bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhalative Nanoparticulate CpG Immunotherapy in Severe Equine Asthma: An Innovative Therapeutic Concept and Potential Animal Model for Human Asthma Treatment
Authors: Klier John , Fuchs Sebastian , Winter Gerhard , Gehlen Heidrun
Published: August 2022

Severe equine asthma is the most common globally widespread non-infectious equine respiratory disease (together with its mild and moderate form), which is associated with exposure to hay dust and mold spores, has certain similarities to human asthma, and continues to represent a therapeutic problem. Immunomodulatory CpG-ODN, bound to gelatin nanoparticles as a drug delivery system, were successfully administered by inhalation to severe equine asthmatic patients in several studies. It was possible to demonstrate a significant, sustained, and allergen-independent one-to-eight-week improvement in key clinical parameters: the arterial partial pressure of oxygen, the quantity and viscosity of tracheal mucus, and neutrophilic inflammatory cells in the respiratory tracts of the severe equine asthmatic subjects. At the immunological level, an upregulation of the regulatory antiallergic and anti-inflammatory cytokine IL-10 as well as a downregulation of the proallergic IL-4 and proinflammatory IFN-γ in the respiratory tracts of the severe equine asthmatic patients were identified in the treatment groups. CD4+ T lymphocytes in the respiratory tracts of the asthmatic horses were demonstrated to downregulate the mRNA expression of Tbet and IL-8. Concentrations of matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2 were significantly decreased directly after the treatment as well as six weeks post-treatment. This innovative therapeutic concept thus opens new perspectives in the treatment of severe equine asthma and possibly also that of human asthma.
IgG Avidity Test as a Tool for Discrimination between Recent and Distant Toxoplasma gondii Infection—Current Status of Studies
Authors: Holec-Gąsior Lucyna , Sołowińska Karolina
Published: August 2022

Toxoplasma gondii, an obligate intracellular protozoan parasite, is the causative agent of one of the most prevalent zoonoses worldwide. T. gondii infection is extremely important from a medical point of view, especially for pregnant women, newborns with congenital infections, and immunocompromised individuals. Thus, an accurate and proper diagnosis of this infection is essential. Among the available diagnostic tests, serology is commonly used. However, traditional serological techniques have certain limitations in evaluating the duration of T. gondii infection, which is problematic, especially for pregnant women. Avidity of T. gondii-specific IgG antibodies seems to be a significant tool for discrimination between recent and distant infections. This article describes the problem of diagnosis of T. gondii infection, with regard to IgG avidity tests. The IgG avidity test is a useful serological indicator of toxoplasmosis, which in many cases can confirm or exclude the active form of the disease. IgG antibodies produced in the recent primary T. gondii infection are of low avidity while IgG antibodies with high avidity are detected in the chronic phase of infection. Furthermore, this paper presents important topics of current research that concern the usage of parasite recombinant antigens that may improve the performance of IgG avidity tests.
Comparing the Outcomes of Ceftaroline plus Vancomycin or Daptomycin Combination Therapy versus Vancomycin or Daptomycin Monotherapy in Adults with Methicillin-Resistant Staphylococcus aureus Bacteremia—A Meta-Analysis
Authors: Huang Chienhsiu , Chen Ihung , Lin Lichen
Published: August 2022

Introduction: Combination therapy with daptomycin plus ceftaroline to treat methicillin-resistant Staphylococcus aureus bacteremia has been reported to reduce methicillin-resistant Staphylococcus aureus bacteremia-related mortality. The purpose of the current meta-analysis was to compare the clinical outcome of methicillin-resistant Staphylococcus aureus bacteremia in patients treated with daptomycin or vancomycin plus ceftaroline combination therapy versus daptomycin or vancomycin monotherapy. Methods: Studies were included if they directly compared the efficacy of daptomycin or vancomycin plus ceftaroline combination therapy with that of daptomycin or vancomycin monotherapy in the treatment of methicillin-resistant Staphylococcus aureus bacteremia in adult patients. Results: One randomized controlled trial and five retrospective studies were included in the meta-analysis. The combination therapy group had an in-hospital mortality, duration of bacteremia, and adverse event rate similar to those patients who had monotherapy. There was less bacteremia recurrence in the combination group. Initial combination therapy with ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia showed a trend of reducing the risk of in-hospital mortality in the current meta-analysis. Conclusions: Randomized controlled trials are needed to further study the role of initial combination therapy with daptomycin or vancomycin plus ceftaroline in the treatment of methicillin-resistant Staphylococcus aureus bacteremia.
Chelation in Antibacterial Drugs: From Nitroxoline to Cefiderocol and Beyond
Authors: Repac Antić Davorka , Parčina Marijo , Gobin Ivana , Petković Didović Mirna
Published: August 2022

In the era of escalating antimicrobial resistance, the need for antibacterial drugs with novel or improved modes of action (MOAs) is a health concern of utmost importance. Adding or improving the chelating abilities of existing drugs or finding new, nature-inspired chelating agents seems to be one of the major ways to ensure progress. This review article provides insight into the modes of action of antibacterial agents, class by class, through the perspective of chelation. We covered a wide scope of antibacterials, from a century-old quintessential chelating agent nitroxoline, currently unearthed due to its newly discovered anticancer and antibiofilm activities, over the commonly used antibacterial classes, to new cephalosporin cefiderocol and a potential future class of tetramates. We show the impressive spectrum of roles that chelation plays in antibacterial MOAs. This, by itself, demonstrates the importance of understanding the fundamental chemistry behind such complex processes.
Surface-Active Compounds Produced by Microorganisms: Promising Molecules for the Development of Antimicrobial, Anti-Inflammatory, and Healing Agents
Authors: Araujo Jéssica , Monteiro Joveliane , Silva Douglas , Alencar Amanda , Silva Kariny , Coelho Lara , Pacheco Wallace , Silva Darlan , Silva Maria , Silva Luís , Monteiro Andrea
Published: August 2022

Surface-active compounds (SACs), biomolecules produced by bacteria, yeasts, and filamentous fungi, have interesting properties, such as the ability to interact with surfaces as well as hydrophobic or hydrophilic interfaces. Because of their advantages over other compounds, such as biodegradability, low toxicity, antimicrobial, and healing properties, SACs are attractive targets for research in various applications in medicine. As a result, a growing number of properties related to SAC production have been the subject of scientific research during the past decade, searching for potential future applications in biomedical, pharmaceutical, and therapeutic fields. This review aims to provide a comprehensive understanding of the potential of biosurfactants and emulsifiers as antimicrobials, modulators of virulence factors, anticancer agents, and wound healing agents in the field of biotechnology and biomedicine, to meet the increasing demand for safer medical and pharmacological therapies.
Supplementation with Two New Standardized Tea Extracts Prevents the Development of Hypertension in Mice with Metabolic Syndrome
Authors: de la Fuente Muñoz Mario , de la Fuente Fernández María , Román-Carmena Marta , Iglesias de la Cruz Maria del Carmen , Amor Sara , Martorell Patricia , Enrique-López María , García-Villalón Angel Luis , Inarejos-García Antonio Manuel , Granado Miriam
Published: August 2022

Hypertension is considered to be both a cardiovascular disease and a risk factor for other cardiovascular diseases, such as coronary ischemia or stroke. In many cases, hypertension occurs in the context of metabolic syndrome (MetS), a condition in which other circumstances such as abdominal obesity, dyslipidemia, and insulin resistance are also present. The high incidence of MetS makes necessary the search for new strategies, ideally of natural origin and with fewer side effects than conventional pharmacological treatments. Among them, the tea plant is a good candidate, as it contains several bioactive compounds such as caffeine, volatile terpenes, organic acids, and polyphenols with positive biological effects. The aim of this study was to assess whether two new standardized tea extracts, one of white tea (WTE) and the other of black and green tea (CTE), exert beneficial effects on the cardiovascular alterations associated with MetS. For this purpose, male C57/BL6J mice were fed a standard diet (Controls), a diet high in fats and sugars (HFHS), HFHS supplemented with 1.6% WTE, or HFHS supplemented with 1.6% CTE for 20 weeks. The chromatography results showed that CTE is more concentrated on gallic acid, xanthines and flavan-3-ols than WTE. In vivo, supplementation with WTE and CTE prevented the development of MetS-associated hypertension through improved endothelial function. This improvement was associated with a lower expression of proinflammatory and prooxidant markers, and—in the case of CTE supplementation—also with a higher expression of antioxidant enzymes in arterial tissue. In conclusion, supplementation with WTE and CTE prevents the development of hypertension in obese mice; as such, they could be an interesting strategy to prevent the cardiovascular disorders associated with MetS.
Properties of Cephalopod Skin Ommochromes to Inhibit Free Radicals, and the Maillard Reaction and Retino-Protective Mechanisms in Cellular Models Concerning Oxidative Stress, Angiogenesis, and Inflammation
Authors: Lewis Luján Lidianys María , Dörschmann Philipp , Seeba Charlotte , Thalenhorst Tabea , Roider Johann , Iloki Assanga Simon Bernard , Ruiz Juan Carlos Gálvez , Del Castillo Castro Teresa , Rosas-Burgos Ema Carina , Plascencia-Jatomea Maribel , Ezquerra Brauer Josafat Marina , Klettner Alexa
Published: August 2022

Ommochromes are pigments of invertebrates that exhibit oxidative stress protection. The aim of this study was to investigate ommochromes extracted from cephalopod’s skin for their ability to inhibit age-related-macular degeneration (AMD)-related factors such as H2O2-induced and iron-dependent oxidative stress (ferroptosis and erastin), accumulation of advanced glycation end-products (AGEs), as well as vascular endothelial growth factor (VEGF), and inflammatory cytokines (interleukin 6 and interleukin 8) secretion. As cell systems, we used primary porcine retinal pigment epithelium (RPE), human retinal pigment epithelium cell line ARPE-19 and uveal melanoma cell line OMM-1. In vitro, ommochromes produced an antiglycation effect by the inhibition of fructosylation reaction. The ommochromes showed protective effects against erastin- induced cell death in ARPE-19. In addition, in long-term stimulation (7 days) ommochromes decreased constitutively secreted VEGF, as well as interleukin 6 and interleukin 8 induced by Poly I:C in primary RPE. No relevant effects were detected in OMM-1 cells. The effects are dependent on the cell system, time of exposition, and concentration. This substance is of interest for further research concerning age-related macular degeneration.
Toward Supporting Maxillo-Facial Surgical Guides Positioning with Mixed Reality—A Preliminary Study
Authors: Piramide Chiara , Ulrich Luca , Piazzolla Pietro , Vezzetti Enrico
Published: August 2022

Following an oncological resection or trauma it may be necessary to reconstruct the normal anatomical and functional mandible structures to ensure the effective and complete social reintegration of patients. In most surgical procedures, reconstruction of the mandibular shape and its occlusal relationship is performed through the free fibula flap using a surgical guide which allows the surgeon to easily identify the location and orientation of the cutting plane. In the present work, we present a Mixed Reality (MR)-based solution to support professionals in surgical guide positioning. The proposed solution, through the use of a Head-Mounted Display (HMD) such as that of the HoloLens 2, visualizes a 3D virtual model of the surgical guide, positioned over the patient’s real fibula in the correct position as identified by the medical team before the procedure. The professional wearing the HMD is then assisted in positioning the real guide over the virtual one by our solution, which is capable of tracking the real guide during the whole process and computing its distance from the final position. The assessment results highlight that Mixed Reality is an eligible technology to support surgeons, combining the usability of the device with an improvement of the accuracy in fibula flap removal surgery.
Machine-Learning-Based Digital Twin System for Predicting the Progression of Prostate Cancer
Authors: Kim Jae-Kwon , Lee Sun-Jung , Hong Sung-Hoo , Choi In-Young
Published: August 2022

Clinical decision support systems (CDSSs) enable users to make decisions based on clinical data from electronic medical records, facilitating personalized precision medicine treatments. A digital twin (DT) approach enables the interoperability between physical and virtual environments through data analysis using machine learning (ML). By combining DT with the prostate cancer (PCa) process, it is possible to predict cancer prognosis. In this study, we propose a DT-based prediction model for clinical decision-making in the PCa process. Pathology and biochemical recurrence (BCR) were predicted with ML using data from a clinical data warehouse and the PCa process. The DT model was developed using data from 404 patients. The BCR prediction accuracy increased according to the amount of data used, and reached as high as 96.25% when all data were used. The proposed DT-based predictive model can help provide a clinical decision support system for PCa. Further, it can be used to improve medical processes, promote health, and reduce medical costs and problems.
Prefermentative Grape Microwave Treatment as a Tool for Increasing Red Wine Phenolic Content and Reduce Maceration Time
Authors: Pérez-Porras Paula , Gómez-Plaza Encarna , Muñoz García Raquel , Díaz-Maroto María Consuelo , Moreno-Olivares Juan Daniel , Bautista-Ortín Ana Belén
Published: August 2022

Phenolic compounds are responsible for color and, with it, the quality of red wines. Its content will depend, among other factors, on the oenological techniques applied in the winery and, among them, the maceration time. Long maceration times can generate logistical problems at the moment of maximum grape entry into the winery. Applying techniques that accelerate the extraction of phenolic compounds from the grape solid parts to the must-wine would allow reducing the maceration time. Among the techniques of interest, microwaves use electromagnetic waves to produce dipole rotation and ion conduction, which can increase the elasticity of cell walls and cause the destruction of the cell membrane, facilitating the phenolic compound extraction. To study this effect, crushed grapes of the Cabernet Sauvignon variety were treated with this technology, macerated for 72 h and 7 days, and compared with respect to a control wine without any treatment. The results showed that the application of microwaves to the crushed grape favored a rapid extraction of the phenolic compounds, increasing the color of the wine and with only 72 h of maceration, the wines from treated grapes showed a similar phenolic content and chromatic characteristics to a control wine with 7 maceration days. The extraction of the less astringent skin tannins and the formation of stable pigments was also favored indicating that this technology may allow reducing the maceration time during the winemaking process without affecting the quality and stability of the wine.
Application of Mechanistic Empirical Pavement Design Guide Software in Saudi Arabia
Authors: Fuhaid Abdulrahman Fahad Al , Arifuzzaman Md , Gul Muhammad Aniq
Published: August 2022

The present study explores the structural pavement design techniques related to pavement distresses in terms of pavement rutting, cracking and International Roughness Index (IRI) based on the materials properties, roadbed characteristics, climate and traffic loads for highway network of Saudi Arabia (KSA). The study was focused on selected site conditions at four regions in KSA: Central (Riyadh); Eastern (Al-Ahsa); Western (Jeddah) and Northern (Arar). Mechanistic-Empirical Pavement Design Guide (MEPDG) software was used to calibrate and predict pavement design life according to the mentioned distresses for different regions in the KSA. This is the first time where the exact weather stations were selected to run analysis on the software determining realistic pavement distresses. In the study, the pavement structure design is different for low traffic (700 AADTT) and high traffic (2000, 6000, and 10,000 AADTT). The tests were run on the MEPDG software to analyze the distresses predicted by the software for an interval of 5, 10, 15, and 20 years. The results predicted by the software show that the preliminary example design satisfies all the target distresses for the mentioned design life, even for 20 years. The study provides a base pavement design for pavement designers that can be modified as per project requirements using the specific data for traffic, material properties, thickness, and distress limit to achieve target design life.
Robust Estimation in Continuous–Discrete Cubature Kalman Filters for Bearings-Only Tracking
Authors: Hu Haoran , Chen Shuxin , Wu Hao , He Renke
Published: August 2022

The model of bearings-only tracking is generally described by discrete–discrete filtering systems. Discrete robust methods are also frequently used to address measurement uncertainty problems in bearings-only tracking. The recently popular continuous–discrete filtering system considers the state model of the target to be continuous in time, and is more suitable for bearings-only tracking because of its higher mathematical solution accuracy. However, the sufficient evaluation of robust methods in continuous–discrete systems is not available. In addition, in the different continuous–discrete measurement environments, the choice of a robust algorithm also needs to be discussed. To fill this gap, this paper firstly establishes the continuous–discrete target tracking model, and then evaluates the performance of proposed robust square-root continuous–discrete cubature Kalman filter algorithms in the measurement of uncertainty problems. From the simulation results, the robust square-root continuous–discrete maximum correntropy cubature Kalman filter algorithm and the variational Bayesian square-root continuous–discrete cubature Kalman filter algorithm have better environmental adaptability, which provides a promising means for solving continuous–discrete robust problems.
Model-Based Firmware Generation for Acquisition Systems Using Heterogeneous Hardware
Authors: Baeyens Rens , Denil Joachim , Steckel Jan , Daems Walter
Published: August 2022

High-performance sensing and control systems have an important role in Industry 4.0. However, with the current solutions, the development effort is high and requires specialized skills in electronic engineering. Therefore, a model-based approach on control and signal processing systems using affordable heterogeneous hardware is proposed. In this work, a model-based code generator is developed to abstract the user from the actual software implementation. Starting from a combined model of a timing diagram and an embedded platform, a model transformation is used to automatically generate functional acquisition firmware. This firmware generator enables system engineers without deep software and hardware knowledge to set up complex control systems. Furthermore, it equips software engineers with a solid framework for faster development.
Periodic Waves and Ligaments on the Surface of a Viscous Exponentially Stratified Fluid in a Uniform Gravity Field
Authors: Chashechkin Yuli D. , Ochirov Artem A.
Published: August 2022

The theory of singular perturbations in a unified formulation is used, for the first time, to study the propagation of two-dimensional periodic perturbations, including capillary and gravitational surface waves and accompanying ligaments in the 10−4<ω<103  s−1 frequency range, in a viscous continuously stratified fluid. Dispersion relations for flow constituents are given, as well as expressions for phase and group velocities for surface waves and ligaments in physically observable variables. When the wave-length reaches values of the order of the stratification scale, the liquid behaves as homogeneous. As the wave frequency approaches the buoyancy frequency, the energy transfer rate decreases: the group velocity of surface waves tends to zero, while the phase velocity tends to infinity. In limiting cases, the expressions obtained are transformed into known wave dispersion expressions for an ideal stratified or actually homogeneous fluid.
Evaluation of Cryptocurrencies for Investment Decisions in the Era of Industry 4.0: A Borda Count-Based Intuitionistic Fuzzy Set Extensions EDAS-MAIRCA-MARCOS Multi-Criteria Methodology
Authors: Ecer Fatih , Böyükaslan Adem , Hashemkhani Zolfani Sarfaraz
Published: August 2022

Blockchain technologies, which form the basis of Industry 4.0, paved the way for cryptocurrencies to emerge as technological innovation in the technology age. Recently, investors worldwide have been interested in cryptocurrencies with increasing acceleration due to high earning expectations though they have no backing and intrinsic value. As such, this paper seeks to identify the most proper cryptocurrencies from an investment standpoint in our technological era. Fifteen well-known cryptocurrencies with the highest market capitalization are evaluated as per sixteen factors. An intuitionistic fuzzy set-driven methodology incorporating Evaluation Based on Distance from Average Solution (EDAS), Multi-Attributive Ideal Real Comparative Analysis (MAIRCA, and Measurement of Alternatives and Ranking according to COmpromise Solution (MARCOS), which is the study’s prominent novelty, has been applied to provide a strong group decision vehicle for cryptocurrency selection. Notwithstanding, although the results obtained with the three approaches are highly consistent, investors would not like to doubt the instrument they will invest in. The Borda count is then applied to obtain a compromise for the rankings obtained from each approach. As per our findings, Ethereum, Tether, and Bitcoin are the most suitable cryptocurrencies, whereas reliable software, ease of inclusion in the wallet, and stability are the foremost factors to consider when investing in cryptocurrencies. The findings are further discussed in detail from a financial perspective. The proposed approach could be employed to select different investment instruments in future studies.
Effects of Cell Design Parameters on Zinc-Air Battery Performance
Authors: Lu Cian-Tong , Zhu Zhi-Yan , Chen Sheng-Wen , Chang Yu-Ling , Hsueh Kan-Lin
Published: August 2022

Zn-air batteries have attracted considerable attention from researchers owing to their high theoretical energy density and the abundance of zinc on Earth. The modification of battery component materials represent a common approach to improve battery performance. The effects of cell design on cell performance are seldom investigated. In this study, we designed four battery structures as follows. Cell 1: close-proximity electrode, Cell 2: equal-area electrode, Cell 3: large zinc electrode, and Cell 4: air channel flow. The effects of four factors: (1) carbon paste, (2) natural and forced air convection, (3) anode/cathode area ratio, and (4) anode–cathode distance were also investigated. Results showed that the addition of carbon paste on the air side of 25BC increased cell power density under forced air convection. Moreover, cell performance also improved by increasing the anode/cathode ratio and by decreasing the anode–cathode distance. These four types of cells were compared based on the oxygen reduction reaction electrode area. Cell 3 displayed the highest power density. In terms of volumetric power density, the proximity cell (Cell 1) exhibited the highest power density among the cells. Therefore, this cell configuration may be suitable for portable applications.
A Deep Learning Computer-Aided Diagnosis Approach for Breast Cancer
Authors: Zaalouk Ahmed M. , Ebrahim Gamal A. , Mohamed Hoda K. , Hassan Hoda Mamdouh , Zaalouk Mohamed M. A.
Published: August 2022

Breast cancer is a gigantic burden on humanity, causing the loss of enormous numbers of lives and amounts of money. It is the world’s leading type of cancer among women and a leading cause of mortality and morbidity. The histopathological examination of breast tissue biopsies is the gold standard for diagnosis. In this paper, a computer-aided diagnosis (CAD) system based on deep learning is developed to ease the pathologist’s mission. For this target, five pre-trained convolutional neural network (CNN) models are analyzed and tested—Xception, DenseNet201, InceptionResNetV2, VGG19, and ResNet152—with the help of data augmentation techniques, and a new approach is introduced for transfer learning. These models are trained and tested with histopathological images obtained from the BreakHis dataset. Multiple experiments are performed to analyze the performance of these models through carrying out magnification-dependent and magnification-independent binary and eight-class classifications. The Xception model has shown promising performance through achieving the highest classification accuracies for all the experiments. It has achieved a range of classification accuracies from 93.32% to 98.99% for magnification-independent experiments and from 90.22% to 100% for magnification-dependent experiments.
Intelligent Epileptic Seizure Detection and Classification Model Using Optimal Deep Canonical Sparse Autoencoder
Authors: Hilal Anwer Mustafa , Albraikan Amani Abdulrahman , Dhahbi Sami , Nour Mohamed K. , Mohamed Abdullah , Motwakel Abdelwahed , Zamani Abu Sarwar , Rizwanullah Mohammed
Published: August 2022

Epileptic seizures are a chronic and persistent neurological illness that mainly affects the human brain. Electroencephalogram (EEG) is considered an effective tool among neurologists to detect various brain disorders, including epilepsy, owing to its advantages, such as its low cost, simplicity, and availability. In order to reduce the severity of epileptic seizures, it is necessary to design effective techniques to identify the disease at an earlier stage. Since the traditional way of diagnosing epileptic seizures is laborious and time-consuming, automated tools using machine learning (ML) and deep learning (DL) models may be useful. This paper presents an intelligent deep canonical sparse autoencoder-based epileptic seizure detection and classification (DCSAE-ESDC) model using EEG signals. The proposed DCSAE-ESDC technique involves two major processes, namely, feature selection and classification. The DCSAE-ESDC technique designs a novel coyote optimization algorithm (COA)-based feature selection technique for the optimal selection of feature subsets. Moreover, the DCSAE-based classifier is derived for the detection and classification of different kinds of epileptic seizures. Finally, the parameter tuning of the DSCAE model takes place via the krill herd algorithm (KHA). The design of the COA-based feature selection and KHA-based parameter tuning shows the novelty of the work. For examining the enhanced classification performance of the DCSAE-ESDC technique, a detailed experimental analysis was conducted using a benchmark epileptic seizure dataset. The comparative results analysis portrayed the better performance of the DCSAE-ESDC technique over existing techniques, with maximum accuracy of 98.67% and 98.73% under binary and multi-classification, respectively.
Defect of IL17 Signaling, but Not Centrinone, Inhibits the Development of Psoriasis and Skin Papilloma in Mouse Models
Authors: Jin Ben , Zhang Yongfeng , Miller Haiyan D. , He Ling , Ge Dongxia , Wang Alun R. , You Zongbing
Published: August 2022

Patients with psoriasis tend to develop skin cancer, and the hyperproliferation of the epidermis is a histopathological hallmark of both psoriasis and cutaneous squamous cell carcinoma (SCC), indicating that they may share pathogenic mechanisms. Interleukin-17 (IL17) stimulates the proliferation of the epidermis, leading to psoriasis. Overexpression of Polo-like kinase 4 (PLK4), which controls centriole duplication, has been identified in SCC, which also shows the hyperproliferation of keratinocytes. To investigate the cooperation between IL17 signaling and centriole duplication in epidermal proliferation, we established psoriasis and skin papilloma models in wild type (WT), IL17 receptor A (T779A) knockin (Il17ra(T779A)-KI), and IL17 receptor C knockout (Il17rc-KO) mouse strains. Bioinformatics, Western blot, immunohistochemical staining, colony formation, and real-time PCR were used to determine the effect of IL17 signaling and centrinone on epithelial proliferation. In the psoriasis model, compared to WT and Il17ra(T779A)-KI, Il17rc-KO dramatically suppressed epidermal thickening. The proliferation of keratinocytes significantly decreased in this order from WT to Il17ra(T779A)-KI and Il17rc-KO mice. In the skin papilloma model, Il17ra(T779A)-KI significantly decreased tumor burden compared to the WT, while Il17rc-KO abolished papilloma development. However, centrinone, a selective inhibitor of PLK4, did not affect skin lesion formation in either model. Our data demonstrated that Il17ra(T779A)-KI and Il17rc-KO prevent the development of psoriasis and tumorigenesis in the skin, while the topical administration of centrinone does not have any effect.
Effects of Cancer Cell-Derived Nanovesicle Vaccines Produced by the Oxidative Stress-Induced Expression of DAMP and Spontaneous Release/Filter Extrusion in the Interplay of Cancer Cells and Macrophages
Authors: Lin Song-Hsien , Tsai Guan-Ying , Wang Meng-Jiy , Chen Szu-Yuan
Published: August 2022

Photodynamic therapy (PDT)-based cancer vaccines are shown to be more effective modalities for treating cancer in animal models compared to other methods used to generate cancer cell-derived vaccines. The higher efficacy seems to stem from the generation of cell membrane nanovesicles or fragments that carry both cancer cell-specific antigens and high surface content of damage-associated molecular pattern (DAMP) molecules induced by oxidative stress. To develop more effective cancer vaccines in this direction, we explored the generation of cancer vaccines by applying different sources of oxidative stress on cancer cell cultures followed by spontaneous release or filter extrusions to produce cancer cell-derived DAMP-expressing nanovesicles. Through an in-vitro test based on the co-culture of cancer cells and macrophages, it was found that the nanovesicle vaccines generated by H2O2 are as effective as those generated by PDT in diminishing cancer cell culture masses, providing a simpler way to manufacture vaccines. In addition, the nanovesicle vaccines produced by filter extrusion are as potent as those produced by spontaneous release, rendering a more stable way for vaccine production.
Infrared-Fused Vision-Based Thermoregulation Performance Estimation for Personal Thermal Comfort-Driven HVAC System Controls
Authors: Ghahramani Ali , Xu Qian , Min Syung , Wang Andy , Zhang Hui , He Yingdong , Merritt Alexander , Levinson Ronnen
Published: August 2022

Thermal comfort is one of the primary factors influencing occupant health, well-being, and productivity in buildings. Existing thermal comfort systems require occupants to frequently communicate their comfort vote via a survey which is impractical as a long-term solution. Here, we present a novel thermal infrared-fused computer vision sensing method to capture thermoregulation performance in a non-intrusive and non-invasive manner. In this method, we align thermal and visible images, detect facial segments (i.e., nose, eyes, face boundary), and accordingly read the temperatures from the appropriate coordinates in the thermal image. We focus on the human face since it is often clearly visible to cameras and is not merged into a hot background (unlike hands). We use a regularized Gaussian Mixture model to track the thermoregulation changes over time and apply a heuristic algorithm to extract hot and cold indices. We present a personalized and a generalized comfort modeling method, selected based on the availability of the occupant historical indices measurements in a neutral environment, and use the time-series of the hot and cold indices to define corrections to HVAC system operations in the form of setpoint constraints. To evaluate the efficacy of our proposed approach in responding to thermal stimuli, we designed a series of controlled experiments to simulate exposure to cold and hot environments. While applying personalized modeling showed an acceptable average accuracy of 91.3%, the generalized model’s average accuracy was only 65.2%. This shows the importance of having access to physiological records in modeling and assessing comfort. We also found that individual differences should be considered in selecting the cooling and heating rates when some knowledge of the occupant’s overall thermal preference is available.
Impact of Patient Age on Postoperative Short-Term and Long-Term Outcome after Pancreatic Resection of Pancreatic Ductal Adenocarcinoma
Authors: Hackner Danilo , Hobbs Mirianna , Merkel Susanne , Siepmann Timo , Krautz Christian , Weber Georg F. , Grützmann Robert , Brunner Maximilian
Published: August 2022

(1) Purpose: to evaluate the impact of age on postoperative short-term and long-term outcomes in patients undergoing curative pancreatic resection for PDAC. (2) Methods: This retrospective single-center study comprised 213 patients who had undergone primary resection of PDAC from January 2000 to December 2018 at the University Hospital of Erlangen, Germany. Patients were stratified according the age into two groups: younger (≤70 years) and older (>70 years) patients. Postoperative outcome and long-term survival were compared between the groups. (3) Results: There were no significant differences regarding inhospital morbidity (58% vs. 67%, p = 0.255) or inhospital mortality (2% vs. 7%, p = 0.073) between the two groups. The median overall survival (OS) and disease-free survival (DFS) were significantly shorter in elderly patients (OS: 29.2 vs. 17.1 months, p < 0.001, respectively; DFS: 14.9 vs. 10.4 months, p = 0.034). Multivariate analysis revealed that age was a significant independent prognostic predictor for OS and DFS (HR 2.23, 95% CI 1.58–3.15; p < 0.001 for OS and HR 1.62, 95% CI 1.17–2.24; p = 0.004 for DFS). (4) Conclusion: patient age significantly influenced overall and disease-free survival in patients with PDAC undergoing primary resection in curative intent.
Clinical Diagnosis of Gastric Cancer by High-Sensitivity THz Fiber-Based Fast-Scanning Near-Field Imaging
Authors: Chen Hua , Han Juan , Ma Shihua , Li Xiao , Qiu Tianzhu , Chen Xiaofeng
Published: August 2022

The distinguishable absorption contrast among healthy gastric tissues, carcinoma in situ and cancer tissues in the THz frequency range is one of the keys to realizing gastric cancer diagnosis by THz imaging. Based on microwave devices and a sub-wavelength fiber, we developed a fast-scanning THz imaging system combined with the principle of surface plasmon resonance enhancement. This imaging system has a near-field λ/17 spatial resolution and imaging S/N ratio as high as 108:1, and the image results are directly displayed within 1 min. We also successfully demonstrated the image diagnostic capability on sliced tissues from eight patients with gastric cancer. The results indicate that THz absorption images can not only clearly distinguish cancer tissue from healthy tissues but also accurately define the margins of cancer. Through a medical statistical study of 40 sliced tissues from 40 patients, we prove that THz imaging can be used as a standalone method to diagnose gastric cancer tissues with a diagnostic specificity and sensitivity of 100%. Compared with the H&E staining method, THz imaging diagnosis makes the automation of tissue-sampling pre-screening procedure possible and assists in quickly determining the boundary between cancerous and healthy tissues.
Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150
Authors: Sho Takuya , Suda Goki , Yamamoto Yoshiya , Furuya Ken , Baba Masaru , Ogawa Koji , Kubo Akinori , Tokuchi Yoshimasa , Fu Qingjie , Yang Zijian , Kimura Megumi , Kitagataya Takashi , Maehara Osamu , Ohnishi Shunsuke , Nakamura Akihisa , Yamada Ren , Ohara Masatsugu , Kawagishi Naoki , Natsuizaka Mitsuteru , Nakai Masato , Suzuki Kazuharu , Izumi Takaaki , Meguro Takashi , Terashita Katsumi , Takagi Tomofumi , Ito Jun , Kobayashi Tomoe , Miyagishima Takuto , Sakamoto Naoya
Published: August 2022

The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria of IMbrave150. Of 115 patients with unresectable HCC treated with atezolizumab and bevacizumab between October 2020 and January 2022, 72 did not meet the eligibility criteria of IMbrave150, most frequently due to a history of systemic therapy (60/72), platelet counts < 75 × 109/L (7/72), Child-Pugh B (9/72), and 2+ proteinuria (8/72). Atezolizumab and bevacizumab therapy was equally effective for patients who did or did not meet the eligibility criteria (PFS, 6.5 vs. 6.9 months, p = 0.765), consistent with subgroup analyses of histories of systemic therapy, platelet counts, Child-Pugh, and proteinuria. Baseline ALBI scores were worse in patients who did not meet the criteria than in those who did and significantly worsened after treatment initiation in patients not meeting the criteria (baseline vs. 12 weeks; 2.35 ± 0.43 vs. −2.18 ± 0.54; p = 0.007). Accordingly, atezolizumab plus bevacizumab was effective for patients not meeting the eligibility criteria of IMbrave150, although careful monitoring for changes in liver functional reserve is needed.
IgG-Based Bispecific Anti-CD95 Antibodies for the Treatment of B Cell-Derived Malignancies and Autoimmune Diseases
Authors: Hörner Sebastian , Moustafa-Oglou Moustafa , Teppert Karin , Hagelstein Ilona , Kauer Joseph , Pflügler Martin , Neumann Kristina , Rammensee Hans-Georg , Metz Thomas , Herrmann Andreas , Salih Helmut R. , Jung Gundram , Zekri Latifa
Published: August 2022

Antibodies against the B cell-specific antigens CD20 and CD19 have markedly improved the treatment of B cell-derived lymphoma and autoimmune diseases by depleting malignant and autoreactive B cells. However, since CD20 and CD19 are also expressed on healthy B cells, such antibodies lack disease specificity. Here, we optimize a previously developed concept that uses bispecific antibodies to induce apoptosis selectively in malignant and autoreactive B cells that express the death receptor CD95. We describe the development and characterization of bispecific antibodies with CD95xCD20 and CD95xCD19 specificity in a new IgG-based format. We could show that especially the CD95xCD20 antibody mediated a strong induction of apoptosis in malignant B cells in vitro. In vivo, the antibody was clearly superior to the previously used Fabsc format with identical specificities. In addition, both IgGsc antibodies depleted activated B cells in vitro, leading to a significant reduction in antibody production and cytokine secretion. The killing of resting B cells and hepatocytes that lack CD95 and CD20/CD19, respectively, was marginal. Thus, our results imply that bispecific anti-CD95 antibodies in the IgGsc format are an attractive tool for a more selective and efficient depletion of malignant as well as autoreactive B cells.
Chemicals Production from Glycerol through Heterogeneous Catalysis: A Review
Authors: Koranian Parvaneh , Huang Qian , Dalai Ajay Kumar , Sammynaiken Ramaswami
Published: August 2022

Utilization of biofuels generated from renewable sources has attracted broad attention due to their benefits such as reducing consumption of fossil fuels, sustainability, and consequently prevention of global warming. The production of biodiesel causes a huge amount of by-product, crude glycerol, to accumulate. Glycerol, because of its unique structure having three hydroxyl groups, can be converted to a variety of industrially valuable products. In recent decades, increasing studies have been carried out on different catalytic pathways to selectively produce a wide range of glycerol derivatives. In the current review, the main routes including carboxylation, oxidation, etherification, hydrogenolysis, esterification, and dehydration to convert glycerol to value-added products are investigated. In order to achieve more glycerol conversion and higher desired product selectivity, acquisition of knowledge on the catalysts, the type of acidic or basic, the supports, and studying various reaction pathways and operating parameters are necessary. This review attempts to summarize the knowledge of catalytic reactions and mechanisms leading to value-added derivatives of glycerol. Additionally, the application of main products from glycerol are discussed. In addition, an overview on the market of glycerol, its properties, applications, and prospects is presented.
Untargeted Multimodal Metabolomics Investigation of the Haemonchus contortus Exsheathment Secretome
Authors: Palevich Nikola , Maclean Paul H. , Candy Paul M. , Taylor Wendy , Mladineo Ivona , Cao Mingshu
Published: August 2022

In nematodes that invade the gastro-intestinal tract of the ruminant, the process of larval exsheathment marks the transition from the free-living to the parasitic stages of these parasites. To investigate the secretome associated with larval exsheathment, a closed in vitro system that effectively reproduces the two basic components of an anaerobic rumen environment (CO2 and 39 °C) was developed to trigger exsheathment in one of the most pathogenic and model gastrointestinal parasitic nematodes, Haemonchus contortus (barber‘s pole worm). This study reports the use of multimodal untargeted metabolomics and lipidomics methodologies to identify the metabolic signatures and compounds secreted during in vitro larval exsheathment in the H. contortus infective third-stage larva (iL3). A combination of statistical and chemoinformatic analyses using three analytical platforms revealed a panel of metabolites detected post exsheathment and associated with amino acids, purines, as well as select organic compounds. The major lipid classes identified by the non-targeted lipidomics method applied were lysophosphatidylglycerols, diglycerides, fatty acyls, glycerophospholipids, and a triglyceride. The identified metabolites may serve as metabolic signatures to improve tractability of parasitic nematodes for characterizing small molecule host–parasite interactions related to pathogenesis, vaccine and drug design, as well as the discovery of metabolic biomarkers.
SARS-CoV-2 Spike Does Not Possess Intrinsic Superantigen-like Inflammatory Activity
Authors: Amormino Carola , Tedeschi Valentina , Paldino Giorgia , Arcieri Stefano , Fiorillo Maria Teresa , Paiardini Alessandro , Tuosto Loretta , Kunkl Martina
Published: August 2022

Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory disease occurring several weeks after SARS-CoV-2 infection. The clinical similarities between MIS-C and the toxic shock syndrome, together with the preferential expansion of T cells with a T-cell receptor variable β chain (TCRVβ) skewing, suggested a superantigen theory of MIS-C. For instance, recent in silico modelling evidenced the presence of a highly conserved motif within SARS-CoV-2 spike protein similar in structure to the superantigenic fragment of staphylococcal enterotoxin B (SEB). However, experimental data on the superantigenic activity of the SARS-CoV-2 spike have not yet been provided. Here, we assessed the superantigenic activity of the SARS-CoV-2 spike by analysing inflammatory cytokine production in both Jurkat cells and the peripheral blood CD4+ T cells stimulated with the SARS-CoV-2 spike or SEB as a control. We found that, unlike SEB, the SARS-CoV-2 spike does not exhibit an intrinsic superantigen-like activity.
The Interaction of Human Papillomavirus Infection and Prostaglandin E2 Signaling in Carcinogenesis: A Focus on Cervical Cancer Therapeutics
Authors: García-Quiroz Janice , Vázquez-Almazán Bismarck , García-Becerra Rocío , Díaz Lorenza , Avila Euclides
Published: August 2022

Chronic infection by high-risk human papillomaviruses (HPV) and chronic inflammation are factors associated with the onset and progression of several neoplasias, including cervical cancer. Oncogenic proteins E5, E6, and E7 from HPV are the main drivers of cervical carcinogenesis. In the present article, we review the general mechanisms of HPV-driven cervical carcinogenesis, as well as the involvement of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and downstream effectors in this pathology. We also review the evidence on the crosstalk between chronic HPV infection and PGE2 signaling, leading to immune response weakening and cervical cancer development. Finally, the last section updates the current therapeutic and preventive options targeting PGE2-derived inflammation and HPV infection in cervical cancer. These treatments include nonsteroidal anti-inflammatory drugs, prophylactic and therapeutical vaccines, immunomodulators, antivirals, and nanotechnology. Inflammatory signaling pathways are closely related to the carcinogenic nature of the virus, highlighting inflammation as a co-factor for HPV-dependent carcinogenesis. Therefore, blocking inflammatory signaling pathways, modulating immune response against HPV, and targeting the virus represent excellent options for anti-tumoral therapies in cervical cancer.
Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma
Authors: Drakulic Danijela , Schwirtlich Marija , Petrovic Isidora , Mojsin Marija , Milivojevic Milena , Kovacevic-Grujicic Natasa , Stevanovic Milena
Published: August 2022

Glioblastoma (GBM) is the most common and highly lethal type of brain tumor, with poor survival despite advances in understanding its complexity. After current standard therapeutic treatment, including tumor resection, radiotherapy and concomitant chemotherapy with temozolomide, the median overall survival of patients with this type of tumor is less than 15 months. Thus, there is an urgent need for new insights into GBM molecular characteristics and progress in targeted therapy in order to improve clinical outcomes. The literature data revealed that a number of different signaling pathways are dysregulated in GBM. In this review, we intended to summarize and discuss current literature data and therapeutic modalities focused on targeting dysregulated signaling pathways in GBM. A better understanding of opportunities for targeting signaling pathways that influences malignant behavior of GBM cells might open the way for the development of novel GBM-targeted therapies.