bluuebunny/crossref_metadata_2025 huggingface dataset:
Variable Weight Matter–Element Extension Model for the Stability Classification of Slope Rock Mass
Authors: Yang Shan , Xu Zitong , Su Kaijun
Published: November 2021

The slope stability in an open-pit mine is closely related to the production safety and economic benefit of the mine. As a result of the increase in the number and scale of mine slopes, slope instability is frequently encountered in mines. Therefore, it is of scientific and social significance to strengthen the study of the stability of the slope rock mass. To accurately classify the stability of the slope rock mass in an open-pit mine, a new stability evaluation model of the slope rock mass was established based on variable weight and matter–element extension theory. First, based on the main evaluation indexes of geology, the environment, and engineering, the stability evaluation index system of the slope rock mass was constructed using the corresponding classification criteria of the evaluation index. Second, the constant weight of the evaluation index value was calculated using extremum entropy theory, and variable weight theory was used to optimize the constant weight to obtain the variable weight of the evaluation index value. Based on matter–element extension theory, the comprehensive correlation between the upper and lower limit indexes in the classification criteria and each classification was calculated, in addition to the comprehensive correlation between the rock mass indexes and the stability grade of each slope. Finally, the grade variable method was used to calculate the grade variable interval corresponding to the classification criteria of the evaluation index and the grade variable value of each slope rock mass, so as to determine the stability grade of the slope rock. The comparison results showed that the classification results of the proposed model are in line with engineering practice, and more accurate than those of the hierarchical-extension model and the multi-level unascertained measure-set pair analysis model.
A Smart Helmet-Based PLS-BPNN Error Compensation Model for Infrared Body Temperature Measurement of Construction Workers during COVID-19
Authors: Li Li , Yu Jiahui , Cheng Hang , Peng Miaojuan
Published: November 2021

In the context of the long-term coexistence between COVID-19 and human society, the implementation of personnel health monitoring in construction sites has become one of the urgent needs of current construction management. The installation of infrared temperature sensors on the helmets required to be worn by construction personnel to track and monitor their body temperature has become a relatively inexpensive and reliable means of epidemic prevention and control, but the accuracy of measuring body temperature has always been a problem. This study developed a smart helmet equipped with an infrared temperature sensor and conducted a simulated construction experiment to collect data of temperature and its influencing factors in indoor and outdoor construction operation environments. Then, a Partial Least Square–Back Propagation Neural Network (PLS-BPNN) temperature error compensation model was established to correct the temperature measurement results of the smart helmet. The temperature compensation effects of different models were also compared, including PLS-BPNN with Least Square Regression (LSR), Partial Least Square Regression (PLSR), and single Back Propagation Neural Network (BPNN) models. The results showed that the PLS-BPNN model had higher accuracy and reliability, and the determination coefficient of the model was 0.99377. After using PLS-BPNN model for compensation, the relative average error of infrared body temperature was reduced by 2.745 °C and RMSE was reduced by 0.9849. The relative error range of infrared body temperature detection was only 0.005~0.143 °C.
Bayesian Inference under Small Sample Sizes Using General Noninformative Priors
Authors: He Jingjing , Wang Wei , Huang Min , Wang Shaohua , Guan Xuefei
Published: November 2021

This paper proposes a Bayesian inference method for problems with small sample sizes. A general type of noninformative prior is proposed to formulate the Bayesian posterior. It is shown that this type of prior can represent a broad range of priors such as classical noninformative priors and asymptotically locally invariant priors and can be derived as the limiting states of normal-inverse-Gamma conjugate priors, allowing for analytical evaluations of Bayesian posteriors and predictors. The performance of different noninformative priors under small sample sizes is compared using the likelihood combining both fitting and prediction performances. Laplace approximation is used to evaluate the likelihood. A realistic fatigue reliability problem was used to illustrate the method. Following that, an actual aeroengine disk lifing application with two test samples is presented, and the results are compared with the existing method.
Modelling Short- and Long-Term Dependencies of Clustered High-Threshold Exceedances in Significant Wave Heights
Authors: Dissanayake Pushpa , Flock Teresa , Meier Johanna , Sibbertsen Philipp
Published: November 2021

The peaks-over-threshold (POT) method has a long tradition in modelling extremes in environmental variables. However, it has originally been introduced under the assumption of independently and identically distributed (iid) data. Since environmental data often exhibits a time series structure, this assumption is likely to be violated due to short- and long-term dependencies in practical settings, leading to clustering of high-threshold exceedances. In this paper, we first review popular approaches that either focus on modelling short- or long-range dynamics explicitly. In particular, we consider conditional POT variants and the Mittag–Leffler distribution modelling waiting times between exceedances. Further, we propose a new two-step approach capturing both short- and long-range correlations simultaneously. We suggest the autoregressive fractionally integrated moving average peaks-over-threshold (ARFIMA-POT) approach, which in a first step fits an ARFIMA model to the original series and then in a second step utilises a classical POT model for the residuals. Applying these models to an oceanographic time series of significant wave heights measured on the Sefton coast (UK), we find that neither solely modelling short- nor long-range dependencies satisfactorily explains the clustering of extremes. The ARFIMA-POT approach, however, provides a significant improvement in terms of model fit, underlining the need for models that jointly incorporate short- and long-range dependence to address extremal clustering, and their theoretical justification.
May Antitransglutaminase Levels Predict Severity of Duodenal Lesions in Adults with Celiac Disease?
Authors: Losurdo Giuseppe , Di Leo Milena , Santamato Edoardo , Giangaspero Antonio , Rendina Maria , Luigiano Carmelo , Ierardi Enzo , Di Leo Alfredo
Published: November 2021

Background and Objective: Pediatric guidelines on celiac disease (CD) state that children with anti-transglutaminase antibodies (TGAs) >×10 upper limit of normal (ULN) may avoid endoscopy and biopsy. We aimed to evaluate whether these criteria may be suitable for villous atrophy diagnosis in CD adults. Materials and Methods: We retrospectively enrolled patients with CD aged >18 years. TGAs were expressed as xULN. Duodenal lesions were classified as atrophic or non-atrophic according to Marsh-Oberhuber. Fisher’s exact and t-test were used for variables comparison. Receiver operating characteristics (ROC) curve analysis was performed with estimation of area under the curve (AUC), sensitivity, specificity, and positive and negative predictive value (PPV/NPV). Results: One hundred and twenty-one patients were recruited. Sixty patients (49.6%) had TGA >×10 ULN, and 93 (76.8%) had villous atrophy. The cut-off of >×10 ULN had sensitivity = 53.7%, specificity = 64.3%, PPV = 83.3%, and NPV = 29.5% to predict atrophy. Therefore, considering pediatric criteria, in 50 (41.3%) patients, biopsy could have been avoided. Patient subgroup with atrophy had higher TGA levels despite being not significant (37.2 ± 15.3 vs. 8.0 ± 1.3 ULN, p = 0.06). In adults, a slightly better diagnostic performance was obtained using a cut-off of TGA >×6.2 ULN (sensitivity = 57.1%, specificity = 65.6%, and AUC = 0.62). Conclusions: Despite our confirmation that villous atrophy is linked to high TGA levels, CD and atrophy diagnosis based only on serology is not reliable in adults.
Technological and Quality Aspects of the Use of Innovative Inorganic Binders in the Production of Castings
Authors: Obzina Tomáš , Merta Václav , Folta Martin , Bradáč Josef , Beňo Jaroslav , Novohradská Nikol , Gawronová Martina , Kroupová Ivana , Lichý Petr , Radkovský Filip , Janovská Kamila , Vasková Iveta , Drobíková Klára , Nguyenová Isabel
Published: November 2021

The production of cores for the pre-casting of holes in castings places high demands on the quality of the molding mixtures used. For this reason, organic binders are still used to a large extent, which, although they meet the technological requirements, are a source of pollutant emissions during the production of castings. The current trend towards greening production is therefore looking for a suitable alternative in ‘green’ inorganic binders. Although for many decades standard inorganic binders could not be compared with organic resins in terms of technological properties, new inorganic binder systems are currently being developed that can largely eliminate these disadvantages, which include, in particular, significantly lower collapsibility and reclaimability, and lower mechanical strength values. Last but not least, the use of these binder systems may be limited by the technological parameter of shelf-life, which is the main focus of this study. The aim of this paper is to evaluate the influence of technological parameters of core production using a new generation of inorganic binder systems on their shelf-life. Shelf-life, defined as the change in mechanical strength and wear resistance as a function of exposure time in a given environment, is evaluated under different climatic conditions.
Comparison of Impact Toughness in Simulated Coarse-Grained Heat-Affected Zone of Al-Deoxidized and Ti-Deoxidized Offshore Steels
Authors: Tervo Henri , Kaijalainen Antti , Javaheri Vahid , Ali Mohammed , Alatarvas Tuomas , Mehtonen Mikko , Anttila Severi , Kömi Jukka
Published: November 2021

The presence of acicular ferrite (AF) in the heat-affected zone (HAZ) of steels used offshore is generally seen as beneficial for toughness. In this study, the effects of varying fractions of AF (0–49 vol.%) were assessed in the simulated, unaltered and coarse-grained heat-affected zones (CGHAZ) of three experimental steels. Two steels were deoxidized using Ti and one using Al. The characterization was carried out by using electron microscopy, energy-dispersive X-ray spectrometry, electron backscatter diffraction and X-ray diffraction. The fraction of AF varied with the heat input and cooling time applied in the Gleeble thermomechanical simulator. AF was present in one of the Ti-deoxidized steels with all the applied cooling times, and its fraction increased with increasing cooling time. However, in other materials, only a small fraction (13–22%) of AF was present and only when the longest cooling time was applied. The impact toughness of the simulated specimens was evaluated using instrumented Charpy V-notch testing. Contrary to the assumption, the highest impact toughness was obtained in the conventional Al-deoxidized steel with little or no AF in the microstructure, while the variants with the highest fraction of AF had the lowest impact toughness. It was concluded that the coarser microstructural and inclusion features of the steels with AF and also the fraction of AF may not have been great enough to improve the CGHAZ toughness of the steels investigated.
Numerical Simulation on Motion Behavior of Inclusions in the Lab-Scale Electroslag Remelting Process with a Vibrating Electrode
Authors: Wang Fang , Sun Boyang , Liu Zhongqiu , Li Baokuan , Huang Shuo , Zhang Beijiang
Published: November 2021

In order to meet the requirement of high-quality ingots, the vibrating electrode technique in the electroslag remelting (ESR) process has been proposed. Non-metallic inclusions in ingots may cause serious defects and deteriorate mechanical properties of final products. Moreover, the dimension, number and distribution of non-metallic inclusions should be strictly controlled during the ESR process in order to produce high-quality ingots. A transient 2-D coupled model is established to analyze the motion behavior of inclusions in the lab-scale ESR process with a vibrating electrode, especially under the influence of the vibration frequency, current, slag layer thickness, and filling ratio, as well as type and diameter of inclusions. Simulation model of inclusions motion behavior is established based on the Euler-Lagrange approach. The continuous phase including metal and slag, is calculated based on the volume of fluid (VOF) method, and the trajectory of inclusions is tracked with the discrete phase model (DPM). The vibrating electrode is simulated by the user-defined function and dynamic mesh. The results show that when the electrode vibration frequency is 0.25 Hz or 1 Hz, the inclusions will gather on one side of the slag layer. When it increases from 0.25 Hz to 1 Hz, the removal ratio of 10 μm and 50 μm inclusions increases by 5% and 4.1%, respectively. When the current increases from 1200 A to 1800 A, the flow following property of inclusions in the slag layer becomes worse. The removal ratio of inclusions reaches the maximum value of 92% with the current of 1500 A. The thickness of slag layer mainly affects the position of inclusions entering the liquid-metal pool. As the slag layer thickens, the inclusions removal ratio increases gradually from 82.73% to 85.91%. As the filling ratio increases, the flow following property of inclusions in the slag layer is enhanced. The removal ratio of 10 μm inclusions increases from 94.82% to 97%. However, for inclusions with a diameter of 50 μm, the maximum removal ratio is 96.04% with a filling ratio of 0.46. The distribution of 50 μm inclusions is significantly different, while the distribution of 10 μm inclusions is almost similar. Because of the influence of a vibrating electrode, 10 μm Al2O3 and MnO have a similar removal ratios of 81.33% and 82.81%, respectively.
Modeling and Compensation of Dynamic Hysteresis with Force-Voltage Coupling for Piezoelectric Actuators
Authors: Wang Wen , Wang Jiahui , Wang Ruijin , Chen Zhanfeng , Han Fuming , Lu Keqing , Wang Chuanyong , Xu Zhenlong , Ju Bingfeng
Published: November 2021

Piezoelectric actuators are widely used in the field of micro- and nanopositioning due to their high frequency response, high stiffness, and high resolution. However, piezoelectric actuators have hysteresis nonlinearity, which severely affects their positioning accuracy. As the driving frequency increases, the performance of piezoelectric actuators further degrades. In addition, the impact of force on piezoelectric actuators cannot be ignored in practical applications. Dynamic hysteresis with force-voltage coupling makes the hysteresis phenomenon more complicated when force and driving voltage are both applied to the piezoelectric actuator. Existing hysteresis models are complicated, or inaccurate in describing dynamic hysteresis with force-voltage coupling. To solve this problem, a force-voltage-coupled Prandtl–Ishlinskii (FVPI) model is proposed in this paper. First, the influence of driving frequency and dynamic force on the output displacement of the piezoelectric actuators are analyzed. Then, the accuracy of the FVPI model is verified through experiments. Finally, a force integrated direct inverse (F-DI) compensator based on the FVPI model is designed. The experimental results from this study show that the F-DI compensator can effectively suppress dynamic hysteresis with force-voltage coupling of piezoelectric actuators. This model can improve the positioning accuracy of piezoelectric actuators, thereby improving the working accuracy of the micro- or nano-operating system.
Sustained Trichodysplasia Spinulosa Polyomavirus Viremia Illustrating a Primary Disseminated Infection in a Kidney Transplant Recipient
Authors: Zanella Marie-Céline , Pastor Damien , Feltkamp Mariet C. W. , Hadaya Karine , Cordey Samuel , Toutous Trellu Laurence
Published: November 2021

Novel human polyomaviruses (HPyV) have been recently identified in solid organ transplant recipients. Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus (TSPyV). We report here a case of primary and disseminated TSPyV infection after kidney transplantation with extensive skin lesions, sustained viremia, and high viral loads in urine specimens, anal, nasal and throat swabs, assessed via specific real-time PCR for TSPyV during a follow-up period of 32 months after transplantation. The detection of TSPyV with a high viral load in respiratory and anal swab samples is compatible with viral replication and thus may suggest potential respiratory and oro-fecal routes of transmission.
Identification of Novel Antagonists Targeting Cannabinoid Receptor 2 Using a Multi-Step Virtual Screening Strategy
Authors: Wang Mukuo , Hou Shujing , Liu Ye , Li Dongmei , Lin Jianping
Published: November 2021

The endocannabinoid system plays an essential role in the regulation of analgesia and human immunity, and Cannabinoid Receptor 2 (CB2) has been proved to be an ideal target for the treatment of liver diseases and some cancers. In this study, we identified CB2 antagonists using a three-step “deep learning–pharmacophore–molecular docking” virtual screening approach. From the ChemDiv database (1,178,506 compounds), 15 hits were selected and tested by radioligand binding assays and cAMP functional assays. A total of 7 out of the 15 hits were found to exhibit binding affinities in the radioligand binding assays against CB2 receptor, with a pKi of 5.15-6.66, among which five compounds showed antagonistic activities with pIC50 of 5.25–6.93 in the cAMP functional assays. Among these hits, Compound 8 with the 4H-pyrido[1,2-a]pyrimidin-4-one scaffold showed the best binding affinity and antagonistic activity with a pKi of 6.66 and pIC50 of 6.93, respectively. The new scaffold could serve as a lead for further development of CB2 drugs. Additionally, we hope that the model in this study could be further utilized to identify more novel CB2 receptor antagonists, and the developed approach could also be used to design potent ligands for other therapeutic targets.
Volatile Compounds and Antioxidant and Antimicrobial Activities of Selected Citrus Essential Oils Originated from Nepal
Authors: Bhandari Devi Prasad , Poudel Darbin Kumar , Satyal Prabodh , Khadayat Karan , Dhami Sital , Aryal Dipa , Chaudhary Pratiksha , Ghimire Aakash , Parajuli Niranjan
Published: November 2021

Citrus species of plants are among the most commercially cultivated crops, mainly for their fruit. Besides, the generally consumed flesh inside the fruit, the peel is quite important too. Essential oils extracted from the peel have a history of being used by humankind for centuries. These essential oils are rich in antioxidants and antimicrobial agents. Comparative investigation of volatile constituents, and antioxidant and antimicrobial activities were undertaken. The essential oils were evaluated through gas chromatography-mass spectrometry (GC–MS), and enantiomeric composition by chiral GC–MS. Similarly, the antioxidant properties were evaluated by 2,2-diphenyl-1-picrylhydrazyl scavenging assay, and antimicrobial activities were assayed using the disk diffusion method. The highest extraction yield of 1.83% was observed in Citrus sinensis Osbeck. GC–MS analysis showed limonene (63.76–89.15%), γ-terpinene (0.24–6.43%), β-pinene (0.15–6.09%), linalool (0.35–3.5%), sabinene (0.77–2.17%), myrcene (0.74–1.75%), α-terpineol (0.28–1.15%), and α-pinene (0.2–0.58%) as the major constituents of the essential oil of the Citrus species studied. For the first time, through our study, chiral terpenoids have been observed from Citrus grandis Osbeck essential oil. The order of antioxidant activity is as follows: Citrus grandis Osbeck red flesh > Citrus reticulata Blanco > Citrus sinensis Osbeck > Citrus grandis Osbeck white flesh. Except for Citrus grandis Osbeck white flesh (52.34 µL/mL), all samples demonstrated stronger antioxidant activities than those of the positive control, quercetin (5.60 µL/mL). Therefore, these essential oils can be used as a safe natural antioxidant to prevent product oxidation. Likewise, citrus peel essential oil showed antimicrobial activity against tested bacterial strains, albeit marginal.
Electrochemical Performance of Thick-Film Li(Ni0.6Mn0.2Co0.2)O2 Cathode with Hierarchic Structures and Laser Ablation
Authors: Song Zelai , Zhu Penghui , Pfleging Wilhelm , Sun Jiyu
Published: November 2021

The electrochemical performance of lithium-ion batteries is directly influenced by type of active material as well as its morphology. In order to evaluate the impact of particle morphology in thick-film electrodes, Li(Ni0.6Mn0.2Co0.2)O2 (NMC 622) cathodes with bilayer structure consisting of two different particle sizes were manufactured and electrochemically characterized in coin cells design. The hierarchical thick-film electrodes were generated by multiple casting using NMC 622 (TA) with small particle size of 6.7 µm and NMC 622 (BA) with large particle size of 12.8 µm. Besides, reference electrodes with one type of active material as well as with two type of materials established during mixing process (BT) were manufactured. The total film thickness of all hierarchical composite electrodes were kept constant at 150 µm, while the thicknesses of TA and BA were set at 1:2, 1:1, and 2:1. Meanwhile, three kinds of thin-film cathodes with 70 µm were applied to represent the state-of-the-art approach. Subsequently, ultrafast laser ablation was applied to generate groove structures inside the electrodes. The results demonstrate that cells with thin-film or thick-film cathode only containing TA, cells with bilayer electrode containing TBA 1:2, and cells with laser-structured electrodes show higher capacity at C/2 to 5C, respectively.
Fasting-Induced Upregulation of MKP-1 Modulates the Hepatic Response to Feeding
Authors: Sellers Jacob , Brooks Abigail , Fernando Savanie , Westenberger Gabrielle , Junkins Sadie , Smith Shauri , Min Kisuk , Lawan Ahmed
Published: November 2021

The liver plays a key role in whole-body, glucose and lipid homeostasis. Nutritional signals in response to fasting and refeeding regulate hepatic lipid synthesis. It is established that activation of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in response to overnutrition regulates MAPK-dependent pathways that control lipid metabolism in the liver. However, the regulatory mechanisms and the impact of the actions of MKP-1 in hepatic response to fasting remains unclear. We investigated the effect of fasting on the expression of MKP-1 and the impact on hepatic response to feeding. In this study, we demonstrate that fasting stress induced upregulation of hepatic MKP-1 protein levels with a corresponding downregulation of p38 MAPK and JNK phosphorylation in mouse livers. We found that MKP-1-deficient livers are resistant to fasting-induced hepatic steatosis. Hepatic MKP-1 deficiency impaired fasting-induced changes in the levels of key transcription factors involved in the regulation of fatty acid and cholesterol metabolism including Srebf2 and Srebf1c. Mechanistically, MKP-1 negatively regulates Srebf2 expression by attenuating p38 MAPK pathway, suggesting its contribution to the metabolic effects of MKP-1 deficiency in the fasting liver. These findings support the hypothesis that upregulation of MKP-1 is a physiological relevant response and might be beneficial in hepatic lipid utilization during fasting in the liver. Collectively, these data unravel some of the complexity and tissue specific interaction of MKP-1 action in response to changes in nutritional cues, including fasting and excess nutrients
One Year Follow-Up of Taste-Related Reward Associations with Weight Loss Suggests a Critical Time to Mitigate Weight Regain Following Bariatric Surgery
Authors: Smith Kimberly R. , Aghababian Anahys , Papantoni Afroditi , Veldhuizen Maria G. , Kamath Vidyulata , Harris Civonnia , Moran Timothy H. , Carnell Susan , Steele Kimberley E.
Published: November 2021

Background: Weight regain is a concerning issue in bariatric patients. We previously demonstrated that taste-related reward processing was associated with six-month weight loss outcomes following Roux-en-Y gastric bypass (RYGB) but not vertical sleeve gastrectomy (VSG). Here, we assessed whether these taste factors persisted in predicting weight loss, and weight regain, at one year post-surgery. Methods: Adult women enrolled in a longitudinal study of taste preferences following bariatric surgery completed behavioral and neuroimaging assessments at one year post-surgery. Results: RYGB produced better weight loss relative to VSG, with weight regain and greater weight loss variability observed from six months to one year post-VSG. Changes in liking for high fat at 2 weeks post-surgery from baseline remained a predictor of weight loss in RYGB, but other predictors did not persist. Average liking ratings rebounded to baseline and higher self-reported food cravings and dietary disinhibition correlated with poorer weight loss at one year post-surgery. Conclusion: Initial anatomical and metabolic changes resulting from RYGB that reset neural processing of reward stimuli in the mesolimbic pathway appear to be temporary and may be contingent upon post-operative eating behaviors returning to preoperative obesogenic tendencies. Six months post-surgery may be a critical window for implementing interventions to mitigate weight gain.
Therapeutic Effects of Dietary Soybean Genistein on Triple-Negative Breast Cancer via Regulation of Epigenetic Mechanisms
Authors: Sharma Manvi , Arora Itika , Chen Min , Wu Huixin , Crowley Michael R. , Tollefsbol Trygve O. , Li Yuanyuan
Published: November 2021

Consumption of dietary natural components such as genistein (GE) found in soy-rich sources is strongly associated with a lower risk of breast cancer. However, bioactive dietary component-based therapeutic strategies are largely understudied in breast cancer treatment. Our investigation sought to elucidate the potential mechanisms linking bioactive dietary GE to its breast cancer chemotherapeutic potential in a special subtype of aggressive breast cancer—triple-negative breast cancer (TNBC)—by utilizing two preclinical patient-derived xenograft (PDX) orthotopic mouse models: BCM-3204 and TM00091. Our study revealed that administration of GE resulted in a delay of tumor growth in both PDX models. With transcriptomics analyses in TNBC tumors isolated from BCM-3204 PDXs, we found that dietary soybean GE significantly influenced multiple tumor-regulated gene expressions. Further validation assessment of six candidate differentially expressed genes (DEGs)—Cd74, Lpl, Ifi44, Fzd9, Sat1 and Wwc1—demonstrated a similar trend at gene transcriptional and protein levels as observed in RNA-sequencing results. Mechanistically, GE treatment-induced Cd74 downregulation regulated the NF-κB/Bcl-xL/TAp63 signal pathway, which may contribute to soybean GE-mediated therapeutic effects on TNBC tumors. Additionally, our findings revealed that GE can modify expression levels of key epigenetic-associated genes such as DNA methyltransferases (Dnmt3b), ten-eleven translocation (Tet3) methylcytosine dioxygenases and histone deacetyltransferase (Hdac2), and their enzymatic activities as well as genomic DNA methylation and histone methylation (H3K9) levels. Collectively, our investigation shows high significance for potential development of a novel therapeutic approach by using bioactive soybean GE for TNBC patients who have few treatment options.
Evaluation of the Anti-Shigellosis Activity of Dietary Isothiocyanates in Galleria mellonella Larvae
Authors: Nowicki Dariusz , Krause Klaudyna , Karczewska Monika , Szalewska-Pałasz Agnieszka
Published: November 2021

Cruciferous vegetables, widely present in daily diets, are a rich source of organosulfur compounds with proven health benefits, especially chemopreventive or antioxidative effects. Isothiocyanate derivatives (ITCs) exhibit a broad spectrum of biological and pharmacological activity and recently, their antibacterial properties have been of particular importance. Here, we have focused on the anti-shigellosis activity of sulforaphane (SFN) and phenethyl ITC (PEITC). The genus Shigella causes gastroenteritis in humans, which constitutes a threat to public health. Production of a potent Stx toxin by S. dysenteriae type 1 results not only in more severe symptoms but also in serious sequela, including the hemolytic uremic syndrome. Here, we present evidence that two aliphatic and aromatic ITCs derivatives, SFN and PEITC, have an effective antibacterial potency against S. dysenteriae, also negatively regulating the stx gene expression. The molecular mechanism of this effect involves induction of the global stress-induced stringent response. ITCs also inhibit bacterial virulence against the Vero and HeLa cells. We present evidence for the therapeutic effect of sulforaphane and phenethyl ITC against a S. dysenteriae infection in the Galleria mellonella larvae model. Thus, our results indicate that isothiocyanates can be effectively used to combat dangerous bacterial infections.
Longitudinal Association of Maternal Pre-Pregnancy BMI and Third-Trimester Glycemia with Early Life Growth of Offspring: A Prospective Study among GDM-Negative Pregnant Women
Authors: Zou Jiaojiao , Yang Yanting , Wei Qian , Zhang Yunhui , Shi Huijing
Published: November 2021

Intrauterine modifiable maternal metabolic factors are essential to the early growth of offspring. The study sought to evaluate the associations of pre-pregnancy BMI and third-trimester fasting plasma glucose (FPG) with offspring growth outcomes within 24 months among GDM-negative pregnant women. Four hundred eighty-three mother –offspring dyads were included from the Shanghai Maternal-Child Pairs Cohort. The pregnant women were categorized into four mutually exclusive groups according to pre-pregnancy BMI as normal or overweight/obesity and third-trimester FPG as controlled or not controlled. Offspring growth in early life was indicated by the BAZ (BMI Z-score), catch-up growth, and overweight/obesity. Among those with controlled third-trimester FPG, pre-pregnancy overweight/obesity significantly increased offspring birth weight, BAZ, and risks of overweight/obesity (RR 1.83, 95% CI 1.23 to 2.73) within 24 months. Those who had uncontrolled third-trimester FPG had a reduced risk of offspring overweight/obesity within 24 months by 47%. The combination of pre-pregnancy overweight/obesity and maternal uncontrolled third-trimester FPG increased 5.24-fold risk of offspring catch-up growth within 24 months (p < 0.05). Maternal pre-pregnancy overweight/obesity and uncontrolled third-trimester glycemia among GDM-negative women both have adverse effects on offspring growth within 24 months. With the combination of increasing pre-pregnancy BMI and maternal third-trimester FPG, the possibility of offspring catch-up growth increases.
Epstein-Barr Virus-Associated Carcinoma of the Larynx: A Systematic Review with Meta-Analysis
Authors: de Lima Marcos Antonio Pereira , Silva Álife Diêgo Lima , do Nascimento Filho Antônio Carlos Silva , Cordeiro Thiago Lima , Bezerra João Pedro de Souza , Rocha Maria Aline Barroso , Pinheiro Sally de França Lacerda , Pinheiro Junior Roberto Flávio Fontenelle , Gadelha Maria do Socorro Vieira , da Silva Cláudio Gleidiston Lima
Published: November 2021

Over the past few decades, several publications have investigated the role of Epstein-Barr virus (EBV) in head and neck squamous cell carcinomas, and an increasing number of them have shown its presence in laryngeal tumors. The purpose of this meta-analysis was to evaluate the association of EBV with laryngeal carcinoma. The search was carried out in two databases, Scopus and PubMed, using the following terms: “Epstein-Barr virus” and “laryngeal carcinoma”. A total of 187 records were found, of which 31 were selected for meeting the inclusion and exclusion criteria. The meta-analysis yielded an overall pooled prevalence of 43.72% (95% confidence interval (CI): 34.35–53.08). Studies carried out in Europe and Eurasia had slightly higher pooled prevalence than other subgroups, while the prevalence of studies performed in developed countries was higher than in developing countries (46.37% vs. 34.02%). Furthermore, laryngeal carcinoma occurred almost three times as often among EBV-infected individuals compared to those without EBV infection (odds ratio = 2.86 (95% CI: 1.18–6.90); Begg’s test, p = 0.843 and Egger’s test, p = 0.866). Our findings support the idea that EBV is related to laryngeal carcinoma. However, further studies are needed before recognizing a definitive etiological role of EBV in the development and/or progression of laryngeal carcinomas.
A Comparison of Peripheral Blood Smears, Autologous Cell Cultures, and Reverse Line Blot Hybridisation in Screening for Anaplasma/Ehrlichia in Roaming Dogs and Symptomatic Dogs in Trinidad
Authors: Georges Karla , Ezeokoli Chuckwudozi , Isitor Godwin , Mutani Alex , Sparagano Olivier , Sant Candice
Published: November 2021

This study compared two methods to detect cases of canine ehrlichiosis in a field setting. One method was a polymerase chain reaction for the 16S rRNA gene followed by reverse line blot hybridisation with genera and species-specific probes for Anaplasma/Ehrlichia. The second method was an autologous cell culture of peripheral leucocytes isolated from heparinised blood and maintained in a homologous canine serum in Dulbecco’s Modified Eagle medium without antibiotics. The cultures were examined under light microscopy for inclusion bodies after 48 h. Leucocytes were successfully propagated for 20 of the 34 samples submitted for autologous cell culture. Inclusion bodies were observed after cell culture in leucocytes of eight dogs. Two dogs were positive to the Anaplasma/Ehrlichia genera probe and six dogs were positive to the E. canis probe after reverse line blot hybridisation. There was acceptable agreement between reverse line blot hybridisation and cell culture results. Both reverse line blot hybridisation and autologous cell cultures can be used to detect E. canis in subclinical and clinical cases of disease. A definitive diagnosis of E. canis is best achieved by a combination of clinical signs, positive autologous cell culture, and reverse line blot hybridisation results.
Lung Deposition of Surfactant Delivered via a Dedicated Laryngeal Mask Airway in Piglets
Authors: Nord Anders , Cunha-Goncalves Doris , Linnér Rikard , Bianco Federico , Salomone Fabrizio , Ricci Francesca , Lombardini Marta , Micaglio Massimo , Trevisanuto Daniele , Perez-de-Sa Valeria
Published: November 2021

It is unknown if the lung deposition of surfactant administered via a catheter placed through a laryngeal mask airway (LMA) is equivalent to that obtained by bolus instillation through an endotracheal tube. We compare the lung deposition of surfactant delivered via two types of LMA with the standard technique of endotracheal instillation. 25 newborn piglets on continuous positive airway pressure support (CPAP) were randomized into three groups: 1—LMA-camera (integrated camera and catheter channel; catheter tip below vocal cords), 2—LMA-standard (no camera, no channel; catheter tip above the glottis), 3—InSurE (Intubation, Surfactant administration, Extubation; catheter tip below end of endotracheal tube). All animals received 100 mg·kg−1 of poractant alfa mixed with 99mTechnetium-nanocolloid. Surfactant deposition was measured by gamma scintigraphy as a percentage of the administered dose. The median (range) total lung surfactant deposition was 68% (10–85), 41% (5–88), and 88% (67–92) in LMA-camera, LMA-standard, and InSurE, respectively, which was higher (p < 0.05) in the latter. The deposition in the stomach and nasopharynx was higher with the LMA-standard. The surfactant deposition via an LMA was lower than that obtained with InSurE. Although not statistically significant, introducing the catheter below the vocal cords under visual control with an integrated camera improved surfactant LMA delivery by 65%.
Data-Enriched Edible Pharmaceuticals (DEEP) with Bespoke Design, Dose and Drug Release
Authors: Chao Meie , Öblom Heidi , Cornett Claus , Bøtker Johan , Rantanen Jukka , Sporrong Sofia Kälvemark , Genina Natalja
Published: November 2021

Data-enriched edible pharmaceuticals (DEEP) is an approach to obtain personalized medicine, in terms of flexible and precise drug doses, while at the same time containing data, embedded in quick response (QR) codes at a single dosage unit level. The aim of this study was to fabricate DEEP with a patient-tailored dose, modify drug release and design to meet patients’ preferences. It also aimed to investigate physical stability in terms of the readability of QR code patterns of DEEP during storage. Cannabinoids, namely, cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), were used as the model active pharmaceutical ingredients (APIs). Three different substrates and two colorants for the ink were tested for their suitability to fabricate DEEP by desktop inkjet printing. Flexible doses and customizable designs of DEEP were obtained by manipulating the digital design of the QR code, particularly, by exploring different pattern types, embedded images and the physical size of the QR code pattern. Modification of the release of both APIs from DEEP was achieved by applying a hydroxypropyl cellulose (HPC) polymer coating. The appearance and readability of uncoated and polymer-coated DEEP did not change on storage in cold and dry conditions; however, the HPC polymer layer was insufficient in preserving the readability of the QR code pattern in the extreme storage condition (40 °C and 75% relative humidity). To sum up, the DEEP concept provides opportunities for the personalization of medicines, considering also patients’ preferences.
Comparative Study on Inhibition of Pancreatic Cancer Cells by Resveratrol Gold Nanoparticles and a Resveratrol Nanoemulsion Prepared from Grape Skin
Authors: Inbaraj Baskaran Stephen , Hua Leng-Huei , Chen Bing-Huei
Published: November 2021

Resveratrol, a phenolic compound possessing vital biological activities such as anti-cancer, is present abundantly in grape skin, a waste produced during the processing of grape juice. The objectives of this study were to prepare resveratrol-gold nanoparticles and a resveratrol nanoemulsion from grape skin and study their inhibition effects on pancreatic cancer cells BxPC-3. The spherical-shaped citrate gold nanoparticles (GNPs) and resveratrol-gold nanoparticles (R-GNPs) were, respectively, prepared with a surface plasmon resonance peak at 528 and 538 nm, mean particle size of 20.8 and 11.9 nm, and zeta-potential at −32.7 and −66.7 mV, by controlling an appropriate concentration of citrate/resveratrol and gold chloride as well as stirring time and temperature. The resveratrol nanoemulsion, composed of soybean oil, Tween 80, and sucrose fatty acid ester in glycerol and water, possessed a high storage stability with a mean particle size of 14.1 nm, zeta-potential of −49.7 mV, and encapsulation efficiency of 95.5%. An antiproliferation study revealed that both R-GNPs and resveratrol nanoemulsion could effectively inhibit the growth of pancreatic cancer cells BxPC-3, with the latter showing a higher inhibition effect. Western blot analysis implied that both can down-regulate expressions of cyclin A, cyclin B, CDK1, and CDK2 and up-regulate expressions of p53 and p21, accompanied by enhancing cytochrome C expression, decreasing BcL-2 expression, increasing Bax expression, and leading to the elevation of caspase-8, caspase-9, and caspase-3 activities for cell apoptosis execution. Future research is needed to study the inhibition of pancreatic tumors in vivo by R-GNPs and resveratrol nanoemulsions.
Photochemical Internalization of Etoposide Using Dendrimer Nanospheres Loaded with Etoposide and Protoporphyrin IX on a Glioblastoma Cell Line
Authors: Lin Martin Hsiu-Chu , Chang Li-Ching , Chung Chiu-Yen , Huang Wei-Chao , Lee Ming-Hsueh , Chen Kuo-Tai , Lai Ping-Shan , Yang Jen-Tsung
Published: November 2021

Glioblastoma multiforme (GBM) is the most common malignant primary neoplasm of the adult central nervous system originating from glial cells. The prognosis of those affected by GBM has remained poor despite advances in surgery, chemotherapy, and radiotherapy. Photochemical internalization (PCI) is a release mechanism of endocytosed therapeutics into the cytoplasm, which relies on the membrane disruptive effect of light-activated photosensitizers. In this study, phototherapy by PCI was performed on a human GBM cell-line using the topoisomerase II inhibitor etoposide (Etop) and the photosensitizer protoporphyrin IX (PpIX) loaded in nanospheres (Ns) made from generation-5 polyamidoamine dendrimers (PAMAM(G5)). The resultant formulation, Etop/PpIX-PAMAM(G5) Ns, measured 217.4 ± 2.9 nm in diameter and 40.5 ± 1.3 mV in charge. Confocal microscopy demonstrated PpIX fluorescence within the endo-lysosomal compartment, and an almost twofold increase in cellular uptake compared to free PpIX by flow cytometry. Phototherapy with 3 min and 5 min light illumination resulted in a greater extent of synergism than with co-administered Etop and PpIX; notably, antagonism was observed without light illumination. Mechanistically, significant increases in oxidative stress and apoptosis were observed with Etop/PpIX-PAMAM(G5) Ns upon 5 min of light illumination in comparison to treatment with either of the agents alone. In conclusion, simultaneous delivery and endo-lysosomal co-localization of Etop and PpIX by PAMAM(G5) Ns leads to a synergistic effect by phototherapy; in addition, the finding of antagonism without light illumination can be advantageous in lowering the dark toxicity and improving photo-selectivity.
Hyaluronic Acid Hydrogels for Controlled Pulmonary Drug Delivery—A Particle Engineering Approach
Authors: Nikjoo Dariush , van der Zwaan Irès , Brülls Mikael , Tehler Ulrika , Frenning Göran
Published: November 2021

Hydrogels warrant attention as a potential material for use in sustained pulmonary drug delivery due to their swelling and mucoadhesive features. Herein, hyaluronic acid (HA) is considered a promising material due to its therapeutic potential, the effect on lung inflammation, and possible utility as an excipient or drug carrier. In this study, the feasibility of using HA hydrogels (without a model drug) to engineer inhalation powders for controlled pulmonary drug delivery was assessed. A combination of chemical crosslinking and spray-drying was proposed as a novel methodology for the preparation of inhalation powders. Different crosslinkers (urea; UR and glutaraldehyde; GA) were exploited in the hydrogel formulation and the obtained powders were subjected to extensive characterization. Compositional analysis of the powders indicated a crosslinked structure of the hydrogels with sufficient thermal stability to withstand spray drying. The obtained microparticles presented a spherical shape with mean diameter particle sizes from 2.3 ± 1.1 to 3.2 ± 2.9 μm. Microparticles formed from HA crosslinked with GA exhibited a reasonable aerosolization performance (fine particle fraction estimated as 28 ± 2%), whereas lower values were obtained for the UR-based formulation. Likewise, swelling and stability in water were larger for GA than for UR, for which the results were very similar to those obtained for native (not crosslinked) HA. In conclusion, microparticles could successfully be produced from crosslinked HA, and the ones crosslinked by GA exhibited superior performance in terms of aerosolization and swelling.
Comparison of PLA-Based Micelles and Microspheres as Carriers of Epothilone B and Rapamycin. The Effect of Delivery System and Polymer Composition on Drug Release and Cytotoxicity against MDA-MB-231 Breast Cancer Cells
Authors: Jelonek Katarzyna , Zajdel Alicja , Wilczok Adam , Kaczmarczyk Bożena , Musiał-Kulik Monika , Hercog Anna , Foryś Aleksander , Pastusiak Małgorzata , Kasperczyk Janusz
Published: November 2021

Co-delivery of epothilone B (EpoB) and rapamycin (Rap) increases cytotoxicity against various kinds of cancers. However, the current challenge is to develop a drug delivery system (DDS) for the simultaneous delivery and release of these two drugs. Additionally, it is important to understand the release mechanism, as well as the factors that affect drug release, in order to tailor this process. The aim of this study was to analyze PLA–PEG micelles along with several types of microspheres obtained from PLA or a mixture of PLA and PLA–PEG as carriers of EpoB and Rap for their drug release properties and cytotoxicity against breast cancer cells. The study showed that the release process of EpoB and Rap from a PLA-based injectable delivery systems depends on the type of DDS, morphology, and polymeric composition (PLA to PLA–PEG ratio). These factors also affect the biological activity of the DDS, because the cytotoxic effect of the drugs against MDA-MB-231 cells depends on the release rate. The release process from all kinds of DDS was well-characterized by the Peppas–Sahlin model and was mainly controlled by Fickian diffusion. The conducted analysis allowed also for the selection of PLA 50/PLA–PEG 50 microspheres and PLA–PEG micelles as a promising co-delivery system of EpoB and Rap.
Biomaterials and Meniscal Lesions: Current Concepts and Future Perspective
Authors: Lombardo Michele D. M. , Mangiavini Laura , Peretti Giuseppe M.
Published: November 2021

Menisci are crucial structures for knee homeostasis. After a meniscal lesion, the golden rule, now, is to save as much meniscus as possible; only the meniscus tissue that is identified as unrepairable should be excised, and meniscal sutures find more and more indications. Several different methods have been proposed to improve meniscal healing. They include very basic techniques, such as needling, abrasion, trephination and gluing, or more complex methods, such as synovial flaps, meniscal wrapping or the application of fibrin clots. Basic research of meniscal substitutes has also become very active in the last decades. The aim of this literature review is to analyze possible therapeutic and surgical options that go beyond traditional meniscal surgery: from scaffolds, which are made of different kind of polymers, such as natural, synthetic or hydrogel components, to new technologies, such as 3-D printing construct or hybrid biomaterials made of scaffolds and specific cells. These recent advances show that there is great interest in the development of new materials for meniscal reconstruction and that, with the development of new biomaterials, there will be the possibility of better management of meniscal injuries