bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Textured Insoles on the Balance of Individuals with Knee Osteoarthritis in Dynamic Perturbations
Authors: Park Hyoungjin
Published: September 2021

The effectiveness of adding plantar-surface texture to improve balance has been demonstrated in a variety of demographics. It is critical to investigate whether textured insoles can improve balance in people with knee osteoarthritis (OA), who have compromised the somatosensory function of the affected joint and, as a result, are at a higher risk of falling. Thus, this study investigated the degree of benefit from the use of textured insoles for improving balance and compared the balance of people with knee OA to healthy matched peers. This study included eighteen people with knee OA and eighteen healthy, aged, gender, height, weight, and BMI matched controls who were assessed on balance using the sensory organization test and the motor control test. Balance was improved in both groups when the textured insoles were worn, and the healthy knee group demonstrated significantly better balance performance than the knee OA group. The benefits of this study for individuals with knee OA are that it may lead to the development of an evidence-based footwear intervention that is noninvasive, simple to use, and inexpensive, in addition to allowing the user to self-manage and the ability to reduce the risk of falls, thereby improving their quality of life.
Investigation of 2DOF PID Controller for Physio-Therapeutic Application for Elbow Rehabilitation
Authors: Roy Rupal , Islam Maidul , Rashid MM , Mounis Shawgi , Ahsan Md Manjurul , Ahad Md Tanvir , Siddique Zahed , Kouzani Abbas Z. , Mahmud M A Parvez
Published: September 2021

The aim of this work is to evaluate the output of a two-degree of freedom (DOF) proportional integral derivative (PID) controller for controlling elbow flexion and extension on an upper limb rehabilitation robot of an existing model. Since the usage of upper limb rehabilitation is increasing dramatically because of human impairment, 2DOF has been proposed in this work as a suitable controller. The 2DOF PID controller offers set-point-weight features and, hence, is fast in removing disturbance from the system and ensuring system stability. Importantly, as the system parameters are unknown in this work, the black-box model approach has been taken into consideration, using the MATLAB System identification toolbox to estimate a model. The best-fitted estimated model is then coupled with the proposed controller in the MATLAB/Simulink environment that, upon successful simulation works, leads, finally, to the hardware implementation. Three different amplitudes of sinusoidal current signals, such as 0.3 amps, 0.2 amps, and 0.1 amps, are applied for hardware measurements. Considering patients’ physical conditions. In this work, the 2DOF controller offers a fast transient response, settling time, negligible tracking error and 0% overshoot and undershoot.
The Current State of Research of Wire Arc Additive Manufacturing (WAAM): A Review
Authors: Treutler Kai , Wesling Volker
Published: September 2021

Wire arc additive manufacturing is currently rising as the main focus of research groups around the world. This is directly visible in the huge number of new papers published in recent years concerning a lot of different topics. This review is intended to give a proper summary of the international state of research in the area of wire arc additive manufacturing. The addressed topics in this review include but are not limited to materials (e.g., steels, aluminum, copper and titanium), the processes and methods of WAAM, process surveillance and the path planning and modeling of WAAM. The consolidation of the findings of various authors into a unified picture is a core aspect of this review. Furthermore, it intends to identify areas in which work is missing and how different topics can be synergetically combined. A critical evaluation of the presented research with a focus on commonly known mechanisms in welding research and without a focus on additive manufacturing will complete the review.
Health Risk Detection and Classification Model Using Multi-Model-Based Image Channel Expansion and Visual Pattern Standardization
Authors: Kim Chang-Min , Hong Ellen J. , Chung Kyungyong , Park Roy C.
Published: September 2021

Although mammography is an effective screening method for early detection of breast cancer, it is also difficult for experts to use since it requires a high level of sensitivity and expertise. A computer-aided detection system was introduced to improve the detection accuracy of breast cancer in mammography, which is difficult to read. In addition, research to find lesions in mammography images using artificial intelligence has been actively conducted in recent days. However, the images generally used for breast cancer diagnosis are high-resolution and thus require high-spec equipment and a significant amount of time and money to learn and recognize the images and process calculations. This can lower the accuracy of the diagnosis since it depends on the performance of the equipment. To solve this problem, this paper will propose a health risk detection and classification model using multi-model-based image channel expansion and visual pattern shaping. The proposed method expands the channels of breast ultrasound images and detects tumors quickly and accurately through the YOLO model. In order to reduce the amount of computation to enable rapid diagnosis of the detected tumors, the model reduces the dimensions of the data by normalizing the visual information and use them as an input for the RNN model to diagnose breast cancer. When the channels were expanded through the proposed brightness smoothing and visual pattern shaping, the accuracy was the highest at 94.9%. Based on the images generated, the study evaluated the breast cancer diagnosis performance. The results showed that the accuracy of the proposed model was 97.3%, CRNN 95.2%, VGG 93.6%, AlexNet 62.9%, and GoogleNet 75.3%, confirming that the proposed model had the best performance.
Characterization of TBM Muck for Construction Applications
Authors: Taqa Ala Abu , Al-Ansari Mohamed , Taha Ramzi , Senouci Ahmed , Al-Marwani Hassan A. , Al-Zubi Ghaleb M. , Mohsen Mohamed O.
Published: September 2021

This paper investigates the potential utilization of the Tunnel Boring Machine (TBM) muck generated from Doha’s Metro Gold Line in different construction applications. The properties of the raw TBM muck were studied, and the results were compared to the specifications of Qatari Construction Standards (QCS 2014) of concrete aggregates, fill material under buildings and road subgrades. Compared to the requirements of concrete aggregates, the results indicated that the gradation of the raw TBM muck does not comply with the QCS 2014 requirements, and hence, sieving and screening may be essential. Moreover, the tests’ results showed that the properties of the muck meet the requirements of the concrete coarse aggregates, except for the water absorption, loss by magnesium sulphate soundness, loss by Los Angeles abrasion and the acid-soluble sulphate. As fill material under buildings or road subgrades, the gradation of the TBM muck complies with the QCS 2014 requirements, while the liquid limit and plasticity index are higher than the QCS 2014 permissible limits. Additionally, the morphological structure and the elemental composition of the raw TBM muck were determined by employing Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX), respectively. Digital images were also taken at larger scale to draw a full picture of the TBM muck morphology. A mixture of rough-rounded to angular-elongated shaped particles with relatively large voids could be observed. The EDX analysis demonstrated the presence of silicon (Si) as the predominant component of the muck, which may alter the Coefficient of Thermal Expansion (CTE) values for mixtures prepared using TBM muck. Hence, further investigations should be performed on the mechanical and thermal properties of mixtures containing TBM muck as aggregates’ replacement, and further work should be directed toward this end.
Modified Neural Architecture Search (NAS) Using the Chromosome Non-Disjunction
Authors: Park Kang-Moon , Shin Donghoon , Chi Sung-Do
Published: September 2021

This paper proposes a deep neural network structuring methodology through a genetic algorithm (GA) using chromosome non-disjunction. The proposed model includes methods for generating and tuning the neural network architecture without the aid of human experts. Since the original neural architecture search (henceforth, NAS) was announced, NAS techniques, such as NASBot, NASGBO and CoDeepNEAT, have been widely adopted in order to improve cost- and/or time-effectiveness for human experts. In these models, evolutionary algorithms (EAs) are employed to effectively enhance the accuracy of the neural network architecture. In particular, CoDeepNEAT uses a constructive GA starting from minimal architecture. This will only work quickly if the solution architecture is small. On the other hand, the proposed methodology utilizes chromosome non-disjunction as a new genetic operation. Our approach differs from previous methodologies in that it includes a destructive approach as well as a constructive approach, and is similar to pruning methodologies, which realizes tuning of the previous neural network architecture. A case study applied to the sentence word ordering problem and AlexNet for CIFAR-10 illustrates the applicability of the proposed methodology. We show from the simulation studies that the accuracy of the model was improved by 0.7% compared to the conventional model without human expert.
Is Perpendicular Double Two-Hole Plates Fixation Superior to Single Four-Hole Plate Fixation to Treat Mandibular Symphysis Fracture?—A Finite Element Study
Authors: Chang Li-Ren , Hou Ya-Pei , Lin Ting-Sheng
Published: September 2021

The effectiveness of a single four-hole plate (S4HP), perpendicularly oriented four-hole and two-hole plate (Per4H2HP), and perpendicularly oriented double two-hole plate (PerD2HP) for the fixation of a mandibular fracture was studied. A finite element analysis of the mandibular symphysis fractures treated with S4HP, Per4H2HP, and PerD2HP was performed. All surface nodes were fixed in the mandibular condyle region and occlusal muscle forces were applied. The maximal von Mises stress (MaxVMS) values of the plates, screws and screw holes were investigated. The displacement of the fracture site on the lower border of the mandibular symphysis was recorded. The displacement on the lower border of the fracture sites in the S4HP group was greater than that in the Per4H2HP group and the PerD2HP group. There was no eversion at the fracture site among all groups. Both the S4HP and Per4H2HP groups showed stress concentrations on the screws close to the fracture site. The MaxVMS increased when the number of screw holes on the mandibular anterior lower border decreased. The displacement of the fracture site and eversion with Per4H2HP and PerD2HP were far lower than those with S4HP. PerD2HP is a stable and green fixation technique for mandibular symphysis fractures.
Geometric Analysis through the Constructal Design of a Sea Wave Energy Converter with Several Coupled Hydropneumatic Chambers Considering the Oscillating Water Column Operating Principle
Authors: de Lima Yuri Theodoro Barbosa , das Neves Gomes Mateus , Isoldi Liércio André , dos Santos Elizaldo Domingues , Lorenzini Giulio , Rocha Luiz Alberto Oliveira
Published: September 2021

The work presents a numerical study of a wave energy converter (WEC) device based on the oscillating water column (OWC) operating principle with a variation of one to five coupled chambers. The main objective is to evaluate the influence of the geometry and the number of coupled chambers to maximize the available hydropneumatic power converted in the energy extraction process. The results were analyzed using the data obtained for hydropneumatic power, pressure, mass flow rate, and the calculated performance indicator’s hydropneumatic power. The Constructal Design method associated with the Exhaustive Search optimization method was used to maximize the performance indicator and determine the optimized geometric configurations. The degrees of freedom analyzed were the ratios between the height and length of the hydropneumatic chambers. A wave tank represents the computational domain. The OWC device is positioned inside it, subject to the regular incident waves. Conservation equations of mass and momentum and one equation for the transport of the water volume fraction are solved with the finite volume method (FVM). The multiphase model volume of fluid (VOF) is used to tackle the water–air mixture. The analysis of the results took place by evaluating the performance indicator in each chamber separately and determining the accumulated power, which represents the sum of all the powers calculated in all chambers. The turbine was ignored, i.e., only the duct without it was analyzed. It was found that, among the cases examined, the device with five coupled chambers converts more energy than others and that there is an inflection point in the performance indicator, hydropneumatic power, as the value of the degree of freedom increases, characterizing a decrease in the value of the performance indicator. With the results of the hydropneumatic power, pressure, and mass flow rate, it was possible to determine a range of geometry values that maximizes the energy conversion, taking into account the cases of one to five coupled chambers and the individual influence of each one.
Experimental Reflection Evaluation for Attitude Monitoring of Space Orbiting Systems with NRL Arch Method
Authors: Delfini Andrea , Pastore Roberto , Piergentili Fabrizio , Santoni Fabio , Marchetti Mario
Published: September 2021

The increasing number of satellites orbiting around Earth has led to an uncontrolled increase in objects within the orbital environment. Since the beginning of the space age on 4 October 1957 (launch of Sputnik I), there have been more than 4900 space launches, leading to over 18,000 satellites and ground-trackable objects currently orbiting the Earth. For each satellite launched, several other objects are also sent into orbit, including rocket upper stages, instrument covers, and so on. Having a reliable system for tracking objects and satellites and monitoring their attitude is at present a mandatory challenge in order to prevent dangerous collisions and an increase in space debris. In this paper, the evaluation of the reflection coefficient of different shaped objects has been carried out by means of the bi-static reflection method, also known as NRL arch measurement, in order to evaluate their visibility and attitude in a wide range of frequencies (12–18 GHz). The test campaign aims to correlate the experimental measures with the hypothetical reflection properties of orbiting systems.
A Computational Intelligence Approach to Predict Energy Demand Using Random Forest in a Cloudera Cluster
Authors: Cáceres Laura , Merino Jose Ignacio , Díaz-Díaz Norberto
Published: September 2021

Society’s energy consumption has shot up in recent years, making the prediction of its demand a current challenge to ensure an efficient and responsible use. Artificial intelligence techniques have proven to be potential tools in handling tedious tasks and making sense of large-scale data to make better business decisions in different areas of knowledge. In this article, the use of random forests algorithms in a Big Data environment is proposed for household energy demand forecasting. The predictions are based on the use of information from different sources, confirming a fundamental role of socioeconomic data in consumer’s behaviours. On the other hand, the use of Big Data architectures is proposed to perform horizontal and vertical scaling of the solution to be used in real environments. Finally, a tool for high-resolution predictions with great efficiency is introduced, which enables energy management in a very accurate way.
Hygroscopicity of Fresh and Aged Salt Mixtures from Saline Lakes
Authors: Li Jun , Liu Wanyu , Li Linjie , Gu Wenjun , Zhang Xiying , Hallquist Mattias , Tang Mingjin , Wang Sen , Kong Xiangrui
Published: September 2021

The high hygroscopicity of salt aerosol particles makes the particles active in aerosol and cloud formations. Inland saline lakes are an important and dynamic source of salt aerosol. The salt particles can be mixed with mineral dust and transported over long distances. During transportation, these particles participate in atmospheric heterogeneous chemistry and further impact the climate and air quality on a global scale. Despite their importance and potential, relatively little research has been done on saline lake salt mixtures from atmospheric perspectives. In this study, we use experimental and model methods to evaluate the hygroscopic properties of saline lake brines, fresh salt aerosol particles, and aged salt aerosol particles. Both original samples and literature data are investigated. The original brine samples are collected from six salt lakes in Shanxi and Qinghai provinces in China. The ionic compositions of the brines are determined and the hygroscopicity measurements are performed on crystallized brines. The experimental results agree well with theoretical deliquescence relative humidity (DRH) values estimated by a thermodynamic model. The correlations between DRHs of different salt components and the correlations between DRHs and ionic concentrations are presented and discussed. Positive matrix factorization (PMF) analysis is performed on the ionic concentrations data and the hygroscopicity results, and the solutions are interpreted and discussed. The fresh and aged salt aerosol particles are analyzed in the same way as the brines, and the comparison shows that the aged salt aerosol particles completely alter their hygroscopic property, i.e., transferring from MgCl2− governed to NH4NO3− governed.
Cluster and Redundancy Analyses of Taiwan Upstream Watersheds Based on Monthly 30 Years AVHRR NDVI3g Data
Authors: Tsai Hui Ping , Wong Wei-Ying
Published: September 2021

The study uses 30 years of the third generation of Advanced Very-High-Resolution Radiometer (AVHRR) NDVI3g monthly data from 1982 to 2012 to identify the natural clusters and important driving factors of the upstream watersheds in Taiwan through hierarchical cluster analysis (HCA) and redundancy analysis (RDA), respectively. Subsequently, as a result of HCA, six clusters were identified based on the 30 years of monthly NDVI data, delineating unique NDVI characteristics of the upstream watersheds. Additionally, based on the RDA results, environmental factors, including precipitation, temperature, slope, and aspect, can explain approximately 52% of the NDVI variance over the entire time series. Among environmental factors, nine factors were identified significantly through RDA analysis for explaining NDVI variance: average slope, temperature, flat slope, northeast-facing slope, rainfall, east-facing slope, southeast-facing slope, west-facing slope, and northwest-facing slope, which reflect an intimate connection between climatic and orthographic factors with vegetation. Furthermore, the rainfall and temperature represent different variations in all scenarios and seasons. With consideration of the characteristics of the clusters and significant environmental factors, corresponding climate change adaptation strategies are proposed for each cluster under climate change scenarios. Thus, the results provide insight to assess the natural clustering of the upstream watersheds in Taiwan, benefitting future sustainable watershed management.
The Role of Aquatic Refuge Habitats for Fish, and Threats in the Context of Climate Change and Human Impact, during Seasonal Hydrological Drought in the Saxon Villages Area (Transylvania, Romania)
Authors: Bănăduc Doru , Sas Alexandru , Cianfaglione Kevin , Barinova Sophia , Curtean-Bănăduc Angela
Published: September 2021

In spite of the obvious climate changes effects on the Carpathian Basin hydrographic nets fish fauna, studies on their potential refuge habitats in drought periods are scarce. Multiannual (2016–2021) research of fish in some streams located in the Saxon Villages area during hydrological drought periods identified, mapped, and revealed the refuge aquatic habitats presence, management needs, and importance for fish diversity and abundance for small rivers. The impact of increasing global temperature and other human activities induced hydrologic net and habitats alteration, decreased the refuge habitats needed by freshwater fish, diminished the fish abundance, and influenced the spatial and temporal variation in fish assemblage structure in the studied area. The sites more than one meter in depth in the studied lotic system were inventoried and all 500 m of these lotic systems were also checked to see what species and how many individuals were present, and if there is was difference in their abundance between refuge and non-refuge 500 m sectors. The scarce number of these refuges due to relatively high soil erosion and clogging in those basins and the cumulative effects of other human types of impact induced a high degree of pressure on the fish fauna. Overall, it reduced the role of these lotic systems as a refuge and for reproduction for the fish of downstream Târnava Mare River, into which all of them flow. Management elements were proposed to maintain and improve these refuges’ ecological support capacity.
Prediction of PM2.5 Concentration Based on the LSTM-TSLightGBM Variable Weight Combination Model
Authors: Jiang Xuchu , Luo Yiwen , Zhang Biao
Published: September 2021

PM2.5 is one of the main pollutants that cause air pollution, and high concentrations of PM2.5 seriously threaten human health. Therefore, an accurate prediction of PM2.5 concentration has great practical significance for air quality detection, air pollution restoration, and human health. This paper uses the historical air quality concentration data and meteorological data of the Beijing Olympic Sports Center as the research object. This paper establishes a long short-term memory (LSTM) model with a time window size of 12, establishes a T-shape light gradient boosting machine (TSLightGBM) model that uses all information in the time window as the next period of prediction input, and establishes a LSTM-TSLightGBM model pair based on an optimal weighted combination method. PM2.5 hourly concentration is predicted. The prediction results on the test set show that the mean squared error (MAE), root mean squared error (RMSE), and symmetric mean absolute percentage error (SMAPE) of the LSTM-TSLightGBM model are 11.873, 22.516, and 19.540%, respectively. Compared with LSTM, TSLightGBM, the recurrent neural network (RNN), and other models, the LSTM-TSLightGBM model has a lower MAE, RMSE, and SMAPE, and higher prediction accuracy for PM2.5 and better goodness-of-fit.
Genetic and Non Genetic Hearing Loss and Associated Disabilities: An Epidemiological Survey in Emilia-Romagna Region
Authors: Genovese Elisabetta , Palma Silvia , Polizzi Valeria , Bianchin Giovanni , Cappai Michela , Kaleci Shaniko , Martini Alessandro , Ciorba Andrea , Stagi Paolo
Published: September 2021

Hearing loss is one of the most common congenital sensory disorders. It can be associated with several comorbidities, in particular developmental disabilities (DD). In Emilia-Romagna (ER), a region in Northern Italy, Child and Adolescent Mental Health Services (CAMHS) provide the diagnostic framework and treatment for these conditions. The aim of the present study is to evaluate the prevalence of hearing loss, both isolated or in association with comorbidities, in the juvenile population. The study draws its data from the ER Childhood and Adolescent Neuropsychiatry Information System (SINPIAER), an Administrative Healthcare Database collecting the clinical data of all those who have attended CAMHS since 2010. The most frequent type of hearing loss was bilateral sensorineural hearing loss, which was present in 69–72% of the cases, while bilateral conductive hearing loss was the second most common type, ranging from 8 to 10%. Among DD, congenital malformations, mental retardation, visual impairment, and cerebral palsy were the most common. In particular, autism spectrum disorders show increasing incidence and prevalence among CAMHS users in ER region. In-depth knowledge of hearing loss epidemiology and related conditions, such as developmental disabilities, in the juvenile population is crucial for disease prevention, health planning, and resource allocation.
Pathogens and Elicitors Induce Local and Systemic Changes in Triacylglycerol Metabolism in Roots and in Leaves of Arabidopsis thaliana
Authors: Schieferle Sebastian , Tappe Beeke , Korte Pamela , Mueller Martin J. , Berger Susanne
Published: September 2021

Interaction of plants with the environment affects lipid metabolism. Changes in the pattern of phospholipids have been reported in response to abiotic stress, particularly accumulation of triacylglycerols, but less is known about the alteration of lipid metabolism in response to biotic stress and leaves have been more intensively studied than roots. This work investigates the levels of lipids in roots as well as leaves of Arabidopsis thaliana in response to pathogens and elicitor molecules by UPLC-TOF-MS. Triacylglycerol levels increased in roots and systemically in leaves upon treatment of roots with the fungus Verticillium longisporum. Upon spray infection of leaves with the bacterial pathogen Pseudomonas syringae, triacylglycerols accumulated locally in leaves but not in roots. Treatment of roots with a bacterial lipopolysaccharide elicitor induced a strong triacylglycerol accumulation in roots and leaves. Induction of the expression of the bacterial effector AVRRPM1 resulted in a dramatic increase of triacylglycerol levels in leaves, indicating that elicitor molecules are sufficient to induce accumulation of triacylglycerols. These results give insight into local and systemic changes to lipid metabolism in roots and leaves in response to biotic stresses.
Romantic Love and Sleep Variations: Potential Proximate Mechanisms and Evolutionary Functions
Authors: Bode Adam , Kuula Liisa
Published: September 2021

This article provides a narrative review of what is known about romantic love and sleep variations and provides possible explanations for the association. Romantic love and sleep are described using a comprehensive, unifying framework advocated by Tinbergen. We summarise the findings of studies investigating the relationship between romantic love and sleep. Sleep variations are associated with romantic love in adolescents and young adults. We then detail some proximate mechanisms that may contribute to sleep variations in people experiencing romantic love before considering potential evolutionary functions of sleep variations in people experiencing romantic love. The relationship between symptoms of psychopathology and sleep variations in people experiencing romantic love is described. With the current state of knowledge, it is not possible to determine whether sleep variations associated with romantic love are adaptations or by-products of romantic love. We conclude by proposing areas for future research.
The Emergence of New Aggressive Leaf Rust Races with the Potential to Supplant the Resistance of Wheat Cultivars
Authors: Omara Reda Ibrahim , Nehela Yasser , Mabrouk Ola Ibrahim , Elsharkawy Mohsen Mohamed
Published: September 2021

Characterization of the genetic structure and the physiological races of Puccinia triticina is a growing necessity to apply host genetic resistance against wheat leaf rust as a successful control strategy. Herein, we collected and identified about 130 isolates of P. triticina from 16 Egyptian commercial wheat cultivars grown at different locations, over two seasons (2019/2020 and 2020/2021). The 130 isolates of P. triticina were segregated into 17 different physiological races. TTTST and TTTKS were the most common virulent races, whereas TTTST and MTTGT were the most frequent races. The races were classified into three groups, based on their distinct DNA band sizes (150 bp, 200 bp, and 300 bp) after RAPD analysis. The new wheat cultivars (Sakha-94, Sakha-95, and Shandweel-1) infected with the most virulent race (TTTST), Gemmeiza-12, and Misr-3 were resistant to all physiological races. The resistance of these cultivars was mostly due to the presence of Lr19- and Lr28-resistant genes. Our results serve as a warning about emerging aggressive races capable of supplanting resistance to leaf rust, and help in the understanding of the pathotype–cultivar–location association and its role in the susceptibility/resistance of new wheat cultivars to P. triticina.
The Role of Intracellular Trafficking of Notch Receptors in Ligand-Independent Notch Activation
Authors: Hounjet Judith , Vooijs Marc
Published: September 2021

Aberrant Notch signaling has been found in a broad range of human malignancies. Consequently, small molecule inhibitors and antibodies targeting Notch signaling in human cancers have been developed and tested; however, these have failed due to limited anti-tumor efficacy because of dose-limiting toxicities in normal tissues. Therefore, there is an unmet need to discover novel regulators of malignant Notch signaling, which do not affect Notch signaling in healthy tissues. This review provides a comprehensive overview of the current knowledge on the role of intracellular trafficking in ligand-independent Notch receptor activation, the possible mechanisms involved, and possible therapeutic opportunities for inhibitors of intracellular trafficking in Notch targeting.
Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure
Authors: Liao Shuyi , Yang Wenmin , Yu Ting , Dai Lu , Liu Xiaoliang , Zhang Jiangping , Zhao Jinghong , Liu Chi
Published: September 2021

Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a Tg(cdh17:Dendra2-NTR) transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.
Anti-SARS-CoV-2 Activity of Extracellular Vesicle Inhibitors: Screening, Validation, and Combination with Remdesivir
Authors: Kongsomros Supasek , Suksatu Ampa , Kanjanasirirat Phongthon , Manopwisedjaroen Suwimon , Prasongtanakij Somsak , Jearawuttanakul Kedchin , Borwornpinyo Suparerk , Hongeng Suradej , Thitithanyanont Arunee , Chutipongtanate Somchai
Published: September 2021

The coronavirus disease 2019 (COVID-19) pandemic severely impacts health, economy, and society worldwide. Antiviral drugs against SARS-CoV-2 are urgently needed to cope with this global crisis. It has been found that the biogenesis and release mechanisms of viruses share a common pathway with extracellular vesicles (EVs). We hypothesized that small molecule inhibitors of EV biogenesis/release could exert an anti-SARS-CoV-2 effect. Here, we screened 17 existing EV inhibitors and found that calpeptin, a cysteine proteinase inhibitor, exhibited the most potent anti-SARS-CoV-2 activity with no apparent cytotoxicity. Calpeptin demonstrated the dose-dependent inhibition against SARS-CoV-2 viral nucleoprotein expression in the infected cells with a half-maximal inhibitory concentration (IC50) of 1.44 µM in Vero-E6 and 26.92 µM in Calu-3 cells, respectively. Moreover, calpeptin inhibited the production of infectious virions with the lower IC50 of 0.6 µM in Vero E6 cells and 10.12 µM in Calu-3 cells. Interestingly, a combination of calpeptin and remdesivir, the FDA-approved antiviral drug against SARS-CoV-2 viral replication, significantly enhanced the anti-SARS-CoV-2 effects compared to monotherapy. This study discovered calpeptin as a promising candidate for anti-SARS-CoV-2 drug development. Further preclinical and clinical studies are warranted to elucidate the therapeutic efficacy of calpeptin and remdesivir combination in COVID-19.
Imaging Changes and Immune-Checkpoint Expression on T Cells in Bronchoalveolar Lavage Fluid from Patients with Pulmonary Sarcoidosis
Authors: Kotetsu Yasuaki , Yanagihara Toyoshi , Suzuki Kunihiro , Ando Hiroyuki , Eto Daisuke , Hata Kentaro , Arimura-Omori Masako , Yamamoto Yuzo , Harada Eiji , Hamada Naoki
Published: September 2021

Sarcoidosis is a systemic, granulomatous disease caused by unknown immunological abnormalities. The organs most vulnerable to sarcoidosis are the lungs. Patients often resolve spontaneously, but the lungs can also be severely affected. Although details regarding prognostic factors in sarcoidosis patients with lung involvement remain unclear, several reports have suggested that immune checkpoint molecules are involved in the pathogenesis of sarcoidosis. In this study, we divided sarcoidosis patients into two groups based on chest computed tomography (CT) findings and compared immune checkpoint molecules expressed on T cells in bronchoalveolar lavage fluid (BALF) in the two groups, using flow cytometry. We found elevated programmed cell death 1 (PD-1) or T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) expression on T cells in BALF in patients with spontaneous improvement in CT findings, compared with those in patients without improvement in CT findings. In conclusion, our study implies that PD-1 or TIM-3 expression on T cells in BALF may be a prognostic factor for pulmonary lesions in sarcoidosis.
Overexpression of Neuron-Derived Orphan Receptor 1 (NOR-1) Rescues Cardiomyocytes from Cell Death and Improves Viability after Doxorubicin Induced Stress
Authors: Berg Per-Christian , Hansson Åse , Røsand Øystein , Marwarha Gurdeep , Høydal Morten
Published: September 2021

Following myocardial infarction, reperfusion injury (RI) is commonly observed due to the excessive formation of, e.g., reactive oxygen species (ROS). Doxorubicin (DOX), a widely used anti-cancer drug, is also known to cause cardiotoxicity due to excessive ROS production. Exercise training has been shown to protect the heart against both RI- and DOX-induced cardiotoxicity, but the exact mechanism is still unknown. Neuron-derived orphan receptor 1 (NOR-1) is an important exercise-responsive protein in the skeletal muscle which has also been reported to facilitate cellular survival during hypoxia. Therefore, we hypothesized that NOR-1 could protect cardiomyocytes (CMs) against cellular stress induced by DOX. We also hypothesized that NOR-1 is involved in preparing the CMs against a stress situation during nonstimulated conditions by increasing cell viability. To determine the protective effect of NOR-1 in CMs stressed with DOX challenge, we overexpressed NOR-1 in AC16 human CMs treated with 5 µM DOX for 12 h or the respective vehicle control, followed by performing Lactate dehydrogenase (LDH) activity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and caspase-3 activity assays to measure cell death, cell viability, and apoptosis, respectively. In addition, Western blotting analysis was performed to determine the expression of key proteins involved in cardioprotection. We demonstrated that NOR-1 overexpression decreased cell death (p < 0.105) and apoptosis (p < 0.01) while increasing cell viability (p < 0.05) in DOX-treated CMs. We also observed that NOR-1 overexpression increased phosphorylation of extracellular signal-regulated kinase (ERK) (p < 0.01) and protein expression levels of B cell lymphoma extra-large (Bcl-xL) (p < 0.01). We did not detect any significant changes in phosphorylation of protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β) and signal transducer and activator of transcription 3 (STAT3) or expression levels of superoxide dismutase 2 (SOD2) and cyclin D1. Furthermore, we demonstrated that NOR-1 overexpression increased the cell viability (p < 0.0001) of CMs during nonstimulated conditions without affecting cell death or apoptosis. Our findings indicate that NOR-1 could serve as a potential cardioprotective protein in response to Doxorubicin-induced cellular stress.
Neutrophils as Regulators and Biomarkers of Cardiovascular Inflammation in the Context of Abdominal Aortic Aneurysms
Authors: Klopf Johannes , Brostjan Christine , Neumayer Christoph , Eilenberg Wolf
Published: September 2021

Neutrophils represent up to 70% of circulating leukocytes in healthy humans and combat infection mostly by phagocytosis, degranulation and NETosis. It has been reported that neutrophils are centrally involved in abdominal aortic aneurysm (AAA) pathogenesis. The natural course of AAA is growth and rupture, if left undiagnosed or untreated. The rupture of AAA has a very high mortality and is currently among the leading causes of death worldwide. The use of noninvasive cardiovascular imaging techniques for patient screening, surveillance and postoperative follow-up is well established and recommended by the current guidelines. Neutrophil-derived biomarkers may offer clinical value to the monitoring and prognosis of AAA patients, allowing for potential early therapeutic intervention. Numerous promising biomarkers have been studied. In this review, we discuss neutrophils and neutrophil-derived molecules as regulators and biomarkers of AAA, and our aim was to specifically highlight diagnostic and prognostic markers. Neutrophil-derived biomarkers may potentially, in the future, assist in determining AAA presence, predict size, expansion rate, rupture risk, and postoperative outcome once validated in highly warranted future prospective clinical studies.
A Review of the Clinical and Therapeutic Implications of Neuropathic Pain
Authors: Balzani Eleonora , Fanelli Andrea , Malafoglia Valentina , Tenti Michael , Ilari Sara , Corraro Annette , Muscoli Carolina , Raffaeli William
Published: September 2021

Understanding neuropathic pain presents several challenges, given the various mechanisms underlying its pathophysiological classification and the lack of suitable tools to assess its diagnosis. Furthermore, the response of this pathology to available drugs is still often unpredictable, leaving the treatment of neuropathic pain still questionable. In addition, the rise of personalized treatments further extends the ramified classification of neuropathic pain. While a few authors have focused on neuropathic pain clustering, by analyzing, for example, the presence of specific TRP channels, others have evaluated the presence of alterations in microRNAs to find tailored therapies. Thus, this review aims to synthesize the available evidence on the topic from a clinical perspective and provide a list of current demonstrations on the treatment of this disease.
Functions of SMC2 in the Development of Zebrafish Liver
Authors: Li Xixi , Song Guili , Zhao Yasong , Ren Jing , Li Qing , Cui Zongbin
Published: September 2021

SMC2 (structural maintenance of chromosomes 2) is the core subunit of condensins, which play a central role in chromosome organization and segregation. However, the functions of SMC2 in embryonic development remain poorly understood, due to the embryonic lethality of homozygous SMC2−/− mice. Herein, we explored the roles of SMC2 in the liver development of zebrafish. The depletion of SMC2, with the CRISPR/Cas9-dependent gene knockout approach, led to a small liver phenotype. The specification of hepatoblasts was unaffected. Mechanistically, extensive apoptosis occurred in the liver of SMC2 mutants, which was mainly associated with the activation of the p53-dependent apoptotic pathway. Moreover, an aberrant activation of a series of apoptotic pathways in SMC2 mutants was involved in the defective chromosome segregation and subsequent DNA damage. Therefore, our findings demonstrate that SMC2 is necessary for zebrafish liver development.
Cell Properties of Lung Tissue-Resident Macrophages Propagated by Co-Culture with Lung Fibroblastic Cells from C57BL/6 and BALB/c Mice
Authors: Tsurutani Mayu , Horie Haruka , Ogawa Kazushige
Published: September 2021

Tissue-resident macrophages (Mø) originating from foetal precursors are maintained by self-renewal under tissue/organ-specific microenvironments (niches). We recently developed a simple propagation method applicable to tissue-resident Mø by co-culturing. Here, we examined the properties of lung tissue-resident Mø propagated by co-culturing with lung interstitial cells. The intracardially and intratracheally perfused lung from BALB/c and C57BL/6 mice could minimise the contamination of alveolar Mø and lung monocytes. Lung tissue-resident Mø could be largely propagated under standard culture media along with the propagation of lung interstitial cells demonstrating a fibroblastic morphology. Propagated lung Mø showed characteristic expression properties for Mø/monocyte markers: high expressions of CD11b, CD64 and CD206; substantial expressions of Mertk; and negative expressions of Ly6C, MHC II and Siglec-F. These properties fit with those of lung interstitial Mø of a certain population that can undergo self-renewal. Propagated fibroblastic cells by co-culturing with lung Mø possessed niche properties such as Csf1 and Tgfb1 expression. Propagated lung Mø from both the mouse types were polarised to an M2 phenotype highly expressing arginase 1 without M2 inducer treatment, whereas the M1 inducers significantly increased the iNOS-positive cell percentages in C57BL/6 mice relative to those in BALB/c mice. This is the first study to demonstrate fundamental properties of lung tissue-resident Mø propagated by co-culturing. Propagated lung Mø showing features of lung interstitial Mø can serve as an indispensable tool for investigating SARS-CoV-2 diseases, although lung interstitial Mø have gained little attention in terms of their involvement in SARS-CoV-2 disease pathology, in contrast to alveolar and recruited Mø.
Circulating Tumor Cells as a Tool to Untangle the Breast Cancer Heterogeneity Issue
Authors: Rossi Tania , Gallerani Giulia , Martinelli Giovanni , Maltoni Roberta , Fabbri Francesco
Published: September 2021

Breast cancer (BC) is a disease characterized by high degrees of heterogeneity at morphologic, genomic, and genetic levels, even within the same tumor mass or among patients. As a consequence, different subpopulations coexist and less represented clones may have a selective advantage, significantly influencing the outcome of BC patients. Circulating tumor cells (CTCs) represent a rare population of cells with a crucial role in metastatic cascade, and in recent years have represented a fascinating alternative to overcome the heterogeneity issue as a “liquid biopsy”. However, besides the raw enumeration of these cells in advanced epithelial tumors, there are no CTC-based assays applied in the clinical practice to improve personalized medicine. In this review, we report the latest findings in the field of CTCs for intra-tumoral heterogeneity unmasking in BC, supporting the need to deepen their analysis to investigate their role in metastatic process and include the molecular characterization in the clinical practice. In the future, CTCs will be helpful in monitoring patients during treatment, as well as to better address therapeutic strategies.
Self-Powered Biosensor for Specifically Detecting Creatinine in Real Time Based on the Piezo-Enzymatic-Reaction Effect of Enzyme-Modified ZnO Nanowires
Authors: Wang Meng , Zi Guangting , Liu Jiajun , Song Yutong , Zhao Xishan , Wang Qi , Zhao Tianming
Published: September 2021

Creatinine has become an important indicator for the early detection of uremia. However, due to the disadvantages of external power supply and large volume, some commercial devices for detecting creatinine concentration have lost a lot of popularity in everyday life. This paper describes the development of a self-powered biosensor for detecting creatinine in sweat. The biosensor can detect human creatinine levels in real time without the need for an external power source, providing information about the body’s overall health. The piezoelectric output voltage of creatininase/creatinase/sarcosine oxidase-modified ZnO nanowires (NWs) is significantly dependent on the creatinine concentration due to the coupling effect of the piezoelectric effect and enzymatic reaction (piezo-enzymatic-reaction effect), which can be regarded as both electrical energy and biosensing signal. Our results can be used for the detection of creatinine levels in the human body and have great potential in the prediction of related diseases.
The Impact of COVID-19 on Cognitive Development and Executive Functioning in Adolescents: A First Exploratory Investigation
Authors: Frolli Alessandro , Ricci Maria Carla , Di Carmine Francesca , Lombardi Agnese , Bosco Antonia , Saviano Emilio , Franzese Luisa
Published: September 2021

Background: The rapid expansion and severity of the COVID-19 contagion has had negative physical and psychological health implications for millions of people around the world, but even more so among children and adolescents. Given the severity of the situation and the small number of studies on the direct influence of viral infection on the cognitive development within adolescents, the present study aims at understanding the consequences of contracting the virus and being hospitalized in relation to cognitive functioning, in particular, for executive functioning, among adolescents. Methods: To all subjects included in the sample, divided into four groups based on the severity of the COVID-19 infection, were administered the WISC-IV in order to evaluate the global cognitive functioning, and subsequently, the subtests Courses and Tower of London (ToL), both part of the BVN 12–18, were administered for the evaluation of executive operation. Results: Our analyses showed that between subjects who did not contract the viral infection and those who contracted it in an asymptomatic form, there are no significant differences in cognitive functioning, but only in executive functioning. Furthermore, in both hospitalized and non-hospitalized subjects, we found lower scores especially for WM skills, while IQ scores are in a medium range. Conclusion: the present study shows that contracting the viral infection and, thus, being hospitalized, caused greater problems and difficulties as compared to those who were not hospitalized, impacting global cognitive (and executive) functioning, especially the WM. We believe that these results could allow an early detection of alterations in cognitive and executive functioning, a fundamental aspect of the interventions that occur in evolutionary phases such as those related to pre-adolescence, allowing, therefore, the activation of functional recovery pathways in a short time.