bluuebunny/crossref_metadata_2025 huggingface dataset:
Bandwidth Extension of a Printed Square Monopole Antenna Loaded with Periodic Parallel-Plate Lines
Authors: Meng Linglong , Wang Weimin , Su Ming , Gao Jinchun , Liu Yuanan
Published: May 2017

A novel wideband monopole antenna employing periodically loaded parallel-plate lines is presented in this paper. The proposed antenna consists of a main square patch, a rectangular ground plane, and a periodical structure which is printed on both sides of substrate. A strong electromagnetic coupling technique is used to design the element that enhances impedance bandwidth and decreases the side-lobe level throughout the effective bandwidth. The antenna achieves a wide impedance bandwidth of about 61.1% or ranging from 2.16 to 4.06 GHz, an omnidirectional far-field pattern, and a peak radiation gain of 2.37 dBi. Finally, the proposed antenna is analyzed and measured. The measured results show satisfactory performance and good agreement with the simulated results.
Potential Utility of a 4K Consumer Camera for Surgical Education in Ophthalmology
Authors: Ichihashi Tsunetomo , Hirabayashi Yutaka , Nagahara Miyuki
Published: May 2017

Purpose. We evaluated the potential utility of a cost-effective 4K consumer video system for surgical education in ophthalmology. Setting. Tokai University Hachioji Hospital, Tokyo, Japan. Design. Experimental study. Methods. The eyes that underwent cataract surgery, glaucoma surgery, vitreoretinal surgery, or oculoplastic surgery between February 2016 and April 2016 were recorded with 17.2 million pixels using a high-definition digital video camera (LUMIX DMC-GH4, Panasonic, Japan) and with 0.41 million pixels using a conventional analog video camera (MKC-501, Ikegami, Japan). Motion pictures of two cases for each surgery type were evaluated and classified as having poor, normal, or excellent visibility. Results. The 4K video system was easily installed by reading the instructions without technical expertise. The details of the surgical picture in the 4K system were highly improved over those of the conventional pictures, and the visual effects for surgical education were significantly improved. Motion pictures were stored for approximately 11 h with 512 GB SD memory. The total price of this system was USD 8000, which is a very low price compared with a commercial system. Conclusion. This 4K consumer camera was able to record and play back with high-definition surgical field visibility on the 4K monitor and is a low-cost, high-performing alternative for surgical facilities.
Twenty-Four-Hour Variation of Intraocular Pressure in Primary Open-Angle Glaucoma Treated with Triple Eye Drops
Authors: Itoh Yoshinori , Nakamoto Kenji , Horiguchi Hiroshi , Ogawa Shumpei , Noro Takahiko , Sato Makoto , Nakano Tadashi , Tsuneoka Hiroshi , Yasuda Noriko
Published: May 2017

Objectives. To evaluate 24-hour intraocular pressure (IOP) variation in patients with primary open-angle glaucoma (POAG) treated with triple eye drops. Subjects and Methods. The IOP was measured in 74 eyes in 74 POAG patients (seated) on triple therapy (PG analogue, β-blocker, carbonic anhydrase inhibitor) at about every 3 hours. Results. The peak IOP was 13.5 ± 3.1 at 1:00, and the trough IOP was at 12.6 ± 2.4 mmHg at 7:00. The IOP at 7:00 was significantly lower than that at 10:00, 1:00, and 3:00 (p<0.05). Based on the time of the peak IOP, we classified the patients into two groups: diurnal (28 eyes) and nocturnal types (37 eyes). There was significant difference at the spherical equivalent between diurnal and nocturnal types (p=0.014). To assess the influence of reflective error, we conducted subanalysis for two groups: high myopic (26 eyes, ≤−6D) and low/nonmyopic (24 eyes, ≥−2D) groups. In the low/nonmyopia group, the IOP was significantly higher at 1:00 and 3:00 than at 13:00, 16:00, and 7: 00 (p<0.05). Conclusion. The mean of IOP elevated outside of clinic hour in the POAG patients on triple therapy. The low/nonmyopia patient should be carefully treated because the IOP of the patients at night elevated significantly.
A Novel Distributed Quantum-Behaved Particle Swarm Optimization
Authors: Li Yangyang , Chen Zhenghan , Wang Yang , Jiao Licheng , Xue Yu
Published: May 2017

Quantum-behaved particle swarm optimization (QPSO) is an improved version of particle swarm optimization (PSO) and has shown superior performance on many optimization problems. But for now, it may not always satisfy the situations. Nowadays, problems become larger and more complex, and most serial optimization algorithms cannot deal with the problem or need plenty of computing cost. Fortunately, as an effective model in dealing with problems with big data which need huge computation, MapReduce has been widely used in many areas. In this paper, we implement QPSO on MapReduce model and propose MapReduce quantum-behaved particle swarm optimization (MRQPSO) which achieves parallel and distributed QPSO. Comparisons are made between MRQPSO and QPSO on some test problems and nonlinear equation systems. The results show that MRQPSO could complete computing task with less time. Meanwhile, from the view of optimization performance, MRQPSO outperforms QPSO in many cases.
Inhibition of Lysyl Oxidases Impairs Migration and Angiogenic Properties of Tumor-Associated Pericytes
Authors: Ribeiro Aline Lopes , Kaid Carolini , Silva Patrícia B. G. , Cortez Beatriz A. , Okamoto Oswaldo Keith
Published: May 2017

Pericytes are important cellular components of the tumor microenviroment with established roles in angiogenesis and metastasis. These two cancer hallmarks are modulated by enzymes of the LOX family, but thus far, information about LOX relevance in tumor-associated pericytes is lacking. Here, we performed a comparative characterization of normal and tumoral pericytes and report for the first time the modulatory effects of LOX enzymes on activated pericyte properties. Tumoral pericytes isolated from childhood ependymoma and neuroblastoma specimens displayed angiogenic properties in vitro and expressed typical markers, including CD146, NG2, and PDGFRβ. Expression of all LOX family members could be detected in both normal and tumor-associated pericytes. In most pericyte samples, LOXL3 was the family member displaying the highest transcript levels. Inhibition of LOX/LOXL activity with the inhibitorβ-aminopropionitrile (βAPN) significantly reduced migration of pericytes, while proliferation rates were kept unaltered. Formation of tube-like structures in vitro by pericytes was also significantly impaired upon inhibition of LOX/LOXL activity withβAPN, which induced more prominent effects in tumor-associated pericytes. These findings reveal a novel involvement of the LOX family of enzymes in migration and angiogenic properties of pericytes, with implications in tumor development and in therapeutic targeting tumor microenvironment constituents.
Not Only Glycaemic But Also Other Metabolic Factors Affect T Regulatory Cell Counts and Proinflammatory Cytokine Levels in Women with Type 1 Diabetes
Authors: Stechova Katerina , Sklenarova-Labikova Jana , Kratzerova Tereza , Pithova Pavlina , Filipp Dominik
Published: May 2017

Type 1 diabetic (T1D) patients suffer from insulinopenia and hyperglycaemia. Studies have shown that if a patient’s hyperglycaemic environment is not compensated, it leads to complex immune dysfunctions. Similarly, T1D mothers with poor glycaemic control exert a negative impact on the immune responses of their newborns. However, questions concerning the impact of other metabolic disturbances on the immune system of T1D mothers (and their newborns) have been raised. To address these questions, we examined 28 T1D women in reproductive age for the relationship between various metabolic, clinical, and immune parameters. Our study revealed several unexpected correlations which are indicative of a much more complex relationship between glucose and lipid factors (namely, glycosylated haemoglobin Hb1Ac, the presence of one but not multiple chronic diabetic complications, and atherogenic indexes) and proinflammatory cytokines (IL-1alpha and TNF-alpha). Regulatory T cell counts correlated with HbA1c, diabetic neuropathy, lipid spectra parameters, and IL-6 levels. Total T-helper cell count was interconnected with BMI and glycaemia variability correlated with lipid spectra parameters, insulin dose, and vitamin D levels. These and other correlations revealed in this study provide broader insight into the association of various metabolic abnormalities with immune parameters that may impact T1D mothers or their developing child.
A Consistent Definition of Phase Resetting Using Hilbert Transform
Authors: Oprisan Sorinel A.
Published: May 2017

A phase resetting curve (PRC) measures the transient change in the phase of a neural oscillator subject to an external perturbation. The PRC encapsulates the dynamical response of a neural oscillator and, as a result, it is often used for predicting phase-locked modes in neural networks. While phase is a fundamental concept, it has multiple definitions that may lead to contradictory results. We used the Hilbert Transform (HT) to define the phase of the membrane potential oscillations and HT amplitude to estimate the PRC of a single neural oscillator. We found that HT’s amplitude and its corresponding instantaneous frequency are very sensitive to membrane potential perturbations. We also found that the phase shift of HT amplitude between the pre- and poststimulus cycles gives an accurate estimate of the PRC. Moreover, HT phase does not suffer from the shortcomings of voltage threshold or isochrone methods and, as a result, gives accurate and reliable estimations of phase resetting.
A New Subclass ofk-Janowski Type Functions Associated with Ruscheweyh Derivative
Authors: Mahmood Shahid , Malik Sarfraz Nawaz , Mustafa Saima , Riaz S. M. Jawwad
Published: May 2017

We introduce and investigate a new subclassVDkA,B,b,δof analytic functions using Ruscheweyh derivative. We derive the coefficient inequalities and other interesting properties and characteristics for functions belonging to the general class, which we have introduced and studied in this article. We also observe that this class is preserved under the Bernardi integral transform.
Myocardial Perfusion in Rheumatoid Arthritis Patients: Associations with Traditional Risk Factors and Novel Biomarkers
Authors: Bernardes Miguel , Vieira Tiago S. , Martins Maria João , Lucas Raquel , Costa Lúcia , Pereira Jorge G. , Ventura Francisco , Martins Elisabete
Published: May 2017

Introduction. Cardiovascular (CV) diseases are a major cause of death in rheumatoid arthritis (RA) patients. Novel biomarkers [B-type natriuretic peptide (BNP); osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL) ratio; and dickkopf-1 (DKK-1)] have been used in CV risk assessment. We analysed, in established RA patients, the presence of silent myocardial ischemia and its association with clinical variables, BNP, and bone and atheroma biomarkers. Methods. From a single-center tertiary referral hospital, RA patients asymptomatic for CV disease were submitted to myocardial perfusion scintigraphy (MPS) under adenosine stress and biomarkers measurements. Logistic regression was used to estimate crude odds ratios (OR) and 95% confidence intervals (CI). Results. In 189 patients, perfusion defects were frequent (25%) and associated with BNP ≥ 100 pg/mL (OR = 5.68; 95% CI: 2.038–15.830), fourth log OPG/RANKL ratio quartile (OR = 2.88; 95% CI: 1.091–7.622), and DKK-1 ≥ 133 pmol/L (OR = 2.69; 95% CI: 1.058–6.840). Similar associations were confirmed in those with C-reactive protein > or ≤ 3 mg/L. No relationship was found with the majority of traditional CV factors nor with disease variables. Conclusions. Our results corroborated the hypothesis that MPS could reveal subclinical CV dysfunction, supported the utility of BNP measurements as a screening tool, and put in perspective the potential usefulness of complementary approaches in CV risk assessment in RA patients.
Innovative 3D Model of the Human Middle Ear in High Resolution with a Histological Microgrinding Method: A Feasibility Study and Comparison with μCT
Authors: Bradel Susanne , Doniga-Crivat Laura , Besdo Silke , Lexow Franziska , Fehr Michael , Lenarz Thomas , Prenzler Nils , Brandes Gudrun
Published: May 2017

Conclusion. The development of a histological 3D model of the tympanic cavity visualizes the exact microanatomy of the sound conduction organ and is therefore essential for finite elements simulations and surgical training. Objectives. So far, no accurate histological 3D model of the sound conduction system existed in literature. For 3D reconstruction of the very fine structures inside and outside the auditory ossicles, a method based on histological slices allows a more differential analysis of both hard and soft tissues and could thus be superior to μCT. Method. A complete temporal bone was embedded in epoxy resin and microground in distances of about 34 μm. After photodocumentation of every plane, a 3D reconstruction was performed by using the Computer Aided Design (CAD) program Rhinoceros 5®. For comparison, a μCT of the same specimen resulted in a 3D model of the calcified structures in the middle ear. Results. The histological 3D model gives an excellent overview to all anatomical soft and bony tissues of the human auditory ossicles. Specifically the fine blood vessel system and the exact dimension of cartilage areas inside the ossicles can be illustrated much more precisely than with μCT data. The present technique also allows the evaluation of the fine connecting ligaments inside the tympanic cavity.
Automated Recognition of a Wall between Windows from a Single Image
Authors: Zhang Yaowen , Huo Linsheng , Li Hongnan
Published: May 2017

To avoid the time-consuming, costly, and expert-dependent traditional assessment of earthquake damaged structures, image-based automatic methods have been developed recently. Since automated recognition of structure elements is the basis by which these methods achieve automatic detection, this study proposes a method to recognize the wall between windows from a single image automatically. It begins from detection of line segments with further selection and linking to obtain longer line segments. The color features of the two sides of each long line segment are employed to pick out line segments as candidate window edges and then label them. Finally, the images are segmented into several subimages, window regions are located, and then the wall between the windows is located. Real images are tested to verify the method. The results indicate that walls between windows can be successfully recognized.
Hepatitis C Virus and Nonliver Solid Cancers: Is There an Association between HCV and Cancers of the Pancreas, Thyroid, Kidney, Oral Cavity, Breast, Lung, and Gastrointestinal Tract?
Authors: Qadwai Saad , Rehman Tayyaba , Barsa Jonathan , Solangi Zeeshan , Lebovics Edward
Published: May 2017

Hepatitis C virus (HCV) is known for its oncogenic potential and has been found to be associated with hepatocellular carcinoma (HCC) and non-Hodgkin lymphoma. It has also been postulated that HCV may play a role in the development of other extrahepatic solid tumors of other organs of the body since it has been isolated from the vessel wall, kidney, and oral mucosa. In this article, we have reviewed epidemiological studies that have been done to look into the relationship of HCV with nonliver solid cancers of the pancreas, thyroid, renal, oral cavity, breast, and lung and nonpancreatic gastrointestinal cancers. Based on this review, HCV might be associated with an increased risk of renal cell and lung cancers.
The Role of Toll-Like Receptors in Autoimmune Diseases through Failure of the Self-Recognition Mechanism
Authors: Farrugia Mark , Baron Byron
Published: May 2017

Toll-like receptors (TLRs), part of the innate immune system that recognises molecular signatures, are important in the recognition of pathogenic components. However, when specific cellular contexts develop in which TLRs are inappropriately activated by self-components, this may lead to sterile inflammation and result in the occurrence of autoimmunity. This review analyses the available data regarding TLR biochemistry, the specific mechanisms which are brought about by TLR activation, and the importance of these mechanisms in the light of any existing and potential therapies in the field of autoimmunity.
Charting Availability of Processed and Unprocessed Foods in School Neighbourhood Nutrition Environments in an Urban Australian Setting
Authors: Oaken Holly , Vaughan Lisa , Fa’avale Nicola , Ware Robert S. , Schubert Lisa
Published: May 2017

School Neighbourhood Nutrition Environments (SNNEs) can facilitate or impede healthy eating. This study describes the SNNEs surrounding 6 Good Start Program (GSP) schools in 5 suburbs in Logan, Queensland. Relative density of healthy and unhealthy food outlets was calculated for SNNEs surrounding GSP (6) and non-GSP (10) schools within the 5 suburbs. Relative accessibility of minimally processed and highly processed food and drink in SNNEs of the 6 GSP schools was determined using shelf measurements of snack foods. Unhealthy outlets greatly outnumber healthy outlets (mean relative density 15.6%, median 19.1%). The majority of outlets stock predominantly highly processed food and drink. Study areas are dominated by unhealthy food outlets and highly processed food.
Serum Sclerostin Levels in Patients with Ankylosing Spondylitis and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis
Authors: Shi Jianfeng , Ying Haijian , Du Juping , Shen Bo
Published: May 2017

Objective. Current studies of serum sclerostin levels in AS and RA patients are inconsistent. This meta-analysis was performed to identify the association of serum sclerostin level with AS and RA patients. Methods. Embase, PubMed, MEDLINE, and Cochrane Library databases (up to 25 January 2017) were used to collect all relevant published articles. Studies were pooled and standard mean difference (SMD) with 95% confidence interval (CI) was calculated. All data analyses were performed using RevMan 5.3. Results. Totally eight studies of AS including 420 AS patients and 317 healthy controls (HC) and three studies of RA including 145 RA patients and 127 HC were finally included in this meta-analysis. The results revealed that the serum sclerostin levels in both AS patients (SMD=-0.14; 95% CI=[-0.39,0.11]; P=0.28) and RA patients (SMD=-0.10; 95% CI=[-0.34,0.15]; P=0.43) were not significantly different from those in HC. Conclusion. The difference of serum sclerostin levels in AS and RA patients was not significantly different from HC, indicating that the sclerostin may not associate with the development of AS and RA.
Frozen Jacobian Multistep Iterative Method for Solving Nonlinear IVPs and BVPs
Authors: Ahmad Fayyaz , Rehman Shafiq Ur , Ullah Malik Zaka , Aljahdali Hani Moaiteq , Ahmad Shahid , Alshomrani Ali Saleh , Carrasco Juan A. , Ahmad Shamshad , Sivasankaran Sivanandam
Published: May 2017

In this paper, we present and illustrate a frozen Jacobian multistep iterative method to solve systems of nonlinear equations associated with initial value problems (IVPs) and boundary value problems (BVPs). We have used Jacobi-Gauss-Lobatto collocation (J-GL-C) methods to discretize the IVPs and BVPs. Frozen Jacobian multistep iterative methods are computationally very efficient. They require only one inversion of the Jacobian in the form of LU-factorization. The LU factors can then be used repeatedly in the multistep part to solve other linear systems. The convergence order of the proposed iterative method is 5m-11, where m is the number of steps. The validity, accuracy, and efficiency of our proposed frozen Jacobian multistep iterative method is illustrated by solving fifteen IVPs and BVPs. It has been observed that, in all the test problems, with one exception in this paper, a single application of the proposed method is enough to obtain highly accurate numerical solutions. In addition, we present a comprehensive comparison of J-GL-C methods on a collection of test problems.
Hey Factors at the Crossroad of Tumorigenesis and Clinical Therapeutic Modulation of Hey for Anticancer Treatment
Authors: Liu Zihao , Sanders Andrew J. , Liang Gehao , Song Erwei , Jiang Wen G. , Gong Chang
Published: May 2017

Hairy and Enhancer-of-split related with YRPW motif (Hey) transcription factors are important regulators of stem cell embryogenesis. Clinical relevance shows that they are also highly expressed in malignant carcinoma. Recent studies have highlighted functions for the Hey factors in tumor metastasis, the maintenance of cancer cell self-renewal, as well as proliferation and the promotion of tumor angiogenesis. Pathways that regulate Hey gene expression, such as Notch and TGFβ signaling, are frequently aberrant in numerous cancers. In addition, Hey factors control downstream targets via recruitment of histone deacetylases (HDAC). Targeting these signaling pathways or HDACs may reverse tumor progression and provide clinical benefit for cancer patients. Thus, some small molecular inhibitors or monoclonal antibodies of each of these signaling pathways have been studied in clinical trials. This review focuses on the involvement of Hey proteins in malignant carcinoma progression and provides valuable therapeutic information for anticancer treatment. Mol Cancer Ther; 16(5); 775–86. ©2017 AACR.
Liver Fibrosis: Understanding the Dynamics of Bidirectional Wound Repair to Inform the Design of Markers and Therapies
Authors: Iredale John P. , Pellicoro Antonella , Fallowfield Jonathan A.
Published: May 2017

Background: Liver fibrosis is the final common pathway of iterative or chronic liver damage. When it reaches an advanced stage, cirrhosis develops and this indicates a loss of normal liver architecture, disruption of normal blood flow, the development of nodules of proliferative hepatocytes and consequent functional failure. Cirrhosis is also associated with life-threatening complications. Importantly, this dysregulation of blood flow involves changes resulting from both architectural disruption and a dynamic rise in portal pressure mediated in part by the contraction of myofibroblasts - the major cell mediator of the fibrogenic process - which are derived from hepatic stellate cells (HSC) and termed activated HSC (myofibroblast/activated HSC). Key Messages: There is now compelling data from both rodent and human models that liver fibrosis is bidirectional. By studying models of progressive and regressing liver fibrosis it has been possible to identify mediators that may be therapeutic targets. Arguably, by identifying the mediators of spontaneous resolution that result in a return of normal architecture, the attributes of a highly effective antifibrotic or pro resolution therapy can be defined. Among these key attributes, understanding the balance of matrix-degrading enzymes and their inhibitors (the metalloproteinases and Tissue inhibitors of metalloproteinases (TIMPs), respectively) led to the identification of both therapeutic targets and the value of TIMP-1 as a serum marker of fibrosis. Furthermore, the action of a potential therapeutic agent, relaxin (RLN) acting through its cognate G-protein coupled receptor (RXFP1) on the surface of activated HSC shows promise. Activation of the RLN-RXFP1-mediated pathway can be detected in vivo by measuring the dynamic contractility of activated HSC and the consequent changes in portal pressure and blood flow as a responsive physical biomarker. Conclusion: By understanding progressive and resolving liver fibrosis, a series of therapeutic targets have been identified. At the same time, key mediators of fibrosis may have an integral role to play as soluble or physical biomarkers.
Current and Future Magnetic Resonance Technologies for Assessing Liver Disease in Clinical and Experimental Medicine
Authors: Bawden Stephen J. , Scott R.A. , Aithal Guruprasad P.
Published: May 2017

Background: In the past decades, a number of non-invasive methods have emerged for detecting and estimating liver fibrosis; these include both serum-based panels and imaging-based technology. Some of these methods are now being incorporated in clinical practice. However, the limitations of the current techniques include lack of organ specificity, sampling errors and limited ability to reflect the efficacy of interventions. Key Messages: Novel magnetic resonance (MR)-based techniques provide an opportunity to bring about further changes in the investigations and management of patients with liver diseases. Multimodal quantitative MR techniques enable the estimation of fat, iron accumulation, degree of liver injury/inflammation and fibrosis within the whole liver without the need for administering contrast agents. Architectural changes within the liver can be evaluated concurrently with portal haemodynamic changes allowing non-invasive assessment of portal hypertension and effects of interventions. A combination ultra-high field (7T) provides greater sensitivity with a potential to distinguish inflammation from fibrosis on imaging and determine specific types of fats (saturated vs. unsaturated) present within the liver using MR spectroscopy. 13C MR spectroscopy can estimate glutathione flux and rate of beta oxidation in-vivo providing novel tools for experimental studies that evaluate the efficacy of interventions as well as underlying mechanisms. Conclusions: Translational research should focus on converting the potentials of these innovative methodologies into clinical applications for the benefit of patients.
Genetic Discoveries Highlight Environmental Factors as Key Drivers of Liver Disease
Authors: Chung Brian K. , Karlsen Tom H.
Published: May 2017

Background: Over the last 50 years, genetic studies have uncovered a spectrum of rare and common alleles that confer susceptibility to both Mendelian and complex forms of liver disease. For disorders of Mendelian inheritance, identification of the causal variants has demonstrated that common environmental exposures can elicit severe liver pathogenesis in predisposed individuals. Specific environmental triggers for complex liver disorders are largely unknown; however, large-scale association studies indicate that environmental triggers are the predominant factors in driving liver pathophysiology. Key Messages: In Mendelian liver disorders, a single rare variant of major effect is often responsible for disease development. Gene-sequencing technologies have greatly facilitated the discovery of causal variants for Mendelian diseases and are increasingly utilized in molecular and clinical genetics for diagnostic and counselling purposes. By contrast, genetic susceptibility for complex liver disorders is heterogeneous, as many different genes acting on multiple distinct pathways influence disease onset and severity. Risk variants for complex liver disorders are relatively common, typically of small effect size and detected by genome-wide association studies (GWAS), which compare the genetic variation of specific loci using thousands of patients and healthy controls. Thus far, GWAS have detected dozens of unique and overlapping risk alleles for complex liver disease, but these account for less than a quarter of the overall disease liability. These observations emphasize that environmental exposures on a background of genetic predisposition are significant drivers of liver pathophysiology. Rare variants of large effect size, undetectable by GWAS, may also affect the development of complex disease on a case-to-case basis but evidence for such a scenario remains to be determined. Conclusions: Genetic technologies have identified numerous risk genes for Mendelian and complex liver disorders transforming disease recognition. For complex liver disorders, deciphering the interplay between genetic risk and environment determinants remains a significant challenge for unlocking the development of novel and personalized interventions.
Hepatitis B Reactivation: The Controversies Continue
Authors: Feld Jordan J.
Published: May 2017

Hepatitis B virus (HBV) reactivation is a serious but largely avoidable complication of immunosuppressive therapy. The consequences of reactivation range from subclinical increases in HBV DNA to fulminant liver failure, which can be prevented with the appropriate use of prophylactic antiviral therapy. However, which patients need to be screened and whether all patients who test positive for any serological test require antiviral therapy are issues that still remain unclear. Additional issues such as the choice of antiviral and the duration of treatment also need clarification. Some of the confusion comes from the use of varying definitions in the literature to define outcomes. In this review, areas of controversy from definitions of reactivation to management of patients who are hepatitis B surface antigen and lone anti-core antibody positive in different clinical settings are discussed. The recently recognized issue of reactivation in the setting of hepatitis C antiviral therapy is also addressed as well as some recommendations for areas of future research to help clarify best practices.
Can Understanding the Pathogenesis of Autoimmune Hepatitis Lead to Rational Therapy?
Authors: Lohse Ansgar W. , Herkel Johannes , Weiler-Normann Christina
Published: May 2017

The pathogenesis of autoimmune hepatitis is still poorly understood and therefore, the therapy administered to treat this condition is broadly targeted immunosuppression. However, the aim of therapy in the future should be more specific; it should be a therapy that interrupts the pathogenetic cascade at defined checkpoints. Even though these checkpoints are not yet defined, possible targets of immunotherapy are emerging. These are specifically enhancing the regulatory T-cell activity, anti-cytokine interventions, in particular targeting the tumor necrosis factor, and hopefully in the foreseeable future, defining the key T-cell receptors used and developing new therapies directed against these.
The Role of a Dedicated Non-Alcoholic Fatty Liver Disease Clinic in 2016
Authors: Townsend Sarah A. , Newsome Philip N.
Published: May 2017

Background: Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of liver disease in the United Kingdom, and is predicted to become the leading indication for liver transplantation (LT) within the next 10 years. Key Messages: With rising demands on liver services, identifying those at risk of developing significant liver disease is important, so that risk factors for disease progression can be addressed. Emerging diagnostic techniques make it possible to diagnose significant fibrosis without the need for liver biopsy, and while there are currently no approved therapies for NAFLD, a specialist clinic can also provide access to clinical trials. For patients who develop cirrhosis, the presence of multiple comorbidities necessitates expertise in the selection and management of individuals requiring LT. Conclusions: A dedicated multidisciplinary NAFLD clinic facilitates rationalisation of services, improves patient outcomes, and provides access to emerging diagnostics and therapies.
Treating Hepatobiliary Cancer: The Immunologic Approach
Authors: Duffy A.G. , Greten T.F.
Published: May 2017

Hepatobiliary cancer comprises a heterogeneous group of malignancies in which the standard treatments for advanced disease are minimally effective and evolve slowly over time. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune-based approaches is yet to be experienced. Notwithstanding this, the etiological background of hepatobiliary cancer - overlapping in almost every known causative or associated factor with inflammation - provides a strong clue that these approaches may have an impact on this group of diseases. This review seeks to put the management of hepatobiliary cancers in the context of its inflammation-based etiology, with the aim of pointing to the therapeutic opportunities in immune-based approaches currently entering the clinic or those that are about to do so.
Translating Our Current Understanding of Ascites Management into New Therapies for Patients with Cirrhosis and Fluid Retention
Authors: Pose Elisa , Cardenas Andres
Published: May 2017

Ascites is the most common complication associated with cirrhosis resulting in poor quality of life, high risk of development of other complications of cirrhosis, increased morbidity and mortality associated with surgical interventions, and poor long-term outcome. Patients with cirrhosis and a first onset of ascites, have a probability of survival of 85% during the first year and 56% at 5 years without liver transplantation. Ascites is caused due to increased renal sodium retention as a result of increased activity of the renin-angiotensin-aldosterone system in response to marked vasodilation of the splanchnic circulation. The practical management of ascites involves the proper evaluation of a patient with a thorough history and physical exam. In addition, complete laboratory, ascitic fluid, and radiological tests should be performed. One of the most important steps in the initial assessment of patients with ascites is to refer the appropriate candidates for liver transplantation, as it offers a definitive cure for cirrhosis and its complications. While the initial management of uncomplicated ascites with low sodium diet and diuretic treatment is straightforward in a majority of patients, approximately 10% of patients fail to respond to diuretics and become a real therapeutic challenge. The initial treatment of choice in patients with refractory ascites is large-volume paracentesis (LVP) associated with intravenous albumin; some patients also benefit from transjugular intrahepatic portosystemic shunts (TIPS). When repeated LVP or TIPS cannot be performed, other approaches using vasoconstrictors such as midodrine can be considered although data are scarce. A newly designed automated low flow pump system (Alfapump), which is designed to move ascites from the peritoneal cavity to the urinary bladder where it is eliminated spontaneously through diuresis is promising, but the data are also limited and safety is still a matter of concern. This article focuses on the practical aspects of the evaluation and treatment of patients with ascites and cirrhosis and also discusses how to translate our current understanding of ascites pathophysiology into new treatment methods for patients with fluid retention.
Recombinant Allergens in Structural Biology, Diagnosis, and Immunotherapy
Authors: Tscheppe Angelika , Breiteneder Heimo
Published: May 2017

The years 1988-1995 witnessed the beginning of allergen cloning and the generation of recombinant allergens, which opened up new avenues for the diagnosis and research of human allergic diseases. Most crystal and solution structures of allergens have been obtained using recombinant allergens. Structural information on allergens allows insights into their evolutionary biology, illustrates clinically observed cross-reactivities, and makes the design of hypoallergenic derivatives for allergy vaccines possible. Recombinant allergens are widely used in molecule-based allergy diagnosis such as protein microarrays or suspension arrays. Recombinant technologies have been used to produce well-characterized, noncontaminated vaccine components with known biological activities including a variety of allergen derivatives with reduced IgE reactivity. Such recombinant hypoallergens as well as wild-type recombinant allergens have been used successfully in several immunotherapy trials for more than a decade to treat birch and grass pollen allergy. As a more recent application, the development of antibody repertoires directed against conformational epitopes during immunotherapy has been monitored by recombinant allergen chimeras. Although much progress has been made, the number and quality of recombinant allergens will undoubtedly increase and keep improving our knowledge in basic scientific investigations, diagnosis, and therapy of human allergic diseases.
Microvascular Function and Endothelial Progenitor Cells in Patients with Severe Hypercholesterolemia and the Familial Hypercholesterolemia Phenotype
Authors: De Lorenzo Andrea , Moreira Annie S.B. , Muccillo Fabiana B. , Assad Marcelo , Tibirica Eduardo V.
Published: May 2017

Objective: To evaluate endothelial progenitor cells (EPCs) and systemic microvascular function in patients with severe hypercholesterolemia, comparing patients with the definite familial hypercholesterolemia (FH) phenotype (DFH) or probable/possible FH phenotype (PFH). There is a large spectrum of atherosclerotic disease between these two clinical phenotypes of FH, and to acquire further knowledge of the pathophysiology of vascular disease in both is desirable. Methods: Subjects with severe hypercholesterolemia, defined as low-density lipoprotein cholesterol (LDL-C) >190 mg/dL, were classified as DFH or PFH and underwent measurement of the number of EPCs by flow cytometry and evaluation of cutaneous microvascular reactivity using a laser speckle contrast-imaging system with iontophoresis of acethylcholine (ACh) or sodium nitroprusside. EPCs were defined as CD45- or CD45low, CD34+CD133+CD309+ cells. Categorical variables were compared using Fisher test and continuous variables with Student t test or Mann-Whitney test, and a value of p < 0.05 was considered statistically significant. Results: Patients with DFH had higher LDL-C than those with PFH. There was no difference in the median number of EPCs between patients with DFH or PFH, but there was a significant reduction of endothelial-dependent, ACh-induced vasodilatation in the former. Conclusion: Patients with DFH have impaired microvascular endothelial-dependent vasodilatation compared to those with PFH, indicating more severe vascular disease in the former.
Sensory Neurons in the Human Geniculate Ganglion
Authors: Sato Tadasu , Yamaguma Yu , Sasaki Yu , Kanda Noriyuki , Sasahara Nobuyuki , Kokubun Souichi , Yajima Takehiro , Ichikawa Hiroyuki
Published: May 2017

The geniculate ganglion (GG) contains visceral and somatic sensory neurons of the facial nerve. In this study, the number and cell size of sensory neurons in the human GG were investigated. The estimated number of GG neurons ranged from 1,580 to 2,561 (mean ± SD = 1,960 ± 364.6). The cell size of GG neurons ranged from 393.0 to 2,485.4 μm2 (mean ± SD = 1,067.4 ± 99.5 μm2). Sensory neurons in the GG were significantly smaller in size than those in the dorsal root (range = 326.6-5343.4 μm2, mean ± SD = 1,683.2 ± 203.8 μm2) or trigeminal ganglia (range = 349.6-4,889.28 μm2, mean ± SD = 1,529.0 ± 198.48 μm2). Sensory neurons had similar cell body sizes in the GG and nodose ganglion (range = 357.2-3,488.33 μm2, mean ± SD = 1,160.4 ± 156.61 μm2). These findings suggest that viscerosensory neurons have smaller cell bodies than somatosensory neurons. In addition, immunohistochemistry for several neurochemical substances was performed on the human GG. In the ganglion, sensory neurons were mostly immunoreactive for secreted protein, acidic and rich in cysteine-like 1 (94.3%). One third of GG neurons showed vesicular glutamate transporter 2 immunoreactivity (31.3%). Only 7.3% of GG neurons were immunoreactive for transient receptor potential cation channel subfamily V member 1. Sensory neurons in the human GG may respond to gustatory, nociceptive, and/or mechanoreceptive stimuli from tongues, soft palates, and external auditory canals.
Making the Case for ‘Power Abuse Disorder' as a Nosologic Entity
Authors: Zernig Gerald , Hiemke Christoph
Published: May 2017

The development of societies and cultures arguably is based on the ability of human primates to form hierarchies in which some individuals acquire and wield power, that is, control resources and influence and control the behavior of their conspecifics. In the following, we focus on the type of human primate power wielding that (a) harms and (b) produces excessive negative emotions in (1) the victim(s) of the power wielder and (2) the power wielder her/himself. If such a harmful behavior of the power wielder is not accompanied by an ethically justifiable benefit for the involved human primate groups, it can be considered “power abuse.” We propose to term the associated behaviors, cognitions, and emotions of the power wielder as “power abuse disorder” (PAD). This behavior results from what we consider addictive behavior of the power abuse disordered (PADed) power wielder. PAD can be diagnosed on the basis of the World Health Organization's criteria for “dependence syndrome” as listed in the International Classification of Diseases version 10. We will demonstrate that many PADed individuals may very likely carry the Zeitgeist diagnosis “burnout.” This article reviews the current understanding of the neural correlates of PAD and suggests future research. Based on the available evidence, PAD seems to be associated with a dysfunction of the mesocorticolimbic dopamine system, rendering PADed individuals vulnerable for psychostimulant abuse/dependence, and suggesting specific pharmacotherapeutic approaches to treat PAD.
Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Ovarian Cancer: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Huang  Qi-tao , Zhou Lin , Zeng Wen-juan , Ma Qian-qian , Wang Wei , Zhong Mei , Yu Yan-hong
Published: May 2017

Background and Aims: Published data on the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in ovarian cancer are controversial. We conducted this meta-analysis to obtain a more accurate assessment of prognostic significance of NLR in ovarian cancer. Materials and Methods: We conducted a systematic literature search using the electronic databases PubMed, Web of Science, and Embase up to May 2016. Hazard ratio (HR) and odd ratio (OR) with 95% confidence interval (95% CI) were calculated. Subgroup analyses were carried out to explore the source of heterogeneity. Statistical analysis was performed using Stata 10.0. Results: A total of 12 studies, consisting of 3,854 patients, which met our criterion were selected in this meta-analysis. Our pooled results showed that high pre-treatment NLR level was significantly associated with poorer overall survival (OS) (HR: 1.69, 95% CI 1.29-2.22) and shorter progression free survival (PFS) (HR 1.63, 95% CI 1.27–2.09). Additionally, increased NLR was also significantly correlated with advanced FIGO stage (OR 2.32, 95% CI1.79-3.00), higher serum level of CA-125 (OR 3.33, 95% CI 2.43-4.58), more extensive ascites (OR 3.54, 95% CI 2.31-5.42) as well as less chemotheraputic response (OR 0.53, 95% CI 0.40-0.70). The findings from most of subgroup meta-analyses were consistent with those from the overall meta-analyses. Conclusions: Elevated pre-treatment NLR could served as a predicative factor of poor prognosis for ovarian cancer patients.
Space metamorphosis:action in preexistence and questioning as project premise
Authors: Duran Nathalia Valença
Published: May 2017

A  ação  em  preexistência  ocorre  a  partir  do  questionamento  do espaço  e  pode  ser   entendida  como  premissa  de  projeto,  recurso substancial  para  uma  ação  crítica  e   propositiva.  Assim,  pretende-se tatear  como  arquitetura  e  arte,  em  suas  diversas   escalas,  enfrentam a  lógica  dos  espaços  e  do  vazio,  buscando  entender  como  é  possível,  com  base  no  questionamento  do  espaço  previamente  dado, lidar  com   tempos  sobrepostos,  colocando-­‐o  como  foco  da  prática artística  e  arquitetônica.  Para   tanto,  foram  selecionados  para  estudo projetos  de  intervenções  que  enfrentam  essa   questão,  mantendo reconhecível  a  preexistência:  a  Pinacoteca  do  Estado  de  São  Paulo,  por  Paulo  Mendes  da  Rocha;  o  Solar  do  Unhão,  por  Lina  Bo  Bardi; a Reforma   Prudência,  de  Andrade  Morettin;  o  cenário  da  peça  The Rotary  Notary,  por  DS+R  e   Susan  Mosakowski;  a  escultura  Tilted arc de  Richard  Serra  e  a  obra  Detetor  de   Ausências,  de  Rubens  Mano
Accuracy of Seattle Heart Failure Model and HeartMate II Risk Score in Non–Inotrope-Dependent Advanced Heart Failure Patients
Authors: Lanfear David E. , Levy Wayne C. , Stehlik Josef , Estep Jerry D. , Rogers Joseph G. , Shah Keyur B. , Boyle Andrew J. , Chuang Joyce , Farrar David J. , Starling Randall C.
Published: May 2017

Background—

Timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients not on inotropes is unclear. Relevant prediction models exist (SHFM [Seattle Heart Failure Model] and HMRS [HeartMate II Risk Score]), but use in this group is not established.

Methods and Results—

ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) is a prospective, multicenter, nonrandomized study of 200 advanced heart failure patients not on inotropes who met indications for LVAD implantation, comparing the effectiveness of HeartMate II support versus optimal medical management. We compared SHFM-predicted versus observed survival (overall survival and LVAD-free survival) in the optimal medical management arm (n=103) and HMRS-predicted versus observed survival in all LVAD patients (n=111) using Cox modeling, receiver–operator characteristic (ROC) curves, and calibration plots. In the optimal medical management cohort, the SHFM was a significant predictor of survival (hazard ratio=2.98;
P
<0.001; ROC area under the curve=0.71;
P
<0.001) but not LVAD-free survival (hazard ratio=1.41;
P
=0.097; ROC area under the curve=0.56;
P
=0.314). SHFM showed adequate calibration for survival but overestimated LVAD-free survival. In the LVAD cohort, the HMRS had marginal discrimination at 3 (Cox
P
=0.23; ROC area under the curve=0.71;
P
=0.026) and 12 months (Cox
P
=0.036; ROC area under the curve=0.62;
P
=0.122), but calibration was poor, underestimating survival across time and risk subgroups.

Conclusions—

In non–inotrope-dependent advanced heart failure patients receiving optimal medical management, the SHFM was predictive of overall survival but underestimated the risk of clinical worsening and LVAD implantation. Among LVAD patients, the HMRS had marginal discrimination and underestimated survival post–LVAD implantation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01452802.