bluuebunny/crossref_metadata_2025 huggingface dataset:
Dehydroflavonolignans from Silymarin Potentiate Transition Metal Toxicity In Vitro but Are Protective for Isolated Erythrocytes Ex Vivo
Authors: Lomozová Zuzana , Tvrdý Václav , Hrubša Marcel , Catapano Maria Carmen , Macáková Kateřina , Biedermann David , Kučera Radim , Křen Vladimír , Mladěnka Přemysl , Valentová Kateřina
Published: April 2021

2,3-Dehydrosilybin (DHS) was previously shown to chelate and reduce both copper and iron ions. In this study, similar experiments with 2,3-dehydrosilychristin (DHSCH) showed that this congener of DHS also chelates and reduces both metals. Statistical analysis pointed to some differences between both compounds: in general, DHS appeared to be a more potent iron and copper chelator, and a copper reducing agent under acidic conditions, while DHSCH was a more potent copper reducing agent under neutral conditions. In the next step, both DHS and DHSCH were tested for metal-based Fenton chemistry in vitro using HPLC with coulometric detection. Neither of these compounds were able to block the iron-based Fenton reaction and, in addition, they mostly intensified hydroxyl radical production. In the copper-based Fenton reaction, the effect of DHSCH was again prooxidant or neutral, while the effect of DHS was profoundly condition-dependent. DHS was even able to attenuate the reaction under some conditions. Interestingly, both compounds were strongly protective against the copper-triggered lysis of red blood cells, with DHSCH being more potent. The results from this study indicated that, notwithstanding the prooxidative effects of both dehydroflavonolignans, their in vivo effect could be protective.
Various Therapeutic Methods for the Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) and Their Limitations: A Narrative Review on New Molecular and Cellular Therapeutic Approaches
Authors: On Sung-Woon , Cho Seoung-Won , Byun Soo-Hwan , Yang Byoung-Eun
Published: April 2021

Medication-related osteonecrosis of the jaw (MRONJ) is one of the most interesting diseases in the field of maxillofacial surgery. In addition to bisphosphonates, the use of antiresorptive and antiangiogenic agents is known to be the leading cause. However, the exact pathogenesis of MRONJ has not been established, and various hypotheses have been proposed, such as oxidative stress-related theory. As a result, a definitive treatment protocol for MRONJ has not been identified, while various therapeutic approaches are applied to manage patients with MRONJ. Although the surgical approach to treat osteomyelitis of the jaw has been proven to be most effective, there are limitations, such as recurrence and delayed healing. Many studies and clinical trials are being conducted to develop another effective therapeutic modality. The use of some materials, including platelet concentrates and bone morphogenetic proteins, showed a positive effect on MRONJ. Among them, teriparatide is currently the most promising material, and it has shown encouraging results when applied to patients with MRONJ. Furthermore, cell therapy using mesenchymal stem cells showed promising results, and it can be the new therapeutic approach for the treatment of MRONJ. This review presents various treatment methods for MRONJ and their limitations while investigating newly developed and researched molecular and cellular therapeutic approaches along with a literature review.
A New Two-Stage Approach to Coordinate Electrical Vehicles for Satisfaction of Grid and Customer Requirements
Authors: Boonseng Trinnapop , Sangswang Anawach , Naetiladdanon Sumate , Gurung Samundra
Published: April 2021

Recently due to air pollution concerns, a large number of electric vehicles have been integrated into the electric distribution system. However, the uncoordinated charging of this technology can cause different voltage issues. This paper proposes a two-stage optimization approach with active and reactive power control to coordinate electric vehicles with both grid-to-vehicle and vehicle-to-grid capabilities to satisfy both grid requirements and electric vehicle prosumer requirements. The system requirements considered are voltage deviation and unbalance and the electric vehicle prosumer requirements considered are minimization of charging and battery degradation costs. The coordination problem is formulated as an optimization problem, where the first stage objectives are: minimization of voltage unbalance, customer charging and battery degradation costs. The first stage optimization problem is solved using the meta-heuristic optimization algorithm known as particle swarm optimization to obtain an optimized real power schedule for the electric vehicles. The second stage is then solved of which the objective is to minimize the bus voltage deviation and provides the reactive power schedule for electric vehicles. All the analyses were carried out on the IEEE 34 bus distribution system and the study results show that the proposed method allows prosumers to charge at a minimum cost without any grid voltage unbalance factors and under/over voltage problems under different scenarios. Thus, this work can be beneficial for system operators or electric vehicle aggregators to create a day-ahead schedule.
Classification Performance of Thresholding Methods in the Mahalanobis–Taguchi System
Authors: Ramlie Faizir , Muhamad Wan Zuki Azman Wan , Harudin Nolia , Abu Mohd Yazid , Yahaya Haryanti , Jamaludin Khairur Rijal , Abdul Talib Hayati Habibah
Published: April 2021

The Mahalanobis–Taguchi System (MTS) is a pattern recognition tool employing Mahalanobis Distance (MD) and Taguchi Robust Engineering philosophy to explore and exploit data in multidimensional systems. The MD metric provides a measurement scale to classify classes of samples (Abnormal vs. Normal) and gives an approach to measuring the level of severity between classes. An accurate classification result depends on a threshold value or a cut-off MD value that can effectively separate the two classes. Obtaining a reliable threshold value is very crucial. An inaccurate threshold value could lead to misclassification and eventually resulting in a misjudgment decision which in some cases caused fatal consequences. Thus, this paper compares the performance of the four most common thresholding methods reported in the literature in minimizing the misclassification problem of the MTS namely the Type I–Type II error method, the Probabilistic thresholding method, Receiver Operating Characteristics (ROC) curve method and the Box–Cox transformation method. The motivation of this work is to find the most appropriate thresholding method to be utilized in MTS methodology among the four common methods. The traditional way to obtain a threshold value in MTS is using Taguchi’s Quadratic Loss Function in which the threshold is obtained by minimizing the costs associated with misclassification decision. However, obtaining cost-related data is not easy since monetary related information is considered confidential in many cases. In this study, a total of 20 different datasets were used to evaluate the classification performances of the four different thresholding methods based on classification accuracy. The result indicates that none of the four thresholding methods outperformed one over the others in (if it is not for all) most of the datasets. Nevertheless, the study recommends the use of the Type I–Type II error method due to its less computational complexity as compared to the other three thresholding methods.
Whole Heart Segmentation Using 3D FM-Pre-ResNet Encoder–Decoder Based Architecture with Variational Autoencoder Regularization
Authors: Habijan Marija , Galić Irena , Leventić Hrvoje , Romić Krešimir
Published: April 2021

An accurate whole heart segmentation (WHS) on medical images, including computed tomography (CT) and magnetic resonance (MR) images, plays a crucial role in many clinical applications, such as cardiovascular disease diagnosis, pre-surgical planning, and intraoperative treatment. Manual whole-heart segmentation is a time-consuming process, prone to subjectivity and error. Therefore, there is a need to develop a quick, automatic, and accurate whole heart segmentation systems. Nowadays, convolutional neural networks (CNNs) emerged as a robust approach for medical image segmentation. In this paper, we first introduce a novel connectivity structure of residual unit that we refer to as a feature merge residual unit (FM-Pre-ResNet). The proposed connectivity allows the creation of distinctly deep models without an increase in the number of parameters compared to the pre-activation residual units. Second, we propose a three-dimensional (3D) encoder–decoder based architecture that successfully incorporates FM-Pre-ResNet units and variational autoencoder (VAE). In an encoding stage, FM-Pre-ResNet units are used for learning a low-dimensional representation of the input. After that, the variational autoencoder (VAE) reconstructs the input image from the low-dimensional latent space to provide a strong regularization of all model weights, simultaneously preventing overfitting on the training data. Finally, the decoding stage creates the final whole heart segmentation. We evaluate our method on the 40 test subjects of the MICCAI Multi-Modality Whole Heart Segmentation (MM-WHS) Challenge. The average dice values of whole heart segmentation are 90.39% (CT images) and 89.50% (MRI images), which are both highly comparable to the state-of-the-art.
Impact of Die Radius in a Streamlined Die during Wire Drawing
Authors: Hwang Joong-Ki
Published: April 2021

The effects of die radius in a streamlined die on design factors, such as the distribution of strain, stress, temperature, damage, and drawing force of a wire, were investigated during wire drawing for a better understanding of streamlined die and improvement in drawing quality of the wire. A numerical simulation was performed with the die radius of the streamlined die. The behavior of the design factors of the drawn wire fabricated by the streamlined die was different from that of the conventional die and was highly dependent on the die radius. The different behaviors of the design factors with the die radius can be explained by the frictional work and redundant work of the wire with die angle. The temperature rise and drawing force were high at a greater die radius because of the great frictional stress and heating effect stemming from the high contact length of the wire and die. Meanwhile, the higher redundant work at the surface area with decreasing die radius led to higher strain inhomogeneity, effective stress, damage value, temperature rise, and drawing force due to the abrupt change in the metal flow of the wire stemming from the high die angle. After the optimization of several design factors with die radius, it was concluded that the optimum IDR values ranged from 0.14 to 0.18, indicating that a streamlined die with a radius of 70 to 90 mm was the most suitable in the present process condition. In particular, the damage value of the wire was reduced in this range of die radii compared to the conventional die.
Mean Square Consensus of Nonlinear Multi-Agent Systems under Markovian Impulsive Attacks
Authors: Luo Huan , Wang Yinhe , Zhang Xuexi , Gao Peitao , Wen Haoxiang
Published: April 2021

This paper focuses primarily on the mean square consensus problem of a class of nonlinear multi-agent systems suffering from stochastic impulsive deception attacks. The attacks here are modeled by completely stochastic destabilizing impulses, where their gains and instants satisfy all distributions and the Markovian process. Compared with existing methods, which assume that only gains are stochastic, it is difficult to deal with systems with different types of random variables. Thus, estimating the influence of these different types on the consensus problem is a key point of this paper. Based on the properties of stochastic processes, some sufficient conditions to solve the consensus problem are derived and some special cases are considered. Finally, a numerical example is given to illustrate the main results. Our results show that the consensus can be obtained if impulsive attacks do not occur too frequently, and it can promote system stability if the gains are below the defined threshold.
An Experimental Study on the Flexural Behavior of Precast Concrete Modular Beam Systems Using Inserted Steel Plates
Authors: Ro Kyong-Min , Kim Min-Sook , Cho Chang-Geun , Lee Young-Hak
Published: April 2021

Recently, interest in using precast concrete (PC) modules has increased due to their better seismic performance than steel modules. However, they must be joined by additional elements to ensure structural integration between the modules. The essential aim of the precast concrete module is to ensure structural performance with appropriate connection methods. However, the technical problem of connecting PC modules still needs to be improved. This study proposed a PC modular beam system for improved structural and splicing performance, and simple construction. This modular system consisted of modules with steel plates inserted to improve integrity of modules, ease of construction, and low cost. The structural performance of the proposed PC modular beam system was evaluated by flexural test on one reinforced concrete (RC) beam specimen consisting of a monolithic beam, and two PC specimens with the proposed modular system. The results demonstrated that the proposed PC modular beam system achieved approximately 80% of the structural performance compared to the monolithic specimen, with approximately 1.3-fold greater ductility.
Poland’s Proposal for a Safe Solution of Waste Treatment during the COVID-19 Pandemic and Circular Economy Connection
Authors: Pikoń Krzysztof , Poranek Nikolina , Czajkowski Adrian , Łaźniewska-Piekarczyk Beata
Published: April 2021

The purpose of the study presented in this text is to show the influence of COVID-19 on waste management systems and circular economy stream, and their impact on circular economy, particularly the economic impact of the pandemic on the waste management sector, impact on circular economy objectives’ implementation as well as additional challenges like the need for hygienization of waste streams during different implementation efforts, such as changes in the municipal solid waste market and different waste processes of their disposal. Additionally, some methods—such as thermal treatment—which seemed to be not fully aligned with the circular economy approach have advantages not taken into account before. Incineration of higher volume of waste affects the waste structure and will change some of the circular economy objectives. The analysis was carried out on the example of the Polish market.
Measurements of the Magnetic Field Variations Related with the Size of V-Shaped Notches in Steel Pipes
Authors: Villegas-Saucillo J. Jesús , Díaz-Carmona José Javier , Escarola-Rosas Marco A. , Vázquez-Leal Héctor , Martínez-Castillo Jaime , Herrera-May Agustín L.
Published: April 2021

Gas and oil pipeline networks require periodic inspections to detect cracks or notches that can cause industrial accidents and environmental contamination. For these inspections, the metal magnetic memory (MMM) method could be used as a non-destructive testing (NDT) technique, which does not need expensive equipment and high-skilled operators. However, more investigations are required to quantify the size and shape of defects in ferromagnetic pipes using the MMM signals. We present experimental measurements of MMM signals around five small V-shaped notches of an ASTM-A36 steel pipe using a three-axis magnetoresistive sensor. The V-shaped notches have different values of depth (500 µm, 1000 µm, 1500 µm, 2000 µm and 2500 µm) and width (1000 µm, 1500 µm, 2000 µm, 3000 µm and 3500 µm). We measured the variations of tangential and normal MMM signals around these defects and their relationships with the size of each defect. The first V-notch defect (500 μm depth and 1000 μm width) registers variations of the tangential and normal MMM signals of 14.32 μT ± 1.62 μT and 27.95 μT ± 1.14 μT, respectively. On the other hand, the fifth V-notch defect (2500 μm depth and 3500 μm width) has variations of the tangential and normal MMM signals of 68.75 μT ± 1.10 μT and 71.37 μT ± 0.72 μT, respectively. The MMM method could be used for real-time monitoring of V-shaped notches in steel pipes. This method does not require special treatment of steel pipes.
Composition of Perinephric Fat and Fuhrman Grade in Clear Cell Renal Cell Carcinoma: The Role of Peritumoral Collateral Vessels
Authors: Greco Federico , Quarta Luigi Giuseppe , Bernetti Caterina , Grasso Rosario Francesco , van Berge Henegouwen Mark Ivo , Beomonte Zobel Bruno , Mallio Carlo Augusto
Published: April 2021

Background: The aim of this study was to investigate whether the presence of peritumoral collateral vessels could be indicative of a high Fuhrman grade (e.g., III and IV) in clear cell renal cell carcinoma (ccRCC). Methods: Between November 2019 and February 2020, a total of 267 ccRCC patients with histology-proven diagnoses were retrospectively analyzed and screened. Imaging analysis was performed on computed tomography (CT) images to assess the presence of peritumoral collateral vessels and understand the potential association with high Fuhrman grades. These vessels are defined as dilated and macroscopically visible peritumoral renal capsular veins. Results: A total of 190 ccRCC patients were included in the study, considering the exclusion criteria. In patients with peritumoral collateral vessels, there was a statistically significant greater presence of ccRCC with a high Fuhrman grade both among the total cohort of patients regardless gender (n = 190) (p < 0.001) as well as among ccRCC male patients only (n = 127) (p < 0.005). Conclusion: Here, we show a novel association between peritumoral collateral vessels and ccRCC with high Fuhrman grades in male patients. The presence of peritumoral collateral vessels in perinephric adipose tissue can be indicative of more aggressive ccRCC.
Spatial Modelling in Environmental Analysis and Civil Engineering
Authors: Janowski Artur , Szulwic Jakub , Tysiąc Paweł
Published: April 2021

Nowadays, practicing research on the principles of sustainable development is very important [...]
In Vitro and In Vivo Assessment of a New Workflow for the Acquisition of Mandibular Kinematics Based on Portable Tracking System with Passive Optical Reflective Markers
Authors: Farronato Marco , Tartaglia Gianluca M. , Maspero Cinzia , Gallo Luigi M. , Colombo Vera
Published: April 2021

Clinical use of portable optical tracking system in dentistry could improve the analysis of mandibular movements for diagnostic and therapeutic purposes. A new workflow for the acquisition of mandibular kinematics was developed. Reproducibility of measurements was tested in vitro and intra- and inter-rater repeatability were assessed in vivo in healthy volunteers. Prescribed repeated movements (n = 10) in three perpendicular directions of the tracking-device coordinate system were performed. Measurement error and coefficient of variation (CV) among repetitions were determined. Mandibular kinematics of maximum opening, left and right laterality, protrusion and retrusion of five healthy subjects were recorded in separate sessions by three different operators. Obtained records were blindly examined by three observers. Intraclass correlation coefficient (ICC) was calculated to estimate inter-rater and intra-rater reliability. Maximum in vitro measurement error was 0.54 mm and CV = 0.02. Overall, excellent intra-rater reliability (ICC > 0.90) for each variable, general excellent intra-rater reliability (ICC = 1.00) for all variables, and good reliability (ICC > 0.75) for inter-rater tests were obtained. A lower score was obtained for retrusion with “moderate reliability” (ICC = 0.557) in the inter-rater tests. Excellent repeatability and reliability in optical tracking of primary movements were observed using the tested portable tracking device and the developed workflow.
Nanobodies for Medical Imaging: About Ready for Prime Time?
Authors: Berland Léa , Kim Lauren , Abousaway Omar , Mines Andrea , Mishra Shruti , Clark Louise , Hofman Paul , Rashidian Mohammad
Published: April 2021

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into the cellular and molecular mechanisms underlying these variable responses will bring us closer to developing more effective therapeutics. To assess these mechanisms, non-invasive imaging techniques provide valuable whole-body information with precise targeting. An example of such is immuno-PET (Positron Emission Tomography), which employs radiolabeled antibodies to detect specific molecules of interest. Nanobodies, as the smallest derived antibody fragments, boast ideal characteristics for this purpose and have thus been used extensively in preclinical models and, more recently, in clinical early-stage studies as well. Their merit stems from their high affinity and specificity towards a target, among other factors. Furthermore, their small size (~14 kDa) allows them to easily disperse through the bloodstream and reach tissues in a reliable and uniform manner. In this review, we will discuss the powerful imaging potential of nanobodies, primarily through the lens of imaging malignant tumors but also touching upon their capability to image a broader variety of nonmalignant diseases.
Natural Products That Changed Society
Authors: Christensen Søren Brøgger
Published: April 2021

Until the end of the 19th century all drugs were natural products or minerals. During the 19th century chemists succeeded in isolating pure natural products such as quinine, morphine, codeine and other compounds with beneficial effects. Pure compounds enabled accurate dosing to achieve serum levels within the pharmacological window and reproducible clinical effects. During the 20th and the 21st century synthetic compounds became the major source of drugs. In spite of the impressive results achieved within the art of synthetic chemistry, natural products or modified natural products still constitute almost half of drugs used for treatment of cancer and diseases like malaria, onchocerciasis and lymphatic filariasis caused by parasites. A turning point in the fight against the devastating burden of malaria was obtained in the 17th century by the discovery that bark from trees belonging to the genus Cinchona could be used for treatment with varying success. However isolation and use of the active principle, quinine, in 1820, afforded a breakthrough in the treatment. In the 20th century the synthetic drug chloroquine severely reduced the burden of malaria. However, resistance made this drug obsolete. Subsequently artemisinin isolated from traditional Chinese medicine turned out to be an efficient antimalarial drug overcoming the problem of chloroquine resistance for a while. The use of synthetic analogues such as chloroquine or semisynthetic drugs such as artemether or artesunate further improved the possibilities for healing malaria. Onchocerciasis (river blindness) made life in large parts of Africa and South America miserable. The discovery of the healing effects of the macrocyclic lactone ivermectin enabled control and partly elimination of the disease by annual mass distribution of the drug. Also in the case of ivermectin improved semisynthetic derivatives have found their way into the clinic. Ivermectin also is an efficient drug for treatment of lymphatic filariasis. The serendipitous discovery of the ability of the spindle toxins to control the growth of fast proliferating cancer cells armed physicians with a new efficient tool for treatment of some cancer diseases. These possibilities have been elaborated through preparation of semisynthetic analogues. Today vincristine and vinblastine and semisynthetic analogues are powerful weapons against cancer diseases.
Lithium and Atypical Antipsychotics: The Possible WNT/β Pathway Target in Glaucoma
Authors: Vallée Alexandre , Vallée Jean-Noël , Lecarpentier Yves
Published: April 2021

Glaucoma is a progressive neurodegenerative disease that represents the major cause of irreversible blindness. Recent findings have shown which oxidative stress, inflammation, and glutamatergic pathway have main roles in the causes of glaucoma. Lithium is the major commonly used drug for the therapy of chronic mental illness. Lithium therapeutic mechanisms remain complex, including several pathways and gene expression, such as neurotransmitter and receptors, circadian modulation, ion transport, and signal transduction processes. Recent studies have shown that the benefits of lithium extend beyond just the therapy of mood. Neuroprotection against excitotoxicity or brain damages are other actions of lithium. Moreover, recent findings have investigated the role of lithium in glaucoma. The combination of lithium and atypical antipsychotics (AAPs) has been the main common choice for the treatment of bipolar disorder. Due to the possible side effects gradually introduced in therapy. Currently, no studies have focused on the possible actions of AAPs in glaucoma. Recent studies have shown a down regulation of the WNT/β-catenin pathway in glaucoma, associated with the overactivation of the GSK-3β signaling. The WNT/β-catenin pathway is mainly associated with oxidative stress, inflammation and glutamatergic pathway. Lithium is correlated with upregulation the WNT/β-catenin pathway and downregulation of the GSK-3β activity. Thus, this review focuses on the possible actions of lithium and AAPs, as possible therapeutic strategies, on glaucoma and some of the presumed mechanisms by which these drugs provide their possible benefit properties through the WNT/β-catenin pathway.
Reproducible In Vitro Tissue Culture Model to Study Basic Mechanisms of Calcific Aortic Valve Disease: Comparative Analysis to Valvular Interstitials Cells
Authors: Weber Andreas , Pfaff Melissa , Schöttler Friederike , Schmidt Vera , Lichtenberg Artur , Akhyari Payam
Published: April 2021

The hallmarks of calcific aortic valve disease (CAVD), an active and regulated process involving the creation of calcium nodules, lipoprotein accumulation, and chronic inflammation, are the significant changes that occur in the composition, organization, and mechanical properties of the extracellular matrix (ECM) of the aortic valve (AV). Most research regarding CAVD is based on experiments using two-dimensional (2D) cell culture or artificially created three-dimensional (3D) environments of valvular interstitial cells (VICs). Because the valvular ECM has a powerful influence in regulating pathological events, we developed an in vitro AV tissue culture model, which is more closely able to mimic natural conditions to study cellular responses underlying CAVD. AV leaflets, isolated from the hearts of 6–8-month-old sheep, were fixed with needles on silicon rubber rings to achieve passive tension and treated in vitro under pro-degenerative and pro-calcifying conditions. The degeneration of AV leaflets progressed over time, commencing with the first visible calcified domains after 14 d and winding up with the distinct formation of calcium nodules, heightened stiffness, and clear disruption of the ECM after 56 d. Both the expression of pro-degenerative genes and the myofibroblastic differentiation of VICs were altered in AV leaflets compared to that in VIC cultures. In this study, we have established an easily applicable, reproducible, and cost-effective in vitro AV tissue culture model to study pathological mechanisms underlying CAVD. The valvular ECM and realistic VIC–VEC interactions mimic natural conditions more closely than VIC cultures or 3D environments. The application of various culture conditions enables the examination of different pathological mechanisms underlying CAVD and could lead to a better understanding of the molecular mechanisms that lead to VIC degeneration and AS. Our model provides a valuable tool to study the complex pathobiology of CAVD and can be used to identify potential therapeutic targets for slowing disease progression.
Parathyroid Disease in Pregnancy and Lactation: A Narrative Review of the Literature
Authors: Tsourdi Elena , Anastasilakis Athanasios D.
Published: April 2021

Pregnancy and lactation are characterized by sophisticated adaptations of calcium homeostasis, aiming to meet fetal, neonatal, and maternal calcium requirements. Pregnancy is primarily characterized by an enhancement of intestinal calcium absorption, whereas during lactation additional calcium is obtained through resorption from the maternal skeleton, a process which leads to bone loss but is reversible following weaning. These maternal adaptations during pregnancy and lactation may influence or confound the presentation, diagnosis, and management of parathyroid disorders such as primary hyperparathyroidism or hypoparathyroidism. Parathyroid diseases are uncommon in these settings but can be severe when they occur and may affect both maternal and fetal health. This review aims to delineate the changes in calcium physiology that occur with pregnancy and lactation, describe the disorders of calcium and parathyroid physiology that can occur, and outline treatment strategies for these diseases in the above settings.
Optimized Synthesis of New N-Mustards Based on 2-Mercaptobenzoxazole Derivatives with Antitumor Activity
Authors: Cheptea Corina , Sunel Valeriu , Morosanu Ana Cezarina , Dimitriu Dan Gheorghe , Dulcescu-Oprea Mihaela Maria , Angheluta Mihai-Daniel , Miron Mihaela , Nechifor Cristina Delia , Dorohoi Dana Ortansa , Malancus Razvan Nicolae
Published: April 2021

New di-(β-chloroethyl)-amides of some acids derived from 2-mercaptobenzoxazole were prepared by reaction of the corresponding pivalic mixed anhydrides with di-(β-chloroethyl)-amine. A study regarding the optimization of the chemical reactions was made for the case of di-(β-chloroethyl)-amines. The quantum chemical analysis by Spartan’14 was made in order to establish the most stable configuration of the ground electronic states for the obtained chemical structures and some physico-chemical parameters of N-mustards reported in this paper. Mercaptobenzoxazoles substituted in the side chain with the cytotoxic group show antitumor activity and they inhibit Ehrlich Ascites in an appreciable proportion compared to the drug I.O.B.-82, as our studies evidenced.
Diagnostic Utility of the Immunohistochemical Expression of Serine and Arginine Rich Splicing Factor 1 (SRSF1) in the Differential Diagnosis of Adult Gliomas
Authors: Broggi Giuseppe , Salvatorelli Lucia , Barbagallo Davide , Certo Francesco , Altieri Roberto , Tirrò Elena , Massimino Michele , Vigneri Paolo , Guadagno Elia , Maugeri Grazia , D’Agata Velia , Musumeci Giuseppe , Ragusa Marco , Barbagallo Giuseppe Maria Vincenzo , Russo Daniela , Caltabiano Rosario
Published: April 2021

Background: The aim of this study was to investigate the immunohistochemical expression and distribution of serine and arginine rich splicing factor 1 (SRSF1) in a series of 102 cases of both diffuse and circumscribed adult gliomas to establish the potential diagnostic role of this protein in the differential diagnosis of brain tumors. Methods: This retrospective immunohistochemical study included 42 glioblastoma cases, 21 oligodendrogliomas, 15 ependymomas, 15 pilocytic astrocytomas, 5 sub-ependymal giant cell astrocytoma and 4 pleomorphic xanthoastrocytomas. Results: Most glioblastoma (81%), oligodendroglioma (71%), sub-ependymal giant cell astrocytoma (80%) and pleomorphic xanthoastrocytoma (75%) cases showed strong SRSF1 immunoexpression, while no detectable staining was found in the majority of ependymomas (87% of cases) and pilocytic astrocytomas (67% of cases). Conclusions: The immunohistochemical expression of SRSF1 may be a promising diagnostic marker of astrocytomas and oligodendrogliomas and its increased expression might allow for excluding entities that often enter into differential diagnosis, such as ependymomas and pilocytic astrocytomas.
Associations between Genetically Predicted Circulating Protein Concentrations and Endometrial Cancer Risk
Authors: Zhu Jingjing , O’Mara Tracy A. , Liu Duo , Setiawan Veronica Wendy , Glubb Dylan , Spurdle Amanda B. , Fasching Peter A. , Lambrechts Diether , Buchanan Daniel , Kho Pik Fang , Cook Linda S. , Friedenreich Christine , Lacey James V. , Chen Chu , Wentzensen Nicolas , De Vivo Immaculata , Sun Yan , Long Jirong , Du Mengmeng , Shu Xiao-Ou , Zheng Wei , Wu Lang , Yu Herbert
Published: April 2021

Endometrial cancer (EC) is the leading female reproductive tract malignancy in developed countries. Currently, genome-wide association studies (GWAS) have identified 17 risk loci for EC. To identify novel EC-associated proteins, we used previously reported protein quantitative trait loci for 1434 plasma proteins as instruments to evaluate associations between genetically predicted circulating protein concentrations and EC risk. We studied 12,906 cases and 108,979 controls of European descent included in the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. We observed associations between genetically predicted concentrations of nine proteins and EC risk at a false discovery rate of <0.05 (p-values range from 1.14 × 10−10 to 3.04 × 10−4). Except for vascular cell adhesion protein 1, all other identified proteins were independent from known EC risk variants identified in EC GWAS. The respective odds ratios (95% confidence intervals) per one standard deviation increase in genetically predicted circulating protein concentrations were 1.21 (1.13, 1.30) for DNA repair protein RAD51 homolog 4, 1.27 (1.14, 1.42) for desmoglein-2, 1.14 (1.07, 1.22) for MHC class I polypeptide-related sequence B, 1.05 (1.02, 1.08) for histo-blood group ABO system transferase, 0.77 (0.68, 0.89) for intestinal-type alkaline phosphatase, 0.82 (0.74, 0.91) for carbohydrate sulfotransferase 15, 1.07 (1.03, 1.11) for D-glucuronyl C5-epimerase, and 1.07 (1.03, 1.10) for CD209 antigen. In conclusion, we identified nine potential EC-associated proteins. If validated by additional studies, our findings may contribute to understanding the pathogenesis of endometrial tumor development and identifying women at high risk of EC along with other EC risk factors and biomarkers.
PARP1-Inhibition Sensitizes Cervical Cancer Cell Lines for Chemoradiation and Thermoradiation
Authors: IJff Marloes , van Bochove Gregor G. W. , Whitton Denise , Winiarczyk Roy , Honhoff Celina , Rodermond Hans , Crezee Johannes , Stalpers Lukas J. A. , Franken Nicolaas A. P. , Oei Arlene L.
Published: April 2021

Radiotherapy plus cisplatin (chemoradiation) is standard treatment for women with locoregionally advanced cervical cancer. Both radiotherapy and cisplatin induce DNA single and double-strand breaks (SSBs and DSBs). These double-strand breaks can be repaired via two major DNA repair pathways: Classical Non-Homologous End-Joining (cNHEJ) and Homologous Recombination. Besides inducing DNA breaks, cisplatin also disrupts the cNHEJ pathway. Patients contra-indicated for cisplatin are treated with radiotherapy plus hyperthermia (thermoradiation). Hyperthermia inhibits the HR pathway. The aim of our study is to enhance chemoradiation or thermoradiation by adding PARP1-inhibition, which disrupts both the SSB repair and the Alternative NHEJ DSB repair pathway. This was studied in cervical cancer cell lines (SiHa, HeLa, C33A and CaSki) treated with hyperthermia (42 °C) ± ionizing radiation (2–6 Gy) ± cisplatin (0.3–0.5 µM) ± PARP1-inhibitor (olaparib, 4.0–5.0 µM). Clonogenic assays were performed to measure cell reproductive death. DSBs were analyzed by γ-H2AX staining and cell death by live cell imaging. Both chemoradiation and thermoradiation resulted in lower survival fractions and increased unrepaired DSBs when combined with a PARP1-inhibitor. A quadruple modality, including ionizing radiation, hyperthermia, cisplatin and PARP1-i, was not more effective than either triple modality. However, both chemoradiation and thermoradiation benefit significantly from additional treatment with PARP1-i.
Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation
Authors: Carvalho Ângela , Ferreira Gabriela , Seixas Duarte , Guimarães-Teixeira Catarina , Henrique Rui , Monteiro Fernando J. , Jerónimo Carmen
Published: April 2021

Despite the intensive efforts dedicated to cancer diagnosis and treatment, lung cancer (LCa) remains the leading cause of cancer-related mortality, worldwide. The poor survival rate among lung cancer patients commonly results from diagnosis at late-stage, limitations in characterizing tumor heterogeneity and the lack of non-invasive tools for detection of residual disease and early recurrence. Henceforth, research on liquid biopsies has been increasingly devoted to overcoming these major limitations and improving management of LCa patients. Liquid biopsy is an emerging field that has evolved significantly in recent years due its minimally invasive nature and potential to assess various disease biomarkers. Several strategies for characterization of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been developed. With the aim of standardizing diagnostic and follow-up practices, microfluidic devices have been introduced to improve biomarkers isolation efficiency and specificity. Nonetheless, implementation of lab-on-a-chip platforms in clinical practice may face some challenges, considering its recent application to liquid biopsies. In this review, recent advances and strategies for the use of liquid biopsies in LCa management are discussed, focusing on high-throughput microfluidic devices applied for CTCs and ctDNA isolation and detection, current clinical validation studies and potential clinical utility.
Determination of Trace Levels of Nickel(II) by Adsorptive Stripping Voltammetry Using a Disposable and Low-Cost Carbon Screen-Printed Electrode
Authors: Padilla Víctor , Serrano Núria , Díaz-Cruz José Manuel
Published: April 2021

A commercial and disposable screen-printed carbon electrode (SPCE) has been proposed for a fast, simple and low-cost determination of Ni(II) at very low concentration levels by differential pulse adsorptive stripping voltammetry (DPAdSV) in the presence of dimethylglyoxime (DMG) as complexing agent. In contrast with previously proposed methods, the Ni(II)-DMG complex adsorbs directly on the screen-printed carbon surface, with no need of mercury, bismuth or antimony coatings. Well-defined stripping peaks and a linear dependence of the peak area on the concentration of Ni(II) was achieved in the range from 1.7 to 150 µg L−1, with a limit of detection of 0.5 µg L−1 using a deposition time of 120 s. An excellent reproducibility and repeatability with 0.3% (n = 3) and 1.5% (n = 15) relative standard deviation, respectively, were obtained. In addition, the suitability of the SPCE as sensing unit has been successfully assessed in a wastewater certificated reference material with remarkable trueness and very good reproducibility.
Low-Cost Inkjet-Printed Temperature Sensors on Paper Substrate for the Integration into Natural Fiber-Reinforced Lightweight Components
Authors: Zikulnig Johanna , Khalifa Mohammed , Rauter Lukas , Lammer Herfried , Kosel Jürgen
Published: April 2021

In a unique approach to develop a “green” solution for in-situ monitoring, low-cost inkjet-printed temperature sensors on paper substrate were fully integrated into natural fiber-reinforced lightweight components for which structural health monitoring is becoming increasingly important. The results showed that the sensors remained functional after the vacuum infusion process; furthermore, the integration of the sensors improved the mechanical integrity and stability of the lightweight parts, as demonstrated by tensile testing. To verify the qualification of the printed sensors for the target application, the samples were exposed to varying temperature and humidity conditions inside of a climate chamber. The sensors showed linear temperature dependence in the temperature range of interest (−20 to 60 °C) with a TCR ranging from 1.576 × 10−3 K−1 to 1.713 × 10−3 K−1. Furthermore, the results from the tests in humid environments indicated that the used paper-based sensors could be made almost insensitive to changes in ambient humidity by embedding them into fiber-reinforced lightweight materials. This study demonstrates the feasibility of fully integrating paper-based printed sensors into lightweight components, which paves the way towards integration of other highly relevant sensing devices, such as strain and humidity sensors, for structural health monitoring of smart, sustainable, and environmentally compatible lightweight composite materials.
Comprehensive Analysis of Prognostic and Genetic Signatures for General Transcription Factor III (GTF3) in Clinical Colorectal Cancer Patients Using Bioinformatics Approaches
Authors: Anuraga Gangga , Tang Wan-Chun , Phan Nam , Ta Hoang , Liu Yen-Hsi , Wu Yung-Fu , Lee Kuen-Haur , Wang Chih-Yang
Published: April 2021

Colorectal cancer (CRC) has the fourth-highest incidence of all cancer types, and its incidence has steadily increased in the last decade. The general transcription factor III (GTF3) family, comprising GTF3A, GTF3B, GTF3C1, and GTFC2, were stated to be linked with the expansion of different types of cancers; however, their messenger (m)RNA expressions and prognostic values in colorectal cancer need to be further investigated. To study the transcriptomic expression levels of GTF3 gene members in colorectal cancer in both cancerous tissues and cell lines, we first performed high-throughput screening using the Oncomine, GEPIA, and CCLE databases. We then applied the Prognoscan database to query correlations of their mRNA expressions with the disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) status of the colorectal cancer patient. Furthermore, proteomics expressions of GTF3 family members in clinical colorectal cancer specimens were also examined using the Human Protein Atlas. Finally, genomic alterations of GTF3 family gene expressions in colorectal cancer and their signal transduction pathways were studied using cBioPortal, ClueGO, CluePedia, and MetaCore platform. Our findings revealed that GTF3 family members’ expressions were significantly correlated with the cell cycle, oxidative stress, WNT/β-catenin signaling, Rho GTPases, and G-protein-coupled receptors (GPCRs). Clinically, high GTF3A and GTF3B expressions were significantly correlated with poor prognoses in colorectal cancer patients. Collectively, our study declares that GTF3A was overexpressed in cancer tissues and cell lines, particularly colorectal cancer, and it could possibly step in as a potential prognostic biomarker.
Application of the Exp-Function and Generalized Kudryashov Methods for Obtaining New Exact Solutions of Certain Nonlinear Conformable Time Partial Integro-Differential Equations
Authors: Kaewta Supaporn , Sirisubtawee Sekson , Sungnul Surattana
Published: April 2021

The key objective of this paper is to construct exact traveling wave solutions of the conformable time second integro-differential Kadomtsev–Petviashvili (KP) hierarchy equation using the Exp-function method and the (2 + 1)-dimensional conformable time partial integro-differential Jaulent–Miodek (JM) evolution equation utilizing the generalized Kudryashov method. These two problems involve the conformable partial derivative with respect to time. Initially, the conformable time partial integro-differential equations can be converted into nonlinear ordinary differential equations via a fractional complex transformation. The resulting equations are then analytically solved via the corresponding methods. As a result, the explicit exact solutions for these two equations can be expressed in terms of exponential functions. Setting some specific parameter values and varying values of the fractional order in the equations, their 3D, 2D, and contour solutions are graphically shown and physically characterized as, for instance, a bell-shaped solitary wave solution, a kink-type solution, and a singular multiple-soliton solution. To the best of the authors’ knowledge, the results of the equations obtained using the proposed methods are novel and reported here for the first time. The methods are simple, very powerful, and reliable for solving other nonlinear conformable time partial integro-differential equations arising in many applications.
Potential Water Recovery from Biomass Boilers: Parametric Analysis
Authors: Dondi Daniele , López Robles Cristina D. , Magrini Anna , Cartesegna Marco
Published: April 2021

A fundamental component of the losses of convection boilers is localized in the warm fumes that are expelled. In the warm fumes, not only energy is lost, but water is also formed from the combustion reaction in the form of steam which is expelled through the exhaust. Modern fuel boilers recover both the heat from the fumes and the latent heat of condensation from water vapor. Depending on the chemical composition of the fuel, different amounts of steam are produced together with heat and different combustion conditions, such as air in excess. In this article, a computational tool was established to simulate a combustion system mainly (but not only) focusing on the prediction of the amount of water produced. In fact, while steam in fossil fuel boilers is commonly condensed, this is not so when the fuel is a biomass. Furthermore, biomasses could contain moisture in different amounts, thus affecting the production of water and the heat of combustion. The study shows that a ten-fold amount of water is formed from biomass combustion with respect to fossil fuels (when the same energy output is produced). As a result, the recovery of water is amenable in biomasses, both from the energetic point of view and for liquid water production. In fact, the water recovered from the fumes might be also reused in other processes such as the cleaning of fumes or agriculture (after treatment).
Towards Developing a Framework to Analyze the Qualities of the University Websites
Authors: Rashida Maliha , Islam Kawsarul , Kayes A. S. M. , Hammoudeh Mohammad , Arefin Mohammad Shamsul , Habib Mohammad Ashfak
Published: April 2021

The website of a university is considered to be a virtual gateway to provide primary resources to its stakeholders. It can play an indispensable role in disseminating information about a university to a variety of audience at a time. Thus, the quality of an academic website requires special attention to fulfil the users’ need. This paper presents a multi-method approach of quality assessment of the academic websites, in the context of universities of Bangladesh. We developed an automated web-based tool that can evaluate any academic website based on three criteria, which are as follows: content of information, loading time and overall performance. Content of information contains many sub criteria, such as university vision and mission, faculty information, notice board and so on. This tool can also perform comparative analysis among several academic websites and generate a ranked list of these. To the best of our knowledge, this is the very first initiative to develop an automated tool for accessing academic website quality in context of Bangladesh. Beside this, we have conducted a questionnaire-based statistical evaluation among several universities to obtain the respective users’ feedback about their academic websites. Then, a ranked list is generated based on the survey result that is almost similar to the ranked list got from the University ranking systems. This validates the effectiveness of our developed tool in accessing academic website.