bluuebunny/crossref_metadata_2025 huggingface dataset:
Corrosion-Resisting Nanocarbon Nanocomposites for Aerospace Application: An Up-to-Date Account
Authors: Kausar Ayesha , Ahmad Ishaq , Zhao Tingkai
Published: May 2023

The design and necessity of corrosion-resisting nanocarbon nanocomposites have been investigated for cutting-edge aerospace applications. In this regard, nanocarbon nanofillers, especially carbon nanotubes, graphene, nanodiamond, etc. have been used to fill in various polymeric matrices (thermosets, thermoplastics, and conducting polymers) to develop anti-rusting space-related nanocomposites. This review fundamentally emphases the design, anti-corrosion properties, and application of polymer/nanocarbon nanocomposites for the space sector. An electron-conducting network is created in the polymers with nanocarbon dispersion to assist in charge transportation, and thus in the polymers’ corrosion resistance features. The corrosion resistance mechanism depends upon the formation of tortuous diffusion pathways due to nanofiller arrangement in the matrices. Moreover, matrix–nanofiller interactions and interface formation play an important role in enhancing the corrosion protection properties. The anticorrosion nanocomposites were tested for their adhesion, contact angle, and impedance properties, and NaCl tests and scratch tests were carried out. Among the polymers, epoxy was found to be superior corrosion-resisting polymer, relative to the thermoplastic polymers in these nanocomposites. Among the carbon nanotubes, graphene, and nanodiamond, the carbon nanotube with a loading of up to 7 wt.% in the epoxy matrix was desirable for corrosion resistance. On the other hand, graphene contents of up to 1 wt.% and nanodiamond contents of 0.2–0.4 wt.% were desirable to enhance the corrosion resistance of the epoxy matrix. The impedance, anticorrosion, and adhesion properties of epoxy nanocomposites were found to be better than those of the thermoplastic materials. Despite the success of nanocarbon nanocomposites in aerospace applications, thorough research efforts are still needed to design high-performance anti-rusting materials to completely replace the use of metal components in the aerospace industry.
Enabling End-Users in Designing and Executing of Complex, Collaborative Robotic Processes
Authors: Zörrer Helmut , Weichhart Georg , Schmoigl Tonis Mathias , Bieg Till , Propst Matthias , Schuster Dominik , Sturm Nadine , Nativel Chloé , Salomon Gabriele , Strohmeier Felix , Sackl Andreas , Eberle Michael , Pichler Andreas
Published: May 2023

Over the last years, capabilities of robotic systems have quantitatively and qualitatively improved. But going beyond isolated robotic systems, the integration and interoperability of robotic capabilities in complex work processes remains a major challenge. This lack of tools to integrate robots needs to be addressed on technical, semantic and organizational level. In the ROBxTASK research project, we developed an approach to support cooperation between different types of users in order to enable domain experts, with no robotic know-how, to work with robot-assisted workflows. By engineering robotic skills at a useful and usable level of abstraction for experts in different domains, we aim to increase re-usability of these skills on two different levels, (robotic) device level, and on level of application specific workflows. The researched prototype consists of a web platform, which allows (a) engineers to register (robotic) devices and the implemented skills of the devices, (b) domain experts to use a graphical task design environment to create workflows across multiple robotic devices and lastly (c) robot co-workers to download and execute the workflow code in a local environment with digital twins or real robots. Additionally skills and workflows can be shared across organisations. Initial user studies have shown that the visual programming environment is accessible and the defined skill-set is easy to understand even for domain experts that are inexperienced in the field of robotics.
Cardiovascular and Respiratory Health Effects of Fine Particulate Matters (PM2.5): A Review on Time Series Studies
Authors: Wan Mahiyuddin Wan Rozita , Ismail Rohaida , Mohammad Sham Noraishah , Ahmad Nurul Izzah , Nik Hassan Nik Muhammad Nizam
Published: May 2023

Ambient air pollution remains one of the most important risk factors for health outcomes. In recent years, there has been a growing number of research linking particulate matter (PM) exposure with adverse health effects, especially on cardiovascular and respiratory systems. The objective of this review is to examine the range and nature of studies on time series analysis of health outcomes affected by PM2.5 across a broad research area. A literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping review framework through a strategic search of PubMed and ScienceDirect online databases for articles from January 2016 to January 2021. Articles were first screened by their titles and abstracts. Then two reviewers independently reviewed and evaluated the full text of the remaining articles for eligibility. Of the 407 potentially relevant studies, 138 articles were included for final analysis. There was an increasing trend in publications from 2016 to 2019 but a decreasing trend in the year 2020. Most studies were conducted in Eastern and South-Eastern Asia (69.6%), Europe and Northern America (14.5%) and Latin America and the Caribbean (8.7%), with the majority coming from high- and upper-middle-income countries (95.6%). The main methodology used was Generalized Additive Model (GAM) with Poisson distribution (74.6%). Morbidity was the most common health outcome studied (60.1%), with vulnerable groups (64.5%) often included. The association between PM2.5 and health effects was stronger for respiratory diseases compared to cardiovascular diseases. In short-term studies (less than 7 years), respiratory diseases showed higher risks compared to cardiovascular. However, in long-term studies (7 years and more), cardiovascular showed higher risks.
Projecting Bioclimatic Change over the South-Eastern European Agricultural and Natural Areas via Ultrahigh-Resolution Analysis of the de Martonne Index
Authors: Charalampopoulos Ioannis , Droulia Fotoula , Tsiros Ioannis X.
Published: May 2023

The changing climate is closely related to changes in the bioclimate. This research deals with the present bioclimate and its projected evolution over the entirety of the natural and agricultural lands of south-eastern Europe and individual countries (Bulgaria, Greece, Kosovo, N. Macedonia, Romania, and Serbia). For this purpose, an ultrahigh spatial resolution of the de Martonne bioclimatic index pattern was elaborated and analysed for the first time. The survey is performed over the reference period (1981–2010) and future time frames (2011–2040; 2041–2070; 2071–2100) under SSP370 and SSP585 emission scenarios. On a territorial level, both natural and agricultural areas appear as highly impacted by the future changes of bioclimate; the highest xerothermic trend is expected to influence the latter areas, mostly in 2071–2100 and under the higher emission scenario. The natural areas will face an expansion in the semidry class from 0.9% (of the total area) during the reference period to 5.6% during 2071–2100 under the RCP8.5 scenario as the dominant extremely humid class falls from 53.5% to 32.9% for the same periods and scenario. On the other hand, agricultural areas will face a more intense xerothermic alteration going from 4.9% to 17.7% for the semidry class and from 41.1% to 23.5% for the dominant very humid class for the same periods and scenario. This study presents the spatial statistics per country for the selected scenarios and periods to provide information for stakeholders. This study’s results highlight the necessity for intensifying adaptation plans and actions aiming at the feasibility of agricultural practices and the conservation of natural areas.
A Study on Radiological Hazard Assessment for Jordan Research and Training Reactor
Authors: Talafha Mohammad , Kim Sora , Suh Kyung-Suk
Published: May 2023

Numerical simulations of atmospheric dispersion and dose assessment were performed for the Jordan Research and Training Reactor (JRTR) to evaluate its radiological effects on surrounding population and the environment. A three-dimensional atmospheric dispersion model was applied to investigate the behavior of the radionuclides released into the air, and a dose assessment model was used to estimate the radiological impact on the population residing in nearby cities around the JRTR. Considering full core meltdown an accidental scenario, most of the source term was assumed to be released from the JRTR. Simulations were performed to calculate the air and deposition concentrations of radioactive materials for July 2013 and January 2014. The monthly averaged values of concentrations, depositions, and dose rates were analyzed to identify the most harmful effects in each month. The results showed that relatively harmful effects occurred in January 2014, and the total annual dose rate was estimated to be approximately 1 mSv outside the 10 km radius from JRTR. However, the impact of a nuclear accident is not as severe as it might seem, as the affected area is not highly populated, and appropriate protective measures can significantly reduce the radiation exposure. This study provides useful information for emergency preparedness and response planning to mitigate the radiological consequences of a nuclear accident at the JRTR.
Climate Variability and Trends in Imotski, Croatia: An Analysis of Temperature and Precipitation
Authors: Vrsalović Adrijana , Andrić Ivo , Bonacci Ognjen , Kovčić Omer
Published: May 2023

This paper examines the long-term changes in temperature and precipitation in the karst region of Imotski, Croatia, which is of particular interest due to its abundance of karst phenomena. This study analyses temperatures and precipitation on monthly and annual scales at two climatological stations in the region, Imotski and Ričice. Linear regression, the Theil–Sen estimator (β), and the Mann–Kendall test were used to determine the trends and statistical significance. The homogeneity of the data was checked using the Standard Normal Homogeneity Test (SNHT), and the F-test and t-test were used to test the significance of the mean shift between the two subseries. Additionally, the coefficient of variability, standardized rainfall anomaly, and precipitation concentration index were employed to analyze the precipitation variability. The study found a statistically significant (p < 0.05) upward trend in the mean (β = 0.0437) and maximum (β = 0.0590) annual air temperature at the Imotski station and the mean (β = 0.0387) annual temperature at the Ričice station. The SNHT test showed a statistically significant (p < 0.05) shift in the mean annual temperatures after 2007 and maximum annual temperatures after 1998 at the Imotski station. Similarly, a statistically significant (p < 0.05) shift in the mean annual temperatures after 2011 and the maximum annual temperatures after 1998 was found at the Ričice station. A seasonal distribution of precipitation is observed at both the Ričice and Imotski stations, with a downward trend (β = −2.7693) at Ričice and an upward trend (β = 6.0575) at Imotski; however, neither trend is statistically significant (p > 0.05). An increase in the intensity of dry periods and the occurrence of extreme events was also noted. The climatological analysis, conducted for the first time in this area, is a crucial step toward understanding local climate patterns and making informed decisions toward sustainable development and adaptation strategies.
Sniffing Drones: A Promising Solution for Measuring Railroad Emissions in Urban Environments
Authors: Baglioli Felipe , Godoi Ricardo H. M.
Published: May 2023

Locomotive emissions from railroads can particularly impact air pollution, making it crucial to understand their impacts on human health and the environment and develop strategies to reduce them. The potential of drone technology equipped with a “sniffing” system for detecting air pollution emissions is promising and can be a valuable tool for assessing dynamic emissions. This research utilized sensor-equipped drones to measure gaseous emissions from cargo and passenger trains on a railway in Curitiba, Brazil. Reference equipment evaluated the accuracy of NO2, SO2, and O3 concentrations. The results showed that before the passage of trains, the average SO2 concentration was 20 µg/m³, with a maximum concentration of 110 µg/m³ detected during transit. The average increase in NO2 concentrations was from 30 µg/m³ to 120 µg/m³, and the average increase in O3 concentrations was from 80 µg/m³ to 135 µg/m³. The vertical profiles were evaluated before and after the passage of locomotives, indicating an accumulation of pollutants above the railroad. These findings demonstrate the potential of sniffing drones to measure railroad emissions in urban environments. They also highlight the need to regulate emissions from diesel-powered locomotives to minimize atmospheric pollution and its negative impact on public health in emerging and developing countries.
State of Charge Estimation for Batteries Based on Common Feature Extraction and Transfer Learning
Authors: Li Xiaoyu , Xu Jianhua , Ding Xuejing , Lyu Hongqiang
Published: May 2023

The state of charge (SOC) of a battery is a key parameter of electrical vehicles (EVs). However, limited by the lack of computing resources, the SOC estimation strategy used in vehicle-mounted battery management systems (V-BMS) is usually simplified. With the development of the new energy vehicle big data platforms, it is possible to obtain the battery SOC through cloud-based BMS (C-BMS). In this paper, a battery SOC estimation method based on common feature extraction and transfer learning is proposed for C-BMS applications. Considering the diversity of driving cycles, a common feature extraction method combining empirical mode decomposition (EMD) and a compensation strategy for C-BMS is designed. The selected features are treated as the new inputs of the SOC estimation model to improve the generalization ability. Subsequently, a long short-term memory (LSTM) recurrent neural network is used to construct a basic model for battery SOC estimation. A parameter-based transfer learning method and an adaptive weighting strategy are used to obtain the C-BMS battery SOC estimation model. Finally, the SOC estimation method is validated on laboratory datasets and cloud platform datasets. The maximum root-mean-square error (RMSE) of battery SOC estimation with the laboratory dataset is 2.2%. The maximum RMSE of battery pack SOC estimation on two different electric vehicles is 1.3%.
LiBH4 as a Solid-State Electrolyte for Li and Li-Ion Batteries: A Review
Authors: Prosini Pier Paolo
Published: May 2023

In this paper, the methods used to enhance the conductivity of LiBH4, a potential electrolyte for the construction of solid-state batteries, are summarized. Since this electrolyte becomes conductive at temperatures above 380 K due to a phase change, numerous studies have been conducted to lower the temperature at which the hydride becomes conductive. An increase in conductivity at lower temperatures has generally been obtained by adding a second component that can increase the mobility of the lithium ion. In some cases, conductivities at room temperature, such as those exhibited by the liquid electrolytes used in current lithium-ion batteries, have been achieved. With these modified electrolytes, both lithium metal and lithium-ion cells have also been constructed, the performances of which are reported in the paper. In some cases, cells characterized by a high capacity and rate capability have been developed. Although it is still necessary to confirm the stability of the devices, especially in terms of cyclability, LiBH4-based doped electrolytes could be employed to produce solid-state lithium or lithium-ion batteries susceptible to industrial development.
Design Proposal for a Virtual Shopping Assistant for People with Vision Problems Applying Artificial Intelligence Techniques
Authors: Villegas-Ch William , Amores-Falconi Rodrigo , Coronel-Silva Eduardo
Published: May 2023

Accessibility is an increasingly important topic for Ecommerce, especially for individuals with vision problems. To improve their online experience, the design of a voice assistant has been proposed to allow these individuals to browse and shop online more quickly and efficiently. This voice assistant forms an intelligent system that can understand and respond to users’ voice commands. The design considers the visual limitations of the users, such as difficulty reading information on the screen or identifying images. The voice assistant provides detailed product descriptions and ideas in a clear, easy-to-understand voice. In addition, the voice assistant has a series of additional features to improve the shopping experience. For example, the assistant can provide product recommendations based on the user’s previous purchases and information about special promotions and discounts. The main goal of this design is to create an accessible and inclusive online shopping experience for the visually impaired. The voice assistant is based on a conversational user interface, allowing users to easily navigate an eCommerce website, search for products, and make purchases.
Hybridization Chain Reaction-Based Electrochemical Biosensors by Integrating the Advantages of Homogeneous Reaction and Heterogeneous Detection
Authors: Xia Ning , Cheng Jiayou , Tian Linxu , Zhang Shuo , Wang Yunqiu , Li Gang
Published: May 2023

The conventional hybridization chain reaction (HCR)-based electrochemical biosensors usually require the immobilization of probes on the electrode surface. This will limit the applications of biosensors due to the shortcomings of complex immobilization processes and low HCR efficiency. In this work, we proposed astrategy for the design of HCR-based electrochemical biosensors by integrating the advantages of homogeneous reaction and heterogeneous detection. Specifically, the targets triggered the autonomous cross-opening and hybridization oftwobiotin-labeled hairpin probes to form long-nicked dsDNA polymers. The HCR products with many biotin tags were then captured by a streptavidin-covered electrode, thus allowing for the attachment of streptavidin-conjugated signal reporters through streptavidin–biotin interactions. By employing DNA and microRNA-21 as the model targets and glucose oxidase as the signal reporter, the analytical performances of the HCR-based electrochemical biosensors were investigated. The detection limits of this method were found to be 0.6 fM and 1 fM for DNA and microRNA-21, respectively. The proposed strategy exhibited good reliability for target analysis in serum and cellular lysates. The strategy can be used to develop various HCR-based biosensors for a wide range of applications because sequence-specific oligonucleotides exhibit high binding affinity to a series of targets. In light of the high stability and commercial availability of streptavidin-modified materials, the strategy can be used for the design of different biosensors by changing the signal reporter and/or the sequence of hairpin probes.
Therapeutic Strategies to Ameliorate Neuronal Damage in Epilepsy by Regulating Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation
Authors: Madireddy Sahithi , Madireddy Samskruthi
Published: May 2023

Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development of new therapeutic strategies against epilepsy could be beneficial. Oxidative stress and mitochondrial dysfunction are frequently observed in epilepsy. Additionally, neuroinflammation is increasingly understood to contribute to the pathogenesis of epilepsy. Mitochondrial dysfunction is also recognized for its contributions to neuronal excitability and apoptosis, which can lead to neuronal loss in epilepsy. This review focuses on the roles of oxidative damage, mitochondrial dysfunction, NAPDH oxidase, the blood–brain barrier, excitotoxicity, and neuroinflammation in the development of epilepsy. We also review the therapies used to treat epilepsy and prevent seizures, including anti-seizure medications, anti-epileptic drugs, anti-inflammatory therapies, and antioxidant therapies. In addition, we review the use of neuromodulation and surgery in the treatment of epilepsy. Finally, we present the role of dietary and nutritional strategies in the management of epilepsy, including the ketogenic diet and the intake of vitamins, polyphenols, and flavonoids. By reviewing available interventions and research on the pathophysiology of epilepsy, this review points to areas of further development for therapies that can manage epilepsy.
IL-10/β-Endorphin-Mediated Neuroimmune Modulation on Microglia during Antinociception
Authors: Belo Thiago Caetano Andrade , Santos Gabriela Xavier , da Silva Bruno Eduardo Gabriel , Rocha Bruno Lopes Gonçalves , Abdala Dennis William , Freire Larissa Alves Moreira , Rocha Fernanda Santos , Galdino Giovane
Published: May 2023

Microglia are glial cells centrally related to pathophysiology and neuroimmunological regulation of pain through microglia–neuron crosstalk mechanisms. In contrast, anti-inflammatory mechanisms guided by immunological effectors such as IL-10 trigger the secretion of analgesic substances, culminating in the differential expression of genes encoding endogenous opioid peptides, especially β-endorphin. Thus, when β-endorphin binds to the µ-opioid receptor, it generates neuronal hyperpolarization, inhibiting nociceptive stimuli. This review aimed to summarize the recent advances in understanding the mechanism by which IL-10/β-endorphin can reduce pain. For this, databases were searched for articles from their inception up until November 2022. Two independent reviewers extracted the data and assessed the methodological quality of the included studies, and seventeen studies were considered eligible for this review. Several studies have demonstrated the impact of IL-10/β-endorphin in reducing pain, where IL-10 can stimulate GLP-1R, GRP40, and α7nAChR receptors, as well as intracellular signaling pathways, such as STAT3, resulting in increased β-endorphin expression and secretion. In addition, molecules such as gabapentinoids, thalidomide, cynandione A, morroniside, lemairamin, and cinobufagin, as well as non-pharmacological treatments such as electroacupuncture, reduce pain through IL-10 mediated mechanisms, reflecting a microglia-dependent β-endorphin differential increase. This process represents a cornerstone in pain neuroimmunology knowledge, and the results obtained by different studies about the theme are presented in this review.
Decision-Making and Risk-Propensity Changes during and after the COVID-19 Pandemic Lockdown
Authors: Zivi Pierpaolo , Sdoia Stefano , Alfonsi Valentina , Gorgoni Maurizio , Mari Emanuela , Quaglieri Alessandro , De Gennaro Luigi , Giannini Anna Maria , Ferlazzo Fabio
Published: May 2023

The imposition of lockdowns during the COVID-19 pandemic placed individuals under conditions of environmental stress, threatening individual and collective wellbeing. This study aimed to investigate the temporal effects of isolation and confinement during and after the Italian lockdown on decision-making, risk propensity, and cognitive control processes. The present study covered almost the entire Italian lockdown period (each week from the end of March to mid-May 2020), plus a follow-up measure (September 2020). At each time-point, respondents completed online behavioral tasks, which involved measuring risk-propensity (Balloon Analogue Risk Task), decision-making (Iowa Gambling Task), and cognitive flexibility (Category Switch Task). They also filled in questionnaires regarding subjective stress and anxiety. The main findings showed that the decision-making abilities of the respondents were affected as the confinement progressed. Furthermore, individuals who were more subjectively impacted by the lockdown/isolation experience exhibited impaired decision-making, especially during the lockdown. The results of the study highlight that prolonged confinement may affect human decision making, and help understand individuals’ misbehaviors during emergencies and develop effective countermeasures aimed at reducing the burden of the healthcare system.
The Role of Alexithymia and Impulsivity in Male Victims and Perpetrators of Intimate Partner Violence
Authors: Mannarini Stefania , Taccini Federica , Rossi Alessandro Alberto
Published: May 2023

(1) Background: Alexithymia and impulsivity appear to represent risk factors for violence perpetration, while mixed results are present with respect to victimization experience. In light of this, the purpose of this study was to compare the roles of both alexithymia and impulsivity among three different samples of men: men who experienced partner victimization (IPVV); male intimate partner violence perpetrators (IPVP); and men from the general population (CG). (2) Methods: Participants were recruited from specialized centers in Italy. A profile analysis was conducted. (3) Results: The results showed that IPVV presented alexithymia and impulsivity comparable to the CG. Furthermore, differences were found between victims and perpetrators in terms of impulsivity and alexithymia. The IPVP group had higher levels of both impulsivity and alexithymia in comparison to IPVV. Moreover, the perpetrators exhibited significantly higher levels of alexithymia compared to the CG. However, despite the medium Cohen’s d (d = 0.441) resulting from the analyses, IPVP’s level of impulsivity was not statistically different from the CG. (4) Conclusion: Alexithymia and impulsivity appear to play a key role in violent behaviors and should be the focus of psychological interventions with perpetrators.
Blinded by Attachment: Examining the Overconfidence Bias of Sports Fans’ Intertemporal Ticket Purchase Decisions
Authors: Jee Wonsok Frank , Hyun Moonsup
Published: May 2023

Optimally deciding on the best deal for sport event tickets requires the ability to evaluate risk and make informed decisions in uncertain environments. This study examines how individual trait factors, such as experience, expertise, and involvement, influence consumers’ decision-making process when purchasing tickets online for sporting events. To examine and test the study hypotheses, 640 respondents from a Qualtrics survey panel were recruited from geographically confined subjects of New York City sports fans over a ten-day data collection period. The research subjects were surveyed to assess their perception of the expected likelihood of obtaining event tickets at a lower rate (ELR) and the expected likelihood that tickets would remain available (ETA) as the event day approached. MANOVA showed that there was a significant effect of the time period on the participants’ ETA and ELR risk assessments [Λ = 0.954, F (18, 1262) = 1.653, p < 0.05]. The ETA was highest ten days before the event and lowest the day before the event, with a similar pattern observed for the ELR. The mediation path analysis showed that fan involvement had a strong positive correlation with confidence (B = 0.496, p < 0.001). Confidence, in turn, was a significant predictor of the ELR (B = 5.729, p < 0.05) but not for the ETA (B = 1.516, p = 0.504). The positive mediation of confidence between fan involvement and the ELR indicates that consumers with higher fan involvement tend to have overconfidence in their ability to evaluate the uncertain purchase environment, which ultimately impacts their risk perception and decision-making. The study highlights the importance of considering both temporal and psychological factors when assessing the likelihood of ticket purchases and provides behavioral insights for sports marketers and ticket distributors.
A Theoretical Framework for a Mathematical Cognitive Model for Adaptive Learning Systems
Authors: Sun Siyu , Wu Xiaopeng , Xu Tianshu
Published: May 2023

The emergence of artificial intelligence has made adaptive learning possible, but building an adaptive system requires a comprehensive understanding of students’ cognition. The cognitive model provides a crucial theoretical framework to explore students’ cognitive attributes, making it vital for learning assessment and adaptive learning. This study investigates 52 experts, including primary and secondary school teachers, mathematics education experts, and graduate students, based on the 16 cognitive attributes in the TIMSS 2015 assessment framework. Through an analysis of their attribute questionnaires, the Interpretive structural modeling (ISM) method is used to construct a five-level mathematical cognitive model. The model is then revised through oral reports and expert interviews, resulting in a final cognitive model ranging from “memorize” to “justify”. The cognitive model describes the relationship between different attributes in detail, enabling the development of adaptive systems and aiding in the diagnosis of students’ cognitive development and learning paths in mathematics.
P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation
Authors: Trias Isabel , Saco Adela , Marimon Lorena , López del Campo Ricardo , Manzotti Carolina , Ordi Oriol , del Pino Marta , Pérez Francisco M. , Vega Naiara , Alós Silvia , Martínez Antonio , Rodriguez-Carunchio Leonardo , Reig Oscar , Jares Pedro , Teixido Cristina , Ajami Tarek , Corral-Molina Juan Manuel , Algaba Ferran , Ribal María J. , Ribera-Cortada Inmaculada , Rakislova Natalia
Published: May 2023

p53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation.
The Role of the p16 and p53 Tumor Suppressor Proteins and Viral HPV16 E6 and E7 Oncoproteins in the Assessment of Survival in Patients with Head and Neck Cancers Associated with Human Papillomavirus Infections
Authors: Lifsics Andrejs , Cistjakovs Maksims , Sokolovska Liba , Deksnis Renars , Murovska Modra , Groma Valerija
Published: May 2023

The role of HPV in the survival prognosis of patients with head and neck squamous cell carcinoma, especially patients with laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC), is still somewhat ambiguous. The present study aimed to explore the significance of tumor suppressor proteins and HPV16 E6 and E7 oncoproteins in the assessment of survival in patients with oropharyngeal squamous cell carcinoma (OPSCC), LSCC, and HPSCC associated with high-risk (HR-) and low-risk (LR-) HPV infections. By utilizing molecular and immunohistochemical investigations of HNSCC samples and patient data, univariate and multivariate survival analyses were conducted. The presence of HPV DNA (LR- and HR-HPV) was associated with a better 5-year OS and DSS for OPSCC and LSCC. The IHC overexpression of HPV16 E6 protein and p16 protein was associated with better survival in the univariate (for OPSCC) and multivariate (OPSCC and HPSCC) survival analyses. The overexpression of p53 was associated with better survival in OPSCC. HPV infection plays a significant role in the tumorigenesis of HNSCC, and the immunohistochemical assessment of HPV16 E6 protein expression should be interpreted as a useful prognostic marker for OPSCC and HPSCC.
Hodgkin Lymphoma—The Spectrum from Diagnostics to Molecular Science, Movement and Current Treatment Approaches
Authors: Hartmann Sylvia
Published: May 2023

A total of fourteen papers on Hodgkin lymphoma (HL) are published within this Special Issue, including six reviews, seven original articles and one commentary [...]
The Role of Lumen Apposing Metal Stents in the Palliation of Distal Malignant Biliary Distal Obstruction
Authors: Voiosu Theodor Alexandru , Rimbaș Mihai , Larghi Alberto
Published: May 2023

Malignant biliary obstruction (DMBO) has been traditionally managed by endoscopic retrograde cholangiopancreatography (ERCP). In the case of ERC failure, percutaneous transhepatic biliary drainage (PT-BD) has been widely utilized as a salvage procedure. However, over the last decade, endoscopic ultrasound-guided biliary drainage (EUS-BD) has gained increasing popularity, especially after the advent of electrocautery-enhanced lumen apposing metal stent devices (EC-LAMSs) which enable a one-step procedure, granting prevention of biliary leakage and minimizing occurrence of adverse events (AEs). In parallel, increasing evidence suggests a possible role of EUS-BD in the management of DMBO as a primary palliative drainage modality. In the current paper, we aim to review all the available evidence on the role of EUS-BD performed with EC-LAMSs and discuss salient technical aspects of this type of procedure.
Factors Predictive of Primary Resistance to Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Huang Yiqing , Zhao Joseph J. , Soon Yu Yang , Kee Adrian , Tay Sen Hee , Aminkeng Folefac , Ang Yvonne , Wong Alvin S. C. , Bharwani Lavina D. , Goh Boon Cher , Soo Ross A.
Published: May 2023

Introduction: Primary resistance to immune checkpoint inhibitors (ICI) is observed in routine clinical practice. We sought to determine factors predictive of primary resistance to ICI monotherapy, defined by the Society for Immunotherapy of Cancer (SITC) as progression within 6 months of ICI treatment with patients receiving at least 6 weeks of ICI monotherapy, in patients with advanced non-small-cell lung cancer (NSCLC). Method: Patients with stage IV NSCLC treated with at least 6 weeks of single-agent ICI at two tertiary hospitals in Singapore were included. A multivariate logistic regression model was utilised to elucidate factors predictive of primary resistance to ICI. Results: Of the 108 eligible patients, 59 (54.6%) experienced primary resistance. The majority were male (65.7%), smokers (66.3%), Chinese (79.6%), had adenocarcinoma (76.9%), received Pembrolizumab (55.6%) and received immunotherapy treatment in the later line setting (≥2 lines) (61.1%). Female gender (aOR = 3.16, p = 0.041), a sixth-week neutrophil-to-lymphocyte ratio (NLR) of ≥3) (aOR = 3.454, p = 0.037) and a later line of immunotherapy treatment (≥2 lines) (aOR = 2.676, p = 0.040) were factors predictive of primary resistance to ICI monotherapy in patients with advanced NSCLC. Conclusions: Using SITC criteria, an elevated NLR (≥3) at 6 weeks, female gender and a later line of immunotherapy treatment (≥2 lines) were predictive factors of developing primary resistance to ICI monotherapy in patients with advanced NSCLC.
Targeting Hypoxia-Inducible Factor-1α for the Management of Hepatocellular Carcinoma
Authors: Huynh Kenneth N. , Rao Sriram , Roth Bradley , Bryan Theodore , Fernando Dayantha M. , Dayyani Farshid , Imagawa David , Abi-Jaoudeh Nadine
Published: May 2023

Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that regulates the cellular response to hypoxia and is upregulated in all types of solid tumor, leading to tumor angiogenesis, growth, and resistance to therapy. Hepatocellular carcinoma (HCC) is a highly vascular tumor, as well as a hypoxic tumor, due to the liver being a relatively hypoxic environment compared to other organs. Trans-arterial chemoembolization (TACE) and trans-arterial embolization (TAE) are locoregional therapies that are part of the treatment guidelines for HCC but can also exacerbate hypoxia in tumors, as seen with HIF-1α upregulation post-hepatic embolization. Hypoxia-activated prodrugs (HAPs) are a novel class of anticancer agent that are selectively activated under hypoxic conditions, potentially allowing for the targeted treatment of hypoxic HCC. Early studies targeting hypoxia show promising results; however, further research is needed to understand the effects of HAPs in combination with embolization in the treatment of HCC. This review aims to summarize current knowledge on the role of hypoxia and HIF-1α in HCC, as well as the potential of HAPs and liver-directed embolization.
Organ Abnormalities Caused by Turner Syndrome
Authors: Yoon Sang Hoon , Kim Ga Yeon , Choi Gyu Tae , Do Jeong Tae
Published: May 2023

Turner syndrome (TS), a genetic disorder due to incomplete dosage compensation of X-linked genes, affects multiple organ systems, leading to hypogonadotropic hypogonadism, short stature, cardiovascular and vascular abnormalities, liver disease, renal abnormalities, brain abnormalities, and skeletal problems. Patients with TS experience premature ovarian failure with a rapid decline in ovarian function caused by germ cell depletion, and pregnancies carry a high risk of adverse maternal and fetal outcomes. Aortic abnormalities, heart defects, obesity, hypertension, and liver abnormalities, such as steatosis, steatohepatitis, biliary involvement, liver cirrhosis, and nodular regenerative hyperplasia, are commonly observed in patients with TS. The SHOX gene plays a crucial role in short stature and abnormal skeletal phenotype in patients with TS. Abnormal structure formation of the ureter and kidney is also common in patients with TS, and a non-mosaic 45,X karyotype is significantly associated with horseshoe kidneys. TS also affects brain structure and function. In this review, we explore various phenotypic and disease manifestations of TS in different organs, including the reproductive system, cardiovascular system, liver, kidneys, brain, and skeletal system.
The RhoA-ROCK1/ROCK2 Pathway Exacerbates Inflammatory Signaling in Immortalized and Primary Microglia
Authors: Glotfelty Elliot J. , Tovar-y-Romo Luis B. , Hsueh Shih-Chang , Tweedie David , Li Yazhou , Harvey Brandon K. , Hoffer Barry J. , Karlsson Tobias E. , Olson Lars , Greig Nigel H.
Published: May 2023

Neuroinflammation is a unifying factor among all acute central nervous system (CNS) injuries and chronic neurodegenerative disorders. Here, we used immortalized microglial (IMG) cells and primary microglia (PMg) to understand the roles of the GTPase Ras homolog gene family member A (RhoA) and its downstream targets Rho-associated coiled-coil-containing protein kinases 1 and 2 (ROCK1 and ROCK2) in neuroinflammation. We used a pan-kinase inhibitor (Y27632) and a ROCK1- and ROCK2-specific inhibitor (RKI1447) to mitigate a lipopolysaccharide (LPS) challenge. In both the IMG cells and PMg, each drug significantly inhibited pro-inflammatory protein production detected in media (TNF-α, IL-6, KC/GRO, and IL-12p70). In the IMG cells, this resulted from the inhibition of NF-κB nuclear translocation and the blocking of neuroinflammatory gene transcription (iNOS, TNF-α, and IL-6). Additionally, we demonstrated the ability of both compounds to block the dephosphorylation and activation of cofilin. In the IMG cells, RhoA activation with Nogo-P4 or narciclasine (Narc) exacerbated the inflammatory response to the LPS challenge. We utilized a siRNA approach to differentiate ROCK1 and ROCK2 activity during the LPS challenges and showed that the blockade of both proteins may mediate the anti-inflammatory effects of Y27632 and RKI1447. Using previously published data, we show that genes in the RhoA/ROCK signaling cascade are highly upregulated in the neurodegenerative microglia (MGnD) from APP/PS-1 transgenic Alzheimer’s disease (AD) mice. In addition to illuminating the specific roles of RhoA/ROCK signaling in neuroinflammation, we demonstrate the utility of using IMG cells as a model for primary microglia in cellular studies.
Toll-like Receptor 4 Is Upregulated in Parkinson’s Disease Patients and Co-Localizes with pSer129αSyn: A Possible Link with the Pathology
Authors: Conte Carmela , Ingrassia Angela , Breve John , Bol John J. , Timmermans-Huisman Evelien , van Dam Anne-Marie , Beccari Tommaso , van de Berg Wilma D. J.
Published: May 2023

Growing evidence suggests a crucial role of neuroinflammation in the pathophysiology of Parkinson’s disease (PD). Neuroinflammation is linked to the accumulation and aggregation of a-synuclein (αSyn), the primary pathological hallmark of PD. Toll-like receptors 4 (TLR4) can have implications in the development and progression of the pathology. In this study, we analyzed the expression of TLR4 in the substantia nigra (SN) and medial temporal gyrus (GTM) of well-characterized PD patients and age-matched controls. We also assessed the co-localization of TLR4 with pSer129 αSyn. Using qPCR, we observed an upregulation of TLR4 expression in the SN and GTM in PD patients compared to controls, which was accompanied by a reduction in αSyn expression likely due to the depletion of dopaminergic (DA) cells. Additionally, using immunofluorescence and confocal microscopy, we observed TLR4-positive staining and co-localization with pSer129-αSyn in Lewy bodies of DA neurons in the SN, as well as in pyramidal neurons in the GTM of PD donors. Furthermore, we observed a co-localization of TLR4 and Iba-1 in glial cells of both SN and GTM. Our findings provide evidence for the increased expression of TLR4 in the PD brain and suggest that the interaction between TLR4 and pSer129-αSyn could play a role in mediating the neuroinflammatory response in PD.
Effect of Synthetic Approaches and Sintering Additives upon Physicochemical and Electrophysical Properties of Solid Solutions in the System (CeO2)1−x(Nd2O3)x for Fuel Cell Electrolytes
Authors: Kalinina Marina V. , Dyuskina Daria A. , Polyakova Irina G. , Mjakin Sergey V. , Kruchinina Irina Yu.
Published: May 2023

Finely dispersed (CeO2)1−x(Nd2O3)x (x = 0.05, 0.10, 0.15, 0.20, 0.25) powders are synthesized via liquid-phase techniques based on the co-precipitation of hydroxides and co-crystallization of nitrates. The prepared powders are used to obtain ceramic materials comprising fluorite-like solid solutions with the coherent scattering region (CSR) of about 88 nm (upon annealing at 1300 °C) and open porosity in the range of 1–15%. The effect of the synthesis procedure and sintering additives (SiO2, ZnO) on physicochemical and electrophysical properties of the resulting ceramics is studied. The prepared materials are found to possess a predominantly ionic type of electric conductivity with ion transfer numbers ti = 0.96–0.71 in the temperature range of 300–700 °C. The conductivity in solid solutions follows a vacancy mechanism with σ700 °C = 0.48 × 10−2 S/cm. Physicochemical properties (density, open porosity, type and mechanism of electrical conductivity) of the obtained ceramic materials make them promising as solid oxide electrolytes for medium temperature fuel cells.
Segregated by Wealth, Health, and Development: An Analysis of Pre-School Child Health in a Medium-Sized German City
Authors: Wagner Karoline , Wienke Andreas , Gröger Christine , Klusmann Jan-Henning , Führer Amand
Published: May 2023

The School Entry Examination (SEE) can be used to identify children with current health issues, developmental delays, and risk factors for later diseases. This study analyzes the health status of preschool children in a German city with considerable socio-economic differences among its quarters. We used secondary data from SEEs 2016–2019 from the entire city (8417 children), which we divided into quarters with low (LSEB), medium (MSEB), and high socioeconomic burden (HSEB). In HSEB quarters, 11.3% of children were overweight as opposed to 5.3% in LSEB quarters. In HSEB quarters, 17.2% of children had sub-par cognitive development in contrast to 1.5% in LSEB quarters. For overall sub-par development, LSEB quarters had a prevalence of 3.3%, whereas, in HSEB quarters, 35.8% of children received this result. Logistic regression was used to determine the influence of the city quarter on the outcome of overall sub-par development. Here, considerable disparities among HSEB and LSEB quarters remained after adjustment for parents’ employment status and education. Pre-school children in HSEB quarters showed a higher risk for later disease than children in LSEB quarters. The city quarter had an association with child health and development that should be considered in the formulation of interventions.
Preclinical Models and Promising Pharmacotherapeutic Strategies in Liver Fibrosis: An Update
Authors: Kolaric Tea Omanovic , Kuna Lucija , Covic Marina , Roguljic Hrvoje , Matic Anita , Sikora Renata , Hefer Marija , Petrovic Ana , Mihaljevic Vjera , Smolic Robert , Bilic-Curcic Ines , Vcev Aleksandar , Smolic Martina
Published: May 2023

Liver fibrosis represents one of the greatest challenges in medicine. The fact that it develops with the progression of numerous diseases with high prevalence (NAFLD, viral hepatitis, etc.) makes liver fibrosis an even greater global health problem. Accordingly, it has received much attention from numerous researchers who have developed various in vitro and in vivo models to better understand the mechanisms underlying fibrosis development. All these efforts led to the discovery of numerous agents with antifibrotic properties, with hepatic stellate cells and the extracellular matrix at the center of these pharmacotherapeutic strategies. This review focuses on the current data on numerous in vivo and in vitro models of liver fibrosis and on various pharmacotherapeutic targets in the treatment of liver fibrosis.
De Novo Design of Anti-COVID Drugs Using Machine Learning-Based Equivariant Diffusion Model Targeting the Spike Protein
Authors: Niranjan Vidya , Uttarkar Akshay , Ramakrishnan Ananya , Muralidharan Anagha , Shashidhara Abhay , Acharya Anushri , Tarani Avila , Kumar Jitendra
Published: May 2023

The drug discovery and research for an anti-COVID-19 drug has been ongoing despite repurposed drugs in the market. Over time, these drugs were discontinued due to side effects. The search for effective drugs is still under process. The role of Machine Learning (ML) is critical in the search for novel drug compounds. In the current work, using the equivariant diffusion model, we built novel compounds targeting the spike protein of SARS-CoV-2. Using the ML models, 196 de novo compounds were generated which had no hits on any major chemical databases. These novel compounds fulfilled all the criteria of ADMET properties to be lead-like and drug-like compounds. Of the 196 compounds, 15 were docked with high confidence in the target. These compounds were further subjected to molecular docking, the best compound having an IUPAC name of (4aS,4bR,8aS,8bS)-4a,8a-dimethylbiphenylene-1,4,5,8(4aH,4bH,8aH,8bH)-tetraone and a binding score of −6.930 kcal/mol. The principal compound is labeled as CoECG-M1. Density Function Theory (DFT) and Quantum optimization was carried out along with the study of ADMET properties. This suggests that the compound has potential drug-like properties. The docked complex was further subjected to MD simulations, GBSA, and metadynamics simulations to gain insights into the stability of binding. The model can be in the future modified to improve the positive docking rate.