bluuebunny/crossref_metadata_2025 huggingface dataset:
Valorization of Kiwiberry Leaves Recovered by Ultrasound-Assisted Extraction for Skin Application: A Response Surface Methodology Approach
Authors: Silva Ana Margarida , Pinto Diana , Moreira Manuela M. , Costa Paulo C. , Delerue-Matos Cristina , Rodrigues Francisca
Published: April 2022

This study aims to evaluate the optimal ultrasound-assisted extraction (UAE) conditions of antioxidants polyphenols from Actinidia arguta (Siebold & Zucc.) Planch. Ex Miq. (kiwiberry) leaves using a response surface methodology (RSM). The effects of solid:liquid ratio (2.5–10.0% w/v), time (20–60 min), and intensity (30–70 W/m2) on the total phenolic content (TPC) and antioxidant/antiradical activities were investigated. The optimal UAE conditions were achieved using a solid:liquid ratio of 10% (w/v) and an ultrasonic intensity of 30 W/m2 for 31.11 min. The results demonstrated that the optimal extract showed a high TPC (97.50 mg of gallic acid equivalents (GAE)/g dw) and antioxidant/antiradical activity (IC50 = 249.46 µg/mL for ABTS assay; IC50 = 547.34 µg/mL for DPPH assay; 1440.13 µmol of ferrous sulfate equivalents (FSE)/g dw for ferric reducing antioxidant power (FRAP)) as well as a good capacity to scavenge superoxide and hypochlorous acid (respectively, IC50 = 220.13 μg/mL and IC50 =10.26 μg/mL), which may be related with the 28 phenolic compounds quantified. The in vitro cell assay demonstrated that the optimal extract did not decrease the keratinocytes’ (HaCaT) viability, while the fibroblasts’ (HFF-1) viability was greater than 70.63% (1000 µg/mL). This study emphasizes the great potential of kiwiberry leaves extracted by UAE for skin application.
Chemical, Antioxidant, and Antimicrobial Properties of the Peel and Male Flower By-Products of Four Varieties of Punica granatum L. Cultivated in the Marche Region for Their Use in Cosmetic Products
Authors: Gigliobianco Maria Rosa , Cortese Manuela , Nannini Samanta , Di Nicolantonio Lucrezia , Peregrina Dolores Vargas , Lupidi Giulio , Vitali Luca Agostino , Bocchietto Elena , Di Martino Piera , Censi Roberta
Published: April 2022

We are now seeing an increase in the production of agri-food waste, which is an essential resource for the recovery of bioactive compounds that may be employed as innovative natural ingredients in cosmetics. To date, the approach to cosmetics preservation has seen a significant shift in the search for biological components that give healthier alternatives for customers and help businesses operate in an environmentally friendly manner. To achieve this goal, we studied pomegranate extracts using the peel and, for the first time, extracts from the male flowers of a wide pomegranate variety cultivated in the Marche region, specifically, the Wonderful, Mollar de Elche, Parfianka, and less-studied G1 varieties. We studied the phenol compounds profile, antioxidant capacity, antimicrobial activity, and cell viability of the obtained pomegranate extracts. The identification and quantification of phenol compounds belonging to different classes, such as hydrolysable tannins, hydroxybenzoic acid, hydroxycinnamic acid, dihydroflavonol, gallocatechin, and anthocyanins, were performed using UPLC-ESI-MS/MS. Punicalagin isomers and punicalin resulted in the most abundant polyphenols found in the peel and male flower extracts. Mollar de Elche 2020 peel extract revealed a high concentration of punicalagin A and B (7206.4 mg/kg and 5812.9), while the content of gallic acid revealed high results in the G1 and Parfianka varieties. All extracts were spectrophotometrically analysed to determine their total phenol content (TPC) using the Folin–Ciocalteu method and their antioxidant capacity (AC). In terms of the total phenol obtained by the Folin–Ciocalteu colorimetric method, Mollar de Elche 2020 extracts reported the highest TPC content of 12.341 µmol GAE/g. Results revealed that the Mollar de Elche and Wonderful 2020 peel extracts demonstrated the highest TPC and AC. Furthermore, AC results indicated that the peel extracts displayed higher AC than the male flower extract due to the high punicalagin content detected by UPLC analysis. The antimicrobial activity testing revealed that the Wonderful and G1 2020 peel extracts resulted active against Escherichia coli, while all extracts exhibited promising anticandidal activity. Additionally, the cytocompatibility was evaluated in keratinocytes HaCaT cells by testing concentrations of pomegranate extracts ranging from 0.15 to 5.00 mg/mL. Extracts were non-toxic for the cells in the tested concentration range. The acquired results may help exploit pomegranate agri-food waste products provided by the Marche region’s short supply chain for their use as an antimicrobial and antioxidant booster in the formulation of cosmetic products.
Constitutive Modelling of Temperature-Dependent Behaviour of Soft Rocks with Fractional-Order Flow Rule
Authors: Li Hai-Chao , Tong Chen-Xi , Chang Xin , Zhang Sheng
Published: April 2022

This paper regards soft rock as a heavily overconsolidated clay and proposes a new fractional elastoplastic model to describe its temperature-dependent mechanical behaviour. Together with the critical state mechanics, the subloading surface concept is adopted to capture the irreversible plastic deformation developed inside the normal yield surface and provides a smooth transition between the elastic and plastic zones. In addition, the proposed model uses a fractional-order flow rule to account for the nonorthogonality between the plastic flow direction and the yield surface without introducing an extra plastic potential. The evolution law of the fractional-order is affected by the degree of overconsolidation and temperature. The proposed model is verified by the drained triaxial test data of Ohya rock under various confining pressures and temperatures with satisfactory performance. It can be found that an increase in the temperature will reduce the peak strength of soft rock and lead to a ductile failure pattern with a smaller tangent modulus.
Graph Neural Network for Senior High Student’s Grade Prediction
Authors: Yu Yang , Fan Jinfu , Xian Yuanqing , Wang Zhongjie
Published: April 2022

Senior high school education (SHSE) forms a connecting link between the preceding junior high school education and the following college education. Through SHSE, a student not only completes k-12 education, but also lays a foundation for subsequent higher education. The grade of the student in SHSE plays a critical role in college application and admission. Therefore, utilizing the grade of the student as an indicator is a reasonable method to instruct and ensure the effect of SHSE. However, due to the complexity and nonlinearity of the grade prediction problem, it is hard to predict the grade accurately. In this paper, a novel grade prediction model aiming to handle the complexity and nonlinearity is proposed to accurately predict the grade of the senior high student. To deal with the complexity, a graph structure is employed to represent the students’ grades in all subjects. To handle the nonlinearity, the multi-layer perceptron (MLP) is used to learn (or fit) the inner relation of the subject grades. The proposed grade prediction model based on graph neural network is tested on the dataset of Ningbo Xiaoshi High School. The results show that the proposed method performs well in the prediction of senior high school student grades.
Research on Damage Localization of Steel Truss–Concrete Composite Beam Based on Digital Orthoimage
Authors: Luo Rui , Zhou Zhixiang , Chu Xi , Liao Xiaoliang , Meng Junhao
Published: April 2022

Most structural health monitoring is carried out for a limited number of key measurement points of a bridge, and incomplete measurement data lead to incomplete mechanical equation inversion results, which is a key problem faced in bridge damage identification. The ability of digital images to holographically describe structural morphology can effectively alleviate the problem of damage identification due to incomplete test data. Based on digital image processing technology, a matrix similarity damage identification method based on a structural digital orthoimage was proposed. Firstly, a steel truss–concrete composite beam specimen with a complex support bar system was designed and fabricated in the laboratory, and the digital orthoimage of the test beam was obtained by the perspective transformation of the original image of the test beam. The body contour of the structure was extracted from the digital orthoimage of the test beam, and wavelet threshold denoising was performed on the lower edge profile to obtain the deflection curves of the structure under different working conditions. The verification results show that the maximum error of the deflection curve is 3.42%, which proves that the digital orthoimage can accurately and completely reflect the deformation of the structure. Finally, based on the digital orthophoto of the test beam, a matrix similarity test before and after the damage was carried out, and the results show that the singularities of the similarity distribution are consistent with the location of the damage; furthermore, the accurate positioning of the damage in different working conditions is achieved.
Numerical Study of Partial Dam–Break Flow with Arbitrary Dam Gate Location Using VOF Method
Authors: Le Thi Thu Hien , Nguyen Van Chien
Published: April 2022

This paper aims to evaluate the crucial influence of the width of dam gate and its position, as well as initial water depth, on the evolution of rarefaction waves on reservoirs, and of shock waves over dry flood plain areas. The large eddy simulation (LES) model and volume of fluid (VOF) method are used to simulate three objectives. Firstly, validation of the presented numerical model, and of mesh sensitivity analysis, are conducted by means of a physical test case, taken from the literature, showing very good accuracy with a small value of RMSE among all hydraulic features in the case of fine mesh. In this direction, the 3D result is also compared with the published 2D one, to prove the necessity of using a 3D model in performing dam–break flow in an early stage. The second aim is to look for insight into the following 3D hydraulic characteristics of dam–break flow: water depth, velocity hydrograph and streamline, vorticity, the q–criterion incorporated with variety of breach size, initial water stage and the reservoir outlet’s location. The influence of the dam gate’s place on peak discharge is pointed out by means of a 3D model, while the existing analytical solution is not specified. With the same conditions of initial water depth, breach width and geometry, an analytical solution gives the same peak discharge, while a 3D numerical one indicates that a symmetrical dam gate provides a greater value than does the asymmetrical case, and also a value greater than that of an analytical result.
Design of Cognitive Assistance Systems in Manual Assembly Based on Quality Function Deployment
Authors: Pokorni Bastian , Popescu Daniela , Constantinescu Carmen
Published: April 2022

Increasing volatility and product individualization are leading to higher complexity in manual assembly. At the same time, production and processes must become more flexible, and humans have to adapt to new products more often and even faster. Industry 5.0 will increasingly focus on human-centric approaches, on the collaboration of humans and machines intensively using cognitive assistance systems. The design of an innovative cognitive assistance system is a complex task due to the many technological opportunities and their interrelationships. In the framework of this research, a method was developed enabling the systematic design of cognitive assistance systems that integrates business and worker requirements aiming at improving productivity, quality, worker satisfaction and well-being. The research question was approached by design science research having, as the main output, a systematic and innovative method for the design of cognitive assistance systems based on quality function deployment (QFD), referred to as cognitive assistance system-QFD (CAS-QFD). The developed methodology is divided into six phases and includes the iterative design of a cognitive assistance system starting from the assembly process. The method considers the information needs of the workers, the definition of the appropriate assistance functions and the selection of the interaction technologies. The exemplarily industrial evaluation highlighted the relevance of CAS-QFD for systematically designing cognitive assistance systems based on holistic requirements, identified at the worker, workplace, production area and, finally, at the enterprise level.
Multi-Physical and Electrochemical Coupling Model for the Protonic Ceramic Fuel Cells with H+/e−/O2− Mixed Conducting Cathodes
Authors: Yan Dongping , Wang Wansheng , Li Runhua , Jiang Shanshan , Lu Liu , Levtsev Aleksey , Chen Daifen
Published: April 2022

A protonic ceramic fuel cell (PCFC) has great potential for medium temperature power generation. Its working process, however, is complicated and quite different from the traditional oxygen ionic solid oxide fuel cell (O2−-SOFC) and proton exchange membrane fuel cell (PEMFC). In this paper, a multi-physical model for the PCFC with H+/e−/O2− mixed conducting cathode is established, in which the fuel- and oxidant-diffusing processes; electron-, oxygen ion-, and proton-conducting processes; three electrochemical reactions; and their coupling working details are carefully considered. Taking Ni-BZCY/BZCY/BZCY-LSCF PCFC as an example, the validation of the model is well verified by good agreements with the experiment iop-Vop curves at different temperatures. The result shows that the cathodic electrochemical reactions will be concentrated to a small thickness near the electrolyte because of the greatly decreased ionic conductivity compared with the high electronic conductivity at an intermediate temperature. O2− within the PCFC cathode is only an intermediate transform substance between the electrons and protons. Thus, there is a peak oxygen ion current distribution within the composite cathode of PCFC. The cathodic oxygen reduction half reaction is found to be a key factor to dominate the total PCFC voltage loss at the intermediate temperature zone. The concentration polarization of anode-supported PCFC is small, due to the vapors that are generated in the cathode side instead of anode side.
Ethical Issues in AI-Enabled Disease Surveillance: Perspectives from Global Health
Authors: Borda Ann , Molnar Andreea , Neesham Cristina , Kostkova Patty
Published: April 2022

Infectious diseases, as COVID-19 is proving, pose a global health threat in an interconnected world. In the last 20 years, resistant infectious diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), H1N1 influenza (swine flu), Ebola virus, Zika virus, and now COVID-19 have been impacting global health defences, and aggressively flourishing with the rise of global travel, urbanization, climate change, and ecological degradation. In parallel, this extraordinary episode in global human health highlights the potential for artificial intelligence (AI)-enabled disease surveillance to collect and analyse vast amounts of unstructured and real-time data to inform epidemiological and public health emergency responses. The uses of AI in these dynamic environments are increasingly complex, challenging the potential for human autonomous decisions. In this context, our study of qualitative perspectives will consider a responsible AI framework to explore its potential application to disease surveillance in a global health context. Thus far, there is a gap in the literature in considering these multiple and interconnected levels of disease surveillance and emergency health management through the lens of a responsible AI framework.
Deriving Situation-Adaptive Policy for Container Stacking in an Automated Container Terminal
Authors: Kim Taekwang , Ryu Kwang Ryel
Published: April 2022

Determining where to stack the containers at the storage yard of a container terminal is an important problem because that decision critically affects the efficiency of container handling in the yard and, eventually, the efficiency of the vessel operations, which is considered the most important for the productivity of the whole terminal. One limitation of the stacking policies previously proposed is that they are static in nature. Although good locations for stacking may change as the workload of vessel operation changes, the previous policies are insensitive to such changes. Failure to recommend good locations leads to elongated operations of yard cranes and thus makes it hard for them to keep up with the workload of vessel operation. In this paper, we propose a method for deriving a dynamic policy that can adapt to the workload of vessel operation that changes over time. Our method derives two boundary policies: one for very high workload and the other for very low. Then, a policy appropriate for any intermediate workload can be synthesized from the two boundary policies through interpolation. Simulation experiments showed that the proposed policy significantly reduced overall container handling time compared to the previous static policy. When measured in terms of the time the transportation vehicles wait for container handling services, the improvement was approximately 19%.
Let AI Perform Better Next Time—A Systematic Review of Medical Imaging-Based Automated Diagnosis of COVID-19: 2020–2022
Authors: Liu Fan , Chen Delong , Zhou Xiaocong , Dai Wenwen , Xu Feng
Published: April 2022

The pandemic of COVID-19 has caused millions of infections, which has led to a great loss all over the world, socially and economically. Due to the false-negative rate and the time-consuming characteristic of the Reverse Transcription Polymerase Chain Reaction (RT-PCR) tests, diagnosing based on X-ray images and Computed Tomography (CT) images has been widely adopted to confirm positive COVID-19 RT-PCR tests. Since the very beginning of the pandemic, researchers in the artificial intelligence area have proposed a large number of automatic diagnosing models, hoping to assist radiologists and improve the diagnosing accuracy. However, after two years of development, there are still few models that can actually be applied in real-world scenarios. Numerous problems have emerged in the research of the automated diagnosis of COVID-19. In this paper, we present a systematic review of these diagnosing models. A total of 179 proposed models are involved. First, we compare the medical image modalities (CT or X-ray) for COVID-19 diagnosis from both the clinical perspective and the artificial intelligence perspective. Then, we classify existing methods into two types—image-level diagnosis (i.e., classification-based methods) and pixel-level diagnosis (i.e., segmentation-based models). For both types of methods, we define universal model pipelines and analyze the techniques that have been applied in each step of the pipeline in detail. In addition, we also review some commonly adopted public COVID-19 datasets. More importantly, we present an in-depth discussion of the existing automated diagnosis models and note a total of three significant problems: biased model performance evaluation; inappropriate implementation details; and a low reproducibility, reliability and explainability. For each point, we give corresponding recommendations on how we can avoid making the same mistakes and let AI perform better in the next pandemic.
A Human Location Prediction-Based Routing Protocol in Mobile Crowdsensing-Based Urban Sensor Networks
Authors: Van Anh Duong Dat , Yoon Seokhoon
Published: April 2022

Mobile crowdsensing (MCS) has recently emerged as an urban-sensing paradigm that takes advantage of smartphone sensing capabilities and user mobility. A major challenge in mobile crowdsensing-based urban sensor networks is how to efficiently transfer data from sensors to the sink (e.g., the server center). Therefore, this study proposes a human location prediction-based routing protocol (HLPRP) in such networks. Specifically, a human location prediction (HLP) model is designed to estimate the location of mobile nodes. The proposed HLP model is based on a recurrent neural network with long short-term memory cells. The movement history of each person is used in the HLP model to predict their future locations. Experimental results on real traces are used to validate the proposed HLP model. Then, using predicted location information from the HLP model, packet delivery predictability is obtained. Packet delivery predictability represents the possibility that a node will deliver a packet to its destination and is used to select optimal relay nodes to maximize the packet delivery ratio, minimize the packet delivery cost, and reduce delivery latency. In addition, the proposed routing protocol considers social strength for relay selection. To evaluate the HLPRP, we conduct simulations and compare results with other routing protocols, showing that the HLPRP can outperform existing protocols.
Experimental Study of Drag Torque between Wet Clutch Discs
Authors: Goszczak Jarosław , Leyko Jacek , Mitukiewicz Grzegorz , Batory Damian
Published: April 2022

The development of automatic gearbox control systems contributes to their increasing popularity. By raising the number of gears and sophisticated algorithms, the reduction of fuel consumption is feasible regarding traditional manual transmissions. The continuously variable transmissions (CVT) are also growing their share of the market. Wet clutches are employed in all types of automatic transmissions, but because of oil viscosity, when such a type of clutch is disengaged, the drag torque phenomenon occurs. This deteriorates the global efficiency of the transmission system. To recognize the nature of this drag torque and how it is influenced by the main parameters (distance between plates, value of oil flow rate lubricating clutch, oil temperature, rotational speed between plates), a new test stand has been designed and assembled. The value of rotational speed has been studied up to 7000 rpm which is novel in literature. Due to strongly nonlinear dependences, the achieved results can contribute to designing more efficient clutch systems due to the strongly nonlinear nature of observed phenomena.
Elemental Profiles of Wild Thymus L. Plants Growing in Different Soil and Climate Conditions
Authors: Vasil’eva Irina E. , Shabanova Elena V. , Tsagaan Byambasuren , Bymbaa Khuukhenkhuu
Published: April 2022

Plants of the genus Thymus L. are traditionally used in medicine and cooking due to the presence of biologically active compounds in them that have fungicidal, antibacterial and other medicinal properties and original taste qualities. Genetic features and growing conditions cause the elemental composition, responsibly of the synthesised medicinal compounds. However, information on the contents and distributions of elements in the organs of Thymus L. is very limited. This study was to set and compare the elements in organs of wild thyme for different soil and climatic conditions. Two species of wild Thymus L. from Mongolian steppe and on the coast of Lake Baikal were collected during flowering. Twenty-four elements, including Si, in soils, roots, stems, leaves and flowers were simultaneously determined by atomic emission spectrometry. Elemental profiles of two species of wild Thymus L. are described. It is assumed that Si is a necessary element of the plant. The predominance of the genetic resistance of plants over the influence of soil and climatic conditions is shown.
Gradient-Free Neural Network Training via Synaptic-Level Reinforcement Learning
Authors: Bhargava Aman , Rezaei Mohammad R. , Lankarany Milad
Published: April 2022

An ongoing challenge in neural information processing is the following question: how do neurons adjust their connectivity to improve network-level task performance over time (i.e., actualize learning)? It is widely believed that there is a consistent, synaptic-level learning mechanism in specific brain regions, such as the basal ganglia, that actualizes learning. However, the exact nature of this mechanism remains unclear. Here, we investigate the use of universal synaptic-level algorithms in training connectionist models. Specifically, we propose an algorithm based on reinforcement learning (RL) to generate and apply a simple biologically-inspired synaptic-level learning policy for neural networks. In this algorithm, the action space for each synapse in the network consists of a small increase, decrease, or null action on the connection strength. To test our algorithm, we applied it to a multilayer perceptron (MLP) neural network model. This algorithm yields a static synaptic learning policy that enables the simultaneous training of over 20,000 parameters (i.e., synapses) and consistent learning convergence when applied to simulated decision boundary matching and optical character recognition tasks. The trained networks yield character-recognition performance comparable to identically shaped networks trained with gradient descent. The approach has two significant advantages in comparison to traditional gradient-descent-based optimization methods. First, the robustness of our novel method and its lack of reliance on gradient computations opens the door to new techniques for training difficult-to-differentiate artificial neural networks, such as spiking neural networks (SNNs) and recurrent neural networks (RNNs). Second, the method’s simplicity provides a unique opportunity for further development of local information-driven multiagent connectionist models for machine intelligence analogous to cellular automata.
A Numerical Study for Tropical Cyclone Atsani (2020) Past Offshore of Southern Taiwan under Topographic Influences
Authors: Huang Ching-Yuang , Lin Jia-Yang , Kuo Hung-Chi , Chen Der-Song , Hong Jing-Shan , Hsiao Ling-Feng , Chen Shu-Ya
Published: April 2022

Tropical Cyclone Atsani occurred in late October 2020 and moved westward offshore south of Taiwan. During its offshore passage, the cyclone deflects northward as it closes to the southern end of Taiwan. A global model MPAS at a multi-resolution of 60-15-3-km is applied to explore the track responses of Atsani and identify the topographic effects of the Central Mountain Range (CMR) on the cyclone circulation and the associated track deflection. With a 3-km resolution targeted at the Taiwan area, the cyclone track deflection can be reasonably simulated, with more sensitivity to physics schemes and dynamic vortex initialization and less sensitivity to initial environmental perturbations. When the Taiwan terrain is removed, the cyclone indeed deflects more northward earlier, in particular for simulations with a stronger cyclone that tends to generate stronger east-west wind asymmetry in the absence of the terrain. Idealized simulations with a regional model WRF at 3-km resolution are also utilized to contrast the track deflection of different departing cyclones, similar to the real case. It was found that northward deflection will be induced near south of the CMR-like terrain for both stronger and weaker westbound cyclones departing at different latitudes south of the terrain. We have explained why a further northward track at earlier stages is induced in the absence of the terrain effects in regard to model initial states. In both real and idealized cases, the track deflection of the cyclone moving around the terrain is dominated by the wavenumber-one horizontal potential vorticity (PV) advection that is somewhat offset by both vertical PV advection and differential diabatic heating.
Hadamard Product Properties for Certain Subclasses of p-Valent Meromorphic Functions
Authors: El-Qadeem Alaa H. , Elshazly Ibrahim S.
Published: April 2022

We study the Hadamard product features of certain subclasses of p-valent meromorphic functions defined in the punctured open-unit disc using the q-difference operator. For functions belonging to these subclasses, we obtained certain coefficient estimates and inclusion characteristics. Furthermore, linkages between the results given here and those found in previous publications are highlighted.
Comparison of Model-Based and Sensor-Based Detection of Thermal Runaway in Li-Ion Battery Modules for Automotive Application
Authors: Klink Jacob , Hebenbrock André , Grabow Jens , Orazov Nury , Nylén Ulf , Benger Ralf , Beck Hans-Peter
Published: April 2022

In recent years, research on lithium–ion (Li-ion) battery safety and fault detection has become an important topic, providing a broad range of methods for evaluating the cell state based on voltage and temperature measurements. However, other measurement quantities and close-to-application test setups have only been sparsely considered, and there has been no comparison in between methods. In this work, the feasibility of a multi-sensor setup for the detection of Thermal Runaway failure of automotive-size Li-ion battery modules have been investigated in comparison to a model-based approach. For experimental validation, Thermal Runaway tests were conducted in a close-to-application configuration of module and battery case—triggered by external heating with two different heating rates. By two repetitions of each experiment, a high accordance of characteristics and results has been achieved and the signal feasibility for fault detection has been discussed. The model-based method, that had previously been published, recognised the thermal fault in the fastest way—significantly prior to the required 5 min pre-warning time. This requirement was also achieved with smoke and gas sensors in most test runs. Additional criteria for evaluating detection approaches besides detection time have been discussed to provide a good starting point for choosing a suitable approach that is dependent on application defined requirements, e.g., acceptable complexity.
Whole Genome Sequencing Contributions and Challenges in Disease Reduction Focused on Malaria
Authors: Akoniyon Olusegun Philip , Adewumi Taiye Samson , Maharaj Leah , Oyegoke Olukunle Olugbenle , Roux Alexandra , Adeleke Matthew A. , Maharaj Rajendra , Okpeku Moses
Published: April 2022

Malaria elimination remains an important goal that requires the adoption of sophisticated science and management strategies in the era of the COVID-19 pandemic. The advent of next generation sequencing (NGS) is making whole genome sequencing (WGS) a standard today in the field of life sciences, as PCR genotyping and targeted sequencing provide insufficient information compared to the whole genome. Thus, adapting WGS approaches to malaria parasites is pertinent to studying the epidemiology of the disease, as different regions are at different phases in their malaria elimination agenda. Therefore, this review highlights the applications of WGS in disease management, challenges of WGS in controlling malaria parasites, and in furtherance, provides the roles of WGS in pursuit of malaria reduction and elimination. WGS has invaluable impacts in malaria research and has helped countries to reach elimination phase rapidly by providing required information needed to thwart transmission, pathology, and drug resistance. However, to eliminate malaria in sub-Saharan Africa (SSA), with high malaria transmission, we recommend that WGS machines should be readily available and affordable in the region.
Dopamine Transporter, PhosphoSerine129 α-Synuclein and α-Synuclein Levels in Aged LRRK2 G2019S Knock-In and Knock-Out Mice
Authors: Domenicale Chiara , Mercatelli Daniela , Albanese Federica , Novello Salvatore , Vincenzi Fabrizio , Varani Katia , Morari Michele
Published: April 2022

The G2019S mutation in leucine rich-repeat kinase 2 (LRRK2) is a major cause of familial Parkinson’s disease. We previously reported that G2019S knock-in mice manifest dopamine transporter dysfunction and phosphoSerine129 α-synuclein (pSer129 α-syn) immunoreactivity elevation at 12 months of age, which might represent pathological events leading to neuronal degeneration. Here, the time-dependence of these changes was monitored in the striatum of 6, 9, 12, 18 and 23-month-old G2019S KI mice and wild-type controls using DA uptake assay, Western analysis and immunohistochemistry. Western analysis showed elevation of membrane dopamine transporter (DAT) levels at 9 and 12 months of age, along with a reduction of vesicular monoamine transporter 2 (VMAT2) levels at 12 months. DAT uptake was abnormally elevated from 9 to up to 18 months. DAT and VMAT2 level changes were specific to the G2019S mutation since they were not observed in LRRK2 kinase-dead or knock-out mice. Nonetheless, dysfunctional DAT uptake was not normalized by acute pharmacological inhibition of LRRK2 kinase activity with MLi-2. Immunoblot analysis showed elevation of pSer129 α-syn levels in the striatum of 12-month-old G2019S KI mice, which, however, was not confirmed by immunohistochemical analysis. Instead, total α-syn immunoreactivity was found elevated in the striatum of 23-month-old LRRK2 knock-out mice. These data indicate mild changes in DA transporters and α-syn metabolism in the striatum of 12-month-old G2019S KI mice whose pathological relevance remains to be established.
A Novel Approach to Enhance the Regenerative Potential of Circulating Endothelial Progenitor Cells in Patients with End-Stage Kidney Disease
Authors: Badawi Amrilmaen , Jefferson Osfred C. , Huuskes Brooke M. , Ricardo Sharon D. , Kerr Peter G. , Samuel Chrishan S. , Murthi Padma
Published: April 2022

Circulating bone marrow-derived endothelial progenitor cells (EPCs) facilitate vascular repair in several organs including the kidney but are progressively diminished in end-stage kidney disease (ESKD) patients, which correlates with cardiovascular outcomes and related mortality. We thus determined if enhancing the tissue-reparative effects of human bone marrow-derived mesenchymal stromal cells (BM-MSCs) with the vasculogenic effects of recombinant human relaxin (RLX) could promote EPC proliferation and function. CD34+ EPCs were isolated from the blood of healthy and ESKD patients, cultured until late EPCs had formed, then stimulated with BM-MSC-derived condition media (CM; 25%), RLX (1 or 10 ng/mL), or both treatments combined. Whilst RLX alone stimulated EPC proliferation, capillary tube formation and wound healing in vitro, these measures were more rapidly and markedly enhanced by the combined effects of BM-MSC-derived CM and RLX in EPCs derived from both healthy and ESKD patients. These findings have important clinical implications, having identified a novel combination therapy that can restore and enhance EPC number and function in ESKD patients.
Workplace Violence among Healthcare Providers during the COVID-19 Health Emergency: A Cross-Sectional Study
Authors: Alfuqaha Othman A. , Albawati Nour M. , Alhiary Sakher S. , Alhalaiqa Fadwa N. , Haha Moh’d Fayeq F. , Musa Suzan S. , Shunnar Ohood , AL Thaher Yazan
Published: April 2022

(1) Background: Workplace violence among healthcare providers (HCPs) is a tangible barrier to patient care. The purpose of this study was to gain insight into physicians’ and nurses’ perceptions of workplace violence and their perceptions of communication skills during the COVID-19 health emergency. We also sought to assess and compare the association between types of workplace violence, communication skills, and several sociodemographic factors of physicians and nurses including gender, marital status, site of work, age, and educational level during this era. (2) Methods: We performed a cross-sectional study of a selected hospital in Jordan using the Arabic version of the workplace violence and communication skills scales for September to November 2020. We included a total of 102 physicians and 190 nurses via a self-reported questionnaire. (3) Results: During the COVID-19 health emergency, physicians (48%) experienced workplace violence more than nurses (31.6%). More than two-thirds of the participants did not formally report any type of violence. Multinomial logistic regression analysis showed that marital status, gender, age, site of work, educational levels, and communication skills were associated with different types of violence among the two samples. (4) Conclusions: A high prevalence of workplace violence is noted among HCPs in Jordan compared with before the pandemic, which highlights the importance of promoting public awareness during crises.
An Innovative Modelling Approach Based on Building Physics and Machine Learning for the Prediction of Indoor Thermal Comfort in an Office Building
Authors: Tardioli Giovanni , Filho Ricardo , Bernaud Pierre , Ntimos Dimitrios
Published: April 2022

The estimation of indoor thermal comfort and the associated occupant feedback in office buildings is important to provide satisfactory and safe working environments, enhance the productivity of personnel, and to reduce complaints. The assessment of thermal comfort is a difficult task due to many environmental, physiological, and cultural variables that influence occupants’ thermal perception and the way they judge their working environment. Traditional physics-based methods for evaluating thermal comfort have shown shortcomings when compared to actual responses from the occupants due to the incapacity of these methods to incorporate information of various natures. In this paper, a hybrid approach based on machine learning and building dynamic simulation is presented for the prediction of indoor thermal comfort feedback in an office building in Le Bour-get-du-Lac, Chambéry, France. The office was equipped with Internet of Things (IoT) environmental sensors. Occupant feedback on thermal comfort was collected during an experimental campaign. A calibrated building energy model was created for the building. Various machine learning models were trained using information from the occupants, environmental data, and data extracted from the calibrated dynamic simulation model for the prediction of thermal comfort votes. When compared to traditional predictive approaches, the proposed method shows an increase in accuracy of about 25%.
High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic Metastasectomy
Authors: Wrana Friederike , Dötzer Katharina , Prüfer Martin , Werner Jens , Mayer Barbara
Published: April 2022

Considering the biology of CRC, distant metastases might support the identification of high-risk patients for early recurrence and targeted therapy. Expression of a panel of druggable, metastasis-related biomarkers was immunohistochemically analyzed in 53 liver (LM) and 15 lung metastases (LuM) and correlated with survival. Differential expression between LM and LuM was observed for the growth factor receptors IGF1R (LuM 92.3% vs. LM 75.8%, p = 0.013), EGFR (LuM 68% vs. LM 41.5%, p = 0.004), the cell adhesion molecules CD44v6 (LuM 55.7% vs. LM 34.9%, p = 0.019) and α2β1 (LuM 88.3% vs. LM 58.5%, p = 0.001) and the check point molecule PD-L1 (LuM 6.1% vs. LM 3.3%, p = 0.005). Contrary, expression of HGFR, Hsp90, Muc1, Her2/neu, ERα and PR was comparable in LuM and LM. In the LM cohort (n = 52), a high CD44v6 expression was identified as an independent factor of poor prognosis (PFS: HR 2.37, 95% CI 1.18–4.78, p = 0.016). High co-expression of CD44v6/α2β1 (HR 4.14, 95% CI 1.65–10.38, p = 0.002) and CD44v6/PD-L1 (HR 2.88, 95% CI 1.21–6.85, p = 0.017) indicated early recurrence after hepatectomy, in a substantial number of patients (CD44v6/α2β1: 11 (21.15%) patients; CD44v6/PD-L1: 12 (23.1%) patients). Dual expression of druggable protein biomarkers may refine prognostic prediction and stratify high-risk patients for new therapeutic concepts, depending on the metastatic location.
Magnetic Resonance-Guided Reirradiation for Local Recurrence within the Prostate or in the Prostate Bed: One-Year Clinical Results of a Prospective Registry Study
Authors: Michalet Morgan , Riou Olivier , Cottet-Moine Jeremy , Castan Florence , Gourgou Sophie , Valdenaire Simon , Debuire Pierre , Ailleres Norbert , Draghici Roxana , Charissoux Marie , Llacer Moscardo Carmen , Farcy-Jacquet Marie-Pierre , Fenoglietto Pascal , Azria David
Published: April 2022

Around 33% of patients treated by EBRT or brachytherapy will present a biochemical recurrence. SBRT is a new option for the treatment of patients with local-only recurrence. MRgRT seems to be interesting for the treatment of these recurrences. This article presents the one-year late tolerance and biochemical recurrence-free survival results of a prospective registry study. Patients with intraprostatic (or in the prostate bed) recurrence were treated with 5 to 9 fractions (median dose of 30 Gy in 5 fractions) with the MRIdian® system. PSA level and toxicities were evaluated before treatment and at three, six and 12 months after treatment. Thirty-seven patients with a median age of 74.5 years old were treated between 21 October 2019 and 7 December 2020. Acute tolerance was excellent with no grade >2 toxicities. Twelve months after treatment, we observed an increase of grade 1–2 dysuria (46% vs. 13% before treatment) and grade 1 polyuria (73% vs. 7%). The six, nine and 12-months biochemical-recurrence free survival were 97.3%, 86.5% and 65.0%. Fifteen patients (40%) presented a biochemical recurrence. Nine of these 15 patients (60%) had a persistent disease within the treated volume. In conclusion, MRgRT is safe and has promising survival results.
Platelet-Derived PDGFB Promotes Recruitment of Cancer-Associated Fibroblasts, Deposition of Extracellular Matrix and Tgfβ Signaling in the Tumor Microenvironment
Authors: Zhang Yanyu , Manouchehri Doulabi Ehsan , Herre Melanie , Cedervall Jessica , Qiao Qi , Miao Zuoxiu , Hamidi Anahita , Hellman Lars , Kamali-Moghaddam Masood , Olsson Anna-Karin
Published: April 2022

Platelets constitute a major reservoir of platelet-derived growth factor B (PDGFB) and are continuously activated in the tumor microenvironment, exposing tumors to the plethora of growth factors contained in platelet granules. To address the specific role of platelet-derived PDGFB in the tumor microenvironment, we have created a mouse model with conditional knockout of PDGFB in platelets (pl-PDGFB KO). Lack of PDGFB in platelets resulted in 10-fold lower PDGFB concentration in the tumor microenvironment, fewer cancer-associated fibroblasts and reduced deposition of the extracellular matrix (ECM) molecules fibronectin and collagen I in the orthotopic RIP1-Tag2 model for pancreatic neuroendocrine cancer. Myosin light chain phosphorylation, promoting cell contraction and, consequently, the mechano-induced release of active transforming growth factor (TGF) β from extracellular compartments, was reduced in tumors from pl-PDGFB KO mice. In agreement, TGFβ signaling, measured as phosphorylated Smad2, was significantly hampered in tumors from mice lacking PDGFB in their platelets, providing a plausible explanation for the reduced deposition of extracellular matrix. These findings indicate a major contribution of platelet-derived PDGFB to a malignant transformation of the tumor microenvironment and address for the first time the role of PDGFB released specifically from platelets in the remodeling of the ECM in tumors.
MicroRNA-like snoRNA-Derived RNAs (sdRNAs) Promote Castration-Resistant Prostate Cancer
Authors: Coley Alexander B. , Stahly Ashlyn N. , Kasukurthi Mohan V. , Barchie Addison A. , Hutcheson Sam B. , Houserova Dominika , Huang Yulong , Watters Brianna C. , King Valeria M. , Dean Meghan A. , Roberts Justin T. , DeMeis Jeffrey D. , Amin Krisha V. , McInnis Cameron H. , Godang Noel L. , Wright Ryan M. , Haider David F. , Piracha Neha B. , Brown Cana L. , Ijaz Zohaib M. , Li Shengyu , Xi Yaguang , McDonald Oliver G. , Huang Jingshan , Borchert Glen M.
Published: April 2022

We have identified 38 specifically excised, differentially expressed snoRNA fragments (sdRNAs) in TCGA prostate cancer (PCa) patient samples as compared to normal prostate controls. SnoRNA-derived fragments sdRNA-D19b and -A24 emerged among the most differentially expressed and were selected for further experimentation. We found that the overexpression of either sdRNA significantly increased PC3 (a well-established model of castration-resistant prostate cancer (CRPC)) cell proliferation, and that sdRNA-D19b overexpression also markedly increased the rate of PC3 cell migration. In addition, both sdRNAs provided drug-specific resistances with sdRNA-D19b levels correlating with paclitaxel resistance and sdRNA-24A conferring dasatinib resistance. In silico and in vitro analyses revealed that two established PCa tumor suppressor genes, CD44 and CDK12, represent targets for sdRNA-D19b and sdRNA-A24, respectively. This outlines a biologically coherent mechanism by which sdRNAs downregulate tumor suppressors in AR-PCa to enhance proliferative and metastatic capabilities and to encourage chemotherapeutic resistance. Aggressive proliferation, rampant metastasis, and recalcitrance to chemotherapy are core characteristics of CRPC that synergize to produce a pathology that ranks second in cancer-related deaths for men. This study defines sdRNA-D19b and -A24 as contributors to AR-PCa, potentially providing novel biomarkers and therapeutic targets of use in PCa clinical intervention.
Evolutionary Transition in the Regulation of Vertebrate Pronephros Development: A New Role for Retinoic Acid
Authors: Schmidt Pascal , Leman Eva , Lagadec Ronan , Schubert Michael , Mazan Sylvie , Reshef Ram
Published: April 2022

The anterior-posterior (AP) axis in chordates is regulated by a conserved set of genes and signaling pathways, including Hox genes and retinoic acid (RA), which play well-characterized roles in the organization of the chordate body plan. The intermediate mesoderm (IM), which gives rise to all vertebrate kidneys, is an example of a tissue that differentiates sequentially along this axis. Yet, the conservation of the spatiotemporal regulation of the IM across vertebrates remains poorly understood. In this study, we used a comparative developmental approach focusing on non-conventional model organisms, a chondrichthyan (catshark), a cyclostome (lamprey), and a cephalochordate (amphioxus), to assess the involvement of RA in the regulation of chordate and vertebrate pronephros formation. We report that the anterior expression boundary of early pronephric markers (Pax2 and Lim1), positioned at the level of somite 6 in amniotes, is conserved in the catshark and the lamprey. Furthermore, RA, driving the expression of Hox4 genes like in amniotes, regulates the anterior pronephros boundary in the catshark. We find no evidence for the involvement of this regulatory hierarchy in the AP positioning of the lamprey pronephros and the amphioxus pronephros homolog, Hatschek’s nephridium. This suggests that despite the conservation of Pax2 and Lim1 expressions in chordate pronephros homologs, the responsiveness of the IM, and hence of pronephric genes, to RA- and Hox-dependent regulation is a gnathostome novelty.
Selectin-Mediated Signaling—Shedding Light on the Regulation of Integrin Activity in Neutrophils
Authors: Cappenberg Anika , Kardell Marina , Zarbock Alexander
Published: April 2022

As a consequence of tissue injury or infection, neutrophils are recruited in a stepwise recruitment process from the bloodstream into the surrounding tissue. Selectins are a family of adhesion molecules comprised of L-, E-, and P-selectin. Differences in expression patterns, protein structure, and ligand binding characteristics mediate distinct functions of each selectin. Interactions of selectins and their counter-receptors mediate the first contact of neutrophils with the endothelium, as well as subsequent neutrophil rolling along the endothelial surface. For efficient neutrophil recruitment, activation of β2-integrins on the cell surface is essential. Integrin activation can be elicited via selectin- as well as chemokine-mediated inside-out signaling resulting in integrin conformational changes and clustering. Dysregulation of selectin-induced integrin activation on neutrophils is involved in the development of severe pathological disease conditions including leukocyte adhesion deficiency (LAD) syndromes in humans. Here, we review molecular mechanisms involved in selectin-mediated signaling pathways in neutrophils and their impact on integrin activation, neutrophil recruitment, and inflammatory diseases.