bluuebunny/crossref_metadata_2025 huggingface dataset:
Discrete Element Study on the Mechanical Response of Soft Rock Considering Water-Induced Softening Effect
Authors: Liu Chi , Liu Xiaoli , Peng Haoyang , Wang Enzhi , Wang Sijing
Published: May 2024

Soft rocks are prone to softening upon contact with water, and their rapid deterioration in mechanical properties is a significant cause of instability and failure soft rock masses. Besides, the macroscopic mechanical response of rocks is closely related to the mineral composition and microstructure. The purpose of this research is to consider the heterogeneity factors and softening effects, and systematically investigate the influence of confining pressure and softening time on the damage and failure characteristics of soft rocks. The Voronoi polygons generated using a built-in Voronoi diagram algorithm and contact elements (the substances with cementing capacity) of UDEC discrete element method are employed to represent the clastic grains and interfacial cemented bonding (ICB) structures in soft rock. Based on the Voronoi probabilistic method, the grain-based discrete element model (GB-DEM) considering the softening effect is established by introducing a meso-scale softening damage factor, along with a detailed calibration method for meso-scale parameters. The damage parameters such as the crack initiation threshold, the crack damage threshold, the damage degree, and the tensile and shear crack ratio are then analyzed. The study results indicate that the simulated strengths of the heterogeneous models under different water immersion time are in good agreement with the experimental results. The thresholds for crack initiation and damage, the proportions of tensile and shear cracks, and the degree of damage are positively correlated with the confining pressure. The attenuation patterns of the crack initiation threshold and damage threshold in the heterogeneous models with water immersion time are highly consistent with the meso-scale softening damage factor. The damage parameters show a trend of increasing first and then decreasing with the extension of water immersion time. The cement–cement contact elements are the main locations for crack initiation and propagation. The research outcomes have significant theoretical and practical implications for understanding and predicting the mechanical behavior of soft rocks under a water–rock interaction.
Cardiorespiratory Response to Workload Volume and Ergonomic Risk: Automotive Assembly Line Operators’ Adaptations
Authors: Furk Dania , Silva Luís , Dias Mariana , Fujão Carlos , Probst Phillip , Liu Hui , Gamboa Hugo
Published: May 2024

Repetitive tasks can lead to long-term cardiovascular problems due to continuous strain and inadequate recovery. The automobile operators on the assembly line are exposed to these risks when workload volume changes according to the workstation type. However, the current ergonomic assessments focus primarily on observational and, in some cases, biomechanical methods that are subjective and time-consuming, overlooking cardiorespiratory adaptations. This study aimed to analyze the cardiorespiratory response to distinct workload volumes and ergonomic risk (ER) scores for an automotive assembly line. Sixteen male operators (age = 38 ± 8 years; BMI = 25 ± 3 kg·m2) volunteered from three workstations (H1, H2, and H3) with specific work cycle duration (1, 3, and 5 min respectively). Electrocardiogram (ECG), respiratory inductance plethysmography (RIP), and accelerometer (ACC) data were collected during their shift. The results showed significant differences from the first to the last 10 min, where H3 had its SDRRi reduced (p = 0.014), H1’s phase synchrony and H2’s coordination between thoracic and abdominal movements decreased (p < 0.001, p = 0.039). In terms of ergonomic risk, the moderate-high rank showed a reduction in SDRRi (p = 0.037) and moderate-risk activities had diminished phase synchrony (p = 0.018) and correlation (p = 0.004). Thus, the explored parameters could have the potential to develop personalized workplace adaptation and risk assessment systems.
Hemp Flour as a Functional Ingredient for the Partial Replacement of Nitrites in a Minced Meat Model: Effect on Nutrient Composition, Antioxidant Profile and Sensory Characteristics
Authors: Papatzimos Georgios , Mitlianga Paraskevi , Basdagianni Zoitsa , Kasapidou Eleni
Published: May 2024

Consumers are becoming increasingly concerned about synthetic preservatives like nitrites in meat, prompting the meat industry to explore alternatives in order to lower nitrite levels. This study investigated the effects of incorporating hemp flour on the chemical and shelf-life characteristics of minced meat products with reduced nitrite content. Three types of products were prepared: HF0 (control) (0% hemp flour, 30 mg/kg NaNO2), HF4 (4% hemp flour, 15 mg/kg NaNO2), and HF6 (6% hemp flour, 15 mg/kg NaNO2). Analyses were conducted on proximate composition, fatty acid composition, antioxidant properties, lipid oxidation, colour, texture, and sensory characteristics. The addition of hemp flour at 6% reduced moisture content and influenced ash and sodium chloride levels in minced meat products. Despite the favorable fatty acid profile of hemp flour, its inclusion did not significantly alter the composition of the products. However, it did lead to significantly lower levels of lipid oxidation and modified the antioxidant capacity. Colour attributes were affected, with a higher hemp flour content resulting in colour deterioration. Cooking loss increased with a higher hemp flour content, and the minced meat products were significantly harder. Visual and olfactory sensory evaluation indicated that there were no significant differences in most traits, suggesting consumer acceptance of hemp-flour-enriched minced meat products. Overall, this study highlights the potential of hemp as a functional ingredient in minced meat products, also exhibiting the ability to reduce lipid oxidation.
Geological Conditions Evaluation of Coalbed Methane of Dacun Block in the Guxu Mining Area, Southern Sichuan Coalfield
Authors: Zhu Xushuang , Zhang Zheng , Wu Yonggui , Long Zhengjiang , Lai Xiaodong
Published: May 2024

The geological conditions evaluation of coalbed methane (CBM) is of great significance to CBM exploration and development. The CBM resources in the Southern Sichuan Coalfield (SSC) of China are very abundant; however, the CBM investigation works in this area are only just beginning, and the basic geological research of CBM is seriously inadequate, restricting CBM exploration and development. Therefore, in this study, a representative CBM block (Dacun) in the SSC was selected, and the CBM geological conditions were evaluated based on field injection/fall-off well testing, gas content and composition measurements, and a series of laboratory experiments. The results show that the CH4 concentrations of coal seams in the Dacun Block, overall, take on an increasing trend as the depth increases, and the CH4 weathering zone depth is 310 m. Due to the coupled control of temperature and formation pressure, the gas content shows a “increase→decrease” trend as the depth increases, and the critical depth is around 700 m. The CBM is enriched in the hinge zone of the Dacun syncline. The moisture content shows a negative correlation with CBM gas content. The porosities of coal seams vary from 4.20% to 5.41% and increase with the Ro,max. The permeabilities of coal seams show a strong heterogeneity with values ranging from 0.001mD to 2.85 mD and present a decreasing trend with the increase in depth. Moreover, a negative relationship exists between coal permeability and minimum horizontal stress magnitude. The reservoir pressure coefficients are between 0.51 and 1.26 and show a fluctuation change trend (increase→decrease→increase) as the depth increases, reflecting that three sets of independent superposed gas-bearing systems possibly exist vertically in the Longtan Formation of the study area. The Langmuir volumes (VL) of coals range from 22.67 to 36.84 m3/t, indicating the coals have strong adsorptivity. The VL presents a parabolic change of first increasing and then decreasing with the increase in depth, and the turning depth is around 700 m, consistent with the critical depth of gas content. The gas saturations of coal seams are, overall, low, with values varying from 29.10% to 116.48% (avg. 68.45%). Both gas content and reservoir pressure show a positive correlation with gas saturation. The CBM development in the Dacun Block needs a large depressurization of reservoir pressure due to the low ratio (avg. 0.37) of critical desorption pressure to reservoir pressure.
Constituents from Ageratina pichinchensis and Their Inhibitory Effect on Nitric Oxide Production
Authors: Sánchez-Ramos Mariana , Guerrero-Alonso Araceli , Romero-Estrada Antonio , González-Christen Judith , Alvarez Laura , Acevedo-Fernández Juan José , Román-Guerrero Angélica , Cruz-Sosa Francisco , Marquina-Bahena Silvia
Published: May 2024

In this study, we report on the isolation, purification, and anti-inflammatory evaluation of compounds from the plant species Ageratina pichinchensis. Using open-column chromatography, 11 known compounds were purified, which chemical structures were elucidated by nuclear magnetic resonance techniques (1D and 2D). All compounds were evaluated in an in vitro model of RAW 264.7 mouse macrophage cells, measuring the nitric oxide inhibition to determine the anti-inflammatory effect. The compound betuletol 3-O-β-glucoside (11) inhibited nitric oxide with a half-maximal inhibitory concentration (IC50) of 75.08 ± 3.07% at 75 µM; additionally, it inhibited the secretion of interleukin 6 (IL-6) and activation of the nuclear factor (NF-kβ). These results suggest that the anti-inflammatory effect attributed to A. pichinchensis species is promoted by compound 11, which could be considered a potential anti-inflammatory agent by suppressing the expression of NF-kβ target genes, such as those involved in the proinflammatory pathway and inducible nitric oxide synthase (iNOS).
Removal of Bisphenol A from Water by Single-Walled Carbon Nanotubes Loaded with Iron Oxide Nanoparticles
Authors: Chen Luying , Jiang Jintao , Sheng Leimei
Published: May 2024

Single-walled carbon nanotubes (SWCNTs) loaded with magnetic iron oxide nanoparticles were prepared by the arc discharge method and air heat treatment. The nanocomposite was characterized by X-ray diffraction, scanning electron microscopy, Raman spectroscopy, vibrating sample magnetometry, etc. The results showed that the heat-treated nanocomposites (SWCNTs/FexOy) had iron oxide phases and superparamagnetic properties with a saturation magnetization of 33.32 emu/g. Compared with the non-heat-treated materials, SWCNTs/FexOy had a larger specific surface area and pore volume. Using SWCNTs/FexOy to remove the organic contaminant (bisphenol A, BPA), it was found that under the conditions of pH = 3 and adsorbent dosage of 0.2 g/L, the maximum adsorption capacity of the composite was 117 mg/g, and the adsorption could reach more than 90% in only 5 min when the BPA content was below 0.05 mmol/L. The fitting results of the Langmuir and D-R models are more consistent with the experimental data, indicating a relatively uniform distribution of the adsorption sites and that the adsorption process is more consistent with physical adsorption. The kinetic calculations showed that the SWCNTs/FexOy exhibits chemical effects on both the surface and the gap, and the adsorption process is controlled by the π-π bonds and the hydrophobicity of the SWCNTs/FexOy.
A Model of an Extending Front Loader
Authors: Gralak Marek , Waluś Konrad Jan
Published: May 2024

Front loaders used in agriculture are characterized by a compact structure, which limits the scope of their application. The loading possibilities are expanded by designing front loaders equipped with telescopic arms. This design increases the loader’s working area, making it easier to load trucks. It is necessary to work on the arm extension drive and perform strength analyses on the new structures. This article presents a FEM numerical analysis of the structure of an extending front loader and an assessment of the state of stress and the value of displacements under the influence of load. This study discusses the advantages and disadvantages of front loaders compared to telehandlers and the legal requirements and standards for the design of front loaders in Europe. This work presents the concept of loader arm movement and assesses the effectiveness of using hydraulic motors coupled with a screw gear. The obtained results prove that the newly designed extending front loader system is safe and stable.
Defining a Water-Soluble Formulation of Arachidonic Acid as a Novel Ferroptosis Inducer in Cancer Cells
Authors: Day Zoe I. , Mayfosh Alyce J. , Baxter Amy A. , Williams Scott A. , Hildebrand Joanne M. , Rau Thomas F. , Poon Ivan K. H. , Hulett Mark D.
Published: May 2024

Here, we describe GS-9, a novel water-soluble fatty acid-based formulation comprising L-lysine and arachidonic acid, that we have shown to induce ferroptosis. GS-9 forms vesicle-like structures in solution and mediates lipid peroxidation, as evidenced by increased C11-BODIPY fluorescence and an accumulation of toxic malondialdehyde, a downstream product of lipid peroxidation. Ferroptosis inhibitors counteracted GS-9-induced cell death, whereas caspase 3 and 7 or MLKL knock-out cell lines are resistant to GS-9-induced cell death, eliminating other cell death processes such as apoptosis and necroptosis as the mechanism of action of GS-9. We also demonstrate that through their role of sequestering fatty acids, lipid droplets play a protective role against GS-9-induced ferroptosis, as inhibition of lipid droplet biogenesis enhanced GS-9 cytotoxicity. In addition, Fatty Acid Transport Protein 2 was implicated in GS-9 uptake. Overall, this study identifies and characterises the mechanism of GS-9 as a ferroptosis inducer. This formulation of arachidonic acid offers a novel tool for investigating and manipulating ferroptosis in various cellular and anti-cancer contexts.
Biological Rhythms, Chrono-Nutrition, and Gut Microbiota: Epigenomics Insights for Precision Nutrition and Metabolic Health
Authors: de Oliveira Melo Nathalia Caroline , Cuevas-Sierra Amanda , Souto Vitória Felício , Martínez J. Alfredo
Published: May 2024

Circadian rhythms integrate a finely tuned network of biological processes recurring every 24 h, intricately coordinating the machinery of all cells. This self-regulating system plays a pivotal role in synchronizing physiological and behavioral responses, ensuring an adaptive metabolism within the environmental milieu, including dietary and physical activity habits. The systemic integration of circadian homeostasis involves a balance of biological rhythms, each synchronically linked to the central circadian clock. Central to this orchestration is the temporal dimension of nutrient and food intake, an aspect closely interwoven with the neuroendocrine circuit, gut physiology, and resident microbiota. Indeed, the timing of meals exerts a profound influence on cell cycle regulation through genomic and epigenetic processes, particularly those involving gene expression, DNA methylation and repair, and non-coding RNA activity. These (epi)genomic interactions involve a dynamic interface between circadian rhythms, nutrition, and the gut microbiota, shaping the metabolic and immune landscape of the host. This research endeavors to illustrate the intricate (epi)genetic interplay that modulates the synchronization of circadian rhythms, nutritional signaling, and the gut microbiota, unravelling the repercussions on metabolic health while suggesting the potential benefits of feed circadian realignment as a non-invasive therapeutic strategy for systemic metabolic modulation via gut microbiota. This exploration delves into the interconnections that underscore the significance of temporal eating patterns, offering insights regarding circadian rhythms, gut microbiota, and chrono-nutrition interactions with (epi)genomic phenomena, thereby influencing diverse aspects of metabolic, well-being, and quality of life outcomes.
Rikkosan’s Short-Term Analgesic Effect on Burning Mouth Syndrome: A Single-Arm Cohort Study
Authors: Itagaki Tatsuki , Nakamura Keisuke , Tanabe Tougo , Shimura Takumi , Nakai Yu , Sakata Ken-ichiro , Sato Jun , Kitagawa Yoshimasa
Published: May 2024

Burning mouth syndrome (BMS) is a chronic oral pain disorder. There is a theory that BMS is a form of nociplastic pain. A standard treatment for BMS has not yet been established. Kampo medicine is a traditional oriental medicine. The purpose of this study is to evaluate the effectiveness of Rikkosan—a traditional Japanese herbal medicine (Kampo)—in the treatment of BMS. A single-center retrospective study was conducted on 20 patients who were diagnosed with BMS and treated with Rikkosan alone (total daily dose; 7.5 g) three times daily for approximately 4 weeks (29.5 ± 6.5 days). Rikkosan was dissolved in hot water and taken internally. They had an average age of 63 years, and 90% were being treated for other illnesses, but their medication status was the same during this study period, except for Rikkosan. No adverse events were observed in patients. Numerical rating scale (NRS) or visual analog scale (VAS)/10 scores decreased significantly between the time of the initiation of Rikkosan and one month after (−2.1 ± 1.2, p < 0.05). Rikkosan has a short-term effect of reducing NRS by two levels in BMS patients.
Inhibition of NF-κB with an Analog of Withaferin-A Restores TDP-43 Homeostasis and Proteome Profiles in a Model of Sporadic ALS
Authors: Mishra Pooja Shree , Phaneuf Daniel , Boutej Hejer , Picher-Martel Vincent , Dupre Nicolas , Kriz Jasna , Julien Jean-Pierre
Published: May 2024

The current knowledge on pathogenic mechanisms in amyotrophic lateral sclerosis (ALS) has widely been derived from studies with cell and animal models bearing ALS-linked genetic mutations. However, it remains unclear to what extent these disease models are of relevance to sporadic ALS. Few years ago, we reported that the cerebrospinal fluid (CSF) from sporadic ALS patients contains toxic factors for disease transmission in mice via chronic intracerebroventricular (i.c.v.) infusion. Thus a 14-day i.c.v. infusion of pooled CSF samples from ALS cases in mice provoked motor impairment as well as ALS-like pathological features. This offers a unique paradigm to test therapeutics in the context of sporadic ALS disease. Here, we tested a new Withaferin-A analog (IMS-088) inhibitor of NF-κB that was found recently to mitigate disease phenotypes in mouse models of familial disease expressing TDP-43 mutant. Our results show that oral intake of IMS-088 ameliorated motor performance of mice infused with ALS-CSF and it alleviated pathological changes including TDP-43 proteinopathy, neurofilament disorganization, and neuroinflammation. Moreover, CSF infusion experiments were carried out with transgenic mice having neuronal expression of tagged ribosomal protein (hNfL-RFP mice), which allowed immunoprecipitation of neuronal ribosomes for analysis by mass spectrometry of the translational peptide signatures. The results indicate that treatment with IMS-088 prevented many proteomic alterations associated with exposure to ALS-CSF involving pathways related to cytoskeletal changes, inflammation, metabolic dysfunction, mitochondria, UPS, and autophagy dysfunction. The effective disease-modifying effects of this drug in a mouse model based on i.c.v. infusion of ALS-CSF suggest that the NF-κB signaling pathway represents a compelling therapeutic target for sporadic ALS.
Efficiency Assessment on Roof Geometry and Trombe Wall Shape for Improving Buildings’ Heating Performance
Authors: Dhahri Maher , Yüksel Ahmet , Aouinet Hana , Wang Di , Arıcı Müslüm , Sammouda Habib
Published: May 2024

It is crucial to consider structural design issues in Trombe wall (T-wall) buildings to promote more suitable indoor climates and thermal comfort standards. Therefore, the present study examined the impact of two different T-wall designs and six different roof types on the energy and operational efficiency of a building located in a low-temperature and high-humidity winter climate. Ansys-CFX 15.0 software was employed to simulate the thermal and fluid dynamics behavior of the T-wall system, and flow, thermal comfort, energy, and exergy analyses were conducted. Three-dimensional simulation results and the pertinent literature data showed a good level of agreement, and the accuracy of the model was ensured. Outcomes revealed an average air velocity variation of 0.186 m/s and maximum average indoor air temperature variation of 3.3 °C between the six roof geometries. The highest air speed (0.988 m/s) was recorded for the gambrel roof while the lowest one (0.802 m/s) was recorded for the typical flat roof. The shed roof right with a rounded T-wall was more comfortable for standing and sitting activity than the others for the two T-wall shapes, and, at Y = 0.6 m and Y = 1.1 m, the average predicted percentages of dissatisfied (PPD) values were 31 and 28%, respectively. Furthermore, it was determined in the study that solar radiation intensity and T-wall and roof geometries had a significant effect on energy and exergy efficiency, and high energy and exergy efficiencies were achieved at higher solar intensity values. The best energy and exergy efficiencies were obtained for the butterfly and shed roof configurations. This study can serve as a reference for the thermal environment design of buildings with T-walls.
Mega-Projects in Construction: Barriers in the Implementation of Circular Economy Concepts in the Kingdom of Saudi Arabia
Authors: Alotaibi Saud , Martinez-Vazquez Pedro , Baniotopoulos Charalampos
Published: May 2024

The construction sector has been subjected to scrutiny due to its propensity for waste generation and the extensive utilisation of finite natural resources. In response to these concerns, a transition towards a novel conceptual framework known as circular economy (CE) has been advocated. Nevertheless, the integration of CE principles within the construction domain encounters numerous impediments to its advancement. Despite scholarly recognition of these challenges, scant research has been devoted to elucidating the intricacies associated with the planning and execution of large-scale projects, particularly within developing nations such as the Kingdom of Saudi Arabia (KSA). This paper intends to fill this gap through the identification and ranking of those barriers encountered when trying to implement CE during construction in KSA. To this end, a comprehensive literature review was completed, alongside a survey conducted amongst 239 participants involved in three mega-projects. A statistical analysis of the data collected was carried out based on the one-way analysis of variance (ANOVA). Following this, a relative importance index (RII) was established to rank 24 barriers categorised as major within the sample. The findings revealed the lack of regulation within the construction sector, the lack of education and training, little awareness and guidance on the subject, and the absence of an incentives policy as primary barriers to adopting CE in KSA. The present study endeavours to enhance the comprehension regarding the principles of circular economy (CE) and the attendant challenges encountered during its implementation. The overarching objective is to provide insights that can inform decision-making processes, thereby facilitating the development of robust mitigation strategies and the adoption of best practices.
Study on the Impact of Design Factors of Piloti Forms on the Thermal Environment in Residential Quarters
Authors: Li Jinhan , Shan Xiaofang , Deng Qinli
Published: May 2024

According to piloti design, the outdoor thermal environment can be improved in cities with hot summer conditions. Taking Chinese cities with a hot summer and cold winter as the research object, this paper discusses the improvement of the outdoor thermal environment of residential districts in summer by considering piloti design factors. In this article, according to our investigation of piloti design in Wuhan, a basic model of the overhead layer in the Wuhan residential area is presented, along with the effects of different piloti ratios (0–80%), piloti heights (2–6 m), and greening rates (30–35%) on the outdoor thermal environment of buildings. The average air temperature and average wind speed at the pedestrian level are used as outdoor thermal environment indicators, the average PET is used as the outdoor thermal comfort indicator, and the comfort wind ratio is used as the outdoor wind comfort indicator. The results show that increasing the ratio of corridor columns has the greatest thermal comfort enhancement effect in the corridor area, and when the piloti ratio increases from 20% to 80%, the PET in piloti areas reduces by 2.926 °C. Improving the greening rate has the greatest thermal comfort enhancement effect in the passageway area, and when the greening rate increases from 20% to 80%, the PET in piloti areas reduces by 0.9 °C. Furthermore, the increases in both the piloti ratio and piloti height have an enhancement effect on the outdoor wind environment and wind comfort, with thresholds of a piloti ratio over 60% and a piloti height over 5 m. In contrast, the increase in the greening rate will deteriorate the outdoor wind environment and wind comfort. The conclusions of this study are of great significance for the planning and design of overhead layers in residential areas in hot and humid areas in summer.
Investigating the Hydration, Mechanical Properties, and Pozzolanic Activity of Cement Paste Containing Co-Combustion Fly Ash
Authors: Ding Xiaobo , Du Hangyu , Wu Enfeng , Yi Peng , Li Yongqiang , Luo Yaoming , Liu Wei
Published: May 2024

The heat of hydration, mechanical properties, pozzolanic activity, and microscopic characteristics of cement pastes incorporating co-combusted fly ash (CCFA) were investigated, and the disparities between the CCFA/cement system and the coal fly ash (CFA) binding system were also compared. The results indicate a decrease in the heat of hydration for both CFA and CCFA samples, with a more pronounced trend observed as the fly ash content increased from 10% to 30%. The distinction in the early hydration between CFA and CCFA samples primarily manifested in the rate of heat release, potentially correlated with variations in the active Al2O3 content in the fly ash. Neither CFA nor CCFA samples exhibited significant cementitious activity at 3 days, functioning solely as inert fillers in the cement paste. By 3 and 28 days, the mechanical properties of both CFA and CCFA samples were inferior to those of pure cement paste. However, by 180 days of hydration, the compressive strength of CCFA-blended mortar notably increased, with the highest strength observed in the 10% CCFA-blended sample. Both CFA and CCFA samples produced the secondary hydration product C-A-S-H and demonstrated comparable consumption of calcium hydroxide (CH). These findings underscore the potential of CCFA as a supplementary cementitious material (SCM) and lay a foundation for its widespread adoption.
Numerical Study on the Dynamic Response and Damage Cumulative of Bolt-Supported Cavern under Adjacent Cyclic Explosion
Authors: Wang Guangyong , Chang Kaiwen , Cao Ansheng
Published: May 2024

Adjacent cyclic explosions significantly impact the stability of underground anchored caverns. Based on the similar model test of the vault explosion of the anchored cavern, the dynamic analysis finite element software ANSYS/LSDYNA(18.0) was used to establish a model of the straight wall side explosion of the underground anchored cavern and conduct a numerical simulation. When the total amount of explosion load is the same, we compared the stress time history curve, displacement time history curve, tunnel wall displacement, and circumferential strain curve of the surrounding rock in the underground anchored cavern (under both a high-level single-side blast and a low-level cyclic side blast). We obtained the dynamic response rules of the surrounding rock. By comparing the damage evolution process of the surrounding rock in the two situations, the damage accumulation law of the surrounding rock was analyzed. At the same time, the axial stress distribution characteristics of underground anchor cavern anchors under the action of cyclic explosion were studied. The findings demonstrate that when the total level of blast load adjacent to the cavern is the same, the displacement and circumferential peak strain of surrounding rock and the axial stress of rock bolt in the high-level single explosion are greater than those in the low-level cyclic explosion. However, compared to a single explosion, the rock mass suffers more damage in the cyclic explosion. This study will provide engineers with information that will assist them with a better understanding of the cumulative damage mechanisms of surrounding rock, as well as the stress characteristics of rock bolts under dynamic loads near the explosion site, which will be used to design underground caves with anti-blast features.
Evaluation of Ground Motion Damage Potential with Consideration of Compound Intensity Measures Using Principal Component Analysis and Canonical Correlation Analysis
Authors: Liu Tingting , Lu Dagang
Published: May 2024

The primary motivation of this study is to develop a compound intensity measure (IM) to evaluate ground motion damage potential based on principal component analysis (PCA) and canonical correlation analysis (CCA). To illustrate this, this study examines the correlation among intragroup IMs and intergroup IMs, as well as the correlation between various IMs and response variables. A compound IM, which can be obtained by a linear combination of ten IMs in the log-scale, is utilized to measure the ground motion damage potential. Elastoplastic, bilinear and hysteretic models are utilized to determine peak deformation and hysteretic energy as the response variables of Single-Degree-of-Freedom (SDOF) systems. On the basis of the SDOF systems, the overall structural damage index is obtained by a nonlinear time–history analysis for two reinforced concrete moment frame systems. It is clear that the developed compound IM shows significantly high-level correlation with structural response. The better the correlations, the more one can measure the earthquake damage potential. A single IM alone inadequately characterizes structural damage, highlighting the necessity of multiple IMs to estimate the possibility of structural damage.
Artificial Intelligence in Urologic Robotic Oncologic Surgery: A Narrative Review
Authors: Bellos Themistoklis , Manolitsis Ioannis , Katsimperis Stamatios , Juliebø-Jones Patrick , Feretzakis Georgios , Mitsogiannis Iraklis , Varkarakis Ioannis , Somani Bhaskar K. , Tzelves Lazaros
Published: May 2024

With the rapid increase in computer processing capacity over the past two decades, machine learning techniques have been applied in many sectors of daily life. Machine learning in therapeutic settings is also gaining popularity. We analysed current studies on machine learning in robotic urologic surgery. We searched PubMed/Medline and Google Scholar up to December 2023. Search terms included “urologic surgery”, “artificial intelligence”, “machine learning”, “neural network”, “automation”, and “robotic surgery”. Automatic preoperative imaging, intraoperative anatomy matching, and bleeding prediction has been a major focus. Early artificial intelligence (AI) therapeutic outcomes are promising. Robot-assisted surgery provides precise telemetry data and a cutting-edge viewing console to analyse and improve AI integration in surgery. Machine learning enhances surgical skill feedback, procedure effectiveness, surgical guidance, and postoperative prediction. Tension-sensors on robotic arms and augmented reality can improve surgery. This provides real-time organ motion monitoring, improving precision and accuracy. As datasets develop and electronic health records are used more and more, these technologies will become more effective and useful. AI in robotic surgery is intended to improve surgical training and experience. Both seek precision to improve surgical care. AI in ‘’master–slave’’ robotic surgery offers the detailed, step-by-step examination of autonomous robotic treatments.
The Current Role of Radiation in the Management of Cholangiocarcinoma—A Narrative Review
Authors: Verma Saurav , Grindrod Natalie , Breadner Daniel , Lock Michael
Published: May 2024

Cholangiocarcinoma (CCA) is a rare cancer of bile ducts. It is associated with a poor prognosis. The incidence of CCA is rising worldwide. Anatomical subgroups have been used to classify patients for treatment and prognosis. There is a growing understanding of clinically important distinctions based on underlying genetic differences that lead to different treatment options and outcomes. Its management is further complicated by a heterogeneous population and relative rarity, which limits the conduct of large trials to guide management. Surgery has been the primary method of therapy for localized disease; however, recurrence and death remain high with or without surgery. Therefore, there have been concerted efforts to investigate new treatment options, such as the use of neoadjuvant treatments to optimize surgical outcomes, targeted therapy, leveraging a new understanding of immunobiology and stereotactic radiation. In this narrative review, we address the evidence to improve suboptimal outcomes in unresectable CCA with radiation, as well as the role of radiation in neoadjuvant and postoperative treatment. We also briefly discuss the recent developments in systemic treatment with targeted therapies and immune checkpoint inhibitors.
Opaganib Downregulates N-Myc Expression and Suppresses In Vitro and In Vivo Growth of Neuroblastoma Cells
Authors: Maines Lynn W. , Keller Staci N. , Smith Ryan A. , Schrecengost Randy S. , Smith Charles D.
Published: May 2024

Neuroblastoma (NB), the most common cancer in infants and the most common solid tumor outside the brain in children, grows aggressively and responds poorly to current therapies. We have identified a new drug (opaganib, also known as ABC294640) that modulates sphingolipid metabolism by inhibiting the synthesis of sphingosine 1-phosphate (S1P) by sphingosine kinase-2 and elevating dihydroceramides by inhibition of dihydroceramide desaturase. The present studies sought to determine the potential therapeutic activity of opaganib in cell culture and xenograft models of NB. Cytotoxicity assays demonstrated that NB cells, including cells with amplified MYCN, are effectively killed by opaganib concentrations well below those that accumulate in tumors in vivo. Opaganib was shown to cause dose-dependent decreases in S1P and hexosylceramide levels in Neuro-2a cells, while concurrently elevating levels of dihydroceramides. As with other tumor cells, opaganib reduced c-Myc and Mcl-1 protein levels in Neuro-2a cells, and also reduced the expression of the N-Myc protein. The in vivo growth of xenografts of human SK-N-(BE)2 cells with amplified MYCN was suppressed by oral administration of opaganib at doses that are well tolerated in mice. Combining opaganib with temozolomide plus irinotecan, considered the backbone for therapy of relapsed or refractory NB, resulted in increased antitumor activity in vivo compared with temozolomide plus irinotecan or opaganib alone. Mice did not lose additional weight when opaganib was combined with temozolomide plus irinotecan, indicating that the combination is well tolerated. Opaganib has additive antitumor activity toward Neuro-2a tumors when combined with the checkpoint inhibitor anti-CTLA-4 antibody; however, the combination of opaganib with anti-PD-1 or anti-PD-L1 antibodies did not provide increased antitumor activity over that seen with opaganib alone. Overall, the data demonstrate that opaganib modulates sphingolipid metabolism and intracellular signaling in NB cells and inhibits NB tumor growth alone and in combination with other anticancer drugs. Amplified MYCN does not confer resistance to opaganib, and, in fact, the drug attenuates the expression of both c-Myc and N-Myc. The safety of opaganib has been established in clinical trials with adults with advanced cancer or severe COVID-19, and so opaganib has excellent potential for treating patients with NB, particularly in combination with temozolomide and irinotecan or anti-CTLA-4 antibody.
How Immunotherapy Has Redefined the Treatment Paradigm of Metastatic or Locally Advanced Muscle-Invasive Urothelial Bladder Carcinoma
Authors: Larroquette Mathieu , Lefort Félix , Domblides Charlotte , Héraudet Luc , Robert Grégoire , Ravaud Alain , Gross-Goupil Marine
Published: May 2024

In the past decade, the therapeutic arsenal for metastatic bladder cancer has expanded considerably, with the development of immune checkpoint inhibitors (ICIs), antibody–drug conjugates such as enfortumab vedotin, and anti-fibroblast growth factor receptor agents. Clinical trials evaluating ICIs as neoadjuvants, adjuvants, or first- or second-line treatments have produced conflicting results. However, first-line therapeutic strategies have been redefined by the recent publication of results from two clinical trials: CheckMate-901, which demonstrated the superiority of combined treatment with nivolumab and chemotherapy in extending overall survival, and EV-302, which demonstrated that combined treatment with pembrolizumab and enfortumab vedotin reduced the risk of death by 53%. In this review, we discuss the role of ICIs, alone or in combination, in bladder cancer management in the metastatic and adjuvant settings in 2024, considering the latest published trials. The potential role of ICIs as neoadjuvants is also discussed.
Two-Year-Span Breast Cancer Screening Uptake in Japan after the COVID-19 Pandemic and Its Association with the COVID-19 Vaccination
Authors: Abubakar Aminu Kende , Kaneda Yudai , Ozaki Akihiko , Saito Hiroaki , Murakami Michio , Hori Daisuke , Gonda Kenji , Tsubokura Masaharu , Tabuchi Takahiro
Published: May 2024

There is limited information on whether the COVID-19 pandemic was associated with decreased breast cancer screening uptake and if COVID-19 vaccination was associated with an increase in screening uptake. Our study explored the uptake of breast cancer screening in Japan after the COVID-19 pandemic and assessed its association with the COVID-19 vaccination. We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), a web-based prospective cohort survey, and we included 6110 women without cancer history who were aged 40 to 74 years that participated in the 2012 and 2022 surveys. We examined the regular breast cancer screening uptake before and after the pandemic and employed a multivariable Poisson regression model to seek any association between COVID-19 vaccination and screening uptake. Of 6110, 38.2% regularly participated in screening before the pandemic and 46.9% did so after the pandemic. Individuals unvaccinated due to health reasons (incidence rate ratio (IRR) = 0.47, 95% CI: 0.29–0.77, p = 0.003) and for other reasons (IRR = 0.73, 95% CI: 0.62–0.86, p < 0.001) were less likely to undergo screening compared to fully vaccinated individuals. There was no long-term decrease in breast cancer screening uptake after the pandemic in Japan. Vaccination was linked to increased uptake, but there was no dose relationship.
Programmed Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor and Monitor of Response to Atezolizumab plus Bevacizumab Treatment in Patients with Hepatocellular Carcinoma
Authors: Nosaka Takuto , Murata Yosuke , Akazawa Yu , Tanaka Tomoko , Takahashi Kazuto , Naito Tatsushi , Matsuda Hidetaka , Ohtani Masahiro , Imamura Yoshiaki , Nakamoto Yasunari
Published: May 2024

There remains no reliable biomarker of therapeutic efficacy in hepatocellular carcinoma (HCC) for the PD-L1 inhibitor atezolizumab and bevacizumab (Atezo/Bev). Circulating tumor cells (CTCs) enable the serial collection of living tumor cells. Pre-treatment and serial CTC gene expression changes and tumor histology were evaluated to identify predictors of response to Atezo/Bev. Peripheral blood from 22 patients with HCC treated with Atezo/Bev and 24 patients treated with lenvatinib was serially collected. The RNA expression in CTCs was analyzed using qRT-PCR. Higher PD-L1 expression in pre-treatment CTCs was associated with response and improved prognosis with Atezo/Bev treatment, but not with lenvatinib. There was no correlation between PD-L1 expression in CTCs and that in liver tumor biopsy specimens scored using imaging software. Furthermore, PD-L1 RNA expression in CTCs was dynamically altered by Atezo/Bev, decreasing during effective response and increasing upon progression. CTC-derived RNA collected during Atezo/Bev indicates that patients with higher PD-L1 expression in CTCs at baseline were 3.9 times more responsive to treatment. Therefore, PD-L1 RNA levels in CTCs are an accurate response predictor and may be a monitorable biomarker that changes dynamically to reflect the response during Atezo/Bev treatment.
Phytochemical Modulation of Ion Channels in Oncologic Symptomatology and Treatment
Authors: Rao Rohan , Mohammed Caroline , Alschuler Lise , Pomeranz Krummel Daniel A. , Sengupta Soma
Published: May 2024

Modern chemotherapies offer a broad approach to cancer treatment but eliminate both cancer and non-cancer cells indiscriminately and, thus, are associated with a host of side effects. Advances in precision oncology have brought about new targeted therapeutics, albeit mostly limited to a subset of patients with an actionable mutation. They too come with side effects and, ultimately, ‘self-resistance’ to the treatment. There is recent interest in the modulation of ion channels, transmembrane proteins that regulate the flow of electrically charged molecules in and out of cells, as an approach to aid treatment of cancer. Phytochemicals have been shown to act on ion channels with high specificity regardless of the tumor’s genetic profile. This paper explores the use of phytochemicals in cancer symptom management and treatment.
A Single Nucleotide Variant in Ankyrin-2 Influencing Ventricular Tachycardia in COVID-19 Associated Myocarditis
Authors: Haase Erin , Kulkarni Chandana , Moore Peyton , Ramanathan Akash , Sathyamoorthy Mohanakrishnan
Published: May 2024

Introduction: This paper explores the potential influence of a single nucleotide variant in the ANK-2 gene on COVID-19 myocarditis-related ventricular tachycardia. Case Description: A 53-year-old female with a history of Crohn’s disease and asthma developed COVID-19. Shortly after infection, she experienced symptoms of chest pressure, palpitations, and shortness of breath, leading to the eventual diagnosis of myocarditis complicated by recurrent ventricular tachycardia. Treatment with mechanistically driven anti-arrhythmic therapy and beta-blockers suppressed this highly symptomatic ventricular tachycardia. Genetic testing to further risk stratify and influence long term care identified a single nucleotide variant in the ANK-2 gene, which is known to be associated with arrhythmic risk. Discussion: This case study highlights the use of rationally selected anti-arrhythmic therapy, mexiletine, in the management of ventricular tachycardia associated with COVID-19 myocarditis and the presence of a single nucleotide variant in ANK-2, raising the possibility of its contribution to VT susceptibility and severity. Our patient demonstrated significant improvement with administered therapeutics, including the resolution of myocarditis and ventricular tachycardia. The normalization of the QT interval during the resolution phase further supports the potential influence of the genetic variant in ANK-2 on potassium channel activity.
Ketone Bodies after Cardiac Arrest: A Narrative Review and the Rationale for Use
Authors: Annoni Filippo , Gouvea Bogossian Elisa , Peluso Lorenzo , Su Fuhong , Moreau Anthony , Nobile Leda , Casu Stefano Giuseppe , Sterchele Elda Diletta , Calabro Lorenzo , Salvagno Michele , Oddo Mauro , Taccone Fabio Silvio
Published: May 2024

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts.
Systemic LPS Administration Stimulates the Activation of Non-Neuronal Cells in an Experimental Model of Spinal Muscular Atrophy
Authors: Karafoulidou Eleni , Kesidou Evangelia , Theotokis Paschalis , Konstantinou Chrystalla , Nella Maria-Konstantina , Michailidou Iliana , Touloumi Olga , Polyzoidou Eleni , Salamotas Ilias , Einstein Ofira , Chatzisotiriou Athanasios , Boziki Marina-Kleopatra , Grigoriadis Nikolaos
Published: May 2024

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deficiency of the survival motor neuron (SMN) protein. Although SMA is a genetic disease, environmental factors contribute to disease progression. Common pathogen components such as lipopolysaccharides (LPS) are considered significant contributors to inflammation and have been associated with muscle atrophy, which is considered a hallmark of SMA. In this study, we used the SMNΔ7 experimental mouse model of SMA to scrutinize the effect of systemic LPS administration, a strong pro-inflammatory stimulus, on disease outcome. Systemic LPS administration promoted a reduction in SMN expression levels in CNS, peripheral lymphoid organs, and skeletal muscles. Moreover, peripheral tissues were more vulnerable to LPS-induced damage compared to CNS tissues. Furthermore, systemic LPS administration resulted in a profound increase in microglia and astrocytes with reactive phenotypes in the CNS of SMNΔ7 mice. In conclusion, we hereby show for the first time that systemic LPS administration, although it may not precipitate alterations in terms of deficits of motor functions in a mouse model of SMA, it may, however, lead to a reduction in the SMN protein expression levels in the skeletal muscles and the CNS, thus promoting synapse damage and glial cells’ reactive phenotype.