bluuebunny/crossref_metadata_2025 huggingface dataset:
Hair Cortisol and DHEA-S in Foals and Mares as a Retrospective Picture of Feto-Maternal Relationship under Physiological and Pathological Conditions
Authors: Lanci Aliai , Mariella Jole , Ellero Nicola , Faoro Alice , Peric Tanja , Prandi Alberto , Freccero Francesca , Castagnetti Carolina
Published: May 2022

Equine fetal hair starts to grow at around 270 days of pregnancy, and hair collected at birth reflects hormones of the last third of pregnancy. The study aimed to evaluate cortisol (CORT) and dehydroepiandrosterone-sulfate (DHEA-S) concentrations and their ratio in the trichological matrix of foals and mares in relation to their clinical parameters; the clinical condition of the neonate (study 1); the housing place at parturition (study 2). In study 1, 107 mare-foal pairs were divided into healthy (group H; n = 56) and sick (group S; n = 51) foals, whereas in study 2, group H was divided into hospital (n = 30) and breeding farm (n = 26) parturition. Steroids from hair were measured using a solid-phase microtiter radioimmunoassay. In study 1, hair CORT concentrations measured in foals did not differ between groups and did not appear to be influenced by clinical parameters. A correlation between foal and mare hair CORT concentrations (p = 0.019; r = 0.312, group H; p = 0.006; r = 0.349, group S) and between CORT and DHEA-S concentrations in foals (p = 0.018; r = 0.282, group H; p < 0.001; r = 0.44, group S) and mares (p = 0.006; r = 0.361, group H; p = 0.027; r = 0.271, group S) exists in both groups. Increased hair DHEA-S concentrations (p = 0.033) and decreased CORT/DHEA-S ratio (p < 0.001) appear to be potential biomarkers of chronic stress in the final third of pregnancy, as well as a potential sign of resilience and allostatic load in sick foals, and deserve further attention in the evaluation of prenatal hypothalamus-pituitary-adrenal (HPA) axis activity in the equine species. In study 2, hormone concentrations in the hair of mares hospitalized for attended parturition did not differ from those that were foaled at the breeding farm. This result could be related to a too brief period of hospitalization to cause significant changes in steroid deposition in the mare’s hair.
Derivatives of Esculentin-1 Peptides as Promising Candidates for Fighting Infections from Escherichia coli O157:H7
Authors: Scotti Raffaella , Casciaro Bruno , Stringaro Annarita , Morgia Fabrizio , Mangoni Maria Luisa , Gabbianelli Roberta
Published: May 2022

New strategies are needed to fight the emergence of multidrug-resistant bacteria caused by an overuse of antibiotics in medical and veterinary fields. Due to the importance of biofilms in clinical infections, antibiofilm peptides have a great potential to treat infections. In recent years, an increased interest has emerged in antimicrobial peptides (AMPs). One of the richest sources of AMPs is represented by amphibian skin. In the present work, we investigated the effects of two peptides derived from the frog skin AMP esculentin-1, namely, Esc(1-21) and Esc(1-18), on the growth, biofilm formation, and gene expression of the non-pathogenic Escherichia coli strain K12 and of enterohemorrhagic E. coli O157:H7. Both peptides showed minimal bactericidal concentrations ranging from 4 to 8 µM for Esc(1-21) and from 32 to 64 µM for Esc(1-18). They also, at sub-MIC doses, reduced the formation of biofilm, as supported by both microbiological assays and scanning electron microscopy, while they displayed no marked activity against the planktonic form of the bacteria. Transcriptional analysis in E. coli O157:H7 showed that both AMPs induced the expression of several genes involved in the regulation of formation and dispersal of biofilm, as well as in the stress response. In conclusion, we demonstrated that these AMPs affect E. coli O157:H7 growth and biofilm formation, thus suggesting a great potential to be developed as novel therapeutics against infections caused by bacterial biofilms.
Metabolic Profile, Biotransformation, Docking Studies and Molecular Dynamics Simulations of Bioactive Compounds Secreted by CG3 Strain
Authors: Messaoudi Omar , Sudarman Enge , Patel Chirag , Bendahou Mourad , Wink Joachim
Published: May 2022

Actinobacteria isolated from untapped environments and exposed to extreme conditions such as saltpans are a promising source of novel bioactive compounds. These microorganisms can provide new molecules through either the biosynthetic pathway or the biotransformation of organic molecules. In the present study, we performed a chemical metabolic screening of secondary metabolites secreted by the new strain CG3, which was isolated from a saltpan located in the Sahara of Algeria, via high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-ESI-HRMS). The results indicated that this strain produced five new polyene macrolactams, kenalactams A–E, along with two known compounds, mitomycin C and 6″-hydroxy-4,2′,3′,4″ tetramethoxy-p-terphenyl. Furthermore, the CG3 isolate could have excellent properties for converting the aglycone isoflavone glycitein to the compounds 6,7-dimethoxy-3-(4-methoxyphenyl)chromen-4-one (50) and 6,7-dimethoxy-3-phenylchromen-4-one (54), and the isoflavone genistein can be converted to 5,7-dimethoxy-3-(4-methoxyphenyl)chromen-4-one (52). Docking studies and molecular dynamics simulations indicated that these three isoflavones, generated via biotransformation, are potent inhibitors of the target protein aromatase (CYP19A1); consequently, they can be used to prevent breast cancer risk in postmenopausal women.
Oxidative Stress in Chronic Obstructive Pulmonary Disease
Authors: Barnes Peter J.
Published: May 2022

There is a marked increase in oxidative stress in the lungs of patients with COPD, as measured by increased exhaled 8-isoprostane, ethane, and hydrogen peroxide in the breath. The lung may be exposed to exogenous oxidative stress from cigarette smoking and indoor or outdoor air pollution and to endogenous oxidative stress from reactive oxygen species released from activated inflammatory cells, particularly neutrophils and macrophages, in the lungs. Oxidative stress in COPD may be amplified by a reduction in endogenous antioxidants and poor intake of dietary antioxidants. Oxidative stress is a major driving mechanism of COPD through the induction of chronic inflammation, induction of cellular senescence and impaired autophagy, reduced DNA repair, increased autoimmunity, increased mucus secretion, and impaired anti-inflammatory response to corticosteroids. Oxidative stress, therefore, drives the pathology of COPD and may increase disease progression, amplify exacerbations, and increase comorbidities through systemic oxidative stress. This suggests that antioxidants may be effective as disease-modifying treatments. Unfortunately, thiol-based antioxidants, such as N-acetylcysteine, have been poorly effective, as they are inactivated by oxidative stress in the lungs, so there is a search for more effective and safer antioxidants. New antioxidants in development include mitochondria-targeted antioxidants, NOX inhibitors, and activators of the transcription factor Nrf2, which regulates several antioxidant genes.
Salicylic Acid Enhances Heat Stress Resistance of Pleurotus ostreatus (Jacq.) P. Kumm through Metabolic Rearrangement
Authors: Hu Yan-Ru , Wang Yue , Chen Yu-Jie , Chai Qian-Qian , Dong Hao-Zhe , Shen Jin-Wen , Qi Yuan-Cheng , Wang Feng-Qin , Wen Qing
Published: May 2022

Pleurotus ostreatus (Jacq.) P. Kumm is cultivated worldwide, and its growth is seriously threatened by heat stress. Here, we performed a comprehensive analysis to investigate the influence of the phytohormone salicylic acid (SA) in P. ostreatus under HS. The results showed that the hyphal growth recovery rate and the antioxidant capacity of P. ostreatus increased with exogenous SA application (0.01 mmol/L and 0.05 mmol/L) after HS treatment. Metabolomic and transcriptomic analyses showed that SA application (0.05 mmol/L) weakened central carbon metabolism to allow cells to survive HS efficiently. In addition, SA shifted glycolysis to one-carbon metabolism to produce ROS scavengers (GSH and NADPH) and reduced ROS production by altering mitochondrial metabolism. SA also maintained nucleotide homeostasis, led to membrane lipid remodeling, activated the MAPK pathway, and promoted the synthesis of cell-wall components. This study provides a reference for further study of SA in microorganisms.
Research on Permanent Magnet Synchronous Motor Control System Based on Adaptive Kalman Filter
Authors: Cui Jiadong , Xing Wenhao , Qin Huibin , Hua Yongzhu , Zhang Xin , Liu Xinran
Published: May 2022

A sensorless control system of a permanent magnet synchronous motor based on an extended Kalman filter (EKF) algorithm faces problems with inaccurate or mismatched process noise statistics. This problem affects the performance of the filter, resulting in an inaccurate estimation of motor speed. To address the above problem, this paper proposes a parameter-adaptive Kalman filter algorithm that does not depend on precise noise system covariance. This method can significantly reduce the negative impact of the noise statistical mismatch on motor speed estimation. In addition, the method uses adaptive covariance prediction and removes the original covariance checks in the EKF, thus reducing the calculation burden. The simulation results show that, compared with the traditional EKF algorithm, the algorithm proposed in this article can effectively reduce the steady-state jitter and improve the filtering adaptability and calculation accuracy.
Accounting for Patient Engagement in Randomized Controlled Trials Evaluating Digital Cognitive Behavioral Therapies
Authors: Sverdlov Oleksandr , Ryeznik Yevgen
Published: May 2022

Background: Cognitive behavioral therapy (CBT) can be a useful treatment option for various mental health disorders. Modern advances in information technology and mobile communication enable delivery of state-of-the-art CBT programs via smartphones, either as stand-alone or as an adjunct treatment augmenting traditional sessions with a therapist. Experimental CBTs require careful assessment in randomized clinical trials (RCTs). Methods: We investigate some statistical issues for an RCT comparing efficacy of an experimental CBT intervention for a mental health disorder against the control. Assuming a linear model for the clinical outcome and patient engagement as an influential covariate, we investigate two common statistical approaches to inference—analysis of covariance (ANCOVA) and a two-sample t-test. We also study sample size requirements for the described experimental setting. Results: Both ANCOVA and a two-sample t-test are appropriate for the inference on treatment difference at the average observed level of engagement. However, ANCOVA produces estimates with lower variance and may be more powerful. Furthermore, unlike the t-test, ANCOVA allows one to perform treatment comparison at the levels of engagement other than the average level observed in the study. Larger sample sizes may be required to ensure experiments are sufficiently powered if one is interested in comparing treatment effects for different levels of engagement. Conclusions: ANCOVA with proper adjustment for engagement should be used for the for the described experimental setting. Uncertainty on engagement patterns should be taken into account at the study design stage.
A Compact Numerical Scheme for the Heat Transfer of Mixed Convection Flow in Quantum Calculus
Authors: Nawaz Yasir , Arif Muhammad Shoaib , Abodayeh Kamaleldin
Published: May 2022

This contribution aims to propose a compact numerical scheme to solve partial differential equations (PDEs) with q-spatial derivative terms. The numerical scheme is based on the q-Taylor series approach, and an operator is proposed, which is useful to discretize second-order spatial q-derivative terms. The compact numerical scheme is constructed using the proposed operator, which gives fourth-order accuracy for second-order q-derivative terms. For time discretization, Crank–Nicolson, and Runge–Kutta methods are applied. The stability for the scalar case and convergence conditions for the system of equations are provided. The mathematical model for the heat transfer of boundary layer flow under the effects of non-linear mixed convection is given in form of PDEs. The governing equations are transformed into dimensionless PDEs using suitable transformations. The velocity and temperature profiles with variations of mixed convection parameters and the Prandtl number are drawn graphically. From considered numerical experiments, it is pointed out that the proposed scheme in space and Crank–Nicolson in time is more effective than that in which discretization for the time derivative term is performed by applying the Runge–Kutta scheme. A comparison with existing schemes is carried out as part of the research. For future fluid-flow investigations in an enclosed industrial environment, the results presented in this study may serve as a useful guide.
A Novel Anti-Jamming Decision-Making Algorithm Based on Knowledge Graph Technology
Authors: Niu Yingtao , Feng Xijin , Kou Shaoqin , Xiang Peng
Published: May 2022

Wireless communications are increasingly vulnerable to malicious jamming attacks due to the inherent openness and broadcast nature. In this regard, a novel anti-jamming scheme based on knowledge graph is proposed in this paper, where the knowledge graph which contains the prior knowledge of the commonly-used jamming patterns is utilized to make the fast anti-jamming decision with low complexity. Specifically, for the known jamming patterns, the anti-jamming strategy is directly extracted based on the search from the knowledge graph by using the sensing information. On the other hand, for the unknown jamming patterns, a time-frequency domain feature extraction method is first proposed to extract the jamming feature and match the jamming patterns in the knowledge graph. As such, multiple anti-jamming strategies can be obtained by the knowledge graph search. Finally, the optimal strategy can be achieved by the two communication decision criteria-based strategy fusion. The simulation results showed that the time-frequency domain feature extraction method can well extract the time-frequency domain feature of the jamming pattern, and the proposed algorithm has high decision accuracy and robustness.
Structural Design and Dynamic Simulation Optimization of the Triggering Device in a Pressure-Holding Controller for Deep in Situ Coring
Authors: Xu Meng , Li Yanyan , Chen Ling , Yang Xun , Duan Zengfeng , Fu Chenghang , Wang Dingming
Published: May 2022

As Earth’s shallow coal resources are gradually depleted, humans turn their mining operations to deeper regions. However, because the mechanics of deep-rock masses have not been fully established, the development of deep resources lacks theoretical guidance, and the continuity of such engineering activities is poor. The basis of deep-rock mechanics theory is to achieve deep in situ rock fidelity coring (including the maintenance of pore pressure and temperature). To achieve this goal, deep in situ pressure-holding coring technology is needed. The pressure-holding controller is the key corer component for realizing deep in situ pressure-holding and coring technology. The flap-valve-type pressure-holding controller driven by an elastic force or gravity alone is not enough to provide the initial sealing pressure for the sealing surface. Therefore, a trigger mechanism that assists the pressure-holding controller in achieving closing and initial sealing was designed. Then, the action and friction characteristics of the triggering mechanism were calculated according to the experimental dynamics simulation calculations of different closing characteristics that are affected by gravity in pressure-holding controller space. Optimization was conducted to determine the optimal values of the trigger mechanism spring stiffness, wedge angle, and other parameters. The mechanism can provide technical support for deep pressure-holding coring and improve the pressure-holding power of deep in situ rock coring.
The Effectiveness of Rubber Bumpers in Reducing the Effects of Earthquake-Induced Pounding between Base-Isolated Buildings
Authors: Khatami Seyed Mohammad , Naderpour Hosein , Mortezaei Alireza , Sharbatdar Alireza , Lasowicz Natalia , Jankowski Robert
Published: May 2022

The methods for preventing earthquake-induced structural pounding between two adjacent buildings include ensuring a sufficient separation distance between them or decreasing their relative displacement during seismic excitation. Some equations or even specific values of such gap sizes between two buildings have been introduced so as to avoid collisions. Increasing the stiffness of buildings, using tuned mass dampers, applying liquid dampers, or decreasing the mass of the structures may reduce lateral displacements, and therefore pounding can be prevented. On the other hand, the application of base isolation systems may result in the elongation of the natural period of the building, thus increasing the probability of structural pounding. The aim of the present paper is to verify the effectiveness of using rubber bumpers to reduce the negative effects of earthquake-induced pounding between base-isolated buildings. The analysis was conducted for different gap sizes between buildings, as well as for various values of the thickness, number and stiffness of rubber bumpers. The results of the study show that the peak impact force decreases with increasing thickness, stiffness, and number of bumpers. Moreover, the peak impact forces are reduced with increasing gap size. The results of the investigation clearly indicate that the use of additional rubber bumpers can be considered an effective method for reducing the negative effects of earthquake-induced pounding between base-isolated buildings.
Detection and Factors That Induce Stenocarpella spp. Survival in Maize Stubble and Soil Suppressiveness under Tropical Conditions
Authors: Pinto Felipe Augusto Moretti Ferreira , Porto Victor Biazzotto Correia , Guimarães Rafaela Araújo , Siqueira Carolina da Silva , Faria Mirian Rabelo de , Machado José da Cruz , Medeiros Henrique Novaes , Silva Dagma Dionísia da , Santos Neto Helon , Pozza Edson Ampelio , Medeiros Flávio Henrique Vasconcelos de
Published: May 2022

Stenocarpella spp. causes stalk and ear rot in maize and overwinters in stubble during the off-season. Understanding the factors that guide saprophytic colonization is a crucial strategy for management. In this study, we analyzed the abiotic factors and crop management practices in relation to the inoculum of Stenocarpella spp. in stubble by qPCR. Soil samples were used for suppressiveness tests against Fusarium verticillioides, Fusarium graminearum, and Stenocarpella maydis. In the 29 fields, different levels of Stenocarpella spp. were detected. Only three fields were considered suppressive for the three pathogens. Heat maps showed that soil suppressiveness was inversely related to the pathogen concentration, and the suppressiveness of one pathogen was correlated with the suppressiveness of other pathogens. Under no-tillage systems in which rotation with soybeans was adopted, Stenocarpella spp. were detected at lower concentrations than in areas that adopted no-tillage systems with maize monocultures. While in tillage systems, the maize–maize monocropping increases the inoculum level of Stenocarpella spp. Crop rotation is a factor related to the observed reduction in the pathogen concentration and increases in the broad-spectrum antagonistic microbial communities. These communities guide the suppressiveness of soil-borne diseases in maize fields cultivated under tropical conditions.
Application of Improved MFDFA and D-S Evidence Theory in Fault Diagnosis
Authors: Liang Xing , Luo Yuanxing , Deng Fei , Li Yan
Published: May 2022

To improve the accuracy of centrifugal pump fault diagnosis, a novel fault diagnosis method based on improved multiple fractal detrended fluctuation analysis (MFDFA), the fusion of multi-sensing information derived from the back propagation (BP) neural network and the Dempster–Shafter (D-S) evidence theory, is accordingly proposed. Firstly, the multifractal spectral parameters of four sensor signals under four different operating conditions were extracted as centrifugal pump fault feature vectors using improved MFDFA and input to the BP neural network. Then, the basic trust assignment function was constructed by calculating trustworthiness (both local and global) as priori information, which is based on the output results of the neural networks specific to of each group of sensors. Finally, the basic trust assignment function was fused with decision processing in accordance with the D-S evidence combination rule in order to effectively achieve the multi-sensor information fusion centrifugal pump fault diagnosis. The experimental results show the multiple fractal spectrum feature parameters extracted by the improved MFDFA can accurately reflect the signal essence, and can be used as the fault feature vector. On this basis, this multi-sensor fault diagnosis reduces the uncertainty of fault classification and demonstrates improved accuracy compared to the single-sensor fault diagnosis thanks to being based on a combination of the BP neural networks and D-S evidence theory. Thereby, this method can facilitate accurate diagnosis of the centrifugal pump fault type with high confidence, subsequently providing a novel and alternative method to existing methods of diagnosis.
Application of Laser-Induced Breakdown Spectroscopy Combined with Chemometrics for Identification of Penicillin Manufacturers
Authors: Wei Kai , Wang Qianqian , Teng Geer , Xu Xiangjun , Zhao Zhifang , Chen Guoyan
Published: May 2022

Due to the differences in raw materials and production processes, the quality of the same type of drug produced by different manufacturers is different. In drug supervision, determining the manufacturer can help to trace drug quality issues. In this study, a method for the quick identification of drug manufacturers based on laser-induced breakdown spectroscopy (LIBS) was proposed for the first time. We obtained the LIBS spectra from 12 samples of three types of penicillin (phenoxymethylpenicillin potassium tablets, amoxicillin capsules, and amoxicillin and clavulanate potassium tablets) produced by 10 manufacturers. The LIBS characteristic lines of the three types of penicillin were ranked by importance based on the decrease in the Gini index of random forest (RF). Three classifiers—the linear discriminant analysis (LDA), support vector machine (SVM) and artificial neural network (ANN)—were used to identify the different manufacturers of the three types of penicillin. RF-ANN provided the best classification result and an accuracy of 100% in penicillin manufacturer identification. The results show that LIBS combined with chemometrics could be used in the identification of penicillin manufacturers, and this method has application potential in drug quality supervision.
Co-Production System Based on Lean Methane and Biogas for Power Generation in Coal Mines
Authors: Yin Feifei , Nie Baisheng , Wei Yueying , Lin Shuangshuang
Published: May 2022

The problem of low efficiency of coal mine methane utilization is caused by the concentration of methane of less than 10%, or a concentration that varies dramatically directly emitted into the atmosphere. This work deals with the concept of a co-production system that blends lean methane and biogas to produce electric energy. It is recommended to add the biogas generated by straws around the mines in a controlled manner to the lean methane flow to obtain the desired gas concentration in order to generate electricity. Potential electricity generation and reduced greenhouse gas emissions were also evaluated. The result shows that the co-production system can significantly improve the utilization efficiency of lean methane in coal mines; the average use of pure methane in three coal mines is 0.18, 1.12, and 5.32 million m3 every year, respectively, and the emission reduction effect of carbon dioxide (CO2) equivalent is, respectively, 3081, 18,796, and 89,050 tons. The electricity generated and the economic environmental benefits of the co-production system are remarkable, and it has economic feasibility and broad perspectives for popularization. It not only has the advantage of improving the utilization rate of methane and biomass and providing power supply and heat source for mines, but also has practical significance in terms of saving energy, reducing environmental pollution, adjusting the energy structure, and achieving the target of carbon emission peak and carbon neutrality.
Investigating Spatial Heterogeneity of the Environmental Kuznets Curve for Haze Pollution in China
Authors: Abdul-Rahim Abdul Samad , Kim Yoomi , Yue Long
Published: May 2022

This study investigates the environmental Kuznets curve (EKC) for haze in 31 cities and provinces across China using the spatial data for a period of 15 years, from 2000 to 2014. We utilized the geographically weighted regression (GWR) model to consider the spatial non-stationary characteristics of the air quality in a vast territory. This approach allowed us to verify the region-specific characteristics, while the global model estimated the average relationship across the entire nation. Although the EKC for haze was statistically significant in the global models, the results only confirmed the existence of an EKC between the overall air quality and economic performance. Thus, it was difficult to determine the regional differences in an EKC. The results of the GWR model found the spatial variability of each variable and showed significant spatial heterogeneity in the EKC across regions. Although six regions—Beijing, Gansu, Heilongjiang, Jiangxi, Jilin, Liaoning, Shanghai, Tianjin, Xinjiang, and Zhejiang—showed inverted U-shaped EKCs, these were only statistically significant in three big cities—Beijing, Tianjin, and Shanghai. The results demonstrated no EKCs in the other 25 provinces and cities. These results provide strong empirical evidence that there is significant spatial heterogeneity in the EKC of China. Thus, a more regionally specialized air pollution control policy is required to create an effective policy for balanced economic growth in China.
Ceratocystiopsis quercina sp. nov. Associated with Platypus cylindrus on Declining Quercus suber in Portugal
Authors: Inácio Maria L. , Marcelino José , Lima Arlindo , Sousa Edmundo , Nóbrega Filomena
Published: May 2022

Platypus cylindrus is the most common ambrosia beetle in stands of Quercus suber in Portugal. This insect farms specialized fungi in sapwood galleries, using its mycangia to carry and store these organisms. Some ectosymbiotic fungi carried by P. cylindrus are phytopathogenic and cause extensive tree mortality and severe economic losses. To understand the role of P. cylindrus fungal symbionts in stands of Q. suber we examined beetle galleries present in declining and/or dying cork oak trees during field surveys. Logs with active galleries were obtained in situ and from captured emerging beetles. Insects were aseptically dissected, and their mycangia and intestine were retrieved. Morphological and molecular profiles of fungal isolates obtained from cultured insect parts were carried out to accurately characterize and identify isolated fungi. Molecular characterizations were performed with DNA sequence data from four loci, i.e., LSU, SSU, 5.8S-ITS2-28S, and TUB. Morphological results consistently showed a collection of Ophiostoma-like fungal axenic isolates, while phylogenies inferred that this collection constitutes an undescribed taxon reported herein for the first time in association with P. cylindrus in Portuguese cork oak stands. The novel species was erected as Ceratocystiopsis quercina sp. nov. and constitutes a new phytopathogenic fungal species associated with symptoms of vegetative cork oak decline.
Altered Expression of Protamine-like and Their DNA Binding Induced by Cr(VI): A Possible Risk to Spermatogenesis?
Authors: Moriello Claudia , Costabile Martina , Spinelli Michele , Amoresano Angela , Palumbo Giancarlo , Febbraio Ferdinando , Piscopo Marina
Published: May 2022

Chromium (VI) is the most dangerous oxidation state among the stable forms of chromium. In this work, we evaluated the effect of exposing Mytilus galloprovincialis for 24 h to 1, 10, and 100 nM chromium (VI) on the properties of Protamine-like (PLs) and their gene levels in the gonads. Specifically, we analyzed, by AU-PAGE and SDS-PAGE, PLs extracted from unexposed and exposed mussels. In addition, via EMSA, we evaluated the ability of PLs to bind DNA and also verified their potential to protect DNA from oxidative damage. Finally, we assessed possible alterations in gonadal expression of mt10, hsp70, and genes encoding for PLs-II/PL-IV and PL-III. We found that for all experimental approaches the most relevant alterations occurred after exposure to 1 nM Cr(VI). In particular, a comigration of PL-II with PL-III was observed by SDS-PAGE; and a reduced ability of PLs to bind and protect DNA from oxidative damage was recorded. This dose of chromium (VI) exposure was also the one that produced the greatest alterations in the expression of both mt10 and PL-II/PL-IV encoding genes. All of these changes suggest that this dose of chromium (VI) exposure could affect the reproductive health of Mytilus galloprovincialis.
CAPTURE of the Human U2 snRNA Genes Expands the Repertoire of Associated Factors
Authors: Guiro Joana , Fagbemi Mathias , Tellier Michael , Zaborowska Justyna , Barker Stephanie , Fournier Marjorie , Murphy Shona
Published: May 2022

In order to identify factors involved in transcription of human snRNA genes and 3′ end processing of the transcripts, we have carried out CRISPR affinity purification in situ of regulatory elements (CAPTURE), which is deadCas9-mediated pull-down, of the tandemly repeated U2 snRNA genes in human cells. CAPTURE enriched many factors expected to be associated with these human snRNA genes including RNA polymerase II (pol II), Cyclin-Dependent Kinase 7 (CDK7), Negative Elongation Factor (NELF), Suppressor of Ty 5 (SPT5), Mediator 23 (MED23) and several subunits of the Integrator Complex. Suppressor of Ty 6 (SPT6); Cyclin K, the partner of Cyclin-Dependent Kinase 12 (CDK12) and Cyclin-Dependent Kinase 13 (CDK13); and SWI/SNF chromatin remodelling complex-associated SWI/SNF-related, Matrix-associated, Regulator of Chromatin (SMRC) factors were also enriched. Several polyadenylation factors, including Cleavage and Polyadenylation Specificity Factor 1 (CPSF1), Cleavage Stimulation Factors 1 and 2 (CSTF1,and CSTF2) were enriched by U2 gene CAPTURE. We have already shown by chromatin immunoprecipitation (ChIP) that CSTF2—and Pcf11 and Ssu72, which are also polyadenylation factors—are associated with the human U1 and U2 genes. ChIP-seq and ChIP-qPCR confirm the association of SPT6, Cyclin K, and CDK12 with the U2 genes. In addition, knockdown of SPT6 causes loss of subunit 3 of the Integrator Complex (INTS3) from the U2 genes, indicating a functional role in snRNA gene expression. CAPTURE has therefore expanded the repertoire of transcription and RNA processing factors associated with these genes and helped to identify a functional role for SPT6.
In Vivo Evaluation of Fibroblast Growth Factor Receptor Inhibition in Mouse Xenograft Models of Gastrointestinal Stromal Tumor
Authors: Schöffski Patrick , Gebreyohannes Yemarshet , Van Looy Thomas , Manley Paul , Growney Joseph D. , Squires Matthew , Wozniak Agnieszka
Published: May 2022

Advanced gastrointestinal stromal tumors (GIST) are typically treated with tyrosine kinase inhibitors, and imatinib is the most commonly used standard of care in first line treatments. The use of this and other tyrosine kinase inhibitors is associated with objective tumor responses and prolongation of progression-free and overall survival, but the treatment of metastatic disease is non-curative due to the selection or acquisition of secondary mutations and the activation of alternative kinase signaling pathways, leading to resistance and disease progression after an initial response. The present preclinical study evaluated the potential use of the fibroblast growth factor receptor inhibitors infigratinib and dovitinib alone or in combination with the mitogen-activated protein kinase inhibitor binimetinib in mouse models of GIST with different sensitivity or resistance to imatinib. Patient- and cell-line-derived GIST xenografts were established by bilateral, subcutaneous transplantation of human GIST tissue in female adult nu/nu NMRI mice. The mice were treated with dovitinib, infigratinib, or binimetinib, either alone or in combination with imatinib. The safety of treated animals was assessed by well-being inspection and body weight measurement. Antitumor effects were assessed by caliper-based tumor measurement. H&E staining and immunohistochemistry were used for assessing anti-mitotic and pro-apoptotic activity of the experimental treatments. Western blotting was used for assessing effects of the agents on kinase signaling pathways. Anti-angiogenic activity was assessed by measuring tumor vessel density. Dovitinib was found to have antitumor efficacy in GIST xenografts characterized by different imatinib resistance patterns. Dovitinib had better efficacy than imatinib (both at standard and increased dose) and was found to be well tolerated. Dovitinib had better efficacy in a KIT exon 9 mutant model, highlighting a role of patient selection in clinical GIST trials with the agent. In a model with KIT exon 11 and 17 mutations, dovitinib induced tumor necrosis, most likely due to anti-angiogenic effects. Additive effects combining dovitinib with binimetinib were limited.
Multilayered Mesoporous Composite Nanostructures for Highly Sensitive Label-Free Quantification of Cardiac Troponin-I
Authors: Saeidi Mohsen , Amidian Mohammad Ali , Sheybanikashani Sana , Mahdavi Hossein , Alimohammadi Homayoon , Syedmoradi Leila , Mohandes Fatemeh , Zarrabi Ali , Tamjid Elnaz , Omidfar Kobra , Simchi Abdolreza
Published: May 2022

Cardiac troponin-I (cTnI) is a well-known biomarker for the diagnosis and control of acute myocardial infarction in clinical practice. To improve the accuracy and reliability of cTnI electrochemical immunosensors, we propose a multilayer nanostructure consisting of Fe3O4-COOH labeled anti-cTnI monoclonal antibody (Fe3O4-COOH-Ab1) and anti-cTnI polyclonal antibody (Ab2) conjugated on Au-Ag nanoparticles (NPs) decorated on a metal–organic framework (Au-Ag@ZIF-67-Ab2). In this design, Fe3O4-COOH was used for separation of cTnI in specimens and signal amplification, hierarchical porous ZIF-67 extremely enhanced the specific surface area, and Au-Ag NPs synergically promoted the conductivity and sensitivity. They were additionally employed as an immobilization platform to enhance antibody loading. Electron microscopy images indicated that Ag-Au NPs with an average diameter of 1.9 ± 0.5 nm were uniformly decorated on plate-like ZIF-67 particles (with average size of 690 nm) without any agglomeration. Several electrochemical assays were implemented to precisely evaluate the immunosensor performance. The square wave voltammetry technique exhibited the best performance with a sensitivity of 0.98 mA mL cm−2 ng−1 and a detection limit of 0.047 pg mL−1 in the linear range of 0.04 to 8 ng mL−1.
Investigating the Migraine Cycle over 21 Consecutive Days Using Proton Magnetic Resonance Spectroscopy and Resting-State fMRI: A Pilot Study
Authors: Filippi Vera , Steiger Ruth , Beliveau Vincent , Frank Florian , Kaltseis Katharina , Gizewski Elke R. , Broessner Gregor
Published: May 2022

Recent neuroimaging studies have revealed important aspects of the underlying pathophysiological mechanisms of migraine suggesting abnormal brain energy metabolism and altered functional connectivity. Proton magnetic resonance spectroscopy (1H-MRS) studies investigated migraine patients in the interictal or ictal state. This first-of-its-kind study aimed to investigate the whole migraine cycle using 1H-MRS and resting-state functional magnetic resonance imaging (fMRI). A migraine patient underwent 1H-MRS and resting-state fMRI for 21 consecutive days, regardless of whether he was in an interictal or ictal state. Metabolite ratios were assessed and compared to the intrinsic connectivity of subcortical brain areas. Probable migraine phase-dependent changes in N-acetyl aspartate (NAA)/total creatine (tCr) and choline (Cho)/tCr levels are found in the left occipital lobe and left basal ganglia. NAA reflects neuronal integrity and Cho cellular membrane turnover. Such abnormalities may increase the susceptibility to excitatory migraine triggers. Functional connectivity between the right hippocampus and right or left pallidum was strongly correlated to the NAA/Cho ratio in the right thalamus, suggesting neurochemical modulation of these brain areas through thalamic connections. To draw statistically significant conclusions a larger cohort is needed.
Gender Differences in the Relationship between Interpersonal Trust and Innovative Behavior: The Mediating Effects of Affective Organizational Commitment and Knowledge-Sharing
Authors: Yuan Hao , Ma Dan
Published: May 2022

The innovative behavior of employees is the micro-foundation of enterprise innovation. The objective of this study was to assess the role of gender differences in the effect of interpersonal trust on employee innovation and the mediating roles of organizational commitment and knowledge-sharing. This study tested research hypotheses with a multi-group structural equation model, using data collected from 688 participants in Shanghai, China. The results showed that interpersonal trust had significant impacts on affective organizational commitment, knowledge-sharing and innovation behavior. Affective organizational commitment and knowledge-sharing mediated the effect of interpersonal trust on employee innovation. Furthermore, the direct impact of interpersonal trust on innovative behavior was significantly higher for women than for men, whereas males’ affective organizational commitment increased their knowledge-sharing behaviors. In addition, there were no significant gender differences in the effect of interpersonal trust on organizational commitment and in the effect of knowledge-sharing on innovative behavior. These results confirmed that interpersonal trust was more important for female knowledge-sharing and innovative behavior, and affective organizational commitment was more important for male knowledge-sharing.
Mammary Paget’s Disease: An Update
Authors: Markarian Sione , Holmes Dennis R.
Published: May 2022

Mammary Paget’s Disease is a non-invasive cutaneous malignancy of the breast involving the nipple-areolar complex that is commonly mistaken for benign breast conditions, leading to delay in diagnosis. This review article discusses Paget’s disease etiology, clinical presentation, differential diagnosis, diagnostic work-up, natural history and prognosis. This article also discusses evolving strategies for the surgical and non-surgical management of Paget’s disease.
13C Natural Isotope Abundance in Urothelium as a New Marker in the Follow-Up of Patients with Bladder Cancer
Authors: Madej Adam , Forma Ewa , Golberg Michał , Kamiński Rafał , Paneth Piotr , Kobos Józef , Różański Waldemar , Lipiński Marek
Published: May 2022

Bladder cancer (BC) is the most common urological malignancy and has a high incidence of recurrence. BC cells alter their nutrient uptake and metabolic pathways in order to continue the production of sufficient levels of ATP and metabolic intermediates for proliferation and survival. Changes in metabolic pathways regarding the rate of the enzymatic reaction and transport lead to differences in the content of natural isotopes (13C, 15N, 34S) between normal and cancerous tissues. The assessment of the stable isotopes of carbon, nitrogen, and sulfur in normal urothelium and bladder cancer samples was performed using Isotope Ratio Mass Spectrometry (IRMS). The natural abundance of 15N and 13C was decreased in bladder cancer samples when compared to normal urothelium. No significant correlation was observed in BC specimens depending on the tumor grade and stage. Samples derived from bladder tumors and normal urothelium had a different pattern of 15N and 13C isotope abundance. Decreased 13C natural isotopes in the normal urothelium of BC patients were significantly associated with a shorter DFS. Our results suggest that isotopic analysis of normal urothelium of BC patients can be used to predict bladder cancer recurrence.
Definition of the Prognostic Role of MGMT Promoter Methylation Value by Pyrosequencing in Newly Diagnosed IDH Wild-Type Glioblastoma Patients Treated with Radiochemotherapy: A Large Multicenter Study
Authors: Caccese Mario , Simonelli Matteo , Villani Veronica , Rizzato Simona , Ius Tamara , Pasqualetti Francesco , Russo Marco , Rudà Roberta , Amoroso Rosina , Bellu Luisa , Bertorelle Roberta , Cavallin Francesco , Dipasquale Angelo , Carosi Mariantonia , Pizzolitto Stefano , Cesselli Daniela , Persico Pasquale , Casini Beatrice , Fassan Matteo , Zagonel Vittorina , Lombardi Giuseppe
Published: May 2022

Background. O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) methylation status is a predictive factor for alkylating treatment efficacy in glioblastoma patients, but its prognostic role is still unclear. We performed a large, multicenter study to evaluate the association between MGMT methylation value and survival. Methods. We evaluated glioblastoma patients with an assessment of MGMT methylation status by pyrosequencing from nine Italian centers. The inclusion criteria were histological diagnosis of IDH wild-type glioblastoma, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤2, and radio-chemotherapy treatment with temozolomide. The relationship between OS and MGMT was investigated with a time-dependent Receiver Operating Characteristics (ROC) curve and Cox regression models. Results. In total, 591 newly diagnosed glioblastoma patients were analyzed. The median OS was 16.2 months. The ROC analysis suggested a cut-off of 15% for MGMT methylation. The 2-year Overall Survival (OS) was 18.3% and 51.8% for MGMT methylation <15% and ≥15% (p < 0.0001). In the multivariable analysis, MGMT methylation <15% was associated with impaired survival (p < 0.00001). However, we also found a non-linear association between MGMT methylation and OS (p = 0.002): median OS was 14.8 months for MGMT in 0–4%, 18.9 months for MGMT in 4–40%, and 29.9 months for MGMT in 40–100%. Conclusions. Our findings suggested a non-linear relationship between OS and MGMT promoter methylation, which implies a varying magnitude of prognostic effect across values of MGMT promoter methylation by pyrosequencing in newly diagnosed IDH wild-type glioblastoma patients treated with chemoradiotherapy.
Current and Emerging Approaches to Study Microenvironmental Interactions and Drug Activity in Classical Hodgkin Lymphoma
Authors: Casagrande Naike , Borghese Cinzia , Aldinucci Donatella
Published: May 2022

Classic Hodgkin lymphoma is characterized by a few tumor cells surrounded by a protective and immunosuppressive tumor microenvironment (TME) composed by a wide variety of noncancerous cells that are an active part of the disease. Therefore, new techniques to study the cHL-TME and new therapeutic strategies targeting specifically tumor cells, reactivating the antitumor immunity, counteracting the protective effects of the TME, were developed. Here, we describe new methods used to study the cell composition, the phenotype, and the spatial distribution of Hodgkin and Reed–Sternberg (HRS) cells and of noncancerous cells in tumor tissues. Moreover, we propose a classification, with increasing complexity, of the in vitro functional studies used to clarify the interactions leading not only to HRS cell survival, growth and drug resistance, but also to the immunosuppressive tumor education of monocytes, T lymphocytes and fibroblasts. This classification also includes new 3-dimensional (3D) models, obtained by cultivating HRS cells in extracellular matrix scaffolds or in sponge scaffolds, under non-adherent conditions with noncancerous cells to form heterospheroids (HS), implanted in developing chick eggs (ovo model). We report results obtained with these approaches and their applications in clinical setting.
Tooth Loss and Risk of Lung Cancer among Urban Chinese Adults: A Cohort Study with Meta-Analysis
Authors: Yoon Hyung-Suk , Shu Xiao-Ou , Gao Yu-Tang , Yang Gong , Cai Hui , Shi Jiajun , Yang Jae Jeong , Rothman Nathaniel , Lan Qing , Zheng Wei , Cai Qiuyin
Published: May 2022

Epidemiological evidence on tooth loss and lung cancer risk remains limited, especially for smoking-specific associations. To investigate the association between tooth loss and lung cancer risk by smoking status, we first analyzed data from the Shanghai Men’s Health Study (n = 49,868) and the Shanghai Women’s Health Study (n = 44,309). Cox regression models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer risk in relation to tooth loss. We also conducted a meta-analysis to summarize epidemiologic findings to date, incorporating results from the current study and six previously published studies. For 7.3 median follow-up years, 973 incident lung cancer cases (613 men and 360 women) were ascertained. After adjustment for major covariates, tooth loss was associated with an increased risk of lung cancer among men (HR [95% CI] for >10 teeth vs. none = 1.59 [1.21–2.11]) but not among women (0.86 [0.50–1.46]). The positive association was stronger among male current smokers (1.75 [1.26–2.45], p-interaction by smoking status = 0.04). In a meta-analysis incorporating 4052 lung cancer cases and 248,126 non-cases, tooth loss was associated with a 1.64-fold increased risk of developing lung cancer (relative risk [RR, 95% CI] for the uppermost with the lowest category = 1.64 [1.44–1.86]). The positive association was more evident among current smokers (1.86 [1.41–2.46]), but no significant associations were found among never or former smokers. Our findings suggest that tooth loss may be associated with an increased risk of lung cancer, and the association could be modified by smoking status.
Immunotherapy in Pancreatic Cancer: Why Do We Keep Failing? A Focus on Tumor Immune Microenvironment, Predictive Biomarkers and Treatment Outcomes
Authors: Di Federico Alessandro , Mosca Mirta , Pagani Rachele , Carloni Riccardo , Frega Giorgio , De Giglio Andrea , Rizzo Alessandro , Ricci Dalia , Tavolari Simona , Di Marco Mariacristina , Palloni Andrea , Brandi Giovanni
Published: May 2022

The advent of immunotherapy and targeted therapies has dramatically changed the outcomes of patients affected by many malignancies. Pancreatic cancer (PC) remains one the few tumors that is not treated with new generation therapies, as chemotherapy still represents the only effective therapeutic strategy in advanced-stage disease. Agents aiming to reactivate the host immune system against cancer cells, such as those targeting immune checkpoints, failed to demonstrate significant activity, despite the success of these treatments in other tumors. In many cases, the proportion of patients who derived benefits in early-phase trials was too small and unpredictable to justify larger studies. The population of PC patients with high microsatellite instability/mismatch repair deficiency is currently the only population that may benefit from immunotherapy; nevertheless, the prevalence of these alterations is too low to determine a real change in the treatment scenario of this tumor. The reasons for the unsuccess of immunotherapy may lie in the extremely peculiar tumor microenvironment, including distinctive immune composition and cross talk between different cells. These unique features may also explain why the biomarkers commonly used to predict immunotherapy efficacy in other tumors seem to be useless in PC. In the current paper, we provide a comprehensive and up-to-date review of immunotherapy in PC, from the analysis of the tumor immune microenvironment to immune biomarkers and treatment outcomes, with the aim to highlight that simply transferring the knowledge acquired on immunotherapy in other tumors might not be a successful strategy in patients affected by PC.