bluuebunny/crossref_metadata_2025 huggingface dataset:
An Efficient Kriging Modeling Method Based on Multidimensional Scaling for High-Dimensional Problems
Authors: Ge Yu , Shi Junjun , Li Yaohui , Shen Jingfang
Published: December 2021

Kriging-based modeling has been widely used in computationally intensive simulations. However, the Kriging modeling of high-dimensional problems not only takes more time, but also leads to the failure of model construction. To this end, a Kriging modeling method based on multidimensional scaling (KMDS) is presented to avoid the “dimensional disaster”. Under the condition of keeping the distance between the sample points before and after the dimensionality reduction unchanged, the KMDS method, which mainly calculates each element in the inner product matrix due to the mapping relationship between the distance matrix and the inner product matrix, completes the conversion of design data from high dimensional to low dimensional. For three benchmark functions with different dimensions and the aviation field problem of aircraft longitudinal flight control, the proposed method is compared with other dimensionality reduction methods. The KMDS method has better modeling efficiency while meeting certain accuracy requirements.
Modeling of the 5G-Band Patch Antennas Using ANNs under the Uncertainty of the Geometrical Design Parameters Associated with the Manufacturing Process
Authors: Górniak Piotr
Published: December 2021

In the paper, the author deals with modeling the stochastic behavior of ordinary patch antennas in terms of the mean and standard deviation of their reflection coefficient |S11| under the geometrical uncertainty associated with their manufacturing process. The Artificial Neural Network is used to model the stochastic reflection coefficient of the antennas. The Polynomial Chaos Expansion and FDTD computations are used to obtain the training and testing data for the Artificial Neural Network. For the first time, the author uses his analytical transformations to reduce the required number of highly time-consuming FDTD simulations for a given set of nominal values of the design parameters of the ordinary patch antenna. An analysis is performed for n257 and n258 frequency bands (24.5–28.7 GHz). The probability distributions of the design parameters are extracted from the measurement results obtained for a series of manufactured patch antenna arrays for three different frequencies in the C, X, and Ka bands. Patch antennas are chosen as the subject of the scientific analysis in this paper because of the popularity of the patch antennas in the scientific literature concerning antennas, as well as because of a simple form of these antennas that is reflected in the time required for computation of training and testing data for the Artificial Neural Network.
Simulation of Landing and Take-Off Noise for Supersonic Transport Aircraft at a Conceptual Design Fidelity Level
Authors: Nöding Michel , Schuermann Martin , Bertsch Lothar , Koch Marc , Plohr Martin , Jaron Robert , Berton Jeffrey J.
Published: December 2021

The German Aerospace Center has launched an internal project to assess the noise impact associated with supersonic transport aircraft during approach and departure. A dedicated simulation process is established to cover all relevant disciplines, i.e., aircraft and engine design, engine installation effects, flight simulation, and system noise prediction. The core of the simulation process is comprised of methods at the complexity and fidelity level of conceptual aircraft design, i.e., typical overall aircraft design methods and a semi-empirical approach for the noise modeling. Dedicated interfaces allow to process data from high fidelity simulation that will support or even replace initial low fidelity results in the long run. All of the results shown and discussed in this study are limited to the fidelity level of conceptual design. The application of the simulation process to the NASA 55t Supersonic Technology Concept Aeroplane, i.e., based on non-proprietary data for this vehicle, yields similar noise level predictions when compared to the published NASA results. This is used as an initial feasibility check of the new process and confirms the underlying methods and models. Such an initial verification of the process is understood as an essential step due to the lack of available noise data for supersonic transport aircraft in general. The advantageous effect of engine noise shielding on the resulting system noise is demonstrated based on predicted level time histories and certification noise levels. After this initial verification, the process is applied to evaluate a conceptual supersonic transport design based on a PhD thesis with two engines mounted under the wing, which is referred to as aircraft TWO. Full access to this vehicle’s design and performance data allows to investigate the influence of flight procedures on the resulting noise impact along approach and departure. These noise results are then assembled according to proposed Federal Aviation Agency regulations in their Notice of Proposed Rulemaking, e.g., speed limitations, for Supersonic transport noise certification and the regulations from Noise Chapters of the Annex 16 from the International Civil Aviation Organization in order to evaluate the resulting levels as a function of the flight procedure.
Disturbance of Vancomycin Infusion Flow during Multidrug Infusion: Influence on Endothelial Cell Toxicity
Authors: Drouet Maryline , Cuvelier Elodie , Chai Feng , Genay Stéphanie , Odou Pascal , Décaudin Bertrand
Published: December 2021

Background: Phlebitis is a common side effect of vancomycin peripheral intravenous (PIV) infusion. As only one PIV catheter is frequently used to deliver several drugs to hospitalized patients through the same Y-site, perturbation of the infusion flow by hydration or other IV medication may influence vancomycin exposure to endothelial cells and modulate toxicity. Methods: We assessed the toxicity of variations in vancomycin concentration induced by drug mass flow variations in human umbilical vein endothelial cells (HUVECs), simulating a 24 h multi-infusion therapy on the same line. Results were expressed as the percentage of viable cells compared with a 100% control, and the Kruskal–Wallis test was used to assess the toxicity of vancomycin. Results: Our results showed that variations in vancomycin concentration did not significantly influence local toxicity compared to a fixed concentration of vancomycin. Nevertheless, the loss of cell viability induced by mechanical trauma mimicking multidrug infusion could increase the risk of phlebitis. Conclusion: To ensure that vancomycin-induced phlebitis must have other causes than variation in drug mass flow, further in vitro experiments should be performed to limit mechanical stress to frequent culture medium change.
NRF2 Activation Ameliorates Oxidative Stress and Improves Mitochondrial Function and Synaptic Plasticity, and in A53T α-Synuclein Hippocampal Neurons
Authors: Brandes Mikah S. , Zweig Jonathan A. , Tang Anita , Gray Nora E.
Published: December 2021

In Parkinson’s disease (PD), brain oxidative stress and mitochondrial dysfunction contribute to neuronal loss as well as motor and cognitive deficits. The transcription factor NRF2 has emerged as a promising therapeutic target in PD because it sits at the intersection of antioxidant and mitochondrial pathways. Here, we investigate the effects of modulating NRF2 activity in neurons isolated from a A53T α-synuclein (A53TSyn) mouse model of synucleinopathy. Embryonic hippocampal neurons were isolated from A53TSyn mice and their wild type (WT) littermates. Neurons were treated with either the NRF2 activator dimethyl fumarate (DMF) or the NRF2 inhibitor ML385. Reactive oxygen species (ROS), dendritic arborization and dendritic spine density were quantified. Mitochondrial bioenergetics were also profiled in these neurons. A53TSyn neurons had increased ROS and reduced basal and maximal mitochondrial respiration relative to WT neurons. A53TSyn neurons also displayed decreased dendritic arborization and reduced spine density. Treatment with DMF reduced ROS levels and improved both mitochondrial function and arborization, while inhibition of NRF2 with ML385 exacerbated these endpoints. Modulation of NRF2 activity had a significant effect on mitochondrial function, oxidative stress, and synaptic plasticity in A53TSyn neurons. These data suggest that NRF2 may be a viable target for therapeutic interventions in PD.
Punicalagin Regulates Signaling Pathways in Inflammation-Associated Chronic Diseases
Authors: Xu Jie , Cao Ke , Liu Xuyun , Zhao Lin , Feng Zhihui , Liu Jiankang
Published: December 2021

Inflammation is a complex biological defense system associated with a series of chronic diseases such as cancer, arthritis, diabetes, cardiovascular and neurodegenerative diseases. The extracts of pomegranate fruit and peel have been reported to possess health-beneficial properties in inflammation-associated chronic diseases. Punicalagin is considered to be the major active component of pomegranate extracts. In this review we have focused on recent studies into the therapeutic effects of punicalagin on inflammation-associated chronic diseases and the regulatory roles in NF-κB, MAPK, IL-6/JAK/STAT3 and PI3K/Akt/mTOR signaling pathways. We have concluded that punicalagin may be a promising therapeutic compound in preventing and treating inflammation-associated chronic diseases, although further clinical studies are required.
Influence of the Mixture of Carrageenan Oligosaccharides and Egg White Protein on the Gelation Properties of Culter alburnus Myofibrillar Protein under Repeated Freezing–Thawing Cycles
Authors: Zhang Zhongli , Xiong Zhouyi , Walayat Noman , Lorenzo Jose M. , Liu Jianhua , Nawaz Asad , Xiong Hanguo
Published: December 2021

This study aims to investigate the influence of the mixture (CGO/EWP) of carrageenan oligosaccharide (CGO) and egg white protein (EWP) (CGO/EWP, CGO: EWP = 1:1, m/m) on the functional, structural, and gelling properties of Culter alburnus myofibrillar protein (MP) during repeated freezing–thawing cycles by treating MP samples separately with EWP, CGO, or CGO/EWP based on the wet weight (1%, m/m), using samples without any cryoprotectant as the blank group. After the second repeated freezing–thawing cycle, the sulfhydryl group content was found to be significantly (p < 0.05) higher in the CGO/EWP (30.57 nmol/mg) and CGO (36.14 nmol/mg) groups than in the EWP group (23.80 nmol/mg), indicating that CGO/EWP and CGO can more effectively delay the oxidative deterioration of functional groups. Additionally, the surface hydrophobicity was shown to be significantly lower in the CGO (25.74) and CGO/EWP (27.46) groups than in the EWP (34.66) and blank (39.32) groups. Moreover, the α-helix content was higher in the CGO (35.2%) and CGO/EWP (32.3%) groups than in the EWP (29.2%) and blank (25.0%) groups. These data indicated that CGO and CGO/EWP could more effectively increase the structural stability, thereby inhibiting the exposure of hydrophobic groups and curbing the decline of α-helix content. During the heat-induced gel-forming process, EWP and CGO/EWP could enhance the gel viscoelasticity and strength. After the second freezing–thawing cycle, when compared with the blank group, the CGO/EWP group showed significantly (p < 0.05) higher water-holding capacity (66.30% versus 53.93%) and shorter T22 relaxation time (413.56 versus 474.99 ms). The integrated results indicated that CGO/EWP could more effectively delay the decrease of protein–water molecular interaction forces in the MP gel. This study shed light on the mechanism of CGO/EWP as a cryoprotective mixture in improving the deterioration of MP gelation properties during repeated freezing–thawing cycles.
Prevalence of Pain and Disability of the Spine and Joints in Selected Types of Sport: Protocol for a Cross-Sectional Study
Authors: Buková Alena , Hagovská Magdaléna , Tomková Petra , Zusková Klaudia , Takáč Peter , Chovanová Erika
Published: December 2021

(1) Background: Joint and back pain are enormous and important clinical and public health problems that significantly affect people of all ages. Although the epidemiology of pain in the general population is well documented, less information is available in athletes. While in the general population joint and back pain have predominantly functional origin, in athletes, pain is a consequence of not only functional, but very often structural changes in the spine, joints, and related tissues. Depending on the sports specialization, character of the training activity, exercises, training load, and many other factors, athletes are exposed to various injuries accompanied by pain. (2) Aim: This study is aimed at evaluating the prevalence of spinal and limb injuries, and back pain and joint pain among athletes of various specializations. A questionnaire survey on back pain, quality of life, and physical activity will be used to collect data from Slovak athletes. The outcomes of the survey will be compared to a physically active group. This article presents a study protocol that aims to evaluate the relationship between back pain and injury prevalence in athletes of various specializations.
Stability Analysis of Surrounding Rock in Multi-Discontinuous Hydraulic Tunnel Based on Microseismic Monitoring
Authors: Zhou Xiang , Li Biao , Yang Chunming , Zhong Weiming , Ding Quanfu , Mao Haoyu
Published: December 2021

The diversion tunnel of a hydropower station is characterized by low quality surrounding rock and weak structural planes. During excavation, rock mass spalling and cracking frequently occur. To evaluate the stability of a rock mass during tunnel excavation, high-precision microseismic monitoring technology was introduced to carry out real-time monitoring. Based on the temporal and spatial distribution characteristics of microseismic events, the main damage areas and their influencing factors of tunnel rock mass were studied. By analyzing the source characteristic parameters of the concentration area of microseismic activities, the rock fracture mechanism of the concentration area was revealed. The 3D numerical model of diversion tunnel was established, and the deformation characteristics of the rock mass under the control of different combination types of weak structural planes were obtained. The results showed that the microseismic event was active between 29 October 2020 and 6 November 2020, and the energy release increased sharply. The main damage areas of the rock mass were located at Stakes K0 + 500–K0 + 600 m. Microseismic source parameters revealed that shear failure or fault-slip failure induced by geological structures had an important influence on the stability of the surrounding rock. The numerical simulation results were consistent with the microseismic monitoring results and indicated that among the three kinds of structural plane combination types, including “upright triangle”, “inverted triangle” and “nearly parallel”, the “upright triangle” structure had the most significant influence on the stability of the surrounding rock. In addition, the maximum displacement of the surrounding rock had a trend of lateral migration to the larger dip angle in the three combined structural plane types. The research results will provide significant references for the safety evaluation and construction design of similar tunnels.
Insulative Phase Formation and Polarization Resistance of PrBaCo2−xCuxO5+δ under Thermal Stress
Authors: Jo Kanghee , Ha Jooyeon , Lim Taeheun , Lee Heesoo
Published: December 2021

The degradation behavior of PrBaCo2−xCuxO5+δ (x = 0, 0.2, 0.5) under thermal stress was investigated in terms of phase formation and polarization resistance. The tetragonal phase was indexed in all compositions of PBCCux, and the secondary phase, BaO, was identified after thermal degradation in the crystal structure analysis. BaO formation is induced by the nature of perovskite to terminate the surface with AO layer. For pristine specimens, the oxygen vacancy peak ratio was increased from 57% to 60% according to the decrease in the average oxidation number of the B-site ion with Cu doping. After thermal deterioration, the oxidation number of B-site ions was increased, and the M = O bonding peak increased due to the decrease in oxygen vacancies and BaO formation according to the thermal stress. In all compositions, the electrical conductivity decreased from 1000 S/cm to 17 S/cm, and the polarization resistance increased approximately 200 times. These results are considered to be related to the increase in the oxidation number of B-site ions along with the formation of secondary phases.
PPIA and YWHAZ Constitute a Stable Pair of Reference Genes during Electrical Stimulation in Mesenchymal Stem Cells
Authors: Steel Lynsey , Ansell David M. , Amaya Enrique , Cartmell Sarah H.
Published: December 2021

Mesenchymal stem cells (MSCs) are multipotent adult stem cells with great potential in regenerative medicine. One method for stimulating proliferation and differentiation of MSCs is via electrical stimulation (ES). A valuable approach for evaluating the response of MSCs to ES is to assess changes in gene expression, relative to one or more reference genes. In a survey of 25 publications that used ES on cells, 70% selected GAPDH as the reference gene. We conducted a study to assess the suitability of six potential reference genes on an immortalized human MSC line following direct current ES at seeding densities of 5000 and 10,000 cells/cm2. We employed three methods to validate the most stable reference genes from qRT-PCR data. Our findings show that GAPDH and ACTB exhibit reduced stability when seeded at 5000 cell/cm2. In contrast, we found that the most stable genes across both plating densities and stimulation regimes were PPIA and YWHAZ. Thus, in ES gene expression studies in MSCs, we support the use of PPIA and YWHAZ as an optimal reference gene pair, and discourage the use of ACTB and GAPDH at lower seeding densities. However, it is strongly recommended that similar verification studies are carried out based on cell type and different ES conditions.
A Survey on TLS-Encrypted Malware Network Traffic Analysis Applicable to Security Operations Centers
Authors: Oh Chaeyeon , Ha Joonseo , Roh Heejun
Published: December 2021

Recently, a majority of security operations centers (SOCs) have been facing a critical issue of increased adoption of transport layer security (TLS) encryption on the Internet, in network traffic analysis (NTA). To this end, in this survey article, we present existing research on NTA and related areas, primarily focusing on TLS-encrypted traffic to detect and classify malicious traffic with deployment scenarios for SOCs. Security experts in SOCs and researchers in academia can obtain useful information from our survey, as the main focus of our survey is NTA methods applicable to malware detection and family classification. Especially, we have discussed pros and cons of three main deployment models for encrypted NTA: TLS interception, inspection using cryptographic functions, and passive inspection without decryption. In addition, we have discussed the state-of-the-art methods in TLS-encrypted NTA for each component of a machine learning pipeline, typically used in the state-of-the-art methods.
Effect of Silica Nanoparticles Silanized by Functional/Functional or Functional/Non-Functional Silanes on the Physicochemical and Mechanical Properties of Dental Nanocomposite Resins
Authors: Karkanis Stefanos , Nikolaidis Alexandros K. , Koulaouzidou Elisabeth A. , Achilias Dimitris S.
Published: December 2021

Dental nanocomposite resins have been proposed as potential restorative materials that are inevitably challenged with dynamic oral conditions. This investigation focused on the contribution of miscellaneous silane blends, used as coupling agents, to the ultimate performance of dental nanocomposite dimethacrylate resins. Herein, silica nanoparticles were initially silanized with functional/functional or functional/non-fuctional silane mixtures (50/50 wt/wt). Fourier transforms infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA) verified the modification of nanosilica. The organomodified nanoparticles were then inserted into Bis-GMA/TEGDMA based resins by hand spatulation process. Scanning electron microscopy (SEM) findings revealed a broad distribution of fillers in the polymer network when reactive silanes and their corresponding blends were used. Furthermore, optical profilometry results showed that the presence of functional/non-functional mixtures can produce relatively smooth composite surfaces. Polymerization shrinkage was found to be limited upon the decrease of the degree of conversion regarding all the tested silane mixtures. The functional/functional silane blend assured the highest flexural properties and the lowest solubility after the storage of the nanocomposite in water for 1 week at 37 °C. The above experimental data could contribute to the proper designing of dental nanocomposite resins which may fit the modern clinical applications.
Analysis of the Causes of the Collapse of a Deep-Buried Large Cross-Section of Loess Tunnel and Evaluation of Treatment Measures
Authors: Wang Dengke , Luo Jianjun , Shen Kaiming , Gao Liping , Li Feilong , Wang Lei
Published: December 2021

To address the problem of the collapse of the roof of the Bailuyuan tunnel during construction, the causes of collapse were analyzed, targeted treatment measures were proposed, and the effects of the treatment measures were evaluated through on-site monitoring and three-dimensional numerical simulations. The results showed that the particular characteristics of loess and the synergy of groundwater were the internal causes of the tunnel’s collapse as well as, to a certain extent, atmospheric precipitation. Therefore, the combination of multiple factors contributed to the tunnel’s collapse. Untimely monitoring and measurement, as well as the low initial support parameters, reflect a lack of human understanding of the collapse. Based on the analysis of the causes of the collapse, comprehensive treatment measures for inside and outside the tunnel are proposed, which are shown to be effective and to be capable of preventing the occurrence of further collapses. After the collapse treatment, the measured maximum settlement of the tunnel vault was 65.1 mm, the maximum horizontal convergence was 25 mm, the maximum surrounding rock pressure was 0.56 MPa, and the maximum stress on the steel arch frame was 54.34 MPa. Compared with the original design plan, the vertical stress, horizontal stress, and shear stress of the surrounding rock obtained from numerical simulation after the collapse treatment were greatly reduced, the reduction rate at the vault reached 50%, and the safety factors of the initial support positions after treatment met the specification requirements. The research results can provide engineering guidance for the design and construction of large-section tunnels crossing deep-loess strata, and they are of important engineering significance.
Estimation of Shear-Wave Velocity Structures in Taichung, Taiwan, Using Array Measurements of Microtremors
Authors: Huang Huey-Chu , Shih Tien-Han , Hsu Cheng-Ta , Wu Cheng-Feng
Published: December 2021

Near-surface S-wave velocity structures (VS) are crucial in site-effect studies and ground-motion simulations or predictions. We explored S-wave velocity structures in Taichung, the second-largest city in Taiwan by population, by employing array measurements of microtremors at a total of 53 sites. First, the fundamental-mode dispersion curves of Rayleigh waves were estimated by adopting the frequency–wavenumber analysis method. Second, the surface-wave inversion technique was used to calculate the S-wave velocity structures of the area. At many sites, observed phase velocities were almost flat, with a phase velocity of approximately 800–1300 m/s in the frequency range of 0.6–2 Hz. A high-velocity zone (VS of 900–1500 m/s) with a convex shape was observed at the shallow S-wave structures of these sites (depths of 50–500 m). On the basis of the inversion results, we constructed two-dimensional and three-dimensional contour maps to elucidate the variations of VS structures in Taichung. According to VS-contour maps at different depths, lowest S-wave velocities are found at the western coastal plain, whereas highest S-wave velocities appear on the eastern side. The S-wave velocity gradually decreases from east to west. Moreover, the S-wave velocity of the Tertiary bedrock is assumed to be 1500 m/s in the area. According to the depth-contour map (VS = 1500 m/s), the depths of the bedrock range from 250 m (the eastern part) to 1550 m (the western part). The thicknesses of the alluvium gradually decrease from west to east. Our results are consistent with the geology of the Taichung area.
Theoretical Study on the Flexural Behavior of Structural Elements Strengthened with External Pre-Stressing Methods
Authors: Mohamed Gouda A. , Eisa Ahmed S. , Purcz Pavol , El-Feky Mohamed H.
Published: December 2021

This study aims to strengthen the flexural behavior of structural elements with external pre-stressing tendons, thereby improving their load-carrying capacity and increasing their resistance against the external load. Different techniques were used to apply external pre-stressed strengthening to RC beams and RC frames. Seven identical RC frames were analyzed: an original sample without an external tendon, two strengthened samples with external tendons at the positive bending zone, two strengthened samples with external tendons at the beam–column connection zone, a strengthened sample with external straight line tendons along the beam and, finally, a strengthened sample with external U-shape tendons along the beam of the frame. The analysis and the results were obtained using ANSYS WORKBENCH finite element (FE) program. Comparisons were performed between these techniques to determine which technique is better for strengthening. The failure mode, vertical deflection, column stress, load-carrying capacity, and ductility of the samples were listed and analyzed under four-point vertical loading. The results show that using external tendons significantly increases the load capacity and the stiffness of structural frames. Moreover, the tendon in the beam zone is more effective than the tendon in the column zone.
On the Use of LoRaWAN for Mobile Internet of Things: The Impact of Mobility
Authors: Al mojamed Mohammad
Published: December 2021

A long-range wide-area network (LoRaWAN) targets both mobile and static Internet of Things (IoT) applications; it is suited to IoT applications, which require a large coverage area while consuming less power at a low data rate; it provides a solution for transferring data between IoT devices with a minimum cost in terms of power, at the expense of higher latency. LoRaWAN was designed for static low-power long-range networks. However, several IoT solution applications involve the use of mobility. Therefore, this study investigates the usage of LoRaWAN in the field of mobile Internet of Things applications such as bike rentals, fleet monitoring, and wildlife and animal tracking applications. Using the OMNeT++ simulator, two different well-known mobility models are used to investigate the influence of mobility on the performance of mobile LoRaWAN. The results show that intense LoRaWAN networks can operate under a high velocity and varying traffic load. It can be observed that the random waypoint model combination yields a better performance, but at the cost of higher collisions and energy consumption. As a consequence, the results suggest the reconsideration of mobile IoT solutions over LoRaWAN.
Role of Neutrophil Extracellular Traps in COVID-19 Progression: An Insight for Effective Treatment
Authors: Blanch-Ruiz María Amparo , Ortega-Luna Raquel , Gómez-García Guillermo , Martínez-Cuesta Maria Ángeles , Álvarez Ángeles
Published: December 2021

The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has resulted in a pandemic with over 270 million confirmed cases and 5.3 million deaths worldwide. In some cases, the infection leads to acute respiratory distress syndrome (ARDS), which is triggered by a cytokine storm and multiple organ failure. Clinical hematological, biochemical, coagulation, and inflammatory markers, such as interleukins, are associated with COVID-19 disease progression. In this regard, neutrophilia, neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-albumin ratio (NAR), have emerged as promising biomarkers of disease severity and progression. In the pathophysiology of ARDS, the inflammatory environment induces neutrophil influx and activation in the lungs, promoting the release of cytokines, proteases, reactive oxygen species (ROS), and, eventually, neutrophil extracellular traps (NETs). NETs components, such as DNA, histones, myeloperoxidase, and elastase, may exert cytotoxic activity and alveolar damage. Thus, NETs have also been described as potential biomarkers of COVID-19 prognosis. Several studies have demonstrated that NETs are induced in COVID-19 patients, and that the highest levels of NETs are found in critical ones, therefore highlighting a correlation between NETs and severity of the disease. Knowledge of NETs signaling pathways, and the targeting of points of NETs release, could help to develop an effective treatment for COVID-19, and specifically for severe cases, which would help to manage the pandemic.
Prophylactic Activation of Shh Signaling Attenuates TBI-Induced Seizures in Zebrafish by Modulating Glutamate Excitotoxicity through Eaat2a
Authors: Hentig James , Campbell Leah J. , Cloghessy Kaylee , Lee Mijoon , Boggess William , Hyde David R.
Published: December 2021

Approximately 2 million individuals experience a traumatic brain injury (TBI) every year in the United States. Secondary injury begins within minutes after TBI, with alterations in cellular function and chemical signaling that contribute to excitotoxicity. Post-traumatic seizures (PTS) are experienced in an increasing number of TBI individuals that also display resistance to traditional anti-seizure medications (ASMs). Sonic hedgehog (Shh) is a signaling pathway that is upregulated following central nervous system damage in zebrafish and aids injury-induced regeneration. Using a modified Marmarou weight drop on adult zebrafish, we examined PTS following TBI and Shh modulation. We found that inhibiting Shh signaling by cyclopamine significantly increased PTS in TBI fish, prolonged the timeframe PTS was observed, and decreased survival across all TBI severities. Shh-inhibited TBI fish failed to respond to traditional ASMs, but were attenuated when treated with CNQX, which blocks ionotropic glutamate receptors. We found that the Smoothened agonist, purmorphamine, increased Eaat2a expression in undamaged brains compared to untreated controls, and purmorphamine treatment reduced glutamate excitotoxicity following TBI. Similarly, purmorphamine reduced PTS, edema, and cognitive deficits in TBI fish, while these pathologies were increased and/or prolonged in cyclopamine-treated TBI fish. However, the increased severity of TBI phenotypes with cyclopamine was reduced by cotreating fish with ceftriaxone, which induces Eaat2a expression. Collectively, these data suggest that Shh signaling induces Eaat2a expression and plays a role in regulating TBI-induced glutamate excitotoxicity and TBI sequelae.
Insomnia, Pre-Sleep Arousal, Psychosocial Factors and Changes in Sleep Pattern during the Second Wave Lockdown of the COVID-19 Pandemic in Georgia
Authors: Basishvili Tamar , Oniani Nikoloz , Sakhelashvili Irine , Eliozishvili Marine , Khizanashvili Manana , Arabidze Mariam , Tsaava Mariam , Charekishvili Tinatini , Tsertsvadze Nino , Darchia Nato
Published: December 2021

Studies performed across the COVID-19 pandemic waves point to the persistent impact of the pandemic on sleep and mental health. We expand these data by examining insomnia, pre-sleep arousal, psychosocial factors, and retrospective changes in sleep pattern during the COVID-19 second wave lockdown period in Georgia. Data were collected through an online survey (n = 1117). The prevalence rate of probable insomnia disorder was 24.2%. Clinically relevant somatic and cognitive pre-sleep arousal was present in 49.8% and 58.0% of participants, and high levels of anxiety, depression and social isolation were found in 47.0%, 37.3%, 47.2% of respondents, respectively. We observed high prevalence rates of worse sleep quality, delayed bedtimes and risetimes, longer sleep latencies, higher awakenings and shorter sleep durations, relative to the pre-pandemic period. COVID-19-infected participants showed more severe sleep and mental problems. Specific predictors differentially affected insomnia, somatic and cognitive pre-sleep arousal. Depression and COVID-19 infection emerged as vulnerability factors for pre-sleep arousal, which, in turn, was associated with a higher predisposition to insomnia disorder. We confirm the strong deteriorating impact of the COVID-19 pandemic on sleep and psychosocial well-being during the second wave lockdown period. The specific association between pre-sleep arousal, insomnia, and psychosocial factors is of clinical relevance for the prevention of severity and persistence of sleep and mental problems across the repeated lockdown/reopening waves. Modulation of pre-sleep arousal may prove beneficial to implement targeted interventions.
Genetic Mutations of Pancreatic Cancer and Genetically Engineered Mouse Models
Authors: Saiki Yuriko , Jiang Can , Ohmuraya Masaki , Furukawa Toru
Published: December 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. Advanced GEMMs permit the temporally and spatially controlled manipulation of multiple target genes using a dual-recombinase system or CRISPR/Cas9 gene editing. GEMMs that express fluorescent proteins allow cell lineage tracing to follow tumor growth and metastasis to understand the contribution of different cell types in cancer progression. GEMMs are widely used for therapeutic optimization. In this review, we summarize the main molecular alterations found in pancreatic neoplasms, developed GEMMs, and the contribution of GEMMs to the current understanding of PDAC pathobiology. Furthermore, we attempted to modify the categorization of altered driver genes according to the most updated findings.
Cost-Effectiveness of Immune Checkpoint Inhibitors in Urothelial Carcinoma—A Review
Authors: Walia Arman S. , Sweis Randy F. , Agarwal Piyush K. , Kader Andrew K. , Modi Parth K.
Published: December 2021

Over the last decade, an increasing number of immune checkpoint inhibitors (ICIs) have been assessed for therapeutic efficacy in urothelial carcinoma (UC). The high cost has prompted multiple cost-effectiveness analyses for the various disease stages, with no established consensus. We reviewed the literature to assess the available cost-effectiveness studies and summarize their findings. Studies were filtered for a calculated incremental cost-effectiveness ratio (ICER) to standardize comparison. Over 2600 articles were narrowed to eight primary investigations: one for BCG-refractory non-muscle invasive (NMI), one for neoadjuvant therapy in muscle-invasive (MI), and six for advanced disease. Cost-effectiveness was not achieved for NMI disease. Atezolizumab met the willingness-to-pay (WTP) threshold as neoadjuvant therapy for MI disease compared to chemotherapy, but with multiple limitations on the interpretation. Of the six studies on advanced disease, the results were mixed. This was at least partially attributable to varied methodologies including extrapolated time horizons, inconsistent cost inputs, and different WTP thresholds. Overall, the aggregate results were not compelling enough to establish ICIs as cost-effective compared to conventional chemotherapy. Value may improve with continued investigation into long-term outcomes, refined patient selection, and pricing discounts.
Comprehensive Statistical Exploration of Prognostic (Bio-)Markers for Responses to Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer
Authors: Hiltbrunner Stefanie , Spohn Meta-Lina , Wechsler Ramona , Akhoundova Dilara , Bankel Lorenz , Kasser Sabrina , Bihr Svenja , Britschgi Christian , Maathuis Marloes H. , Curioni-Fontecedro Alessandra
Published: December 2021

Metastatic non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) may suffer from heavy side effects and not all patients benefit from the treatment. We conducted a comprehensive statistical analysis to identify promising (bio-)markers for treatment response. We analyzed retrospective data from NSCLC patients treated with ICIs in first- or further-line therapy settings at the University Hospital Zurich. We investigated 16 possible prognostic markers with respect to overall survival, tumor size reduction, and the development of an immune-related adverse event (irAE) and assessed the robustness of our results. For the further-line patient group, the most significant result was that increased basophil counts were associated with increased odds of tumor size reduction within three months and with the development of an irAE. For the first-line patient group, the most significant results were that increased lymphocyte counts, the histology of adenocarcinoma, and the intake of non-steroidal anti-rheumatic drugs (NSAR) were associated with decreased hazards of dying. Our study yielded new hypotheses for predictive (bio-)markers for response to ICIs in NSCLC patients. The possibly beneficial role of high basophil counts is a particularly interesting finding. Our results should be tested on independent data in a prospective fashion.
Systematic Investigation of Biocompatible Cationic Polymeric Nucleic Acid Carriers for Immunotherapy of Hepatocellular Carcinoma
Authors: Chen Mingsheng , Wang Hao , Guo Hongying , Zhang Ying , Chen Liang
Published: December 2021

Hepatocellular carcinoma (HCC) is the third-largest cause of cancer death worldwide, while immunotherapy is rapidly being developed to fight HCC with great potential. Nucleic acid drugs are the most important modulators in HCC immunotherapy. To boost the efficacy of therapeutics and amplify the efficiency of genetic materials, biocompatible polymers are commonly used. However, under the strong need of a summary for current developments of biocompatible polymeric nucleic acid carriers for immunotherapy of HCC, there is rare review article specific to this topic to our best knowledge. In this article, we will discuss the current progress of immunotherapy for HCC, biocompatible cationic polymers (BCPs) as nucleic acid carriers used (or potential) to fight HCC, the roles of biocompatible polymeric carriers for nucleic acid delivery, and nucleic acid delivery by biocompatible polymers for immunotherapy. At the end, we will conclude the review and discuss future perspectives. This article discusses biocompatible polymeric nucleic acid carriers for immunotherapy of HCC from multidiscipline perspectives and provides a new insight in this domain. We believe this review will be interesting to polymer chemists, pharmacists, clinic doctors, and PhD students in related disciplines.
Editorial on Special Issue “Immunotherapy, Tumor Microenvironment and Survival Signaling”
Authors: Golubovskaya Vita
Published: December 2021

Recently, novel types of immunotherapies such as CAR-T cell therapy demonstrated efficacy in leukemia, lymphoma, and multiple myeloma [...]
CRISPR-Powered Microfluidics in Diagnostics: A Review of Main Applications
Authors: Azimzadeh Mostafa , Mousazadeh Marziyeh , Jahangiri-Manesh Atieh , Khashayar Pouria , Khashayar Patricia
Published: December 2021

In the past few years, the CRISPR (clustered regularly interspaced short palindromic repeats) applications in medicine and molecular biology have broadened. CRISPR has also been integrated with microfluidic-based biosensors to enhance the sensitivity and selectivity of medical diagnosis due to its great potentials. The CRISPR-powered microfluidics can help quantify DNAs and RNAs for different diseases such as cancer, and viral or bacterial diseases among others. Here in this review, we discussed the main applications of such tools along with their advantages and limitations.
Pill Detection Model for Medicine Inspection Based on Deep Learning
Authors: Kwon Hyuk-Ju , Kim Hwi-Gang , Lee Sung-Hak
Published: December 2021

This paper proposes a deep learning algorithm that can improve pill identification performance using limited training data. In general, when individual pills are detected in multiple pill images, the algorithm uses multiple pill images from the learning stage. However, when there is an increase in the number of pill types to be identified, the pill combinations in an image increase exponentially. To detect individual pills in an image that contains multiple pills, we first propose an effective database expansion method for a single pill. Then, the expanded training data are used to improve the detection performance. Our proposed method shows higher performance improvement than the existing algorithms despite the limited imaging and data set size. Our proposed method will help minimize problems, such as loss of productivity and human error, which occur while inspecting dispensed pills.
Consequences of Prematurity on Cortisol Regulation and Adjustment Difficulties: A 9-Year Longitudinal Study
Authors: Urfer Auriana , Turpin Hélène , Dimitrova Nevena , Borghini Ayala , Plessen Kerstin Jessica , Morisod Harari Mathilde , Urben Sébastien
Published: December 2021

A preterm birth represents a stressful event having potentially negative long-term consequences. Thirty-three children born preterm (<33 weeks gestational age) and eleven full-term children participated in a nine-year longitudinal study. Perinatal Risk Inventory (PERI) was used at birth to assess the perinatal stress. Salivary cortisol, collected four times a day over two consecutive days, was measured with radioimmunoassay technique at six months and nine years to assess the hypothalamic-pituitary-adrenal (HPA) axis. Mothers reported post-traumatic symptoms on a self-report questionnaire 12 months after their child’s birth and children’s adjustment problems at 9 years of child age on the Child Behavior Checklist. Results showed a significant difference in cortisol regulation at nine years between preterm and full-term children but no differences in adjustment problems. Whereas biological factors (i.e., PERI, cortisol regulation at six months) explained cortisol at nine years, maternal post-traumatic symptoms were predictive of adjustment problems in their child. In conclusion, very preterm birth has some long-term consequences on the HPA-axis regulation at nine years. Although cortisol regulation is mostly influenced by biological factors, the presence of maternal post-traumatic symptoms predicts the manifestation of adjustment problems in both groups. This shows the importance of maternal psychological well-being for child development. Further research is needed to understand the exact consequences of premature birth on cortisol regulation and the implication for the child’s development and health.
RETRACTED: Efficacy of Vanadyl Sulfate and Selenium Tetrachloride as Anti-Diabetic Agents against Hyperglycemia and Oxidative Stress Induced by Diabetes Mellitus in Male Rats
Authors: Al-Salmi Fawziah , Hamza Reham
Published: December 2021

The use of metals in medicine has grown in popularity in clinical and commercial settings. In this study, the immune-protecting effects and the hypoglycemic and antioxidant activity of vanadyl sulfate (VOSO4) and/or selenium tetrachloride (Se) on oxidative injury, DNA damage, insulin resistance, and hyperglycemia were assessed. Fifty male albino rats were divided into five groups, and all treatments were administrated at 9:00 a.m. daily for 60 successive days: control, STZ (Streptozotocin; 50 mg/kg of STZ was given to 6 h fasted animals in a single dose, followed by confirmation of diabetic state occurrence after 72 h by blood glucose estimation at >280 mg/dl), STZ (Diabetic) plus administration of VOSO4 (15 mg/kg) for 60 days, STZ (Diabetic) plus administration of selenium tetrachloride (0.87 mg/Kg), and STZ plus VOSO4 and, after 1/2 h, administration of selenium tetrachloride at the above doses. The test subjects’ blood glucose, insulin hormone, HbA1C, C-peptide, antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, myeloperoxidase, and xanthine oxidase), markers of lipid peroxidation (MDA), and histological sections of pancreatic tissues were evaluated, and a comet assay was performed. Histological sections in pancreas tissues were treated as indicators of both VOSO4 and selenium tetrachloride efficacy, either alone or combined, for the alleviation of STZ toxicity. The genotoxicity of diabetes mellitus was assessed, and the possible therapeutic roles of VOSO4 or selenium tetrachloride, or both, on antioxidant enzymes were studied. The findings show that the administration of VOSO4 with selenium tetrachloride reduced oxidative stress to normal levels, lowered blood glucose levels, and elevated insulin hormone. Additionally, VOSO4 with selenium tetrachloride had a synergistic effect and significantly decreased pancreatic genotoxicity. The data clearly show that both VOSO4 and selenium tetrachloride inhibit pancreatic and DNA injury and improve the oxidative state in male rats, suggesting that the use of VOSO4 with selenium tetrachloride is a promising synergistic potential ameliorative agent in the diabetic animal model.
High-Precision X-ray Total Scattering Measurements Using a High-Accuracy Detector System
Authors: Kato Kenichi , Shigeta Kazuya
Published: December 2021

The total scattering method, which is based on measurements of both Bragg and diffuse scattering on an equal basis, has been still challenging even by means of synchrotron X-rays. This is because such measurements require a wide coverage in scattering vector Q, high Q resolution, and a wide dynamic range for X-ray detectors. There is a trade-off relationship between the coverage and resolution in Q, whereas the dynamic range is defined by differences in X-ray response between detector channels (X-ray response non-uniformity: XRNU). XRNU is one of the systematic errors for individual channels, while it appears to be a random error for different channels. In the present study, taking advantage of the randomness, the true sensitivity for each channel has been statistically estimated. Results indicate that the dynamic range of microstrip modules (MYTHEN, Dectris, Baden-Daettwil, Switzerland), which have been assembled for a total scattering measurement system (OHGI), has been successfully restored from 104 to 106. Furthermore, the correction algorithm has been optimized to increase time efficiencies. As a result, the correcting time has been reduced from half a day to half an hour, which enables on-demand correction for XRNU according to experimental settings. High-precision X-ray total scattering measurements, which has been achieved by a high-accuracy detector system, have demonstrated valence density studies from powder and PDF studies for atomic displacement parameters.