bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Tract Infections in Elderly Patients: A 10-Year Study on Their Epidemiology and Antibiotic Resistance Based on the WHO Access, Watch, Reserve (AWaRe) Classification
Authors: Gajdács Márió , Ábrók Marianna , Lázár Andrea , Burián Katalin
Published: September 2021

The ageing of the population—especially in developed countries—has brought on many societal challenges and has significantly contributed to the burden on healthcare infrastructures worldwide. Elderly persons (aged ≥ 65 years) are at higher risk for developing UTIs, due to a range of intrinsic and extrinsic risk factors, and they often delay seeking treatment. A retrospective observational study was performed regarding the epidemiology and resistance of UTIs in elderly patients. Identification of the isolates was carried out using VITEK 2 ID/AST and MALDI-TOF mass spectrometry. Antibiotic resistance in these isolates was assessed based on EUCAST guidelines, and were grouped into the WHO AWaRe (Access, Watch, Reserve) classification of antimicrobials. During the 10-year study period, n = 4214 (421.4 ± 118.7/year) and n = 4952 (495.2 ± 274.6) laboratory-confirmed UTIs were recorded in inpatients and outpatients, respectively. The causative agents showed differentiation among outpatients and inpatients: Escherichia coli (48.14% vs. 25.65%; p = 0.001), Enterococcus spp. (20.15% vs. 21.52%; p > 0.05), Klebsiella spp. (16.28% vs. 16.26%; p > 0.05), Pseudomonas spp. (4.40%vs. 13.36%; p = 0.001); Proteus-Providencia-Morganella group (4.56% vs. 10.96%; p = 0.001); Candida spp. (0.53% vs. 5.98%; p = 0.001); Citrobacter-Enterobacter-Serratia group (1.90% vs. 2.71%; p < 0.05). Significantly higher resistance rates were observed in inpatient isolates for many Access and Watch antibiotics compared to isolates of outpatient origin; in addition, resistance rates were higher in these uropathogens compared to the previously recorded rates in the region. More care should be taken for the diagnosis and treatment of UTIs affecting elderly patients, as they represent a particularly vulnerable patient population.
Learning Spatial–Temporal Background-Aware Based Tracking
Authors: Gu Peiting , Liu Peizhong , Deng Jianhua , Chen Zhi
Published: September 2021

Discriminative correlation filter (DCF) based tracking algorithms have obtained prominent speed and accuracy strengths, which have attracted extensive attention and research. However, some unavoidable deficiencies still exist. For example, the circulant shifted sampling process is likely to cause repeated periodic assumptions and cause boundary effects, which degrades the tracker’s discriminative performance, and the target is not easy to locate in complex appearance changes. In this paper, a spatial–temporal regularization module based on BACF (background-aware correlation filter) framework is proposed, which is performed by introducing a temporal regularization to deal effectively with the boundary effects issue. At the same time, the accuracy of target recognition is improved. This model can be effectively optimized by employing the alternating direction multiplier (ADMM) method, and each sub-problem has a corresponding closed solution. In addition, in terms of feature representation, we combine traditional hand-crafted features with deep convolution features linearly enhance the discriminative performance of the filter. Considerable experiments on multiple well-known benchmarks show the proposed algorithm is performs favorably against many state-of-the-art trackers and achieves an AUC score of 64.4% on OTB-100.
Contributing towards Representative PM Data Coverage by Utilizing Artificial Neural Networks
Authors: Tzanis Chris G. , Alimissis Anastasios
Published: September 2021

Atmospheric aerosol particles have a significant impact on both the climatic conditions and human health, especially in densely populated urban areas, where the particle concentrations in several cases can be extremely threatening (increased anthropogenic emissions). Most large cities located in high-income countries have stations responsible for measuring particulate matter and various other parameters, collectively forming an operating monitoring network, which is essential for the purposes of environmental control. In the city of Athens, which is characterized by high population density and accumulates a large number of economic activities, the currently operating monitoring network is responsible, among others, for PM10 and PM2.5 measurements. The need for satisfactory data availability though can be supported by using machine learning methods, such as artificial neural networks. The methodology presented in this study uses a neural network model to provide spatiotemporal estimations of PM10 and PM2.5 concentrations by utilizing the existing PM data in combination with other climatic parameters that affect them. The overall performance of the predictive neural network models’ scheme is enhanced when meteorological parameters (wind speed and temperature) are included in the training process, lowering the error values of the predicted versus the observed time series’ concentrations. Furthermore, this work includes the calculation of the contribution of each predictor, in order to provide a clearer understanding of the relationship between the model’s output and input. The results of this procedure showcase that all PM input stations’ concentrations have an important impact on the estimations. Considering the meteorological variables, the results for PM2.5 seem to be affected more than those for PM10, although when examining PM10 and PM2.5 individually, the wind speed and temperature contribution is on a similar level with the corresponding contribution of the available PM concentrations of the neighbouring stations.
Investigation of Degradation Mechanism from Shear Deformation and the Relationship with Mechanical Properties, Lamellar Size, and Morphology of High-Density Polyethylene
Authors: Kaneyasu Haruka , Phanthong Patchiya , Okubo Hikaru , Yao Shigeru
Published: September 2021

The degradation of mechanical properties is the most challenging point for the development of plastic mechanical recycling processes. Remelting and shear deformation contained in the mechanical process are a part of degradation in recycled plastics. In this study, virgin high-density polyethylene (HDPE) was simulated to be recycled by remelting and treating with shear deformation being measured at different shear treatment rates (0–100/s) using a cone-plate rheometer. The obtained shear treatment product was remolded as a thin film. The evaluation was performed comparing virgin HDPE (VPE) without any processing with shear-treated HDPE with various shear treatment rates. Tensile property, X-ray crystallography, and morphological observations were performed in order to investigate the relationship between mechanical properties, thickness of lamellar size, and the morphology of shear-treated HDPE as compared to VPE. It can be found that the elongation at break of shear-treated HDPE at a high shear treatment rate (100/s) was significantly decreased from VPE. This degradation mechanism was related to the decreased degree of crystallinity, thickness of the crystalline layer, intermediate layer, and occurrence of crystalline orientation. This study expected to explain the degradation mechanism of HDPE from shear deformation which can be further improved by the processing conditions of the mechanical plastic recycling process.
An Adaptive and Scalable Protection Coordination System of Overcurrent Relays in Distributed-Generator-Integrated Distribution Networks
Authors: Bui Duong Minh , Le Phuc Duy , Nguyen Thanh Phuong , Nguyen Hung
Published: September 2021

Integration of distributed generators (DGs) into a distribution network (DN) can cause coordination challenges of overcurrent relays (OCRs) because of different fault-current contributions of DGs as well as the directional change in fault currents. Therefore, the OCRs should be properly coordinated to maintain their adaptability and scalability to protect the DG-integrated distribution network. In this study, an adaptive and scalable protection coordination (ASPC) approach has been developed for the OCRs in a DG-contained distribution network based on two implementation stages. At the first stage, the reliability improvement of fault-current calculation results is performed by determining the min-max confidence interval of fault current for each different fault type, which is the basis for properly selecting tripping and pick-up thresholds of definite-time and inverse-time OC functions in the same OCR. At the second stage, optimization algorithms are used for calculating protection-curve coefficients and Time-Dial Setting (TDS) multiplier for the inverse-time OC functions in the OCR. A real 22 kV DG-integrated distribution network which is simulated by ETAP software is considered a reliable test-bed to validate the proposed ASPC system of OCRs in the multiple-DG-contained distribution network. In addition, the coordination results of OCRs can be obtained by three common optimization algorithms, Particle Swarm Optimization (PSO), Gravitational Search Algorithm (GSA), and Genetic Algorithm (GA). These relay coordination results have shown an effective protection combination of the definite-time OC functions (50P and 50G) and the inverse-time OC functions (51P and 51G) in the same OCR to get the adaptable and scalable DN protection system.
Functionally Graded Plate Fracture Analysis Using the Field Boundary Element Method
Authors: Palladino Simone , Esposito Luca , Ferla Paolo , Zona Renato , Minutolo Vincenzo
Published: September 2021

This paper describes the Field Boundary Element Method (FBEM) applied to the fracture analysis of a 2D rectangular plate made of Functionally Graded Material (FGM) to calculate Mode I Stress Intensity Factor (SIF). The case study of this Field Boundary Element Method is the transversely isotropic plane plate. Its material presents an exponential variation of the elasticity tensor depending on a scalar function of position, i.e., the elastic tensor results from multiplying a scalar function by a constant taken as a reference. Several examples using a parametric representation of the structural response show the suitability of the method that constitutes a Stress Intensity Factor evaluation of Functionally Graded Materials plane plates even in the case of more complex geometries.
Study on Air Pollution Behavior of VOCs with Photochemical Monitoring Stations Using EGARCH Model in Southern Taiwan
Authors: Wu Edward Ming-Yang , Kuo Shu-Lung
Published: September 2021

This study adopted the exponential generalized autoregressive conditional heteroscedasticity (EGARCH) model to examine the 10 ozone precursors of the highest concentrations among the 54 that were assessed over a number of years at the four photochemical assessment monitoring stations (PAMSs) in the Kaohsiung–Pingtung Area in Taiwan. First, the 10 ozone precursors, which were all volatile organic compounds (VOCs), were analyzed using the factor analyses in multiple statistical analyses that had the most significant impact on the area’s ozone formation: mobile pollution factor, which included 1,2,4-Trimethylbenzene (C9H12), toluene (C7H8), and Isopropyl benzene (C9H12). Then, taking into consideration that the number sequences might be affected by standardized residuals, this study applied the vector autoregressive moving average-EGARCH (VARMA-EGARCH) model to analyze the correlation between the three VOCs under different polluting activities. The VARMA-EGARCH model in this research included dummy variables representing changing points of variance structures in the variance formula to predict the conditional variance. This process proved able to effectively estimate the relevant coefficients of the three VOCs’ dynamic conditions that changed with time. The model also helped to prevent errors from occurring when estimating the conditional variance. Based on the testing results, this study determined the VARMA(2,1)-EGARCH(1,0) as the most suitable model for exploring the correlation between the three VOCs and meteorological phenomena, as well as the interplay between them in regard to interaction and formation. With the most representative of the three, toluene (TU), as the dependent variable and 1,2,4-Trimethylbenzene (TB) and Isopropyl benzene (IB) as the independent variables, this study found it impossible to calculate the TU concentration with TB and IB concentrations in the same period; estimations of TB and IB concentrations with a period of lag time were required because TU was mainly contributed by automobiles and motorcycles in Kaohsiung. TB and IB resulted from other stationary pollution sources in the region besides cars and motorbikes. When TU was evenly distributed and stayed longer in the atmosphere, the TB and IB concentrations were lower, so distribution conditions and concentrations could not be used to effectively estimate the concentration of toluene. This study had to wait until the next period, or when stationary pollution sources started producing TB and IB of higher concentrations during the daytime, in order to estimate the TU concentrations in a better photochemical situation.
Exercise under Exposure to Air Pollution and Spirometry in Healthy Adults with and without Allergy
Authors: Kocot Krzysztof , Barański Kamil , Melaniuk-Wolny Edyta , Zajusz-Zubek Eliwra , Kowalska Małgorzata
Published: September 2021

Ambient air pollution is a major environmental threat to human health. The acute effects of exposure to ambient air pollution during physical exercise may depend on allergy status. The aim of the study was to assess the acute respiratory responses to air pollution exposure during physical training in young adults with and without allergies. The studied group included 71 healthy young adults (n = 16 with allergy and n = 55 without allergy). Students completed two indoor physical training trials lasting 45–60 min: when air pollutants concentrations were high (exposure trial) and low (control trial). During each trial, we monitored outdoor and indoor environmental conditions. Participants performed spirometry at baseline and directly after the exercise. Exercise during exposure trials led to a small decrease in the percentage of predicted forced expiratory volume in 1 s (FEV1 ref). Only during the control trials did the FEV1/forced vital capacity quotient (FEV1/FVC) statistically significantly increase. Moreover, just in the allergy group, there were statistically significant negative correlations between post-exercise FEV1/FVC change and 3 h average outdoor particulate matter with aerodynamic diameter <10 µm (PM10) and nitrogen dioxide (NO2) concentrations (PM10: r = −0.54, p = 0.02, NO2: r = −0.60, p = 0.02). In young and healthy adults, sports training under exposure to high levels of ambient air pollutants leads to a small decrease in FEV1. The allergy might be a modifying factor in the respiratory responses to air pollution. Post-exercise decrease in FEV1/FVC was related to pre-exercise 3 h averages of PM10 and NO2 only in people with ever-diagnosed upper-respiratory allergy.
Evaluating the Applicability of a Quantile–Quantile Adjustment Approach for Downscaling Monthly GCM Projections to Site Scale over the Qinghai-Tibet Plateau
Authors: Yin Ziyun , Nan Zhuotong , Cao Zetao , Zhang Guofei
Published: September 2021

In the context of global climate change, the Qinghai-Tibetan plateau (QTP) has experienced unprecedented changes in its local climate. While general circulation models (GCM) are able to forecast global-scale future climate change trends, further work needs to be done to develop techniques to apply GCM-predicted trends at site scale to facilitate local ecohydrological response studies. Given the QTP’s unique altitude-controlled climate pattern, the applicability of the quantile–quantile (Q-Q) adjustment approach for this purpose remains largely unknown and warrants investigation. In this study, this approach was evaluated at 36 sites to ensure the results are representative of different climatic and surface conditions on the QTP. Considering the practical needs of QTP studies, the study aims to assess its capability for downscaling monthly GCM simulations of major variables onto the site scale, including precipitation, air temperature, wind speed, relative humidity, and air pressure, based on two GCMs. The calibrated projections at the sites were verified against the observations and compared with those from two commonly used adjustment methods—the quantile-mapping method and the delta method. The results show that the general trends of most variables considered are well adjusted at all sites, with a quantile pair of 25–75% for all the variables except precipitation where 10–90% is used. The calibrated results are generally close to the observed values, with the best performance in air pressure, followed by air temperature and relative humidity. The performance is relatively limited in adjusting wind speed and precipitation. The accuracies decline as the adjustment extends into the future; a wider adjustment window may help increase the performance for the variables subject to climate changes. It is found that the performance of the adjustment is generally independent of the locations and seasons, but is strongly determined by the quality of GCM simulations. The Q-Q adjustment works better for the meteorological variables with fewer fluctuations and daily extremes. Variables with more similarities in probability density functions between the observations and GCM simulations tend to perform better in adjustment. Generally, this approach outperforms the two peer methods with broader applicability and higher accuracies for most major variables.
Distinct Methodologies to Produce Capped Mesoporous Silica with Hydroxyapatite and the Influence in Intracellular Signaling as Cytotoxicity on Human Umbilical Vein Endothelial Cells
Authors: da Silva de Barros Aline Oliveira , Rebêlo Alencar Luciana Magalhães , Alexis Frank , Santos-Oliveira Ralph
Published: September 2021

Mesoporous silica has unique properties such as controllable mesoporous structure and size, good biocompatibility, high specific surface area, and large pore volume. For that reason, this material has been broadly functionalized for biomedical applications, such as optical imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound imaging, and widely employed as drug delivery systems. In this study, we synthesized fiber-type mesoporous silica capped with hydroxyapatite (ordered SiO2–CaO–P2O5 mesoporous silica). Its biological activity was evaluated through a cellular and molecular approach using HUVEC cell culture. Two distinct methodologies have produced the ordered SiO2–CaO–P2O5 mesoporous silica: (i) two-step Ca-doped silica matrix followed by hydroxyapatite crystallization inside the Ca-doped silica matrix and (ii) one-step Ca-doped silica matrix formed with the hydroxyapatite crystallization. Further analysis included: elemental analysis, transmission, scanning electron microscopy images, Small and Wide-Angle X-ray Diffraction analysis, Fourier Transform Infrared, and in vitro assays with HUVEC (cytotoxicity and immunoblotting). The hydroxyapatite capping methodology significantly affected the original mesoporous material structure. Furthermore, no cellular or molecular effect has been observed. The promising results presented here suggest that the one-step method to obtain hydroxyapatite capped mesoporous silica was effective, also demonstrating that this material has potential in biomedical applications.
The Carbon Source Controls the Secretion and Yield of Polysaccharide-Hydrolyzing Enzymes of Basidiomycetes
Authors: Metreveli Eka , Khardziani Tamar , Elisashvili Vladimir
Published: September 2021

In the present study, the polysaccharide-hydrolyzing secretomes of Irpex lacteus (Fr.) Fr. (1828) BCC104, Pycnoporus coccineus (Fr.) Bondartsev and Singer (1941) BCC310, and Schizophyllum commune Fr. (1815) BCC632 were analyzed in submerged fermentation conditions to elucidate the effect of chemically and structurally different carbon sources on the expression of cellulases and xylanase. Among polymeric substrates, crystalline cellulose appeared to be the best carbon source providing the highest endoglucanase, total cellulase, and xylanase activities. Mandarin pomace as a growth substrate for S. commune allowed to achieve comparatively high volumetric activities of all target enzymes while wheat straw induced a significant secretion of cellulase and xylanase activities of I. lacteus and P. coccineus. An additive effect on the secretion of cellulases and xylanases by the tested fungi was observed when crystalline cellulose was combined with mandarin pomace. In I. lacteus the cellulase and xylanase production is inducible in the presence of cellulose-rich substrates but is suppressed in the presence of an excess of easily metabolizable carbon source. These enzymes are expressed in a coordinated manner under all conditions studied. It was shown that the substitution of glucose in the inoculum medium with Avicel provides accelerated enzyme production by I. lacteus and higher cellulase and xylanase activities of the fungus. These results add new knowledge to the physiology of basidiomycetes to improve cellulase production.
Computational Analysis of Naturally Occurring Aristolochic Acid Analogues and Their Biological Sources
Authors: Xu Tingjun , Chen Weiming , Zhou Junhong , Dai Jingfang , Li Yingyong , Zhao Yingli
Published: September 2021

Aristolochic acids are known for nephrotoxicity, and implicated in multiple cancer types such as hepatocellular carcinomas demonstrated by recent studies. Natural products that are analogues to aristolochic acids have been constantly isolated from organisms; a larger chemical space of these compounds and a wider coverage of biological sources should be determined in consideration of the potential hazard of aristolochic acid analogues and the wide distribution of their biological sources in the nature. Therefore, we carried out an in silico research of naturally occurring aristolochic acid analogues and their biological sources, as a supplement to existing studies. The result shows a chemical space of 238 naturally occurring aristolochic acid analogues that are present in 175 species of biological sources including 44 traditional medicines. With the computational estimation for toxicity and the implication in hazard assessment of a biological source with the presence of aristolochic acid analogues, we propose that additional awareness should be raised to the public for avoidance of toxic species, especially those that are used as herbal medicines and easily accessible.
Advanced Molecular Dynamics Approaches to Model a Tertiary Complex APRIL/TACI with Long Glycosaminoglycans
Authors: Marcisz Mateusz , Maszota-Zieleniak Martyna , Huard Bertrand , Samsonov Sergey A.
Published: September 2021

Glycosaminoglycans (GAGs) are linear anionic periodic polysaccharides participating in a number of biologically relevant processes in the extracellular matrix via interactions with their protein targets. Due to their periodicity, conformational flexibility, pseudo-symmetry of the sulfation pattern, and the key role of electrostatics, these molecules are challenging for both experimental and theoretical approaches. In particular, conventional molecular docking applied for GAGs longer than 10-mer experiences severe difficulties. In this work, for the first time, 24- and 48-meric GAGs were docked using all-atomic repulsive-scaling Hamiltonian replica exchange molecular dynamics (RS-REMD), a novel methodology based on replicas with van der Waals radii of interacting molecules being scaled. This approach performed well for proteins complexed with oligomeric GAGs and is independent of their length, which distinguishes it from other molecular docking approaches. We built a model of long GAGs in complex with a proliferation-inducing ligand (APRIL) prebound to its receptors, the B cell maturation antigen and the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Furthermore, the prediction power of the RS-REMD for this tertiary complex was evaluated. We conclude that the TACI–GAG interaction could be potentially amplified by TACI’s binding to APRIL. RS-REMD outperformed Autodock3, the docking program previously proven the best for short GAGs.
In Vitro Secretome Analysis Suggests Differential Pathogenic Mechanisms between Fusarium oxysporum f. sp. cubense Race 1 and Race 4
Authors: He Yanqiu , Zhou Xiaofan , Li Jieling , Li Huaping , Li Yunfeng , Nie Yanfang
Published: September 2021

Banana Fusarium wilt, caused by the fungus pathogen Fusarium oxysporum f. sp. cubense (Foc), is a devastating disease that causes tremendous reductions in banana yield worldwide. Secreted proteins can act as pathogenicity factors and play important roles in the Foc–banana interactions. In this study, a shotgun-based proteomic approach was employed to characterize and compare the secretomes of Foc1 and Foc4 upon banana extract treatment, which detected 1183 Foc1 and 2450 Foc4 proteins. Comprehensive in silico analyses further identified 447 Foc1 and 433 Foc4 proteins in the classical and non-classical secretion pathways, while the remaining proteins might be secreted through currently unknown mechanisms. Further analyses showed that the secretomes of Foc1 and Foc4 are similar in their overall functional characteristics and share largely conserved repertoires of CAZymes and effectors. However, we also identified a number of potentially important pathogenicity factors that are differentially present in Foc1 and Foc4, which may contribute to their different pathogenicity against banana hosts. Furthermore, our quantitative PCR analysis revealed that genes encoding secreted pathogenicity factors differ significantly between Foc1 and Foc4 in their expression regulation in response to banana extract treatment. To our knowledge, this is the first experimental secretome analysis that focused on the pathogenicity mechanism in different Foc races. The results of this study provide useful resources for further exploration of the complicated pathogenicity mechanisms in Foc.
Identification of CDK7 Inhibitors from Natural Sources Using Pharmacoinformatics and Molecular Dynamics Simulations
Authors: Kumar Vikas , Parate Shraddha , Thakur Gunjan , Lee Gihwan , Ro Hyeon-Su , Kim Yongseong , Kim Hong Ja , Kim Myeong Ok , Lee Keun Woo
Published: September 2021

The cyclin-dependent kinase 7 (CDK7) plays a crucial role in regulating the cell cycle and RNA polymerase-based transcription. Overexpression of this kinase is linked with various cancers in humans due to its dual involvement in cell development. Furthermore, emerging evidence has revealed that inhibiting CDK7 has anti-cancer effects, driving the development of novel and more cost-effective inhibitors with enhanced selectivity for CDK7 over other CDKs. In the present investigation, a pharmacophore-based approach was utilized to identify potential hit compounds against CDK7. The generated pharmacophore models were validated and used as 3D queries to screen 55,578 natural drug-like compounds. The obtained compounds were then subjected to molecular docking and molecular dynamics simulations to predict their binding mode with CDK7. The molecular dynamics simulation trajectories were subsequently used to calculate binding affinity, revealing four hits—ZINC20392430, SN00112175, SN00004718, and SN00262261—having a better binding affinity towards CDK7 than the reference inhibitors (CT7001 and THZ1). The binding mode analysis displayed hydrogen bond interactions with the hinge region residues Met94 and Glu95, DFG motif residue Asp155, ATP-binding site residues Thr96, Asp97, and Gln141, and quintessential residue outside the kinase domain, Cys312 of CDK7. The in silico selectivity of the hits was further checked by docking with CDK2, the close homolog structure of CDK7. Additionally, the detailed pharmacokinetic properties were predicted, revealing that our hits have better properties than established CDK7 inhibitors CT7001 and THZ1. Hence, we argue that proposed hits may be crucial against CDK7-related malignancies.
Origami Paper-Based Electrochemical (Bio)Sensors: State of the Art and Perspective
Authors: Colozza Noemi , Caratelli Veronica , Moscone Danila , Arduini Fabiana
Published: September 2021

In the last 10 years, paper-based electrochemical biosensors have gathered attention from the scientific community for their unique advantages and sustainability vision. The use of papers in the design the electrochemical biosensors confers to these analytical tools several interesting features such as the management of the solution flow without external equipment, the fabrication of reagent-free devices exploiting the porosity of the paper to store the reagents, and the unprecedented capability to detect the target analyte in gas phase without any sampling system. Furthermore, cost-effective fabrication using printing technologies, including wax and screen-printing, combined with the use of this eco-friendly substrate and the possibility of reducing waste management after measuring by the incineration of the sensor, designate these type of sensors as eco-designed analytical tools. Additionally, the foldability feature of the paper has been recently exploited to design and fabricate 3D multifarious biosensors, which are able to detect different target analytes by using enzymes, antibodies, DNA, molecularly imprinted polymers, and cells as biocomponents. Interestingly, the 3D structure has recently boosted the self-powered paper-based biosensors, opening new frontiers in origami devices. This review aims to give an overview of the current state origami paper-based biosensors, pointing out how the foldability of the paper allows for the development of sensitive, selective, and easy-to-use smart and sustainable analytical devices.
Differential Influence of the Dorsal Premotor and Primary Somatosensory Cortex on Corticospinal Excitability during Kinesthetic and Visual Motor Imagery: A Low-Frequency Repetitive Transcranial Magnetic Stimulation Study
Authors: Oldrati Viola , Finisguerra Alessandra , Avenanti Alessio , Aglioti Salvatore Maria , Urgesi Cosimo
Published: September 2021

Consistent evidence suggests that motor imagery involves the activation of several sensorimotor areas also involved during action execution, including the dorsal premotor cortex (dPMC) and the primary somatosensory cortex (S1). However, it is still unclear whether their involvement is specific for either kinesthetic or visual imagery or whether they contribute to motor activation for both modalities. Although sensorial experience during motor imagery is often multimodal, identifying the modality exerting greater facilitation of the motor system may allow optimizing the functional outcomes of rehabilitation interventions. In a sample of healthy adults, we combined 1 Hz repetitive transcranial magnetic stimulation (rTMS) to suppress neural activity of the dPMC, S1, and primary motor cortex (M1) with single-pulse TMS over M1 for measuring cortico-spinal excitability (CSE) during kinesthetic and visual motor imagery of finger movements as compared to static imagery conditions. We found that rTMS over both dPMC and S1, but not over M1, modulates the muscle-specific facilitation of CSE during kinesthetic but not during visual motor imagery. Furthermore, dPMC rTMS suppressed the facilitation of CSE, whereas S1 rTMS boosted it. The results highlight the differential pattern of cortico-cortical connectivity within the sensorimotor system during the mental simulation of the kinesthetic and visual consequences of actions.
Reduced Effective Connectivity in the Motor Cortex in Parkinson’s Disease
Authors: Formaggio Emanuela , Rubega Maria , Rupil Jessica , Antonini Angelo , Masiero Stefano , Toffolo Gianna Maria , Del Felice Alessandra
Published: September 2021

Fast rhythms excess is a hallmark of Parkinson’s Disease (PD). To implement innovative, non-pharmacological, neurostimulation interventions to restore cortical-cortical interactions, we need to understand the neurophysiological mechanisms underlying these phenomena. Here, we investigated effective connectivity on source-level resting-state electroencephalography (EEG) signals in 15 PD participants and 10 healthy controls. First, we fitted multivariate auto-regressive models to the EEG source waveforms. Second, we estimated causal connections using Granger Causality, which provide information on connections’ strength and directionality. Lastly, we sought significant differences connectivity patterns between the two populations characterizing the network graph features—i.e., global efficiency and node strength. Causal brain networks in PD show overall poorer and weaker connections compared to controls quantified as a reduction of global efficiency. Motor areas appear almost isolated, with a strongly impoverished information flow particularly from parietal and occipital cortices. This striking isolation of motor areas may reflect an impaired sensory-motor integration in PD. The identification of defective nodes/edges in PD network may be a biomarker of disease and a potential target for future interventional trials.
Atomic Force Microscope Nanoindentation Analysis of Diffuse Astrocytic Tumor Elasticity: Relation with Tumor Histopathology
Authors: Tsitlakidis Abraham , Tsingotjidou Anastasia S. , Kritis Aristeidis , Cheva Angeliki , Selviaridis Panagiotis , Aifantis Elias C. , Foroglou Nicolas
Published: September 2021

This study aims to investigate the influence of isocitrate dehydrogenase gene family (IDH) mutations, World Health Organization (WHO) grade, and mechanical preconditioning on glioma and adjacent brain elasticity through standard monotonic and repetitive atomic force microscope (AFM) nanoindentation. The elastic modulus was measured ex vivo on fresh tissue specimens acquired during craniotomy from the tumor and the peritumoral white matter of 16 diffuse glioma patients. Linear mixed-effects models examined the impact of tumor traits and preconditioning on tissue elasticity. Tissues from IDH-mutant cases were stiffer than those from IDH-wildtype ones among anaplastic astrocytoma patients (p = 0.0496) but of similar elasticity to IDH-wildtype cases for diffuse astrocytoma patients (p = 0.480). The tumor was found to be non-significantly softer than white matter in anaplastic astrocytomas (p = 0.070), but of similar elasticity to adjacent brain in diffuse astrocytomas (p = 0.492) and glioblastomas (p = 0.593). During repetitive indentation, both tumor (p = 0.002) and white matter (p = 0.003) showed initial stiffening followed by softening. Stiffening was fully reversed in white matter (p = 0.942) and partially reversed in tumor (p = 0.015). Tissue elasticity comprises a phenotypic characteristic closely related to glioma histopathology. Heterogeneity between patients should be further explored.
Dosimetry, Efficacy, Safety, and Cost-Effectiveness of Proton Therapy for Non-Small Cell Lung Cancer
Authors: Qiu Bin , Men Yu , Wang Junjie , Hui Zhouguang
Published: September 2021

Non-small cell lung cancer (NSCLC) is the most common malignancy which requires radiotherapy (RT) as an important part of its multimodality treatment. With the advent of the novel irradiation technique, the clinical outcome of NSCLC patients who receive RT has been dramatically improved. The emergence of proton therapy, which allows for a sharper dose of build-up and drop-off compared to photon therapy, has potentially improved clinical outcomes of NSCLC. Dosimetry studies have indicated that proton therapy can significantly reduce the doses for normal organs, especially the lung, heart, and esophagus while maintaining similar robust target volume coverage in both early and advanced NSCLC compared with photon therapy. However, to date, most studies have been single-arm and concluded no significant changes in the efficacy for early-stage NSCLC by proton therapy over stereotactic body radiation therapy (SBRT). The results of proton therapy for advanced NSCLC in these studies were promising, with improved clinical outcomes and reduced toxicities compared with historical photon therapy data. However, these studies were also mainly single-arm and lacked a direct comparison between the two therapies. Currently, there is much emerging evidence focusing on dosimetry, efficacy, safety, and cost-effectiveness of proton therapy for NSCLC that has been published, however, a comprehensive review comparing these therapies is, to date, lacking. Thus, this review focuses on these aspects of proton therapy for NSCLC.
Therapeutic ROS and Immunity in Cancer—The TRIC-21 Meeting
Authors: Bekeschus Sander , Emmert Steffen , Clemen Ramona , Boeckmann Lars
Published: September 2021

The first Therapeutic ROS and Immunity in Cancer (TRIC) meeting was organized by the excellence research center ZIK plasmatis (with its previous Frontiers in Redox Biochemistry and Medicine (FiRBaM) and Young Professionals’ Workshop in Plasma Medicine (YPWPM) workshop series in Northern Germany) and the excellence research program ONKOTHER-H (Rostock/Greifswald, Germany). The meeting showcased cutting-edge research and liberated discussions on the application of therapeutic ROS and immunology in cancer treatment, primarily focusing on gas plasma technology. The 2-day hybrid meeting took place in Greifswald and online from 15–16 July 2021, facilitating a wide range of participants totaling 66 scientists from 12 countries and 5 continents. The meeting aimed at bringing together researchers from a variety of disciplines, including chemists, biochemists, biologists, engineers, immunologists, physicists, and physicians for interdisciplinary discussions on using therapeutic ROS and medical gas plasma technology in cancer therapy with the four main sessions: “Plasma, Cancer, Immunity”, “Plasma combination therapies”, “Plasma risk assessment and patients studies”, and “Plasma mechanisms and treated liquids in cancer”. This conference report outlines the abstracts of attending scientists submitted to this meeting.
Promoter Hypermethylation Promotes the Binding of Transcription Factor NFATc1, Triggering Oncogenic Gene Activation in Pancreatic Cancer
Authors: Wu Yenan , Kröller Lea , Miao Beiping , Boekhoff Henning , Bauer Andrea S. , Büchler Markus W. , Hackert Thilo , Giese Nathalia A. , Taipale Jussi , Hoheisel Jörg D.
Published: September 2021

Studies have indicated that some genes involved in carcinogenesis are highly methylated in their promoter regions but nevertheless strongly transcribed. It has been proposed that transcription factors could bind specifically to methylated promoters and trigger transcription. We looked at this rather comprehensively for pancreatic ductal adenocarcinoma (PDAC) and studied some cases in more detail. Some 2% of regulated genes in PDAC exhibited higher transcription coupled to promoter hypermethylation in comparison to healthy tissue. Screening 661 transcription factors, several were found to bind specifically to methylated promoters, in particular molecules of the NFAT family. One of them—NFATc1—was substantially more strongly expressed in PDAC than control tissue and exhibited a strong oncogenic role. Functional studies combined with computational analyses allowed determining affected genes. A prominent one was gene ALDH1A3, which accelerates PDAC metastasis and correlates with a bad prognosis. Further studies confirmed the direct up-regulation of ALDH1A3 transcription by NFATc1 promoter binding in a methylation-dependent process, providing insights into the oncogenic role of transcription activation in PDAC that is promoted by DNA methylation.
The Stress-Inducible BCL2A1 Is Required for Ovarian Cancer Metastatic Progression in the Peritoneal Microenvironment
Authors: Liang Rui , Yung Mingo M. H. , He Fangfang , Jiao Peili , Chan Karen K. L. , Ngan Hextan Y. S. , Chan David W.
Published: September 2021

Emerging evidence indicates that hypoxia plays a critical role in governing the transcoelomic metastasis of ovarian cancer. Hence, targeting hypoxia may be a promising approach to prevent the metastasis of ovarian cancer. Here, we report that BCL2A1, a BCL2 family member, acts as a hypoxia-inducible gene for promoting tumor progression in ovarian cancer peritoneal metastases. We demonstrated that BCL2A1 was induced not only by hypoxia but also other physiological stresses through NF-κB signaling and then was gradually reduced by the ubiquitin-proteasome pathway in ascites-derived ovarian cancer cells. The upregulated BCL2A1 was frequently found in advanced metastatic ovarian cancer cells, suggesting its clinical relevance in ovarian cancer metastatic progression. Functionally, BCL2A1 enhanced the foci formation ability of ovarian cancer cells in a stress-conditioned medium, colony formation in an ex vivo omental tumor model, and tumor dissemination in vivo. Under stress conditions, BCL2A1 accumulated and colocalized with mitochondria to suppress intrinsic cell apoptosis by interacting with the BH3-only subfamily BCL2 members HRK/BAD/BID in ovarian cancer cells. These findings indicate that BCL2A1 is an early response factor that maintains the survival of ovarian cancer cells in the harsh tumor microenvironment.
Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges
Authors: Riva Giovanni , Nasillo Vincenzo , Ottomano Anna Maria , Bergonzini Giuliano , Paolini Ambra , Forghieri Fabio , Lusenti Beatrice , Barozzi Patrizia , Lagreca Ivana , Fiorcari Stefania , Martinelli Silvia , Maffei Rossana , Marasca Roberto , Potenza Leonardo , Comoli Patrizia , Manfredini Rossella , Tagliafico Enrico , Trenti Tommaso , Luppi Mario
Published: September 2021

Along with the evolution of immunophenotypic and molecular diagnostics, the assessment of Minimal Residual Disease (MRD) has progressively become a keystone in the clinical management of hematologic malignancies, enabling valuable post-therapy risk stratifications and guiding risk-adapted therapeutic approaches. However, specific prognostic values of MRD in different hematological settings, as well as its appropriate clinical uses (basically, when to measure it and how to deal with different MRD levels), still need further investigations, aiming to improve standardization and harmonization of MRD monitoring protocols and MRD-driven therapeutic strategies. Currently, MRD measurement in hematological neoplasms with bone marrow involvement is based on advanced highly sensitive methods, able to detect either specific genetic abnormalities (by PCR-based techniques and next-generation sequencing) or tumor-associated immunophenotypic profiles (by multiparametric flow cytometry, MFC). In this review, we focus on the growing clinical role for MFC-MRD diagnostics in hematological malignancies—from acute myeloid and lymphoblastic leukemias (AML, B-ALL and T-ALL) to chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)—providing a comparative overview on technical aspects, clinical implications, advantages and pitfalls of MFC-MRD monitoring in different clinical settings.
Catalytic Diesel and Gasoline Particulate Filters
Authors: Di Sarli Valeria
Published: September 2021

I am honored to be the Guest Editor of this Special Issue of the journal Catalysts dedicated to “Catalytic Diesel and Gasoline Particulate Filters” [...]
Design of Co3O4@SiO2 Nanorattles for Catalytic Toluene Combustion Based on Bottom-Up Strategy Involving Spherical Poly(styrene-co-acrylic Acid) Template
Authors: Rokicińska Anna , Żurowska Magdalena , Łątka Piotr , Drozdek Marek , Michalik Marek , Kuśtrowski Piotr
Published: September 2021

Bearing in mind the need to develop optimal transition metal oxide-based catalysts for the combustion of volatile organic compounds (VOCs), yolk-shell materials were proposed. The constructed composites contained catalytically active Co3O4 nanoparticles, protected against aggregation and highly dispersed in a shell made of porous SiO2, forming a specific type of nanoreactor. The bottom-up synthesis started with obtaining spherical poly(styrene-co-acrylic acid) copolymer (PS30) cores, which were then covered with the SiO2 layer. The Co3O4 active phase was deposited by impregnation using the PS30@SiO2 composite as well as hollow SiO2 spheres with the removed copolymer core. Structure (XRD), morphology (SEM), chemical composition (XRF), state of the active phase (UV-Vis-DR and XPS) and reducibility (H2-TPR) of the obtained catalysts were studied. It was proven that the introduction of Co3O4 nanoparticles into the empty SiO2 spheres resulted in their loose distribution, which facilitated the access of reagents to active sites and, on the other hand, promoted the involvement of lattice oxygen in the catalytic process. As a result, the catalysts obtained in this way showed a very high activity in the combustion of toluene, which significantly exceeded that achieved over a standard silica gel supported Co3O4 catalyst.
Effects of Extracellular Osteoanabolic Agents on the Endogenous Response of Osteoblastic Cells
Authors: Alloisio Giulia , Ciaccio Chiara , Fasciglione Giovanni Francesco , Tarantino Umberto , Marini Stefano , Coletta Massimo , Gioia Magda
Published: September 2021

The complex multidimensional skeletal organization can adapt its structure in accordance with external contexts, demonstrating excellent self-renewal capacity. Thus, optimal extracellular environmental properties are critical for bone regeneration and inextricably linked to the mechanical and biological states of bone. It is interesting to note that the microstructure of bone depends not only on genetic determinants (which control the bone remodeling loop through autocrine and paracrine signals) but also, more importantly, on the continuous response of cells to external mechanical cues. In particular, bone cells sense mechanical signals such as shear, tensile, loading and vibration, and once activated, they react by regulating bone anabolism. Although several specific surrounding conditions needed for osteoblast cells to specifically augment bone formation have been empirically discovered, most of the underlying biomechanical cellular processes underneath remain largely unknown. Nevertheless, exogenous stimuli of endogenous osteogenesis can be applied to promote the mineral apposition rate, bone formation, bone mass and bone strength, as well as expediting fracture repair and bone regeneration. The following review summarizes the latest studies related to the proliferation and differentiation of osteoblastic cells, enhanced by mechanical forces or supplemental signaling factors (such as trace metals, nutraceuticals, vitamins and exosomes), providing a thorough overview of the exogenous osteogenic agents which can be exploited to modulate and influence the mechanically induced anabolism of bone. Furthermore, this review aims to discuss the emerging role of extracellular stimuli in skeletal metabolism as well as their potential roles and provide new perspectives for the treatment of bone disorders.