bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Degradation Prognosis Based on Relative Characteristic and Long Short-Term Memory Network for Components of Brake Systems of in-Service Trains
Authors: Ding Jingxian , Zuo Jianyong
Published: November 2022

During the service life of brake systems, performance degradation of the components is inevitable. In order to grasp the health status of components of brake systems, and aiming at the problem that the performance degradation trend of the components of the brake system is not completely clear due to signal coupling between components, the influence of variable working conditions, and the long performance degradation cycle, a performance degradation prognosis method of the components of the brake system based on relative characteristic (RC) and the long short-term memory (LSTM) network was proposed. The input and output signals of the components were isolated and fused, the working condition-independent RC was extracted to construct the health indicator (HI), and the validity of the HI was tested by using the monotonicity, correlation, and robustness metrics. Moreover, considering the time memory characteristics, the trend prediction of the HI curve of the components of the brake system was carried out based on the LSTM network. Furthermore, data augmentation for the training and testing sets was performed. Taking the typical component of brake systems as an example, a performance degradation test was carried out. The analysis results of the test data show that the accuracy of the performance degradation prognosis of the intake filter was over 99%, which validates the effectiveness and accuracy of the proposed method. The research results could provide a reference for health management and to improve the active safety protection capability of brake systems of in-service trains.
Probiotics and Beneficial Microorganisms in Biopreservation of Plant-Based Foods and Beverages
Authors: Udayakumar Srusti , Rasika Dissanayake M. D. , Priyashantha Hasitha , Vidanarachchi Janak K. , Ranadheera Chaminda Senaka
Published: November 2022

Maintaining the overall quality and shelf life of plant-based food and beverages is particularly important yet challenging to the food industry. Demand for natural preservation techniques has increased with the rising concerns over food safety and consumer awareness, e.g., health consciousness and food trends such as veganism and the demand for clean, labelled foods. Thus, a technique such as biopreservation has the potential to enhance food safety while fostering the quality, originality and naturalness of food. The application of probiotic microorganisms to foods and beverages provides various health benefits in addition to improved shelf life, stability and microbial safety of the food. The provision of probiotics is known to deliver various health benefits for the host’s gut health. Therefore, this review aims to investigate the importance of biopreservation and the role of probiotics in the food industry. An attempt was made to explore the various possibilities of shelf-life enhancement through the use of probiotic microorganisms as biopreservatives. Noticeable improvements in the shelf life of plant-based foods and beverages were observed due to the antimicrobial effects exerted by probiotics and potential probiotic strains which make them useful alternatives to artificially synthesized chemical preservatives.
Explainable-AI in Automated Medical Report Generation Using Chest X-ray Images
Authors: Ahmed Saad Bin , Solis-Oba Roberto , Ilie Lucian
Published: November 2022

The use of machine learning in healthcare has the potential to revolutionize virtually every aspect of the industry. However, the lack of transparency in AI applications may lead to the problem of trustworthiness and reliability of the information provided by these applications. Medical practitioners rely on such systems for clinical decision making, but without adequate explanations, diagnosis made by these systems cannot be completely trusted. Explainability in Artificial Intelligence (XAI) aims to improve our understanding of why a given output has been produced by an AI system. Automated medical report generation is one area that would benefit greatly from XAI. This survey provides an extensive literature review on XAI techniques used in medical image analysis and automated medical report generation. We present a systematic classification of XAI techniques used in this field, highlighting the most important features of each one that could be used by future research to select the most appropriate XAI technique to create understandable and reliable explanations for decisions made by AI systems. In addition to providing an overview of the state of the art in this area, we identify some of the most important issues that need to be addressed and on which research should be focused.
Research on the Classification of ECG and PCG Signals Based on BiLSTM-GoogLeNet-DS
Authors: Li Jinghui , Ke Li , Du Qiang , Ding Xiaodi , Chen Xiangmin
Published: November 2022

Because a cardiac function signal cannot reflect cardiac health in all directions, we propose a classification method using ECG and PCG signals based on BiLSTM-GoogLeNet-DS. The electrocardiogram (ECG) and phonocardiogram (PCG) signals used as research objects were collected synchronously. Firstly, the obtained ECG and PCG signals were filtered, and then the ECG and PCG signals were fused and classified by using a bi-directional long short-term memory network (BiLSTM). After that, the time-frequency processing was performed on the filtered ECG and PCG signals to obtain the time-frequency diagram of each signal; the one-dimensional signal was changed into a two-dimensional image signal, and the size of each image signal was adjusted to input the improved GoogLeNet network for classification. Then we obtained the two-channel classification results. The three-channel classification results, combined with the classification results of the above BiLSTM network, were finally obtained. The classification results of these three channels were used to make a decision via the fusion strategy of the improved D-S theory. Finally, we obtained the classification results. Taking 70% of the signals in the database as training data and 30% as test data, the obtained classification accuracy was 96.13%, the sensitivity was 98.48%, the specificity was 90.8%, and the F1 score was 97.24%. From the experimental results, the method proposed in this paper obtained high classification accuracy, and the classification effect was better than a cardiac function signal, which makes up for the low accuracy of the cardiac function signal for judging cardiac disease.
W-IFL: An Improved Maximum Power Point Control Model to Promote Renewable-Powered Vehicles
Authors: Jin Shuxin , Hao Mai , Cai Ming
Published: November 2022

Driven by economic development and environmental protection, vehicles are gradually renovating their power to renewable energy. As an essential part of renewable energy, photovoltaic (PV) energy is highly valued and studied worldwide. Future social development is inseparable from it when facing the current situation of exhausting fossil energy and highly polluting. To solve the problem of the low utilization of converting solar power to electrical energy, this paper proposes a wavelet-improved fuzzy logic (W-IFL) maximum power point (MPP) control model. The W-IFL designs a wavelet network for predicting the MPP and fuzzy rules for tracking the MPP, which achieves full online control on the basis of a neural-fuzzy structure. Comparative analysis indicates that W-IFL outperforms other widely used MPP tracking (MPPT) methods, which reduces oscillation at MPP, prediction error, and tracking time, and improves training efficiency and controlling ability, thus making it more rational to promote the development of the vehicle industry.
Prediction of Ply Angles of Air Springs According to Airbag Positions and Their Effects on Lateral and Torsional Stiffness
Authors: Lee Hyoungwook , Kim Chul-Su
Published: November 2022

The stiffness in various directions of air springs have a great influence on the stability of high-speed trains. Due to the change in the bogie structure, the required functions of the air springs have also diversified, and the damping of various loading modes such as vertical, lateral, and torsional movements is emerging as important. The stiffnesses are affected by the shape of the air bag, the material, and the ply angles. In this paper, the relationship between the ply angle and the radial position is proposed by equations from deformation modes. The variable angles in the plies were compared and demonstrated in air-spring analysis using the rebar elements. The vertical, lateral, and torsional stiffness of air springs without auxiliary springs were compared between constant ply angles and variable ply angles with respect to the positions. When mainly dealing with the vertical stiffness, the effect of the angle variation was small; however, it was found that it had a large effect of more than 24% and 30% on the stiffness in the lateral direction and torsional direction, respectively.
Route Planning for Autonomous Driving Based on Traffic Information via Multi-Objective Optimization
Authors: Zhang Meng-Yue , Yang Shi-Chun , Feng Xin-Jie , Chen Yu-Yi , Lu Jia-Yi , Cao Yao-Guang
Published: November 2022

Route planning for autonomous driving is a global road planning method based on a given starting point and target point combined with current traffic flow information. The optimal global route can reduce traffic jams and improve the safety and economy of autonomous vehicles. The current optimization method of route planning for autonomous driving only considers a single objective or a chain of single objectives, which cannot meet the requirements of drivers. In this paper, we devise a general framework for the route planning method based on multi-objective optimization. Different from planning optimization based on not only traffic information, the framework considers travel time, distance, cost and personal preference, but focuses more on vehicle status and driver requirements. We use an improved depth-first search algorithm to find the optimal route. The evaluations of our method on real-world traffic data indicate the feasibility and applicability of the framework. Our study contributes to a better understanding of route planning and reveals that exploitation of personal preference can more flexibly configure the corresponding route according to the driver’s requirements.
Spatial-Temporal Variations of Extreme Precipitation Characteristics and Its Correlation with El Niño-Southern Oscillation during 1960–2019 in Hubei Province, China
Authors: Wang Weizheng , Tang Huiya , Li Jinping , Hou Yukun
Published: November 2022

Extreme precipitation could result in many disasters, such as floods, drought, and soil erosion, further bringing severe economic loss. Based on the daily precipitation records during 1960–2019 of 26 stations obtained from the National Meteorological Science Data Center of China, 10 extreme precipitation indices (EPIs: annual total precipitation (PRCPTOT), max-1-day precipitation amount (RX1day), max-5-day precipitation amount (RX5day), number of heavy rain days (R10), number of very heavy rain days (R10), simple daily intensity index (SDII), consecutive dry days (CDD), continued wet days (CWD), very wet days (R95p) and extremely wet days (R99p)) were chosen and used to analyze the spatial-temporal variation of extreme precipitation within Hubei province, China, which is an important industrial and agricultural base in China. Finally, the correlation between El Niño-Southern Oscillation and EPIs was analyzed by cross-wavelet analysis. Results showed that the annual EPIs varied obviously during 1960–2019, and CWD decreased significantly (p < 0.05). The chosen EPIs were higher in eastern and southwestern Hubei compared to other regions, and RX1day, RX5day, R95p, and R99p were increased in most regions. The spatial-temporal variations of spring and summer EPIs were more obvious than those on an annual scale. In summer, all EPIs except CDD should increase in the near future. More attention should be paid to Wuhan, Enshi, and Macheng, where the RX1day, RX5day, R95p, and R99p will increase in these regions. Finally, the RX1day and R10 were positively correlated with MEI (p < 0.05), while the RX5day, CDD, CWD, and R99p were negatively correlated with MEI (p < 0.05). The extreme precipitation events within Hubei were affected by the El Niño-Southern Oscillation. The results could provide a possible driving factor for precipitation prediction and natural hazard prevention within Hubei province, China.
Detection of Hand Poses with a Single-Channel Optical Fiber Force Myography Sensor: A Proof-of-Concept Study
Authors: Gomes Matheus K. , da Silva Willian H. A. , Ribas Neto Antonio , Fajardo Julio , Rohmer Eric , Fujiwara Eric
Published: November 2022

Force myography (FMG) detects hand gestures based on muscular contractions, featuring as an alternative to surface electromyography. However, typical FMG systems rely on spatially-distributed arrays of force-sensing resistors to resolve ambiguities. The aim of this proof-of-concept study is to develop a method for identifying hand poses from the static and dynamic components of FMG waveforms based on a compact, single-channel optical fiber sensor. As the user performs a gesture, a micro-bending transducer positioned on the belly of the forearm muscles registers the dynamic optical signals resulting from the exerted forces. A Raspberry Pi 3 minicomputer performs data acquisition and processing. Then, convolutional neural networks correlate the FMG waveforms with the target postures, yielding a classification accuracy of (93.98 ± 1.54)% for eight postures, based on the interrogation of a single fiber transducer.
Fractional Clique Collocation Technique for Numerical Simulations of Fractional-Order Brusselator Chemical Model
Authors: Izadi Mohammad , Srivastava Hari
Published: November 2022

The primary focus of this research study is in the development of an effective hybrid matrix method to solve a class of nonlinear systems of equations of fractional order arising in the modeling of autocatalytic chemical reaction problems. The fractional operator is considered in the sense of Liouville–Caputo. The proposed approach relies on the combination of the quasi-linearization technique and the spectral collocation strategy based on generalized clique bases. The main feature of the hybrid approach is that it converts the governing nonlinear fractional-order systems into a linear algebraic system of equations, which is solved in each iteration. In a weighted L2 norm, we prove the error and convergence analysis of the proposed algorithm. By using various model parameters in the numerical examples, we show the computational efficacy as well as the accuracy of our approach. Comparisons with existing available schemes show the high accuracy and robustness of the designed hybrid matrix collocation technique.
Certain New Class of Analytic Functions Defined by Using a Fractional Derivative and Mittag-Leffler Functions
Authors: Khan Mohammad Faisal , Khan Shahid , Hussain Saqib , Darus Maslina , Matarneh Khaled
Published: November 2022

Fractional calculus has a number of applications in the field of science, specially in mathematics. In this paper, we discuss some applications of fractional differential operators in the field of geometric function theory. Here, we combine the fractional differential operator and the Mittag-Leffler functions to formulate and arrange a new operator of fractional calculus. We define a new class of normalized analytic functions by means of a newly defined fractional operator and discuss some of its interesting geometric properties in open unit disk.
Comparison of the Chemical Properties of Vinegar Obtained via One-Step Fermentation and Sequential Fermentation from Dragon Fruit and Pineapple
Authors: Niyomvong Nanthavut , Sritawan Rachcha , Keabpimai Jureeporn , Trakunjae Chanaporn , Boondaeng Antika
Published: November 2022

Dragon fruit has many potential health benefits. It is inexpensive and widely cultivated in Thailand. The addition of dragon fruit to pineapple vinegar may help enhance the total phenolic compounds and antioxidant activity. This study aimed to study and compare the chemical characteristics of vinegar produced via one-step fermentation of a mixture of pineapple and dragon fruit juice from Krok Phra District of Thailand using Saccharomyces cerevisiae var. burgundy with that obtained using sequential fermentation using Saccharomyces cerevisiae var. burgundy and Acetobacter aceti. When the two fermentation methods were compared on day 20, the maximum acetic acid concentration obtained from sequential fermentation was 5.79 ± 0.25%, which was higher than that obtained in one-step fermentation (1.93%). The total phenolic compound content in the mixed fruit vinegar obtained from sequential fermentation and one-step fermentation was 228.01 and 242.2 mg/L gallic acid equivalents, respectively. The antioxidant content of the products obtained in sequential and one-step fermentations was 187.91 mg/L GAE and 209.33 µg/g of Trolox equivalents, respectively, which was consistent with the total phenolic compound content. This indicated that the acetic acid content in the mixed pineapple and dragon fruit juice vinegar obtained using sequential fermentation was higher than that obtained using one-step fermentation although its total phenolic content and the antioxidant activities were slightly lower. These observations will be useful for improving vinegar fermentation in the area.
Antibiotics from Insect-Associated Actinobacteria
Authors: Baranova Anna A. , Zakalyukina Yuliya V. , Ovcharenko Anna A. , Korshun Vladimir A. , Tyurin Anton P.
Published: November 2022

Actinobacteria are involved into multilateral relationships between insects, their food sources, infectious agents, etc. Antibiotics and related natural products play an essential role in such systems. The literature from the January 2016–August 2022 period devoted to insect-associated actinomycetes with antagonistic and/or enzyme-inhibiting activity was selected. Recent progress in multidisciplinary studies of insect–actinobacterial interactions mediated by antibiotics is summarized and discussed.
Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies
Authors: Fraile Maria , Eiro Noemi , Costa Luis A. , Martín Arancha , Vizoso Francisco J.
Published: November 2022

Aging and frailty are complex processes implicating multifactorial mechanisms, such as replicative senescence, oxidative stress, mitochondrial dysfunction, or autophagy disorder. All of these mechanisms drive dramatic changes in the tissue environment, such as senescence-associated secretory phenotype factors and inflamm-aging. Thus, there is a demand for new therapeutic strategies against the devastating effects of the aging and associated diseases. Mesenchymal stem cells (MSC) participate in a “galaxy” of tissue signals (proliferative, anti-inflammatory, and antioxidative stress, and proangiogenic, antitumor, antifibrotic, and antimicrobial effects) contributing to tissue homeostasis. However, MSC are also not immune to aging. Three strategies based on MSC have been proposed: remove, rejuvenate, or replace the senescent MSC. These strategies include the use of senolytic drugs, antioxidant agents and genetic engineering, or transplantation of younger MSC. Nevertheless, these strategies may have the drawback of the adverse effects of prolonged use of the different drugs used or, where appropriate, those of cell therapy. In this review, we propose the new strategy of “Exogenous Restitution of Intercellular Signalling of Stem Cells” (ERISSC). This concept is based on the potential use of secretome from MSC, which are composed of molecules such as growth factors, cytokines, and extracellular vesicles and have the same biological effects as their parent cells. To face this cell-free regenerative therapy challenge, we have to clarify key strategy aspects, such as establishing tools that allow us a more precise diagnosis of aging frailty in order to identify the therapeutic requirements adapted to each case, identify the ideal type of MSC in the context of the functional heterogeneity of these cellular populations, to optimize the mass production and standardization of the primary materials (cells) and their secretome-derived products, to establish the appropriate methods to validate the anti-aging effects and to determine the most appropriate route of administration for each case.
Prevalence of Spotted Fever Group Rickettsia and Candidatus Lariskella in Multiple Tick Species from Guizhou Province, China
Authors: Lu Miao , Meng Chao , Zhang Bing , Wang Xiao , Tian Junhua , Tang Guangpeng , Wang Wen , Li Na , Li Mengyao , Xu Xiaoyu , Sun Yue , Duan Chengyu , Qin Xincheng , Li Kun
Published: November 2022

Rickettsiales (Rickettsia spp., Ehrlichia spp., and Anaplasma spp., etc.) are generally recognized as potentially emerging tick-borne pathogens. However, some bacteria and areas in China remain uninvestigated. In this study, we collected 113 ticks from mammals in Guizhou Province, Southwest China, and screened for the Rickettsiales bacteria. Subsequently, two spotted fever group Rickettsia species and one Candidatus Lariskella sp. were detected and characterized. “Candidatus Rickettsia jingxinensis” was detected in Rhipicephalus microplus (1/1), Haemaphysalis flava (1/3, 33.33%), Haemaphysalis kitaokai (1/3), and Ixodes sinensis (4/101, 3.96%), whereas Rickettsia monacensis was positive in H. flava (1/3), H. kitaokai (2/3), and I. sinensis ticks (74/101, 73.27%). At least two variants/sub-genotypes were identified in the R. monacensis isolates, and the strikingly high prevalence of R. monacensis may suggest a risk of human infection. Unexpectedly, a Candidatus Lariskella sp. belonging to the family Candidatus Midichloriaceae was detected from Ixodes ovatus (1/4) and I. sinensis (10/101, 9.90%). The gltA and groEL gene sequences were successfully obtained, and they show the highest (74.63–74.89% and 73.31%) similarities to “Candidatus Midichloria mitochondrii”, respectively. Herein, we name the species “Candidatus Lariskella guizhouensis”. These may be the first recovered gltA and groEL sequences of the genus Candidatus Lariskella.
Inter-Site Cooperativity of Calmodulin N-Terminal Domain and Phosphorylation Synergistically Improve the Affinity and Selectivity for Uranyl
Authors: Beccia Maria Rosa , Sauge-Merle Sandrine , Brémond Nicolas , Lemaire David , Henri Pierre , Battesti Christine , Guilbaud Philippe , Crouzy Serge , Berthomieu Catherine
Published: November 2022

Uranyl–protein interactions participate in uranyl trafficking or toxicity to cells. In addition to their qualitative identification, thermodynamic data are needed to predict predominant mechanisms that they mediate in vivo. We previously showed that uranyl can substitute calcium at the canonical EF-hand binding motif of calmodulin (CaM) site I. Here, we investigate thermodynamic properties of uranyl interaction with site II and with the whole CaM N-terminal domain by spectrofluorimetry and ITC. Site II has an affinity for uranyl about 10 times lower than site I. Uranyl binding at site I is exothermic with a large enthalpic contribution, while for site II, the enthalpic contribution to the Gibbs free energy of binding is about 10 times lower than the entropic term. For the N–terminal domain, macroscopic binding constants for uranyl are two to three orders of magnitude higher than for calcium. A positive cooperative process driven by entropy increases the second uranyl-binding event as compared with the first one, with ΔΔG = −2.0 ± 0.4 kJ mol−1, vs. ΔΔG = −6.1 ± 0.1 kJ mol−1 for calcium. Site I phosphorylation largely increases both site I and site II affinity for uranyl and uranyl-binding cooperativity. Combining site I phosphorylation and site II Thr7Trp mutation leads to picomolar dissociation constants Kd1 = 1.7 ± 0.3 pM and Kd2 = 196 ± 21 pM at pH 7. A structural model obtained by MD simulations suggests a structural role of site I phosphorylation in the affinity modulation.
E-Cadherin Expression Distinguishes Mouse from Human Hematopoiesis in the Basophil and Erythroid Lineages
Authors: Krimpenfort Rosa A. , Behr Felix M. , Nieuwland Marja , Rink Iris de , Kerkhoven Ron , Lindern Marieke von , Nethe Micha
Published: November 2022

E-cadherin is a key regulator of epithelial cell–cell adhesion, the loss of which accelerates tumor growth and invasion. E-cadherin is also expressed in hematopoietic cells as well as epithelia. The function of hematopoietic E-cadherin is, however, mostly elusive. In this study, we explored the validity of mouse models to functionally investigate the role of hematopoietic E-cadherin in human hematopoiesis. We generated a hematopoietic-specific E-cadherin knockout mouse model. In mice, hematopoietic E-cadherin is predominantly expressed within the basophil lineage, the expression of which is dispensable for the generation of basophils. However, neither E-cadherin mRNA nor protein were detected in human basophils. In contrast, human hematopoietic E-cadherin marks the erythroid lineage. E-cadherin expression in hematopoiesis thereby revealed striking evolutionary differences between the basophil and erythroid cell lineage in humans and mice. This is remarkable as E-cadherin expression in epithelia is highly conserved among vertebrates including humans and mice. Our study therefore revealed that the mouse does not represent a suitable model to study the function of E-cadherin in human hematopoiesis and an alternative means to study the role of E-cadherin in human erythropoiesis needs to be developed.
Extracellular Hemoglobin: Modulation of Cellular Functions and Pathophysiological Effects
Authors: Drvenica Ivana T. , Stančić Ana Z. , Maslovarić Irina S. , Trivanović Drenka I. , Ilić Vesna Lj.
Published: November 2022

Hemoglobin is essential for maintaining cellular bioenergetic homeostasis through its ability to bind and transport oxygen to the tissues. Besides its ability to transport oxygen, hemoglobin within erythrocytes plays an important role in cellular signaling and modulation of the inflammatory response either directly by binding gas molecules (NO, CO, and CO2) or indirectly by acting as their source. Once hemoglobin reaches the extracellular environment, it acquires several secondary functions affecting surrounding cells and tissues. By modulating the cell functions, this macromolecule becomes involved in the etiology and pathophysiology of various diseases. The up-to-date results disclose the impact of extracellular hemoglobin on (i) redox status, (ii) inflammatory state of cells, (iii) proliferation and chemotaxis, (iv) mitochondrial dynamic, (v) chemoresistance and (vi) differentiation. This review pays special attention to applied biomedical research and the use of non-vertebrate and vertebrate extracellular hemoglobin as a promising candidate for hemoglobin-based oxygen carriers, as well as cell culture medium additive. Although recent experimental settings have some limitations, they provide additional insight into the modulatory activity of extracellular hemoglobin in various cellular microenvironments, such as stem or tumor cells niches.
GOProFormer: A Multi-Modal Transformer Method for Gene Ontology Protein Function Prediction
Authors: Kabir Anowarul , Shehu Amarda
Published: November 2022

Protein Language Models (PLMs) are shown to be capable of learning sequence representations useful for various prediction tasks, from subcellular localization, evolutionary relationships, family membership, and more. They have yet to be demonstrated useful for protein function prediction. In particular, the problem of automatic annotation of proteins under the Gene Ontology (GO) framework remains open. This paper makes two key contributions. It debuts a novel method that leverages the transformer architecture in two ways. A sequence transformer encodes protein sequences in a task-agnostic feature space. A graph transformer learns a representation of GO terms while respecting their hierarchical relationships. The learned sequence and GO terms representations are combined and utilized for multi-label classification, with the labels corresponding to GO terms. The method is shown superior over recent representative GO prediction methods. The second major contribution in this paper is a deep investigation of different ways of constructing training and testing datasets. The paper shows that existing approaches under- or over-estimate the generalization power of a model. A novel approach is proposed to address these issues, resulting in a new benchmark dataset to rigorously evaluate and compare methods and advance the state-of-the-art.
Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke
Authors: Rao Nivedita L. , Kotian Greeshma B. , Shetty Jeevan K. , Shelley Bhaskara P. , Dmello Mackwin Kenwood , Lobo Eric C. , Shankar Suchetha Padar , Almeida Shellette D. , Shah Saiqa R.
Published: November 2022

Diabetes mellitus, a well-established risk factor for stroke, is related to higher mortality and poorer outcomes following the stroke event. Advanced glycation end products(AGEs), their receptors RAGEs, other ligands, and several other processes contribute to the cerebrovascular pathomechanism interaction in the diabetes–ischemic stroke combination. Critical reappraisal of molecular targets and therapeutic agents to mitigate them is required to identify key elements for therapeutic interventions that may improve patient outcomes. This scoping review maps evidence on the key roles of AGEs, RAGEs, other ligands such as Leukotriene B4 (LTB4), High-mobility group box 1 (HMGB1) nuclear protein, brain–kidney–muscle crosstalk, alternate pathomechanisms in neurodegeneration, and cognitive decline related to diabetic ischemic stroke. RAGE, HMGB1, nitric oxide, and polyamine mechanisms are important therapeutic targets, inflicting common consequences of neuroinflammation and oxidative stress. Experimental findings on a number of existing–emerging therapeutic agents and natural compounds against key targets are promising. The lack of large clinical trials with adequate follow-up periods is a gap that requires addressing to validate the emerging therapeutic agents. Five therapeutic components, which include agents to mitigate the AGE–RAGE axis, improved biomarkers for risk stratification, better renal dysfunction management, adjunctive anti-inflammatory–antioxidant therapies, and innovative neuromuscular stimulation for rehabilitation, are identified. A comprehensive therapeutic strategy that features all the identified components is needed for outcome improvement in diabetic stroke patients.
Chelation Combination—A Strategy to Mitigate the Neurotoxicity of Manganese, Iron, and Copper?
Authors: Aaseth Jan O. , Nurchi Valeria M.
Published: November 2022

The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead (Pb) in poisoned individuals. However, DMSA, PSH, EDTA (ethylenediamine tetraacetate), and deferoxamine (DFOA) are water-soluble agents with limited access to the central nervous system (CNS). Strategies for mobilization of metals such as manganese (Mn), iron (Fe), and Cu from brain deposits may require the combined use of two agents: one water-soluble agent to remove circulating metal into urine, in addition to an adjuvant shuttler to facilitate the brain-to-blood mobilization. The present review discusses the chemical basis of metal chelation and the ligand exchange of metal ions. To obtain increased excretion of Mn, Cu, and Fe, early experiences showed promising results for CaEDTA, PSH, and DFOA, respectively. Recent experiments have indicated that p-amino salicylate (PAS) plus CaEDTA may be a useful combination to remove Mn from binding sites in CNS, while the deferasirox–DFOA and the tetrathiomolybdate–DMSA combinations may be preferable to promote mobilization of Fe and Cu, respectively, from the CNS. Further research is requested to explore benefits of chelator combinations.
Combinational Growth Factor and Gas Delivery for Thrombosis Prevention
Authors: Cao Huan , Xu Xuejuan , Zhu Fuyu , Sheng Yanhui
Published: November 2022

Cardiovascular stents enable the rapid re-endothelialization of endothelial cells (ECs), and the constant suppression of smooth muscle cell (SMC) proliferation has been proved to effectively prevent thrombosis. However, the development and application of such stents are still insufficient due the delayed re-endothelialization progress, as well as the poor durability of the SMC inhibition. In this paper, we developed a mussel-inspired coating with the ability for the dual delivery of both growth factor (e.g., platelet-derived growth factor, PDGF) and therapeutic gas (e.g., nitric oxide, NO) for thrombosis prevention. We firstly synthesized the mussel-inspired co-polymer (DMHM) of dopamine methacrylamide (DMA) and hydroxyethyl methacrylate (HEMA) and then coated the DMHM on 316L SS stents combined with CuII. Afterwards, we immobilized the PDGF on the DMHM-coated stent and found that the PDGF could be released in the first 3 days to enhance the recruitment, proliferation, and migration of human umbilical vein endothelial cells (HUVECs) to promote re-endothelialization. The CuII could be “sealed” in the DMHM coating, with extended durability (2 months), with the capacity for catalyzed NO generation for up to 2 months to suppress the proliferation of SMCs. Such a stent surface modification strategy could enhance the development of the cardiovascular stents for thrombosis prevention.
Bicalutamide Anticancer Activity Enhancement by Formulation of Soluble Inclusion Complexes with Cyclodextrins
Authors: De Gaetano Federica , Cristiano Maria Chiara , Paolino Donatella , Celesti Consuelo , Iannazzo Daniela , Pistarà Venerando , Iraci Nunzio , Ventura Cinzia Anna
Published: November 2022

Bicalutamide (BCL) is a nonsteroidal antiandrogen drug that represents an alternative to castration in the treatment of prostate cancer, due to its relatively long half-life and tolerable side effects. However, it possesses a very low water solubility that can affect its oral bioavailability. In this work, we developed inclusion complexes of BCL with the highly soluble hydroxypropyl-β-cyclodextrin (HP-β-CyD) and sulfobutylether-β-cyclodextrin (SBE-β-CyD) to increase the water solubility and anticancer activity of BCL. The inclusion complexes were prepared using the freeze-drying method and were then characterized in a solid state via differential scanning calorimetry and X-ray analysis and in solution via phase-solubility studies and UV-vis and NMR spectroscopy. The BCL/HP-β-CyD and BCL/SBE-β-CyD inclusion complexes were amorphous and rapidly dissolved in water. Both the 1H-NMR spectra and molecular modeling studies confirmed the penetration of the 2-(trifluoromethyl)benzonitrile ring of BCL within the cavity of both cyclodextrins (CyDs). Due to the consistent improvement of the water solubility of BCL, the inclusion complexes showed higher antiproliferative activity toward the human prostate androgen-independent cell lines, DU-145 and PC-3, with respect to free BCL. These results demonstrate the ability of HP-β-CyD and SBE-β-CyD to complex BCL, permitting the realization of liquid formulations with potentially high oral bioavailability and/or possible parenteral administration.
Linking Cerebrovascular Dysfunction to Age-Related Hearing Loss and Alzheimer’s Disease—Are Systemic Approaches for Diagnosis and Therapy Required?
Authors: Förster Carola Y. , Shityakov Sergey , Scheper Verena , Lenarz Thomas
Published: November 2022

Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction, cognitive decline, and the accumulation of amyloid β peptide (Aβ) in the brain and tau-related lesions in neurons termed neurofibrillary tangles (NFTs). Aβ deposits and NFT formation are the central pathological hallmarks in AD brains, and the majority of AD cases have been shown to exhibit a complex combination of systemic comorbidities. While AD is the foremost common cause of dementia in the elderly, age-related hearing loss (ARHL) is the most predominant sensory deficit in the elderly. During aging, chronic inflammation and resulting endothelial dysfunction have been described and might be key contributors to AD; we discuss an intriguing possible link between inner ear strial microvascular pathology and blood–brain barrier pathology and present ARHL as a potentially modifiable and treatable risk factor for AD development. We present compelling evidence that ARHL might well be seen as an important risk factor in AD development: progressive hearing impairment, leading to social isolation, and its comorbidities, such as frailty, falls, and late-onset depression, link ARHL with cognitive decline and increased risk of dementia, rendering it tempting to speculate that ARHL might be a potential common molecular and pathological trigger for AD. Additionally, one could speculate that amyloid-beta might damage the blood–labyrinth barrier as it does to the blood–brain barrier, leading to ARHL pathology. Finally, there are options for the treatment of ARHL by targeted neurotrophic factor supplementation to the cochlea to improve cognitive outcomes; they can also prevent AD development and AD-related comorbidity in the future.
Bacterial and Cellular Response to Yellow-Shaded Surface Modifications for Dental Implant Abutments
Authors: Genova Tullio , Chinigò Giorgia , Munaron Luca , Rivolo Paola , Luganini Anna , Gribaudo Giorgio , Cavagnetto Davide , Mandracci Pietro , Mussano Federico
Published: November 2022

Dental implants have dramatically changed the rehabilitation procedures in dental prostheses but are hindered by the possible onset of peri-implantitis. This paper aims to assess whether an anodization process applied to clinically used surfaces could enhance the adhesion of fibroblasts and reduce bacterial adhesion using as a reference the untreated machined surface. To this purpose, four different surfaces were prepared: (i) machined (MAC), (ii) machined and anodized (Y-MAC), (iii) anodized after sand-blasting and acid etching treatment (Y-SL), and (iv) anodized after double acid etching (Y-DM). All specimens were characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Moreover, the mean contact angle in both water and diiodomethane as well as surface free energy calculation was assessed. To evaluate changes in terms of biological responses, we investigated the adhesion of Streptococcus sanguinis (S. sanguinis) and Enterococcus faecalis (E. faecalis), fetal bovine serum (FBS) adsorption, and the early response of fibroblasts in terms of cell adhesion and viability. We found that the anodization reduced bacterial adhesion, while roughened surfaces outperformed the machined ones for protein adsorption, fibroblast adhesion, and viability independently of the treatment. It can be concluded that surface modification techniques such as anodization are valuable options to enhance the performance of dental implants.
A Review of the Role of Stereotactic Radiosurgery and Immunotherapy in the Management of Primary Central Nervous System Tumors
Authors: Lehrer Eric J. , Jones Brianna M. , Sindhu Kunal K. , Dickstein Daniel R. , Cohen Mira , Lazarev Stanislav , Quiñones-Hinojosa Alfredo , Green Sheryl , Trifiletti Daniel M.
Published: November 2022

Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs) are widely used in the management of brain metastases. These therapies are commonly administered concurrently; as SRS may enhance anti-tumor immunity and responsiveness to ICIs. However, the use of ICIs with and without SRS in the management of primary brain tumors remains a controversial topic. Meningiomas are the most common nonmalignant and extra-parenchymal brain tumor, which often respond well to surgery and radiotherapy. However, higher grade meningiomas tend to be resistant to these treatments, and the use of chemotherapy and targeted agents in this setting have yielded disappointing results. Thus, there is heightened interest in the utilization of ICIs. Glioblastoma is the most common malignant primary intraparenchymal brain tumor. It is associated with a grim prognosis with a median overall survival of approximately 20 months, despite optimal therapy. While SRS in the adjuvant setting, and ICI in the recurrent setting, have failed to demonstrate a survival benefit, SRS in the preoperative setting has the potential to enhance anti-tumor immunity and responsiveness to ICIs. Thus, these treatments represent an attractive option to add to the armamentarium of meningioma and glioblastoma management. In this review, we provide a detailed overview of the evidence supporting the use of ICIs and SRS in each of these settings.
Molecular Mechanisms Linking Empagliflozin to Renal Protection in the LLC-PK1 Model of Diabetic Nephropathy
Authors: Mihaljević Vjera , Zjalić Milorad , Kizivat Tomislav , Omanović Kolarić Tea , Smolić Martina , Rođak Edi , Čović Marina , Kuna Lucija , Smolić Robert , Včev Aleksandar , Bilić Ćurčić Ines
Published: November 2022

Aims: Chronic diabetes complications, including diabetic nephropathy (DN), frequently result in end-stage renal failure. This study investigated empagliflozin (SGLT2i) effects on collagen synthesis, oxidative stress, cell survival, and protein expression in an LLC-PK1 model of DN. Methods: Combinations of high glucose (HG) and increasing empagliflozin concentrations (100 nM and 500 nM), as well as combinations of HG, H2O2, and empagliflozin, were used for cell culture treatment. The cell viability, glutathione (tGSH), ECM expression, and TGF-β1 concentration were measured. In addition, the protein expression of Akt, pAkt, GSK3, pGSK3, pSTAT3, and SMAD7 was determined. Results: The addition of both concentrations of empagliflozin to cells previously exposed to glucose and oxidative stress generally improved cell viability and increased GSH levels (p < 0.001, p < 0.05). In HG30/H2O2/Empa500-treated cells, significant increase in pSTAT3, pGSK3β, GSK3β, SMAD7, and pAKT levels (p < 0.001, p < 0.001, p < 0.05) was observed except for AKT. Lower drug concentrations did not affect the protein expression levels. Furthermore, empagliflozin treatment (100 nM and 500 nM) of HG30/H2O2-injured cells led to a decrease in TGF-β1 levels (p < 0.001). In cells exposed to oxidative stress and hyperglycemia, collagen production remained unchanged. Conclusion: Renoprotective effects of empagliflozin, in this LLC-PK1 cell model of DN, are mediated via activation of the Akt/GSK-3 signalling pathway, thus reducing oxidative stress-induced damage, as well as enhanced SMAD7 expression leading to downregulation of TGF-β1, one of the key mediators of inflammation and fibrosis.
The Role of Cannabinoid Type 2 Receptors in Parkinson’s Disease
Authors: Basile Maria Sofia , Mazzon Emanuela
Published: November 2022

Parkinson’s disease (PD) is the second most frequent neurodegenerative disease and currently represents a clear unmet medical need. Therefore, novel preventive and therapeutic strategies are needed. Cannabinoid type 2 (CB2) receptors, one of the components of the endocannabinoid system, can regulate neuroinflammation in PD. Here, we review the current preclinical and clinical studies investigating the CB2 receptors in PD with the aim to clarify if these receptors could have a role in PD. Preclinical data show that CB2 receptors could have a neuroprotective action in PD and that the therapeutic targeting of CB2 receptors could be promising. Indeed, it has been shown that different CB2 receptor-selective agonists exert protective effects in different PD models. Moreover, the alterations in the expression of CB2 receptors observed in brain tissues from PD animal models and PD patients suggest the potential value of CB2 receptors as possible novel biomarkers for PD. However, to date, there is no direct evidence of the role of CB2 receptors in PD. Further studies are strongly needed in order to fully clarify the role of CB2 receptors in PD and thus pave the way to novel possible diagnostic and therapeutic opportunities for PD.
A Non-Flat Terrain Biped Gait Planner Based on DIRCON
Authors: Chen Boyang , Zang Xizhe , Zhang Yue , Gao Liang , Zhu Yanhe , Zhao Jie
Published: November 2022

Various constraints exist in bipedal movement. Due to the natural ability of effectively handling constraints, trajectory optimization has become one of the mainstream methods in biped gait planning, especially when constraints become much more complex on non-flat terrain. In this paper, we propose a multi-modal biped gait planner based on DIRCON, which can generate different gaits for multiple, non-flat terrains. Firstly, a virtual knot is designed to model the state transitions when the swing foot contacts terrain and is inserted as the first knot of the target trajectory of the current support phase. Thus, a complete gait or multi-modal gaits sequence can be generated at one time. Then, slacked complementary constraints, which can avoid undesired trajectories, are elaborated to describe the coupling relationships between terrain information and bipedal motion for trajectory optimization based gait planning. The concrete form of the gait planner is also delivered. Finally, we verify the performance of the planner, as well as the structural design of our newly designed biped robot in CoppeliaSim through flat terrain walking, stairs terrain walking and quincuncial piles walking. The three experiments show that the gaits planned by the proposed planner can enable the robot to walk stably over non-flat terrains, even through simple PD control.
Spectroelectrochemical Enzyme Sensor System for Acetaldehyde Detection in Wine
Authors: Ibáñez David , González-García María Begoña , Hernández-Santos David , Fanjul-Bolado Pablo
Published: November 2022

A new spectroelectrochemical two-enzyme sensor system has been developed for the detection of acetaldehyde in wine. A combination of spectroscopy and electrochemistry improves the analytical features of the electrochemical sensor because the optical information collected with this system is only associated with acetaldehyde and avoids the interferents also present in wines as polyphenols. Spectroelectrochemical detection is achieved by the analysis of the optical properties of the K3[Fe(CN)6]/K4[Fe(CN)6] redox couple involved in the enzymatic process: aldehyde dehydrogenase catalyzes the aldehyde oxidation using β-nicotinamide adenine dinucleotide hydrate (NAD+) as a cofactor and, simultaneously, diaphorase reoxidizes the NADH formed in the first enzymatic process due to the presence of K3[Fe(CN)6]. An analysis of the characteristic UV-vis bands of K3[Fe(CN)6] at 310 and 420 nm allows the detection of acetaldehyde, since absorption bands are only related to the oxidation of this substrate, and avoids the contribution of other interferents.