bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Pod Sealant Application on the Quantitative and Qualitative Traits of Field Pea (Pisum sativum L.) Seed Yield
Authors: Serafin-Andrzejewska Magdalena , Kozak Marcin , Kotecki Andrzej
Published: July 2021

Field pea is used for human consumption or as livestock feed. The yield of pea seeds can be significantly decreased due to the genetically determined tendency of peas to pod shattering. This study aimed to evaluate the effect of pod sealant application on the quantitative and qualitative traits of the seed yield of two pea cultivars: Arwena and Tarchalska grown in south-western Poland in the years 2018–2019. Pod sealant application showed higher values of analysed quantitative and qualitative traits: number of pods per plant, number of seeds per plant, seed weight per pod, 1000-seed weight, seed yield, dry matter of seeds, protein content in seeds, and total protein productivity, except the number of seeds per pod. For both years (2018–2019), the interaction of cultivar and pod sealant application showed a significant effect on the number of seeds per plant, total protein content, total protein productivity, and seed weight per pod in 2019. Therefore, the pod sealant application can be a relatively simple way to improve the yielding of field peas.
Tomato Leaf Diseases Classification Based on Leaf Images: A Comparison between Classical Machine Learning and Deep Learning Methods
Authors: Tan Lijuan , Lu Jinzhu , Jiang Huanyu
Published: July 2021

Tomato production can be greatly reduced due to various diseases, such as bacterial spot, early blight, and leaf mold. Rapid recognition and timely treatment of diseases can minimize tomato production loss. Nowadays, a large number of researchers (including different institutes, laboratories, and universities) have developed and examined various traditional machine learning (ML) and deep learning (DL) algorithms for plant disease classification. However, through pass survey analysis, we found that there are no studies comparing the classification performance of ML and DL for the tomato disease classification problem. The performance and outcomes of different traditional ML and DL (a subset of ML) methods may vary depending on the datasets used and the tasks to be solved. This study generally aimed to identify the most suitable ML/DL models for the PlantVillage tomato dataset and the tomato disease classification problem. For machine learning algorithm implementation, we used different methods to extract disease features manually. In our study, we extracted a total of 52 texture features using local binary pattern (LBP) and gray level co-occurrence matrix (GLCM) methods and 105 color features using color moment and color histogram methods. Among all the feature extraction methods, the COLOR+GLCM method obtained the best result. By comparing the different methods, we found that the metrics (accuracy, precision, recall, F1 score) of the tested deep learning networks (AlexNet, VGG16, ResNet34, EfficientNet-b0, and MobileNetV2) were all better than those of the measured machine learning algorithms (support vector machine (SVM), k-nearest neighbor (kNN), and random forest (RF)). Furthermore, we found that, for our dataset and classification task, among the tested ML/DL algorithms, the ResNet34 network obtained the best results, with accuracy of 99.7%, precision of 99.6%, recall of 99.7%, and F1 score of 99.7%.
Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing–Preliminary Investigation
Authors: Chapuis Ronan J. J. , Smith Joe S. , French Hilari M. , Toka Felix Ngosa , Peterson Erik W. , Little Erika L.
Published: July 2021

Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administration. Doxycycline concentration was measured by competitive enzyme immunoassay. Serum concentrations versus time data were fitted simultaneously using the stochastic approximation expectation-maximization algorithm for nonlinear mixed effects. A one-compartment model with linear elimination and first-order absorption after intragastric administration, best described the available pharmacokinetic data. Final parameter estimates indicate that DXC has a high volume of distribution (108 L/kg) as well as high absorption (10.3 h−1) in donkeys. However, results suggest that oral DXC at 10 mg/kg q12 h in donkeys would not result in a therapeutic concentration in serum, urine, synovial fluid or endometrium by comparison to the minimum inhibitory concentration of common equine pathogens. Further studies are recommended to identify appropriate dosage and dosing intervals of oral DXC in donkeys.
Causes, Effects and Methods of Monitoring Gas Exchange Disturbances during Equine General Anaesthesia
Authors: Stefanik Elżbieta , Drewnowska Olga , Lisowska Barbara , Turek Bernard
Published: July 2021

Horses, due to their unique anatomy and physiology, are particularly prone to intraoperative cardiopulmonary disorders. In dorsally recumbent horses, chest wall movement is restricted and the lungs are compressed by the abdominal organs, leading to the collapse of the alveoli. This results in hypoventilation, leading to hypercapnia and respiratory acidosis as well as impaired tissue oxygen supply (hypoxia). The most common mechanisms disturbing gas exchange are hypoventilation, atelectasis, ventilation–perfusion (V/Q) mismatch and shunt. Gas exchange disturbances are considered to be an important factor contributing to the high anaesthetic mortality rate and numerous post-anaesthetic side effects. Current monitoring methods, such as a pulse oximetry, capnography, arterial blood gas measurements and spirometry, may not be sufficient by themselves, and only in combination with each other can they provide extensive information about the condition of the patient. A new, promising, complementary method is near-infrared spectroscopy (NIRS). The purpose of this article is to review the negative effect of general anaesthesia on the gas exchange in horses and describe the post-operative complications resulting from it. Understanding the changes that occur during general anaesthesia and the factors that affect them, as well as improving gas monitoring techniques, can improve the post-aesthetic survival rate and minimize post-operative complications.
SARS-CoV-2 Clinical Outcome in Domestic and Wild Cats: A Systematic Review
Authors: Giraldo-Ramirez Sebastian , Rendon-Marin Santiago , Jaimes Javier A. , Martinez-Gutierrez Marlen , Ruiz-Saenz Julian
Published: July 2021

Recently, it has been proved that SARS-CoV-2 has the ability to infect multiple species. This work was aimed at identifying the clinical signs of SARS-CoV-2 infection in domestic and wild felids. A PRISMA-based systematic review was performed on case reports on domestic and wild cats, reports on experimental infections, case reports in databases, preprints and published press releases. Descriptive statistical analysis of the data was performed. A total of 256 articles, 63 detailed official reports and 2 press articles on SARS-CoV-2 infection in domestic and wild cats were analyzed, of which 19 articles and 65 reports were finally included. In domestic cats, most cats’ infections are likely to be asymptomatic, and 46% of the reported infected animals were symptomatic and predominantly presented respiratory signs such as sneezing and coughing. In wild felines, respiratory clinical signs were most frequent, and up to 96.5% of the reported affected animals presented coughing. It is noteworthy that, to date, symptomatic animals with SARS-CoV-2 infection have been reported to belong to two different subfamilies (Phanterinae and Felinae), with up to five different felid species affected within the Felidae family. Reported results evince that the signs developed in felids show similar progression to those occurring in humans, suggesting a relationship between the viral cycle and target tissues of the virus in different species. While viral transmission to humans in contact with animal populations has not been reported, spill-back could result in the emergence of immune-escape mutants that might pose a risk to public health. Despite the clear results in the identification of the typical clinical picture of SARS-CoV-2 infection in felines, the number of detailed academic reports and papers on the subject is scarce. Therefore, further description of these cases will allow for more accurate and statistically robust clinical approaches in the future.
Correlations between Total Antioxidant Capacity, Polyphenol and Fatty Acid Content of Native Grape Seed and Pomace of Four Different Grape Varieties in Hungary
Authors: Szabó Éva , Marosvölgyi Tamás , Szilágyi Gábor , Kőrösi László , Schmidt János , Csepregi Kristóf , Márk László , Bóna Ágnes
Published: July 2021

Grape pomace is a valuable source of various bioactive compounds such as plant-derived polyphenols and polyunsaturated fatty acids (PUFAs). The commercial demand of grape skin and seed powders as nutraceuticals is still growing. However, no distinction is currently made between unfermented native grape seed and grape seed pomace powders regarding their antioxidant activities. Our aim was to find the relationship between the polyphenol and fatty acid content as well as the antioxidant capacity of native and fermented grape seeds of four different grape varieties harvested in the Villány wine region. According to our results, none of the three investigated polyphenols (resveratrol, rutin, quercetin) could be detected in native grape seed samples in correlation with their significantly lower total antioxidant capacities compared to fermented seed samples. Pinot Noir (PN) grape seed pomace samples with the highest resveratrol and oil content showed significantly higher total antioxidant capacity than Cabernet Sauvignon (CS), Syrah (S) and Blue Portugal (BP) samples. Based on the statistical analysis, positive correlation was found between the fatty acid content and the resveratrol concentration in the pomace samples of different grape varieties. In contrast, rutin concentrations were negatively proportional to the fatty acid content of the fermented samples. No significant correlation was found considering the quercetin content of the samples. According to our findings, grape pomace seems a more promising source in the production of nutraceuticals, since it contains polyphenols in higher concentration and exerts significantly higher antioxidant activity than native grape seeds.
Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study
Authors: Rodriguez-Niño Angelica , Pastene Diego O. , Post Adrian , Said M. Yusof , Gomes-Neto Antonio W. , Kieneker Lyanne M. , Heiner-Fokkema M. Rebecca , Esatbeyoglu Tuba , Rimbach Gerald , Schnuelle Peter , Yard Benito A. , Bakker Stephan J. L.
Published: July 2021

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.
Static and Dynamic Response of Micropiles Used for Reinforcing Slopes
Authors: Yang Tong , Men Yuming , Rutherford Cassandra J. , Zhang Zhen
Published: July 2021

To study the static and dynamic response of micropile-reinforced slopes, static model tests and shaking table tests were performed. The failure modes, the pile-slope interaction, the displacement, and the static/dynamic earth pressure distributions were analyzed based on static and dynamic model tests with a prescribed sliding surface. The test results indicated: (1) The micropile failure mode is mainly bending failure under both loading conditions. As far as the damage to the pile body is concerned, under static loading, the rear row piles showed more damage than the middle row piles followed by the front row piles. Under dynamic loading, the damage of the rear row piles was approximately the same as the middle row piles, which was greater than the front row piles; (2) The earth pressures in front of and behind each row of micropiles and the axial force of the pile body distributed triangularly for both loading conditions, with the bending moment of the pile body distributed in an “S” shape; (3) The landslide thrust experienced by the micropiles has a relatively large group effect. The group effect or shear ratio parameters are recommended for each loading case; (4) The interaction between the micropiles and the soil landslide presents evident progressive failure and load transfer between the rows.
Effect of Different Titanium Dental Implant Surfaces on Human Adipose Mesenchymal Stem Cell Behavior. An In Vitro Comparative Study
Authors: D’Esposito Vittoria , Sammartino Josè Camilla , Formisano Pietro , Parascandolo Alessia , Liguoro Domenico , Adamo Daniela , Sammartino Gilberto , Marenzi Gaetano
Published: July 2021

Background: The aim of this research was to evaluate the effects of three different titanium (Ti) implant surfaces on the viability and secretory functions of mesenchymal stem cells isolated from a Bichat fat pad (BFP-MSCs). Methods: Four different Ti disks were used as substrate: (I) D1: smooth Ti, as control; (II) D2: chemically etched, resembling the Kontact S surface; (III) D3: sandblasted, resembling the Kontact surface; (IV) D4: blasted/etched, resembling the Kontact N surface. BFP-MSCs were plated on Ti disks for 72 h. Cell viability, adhesion on disks and release of a panel of cytokines, chemokines and growth factor were evaluated. Results: BFP-MSCs plated in wells with Ti surface showed a viability rate (~90%) and proliferative rate comparable to cells plated without disks and to cells plated on D1 disks. D2 and D4 showed the highest adhesive ability. All the Ti surfaces did not interfere with the release of cytokines, chemokines and growth factors by BFP-MSCs. However, BFP-MSCs cultured on D4 surface released a significantly higher amount of Granulocyte Colony-Stimulating Factor (G-CSF) compared either to cells plated without disks and to cells plated on D1 and D2. Conclusions: The implant surfaces examined do not impair the BFP-MSCs cell viability and preserve their secretion of cytokines and chemokines. Further in vitro and in vivo studies are necessary to define the implant surface parameters able to assure the chemokines’ optimal release for a real improvement of dental implant osseointegration.
Entropy-Based Time Window Features Extraction for Machine Learning to Predict Acute Kidney Injury in ICU
Authors: Huang Chun-Te , Chang Rong-Ching , Tsai Yi-Lu , Pai Kai-Chih , Wang Tsai-Jung , Hsu Chia-Tien , Chen Cheng-Hsu , Huang Chien-Chung , Wang Min-Shian , Chen Lun-Chi , Sheu Ruey-Kai , Wu Chieh-Liang , Lai Chun-Ming
Published: July 2021

Acute kidney injury (AKI) refers to rapid decline of kidney function and is manifested by decreasing urine output or abnormal blood test (elevated serum creatinine). Electronic health records (EHRs) is fundamental for clinicians and machine learning algorithms to predict the clinical outcome of patients in the Intensive Care Unit (ICU). Early prediction of AKI could automatically warn the clinicians to review the possible risk factors and act in advance to prevent it. However, the enormous amount of patient data usually consists of a relatively incomplete data set and is very challenging for supervised machine learning process. In this paper, we propose an entropy-based feature engineering framework for vital signs based on their frequency of records. In particular, we address the missing at random (MAR) and missing not at random (MNAR) types of missing data according to different clinical scenarios. Regarding its applicability, we applied it to establish a prediction model for future AKI in ICU patients using 4278 ICU admissions from a tertiary hospital. Our result shows that the proposed entropy-based features are feasible to be used in the AKI prediction model and its performance improves as the data availability increases. In addition, we study the performance of AKI prediction model by comparing different time gaps and feature windows with the proposed vital sign entropy features. This work could be used as a guidance for feature windows selection and missing data processing during the development of a prediction model in ICU.
Modeling and Spatial Diversity-Based Receiving Improvement of In-Flight UAV FSO Communication Links
Authors: Zheng Anrui , Huang Yang , Gao Shiming
Published: July 2021

An in-flight unmanned aerial vehicle (UAV) free-space optical (FSO) communication channel model is proposed by considering the beam deviation of the UAV under different motion states and the phase distortion caused by atmospheric turbulences. The influence of the different motion states and turbulences on the communication quality is evaluated through phase screen and Monte Carlo methods. When the average bit error rate (BER) is 10−5, the signal-to-noise ratio (SNR) should be increased from 13 dB to 20 dB when the tilt angle of the UAV increases from 0 to 5 mrad. An SNR of up to 20 dB is required when the variance of the wind σα2 is 2 mrad. The performance of the in-flight UAV FSO link can be effectively improved through spatial diversity receiving technology. The BER of lower than 10−5 can be obtained just with an SNR of 13 dB if the spatial diversity array with four receivers is used.
Monitoring a Reverse Osmosis Process with Kernel Principal Component Analysis: A Preliminary Approach
Authors: Quatrini Elena , Costantino Francesco , Mba David , Li Xiaochuan , Gan Tat-Hean
Published: July 2021

The water purification process is becoming increasingly important to ensure the continuity and quality of subsequent production processes, and it is particularly relevant in pharmaceutical contexts. However, in this context, the difficulties arising during the monitoring process are manifold. On the one hand, the monitoring process reveals various discontinuities due to different characteristics of the input water. On the other hand, the monitoring process is discontinuous and random itself, thus not guaranteeing continuity of the parameters and hindering a straightforward analysis. Consequently, further research on water purification processes is paramount to identify the most suitable techniques able to guarantee good performance. Against this background, this paper proposes an application of kernel principal component analysis for fault detection in a process with the above-mentioned characteristics. Based on the temporal variability of the process, the paper suggests the use of past and future matrices as input for fault detection as an alternative to the original dataset. In this manner, the temporal correlation between process parameters and machine health is accounted for. The proposed approach confirms the possibility of obtaining very good monitoring results in the analyzed context.
Secure Data of Industrial Internet of Things in a Cement Factory Based on a Blockchain Technology
Authors: Umran Samir M. , Lu Songfeng , Abduljabbar Zaid Ameen , Zhu Jianxin , Wu Junjun
Published: July 2021

The Industrial Internet of Things (IIoT) has become a pivotal field of development that can increase the efficiency of real-time collection, recording, analysis, and control of the entire activities of various machines, and can actively enhance quality and reduce costs. The traditional IIoT depends on centralized architectures that are vulnerable to several kinds of cyber-attacks, such as bottlenecks and single points of failure. Blockchain technology has emerged to change these architectures to a decentralized form. In modern industrial settings, blockchain technology is utilized for its ability to provide high levels of security, low computational complexity, P2P communication, transparent logs, and decentralization. The present work proposes the use of a private blockchain mechanism for an industrial application in a cement factory, which offers low power consumption, scalability, and a lightweight security scheme; and which can play an efficient role in controlling access to valuable data generated by sensors and actuators. A low-power ARM Cortex-M processor is utilized due to its efficiency in terms of processing cryptographic algorithms, and this plays an important part in improving the computational execution of the proposed architecture. In addition, instead of proof of work (PoW), our blockchain network uses proof of authentication (PoAh) as a consensus mechanism to ensure secure authentication, scalability, speed, and energy efficiency. Our experimental results show that the proposed framework achieves high levels of security, scalability and ideal performance for smart industrial environments. Moreover, we successfully realized the integration of blockchain technology with the industrial internet of things devices, which provides the blockchain technology features and efficient resistance to common cyber-security attacks.
Particle Number Emissions of Gasoline, Compressed Natural Gas (CNG) and Liquefied Petroleum Gas (LPG) Fueled Vehicles at Different Ambient Temperatures
Authors: Lähde Tero , Giechaskiel Barouch
Published: July 2021

Compressed natural gas (CNG) and liquefied petroleum gas (LPG) are included in the group of promoted transport fuel alternatives for traditional fossil fuels in Europe. Both CNG and LPG fueled vehicles are believed to have low particle number and mass emissions. Here, we studied the solid particle number (SPN) emissions >4 nm, >10 nm and >23 nm of bi-fuel vehicles applying CNG, LPG and gasoline fuels in laboratory at 23 °C and sub-zero (−7 °C) ambient temperature conditions. The SPN23 emissions in CNG or LPG operation modality at 23 °C were below the regulated SPN23 limit of diesel and gasoline direct injection vehicles 6×1011 1/km. Nevertheless, the limit was exceeded at sub-zero temperatures, when sub-23 nm particles were included, or when gasoline was used as a fuel. The key message of this study is that gas-fueled vehicles produced particles mainly <23 nm and the current methodology might not be appropriate. However, only in a few cases absolute SPN >10 nm emission levels exceeded 6×1011 1/km when >23 nm levels were below 6×1011 1/km. Setting a limit of 1×1011 1/km for >10 nm particles would also limit most of the >4 nm SPN levels below 6×1011 1/km.
Atmospheric PM2.5 Prediction Using DeepAR Optimized by Sparrow Search Algorithm with Opposition-Based and Fitness-Based Learning
Authors: Jiang Feng , Han Xingyu , Zhang Wenya , Chen Guici
Published: July 2021

There is an important significance for human health in predicting atmospheric concentration precisely. However, due to the complexity and influence of contingency, atmospheric concentration prediction is a challenging topic. In this paper, we propose a novel hybrid learning method to make point and interval predictions of PM2.5 concentration simultaneously. Firstly, we optimize Sparrow Search Algorithm (SSA) by opposition-based learning, fitness-based learning, and Lévy flight. The experiments show that the improved Sparrow Search Algorithm (FOSSA) outperforms SSA-based algorithms. In addition, the improved Sparrow Search Algorithm (FOSSA) is employed to optimize the initial weights of probabilistic forecasting model with autoregressive recurrent network (DeepAR). Then, the FOSSA–DeepAR learning method is utilized to achieve the point prediction and interval prediction of PM2.5 concentration in Beijing, China. The performance of FOSSA–DeepAR is compared with other hybrid models and a single DeepAR model. Furthermore, hourly data of PM2.5 and O3 concentration in Taian of China, O3 concentration in Beijing, China are used to verify the effectiveness and robustness of the proposed FOSSA–DeepAR learning method. Finally, the empirical results illustrate that the proposed FOSSA–DeepAR learning model can achieve more efficient and accurate predictions in both interval and point prediction.
Urban Pit-Building Insects Are Attracted to Walls for Multiple Reasons
Authors: Scharf Inon , Gilad Tomer , Taichman Yuval , Subach Aziz
Published: July 2021

Whereas most animals find urban habitats to be inferior to natural habitats, some “urban specialist” species thrive there. Wormlions present such an example. Common in Mediterranean cities, they cluster in thin layers of loose soil below man-made shelters. Wormlions are fly larvae that dig pit-traps in loose soil and hunt small arthropods. Our first aim was to determine whether wormlion pits accumulate next to walls. Wormlion pits were indeed closer to walls than expected by chance at most of the study sites. We examined possible factors behind this apparent preference, combining field observations and experiments, laboratory work, and theoretical analysis. We examined the effect of soil depth, particle size, shade, and prey abundance. Each factor provided a partial explanation for the wormlions’ proximity to walls, but none provided an overall explanation. We developed a spatially explicit simulation model, demonstrating under which conditions wall-adjacent positions are favored. Finally, we created artificial microhabitats, and placed wormlions either in the center or next to the wall. The wormlions in the center moved over longer distances than those next to the wall and did so more in the wall’s direction. The abundance of walls may help to explain the success of wormlions in urban habitats.
Effect of Electrical Stimulation on Diabetic Human Skin Fibroblast Growth and the Secretion of Cytokines and Growth Factors Involved in Wound Healing
Authors: Abedin-Do Atieh , Zhang Ze , Douville Yvan , Méthot Mireille , Rouabhia Mahmoud
Published: July 2021

Diabetic foot ulcers are indicative of an impaired wound healing process. This delay may be resolved through electrical stimulation (ES). The goal of the present study was to evaluate the effect of ES on diabetic fibroblast adhesion and growth, and the secretion of cytokines and growth factors. Diabetic human skin fibroblasts (DHSF) were exposed to various intensities of direct current ES (100, 80, 40 and 20 mV/mm). The effect of ES on fibroblast adhesion and growth was evaluated using Hoechst staining, MTT and trypan blue exclusion assays. The secretion of cytokine and growth factor was assessed by cytokine array and ELISA assay. The long-term effects of ES on DHSF shape and growth were determined by optical microscopy and cell count. We demonstrated that ES at 20 and 40 mV/mm promoted cell adhesion, viability and growth. ES also decreased the secretion of pro-inflammatory cytokines IL-6 and IL-8 yet promoted growth factor FGF7 secretion during 48 h post-ES. Finally, the beneficial effect of ES on fibroblast growth was maintained up to 5 days post-ES. Overall results suggest the possible use of low-intensity direct current ES to promote wound healing in diabetic patients.
The Influence of Bloom Index, Endotoxin Levels and Polyethylene Glycol Succinimidyl Glutarate Crosslinking on the Physicochemical and Biological Properties of Gelatin Biomaterials
Authors: Wu Zhuning , Korntner Stefanie H. , Olijve Jos , Mullen Anne Maria , Zeugolis Dimitios I.
Published: July 2021

In the medical device sector, bloom index and residual endotoxins should be controlled, as they are crucial regulators of the device’s physicochemical and biological properties. It is also imperative to identify a suitable crosslinking method to increase mechanical integrity, without jeopardising cellular functions of gelatin-based devices. Herein, gelatin preparations with variable bloom index and endotoxin levels were used to fabricate non-crosslinked and polyethylene glycol succinimidyl glutarate crosslinked gelatin scaffolds, the physicochemical and biological properties of which were subsequently assessed. Gelatin preparations with low bloom index resulted in hydrogels with significantly (p < 0.05) lower compression stress, elastic modulus and resistance to enzymatic degradation, and significantly higher (p < 0.05) free amine content than gelatin preparations with high bloom index. Gelatin preparations with high endotoxin levels resulted in films that induced significantly (p < 0.05) higher macrophage clusters than gelatin preparations with low endotoxin level. Our data suggest that the bloom index modulates the physicochemical properties, and the endotoxin content regulates the biological response of gelatin biomaterials. Although polyethylene glycol succinimidyl glutarate crosslinking significantly (p < 0.05) increased compression stress, elastic modulus and resistance to enzymatic degradation, and significantly (p < 0.05) decreased free amine content, at the concentration used, it did not provide sufficient structural integrity to support cell culture. Therefore, the quest for the optimal gelatin crosslinker continues.
Exogenously Applied Gibberellic Acid Enhances Growth and Salinity Stress Tolerance of Maize through Modulating the Morpho-Physiological, Biochemical and Molecular Attributes
Authors: Shahzad Kashif , Hussain Sadam , Arfan Muhammad , Hussain Saddam , Waraich Ejaz Ahmad , Zamir Shahid , Saddique Maham , Rauf Abdur , Kamal Khaled Y. , Hano Christophe , El-Esawi Mohamed A.
Published: July 2021

Soil salinity is the major limiting factor restricting plant growth and development. Little is known about the comparative and combined effects of gibberellic acid (GA3) seed priming and foliar application on maize under salt stress. The current study determined the impact of different application methods of GA3 on morpho-physiological, biochemical and molecular responses of maize seedlings under three salinity stress treatments (no salinity, moderate salinity-6 dS m−1, and severe salinity-12 dS m−1). The GA3 treatments consisted of control, hydro-priming (HP), water foliar spray (WFS), HP + WFS, seed priming with GA3 (GA3P, 100 mg L−1), foliar spray with GA3 (GA3FS, 100ppm) and GA3P + GA3FS. Salt stress particularly at 12 dS m−1 reduced the length of shoots and roots, fresh and dry weights, chlorophyll, and carotenoid contents, K+ ion accumulation and activities of antioxidant enzymes, while enhanced the oxidative damage and accumulation of the Na+ ion in maize plants. Nevertheless, the application of GA3 improved maize growth, reduced oxidative stress, and increased the antioxidant enzymes activities, antioxidant genes expression, and K+ ion concentration under salt stress. Compared with control, the GA3P + GA3FS recorded the highest increase in roots and shoots length (19–37%), roots fresh and dry weights (31–43%), shoots fresh and dry weights (31–47%), chlorophyll content (21–70%), antioxidant enzymes activities (73.03–150.74%), total soluble protein (13.05%), K+ concentration (13–23%) and antioxidants genes expression levels under different salinity levels. This treatment also reduced the H2O2 content, and Na+ ion concentration. These results indicated that GA3P + GA3FS could be used as an effective tool for improving the maize growth and development, and reducing the oxidative stress in salt-contaminated soils.
Immunometabolism Modulation in Therapy
Authors: Monferrer Ezequiel , Sanegre Sabina , Vieco-Martí Isaac , López-Carrasco Amparo , Fariñas Fernando , Villatoro Antonio , Abanades Sergio , Mañes Santos , de la Cruz-Merino Luis , Noguera Rosa , Álvaro Naranjo Tomás
Published: July 2021

The study of cancer biology should be based around a comprehensive vision of the entire tumor ecosystem, considering the functional, bioenergetic and metabolic state of tumor cells and those of their microenvironment, and placing particular importance on immune system cells. Enhanced understanding of the molecular bases that give rise to alterations of pathways related to tumor development can open up new therapeutic intervention opportunities, such as metabolic regulation applied to immunotherapy. This review outlines the role of various oncometabolites and immunometabolites, such as TCA intermediates, in shaping pro/anti-inflammatory activity of immune cells such as MDSCs, T lymphocytes, TAMs and DCs in cancer. We also discuss the extraordinary plasticity of the immune response and its implication in immunotherapy efficacy, and highlight different therapeutic intervention possibilities based on controlling the balanced systems of specific metabolites with antagonistic functions.
Metabolic Phenotypes and Step by Step Evolution of Type 2 Diabetes: A New Paradigm
Authors: Cooper Isabella D. , Brookler Kenneth H. , Kyriakidou Yvoni , Elliott Bradley T. , Crofts Catherine A. P.
Published: July 2021

Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these processes are dysregulated, such as in type 2 diabetes (T2DM), cardiovascular disease (CVD), certain cancers and dementias. Chronic hyperinsulinaemia enforces glucose fueling, depleting the NAD+ dependent antioxidant activity that increases mitochondrial reactive oxygen species (mtROS). Consequently, beta-cell mitochondria increase uncoupling protein expression, which decreases the mitochondrial ATP surge generation capacity, impairing bolus mediated insulin exocytosis. Excessive ROS increases the Drp1:Mfn2 ratio, increasing mitochondrial fission, which increases mtROS; endoplasmic reticulum-stress and impaired calcium homeostasis ensues. Healthy individuals in habitual ketosis have significantly lower glucagon and insulin levels than T2DM individuals. As beta-hydroxybutyrate rises, hepatic gluconeogenesis and glycogenolysis supply extra-hepatic glucose needs, and osteocalcin synthesis/release increases. We propose insulin’s primary role is regulating beta-hydroxybutyrate synthesis, while the role of bone regulates glucose uptake sensitivity via osteocalcin. Osteocalcin regulates the alpha-cell glucagon secretory profile via glucagon-like peptide-1 and serotonin, and beta-hydroxybutyrate synthesis via regulating basal insulin levels. Establishing metabolic phenotypes aids in resolving basal insulin secretion regulation, enabling elucidation of the pathological changes that occur and progress into chronic diseases associated with ageing.
Stress and Psychopathology Reduction in Pregnant Women through Online Cognitive Behavioural Therapy during COVID-19: A Feasibility Study
Authors: Puertas-Gonzalez Jose A. , Mariño-Narvaez Carolina , Romero-Gonzalez Borja , Peralta-Ramirez Maria Isabel
Published: July 2021

Background: The global pandemic has affected the psychological health of the population, including pregnant women. Due to the difficulty of offering conventional therapies to reduce stress in this population, studies are needed to show the effect of online therapies. Therefore, the objective was to test the effect of online cognitive behavioural therapy in pregnant women during the pandemic on the main variables of stress and psychopathology. Methods: The sample consisted of 16 pregnant women who participated in a weekly cognitive behavioural intervention for 8 weeks. Prenatal concerns, general stress, stress vulnerability, resilience and psychopathology were assessed. Results: The results show a reduction in prenatal concerns, perceived stress, stress vulnerability and psychopathology, as well as an increase in resilience. Conclusions: Online cognitive behavioural intervention may be effective in pregnant women, so it is important to conduct a randomised controlled trial to certify these findings.
18F-FMISO-PET Hypoxia Monitoring for Head-and-Neck Cancer Patients: Radiomics Analyses Predict the Outcome of Chemo-Radiotherapy
Authors: Carles Montserrat , Fechter Tobias , Grosu Anca L. , Sörensen Arnd , Thomann Benedikt , Stoian Raluca G. , Wiedenmann Nicole , Rühle Alexander , Zamboglou Constantinos , Ruf Juri , Martí-Bonmatí Luis , Baltas Dimos , Mix Michael , Nicolay Nils H.
Published: July 2021

Tumor hypoxia is associated with radiation resistance and can be longitudinally monitored by 18F-fluoromisonidazole (18F-FMISO)-PET/CT. Our study aimed at evaluating radiomics dynamics of 18F-FMISO-hypoxia imaging during chemo-radiotherapy (CRT) as predictors for treatment outcome in head-and-neck squamous cell carcinoma (HNSCC) patients. We prospectively recruited 35 HNSCC patients undergoing definitive CRT and longitudinal 18F-FMISO-PET/CT scans at weeks 0, 2 and 5 (W0/W2/W5). Patients were classified based on peritherapeutic variations of the hypoxic sub-volume (HSV) size (increasing/stable/decreasing) and location (geographically-static/geographically-dynamic) by a new objective classification parameter (CP) accounting for spatial overlap. Additionally, 130 radiomic features (RF) were extracted from HSV at W0, and their variations during CRT were quantified by relative deviations (∆RF). Prediction of treatment outcome was considered statistically relevant after being corrected for multiple testing and confirmed for the two 18F-FMISO-PET/CT time-points and for a validation cohort. HSV decreased in 64% of patients at W2 and in 80% at W5. CP distinguished earlier disease progression (geographically-dynamic) from later disease progression (geographically-static) in both time-points and cohorts. The texture feature low grey-level zone emphasis predicted local recurrence with AUCW2 = 0.82 and AUCW5 = 0.81 in initial cohort (N = 25) and AUCW2 = 0.79 and AUCW5 = 0.80 in validation cohort. Radiomics analysis of 18F-FMISO-derived hypoxia dynamics was able to predict outcome of HNSCC patients after CRT.
Interplay of Epidermal Growth Factor Receptor and Signal Transducer and Activator of Transcription 3 in Prostate Cancer: Beyond Androgen Receptor Transactivation
Authors: Lin Shian-Ren , Yeh Hsiu-Lien , Liu Yen-Nien
Published: July 2021

Prostate cancer (PCa) is one of the most common cancers in the world and causes thousands of deaths every year. Conventional therapy for PCa includes surgery and androgen deprivation therapy (ADT). However, about 10–20% of all PCa cases relapse; there is also the further development of castration resistant adenocarcinoma (CRPC-Adeno) or neuroendocrine (NE) PCa (CRPC-NE). Due to their androgen-insensitive properties, both CRPC-Adeno and CRPC-NE have limited therapeutic options. Accordingly, this study reveals the inductive mechanisms of CRPC (for both CRPC-Adeno and CRPC-NE) and fulfils an urgent need for the treatment of PCa patients. Although previous studies have illustrated the emerging roles of epidermal growth factor receptors (EGFR), signal transducer, and activator of transcription 3 (STAT3) signaling in the development of CRPC, the regulatory mechanisms of this interaction between EGFR and STAT3 is still unclear. Our recent studies have shown that crosstalk between EGFR and STAT3 is critical for NE differentiation of PCa. In this review, we have collected recent findings with regard to the involvement of EGFR and STAT3 in malignancy progression and discussed their interactions during the development of therapeutic resistance for PCa.
Albumin Nanostructures for Nucleic Acid Delivery in Cancer: Current Trend, Emerging Issues, and Possible Solutions
Authors: Prajapati Rama , Somoza Álvaro
Published: July 2021

Cancer is one of the major health problems worldwide, and hence, suitable therapies with enhanced efficacy and reduced side effects are desired. Gene therapy, involving plasmids, small interfering RNAs, and antisense oligonucleotides have been showing promising potential in cancer therapy. In recent years, the preparation of various carriers for nucleic acid delivery to the tumor sites is gaining attention since intracellular and extracellular barriers impart major challenges in the delivery of naked nucleic acids. Albumin is a versatile protein being used widely for developing carriers for nucleic acids. It provides biocompatibility, tumor specificity, the possibility for surface modification, and reduces toxicity. In this review, the advantages of using nucleic acids in cancer therapy and the challenges associated with their delivery are presented. The focus of this article is on the different types of albumin nanocarriers, such as nanoparticles, polyplexes, and nanoconjugates, employed to overcome the limitations of the direct use of nucleic acids in vivo. This review also highlights various approaches for the modification of the surface of albumin to enhance its transfection efficiency and targeted delivery in the tumor sites.
In Silico Analysis of the Longevity and Timeline of Individual Germinal Center Reactions in a Primary Immune Response
Authors: Arulraj Theinmozhi , Binder Sebastian C. , Meyer-Hermann Michael
Published: July 2021

Germinal centers (GCs) are transient structures in the secondary lymphoid organs, where B cells undergo affinity maturation to produce high affinity memory and plasma cells. The lifetime of GC responses is a critical factor limiting the extent of affinity maturation and efficiency of antibody responses. While the average lifetime of overall GC reactions in a lymphoid organ is determined experimentally, the lifetime of individual GCs has not been monitored due to technical difficulties in longitudinal analysis. In silico analysis of the contraction phase of GC responses towards primary immunization with sheep red blood cells suggested that if individual GCs had similar lifetimes, the data would be consistent only when new GCs were formed until a very late phase after immunization. Alternatively, there could be a large variation in the lifetime of individual GCs suggesting that both long and short-lived GCs might exist in the same lymphoid organ. Simulations predicted that such differences in the lifetime of GCs could arise due to variations in antigen availability and founder cell composition. These findings identify the potential factors limiting GC lifetime and contribute to an understanding of overall GC responses from the perspective of individual GCs in a primary immune response.
The Emergence of Senescent Surface Biomarkers as Senotherapeutic Targets
Authors: Rossi Martina , Abdelmohsen Kotb
Published: July 2021

Senescence is linked to a wide range of age-associated diseases and physiological declines. Thus, senotherapeutics are emerging to suppress the detrimental effects of senescence either by senomorphics or senolytics. Senomorphics suppress the traits associated with senescence phenotypes, while senolytics aim to clear senescent cells by suppressing their survival and enhancing the apoptotic pathways. The main goal of these approaches is to suppress the proinflammatory senescence-associated secretory phenotype (SASP) and to promote the immune recognition and elimination of senescent cells. One increasingly attractive approach is the targeting of molecules or proteins specifically present on the surface of senescent cells. These proteins may play roles in the maintenance and survival of senescent cells and hence can be targeted for senolysis. In this review, we summarize the recent knowledge regarding senolysis with a focus on novel surface biomarkers of cellular senescence and discuss their emergence as senotherapeutic targets.
Fostering “Education”: Do Extracellular Vesicles Exploit Their Own Delivery Code?
Authors: Paolillo Mayra , Comincini Sergio , Schinelli Sergio
Published: July 2021

Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV “delivery code” and on the combinations of the hypothesized EV surface membrane “sender” and “recipient” molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.
Evaluation of Streptococcus mutans Adhesion to Stainless Steel Surfaces Modified Using Different Topographies Following a Biomimetic Approach
Authors: Arango-Santander Santiago , Serna Lina , Sanchez-Garzon Juliana , Franco John
Published: July 2021

Bacterial adhesion to surfaces is the first step in biofilm formation, which leads to the development of conditions that may compromise the health status of patients. Surface modification has been proposed to reduce bacterial adhesion to biomaterials. The objective of this work was to assess and compare Streptococcus mutans adhesion to the surface of biomimetically-modified stainless steel using different topographies. Stainless steel plates were modified using a soft lithography technique following a biomimetic approach. The leaves from Colocasia esculenta, Crocosmia aurea and Salvinia molesta were used as surface models. Silica sol was synthesized using the sol-gel method. Following a soft lithography technique, the surface of the leaves were transferred to the surface of the SS plates. Natural and modified surfaces were characterized by means of atomic force microscopy and contact angle. Streptococcus mutans was used to assess bacterial adhesion. Contact angle measurements showed that natural leaves are highly hydrophobic, but such hydrophobicity could not be transferred to the metallic plates. Roughness varied among the leaves and increased after transference for C. esculenta and decreased for C. aurea. In general, two of the surface models used in this investigation showed positive results for reduction of bacterial adhesion (C. aurea and C. esculenta), while the other showed an increase in bacterial adhesion (S. molesta). Therefore, since a biomimetic approach using natural surfaces showed opposite results, careful selection of the surface model needs to be taken into consideration.