bluuebunny/crossref_metadata_2025 huggingface dataset:
Diverse and Complex Challenges to Migrant and Refugee Mental Health: Reflections of the M8 Alliance Expert Group on Migrant Health
Authors: Sheath Danny , Flahault Antoine , Seybold Joachim , Saso Luciano
Published: May 2020

Forced migration is likely to continue to grow in the coming years due to climate change, disease outbreaks, conflict, and other factors. There are a huge number of challenges to maintaining good health, and specifically good mental health, among migrants at all stages of migration. It is vital to fully understand these diverse challenges so that we can work towards overcoming them. In 2017, as a response to the growing health challenges faced by migrants and refugees, the M8 Alliance created an expert group focussing on migrant and refugee health. The group meets annually at the Sapienza University of Rome, Italy, and this article is based on the discussions that took place at the third annual meeting (6–7 June 2019) and a special session on “Protecting the Mental Health of Refugees and Migrants,” which took place on 27 October at the World Health Summit 2019 in Berlin. Our discussions are also supported by supplementary literature to present the diverse and complex challenges to the mental health of migrants and refugees. We conclude with some lessons learned and hope for the future.
Influence of Body Dissatisfaction on the Self-Esteem of Brazilian Adolescents: A Cross-Sectional Study
Authors: Macêdo Uchôa Francisco Nataniel , Uchôa Natalia Macêdo , Daniele Thiago Medeiros da Costa , Lustosa Romário Pinheiro , Nogueira Paulo Roberto de Castro , Reis Victor Machado , Andrade Joaquim Huaina Cintra , Deana Naira Figueiredo , Aranha Ágata Marques , Alves Nilton
Published: May 2020

Background: The present study investigated the influence of body dissatisfaction (BD) on the self-esteem of Brazilian adolescents. Methods: A cross-sectional study was carried out with 1011 students at public and private schools in the city of Fortaleza, Brazil. The body shape questionnaire and the Rosenberg self-esteem scale were applied. Chi-square test, Student’s t-test, Pearson’s correlation, the odds ratio and binary logistic regression were used. Results: The rate of low self-esteem was 33.8% in the adolescents; 27.8% of the adolescents presented some degree of BD, with severe BD in 5.8%. A significant low negative correlation was found between self-esteem and BD in all the adolescents. In the Odds Ratio analysis, it was observed that the odds of having low self-esteem increased in adolescents with BD as compared to adolescents without BD, being 3.85 times higher in females (CI 95%, 2.12–6.99), 2.83 times higher in males (CI 95%, 1.22–6.58), 5.79 times higher in adolescents attending public schools (CI 95% 2.06–16.26), and 2.96 times higher in adolescents attending private schools (CI 95%, 1.79–4.88). Conclusions: Low self-esteem affected one-third of the adolescents, both male and female. BD and education in public schools are predictor variables of low self-esteem in adolescents.
CARs: Beyond T Cells and T Cell-Derived Signaling Domains
Authors: Sievers Nico M. , Dörrie Jan , Schaft Niels
Published: May 2020

When optimizing chimeric antigen receptor (CAR) therapy in terms of efficacy, safety, and broadening its application to new malignancies, there are two main clusters of topics to be addressed: the CAR design and the choice of transfected cells. The former focuses on the CAR construct itself. The utilized transmembrane and intracellular domains determine the signaling pathways induced by antigen binding and thereby the cell-specific effector functions triggered. The main part of this review summarizes our understanding of common signaling domains employed in CARs, their interactions among another, and their effects on different cell types. It will, moreover, highlight several less common extracellular and intracellular domains that might permit unique new opportunities. Different antibody-based extracellular antigen-binding domains have been pursued and optimized to strike a balance between specificity, affinity, and toxicity, but these have been reviewed elsewhere. The second cluster of topics is about the cellular vessels expressing the CAR. It is essential to understand the specific attributes of each cell type influencing anti-tumor efficacy, persistence, and safety, and how CAR cells crosstalk with each other and bystander cells. The first part of this review focuses on the progress achieved in adopting different leukocytes for CAR therapy.
Vitamin D and Cardiovascular Risk: Which Implications in Children?
Authors: Savastio Silvia , Pozzi Erica , Tagliaferri Francesco , Degrandi Roberta , Cinquatti Roberta , Rabbone Ivana , Bona Gianni
Published: May 2020

Vitamin D (25OHD) pleiotropic effects are widely recognized and studied. Recently, vitamin D cardiovascular effects are gaining interest, especially in children, although the studies present conflicting data. Some randomized controlled trials (RCTs) have demonstrated that cardiovascular risk markers, such as lipid parameters, inflammation markers, blood pressure, and arterial stiffness, are unaffected by vitamin D supplementation. By contrast, other studies show that low vitamin D levels are associated with higher risk of cardiovascular disease (CVD) and mortality, and support that increased risk of these diseases occurs primarily in people with vitamin D deficiency. An update on these points in pediatric patients is certainly of interest to focus on possible benefits of its supplementation.
Reduction of Secreted Frizzled-Related Protein 5 Drives Vascular Calcification through Wnt3a-Mediated Rho/ROCK/JNK Signaling in Chronic Kidney Disease
Authors: Oh Yun Jung , Kim Hyunsook , Kim Ae Jin , Ro Han , Chang Jae Hyun , Lee Hyun Hee , Chung Wookyung , Jun Hee-Sook , Jung Ji Yong
Published: May 2020

Vascular calcification (VC) is commonly associated with bone loss in patients with chronic kidney disease (CKD). The Wingless-related integration site (Wnt) regulates osteoblast activation through canonical signaling pathways, but the common pathophysiology of these pathways during VC and bone loss has not been identified. A rat model of adenine-induced CKD with VC was used in this study. The rats were fed 0.75% adenine (2.5% protein, 0.92% phosphate) with or without intraperitoneal injection of calcitriol (0.08 µg/kg/day) for 4 weeks. Angiotensin II (3 µM)-induced VC was achieved in high phosphate medium (3 mM) through its effect on vascular smooth muscle cells (VSMCs). In an mRNA profiler polymerase chain reaction assay of the Wnt signaling pathway, secreted frizzled-related protein 5 (sFRP5) levels were significantly decreased in the CKD rat model compared with the control group. The repression of sFRP5 on VSMC trans-differentiation was mediated through Rho/Rho-associated coiled coil containing protein kinase (ROCK) and c-Jun N-terminal kinase (JNK) pathways activated by Wnt3a. In a proof of concept study conducted with patients with CKD, serum sFRP5 concentrations were significantly lower in subjects with VC than in those without VC. Our findings suggest that repression of sFRP5 is associated with VC in the CKD environment via activation of the noncanonical Wnt pathway, and thus that sFRP5 might be a novel therapeutic target for VC in CKD.
Single-Nucleotide Polymorphisms (SNPs) Both Associated with Hypertension and Contributing to Accelerated-Senescence Traits in OXYS Rats
Authors: Devyatkin Vasiliy A. , Redina Olga E. , Muraleva Natalia A. , Kolosova Nataliya G.
Published: May 2020

Aging is a major risk factor of numerous human diseases. Adverse genetic variants may contribute to multiple manifestations of aging and increase the number of comorbid conditions. There is evidence of links between hypertension and age-related diseases, although the genetic relationships are insufficiently studied. Here, we investigated the contribution of hypertension to the development of accelerated-senescence syndrome in OXYS rats. We compared transcriptome sequences of the prefrontal cortex, hippocampus, and retina of OXYS rats with the genotypes of 45 rat strains and substrains (which include models with hypertension) to find single-nucleotide polymorphisms (SNPs) both associated with hypertension and possibly contributing to the development of age-related diseases. A total of 725 polymorphisms were common between OXYS rats and one or more hypertensive rat strains/substrains being analyzed. Multidimensional scaling detected significant similarities between OXYS and ISIAH rat genotypes and significant differences between these strains and the other hypertensive rat strains/substrains. Nonetheless, similar sets of SNPs produce a different phenotype in OXYS and ISIAH rats depending on hypertension severity. We identified 13 SNPs causing nonsynonymous amino-acid substitutions having a deleterious effect on the structure or function of the corresponding proteins and four SNPs leading to functionally significant structural rearrangements of transcripts in OXYS rats. Among them, SNPs in genes Ephx1, Pla2r1, and Ccdc28b were identified as candidates responsible for the concomitant manifestation of hypertension and signs of accelerated aging in OXYS rats.
The Regulation of Intestinal Mucosal Barrier by Myosin Light Chain Kinase/Rho Kinases
Authors: Jin Younggeon , Blikslager Anthony T.
Published: May 2020

The intestinal epithelial apical junctional complex, which includes tight and adherens junctions, contributes to the intestinal barrier function via their role in regulating paracellular permeability. Myosin light chain II (MLC-2), has been shown to be a critical regulatory protein in altering paracellular permeability during gastrointestinal disorders. Previous studies have demonstrated that phosphorylation of MLC-2 is a biochemical marker for perijunctional actomyosin ring contraction, which increases paracellular permeability by regulating the apical junctional complex. The phosphorylation of MLC-2 is dominantly regulated by myosin light chain kinase- (MLCK-) and Rho-associated coiled-coil containing protein kinase- (ROCK-) mediated pathways. In this review, we aim to summarize the current state of knowledge regarding the role of MLCK- and ROCK-mediated pathways in the regulation of the intestinal barrier during normal homeostasis and digestive diseases. Additionally, we will also suggest potential therapeutic targeting of MLCK- and ROCK-associated pathways in gastrointestinal disorders that compromise the intestinal barrier.
The Role of TRM Cells in the Pathogenesis of Vitiligo—A Review of the Current State-Of-The-Art
Authors: Frączek Alicja , Owczarczyk-Saczonek Agnieszka , Placek Waldemar
Published: May 2020

Vitiligo is the most common hypopigmentation disease affecting both the skin and mucous membranes. The pathogenesis of this disorder is complex and involves the influence of genetic and environmental factors, oxidative stress, and autoimmune responses. Recent studies have indicated that skin lesions observed in vitiligo tend to recur in the same places where they were found before treatment. This phenomenon is explained by the presence of recently discovered tissue-resident memory T cells (TRM), whose primary function is to provide antiviral and antibacterial protection in non-lymphoid tissues. TRM cells show the presence of CD49a, CD69, and CD103 markers on their surface, although not all of them express these particles. Due to their ability to produce and secrete perforin, IFN-γ, and granzyme B, TRM cells demonstrate a cytotoxic effect on melanocytes, thus inducing depigmented lesions in the course of the vitiligo. It has been proved that the occurrence of TRM cells largely depends on IL-15, which promotes the TRM function ex vivo. The findings above, as well as their reference to the pathogenesis of autoimmune skin diseases will have a considerable influence on the development of new therapeutic strategies in the near future. This article presents an up-to-date review of information regarding the role of TRM cells in the development and progression of vitiligo.
Ion Channels of Nociception
Authors: Giniatullin Rashid
Published: May 2020

The special issue “Ion Channels of Nociception” contains 13 articles published by 73 authors from different countries united by the main focusing on the peripheral mechanisms of pain. The content covers the mechanisms of neuropathic, inflammatory, and dental pain as well as pain in migraine and diabetes, nociceptive roles of P2X3, ASIC, Piezo and TRP channels, pain control through GPCRs and pharmacological agents and non-pharmacological treatment with electroacupuncture.
Antibacterial Action of Nanoparticle Loaded Nanocomposites Based on Graphene and Its Derivatives: A Mini-Review
Authors: Díez-Pascual Ana María
Published: May 2020

Bacterial infections constitute a severe problem in various areas of everyday life, causing pain and death, and adding enormous costs to healthcare worldwide. Besides, they cause important concerns in other industries, such as cloth, food packaging, and biomedicine, among others. Despite the intensive efforts of academics and researchers, there is lack of a general solutions to restrict bacterial growth. Among the various approaches, the use of antibacterial nanomaterials is a very promising way to fight the microorganisms due to their high specific surface area and intrinsic or chemically incorporated antibacterial action. Graphene, a 2D carbon-based ultra-thin biocompatible nanomaterial with excellent mechanical, thermal, and electrical properties, and its derivatives, graphene oxide (GO) and reduced graphene oxide (rGO), are highly suitable candidates for restricting microbial infections. However, the mechanisms of antimicrobial action, their cytotoxicity, and other issues remain unclear. This mini-review provides select examples on the leading advances in the development of antimicrobial nanocomposites incorporating inorganic nanoparticles and graphene or its derivatives, with the aim of providing a better understanding of the antibacterial properties of graphene-based nanomaterials.
Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes
Authors: di Giacomo Viviana , Chiavaroli Annalisa , Recinella Lucia , Orlando Giustino , Cataldi Amelia , Rapino Monica , Di Valerio Valentina , Ronci Maurizio , Leone Sheila , Brunetti Luigi , Menghini Luigi , Zengin Gokhan , Ak Gunes , Abdallah Hassan H. , Ferrante Claudio
Published: May 2020

Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols. Although CBD’s effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.
The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening
Authors: Priestley Jessica R. C. , Alharbi Hana , Callahan Katharine Press , Guzman Herodes , Payan-Walters Irma , Smith Ligia , Ficicioglu Can , Ganetzky Rebecca D. , Ahrens-Nicklas Rebecca C.
Published: May 2020

Tyrosinemia type I (TT1) is an inborn error of tyrosine metabolism with features including liver dysfunction, cirrhosis, and hepatocellular carcinoma; renal dysfunction that may lead to failure to thrive and bone disease; and porphyric crises. Once fatal in most infantile-onset cases, pre-symptomatic diagnosis through newborn screening (NBS) protocols, dietary management, and pharmacotherapy with nitisinone have improved outcomes. Succinylacetone provides a sensitive and specific marker for the detection of TT1 but is not universally utilized in screening protocols for the disease. Here, we report an infant transferred to our facility for evaluation and management of hyperinsulinism who subsequently developed acute-onset liver, respiratory, and renal failure around one month of life. She was found to have TT1 caused by novel pathogenic variant in fumarylacetoacetate hydrolase (c.1014 delC, p.Cys 338 Ter). Her NBS, which utilized tyrosine as a primary marker, had been reported as normal, with a tyrosine level of 151 µmol/L (reference: <280 µmol/L). Retrospective analysis of dried blood spot samples via tandem mass spectrometry showed detectable succinylacetone ranging 4.65–10.34 µmol/L. To our knowledge, this is the first patient with TT1 whose initial presenting symptom was hyperinsulinemic hypoglycemia. The case highlights the importance of maintaining a high suspicion for metabolic disease in critically ill children, despite normal NBS. We also use the case to advocate for NBS for TT1 using succinylacetone quantitation.
Reliable Estimation of Urban Link Travel Time Using Multi-Sensor Data Fusion
Authors: Guo Yajuan , Yang Licai
Published: May 2020

Travel time is one of the most critical indexes to describe urban traffic operating states. How to obtain accurate and robust travel time estimates, so as to facilitate to make traffic control decision-making for administrators and trip-planning for travelers, is an urgent issue of wide concern. This paper proposes a reliable estimation method of urban link travel time using multi-sensor data fusion. Utilizing the characteristic analysis of each individual traffic sensor data, we first extract link travel time from license plate recognition data, geomagnetic detector data and floating car data, respectively, and find that their distribution patterns are similar and follow logarithmic normal distribution. Then, a support degree algorithm based on similarity function and a credibility algorithm based on membership function are developed, aiming to overcome the conflicts among multi-sensor traffic data and the uncertainties of single-sensor traffic data. The reliable fusion weights for each type of traffic sensor data are further determined by integrating the corresponding support degree with credibility. A case study was conducted using real-world data from a link of Jingshi Road in Jinan, China and demonstrated that the proposed method can effectively improve the accuracy and reliability of link travel time estimations in urban road systems.
MNCE: Multi-Hop Node Localization Algorithm for Wireless Sensor Network Based on Error Correction
Authors: Meng Yinghui , Chen Yuewen , Zhang Qiuwen , Zhang Weiwei
Published: May 2020

Considering the problems of large error and high localization costs of current range-free localization algorithms, a MNCE algorithm based on error correction is proposed in this study. This algorithm decomposes the multi-hop distance between nodes into several small hops. The distance of each small hop is estimated by using the connectivity information of adjacent nodes; small hops are accumulated to obtain the initial estimated distance. Then, the error-correction rate based on the error-correction concept is proposed to correct the initial estimated distance. Finally, the location of the target node is resolved by total least square methods, according to the information on the anchor nodes and estimated distances. Simulation experiments show that the MNCE algorithm is superior to the similar types of localization algorithms.
Modeling Road Accident Severity with Comparisons of Logistic Regression, Decision Tree and Random Forest
Authors: Chen Mu-Ming , Chen Mu-Chen
Published: May 2020

To reduce the damage caused by road accidents, researchers have applied different techniques to explore correlated factors and develop efficient prediction models. The main purpose of this study is to use one statistical and two nonparametric data mining techniques, namely, logistic regression (LR), classification and regression tree (CART), and random forest (RF), to compare their prediction capability, identify the significant variables (identified by LR) and important variables (identified by CART or RF) that are strongly correlated with road accident severity, and distinguish the variables that have significant positive influence on prediction performance. In this study, three prediction performance evaluation measures, accuracy, sensitivity and specificity, are used to find the best integrated method which consists of the most effective prediction model and the input variables that have higher positive influence on accuracy, sensitivity and specificity.
Optimal Speed Plan for the Overtaking of Autonomous Vehicles on Two-Lane Highways
Authors: Easa Said M. , Diachuk Maksym
Published: May 2020

In passing maneuvers on two-lane highways, assessing the needed distance and the potential power reserve to ensure the required speed mode of the passing vehicle is a critical task of speed planning. This task must meet several mutually exclusive conditions that lead to successful maneuvers. This paper addresses three main aspects. First, the issues associated with a rational distribution of the speed of the passing vehicle for overtaking a long commercial vehicle on two-lane highways are discussed. The factors that affect the maneuver effectiveness are analyzed, considering the safety and cost. Second, a heuristic algorithm is proposed based on the rationale for choosing the necessary space and time for overtaking. The initial prediction’s sensitivity to fluctuations of the current measurements of the position and speed of the overtaking participants is examined. Third, an optimization technique for the passing vehicle speed distribution during the overtaking time using the finite element method is presented. Adaptive model predictive control is applied for tracking the references being generated. The presented model is illustrated using a simulation.
Drench Application of Systemic Insecticides Disrupts Probing Behavior of Diaphorina citri (Hemiptera: Liviidae) and Inoculation of Candidatus Liberibacter asiaticus
Authors: Carmo-Sousa Michele , Garcia Rafael Brandão , Wulff Nelson Arno , Fereres Alberto , Miranda Marcelo Pedreira
Published: May 2020

Candidatus Liberibacter asiaticus (CLas) is a phloem-limited bacterium that is associated with the Huanglongbing (HLB) disease of citrus and transmitted by the psyllid, Diaphorina citri. There are no curative methods to control HLB and the prevention of new infections is essential for HLB management. Therefore, the objective of our study was to determine the effects of systemic insecticides, such as the neonicotinoids imidacloprid, thiamethoxam, and a mixture of thiamethoxam and chlorantraniliprole (diamide) on the probing behavior of CLas-infected D. citri and their effect on CLas transmission. The electrical penetration graph (EPG-DC) technique was used to monitor the stylet penetration activities of CLas-infected D. citri on sweet orange [Citrus sinensis (L.) Osbeck] ‘Valencia’ treated with systemic insecticides. Systemic insecticides disrupted the probing behavior of CLas-infected D. citri, in a way that affected CLas transmission efficiency, particularly by negatively affecting the stylet activities related to the phloem phase. All insecticides reduced (by 57–73%) the proportion of psyllids that exhibited sustainable phloem ingestion (waveform E2 > 10 min), with significant differences observed on plants treated with thiamethoxam and thiamethoxam + chlorantraniliprole. The transmission rate of CLas with high inoculum pressure (five CLas-infected D. citri per plant and a seven-day inoculation access period) to untreated control plants was 93%. In contrast, CLas transmission was reduced to 38.8% when test plants were protected by systemic insecticides. Our results indicated that all insecticides tested presented a potential to reduce CLas inoculation by an average of 59%; therefore, these insecticides can be used to reduce the spread of HLB.
Seventh User Workshop on High-Power Lasers at the Linac Coherent Light Source
Authors: Dyer Gilliss , Bolme Cindy , Glenzer Siegfried
Published: May 2020

We report on a seventh annual workshop in a series focused on science realized by the combination of hard X-ray free electron lasers with high power optical lasers, hosted at the SLAC National Accelerator Laboratory in Menlo Park, CA. Members from the user community of the Matter in Extreme Conditions (MEC) endstation of the Linac Coherent Light Source (LCLS) and other scientists met with local scientists to discuss developments at LCLS and MEC and related facilities, including experimental results and future plans.
Contemporary Management of Acute Lower Limb Ischemia: Determinants of Treatment Choice
Authors: Lukasiewicz Aleksander
Published: May 2020

The role of endovascular procedures in the treatment of acute lower limb ischemia (ALI) is expanding. For treatment, the choice between surgical or endovascular is still debated. The aim of this study was to identify factors that determine the selection of treatment. This study included 307 ALI patients (209 with thrombosis). Patient details, factors affecting the procedure choice, and outcomes were analyzed. The majority of patients were operated on (52.4%). Surgery was more frequent in embolic patients with embolus (odds ratio (OR) 33.85; 95% confidence interval (CI) 6.22–184.19, p < 0.0001), severe ischemia (OR 1.79; 95% CI 1.2–2.66, p = 0.0041), and active cancer (OR 4.99; 95% CI 1.26–19.72, p = 0.02). Tibial arteries involvement was negatively related to surgery (OR 0.25; 95% CI 0.06–0.95, p = 0.04). The complications and amputation rates were comparable. Reinterventions were more common in the endovascular group (19 (20.2%) vs. 17 (8.9%), p = 0.007). The six-month mortality was higher in the operated patients (12.6% vs. 3.2%, respectively, p = 0.001). The determinants of the treatment path are ischemia severity, concurrent cancer, embolus, and peripheral lesion location. Modification of the Rutherford acute lower limb ischemia classification is required to improve the decision-making in patients with profound ischemia.
Different Shades of L1CAM in the Pathophysiology of Cancer Stem Cells
Authors: Giordano Marco , Cavallaro Ugo
Published: May 2020

L1 cell adhesion molecule (L1CAM) is aberrantly expressed in several tumor types where it is causally linked to malignancy and therapy resistance, acting also as a poor prognosis factor. Accordingly, several approaches have been developed to interfere with L1CAM function or to deliver cytotoxic agents to L1CAM-expressing tumors. Metastatic dissemination, tumor relapse and drug resistance can be fueled by a subpopulation of neoplastic cells endowed with peculiar biological properties that include self-renewal, efficient DNA repair, drug efflux machineries, quiescence, and immune evasion. These cells, known as cancer stem cells (CSC) or tumor-initiating cells, represent, therefore, an ideal target for tumor eradication. However, the molecular and functional traits of CSC have been unveiled only to a limited extent. In this context, it appears that L1CAM is expressed in the CSC compartment of certain tumors, where it plays a causal role in stemness itself and/or in biological processes intimately associated with CSC (e.g., epithelial-mesenchymal transition (EMT) and chemoresistance). This review summarizes the role of L1CAM in cancer focusing on its functional contribution to CSC pathophysiology. We also discuss the clinical usefulness of therapeutic strategies aimed at targeting L1CAM in the context of anti-CSC treatments.
EPICANCER—Cancer Patients Presenting to the Emergency Departments in France: A Prospective Nationwide Study
Authors: Peyrony Olivier , Fontaine Jean-Paul , Beaune Sébastien , Khoury Abdo , Truchot Jennifer , Balen Frédéric , Vally Rishad , Schmitt Jacques , Ben Hammouda Kasarra , Roussel Mélanie , Borzymowski Céline , Vallot Cécile , Sanh Veronique , Azoulay Elie , Chevret Sylvie
Published: May 2020

Background: We aimed to estimate the prevalence of cancer patients who presented to Emergency Departments (EDs), report their chief complaint and identify the predictors of 30-day all-cause mortality. Patients and methods: we undertook a prospective, cross-sectional study during three consecutive days in 138 EDs and performed a logistic regression to identify the predictors of 30-day mortality in hospitalized patients. Results: A total of 1380 cancer patients were included. The prevalence of cancer patients among ED patients was 2.8%. The most frequent reasons patients sought ED care were fatigue (16.6%), dyspnea (16.3%), gastro-intestinal disorders (15.1%), trauma (13.0%), fever (12.5%) and neurological disorders (12.5%). Patients were admitted to the hospital in 64.9% of cases, of which 13.4% died at day 30. Variables independently associated with a higher mortality at day 30 were male gender (Odds Ratio (OR), 1.63; 95% CI, 1.04–2.56), fatigue (OR, 1.65; 95% CI, 1.01–2.67), poor performance status (OR, 3.00; 95% CI, 1.87–4.80), solid malignancy (OR, 3.05; 95% CI, 1.26–7.40), uncontrolled malignancy (OR, 2.27; 95% CI, 1.36–3.80), ED attendance for a neurological disorder (OR, 2.38; 95% CI, 1.36–4.19), high shock-index (OR, 1.80; 95% CI, 1.03–3.13) and oxygen therapy (OR, 2.68; 95% CI, 1.68–4.29). Conclusion: Cancer patients showed heterogeneity among their reasons for ED attendance and a high need for hospitalization and case fatality. Malignancy and general health status played a major role in the patient outcomes. This study suggests that the emergency care of cancer patients may be complex. Thus, studies to assess the impact of a dedicated oncology curriculum for ED physicians are warranted.
Advancing the Science and Management of Renal Cell Carcinoma: Bridging the Divide between Academic and Community Practices
Authors: Salgia Nicholas J. , Philip Errol J. , Ziari Mohammadbagher , Yap Kelly , Pal Sumanta Kumar
Published: May 2020

The treatment of metastatic renal cell carcinoma (mRCC) has rapidly evolved; however, the progress made in the field is heavily contingent upon timely and efficient accrual to clinical trials. While a substantial proportion of accrual occurs at tertiary care centers, community sites are playing an increasing role in patient recruitment. In this article, we discuss strategies to optimize collaborations between academic and community sites to facilitate clinical research. Further, as the role of biomarker discovery has become increasingly important in tailoring therapy, we will discuss opportunities to bridge diverse accrual sites for the purpose of translational research.
Location First: Targeting Acute Myeloid Leukemia Within Its Niche
Authors: Pievani Alice , Biondi Marta , Tomasoni Chiara , Biondi Andrea , Serafini Marta
Published: May 2020

Despite extensive research and development of new treatments, acute myeloid leukemia (AML)-backbone therapy has remained essentially unchanged over the last decades and is frequently associated with poor outcomes. Eradicating the leukemic stem cells (LSCs) is the ultimate challenge in the treatment of AML. Emerging evidence suggests that AML remodels the bone marrow (BM) niche into a leukemia-permissive microenvironment while suppressing normal hematopoiesis. The mechanism of stromal-mediated protection of leukemic cells in the BM is complex and involves many adhesion molecules, chemokines, and cytokines. Targeting these factors may represent a valuable approach to complement existing therapies and overcome microenvironment-mediated drug resistance. Some strategies for dislodging LSCs and leukemic blasts from their protective niche have already been tested in patients and are in different phases of the process of clinical development. Other strategies, such as targeting the stromal cells remodeling processes, remain at pre-clinical stages. Development of humanized xenograft mouse models, which overcome the mismatch between human leukemia cells and the mouse BM niche, is required to generate physiologically relevant, patient-specific human niches in mice that can be used to unravel the role of human AML microenvironment and to carry out preclinical studies for the development of new targeted therapies.
The Role of the CYP11B2 Promoter Polymorphism in the Diagnosis of Primary Aldosteronism
Authors: Żukowski Łukasz , Wawrusiewicz-Kurylonek Natalia , Szumowski Piotr , Mojsak Małgorzata , Abdelrazek Saeid , Myśliwiec Janusz
Published: May 2020

Background: nowadays, primary aldosteronism (PA) is suggested to be the most frequent cause of secondary hypertension and it reaches 10% of whole hypertensive population. The CYP11B2 promoter polymorphism might cause aldosterone overproduction. The aim of this study was to establish whether the polymorphism CYP11B2 promoter has a significant impact on diagnostic of PA. Material and Methods: study group consisted of 239 hypertensive patients previously diagnosed with adrenal incidentaloma. For diagnose of PA were performed: screening test–aldosterone-renin ratio (ARR) and saline suppression test (SIT) as a confirmatory test. Genotyping was carried out by the real time PCR method. The significance of differences between the groups was evaluated through Student’s t-test. Results: our study revealed that genotype TT had plasma aldosterone concentration (PAC), ARR and SIT significantly higher in comparison with CC patients. The mean PAC in CC was 12.71 ng/dL vs. 20.55 ng/dL in TT patients (p = 0.037), which consequently gave a higher ARR in TT patients (119 vs. 44, p = 0.034). Mean aldosterone concentration in SIT was 2.40 ng/dL in CC patients and 9.99 ng/dL in TT patients (p = 0.046). Patients with CC genotype required less hypotensive drugs in comparison with TT genotype (p = 0.044). PA was recognized in 16 patients. Nine patients had TC genotype, six TT, and one with CC genotype. Conclusion: our study revealed predisposing TT genotype to PA. Additionally, patients with TT genotype, regardless of the PA presence, had more severe hypertension. The determination of the CYP11B2 promoter polymorphism seems to be useful in the diagnosis of PA, especially in cases where it is difficult to properly prepare patients for hormonal tests or even results of the hormonal test are incoherent.
Does Motor Cortex Engagement During Movement Preparation Differentially Inhibit Nociceptive Processing in Patients with Chronic Whiplash Associated Disorders, Chronic Fatigue Syndrome and Healthy Controls? An Experimental Study
Authors: Goudman Lisa , Mouraux André , Daenen Liesbeth , Nijs Jo , Cras Patrick , Roussel Nathalie , Moens Maarten , Lenoir Dorine , Coppieters Iris , Huysmans Eva , De Kooning Margot
Published: May 2020

Background: Patients with chronic fatigue syndrome (CFS) and chronic whiplash associated disorders (cWAD) present a reduced ability to activate central descending nociceptive inhibition after exercise, compared to measurements before exercise. It was hypothesised that a dysfunctional motor-induced inhibition of nociception partly explains this dysfunctional exercise-induced hypoalgesia. This study investigates if engagement of the motor system during movement preparation inhibits nociception-evoked brain responses in these patients as compared to healthy controls (HC). Methods: The experiment used laser-evoked potentials (LEPs) during three conditions (no task, mental task, movement preparation) while recording brain activity with a 32-channel electroencephalogram in 21 patients with cWAD, 20 patients with CFS and 18 HC. Two-factor mixed design Analysis of variance were used to evaluate differences in LEP amplitudes and latencies. Results: No differences in N1, N2, N2P2, and P2 LEP amplitudes were found between the HC, CFS, and cWAD groups. After nociceptive stimulation, N1, N2 (only at hand location), N2P2, and P2 LEP amplitudes significantly decreased during movement preparation compared to no task (within group differences). Conclusion: Movement preparation induces a similar attenuation of LEPs in patients with CFS, patients with cWAD and HC. These findings do not support reduced motor-induced nociceptive inhibition in these patients.
Optimum Arrangement Design of Mastic Ropes for Membrane-Type LNG Tanks Considering the Flatness of Thermal Insulation Panel and Production Cost
Authors: Chun Do-Hyun , Roh Myung-Il , Ham Seung-Ho
Published: May 2020

Thermal insulation panels are installed on the inner walls of liquefied natural gas (LNG) tanks of an LNG carrier to maintain the cryogenic temperature. Mastic ropes are used to attach thermal insulation panels to the inner walls and to fill the gap between the walls and panels. Because the inner walls of the LNG tanks can be corrugated owing to production errors, a large amount of mastic ropes are required to maintain the flatness of the thermal insulation panels. Therefore, in this study, an optimization method is proposed to minimize the total amount of mastic ropes for satisfying the flatness criterion of thermal insulation panels. For this purpose, an optimization problem is mathematically formulated. An objective function is used to minimize the total amount of mastic ropes considering constraints to flatten the thermal insulation panels. This function is applied to the design of membrane-type LNG tanks to verify the effectiveness and feasibility of the proposed method. Consequently, we confirm that the proposed method can provide a more effective arrangement design of mastic ropes compared with manual design.
A Novel Vision-Based Towing Angle Estimation for Maritime Towing Operations
Authors: Zou Xiong , Zhan Wenqiang , Xiao Changshi , Zhou Chunhui , Chen Qianqian , Yang Tiantian , Liu Xin
Published: May 2020

The demand for non-powered facility towing is increasing with the development of large-scale offshore projects. It is of great interest for its safe operation to measure the state of the towing process in real time. This paper proposed a computer vision algorithm designed to measure the tug yawing during the towing operation by estimating the towing line angle. The geometrical projection of the towing line from 3D to 2D is described in detail. By fixing the camera at specific locations and simplifying the calculation procedure, the towing line angle in the 3D world can be estimated by the line angle in the image. Firstly, the sea–sky line is detected to estimate the rolling angle of the tug in the captured image. Then, the towing line angle is calculated by an image processing method. At the same time, the estimation of the towing angle is achieved through the captured video data analysis. Finally, field experiments were carried out and the results demonstrated that this method is suitable for real-time calculation of the towing angle during the towing operation.
Innovation and Firm Performance: The Moderating and Mediating Roles of Firm Size and Small and Medium Enterprise Finance
Authors: Kijkasiwat Ploypailin , Phuensane Pongsutti
Published: May 2020

This study examines the moderating effect of firm size on the relationship between innovation and firm performance of small and medium enterprises in 29 countries in Eastern European and Central Asia. The study also investigates whether the impact of innovation in products and processes on firm performance is affected by financial capital. The method applied is partial least square structural equation modelling. The findings indicate that firm size and the financial capital both moderate and mediate the impact of innovation on firm performance, positively or negatively. The findings have implications for decision makers by highlighting the significance of firm size and financial sources when planning to introduce innovations to enhance firm performance.
The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model
Authors: Vigil Jacob M. , Montera Marena A. , Pentkowski Nathan S. , Diviant Jegason P. , Orozco Joaquin , Ortiz Anthony L. , Rael Lawrence J. , Westlund Karin N.
Published: May 2020

Background: Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring ‘Cannabis’ pharmacodynamics. We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of “full-spectrum” whole plant extracted hemp oil on chronic neuropathic pain sensitivity in mice. Methods: Male BALBc mice were submitted to the FRICT-ION chronic neuropathic pain model with oral insertion through an incision in the buccal/cheek crease of 3 mm of chromic gut suture (4-0). The suture, wedged along the V2 trigeminal nerve branch, creates a continuous irritation that develops into secondary mechanical hypersensitivity on the snout. Von Frey filament stimuli on the mouse whisker pad was used to assess the mechanical pain threshold from 0–6 h following dosing among animals (n = 6) exposed to 5 μL of whole plant extracted hemp oil combined with a peanut butter vehicle (0.138 mg/kg), the vehicle alone (n = 3) 7 weeks post-surgery, or a naïve control condition (n = 3). Results: Mechanical allodynia was alleviated within 1 h (d = 2.50, p < 0.001) with a peak reversal effect at 4 h (d = 7.21, p < 0.001) and remained significant throughout the 6 h observation window. There was no threshold change on contralateral whisker pad after hemp oil administration, demonstrating the localization of anesthetic response to affected areas. Conclusion: Future research should focus on how whole plant extracted hemp oil affects multi-sensory and cognitive-attentional systems that process pain.
Kinetically Limited Phase Formation of Pt-Ir Based Compositionally Complex Thin Films
Authors: Saksena Aparna , Bogdanovski Dimitri , Sahasrabuddhe Hrushikesh , Music Denis , Schneider Jochen M.
Published: May 2020

The phase formation of PtIrCuAuX (X = Ag, Pd) compositionally complex thin films is investigated to critically appraise the criteria employed to predict the formation of high entropy alloys. The formation of a single-phase high entropy alloy is predicted if the following requirements are fulfilled: 12 J∙K−1 mol−1 ≤ configurational entropy ≤ 17.5 J∙K−1 mol−1, −10 kJ∙mol−1 ≤ enthalpy of mixing ≤ 5 kJ∙mol−1 and atomic size difference ≤ 5%. Equiatomic PtIrCuAuX (X = Ag, Pd) fulfill all of these requirements. Based on X-ray diffraction and energy-dispersive X-ray spectroscopy data, near-equiatomic Pt22Ir23Cu18Au18Pd19 thin films form a single-phase solid solution while near-equiatomic Pt22Ir23Cu20Au17Ag18 thin films exhibit the formation of two phases. The latter observation is clearly in conflict with the design rules for high entropy alloys. However, the observed phase formation can be rationalized by considering bond strengths and differences in activation energy barriers for surface diffusion. Integrated crystal orbital Hamilton population values per bond imply a decrease in bond strength for all the interactions when Pd is substituted by Ag in PtIrCuAuX which lowers the surface diffusion activation energy barrier by 35% on average for each constituent. This enables the surface diffusion-mediated formation of two phases, one rich in Au and Ag and a second phase enriched in Pt and Cu. Hence, phase formation in these systems appears to be governed by the complex interplay between energetics and kinetic limitations rather than by configurational entropy.
Characterization of Microstructure, Precipitations and Microsegregation in Laser Additive Manufactured Nickel-Based Single-Crystal Superalloy
Authors: Liu Zhaoyang , Shu Jiayang
Published: May 2020

In this study, the microstructure, precipitations, and microsegregation in the laser additive manufactured thin-wall structure of a single-crystal superalloy are synthetically characterized. The influence of a subsequent heat treatment on the microstructure and precipitations is discussed. The results show that under the given processing conditions, the single-crystal microstructure is regenerated perfectly with small misorientation angles in the thin-wall structure. The crystal morphology shows obvious diversity and instability with the incremental height of thin-wall structure. With the increase of manufacturing height, both the primary and secondary dendritic arm spacings of epitaxial columnar dendrites first increase rapidly and then reach a dynamic balanced state. The distribution of precipitations and pores keeps symbiosis in the interdendritic region and shows periodic band characteristic with high density in the band region and low density in the inner region of plate layers. The microsegregation of element atoms in the microstructure shows a three-dimensional network distribution. The concentration of element atoms keeps good consistency with high value in the three-dimensional network and nearly standard value in the outside region. The subsequent heat treatment process contributes to the occupation of as-processed pores by the expanded mature precipitations with good blocky shape. Further optimization of the heat treatment process for improving the lattice coherency of precipitated γ’ phase and γ matrix in the laser additive manufactured single-crystal superalloy is needed and valuable.
Co-Substitution Effect in Room-Temperature Ferromagnetic Oxide Sr3.1Y0.9Co4O10.5
Authors: Tsuruta Akihiro , Kawasaki Shuji , Mikami Masashi , Kinemuchi Yoshiaki , Masuda Yoshitake , Fujita Asaya , Terasaki Ichiro
Published: May 2020

We investigated the Co substitution effect for the magnetic properties in room-temperature ferromagnetic oxide Sr3.1Y0.9Co4O10.5. The substituted element (Al and Ga) and low-spin state Co3+, which was changed from a high-spin or intermediate-spin state by Al or Ga substitution, reduced the Curie temperature to even 1.5 times lower than the temperature estimated from a simple dilution effect. Al3+ preferentially substituted for intermediate-spin-state Co3+ in the ferrimagnetic CoO6 layer and deteriorated the saturation magnetization of Sr3.1Y0.9Co4O10.5. By contrast, Ga3+ substituted for high-spin-state Co3+ in the CoO6 layer and/or the antiferromagnetic CoO4.25 layer and enhanced the saturation magnetization per Co ion. These results indicate that the magnetic properties of Sr3.1Y0.9Co4O10.5 can be controlled by selectively substituting for Co3+ with different spin states.
AFM-Based Method for Measurement of Normal and Osteoarthritic Human Articular Cartilage Surface Roughness
Authors: Ihnatouski Mikhail , Pauk Jolanta , Karev Dmitrij , Karev Boris
Published: May 2020

In osteoarthrosis, pathological features of articular cartilage are associated with degeneration and nanomechanical changes. The aim of this paper is to show that indentation-atomic force microscopy can monitor wear-related biomechanical changes in the hip joint of patients with osteoarthritis. Fifty patients (N = 50), aged 40 to 65, were included in the study. The mechanical properties and the submicron surface morphology of hyaline cartilage were investigated using atomic force microscopy. Measurements of the roughness parameters of cartilage surfaces were performed, including the arithmetic average of absolute values (Ra), the maximum peak height (Rp), and the mean spacing between local peaks (S). The arithmetic mean of the absolute values of the height of healthy cartilage was 86 nm, while wear began at Ra = 73 nm. The maximum changes of values of the roughness parameters differed from the healthy ones by 71%, 80%, and 51% for Ra, Rp, and S, respectively. Young’s modulus for healthy cartilage surfaces ranged from 1.7 to 0.5 MPa. For the three stages of cartilage wear, Young’s modulus increased, and then it approached the maximum value and decreased. AFM seems to be a powerful tool for surface analysis of biological samples as it enables indentation measurements in addition to imaging.