bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex Organisms Must Deal with Complex Threats: How Does Amphibian Conservation Deal with Biphasic Life Cycles?
Authors: Nolan Nadine , Hayward Matthew W. , Klop-Toker Kaya , Mahony Michael , Lemckert Frank , Callen Alex
Published: May 2023

The unprecedented rate of global amphibian decline is attributed to The Anthropocene, with human actions triggering the Sixth Mass Extinction Event. Amphibians have suffered some of the most extreme declines, and their lack of response to conservation actions may reflect challenges faced by taxa that exhibit biphasic life histories. There is an urgent need to ensure that conservation measures are cost-effective and yield positive outcomes. Many conservation actions have failed to meet their intended goals of bolstering populations to ensure the persistence of species into the future. We suggest that past conservation efforts have not considered how different threats influence multiple life stages of amphibians, potentially leading to suboptimal outcomes for their conservation. Our review highlights the multitude of threats amphibians face at each life stage and the conservation actions used to mitigate these threats. We also draw attention to the paucity of studies that have employed multiple actions across more than one life stage. Conservation programs for biphasic amphibians, and the research that guides them, lack a multi-pronged approach to deal with multiple threats across the lifecycle. Conservation management programs must recognise the changing threat landscape for biphasic amphibians to reduce their notoriety as the most threatened vertebrate taxa globally.
How to Increase Cellular Glutathione
Authors: Giustarini Daniela , Milzani Aldo , Dalle-Donne Isabella , Rossi Ranieri
Published: May 2023

Glutathione (GSH) has special antioxidant properties due to its high intracellular concentration, ubiquity, and high reactivity towards electrophiles of the sulfhydryl group of its cysteine moiety. In most diseases where oxidative stress is thought to play a pathogenic role, GSH concentration is significantly reduced, making cells more susceptible to oxidative damage. Therefore, there is a growing interest in determining the best method(s) to increase cellular glutathione for both disease prevention and treatment. This review summarizes the major strategies for successfully increasing cellular GSH stores. These include GSH itself, its derivatives, NRf-2 activators, cysteine prodrugs, foods, and special diets. The possible mechanisms by which these molecules can act as GSH boosters, their related pharmacokinetic issues, and their advantages and disadvantages are discussed.
Customer Complaint Analysis via Review-Based Control Charts and Dynamic Importance–Performance Analysis
Authors: Kim Suah , Kwak Minjung
Published: May 2023

Review-based control charts that integrate sentiment analysis with traditional control charts are emerging as effective tools for analyzing customer complaints. However, existing approaches face significant challenges due to their lack of alignment with the natural characteristics of online reviews, such as limited review volumes or imbalanced mentions of attributes. To address these challenges, which are commonly encountered in real-world applications, this study proposes a novel framework for review-based complaint analysis that combines a bi-level control chart with dynamic importance–performance analysis. The proposed method converts unstructured reviews into a set of statistical control charts, analyzes how the average of and variation in attribute importance and performance change over time, and identifies whether the changes are a natural event, a temporal aberration, or a gradual trend. This allows for conducting apples-to-apples quality comparison among multiple attributes and establishing appropriate improvement strategies in real-time and proactive manners. To demonstrate the applicability and effectiveness of the method, an empirical case study using online hotel reviews is presented.
A High-Performance Computing Cluster for Distributed Deep Learning: A Practical Case of Weed Classification Using Convolutional Neural Network Models
Authors: López-Martínez Manuel , Díaz-Flórez Germán , Villagrana-Barraza Santiago , Solís-Sánchez Luis O. , Guerrero-Osuna Héctor A. , Soto-Zarazúa Genaro M. , Olvera-Olvera Carlos A.
Published: May 2023

One of the main concerns in precision agriculture (PA) is the growth of weeds within a crop field. Currently, to prevent the spread of weeds, automatic techniques and computational tools are used to help to identify, classify, and detect the different types of weeds found in agricultural fields. One of the technologies that can help us to process digital information gathered from the agricultural fields is high-performance computing (HPC); this technology has been adopted to carry out projects requiring extra processing and storage in order to execute tasks with a large computational cost. This paper shows the implementation of an HPC cluster (HPCC), in which image processing (IP) and analysis are executed using deep learning (DL) techniques, specifically, convolutional neural networks (CNNs) with the VGG16 and InceptionV3 models, to classify different weed species. The results show the great benefits of using high-performance computing clusters in PA, specifically for classifying images. To apply distributed computing within the HPCC, the Keras and Horovod frameworks were used to train the CNN models, obtaining the best time with the InceptionV3 model with a value of 37 min 55.193 s using six HPCC cores, obtaining an accuracy of 0.65 as a result.
Detection and Analysis of Ethereum Energy Smart Contracts
Authors: Lashkari Bahareh , Musilek Petr
Published: May 2023

As blockchain technology advances, so has the deployment of smart contracts on blockchain platforms, making it exceedingly challenging for users to explicitly identify application services. Unlike traditional contracts, smart contracts are not written in a natural language, making it difficult to determine their provenance. Automatic classification of smart contracts offers blockchain users keyword-based contract queries and a streamlined effective management of smart contracts. In addition, the advancement in smart contracts is accompanied by security challenges, which are generally caused by domain-specific security breaches in smart contract implementation. The development of secure and reliable smart contracts can be extremely challenging due to domain-specific vulnerabilities and constraints associated with various business logics. Accordingly, contract classification based on the application domain and the transaction context offers greater insight into the syntactic and semantic properties of that class. However, despite initial attempts at classifying Ethereum smart contracts, there has been no research on the identification of smart contracts deployed in transactive energy systems for energy exchange purposes. In this article, in response to the widely recognized prospects of blockchain-enabled smart contracts towards an economical and transparent energy sector, we propose a methodology for the detection and analysis of energy smart contracts. First, smart contracts are parsed by transforming code elements into vectors that encapsulate the semantic and syntactic characteristics of each term. This generates a corpus of annotated text as a balanced, representative collection of terms in energy contracts. The use of a domain corpus builder as an embedding layer to annotate energy smart contracts in conjunction with machine learning models results in a classification accuracy of 98.34%. Subsequently, a source code analysis scheme is applied to identified energy contracts to uncover patterns in code segment distribution, predominant adoption of certain functions, and recurring contracts across the Ethereum network.
The Effect of Blue Noise on the Optimization Ability of Hopfield Neural Network
Authors: Zhang Yu , Chen Bin , Li Lan , Xu Yaoqun , Wei Sifan , Wang Yu
Published: May 2023

Noise is ubiquitous in the real-world environment. At present, most scholars only include the stage of Gaussian white noise when applying noise in neural networks and regard white noise as a tool to optimize the network model, which is far from enough, because noise not only affects the optimization ability of the Hopfield neural network but can also better fit the needs of the actual use of the scene. Therefore, according to the problems in the existing research, a method is proposed to combine the neural network with colored noise according to the signal-to-noise ratio. Taking blue noise as an example, the anti-interference ability of the Hopfield neural network regarding colored noise is studied. The results show that for the Hopfield neural network driven by blue noise, by adjusting the neural network step size, excitation function and signal-to-noise ratio, it not only provides ideas for adding colored noise to the neural network but also enables the neural network model to have better optimization-seeking ability. The research results have some reference significance for improving the practical application of neural networks in noisy environments.
XFilter: An Extension of the Integrity Measurement Architecture Based on Fine-Grained Policies
Authors: Litchfield Alan , Du Weihua
Published: May 2023

The Integrity Measurement Architecture subsystem on the Linux platform is a critical security component in the kernel to ensure the integrity of the running system. However, the default Integrity Measurement Architecture policy mechanisms based on options such as file owner and FSMAGIC cannot achieve a file-level configuration. Although Integrity Measurement Architecture supports the Linux Security Module policy rules to be close to the goal of fine-grained configuration, it is not easy to be managed because the Linux Security Module was not originally designed for integrity measurement. Moreover, the Linux Security Module-based policy does not apply in some use cases considering the type of Mandatory Access Control tools chosen by users. This paper presents a new policy configuration option, named XFilter, that achieves a fine-grained policy configuration method. The XFilter includes two policy matching mechanisms, XLabel and XList, which share the same policy token created for XFilter exclusively. XLabel marks the files for measurement using a label in the file’s extended attribute (xattr). By contrast, XList stores the measurement information in a list of file paths. To simplify the deployment, an automatic configuration process is implemented for integrating into the package management system. The evaluation results suggest that both mechanisms satisfy the requirements of file-level IMA policy control and create a performance burden for system operation in the acceptable range. They also reveal a positive correlation between the increment of the system latency and the growth of the length of file paths list for the XList mechanism.
Free Vibration of Single-Walled Carbon Nanotubes Using Nonlocal Truncated Timoshenko-Ehrenfest Beam Theory
Authors: De Rosa Maria Anna , Lippiello Maria , Onorato Antonella , Elishakoff Isaac
Published: May 2023

Carbon nanotubes with their outstanding mechanical, physical and electrical properties have stimulated a significant amount of scientific and technological research due to their uniqueness compared to conventional materials. As a result, an extensive study on their mechanical properties has been conducted, and the static and dynamic behavior of single- walled and multi-walled carbon nanotubes has been examined using Euler-Bernoulli and Timoshenko beam models. The main objective of this paper is to study the free vibration behaviour of single-walled carbon nanotubes (SWCNT) using the nonlocal truncated Timoshenko beam theory. According to the Hamilton principle, the equation of motion of Timoshenko single-walled carbon nanotubes is calculated taking into account the truncated theory; and the general corresponding boundary conditions are derived. Finally, some numerical examples are performed to evaluate the effects of the nonlocal coefficient and the length of the nanotube. The obtained results are validated by comparing them with those found in the literature, and they show the accuracy and efficiency of the developed model. Particularly, the results demonstrate that the present formulation is highly efficient and capable of satisfactorily describing the behavior of nanobeams.
Air Pollutants and Their Impact on Chronic Diseases—A Retrospective Study in Bucharest, Romania
Authors: Mahler Beatrice , Băiceanu Dragoș , Panciu Traian Constantin , Florea Radu Marian , Iorga Ana Luiza , Gnat Marcin , German Cornelia Florina , Pârvu Simona , Paraschiv Dorel , Manea Daniela , Mihai Mihaela , Ibraim Elmira , Timar Bogdan , Mihălțan Florin Dumitru
Published: May 2023

Air pollution is a serious problem in Romania, with the country ranking 13th among the most polluted countries in Europe in the 2021 World Air Quality Report. Despite the recognized impact of pollutants on health, there has been a lack of large-scale studies conducted in Romania. This study investigated the impact of air pollutants on patients with chronic respiratory, cardiovascular, cerebrovascular, or metabolic diseases in Bucharest and its metropolitan area from 20 August 2018 to 1 June 2022. The daily limit values for particulate matter PM10 and PM2.5 were exceeded every month, especially during the cold season, with a decrease during the COVID-19 pandemic restrictions. A significant statistical correlation was found between the monthly average values of PM2.5 and PM10 and hospitalizations for respiratory and cardiovascular diseases. A 10 µg/m3 increase in monthly average values resulted in a 40–60% increase in admissions for each type of pathology, translating to more than 2000 admissions for each pathology for the study period. This study highlights the urgent need for national and local measures to ensure a cleaner environment and enhance public health in Romania according to international regulations.
A Hybrid Autoformer Network for Air Pollution Forecasting Based on External Factor Optimization
Authors: Pan Kai , Lu Jiang , Li Jiaren , Xu Zhenyi
Published: May 2023

Exposure to air pollution will pose a serious threat to human health. Accurate air pollution forecasting can help people to reduce exposure risks and promote environmental pollution control, and it is also an extremely important part of smart city management. However, the current deep-learning-based models for air pollution forecasting usually focus on prediction accuracy improvement without considering the model interpretability. These models usually fail to explain the complex relationships between prediction targets and external factors (e.g., ozone concentration (O3), wind speed, temperature variation, etc.) The relationships between variables in air pollution time series prediction problems are very complex, with intricate relationships between different types of variables, often with nonlinear multivariate dependencies. To address these problems mentioned above, we proposed a hybrid autoformer network with a genetic algorithm optimization to predict air pollution temporal variation as well as establish interpretable relationships between pollutants and external variables. Furthermore, an elite variable voting operator was designed to better filter out more important external factors such as elite variables, so as to perform a more refined search for elite variables. Moreover, we designed an archive storage operator to reduce the effect of neural network model initialization on the search for external variables. Finally, we conducted comprehensive experiments on the Ma’anshan air pollution dataset to verify the proposed model, where the prediction accuracy was improved by 2–8%, and the selection of model influencing factors was more interpretable.
Cochlear Aqueduct Morphology in Superior Canal Dehiscence Syndrome
Authors: Nagururu Nimesh V. , Jung Diane , Hui Ferdinand , Pearl Monica S. , Carey John P. , Ward Bryan K.
Published: May 2023

The cochlear aqueduct (CA) connects the scala tympani to the subarachnoid space and is thought to assist in pressure regulation of perilymph in normal ears, however, its role and variation in inner ear pathology, such as in superior canal dehiscence syndrome (SCDS), is unknown. This retrospective radiographic investigation compared CA measurements and classification, as measured on flat-panel computerized tomography, among three groups of ears: controls, n = 64; anatomic superior canal dehiscence without symptoms (SCD), n = 28; and SCDS, n = 64. We found that in a multinomial logistic regression adjusted for age, sex, and BMI, an increase in CA length by 1 mm was associated with a lower odds for being in the SCDS group vs. control (Odds ratio 0.760 p = 0.005). Hierarchical clustering of continuous CA measures revealed a cluster with small CAs and a cluster with large CAs. Another multinomial logistic regression adjusted for the aforementioned clinical covariates showed an odds ratio of 2.97 for SCDS in the small CA cluster as compared to the large (p = 0.004). Further, no significant association was observed between SCDS symptomatology—vestibular and/or auditory symptoms—and CA structure in SCDS ears. The findings of this study lend support to the hypothesis that SCDS has a congenital etiology.
Circulating Small RNA Profiling of Patients with Alveolar and Cystic Echinococcosis
Authors: Cucher Marcela A. , Mariconti Mara , Manciulli Tommaso , Vola Ambra , Rosenzvit Mara C. , Brehm Klaus , Kamenetzky Laura , Brunetti Enrico
Published: May 2023

Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers for several diseases. Here, we profiled the sRNA transcriptomes of AE and CE patients to identify novel biomarkers to aid in medical decisions when current diagnostic procedures are inconclusive. For this, endogenous and parasitic sRNAs were analyzed by sRNA sequencing in serum from disease negative, positive, and treated patients and patients harboring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE, and/or non-parasitic lesion were identified. Our results represent an in-depth characterization of the effect E. multilocularis and E. granulosus s. l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection.
Role of Complement in the Onset of Age-Related Macular Degeneration
Authors: Piri Niloofar , Kaplan Henry J.
Published: May 2023

Age-related macular degeneration (AMD) is a progressive degenerative disease of the central retina and the leading cause of severe loss of central vision in people over age 50. Patients gradually lose central visual acuity, compromising their ability to read, write, drive, and recognize faces, all of which greatly impact daily life activities. Quality of life is significantly affected in these patients, and there are worse levels of depression as a result. AMD is a complex, multifactorial disease in which age and genetics, as well as environmental factors, all play a role in its development and progression. The mechanism by which these risk factors interact and converge towards AMD are not fully understood, and therefore, drug discovery is challenging, with no successful therapeutic attempt to prevent the development of this disease. In this review, we describe the pathophysiology of AMD and review the role of complement, which is a major risk factor in the development of AMD.
Structural Changes, Biological Consequences, and Repurposing of Colchicine Site Ligands
Authors: Montecinos Felipe , Sackett Dan L.
Published: May 2023

Microtubule-targeting agents (MTAs) bind to one of several distinct sites in the tubulin dimer, the subunit of microtubules. The binding affinities of MTAs may vary by several orders of magnitude, even for MTAs that specifically bind to a particular site. The first drug binding site discovered in tubulin was the colchicine binding site (CBS), which has been known since the discovery of the tubulin protein. Although highly conserved throughout eukaryotic evolution, tubulins show diversity in their sequences between tubulin orthologs (inter-species sequence differences) and paralogs (intraspecies differences, such as tubulin isotypes). The CBS is promiscuous and binds to a broad range of structurally distinct molecules that can vary in size, shape, and affinity. This site remains a popular target for the development of new drugs to treat human diseases (including cancer) and parasitic infections in plants and animals. Despite the rich knowledge about the diversity of tubulin sequences and the structurally distinct molecules that bind to the CBS, a pattern has yet to be found to predict the affinity of new molecules that bind to the CBS. In this commentary, we briefly discuss the literature evidencing the coexistence of the varying binding affinities for drugs that bind to the CBS of tubulins from different species and within species. We also comment on the structural data that aim to explain the experimental differences observed in colchicine binding to the CBS of β-tubulin class VI (TUBB1) compared to other isotypes.
The Acute Radiation Syndrome-Mitigator Romiplostim and Secreted Extracellular Vesicles Improved Survival in Mice Acutely Exposed to Myelosuppressive Doses of Ionizing Radiation
Authors: Yamaguchi Masaru , Kashiwakura Ikuo
Published: May 2023

In cases of accidental high-dose total-body irradiation (TBI), acute radiation syndrome (ARS) can cause death. We reported that the thrombopoietin receptor agonist romiplostim (RP) has the potential to completely rescue mice exposed to lethal TBI. Extracellular vesicles (EVs) are involved in cell-to-cell communication, and the mechanism of RP action may be related to EVs that reflect the radio-mitigative information. We investigated the radio-mitigative effects of EVs on mice with severe ARS. C57BL/6 mice exposed to lethal TBI were treated with RP, and the EVs were isolated from the serum and intraperitoneally injected into other mice with severe ARS. The 30-day survival rate of lethal TBI mice drastically improved by 50–100% with the administration of EVs in the sera collected weekly from the mice in which radiation damage was alleviated and mortality was avoided by the administration of RP. Four responsive miRNAs, namely, miR-144-5p, miR-3620-5p, miR-6354, and miR-7686-5p showed significant expression changes in an array analysis. In particular, miR-144-5p was expressed only in the EVs of RP-treated TBI mice. Specific EVs may exist in the circulating blood of mice that escaped mortality with an ARS mitigator, and their membrane surface and endogenous molecules may be the key to the survival of mice with severe ARS.
Plant-Derived Extracellular Vesicles and Their Exciting Potential as the Future of Next-Generation Drug Delivery
Authors: Alzahrani Faisal A. , Khan Mohammad Imran , Kameli Nader , Alsahafi Elham , Riza Yasir Mohamed
Published: May 2023

Plant cells release tiny membranous vesicles called extracellular vesicles (EVs), which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. These plant-derived EVs (PDEVs) are safe and easily extractable and have been shown to have therapeutic effects against inflammation, cancer, bacteria, and aging. They have shown promise in preventing or treating colitis, cancer, alcoholic liver disease, and even COVID-19. PDEVs can also be used as natural carriers for small-molecule drugs and nucleic acids through various administration routes such as oral, transdermal, or injection. The unique advantages of PDEVs make them highly competitive in clinical applications and preventive healthcare products in the future. This review covers the latest methods for isolating and characterizing PDEVs, their applications in disease prevention and treatment, and their potential as a new drug carrier, with special attention to their commercial viability and toxicological profile, as the future of nanomedicine therapeutics. This review champions the formation of a new task force specializing in PDEVs to address a global need for rigor and standardization in PDEV research.
Proportional Reasoning Deficit in Dyslexia
Authors: Cappagli Giulia , Carzola Beatrice , Potente Cristina , Gori Monica
Published: May 2023

Dyslexia has been linked to an altered perception of metrical structures in language, but no study to date has explored the link between reading impairments and other forms of metrical thinking (e.g., proportional reasoning). In the present study, we assessed proportional reasoning in 16 dyslexic children and 16 age-matched controls from 7 to 10 years of age in order to investigate whether dyslexia might be also linked to an altered form of metrical thinking. We found that dyslexic children are less accurate in performing judgments about proportionality compared to typical peers and that reading accuracy correlates with proportional reasoning abilities for 7–8-year-old children. Overall, these findings suggest that a link exists between reading and proportional reasoning abilities. We might speculate that fostering reasoning based on the meter can facilitate reading because it permits the segmentation of words in syllables and that dyslexia can be identified early with alternative non-reading tasks such as the proportional reasoning task used in this work.
The Effect of Diagonal Exercise Training for Neurorehabilitation on Functional Activity in Stroke Patients: A Pilot Study
Authors: Lee Jung-Ho , Kim Eun-Ja
Published: May 2023

Functional movements of the human body occur multifacetedly. This pilot study investigated the effects of neurorehabilitation training, including diagonal movements, balance, gait, fall efficacy, and activities of daily living in stroke patients. Twenty-eight patients diagnosed with stroke by a specialist were divided into experimental groups applying diagonal exercise training and control groups applying sagittal exercise training. The five times sit-to-stand test (FTSST), timed up and go (TUG) test, and Berg balance scale (BBS) were used to evaluate balance ability, the falls efficacy scale (FES) was used to evaluate fall efficacy, and the modified Barthel index (MBI) was used to evaluate activities of daily living. All evaluations were conducted once prior to intervention implementation and again six weeks after the final intervention. In the study results, the experimental group to which the diagonal exercise training was applied had statistically significant changes in FTSST, BBS, and FES compared to the control group. In conclusion, the rehabilitation program, including diagonal exercise training, increased the patient’s balance and reduced the fear of falling.
The Relationship between Handgrip Strength, Timed Up-and-Go, and Mild Cognitive Impairment in Older People during COVID-19 Pandemic Restrictions
Authors: Griffiths Jiranan , Seesen Mathuramat , Sirikul Wachiranun , Siviroj Penprapa
Published: May 2023

The COVID-19 lockdown restrictions affected physical performance and cognitive function in older people as they were confined to their homes. There is an association between physical and cognitive functions. Mild Cognitive Impairment (MCI) is a condition that risks progressing to dementia. This study aimed to identify the relationship between handgrip strength (HGS), Timed Up-and-Go (TUG), and MCI in older people during the COVID-19 pandemic restrictions. The cross-sectional study recruited 464 eligible participants for an interview and anthropometric measurement. The Montreal Cognitive Assessment-Basic (MoCA-B), HGS, and TUG were measured in addition to demographic and health characteristics. A total of 398 participants (85.8%) were found to have MCI when screened with the MoCA-B. Their mean age was 71.09 ± 5.81 years. Forward multiple regression analysis demonstrated that HGS (β = 0.032, p < 0.001), education level (β = 2.801, p < 0.001), TUG (β = −0.022, p = 0.013), Thai Geriatric Depression Score, TGDS (β = −0.248, p = 0.011), and age (β = −1.677, p = 0.019) were associated with MCI. A decrease in HGS and an increased TUG might allow for the early detection of MCI and promote physical training in order to reduce the risk of MCI. Further studies can investigate multidomain indicators for MCI, for example, fine motor skills and pinch strength as components of the motor abilities.
Mechanical Behavior of Crimping Composite Post Insulator: Experimental and Simulation Study
Authors: Xiao Jin , Zhang Yanhong , Xing Yichuan , Jiao Yangyang , Zhang Lihong
Published: May 2023

The composite post insulator composed of a large diameter mandrel and flange pressed by a one-time integral pultrusion has high strength and good toughness and is widely used in the existing flexible converter valve. For constructing the finite element model of the crimped post insulator, most of the flange surface and the mandrel surface are directly connected, making the simulation model’s stiffness deviate from the actual model and the model distortion. Based on this, this study proposes a new finite element simplified model of crimped composite post insulator based on multi-point constraints (MPC), which accurately simulates the crimping area of mandrel and flange in engineering practice. It verifies the model’s reliability through static tests and characteristic vibration tests. The results show that the difference between the finite element simulation and the test results is within 5%. The finite element modeling method based on MPC local constraints is very reliable in applying crimped composite post insulators. Based on the proposed model, the influence of flange height and thickness on the mechanical properties of composite post insulators is further explored. The results show that the influence of flange height on mechanical properties can be ignored when the height of the insulator stiffener (non-press common area) is constant. Within the allowable thickness range of the flange crimping process, the increase in flange thickness will significantly reduce the maximum bending stress of the insulator and increase its safety margin. It provides a good design idea for the design of crimping composite insulators.
Experimental Study on the Coefficient of Earth Pressure at Rest for Sand
Authors: Li Libing , Dai Zhiyu , Liu Ruiming , Jian Fuxian
Published: May 2023

The coefficient of earth pressure at rest K0 is a state soil variable correlated with relative density Dr. As previously conducted K0 tests could not guarantee zero lateral deformation in the sand specimens, significant errors occurred in the test results. In this paper, a centrifugal model test method is used to study the K0 of sand with varying densities. The sand specimens with varying relative densities are prepared by sand pluviation, and a 50 g-ton centrifugal force is applied. Subsequently, the relationship of K0 and Dr with different densities is analyzed. The test results show that for the same type of sand, the value of K0 gradually increased with Dr. Based on the meso-evolution characteristics of sand particle recombination, various relationships between K0, the displacement deflection angle, and the friction offset angle between particles are analyzed. Furthermore, the relationship between particle volume fraction and K0 is derived, the assumption of increasing the coefficient K0 with the increase in Dr is verified, and the effect of Dr of sand on the force transfer behavior of the internal particle fabric is briefly discussed. The research results could significantly improve the current earth pressure theories.
Positive Mental Health Scale (PMHS) in Parents of Children with Cancer: A Psychometric Evaluation Using Item Response Theory
Authors: Toledano-Toledano Filiberto , Jiménez Said , Moral de la Rubia José , Merino-Soto Cesar , Rivera-Rivera Leonor
Published: May 2023

Mental health is currently a public health issue worldwide. However, evidence is lacking regarding the validity of the instruments used to measure and assess positive mental health in specific populations. The objective of this study was to evaluate the psychometric properties of the PMHS using IRT. A cross-sectional retrospective study with non-probabilistic convenience sampling was conducted with 623 parents of children undergoing cancer treatment at the National Institute of Health in Mexico City. The participants responded to a battery of tests, including a sociodemographic questionnaire, the PMHS, Measurement Scale of Resilience, Beck Depression Inventory, Inventory of Quality of Life, Beck Anxiety Inventory, an interview regarding caregiver burden, and the World Health Organization Well-Being Index. PMHS responses were analyzed using Samejima’s graded response model. The PMHS findings indicated that the IRT-based graded response model validated the single latent trait model. The scale scores were independent of depression, anxiety, well-being, caregiver burden, quality of life, and resilience. The PMHS scores were associated with low subjective well-being. The PMHS findings reveal that from an IRT-based perspective, this scale is unidimensional and is a valid, reliable, and culturally relevant instrument for assessing positive mental health in parents of children with chronic diseases.
Principles of Molecular Utility for CMS Classification in Colorectal Cancer Management
Authors: Rejali Leili , Seifollahi Asl Romina , Sanjabi Fatemeh , Fatemi Nayeralsadat , Asadzadeh Aghdaei Hamid , Saeedi Niasar Mahsa , Ketabi Moghadam Pardis , Nazemalhosseini Mojarad Ehsan , Mini Enrico , Nobili Stefania
Published: May 2023

Colorectal cancer (CRC) is the second cause of cancer-related deaths in both sexes globally and presents different clinical outcomes that are described by a range of genomic and epigenomic alterations. Despite the advancements in CRC screening plans and treatment strategies, the prognosis of CRC is dismal. In the last two decades, molecular biomarkers predictive of prognosis have been identified in CRC, although biomarkers predictive of treatment response are only available for specific biological drugs used in stage IV CRC. Translational clinical trials mainly based on “omic” strategies allowed a better understanding of the biological heterogeneity of CRCs. These studies were able to classify CRCs into subtypes mainly related to prognosis, recurrence risk, and, to some extent, also to treatment response. Accordingly, the comprehensive molecular characterizations of CRCs, including The Cancer Genome Atlas (TCGA) and consensus molecular subtype (CMS) classifications, were presented to improve the comprehension of the genomic and epigenomic landscapes of CRCs for a better patient management. The CMS classification obtained by the CRC subtyping consortium categorizes CRC into four consensus molecular subtypes (CMS1–4) characterized by different prognoses. In this review, we discussed the CMS classification in different settings with a focus on its relationships with precursor lesions, tumor immunophenotype, and gut microbiota, as well as on its role in predicting prognosis and/or response to pharmacological treatments, as a crucial step towards precision medicine.
Androgen Receptor Is Expressed in the Majority of Breast Cancer Brain Metastases and Is Subtype-Dependent
Authors: Fan Kevin Yijun , Chehade Rania , Qazi Maleeha , Moravan Veronika , Nofech-Mozes Sharon , Jerzak Katarzyna J.
Published: May 2023

We aimed to evaluate the expression of the “targetable” androgen receptor (AR) in breast cancer brain metastases (BrM). An established, retrospective 57-patient cohort with metastatic breast cancer who underwent surgery for BrM at the Sunnybrook Odette Cancer Centre between 1999–2013 was studied. AR expression in BrM samples was assessed in triplicate using immunohistochemistry (IHC). AR positive status was defined as nuclear AR expression ≥ 10% by IHC using the SP107 antibody. The median age of patients was 52 years (range 32–85 years). 28 (49%) of BrM were HER2+, 17 (30%) were hormone receptor positive (HR+)/HER2−, and 12 (21%) were triple negative breast cancers (TNBCs). 56% (n = 32/57) of BrM were AR positive, and median AR expression was 20% (CI 1.6–38.3%). AR expression was different across breast cancer subtypes; AR was most frequently expressed in HER2+ (n = 21/28), followed by HR+/HER2− (n = 9/17), and lowest in TNBC (n = 2/12) BrM (p = 0.003). Patients with AR positive versus AR negative BrM had similar overall survival (12.5 vs. 7.9 months, p = 0.6), brain-specific progression-free survival (8.0 vs. 5.1 months, p = 0.95), and time from breast cancer diagnosis to BrM diagnosis (51 vs. 29 months, p = 0.16). AR is expressed in the majority of breast cancer BrM and represents a potential therapeutic target.
Novel Drugs and Radiotherapy in Relapsed Lymphomas: Abscopal Response and Beyond
Authors: Perrone Salvatore , Lopedote Paolo , De Sanctis Vitaliana , Iamundo De Cumis Ilenia , Pulsoni Alessandro , Strati Paolo
Published: May 2023

Combined modality has represented a mainstay of treatment across many lymphoma histologies, given their sensitivity to both multi-agent chemotherapy and intermediate-dose radiotherapy. More recently, several new agents, including immunotherapies, have reshaped the therapeutic panorama of some lymphomas. In parallel, radiotherapy techniques have witnessed substantial improvement, accompanied by a growing understanding that radiation itself comes with an immune-mediated effect. Six decades after a metastatic lesion regression outside the irradiated field was first described, there is increasing evidence that a combination of radiotherapy and immunotherapy could boost an abscopal effect. This review focuses on the mechanisms underlying this interaction in the setting of lymphomas, and on the results of pivotal prospective studies. Furthermore, the available evidence on the concomitant use of radiotherapy and small molecules (i.e., lenalidomide, venetoclax, and ibrutinib), as well as brentuximab vedotin, and chimeric antigen receptor (CAR) T-cell therapy, is summarized. Currently, combining radiotherapy with new agents in patients who are affected by lymphomas appears feasible, particularly as a bridge to anti-CD19 autologous CAR T-cell infusion. However, more studies are required to assess these combinations, and preliminary data suggest only a synergistic rather than a curative effect.
Comparison of the Survival Outcomes of Minimally Invasive Surgery with Open Surgery in Patients with Uterine-Confined and Node-Negative Cervical Cancer: A Population-Based Study
Authors: Mabuchi Seiji , Sasano Tomoyuki , Komura Naoko , Maeda Michihide , Matsuzaki Shinya , Hisa Tsuyoshi , Kamiura Shoji , Morishima Toshitaka , Miyashiro Isao
Published: May 2023

We aimed to compare the oncological outcomes between Japanese women with uterine-confined and node-negative cervical cancer who underwent open surgery and those who underwent minimally invasive surgery (MIS). A population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry that ranged from 2011 to 2018. A total of 2279 patients who underwent surgical treatment for uterine-confined and node-negative cervical cancer were identified. The patients were classified into groups according to surgery type (open and MIS groups) and year of diagnosis (group one, 2011–2014; group two, 2015–2018). The oncologic outcomes were compared between the MIS and open groups. When the MIS group (n = 225) was compared with open group (n = 2054), overall, there was no significant between-group difference in terms of overall survival. Based on Kaplan–Meier estimates, the probability of overall survival at four years was 99.5% in the MIS group and 97.2% in the open group (p = 0.1110). When examined according to the year of diagnosis, there were no significant between-group differences in the overall survival in both groups one and two. In this population-based cohort study, MIS did not compromise survival outcomes when compared with conventional open surgery in Japanese patients with uterine-confined and node-negative (FIGO 2018 stage I) cervical cancer.
Inhibitory Potential of Resveratrol in Cancer Metastasis: From Biology to Therapy
Authors: Song Baohong , Wang Wei , Tang Xuemei , Goh Robby Miguel Wen-Jing , Thuya Win Lwin , Ho Paul Chi Lui , Chen Lu , Wang Lingzhi
Published: May 2023

Cancer metastasis is a significant challenge in cancer treatment, and most existing drugs are designed to inhibit tumor growth but are often ineffective in treating metastatic cancer, which is the leading cause of cancer-related deaths. Resveratrol, a polyphenol found in grapes, berries, and peanuts, has shown potential in preclinical studies as an anticancer agent to suppress metastasis. However, despite positive results in preclinical studies, little progress has been made in clinical trials. To develop resveratrol as an effective anticancer agent, it is crucial to understand its cellular processes and signaling pathways in tumor metastasis. This review article evaluates the current state and future development strategies of resveratrol to enhance its potency against cancer metastasis within its therapeutic dose. In addition, we critically evaluate the animal models used in preclinical studies for cancer metastasis and discuss novel techniques to accelerate the translation of resveratrol from bench to bedside. The appropriate selection of animal models is vital in determining whether resveratrol can be further developed as an antimetastatic drug in cancer therapy.
Perifocal Zone of Brain Gliomas: Application of Diffusion Kurtosis and Perfusion MRI Values for Tumor Invasion Border Determination
Authors: Zakharova Natalia E. , Batalov Artem I. , Pogosbekian Eduard L. , Chekhonin Ivan V. , Goryaynov Sergey A. , Bykanov Andrey E. , Tyurina Anastasia N. , Galstyan Suzanna A. , Nikitin Pavel V. , Fadeeva Lyudmila M. , Usachev Dmitry Yu. , Pronin Igor N.
Published: May 2023

(1) Purpose: To determine the borders of malignant gliomas with diffusion kurtosis and perfusion MRI biomarkers. (2) Methods: In 50 high-grade glioma patients, diffusion kurtosis and pseudo-continuous arterial spin labeling (pCASL) cerebral blood flow (CBF) values were determined in contrast-enhancing area, in perifocal infiltrative edema zone, in the normal-appearing peritumoral white matter of the affected cerebral hemisphere, and in the unaffected contralateral hemisphere. Neuronavigation-guided biopsy was performed from all affected hemisphere regions. (3) Results: We showed significant differences between the DKI values in normal-appearing peritumoral white matter and unaffected contralateral hemisphere white matter. We also established significant (p < 0.05) correlations of DKI with Ki-67 labeling index and Bcl-2 expression activity in highly perfused enhancing tumor core and in perifocal infiltrative edema zone. CBF correlated with Ki-67 LI in highly perfused enhancing tumor core. One hundred percent of perifocal infiltrative edema tissue samples contained tumor cells. All glioblastoma samples expressed CD133. In the glioblastoma group, several normal-appearing white matter specimens were infiltrated by tumor cells and expressed CD133. (4) Conclusions: DKI parameters reveal changes in brain microstructure invisible on conventional MRI, e.g., possible infiltration of normal-appearing peritumoral white matter by glioma cells. Our results may be useful for plotting individual tumor invasion maps for brain glioma surgery or radiotherapy planning.
Graft-Versus-Host Disease Prophylaxis with Antithymocyte Globulin in Patients Receiving Stem Cell Transplantation from Unrelated Donors: An Observational Retrospective Single-Center Study
Authors: Lo Schirico Mariella , Passera Roberto , Gill Jessica , Dellacasa Chiara , Dogliotti Irene , Giaccone Luisa , Zompi Sofia , Busca Alessandro
Published: May 2023

Graft-versus-host disease (GVHD) is one of the most important complications of allogeneic hematopoietic stem cell transplantation. Rabbit antilymphocyte serum (ATG/ATLG) is recommended for GVHD prophylaxis, while its appropriate dosing is debated. We performed a retrospective single-center study to examine the outcome of patients receiving ATG at the dose of 5 mg/kg as GVHD prophylaxis for unrelated donor (URD) HSCT. We collected data from all consecutive adult patients with hematological malignancies who had undergone allogeneic HSCT from URDs at the Stem Cell Transplant Center of the Città della Salute e della Scienza Hospital of Torino between July 2008 and July 2021. The primary aim was to ascertain the cumulative incidence (CI) for acute GVHD (aGVHD) and chronic GVHD (cGVHD); the secondary aim was to ascertain the CI for NRM (Non-Relapse Mortality) and RI (Relapse Incidence), as well the overall survival (OS) and infection incidence within 30 days of transplantation. We included in the analysis 226 patients who collectively underwent 231 HSCTs. The CI of grade II–IV aGVHD was found to be 29.9%, while that of moderate to severe cGVHD was 29.8%. The CI of NRM recorded at 1, 2, and 3 years after transplant was 18.2%, 19.6%, and 20.2%, respectively. The CI of RI at 1, 2, and 3 years from transplant was recorded to be 17.8%, 21.0%, and 21.6%, respectively. The median follow-up was 56 months, while the median OS for the whole cohort was not established; the OS at 1, 3, and 5 years from transplant was 69.6%, 59.3%, and 57.2%, respectively. We registered 88 bacteremias in 82/231 patients (35.5%), while invasive fungal infections occurred in 12/231 patients (5.2%). Our study suggests that the use of ATG at 5 mg/kg is highly effective in limiting the occurrence of both aGVHD and cGVHD, ensuring a low NRM, RI, and infection incidence.
Viability Analysis and High-Content Live-Cell Imaging for Drug Testing in Prostate Cancer Xenograft-Derived Organoids
Authors: Van Hemelryk Annelies , Erkens-Schulze Sigrun , Lim Lifani , de Ridder Corrina M. A. , Stuurman Debra C. , Jenster Guido W. , van Royen Martin E. , van Weerden Wytske M.
Published: May 2023

Tumor organoids have been pushed forward as advanced model systems for in vitro oncology drug testing, with the eventual goal to direct personalized cancer treatments. However, drug testing efforts suffer from a large variation in experimental conditions for organoid culturing and organoid treatment. Moreover, most drug tests are restricted to whole-well viability as the sole read-out, thereby losing important information about key biological aspects that might be impacted due to the use of administered drugs. These bulk read-outs also discard potential inter-organoid heterogeneity in drug responses. To tackle these issues, we developed a systematic approach for processing organoids from prostate cancer (PCa) patient-derived xenografts (PDXs) for viability-based drug testing and identified essential conditions and quality checks for consistent results. In addition, we generated an imaging-based drug testing procedure using high-content fluorescence microscopy in living PCa organoids to detect various modalities of cell death. Individual organoids and cell nuclei in organoids were segmented and quantified using a dye combination of Hoechst 33342, propidium iodide and Caspase 3/7 Green, allowing the identification of cytostatic and cytotoxic treatment effects. Our procedures provide important insights into the mechanistic actions of tested drugs. Moreover, these methods can be adapted for tumor organoids originating from other cancer types to increase organoid-based drug test validity, and ultimately, accelerate clinical implementation.