and those unfit for surgery. Pain in chronic pancreatitis as well as treatment of pancreatic exocrine insufficiency follows established guidelines.
Nonneoplastic and Neoplastic Barrett's Esophagus: The European Perspective
Authors: Pech Oliver
Published: June 2013

The cancer risk of nondysplastic Barrett's esophagus is very low (0.33-0.5 per year). Therefore, any endoscopic ablation technique is an overtreatment. Patients with low-grade intraepithelial neoplasia confirmed by a specialized GI pathologist seem to have a significant risk for developing high-grade intraepithelial neoplasia (HGIN) or cancer. Therefore, endoscopic treatment in this case seems to be justified. However, up to now there has been no prospective study supporting this. In recent years, endoscopic treatment of HGIN and mucosal Barrett's cancer has become a widely accepted treatment approach and even the therapy of choice in many countries. Endoscopic resection (ER) is the best validated treatment method in patients with HGIN and mucosal Barrett's cancer, and is widely used all over the world. In contrast to ablative treatment methods like argon plasma coagulation and radiofrequency ablation, ER allows histological assessment of the resected specimen in order to assess the depth of infiltration of the tumor. However, ER of the neoplastic lesions should always be followed by ablation of the nondysplastic remaining Barrett's esophagus in order to reduce the risk of recurrence or metachronous neoplasia. The long-time complete remission rate with this two-step strategy is ≥95%. A matter of continuing debate is whether patients with Barrett's cancer infiltrating the upper third of the mucosal layer (pT1sm1) can be treated by ER. Data from our and other centers indicate that a subgroup of patients with pT1sm1 adenocarcinomas without the presence of risk factors (poor differentiation grade, lymph or blood vessel infiltration, size >20 mm, ulcerated lesion) have a very low risk for lymph node metastasis (<2%) and endoscopic therapy can be an alternative to radical surgery.
MALT Lymphoma: Forget Surgery?
Authors: Fischbach Wolfgang
Published: June 2013

Treatment of gastric marginal zone B cell lymphoma of MALT (mucosa-associated lymphoid tissue) is nowadays standardized as outlined in the German S3 guideline of 2009 and the European (EGILS) consensus report of 2011. The first choice of treatment is Helicobacter pylori eradication in any case irrespective of H. pylori status and lymphoma stage. Some 70-80% of patients reveal complete remission of MALT lymphoma following successful eradication of the bacterium. Those patients with histologically persisting lymphoma residuals are managed by a watch-and-wait strategy. Nonresponders to H. pylori eradication are referred to radiation with a curative intention in stages I and II. The rare cases of MALT lymphoma of stage III and IV should be treated by chemotherapy. Surgery no longer plays a role in the therapy of gastric MALT lymphoma except for very rare complications such as perforation or bleeding that cannot be controlled endoscopically. Diffuse large B cell lymphoma (DLBCL) is the second most common gastric lymphoma. H. pylori eradication may lead to regression of DLBCL in the individual case. However, immunochemotherapy by a combination of rituximab and the CHOP protocol represents the standard treatment approach in patients with DLBCL and offers a good curative chance.
Pancreatic Cancer: Advances in Treatment, Results and Limitations
Authors: Hackert Thilo , Büchler Markus W.
Published: June 2013

Background/Aims: Pancreatic cancer remains a therapeutic challenge. Surgery is the only treatment with the chance of cure. The aim of this review is to summarize the present state-of-the-art surgical procedures in pancreatic cancer. Methods: The current literature was reviewed with regard to surgical approaches in pancreatic cancer. A focus was put on high-quality studies, reviews, systematic reviews and meta-analyses as well as recruiting studies highlighting innovative approaches. Results: Today, standard resections can be performed with mortality rates below 5% in specialized high-volume institutions. Extended approaches for locally advanced cancer are technically feasible, including venous resections, multivisceral resections and recurrence surgery. They can be carried out without increased morbidity and mortality, are not compromised by higher R1 or N+ rates, and can improve survival. Arterial tumor invasion is still regarded controversially and is oncologically questionable. All surgical approaches should be part of interdisciplinary multimodal treatment concepts to improve the patients' prognosis. Conclusion: Surgery is the backbone of pancreatic cancer treatment in localized disease. Extended approaches are feasible in centers and show - except for arterial resections - good long-term outcome. Interdisciplinary therapy is an essential supplementation of all surgical approaches.
Gluten-Free Diet in Gluten-Related Disorders
Authors: Mulder Chris J.J. , van Wanrooij R.L.J. , Bakker S.F. , Wierdsma N. , Bouma G.
Published: June 2013

A gluten-free diet (GFD) is recommended for all patients with coeliac disease (CD). The spectrum of gluten-related disorders in the early 1980s was simple: CD and dermatitis herpetiformis. In the last few years, wheat allergy, gluten ataxia and noncoeliac gluten sensitivity have become new gluten-related topics. Adherence to GFDs in CD is limited and factors influencing adherence are poorly understood. Noncoeliac gluten sensitivity has stimulated the GFD food industry not only in Australia but all over the world. This article provides an overview of GFD in daily practice.
Modern Imaging Techniques: Which - When - Why?
Authors: May Andrea
Published: June 2013

Within the last decade, the technological development improved the diagnostic work-up of small bowel diseases. In addition to abdominal ultrasound and radiological methods, the importance of endoscopy is increasing. Nowadays, five nonsurgical flexible endoscopy techniques are available for small bowel endoscopy: push enteroscopy and balloon-guided enteroscopy for evaluation of the proximal small bowel, balloon-assisted enteroscopy using two balloons (double-balloon enteroscopy) or one balloon (single-balloon enteroscopy), and spiral enteroscopy for evaluation of the deep small bowel. Intraoperative enteroscopy has become a reserve method.
Top-Down or Step-Up Treatment in Crohn's Disease?
Authors: Rogler Gerhard
Published: June 2013

In recent years, a change in the treatment goals for patients with Crohn's disease (CD) has come under intense discussion. Whereas 10 years ago treatment was initiated mainly in reaction to acute flares of the disease aimed to improve clinical symptoms, the focus now has changed to the prevention of damage to the intestinal wall. The prevention of structural damage by achievement of ‘mucosal healing', however, is associated with the more ‘aggressive' treatment and an earlier use of immunosuppressants and biologicals. The use of immunosuppressants and biologicals especially in patients with CD has decreased the rates of surgery and hospitalizations, indicating that there is a group of patients definitely profiting from such an early use of immunosuppressive treatment. In this group of patients, the benefits outweigh the disadvantages of immunosuppression: the increased risk of severe infections. However, it remains questionable whether this improvement can only be achieved by completely reversing established treatment strategies. The dispute has been condensed to the questions whether ‘top-down' (e.g. start with a combination of biological and immunosuppressant and ‘de-escalate' if possible) or ‘step-up' treatment (e.g. start with topical steroids, step up to systemic steroid, go to immunosuppression and biologicals if necessary) may be better. In general, in an upcoming era of individualized and personalized medicine, a ‘one-size-fits-all' approach does not appear to be desirable. CD patients definitely should not be undertreated (which is still frequently the case) or remain on steroid treatment (which is inappropriate); however, overtreatment (putting patients at risk of side effects without benefit) is against a fundamental principle of medicine: nihil nocere (do no harm).
Systemic Therapy and Synergies by Combination
Authors: Wörns Marcus-Alexander
Published: June 2013

After years of therapeutic nihilism due to the inefficacy of conventional cytotoxic chemotherapy, the multikinase inhibitor sorafenib was the first agent to demonstrate a significant improvement in the survival of patients with advanced hepatocellular carcinoma (HCC). However, survival benefits on sorafenib treatment remain modest in clinical practice and developing more effective systemic therapies is challenging. No other targeted agent or regimen has proven efficacy to improve survival in a phase III trial in the first- or second-line setting, and no standard treatment option currently exists outside of clinical trials for patients with acquired resistance or intolerance to sorafenib. In contrast to other malignancies, no oncogene addiction has been identified in hepatocarcinogenesis thus far, which may explain why currently tested agents do not achieve sustained partial or complete response in the majority of patients. Several agents with mainly antiangiogenic properties are currently in phase II and III development, including brivanib, ramucirumab, everolimus, tivantinib and resminostat. In addition, the role of molecularly targeted therapy (MTT) in earlier stages of the disease in combination with transcatheter arterial chemoembolization or in the adjuvant setting after potentially curative approaches is under investigation. The identification of the key driver mutations and the assessment of relevant targets for specific subpopulations of patients according to their biomarker-based profile will hopefully lead to a more personalized medicine. This article attempts to provide a concise overview on recent developments of MTT in the phase II-III setting in advanced HCC with an additional focus on synergistic combinations and combined treatment approaches.
Multimodal Treatment Strategies in Patients Undergoing Surgery for Hepatocellular Carcinoma
Authors: Lurje Georg , Lesurtel Mickaël , Clavien Pierre-Alain
Published: June 2013

Hepatocellular carcinoma (HCC) is one of the major health problems worldwide, and continues to grow because of its association with hepatitis B and C viruses. In patients with HCC, liver transplantation (LT) and liver resection are the only two curative treatment options. LT remains the best option since it not only removes the tumor, but also the underlying disease. The prerequisite for long-term success of LT for HCC depends on the tumor load and strict selection criteria with regard to the size and number of existing HCC lesions. The need to obtain the optimal benefit from a limited number of grafts has prompted the implementation of well-defined selection criteria that identify patients with early HCC who may benefit from better long-term outcome after LT. Unfortunately, LT can only be proposed in approximately 30% of patients with HCC due to limitations in donor graft availability. In this particular setting, open and laparoscopic surgical resection represent reasonable treatment modalities in noncirrhotic HCC patients. The decision-making process for liver resection should integrate the tumor stage, quality and function of the underlying liver parenchyma, volume of the future liver remnant, and general condition of the patient. In patients with favorable features (solitary tumor, compensated Child-Pugh A cirrhosis, no portal hypertension), the reported 5-year survival rates range between 50 and 70%. In specific cases, liver resection and LT may be combined in the same patient.
Primary Sclerosing Cholangitis and Cholangiocarcinoma: Pathogenesis and Modes of Diagnostics
Authors: Ehlken Hanno , Schramm Christoph
Published: June 2013

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease caused by progressive inflammation of the intra- and extrahepatic bile duct system. PSC patients have an increased risk to develop hepatobiliary as well as extrahepatic malignancies. The goal of a surveillance strategy for hepatobiliary malignancy in these patients is the detection of early cancer which will allow a potentially curative therapy. Here, we focus on a conceptual review of the pathogenesis of cholangiocellular carcinoma and gallbladder cancer and we will discuss a rational approach for the surveillance of these malignancies in PSC patients.
Hepatobiliary Malignancies: Lessons from Asia
Authors: Wong Tiffany C.L. , Poon Ronnie T.P.
Published: June 2013

With the higher incidences of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) in the East compared with the West, Asian centers have made significant contributions to the management of these malignancies. The major risk factor for HCC is hepatitis B infection in Asia in contrast to hepatitis C in Western populations. Barcelona Clinic for Liver Cancer (BCLC) staging that guides the treatment of patients with HCC in the West is considered too conservative by many Asian centers. In Asia, liver resection is widely offered to patients with multifocal, bilobar tumor or tumor invasion to the portal vein. The criteria for liver transplantation for HCC are also often more extended in Asian centers. Asian surgeons pioneered the development of living donor liver transplantation, which plays a major role in the management of early HCC associated with severe cirrhosis in Asia due to shortage of deceased donor graft. Asian centers have also made significant contributions to the modern management of CCA. A more aggressive surgical approach is generally adopted in Asia, including radical lymphadenectomy for intrahepatic CCA and simultaneous hepatic artery and portal vein resection with hepatectomy for hilar CCA. Eastern and Western centers should collaborate in further studies to establish the optimal treatment strategies for hepatobiliary malignancies.