bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA and cDNA-Microarray as Potential Targets against Abiotic Stress Response in Plants: Advances and Prospects
Authors: Pervaiz Tariq , Amjid Muhammad Waqas , El-kereamy Ashraf , Niu Shi-Hui , Wu Harry X.
Published: December 2021

Abiotic stresses, such as temperature (heat and cold), salinity, and drought negatively affect plant productivity; hence, the molecular responses of abiotic stresses need to be investigated. Numerous molecular and genetic engineering studies have made substantial contributions and revealed that abiotic stresses are the key factors associated with production losses in plants. In response to abiotic stresses, altered expression patterns of miRNAs have been reported, and, as a result, cDNA-microarray and microRNA (miRNA) have been used to identify genes and their expression patterns against environmental adversities in plants. MicroRNA plays a significant role in environmental stresses, plant growth and development, and regulation of various biological and metabolic activities. MicroRNAs have been studied for over a decade to identify those susceptible to environmental stimuli, characterize expression patterns, and recognize their involvement in stress responses and tolerance. Recent findings have been reported that plants assign miRNAs as critical post-transcriptional regulators of gene expression in a sequence-specific manner to adapt to multiple abiotic stresses during their growth and developmental cycle. In this study, we reviewed the current status and described the application of cDNA-microarray and miRNA to understand the abiotic stress responses and different approaches used in plants to survive against different stresses. Despite the accessibility to suitable miRNAs, there is a lack of simple ways to identify miRNA and the application of cDNA-microarray. The elucidation of miRNA responses to abiotic stresses may lead to developing technologies for the early detection of plant environmental stressors. The miRNAs and cDNA-microarrays are powerful tools to enhance abiotic stress tolerance in plants through multiple advanced sequencing and bioinformatics techniques, including miRNA-regulated network, miRNA target prediction, miRNA identification, expression profile, features (disease or stress, biomarkers) association, tools based on machine learning algorithms, NGS, and tools specific for plants. Such technologies were established to identify miRNA and their target gene network prediction, emphasizing current achievements, impediments, and future perspectives. Furthermore, there is also a need to identify and classify new functional genes that may play a role in stress resistance, since many plant genes constitute an unexplained fraction.
Opportunities to Harness High-Throughput and Novel Sensing Phenotypes to Improve Feed Efficiency in Dairy Cattle
Authors: Siberski-Cooper Cori J. , Koltes James E.
Published: December 2021

Feed for dairy cattle has a major impact on profitability and the environmental impact of farms. Sustainable dairy production relies on continued improvement in feed efficiency as a way to reduce costs and nutrient loss from feed. Advances in breeding, feeding and management have led to the dilution of maintenance energy and thus more efficient dairy cattle. Still, many additional opportunities are available to improve individual animal feed efficiency. Sensing technologies such as wearable sensors, image-based and high-throughput phenotyping technologies (e.g., milk testing) are becoming more available on commercial farm. The application of these technologies as indicator traits for feed intake and efficiency related traits would be advantageous to provide additional information to predict and manage feed efficiency. This review focuses on precision livestock technologies and high-throughput phenotyping in use today as well as those that could be developed in the future as possible indicators of feed intake. Several technologies such as milk spectral data, activity, rumen measures, and image-based phenotypes have been associated with feed intake. Future applications will depend on the ability to repeatably measure and calibrate these data across locations, so that they can be integrated for use in predicting and managing feed intake and efficiency on farm.
Relationships between Skin Carotenoid Levels and Metabolic Syndrome
Authors: Takayanagi Yuji , Obana Akira , Muto Shigeki , Asaoka Ryo , Tanito Masaki , Ermakov Igor V. , Bernstein Paul S. , Gellermann Werner
Published: December 2021

Carotenoids have potential antioxidant and anti-inflammatory effects; their protective roles are of particular interest in the pathogenesis of metabolic syndrome (MetS). The reflection spectroscopy method has been recently developed to noninvasively measure skin carotenoid (SC) levels, which highly correlates with serum concentration of carotenoids. The relationship between SC levels and metabolic syndrome has been investigated. We aimed to identify the differences in patient characteristics and SC levels between participants with and without MetS in a large health examination population. In addition, the relationships between SC levels and various clinical parameters related to MetS were investigated. SC levels were measured using a reflection spectroscopy. A total of 1812 Japanese participants (859 male, 953 female; mean age ± standard deviation (SD), 57.8 ± 11.0 years) comprised the study population, i.e., participants with MetS (n = 151) and those without MetS (n = 1661). Multivariate logistic regression analysis was performed to identify variables associated with MetS. Compared to controls (377.3 ± 122.8), SC indices were significantly lower in patients with MetS (340.7 ± 112.5, p = 0.0004). Multivariate models also suggested that lower SC was significantly associated with MetS after adjustment for age, sex, smoking habit, and other potential risk factors for MetS. Furthermore, male gender (p < 0.0001), smoking habit (p < 0.0001) and worse lipid profiles (i.e., serum triglyceride (r = −0.1039, p < 0.0001), high-density lipoprotein (r = 0.1259, p < 0.0001), and usage of hypolipidemic agents (p = 0.0340)) were significantly associated with lower SC levels. The current study indicated that lower SC levels were significantly associated with MetS. This study highlights the antioxidant capacity of carotenoids in patients with MetS and the clinical utility of non-invasive and cost-effective SC measurement to detect participants who are at risk of developing MetS in a large population.
Space-Time Effect Prediction of Blasting Vibration Based on Intelligent Automatic Blasting Vibration Monitoring System
Authors: Chen Fan , He Gengsheng , Dong Shun , Zhao Shunjun , Shi Lin , Liu Xian , Zhang Baichuan , Qi Ning , Deng Shenggui , Zhang Jin
Published: December 2021

The vibration produced by blasting excavation in urban underground engineering has a significant influence on the surrounding environment, and the strength of vibration intensity involves many influencing factors. In order to predict the space-time effects of blasting vibration more accurately, an automatic intelligent monitoring system is constructed based on the rough set fuzzy neural network blasting vibration characteristic parameter prediction model and the network blasting vibrator (TC-6850). By setting up the regional monitoring network of monitoring points, the obtained monitoring data are analyzed. An artificial intelligence model is used to predict the influence of stratum condition, excavation hole, and high-rise building on blasting vibration velocity and frequency propagation. The results show that the artificial intelligence prediction model based on a rough set fuzzy neural network can accurately reflect the formation attenuation effect, hollow effect, and building amplification effect of blasting vibration by effectively fuzzing and standardizing the influencing factors. The propagation of blasting vibration in a soil–rock composite stratum is closely related to the surrounding rock conditions with a noticeable elastic modulus effect. The hollow effect is regional, which has a significant influence on the surrounding ground and buildings. Besides, the blasting vibration of the excavated area is stronger than that of the unexcavated area. The propagation of blasting vibration on high-rise buildings was complicated, of which the peak vibration velocity is maximum at the lower level of the building and decreased with the rise of the floor gradually. The whip sheath effect appears at the top floor, which is related to the blasting vibration frequency and the building’s natural vibration frequency.
Estimation Formula of Modal Frequency of High-Rise Buildings under Different Wind Speeds during Typhoons
Authors: Hu Jiaxing , Li Zhengnong , Zhao Zhefei
Published: December 2021

On 18 October 2016, the wind-induced effects of a high-rise building with square section was measured by the monitoring system in Haikou of China during Typhoon Sarika. The wind characteristics atop the building and the time-history responses of the translational and rotational accelerations on different floors were measured by the monitoring system; the first three modal parameters were identified according to the measured acceleration. The results show that the combinations of the cross spectral density function, phase spectrum, and coherence function can clearly judge the phase of the measured floors in the frequency resonance area as well as its modal frequencies at the first three orders. The modal frequencies at the first three orders decrease linearly with the growth of mean wind speed within the range of 0~20m/s. The estimation formula of the modal frequencies of high-rise buildings considering the influences of different wind speeds is put forward, which is expected to fill the gap in the existing specification for the quantitative analysis of the influences of wind-loads on the fundamental frequencies of high-rise buildings.
Future Prospective of Oral Microbiome Research
Authors: Nomura Yoshiaki , Okada Ayako , Hanada Nobuhiro
Published: December 2021

Oral microbiome has complex structure. It consisted of more than 700 species of bacteria. These bacteria contains pathogens for human health. In contrast, some beneficial bacteria were included. Perspective of oral microbiome is not still elucidated. In this paper, information regarding oral microbiome of health older adults and oral diseases are included. Additionally, concise review of oral microbiome are presented.
Economic Evaluation of the Urban Road Public Transport System Efficiency Based on Data Envelopment Analysis
Authors: Romero-Ania Alberto , De Vicente Oliva María Auxiliadora , Rivero Gutiérrez Lourdes
Published: December 2021

Air pollution resulting from massive urban development and increased use of private vehicles is a major environmental concern, with particular relevance in urban areas. Urban public road transport has a significant impact on shaping land use patterns, air pollution and welfare. It must therefore be efficient in terms of air pollution in order to contribute to sustainable metropolitan mobility and economic growth. This study proposes a novel and consistent data envelopment analysis, aiming to identify which urban public transport vehicle is the most efficient in terms of air pollution and therefore environmentally suitable for use in public road transport systems. The case of Madrid has been analyzed, as it is representative of other large cities, which have similar bus alternatives and the common objective of reducing air pollution. Madrid City Council data has been compiled by authors and assessed by a panel of twenty experts to determine the model criteria weights. The results show that the plug-in electric vehicle has the lowest pollutant emission values while delivering the highest performance. Useful recommendations are provided to support public policy decisions related to the complex relationships between urban land use, urban transport and air pollution in urban areas.
Investigation of THz Absorptive Signatures in Opioids
Authors: Zhang Weidong , Bykhovski Alexei , Brown Elliott R.
Published: December 2021

We investigate the possibility of sensing opioid drugs, such as fentanyl, by their THz electromagnetic signatures. The methods include both computer modeling and experiments. Molecular dynamics simulations predict that fentanyl should display THz resonances, with several of them occurring below 1.0 THz; the lowest one is at around 0.337 THz (337 GHz). Spectroscopy measurements were conducted on oxycodone, which was used as a surrogate for fentanyl. They display vibrational absorption resonances between ∼1.4 and 1.6 THz.
Digital Holographic Microscopy as Identifier of Ultrafine Particles Emitted during Fused Deposition Modelling
Authors: García-Espinosa Daniel Alberto , León-Rodríguez Miguel , Yañez-Contreras Pedro , Miguel-Andrés Israel , Padilla-Medina José Alfredo , Cruz-Bernal Alejandra , Ibarra-Torres Patricia
Published: December 2021

Additive manufacturing has acquired a global industrial panorama for being an alternative to redirect the industry towards sustainability. However, previous studies have indicated that fused deposition modelling (FDM) techniques are potential sources of particles that are harmful to health. For this reason, this work is focused on exploring the behaviour and distribution of FDM resultant nanoparticles from the most commonly used printable materials through alternative methods as digital holographic microscopy (DHM). In this paper, we present the feasibility of using DHM to determine the presence of nanoparticles in the FDM process. Experimental results validate this technology’s precision and provide extensive knowledge about the implications of the FDM on health. The measure of the thin films deposited in glass substrates was between a minimum of 9 nm to a maximum of 200 nm, in agreement with the previous studies.
Improving PM2.5 Concentration Forecast with the Identification of Temperature Inversion
Authors: Yin Peng-Yeng , Chang Ray-I , Day Rong-Fuh , Lin Yen-Cheng , Hu Ching-Yuan
Published: December 2021

The rapid development of industrialization and urbanization has had a substantial impact on the increasing air pollution in many populated cities around the globe. Intensive research has shown that ambient aerosols, especially the fine particulate matter PM2.5, are highly correlated with human respiratory diseases. It is critical to analyze, forecast, and mitigate PM2.5 concentrations. One of the typical meteorological phenomena seducing PM2.5 concentrations to accumulate is temperature inversion which forms a warm-air cap to blockade the surface pollutants from dissipating. This paper analyzes the meteorological patterns which coincide with temperature inversion and proposes two machine learning classifiers for temperature inversion classification. A separate multivariate regression model is trained for the class with or without manifesting temperature inversion phenomena, in order to improve PM2.5 forecasting performance. We chose Puli township as the studied site, which is a basin city easily trapping PM2.5 concentrations. The experimental results with the dataset spanning from 1 January 2016 to 31 December 2019 show that the proposed temperature inversion classifiers exhibit satisfactory performance in F1-Score, and the regression models trained from the classified datasets can significantly improve the PM2.5 concentration forecast as compared to the model using a single dataset without considering the temperature inversion factor.
Implementation of a Blockchain System Using Improved Elliptic Curve Cryptography Algorithm for the Performance Assessment of the Students in the E-Learning Platform
Authors: Alshahrani Mohammad Y.
Published: December 2021

Blockchain technology allows for the decentralized creation of a propagated record of digital events, in which third parties do not control information and associated transactions. This methodology was initially developed for value transmission. Still, it now has a broad array of utilization in various industries, including health, banking, the internet of things, and several others. With its numerous added benefits, a blockchain-based learning management system is a commonly utilized methodology at academic institutes, and more specifically during and after the COVID-19 period. It also presents several potentials for decentralized, interoperable record management in the academic system in education. Integrity, authenticity, and peer-executed smart contracts (SC) are some of the qualities of a blockchain that could introduce a new degree of safety, trustworthiness, and openness to e-learning. This research proposes a unique encryption technique for implementing a blockchain system in an e-learning (EL) environment to promote transparency in assessment procedures. Our methodology may automate evaluations and provide credentials. We built it to be analytical and content-neutral in order to demonstrate the advantages of a blockchain back-end to end-users, including student and faculty members particularly during this COVID-19 era. This article explains the employment of blockchain and SC in e-learning. To improve the trust in the assessment, we propose a novel improved elliptic curve cryptography algorithm (IECCA) for data encryption and decryption. The performance of the suggested method is examined by comparing it with various existing algorithms of encryption. The evaluation of the behaviour of the presented method demonstrates that the technique shall enhance trust in online educational systems, assessment processes, educational history, and credentials.
Analysis of Vertical Earth Pressure Acting on Box Culverts through Centrifuge Model Test
Authors: Chu Inyeop , Woo Sang-Kyun , Woo Sang Inn , Kim Joonyoung , Lee Kicheol
Published: December 2021

Due to the lack of surface space, most structures are heading underground. The box culvert is underground infrastructure and serves to protect the buried structure from the underground environments, but it has a different characteristic from other structures in that the inner space is empty. Therefore, in this study, the vertical earth pressure which is the most significant effective stress acting on a box culvert was measured by conducting a geotechnical centrifuge model test. A box culvert was installed following the embankment installation method, and the vertical earth pressure acting on it was measured considering the cover depth, gravitational acceleration, and loading and unloading conditions. The soil pressure measured was greater than the existing theoretical value under high cover depth and the unloading condition, which is considered as the variability of many soils or the residual stress acting under the loading condition. Finally, a goodness-of-fit test was conducted as a part of variability analysis. The measured earth pressure was found to be considerably larger than the existing theoretical value, and the variability was large as well. This means the existing theoretical equation is under-designed, which should be reflected in future designs.
Subspace Reduction for Stochastic Planar Elasticity
Authors: Hakula Harri , Laaksonen Mikael
Published: December 2021

Stochastic eigenvalue problems are nonlinear and multiparametric. They require their own solution methods and remain one of the challenge problems in computational mechanics. For the simplest possible reference problems, the key is to have a cluster of at the low end of the spectrum. If the inputs, domain or material, are perturbed, the cluster breaks and tracing of the eigenpairs become difficult due to possible crossing of the modes. In this paper we have shown that the eigenvalue crossing can occur within clusters not only by perturbations of the domain, but also of material parameters. What is new is that in this setting, the crossing can be controlled; that is, the effect of the perturbations can actually be predicted. Moreover, the basis of the subspace is shown to be a well-defined concept and can be used for instance in low-rank approximation of solutions of problems with static loading. In our industrial model problem, the reduction in solution times is significant.
Ambient BTEX Concentrations during the COVID-19 Lockdown in a Peri-Urban Environment (Orléans, France)
Authors: Cai Min , Ren Yangang , Gibilisco Rodrigo G. , Grosselin Benoit , McGillen Max R. , Xue Chaoyang , Mellouki Abdelwahid , Daële Véronique
Published: December 2021

During the period from 17 March to 10 May 2020, France saw dramatic shifts in domestic, industrial and transport activities as a national lockdown was introduced. So far, studies have generally focused on urban settings, by contrast, this work reports data for a peri-urban location. Air samples were collected and analyzed using a fully automated GC-MS-FID system in an air quality monitoring station situated in the suburbs of Orléans, France. Average concentrations of BTEX (benzene, toluene, ethylbenzene, and xylenes) before, during, and after lockdown, were 402 ± 143, 800 ± 378 and 851 ± 445 pptv, respectively. Diurnal variation in BTEX and correlations between each of its components were analyzed to determine its various sources. The toluene/benzene (T/B) and m,p-xylene/ethylbenzene (MP/E) ratios, photochemical ages were used to explore whether the BTEX were from local or more distant sources. Together with a host of complementary measurements including NOx, O3, black carbon, meteorological parameters, and anthropogenic activities, we were able to make some inferences on the sources of BTEX. The results suggest that although anomalous local anthropogenic activity can lead to significant changes in BTEX concentrations, pollution levels in Orléans are mostly dependent on meteorological conditions, specifically whether the winds are coming from the Paris region. It appears, based on these measurements, that the pollution in the Orléans area is very much tied to the nearby megacity of Paris, this may be true for other peri-urban sites with implications for city planning and pollution mitigation strategies.
Characterization of Macrophage and Cytokine Interactions with Biomaterials Used in Negative-Pressure Wound Therapy
Authors: Veerasubramanian Praveen Krishna , Joe Victor C. , Liu Wendy F. , Downing Timothy L.
Published: December 2021

Macrophages are innate immune cells that help wounds heal. Here, we study the potential immunomodulatory effects of negative-pressure wound therapy (NPWT) materials on the macrophage inflammatory response. We compared the effects of two materials, Granufoam™ (GF) and Veraflo Cleanse™ (VC), on macrophage function in vitro. We find that both materials cause reduced expression of inflammatory genes, such as TNF and IL1B, in human macrophages stimulated with bacterial lipopolysaccharide (LPS) and interferon-gamma (IFNγ). Relative to adherent glass control surfaces, VC discourages macrophage adhesion and spreading, and may potentially sequester LPS/IFNγ and cytokines that the cells produce. GF, on the other hand, was less suppressive of inflammation, supported macrophage adhesion and spreading better than VC, and sequestered lesser quantities of LPS/IFNγ in comparison to VC. The control dressing material cotton gauze (CT) was also immunosuppressive, capable of TNF-α retention and LPS/IFNγ sequestration. Our findings suggest that NPWT material interactions with cells, as well as soluble factors including cytokines and LPS, can modulate the immune response, independent of vacuum application. We have also established methodological strategies for studying NPWT materials and reveal the potential utility of cell-based in vitro studies for elucidating biological effects of NPWT materials.
Membrane Technological Pathways and Inherent Structure of Bacterial Cellulose Composites for Drug Delivery
Authors: Mensah Alfred , Chen Yajun , Christopher Narh , Wei Qufu
Published: December 2021

This report summarizes efforts undertaken in the area of drug delivery, with a look at further efforts made in the area of bacterial cellulose (BC) biomedical applications in general. There are many current methodologies (past and present) for the creation of BC membrane composites custom-engineered with drug delivery functionality, with brief consideration for very close applications within the broader category of biomedicine. The most emphasis was placed on the crucial aspects that open the door to the possibility of drug delivery or the potential for use as drug carriers. Additionally, consideration has been given to laboratory explorations as well as already established BC-drug delivery systems (DDS) that are either on the market commercially or have been patented in anticipation of future commercialization. The cellulose producing strains, current synthesis and growth pathways, critical aspects and intrinsic morphological features of BC were given maximum consideration, among other crucial aspects of BC DDS.
Organized Chaos: Deciphering Immune Cell Heterogeneity’s Role in Inflammation in the Heart
Authors: Corker Alexa , Neff Lily S. , Broughton Philip , Bradshaw Amy D. , DeLeon-Pennell Kristine Y.
Published: December 2021

During homeostasis, immune cells perform daily housekeeping functions to maintain heart health by acting as sentinels for tissue damage and foreign particles. Resident immune cells compose 5% of the cellular population in healthy human ventricular tissue. In response to injury, there is an increase in inflammation within the heart due to the influx of immune cells. Some of the most common immune cells recruited to the heart are macrophages, dendritic cells, neutrophils, and T-cells. In this review, we will discuss what is known about cardiac immune cell heterogeneity during homeostasis, how these cell populations change in response to a pathology such as myocardial infarction or pressure overload, and what stimuli are regulating these processes. In addition, we will summarize technologies used to evaluate cell heterogeneity in models of cardiovascular disease.
Biogenic Polyamines and Related Metabolites
Authors: Ivanov Alexander V. , Khomutov Alex R.
Published: December 2021

The specific regulation of cell metabolism is one of cornerstones of biochemistry [...]
Connexin 43 Gene Ablation Does Not Alter Human Pluripotent Stem Cell Germ Lineage Specification
Authors: Christopher Grace A. , Noort Rebecca J. , Esseltine Jessica L.
Published: December 2021

During embryonic germ layer development, cells communicate with each other and their environment to ensure proper lineage specification and tissue development. Connexin (Cx) proteins facilitate direct cell–cell communication through gap junction channels. While previous reports suggest that gap junctional intercellular communication may contribute to germ layer formation, there have been limited comprehensive expression analyses or genetic ablation studies on Cxs during human pluripotent stem cell (PSC) germ lineage specification. We screened the mRNA profile and protein expression patterns of select human Cx isoforms in undifferentiated human induced pluripotent stem cells (iPSCs), and after directed differentiation into the three embryonic germ lineages: ectoderm, definitive endoderm, and mesoderm. Transcript analyses by qPCR revealed upregulation of Cx45 and Cx62 in iPSC-derived ectoderm; Cx45 in mesoderm; and Cx30.3, Cx31, Cx32, Cx36, Cx37, and Cx40 in endoderm relative to control human iPSCs. Generated Cx43 (GJA1) CRISPR-Cas9 knockout iPSCs successfully differentiated into cells of all three germ layers, suggesting that Cx43 is dispensable during directed iPSC lineage specification. Furthermore, qPCR screening of select Cx transcripts in our GJA1-/- iPSCs showed no significant Cx upregulation in response to the loss of Cx43 protein. Future studies will reveal possible compensation by additional Cxs, suggesting targets for future CRISPR-Cas9 ablation studies in human iPSC lineage specification.
Sensitive Electrochemical Detection of Phosphorylated-Tau Threonine 231 in Human Serum Using Interdigitated Wave-Shaped Electrode
Authors: Le Hien T. Ngoc , Cho Sungbo
Published: December 2021

The development of an electrochemical biosensor for the detection of phosphorylated-tau threonine 231 (p-tau231), a biomarker of Alzheimer’s disease (AD), has yet to be achieved. Therefore, in this study, we developed a simple, small size, cheap, and sensitive electrochemical biosensor based on an interdigitated wave-shaped electrode via an activated self-assembled monolayer to preserve a specific anti–p-tau231 antibody (IWE/SAM/EDC-NHS/anti–p-tau231). Detection of p-tau231 in human serum (HS) using the biosensor was undertaken using electrochemical impedance spectroscopy (EIS). The change in charge-transfer resistance (Rct) in the EIS analysis of the biosensor indicated the detection of p-tau231 in HS within a wide linear range of detection (10−4–101 ng mL−1), and a low limit of detection (140 pg mL−1). This lower limit is less than the detection level of p-tau231 in cerebrospinal fluid (CSF) (700 pg mL−1) of AD patients and the level of CSF p-tau231 of patients with mild cognitive impairment (501 pg mL−1), demonstrating the possibility of using the biosensor in detection of p-tau231 at early stage AD. A high binding affinity and low dissociation constant (Kd) between anti–p-tau231 and p-tau231 in HS was demonstrated by using a biosensor and Kd was 7.6 pM, demonstrating the high specific detection of p-tau231 by the biosensor. The good selectivity of the biosensor for the detection of p-tau231 with differential analytes was also examined in this study.
Screening of the Promising Direct Thrombin Inhibitors from Haematophagous Organisms. Part I: Recombinant Analogues and Their Antithrombotic Activity In Vitro
Authors: Kostromina Maria A. , Tukhovskaya Elena A. , Shaykhutdinova Elvira R. , Slashcheva Gulsara A. , Ismailova Alina M. , Palikov Victor A. , Palikova Yuliya A. , Dyachenko Igor A. , Kravchenko Irina N. , Sadovnikova Elena S. , Novikova Nadezhda I. , Perepechenova Natalia A. , Zayats Evgeniy A. , Abramchik Yuliya A. , Lykoshin Dmitry D. , Mamaev Andrey N. , Grigorieva Elena V. , Momot Andrey P. , Murashev Arkady N. , Esipov Roman S.
Published: December 2021

The success in treatment of venous thromboembolism and acute coronary syndromes using direct thrombin inhibitors has stimulated research aimed at finding a new anticoagulant from haematophagous organisms. This study deals with the comparison between hirudin-1 from Hirudomedicinalis(desirudin), being the first-known and most well-studied natural anticoagulant, along with recombinant analogs of haemadin from the leech Haemadipsa sylvestris, variegin from the tick Amblyomma variegatum, and anophelin from Anopheles albimanus. These polypeptides were chosen due to their high specificity and affinity for thrombin, as well as their distinctive inhibitory mechanisms. We have developed a universal scheme for the biotechnological production of these recombinant peptides as pharmaceutical substances. The anticoagulant activities of these peptides were compared using the thrombin amidolytic activity assay and prolongation of coagulation time (thrombin time, prothrombin time, and activated partial thromboplastin time) in mouse and human plasma. The preliminary results obtained suggest haemadin as the closest analog of recombinant hirudin-1, the active substance of the medicinal product Iprivask (Aventis Pharmaceuticals, USA) for the prevention of deep venous thrombosis in patients undergoing elective hip or knee replacement surgery. In contrast, variegin can be regarded as a natural analog of bivalirudin (Angiomax, The Medicines Company), a synthetic hirudin-1 derivative certified for the treatment of patients undergoing percutaneous coronary intervention and of patients with unstable angina pectoris after percutaneous transluminal coronary angioplasty.
Explainable Artificial Intelligence (XAI) in Biomedicine: Making AI Decisions Trustworthy for Physicians and Patients
Authors: Lötsch Jörn , Kringel Dario , Ultsch Alfred
Published: December 2021

The use of artificial intelligence (AI) systems in biomedical and clinical settings can disrupt the traditional doctor–patient relationship, which is based on trust and transparency in medical advice and therapeutic decisions. When the diagnosis or selection of a therapy is no longer made solely by the physician, but to a significant extent by a machine using algorithms, decisions become nontransparent. Skill learning is the most common application of machine learning algorithms in clinical decision making. These are a class of very general algorithms (artificial neural networks, classifiers, etc.), which are tuned based on examples to optimize the classification of new, unseen cases. It is pointless to ask for an explanation for a decision. A detailed understanding of the mathematical details of an AI algorithm may be possible for experts in statistics or computer science. However, when it comes to the fate of human beings, this “developer’s explanation” is not sufficient. The concept of explainable AI (XAI) as a solution to this problem is attracting increasing scientific and regulatory interest. This review focuses on the requirement that XAIs must be able to explain in detail the decisions made by the AI to the experts in the field.
Old Enzyme, New Role: The β-Glucosidase BglC of Streptomyces scabiei Interferes with the Plant Defense Mechanism by Hydrolyzing Scopolin
Authors: Deflandre Benoit , Rigali Sébastien
Published: December 2021

The beta-glucosidase BglC fulfills multiple functions in both primary metabolism and induction of pathogenicity of Streptomyces scabiei, the causative agent of common scab in root and tuber crops. Indeed, this enzyme hydrolyzes cellobiose and cellotriose to feed glycolysis with glucose directly and modifies the intracellular concentration of these cello-oligosaccharides, which are the virulence elicitors. The inactivation of bglC led to unexpected phenotypes such as the constitutive overproduction of thaxtomin A, the main virulence determinant of S. scabiei. In this work, we reveal a new target substrate of BglC, the phytoalexin scopolin. Removal of the glucose moiety of scopolin generates scopoletin, a potent inhibitor of thaxtomin A production. The hydrolysis of scopolin by BglC displayed substrate inhibition kinetics, which contrasts with the typical Michaelis–Menten saturation curve previously observed for the degradation of its natural substrate cellobiose. Our work, therefore, reveals that BglC targets both cello-oligosaccharide elicitors emanating from the hosts of S. scabiei, and the scopolin phytoalexin generated by the host defense mechanisms, thereby occupying a key position to fine-tune the production of the main virulence determinant thaxtomin A.
Powerful Electron-Transfer Screen-Printed Platforms as Biosensing Tools: The Case of Uric Acid Biosensor
Authors: Cancelliere Rocco , Tinno Alessio Di , Cataldo Antonino , Bellucci Stefano , Micheli Laura
Published: December 2021

The use of carbon nanomaterials (CNMs) in sensors and biosensor realization is one of the hottest topics today in analytical chemistry. In this work, a comparative in-depth study, exploiting different nanomaterial (MWNT-CO2H, -NH2, -OH and GNP) modified screen-printed electrodes (SPEs), is reported. In particular, the sensitivity, the heterogeneous electron transfer constant (k0), and the peak-to-peak separation (ΔE) have been calculated and analyzed. After which, an electrochemical amperometric sensor capable of determining uric acid (UA), based on the nano-modified platforms previously characterized, is presented. The disposable UA biosensor, fabricated modifying working electrode (WE) with Prussian Blue (PB), carbon nanotubes, and uricase enzyme, showed remarkable analytical performances toward UA with high sensitivity (CO2H 418 μA μM−1 cm−2 and bare SPE-based biosensor, 33 μA μM−1 cm−2), low detection limits (CO2H 0.5 nM and bare SPE-based biosensors, 280 nM), and good repeatability (CO2H and bare SPE-based biosensors, 5% and 10%, respectively). Moreover, the reproducibility (RSD%) of these platforms in tests conducted for UA determination in buffer and urine samples results are equal to 6% and 15%, respectively. These results demonstrate that the nanoengineered electrode exhibited good selectivity and sensitivity toward UA even in the presence of interfering species, thus paving the way for its application in other bio-fluids such as simple point-of-care (POC) devices.
Biomechanical Analysis and Design Method for Patient-Specific Reconstructive Implants for Large Bone Defects of the Distal Lateral Femur
Authors: Wu Po-Kuei , Lee Cheng-Wei , Sun Wei-Hsiang , Lin Chun-Li
Published: December 2021

This study aims to develop a generalizable method for designing a patient-specific reconstructive scaffold implant for a large distal lateral femur defect using finite element (FE) analysis and topology optimization. A 3D solid-core implant for the distal femur defect was designed to withhold the femur load. Data from FE analysis of the solid implant were use for topology optimization to obtain a ‘bone scaffold implant’ with light-weight internal cavity and surface lattice features to allow for filling with bone material. The bone scaffold implant weighed 69.6% less than the original solid-core implant. The results of FE simulation show that the bone repaired with the bone scaffold implant had lower total displacement (12%), bone plate von Mises stress (34%), bone maximum first principal stress (33%), and bone maximum first principal strain (32%) than did bone repaired with bone cement. The trend in experimental strain with increasing load on the composite femur was greater with bone cement than with the bone scaffold implant. This study presents a generalizable method for designing a patient-specific reconstructive scaffold implant for the distal lateral femur defect that has sufficient strength and space for filling with allograft bone.
Tuning the Sensitivity and Dynamic Range of Optical Oxygen Sensing Films by Blending Various Polymer Matrices
Authors: Zhang Kaiheng , Lu Siyuan , Qu Zhe , Feng Xue
Published: December 2021

In this work, eight different types of optical oxygen sensing films were prepared by impregnating indicator and matrix solution on the surface of a polypropylene microporous filter membrane. The polymer matrix of the sensing films was ethyl cellulose (EC), polymethyl methacrylate (PMMA), and their blends with different mixing ratios. Scanning electron microscopy (SEM), laser confocal microscopy, and fluorescence spectrometer were used to investigate the morphologies and optical properties of the sensing films. Phase delay measurements under different oxygen partial pressures (PO2) and temperatures were applied to investigate the analytical performances of the sensing film for gaseous O2 monitoring. Results show that the response time of all the sensing films was extremely fast. The sensitivities and dynamic ranges of the sensing films with the blended polymer matrix were separately decreased and increased as the EC/PMMA ratio decreased, and the S-V curve of the sensing films blended with equal content of EC and PMMA exhibited good linearity under different temperatures, showing a promising prospect in practical application.
Identification of Factors Affecting Risk Appetite of Organizations in Selection of Mega Construction Projects
Authors: Ullah Sanna , Mufti Nadeem Ahmad , Qaiser Saleem Muhammad , Hussain Amjad , Lodhi Rab Nawaz , Asad Rehan
Published: December 2021

Risk appetite is a crucial component that plays a key role in the decision-making process of project risk management. Despite rising scholarly interest in project risk management, risk appetite has received little attention thus far. A well-defined risk appetite ensures that all decisions taken throughout the course of a project are consistent with an organization’s ultimate strategic aim. This research aims to identify the factors affecting the risk appetite of megaproject selection in the construction sector. The study adds to the knowledge of risk appetite in mega construction project selection and qualitatively examines the factors affecting risk appetite. Exploratory research design is used to identify these factors. The factors are identified using semi-structured interviews of 30 practitioners from the top and middle management working on mega construction projects. Thematic analysis was performed using NVIVO academic software. The most highlighted factors are financial attributes, board of directors’ agility, political factors, project location and demographics. The proposed conceptual framework identifies the factors affecting the risk appetite of mega construction project selection. These factors may be utilized as a starting point by construction project organizations to evaluate the risk appetite of a mega construction project. Risk appetite-based project selection will decrease chances of failures, delays, and cost overruns in mega-projects. These factors can be used by researchers as a rationale for developing predictive or descriptive models of project selection based on risk appetite.
Informed Finite Element Modelling for Wire and Arc Additively Manufactured Metallics—A Case Study on Modular Building Connections
Authors: Dissanayake Madhushan , Suntharalingam Thadshajini , Tsavdaridis Konstantinos Daniel , Poologanathan Keerthan , Perampalam Gatheeshgar
Published: December 2021

The use of 3D printing in modular building connections is a novel and promising technique. However, the performance of 3D printed steel modular building connections has not been investigated adequately to date. Therefore, this paper presents a three-dimensional finite element model (FEM), using the multi-purpose software Abaqus, to study the effect of different geometrical and material parameters on the ultimate behaviour of modular building connections (herein named 3DMBC) using a wire and arc additive manufacturing (WAAM) method, as part of the UK’s 3DMBC (3D Modular Building Connections) project. The proposed model considers material and geometrical non-linearities, initial imperfections, and the contact between adjacent surfaces. The finite element results are compared with the currently available experimental results and validated to ensure developed FEM can be used to analyse the behaviour of 3DMBC with some adjustments. Case studies were investigated using the validated model to analyse the ultimate behaviour with different nominal and WAAM-produced materials under various loading arrangements. Based on the results, it is recommended to conservatively use the treated or untreated WAAM material properties obtained in θ = 90° print orientation in the finite element modelling of 3DMBCs considering the complex component arrangements and multi-directional loading in the modular connections. It is also noted that the thickness of beams and columns of fully 3D printed connections can be increased to achieve the same level of performance as traditional modular connections. For the 3DMBCs printed using untreated WAAM, the thickness increment was found to be 50% in this study.
Low BACH2 Expression Predicts Adverse Outcome in Chronic Lymphocytic Leukaemia
Authors: Ciardullo Carmela , Szoltysek Katarzyna , Zhou Peixun , Pietrowska Monika , Marczak Lukasz , Willmore Elaine , Enshaei Amir , Walaszczyk Anna , Ho Jia Yee , Rand Vikki , Marshall Scott , Hall Andrew G. , Harrison Christine J. , Soundararajan Meera , Eswaran Jeyanthy
Published: December 2021

Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease with a highly variable clinical outcome. There are well-established CLL prognostic biomarkers that have transformed treatment and improved the understanding of CLL biology. Here, we have studied the clinical significance of two crucial B cell regulators, BACH2 (BTB and CNC homology 1, basic leucine zipper transcription factor 2) and BCL6 (B-cell CLL/lymphoma 6), in a cohort of 102 CLL patients and determined the protein interaction networks that they participate in using MEC-1 CLL cells. We observed that CLL patients expressing low levels of BCL6 and BACH2 RNA had significantly shorter overall survival (OS) than high BCL6- and BACH2-expressing cases. Notably, their low expression specifically decreased the OS of immunoglobulin heavy chain variable region-mutated (IGHV-M) CLL patients, as well as those with 11q and 13q deletions. Similar to the RNA data, a low BACH2 protein expression was associated with a significantly shorter OS than a high expression. There was no direct interaction observed between BACH2 and BCL6 in MEC-1 CLL cells, but they shared protein networks that included fifty different proteins. Interestingly, a prognostic index (PI) model that we generated, using integrative risk score values of BACH2 RNA expression, age, and 17p deletion status, predicted patient outcomes in our cohort. Taken together, these data have shown for the first time a possible prognostic role for BACH2 in CLL and have revealed protein interaction networks shared by BCL6 and BACH2, indicating a significant role for BACH2 and BCL6 in key cellular processes, including ubiquitination mediated B-cell receptor functions, nucleic acid metabolism, protein degradation, and homeostasis in CLL biology.
Genomic Instability and Replicative Stress in Multiple Myeloma: The Final Curtain?
Authors: Botrugno Oronza A. , Tonon Giovanni
Published: December 2021

Multiple Myeloma (MM) is a genetically complex and heterogeneous hematological cancer that remains incurable despite the introduction of novel therapies in the clinic. Sadly, despite efforts spanning several decades, genomic analysis has failed to identify shared genetic aberrations that could be targeted in this disease. Seeking alternative strategies, various efforts have attempted to target and exploit non-oncogene addictions of MM cells, including, for example, proteasome inhibitors. The surprising finding that MM cells present rampant genomic instability has ignited concerted efforts to understand its origin and exploit it for therapeutic purposes. A credible hypothesis, supported by several lines of evidence, suggests that at the root of this phenotype there is intense replicative stress. Here, we review the current understanding of the role of replicative stress in eliciting genomic instability in MM and how MM cells rely on a single protein, Ataxia Telangiectasia-mutated and Rad3-related protein, ATR, to control and survive the ensuing, potentially fatal DNA damage. From this perspective, replicative stress per se represents not only an opportunity for MM cells to increase their evolutionary pool by increasing their genomic heterogeneity, but also a vulnerability that could be leveraged for therapeutic purposes to selectively target MM tumor cells.
Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2α Modulation
Authors: Pereira Marcelo G. , Voltarelli Vanessa A. , Tobias Gabriel C. , de Souza Lara , Borges Gabriela S. , Paixão Ailma O. , de Almeida Ney R. , Bowen Thomas Scott , Demasi Marilene , Miyabara Elen H. , Brum Patricia C.
Published: December 2021

Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2α activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia.