bluuebunny/crossref_metadata_2025 huggingface dataset:
Texture-Based Analysis of 18F-Labeled Amyloid PET Brain Images
Authors: Seiffert Alexander P. , Gómez-Grande Adolfo , Milara Eva , Llamas-Velasco Sara , Villarejo-Galende Alberto , Gómez Enrique J. , Sánchez-González Patricia
Published: February 2021

Amyloid positron emission tomography (PET) brain imaging with radiotracers like [18F]florbetapir (FBP) or [18F]flutemetamol (FMM) is frequently used for the diagnosis of Alzheimer’s disease. Quantitative analysis is usually performed with standardized uptake value ratios (SUVR), which are calculated by normalizing to a reference region. However, the reference region could present high variability in longitudinal studies. Texture features based on the grey-level co-occurrence matrix, also called Haralick features (HF), are evaluated in this study to discriminate between amyloid-positive and negative cases. A retrospective study cohort of 66 patients with amyloid PET images (30 [18F]FBP and 36 [18F]FMM) was selected and SUVRs and 6 HFs were extracted from 13 cortical volumes of interest. Mann–Whitney U-tests were performed to analyze differences of the features between amyloid positive and negative cases. Receiver operating characteristic (ROC) curves were computed and their area under the curve (AUC) was calculated to study the discriminatory capability of the features. SUVR proved to be the most significant feature among all tests with AUCs between 0.692 and 0.989. All HFs except correlation also showed good performance. AUCs of up to 0.949 were obtained with the HFs. These results suggest the potential use of texture features for the classification of amyloid PET images.
Effect of Fiber Optic Plate on Centroid Locating Accuracy of Monocentric Imager
Authors: Huang Yawei , Xie Dandan , Yan Changxiang , Wu Congjun
Published: February 2021

We propose a method for obtaining the centroid locating accuracy (CLA) of a monocentric imager with a fiber optic plate (FOP) as a relay image transmission element in order to reduce the loss of CLA due to the addition of FOP. We constructed a two-stage image transmission coupling model of spherical focal surface (FOP) image sensor. By analyzing the influences of FOP parameters, including the fill factor and the fiber diameter, and FOP in-plane displacements, including rotation and translation on CLA, the loss of the lowest CLA that the monocentric imager can withstand caused by the addition of the FOP was reduced by 20%.
Wankelmut: A Simple Benchmark for the Evolvability of Behavioral Complexity
Authors: Schmickl Thomas , Zahadat Payam , Hamann Heiko
Published: February 2021

In evolutionary robotics, an encoding of the control software that maps sensor data (input) to motor control values (output) is shaped by stochastic optimization methods to complete a predefined task. This approach is assumed to be beneficial compared to standard methods of controller design in those cases where no a priori model is available that could help to optimize performance. For robots that have to operate in unpredictable environments as well, an evolutionary robotics approach is favorable. We present here a simple-to-implement, but hard-to-pass benchmark to allow for quantifying the “evolvability” of such evolving robot control software towards increasing behavioral complexity. We demonstrate that such a model-free approach is not a free lunch, as already simple tasks can be unsolvable barriers for fully open-ended uninformed evolutionary computation techniques. We propose the “Wankelmut” task as an objective for an evolutionary approach that starts from scratch without pre-shaped controller software or any other informed approach that would force the behavior to be evolved in a desired way. Our main claim is that “Wankelmut” represents the simplest set of problems that makes plain-vanilla evolutionary computation fail. We demonstrate this by a series of simple standard evolutionary approaches using different fitness functions and standard artificial neural networks, as well as continuous-time recurrent neural networks. All our tested approaches failed. From our observations, we conclude that other evolutionary approaches will also fail if they do not per se favor or enforce the modularity of the evolved structures and if they do not freeze or protect already evolved functionalities from being destroyed again in the later evolutionary process. However, such a protection would require a priori knowledge of the solution of the task and contradict the “no a priori model” approach that is often claimed in evolutionary computation. Thus, we propose a hard-to-pass benchmark in order to make a strong statement for self-complexifying and generative approaches in evolutionary computation in general and in evolutionary robotics specifically. We anticipate that defining such a benchmark by seeking the simplest task that causes the evolutionary process to fail can be a valuable benchmark for promoting future development in the fields of artificial intelligence, evolutionary robotics, and artificial life.
Blockchain Based Trust Model Using Tendermint in Vehicular Adhoc Networks
Authors: Arora Sandeep Kumar , Kumar Gulshan , Kim Tai-hoon
Published: February 2021

Blockchain is the consensus-based technology used to resolve conflicts in Byzantine environments. Vehicles validate the messages received from neighboring vehicles using the gradient boosting technique (GBT). Based on the validation results, the message source vehicle generates the ratings that are to be uploaded to roadside units (RSUs), and through that, the trust offset value can be calculated. All RSUs maintain the trust blockchain, and each RSU tries to add their blocks to the trust blockchain. We proposed a blockchain-based trust management model for the vehicular adhoc network (VANET) based on Tendermint. It eliminates the problem of malicious nodes entering the network, and will also overcome the problem of power consumption. Simulation results also show that the proposed system is 7.8% and 15.6% effective and efficient in terms of packet delivery ratio (PDR) and end-to-end delay (EED), respectively, to collect the trusted data between the vehicles.
Structural Health Monitoring of 2D Plane Structures
Authors: Mobaraki Behnam , Ma Haiying , Lozano Galant Jose Antonio , Turmo Jose
Published: February 2021

This paper presents the application of the observability technique for the structural system identification of 2D models. Unlike previous applications of this method, unknown variables appear both in the numerator and the denominator of the stiffness matrix system, making the problem non-linear and impossible to solve. To fill this gap, new changes in variables are proposed to linearize the system of equations. In addition, to illustrate the application of the proposed procedure into the observability method, a detailed mathematical analysis is presented. Finally, to validate the applicability of the method, the mechanical properties of a state-of-the-art plate are numerically determined.
Stenosis of Carotid Arteries and Concentration of Some Blood Lipid Parameters amongst Tobacco Smokers in Abha: A Case–Control Study
Authors: Alelyani Magbool , Al-Saleem Alshahrani Safar Abadi Saeed , Zaman Gaffar Sarwar , Hadadi Ibrahim , Musa Mustafa Jafar , Adam Mohamed , Mohammed Mohammed Elimam Ahamed
Published: February 2021

Smoking is well known to be correlated with cardiovascular abnormalities, in particular atherosclerosis and heart diseases. This article investigates the effect and relationship of smoking tobacco on the thickness of the intima–media (IMT) belonging to the common carotid arteries (CCAs), and also blood concentration of the lipid profile (LP), mainly the total cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and also triglycerides. Nineteen male tobacco smokers and thirty-five healthy male non-smoking Saudi participants were involved in this study after obtaining their informed consent. An ultrasound and a spectrophotometer were used to determine the IMTs and lipid parameters, respectively. The thicknesses of the smokers’ right (RCA) and left carotid (LCA) arteries (0.72 and 0.7 mm, respectively) were significantly greater than the thicknesses of the arteries of the non-smokers (0.58 and 0.62 mm, respectively) (p-value = 0.005 and 0.04). Insignificant differences between the means of the other parameters in the two groups were studied. Smoking is a risk factor for stroke, because it significantly increases the IMTs of both the right and left carotid arteries.
Non-Thermal Intervention of Lung Tumor by Core-Shell Magnetic Nanoparticles in a Magnetic Field
Authors: Zhang Naming , Wang Ziang , Ning Shuya , Wang Shuhong , Wang Song , Qiu Hao
Published: February 2021

K-Ras mutations result in normal cells dividing uncontrollably and becoming cancerous. The prognosis is currently poor for patients due to the lack of drugs that can effectively target these mutations. In this study, magnetic nanoparticles (MNPs) were prepared, characterized, and cooperated with a magnetic field to intervene in the growth of lung tumor cells. The rise in temperature of a stimulation coil was studied by numerical calculation. The non-thermal effects of MNPs under a magnetic force were analyzed. The cell experiments showed that the growth of A549 tumor cells slowed down. The result of a wound-healing assay also indicated that the migration of tumor cells was suppressed. Compared with magnetic stimulation without MNPs, MNPs enhanced the inhibitory effects of a magnetic field. This study suggests a new way to treat K-Ras driven lung tumors using non-thermal effects of MNPs without the side effects caused by thermal effects.
Anthropometric Profile and Physical Fitness Performance Comparison by Game Position in the Chile Women’s Senior National Football Team
Authors: Villaseca-Vicuña Rodrigo , Molina-Sotomayor Edgardo , Zabaloy Santiago , Gonzalez-Jurado Jose Antonio
Published: February 2021

The aim of this study was to explore the anthropometric profile and evaluate physical fitness variables of the members of the Chile women’s national football team based on their playing positions. Fifty football players participated in this study, which was carried out during the period of training for the France 2019 Women’s World Cup and the Japan 2020 Olympic Games. Body composition and physical condition (muscular strength, sprint, agility, and aerobic fitness) were assessed. The goalkeepers showed greater weight (p < 0.001), height (p = 0.002), and %Fat (p = 0.010) compared to the rest of the playing positions. There were also differences between positions in relative strength (RS) (p = 0.001), running speed at 10 and 30 m (T10 and T30, respectively), agility (AGI) (p < 0.001), and yo-yo test (MYYR1) (p < 0.001). RS, T10, T30, and countermovement jump (CMJ) were significantly correlated (p ≤ 0.05) with anthropometric variables (p ≤ 0.05). MYYR1 was also significantly correlated with anthropometric variables (p ≤ 0.05). In conclusion, goalkeepers show greater weight and height, as well as worse results in MYYR1, AGI, T10, T30, and RS compared to the rest of the players. Forwards present better performance in running speed and agility. Better performance in physical condition is associated with better body composition values (greater muscle mass and lower fat mass). Greater relative strength indicates greater performance in explosive actions. Therefore, to meet the demands of high competition, it is important to establish ideal profiles in anthropometry and physical condition variables based on the playing position.
Deep Fusion Feature Extraction for Caries Detection on Dental Panoramic Radiographs
Authors: Bui Toan Huy , Hamamoto Kazuhiko , Paing May Phu
Published: February 2021

Caries is the most well-known disease and relates to the oral health of billions of people around the world. Despite the importance and necessity of a well-designed detection method, studies in caries detection are still limited and show a restriction in performance. In this paper, we proposed a computer-aided diagnosis (CAD) method to detect caries among normal patients using dental radiographs. The proposed method mainly consists of two processes: feature extraction and classification. In the feature extraction phase, the chosen 2D tooth image was employed to extract deep activated features using a deep pre-trained model and geometric features using mathematic formulas. Both feature sets were then combined, called fusion feature, to complement each other defects. Then, the optimal fusion feature set was fed into well-known classification models such as support vector machine (SVM), k-nearest neighbor (KNN), decision tree (DT), Naïve Bayes (NB), and random forest (RF) to determine the best classification model that fit the fusion features set and perform the most preeminent result. The results show 91.70%, 90.43%, and 92.67% for accuracy, sensitivity, and specificity, respectively. The proposed method has outperformed the previous state-of-the-art and shows promising results when none of the measured factors is less than 90%; therefore, the method is promising for dentists and capable of wide-scale implementation caries detection in hospitals.
Self-Care IoT Platform for Diabetic Mellitus
Authors: Park Jai-Chang , Kim Seongbeom , Lee Je-Hoon
Published: February 2021

Diabetes mellitus is a severe chronic disease, and the number of patients has increased. To manage blood glucose levels, patients should frequently measure their blood glucose and analyze which lifestyle habits affect blood glucose levels. However, it is hard to record and analyze the relationship between their blood glucose levels and lifestyle. The internet of things (IoT) is useful to interconnect, monitor, obtain, and process data between various devices used in everyday life to fulfill a common objective. This paper proposes an intelligent self-care platform using IoT technology that helps patients with chronic diabetes manage their blood glucose levels in their target range. In particular, we developed various devices called the self-care IoT pack. It consists of five different types of devices to obtain blood glucose levels, physical activities, food intake, medication, sleeping, and so on. They can collect blood glucose levels with lifestyles that automatically impact the patient’s blood glucose level. We also devised a self-care application to display and analyze the data obtained from the IoT pack. Consequently, the proposed self-care IoT platform collects the blood glucose levels and the lifestyles without any burden of record. By reviewing the accumulated information, the patients can find bad habits in blood glucose management and improve their lifestyle.
An Improved Rectifier Circuit for Piezoelectric Energy Harvesting from Human Motion
Authors: Edla Mahesh , Lim Yee Yan , Padilla Ricardo Vasquez , Deguchi Mikio
Published: February 2021

Harvesting energy from human motion for powering small scale electronic devices is attracting research interest in recent years. A piezoelectric device (PD) is capable of harvesting energy from mechanical motions, in the form of alternating current (AC) voltage. The AC voltage generated is of low frequency and is often unstable due to the nature of human motion, which renders it unsuitable for charging storage device. Thus, an electronic circuit such as a full bridge rectifier (FBR) is required for direct current (DC) conversion. However, due to forward voltage loss across the diodes, the rectified voltage and output power are low and unstable. In addition, the suitability of existing rectifier circuits in converting AC voltage generated by PD as a result of low frequency human motion induced non-sinusoidal vibration is unknown. In this paper, an improved H-Bridge rectifier circuit is proposed to increase and to stabilise the output voltage. To study the effectiveness of the proposed circuit for human motion application, a series of experimental tests were conducted. Firstly, the performance of the H-Bridge rectifier circuit was studied using a PD attached to a cantilever beam subject to low frequency excitations using a mechanical shaker. Real-life testing was then conducted with the source of excitation changed to a human performing continuous cycling and walking motions at a different speed. Results show that the H-Bridge circuit prominently increases the rectified voltage and output power, while stabilises the voltage when compared to the conventional FBR circuit. This study shows that the proposed circuit is potentially suitable for PEH from human motion.
Life Cycle Energy Consumption and Carbon Dioxide Emissions of Agricultural Residue Feedstock for Bioenergy
Authors: Havrysh Valerii , Kalinichenko Antonina , Brzozowska Anna , Stebila Jan
Published: February 2021

The depletion of fossil fuels and climate change concerns are drivers for the development and expansion of bioenergy. Promoting biomass is vital to move civilization toward a low-carbon economy. To meet European Union targets, it is required to increase the use of agricultural residues (including straw) for power generation. Using agricultural residues without accounting for their energy consumed and carbon dioxide emissions distorts the energy and environmental balance, and their analysis is the purpose of this study. In this paper, a life cycle analysis method is applied. The allocation of carbon dioxide emissions and energy inputs in the crop production by allocating between a product (grain) and a byproduct (straw) is modeled. Selected crop yield and the residue-to-crop ratio impact on the above indicators are investigated. We reveal that straw formation can consume between 30% and 70% of the total energy inputs and, therefore, emits relative carbon dioxide emissions. For cereal crops, this energy can be up to 40% of the lower heating value of straw. Energy and environmental indicators of a straw return-to-field technology and straw power generation systems are examined.
Thermal Strain-Based Simplified Prediction of Thermal Deformation Caused by Flame Bending
Authors: Hwang Se-Yun , Park Kyoung-Geun , Heo Jeeyeon , Lee Jang-Hyun
Published: February 2021

This paper describes a quick and accurate method for predicting thermal deformation due to flame bending of the curved plate located before and after the hull. Flame bending is a common method to deform the curved plate used in shipyards. Three-dimensional thermo-elasto-plastic analysis is known as the most accurate method for predicting deformed shape in the automation of frame bending. However, the three-dimensional analysis takes a lot of computational time. The quick prediction method, strain as direct boundary (SDB), was introduced, which is a simplified prediction method based on thermal strain. This simplified method implements an equivalent load as a temperature difference that can simulate thermal deformation by flame. In the case of multiple heating lines by the flame bending, the residual strain generated by the first heating line affects the other lines. To consider the effect of residual strain, the plastic material properties are also considered. Then, the distance ratio from the center line is used to generate the same temperature field in grid mesh. The results of the prediction were evaluated for the heat affected zone (HAZ) of the specimen obtained through the flame bending experiment. Therefore, this paper introduced detail procedure of the proposed SDB method and the experimental results for the practical application.
Optimization of a Depiction Procedure for an Artificial Intelligence-Based Network Protection System Using a Genetic Algorithm
Authors: Dolezel Petr , Holik Filip , Merta Jan , Stursa Dominik
Published: February 2021

The current demand for remote work, remote teaching and video conferencing has brought a surge not only in network traffic, but unfortunately, in the number of attacks as well. Having reliable, safe and secure functionality of various network services has never been more important. Another serious phenomenon that is apparent these days and that must not be discounted is the growing use of artificial intelligence techniques for carrying out network attacks. To combat these attacks, effective protection methods must also utilize artificial intelligence. Hence, we are introducing a specific neural network-based decision procedure that can be considered for application in any flow characteristic-based network-traffic-handling controller. This decision procedure is based on a convolutional neural network that processes the incoming flow characteristics and provides a decision; the procedure can be understood as a firewall rule. The main advantage of this decision procedure is its depiction process, which has the ability to transform the incoming flow characteristics into a graphical structure. Graphical structures are regarded as very efficient data structures for processing by convolutional neural networks. This article’s main contribution consists of the development and improvement of the depiction process using a genetic algorithm. The results presented at the end of the article show that the decision procedure using an optimized depiction process brings significant improvements in comparison to previous experiments.
Daydriex: Translating Nighttime Scenes towards Daytime Driving Experience at Night
Authors: Lee Euihyeok , Kang Seungwoo
Published: February 2021

What if the window of our cars is a magic window, which transforms dark views outside of the window at night into bright ones as we can see in the daytime? To realize such a window, one of important requirements is that the stream of transformed images displayed on the window should be of high quality so that users perceive it as real scenes in the day. Although image-to-image translation techniques based on Generative Adversarial Networks (GANs) have been widely studied, night-to-day image translation is still a challenging task. In this paper, we propose Daydriex, a processing pipeline to generate enhanced daytime translation focusing on road views. Our key idea is to supplement the missing information in dark areas of input image frames by using existing daytime images corresponding to the input images from street view services. We present a detailed processing flow and address several issues to realize our idea. Our evaluation shows that the results by Daydriex achieves lower Fréchet Inception Distance (FID) scores and higher user perception scores compared to those by CycleGAN only.
Which Meteorological and Climatological Information Is Requested for Better Surfing Experiences? A Survey-Based Analysis
Authors: Boqué Ciurana Anna , Aguilar Enric
Published: February 2021

This paper extends the work of previous research by investigating surfing practices and surf-recreation companies from a behavioral perspective. The study’s main aim is to gain insights into the role of meteorological/climatological information in decision-making related to the surf-tourism activities market. This information was gathered employing an online survey that asked respondents about where they surf and how they check forecasts for surfing. Climate services (CS) are promoted to support the decision-making process to better prepare for and adapt to the risks and opportunities of climate variability and change. The current market for CS is still in its early stages. In this paper, we report the findings from our recent investigation into the actual and potential market for CS for the Iberian Peninsula surf-tourism sector. Based on surfers’ and surf companies’ demands, it was found that an improved surfing climate service (herein, SCS) will have clear implications in the management of these tourism areas and provide insights into whether surfing activities may be successful. At the same time, such services can help to manage adaptive actions in regard to the impacts of climate change in surfing areas.
A Synoptic Scale Perspective on Greenland Ice Core δ18O Variability and Related Teleconnection Patterns
Authors: Rimbu Norel , Ionita Monica , Lohmann Gerrit
Published: February 2021

The variability of stable oxygen isotope ratios (δ18O) from Greenland ice cores is commonly linked to changes in local climate and associated teleconnection patterns. In this respect, in this study we investigate ice core δ18O variability from a synoptic scale perspective to assess the potential of such records as proxies for extreme climate variability and associated weather patterns. We show that positive (negative) δ18O anomalies in three southern and central Greenland ice cores are associated with relatively high (low) Rossby Wave Breaking (RWB) activity in the North Atlantic region. Both cyclonic and anticyclonic RWB patterns associated with high δ18O show filaments of strong moisture transport from the Atlantic Ocean towards Greenland. During such events, warm and wet conditions are recorded over southern, western and central part of Greenland. In the same time the cyclonic and anticyclonic RWB patterns show enhanced southward advection of cold polar air masses on their eastern side, leading to extreme cold conditions over Europe. The association between high δ18O winters in Greenland ice cores and extremely cold winters over Europe is partly explained by the modulation of the RWB frequency by the tropical Atlantic sea surface temperature forcing, as shown in recent modeling studies. We argue that δ18O from Greenland ice cores can be used as a proxy for RWB activity in the Atlantic European region and associated extreme weather and climate anomalies.
Extracellular Matrix Remodeling in the Retina and Optic Nerve of a Novel Glaucoma Mouse Model
Authors: Reinhard Jacqueline , Wiemann Susanne , Hildebrandt Sebastian , Faissner Andreas
Published: February 2021

Glaucoma is a neurodegenerative disease that is characterized by the loss of retinal ganglion cells (RGC) and optic nerve fibers. Increased age and intraocular pressure (IOP) elevation are the main risk factors for developing glaucoma. Mice that are heterozygous (HET) for the mega-karyocyte protein tyrosine phosphatase 2 (PTP-Meg2) show chronic and progressive IOP elevation, severe RGCs loss, and optic nerve damage, and represent a valuable model for IOP-dependent primary open-angle glaucoma (POAG). Previously, evidence accumulated suggesting that glaucomatous neurodegeneration is associated with the extensive remodeling of extracellular matrix (ECM) molecules. Unfortunately, little is known about the exact ECM changes in the glaucomatous retina and optic nerve. Hence, the goal of the present study was to comparatively explore ECM alterations in glaucomatous PTP-Meg2 HET and control wild type (WT) mice. Due to their potential relevance in glaucomatous neurodegeneration, we specifically analyzed the expression pattern of the ECM glycoproteins fibronectin, laminin, tenascin-C, and tenascin-R as well as the proteoglycans aggrecan, brevican, and members of the receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) family. The analyses were carried out in the retina and optic nerve of glaucomatous PTP-Meg2 HET and WT mice using quantitative real-time PCR (RT-qPCR), immunohistochemistry, and Western blot. Interestingly, we observed increased fibronectin and laminin levels in the glaucomatous HET retina and optic nerve compared to the WT group. RT-qPCR analyses of the laminins α4, β2 and γ3 showed an altered isoform-specific regulation in the HET retina and optic nerve. In addition, an upregulation of tenascin-C and its interaction partner RPTPβ/ζ/phosphacan was found in glaucomatous tissue. However, comparable protein and mRNA levels for tenascin-R as well as aggrecan and brevican were observed in both groups. Overall, our study showed a remodeling of various ECM components in the glaucomatous retina and optic nerve of PTP-Meg2 HET mice. This dysregulation could be responsible for pathological processes such as neovascularization, inflammation, and reactive gliosis in glaucomatous neurodegeneration.
MLST-Based Analysis and Antimicrobial Resistance of Staphylococcus epidermidis from Cases of Sheep Mastitis in Greece
Authors: Katsarou Eleni I. , Chatzopoulos Dimitris C. , Giannoulis Themis , Ioannidi Katerina S. , Katsafadou Angeliki I. , Kontou Panagiota I. , Lianou Daphne T. , Mamuris Zissis , Mavrogianni Vasia S. , Michael Charalambia K. , Papadopoulos Elias , Petinaki Efthymia , Sarrou Styliani , Vasileiou Natalia G. C. , Fthenakis George C.
Published: February 2021

Staphylococcus epidermidis is an important causal agent of ovine mastitis. A literature search indicated a lack of systematic studies of causal agents of the infection by using multi-locus sequence typing (MLST). The objectives were to analyse MLST-based data and evaluate the antimicrobial resistance of S. epidermidis isolates from ovine mastitis in Greece. The database included 1593 isolates from 46 countries: 1215 of human, 195 of environmental and 134 of animal origin, distributed into 949 sequence types (STs) and cumulatively with 450 alleles therein. Among mastitis isolates, bovine isolates were distributed into 36 different STs and ovine ones into 15 STs. The 33 isolates from ovine mastitis in Greece were in 15 different STs, 6 of these (ST677, ST678, ST700, ST 709, ST710, ST711) assigned for the first time; in addition, 5 alleles (65 for arcC, 59 for aroE, 56 and 57 for gtr and 48 for tpiA) were identified for the first time. The spanning tree of these isolates included 15 nodes and 14 edges (i.e., branches). Among these isolates, 19 showed resistance to antimicrobial agents (tetracycline, penicillin, fucidic adic, erythromycin, clindamycin, cefoxitin). Resistance-related genes (tetK, tetT, msrA, tetM, tetS, ermC, mecA) were detected. There was no association between STs and resistance to antimicrobial agents. Isolates with antimicrobial resistance were recovered more often from flocks where hand-milking was practised.
Mesenchymal Stem Cell-Derived Extracellular Vesicles: Regenerative Potential and Challenges
Authors: Fuloria Shivkanya , Subramaniyan Vetriselvan , Dahiya Rajiv , Dahiya Sunita , Sudhakar Kalvatala , Kumari Usha , Sathasivam Kathiresan , Meenakshi Dhanalekshmi Unnikrishnan , Wu Yuan Seng , Sekar Mahendran , Malviya Rishabha , Singh Amit , Fuloria Neeraj Kumar
Published: February 2021

Evidence suggests that stem cells exert regenerative potential via the release of extracellular vesicles. Mesenchymal stem cell extracellular vesicles (MSCEVs) offer therapeutic benefits for various pathophysiological ailments by restoring tissues. Facts suggest that MSCEV action can be potentiated by modifying the mesenchymal stem cells culturing methodology and bioengineering EVs. Limited clinical trials of MSCEVs have questioned their superiority, culturing quality, production scale-up and isolation, and administration format. Translation of preclinically successful MSCEVs into a clinical platform requires paying attention to several critical matters, such as the production technique, quantification/characterization, pharmacokinetics/targeting/transfer to the target site, and the safety profile. Keeping these issues as a priority, the present review was designed to highlight the challenges in translating preclinical MSCEV research into clinical platforms and provide evidence for the regenerative potential of MSCEVs in various conditions of the liver, kidney, heart, nervous system, bone, muscle, cartilage, and other organs/tissues.
Circulating Levels of the Heparan Sulfate Proteoglycan Syndecan-4 Positively Associate with Blood Pressure in Healthy Premenopausal Women
Authors: De Luca Maria , Bryan David R. , Hunter Gary R.
Published: February 2021

Syndecans (SDCs) are transmembrane proteins that are present on most cell types where they play a role in multiple physiological processes, including cell–matrix adhesion and inflammation. Growing evidence suggests that elevated levels of both shed SDC1 and SDC4 are associated with hypertension and cardiovascular diseases, but their relationships with cardiovascular risk factors in healthy individuals are unknown. The primary objective of this study was to investigate whether serum levels of SDC4 and SDC1 were associated with body composition, hemodynamic parameters, pro-inflammatory cytokine concentrations, and urinary noradrenaline and dopamine levels in healthy women (17 African American and 20 European American) between the ages of 20 and 40 years old. Univariate analyses revealed only a significant (p < 0.05) inverse correlation between serum SDC1 and body fat percentage. On the other hand, serum SDC4 was positively correlated with systolic blood pressure, diastolic blood pressure, and urinary levels of noradrenaline and dopamine. Serum SDC4 was also a significant predictor of systolic blood pressure in a multivariate regression model that included fat-free mass and urinary dopamine levels as significant independent variables. The result did not change even adjusting for race. Our findings indicate that SDC4 has an important role in the physiological regulation of blood pressure.
Optimizing Calcium Detection Methods in Animal Systems: A Sandbox for Synthetic Biology
Authors: Li Elizabeth S. , Saha Margaret S.
Published: February 2021

Since the 1970s, the emergence and expansion of novel methods for calcium ion (Ca2+) detection have found diverse applications in vitro and in vivo across a series of model animal systems. Matched with advances in fluorescence imaging techniques, the improvements in the functional range and stability of various calcium indicators have significantly enhanced more accurate study of intracellular Ca2+ dynamics and its effects on cell signaling, growth, differentiation, and regulation. Nonetheless, the current limitations broadly presented by organic calcium dyes, genetically encoded calcium indicators, and calcium-responsive nanoparticles suggest a potential path toward more rapid optimization by taking advantage of a synthetic biology approach. This engineering-oriented discipline applies principles of modularity and standardization to redesign and interrogate endogenous biological systems. This review will elucidate how novel synthetic biology technologies constructed for eukaryotic systems can offer a promising toolkit for interfacing with calcium signaling and overcoming barriers in order to accelerate the process of Ca2+ detection optimization.
Novel Method for Quantifying AhR-Ligand Binding Affinities Using Microscale Thermophoresis
Authors: Stinn Anne , Furkert Jens , Kaufmann Stefan H. E. , Moura-Alves Pedro , Kolbe Michael
Published: February 2021

The aryl hydrocarbon receptor (AhR) is a highly conserved cellular sensor of a variety of environmental pollutants and dietary-, cell- and microbiota-derived metabolites with important roles in fundamental biological processes. Deregulation of the AhR pathway is implicated in several diseases, including autoimmune diseases and cancer, rendering AhR a promising target for drug development and host-directed therapy. The pharmacological intervention of AhR processes requires detailed information about the ligand binding properties to allow specific targeting of a particular signaling process without affecting the remaining. Here, we present a novel microscale thermophoresis-based approach to monitoring the binding of purified recombinant human AhR to its natural ligands in a cell-free system. This approach facilitates a precise identification and characterization of unknown AhR ligands and represents a screening strategy for the discovery of potential selective AhR modulators.
Sonographic Features Differentiating Follicular Thyroid Cancer from Follicular Adenoma–A Meta-Analysis
Authors: Borowczyk Martyna , Woliński Kosma , Więckowska Barbara , Jodłowska-Siewert Elżbieta , Szczepanek-Parulska Ewelina , Verburg Frederik A. , Ruchała Marek
Published: February 2021

Certain ultrasound features are associated with an increased risk of thyroid malignancy. However, they were studied mainly in papillary thyroid cancers (PTCs); these results cannot be simply extrapolated for the differentiation of follicular thyroid adenomas and cancers (FTAs and FTCs). The aim of our study was to perform a meta-analysis to identify sonographic features suggesting malignancy in the case of follicular lesions, potentially differentiating FTA and FTC. We searched thirteen databases from January 2006 to December 2020 to find all relevant, full-text journal articles written in English. Analyses assessed the accuracy of malignancy detection in case of follicular lesions, potentially differentiating FTA and FTC included the odds ratio (OR), sensitivity, specificity, positive and negative predictive values. A random-effects model was used to summarize collected data. Twenty studies describing sonographic features of 10,215 nodules met the inclusion criteria. The highest overall ORs to increase the risk of malignancy were calculated for tumor protrusion (OR = 10.19; 95% confidence interval: 2.62–39.71), microcalcifications or mixed type of calcifications (coexisting micro and macrocalcifications): 6.09 (3.22–11.50), irregular margins: 5.11 (2.90–8.99), marked hypoechogenicity: 4.59 (3.23–6.54), and irregular shape: 3.6 (1.19–10.92). The most crucial feature associated with an increased risk of FTC is capsule protrusion, followed by the presence of calcifications, irrespectively of their type.
Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma
Authors: Carmell Natasha , Rominiyi Ola , Myers Katie N. , McGarrity-Cottrell Connor , Vanderlinden Aurelie , Lad Nikita , Perroux-David Eva , El-Khamisy Sherif F. , Fernando Malee , Finegan Katherine G. , Brown Stephen , Collis Spencer J.
Published: February 2021

Brain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)—the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease.
Development of a Sensitive Bioassay for the Analysis of IGF-Related Activation of AKT/mTOR Signaling in Biological Matrices
Authors: Walz Michael , Höflich Christine , Walz Christina , Ohde Daniela , Brenmoehl Julia , Sawitzky Mandy , Vernunft Andreas , Zettl Uwe K. , Holtze Susanne , Hildebrandt Thomas B. , Wolf Eckhard , Hoeflich Andreas
Published: February 2021

The bioactivity of the IGF system is not a function of isolated hormone concentrations in a given biological matrix. Instead, the biological activities of IGFs are regulated by IGFBPs, IGFBP proteases, and inhibitors of IGFBP proteases. Therefore, assays based on IGF-related bioactivity may describe functions of the complete IGF system in a given biological matrix. Of particular interest are the IGF system effects on the AKT/mTOR pathway, as a dominant system for controlling growth, metabolism, and aging. In order to improve the sensitivity of IGF-dependent bioactivity, we made use of the known short-term and enhancing effects of IGFBP2 on the intracellular PI3K pathway. As a specific readout of this pathway, and further as a marker of the mTOR pathway, we assessed the phosphorylation of AKT-Ser473. Preincubation using IGFBP2 enhanced IGF1-dependent AKT-Ser473 phosphorylation in our experimental system. The assay’s specificity was demonstrated by inhibition of IGF1 receptors outside or inside the cell, using antiserum or small molecule inhibitors, which reduced AKT phosphorylation in response to exogenous IGF1 (p < 0.05). The maximal response of AKT phosphorylation was recorded 15 to 60 min after the addition of IGF1 to cell monolayers (p < 0.001). In our cellular system, insulin induced AKT phosphorylation only at supra-physiological concentrations (µM). Using this novel assay, we identified the differential biological activity of the IGF system in AKT-Ser473 phosphorylation in serum (mouse, naked mole rat, and human), in cerebrospinal fluid (human), and in colostrum or mature milk samples (dairy cow). We have developed a sensitive and robust bioassay to assess the IGF-related activation of the AKT/mTOR pathway. The assay works efficiently and does not require expensive cell culture systems. By using capillary immuno-electrophoresis, the readout of IGF-related bioactivity is substantially accelerated, requiring a minimum of hands-on time. Importantly, the assay system is useful for studying IGF-related activity in the AKT/mTOR pathway in a broad range of biological matrices.
Organoids Are Limited in Modeling the Colon Adenoma–Carcinoma Sequence
Authors: Tokumaru Yoshihisa , Oshi Masanori , Patel Ankit , Tian Wanqing , Yan Li , Matsuhashi Nobuhisa , Futamura Manabu , Yoshida Kazuhiro , Takabe Kazuaki
Published: February 2021

The colon adenoma–carcinoma sequence is a multistep genomic-altering process that occurs during colorectal cancer (CRC) carcinogenesis. Organoids are now commonly used to model both non-cancerous and cancerous tissue. This study aims to investigate how well organoids mimic tissues in the adenoma–carcinoma sequence by comparing their transcriptomes. A total of 234 tissue samples (48 adenomas and 186 CRC) and 60 organoid samples (15 adenomas and 45 CRC) were analyzed. We found that cell-proliferation-related gene sets were consistently enriched in both CRC tissues and organoids compared to adenoma tissues and organoids by gene set enrichment analysis (GSEA). None of the known pathways in the colon adenoma–carcinoma sequence were consistently enriched in CRC organoids. There was no enrichment of the tumor microenvironment-related gene sets in CRC organoids. CRC tissues enriched immune-response-related gene sets, whereas CRC organoids did not. The proportions of infiltrating immune cells were different between tissues and organoids, whereas there was no difference between cancer and adenoma organoids. The amounts of cancer stem cells and progenitor cells were not different between CRC and adenoma organoids, whereas a difference was noted between CRC and adenoma tissues. In conclusion, we demonstrated that organoids model only part of the adenoma–carcinoma sequence and should be used with caution after considering their limitations.
Cost of Illness in Young Children: A Prospective Birth Cohort Study
Authors: Nørgaard Sarah Kristine , Vissing Nadja Hawwa , Chawes Bo Lund , Stokholm Jakob , Bønnelykke Klaus , Bisgaard Hans
Published: February 2021

Childhood illness is extremely common and imposes a considerable economic burden on society. We aimed to quantify the overall economic burden of childhood illness in the first three years of life and the impact of environmental risk factors. The study is based on the prospective, clinical mother–child cohort Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) of 700 children with embedded randomized trials of fish-oil and vitamin D supplementations during pregnancy. First, descriptive analyses were performed on the total costs of illness, defined as both the direct costs (hospitalizations, outpatient visits, visit to the practitioner) and the indirect costs (lost earnings) collected from the Danish National Health Registries. Thereafter, linear regression analyses on log-transformed costs were used to investigate environmental determinants of the costs of illness. The median standardized total cost of illness at age 0–3 years among the 559 children eligible for analyses was EUR 14,061 (IQR 9751–19,662). The exposures associated with reduced costs were fish-oil supplementation during pregnancy (adjusted geometric mean ratio (GMR) 0.89 (0.80; 0.98), p = 0.02), gestational age in weeks (aGMR = 0.93 (0.91; 0.96), p < 0.0001), and birth weight per 100 g (aGMR 0.98 (0.97; 0.99), p = 0.0003), while cesarean delivery was associated with higher costs (aGMR = 1.30 (1.15; 1.47), p < 0.0001). In conclusion, common childhood illnesses are associated with significant health-related costs, which can potentially be reduced by targeting perinatal risk factors, including maternal diet during pregnancy, cesarean delivery, preterm birth and low birth weight.
Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates
Authors: Samiee-Zafarghandy Samira , van Donge Tamara , Allegaert Karel , van den Anker John
Published: February 2021

In methadone-exposed preterm neonates, early identification of those at risk of severe neonatal abstinence syndrome (NAS) and use of a methadone dosing regimen that can provide effective and safe drug exposure are two important aspects of optimal care. To this end, we reviewed 17 methadone dosing recommendations in the international guidelines and literature and explored their variability in key dosing strategies. We selected three of the reviewed dosing regimens for their pharmacokinetics (PK) characteristics and their exposure–response relationship in three gestational age groups of preterm neonates (28, 32 and 36 gestational age weeks) at risk for development of severe NAS (defined as an umbilical cord methadone concentration of ≤60 ng/mL, following fetal exposure). We applied early (12 h after birth) vs. typical (36 h after birth) initiation of treatment. We observed that use of universally recommended dosing regimens in preterm neonates can result in under- or over-exposure. Use of a PK-guided dosing regimen resulted in effective target exposures within 24 h after birth with early initiation of treatment (12 h after birth). Future prospective studies should explore the incorporation of umbilical cord methadone concentrations for early identification of preterm neonates at risk of developing severe NAS and investigate the use of a PK-guided methadone dosing regimen, so that treatment failure, prolonged length of stay and opioid over-exposure can be avoided.
In-Situ Investigation of the Oxidation Behaviour of Chemical Vapour Deposited Zr(C,N) Hard Coatings Using Synchrotron X-ray Diffraction
Authors: Frank Florian , Tkadletz Michael , Saringer Christian , Stark Andreas , Schell Norbert , Deluca Marco , Czettl Christoph , Schalk Nina
Published: February 2021

The oxidation behaviour of chemical vapour deposited ZrN, ZrC and ZrCN coatings was investigated using in-situ synchrotron X-ray diffraction (XRD). To obtain a precise analysis of the temperature–dependent phase evolution during oxidation, coating powders were annealed in air between 100 °C and 1000 °C. Simultaneously, 2D XRD patterns were recorded in ~2 °C increments, which were subsequently evaluated using parametric Rietveld refinement. The results were correlated with differential scanning calorimetry and thermogravimetric analysis measurements, to further illuminate the oxidation mechanism of each coating system. ZrCN exhibited the highest oxidation onset temperature, followed by ZrC and ZrN. Furthermore, ZrCN was completely oxidised at a temperature of ~720 °C, which was ~50–70 °C higher than for ZrN and ZrC. The in-situ experiments revealed a similar oxidation sequence for all three samples: first, tetragonal and/or cubic (c/t)–ZrO2 is formed, which subsequently transforms into the more stable monoclinic (m)–ZrO2 phase. ZrCN and ZrC showed a higher c/t–ZrO2 fraction than the ZrN sample at 1000 °C. Furthermore, ex-situ Raman and XRD investigations of the oxidised samples revealed the ongoing c/t–ZrO2 → m–ZrO2 phase transformation during cooling.