bluuebunny/crossref_metadata_2025 huggingface dataset:
Contributions of Machine Learning Models towards Student Academic Performance Prediction: A Systematic Review
Authors: Balaji Prasanalakshmi , Alelyani Salem , Qahmash Ayman , Mohana Mohamed
Published: October 2021

Machine learning is emerging nowadays as an important tool for decision support in many areas of research. In the field of education, both educational organizations and students are the target beneficiaries. It facilitates the educational sector in predicting the student’s outcome at the end of their course and for the students in deciding to choose a suitable course for them based on their performances in previous exams and other behavioral features. In this study, a systematic literature review is performed to extract the algorithms and the features that have been used in the prediction studies. Based on the search criteria, 2700 articles were initially considered. Using specified inclusion and exclusion criteria, quality scores were provided, and up to 56 articles were filtered for further analysis. The utmost care was taken in studying the features utilized, database used, algorithms implemented, and the future directions as recommended by researchers. The features were classified as demographic, academic, and behavioral features, and finally, only 34 articles with these features were finalized, whose details of study are provided. Based on the results obtained from the systematic review, we conclude that the machine learning techniques have the ability to predict the students’ performance based on specified features as categorized and can be used by students as well as academic institutions. A specific machine learning model identification for the purpose of student academic performance prediction would not be feasible, since each paper taken for review involves different datasets and does not include benchmark datasets. However, the application of the machine learning techniques in educational mining is still limited, and a greater number of studies should be carried out in order to obtain well-formed and generalizable results. We provide future guidelines to practitioners and researchers based on the results obtained in this work.
Multi-Zone Active Noise Control Strategy for the Scattered Sound Control of an Infinite Rigid Cylinder
Authors: Feng Yuwei , Wang Xiaolin , Cui Xiaoyan , Wu Ming , Yang Jun
Published: October 2021

Active noise control can be used to reduce the scattered sound of a reflecting object to make it invisible to incident acoustic waves. For the multi-zone active noise control of scattered sound from an infinite rigid cylinder, an active control strategy is proposed that combines the least absolute shrinkage and selection operator (LASSO) algorithm with constraint points and regularized least squares (RLS) algorithm. The proposed control strategy is used to promote control performance through optimizing the secondary loudspeaker placement of an active noise control system. Compared with the RLS algorithm employing the uniformly placed loudspeakers and the traditional LASSO algorithm, the proposed strategy has better reduction performance both in the forward-scattered and backward-scattered sound target areas, and there is less sound amplification in the far field. From 400 Hz–1100 Hz, the proposed strategy provides a 5 dB–16 dB reduction performance advantage in the target area compared to the RLS algorithm employing uniformly placed loudspeakers.
Peer-to-Peer System Design Trade-Offs: A Framework Exploring the Balance between Blockchain and IPFS
Authors: Tenorio-Fornés Ámbar , Hassan Samer , Pavón Juan
Published: October 2021

The current state of the web, which is dominated by centralized cloud services, raises several concerns regarding different aspects such as governance, privacy, surveillance, and security. A way to address these issues is to decentralize the platforms by adopting new distributed technologies, such as IPFS and Blockchain, which follow a full peer-to-peer model. This work proposes a set of guidelines to design decentralized systems, taking the different trade-offs these technologies face with regard to their consistency requirements into consideration. These guidelines are then illustrated with the design of a decentralized questions and answers system. This system serves to illustrate a framework to create decentralized services and applications that uses IPFS and Blockchain technologies and incorporates the discussion and guidelines of the paper, providing solutions for data access, data provenance, and data discovery. Thus, this work proposes a framework to assist in the design of new decentralized systems, proposing a set of guidelines to choose the appropriate technologies depending on the relevant requirements; e.g., considering if Blockchain technology may be required or IPFS might be sufficient.
Assessment of Lightweight Concrete Thermal Properties at Elevated Temperatures
Authors: Martínez-Martínez Juan Enrique , Álvarez Rabanal Felipe Pedro , Lázaro Mariano , Alonso-Martínez Mar , Alvear Daniel , del Coz-Díaz Juan José
Published: October 2021

Structural lightweight concrete (LWC) has recently acquired research importance because of its good thermal insulation properties. However, there is a lack of knowledge about its thermal properties at elevated temperatures. The thermal properties, such as thermal conductivity and specific heat, of porous LWC vary depending on the aggregates, air voids, and moisture content of the LWC in question. To study these effects, in this paper, we measured the thermal properties of three types of structural LWCs at different temperatures, combining different characterization techniques, namely, differential scanning calorimetry (DSC), laser flash analysis (LFA), and modified transient plane source (MTPS). Bulk density and porosity were also evaluated. Specific heat is analyzed by the DSC technique from 20 to 1000 °C and the MTPS technique from 20 to 160 °C. Thermal conductivity is studied using MTPS and LFA techniques at temperatures ranging from 20 to 160 °C and 100 to 300 °C, respectively. The results indicate that the thermal properties of LWC are highly affected by moisture content, temperature, and porosity. For LWC, the current Eurocodes 2 and 4 assume a constant value of specific heat (840 J/kg°C). This research reveals variability in temperatures near 150, 450, and 850 °C due to endothermic reactions. Furthermore, for low temperatures, the higher the porosity, the higher the thermal conductivity, while, at high temperatures, the higher the porosity, the lower the thermal conductivity. Thus, Eurocodes 2 and 4 should be updated accordingly. This research contributes to a deeper understanding and more accurate prediction of LWC’s effects on thermal properties at elevated temperatures.
Comparison of Structure and Magnetic Properties of Ni/C Composites Synthesized from Wheat Straw by Different Methods
Authors: Bordun Ihor , Chwastek Krzysztof , Całus Dariusz , Chabecki Piotr , Ivashchyshyn Fedir , Kohut Zenoviy , Borysiuk Anatoliy , Kulyk Yuriy
Published: October 2021

Synthesis of Ni/C nanostructured composites based on a natural raw material, i.e., wheat straw, is carried out in this work. The synthesis is performed by one- and two-stage methods using NiCl2 as the activating agent. The X-ray diffraction and EDS analyses reveal the presence of metallic nickel in the structure of the composites, whereas magnetic measurements showed that nickel was contained in the porous carbon matrix in the nanoparticle state. For nanocomposites synthesized by the one-stage method, the largest contribution to the formation of the porous structure might be attributed to pores with radii from 5 to 30 nm; for a nanocomposite synthesized in two stages, the pore distribution function exhibits a narrow isolated peak with a maximum of around 2.6 nm. Based on the obtained magnetic data, the coercive force, specific saturation magnetization and nickel content in nanocomposites are calculated. For the measured values of the coercive force, the average size of magnetic moment carriers is determined to be ~100 nm for the two-stage synthesis nanocomposite and ~100 ÷ 110 nm for the one-stage synthesis nanocomposites. The developed Ni/C nanocomposites might be used as a cheap material for energy storage applications or as magnetically controlled adsorbents.
A Review on Methods and Systems for Remote Collaboration
Authors: Druta Romina , Druta Cristian , Negirla Paul , Silea Ioan
Published: October 2021

Due to the appearance of COVID-19 in 2019, person-to-person interactions were drastically reduced. The impact of these restrictions on the economic environment was significant. For example, technical assistance for commissioning or adjusting the parameters of some complex machines/installations had to be postponed. Economic operators became interested in the possibility of remote collaboration, depending on the manufactured products and the performance of the production lines that they owned. This bibliographic research was undertaken to address these needs. The purpose of this review was to analyze the current solutions, approaches, and technologies that workers and specialists can implement to obtain a reliable remote collaboration system. This survey focuses on techniques, devices, and tools that are being used in different contexts to provide remote guidance. We present communication cues and methods being employed, the implemented technological support, and the areas that benefit from remote collaboration. We hope that our effort will be useful to those who develop such systems and people who want to learn about the existence of collaborative solutions, and that it will increase awareness about the applications and the importance of the domain. We are convinced that, with the development of communication systems, the advancement of remote support systems will be a goal for many economic operators.
Evaluation of Anti-Photoaging Effects of a Novel Cosmeceutical Containing a Retinoids Mixture Using In Vitro Cell Models
Authors: Zerbinati Nicola , Sommatis Sabrina , Maccario Cristina , Capillo Maria Chiara , Di Francesco Serena , Liga Elsa , Rauso Raffaele , D’Este Edoardo , Dalla Gasperina Daniela , Guida Stefania , Mocchi Roberto
Published: October 2021

Physiological ageing due to the passing of time and prolonged exposure to harmful sun rays generate wrinkles and reduce skin elasticity. These visible and clinical signs can be prevented or reversed by known strategies, such as the daily use of cosmetic products with antioxidant combinations or retinoids. A new dermocosmetic formulation enriched with a complex of retinoids, called RETINOIDS SERUM, was investigated through in vitro assays using human skin cells. The experiments were carried out to assess the anti-ageing activity in normal human dermal fibroblasts (NHDF) and epidermal keratinocytes (HaCaT). After the preliminary MTT assay, the proliferation together with the synthesis of collagen and elastin fibers was performed on NHDF cells after 24 h treatment with the two non-cytotoxic concentrations. Using UVB-irradiated HaCaT cells, the measurement of matrix metalloproteinase-1 (MMP-1) levels was also investigated. In vitro studies show that the dermocosmetic product improves collagen and elastin synthesis and the renewal of dermal fibroblasts. Moreover, a reduction in the MMP-1 secretion was also highlighted in UVB-irradiated HaCaT cells. These results suggest that the cosmetic formulation containing functional compounds such as retinoids can be useful to prevent the natural sign of ageing.
An Intelligent Clustering-Based Routing Protocol (CRP-GR) for 5G-Based Smart Healthcare Using Game Theory and Reinforcement Learning
Authors: Ahad Abdul , Tahir Mohammad , Sheikh Muhammad Aman , Ahmed Kazi Istiaque , Mughees Amna
Published: October 2021

With advantages such as short and long transmission ranges, D2D communication, low latency, and high node density, the 5G communication standard is a strong contender for smart healthcare. Smart healthcare networks based on 5G are expected to have heterogeneous energy and mobility, requiring them to adapt to the connected environment. As a result, in 5G-based smart healthcare, building a routing protocol that optimizes energy consumption, reduces transmission delay, and extends network lifetime remains a challenge. This paper presents a clustering-based routing protocol to improve the Quality of services (QoS) and energy optimization in 5G-based smart healthcare. QoS and energy optimization are achieved by selecting an energy-efficient clustering head (CH) with the help of game theory (GT) and best multipath route selection with reinforcement learning (RL). The cluster head selection is modeled as a clustering game with a mixed strategy considering various attributes to find equilibrium conditions. The parameters such as distance between nodes, the distance between nodes and base station, the remaining energy and speed of mobility of the nodes were used for cluster head (CH) selection probability. An energy-efficient multipath routing based on reinforcement learning (RL) having (Q-learning) is proposed. The simulation result shows that our proposed clustering-based routing approach improves the QoS and energy optimization compared to existing approaches. The average performances of the proposed schemes CRP-GR and CRP-G are 78% and 71%, respectively, while the existing schemes, such as FBCFP, TEEN and LEACH have average performances of 63%, 48% and 35% accordingly.
Experimental Investigation into the Influence of Plasma Technology on Seed Surface Wettability
Authors: Kriz Pavel , Olsan Pavel , Havelka Zbynek , Bohata Andrea , Krishna Syam , Cerny Pavel , Filip Martin , Bartos Petr , Kocira Sławomir , Spatenka Petr
Published: October 2021

The influence of atmospheric plasma discharge (APD) of the Gliding Arc type and low-pressure microwave plasma discharge (LPMD) on the class of various seeds was investigated. Pea, wheat, and sunflower seeds, representing legumes, cereals, and oilseeds, respectively, were selected for the treatment. Our study aimed to verify the effect of plasma treatment on the water contact angle and the wettability of the seeds. Treatment time, working gas flow and microwave power were varied to determine their impact. All treated and untreated variants were used to conduct the water contact angle measurements to compare their wettability. APD treatment seemed to be utterly ineffective for improving the wettability for most process parameters. On the contrary, LPMD manifested a much more efficient impact. The maximum effect was found for the 800 W microwave power applied to the pea seed for 30 s. The contact angle achieved decreased by approximately 50% compared to the untreated sample. These results indicate that LPMD may be an effective alternative to traditional pre-sowing seed treatments used in agriculture for water intake enhancement. Still, it is strongly dependent on the seed’s type and the used process parameters.
A Novel Secure Blockchain Framework for Accessing Electronic Health Records Using Multiple Certificate Authority
Authors: Ali Aitizaz , Rahim Hasliza A , Ali Jehad , Pasha Muhammad Fermi , Masud Mehedi , Rehman Ateeq Ur , Chen Can , Baz Mohammed
Published: October 2021

Blockchain is a promising technology in the context of digital healthcare systems, but there are issues related to the control of accessing the electronic health records. In this paper, we propose a novel framework based on blockchain and multiple certificate authority that implement smart contracts and access health records securely. Our proposed solution provides the facilities of flexible policies to update a record or invoke the policy such that a patient has complete authority. A novel approach towards multiple certificate’s authority (CA) is introduced in the design through our proposed framework. Our proposed policies and methods overcome the shortcoming and security breaches faced by single certificate authority. Our proposed scheme provides a flexible access control mechanism for securing electronic health records as compared to the existing benchmark models. Moreover, our proposed method provides a re-enrolment facility in the case of a user lost enrolment.
The Impact of a Hydroelectric Power Plant on a Regional Climate in Portugal
Authors: Fonseca André , Santos João A.
Published: October 2021

This paper summarizes the results from microclimatic monitoring of the impacts related to the construction and exploration phase of a hydroelectric powerplant in the upper Douro River (Portugal). Reference climatic elements for both periods were obtained and the impacts of the reservoir water mass on the region’s microclimate were evaluated. For this purpose, Sen’s slope estimate non-parametric test was used to detect the meteorological variables’ trends over 10 years, considering the division into the construction (2011–2015) and exploration (2016–2020) phases. A network of meteorological stations located close to the dam, in addition to a control station relatively distant from the dam, was used to collect the meteorological data. The control station is still integrated into the same regional climatic context but not exposed to the direct influence of the resulting reservoirs. As a result, temporal differences were determined for temperature and relative humidity. The results show a statistically significant increase in the minimum relative humidity, accompanied by a statistically significant decrease in the daily and seasonal temperature amplitudes between the construction and the exploration phase periods. These outcomes thereby suggest that large reservoirs affect the local climate and may create new microclimates, in the surrounding area, with both positive and negative potential effects.
Aerosol Particle Transport and Deposition in Upper and Lower Airways of Infant, Child and Adult Human Lungs
Authors: Rahman Md. M. , Zhao Ming , Islam Mohammad S. , Dong Kejun , Saha Suvash C.
Published: October 2021

Understanding transportation and deposition (TD) of aerosol particles in the human respiratory system can help clinical treatment of lung diseases using medicines. The lung airway diameters and the breathing capacity of human lungs normally increase with age until the age of 30. Many studies have analyzed the particle TD in the human lung airways. However, the knowledge of the nanoparticle TD in airways of infants and children with varying inhalation flow rates is still limited in the literature. This study investigates nanoparticle (5 nm ≤ dp ≤ 500 nm) TD in the lungs of infants, children, and adults. The inhalation air flow rates corresponding to three ages are considered as Qin=3.22 L/min (infant), 8.09 L/min (Child), and Qin=14 L/min (adult). It is found that less particles are deposited in upper lung airways (G0–G3) than in lower airways (G12–G15) in the lungs of all the three age groups. The results suggest that the particle deposition efficiency in lung airways increases with the decrease of particle size due to the Brownian diffusion mechanism. About 3% of 500 nm particles are deposited in airways G12–G15 for the three age groups. As the particle size is decreased to 5 nm, the deposition rate in G12–G15 is increased to over 95%. The present findings can help medical therapy by individually simulating the distribution of drug-aerosol for the patient-specific lung.
Climatology and Formation Environments of Severe Convective Windstorms and Tornadoes in the Perm Region (Russia) in 1984–2020
Authors: Shikhov Andrey , Chernokulsky Alexander , Kalinin Nikolay , Bykov Alexey , Pischalnikova Evgeniya
Published: October 2021

Severe convective windstorms and tornadoes regularly hit the territory of Russia causing substantial damage and fatalities. An analysis of the climatology and formation environments of these events is essential for risk assessments, forecast improvements and identifying of links with the observed climate change. In this paper, we present an analysis of severe convective windstorms, i.e., squalls and tornadoes reported between 1984 and 2020 in the Perm region (northeast of European Russia), where a local maximum in the frequency of such events was previously found. The analysed database consists of 165 events and includes 100 squalls (convective windstorms), 59 tornadoes, and six cases with both tornadoes and squalls. We used various information to compile the database including weather station reports, damage surveys, media reports, previously presented databases, and satellite images for windthrow. We found that the satellite images of damaged forests are the main data source on tornadoes, but their role is substantially lower for windstorm events due to the larger spatial and temporal scale of such events. Synoptic-scale environments and associated values of convective indices were determined for each event with a known date and time. Similarities and differences for the formation conditions of tornadoes and windstorms were revealed. Both squalls and tornadoes occur mostly on rapidly moving cold fronts or on waving quasi-stationary fronts, associated with low-pressure systems. Analyses of 72-h air parcel backward trajectories shows that the Caspian and Aral Seas are important sources of near-surface moisture for the formation of both squalls and tornadoes. Most of these events are formed within high CAPE and high shear environments, but tornadic storms are generally characterised by a higher wind shear and helicity. We also differentiated convective storms that caused forest damage and those did not. We found the composite parameter WMAXSHEAR is the best discriminator between these two groups. In general, storm events causing windthrow mainly occur under conditions more favourable for deep well-organised convection. Thus, forest damage can be considered as an indicator of the storm severity in the Perm region and in adjacent regions with forest-covered area exceeding 50%.
Spatial Distributions of Atmospheric Ammonia in a Rural Area in South Korea and the Associated Impact on a Nearby Urban Area
Authors: Oh Sangmin , Kim Seung-Gi , Lee Jae Bong , Park Junsu , Jee Joon-Bum , Hong Se-Woon , Kwon Kyeong-Seok , Song Mijung
Published: October 2021

Ammonia (NH3) plays an important role in air quality and atmospheric chemistry, yet studies on the characteristics and impacts of NH3 are limited. Herein, we revealed the spatial distribution of atmospheric NH3, as measured by passive samplers, at three different sites (R1, R2, and R3) in the rural area (livestock environment) of Jeongeup, South Korea, from September 2019 to August 2020. At site R1, the boundary of a large-scale pig farm, dramatically high daily mean concentrations of NH3 were observed (118.7 ppb), whereas sites R2 and R3, located ~1 km from R1, exhibited lower concentrations of 18.2 and 30.4 ppb, respectively. In the rural environment, the monthly NH3 variations showed a peak in June (34.2 ppb), which was significantly higher than in the urban and remote areas. To examine the impact of NH3 from the rural area on a nearby urban area in June 2020, simultaneous measurements were performed using a real-time instrument in Jeonju. When high NH3 events occurred in the urban area in June, the results for the NH3 concentrations and observed meteorological conditions in the rural and urban areas showed that the rural area influenced the NH3 levels in the adjacent urban area.
Altered Development of Mesencephalic Dopaminergic Neurons in SIDS: New Insights into Understanding Sudden Infant Death Pathogenesis
Authors: Lavezzi Anna Maria
Published: October 2021

Sudden infant death syndrome (SIDS) is defined as the unexpected sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation. The SIDS pathogenesis is still unknown; however, abnormalities in brain centers that control breathing and arousal from sleep, including dramatic changes in neurotransmitter levels, have been supposed in these deaths. This is the first study focusing on mesencephalic dopaminergic neurons, so far extensively studied only in animals and human neurological diseases, in SIDS. Dopaminergic structures in midbrain sections of a large series of sudden infant deaths (36 SIDS and 26 controls) were identified using polyclonal rabbit antibodies against tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, and the dopamine transporter, a membrane protein specifically expressed in dopaminergic cells. Dopamine-immunolabeled neurons were observed concentrated in two specific structures: the pars compacta of the substantia nigra and in the subnucleus medialis of the periaqueductal gray matter. Anatomical and functional degenerations of dopaminergic neurons in these regions were observed in most SIDS cases but never in controls. These results indicate that dopamine depletion, which is already known to be linked especially to Parkinson’s disease, is strongly involved even in SIDS pathogenesis.
Placenta Previa Complicated with Endometriosis: Contemporary Clinical Management, Molecular Mechanisms, and Future Research Opportunities
Authors: Matsuzaki Shinya , Nagase Yoshikazu , Ueda Yutaka , Kakuda Mamoru , Maeda Michihide , Matsuzaki Satoko , Kamiura Shoji
Published: October 2021

Endometriosis is a common gynecological disease characterized by chronic inflammation, with an estimated prevalence of approximately 5–15% in reproductive-aged women. This study aimed to assess the relationship between placenta previa (PP) and endometriosis. We performed a systematic review of the literature until 30 June 2021, and 24 studies met the inclusion criteria. Using an adjusted pooled analysis, we found that women with endometriosis had a significantly increased rate of PP (adjusted odds ratio (OR) 3.17, 95% confidence interval (CI) 2.58–3.89) compared to those without endometriosis. In an unadjusted analysis, severe endometriosis was associated with an increased prevalence of PP (OR 11.86, 95% CI 4.32–32.57), whereas non-severe endometriosis was not (OR 2.16, 95% CI 0.95–4.89). Notably, one study showed that PP with endometriosis was associated with increased intraoperative bleeding (1.515 mL versus 870 mL, p < 0.01) compared to those without endometriosis. Unfortunately, no studies assessed the molecular mechanisms underlying PP in patients with endometriosis. Our findings suggest that there is a strong association between endometriosis and a higher incidence of PP, as well as poor surgical outcomes during cesarean delivery. Therefore, the development of novel therapeutic agents or methods is warranted to prevent PP in women with endometriosis.
Smart and Biomimetic 3D and 4D Printed Composite Hydrogels: Opportunities for Different Biomedical Applications
Authors: Malekmohammadi Samira , Sedghi Aminabad Negar , Sabzi Amin , Zarebkohan Amir , Razavi Mehdi , Vosough Massoud , Bodaghi Mahdi , Maleki Hajar
Published: October 2021

In recent years, smart/stimuli-responsive hydrogels have drawn tremendous attention for their varied applications, mainly in the biomedical field. These hydrogels are derived from different natural and synthetic polymers but are also composite with various organic and nano-organic fillers. The basic functions of smart hydrogels rely on their ability to change behavior; functions include mechanical, swelling, shaping, hydrophilicity, and bioactivity in response to external stimuli such as temperature, pH, magnetic field, electromagnetic radiation, and biological molecules. Depending on the final applications, smart hydrogels can be processed in different geometries and modalities to meet the complicated situations in biological media, namely, injectable hydrogels (following the sol-gel transition), colloidal nano and microgels, and three dimensional (3D) printed gel constructs. In recent decades smart hydrogels have opened a new horizon for scientists to fabricate biomimetic customized biomaterials for tissue engineering, cancer therapy, wound dressing, soft robotic actuators, and controlled release of bioactive substances/drugs. Remarkably, 4D bioprinting, a newly emerged technology/concept, aims to rationally design 3D patterned biological matrices from synthesized hydrogel-based inks with the ability to change structure under stimuli. This technology has enlarged the applicability of engineered smart hydrogels and hydrogel composites in biomedical fields. This paper aims to review stimuli-responsive hydrogels according to the kinds of external changes and t recent applications in biomedical and 4D bioprinting.
A Short Corticosteroid Course Reduces Symptoms and Immunological Alterations Underlying Long-COVID
Authors: Utrero-Rico Alberto , Ruiz-Ruigómez María , Laguna-Goya Rocío , Arrieta-Ortubay Estíbaliz , Chivite-Lacaba Marta , González-Cuadrado Cecilia , Lalueza Antonio , Almendro-Vazquez Patricia , Serrano Antonio , Aguado José María , Lumbreras Carlos , Paz-Artal Estela
Published: October 2021

Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and after a 4-day prednisone course, and five post-COVID-19 patients without persistent symptoms (NSP). PSP showed a perturbed distribution of circulating mononuclear cell populations. Symptoms in PSP were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration. The current work highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID.
Enhancement of Osteoblast Differentiation Using No-Ozone Cold Plasma on Human Periodontal Ligament Cells
Authors: Choi Byul-Bora , Choi Jeong-Hae , Kang Tae-Hyung , Lee Seok-Jun , Kim Gyoo-Cheon
Published: October 2021

Periodontitis is an inflammatory disease that leads to periodontal tissue destruction and bone resorption. Proliferation and differentiation of cells capable of differentiating into osteoblasts is important for reconstructing periodontal tissues destroyed by periodontitis. In this study, the effects of the nozone (no-ozone) cold plasma (NCP) treatment on osteoblastic differentiation in periodontal ligament (PDL) cells were investigated. To test the toxicity of NCP on PDL cells, various NCP treatment methods and durations were tested, and time-dependent cell proliferation was analyzed using a water-soluble tetrazolium salts-1 assay. To determine the effect of NCP on PDL cell differentiation, the cells were provided with osteogenic media immediately after an NCP treatment to induce differentiation; the cells were then analyzed using alkaline phosphatase (ALP) staining, an ALP activity assay, real time PCR, and Alizarin Red S staining. The NCP treatment without toxicity on PDL cells was the condition of 1-min NCP treatment immediately followed by the replacement with fresh media. NCP increased ALP, osteocalcin, osteonectin, and osteopontin expression, as well as mineralization nodule formation. NCP treatment promotes osteoblastic differentiation of PDL cells; therefore, it may be beneficial for treating periodontitis.
Ovotransferrin Supplementation Improves the Iron Absorption: An In Vitro Gastro-Intestinal Model
Authors: Galla Rebecca , Grisenti Paride , Farghali Mahitab , Saccuman Laura , Ferraboschi Patrizia , Uberti Francesca
Published: October 2021

Transferrins constitute the most important iron regulation system in vertebrates and some invertebrates. Soluble transferrins, such as bovine lactoferrin and hen egg white ovotransferrin, are glycoproteins with a very similar structure with lobes that complex with iron. In this in vitro study, a comparison of bovine lactoferrin and ovotransferrin was undertaken to confirm the comparability of biological effects. An in vitro gastric barrier model using gastric epithelial cells GTL-16 and an in vitro intestinal barrier model using CaCo-2 cells was employed to evaluate iron absorption and barrier integrity. An analysis of the molecular pathways involving DMT-1 (divalent metal transporter 1), ferritin and ferroportin was also carried out. These in vitro data demonstrate the activity of both 15% saturated and 100% saturated ovotransferrin on the iron regulation system. Compared with the commercial bovine lactoferrin, both 15% saturated and 100% saturated ovotransferrin were found to act in a more physiological manner. Based on these data, it is possible to hypothesise that ovotransferrin may be an excellent candidate for iron supplementation in humans; in particular, 15% saturated ovotransferrin is the overall best performing product. In vivo studies should be performed to confirm this in vitro data.
The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo
Authors: Arndt Stephanie , Unger Petra , Bosserhoff Anja-Katrin , Berneburg Mark , Karrer Sigrid
Published: October 2021

Cold Atmospheric Plasma (CAP) has shown promising results in the treatment of various skin diseases. The therapeutic effect of CAP on localized scleroderma (LS), however, has not yet been evaluated. We investigated the effects of CAP on LS by comparing human normal fibroblasts (hNF), human TGF-β-activated fibroblasts (hAF), and human localized scleroderma-derived fibroblasts (hLSF) after direct CAP treatment, co-cultured with plasma-treated human epidermal keratinocytes (hEK) and with an experimental murine model of scleroderma. In hAF and hLSF, 2 min CAP treatment with the MicroPlaSterβ® plasma torch did not affect pro-fibrotic gene expression of alpha smooth muscle actin, fibroblast activating protein, and collagen type I, however, it promoted re-expression of matrix metalloproteinase 1. Functionally, CAP treatment reduced cell migration and stress fiber formation in hAF and hLSF. The relevance of CAP treatment was confirmed in an in vivo model of bleomycin-induced dermal fibrosis. In this model, CAP-treated mice showed significantly reduced dermal thickness and collagen deposition as well as a decrease in both alpha smooth muscle actin-positive myofibroblasts and CD68-positive macrophages in the affected skin in comparison to untreated fibrotic tissue. In conclusion, this study provides the first evidence for the successful use of CAP for treating LS and may be the basis for clinical trials including patients with LS.
Evaluation of Macular Retinal Vessels and Histological Changes in Two Cases of COVID-19
Authors: Hernandez Maria , González-Zamora Jorge , Recalde Sergio , Moreno-Orduña Maite , Bilbao-Malavé Valentina , Saenz de Viteri Manuel , Landecho Manuel F. , Fernandez-Robredo Patricia , García-Layana Alfredo
Published: October 2021

The purpose of this study was to assess vascular and histological alterations in two COVID-19 and three control post-mortem retinas. The macular areas of flat-mounted samples were processed for immunofluorescence. Lectin and collagen IV positive vessels were captured under confocal microscopy, and endothelium loss and tortuosity were analyzed. Expression of ACE2 (angiotensin-converting enzyme 2) (the receptor for SARS-CoV-2), Iba1 (ionized calcium-binding adaptor molecule 1) and GFAP (glial fibrillary acidic protein) were quantified in retinal sections. The number of lectin vessels in COVID-19 retinas decreased by 27% compared to the control (p < 0.01) and the tortuosity increased in COVID-19 retinas (7.3 ± 0.2) vs. control retinas (6.8 ± 0.07) (p < 0.05). Immunofluorescence analysis revealed an increase in ACE2 (2.3 ± 1.3 vs. 1.0 ± 0.1; p < 0.0001) and Iba1 expression (3.06 ± 0.6 vs. 1.0 ± 0.1; p < 0.01) in COVID-19 sections whereas no changes in GFAP were observed. Analysis of the COVID-19 macular retinal tissue suggested that endothelial cells are a preferential target of SARS-CoV-2 with subsequent changes through their ACE2 receptor expression and morphology. Thus, microglial activation was hyperactive when facing an ensuing immunological challenge after SARS-CoV-2 infection.
Breast Mass Classification Using Diverse Contextual Information and Convolutional Neural Network
Authors: Busaleh Mariam , Hussain Muhammad , Aboalsamh Hatim A. , Amin Fazal-e-
Published: October 2021

Masses are one of the early signs of breast cancer, and the survival rate of women suffering from breast cancer can be improved if masses can be correctly identified as benign or malignant. However, their classification is challenging due to the similarity in texture patterns of both types of mass. The existing methods for this problem have low sensitivity and specificity. Based on the hypothesis that diverse contextual information of a mass region forms a strong indicator for discriminating benign and malignant masses and the idea of the ensemble classifier, we introduce a computer-aided system for this problem. The system uses multiple regions of interest (ROIs) encompassing a mass region for modeling diverse contextual information, a single ResNet-50 model (or its density-specific modification) as a backbone for local decisions, and stacking with SVM as a base model to predict the final decision. A data augmentation technique is introduced for fine-tuning the backbone model. The system was thoroughly evaluated on the benchmark CBIS-DDSM dataset using its provided data split protocol, and it achieved a sensitivity of 98.48% and a specificity of 92.31%. Furthermore, it was found that the system gives higher performance if it is trained and tested using the data from a specific breast density BI-RADS class. The system does not need to fine-tune/train multiple CNN models; it introduces diverse contextual information by multiple ROIs. The comparison shows that the method outperforms the state-of-the-art methods for classifying mass regions into benign and malignant. It will help radiologists reduce their burden and enhance their sensitivity in the prediction of malignant masses.
LINCS Dataset-Based Repositioning of Dutasteride as an Anti-Neuroinflammation Agent
Authors: Luo Dan , Han Lu , Gao Shengqiao , Xiao Zhiyong , Zhou Qingru , Cheng Xiaorui , Zhang Yongxiang , Zhou Wenxia
Published: October 2021

Neuroinflammation is often accompanied by central nervous system (CNS) injury seen in various CNS diseases, with no specific treatment. Drug repurposing is a strategy of finding new uses for approved or investigational drugs, and can be enabled by the Library of Integrated Network-based Cellular Signatures (LINCS), a large drug perturbation database. In this study, the signatures of Lipopolysaccharide (LPS) were compared with the signatures of compounds contained in the LINCS dataset. To the top 100 compounds obtained, the Quantitative Structure-Activity Relationship (QSAR)-based tool admetSAR was used to identify the top 10 candidate compounds with relatively high blood–brain barrier (BBB) penetration. Furthermore, the seventh-ranked compound, dutasteride, a 5-α-reductase inhibitor, was selected for in vitro and in vivo validation of its anti-neuroinflammation activity. The results showed that dutasteride significantly reduced the levels of IL-6 and TNF-α in the supernatants of LPS-stimulated BV2 cells, and decreased the levels of IL-6 in the hippocampus and plasma, and the number of activated microglia in the brain of LPS administration mice. Furthermore, dutasteride also attenuated the cognitive impairment caused by LPS stimulation in mice. Taken together, this study demonstrates that the LINCS dataset-based drug repurposing strategy is an effective approach, and the predicted candidate, dutasteride, has the potential to ameliorate LPS-induced neuroinflammation and cognitive impairment.
Response of Normal Tissues to Boron Neutron Capture Therapy (BNCT) with 10B-Borocaptate Sodium (BSH) and 10B-Paraboronophenylalanine (BPA)
Authors: Fukuda Hiroshi
Published: October 2021

Boron neutron capture therapy (BNCT) is a cancer-selective radiotherapy that utilizes the cancer targeting 10B-compound. Cancer cells that take up the compound are substantially damaged by the high liner energy transfer (LET) particles emitted mainly from the 10B(n, α7Li reaction. BNCT can minimize the dose to normal tissues, but it must be performed within the tolerable range of normal tissues. Therefore, it is important to evaluate the response of normal tissues to BNCT. Since BNCT yields a mixture of high and low LET radiations that make it difficult to understand the radiobiological basis of BNCT, it is important to evaluate the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors for assessing the responses of normal tissues to BNCT. BSH and BPA are the only 10B-compounds that can be used for clinical BNCT. Their biological behavior and cancer targeting mechanisms are different; therefore, they affect the CBE values differently. In this review, we present the RBE and CBE values of BPA or BSH for normal tissue damage by BNCT irradiation. The skin, brain (spinal cord), mucosa, lung, and liver are included as normal tissues. The CBE values of BPA and BSH for tumor control are also discussed.
Identification of a Novel Mutation Exacerbated the PSI Photoinhibition in pgr5/pgrl1 Mutants; Caution for Overestimation of the Phenotypes in Arabidopsis pgr5-1 Mutant
Authors: Wada Shinya , Amako Katsumi , Miyake Chikahiro
Published: October 2021

PSI photoinhibition is usually avoided through P700 oxidation. Without this protective mechanism, excess light represents a potentially lethal threat to plants. PGR5 is suggested to be a major component of cyclic electron transport around PSI and is important for P700 oxidation in angiosperms. The known Arabidopsis PGR5 deficient mutant, pgr5-1, is incapable of P700 oxidation regulation and has been used in numerous photosynthetic studies. However, here it was revealed that pgr5-1 was a double mutant with exaggerated PSI photoinhibition. pgr5-1 significantly reduced growth compared to the newly isolated PGR5 deficient mutant, pgr5hope1. The introduction of PGR5 into pgr5-1 restored P700 oxidation regulation, but remained a pale-green phenotype, indicating that pgr5-1 had additional mutations. Both pgr5-1 and pgr5hope1 tended to cause PSI photoinhibition by excess light, but pgr5-1 exhibited an enhanced reduction in PSI activity. Introducing AT2G17240, a candidate gene for the second mutation into pgr5-1 restored the pale-green phenotype and partially restored PSI activity. Furthermore, a deficient mutant of PGRL1 complexing with PGR5 significantly reduced PSI activity in the double-deficient mutant with AT2G17240. From these results, we concluded that AT2G17240, named PSI photoprotection 1 (PTP1), played a role in PSI photoprotection, especially in PGR5/PGRL1 deficient mutants.
Somatic Reprogramming—Above and Beyond Pluripotency
Authors: Meir Yaa-Jyuhn James , Li Guigang
Published: October 2021

Pluripotent stem cells, having long been considered the fountain of youth, have caught the attention of many researchers from diverse backgrounds due to their capacity for unlimited self-renewal and potential to differentiate into all cell types. Over the past 15 years, the advanced development of induced pluripotent stem cells (iPSCs) has displayed an unparalleled potential for regenerative medicine, cell-based therapies, modeling human diseases in culture, and drug discovery. The transcription factor quartet (Oct4, Sox2, Klf4, and c-Myc) reprograms highly differentiated somatic cells back to a pluripotent state recapitulated embryonic stem cells (ESCs) in different aspects, including gene expression profile, epigenetic signature, and functional pluripotency. With the prior fruitful studies in SCNT and cell fusion experiments, iPSC finds its place and implicates that the differentiated somatic epigenome retains plasticity for re-gaining the pluripotency and further stretchability to reach a totipotency-like state. These achievements have revolutionized the concept and created a new avenue in biomedical sciences for clinical applications. With the advent of 15 years’ progress-making after iPSC discovery, this review is focused on how the current concept is established by revisiting those essential landmark studies and summarizing its current biomedical applications status to facilitate the new era entry of regenerative therapy.
Functional Inhibition of Valosin-Containing Protein Induces Cardiac Dilation and Dysfunction in a New Dominant-Negative Transgenic Mouse Model
Authors: Sun Xiaonan , Zhou Ning , Ma Ben , Wu Wenqian , Stoll Shaunrick , Lai Lo , Qin Gangjian , Qiu Hongyu
Published: October 2021

Valosin-containing protein (VCP) was found to play a vital protective role against cardiac stresses. Genetic mutations of VCP are associated with human dilated cardiomyopathy. However, the essential role of VCP in the heart during the physiological condition remains unknown since the VCP knockout in mice is embryonically lethal. We generated a cardiac-specific dominant-negative VCP transgenic (DN-VCP TG) mouse to determine the effects of impaired VCP activity on the heart. Using echocardiography, we showed that cardiac-specific overexpression of DN-VCP induced a remarkable cardiac dilation and progressively declined cardiac function during the aging transition. Mechanistically, DN-VCP did not affect the endogenous VCP (EN-VCP) expression but significantly reduced cardiac ATPase activity in the DN-VCP TG mouse hearts, indicating a functional inhibition. DN-VCP significantly impaired the aging-related cytoplasmic/nuclear shuffling of EN-VCP and its co-factors in the heart tissues and interrupted the balance of the VCP-cofactors interaction between the activating co-factors, ubiquitin fusion degradation protein 1 (UFD-1)/nuclear protein localization protein 4 (NPL-4) complex, and its inhibiting co-factor P47, leading to the binding preference with the inhibitory co-factor, resulting in functional repression of VCP. This DN-VCP TG mouse provides a unique functional-inactivation model for investigating VCP in the heart in physiological and pathological conditions.
Pulmonary Alveolar Stem Cell Senescence, Apoptosis, and Differentiation by p53-Dependent and -Independent Mechanisms in Telomerase-Deficient Mice
Authors: Zhang Kexiong , Wang Lihui , Hong Xiaojing , Chen Hao , Shi Yao , Liu Yingying , Liu Jun , Liu Jun-Ping
Published: October 2021

Pulmonary premature ageing and fibrogenesis as in idiopathic pulmonary fibrosis (IPF) occur with the DNA damage response in lungs deficient of telomerase. The molecular mechanism mediating pulmonary alveolar cell fates remains to be investigated. The present study shows that naturally occurring ageing is associated with the DNA damage response (DDR) and activation of the p53 signalling pathway. Telomerase deficiency induced by telomerase RNA component (TERC) knockout (KO) accelerates not only replicative senescence but also altered differentiation and apoptosis of the pulmonary alveolar stem cells (AEC2) in association with increased innate immune natural killer (NK) cells in TERC KO mice. TERC KO results in increased senescence-associated heterochromatin foci (SAHF) marker HP1γ, p21, p16, and apoptosis-associated cleaved caspase-3 in AEC2. However, additional deficiency of the tumour suppressor p53 in the Trp53−/− allele of the late generation of TERC KO mice attenuates the increased senescent and apoptotic markers significantly. Moreover, p53 deficiency has no significant effect on the increased gene expression of T1α (a marker of terminal differentiated AEC1) in AEC2 of the late generation of TERC KO mice. These findings demonstrate that, in natural ageing or premature ageing accelerated by telomere shortening, pulmonary senescence and IPF develop with alveolar stem cell p53-dependent premature replicative senescence, apoptosis, and p53-independent differentiation, resulting in pulmonary senescence-associated low-grade inflammation (SALI). Our studies indicate a natural ageing-associated molecular mechanism of telomerase deficiency-induced telomere DDR and SALI in pulmonary ageing and IPF.