bluuebunny/crossref_metadata_2025 huggingface dataset:
INNOVATION MANAGEMENT CHALLENGES: FROM FADS TO FUNDAMENTALS
Authors: TIDD JOE , BESSANT JOHN
Published: April 2018

Innovation management is inherently inter-disciplinary, but it is much more than simply applying business and management disciplines to innovation, and over time the field has developed a distinct body of knowledge. However, in this paper, we argue that the field of innovation management has failed to fully benefit from the proliferation of relevant research because much of this work has not been sufficiently coherent and cumulative. One reason for this, we propose, is the propensity to follow and fit research and publications into contemporary fads rather than to ground work in more fundamental themes and challenges. We present two examples of such fads, open innovation and business model innovation, to illustrate the trend. Finally, we suggest some more fundamental integrating themes and management challenges, drawing upon the latest edition of Managing Innovation (Tidd, J and J Bessant (2018). Managing Innovation: Integrating Technological, Market and Organizational Change, Sixth Edition. New York: Wiley).1
The structure of ℤ2ℤ2s-additive cyclic codes
Authors: Aydogdu Ismail , Abualrub Taher
Published: April 2018

[Formula: see text]-additive codes for any integer [Formula: see text] are considered as codes over mixed alphabets. They are a generalization of binary linear codes and linear codes over [Formula: see text] In this paper, we are interested in studying [Formula: see text]-additive cyclic codes. We will give the generator polynomials of these codes. We will also give the minimal spanning sets for these codes. We will define separable [Formula: see text]-additive codes and provide conditions on the generator polynomials for a [Formula: see text]-additive cyclic code to be separable. Finally, we present some examples of optimal parameter binary codes obtained as images of [Formula: see text]-additive cyclic codes.
A Hierarchical Distributed Runtime Resource Management Scheme for NoC-Based Many-Cores
Authors: Tsoutsouras Vasileios , Anagnostopoulos Iraklis , Masouros Dimosthenis , Soudris Dimitrios
Published: April 2018

As technology constantly strengthens its presence in all aspects of human life, computing systems integrate a high number of processing cores, whereas applications become more complex and greedy for computational resources. Inevitably, this high increase in processing elements combined with the unpredictable resource requirements of executed applications at design time impose new design constraints to resource management of many-core systems, turning the distributed functionality into a necessity. In this work, we present a distributed runtime resource management framework for many-core systems utilizing a network-on-chip (NoC) infrastructure. Specifically, we couple the concept of distributed management with parallel applications by assigning different roles to the available computing resources. The presented design is based on the idea of local controllers and managers, whereas an on-chip intercommunication scheme ensures decision distribution. The evaluation of the proposed framework was performed on an Intel Single-Chip Cloud Computer, an actual NoC-based, many-core system. Experimental results show that the proposed scheme manages to allocate resources efficiently at runtime, leading to gains of up to 30% in application execution latency compared to relevant state-of-the-art distributed resource management frameworks.
Consensus Guided Multi-View Clustering
Authors: Liu Hongfu , Fu Yun
Published: April 2018

In recent decades, tremendous emerging techniques thrive the artificial intelligence field due to the increasing collected data captured from multiple sensors. These multi-view data provide more rich information than traditional single-view data. Fusing heterogeneous information for certain tasks is a core part of multi-view learning, especially for multi-view clustering. Although numerous multi-view clustering algorithms have been proposed, most scholars focus on finding the common space of different views, but unfortunately ignore the benefits from partition level by ensemble clustering. For ensemble clustering, however, there is no interaction between individual partitions from each view and the final consensus one. To fill the gap, we propose a Consensus Guided Multi-View Clustering (CMVC) framework, which incorporates the generation of basic partitions from each view and fusion of consensus clustering in an interactive way, i.e., the consensus clustering guides the generation of basic partitions, and high quality basic partitions positively contribute to the consensus clustering as well. We design a non-trivial optimization solution to formulate CMVC into two iterative
k
-means clusterings by an approximate calculation. In addition, the generalization of CMVC provides a rich feasibility for different scenarios, and the extension of CMVC with incomplete multi-view clustering further validates the effectiveness for real-world applications. Extensive experiments demonstrate the advantages of CMVC over other widely used multi-view clustering methods in terms of cluster validity, and the robustness of CMVC to some important parameters and incomplete multi-view data.
Co-design in health
Authors: Piper Anne Marie , Lazar Amanda
Published: April 2018

This forum is dedicated to personal health in all its many facets: decision making, goal setting, celebration, discovery, reflection, and coordination, among others. We look at innovations in interactive technologies and how they help address current critical healthcare challenges.
---Yunan Chen, Editor
Chronic Consumption of Sweeteners and Its Effect on Glycaemia, Cytokines, Hormones, and Lymphocytes of GALT in CD1 Mice
Authors: Rosales-Gómez Cristian Angel , Martínez-Carrillo Beatriz Elina , Reséndiz-Albor Aldo Arturo , Ramírez-Durán Ninfa , Valdés-Ramos Roxana , Mondragón-Velásquez Talia , Escoto-Herrera Jorge Alberto
Published: April 2018

Background. The consumption of sweeteners has increased in recent years, being used to control body weight and blood glucose. However, they can cause increased appetite, modification of immune function, and secretion of hormones in the GALT.Objective. To assess the effect of chronic sweetener consumption on glycaemia, cytokines, hormones, and GALT lymphocytes in CD1 mice.Material and Methods. 72 CD1 mice divided into 3 groups were used: (a) baseline, (b) middle, and (c) final. Groups (b) and (c) were divided into 4 subgroups: (i) Control, (ii) Sucrose, (iii) Sucralose, and (iv) Stevia. The following were determined: body weight, hormones (GIP, insulin, and leptin), lymphocytes CD3+T cells and CD19+B cells, IgA+plasma cells, and cytokines (IL-4, IL-5, IFN-γ, and TNF-α).Results. Sucralose reduces secretion of GIP and glycaemia but does not modify insulin concentration, increases body weight, and reduces food intake. Stevia increases the secretion of GIP, insulin, leptin, body weight, and glycaemia but keeps food consumption normal. Sucralose and Stevia showed a higher percentage of CD3+T cells, CD19+B cells, and IgA+plasma cells in Peyer’s patches, but only Stevia in lamina propria.Conclusion. Sweeteners modulate the hormonal response of cytokines and the proliferation of lymphocytes in the intestinal mucosa.
Existence Results for Fractional Differential Equations with Multistrip Riemann–Stieltjes Integral Boundary Conditions
Authors: Lv Tongling , Pang Huihui , Cao Limei
Published: April 2018

This paper is concerned with the existence and multiplicity of the positive solutions for a fractional boundary value problem with multistrip Riemann–Stieltjes integral boundary conditions. Our results are based on the Leggett–Williams fixed point theorem. In the end, two examples are worked out to illustrate our main work.
Two‐Degree Vibration Analysis of a Horizontal Axis Turbine Blade by Finite Differential Methods
Authors: Zhu Youfeng , Zang Hongyu , Kong Xiaofei , Ban Peng
Published: April 2018

Two‐degree vibration partial differential equations of large horizontal axis turbine blades were established by Kallesøe’s model and Greenberg unsteady aerodynamic theory. By means of the finite difference discretization and cantilever beam boundary condition, the equations of blades can be simplified as a general vibration system. Then a linear stationary state space on the system was built. The blade tip vibration in autonomous and nonautonomous system can be simulated by MATLAB vibration toolboxes in time domain. The convergent, flutter, and divergent vibration curves were plotted in the directions of lead‐lag and flapping.
Convective Drying of Osmo-Treated Abalone (Haliotis rufescens) Slices: Diffusion, Modeling, and Quality Features
Authors: Lemus-Mondaca Roberto , Pizarro-Oteíza Sebastian , Perez-Won Mario , Tabilo-Munizaga Gipsy
Published: April 2018

The focus of this research was based on the application of an osmotic pretreatment (15% NaCl) for drying abalone slices, and it evaluates the influence of hot-air drying temperature (40–80°C) on the product quality. In addition, the mass transfer kinetics of salt and water was also studied. The optimal time of the osmotic treatment was established until reaching a pseudo equilibrium state of the water and salt content (290 min). The water effective diffusivity values during drying ranged from 3.76 to 4.75 × 10−9 m2/s for three selected temperatures (40, 60, and 80°C). In addition, experimental data were fitted by Weibull distribution model. The modified Weibull model provided good fitting of experimental data according to applied statistical tests. Regarding the evaluated quality parameters, the color of the surface showed a change more significant at high temperature (80°C), whereas the nonenzymatic browning and texture showed a decrease during drying process mainly due to changes in protein matrix and rehydration rates, respectively. In particular, working at 60°C resulted in dried samples with the highest quality parameters.
Impact of Participatory Health Research: A Test of the Community-Based Participatory Research Conceptual Model
Authors: Oetzel John G. , Wallerstein Nina , Duran Bonnie , Sanchez-Youngman Shannon , Nguyen Tung , Woo Kent , Wang Jun , Schulz Amy , Keawe‘aimoku Kaholokula Joseph , Israel Barbara , Alegria Margarita
Published: April 2018

Objectives. A key challenge in evaluating the impact of community-based participatory research (CBPR) is identifying what mechanisms and pathways are critical for health equity outcomes. Our purpose is to provide an empirical test of the CBPR conceptual model to address this challenge. Methods. A three-stage quantitative survey was completed: (1) 294 US CBPR projects with US federal funding were identified; (2) 200 principal investigators completed a questionnaire about project-level details; and (3) 450 community or academic partners and principal investigators completed a questionnaire about perceived contextual, process, and outcome variables. Seven in-depth qualitative case studies were conducted to explore elements of the model not captured in the survey; one is presented due to space limitations. Results. We demonstrated support for multiple mechanisms illustrated by the conceptual model using a latent structural equation model. Significant pathways were identified, showing the positive association of context with partnership structures and dynamics. Partnership structures and dynamics showed similar associations with partnership synergy and community involvement in research; both of these had positive associations with intermediate community changes and distal health outcomes. The case study complemented and extended understandings of the mechanisms of how partnerships can improve community conditions. Conclusions. The CBPR conceptual model is well suited to explain key relational and structural pathways for impact on health equity outcomes.
Numerical Prediction of Chloride Penetration in Concrete Exposed to a Marine Environment at Tide
Authors: Hong Sung In , Ann Ki Yong
Published: April 2018

Reinforced concrete structures under cyclic exposure to the corrosive environment such as the tidal zone as a part of marine structure entail the higher risk of steel corrosion. In this paper, chloride penetration in concrete exposed to the tidal zone was predicted using a combined moisture and chloride transport model. For the analysis of moisture transport, pore size distribution in concrete was determined from the experimental observation and used to determine the moisture permeability and degree of saturation. Then, the chloride profile through nonsaturated concrete cover was calculated by applying the moisture distribution along the penetration depth to the chloride convection and diffusion model. To assess sensitivity of the service life to the environment and concrete mix conditions, this study used three types of tide levels and water to cement ratios in the simulation. Under 10 years of tidal exposure condition, the minimum required cover depth at which the threshold chloride concentration reaches on the steel embedment increases only about 1.13 times as the tide level increases from the minimum to the highest while that for the w/c ratio increases about 1.69 times.
An Improved Rollover Index Based on BP Neural Network for Hydropneumatic Suspension Vehicles
Authors: Dong Xiaotong , Jiang Yi , Zhong Zhou , Zeng Wei , Liu Wei
Published: April 2018

The 3-DOF rollover model has been established by the Lagrangian second-class equation, taking the road inclination angle, the steering strategy, and the hydropneumatic suspension characteristics into consideration. A 3-layer BP (backpropagation) neural network is applied to predict the road inclination angle and to optimize the rollover model in real-time. The number of the hidden layer neurons for the BP network is also discussed. The numerical calculation of the optimized rollover model is in good agreement with the full-scale vehicle test. Different rollover indexes are compared, and the results indicate that the rollover index of dynamic LTR optimized by the BP neural network can evaluate the rollover tendency more accurately in the ramp steering test and the snake steering test. This study provides practical meanings for developing a rollover warning system.
ADC Benchmark Range for Correct Diagnosis of Primary and Recurrent Middle Ear Cholesteatoma
Authors: Russo Camilla , Elefante Andrea , Di Lullo Antonella M. , Carotenuto Barbara , D’Amico Alessandra , Cavaliere Michele , Iengo Maurizio , Brunetti Arturo
Published: April 2018

Objectives. Magnetic resonance imaging (MRI) and in particular diffusion-weighted imaging (DWI) have been broadly proven to be the reference imaging method to discriminate between cholesteatoma and noncholesteatomatous middle ear lesions, especially when high tissue specificity is required. The aim of this study is to define a range of apparent diffusion coefficient (ADC) values within which the diagnosis of cholesteatoma is almost certain. Methods. The study was retrospectively conducted on a cohort of 124 patients. All patients underwent first- or second-look surgery because primary or secondary acquired cholesteatoma was clinically suspected; they all had preoperative MRI examination 15 days before surgery, including DWI from which the ADC maps were calculated. Results. Average ADC value for cholesteatomas was 859,4 × 10−6 mm2/s (range 1545 × 10−6 mm2/s; IQR = 362 × 10−6 mm2/s; σ = 276,3 × 10−6 mm2/s), while for noncholesteatomatous inflammatory lesions, it was 2216,3 × 10−6 mm2/s (range 1015 × 10−6 mm2/s; IQR = 372,75 × 10−6 mm2/s; σ = 225,6 × 10−6 mm2/s). Interobserver agreement with Fleiss’ Kappa statistics was 0,96. No overlap between two groups’ range of values was found and the difference was statistically significant for p<0.0001. Conclusions. We propose an interval of ADC values that should represent an appropriate benchmark range for a correct differentiation between cholesteatoma and granulation tissue or fibrosis of noncholesteatomatous inflammatory lesions.
Applied Artificial Bee Colony Optimization Algorithm in Fire Evacuation Routing System
Authors: Wang Chen , Wood Lincoln C. , Li Heng , Aw Zhenye , Keshavarzsaleh Abolfazl
Published: April 2018

Every minute counts in an event of fire evacuation where evacuees need to make immediate routing decisions in a condition of low visibility, low environmental familiarity, and high anxiety. However, the existing fire evacuation routing models using various algorithm such as ant colony optimization or particle swarm optimization can neither properly interpret the delay caused by congestion during evacuation nor determine the best layout of emergency exit guidance signs; thus bee colony optimization is expected to solve the problem. This study aims to develop a fire evacuation routing model “Bee-Fire” using artificial bee colony optimization (BCO) and to test the routing model through a simulation run. Bee-Fire is able to find the optimal fire evacuation routing solutions; thus not only the clearance time but also the total evacuation time can be reduced. Simulation shows that Bee-Fire could save 10.12% clearance time and 15.41% total evacuation time; thus the congestion during the evacuation process could be effectively avoided and thus the evacuation becomes more systematic and efficient.
Eventually Periodic Solutions of a Max-Type System of Difference Equations of Higher Order
Authors: Su Guangwang , Sun Taixiang , Qin Bin
Published: April 2018

We study in this paper the following max-type system of difference equations of higher order: xn=max{A,yn-k/xn-1} and yn=max{B,xn-k/yn-1}, n∈{0,1,2,…}, where A≥B>0, k≥1, and the initial conditions x-k,y-k,x-k+1,y-k+1,…,x-1,y-1∈(0,+∞). We show that (1) if AB>1, then every solution of the above system is periodic with period 2 eventually. (2) If AB=1>B, then every solution of the above system is periodic with period 2k or 2 eventually. (3) If A=B=1 or AB<1, then the above system has a solution which is not periodic eventually.
High USP6NL Levels in Breast Cancer Sustain Chronic AKT Phosphorylation and GLUT1 Stability Fueling Aerobic Glycolysis
Authors: Avanzato Daniele , Pupo Emanuela , Ducano Nadia , Isella Claudio , Bertalot Giovanni , Luise Chiara , Pece Salvatore , Bruna Alejandra , Rueda Oscar M. , Caldas Carlos , Di Fiore Pier Paolo , Sapino Anna , Lanzetti Letizia
Published: April 2018

USP6NL, also named RN-tre, is a GTPase-activating protein involved in control of endocytosis and signal transduction. Here we report that USP6NL is overexpressed in breast cancer, mainly of the basal-like/integrative cluster 10 subtype. Increased USP6NL levels were accompanied by gene amplification and were associated with worse prognosis in the METABRIC dataset, retaining prognostic value in multivariable analysis. High levels of USP6NL in breast cancer cells delayed endocytosis and degradation of the EGFR, causing chronic AKT (protein kinase B) activation. In turn, AKT stabilized the glucose transporter GLUT1 at the plasma membrane, increasing aerobic glycolysis. In agreement, elevated USP6NL sensitized breast cancer cells to glucose deprivation, indicating that their glycolytic capacity relies on this protein. Depletion of USP6NL accelerated EGFR/AKT downregulation and GLUT1 degradation, impairing cell proliferation exclusively in breast cancer cells that harbored increased levels of USP6NL. Overall, these findings argue that USP6NL overexpression generates a metabolic rewiring that is essential to foster the glycolytic demand of breast cancer cells and promote their proliferation.

Significance: USP6NL overexpression leads to glycolysis addiction of breast cancer cells and presents a point of metabolic vulnerability for therapeutic targeting in a subset of aggressive basal-like breast tumors.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3432/F1.large.jpg. Cancer Res; 78(13); 3432–44. ©2018 AACR.
Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2
Authors: Cazzamalli Samuele , Ziffels Barbara , Widmayer Fontaine , Murer Patrizia , Pellegrini Giovanni , Pretto Francesca , Wulhfard Sarah , Neri Dario
Published: April 2018

Purpose: Antibody–drug conjugates and small-molecule-drug conjugates have been proposed as alternatives to conventional anticancer cytotoxic agents, with the potential to deliver bioactive payloads to the site of disease, helping spare normal tissues.

Experimental Design: Here, we describe a novel small-molecule-drug conjugate, based on a high-affinity ligand specific to carbonic anhydrase IX. The product featured a peptidic linker, suitable for cleavage in the tumor extracellular environment, and monomethyl auristatin E as cytotoxic payload.

Results: A potent anticancer activity was observed in nude mice bearing SKRC-52 renal cell carcinoma xenografts, but no durable complete responses could be observed in this model. However, when the product was administered together with L19-IL2 (a clinical-stage fusion protein capable of delivering IL2 to the tumor neovasculature), all treated mice in the combination group could be rendered tumor free, in a process that favored the influx of natural killer cells into the tumor mass. The combination of L19-IL2 and the new small-molecule-drug conjugate also eradicated cancer in 100% of immunocompetent mice, bearing subcutaneously grafted CT26 colorectal cancer cells, which stably expressed carbonic anhydrase IX.

Conclusions: These findings may be of clinical significance, because carbonic anhydrase IX is overexpressed in the majority of clear cell renal cell carcinomas and in approximately 30% of colorectal cancers. The targeted delivery of IL2 helps potentiate the action of targeted cytotoxics, leading to cancer eradication in models that cannot be cured by conventional chemotherapy. Clin Cancer Res; 24(15); 3656–67. ©2018 AACR.
Reciprocal Network between Cancer Stem-Like Cells and Macrophages Facilitates the Progression and Androgen Deprivation Therapy Resistance of Prostate Cancer
Authors: Huang Hai , Wang Chao , Liu Fei , Li Hui-Zhen , Peng Guang , Gao Xu , Dong Ke-Qin , Wang Hong-Ru , Kong De-Pei , Qu Min , Dai Li-He , Wang Kai-Jian , Zhou Zhe , Yang Jun , Yang Ze-Yu , Cheng Yan-Qiong , Tian Qin-Qin , Liu Dan , Xu Chuan-Liang , Xu Dan-Feng , Cui Xin-Gang , Sun Ying-Hao
Published: April 2018

Purpose: Cancer stem-like cells (CSC) contribute to the progression and androgen deprivation therapy (ADT) resistance of prostate cancer. As CSCs depend on their specific niche, including tumor-associated macrophages (TAM), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer.

Experimental Design: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA sequencing, co-immunoprecipitation, chromatin immunoprecipitation, and other assays. A coculture system and cytokine antibody arrays were used to examine the interaction network between CSCs and TAMs. In addition, an orthotopic prostate cancer model was established to evaluate the in vivo effects of the combined targeting of CSCs and their interaction with TAMs on ADT resistance.

Results: Autophagy-related gene 7 (ATG7) facilitated the transcription of OCT4 via β-catenin, which binds to the OCT4 promoter, promoting CSC characteristics in prostate cancer, including self-renewal, tumor initiation, and drug resistance. In addition, CSCs remodeled their specific niche by educating monocytes/macrophages toward TAMs, and the CSC-educated TAMs reciprocally promoted the stem-like properties of CSCs, progression and ADT resistance of prostate cancer via IL6/STAT3. Furthermore, the combined targeting of CSCs and their interaction with TAMs by inhibiting ATG7/OCT4 and IL6 receptor effectively ameliorated ADT resistance in an orthotopic prostate cancer model.

Conclusions: Targeting CSCs and their niche may prove to be a more powerful strategy than targeting CSCs alone, providing a rational approach to ameliorating ADT resistance in prostate cancer. Clin Cancer Res; 24(18); 4612–26. ©2018 AACR.
Elevated Choroidal Thickness and Central Serous Chorioretinopathy in the Fellow Eyes of Patients with Circumscribed Choroidal Hemangioma
Authors: Kim Ryan S. , Jain Rishabh R. , Brown David M. , Bretana Maria E. , Kegley Eric N. , Singer Michael A. , Aragon Antonio V. , Schefler Amy C.
Published: April 2018

Objective: To determine whether increased choroidal thickness (CT) is associated with circumscribed choroidal hemangioma (CCH) and whether patients with CCH are predisposed to central serous chorioretinopathy (CSCR). Methods: We performed a retrospective consecutive observational study of 15 fellow eyes of 15 patients who had CCH. A- and B-scan ultrasonography, fluorescein angiography (FA), and optical coherence tomography (OCT) findings were reviewed to confirm the diagnosis of CCH. Fellow eye CT was measured using enhanced depth imaging OCT. FA, indocyanine green angiography, and OCT images of fellow eyes were reviewed for signs of CSCR. Results: Mean subfoveal CT was significantly greater in the fellow eyes of patients with CCH than in age-matched normal eyes (p = 0.004). Three of 15 (20.0%) fellow eyes of CCH patients had retinal pigment epithelium disruptions and/or pigment epithelial detachments indicative of previous asymptomatic CSCR. Conclusion: In this pilot study, elevated CT was associated with a risk of developing CCH as well as CSCR in patients of varying ages. Patients diagnosed with CCH should be screened for CSCR in the fellow eye. Further exploration of this association may reveal useful clues about the biology of abnormally elevated choroidal hyperpermeability and its various clinical manifestations.
Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes
Authors: Hadefi Alia , Huberty Vincent , Lemmers Arnaud , Arvanitakis Marianna , Maggs David , Costamagna Guido , Devière Jacques
Published: April 2018

Type 2 diabetes is a pandemic disease with an incidence that has risen steadily over recent decades. Experimental evidence in animals has demonstrated that intestinal bypass surgery of the upper small intestine, particularly the duodenum, has an important role in glucose homoeostasis. Furthermore, Roux-en-Y bypass performed as bariatric surgery has shown to correct hyperglycaemia from the first postoperative days in obese diabetic patients. Therefore, on the basis of these considerations, duodenal mucosal resurfacing was studied in type 2 diabetes patients as a minimally invasive procedure that could offer an alternative treatment for these patients. Further studies, and particularly large controlled trials, are needed to determine the place of this procedure in the treatment of type 2 diabetes as well as other metabolic diseases such as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.
Ectopic Pancreatic Tissue Adherent to the External Gallbladder Wall
Authors: Koukourakis Ioannis M. , Perente Memet Meltem S. , Kouroupi Maria , Simopoulos Konstantinos
Published: April 2018

Heterotopic pancreatic tissue can be found in the gastrointestinal tract, with the stomach and small bowel being the most common sites of localization. The gallbladder is seldom affected. Here, we report 2 cases of ectopic pancreas within the fatty tissue adherent to the organ wall. Both cases concerned young women (31 and 36 years old) who were treated with a laparoscopic cholecystectomy due to persistent abdominal symptoms thought to be related to chronic cholecystitis. Pathological examination revealed the presence of ectopic pancreatic tissue type 1.
Adult-Onset Orbital Sinus Pericranii with T2 Hyperintensity Lesion: A Case Report
Authors: Osanai Toshiya , Houkin Kiyohiro
Published: April 2018

Sinus pericranii is a rare vascular anomaly, and most cases occur in children and develop at the midline. In previous reports of sinus pericranii, T2 hyperintensity lesion has not been regarded as a common sequela. We report an extremely rare case of orbital sinus pericranii with associated T2 hyperintensity lesion. A 50-year-old man was admitted to our hospital with a history of right upper eyelid swelling that had been present for several years. Computed tomography, magnetic resonance imaging, and digital subtraction angiography demonstrated a connection between the lesion and normal cerebral venous system. Thus, we diagnosed the lesion as a sinus pericranii despite its atypical features. We elected to observe the patient, and the lesion had remained the same size without any adverse events, such as hemorrhage, occurring throughout the 5-year follow-up. An atypical sinus pericranii should be considered in patients with a soft compressible swelling on the head, even if the lesion is located off the midline.
Renal Infarction during Anticoagulant Therapy after Living Donor Liver Transplantation
Authors: Onda Shinji , Shiba Hiroaki , Takano Yuki , Furukawa Kenei , Hata Taigo , Yanaga Katsuhiko
Published: April 2018

Introduction: Liver transplant recipients are at risk for complications of vascular thrombosis. The reconstructed hepatic artery and portal vein thrombosis potentially result in hepatic failure and graft loss. Renal infarction is a rare clinical condition, but in severe cases, it may lead to renal failure. We herein report a case of renal infarction after living donor liver transplantation (LDLT) during anticoagulant therapy. Case Presentation: A 60-year-old woman with end-stage liver disease due to primary biliary cholangitis underwent LDLT with splenectomy. Postoperatively, tacrolimus, mycophenolate mofetil, and steroid were used for initial immunosuppression therapy. On postoperative day (POD) 5, enhanced computed tomography (CT) revealed splenic vein thrombosis, and anticoagulant therapy with heparin followed by warfarin was given. Follow-up enhanced CT on POD 20 incidentally demonstrated right renal infarction. The patient’s renal function was unchanged and the arterial flow was good, and the splenic vein thrombosis resolved. At 4 months postoperatively, warfarin was discontinued, but she developed recurrent splenic vein thrombosis 11 months later, and warfarin was resumed. As of 40 months after transplantation, she discontinued warfarin and remains well without recurrence of splenic vein thrombosis or renal infarction. Conclusion: Renal infarction is a rare complication of LDLT. In this case, renal infarction was incidentally diagnosed during anticoagulant therapy and was successfully treated.
A Novel MGP Gene Mutation Causing Keutel Syndrome in a Brazilian Patient
Authors: Perrone Eduardo , Chen Kelin , Ramos Marco , Milanezi Maria Fernanda , Nakano Viviane , Falconi Ariane , Silva Juliana , Campos Jamille , Silva Celia M.C. , Filho Joao B.O. , Perez Ana B.A.
Published: April 2018

Keutel syndrome is caused by mutations in the matrix gamma-carboxyglutamic acid (MGP) gene (OMIM 154870) and is inherited in an autosomal recessive fashion. It is characterized by brachydactyly, pulmonary artery stenosis, a distinctive facial phenotype, and cartilage calcification. To date, only 36 cases have been reported worldwide. We describe clinical and molecular findings of the first Brazilian patient with Keutel syndrome. Keutel syndrome was suspected based on clinical and morphological evaluation, so we sequenced the MGP gene using the TruSight One Sequencing Panel (Illumina). The obtained MGP gene sequence was then validated by Sanger sequencing. We identified a novel pathogenic homozygous variant of the MGP gene (c.2T>C; p.Met1Thr) confirming Keutel syndrome. Proper diagnosis of this syndrome is important for clinical management and is an indication for genetic counseling. Keutel syndrome should be suspected in patients with cartilage calcifications and brachydactyly when associated with a distinctive facial phenotype and pulmonary artery stenosis.
Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Lambda Deposits: Report of the First Pediatric Case
Authors: Torrealba Jose , Gattineni Jyothsna , Hendricks Allen R.
Published: April 2018

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) is a recently described, uncommon renal disorder which is considered a monoclonal gammopathy of renal significance. Although some patients will have a detectable monoclonal spike, overt hematologic malignancy is found in only a minority. Most patients with PGNMID are over the age of 50 years, and to our knowledge no cases have been reported in children or adolescents. Renal biopsy shows variable histologic patterns by light microscopy, with membranoproliferative and membranous patterns being most common. Immunofluorescence microscopy demonstrates restriction to a single immunoglobulin G heavy chain isotype and a single light chain subtype. Electron microscopy reveals granular, unorganized deposits. We report a rare pediatric case which occurred in a 17-year-old female. The rarity of this entity in the adult population has not permitted a standard treatment regimen to be established. Our adolescent patient was treated with multiple treatment regimens including prednisone, mycophenolate mofetil, rituximab, bortezomib, and daratumumab. Our case demonstrates that awareness of this disorder by pediatric nephrologists and pathologists is vital to guide accurate disease classification, prognosis, and treatment.
Juvenile Localized Scleroderma with Hyaline Deposits in the Renal Arteriole
Authors: Tabata Nobuko , Nagano Inoue Chiyoko
Published: April 2018

We report a 10-year-old boy with localized scleroderma of the linear and plaque type, who showed proteinuria and hematuria. In this patient, skin, articular, and renal manifestations appeared successively and then began to resolve in the same order. A renal biopsy specimen demonstrated mild mesangial cell proliferation, exudate of immunoglobulin in the glomerular capillary, and large electron-dense deposits in the afferent arteriole. We consider that there were some transient factors that had caused the skin and articular manifestations, which also induced renal vascular inflammatory responses.
AMPK Contributes to Cardioprotective Effects of Pterostilbene Against Myocardial Ischemia- Reperfusion Injury in Diabetic Rats by Suppressing Cardiac Oxidative Stress and Apoptosis
Authors: Kosuru Ramoji , Cai Yin , Kandula Vidya , Yan Dan , Wang Chunyan , Zheng Hong , Li Yalan , Irwin Michael G. , Singh Sanjay , Xia Zhengyuan
Published: April 2018

Background/Aims: Pterostilbene (PT) exerts antidiabetic effects by decreasing blood glucose and modulating lipid metabolism and has been shown to attenuate myocardial ischemia-reperfusion (IR) injury in non-diabetic subjects. However, whether PT can protect against myocardial IR injury in diabetes is unknown. AMPK stimulation is indispensable in offering cardioprotection against myocardial IR injury in diabetes by limiting cardiac apoptosis. Thus, we hypothesized that PT may confer protection against myocardial IR injury in diabetes via AMPK activation. Methods: Sprague-Dawley rats at eight weeks of diabetes induction (induced by an intravenous dose of 65 mg/kg streptozotocin) were administered with vehicle or PT (20 and 40 mg/kg/day, p.o.) for four weeks (starting from week 9 to 12). At the end of week 12, myocardial IR injury was induced by subjecting the diabetic rats to 30 minutes of coronary artery ligation and followed by 2 hours of reperfusion. In in vitro studies, rat primary cardiomyocytes were incubated with low glucose (LG, 5.5 mM) or high glucose (HG, 30 mM) and exposed to 45 minutes hypoxia and 2 hours reoxygenation in the presence or absence of PT (0.5 µM) or the AMPK inhibitor compound C (CC, 5 µM). Results: PT significantly reduced post-ischemic cardiac infarct size, oxidative stress, plasma lactate dehydrogenase (LDH), creatine kinase-MB levels and apoptosis in diabetic rats. In cardiomyocytes, PT decreased hypoxia/ reoxygenation-induced oxidative stress, attenuated LDH and cleaved caspase3/caspase3 ratio and increased Bcl-2/Bax ratio and AMPK phosphorylation. However, CC administration blunted the cardioprotective effects of PT both in vivo and in vitro. Conclusion: Suppressing cardiac oxidative stress and apoptosis via AMPK stimulation may represent a primary mechanism whereby pterostilbene attenuates diabetic myocardial IR injury.
Upregulation of TREM2 Ameliorates Neuroinflammatory Responses and Improves Cognitive Deficits Triggered by Surgical Trauma in Appswe/PS1dE9 Mice
Authors: Jiang Yanhua , Li Zhe , Ma Hong , Cao Xuezhao , Liu Fang , Tian Ayong , Sun Xijia , Li Xiaoqian , Wang Jun
Published: April 2018

Background/Aims: TREM2 plays a crucial role in modulating microglial function through interaction with DAP12, the adapter for TREM2. Emerging evidence has demonstrated that TREM2 could suppress neuroinflammatory responses by repression of microglia-mediated cytokine production. This study investigated the potential role of TREM2 in surgery-induced cognitive deficits and neuroinflammatory responses in wild-type (WT) and APPswe/PS1dE9 mice. Methods: Adult APPswe/PS1dE9 transgenic male mice (a classic transgenic model of Alzheimer’s disease, 3 months old) and their age-matched WT mice received intracerebral lentiviral particles encoding the mouse TREM2 gene and then were subjected to partial hepatectomy at 1 month after the lentiviral particle injection. The behavioral changes were evaluated with an open-field test and Morris water maze test on postoperative days 3, 7, and 14. Hippocampal TREM2, DAP12, and interleukin (IL)-1β were measured at each time point. Ionized calcium-binding adapter molecule 1 (Iba-1), microglial M2 phenotype marker Arg1, synaptophysin, tau hyperphosphorylation (T396), and glycogen synthase kinase-3β (GSK-3β) were also examined in the hippocampus. Results: Surgical trauma induced an exacerbated cognitive impairment and enhanced hippocampal IL-1β expression in the transgenic mice on postoperative days 3 and 7. A corresponding decline in the levels of TREM2 was also found on postoperative days 3, 7, and 14. Overexpression of TREM2 downregulated the levels of IL-1β, ameliorated T396 expression, inhibited the activity of GSK-3β, and improved sickness behavior. Increased Arg1 expression and a high level of synaptophysin were also observed in the transgenic mice following TREM2 overexpression. Conclusion: The downregulation of TREM2 exacerbated surgery-induced cognitive deficits and exaggerated neuroinflammatory responses in this rodent model. Overexpression of TREM2 potentially attenuated these effects by decreasing the associated production of proinflammatory cytokines, inhibiting tau hyperphosphorylation, and enhancing synaptophysin expression.
A juridicização e o campo indigenista no Brasil: uma abordagem interdisciplinar
Authors: Villas Bôas Filho Orlando
Published: April 2018

Este artigo analisa a relação ambivalente entre o processo de juridicização e as disputas travadas no campo indigenista. Enfoca, inicialmente, a conformação original e a reconfiguração experimentada pelo campo indigenista. Em seguida, realiza uma breve reconstrução conceitual da juridicização. Por fim, procura indicar, em caráter ilustrativo, alguns traços do impacto exercido pelo processo de juridicização no campo indigenista mediante a análise de três questões: a) a juridicização como expressão da supremacia da “ordem imposta”; b) a tendência de desconsideração das categorias autóctones no âmbito do processo de juridicização; c) a assimetria de forças entre os agentes que, mediante a juridicização, manejam a regulação jurídica estatal para a satisfação de interesses contrários aos dos povos indígenas.
Lex Salica
Authors: Brunner Murilo Castineira
Published: April 2018

O presente trabalho tem por objetivo o estudo da Lex Salica, aplicável inicialmente aos Francos Sálios, durante a Idade Média, a fim de se apreender, pela exposição de suas disposições, os principais aspectos da sociedade Franca, que em certa medida refletem o período histórico de sua elaboração.
Os novos rumos da mediação no Brasil
Authors: Lara Mariana Alves
Published: April 2018

O presente trabalho busca analisar as recentes alterações introduzidas pelo novo Código de Processo Civil e pela Lei n. 13.105 de 2015 no tocante à mediação. Para tanto, parte-se da definição de mediação como meio complementar e consensual de resolução de controvérsias, destacando suas principais características. Após um breve histórico acerca da regulamentação da mediação no Brasil e da tendência mundial, serão tratadas as novas regras que passarão a disciplinar o instituto para, ao final, concluir que foi dado um importante passo no Brasil em direção à cultura de pacificação dos conflitos.
Onerosidade excessiva nos contratos comerciais internacionais. Uma análise comparada das soluções do Direito Comercial transnacional
Authors: Barreto Gabriel De Almeida
Published: April 2018

Os contratos desempenham função imprescindível na economia moderna, estabelecendo expectativas de partes que desejam negociar. Estas partes devem ter autonomia para contratar, desde que respeitado o princípio da pacta sunt servanda. Por outro lado, pela racionalidade econômica dos agentes, eles buscarão a resolução do contrato (ou, pelo menos, sua renegociação) a partir do momento em que este deixar de se tornar vantajoso, o que pode ocorrer devido a acontecimentos supervenientes que frustrem a função econômica idealizada. Caso as partes não contratem essa alocação de riscos, é necessário buscar mecanismos que solucionem o problema. Várias normas internacionais buscaram tratar dessa questão, como a Convenção de Viena sobre Compra e Venda Internacional de Mercadorias (CISG), os Princípios UNIDROIT e os Princípios de Direito Contratual Europeu. Se, por um lado, os dois últimos tratam expressamente de casos de hardship, por outro lado a CISG possui somente uma cláusula genérica de exoneração que cria dúvidas quanto ao seu escopo de aplicação. Diante deste cenário plural, este artigo discute como interpretar situações de hardship em contratos comerciais internacionais sob este conjunto de normas, quais soluções são mais apropriadas para as necessidades do comércio e como estas normas internacionais interagem entre si para harmonizar o direito comercial internacional.
O legado do Código Civil de 1916
Authors: Tomasevicius Filho Eduardo
Published: April 2018

Em 2016, a comunidade jurídica brasileira comemora o centenário do Código Civil de 1916, elaborado por Clóvis Beviláqua. Nesse artigo, o autor defende que o Código Civil de 1916, apesar de sua vigência ter ocorrido em um século de profundas transformações políticas, culturais, sociais e econômicas, deixou um legado para o direito brasileiro, ao servir de base para a preservação da tradição jurídica brasileira, tanto por ter absorvido o pensamento oitocentista quanto pelo fato de o Código Civil de 2002 ter recepcionado boa parte dos artigos do Código Civil de 1916.
Topological Arrangement of Cardiac Fibroblasts Regulates Cellular Plasticity
Authors: Yu Jingyi , Seldin Marcus M. , Fu Kai , Li Shen , Lam Larry , Wang Ping , Wang Yijie , Huang Dian , Nguyen Thang L. , Wei Bowen , Kulkarni Rajan P. , Di Carlo Dino , Teitell Michael , Pellegrini Matteo , Lusis Aldons J. , Deb Arjun
Published: April 2018

Rationale:

Cardiac fibroblasts do not form a syncytium but reside in the interstitium between myocytes. This topological relationship between fibroblasts and myocytes is maintained throughout postnatal life until an acute myocardial injury occurs, when fibroblasts are recruited to, proliferate and aggregate in the region of myocyte necrosis. The accumulation or aggregation of fibroblasts in the area of injury thus represents a unique event in the life cycle of the fibroblast, but little is known about how changes in the topological arrangement of fibroblasts after cardiac injury affect fibroblast function.

Objective:

The objective of the study was to investigate how changes in topological states of cardiac fibroblasts (such as after cardiac injury) affect cellular phenotype.

Methods and Results:

Using 2 and 3-dimensional (2D versus 3D) culture conditions, we show that simple aggregation of cardiac fibroblasts is sufficient by itself to induce genome-wide changes in gene expression and chromatin remodeling. Remarkably, gene expression changes are reversible after the transition from a 3D back to 2D state demonstrating a topological regulation of cellular plasticity. Genes induced by fibroblast aggregation are strongly associated and predictive of adverse cardiac outcomes and remodeling in mouse models of cardiac hypertrophy and failure. Using solvent-based tissue clearing techniques to create optically transparent cardiac scar tissue, we show that fibroblasts in the region of dense scar tissue express markers that are induced by fibroblasts in the 3D conformation. Finally, using live cell interferometry, a quantitative phase microscopy technique to detect absolute changes in single cell biomass, we demonstrate that conditioned medium collected from fibroblasts in 3D conformation compared with that from a 2D state significantly increases cardiomyocyte cell hypertrophy.

Conclusions:

Taken together, these findings demonstrate that simple topological changes in cardiac fibroblast organization are sufficient to induce chromatin remodeling and global changes in gene expression with potential functional consequences for the healing heart.
Morphological and molecular characterisation of Pratylenchus rwandae n. sp. (Tylenchida: Pratylenchidae) associated with maize in Rwanda
Authors: Singh Phougeishangbam Rolish , Nyiragatare Alliance , Janssen Toon , Couvreur Marjolein , Decraemer Wilfrida , Bert Wim
Published: April 2018

Pratylenchus rwandae n. sp., a root-lesion nematode associated with maize (Zea mays) from Rwanda, is described. This new species is characterised by females of medium to large size (469-600 μm) having an offset lip region with three annuli, stylet of 13-14.6 μm long with prominent rounded or anteriorly concave knobs, short to long pharyngeal gland overlap of 10.9-34.7 μm long, variable number of lateral lines (4-14) in different regions of the body, lateral field consisting of smooth bands, oval to slightly rounded spermatheca, vulva located at 75-80% of the total body length, post-vulval uterine sac (PUS) 20.3-26.5 μm long, tail subcylindrical to conoid with variation in tail tip shape from rounded to truncate or indented with generally smooth tip, and male unknown. The results of the phylogenetic analyses based on sequences of the D2-D3 expansion regions of 28S, partial 18S and ITS of rDNA and COI of mitochondrial DNA indicate that P. rwandae n. sp. is a species within the Penetrans group and appears as a sister species to a group comprising P. convallariae, P. dunensis, P. fallax, P. oleae, P. penetrans, P. pinguicaudatus, and three other unidentified species. A comparison of important morphological characters of the closely related Pratylenchus spp. is provided.