bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications
Authors: Allcock Benjamin , Wei Wenbin , Goncalves Kirsty , Hoyle Henry , Robert Alisha , Quelch-Cliffe Rebecca , Hayward Adam , Cooper Jim , Przyborski Stefan
Published: October 2023

It is widely recognised that cells respond to their microenvironment, which has implications for cell culture practices. Growth cues provided by 2D cell culture substrates are far removed from native 3D tissue structure in vivo. Geometry is one of many factors that differs between in vitro culture and in vivo cellular environments. Cultured cells are far removed from their native counterparts and lose some of their predictive capability and reliability. In this study, we examine the cellular processes that occur when a cell is cultured on 2D or 3D surfaces for a short period of 8 days prior to its use in functional assays, which we term: “priming”. We follow the process of mechanotransduction from cytoskeletal alterations, to changes to nuclear structure, leading to alterations in gene expression, protein expression and improved functional capabilities. In this study, we utilise HepG2 cells as a hepatocyte model cell line, due to their robustness for drug toxicity screening. Here, we demonstrate enhanced functionality and improved drug toxicity profiles that better reflect the in vivo clinical response. However, findings more broadly reflect in vitro cell culture practises across many areas of cell biology, demonstrating the fundamental impact of mechanotransduction in bioengineering and cell biology.
Spillover Effects of Green Finance on Attaining Sustainable Development: Spatial Durbin Model
Authors: Kwilinski Aleksy , Lyulyov Oleksii , Pimonenko Tetyana
Published: October 2023

Attaining sustainable development goals is a complex process that involves a range of economic, social, and environmental factors. It requires investments in infrastructure, technology, and human capital. In this case, green finance is conducive to channel investments toward sustainable projects and initiatives by providing incentives for environmentally friendly practices and technologies and by encouraging companies and investors to adopt sustainable business models. This paper aims to check the spatial spillover effect of green finance on attaining sustainable development for European Union (EU) countries for 2008–2021. The study applies the spatial Durbin model to explore the research hypothesis. The findings confirm that green finance promotes the achievement of sustainable development goals. However, the impact of green finance on attaining sustainable development is heterogeneous depending on the EU region. In this case, the EU should intensify its green finance policy considering the regional features that significantly affect the achievement of sustainable development goals by reducing greenhouse gas emissions, improving energy efficiency, and promoting renewable energy. In addition, it is necessary to develop alternative financial sources involving green bonds that could be used to fund green projects on renewable energy projects, green building construction, etc.
Prevention of Type 2 Diabetes with Lifestyle Interventions: Evidence vs. Reality
Authors: Sathish Thirunavukkarasu , MacMillan Freya
Published: October 2023

Type 2 diabetes is a serious global public health concern that affects every country in the world [...]
Phenotypes of Sarcoidosis-Associated Pulmonary Hypertension—A Challenging Mystery
Authors: Kacprzak Aneta , Tomkowski Witold , Szturmowicz Monika
Published: October 2023

Sarcoidosis has been a well-recognised risk factor for pulmonary hypertension (PH) for a long time, but still, the knowledge about this concatenation is incomplete. Sarcoidosis-associated PH (SAPH) is an uncommon but serious complication associated with increased morbidity and mortality among sarcoidosis patients. The real epidemiology of SAPH remains unknown, and its pathomechanisms are not fully explained. Sarcoidosis is a heterogeneous and dynamic condition, and SAPH pathogenesis is believed to be multifactorial. The main roles in SAPH development play: parenchymal lung disease with the destruction of pulmonary vessels, the extrinsic compression of pulmonary vessels by conglomerate masses, lymphadenopathy or fibrosing mediastinitis, pulmonary vasculopathy, LV dysfunction, and portal hypertension. Recently, it has been recommended to individually tailor SAPH management according to the predominant pathomechanism, i.e., SAPH phenotype. Unfortunately, SAPH phenotyping is not a straightforward process. First, there are gaps in our understanding of undergoing processes. Second, the assessment of such a pivotal element as pulmonary vasculature on a microscopic level is non-feasible in SAPH patients antemortem. Finally, SAPH is a dynamic condition, multiple phenotypes usually coexist, and patients can switch between phenotypes during the course of sarcoidosis. In this article, we summarise the basic knowledge of SAPH, describe SAPH phenotypes, and highlight some practical problems related to SAPH phenotyping.
Video Analysis of Small Bowel Capsule Endoscopy Using a Transformer Network
Authors: Oh SangYup , Oh DongJun , Kim Dongmin , Song Woohyuk , Hwang Youngbae , Cho Namik , Lim Yun
Published: October 2023

Although wireless capsule endoscopy (WCE) detects small bowel diseases effectively, it has some limitations. For example, the reading process can be time consuming due to the numerous images generated per case and the lesion detection accuracy may rely on the operators’ skills and experiences. Hence, many researchers have recently developed deep-learning-based methods to address these limitations. However, they tend to select only a portion of the images from a given WCE video and analyze each image individually. In this study, we note that more information can be extracted from the unused frames and the temporal relations of sequential frames. Specifically, to increase the accuracy of lesion detection without depending on experts’ frame selection skills, we suggest using whole video frames as the input to the deep learning system. Thus, we propose a new Transformer-architecture-based neural encoder that takes the entire video as the input, exploiting the power of the Transformer architecture to extract long-term global correlation within and between the input frames. Subsequently, we can capture the temporal context of the input frames and the attentional features within a frame. Tests on benchmark datasets of four WCE videos showed 95.1% sensitivity and 83.4% specificity. These results may significantly advance automated lesion detection techniques for WCE images.
HEM: An Improved Parametric Link Prediction Algorithm Based on Hybrid Network Evolution Mechanism
Authors: Ke Dejing , Pu Jiansu
Published: October 2023

Link prediction plays an important role in the research of complex networks. Its task is to predict missing links or possible new links in the future via existing information in the network. In recent years, many powerful link prediction algorithms have emerged, which have good results in prediction accuracy and interpretability. However, the existing research still cannot clearly point out the relationship between the characteristics of the network and the mechanism of link generation, and the predictability of complex networks with different features remains to be further analyzed. In view of this, this article proposes the corresponding link prediction indexes Reg, DFPA and LW on a regular network, scale-free network and small-world network, respectively, and studies their prediction properties on these three network models. At the same time, we propose a parametric hybrid index HEM and compare the prediction accuracies of HEM and many similarity-based indexes on real-world networks. The experimental results show that HEM performs better than other Birnbaum–Saunders. In addition, we study the factors that play a major role in the prediction of HEM and analyze their relationship with the characteristics of real-world networks. The results show that the predictive properties of factors are closely related to the features of networks.
On the Spot Presentation-Based Assessment (OTSPA): Student Perception and Predictive Value of a Novel Summative Assessment with a Formative Assessment Flavour
Authors: Paramasivam Sharmini Julita , Abou-Amer Yasmin , Saadeh Khalil
Published: October 2023

University of Surrey’s School of Veterinary Medicine introduced an assessment called On The Spot Presentation-based Assessment (OTSPA) into the 3rd and 4th year of a 5-year veterinary degree programme. The OTSPA is designed as a low-weightage summative assessment, conducted in a supportive learning environment to create a better learning experience. The OTSPA is a timed oral assessment with an ‘on the spot’ selection of taught topics, i.e., students prepare to be assessed on all topics but a subset is chosen on the day. The OTSPA was designed to test the students’ depth of knowledge while promoting skills like communication and public speaking. The aim of this study is to describe the design and operation of the OTSPA, to evaluate student perception of the approach, and to assess the OTSPA’s predictive value in relation to the final written summative assessment (FWSA), which is an indicator of academic performance. This study assessed the student perceptions (N = 98) and predictive value of the OTSPA on the FWSA in three modules: Zoological Medicine (ZM), Fundamentals of Veterinary Practice (FVP), and Veterinary Research and Evidence-based Veterinary Medicine (VREBVM). In the perception study, 79.6% of students felt that their preparation for OTSPAs drove an understanding and learning of topics that formed part of the module learning outcomes. Only a small group (21.4%) reported the assessment to be enjoyable; however, 54.1% saw value in it being an authentic assessment, reflecting real-life situations. The majority of students felt that the OTSPA helped with improving communication skills (80.4%). There was a small but significant positive correlation between the performance in OTSPAs and the FWSA in all modules. This suggests that OTSPAs can be useful in predicting the outcomes of the FWSA and, furthermore, could have utility in identifying where support may be helpful for students to improve academic performance. Outcomes from this study indicate that the OTSPA is an effective low stake summative assessment within the Surrey veterinary undergraduate programme.
Synthesis of LaXO3 (X = Fe, Mn, Cr, Ni) Thin Films Using a Simple Spin Coating Set-Up for Resistive Switching Memory Devices
Authors: Aljurays Raghad K. , Loucif Aicha , Albadri Abdulrahman M.
Published: October 2023

This study focuses on the preparation of LaXO3(X=Fe,Mn,Cr,Ni) perovskite thin films using a simple set-up spin coating technique and the evaluation of their properties for application in switching memory devices. The properties of as-deposited films were thoroughly characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), UV-Vis spectroscopy, and a vibrating sample magnetometer (VSM). The results obtained revealed that the as-deposited films have a polycrystalline cubic structure. The film surfaces were uniform and densely packed without any voids, cracks, or pinholes. In addition, irregularly shaped grains were observed having an average size of 140, 120, 89, and 70 nm for LaFeO3, LaMnO3, LaCrO3, and LaNiO3 films, respectively. VSM analysis demonstrated that LaFeO3 film exhibited superior magnetic properties compared to the other films. Furthermore, memory devices with Au/LaXO3(X=Fe,Mn,Cr,Ni)/FTO structures were fabricated, and their I-V characteristics were measured. In order to assess their performance, an endurance test was conducted. The findings indicated that Au/LaFeO3/FTO device exhibited higher RHRSRLRS ratio (~7×105), low Set/Reset voltages, lower power consumption (2.7×10−4 W), and stable endurance with no significant degradation was observed in the LRS and HRS after 20 sweep cycles. These favorable parameters can be attributed to the reduced thickness, larger grain size, and excellent magnetic properties of the active-layer LaFeO3. Moreover, the conduction mechanism of the fabricated devices was investigated, revealing that the conduction in the LRS is primarily dominated by Ohmic behavior, while the HRS exhibited different conduction mechanisms.
Predicting DDoS Attacks Using Machine Learning Algorithms in Building Management Systems
Authors: Avcı İsa , Koca Murat
Published: October 2023

The rapid growth of the Internet of Things (IoT) in smart buildings necessitates the continuous evaluation of potential threats and their implications. Conventional methods are increasingly inadequate in measuring risk and mitigating associated hazards, necessitating the development of innovative approaches. Cybersecurity systems for IoT are critical not only in Building Management System (BMS) applications but also in various aspects of daily life. Distributed Denial of Service (DDoS) attacks targeting core BMS software, particularly those launched by botnets, pose significant risks to assets and safety. In this paper, we propose a novel algorithm that combines the power of the Slime Mould Optimization Algorithm (SMOA) for feature selection with an Artificial Neural Network (ANN) predictor and the Support Vector Machine (SVM) algorithm. Our enhanced algorithm achieves an outstanding accuracy of 97.44% in estimating DDoS attack risk factors in the context of BMS. Additionally, it showcases a remarkable 99.19% accuracy in predicting DDoS attacks, effectively preventing system disruptions, and managing cyber threats. To further validate our work, we perform a comparative analysis using the K-Nearest Neighbor Classifier (KNN), which yields an accuracy rate of 96.46%. Our model is trained on the Canadian Institute for Cybersecurity (CIC) IoT Dataset 2022, enabling behavioral analysis and vulnerability testing on diverse IoT devices utilizing various protocols, such as IEEE 802.11, Zigbee-based, and Z-Wave.
Energy Harvesting and Energy Storage Systems, Volume II
Authors: Rajput Shailendra
Published: October 2023

Systems for sustainable development are built on three pillars: economic development, environmental stewardship, and social value [...]
A Simplified Design Method for Quasi-Resonant Inverter Used in Induction Hob
Authors: Ozturk Metin
Published: October 2023

Induction heating (IH) technology is widely recognized and utilized in residential applications due to its high efficiency and safe operating characteristics. Resonant inverter circuits are widely used in IH systems because of their high efficiency and ability to perform soft switching. Among the various resonant inverters used in IH systems, the single-switch quasi-resonant (SSQR) inverter topology is typically preferred for low-cost and low-output-power applications. Despite its cost advantage, the SSQR topology has a relatively narrow soft-switching range, which can be unstable depending on the electrical parameters of the load and the resonant converter circuit. Accurately determining the capacitance value of the resonant capacitor and the inductance value of the induction coil, which are the key circuit elements of the SSQR induction cooker, is crucial for designing a reliable, efficient, and durable cooking system. In other words, there exists a critical relationship between the resonant converter circuit parameters, load characteristics, and safe operating conditions. Additionally, when considering closed-loop control methods used for power control and safety, selecting appropriate resonant circuit elements becomes vital in ensuring both reliable and efficient operation. This paper focuses on a novel and simplified design method for the SSQR inverter utilized in household appliances. The proposed method and its advantages in terms of the safe operating area of the switch are theoretically investigated and verified through simulations and prototype circuits.
55 nm CMOS Mixed-Signal Neuromorphic Circuits for Constructing Energy-Efficient Reconfigurable SNNs
Authors: Quan Jiale , Liu Zhen , Li Bo , Zeng Chuanbin , Luo Jiajun
Published: October 2023

The development of brain-inspired spiking neural networks (SNNs) has great potential for neuromorphic edge computing applications, while challenges remain in optimizing power-efficiency and silicon utilization. Neurons, synapses and spike-based learning algorithms form the fundamental information processing mechanism of SNNs. In an effort to achieve compact and biologically plausible SNNs while restricting power consumption, we propose a set of new neuromorphic building circuits, including an analog Leaky Integrate-and-Fire (LIF) neuron circuit, configurable synapse circuits and Spike Driven Synaptic Plasticity (SDSP) learning algorithm circuits. Specifically, we explore methods to minimize large leakage current and device mismatch effects, and optimize the design of these neuromorphic circuits to enable low-power operation. A reconfigurable mixed-signal SNN is proposed based on the building circuits, allowing flexible configuration of synapse weights and attributes, resulting in enhanced SNN functionality and reduced unnecessary power consumption. This SNN chip is fabricated using 55 nm CMOS technology, and test results indicate that the proposed circuits have the ability to closely mimic the behaviors of LIF neurons, synapses and SDSP mechanisms. By configuring synaptic arrays, we established varied connections between neurons in the SNN and demonstrated that this SNN chip can implement Pavlov’s dog associative learning and binary classification tasks, while dissipating less energy per spike of the order of Pico Joules per spike at a firing rate ranging from 30 Hz to 1 kHz. The proposed circuits can be used as building blocks for constructing large-scale SNNs in neuromorphic processors.
Probabilistic Evaluation of Geomechanical Risks in CO2 Storage: An Exploration of Caprock Integrity Metrics Using a Multilaminate Model
Authors: Lee Si-Yong , Mohamed Farid Reza , Lee Kwang-Ho , McPherson Brian , Balch Robert , Yoon Sangcheol
Published: October 2023

The probabilistic uncertainty assessment of geomechanical risk—specifically, caprock failure—attributable to CO2 injection, as presented in a simplified hypothetical geological model, was the focus of this study. Our approach amalgamates the implementation of a multilaminate model, the creation of a response surface model in conjunction with the Box–Behnken sampling design, the execution of associated numerical modeling experiments, and the utilization of Monte Carlo simulations. Probability distributions to encapsulate the inherent variability (elastic and mechanical properties of the caprock and reservoir) and uncertainty in prediction estimates (vertical displacement, total strain, and F value) were employed. Our findings reveal that the Young modulus of the caprock is a key factor controlling equivalent total strain but is insufficient as a stand-alone indicator of caprock integrity. It is confirmed that the caprock can accommodate significant deformation without failure, if it possesses a low Young’s modulus and high mechanical strength properties, such as the friction angle and uniaxial compressive strength. Similarly, vertical displacement was found to be an unreliable indicator for caprock integrity, as caprock failure can occur across a broad spectrum of vertical displacements, particularly when both the Young modulus and mechanical strength properties have wide ranges. This study introduces the F value as the most dependable indicator for caprock failure, although it is a theoretical attribute (the shortest distance between the Mohr circle and the nearest failure envelope used to measure the sensitivity to failure) and not physically measurable in the field. Deviatoric stress levels were found to vary based on stress regimes, with the maximum levels observed under extensive and compressive stress regimes. In conjunction with the use of the response surface method, this study demonstrates the efficacy of the multilaminate framework and the Mohr–Coulomb constitutive model in providing a simplified, yet effective, probabilistic model of the mechanical behavior of caprock failure, reducing mathematical and computational complexities.
The Impact of the Level of Training of Airport Security Control Operators on the Energy Consumption of the Baggage Control Process
Authors: Ryczyński Jacek , Kierzkowski Artur
Published: October 2023

The article focuses on the study of the impact of the level of training of security control operators (SCOs) at airports on the energy consumption of the passenger baggage control process. With the constant growing emphasis on security at airports, the intensification of training processes for security personnel, especially those dealing with baggage control, has become very dynamic. An essential aspect in times of sustainable development is optimizing all kinds of processes (including training processes) to reduce energy consumption. The analysis of the demand for energy used to conduct this type of training and the impact of the operator’s training level on the energy consumption of the control process are entirely ignored and have not been the subject of research by scientists so far. Therefore, this is a research gap that the authors are trying to fill in this article. The impact of safety system operator training levels on ensuring optimal energy efficiency was critically analyzed. The added value of the article is the authors’ model assessing the influence of the level of training of the SCO on the energy consumption of the control process. The effects of the frequency, duration and level of operator training on energy consumption rates were investigated. The authors’ activities aimed to identify the most energy-efficient approaches to training without compromising its quality and, thus, the safety of passengers. The article discusses potential strategies for minimizing energy use and draws conclusions that can help airport administrations and training providers adopt sustainable and energy-efficient training practices.
Impact of Environmental Conditions on Seed Germination of Glossy Buckthorn (Frangula alnus (Mill)) in Eastern Canada
Authors: Custodio Tiana , Houle Daniel , Girard Francois
Published: October 2023

Understanding seed characteristics, germination, and seedling establishment patterns is essential for formulating effective management strategies to control invasive species. Glossy buckthorn (Frangula alnus) is a shrub or small tree from Eurasia that has become invasive in North America, and which has negative impacts on plant communities and ecosystems. In this study, we analyzed the germination response of glossy buckthorn seeds to different temperatures (12, 14, 16, 18, 20, 24, and 28 °C), various stratification lengths (4 to 20 weeks), and scarification conditions to measure the impact on breaking seed dormancy, and the effect of light in triggering germination. Analysis using distinct time-to-event approaches, including the Kaplan–Meier estimator and Cox proportional hazard model, was employed to interpret germination data. Glossy buckthorn seeds exhibited physiological dormancy and required cold stratification to germinate. At 12 °C, only 14% of the seeds could germinate. At warmer temperatures, germination rates increased, reaching a peak of 70% at 20 °C. At 24 °C and 28 °C, germination declined, and seeds were probably induced into secondary dormancy. Scarified seeds had a higher probability of germination than non-scarified ones, even at the lowest temperatures. Darkness had a negative impact on germination at all tested temperatures. This study significantly advances our understanding of how temperature, light, stratification, and scarification impact glossy buckthorn seeds, elucidating the species’ seasonal germination patterns in North America. The results emphasize that glossy buckthorn utilizes seed banks as a primary strategy for invading and establishing in new habitats. The ungerminated seeds form persistent seed banks, ensuring F. alnus’ survival and bolstering its chances of successful establishment and invasion. As climate change drives temperature increases, it may affect seeds in the soil, altering stratification periods and consequently shifting the timing of germination.
Green Synthesis of Au Magnetic Nanocomposites Using Waste Chestnut Skins and Their Application as a Peroxidase Mimic Nanozyme Electrochemical Sensing Platform for Sodium Nitrite
Authors: Guan Huanan , Xing Ke , Liu Shuping
Published: October 2023

An electrochemical sensor with high sensitivity for the detection of sodium nitrite was constructed based on the peroxidase-like activity of Au magnetic nanocomposites (Au@Fe3O4). The Au@Fe3O4 composite nanoparticles were green-synthesized via the reduction of gold nanoparticles (AuNPs) from waste chestnut skins combined with the sonochemical method. The nanoparticles have both the recoverability of Fe3O4 and the advantage of being able to amplify electrical signals. Furthermore, the synergistic effect of green reduction and sonochemical synthesis provides a functional approach for the preparation of Au@Fe3O4 with significant peroxidase-like activities. The physicochemical properties were characterized using transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), the Brunauer–Emmett–Teller (BET) method, and Fourier transform infrared spectroscopy (FT-IR). The electrochemical properties of sodium nitrite were determined with cyclic voltammetry (CV) and chronoamperometry (i-t). The results revealed that Au@Fe3O4 acted as a peroxidase mimic to decompose hydrogen peroxide to produce free radicals, while ·OH was the primary free radical that promoted the oxidation of sodium nitrite. With the optimal detection system, the constructed electrochemical sensor had a high sensitivity for sodium nitrite detection. In addition, the current response had a good linear relationship with the sodium nitrite concentration in the range of 0.01–100 mmol/L. The regression equation of the working curve was y = 1.0752x + 4.4728 (R2 = 0.9949), and the LOD was 0.867 μmol/L (S/N = 3). Meanwhile, the constructed detection system was outstanding in terms of recovery and anti-interference and had a good detection stability of more than 96.59%. The sensor has been successfully applied to a variety of real samples. In view of this, the proposed novel electrochemical analysis method has great prospects for application in the fields of food quality and environmental testing.
Consumer Preferences for Cured Meat Products from the Autochthonous Black Slavonian Pig
Authors: Jelić Milković Sanja , Crnčan Ana , Kristić Jelena , Kralik Igor , Djurkin Kušec Ivona , Gvozdanović Kristina , Kušec Goran , Kralik Zlata , Lončarić Ružica
Published: October 2023

This study investigated the attitudes of Croatian consumers regarding their preferences for cured meat products from the Black Slavonian Pig. The survey was conducted on a sample of 410 consumers who completed an online survey about their consumption habits, knowledge about the pig breed, and socio-demographic characteristics. In this study, the independent samples t-test and ANOVA were conducted to determine the significant differences between the most important attributes in the purchase of cured Black Slavonian Pig products and the socio-demographic characteristics, consumption, and purchase habits of the respondents. Statistically significant differences were found between the studied intrinsic (color, odor, fat content, and salt content) and extrinsic variables (production method, brand, quality mark, and origin) in relation to the socio-demographic characteristics of the respondents (gender, age, employment status, number of household members, and number of children under 15 in the household) and place of purchase, knowledge about the breed, and frequency of consumption of Black Slavonian Pig meat and products. Principal component analysis (PCA) and cluster analysis (CA) were used to determine the consumer segments. Based on the responses received, three homogeneous consumer segments were identified: intrinsically oriented meat consumers, extrinsically oriented meat consumers, and uninterested meat consumers. The information obtained in the study is important for producers and retailers, as they can use our findings to develop successful marketing tools and different marketing strategies to promote cured Black Slavonian Pig products.
Multivariate Statistical Analysis for Water Quality Assessment: A Review of Research Published between 2001 and 2020
Authors: Muniz Daphne H. F. , Oliveira-Filho Eduardo C.
Published: October 2023

Research on water quality is a fundamental step in supporting the maintenance of environmental and human health. The elements involved in water quality analysis are multidimensional, because numerous characteristics can be measured simultaneously. This multidimensional character encourages researchers to statistically examine the data generated through multivariate statistical analysis (MSA). The objective of this review was to explore the research on water quality through MSA between the years 2001 and 2020, present in the Web of Science (WoS) database. Annual results, WoS subject categories, conventional journals, most cited publications, keywords, water sample types analyzed, country or territory where the study was conducted and most used multivariate statistical analyses were topics covered. The results demonstrate a considerable increase in research using MSA in water quality studies in the last twenty years, especially in developing countries. River, groundwater and lake were the most studied water sample types. In descending order, principal component analysis (PCA), hierarchical cluster analysis (HCA), factor analysis (FA) and discriminant analysis (DA) were the most used techniques. This review presents relevant information for researchers in choosing the most appropriate methods to analyze water quality data.
How Nitric Oxide Hindered the Search for Hemoglobin-Based Oxygen Carriers as Human Blood Substitutes
Authors: Samaja Michele , Malavalli Ashok , Vandegriff Kim D.
Published: October 2023

The search for a clinically affordable substitute of human blood for transfusion is still an unmet need of modern society. More than 50 years of research on acellular hemoglobin (Hb)-based oxygen carriers (HBOC) have not yet produced a single formulation able to carry oxygen to hemorrhage-challenged tissues without compromising the body’s functions. Of the several bottlenecks encountered, the high reactivity of acellular Hb with circulating nitric oxide (NO) is particularly arduous to overcome because of the NO-scavenging effect, which causes life-threatening side effects as vasoconstriction, inflammation, coagulopathies, and redox imbalance. The purpose of this manuscript is not to add a review of candidate HBOC formulations but to focus on the biochemical and physiological events that underly NO scavenging by acellular Hb. To this purpose, we examine the differential chemistry of the reaction of NO with erythrocyte and acellular Hb, the NO signaling paths in physiological and HBOC-challenged situations, and the protein engineering tools that are predicted to modulate the NO-scavenging effect. A better understanding of two mechanisms linked to the NO reactivity of acellular Hb, the nitrosylated Hb and the nitrite reductase hypotheses, may become essential to focus HBOC research toward clinical targets.
Preventive Effect of Molecular Iodine in Pancreatic Disorders from Hypothyroid Rabbits
Authors: Rodríguez-Castelán Julia , Delgado-González Evangelina , Rodríguez-Benítez Esteban , Castelán Francisco , Cuevas-Romero Estela , Anguiano Brenda , Jeziorski Michael C. , Aceves Carmen
Published: October 2023

Pancreatic alterations such as inflammation and insulin resistance accompany hypothyroidism. Molecular iodine (I2) exerts antioxidant and differentiation actions in several tissues, and the pancreas is an iodine-uptake tissue. We analyzed the effect of two oral I2 doses on pancreatic disorders in a model of hypothyroidism for 30 days. Adult female rabbits were divided into the following groups: control, moderate oral dose of I2 (0.2 mg/kg, M-I2), high oral dose of I2 (2.0 mg/kg, H-I2), oral dose of methimazole (MMI; 10 mg/kg), MMI + M-I2,, and MMI + H-I2. Moderate or high I2 supplementation did not modify circulating metabolites or pancreatic morphology. The MMI group showed reductions of circulating thyroxine (T4) and triiodothyronine (T3), moderate glucose increments, and significant increases in cholesterol and low-density lipoproteins. Acinar fibrosis, high insulin content, lipoperoxidation, and overexpression of GLUT4 were observed in the pancreas of this group. M-I2 supplementation normalized the T4 and cholesterol, but T3 remained low. Pancreatic alterations were prevented, and nuclear factor erythroid-2-related factor-2 (Nrf2), antioxidant enzymes, and peroxisome proliferator-activated receptor gamma (PPARG) maintained their basal values. In MMI + H-I2, hypothyroidism was avoided, but pancreatic alterations and low PPARG expression remained. In conclusion, M-I2 supplementation reestablishes thyronine synthesis and diminishes pancreatic alterations, possibly related to Nrf2 and PPARG activation.
Analysis of Potential Biomarkers in Frontal Temporal Dementia: A Bioinformatics Approach
Authors: Momin Inara Deedar , Rigler Jessica , Chitrala Kumaraswamy Naidu
Published: October 2023

Frontal temporal dementia (FTD) is a neurological disorder known to have fewer therapeutic options. So far, only a few biomarkers are available for FTD that can be used as potential comorbidity targets. For example, genes such as VCP, which has a role in breast cancer, and WFS1, which has a role in COVID-19, are known to show a role in FTD as well. To this end, in the present study, we aim to identify potential biomarkers or susceptible genes for FTD that show comorbidities with diseases such as COVID-19 and breast cancer. A dataset from Gene Expression Omnibus containing FTD expression profiles from African American and white ethnicity backgrounds was included in our study. In FTD samples of the GSE193391 dataset, we identified 305 DEGs, with 168 genes being up-regulated and 137 genes being down-regulated. We conducted a comorbidity analysis for COVID-19 and breast cancer, followed by an analysis of potential drug interactions, pathogenicity, analysis of genetic variants, and functional enrichment analysis. Our results showed that the genes AKT3, GFAP, ADCYAP1R1, VDAC1, and C4A have significant transcriptomic alterations in FTD along with the comorbidity status with COVID-19 and breast cancer. Functional pathway analysis revealed that these comorbid genes were significantly enriched in the pathways such as glioma, JAK/STAT signaling, systematic lupus erythematosus, neurodegeneration-multiple diseases, and neuroactive ligand–receptor interaction. Overall, from these results, we concluded that these genes could be recommended as potential therapeutic targets for the treatment of comorbidities (breast cancer and COVID-19) in patients with FTD.
Properties of Degradable Polyhydroxyalkanoates Synthesized from New Waste Fish Oils (WFOs)
Authors: Zhila Natalia O. , Kiselev Evgeniy G. , Volkov Vladimir V. , Mezenova Olga Ya. , Sapozhnikova Kristina Yu. , Shishatskaya Ekaterina I. , Volova Tatiana G.
Published: October 2023

The synthesis of PHA was first investigated using WFOs obtained from smoked-sprat heads, substandard fresh sprats, and fresh mackerel heads and backbones. All the WFOs ensured the growth of the wild-type strain Cupriavidus necator B-10646 and the synthesis of PHA, regardless of the degree of lipid saturation (from 0.52 to 0.65) and the set and ratio of fatty acids (FA), which was represented by acids with chain lengths from C14 to C24. The bacterial biomass concentration and PHA synthesis were comparable (4.1–4.6 g/L and about 70%) when using WFO obtained from smoked-sprat heads and fresh mackerel, and it was twice as high as the bacterial biomass concentration from the fresh sprat waste. This depended on the type of WFO, the bacteria synthesized P(3HB) homopolymer or P(3HB-co-3HV-co-3HHx) copolymer, which had a lower degree of crystallinity (Cx 71%) and a lower molecular weight (Mn 134 kDa) compared to the P(3HB) (Mn 175–209 kDa and Cx 74–78%) at comparable temperatures (Tmelt and Tdegr of 158–168 °C and 261–284 °C, respectively). The new types of WFO, studied for the first time, are suitable as a carbon substrates for PHA synthesis. The WFOs obtained in the production of canned Baltic sprat and Baltic mackerel can be considered a promising and renewable substrate for PHA biosynthesis.
Methanolic Extracts of D. viscosa Specifically Affect the Cytoskeleton and Exert an Antiproliferative Effect on Human Colorectal Cancer Cell Lines, According to Their Proliferation Rate
Authors: Anglana Chiara , Rojas Makarena , Girelli Chiara Roberta , Barozzi Fabrizio , Quiroz-Troncoso Josefa , Alegría-Aravena Nicolás , Montefusco Anna , Durante Miriana , Fanizzi Francesco Paolo , Ramírez-Castillejo Carmen , Di Sansebastiano Gian-Pietro
Published: October 2023

Numerous studies have reported the pharmacological effects exhibited by Dittrichia viscosa, (D. viscosa) including antioxidant, cytotoxic, antiproliferative, and anticancer properties. In our research, our primary objective was to validate a prescreening methodology aimed at identifying the fraction that demonstrates the most potent antiproliferative and anticancer effects. Specifically, we investigated the impact of various extract fractions on the cytoskeleton using a screening method involving transgenic plants. Tumors are inherently heterogeneous, and the components of the cytoskeleton, particularly tubulin, are considered a strategic target for antitumor agents. To take heterogeneity into account, we used different lines of colorectal cancer, specifically one of the most common cancers regardless of gender. In patients with metastasis, the effectiveness of chemotherapy has been limited by severe side effects and by the development of resistance. Additional therapies and antiproliferative molecules are therefore needed. In our study, we used colon-like cell lines characterized by the expression of gastrointestinal differentiation markers (such as the HT-29 cell line) and undifferentiated cell lines showing the positive regulation of epithelial–mesenchymal transition and TGFβ signatures (such as the DLD-1, SW480, and SW620 cell lines). We showed that all three of the D. viscosa extract fractions have an antiproliferative effect but the pre-screening on transgenic plants anticipated that the methanolic fraction may be the most promising, targeting the cytoskeleton specifically and possibly resulting in fewer side effects. Here, we show that the preliminary use of screening in transgenic plants expressing subcellular markers can significantly reduce costs and focus the advanced characterization only on the most promising therapeutic molecules.
Incorporating Ceragenins into Coatings Protects Peripherally Inserted Central Catheter Lines against Pathogen Colonization for Multiple Weeks
Authors: Zaugg Aaron , Sherren Elliot , Yi Rebekah , Larsen Tessa , Dyck Brayden , Stump Sierra , Pauga Fetutasi , Linder Anna , Takara Meg , Gardner Emily , Shin Spencer , Pulsipher Jace , Savage Paul B.
Published: October 2023

Healthcare-acquired infections and multi-drug resistance in pathogens pose a major crisis for the healthcare industry. Novel antibiotics which are effective against resistant strains and unlikely to elicit strong resistance are sought after in these settings. We have previously developed synthetic mimics of ubiquitous antimicrobial peptides and have worked to apply a lead compound, CSA-131, to the crisis. We aimed to generate a system of CSA-131-containing coatings for medical devices that can be adjusted to match elution and compound load for various environments and establish their efficacy in preventing the growth of common pathogens in and around these devices. Peripherally inserted central catheter (PICC) lines were selected for our substrate in this work, and a polyurethane-based system was used to establish coatings for evaluation. Microbial challenges by methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans were performed and SEM was used to evaluate coating structure and colonization. The results indicate that selected coatings show activity against selected planktonic pathogens that extend between 16 and 33 days, with similar periods of biofilm prevention.
Osteoimmunology of Spondyloarthritis
Authors: Fassio Angelo , Atzeni Fabiola , Rossini Maurizio , D’Amico Valeria , Cantatore Francesco , Chimenti Maria Sole , Crotti Chiara , Frediani Bruno , Giusti Andrea , Peluso Giusy , Rovera Guido , Scolieri Palma , Raimondo Vincenzo , Gatti Davide ,   on behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology
Published: October 2023

The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA.
Dysautonomia in Amyotrophic Lateral Sclerosis
Authors: Oprisan Alexandra L. , Popescu Bogdan Ovidiu
Published: October 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized in its typical presentation by a combination of lower and upper motor neuron symptoms, with a progressive course and fatal outcome. Due to increased recognition of the non-motor symptoms, it is currently considered a multisystem disorder with great heterogeneity, regarding genetical, clinical, and neuropathological features. Often underestimated, autonomic signs and symptoms have been described in patients with ALS, and various method analyses have been used to assess autonomic nervous system involvement. The aim of this paper is to offer a narrative literature review on autonomic disturbances in ALS, based on the scarce data available to date.
The Potential Role of Railway Stations and Public Transport Nodes in the Development of “15-Minute Cities”
Authors: Wolański Michał
Published: October 2023

In 2016, Carlos Moreno proposed the concept of “15-minute cities” based on the principles of proximity, diversity, density, and ubiquity. In fact, he re-formulated (“re-invented”) some of the already existing planning principles, making them recognized and desired by non-professionals. Moreno, however, paid little attention to the external connectivity of neighborhoods, assuming that most needs would be satisfied locally. This paper aims to discuss the concept of “15-minute cities” from the transport planning point of view and investigate how the concept can contribute to such planning. The research review conducted in this paper suggests that similar actions in the past caused a modal shift from the use of cars to public transport, rather than a radical limitation of total transport needs. To simplify, if a neighborhood is well designed, people are more likely to walk, ride a bike, and use public transport, but the majority will still commute outside of the neighborhood for work. In the metropolis of the ideal “15-minute city”, Barcelona, the majority of the inhabitants travel to work either by car or public transport, which proves that they need to move outside the neighborhood. This leads us to the conclusions that (1) “15-minute cities” should incorporate the transit-oriented development concept and include public transport nodes, such as railways or underground stations, as the central point of walkable, multifunctional neighborhoods, and (2) railway/underground station planners should pay more attention to the creation of a proper mix of services at and around the stations according to “15-minute cities” principles. In the future, there should also be more emphasis on re-allocating workplaces to neighborhoods, as well as on researching the actual impact of the (improved and current) “15-minute cities” design on transport volumes.
Thyroid Autoimmunity and SARS-CoV-2 Infection
Authors: Fallahi Poupak , Elia Giusy , Ragusa Francesca , Paparo Sabrina Rosaria , Patrizio Armando , Balestri Eugenia , Mazzi Valeria , Benvenga Salvatore , Varricchi Gilda , Gragnani Laura , Botrini Chiara , Baldini Enke , Centanni Marco , Ferri Clodoveo , Antonelli Alessandro , Ferrari Silvia Martina
Published: October 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological culprit of COronaVIrus Disease 19 (COVID-19), can enter the cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which has been found in several tissues including in endocrine organs, such as the ovaries, testes, pancreas, and thyroid. Several thyroid disorders have been associated with SARS-CoV-2 infection [subacute thyroiditis (SAT), thyrotoxicosis, and non-thyroidal illness syndrome (NTIS)] and, in part, they are believed to be secondary to the local virus replication within the gland cells. However, as documented for other viruses, SARS-CoV-2 seems to interfere with several aspects of the immune system, inducing the synthesis of autoantibodies and triggering latent or new onset autoimmune disease (AID), including autoimmune thyroid disease (AITD), such as Hashimoto Thyroiditis (HT) and Graves’ disease (GD). Several mechanisms have been hypothesized to explain this induction of autoimmunity by SARS-CoV-2 infection: the immune system hyper-stimulation, the molecular mimicry between the self-antigens of the host and the virus, neutrophils extracellular traps, and finally, the virus induced transcriptional changes in the immune genes; nonetheless, more evidence is needed especially from large, long-term cohort studies involving COVID-19 patients, to establish or reject this pathogenetic relationship.