bluuebunny/crossref_metadata_2025 huggingface dataset:
Legitimacy in Areas of Limited Statehood
Authors: Risse Thomas , Stollenwerk Eric
Published: February 2018

Empirical legitimacy, defined as social acceptance of the right to rule, constitutes a key condition for effective governance in areas of limited statehood. Most work on legitimacy, however, is state centric and has exclusively focused on the state as the governance actor of interest. We argue that understanding the legitimacy of external and nonstate actors is essential for analyzing governance in areas of limited statehood. Moreover, subnational variations in legitimacy matter. While most studies of the legitimacy of governance actors have focused on the macroregional and national levels, a governance actor may enjoy high legitimacy in one part of a country but be considered illegitimate in other parts. Finally, the multiple sources and consequences of empirical legitimacy in areas of limited statehood have to be analyzed in greater depth. There is no single source of legitimacy, nor is there a single guaranteed consequence of legitimacy.
Radicalization: A Relational Perspective
Authors: della Porta Donatella
Published: February 2018

Radicalization is a process of escalation from nonviolent to increasingly violent repertoires of action that develops through a complex set of interactions unfolding over time. Looking at radicalization mainly through the lenses of a relational approach, this article suggests that social movement studies allow us to bridge structural and agentic explanations in an analysis of the impact of political opportunities and organizational resources, as well as framing, in explaining forms of action and inaction. Available political opportunities influence the reactions of political actors in general to movement demands, thus affecting social movements’ strategic choices. Moreover, the availability (or lack) of material and symbolic resources affects the choice of radical repertoire. Finally, organizational resources and contextual opportunities are framed differently by social movement actors, in some cases facilitating radicalization. At the individual level, different paths of radicalization are singled out.
Violent Conflict and Political Development Over the Long Run: China Versus Europe
Authors: Dincecco Mark , Wang Yuhua
Published: February 2018

Is the traditional logic by which violent conflict fosters long-run political development universal? To help address this question, this article compares Europe with China. While historical warfare was very common across both units, representative government flourished only in Europe. We suggest that the relationship between violent conflict and political development depends on the underlying political geography context. In Europe, political fragmentation was rampant. Thus, conflict tended to be external (i.e., interstate), and attack threats were multidirectional. Furthermore, exit ability was high in this context. Elites were therefore in a strong bargaining position to demand political representation in return for new tax revenue. China, by contrast, was politically centralized. Here, conflict tended to be internal, attack threats were unidirectional, and exit ability was low. The emperor was thus powerful enough to extract tax funds without surrendering political control. In this context, violent conflict promoted autocratic re-entrenchment. We conclude by briefly analyzing the relationships between political geography, historical conflict, and political development in sub-Saharan Africa and Latin America.
Theories of Institutional Corruption
Authors: Thompson Dennis F.
Published: February 2018

Normative theorists of corruption have developed an institutional conception that is distinct from both the individualist approaches focused on quid pro quo exchanges and other institutional approaches found in the literature on developing societies. These theorists emphasize the close connection between patterns of corruption and the legitimate functions of institutions. The corruption benefits the institution while undermining it. Reforms therefore should be directed toward finding alternatives for the functions the corruption serves. Also, institutional corruption does not require that its perpetrators have corrupt motives, and it is not limited to political institutions. This review examines four leading theories and discusses criticisms of their approach. A tripartite framework for analyzing the elements of institutional corruption is proposed. Although the theories are useful for distinguishing institutional corruption from the more familiar forms of individual corruption, they could be enriched by giving greater attention to the work on individual corruption in its structural forms in developing societies.
Increasing Concentration in the Agricultural Supply Chain: Implications for Market Power and Sector Performance
Authors: Sexton Richard J. , Xia Tian
Published: February 2018

Increasing consolidation and vertical coordination in the food chain have made the prospect of market power abuses by powerful food manufacturers and retailers an issue and a policy concern worldwide, in terms of potential impacts on farmer and consumer welfare and sector efficiency. We address the extent to which traditional wisdom and standard conceptual and empirical models that have girded thought about market power in the food chain for decades apply in modern food-market contexts and examine recent work on competition in the food chain to gauge the most promising paths forward. A key conclusion is that considerations that go beyond the bounds of standard models likely cause market power to be less than would be predicted based on the highly concentrated structures of many modern agricultural and food markets. These considerations include downstream buyers who rationally internalize long-run implications of their pricing decisions to farmers, powerful food manufacturers and retailers who countervail each other's market power, and the complex pricing decisions of multistore and multiproduct food retailers.
Hemicentin 1 influences podocyte dynamic changes in glomerular diseases
Authors: Toffoli Barbara , Zennaro Cristina , Winkler Carine , Giordano Attianese Greta Maria Paola , Bernardi Stella , Carraro Michele , Gilardi Federica , Desvergne Béatrice
Published: February 2018

Different complex mechanisms control the morphology of podocyte foot processes and their interactions with the underlying basement membrane. Injuries to this system often cause glomerular dysfunction and albuminuria. The present study aimed at identifying early markers of glomerular damage in diabetic nephropathy. For this purpose, we performed a microarray analysis on kidneys of 3-wk-old peroxisome proliferator-activated receptor-γ (PPARγ)-null and AZIP/F1 mice, which are two models of diabetic nephropathy due to lipodystrophy. This was followed by functional annotation of the enriched clusters of genes. One of the significant changes in the early stages of glomerular damage was the increase of hemicentin 1 (HMCN1). Its expression and distribution were then studied by real-time PCR and immunofluorescence in various models of glomerular damage and on podocyte cell cultures. HMCN1 progressively increased in the glomeruli of diabetic mice, according to disease severity, as well as in puromycin aminonucleoside (PA)-treated rats. Studies on murine and human podocytes showed an increased HMCN1 deposition upon different pathological stimuli, such as hyperglycemia, transforming growth factor-β (TGF-β), and PA. In vitro silencing studies showed that HMCN1 mediated the rearrangements of podocyte cytoskeleton induced by TGF-β. Finally, we demonstrated an increased expression of HMCN1 in the kidneys of patients with proteinuric nephropathies. In summary, our studies identified HMCN1 as a new molecule involved in the dynamic changes of podocyte foot processes. Its increased expression associated with podocyte dysfunction points to HMCN1 as a possible marker for the early glomerular damage occurring in different proteinuric nephropathies.
Sensorimotor control of the trunk in sitting sway referencing
Authors: Goodworth Adam D. , Tetreault Kimberly , Lanman Jeffrey , Klidonas Tate , Kim Seyoung , Saavedra Sandra
Published: February 2018

We developed a sway-referenced system for sitting to highlight the role of vestibular and visual contributions to trunk control. Motor control was investigated by measuring trunk kinematics in the frontal plane while manipulating visual availability and introducing a concurrent cognitive task. We examined motor learning on three timescales (within the same trial, minutes), within the same test session (1 h), and between sessions (1 wk). Posture sway was analyzed through time-based measures [root mean square (RMS) sway and RMS velocity], frequency-based measures (amplitude spectra), and parameterized feedback modeling. We found that posture differed in both magnitude and frequency distribution during sway referencing compared with quiet sitting. Modeling indicated that sway referencing caused greater uncertainty/noise in sensory feedback and motor outputs. Sway referencing was also associated with lower active stiffness and damping model parameters. The influence of vision and a cognitive task was more apparent during sway referencing compared with quiet sitting. Short-term learning was reflected by reduced RMS velocity in quiet sitting immediately following sway referencing. Longer term learning was evident from one week to the next, with a 23% decrease in RMS sway and 9% decrease in RMS velocity. These changes occurred predominantly during cognitive tests at lower frequencies and were associated with lower sensory noise and higher stiffness and integral gains in the model. With the findings taken together, the sitting sway-referenced test elicited neural changes consistent with optimal integration and sensory reweighting, similar to standing, and should be a valuable tool to closely examine sensorimotor control of the trunk.

NEW & NOTEWORTHY We developed the first sway-referenced system for sitting to highlight the role of vestibular and visual contributions to trunk control. A parametric feedback model explained sensorimotor control and motor learning in the task with and between two test sessions. The sitting sway-referenced test elicited neural changes consistent with optimal integration and sensory reweighting, similar to standing, and should be a valuable tool to closely examine sensorimotor control of the trunk.
Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection
Authors: Hakansson A. P. , Orihuela C. J. , Bogaert D.
Published: February 2018

It has long been thought that respiratory infections are the direct result of acquisition of pathogenic viruses or bacteria, followed by their overgrowth, dissemination, and in some instances tissue invasion. In the last decades, it has become apparent that in contrast to this classical view, the majority of microorganisms associated with respiratory infections and inflammation are actually common members of the respiratory ecosystem and only in rare circumstances do they cause disease. This suggests that a complex interplay between host, environment, and properties of colonizing microorganisms together determines disease development and its severity. To understand the pathophysiological processes that underlie respiratory infectious diseases, it is therefore necessary to understand the host-bacterial interactions occurring at mucosal surfaces, along with the microbes inhabiting them, during symbiosis. Current knowledge regarding host-bacterial interactions during asymptomatic colonization will be discussed, including a plausible role for the human microbiome in maintaining a healthy state. With this as a starting point, we will discuss possible disruptive factors contributing to dysbiosis, which is likely to be a key trigger for pathobionts in the development and pathophysiology of respiratory diseases. Finally, from this renewed perspective, we will reflect on current and potential new approaches for treatment in the future.
Dentists’ Awareness of Physical Therapy in the Treatment of Temporomandibular Disorders: A Preliminary Study
Authors: Gadotti Inae C. , Hulse Corey , Vlassov Julia , Sanders Derek , Biasotto-Gonzalez Daniela A.
Published: February 2018

Background. Physical therapy (PT) has been shown to be one of the most effective conservative treatments for temporomandibular disorders (TMD). Not all dentists are aware of the importance of the collaboration with physical therapists in the treatment of TMD pain.Objectives. To determine the awareness of dentists in Florida about the importance of PT for TMD pain and to create awareness related to collaborations.Methods. An online questionnaire was used. A contact list of dentists was obtained from the Florida Dental Association. The overall awareness and information on patient referral were presented per dentist specialty.Results. A total of 256 dentists completed the survey. Prior to the survey, 41% of the dentists reported not aware that PTs can treat TMD patients. Oral surgeons and orthodontists were more aware about PT compared to other specialties. After the survey, 81% of the dentists were more likely to refer their TMD patients to PT, and 80% were interested to know more about the benefits of collaborations.Conclusion. This study shows the lack of dentists’ awareness in Florida about the benefits of PT for TMD treatment. This study increased the awareness of the surveyed dentists in Florida about the benefit from a multidisciplinary approach.
A New Prime Code for Synchronous Optical Code Division Multiple-Access Networks
Authors: Abbas Huda Saleh , Gregory Mark A. , Austin Michael W.
Published: February 2018

A new spreading code based on a prime code for synchronous optical code-division multiple-access networks that can be used in monitoring applications has been proposed. The new code is referred to as “extended grouped new modified prime code.” This new code has the ability to support more terminal devices than other prime codes. In addition, it patches subsequences with “0s” leading to lower power consumption. The proposed code has an improved cross-correlation resulting in enhanced BER performance. The code construction and parameters are provided. The operating performance, using incoherent on-off keying modulation and incoherent pulse position modulation systems, has been analyzed. The performance of the code was compared with other prime codes. The results demonstrate an improved performance, and a BER floor of 10−9 was achieved.
Parenterally Administered Norovirus GII.4 Virus-Like Particle Vaccine Formulated with Aluminum Hydroxide or Monophosphoryl Lipid A Adjuvants Induces Systemic but Not Mucosal Immune Responses in Mice
Authors: Heinimäki Suvi , Malm Maria , Vesikari Timo , Blazevic Vesna
Published: February 2018

Norovirus (NoV) is a main cause of acute gastroenteritis across all ages worldwide. NoV vaccine candidates currently in clinical trials are based on noninfectious highly immunogenic virus-like particles (VLPs) delivered intramuscularly (IM). Since NoV is an enteric pathogen, it is likely that mucosal immunity has a significant role in protection from infection in the intestine. Due to the fact that IM delivery of NoV VLPs does not generate mucosal immunity, we investigated whether NoV genotype GII.4 VLPs coadministered with aluminum hydroxide (Al(OH)3) or monophosphoryl lipid A (MPLA) would induce mucosal antibodies in mice. Systemic as well as mucosal IgG and IgA antibodies in serum and intestinal and nasal secretions were measured. As expected, strong serum IgG, IgG1, and IgG2a antibodies as well as a dose sparing effect were induced by both Al(OH)3and MPLA, but no mucosal IgA antibodies were detected. In contrast, IN immunization with GII.4 VLPs without an adjuvant induced systemic as well as mucosal IgA antibody response. These results indicate that mucosal delivery of NoV VLPs is needed for induction of mucosal responses.
CYP1A1 Relieves Lipopolysaccharide-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells
Authors: Zhang Wen-Yao , Wang Hao , Qi Shaopei , Wang Xixi , Li Xueru , Zhou Kun , Zhang Yong , Gao Ming-Qing
Published: February 2018

The expression of cytochrome P4501A1 (CYP1A1) enzyme is changed in various organs during the host response to inflammation or infection, leading to alterations in the metabolism of endogenous and exogenous compounds. Results of this study showed that CYP1A1 expression was significantly downregulated in the mammary tissue of bovine with mastitis, in inflammatory epithelial cells (INEs) extracted from the tissue, and in lipopolysaccharide- (LPS-) induced INEs compared with their corresponding counterparts. Overexpression of CYP1A1 in bovine mammary epithelial cells alleviated the LPS-induced inhibition of epithelial proliferation, abated the LPS-induced increase of gene expression and protein secretion of inflammatory cytokine tumor necrosis factor-α and interleukin-6, and attenuated the LPS-induced activation of NF-κB signaling. These findings suggest that CYP1A1 has immense potential in the regulation of inflammatory responses in bovine mammary epithelial cells during mastitis and may serve as a useful therapeutic target in mitigating injuries caused by inflammatory overreaction.
Development and Optimization of a Condition-Based Maintenance Policy with Sustainability Requirements for Production System
Authors: Jiang Aiping , Dong Ning , Tam Kwok Leung , Lyu Chonghao
Published: February 2018

In the field of condition-based maintenance, maintenance costs and system reliability criteria are the primary considerations for traditional maintenance management. These methods lack consideration of the environmental impact caused by equipment degradation, such as excessive emissions and energy consumption. In addition, because equipment degradation has various impacts on the ecological environment, companies with excessive emissions and energy consumption can receive huge fines, making it of great value to study ecoconscious maintenance strategies. In this paper, we propose a condition-based maintenance strategy considering energy consumption and carbon dioxide emissions. The major objective of the research is to extend a model which integrates ecological aspects with maintenance decision-making and optimization. The simulation and sensitivity analyses conducted verify that the model proposed can minimize total costs, as well as the environmental impact.
Pathology and Treatment of Traumatic Cervical Spine Syndrome: Whiplash Injury
Authors: Tanaka Nobuhiro , Atesok Kivanc , Nakanishi Kazuyoshi , Kamei Naosuke , Nakamae Toshio , Kotaka Shinji , Adachi Nobuo
Published: February 2018

Traumatic cervical syndrome comprises the various symptoms that occur as a result of external force such as that of a traffic accident. In 1995, the Quebec Task Force on whiplash-associated disorders (WAD) formulated the Quebec classification, with accompanying clinical practice guidelines. These guidelines were in accordance with the stated clinical isolated or combined symptoms of the syndrome: neck pain, headaches, dizziness, numbness of head or face, eye pain, vision loss, double vision, tinnitus, hearing loss, nausea, and numbness and/or weakness of extremities. In recent years, cerebrospinal fluid hypovolemia or fibromyalgia has been recognized as a major notable cause of a variety of symptoms, although many clinical questions remain regarding the pathology of this syndrome. Therefore, its diagnosis and treatment should be conducted extremely carefully. While the Quebec classification and its guidelines are very useful for the normalization and standardization of symptoms of traumatic cervical syndrome, in the future, we would like to see the emergence of new guidelines that better address the diversity of this disease.
The Development of a Design and Construction Process Protocol to Support the Home Modification Process Delivered by Occupational Therapists
Authors: Russell Rachel , Ormerod Marcus , Newton Rita
Published: February 2018

Modifying the home environments of older people as they age in place is a well-established health and social care intervention. Using design and construction methods to redress any imbalance caused by the ageing process or disability within the home environment, occupational therapists are seen as the experts in this field of practice. However, the process used by occupational therapists when modifying home environments has been criticised for being disorganised and not founded on theoretical principles and concepts underpinning the profession. To address this issue, research was conducted to develop a design and construction process protocol specifically for home modifications. A three-stage approach was taken for the analysis of qualitative data generated from an online survey, completed by 135 occupational therapists in the UK. Using both the existing occupational therapy intervention process model and the design and construction process protocol as the theoretical frameworks, a 4-phase, 9-subphase design and construction process protocol for home modifications was developed. Overall, the study is innovative in developing the first process protocol for home modifications, potentially providing occupational therapists with a systematic and effective approach to the design and delivery of home modification services for older and disabled people.
Urachal Adenocarcinoma: A Case Report with Key Imaging Findings and Radiologic-Pathologic Correlation
Authors: Schmitt Willian , Baptista Marta , Ferreira Marco , Gomes António , Germano Ana
Published: February 2018

Urachal pathologies are rare and can mimic numerous abdominal and pelvic diseases. Differential diagnosis of urachal anomalies can be narrowed down by proper assessment of lesion location, morphology, imaging findings, patient demographics, and clinical history. We report a case of a 60-year-old male, with a history of unintentional weight loss without associated symptoms, who was diagnosed with locally invasive urachal adenocarcinoma. With this article, we pretend to emphasize urachal adenocarcinoma clinical features along with its key imaging findings with radiologic-pathologic correlation.
Prevalence and Associated Factors of Depression among PLHIV in Ethiopia: Systematic Review and Meta-Analysis, 2017
Authors: Amare Tadele , Getinet Wondale , Shumet Shegaye , Asrat Biksegn
Published: February 2018

Background. Depression is a substantial contributor to the global burden of disease and affects people in all communities across the globe. Depression is the most common psychiatric problem associated with HIV/AIDS and half of all PLWHIV with depression go underdiagnosed and untreated. Psychiatric complications of HIVAIDS delay mental health services in less affluent countries. However, there is lack of study with regard to the pooled estimation prevalence of depression in PLWHIV in Ethiopia. Objectives. The aim of this systematic review and meta-analysis is to summarize the most current available evidence from 2010 to March 2017 among adult PLWHIV in Ethiopia. Methods. The team explored multiple databases searching methods including MEDLINE/PubMed, PsycINFO, Google Advance Scholar, and Google Scholar to find studies published with the data on the prevalence of depression among PLWHIV. We searched 150 research articles; of these 143 articles were excluded. Subsequently, thirteen articles were used for synthesis prevalence and four studies were included in the synthesis effect of sex on depression among PLWHIV. Results. The total of pooled estimated prevalence of depression in PLWHIV was 36.65. Estimated prevalence of depression in three studies by using CES-D was 31.19% and in six studies by using PHQ-9 was 37.91%. The remaining four studies used a single tool: Kessler-6 Scale (15.5%), HADS (41.2%), HDSQ (43.9%), and BDI (55.8%). Factors such as age, marital status, living alone, poor medication adherence, poor social support, clinical stages II and III of HIV, stigma, income, and occupation were significantly associated with depression. Conclusions and Recommendation. The pooled estimate prevalence of depression among PLWHIV was higher than that in the general population. It is better to offer special attention to these populations.
Fuzzy Fractional-Order PID Controller for Fractional Model of Pneumatic Pressure System
Authors: Al-Dhaifallah M. , Kanagaraj N. , Nisar K. S.
Published: February 2018

This article presents a fuzzy fractional-order PID (FFOPID) controller scheme for a pneumatic pressure regulating system. The industrial pneumatic pressure systems are having strong dynamic and nonlinearity characteristics; further, these systems come across frequent load variations and external disturbances. Hence, for the smooth and trouble-free operation of the industrial pressure system, an effective control mechanism could be adopted. The objective of this work is to design an intelligent fuzzy-based fractional-order PID control scheme to ensure a robust performance with respect to load variation and external disturbances. A novel model of a pilot pressure regulating system is developed to validate the effectiveness of the proposed control scheme. Simulation studies are carried out in a delayed nonlinear pressure regulating system under different operating conditions using fractional-order PID (FOPID) controller with fuzzy online gain tuning mechanism. The results demonstrate the usefulness of the proposed strategy and confirm the performance improvement for the pneumatic pressure system. To highlight the advantages of the proposed scheme a comparative study with conventional PID and FOPID control schemes is made.
A Structural Approach to Disentangle the Visualization of Bipartite Biological Networks
Authors: Garcia-Algarra J. , Pastor J. M. , Mouronte M. L. , Galeano J.
Published: February 2018

Interactions between two different guilds of entities are pervasive in biology. They may happen at molecular level, like in a diseasome, or amongst individuals linked by biotic relationships, such as mutualism or parasitism. These sets of interactions are complex bipartite networks. Visualization is a powerful tool to explore and analyze them, but the most common plots, the bipartite graph and the interaction matrix, become rather confusing when working with real biological networks. We have developed two new types of visualization which exploit the structural properties of these networks to improve readability. A technique called k-core decomposition identifies groups of nodes that share connectivity properties. With the results of this analysis it is possible to build a plot based on information reduction (polar plot) and another which takes the groups as elementary blocks for spatial distribution (ziggurat plot). We describe the applications of both plots and the software to create them.
Extraosseous Intradural Chondrosarcoma of the Cervical Spine: A Case Report with Brief Review of Literature
Authors: Presutto Elizabeth , Patel Sejal , Fullmer Joseph , Ezhapilli Sajeev
Published: February 2018

Mesenchymal chondrosarcoma (MCS) is a malignant cancer of the cartilage that accounts for less than 1% of all chondrosarcomas and typically occurs within the bone. One-third of all mesenchymal chondrosarcomas are extraosseous soft tissue sarcomas, rendering this as an uncommon entity. We report a rare case of an extraosseous chondrosarcoma with the cervical spinal canal in a 21-year-old male. The purpose of this case report is to discuss the imaging characteristics of this pathology proven diagnosis.
Vitamin D Promotes MSC Osteogenic Differentiation Stimulating Cell Adhesion and αVβ3 Expression
Authors: Posa Francesca , Di Benedetto Adriana , Cavalcanti-Adam Elisabetta A. , Colaianni Graziana , Porro Chiara , Trotta Teresa , Brunetti Giacomina , Lo Muzio Lorenzo , Grano Maria , Mori Giorgio
Published: February 2018

Vitamin D (Vit D) by means of its biological active form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), has a protective effect on the skeleton by acting on calcium homeostasis and bone formation. Furthermore, Vit D has a direct effect on mesenchymal stem cells (MSCs) in stimulating their osteogenic differentiation. In this work, we present for the first time the effect of 1,25(OH)2D3 on MSC adhesion. Considering that cell adhesion to the substrate is fundamental for cell commitment and differentiation, we focused on the expression of αVβ3 integrin, which has a key role in the commitment of MSCs to the osteoblastic lineage. Our data indicate that Vit D increases αVβ3 integrin expression inducing the formation of focal adhesions (FAs). Moreover, we assayed MSC commitment in the presence of the extracellular matrix (ECM) glycoprotein fibronectin (FN), which is able to favor cell adhesion on surfaces and also to induce osteopontin (OPN) expression: this suggests that Vit D and FN synergize in supporting cell adhesion. Taken together, our findings provide evidence that Vit D can promote osteogenic differentiation of MSCs through the modulation of αVβ3 integrin expression and its subcellular organization, thus favoring binding with the matrix protein (FN).
A Cosimulation Architecture for Power System, Communication, and Market in the Smart Grid
Authors: Mirz Markus , Razik Lukas , Dinkelbach Jan , Tokel Halil Alper , Alirezaei Gholamreza , Mathar Rudolf , Monti Antonello
Published: February 2018

Smart grids evolve rapidly towards a system that includes components from different domains, which makes interdisciplinary modelling and analysis indispensable. In this paper, we present a cosimulation architecture for smart grids together with a comprehensive data model for the holistic representation of the power system, the communication network, and the energy market. Cosimulation is preferred over a monolithic approach since it allows leveraging the capabilities of existing, well‐established domain‐specific software. The challenges that arise in a multidomain smart grid cosimulation are identified for typical use cases through a discussion of the recent literature. Based on the identified requirements and use cases, a joint representation of the smart grid ecosystem is facilitated by a comprehensive data model. The proposed data model is then integrated in a software architecture, where the domain‐specific simulators for the power grid, the communication network, and the market mechanisms are combined in a cosimulation framework. The details of the software architecture and its implementation are presented. Finally, the implemented framework is used for the cosimulation of a virtual power plant, where battery storages are controlled by a novel peak‐shaving algorithm, and the battery storages and the market entity are interfaced through a communication network.
Myeloid Sarcoma after Allogenic Stem Cell Transplantation for Acute Myeloid Leukemia: Successful Consolidation Treatment Approaches in Two Patients
Authors: Johansen Silje , Kollsete Gjelberg Hilde , Ahmed Aymen Bushra , Bruserud Øystein , Reikvam Håkon
Published: February 2018

Myeloid sarcoma is an extramedullary (EM) manifestation (i.e., manifestation outside the bone marrow) of acute myeloid leukemia (AML); it is assumed to be relatively uncommon and can be the only manifestation of leukemia relapse after allogenic stem cell transplantation (allo-SCT). An EM sarcoma can manifest in any part of the body, although preferentially manifesting in immunological sanctuary sites as a single or multiple tumors. The development of myeloid sarcoma after allo-SCT is associated with certain cytogenetic abnormalities, developing of graft versus host disease (GVHD), and treatment with donor lymphocytes infusion (DLI). It is believed that posttransplant myeloid sarcomas develop because the EM sites evade immune surveillance. We present two patients with EM myeloid sarcoma in the breast and epipharynx, respectively, as the only manifestation of leukemia relapse. Both patients were treated with a combination of local and systemic therapy, with successfully longtime disease-free survival. Based on these two case reports, we give an updated review of the literature and discuss the pathogenesis, diagnosis, and treatment of EM sarcoma as the only manifestation of AML relapse after allo-SCT. There are no standard guidelines for the treatment of myeloid sarcomas in allotransplant recipients. In our opinion, the treatment of these patients needs to be individualized and should include local treatment (i.e., radiotherapy) combined with systemic therapy (i.e., chemotherapy, immunotherapy, DLI, or retransplantation). The treatment has to consider both the need for sufficient antileukemic efficiency versus the risk of severe complications due to cumulative toxicity.
Comparison among Reconstruction Algorithms for Quantitative Analysis of 11C-Acetate Cardiac PET Imaging
Authors: Shi Ximin , Li Nan , Ding Haiyan , Dang Yonghong , Hu Guilan , Liu Shuai , Cui Jie , Zhang Yue , Li Fang , Zhang Hui , Huo Li
Published: February 2018

Objective. Kinetic modeling of dynamic 11C-acetate PET imaging provides quantitative information for myocardium assessment. The quality and quantitation of PET images are known to be dependent on PET reconstruction methods. This study aims to investigate the impacts of reconstruction algorithms on the quantitative analysis of dynamic 11C-acetate cardiac PET imaging. Methods. Suspected alcoholic cardiomyopathy patients (N=24) underwent 11C-acetate dynamic PET imaging after low dose CT scan. PET images were reconstructed using four algorithms: filtered backprojection (FBP), ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), and OSEM with both time-of-flight and point-spread-function (TPSF). Standardized uptake values (SUVs) at different time points were compared among images reconstructed using the four algorithms. Time-activity curves (TACs) in myocardium and blood pools of ventricles were generated from the dynamic image series. Kinetic parameters K1 and k2 were derived using a 1-tissue-compartment model for kinetic modeling of cardiac flow from 11C-acetate PET images. Results. Significant image quality improvement was found in the images reconstructed using iterative OSEM-type algorithms (OSME, TOF, and TPSF) compared with FBP. However, no statistical differences in SUVs were observed among the four reconstruction methods at the selected time points. Kinetic parameters K1 and k2 also exhibited no statistical difference among the four reconstruction algorithms in terms of mean value and standard deviation. However, for the correlation analysis, OSEM reconstruction presented relatively higher residual in correlation with FBP reconstruction compared with TOF and TPSF reconstruction, and TOF and TPSF reconstruction were highly correlated with each other. Conclusion. All the tested reconstruction algorithms performed similarly for quantitative analysis of 11C-acetate cardiac PET imaging. TOF and TPSF yielded highly consistent kinetic parameter results with superior image quality compared with FBP. OSEM was relatively less reliable. Both TOF and TPSF were recommended for cardiac 11C-acetate kinetic analysis.
On the Use of Singular Vectors for the Flexibility‐Based Damage Detection under the Assumption of Unknown Structural Masses
Authors: Quqa Said , Landi Luca , Diotallevi Pier Paolo
Published: February 2018

The main purpose of this work is to investigate the usability of easily obtainable parameters instead of the modal traditional ones, in the context of a flexibility‐based damage detection procedure, under the assumption of unknown structural masses. To this aim, a comparison is made between two different approaches: the first involves the calculation of the flexibility matrix by using traditional modal parameters, such as natural frequencies and modal vectors, normalized to unitary values, while the second involves the use of singular vectors, obtained through a simple matrix factorization. The modal parameters and the singular vectors necessary for the implementation of the damage detection procedure are evaluated through two different techniques: the Eigensystem Realization Algorithm and a wavelet‐based procedure, for which a variant is proposed by introducing the energy reassignment concept into the original algorithm. Through the latter approach, in particular, it is possible to obtain a high number of singular vectors even in the case of reduced availability of sensors. The study is performed under the assumption of nonstationary excitation, in order to achieve general results, and the effectiveness of the procedures is evaluated through simulated tests regarding different structural schemes.
Zeb1 in Stromal Myofibroblasts Promotes Kras-Driven Development of Pancreatic Cancer
Authors: Sangrador Irene , Molero Xavier , Campbell Fiona , Franch-Expósito Sebastià , Rovira-Rigau Maria , Samper Esther , Domínguez-Fraile Manuel , Fillat Cristina , Castells Antoni , Vaquero Eva C.
Published: February 2018

The transcription factor Zeb1 has been identified as a crucial player in Kras-dependent oncogenesis. In pancreatic ductal adenocarcinoma (PDAC), Zeb1 is highly expressed in myofibroblasts and correlates with poor prognosis. As Kras mutations are key drivers in PDAC, we aimed here to assess the necessity of Zeb1 for Kras-driven PDAC and to define the role of Zeb1-expressing myofibroblasts in PDAC development. Genetically engineered mice with conditional pancreatic KrasG12D and Trp53 mutations (KPC) were crossed with Zeb1 haploinsufficient mice (Z+/−). Extensive PDAC was prominent in all 20-week-old KPC;Z+/+ mice, whereas only low-grade precursor lesions were detected in age-matched KPC;Z+/− littermates, with PDAC developing eventually in KPC;Z+/− aged animals. Zeb1 expression in myofibroblasts occurred early in tumorigenesis and Zeb1 haploinsufficiency retarded native expansion of stromal myofibroblasts during precursor-to-cancer progression. Zeb1 downregulation in mPSC repressed their activated gene profile, impaired their migratory and proliferative activity, and attenuated their tumor-supporting features. Conditioned media from Z+/+ mouse-activated (myofibroblast-like) pancreatic stellate cells (mPSC) boosted Ras activity in pancreatic cancer cells carrying mutant Kras; this effect was not observed when using conditioned media from Z+/− mPSC, revealing a paracrinal cooperative axis between Zeb1-expressing PSC and oncogenic Kras-bearing tumor cells. We conclude that Zeb1-expressing stromal myofibroblasts enable a heterotypic collaboration with the Kras-fated epithelial compartment, thus supporting pancreatic malignancy.

Significance: Zeb1 expression in stromal myofibroblasts supports PDAC development via collaboration with the epithelial compartment bearing oncogenic Kras mutations. Cancer Res; 78(10); 2624–37. ©2018 AACR.
Discovery and Validation of Circulating Biomarkers of Colorectal Adenoma by High-Depth Small RNA Sequencing
Authors: Roberts Brian S. , Hardigan Andrew A. , Moore Dianna E. , Ramaker Ryne C. , Jones Angela L. , Fitz-Gerald Meredith B. , Cooper Gregory M. , Wilcox C. Mel , Kimberly Robert P. , Myers Richard M.
Published: February 2018

Purpose: Colorectal cancer is the third most common cancer worldwide, causing approximately 700,000 deaths each year. The majority of colorectal cancers begin as adenomas. Definitive screening for colorectal adenomas is currently accomplished through colonoscopy but, owing largely to costs and invasiveness, is typically limited to patient groups at higher risk by virtue of age or family history. We sought to determine if blood-based small RNA markers could detect colorectal adenoma.

Experimental Design: We applied high-depth small RNA sequencing to plasma from a large (n = 189) cohort of patients, balanced for age, sex, and ancestry. Our analytical methodology allowed for the detection of both microRNAs and other small RNA species. We replicated sequencing results by qPCR on plasma samples from an independent cohort (n = 140).

Results: We found several small RNA species with significant associations to colorectal adenoma, including both microRNAs and non-microRNA small RNAs. These associations were robust to correction for patient covariates, including age. Among the adenoma-associated small RNAs, two, a miR-335-5p isoform and an un-annotated small RNA, were validated by qPCR in an independent cohort. A classifier trained on measures of these two RNAs in the discovery cohort yields an AUC of 0.755 (0.775 with age) for adenoma detection in the independent cohort. This classifier accurately detects adenomas in patients under 50 and is robust to sex or ancestry.

Conclusions: Circulating small RNAs (including but not limited to miRNAs) discovered by sequencing and validated by qPCR identify patients with colorectal adenomas effectively. Clin Cancer Res; 24(9); 2092–9. ©2018 AACR.
A Genetic Polymorphism in CTLA-4 Is Associated with Overall Survival in Sunitinib-Treated Patients with Clear Cell Metastatic Renal Cell Carcinoma
Authors: Liu Xiaoyan , Swen Jesse J. , Diekstra Meta H.M. , Boven Epie , Castellano Daniel , Gelderblom Hans , Mathijssen Ron H.J. , Vermeulen Sita H. , Oosterwijk Egbert , Junker Kerstin , Roessler Max , Alexiusdottir Kristin , Sverrisdottir Asgerdur , Radu Marius T. , Ambert Valentin , Eisen Tim , Warren Anne , Rodríguez-Antona Cristina , García-Donas Jesus , Böhringer Stefan , Koudijs Karel K.M. , Kiemeney Lambertus A.L.M. , Rini Brian I. , Guchelaar Henk-Jan
Published: February 2018

Purpose: The survival of patients with clear cell metastatic renal cell carcinoma (cc-mRCC) has improved substantially since the introduction of tyrosine kinase inhibitors (TKI). With the fact that TKIs interact with immune responses, we investigated whether polymorphisms of genes involved in immune checkpoints are related to the clinical outcome of cc-mRCC patients treated with sunitinib as first TKI.

Experimental Design: Twenty-seven single-nucleotide polymorphisms (SNP) in CD274 (PD-L1), PDCD1 (PD-1), and CTLA-4 were tested for a possible association with progression-free survival (PFS) and overall survival (OS) in a discovery cohort of 550 sunitinib-treated cc-mRCC patients. SNPs with a significant association (P < 0.05) were tested in an independent validation cohort of 138 sunitinib-treated cc-mRCC patients. Finally, data of the discovery and validation cohort were pooled for meta-analysis.

Results: CTLA-4 rs231775 and CD274 rs7866740 showed significant associations with OS in the discovery cohort after correction for age, gender, and Heng prognostic risk group [HR, 0.84; 95% confidence interval (CI), 0.72–0.98; P = 0.028, and HR, 0.73; 95% CI, 0.54–0.99; P = 0.047, respectively]. In the validation cohort, the associations of both SNPs with OS did not meet the significance threshold of P < 0.05. After meta-analysis, CTLA-4 rs231775 showed a significant association with OS (HR, 0.83; 95% CI, 0.72–0.95; P = 0.008). Patients with the GG genotype had longer OS (35.1 months) compared with patients with an AG (30.3 months) or AA genotype (24.3 months). No significant associations with PFS were found.

Conclusions: The G-allele of rs231775 in the CTLA-4 gene is associated with an improved OS in sunitinib-treated cc-mRCC patients and could potentially be used as a prognostic biomarker. Clin Cancer Res; 24(10); 2350–6. ©2018 AACR.
Case Reports of Acne and Homeopathy
Authors: Nwabudike Lawrence C.
Published: February 2018

Background: Acne vulgaris is a self-limiting disorder of the pilosebaceous unit. The aesthetic aspect of the disorder may provoke depression and diminish the quality of life. A number of agents are used for acne treatment, e.g., retinoids, antibiotics, benzoic acid, azelaic acid, and hormones. These agents have side-effects, sometimes severe ones. Case Reports: Presented are 2 cases of severe acne treated with individualized homeopathic medicines. Both patients were treated using the classical method of homeopathy, i.e., a single medicine based on the patient's individual characteristics was prescribed. The cases were documented photographically at onset and during the course of treatment. Both patients went into remission following treatment, and long-term follow-up suggested that the therapy remained efficacious long after cessation of treatment. No significant side effects were noted. Conclusions: Homeopathic medicines may be useful as stand-alone treatment of patients with severe acne vulgaris. A case series suggested a remission rate of more than 80% using individualized homeopathic treatment. The treatment remained efficacious long after cessation and is not accompanied by significant side-effects. It is to be hoped that this presentation will stimulate research interest into homeopathic medicines as stand-alone or adjunct treatments of acne.
High Right Ventricular Stroke Work Index Is Associated with Worse Kidney Function in Patients with Heart Failure with Preserved Ejection Fraction
Authors: Kanjanahattakij Napatt , Sirinvaravong Natee , Aguilar Francisco , Agrawal Akanksha , Krishnamoorthy Parasuram , Gupta Shuchita
Published: February 2018

Background: In patients with heart failure with preserved ejection fraction (HFpEF), worse kidney function is associated with worse overall cardiac mechanics. Right ventricular stroke work index (RVSWI) is a parameter of right ventricular function. The aim of our study was to determine the relationship between RVSWI and glomerular filtration rate (GFR) in patients with HFpEF. Method: This was a single-center cross-sectional study. HFpEF is defined as patients with documented heart failure with ejection fraction > 50% and pulmonary wedge pressure > 15 mm Hg from right heart catheterization. RVSWI (normal value 8–12 g/m/beat/m2) was calculated using the formula: RVSWI = 0.0136 × stroke volume index × (mean pulmonary artery pressure – mean right atrial pressure). Univariate and multivariate linear regression analysis was performed to study the correlation between RVSWI and GFR. Result: Ninety-one patients were included in the study. The patients were predominantly female (n = 64, 70%) and African American (n = 61, 67%). Mean age was 66 ± 12 years. Mean GFR was 59 ± 35 mL/min/1.73 m2. Mean RVSWI was 11 ± 6 g/m/beat/m2. Linear regression analysis showed that there was a significant independent inverse relationship between RVSWI and GFR (unstandardized coefficient = –1.3, p = 0.029). In the subgroup with combined post and precapillary pulmonary hypertension (Cpc-PH) the association remained significant (unstandardized coefficient = –1.74, 95% CI –3.37 to –0.11, p = 0.04). Conclusion: High right ventricular workload indicated by high RVSWI is associated with worse renal function in patients with Cpc-PH. Further prospective studies are needed to better understand this association.
TOP3B: A Novel Candidate Gene in Juvenile Myoclonic Epilepsy?
Authors: Daghsni Marwa , Lahbib Saida , Fradj Mohamed , Sayeb Marwa , Kelmemi Wided , Kraoua Lilia , Kchaou Mariem , Maazoul Faouzi , Echebbi Slim , Ben Ali Nadia , Abdelhak Sonia , M'rad Ridha
Published: February 2018

Juvenile myoclonic epilepsy (JME) is characterized by seizures, severe cognitive abnormalities, and behavior impairments. These features could evolve over time and get worse, especially when the encephalopathy is pharmacoresistant. Thus, genetic studies should provide a better understanding of infantile epilepsy syndromes. Herein, we investigate the genetics of JME in a consanguineous family analyzing the copy number variations detected using over 700 K SNP arrays. We identified a 254-kb deletion in the 22q11.2 region, including only the TOP3B gene, detected in the patient and her father. TOP3B encodes a topoisomerase DNA (III) β protein and has been implicated in several neurological diseases such as schizophrenia and autism. In this study, we discuss the implication of the 22q11.2 region in neurodevelopmental disorders and the association of TOP3B with epilepsy.