bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of Tissue-Specific CD8
+
T Cell Responses during West Nile Virus Infection
Authors: Aguilar-Valenzuela Renan , Netland Jason , Seo Young-Jin , Bevan Michael J. , Grakoui Arash , Suthar Mehul S.
Published: March 2018

The mouse model of West Nile virus (WNV), which is a leading cause of mosquito-borne encephalitis worldwide, has provided fundamental insights into the host and viral factors that regulate viral pathogenesis and infection outcome. In particular, CD8
+
T cells are critical for controlling WNV replication and promoting protection against infection. Here, we present the characterization of a T cell receptor (TCR)-transgenic mouse with specificity for the immunodominant epitope in the WNV NS4B protein (here referred to as transgenic WNV-I mice). Using an adoptive-transfer model, we found that WNV-I CD8
+
T cells behave similarly to endogenous CD8
+
T cell responses, with an expansion phase in the periphery beginning around day 7 postinfection (p.i.) followed by a contraction phase through day 15 p.i. Through the use of
in vivo
intravascular immune cell staining, we determined the kinetics, expansion, and differentiation into effector and memory subsets of WNV-I CD8
+
T cells within the spleen and brain. We found that red-pulp WNV-I CD8
+
T cells were more effector-like than white-pulp WNV-I CD8
+
T cells, which displayed increased differentiation into memory precursor cells. Within the central nervous system (CNS), we found that WNV-I CD8
+
T cells were polyfunctional (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), displayed tissue-resident characteristics (CD69
+
and CD103
+
), persisted in the brain through day 15 p.i., and reduced the viral burden within the brain. The use of these TCR-transgenic WNV-I mice provides a new resource to dissect the immunological mechanisms of CD8
+
T cell-mediated protection during WNV infection.

IMPORTANCE
West Nile Virus (WNV) is the leading cause of mosquito-borne encephalitis worldwide. There are currently no approved therapeutics or vaccines for use in humans to treat or prevent WNV infection. CD8
+
T cells are critical for controlling WNV replication and protecting against infection. Here, we present a comprehensive characterization of a novel TCR-transgenic mouse with specificity for the immunodominant epitope in the WNV NS4B protein. In this study, we determine the kinetics, proliferation, differentiation into effector and memory subsets, homing, and clearance of WNV in the CNS. Our findings provide a new resource to dissect the immunological mechanisms of CD8
+
T cell-mediated protection during WNV infection.
Spatial Analyses of Specialized Metabolites: The Key to Studying Function in Hosts
Authors: Galey Melissa M. , Sanchez Laura M.
Published: March 2018

Microbial communities contribute to a wide variety of biological functions in hosts and have the ability to specifically influence the health of those organisms through production of specialized metabolites. However, the structures or molecular mechanisms related to health or disease in host-microbe interactions represent a knowledge gap.
Neuroretinal atrophy following resolution of macular oedema in retinal vein occlusion
Authors: Podkowinski Dominika , Philip Ana-Maria , Vogl Wolf-Dieter , Gamper Jutta , Bogunovic Hrvoje , Gerendas Bianca S , Haj Najeeb Bilal , Waldstein Sebastian M , Schmidt-Erfurth Ursula
Published: March 2018

Background/aims

To characterise neuroretinal atrophy in retinal vein occlusion (RVO).

Methods

We included patients with central/branch RVO (CRVO=196, BRVO=107) who received ranibizumab according to a standardised protocol for 6 months. Retinal atrophy was defined as the presence of an area of retinal thickness (RT) <260 µm outside the foveal centre. Moreover, the thickness of three distinct retinal layer compartments was computed as follows: (1) retinal nerve fibre layer to ganglion cell layer, (2) inner plexiform layer (IPL) to outer nuclear layer (ONL) and (3) inner segment/outer segment junction to retinal pigment epithelium. To characterise atrophy further, we assessed perfusion status on fluorescein angiography and best-corrected visual acuity (BCVA), and compared these between eyes with/without atrophy.

Results

23 patients with CRVO and 11 patients with BRVO demonstrated retinal atrophy, presenting as sharply demarcated retinal thinning confined to a macular quadrant. The mean RT in the atrophic quadrant at month 6 was 249±26 µm (CRVO) and 244±29 µm (BRVO). Individual layer analysis revealed pronounced thinning in the IPL to ONL compartment. Change in BCVA at 6 months was similar between the groups (BRVO, +15 vs +18 letters; CRVO, +14 vs +18 letters).

Conclusions

In this exploratory analysis, we describe the characteristics of neuroretinal atrophy in RVO eyes with resolved macular oedema after ranibizumab therapy. Our analysis shows significant, predominantly retinal thinning in the IPL to ONL compartment in focal macular areas in 11% of patients with RVO. Eyes with retinal atrophy did not show poorer BCVA outcomes.
Clustering of risk factors and the risk of incident cardiovascular disease in Asian and Caucasian populations: results from the Asia Pacific Cohort Studies Collaboration
Authors: Peters Sanne A E , Wang Xin , Lam Tai-Hing , Kim Hyeon Chang , Ho Suzanne , Ninomiya Toshiharu , Knuiman Matthew , Vaartjes Ilonca , Bots Michael L , Woodward Mark
Published: March 2018

Objective

To assess the relationship between risk factor clusters and cardiovascular disease (CVD) incidence in Asian and Caucasian populations and to estimate the burden of CVD attributable to each cluster.

Setting

Asia Pacific Cohort Studies Collaboration.

Participants

Individual participant data from 34 population-based cohorts, involving 314 024 participants without a history of CVD at baseline.

Outcome measures

Clusters were 11 possible combinations of four individual risk factors (current smoking, overweight, blood pressure (BP) and total cholesterol). Cox regression models were used to obtain adjusted HRs and 95% CIs for CVD associated with individual risk factors and risk factor clusters. Population-attributable fractions (PAFs) were calculated.

Results

During a mean follow-up of 7 years, 6203 CVD events were recorded. The ranking of HRs and PAFs was similar for Australia and New Zealand (ANZ) and Asia; clusters including BP consistently showed the highest HRs and PAFs. The BP–smoking cluster had the highest HR for people with two risk factors: 4.13 (3.56 to 4.80) for Asia and 3.07 (2.23 to 4.23) for ANZ. Corresponding PAFs were 24% and 11%, respectively. For individuals with three risk factors, the BP–smoking–cholesterol cluster had the highest HR (4.67 (3.92 to 5.57) for Asia and 3.49 (2.69 to 4.53) for ANZ). Corresponding PAFs were 13% and 10%.

Conclusions

Risk factor clusters act similarly on CVD risk in Asian and Caucasian populations. Clusters including elevated BP were associated with the highest excess risk of CVD.
PmpI antibody reduces the inhibitory effect of Vp1 on Chlamydia trachomatis infectivity
Authors: Ren Jie , Lian Tingting , Shao Lili , Liu Yuanjun , Liu Quanzhong
Published: March 2018

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infections. The effect of antibiotic treatment is not satisfactory, and there is currently no vaccine to prevent C. trachomatis infection. Our results showed that Chlamydia virus CPG1 capsid protein Vp1 treatment significantly inhibited C. trachomatis growth in cell culture, and the inclusion numbers of different C. trachomatis serotypes were decreased. In addition, we conducted a preliminary investigation of the possible mechanisms behind the Vp1 inhibition effects and the C. trachomatis molecules targeted by Vp1. Using far-western blot and GST pull-down assay, we found that purified Vp1 can bind to the C. trachomatis outer membrane protein PmpI. PmpI polyclonal antibody treatment markedly reduced the inhibitory effect of Vp1 on C. trachomatis infectivity. On the basis of these experimental results, we infer that PmpI participates in the inhibitory effect of Vp1 and may be a potential receptor of Vp1 in the outer membrane of C. trachomatis. Our research provides clues regarding the molecular mechanisms underlying the interactions between chlamydia virus and chlamydia.
Fourier transform infrared spectroscopic study of gamma irradiated SiO2 nanoparticles
Authors: Huseynov Elchin , Garibov Adil , Mehdiyeva Ravan , Huseynova Efsane
Published: March 2018

In the present work, nano SiO2 particles are investigated before and after gamma irradiation (25, 50, 75, 100 and 200 kGy) using Fourier transform infrared (FTIR) spectroscopy method for the wavenumber between 400–4000 cm[Formula: see text]. It is found that as a result of spectroscopic analysis, five new peaks have appeared after gamma radiation. Two of new obtained peaks (which are located at 687 cm[Formula: see text] and 2357 cm[Formula: see text] of wavenumber) were formed as a result of gamma radiation interaction with Si–O bonds. Another three new peaks (peaks appropriate to 941, 2052 and 2357 cm[Formula: see text] values of wavenumber) appear as a result of interaction of water with nano SiO2 particles after gamma irradiation. It has been defined as asymmetrical bending vibration, symmetrical bending vibration, symmetrical stretching vibration and asymmetrical stretching vibration of Si–O bonds appropriate to peaks.
Effect of compressive deformation on thermal and corrosive properties of Zr61.7Al8Ni13Cu17Sn0.3 bulk metallic glass
Authors: Xu Yuanli , Shi Bo
Published: March 2018

The effect of compressive deformation on thermal stability and corrosive property of Zr[Formula: see text]Al8Ni[Formula: see text]Cu[Formula: see text]Sn[Formula: see text] bulk metallic glass with a strain of 80% was investigated in this work. The corresponding thermal stability is found to decrease after deformation and this can probably be attributed to the reduction of the viscosity and the increase of the Gibbs free energy after compressive deformation. In addition, the corrosion current density increases and this suggests that the corrosion resistance decreases for the deformed sample in comparison with the as-cast sample.
The effect of adding side group and changing contact geometry in single pyrene molecular devices
Authors: Jamali M. F. , Soleimani H. Rahimpour , Tagani M. Bagheri
Published: March 2018

In this study, the thermopower of pyrene molecule in both symmetric and asymmetric junctions to gold electrodes and the role of adding side group have been studied using density functional theory and Green’s function formalism in the linear response regime. We have considered four different configurations and investigated the thermopower property of them. Calculations show that adding electron donating side groups to both symmetrical and anti-symmetrical junction will increase the thermopower. However, the increase is more evident in asymmetric junction. Additionally, the Seebeck coefficient sign is positive which indicates p-type conduction.
Local and global Hopf bifurcation analysis in a neutral-type neuron system with two delays
Authors: Lv Qiuyu , Liao Xiaofeng
Published: March 2018

In recent years, neutral-type differential-difference equations have been applied extensively in the field of engineering, and their dynamical behaviors are more complex than that of the delay differential-difference equations. In this paper, the equations used to describe a neutral-type neural network system of differential difference equation with two delays are studied (i.e. neutral-type differential equations). Firstly, by selecting [Formula: see text], [Formula: see text] respectively as a parameter, we provide an analysis about the local stability of the zero equilibrium point of the equations, and sufficient conditions of asymptotic stability for the system are derived. Secondly, by using the theory of normal form and applying the theorem of center manifold introduced by Hassard et al., the Hopf bifurcation is found and some formulas for deciding the stability of periodic solutions and the direction of Hopf bifurcation are given. Moreover, by applying the theorem of global Hopf bifurcation, the existence of global periodic solution of the system is studied. Finally, an example is given, and some computer numerical simulations are taken to demonstrate and certify the correctness of the presented results.
Evaluation of Room-Temperature Performance of Ultra-Small Single-Electron Transistor-Based Analog-to-Digital Convertors
Authors: Miralaie Mostafa , Mir Ali
Published: March 2018

In this paper, in order to analyze the performance of single-electron transistor (SET)-based analog-to-digital converter (ADC) circuits at room temperature, first, the quantum Coulomb blockade regime is explained and based on it we calculate and discuss the inherent Coulomb oscillation characteristics of room-temperature-operating SETs (or, in other words, ultra-small SETs). Then, to explain the performance of SET-based ADC structures, we explore the sensitivity of converter section of these structures to the inherent periodic oscillation characteristics. By simulating two different temperatures of 100[Formula: see text]K and 300[Formula: see text]K, we demonstrate that for proper performance of converter section of the SET-based ADCs, SETs must have inherent Coulomb oscillations with the same and high peak-to-valley current ratio (PVCR) and equal Coulomb peak spacing (i.e., equal [Formula: see text]. The Coulomb oscillation characteristics of the room-temperature-operating silicon SET show the Coulomb oscillations with unequal PVCRs and unequal Coulomb peak spacings (i.e., unequal [Formula: see text]. As a result, it can be seen that the room-temperature-operating SET-based ADCs never have a suitable output.
Performance Evaluation of Numerical Finite Element Coupled Algorithms for Structure–Electric Interaction Analysis of MEMS Piezoelectric Actuator
Authors: Ramegowda Prakasha Chigahalli , Ishihara Daisuke , Niho Tomoya , Horie Tomoyoshi
Published: March 2018

This work presents multiphysics numerical analysis of piezoelectric actuators realized using the finite element method (FEM) and their performances to analyze the structure-electric interaction in three-dimensional (3D) piezoelectric continua. Here, we choose the piezoelectric bimorph actuator without the metal shim and with the metal shim as low-frequency problems and a surface acoustic wave device as a high-frequency problem. More attention is given to low-frequency problems because in our application micro air vehicle’s wings are actuated by piezoelectric bimorph actuators at low frequency. We employed the Newmark’s time integration and the central difference time integration to study the dynamic response of piezoelectric actuators. Monolithic coupling, noniterative partitioned coupling and partitioned iterative coupling schemes are presented. In partitioned iterative coupling schemes, the block Jacobi and the block Gauss–Seidel methods are employed. Resonance characteristics are very important in micro-electro-mechanical system (MEMS) applications. Therefore, using our proposed coupled algorithms, the resonance characteristics of bimorph actuator is analyzed. Comparison of the accuracy and computational efficiency of the proposed numerical finite element coupled algorithms have been carried out for 3D structure–electric interaction problems of a piezoelectric actuator. The numerical results obtained by the proposed algorithms are in good agreement with the theoretical solutions.
Diversity of Chlorophototrophic Bacteria Revealed in the Omics Era
Authors: Thiel Vera , Tank Marcus , Bryant Donald A.
Published: March 2018

Because of recent advances in omics methodologies, knowledge of chlorophototrophy (i.e., chlorophyll-based phototrophy) in bacteria has rapidly increased. Chlorophototrophs currently are known to occur in seven bacterial phyla: Cyanobacteria, Proteobacteria, Chlorobi, Chloroflexi, Firmicutes, Acidobacteria, and Gemmatimonadetes. Other organisms that can produce chlorophylls and photochemical reaction centers may still be undiscovered. Here we summarize the current status of the taxonomy and phylogeny of chlorophototrophic bacteria as revealed by genomic methods. In specific cases, we briefly describe important ecophysiological and metabolic insights that have been gained from the application of genomic methods to these bacteria. In the 20 years since the completion of the Synechocystis sp. PCC 6803 genome in 1996, approximately 1,100 genomes have been sequenced, which represents nearly the complete diversity of known chlorophototrophic bacteria. These data are leading to new insights into many important processes, including photosynthesis, nitrogen and carbon fixation, cellular differentiation and development, symbiosis, and ecosystem functionality.
Evidence for Interspecific Brood Parasite Detection and Removal in Burying Beetles
Authors: Smith Ashlee N. , Belk Mark C.
Published: March 2018

We tested whether brood parasitism could be successful between two co-occurring species of burying beetles, Nicrophorus guttula and Nicrophorus marginatus, and whether these species exhibit an adaptive response to brood parasitism by detecting and removing parasites. We cross-fostered larvae between broods of the two species and created mixed-species broods to simulate the addition of brood parasites. Brood parasites survived in both species’ broods. Nicrophorus marginatus culled 86% of brood parasites compared to 56% of their own larvae, and N. guttula culled 50% of brood parasites compared to 22% of their own larvae. Additionally, N. guttula brood parasites were significantly smaller than N. guttula that were raised by N. guttula parents, but N. marginatus brood parasites were significantly larger than N. marginatus that were raised by N. marginatus parents. This paper provides the first evidence that burying beetles can discriminate between their own larvae and other species’ larvae. We suggest that brood parasitism may be the selective force responsible for this ability.
A Solvable Dynamic Principal-Agent Model with Linear Marginal Productivity
Authors: Liu Bing , Yin Zheng , Lai Chong
Published: March 2018

We study how to design an optimal contract which provides incentives for agent to put forth the desired effort in a continuous time dynamic moral hazard model with linear marginal productivity. Using exponential utility and linear production, three different information structures, full information, hidden actions and hidden savings, are considered in the principal-agent model. Applying the stochastic maximum principle, we solve the model explicitly, where the agent’s optimization problem becomes the principal’s problem of choosing an optimal contract. The explicit solutions to our model allow us to analyze the distortion of allocations. The main effect of hidden actions is a reduction of effort, but the a smaller effect is on the consumption allocation. In the hidden saving case, the consumption distortion almost vanishes but the effort distortion is expanded. In our setting, the agent’s optimal effort is also reduced with the decline of marginal productivity.
Optical Coherence Tomography Angiography of Retinal Arterial Macroaneurysm before and after Treatment
Authors: Chang Victoria S. , Schwartz Stephen G. , Flynn Harry W.
Published: March 2018

A case of retinal arterial macroaneurysm (RAM) is presented with multimodal imaging, including commercially available optical coherence tomography angiography (OCT-A). Following treatment with intravitreal bevacizumab, reduction of flow signal through the RAM is documented. OCT-A provides useful information for the diagnosis and management of at least some patients with RAM, without the need for traditional fluorescein angiography.
Systemic Inflammatory Cytokines Predict the Infectious Complications but Not Prolonged Postoperative Ileus after Colorectal Surgery
Authors: Boersema G. S. A. , Wu Z. , Menon A. G. , Kleinrensink G. J. , Jeekel J. , Lange J. F.
Published: March 2018

Aim. Postoperative ileus (POI) is common after surgery. Animal studies indicate that the POI mechanism involves an inflammatory response, which is also activated during postoperative complications. This study aimed to determine whether inflammatory biomarkers might facilitate an early detection of prolonged POI (PPOI) or infectious complications. Methods. Forty-seven adult patients who underwent oncological colorectal surgery were included. They filled out a perioperative diary to report their gastrointestinal symptoms. Blood samples were collected preoperatively, and on postoperative day (POD) 1 and 3. Levels of leucocytes, C-reactive protein (CRP), interleukin (IL)-6, TNF-α, and IL-1β were analyzed. Results. Patients with PPOI had significantly longer stay in hospital than patients without (13.6 ± 10.5 versus 7.4 ± 3.2 days, p<0.001); they also had higher levels of IL-6 ratios, leucocytes, and CRP levels, but did not reach significance. Higher levels of postoperative IL-6 and CRP levels (p<0.05, resp.) were found in patients with infectious complications. The receiver operating characteristic (ROC) analysis found better diagnostic values of IL-6 ratio on both POD 1 and 3 than that of CRP (POD 1: ROC 0.825, p<0.001). Conclusion. Blood levels of inflammatory cytokines cannot predict PPOI after colorectal surgery. Instead, postoperative IL-6 changes may predict the infectious complications with a better diagnostic value than the current leukocytes or CRP tests.
Flexural Modelling and Finite Element Analysis of FRC Beams Reinforced with PVA and Basalt Fibres and Their Validation
Authors: Ayub Tehmina , Khan Sadaqat Ullah , Shafiq Nasir
Published: March 2018

A flexural capacity model for fibre‐reinforced concrete (FRC) beams reinforced with PVA and basalt fibres is suggested for the rectangular beam sections. The proposed models are based on the concept of equivalent stress block parameters for both compressive and tensile stresses, similar to Eurocode and ACI code. The parameters are defined by allowing the conversion of the stress‐strain models into equivalent rectangular stress blocks, similar to Eurocode 2. The flexural model is suggested to determine the loading capacity of 21 FRC beams containing up to 3% volume fraction of PVA and basalt fibres without reinforcing bars. In order to investigate the accuracy of the proposed flexure models, finite element analysis (FEA) of the same beams was carried out using the compressive and tensile stress‐strain curves. Furthermore, 21 FRC beams subjected to three‐point bending were tested. The results of the flexural models showed good agreement with the load‐carrying capacity of the tested FRC beams, and the results of FEA of all beams showed a good correlation with the experimental results in terms of the maximum load, load versus midspan deflection patterns, and the maximum tensile strains.
Severe Bilateral Breast Mucinous Carcinoma with Bilateral Lungs and Cutaneous Metastasis: A Case Report and Literature Review
Authors: Pu Rong , Li Yanchu , Li Xianyong
Published: March 2018

The case of a female who had severe, rare, terminal breast mucinous carcinoma (BMC) and failed to receive surgery and chemotherapy was reported. The patient was diagnosed with pure BMC (ER++, PR++, CerbB-2−, and Ki-67 10%) accompanied with bilateral lungs, bilateral chest walls with skin ulcer (D = 14 cm), lymph nodes of bilateral armpits, and right supraclavicular metastases. ECOG (Eastern Cooperative Oncology Group) and NRS (Numeric Rating Scale) pain scores were 4 and 6, respectively. Because the patient refused traditional chemotherapy and radiotherapy on religious grounds, an herbal medicine containing Panax ginseng, Agrimonia pilosa, and white flower Patrinia herb was administered; extensive nursing for tumor debridement was also provided. Quality of Life (QOL) improved and pain reduced. Tumor-bearing survival time was prolonged. The present case dictates that herbal extract medicines and supportive treatment can be helpful for uncommon severe BMC as an appropriate alternative treatment.
Theory and Application of Audio-Based Assessment of Cough
Authors: Shi Yan , Liu He , Wang Yixuan , Cai Maolin , Xu Weiqing
Published: March 2018

Cough is a common symptom of many respiratory diseases. Many medical literatures underline that a system for the automatic, objective, and reliable detection of cough events is important and very promising to detect pathology severity in chronic cough disease. In order to track the development status of an audio-based cough monitoring system, we briefly described the history of objective cough detection and then illustrated the cough sound generating principle. The probable endpoints of cough clinical studies, including cough frequency, intensity of coughing, and acoustic properties of cough sound, were analyzed in this paper. Finally, we introduce some successful cough monitoring equipment and their recognition algorithm in detail. It can be obtained that, firstly, acoustic variability of cough sounds within and between individuals makes it difficult to assess the intensity of coughing. Furthermore, now great progress in audio-based cough detection is being made. Moreover, accurate portable objective monitoring systems will be available and widely used in home care and clinical trials in the near future.
Abciximab (ReoPro) Dosing Strategy for the Management of Acute Intraprocedural Thromboembolic Complications during Pipeline Flow Diversion Treatment of Intracranial Aneurysms
Authors: Lin Li-Mei , Jiang Bowen , Campos Jessica K. , Beaty Narlin B. , Bender Matthew T. , Tamargo Rafael J. , Huang Judy , Colby Geoffrey P. , Coon Alexander L.
Published: March 2018

Background: Flow diversion with the Pipeline embolization device (PED) is an effective neuro­endovascular method and increasingly accepted for the treatment of cerebral aneurysms. Acute in situ thrombosis is a known complication of PED procedures. There is limited experience in the flow diversion literature on the use of abciximab (ReoPro) for the management of acute thrombus formation in PED cases. Methods: Data were collected retrospectively on patients who received intra-arterial (IA) ReoPro with or without subsequent intravenous (IV) infusion during PED flow diversion treatment of intracranial aneurysms. Results: A total of 30 cases in patients with a mean age of 56.7 years (range 36–84) and a mean aneurysm size of 8.6 mm (range 2–25) were identified to have intraprocedural thromboembolic complications during PED treatment. IA ReoPro was administered in all cases, with 20 cases receiving increments of 5-mg boluses and 10 cases receiving a 0.125 mg/kg IA bolus (half cardiac dosing). Complete or partial recanalization was achieved in 100% of the cases. IV ReoPro infusion at 0.125 μg/kg/min for 12 h was administered postprocedurally in 22 cases with a residual thrombus. Postprocedurally, 18 patients were transitioned from clopidogrel (Plavix) to prasugrel (Effient). The majority of the cases (23/30; 77%) were discharged home. Periprocedural intracranial hemorrhage was noted in 2 cases (7%) and radiographic infarct was noted in 4 cases (13%), with an overall mortality of 0% at the time of initial discharge. Clinical follow-up was available for 28/30 patients. The average duration of follow-up was 11.7 months, at which time 23/28 (82%) of the patients had a modified Rankin Scale score of 0. Conclusions: IA ReoPro administration is an effective and safe rescue strategy for the management of acute intraprocedural thromboembolic complications during PED treatment. Using a dosing strategy of either 5-mg increments or a 0.125 mg/kg IA bolus (half cardiac dosing) can provide high rates of recanalization with low rates of hemorrhagic complications and long-term morbidity.
Genetic Variability and Sequence Relatedness of Matrix Protein in Viruses of the Families Paramyxoviridae and Pneumoviridae
Authors: Slovic Anamarija , Kosutic-Gulija Tanja , Santak Maja , Ivancic-Jelecki Jelena , Jagusic Maja , Ljubin-Sternak Sunčanica , Mlinarić-Galinović Gordana , Vilibić-Čavlek Tatjana , Tabain Irena , Forcic Dubravko
Published: March 2018

Background: The families Paramyxoviridae and Pneumoviridae comprise a broad spectrum of viral pathogens that affect human health. The matrix (M) protein of these viruses has a central role in their life cycle. In line with this, molecular characteristics of the M proteins from variable viruses that circulated in Croatia were investigated. Methods: Sequences of the M proteins of human parainfluenza virus (HPIV) 1–3 within the family Paramyxoviridae, human metapneumovirus (HMPV), and human respiratory syncytial virus from the family Pneumoviridae were obtained and analyzed. Results: M proteins were very diverse among HPIVs, but highly conserved within each virus. More variability was seen in nucleotide sequences of M proteins from the Pneumoviridae family. An insertion of 8 nucleotides in the 3′ untranslated region in 1 HMPV M gene sequence was discovered (HR347-12). As there are no samples with such an insertion in the database, this insertion is of interest and requires further research. Conclusion: While we have confirmed that M proteins were conserved among individual viruses, any changes that are observed should be given attention and further researched. Of special interest is inclusion of HPIV2 M proteins in this analysis, as these proteins have not been studied to the same extent as other paramyxoviruses.
Distant Thromboembolic Disease Diagnosed by Endoscopic Ultrasound in Pancreatic Cancer: A Case Series
Authors: Atalaia-Martins Catarina , Pinto-Marques Pedro , Mocanu Irina , Cortêz-Pinto João , Serra David
Published: March 2018

Thrombosis and cancer have a very well-known association. Pancreatic cancer has the highest risk for thrombotic events amongst gastrointestinal cancers and is a leading direct cause of death in cancer patients. We assessed the role of endoscopic ultrasound (EUS) in identifying distant thrombotic events in pancreatic cancer patients. We performed a retrospective review of all EUS cases for pancreatic cancer in two centers and assessed all remotely located thrombotic events diagnosed. In a period of 6 months, a total of 55 EUS for pancreatic neoplasm were performed and the following thrombotic events were identified in 4 patients (7.3%): pulmonary thromboembolism (75%) and vena cava thrombosis (25%). The authors present these 4 cases of thrombotic disease identified by EUS, 50% of them previously missed by noninvasive imaging. EUS evaluation is not seldom limited to the targeted lesion prior identified in other imaging studies. Vascular thrombus can be an incidental finding on EUS. If untreated, pulmonary embolism has a high overall mortality. This series underlines the importance of a systematic, station approach EUS technique, namely in the mediastinum, regardless of the clinical indication.
Acceptance of Adjuvant and Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer in Germany: A Survey of Current Practice
Authors: Dogan Serkan , Hennig Martin , Frank Tanja , Struck Julian P. , Cebulla Angelika , Salem Johannes , Borgmann Hendrik , Klatte Tobias , Merseburger Axel S. , Kramer Mario , Hofbauer Sebastian L.
Published: March 2018

Background: Guidelines support the use of neoadjuvant (NAC) and adjuvant (AC) chemotherapy in muscle-invasive bladder cancer. However, data from North America reported the underutilization of NAC in favor of AC despite the lower level of scientific evidence supporting AC. We aimed to assess current practice patterns of NAC and AC in ­Germany. Methods: A 15-question online survey was developed and sent via email newsletters to members of the ­German Association of Urology and of the German Society of Residents in Urology in October 2016 to analyze current practice patterns. Results: The survey yielded 141 individual responses from 61 different German urology departments. Eighty-nine (69.0%) and 119 (93.0%) participants were stated to regularly use NAC and AC respectively. The number of participants who were stated to use NAC and AC regularly was not associated with the type of institution (academic vs. nonacademic), number of hospital beds, and number of cystectomies performed annually. Gemcitabine/cisplatin combination chemotherapy was named as the primarily used NAC regimen by 80 (95%) respondents. The median number of administered cycles was 3 for NAC and 4 for AC. In the case of cisplatin ineligibility, combination chemotherapy with gemcitabine/carboplatin was the most common regimen. Respondents stated that chemotherapy was generally administered by urologists (81% for NAC and 85% for AC). Conclusions: Our survey of current practice shows a high acceptance rate of NAC in Germany, which was independent of the type of institution. Although the scientific level of evidence for AC is lower, it still seems to be more widely accepted than NAC. NAC and AC were generally administered by urologists.
Enteral Feeding as an Adjunct to Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy
Authors: Chang Lilly L. , Wynn James L. , Pacella Marisa J. , Rossignol Candace C. , Banadera Felix , Alviedo Neil , Vargas Alfonso , Bennett Jeffrey , Huene Melissa , Copenhaver Nicole , Sura Livia , Barnette Kimberly , Solomon Jayne , Bliznyuk Nikolay A. , Neu Josef , Weiss Michael D.
Published: March 2018

Background: Withholding enteral feedings during hypothermia lacks supporting evidence. Objectives: We aimed to determine if minimal enteral nutrition (MEN) during hypothermia in patients with hypoxic-ischemic encephalopathy was associated with a reduced duration of parenteral nutrition, time to full oral feeds, and length of stay, but would not be associated with increased systemic inflammation or feeding complications. Methods: We performed a pilot, retrospective, matched case-control study within the Florida Neonatal Neurologic Network from December 2012 to May 2016 of patients who received MEN during hypothermia (n = 17) versus those who were not fed (n = 17). Length of stay, feeding-related outcomes, and brain injury identified by MRI were compared. Serum inflammatory mediators were measured at 0–6, 24, and 96 h of life by multiplex assay. MRI were scored using the Barkovich system. Results: MEN subjects had a reduced length of hospital stay (mean 15 ± 11 vs. 24 ± 19 days, p < 0.05), days receiving parenteral nutrition (7 ± 2 vs. 11 ± 6, p < 0.05), and time to full oral feeds (8 ± 5 vs. 18 ± 18, p < 0.05). MEN was associated with a significantly reduced serum IL-12p70 at 24 and 96 h (p < 0.05). Brain MRI scores were not significantly different between groups. Conclusion: MEN during hypothermia was associated with a reduced length of stay and time to full feeds, but did not increase feeding complications or systemic inflammation.
Polymorphisms of IKZF3 Gene and Autoimmune Thyroid Diseases: Associated with Graves’ Disease but Not with Hashimoto’s Thyroiditis
Authors: Li Ling , Ding Xiaolian , Wang Xuan , Yao Qiuming , Shao Xiaoqing , An Xiaofei , Yan Ni , Jiang Yanfei , Wang Wen , Shi Liangfeng , Qin Qiu , Song Ronghua , Zhang Jin-an , Sun Peilong
Published: March 2018

Background/Aims: The IKZF3 gene encodes a zinc-finger protein that plays an important role in the proliferation and differentiation of B lymphocytes. Autoimmune thyroid diseases (AITDs), mainly include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are probably caused by the aberrant proliferation of B cells. The objective of this study was to explore the association between IKZF3 polymorphisms and AITDs. Methods: We examined 915 AITD patients (604 GD and 311 HT) and 814 healthy controls. IKZF3 variants (rs2941522, rs907091, rs1453559, rs12150079 and rs2872507) were tested by PCR-ligase detection reaction. Results: It was manifested that that the minor alleles of the five loci increased susceptibility to GD (p<0.05 for rs2941522, and p<0.01 for rs907091, rs1453559, rs12150079 and rs2872507) but in HT patients, these loci showed no significant difference compared with controls. Similarly, the genotype distributions of GD patients manifested obvious differences in all these loci compared with the control group, whereas no statistical differences were observed between HT patients and controls. Furthermore, bioinformatics tools were used to analyze rs1453559, rs12150079 and rs907091. These variants were believed to be the transcription regulator. Conclusion: It is the first time we reported the association between the IKZF3 polymorphisms and GD, indicating that IKZF3 gene tends to bean important risk factor for the development of GD.
ETS-1 Induces Endothelial-Like Differentiation and Promotes Metastasis in Non-Small Cell Lung Cancer
Authors: Zhou Xiaoshu , Zhou Rui , Zhou Hongxia , Li Qianwen , Hong Jiaxin , Meng Rui , Zhu Fang , Zhang Sheng , Dai Xiaofang , Peng Gang , Wu Gang , Li Zhenyu
Published: March 2018

Background/Aims: Recently, endothelial-like cells originating directly from tumor cells have been revealed. However, the mechanism remains unclear. ETS-1 (E26 transformation specific-1), a key transcription factor in the generation and maturation of ECs (endothelial cells), has been reported to be overexpressed in several cancers. Here, we reveal novel regulation of the endothelial-like differentiation of NSCLC (non-small cell lung cancer) cells by ETS-1. Methods: We up-regulated the expression of ETS-1 in NSCLC cell lines by H2O2 or lentiviral vector. Endothelial phenotypes, such as vWF (von Willebrand factor) and VE-cadherin were examined by Western blot analysis and immunofluorescence assay. Tube formation assay and phagocytotic activity assay were performed to evaluate ECs’ specific features on NSCLC cells. The effect of ETS-1 on metastasis was determined by wound healing assays, transwell assays and a xenograft tumor model. To explore the role of ETS-1 in the initiation and progression of NSCLC, we examined ETS-1 levels in NSCLC cancerous tissues and paired adjacent normal tissues by immunohistochemstry and analyzed the relationship between ETS-1 levels and clinicopathological parameters, as well as patient survival. Kaplan Meier plotter database was used to assess the prognostic value of ETS-1 in NSCLC. The association between ETS-1 levels and MVD (microvessel density) was analyzed to determine their role in angiogenesis. Results: With ETS-1 up-regulation, the expression of vWF and VE-cadherin was increased in NSCLC cells. Additionally, cells adopted several ECs’ specific features, including enhanced tube formation ability and uptake of Dil-ac-LDL (acetylated low-density lipoprotein) and lectin. ETS-1 up-regulation also promoted cell migration, invasion and adhesion. In addition, xenograft mice arising from ETS-1 over-expressing cells had more liver metastases. In the clinical specimens, ETS-1 expression was significantly higher in NSCLC cancerous tissues than adjacent nontumorous tissues and positively associated with tumor size, T stage, N stage and clinical stage. Patients with high levels of ETS-1 expression had significantly poorer OS (overall survival) and FP (first progression) than those with low expression. Furthermore, there was a positive correlation between ETS-1 level and MVD. Conclusion: Collectively, our data reveal that ETS-1 can induce the differentiation of tumor cells into endothelial-like cells and further promote metastatic dissemination in NSCLC.
A STAT6 Inhibitor AS1517499 Reduces Preventive Effects of Apoptotic Cell Instillation on Bleomycin-Induced Lung Fibrosis by Suppressing PPARγ
Authors: Kim Myeong-Joo , Lee Ye-Ji , Yoon Young-So , Lim Jae H. , Park Eun-Mi , Chong Young H. , Kang Jihee Lee
Published: March 2018

Background/Aims: The signal transducer and activator of transcription 6 (STAT6) transcription factor mediates PPARγ-regulated gene expression in macrophages. However, it remains largely unknown how proximal membrane signaling events initiated by apoptotic cell recognition upregulate PPARγ expression and activate the lung homeostatic program. Methods: The STAT6 inhibitor AS1517499 was used to determine the role of STAT6 in mediating PPARγ activity, anti-inflammatory effects, and anti-fibrotic effects induced by apoptotic cell instillation after bleomycin treatment into C57BL/6 mice. Bronchoalveolar lavage fluid, alveolar macrophages and lungs were harvested at days 2, 7, and 14 and then analyzed by real-time PCR, immunoblotting, ELISA, immunocytochemistry and immunohistochemistry assays. Results: Our data demonstrate that apoptotic cell instillation after bleomycin results in prolonged enhancement of STAT6 phosphorylation in alveolar macrophages and lung. Co-administration of the STAT6 inhibitor, AS1517499, reversed the enhanced PPARγ expression and activity induced by apoptotic cell instillation after bleomycin treatment. By reducing the expression of PPARγ target genes, including CD36, macrophage mannose receptor, and arginase 1, AS1517499 inhibited efferocytosis and restored pro-inflammatory cytokine expression, neutrophil recruitment, protein levels, hydroxyproline content, and expression of fibrosis markers, including type 1 collagen α2, fibronectin, and α-smooth muscle actin. STAT6 inhibition reversed the expression profile of hepatocyte growth factor and interleukin-10. Conclusion: These results indicate that prolonged STAT6 activation following one-time apoptotic cell instillation facilitates continuous PPARγ activation, resulting in the resolution of bleomycin-induced lung inflammation and fibrosis.
Endothelial Progenitor Cell Secretome and Oligovascular Repair in a Mouse Model of Prolonged Cerebral Hypoperfusion
Authors: Maki Takakuni , Morancho Anna , Martinez-San Segundo Pablo , Hayakawa Kazuhide , Takase Hajime , Liang Anna C. , Gabriel-Salazar Marina , Medina-Gutiérrez Esperanza , Washida Kazuo , Montaner Joan , Lok Josephine , Lo Eng H. , Arai Ken , Rosell Anna
Published: March 2018

Background and Purpose—

Endothelial progenitor cells (EPCs) have been extensively investigated as a therapeutic approach for repairing the vascular system in cerebrovascular diseases. Beyond vascular regeneration per se, EPCs may also release factors that affect the entire neurovascular unit. Here, we aim to study the effects of the EPC secretome on oligovascular remodeling in a mouse model of white matter injury after prolonged cerebral hypoperfusion.

Methods—

The secretome of mouse EPCs was analyzed with a proteome array. In vitro, the effects of the EPC secretome and its factor angiogenin were assessed on primary oligodendrocyte precursor cells and mature human cerebral microvascular endothelial cells (hCMED/D3). In vivo, mice were subjected to permanent bilateral common carotid artery stenosis, then treated with EPC secretome at 24 hours and at 1 week, and cognitive outcome was evaluated with the Y maze test together with oligodendrocyte precursor cell proliferation/differentiation and vascular density in white matter at 4 weeks.

Results—

Multiple growth factors, cytokines, and proteases were identified in the EPC secretome, including angiogenin. In vitro, the EPC secretome significantly enhanced endothelial and oligodendrocyte precursor cell proliferation and potentiated oligodendrocyte precursor cell maturation. Angiogenin was proved to be a key factor since pharmacological blockade of angiogenin signaling negated the positive effects of the EPC secretome. In vivo, treatment with the EPC secretome increased vascular density, myelin, and mature oligodendrocytes in white matter and rescued cognitive function in the mouse hypoperfusion model.

Conclusions—

Factors secreted by EPCs may ameliorate white matter damage in the brain by boosting oligovascular remodeling.
Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats
Authors: Cao Shenglong , Hua Ya , Keep Richard F. , Chaudhary Neeraj , Xi Guohua
Published: March 2018

Background and Purpose—

Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined.

Methods—

Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points.

Results—

ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits (
P
<0.05).

Conclusions—

Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats.
The EU Influence on Norwegian Domestic Legislation for the Protection of the Arctic Marine Environment
Authors: Johansen Elise
Published: March 2018

In the last several decades, the European Union (EU) has demonstrated its intention to play an important role in supporting Arctic cooperation and helping to meet the challenges now facing the region. Norway, one of the five Arctic coastal states, and the EU have cooperated closely in this regard, particularly through the Agreement on the European Economic Area (EEA Agreement). This article examines how Norway’s domestic legislation applicable to its Arctic marine areas has been influenced by the development of EU environmental legislation. Specifically, this paper provides a discussion and analysis of the relevant Norwegian laws and mechanisms used to regulate how EU environmental legislation has been incorporated into Norway’s domestic legislation through the EEA Agreement.
Abuse of Constitutional Identity. The Hungarian Constitutional Court on Interpretation of Article E) (2) of the Fundamental Law
Authors: Halmai Gábor
Published: March 2018

This paper discusses a decision of the Hungarian Constitutional Court issued in December 2016, in which the judges refer to the country’s constitutional identity to justify the government’s refusal to apply the eu’s refugee relocation scheme in Hungary. The paper concludes that this abuse of constitutional identity for merely nationalistic political purposes discredits every genuine and legitimate reference to national constitutional identity claims, and strengthens calls for an end to constitutional pluralism in the eu altogether.
The Protection of Invaluable Natural Resources: Illustrating the Example of the Bialowieza Forest
Authors: Perkowski Maciej , Zoń Wojciech
Published: March 2018

Invaluable natural resources require special legal protection. Their protection often does not fully correspond with their unique character. The protection of invaluable natural resources should be modelled in such a way as to provide full protection of their uniqueness, regardless of unstable political and legal circumstances. The authors argue for the implementation of such a solution in the example of the Bialowieza Forest. Under Polish and Belarusian laws, international law and partially also European Union law, the Forest is entangled in a complex socio-economic turnover, which often proves controversial or even problematical. The Bialowieza Forest is a complete natural system, so it ought to be protected as a whole. A well-planned international regulation of a localised nature (with Poland and Belarus as well as countries and international organisations willing to assume co-responsibility for its good as its parties), supported by appropriate social education, are strongly recommended.