bluuebunny/crossref_metadata_2025 huggingface dataset:
Research of the Photo-Optical Method Application for Measuring Selected Data on the Movement of a Parachute for Type M-282
Authors: Kaľavský Peter , Rozenberg Róbert , Korba Peter , Kelemen Martin , Antoško Matej , Sabo Jozef , Džunda Milan
Published: June 2021

Testing in the field of parachute technology provides space for the application of new and innovative methods of measuring operating and functional parameters. The main aim of the paper is to present the results of research for the verification of the photo-optical method of measuring the vertical speed of the M-282 parachutes, and for its use in testing, collecting, and investigating motion data in parachuting. As part of this measuring technology, twelve jumps were performed. It was verified that the experiment was completed for the M-282 parachute according to the regulation of SAE AS 8015B “Minimum Performance Standard Parachute Assemblies and Components”. An analysis of the influencing factors and quantification of their influence on the uncertainty of the measurement results was also performed. The results of the measurement achieved by using the photo-optical method were compared with the measurement with the electronic variometer FLYTEC 4030. The vertical speed of the M-282 parachute (4.655 m·s−1) defined by the photo-optical method is significantly similar to the vertical speed of the M-282 parachute (4.662 m·s−1) defined by FLYTEC 4030. We can state that the process of identifying the vertical speed of the parachute by the photo-optical method was correct. This is a suitable method of evaluating motion data in the operation of M-282 type parachutes. In the following research for generalization of the methodology, we assume the performance of more than 60 experimental jumps using different types of parachutes, digital sensors (cameras), and a photo-optical method to examine motion data and formulate recommendations for testing, investigative applications, individualized training programs, and aspects of parachuting injury prevention.
Leader-Follower Formation Control of Wheeled Mobile Robots without Attitude Measurements
Authors: Hirata-Acosta Jonathan , Pliego-Jiménez Javier , Cruz-Hernádez César , Martínez-Clark Rigoberto
Published: June 2021

The problem of leader-follower formation of a platoon of differential-drive wheeled mobile robots without using attitude measurements is addressed in this paper. Contrary to the position-distance approaches existing in the literature, the formation and collision avoidance is achieved by introducing a state-dependent delay in the desired trajectory. The delay is obtained as the output of a dynamical system and its magnitude will decrease/increase depending on the distance between the robots. To guarantee trajectory tracking and to overcome the lack of orientation measurements, an output feedback control and attitude observer are proposed based on the kinematic model of the robots. The attitude observer is designed directly on the special orthogonal group SO(2) and it can be used in open-loop schemes. The proposed control-observer scheme ensures asymptotic convergence of the tracking and observer errors. Finally, experimental results are presented to show the performance of the proposed approach.
Identifying General Stress in Commercial Tomatoes Based on Machine Learning Applied to Plant Electrophysiology
Authors: Najdenovska Elena , Dutoit Fabien , Tran Daniel , Rochat Antoine , Vu Basile , Mazza Marco , Camps Cédric , Plummer Carrol , Wallbridge Nigel , Raileanu Laura Elena
Published: June 2021

Automated monitoring of plant health is becoming a crucial component for optimizing agricultural production. Recently, several studies have shown that plant electrophysiology could be used as a tool to determine plant status related to applied stressors. However, to the best of our knowledge, there have been no studies relating electrical plant response to general stress responses as a proxy for plant health. This study models general stress of plants exposed to either biotic or abiotic stressors, namely drought, nutrient deficiencies or infestation with spider mites, using electrophysiological signals acquired from 36 plants. Moreover, in the signal processing procedure, the proposed workflow reuses information from the previous steps, therefore considerably reducing computation time regarding recent related approaches in the literature. Careful choice of the principal parameters leads to a classification of the general stress in plants with more than 80% accuracy. The main descriptive statistics measured together with the Hjorth complexity provide the most discriminative information for such classification. The presented findings open new paths to explore for improved monitoring of plant health.
Variable Admittance Control Based on Trajectory Prediction of Human Hand Motion for Physical Human-Robot Interaction
Authors: Wang Yu , Yang Yuanyuan , Zhao Baoliang , Qi Xiaozhi , Hu Ying , Li Bing , Sun Lining , Zhang Lihai , Meng Max Q.-H.
Published: June 2021

In order to achieve effective physical human–robot interaction, human dynamic characteristics needs to be considered in admittance control. This paper proposes a variable admittance control method for physical human–robot interaction based on trajectory prediction of human hand motion. By predicting the moving direction of the robot end tool under human guidance, the admittance control parameters are adjusted to reduce the interaction force. The end tool trajectory of the robot under human guidance is used for offline training of long and short-term memory neural network to generate trajectory predictors. Then the trajectory predictors are used in variable admittance control to predict the trajectory and movement direction of the robot end tool in real time. The variable admittance controller adjusts the damping matrix to reduce the damping value in the moving direction. Experiment results show that, using the constant admittance method as a benchmark, the interaction force of the proposed method is reduced by 23%, the trajectory error is reduced by 51%, and the operating jerk is reduced by at least 21%, which proves that the proposed method improves the accuracy and compliance of the operation.
Ginsenoside Rh1 Exerts Neuroprotective Effects by Activating the PI3K/Akt Pathway in Amyloid-β Induced SH-SY5Y Cells
Authors: Park Miey , Kim So-Hyeun , Lee Hae-Jeung
Published: June 2021

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of β-amyloid plaques and hyperphosphorylated tau proteins in the brain. Cell signaling pathways such as PI3K/Akt are known to play an essential role in regulating cell survival, motility, transcription, metabolism, and progression of the cell cycle. Recent studies demonstrated that the disruption of these signaling pathways in neurodegenerative disorders leads to oxidative stress and cell death. Targeting these altered signaling pathways could be considered as the therapeutic approach for neurodegenerative disorders. Ginsenoside Rh1 is known to provide beneficial effects in various diseases such as cancer, diabetes, and inflammation. In this study, human neuroblastoma SH-SY5Y cells were treated with the β-amyloid oligomers alone or in combination with ginsenoside Rh1. We observed that ginsenoside Rh1 was able to attenuate β-amyloid induced oxidative stress and cell death by activating the PI3K/Akt signaling pathway. Based on these findings, we suggest that ginsenoside Rh1 might be an efficacious therapeutic agent for AD.
Investigation of the Thermal Conductivity of Silicon-Base Composites: The Effect of Filler Materials and Characteristic on Thermo-Mechanical Response of Silicon Composite
Authors: Riccucci Giacomo , Pezzana Lorenzo , Lantean Simone , Tori Alice , Spriano Silvia , Sangermano Marco
Published: June 2021

Thermal conductivity is a key property in many applications from electronic to informatics. The interaction of fillers with Sylgard 184 was studied; this study explores new composites and the influence of metal particles (copper and nickel), carbon-based materials (carbon nanotubes and carbon black), and ceramic nanoparticles (boron nitride) as fillers to enhance thermal properties of silicon-based composites. The effect of the fillers on the final performances of the composite materials was evaluated. The influence of filler volume, dimension, morphology, and chemical nature is studied. Specifically, FT-IR analysis was used to evaluate curing of the polymer matrix. DSC was used to confirm the data and to further characterize the composites. Thermo-mechanical properties were studied by DMTA. The filler morphology was analyzed by SEM. Finally, thermal conductivity was studied and compared, enlightening the correlation with the features of the fillers. The results demonstrate a remarkable dependence among the type, size, and shape of the filler, and thermal properties of the composite materials. Underlining a that the volume filler influenced the thermal conductivity obtaining the best results with the highest added volume filler and higher positive impact on the k of the composites is reached with large particles and with irregular shapes. In contrast, the increase of filler amount affects the rigidity of the silicon-matrix, increasing the rigidity of the silicon-based composites.
Helmholtz Resonance Frequency of the Synthetic Jet Actuator
Authors: Gil Paweł , Wilk Joanna , Korzeniowski Michał
Published: June 2021

This paper presents the results of experimental investigations of 108 geometrical configurations of a loudspeaker-driven synthetic jet (SJ) actuator. The considered cases of the SJ actuator were characterized by a high coupling ratio. The experiment was performed to determine the impact of geometry on the Helmholtz resonance frequency. Geometrical parameters of the orifice diameter, orifice length, and cavity volume were changed within a wide range. The dependences of electrical and flow parameters that characterized the synthetic jet actuators as a function of the excitation frequency were also identified. The main goal of the research was to identify the optimal mathematical formula of the model to calculate the Helmholtz resonance frequency in the case of synthetic jet actuators. To determine the model that was characterized by the best fit of the experimental results, an additional geometrical dimensionless parameter, representing the ratio of the orifice cross-section area to the cross-section area of the cavity, was introduced. A significant impact of this parameter on the effective orifice length was noted. Based on the research findings, a model was obtained for which the results of the experiment were in the error range of ±6% for 95% of the measurement data. The obtained model is an improved version of the classical model used in the description of the resonance frequency in the case of a synthetic jet actuator. The model enables highly accurate determination of the Helmholtz resonance frequency at which the maximum synthetic jet actuator parameters occur.
Natural Clays as Potential Amino Acids Carriers for Animal Nutrition Application
Authors: Cristiani Cinzia , Finocchio Elisabetta , Rossi Luciana , Giromini Carlotta , Dell’Anno Matteo , Panseri Sara , Bellotto Maurizio
Published: June 2021

This study has the main purpose of testing natural carriers as more sustainable alternatives to polymeric coating. New clay-based hybrid organic–inorganic materials have been prepared. An innovative procedure for the intercalation of the bioactive molecule is proposed. The synthesis process implies the use of mild operating conditions and does not require the use of organic reactants or solvents. Moreover, the use of natural carriers, and milder environmentally friendly process conditions, fulfill the requirement of a mostly safe, greener production. The capture and the release properties of the final material mainly depend on the carrier morphology. Large zeolite content in the mineral clays can favor the capture of very large methionine loadings, but due to the trapping mechanism, typical of these structures, zeolites prevent a satisfactory release in mild condition and physiological condition. The Freundlich adsorption model has been found to be able to predict the capture behavior. Once the proper carrier is selected, the preparation procedure guarantees the protection of the amino acid in the right form. Neither the structure of the inorganic matrix nor the amino acid structure was changed in the preparation process. Methionine was detected in its zwitterionic form, showing the main IR bands only slightly affected by the interaction. Further studies on methionine bioaccessibility and intestinal absorption from methionine–Adsorbene (MET–ADS) are required to optimize the application of natural clay in in-field animal nutrition.
Spatial–Temporal Assessment of Historical and Future Meteorological Droughts in China
Authors: Han Rucun , Li Zhanling , Li Zhanjie , Han Yuanyuan
Published: June 2021

Drought is a natural phenomenon in which the natural amount of water in an area is below the normal level. It has negative impacts on production in numerous industries and people’s lives, especially in the context of climate change. Investigating the spatial–temporal variation of drought is of great importance in water resource allocation and management. For a better understanding of how drought has changed in China from 1961 to 2020 and will change in the future period of this century (2021–2100), a spatial–temporal assessment of drought based on the standardized precipitation evapotranspiration index (SPEI) was carried out. The trends and characteristics (number, duration, and severity) of historical and future droughts in China were evaluated based on 12-month SPEI by employing the Mann–Kendall test, Sen’s slope and run theory. The similarities, differences, and spatial–temporal evolution of droughts in these two periods were analyzed. The results showed that in the historical period the number of droughts decreased gradually from the south of China to the north. Less frequent drought but with longer duration and stronger severity occurred in the northeast and the northern areas. In the future period, most parts of China are projected to suffer more severe droughts with longer duration, especially for Northeast China, North China, Qinghai–Tibetan Plateau, and Southwest China. The likely increasing severity and duration of droughts in most areas of China in the future makes it very necessary to formulate the corresponding drought prevention and relief strategies to reduce the possible losses caused by droughts.
BioChem: A New International and Interdisciplinary Journal
Authors: Ma Buyong
Published: June 2021

The advances of biological science have fundamentally changed our world and our understanding of human beings [...]
Coronavirus Disease 2019 (COVID-19) Crisis: Losing Our Immunity When We Need It the Most
Authors: Ghanemi Abdelaziz , Yoshioka Mayumi , St-Amand Jonny
Published: June 2021

The ongoing coronavirus disease 2019 (COVID-19) crisis has led to a new socioeconomic reality with the acquisition of novel habits. Measures imposed by governments and health authorities such as confinement and lockdown have had important consequences, including mental health problems, economic crisis, and social isolation. Combined with newly acquired habits such as hand washing, sanitization, and face masks, these have all directly and indirectly led to reduced immunity. Such effects on the immune system not only impact the epidemiological profile with respect to COVID-19 and other infectious diseases but also limit the efficacy of the ongoing anti-COVID-19 vaccination campaign. Therefore, there is a need to review these approaches and optimize measures towards better population immunity, which is much needed during such an epidemic.
Acute and Sub-Chronic Exposure to Artificial Sweeteners at the Highest Environmentally Relevant Concentration Induce Less Cardiovascular Physiology Alterations in Zebrafish Larvae
Authors: Saputra Ferry , Lai Yu-Heng , Fernandez Rey Arturo T. , Macabeo Allan Patrick G. , Lai Hong-Thih , Huang Jong-Chin , Hsiao Chung-Der
Published: June 2021

Artificial sweeteners are widely used food ingredients in beverages and drinks to lower calorie intake which in turn helps prevent lifestyle diseases such as obesity. However, as their popularity has increased, the release of artificial sweetener to the aquatic environment has also increased at a tremendous rate. Thus, our study aims to systematically explore the potential cardiovascular physiology alterations caused by eight commercial artificial sweeteners, including acesulfame-K, alitame, aspartame, sodium cyclamate, dulcin, neotame, saccharine and sucralose, at the highest environmentally relevant concentration on cardiovascular performance using zebrafish (Danio rerio) as a model system. Embryonic zebrafish were exposed to the eight artificial sweeteners at 100 ppb and their cardiovascular performance (heart rate, ejection fraction, fractional shortening, stroke volume, cardiac output, heartbeat variability, and blood flow velocity) was measured and compared. Overall, our finding supports the safety of artificial sweetener exposure. However, several finding like a significant increase in the heart rate and heart rate variability after incubation in several artificial sweeteners are noteworthy. Biomarker testing also revealed that saccharine significantly increase the dopamine level in zebrafish larvae, which is might be the reason for the cardiac physiology changes observed after saccharine exposure.
Pharmacokinetics and Molecular Modeling Indicate nAChRα4-Derived Peptide HAEE Goes through the Blood–Brain Barrier
Authors: Zolotarev Yurii A. , Mitkevich Vladimir A. , Shram Stanislav I. , Adzhubei Alexei A. , Tolstova Anna P. , Talibov Oleg B. , Dadayan Alexander K. , Myasoyedov Nikolai F. , Makarov Alexander A. , Kozin Sergey A.
Published: June 2021

One of the treatment strategies for Alzheimer’s disease (AD) is based on the use of pharmacological agents capable of binding to beta-amyloid (Aβ) and blocking its aggregation in the brain. Previously, we found that intravenous administration of the synthetic tetrapeptide Acetyl-His-Ala-Glu-Glu-Amide (HAEE), which is an analogue of the 35–38 region of the α4 subunit of α4β2 nicotinic acetylcholine receptor and specifically binds to the 11–14 site of Aβ, reduced the development of cerebral amyloidogenesis in a mouse model of AD. In the current study on three types of laboratory animals, we determined the biodistribution and tissue localization patterns of HAEE peptide after single intravenous bolus administration. The pharmacokinetic parameters of HAEE were established using uniformly tritium-labeled HAEE. Pharmacokinetic data provided evidence that HAEE goes through the blood–brain barrier. Based on molecular modeling, a role of LRP1 in receptor-mediated transcytosis of HAEE was proposed. Altogether, the results obtained indicate that the anti-amyloid effect of HAEE, previously found in a mouse model of AD, most likely occurs due to its interaction with Aβ species directly in the brain.
White Matter Survival within and around the Hematoma: Quantification by MRI in Patients with Intracerebral Hemorrhage
Authors: Novakovic Nemanja , Linzey Joseph R. , Chenevert Thomas L. , Gemmete Joseph J. , Troost Jonathan P. , Xi Guohua , Keep Richard F. , Pandey Aditya S. , Chaudhary Neeraj
Published: June 2021

White matter (WM) injury and survival after intracerebral hemorrhage (ICH) has received insufficient attention. WM disruption surrounding the hematoma has been documented in animal models with histology, but rarely in human ICH with noninvasive means, like magnetic resonance imaging (MRI). A few human MRI studies have investigated changes in long WM tracts after ICH remote from the hematoma, like the corticospinal tract, but have not attempted to obtain an unbiased quantification of WM changes within and around the hematoma over time. This study attempts such quantification from 3 to 30 days post ictus. Thirteen patients with mild to moderate ICH underwent diffusion tensor imaging (DTI) MRI at 3, 14, and 30 days. Fractional anisotropy (FA) maps were used to calculate the volume of tissue with FA > 0.5, both within the hematoma (lesion) and in the perilesional tissue. At day 3, the percentages of both lesional and perilesional tissue with an FA > 0.5 were significantly less than contralateral, unaffected, anatomically identical tissue. This perilesional contralateral difference persisted at day 14, but there was no significant difference at day 30. The loss of perilesional tissue with FA > 0.5 increased with increasing hematoma size at day 3 and day 14. All patients had some tissue within the lesion with FA > 0.5 at all time points. This did not decrease with duration after ictus, suggesting the persistence of white matter within the hematoma/lesion. These results outline an approach to quantify WM injury, both within and surrounding the hematoma, after mild to moderate ICH using DTI MRI. This may be important for monitoring treatment strategies, such as hematoma evacuation, and assessing efficacy noninvasively.
Fabrication of an Electrochemical Aptasensor Composed of Multifunctional DNA Three-Way Junction on Au Microgap Electrode for Interferon Gamma Detection in Human Serum
Authors: Noh Seungwoo , Kim Jinmyeong , Park Chulhwan , Min Junhong , Lee Taek
Published: June 2021

Interferon gamma (IFN-γ) is an important cytokine with antiviral, antibacterial, and immunosuppressive properties. It has been used as a biomarker for the early detection of several diseases, including cancer, human immunodeficiency virus (HIV), tuberculosis, and paratuberculosis. In this study, we developed an electrochemical biosensor composed of multifunctional DNA 3WJ to detect IFN-γ level with high sensitivity. Each multifunctional triple-stranded aptamer (MF-3WJ) was designed to have an IFN-γ aptamer sequence, anchoring region (thiol group), and 4C–C (cytosine–cytosine) mismatch sequence (signal generation), which could introduce silver ions. To generate the electrochemical signal, four Ag+ ions were intercalated (3wj b-3wj c) in the 4C–C mismatch sequence. MF-3WJ was assembled through the annealing step, and the assembly of MF-3WJ was confirmed by 8% tris–boric–EDTA native polyacrylamide gel electrophoresis. The Au microgap electrode was manufactured to load sample volumes of 5 µL. The reliability of electrochemical biosensor measurement was established by enabling the measurement of seven samples from one Au microgap electrode. MF-3WJ was immobilized on the Au microgap electrode. Then, cyclic voltammetry and electrochemical impedance spectroscopy were performed to confirm the electrochemical properties of MF-3WJ. To test the electrochemical biosensor’s ability to detect IFN-γ, the limit of detection (LOD) and selectivity tests were performed by square wave voltammetry. A linear region was observed in the concentration range of 1 pg/mL–10 ng/mL of IFN-γ. The LOD of the fabricated electrochemical biosensor was 0.67 pg/mL. In addition, for the clinical test, the LOD test was carried out for IFN-γ diluted in 10% human serum samples in the concentration range of 1 pg/mL–10 ng/mL, and the LOD was obtained at 0.42 pg/mL.
Ovarian Cancer: Biomarkers and Targeted Therapy
Authors: Radu Mihaela Raluca , Prădatu Alina , Duică Florentina , Micu Romeo , Creţoiu Sanda Maria , Suciu Nicolae , Creţoiu Dragoş , Varlas Valentin Nicolae , Rădoi Viorica Elena
Published: June 2021

Ovarian cancer is one of the most common causes of death in women as survival is highly dependent on the stage of the disease. Ovarian cancer is typically diagnosed in the late stage due to the fact that in the early phases is mostly asymptomatic. Genomic instability is one of the hallmarks of ovarian cancer. While ovarian cancer is stratified into different clinical subtypes, there still exists extensive genetic and progressive diversity within each subtype. Early detection of the disorder is one of the most important steps that facilitate a favorable prognosis and a good response to medical therapy for the patients. In targeted therapies, individual patients are treated by agents targeting the changes in tumor cells that help them grow, divide and spread. Currently, in gynecological malignancies, potential therapeutic targets include tumor-intrinsic signaling pathways, angiogenesis, homologous-recombination deficiency, hormone receptors, and immunologic factors. Ovarian cancer is usually diagnosed in the final stages, partially due to the absence of an effective screening strategy, although, over the times, numerous biomarkers have been studied and used to assess the status, progression, and efficacy of the drug therapy in this type of disorder.
Opioid Antagonist in the Treatment of Ischemic Stroke
Authors: Ortiz Juan Fernando , Cruz Claudio , Patel Amrapali , Khurana Mahika , Eissa-Garcés Ahmed , Alzamora Ivan Mateo , Halan Taras , Altamimi Abbas , Ruxmohan Samir , Patel Urvish K.
Published: June 2021

Stroke is a leading cause of death and disability, and novel treatments need to be found, particularly drugs with neuroprotective and restorative effects. Lately, there has been an increased interest in the relationship between opioids and ischemic stroke. To further appreciate this association between opioids and stroke, we conducted a systematic review to investigate anti-opioid medication’s effectiveness in treating ischemic stroke. We used PubMed advanced-strategy and Google Scholar searches and only included full-text clinical trials on humans and written in the English language. After applying the inclusion/exclusion criteria, seven clinical trials were reviewed. Only one of the naloxone and nalmefene clinical trials showed statistically favorable results. Overall, the nalmefene clinical trials used more updated measures (NIHSS, GOS) to evaluate recovery and functional status in ischemic stroke patients than the naloxone clinical trials. There was less bias in the nalmefene clinical trials. Animal and in vitro studies have showed promising results. Additional research should be conducted with new clinical trials of both drugs with larger samples in patients less than 70 years old and moderate to severe infarcts.
Transcranial Direct Current Stimulation as a Treatment Tool for Mild Traumatic Brain Injury
Authors: Rudroff Thorsten , Workman Craig D.
Published: June 2021

Mild traumatic brain injury (mTBI) has been defined as a transient (<24 h) condition of confusion and/or loss of consciousness for less than 30 min after brain injury and can result in short- and long-term motor and cognitive impairments. Recent studies have documented the therapeutic potential of non-invasive neuromodulation techniques for the enhancement of cognitive and motor function in mTBI. Alongside repetitive transcranial magnetic stimulation (rTMS), the main technique used for this purpose is transcranial direct current stimulation (tDCS). The focus of this review was to provide a detailed, comprehensive (i.e., both cognitive and motor impairment) overview of the literature regarding therapeutic tDCS paradigms after mTBI. A publication search of the PubMed, Scopus, CINAHL, and PsycINFO databases was performed to identify records that applied tDCS in mTBI. The publication search yielded 14,422 records from all of the databases, however, only three met the inclusion criteria and were included in the final review. Based on the review, there is limited evidence of tDCS improving cognitive and motor performance. Surprisingly, there were only three studies that used tDCS in mTBI, which highlights an urgent need for more research to provide additional insights into ideal therapeutic brain targets and optimized stimulation parameters.
Microglia Morphological Changes in the Motor Cortex of hSOD1G93A Transgenic ALS Mice
Authors: Migliarini Sara , Scaricamazza Silvia , Valle Cristiana , Ferri Alberto , Pasqualetti Massimo , Ferraro Elisabetta
Published: June 2021

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of spinal motor neurons as well as corticospinal (CSN) large pyramidal neurons within cortex layer V. An intense microglia immune response has been associated with both upper and lower motor neuron degeneration in ALS patients, whereas microgliosis occurrence in the motor cortex of hSOD1G93A mice—the best characterized model of this disease—is not clear and remains under debate. Since the impact of microglia cells in the neuronal environment seems to be crucial for both the initiation and the progression of the disease, here we analyzed the motor cortex of hSOD1G93A mice at the onset of symptoms by the immunolabeling of Iba1/TMEM119 double positive cells and confocal microscopy. By means of Sholl analysis, we were able to identify and quantify the presence of presumably activated Iba1/TMEM119-positive microglia cells with shorter and thicker processes as compared to the normal surveilling and more ramified microglia present in WT cortices. We strongly believe that being able to analyze microglia activation in the motor cortex of hSOD1G93A mice is of great importance for defining the timing and the extent of microglia involvement in CSN degeneration and for the identification of the initiation stages of this disease.
Psychological Impact of COVID-19 Outbreak on Families of Children with Autism Spectrum Disorder and Typically Developing Peers: An Online Survey
Authors: Levante Annalisa , Petrocchi Serena , Bianco Federica , Castelli Ilaria , Colombi Costanza , Keller Roberto , Narzisi Antonio , Masi Gabriele , Lecciso Flavia
Published: June 2021

Background: When COVID-19 was declared as a pandemic, many countries imposed severe lockdowns that changed families’ routines and negatively impacted on parents’ and children’s mental health. Several studies on families with children with autism spectrum disorder (ASD) revealed that lockdown increased the difficulties faced by individuals with ASD, as well as parental distress. No studies have analyzed the interplay between parental distress, children’s emotional responses, and adaptive behaviors in children with ASD considering the period of the mandatory lockdown. Furthermore, we compared families with children on the spectrum and families with typically developing (TD) children in terms of their distress, children’s emotional responses, and behavioral adaptation. Methods: In this study, 120 parents of children aged 5–10 years (53 with ASD) participated. Results: In the four tested models, children’s positive and negative emotional responses mediated the impact of parental distress on children’s playing activities. In the ASD group, parents reported that their children expressed more positive emotions, but fewer playing activities, than TD children. Families with children on the spectrum reported greater behavioral problems during the lockdown and more parental distress. Conclusions: Our findings inform the interventions designed for parents to reduce distress and to develop coping strategies to better manage the caregiver–child relationship.
A CNN-Based Autoencoder and Machine Learning Model for Identifying Betel-Quid Chewers Using Functional MRI Features
Authors: Ho Ming-Chou , Shen Hsin-An , Chang Yi-Peng Eve , Weng Jun-Cheng
Published: June 2021

Betel quid (BQ) is one of the most commonly used psychoactive substances in some parts of Asia and the Pacific. Although some studies have shown brain function alterations in BQ chewers, it is virtually impossible for radiologists’ to visually distinguish MRI maps of BQ chewers from others. In this study, we aimed to construct autoencoder and machine-learning models to discover brain alterations in BQ chewers based on the features of resting-state functional magnetic resonance imaging. Resting-state functional magnetic resonance imaging (rs-fMRI) was obtained from 16 BQ chewers, 15 tobacco- and alcohol-user controls (TA), and 17 healthy controls (HC). We used an autoencoder and machine learning model to identify BQ chewers among the three groups. A convolutional neural network (CNN)-based autoencoder model and supervised machine learning algorithm logistic regression (LR) were used to discriminate BQ chewers from TA and HC. Classifying the brain MRIs of HC, TA controls, and BQ chewers by conducting leave-one-out-cross-validation (LOOCV) resulted in the highest accuracy of 83%, which was attained by LR with two rs-fMRI feature sets. In our research, we constructed an autoencoder and machine-learning model that was able to identify BQ chewers from among TA controls and HC, which were based on data from rs-fMRI, and this might provide a helpful approach for tracking BQ chewers in the future.
Translation and Transcultural Adaptation of the Wessex Head Injury Matrix, Italian Version: A Preliminary Report
Authors: Pistoia Francesca , Shiel Agnes , Ornello Raffaele , Saporito Gennaro , Gentili Luca , Carolei Antonio , Marini Carmine , Sacco Simona , Marinangeli Franco
Published: June 2021

Background: Patients who are in a coma, a vegetative state or a minimally conscious state present a clinical challenge for neurological assessment, which is a prerequisite for establishing a prognosis and planning management. Several scales have been developed to evaluate these patients. The Wessex Head Injury Matrix is a comprehensive tool but is currently available only in the French and English languages. The aim of this study was to translate and evaluate the reliability of the Italian version of the scale. Methods: The original scale was translated according to a standard protocol: three separate translations were made, and a selected version was back-translated to check for any errors in order to obtain the most accurate Italian translation. A final back translation of the agreed version was made as a further check. The final version was then administered blind to a consecutive series of patients with severe acquired brain injury by two examiners. Inter-rater and test-retest reliability were assessed using a weighted Cohen’s kappa (Kw). Concurrent validity of the WHIM was evaluated by ρ Spearman’s correlation coefficient using the Glasgow Coma Scale (GCS) and the Coma Recovery Scale Revised (CRS-R) as the available gold standard. Results: Twenty-four patients (12 males and 12 females; mean age 59.9 ± 20.1; mean duration from index event 17.7 ± 20.0 days) with stroke (n = 15), traumatic brain injury (n = 7) and anoxic encephalopathy (n = 2) were included. Inter-rater [Kw 0.80 (95% CI 0.75–0.84)] and test-retest reliability [Kw 0.77 (95% CI 0.72–0.81)] showed good values. WHIM total scores correlated significantly with total scores on the GCS (ρ = 0.776; p < 0.001) and the CRS-R (ρ = 0.881; p < 0.001) demonstrating concurrent validity; Conclusion: The Italian version of the scale is now available for clinical practice and research.
Reply to Dravet, C. Different Outcomes of Acute Encephalopathy after Status Epilepticus in Patients with Dravet Syndrome. How to Avoid Them? Comment on “De Liso et al. Fatal Status Epilepticus in Dravet Syndrome. Brain Sci. 2020, 10, 889”
Authors: De Liso Paola , Pironi Virginia , Mastrangelo Massimo , Battaglia Domenica , Craiu Dana , Trivisano Marina , Specchio Nicola , Nabbout Rima , Vigevano Federico
Published: June 2021

It has been an honor for us to receive a comment on our article “Fatal Status Epilepticus in Dravet Syndrome” [...]
All-Trans Retinoic Acid Fosters the Multifarious U87MG Cell Line as a Model of Glioblastoma
Authors: Pokorná Markéta , Hudec Michael , Juříčková Iva , Vácha Michael , Polívková Zdeňka , Kútna Viera , Pala Jan , Ovsepian Saak V. , Černá Marie , O’Leary Valerie Bríd
Published: June 2021

Glioblastoma multiforme (GBM) is a primary brain cancer of poor prognosis, with existing treatments remaining essentially palliative. Current GBM therapy fails due to rapid reappearance of the heterogeneous neoplasm, with models suggesting that the recurrent growth is from treatment-resistant glioblastoma stem-like cells (GSCs). Whether GSCs depend on survival/proliferative cues from their surrounding microenvironmental niche, particularly surrounding the leading edge after treatment remains unknown. Simulating human GBM in the laboratory relies on representative cell lines and xenograft models for translational medicine. Due to U87MG source discrepancy and differential proliferation responses to retinoic acid treatment, this study highlights the challenges faced by laboratory scientists working with this representative GBM cell line. Investigating the response to all trans-retinoic acid (ATRA) revealed its sequestering of the prominin-1 stem cell marker. ICAM-1 universally present throughout U87MG was enhanced by ATRA, of interest for chemotherapy targeting studies. ATRA triggered diverse expression patterns of long non-coding RNAs PARTICLE and GAS5 in the leading edge and established monolayer growth zone microenvironment. Karyotyping confirmed the female origin of U87MG sourced from Europe. Passaging U87MG revealed the presence of chromosomal anomalies reflective of structural genomic alterations in this glioblastoma cell line. All evidence considered, this study exposes further phenotypic nuances of U87MG which may belie researchers seeking data contributing towards the elusive cure for GBM.
A Case Study of a Negotiated Tender within a Small-to-Medium Construction Contractor: Modelling Project Cost Variance
Authors: Ellis James , Edwards David John , Thwala Wellington Didibhuku , Ejohwomu Obuks , Ameyaw Ernest Effah , Shelbourn Mark
Published: June 2021

This research explores the failure of competitively tendered projects in the UK construction industry to procure the most suited contractor(s) to conduct the works. Such work may have equal relevance for other developed nations globally. This research seeks to teach clients and their representatives that “lowest price” does not mean “best value”, by presenting a case study of a successfully negotiated tender undertaken by a small-to-medium enterprise (SME) contractor; SME studies are relatively scant in academic literature. By applying the “lessons learnt” principle, this study seeks to improve future practice through the development of a novel alternative procurement option (i.e., negotiation). A mixed philosophical stance combining interpretivism and pragmatism was used—interpretivism to critically review literature in order to form the basis of inductive research to discuss negotiation as a viable procurement route, and pragmatism to analyse perceptions of tendering and procurement. The methods used follow a three-stage waterfall process including: (1) literature review and pilot study; (2) quantitative analysis of case study data; and (3) qualitative data collection via a focus group. Our research underscores the need to advise clients and their representatives of the importance of understanding the scope of works allowed within a tender submission before discounting it based solely on price. In addition, we highlight the failings of competitive tendering, which results in increased costs and project duration once the works commence on site. These findings provide new contemporary insight into procurement and tendering in the construction industry, with emphasis on SME contractors, existing relationships, and open-book negotiation. This research illustrates the adverse effects of early cost estimates produced without first securing a true understanding of project buildability and programming. Our work concludes with a novel insight into an alternative procurement option that involves early SME contractor involvement in an open-book environment, without the need for a third-party cost control.
Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma
Authors: Burgy Mickaël , Jehl Aude , Conrad Ombline , Foppolo Sophie , Bruban Véronique , Etienne-Selloum Nelly , Jung Alain C. , Masson Murielle , Macabre Christine , Ledrappier Sonia , Burckel Hélène , Mura Carole , Noël Georges , Borel Christian , Fasquelle François , Onea Mihaela-Alina , Chenard Marie-Pierre , Thiéry Alicia , Dontenwill Monique , Martin Sophie
Published: June 2021

The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC.
Targeting CDK9 for the Treatment of Glioblastoma
Authors: Ranjan Alice , Pang Ying , Butler Madison , Merchant Mythili , Kim Olga , Yu Guangyang , Su Yu-Ting , Gilbert Mark R. , Levens David , Wu Jing
Published: June 2021

Glioblastoma is the most common and aggressive primary malignant brain tumor, and more than two-thirds of patients with glioblastoma die within two years of diagnosis. The challenges of treating this disease mainly include genetic and microenvironmental features that often render the tumor resistant to treatments. Despite extensive research efforts, only a small number of drugs tested in clinical trials have become therapies for patients. Targeting cyclin-dependent kinase 9 (CDK9) is an emerging therapeutic approach that has the potential to overcome the challenges in glioblastoma management. Here, we discuss how CDK9 inhibition can impact transcription, metabolism, DNA damage repair, epigenetics, and the immune response to facilitate an anti-tumor response. Moreover, we discuss small-molecule inhibitors of CDK9 in clinical trials and future perspectives on the use of CDK9 inhibitors in treating patients with glioblastoma.
Novel Cyclophilin Inhibitor Decreases Cell Proliferation and Tumor Growth in Models of Hepatocellular Carcinoma
Authors: Simón Serrano Sonia , Tavecchio Michele , Grönberg Alvar , Sime Wondossen , Jemaà Mohamed , Moss Steven , Gregory Matthew Alan , Gallay Philippe , Elmér Eskil , Hansson Magnus Joakim , Massoumi Ramin
Published: June 2021

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed in its late state. Tyrosine kinase inhibitors such as sorafenib and regorafenib are one of the few treatment options approved for advanced HCC and only prolong the patient’s life expectancy by a few months. Therefore, there is a need for novel effective treatments. Cyclophilins are intracellular proteins that catalyze the cis/trans isomerization of peptide bonds at proline residues. Cyclophilins are known to be overexpressed in HCC, affecting therapy resistance and cell proliferation. In the present study, we explored the potential of cyclophilin inhibitors as new therapeutic options for HCC in vitro and in vivo. Our results showed that the novel cyclophilin inhibitor, NV651, was able to significantly decrease proliferation in a diverse set of HCC cell lines. The exposure of HCC cells to NV651 caused an accumulation of cells during mitosis and consequent accumulation in the G2/M phase of the cell cycle. NV651 reduced tumor growth in vivo using an HCC xenograft model without affecting the body weights of the animals. The safety aspects of NV651 were also confirmed in primary human hepatocytes without any cytotoxic effects. Based on the results obtained in this study, we propose NV651 as a potential treatment strategy for HCC.
Mutant p53L194F Harboring Luminal-A Breast Cancer Cells Are Refractory to Apoptosis and Cell Cycle Arrest in Response to MortaparibPlus, a Multimodal Small Molecule Inhibitor
Authors: Elwakeel Ahmed , Sari Anissa Nofita , Dhanjal Jaspreet Kaur , Meidinna Hazna Noor , Sundar Durai , Kaul Sunil C. , Wadhwa Renu
Published: June 2021

We previously performed a drug screening to identify a potential inhibitor of mortalin–p53 interaction. In four rounds of screenings based on the shift in mortalin immunostaining pattern from perinuclear to pan-cytoplasmic and nuclear enrichment of p53, we had identified MortaparibPlus (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole) as a novel synthetic small molecule. In order to validate its activity and mechanism of action, we recruited Luminal-A breast cancer cells, MCF-7 (p53wild type) and T47D (p53L194F) and performed extensive biochemical and immunocytochemical analyses. Molecular analyses revealed that MortaparibPlus is capable of abrogating mortalin–p53 interaction in both MCF-7 and T47D cells. Intriguingly, upregulation of transcriptional activation function of p53 (as marked by upregulation of the p53 effector gene—p21WAF1—responsible for cell cycle arrest and apoptosis) was recorded only in MortaparibPlus-treated MCF-7 cells. On the other hand, MortaparibPlus-treated T47D cells exhibited hyperactivation of PARP1 (accumulation of PAR polymer and decrease in ATP levels) as a possible non-p53 tumor suppression program. However, these cells did not show full signs of either apoptosis or PAR-Thanatos. Molecular analyses attributed such a response to the inability of MortaparibPlus to disrupt the AIF–mortalin complexes; hence, AIF did not translocate to the nucleus to induce chromatinolysis and DNA degradation. These data suggested that the cancer cells possessing enriched levels of such complexes may not respond to MortaparibPlus. Taken together, we report the multimodal anticancer potential of MortaparibPlus that warrants further attention in laboratory and clinical studies.
Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level
Authors: Pillozzi Serena , Bernini Andrea , Palchetti Ilaria , Crociani Olivia , Antonuzzo Lorenzo , Campanacci Domenico , Scoccianti Guido
Published: June 2021

Soft tissue sarcomas (STSs) are a heterogeneous group of rare tumors. Although constituting only 1% of all human malignancies, STSs represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. Over 100 histologic subtypes have been characterized to date (occurring predominantly in the trunk, extremity, and retroperitoneum), and many more are being discovered due to molecular profiling. STS mortality remains high, despite adjuvant chemotherapy. New prognostic stratification markers are needed to help identify patients at risk of recurrence and possibly apply more intensive or novel treatments. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the most relevant cellular, molecular and metabolic biomarkers for STS, and highlight advances in STS-related biomarker research.