bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic Effects of Transferrin-Conjugated Gold Nanoparticles on the Antioxidant Glutathione-Thioredoxin Pathway
Authors: Sebastian Sonia , Hoffmann Manuela Klingler , Howard Douglas , Young Clifford , Washington Jenni , Unterweger Harald , Alexiou Christoph , Turnbull Tyron , D’Andrea Richard , Hoffmann Peter , Kempson Ivan
Published: August 2023

Nanoparticle-based therapeutics are being clinically translated for treating cancer. Even when thought to be biocompatible, nanoparticles are being increasingly identified as altering cell regulation and homeostasis. Antioxidant pathways are important for maintaining cell redox homeostasis and play important roles by maintaining ROS levels within tolerable ranges. Here, we sought to understand how a model of a relatively inert nanoparticle without any therapeutic agent itself could antagonize a cancer cell lines’ antioxidant mechanism. A label-free protein expression approach was used to assess the glutathione-thioredoxin antioxidative pathway in a prostate cancer cell line (PC-3) after exposure to gold nanoparticles conjugated with a targeting moiety (transferrin). The impact of the nanoparticles was also corroborated through morphological analysis with TEM and classification of pro-apoptotic cells by way of the sub-G0/G1 population via the cell cycle and annexin V apoptosis assay. After a two-hour exposure to nanoparticles, major proteins associated with the glutathione-thioredoxin antioxidant pathway were downregulated. However, this response was acute, and in terms of protein expression, cells quickly recovered within 24 h once nanoparticle exposure ceased. The impact on PRDX-family proteins appears as the most influential factor in how these nanoparticles induced an oxidative stress response in the PC-3 cells. An apparent adaptive response was observed if exposure to nanoparticles continued. Acute exposure was observed to have a detrimental effect on cell viability compared to continuously exposed cells. Nanoparticle effects on cell regulation likely provide a compounding therapeutic advantage under some circumstances, in addition to the action of any cytotoxic agents; however, any therapeutic advantage offered by nanoparticles themselves with regard to vulnerabilities specific to the glutathione-thioredoxin antioxidative pathway is highly temporal.
Current Limitations for Predicting Liquid Dispersion in Continuous Flow Bubble Columns Using CFD
Authors: Gallardo-Rodríguez Juan José , Velasco-Amate Javier , Lorenzo-Horcajo Erika , López-Rosales Lorenzo , Chisti Yusuf , Battaglia Francine , Sánchez-Mirón Asterio , García-Camacho Francisco
Published: August 2023

Liquid-phase dispersion in a continuous flow bubble column was studied using computational fluid dynamics (CFD) and different combinations of turbulence and biphasic models. The results were compared with the experimental data obtained by the stimulus-response method in an air-water pilot-scale bubble column (2 m tall, 0.234 m internal diameter). Two flow combinations were examined: high flow rates of 3.2 m3 h−1 and 4.5 m3 h−1 and low flow rates of 1.98 m3 h−1 and 0.954 m3 h−1 for water and air, respectively. The objective was to evaluate commercial CFD 16.1 software to predict flow behavior beyond macroscale parameters such as hold-up or mixing time. The turbulence models that best replicated the experimental tracer dispersion were large eddy simulation-type models: scale-adaptive simulation (SAS) and shear stress transport-SAS. The simulations qualitatively predicted the tracer concentration with time but were unable to reveal the small-scale perturbations in the biphasic system. The predicted tracer residence time was double or triple the measured times for low and high flow, respectively.
Comparative Sensitivity Analysis of Hydrology and Relative Corn Yield under Different Subsurface Drainage Design Using DRAINMOD
Authors: Timalsina Haribansha , Hwang Soonho , Cooke Richard A. , Bhattarai Rabin
Published: August 2023

DRAINMOD is a process-based hydrologic model used to analyze the effectiveness of various drainage systems and management strategies. In this study, a sensitivity analysis of DRAINMOD hydrologic parameters for two different field settings located at Champaign, Illinois, was performed to determine the most sensitive parameters that affect the subsurface flow and relative productivity of corn. Latin-Hypercube One-Factor-at-a-Time (LH-OAT) was used to determine the sensitivity index of 17 parameters for six objective functions for daily flow, water balance, and relative yield for the productivity of corn. The results indicated that flow and yield were highly sensitive to drainage design parameters such as drainage depth and spacing. Winter flow and the water balance were sensitive to soil thermal conductivity parameters; however, they had no impact on the relative corn yield. The significant difference in sensitivity of the two fields was observed in the hydraulic conductivity of soil layers due to varying thicknesses for different soil types. This study highlights the need for more careful calibration of these sensitive parameters to reduce equifinality and model output uncertainty and appropriate drainage design for optimizing crop productivity and drainage outflow.
Behavioural Analysis of Dogs’ Response to Threatening and Neutral Conspecific Video Stimuli
Authors: Pedretti Giulia , Canori Chiara , Marshall-Pescini Sarah , Pavan Gianni , Valsecchi Paola
Published: August 2023

Dogs’ displacement behaviours and some facial expressions have been suggested to function as appeasement signals, reducing the occurrences of aggressive interactions. The present study had the objectives of using naturalistic videos, including their auditory stimuli, to expose a population of dogs to a standardised conflict (threatening dog) and non-conflict (neutral dog) situation and to measure the occurrence of displacement behaviours and facial expressions under the two conditions. Video stimuli were recorded in an ecologically valid situation: two different female pet dogs barking at a stranger dog passing by (threatening behaviour) or panting for thermoregulation (neutral behaviour). Video stimuli were then paired either with their natural sound or an artificial one (pink noise) matching the auditory characteristics. Fifty-six dogs were exposed repeatedly to the threatening and neutral stimuli paired with the natural or artificial sound. Regardless of the paired auditory stimuli, dogs looked significantly more at the threatening than the neutral videos (χ2(56, 1) = 138.867, p < 0.001). They kept their ears forward more in the threatening condition whereas ears were rotated more in the neutral condition. Contrary to the hypotheses, displacement behaviours of sniffing, yawning, blinking, lip-wiping (the tongue wipes the lips from the mouth midpoint to the mouth corner), and nose-licking were expressed more in the neutral than the threatening condition. The dogs tested showed socially relevant cues, suggesting that the experimental paradigm is a promising method to study dogs’ intraspecific communication. Results suggest that displacement behaviours are not used as appeasement signals to interrupt an aggressive encounter but rather in potentially ambiguous contexts where the behaviour of the social partner is difficult to predict.
Evaluation and Driving Determinants of the Coordination between Ecosystem Service Supply and Demand: A Case Study in Shanxi Province
Authors: Zhang Yushuo , Liu Boyu , Sui Renjing
Published: August 2023

Understanding the coordination relationship between ecosystem service (ES) supply and demand and elucidating the impact of driving factors is critical for regional land use planning and ecological sustainability. We use a large watershed area as a case to map and analyze ES supply, demand and the coordination relationship, and identify the associated socio-ecological driving variables. This study assessed the supply and demand of five ESs (crop production, water retention, soil conservation, carbon sequestration, and outdoor recreation) in 2000 and 2020, and evaluated the coordination between them employing the coupling coordination degree model (CCDM). Additionally, we utilized the geo-detector model (GDM) to identify driving determinants and their interactive effects on the spatial pattern of the coupling coordination degree (CCD) between ES supply and demand. The results showed that mountainous regions with abundant forest coverage were high-value areas for ES supply, while the ESs were predominantly required in city center areas within each basin area. From 2000 to 2020, there was a slight decline in ES supply and a significant increase in ES demand. Counties were grouped into four coordination zones in the study area: extreme incoordination, moderate incoordination, reluctant coordination, and moderate coordination. The number of counties with extreme incoordination linked to regions with a mountain ecosystem is increasing, where the ES supply is much greater than the demand. The moderate incoordination counties dominated by a cropland ecosystem exhibited slightly higher levels of ES supply than demand. The moderate and reluctant coordination were linked to counties with distinct ecological characteristics. Construction land played a major role in the characteristics of the CCD, followed by grassland. The interaction between construction land and all other factors significantly increased the influence on the CCD. These findings offered valuable insights for land managers to identify areas characterized by incoordination between ES supply and demand and understand associated factors to develop optimal ES management strategies.
Cause Analysis of Coal Mine Gas Accidents in China Based on Association Rules
Authors: Liu Ying , Liang Yunpei , Li Quangui
Published: August 2023

Coal mine gas accidents will cause great economic losses and casualties. It is of great significance to find out the essential causes of coal mine gas accidents and put forward measures to prevent them. In this paper, 110 coal mine gas accidents which occurred in China from 2001 to 2022 are selected to analyze the causes of the accidents by extracting the keywords of human factors, equipment factors, environment factors, and management factors from the accident investigation reports. Firstly, the accident statistical analysis is carried out from three dimensions of factor frequency, accident type, and accident grade. Secondly, the Apriori algorithm is used for data mining to obtain frequent item sets and association rules of coal mine gas accident factors. Finally, the coal mine gas accident cause chains which are obtained by using the association rule. The frequent terms of 9 factors, 23 association rules, and 3 coal mine gas accident cause chains are obtained. The results show that the production of coal mine enterprises by illegal organizations is an important reason for the occurrence of coal mine gas accidents. The lack of good management culture easily leads to habitual violations of personnel and decision-making errors, and then causes equipment problems, reflected in the ventilation system which is not perfect, resulting in gas accumulation. The occurrence of coal mine gas accidents can be prevented to a large extent by preventing the absence of good management culture in enterprise management and the occurrence of illegal production behaviors.
The Role of Nitrogen and Phosphorus in Eutrophication of the Northern Adriatic Sea: History and Future Scenarios
Authors: Marini Mauro , Grilli Federica
Published: August 2023

In the last two decades of the 21st century, a gradual decrease in nitrogen and phosphorus has been observed along the coastal area of the Northern Adriatic Sea. This depletion is attributed to reduced river flows. Studies conducted over the past four decades have indicated that the N/P ratio in the open sea is unlikely to undergo significant change. In fact, it tends to increase due to the unique characteristics of the Northern Adriatic Sea, which experiences slow water turnover and is influenced by strong winds. Additionally, the Northern Adriatic Sea receives a substantial amount of freshwater from rivers, accounting for about one-third of the total freshwater flow into the Mediterranean. These rivers carry nutrient loads that contribute to the high productivity and abundance of fish in this sea, making it one of the most productive areas in the Mediterranean. It has been observed that the cessation of anthropogenic phosphorus input, which has been regulated since the late 1980s with legislation limiting its use in detergents, has significantly affected the trophic chain. The aim of this review is to provide an overview of the eutrophication trend in the Northern Adriatic Sea, highlighting the importance long-term data series.
Coreference Resolution for Improving Performance Measures of Classification Tasks
Authors: Šteflovič Kirsten , Kapusta Jozef
Published: August 2023

There are several possibilities to improve classification in natural language processing tasks. In this article, we focused on the issue of coreference resolution that was applied to a manually annotated dataset of true and fake news. This dataset was used for the classification task of fake news detection. The research aimed to determine whether performing coreference resolution on the input data before classification or classifying them without performing coreference resolution is more effective. We also wanted to verify whether it is possible to enhance classifier performance metrics by incorporating coreference resolution into the data preparation process. A methodology was proposed, in which we described the implementation methods in detail, starting from the identification of entity mentions in the text using the neuralcoref algorithm, then through word-embedding models (TF–IDF, Doc2Vec), and finally to several machine learning methods. The result was a comparison of the implemented classifiers based on the performance metrics described in the theoretical part. The best result for accuracy was observed for the dataset with coreference resolution applied, which had a median value of 0.8149, while for the F1 score, the best result had a median value of 0.8101. However, the more important finding is that the processed data with the application of coreference resolution led to an improvement in performance metrics in the classification tasks.
Adaptive Leakage Protection for Low-Voltage Distribution Systems Based on SSA-BP Neural Network
Authors: Liu Zhenguo , Yu Hai , Jin Wei
Published: August 2023

The fluctuation of normal leakage current has a great influence on the fixed-threshold leakage protector. To address this issue, this paper proposes an adaptive leakage protection method based on the sparrow search algorithm (SSA)-backpropagation (BP) neural network. Based on the analysis of the normal leakage current generation mechanism, this method uses the SSA optimized BP neural network to construct a prediction model of normal leakage current. By dividing the normal leakage range into several intervals and setting the corresponding action threshold, the action threshold of the interval is automatically selected in advance, based on the predicted value of the model, so as to realize the adaptive protection of the leakage current faults. Experiments have proved that the leakage protector can identify the leakage fault more sensitively and increase the ratio of the protector put into operation by predicting the development of normal leakage current and adjusting the protection action threshold in advance.
Laboratory Testing and Analysis of Clay Soil Stabilization Using Waste Marble Powder
Authors: Umar Ibrahim Haruna , Lin Hang , Ibrahim Awaisu Shafiu
Published: August 2023

Soil stabilization is a critical step in numerous engineering projects, preventing soil erosion, increasing soil strength, and reducing the risk of subsidence. Due to its inexpensive cost and potential environmental benefits, waste materials, such as waste marble powder (WMP), have been used as additives for soil stabilization in recent years. This study investigates waste marble powder’s effects on unconfined compressive strength (UCS) and clayey soil’s ultrasonic pulse velocity (UPV) at different water contents and curing times, and artificial neural networks (ANNs) are also used to predict the UCS and UPV values based on three input variables (percentage of waste marble dust, curing time, and moisture content). Geo-engineering experiments (Atterberg limits, compaction characteristics, specific gravity, UCS, and UPV) and analytical methods (ANNs) are used. The study results indicate that the soil is high-plasticity clay (CH) using the Unified Soil Classification System (USCS), and adding waste marble powder (WMP) can significantly improve the UCS and UPV of clay soils, especially at optimal water content, curing times of 28 days, and 60% WMP. It is found that the ANN models accurately predict the UCS and UPV values with high correlation coefficients approaching 1. In addition, this study shows that the optimum water content and curing time for stabilized clay soils depend on the grade and amount of waste marble powder utilized. Overall, the study demonstrates the potential of waste marble dust as a soil stabilization additive and the usefulness of ANNs in predicting UCS and UPV values. This study’s results are relevant to engineers and researchers working on soil stabilization projects, such as foundations and backfills. They can contribute to the development of sustainable and cost-effective soil stabilization solutions.
Dynamic Torsional Stiffness of Reducers and Its Testing Method
Authors: Cheng Huiming , Shi Zhaoyao , Yu Zhiyong , Zuo Guangxiang
Published: August 2023

The torsional stiffness of the reducer is commonly assumed to be static and tested using the hysteresis curve method. However, practical engineering experience shows that the torsional stiffness is dynamic rather than static, and the hysteresis curve method cannot accurately represent the reducer’s torsional stiffness during actual operation. To address these issues, this study conducts theoretical research on the dynamic characteristics of torsional stiffness, introduces a new concept called dynamic torsional stiffness, and provides its analytical formula. A dynamic torsional stiffness testing method based on the transmission error method is proposed, and its feasibility and consistency with the hysteresis curve method are theoretically demonstrated. This method allows the torsional stiffness information of the reducer to be obtained under all operating conditions. Through experimental research, the limitations of the hysteresis curve method are explained, and the dynamic characteristics of the reducer’s torsional stiffness, along with the effectiveness of the transmission error method, are verified. Consequently, the torsional stiffness information of the reducer under all operating conditions is obtained. In conclusion, this method is valuable for both theoretical and engineering applications, as it offers a more accurate representation of the dynamic torsional stiffness of the reducer in real-world scenarios.
The Efficiency of Lichens in Air Biomonitoring in Teleorman County
Authors: Cernat Popa Maria Magdalena , Rusănescu Carmen Otilia
Published: August 2023

In this work, we collected samples of lichens from the oaks of Pădurea Troianul, in the area of Teleorman county, to analyze the air quality, using the lichen biodiversity index and its determining factor. We transplanted them to the points to be monitored and analyzed them to detect and quantify the concentration of heavy metals or other toxic substances accumulated in the lichen biomass. This research was conducted at transplant sites, where five sample sites were chosen. We investigated the concentrations of the heavy metals Cd, Pb and Hg, making a comparison between the concentrations indicated by lichens and conventional measurements. The sampling, observation and analysis of lichens, we carried out in the months of September, October and November 2021, because in September the temperatures are higher and the degree of precipitation is lower than in November, so we followed a development of lichens covering different periods in terms of temperature and humidity. The comparison was made starting from the contamination factors obtained and measured in the sampling station. The application of the biomonitoring method allows obtaining an exact index of the purity of the atmosphere based on the tolerance of the transplanted lichens, the results being obtained quickly.
Forecasting Turning Points of Carbon Emissions in Beijing Based on Interpretable Machine Learning
Authors: Yao Tianen , Wang Yaqi , Li Xinhao , Lian Xinyao , Li Jing
Published: August 2023

For curbing the global climate crisis, China has set an ambitious target of peak carbon emissions by 2030. Beijing, the capital of China, has implemented a carbon reduction policy since 2012. Using the reduced and generalized forms of the Environmental Kuznets Curve (EKC), we deduce that both the cubic EKC and the genetic algorithm-based EKC have an N-shape. The first turning point of the three-order EKC occurs around 2011, demonstrating the effectiveness of the carbon reduction policy. However, the time series model predicts that Beijing will reach the second turning point around 2026, when the gross domestic product (GDP) is about CNY 5000 billion and carbon emissions will begin to increase again. Interpretable machine learning is proposed to explore the socio-economic drivers in carbon emissions, indicating that total energy consumption and GDP contribute the most. Therefore, we should accelerate the upgrading of energy consumption and adjust the industrial structure, thus facilitating Beijing to its peak carbon emissions and achieving carbon neutrality.
Analysis of Interannual Anomalies and Causes of Compound Extreme Wind and Precipitation Events in Spring over the Jiangsu–Anhui Region
Authors: Zhou Jing , Sun Yan , Liu Lei , Zhai Lingli
Published: August 2023

By using the daily average wind speed and precipitation data of 125 stations in Jiangsu and Anhui Provinces of China from 1961 to 2020 and the monthly NCEP/NCAR reanalysis data, the interannual variation characteristics and its possible reasons of spring compound extreme wind and precipitation events in the Jiangsu–Anhui region were discussed. Results show that the spring compound extreme wind and precipitation events generally present a lesser distribution in the south and more in the north. The events occurring in south (north) of 32° N are basically less than (above) three days, and in some areas of northern Jiangsu, it can reach more than four days. On a regional average, the spring compound extreme wind and precipitation events have presented a significant downward trend in the past 60 years. In addition, there was an interdecadal mutation from more to less in the early 1990s, with the most significant decline in the coastal areas of northern Jiangsu. Further analysis reveals that the synthetic height anomaly field at 500 hPa corresponding to the frequent occurrence of the spring compound extreme wind and precipitation events is positive in the northern region of 45° N, while it is negative in the southern region of 45° N, which enhances the high pressure in high latitudes, increases the meridional gradient of circulation, and promotes the activity of high-latitude short-wave trough ridges and cold air. Meanwhile, a strong southwest airflow exists in the corresponding middle and low latitudes at 850 hPa, so the water vapor from the Bay of Bengal can be continuously transported to the Jiangsu–Anhui region. Overall, the abundant water vapor transportation and the convergence of southward cold air in high latitudes are conducive to the occurrence of extreme wind and precipitation events.
Insulin Resistance and Hypertension: Mechanisms Involved and Modifying Factors for Effective Glucose Control
Authors: Sakr Hussein F. , Sirasanagandla Srinivasa Rao , Das Srijit , Bima Abdulhadi I. , Elsamanoudy Ayman Z.
Published: August 2023

Factors such as aging, an unhealthy lifestyle with decreased physical activity, snacking, a standard Western diet, and smoking contribute to raising blood pressure to a dangerous level, increasing the risk of coronary artery disease and heart failure. Atherosclerosis, or aging of the blood vessels, is a physiological process that has accelerated in the last decades by the overconsumption of carbohydrates as the primary sources of caloric intake, resulting in increased triglycerides and VLDL-cholesterol and insulin spikes. Classically, medications ranging from beta blockers to angiotensin II blockers and even calcium channel blockers were used alone or in combination with lifestyle modifications as management tools in modern medicine to control arterial blood pressure. However, it is not easy to control blood pressure or the associated complications. A low-carbohydrate, high-fat (LCHF) diet can reduce glucose and insulin spikes, improve insulin sensitivity, and lessen atherosclerosis risk factors. We reviewed articles describing the etiology of insulin resistance (IR) and its impact on arterial blood pressure from databases including PubMed, PubMed Central, and Google Scholar. We discuss how the LCHF diet is beneficial to maintaining arterial blood pressure at normal levels, slowing down the progression of atherosclerosis, and reducing the use of antihypertensive medications. The mechanisms involved in IR associated with hypertension are also highlighted.
In-Vivo Bactericidal Potential of Mangifera indica Mediated Silver Nanoparticles against Aeromonas hydrophila in Cirrhinus mrigala
Authors: Raza Muhammad Akram , Kanwal Zakia , Riaz Saira , Amjad Maira , Rasool Shafqat , Naseem Shahzad , Abbas Nadeem , Ahmad Naushad , Alomar Suliman Yousef
Published: August 2023

The present study reports the green synthesis of silver nanoparticles from leaves’ extract of Mangifera indica (M. indica) and their antibacterial efficacy against Aeromonas hydrophila (A. hydrophila) in Cirrhinus mrigala (C. mrigala). The prepared M. indica mediated silver nanoparticles (Mi-AgNPs) were found to be polycrystalline in nature, spherical in shapes with average size of 62 ± 13 nm. C. mrigala (n = ±15/group) were divided into six groups i.e., G1: control, G2: A. hydrophila challenged, G3: A. hydrophila challenged + Mi-AgNPs (0.01 mg/L), G4: A. hydrophila challenged + Mi-AgNPs (0.05 mg/L), G5: A. hydrophila challenged + Mi-AgNPs (0.1 mg/L) and G6: A. hydrophila challenged + M. indica extract (0.1 mg/L). Serum biochemical, hematological, histological and oxidative biomarkers were evaluated after 15 days of treatment. The liver enzyme activities, serum proteins, hematological parameters and oxidative stress markers were found to be altered in the challenged fish but showed retrieval effects with Mi-AgNPs treatment. The histological analysis of liver, gills and kidney of the challenged fish also showed regaining effects following Mi-AgNPs treatment. A CFU assay from muscle tissue provided quantitative data that Mi-AgNPs can hinder the bacterial proliferation in challenged fish. The findings of this work suggest that M. indica based silver nanoparticles can be promising candidates for the control and treatment of microbial infections in aquaculture.
WSCNet: Biomedical Image Recognition for Cell Encapsulated Microfluidic Droplets
Authors: Zhou Xiao , Mao Yuanhang , Gu Miao , Cheng Zhen
Published: August 2023

Microfluidic droplets accommodating a single cell as independent microreactors are frequently demanded for single-cell analysis of phenotype and genotype. However, challenges exist in identifying and reducing the covalence probability (following Poisson’s distribution) of more than two cells encapsulated in one droplet. It is of great significance to monitor and control the quantity of encapsulated content inside each droplet. We demonstrated a microfluidic system embedded with a weakly supervised cell counting network (WSCNet) to generate microfluidic droplets, evaluate their quality, and further recognize the locations of encapsulated cells. Here, we systematically verified our approach using encapsulated droplets from three different microfluidic structures. Quantitative experimental results showed that our approach can not only distinguish droplet encapsulations (F1 score > 0.88) but also locate each cell without any supervised location information (accuracy > 89%). The probability of a “single cell in one droplet” encapsulation is systematically verified under different parameters, which shows good agreement with the distribution of the passive method (Residual Sum of Squares, RSS < 0.5). This study offers a comprehensive platform for the quantitative assessment of encapsulated microfluidic droplets.
Skilled Performers Show Right Parietal Lateralization during Anticipation of Volleyball Attacks
Authors: DeCouto Brady S. , Smeeton Nicholas J. , Williams A. Mark
Published: August 2023

Global and local biological motion processing are likely influenced by an observer’s perceptual experience. Skilled athletes anticipating an opponent’s movements use globally distributed motion information, while less skilled athletes focus on single kinematic cues. Published reports have demonstrated that attention can be primed globally or locally before perceptual tasks; such an intervention could highlight motion processing mechanisms used by skilled and less skilled observers. In this study, we examined skill differences in biological motion processing using attentional priming. Skilled (N = 16) and less skilled (N = 16) players anticipated temporally occluded videos of volleyball attacks after being primed using a Navon matching task while parietal EEG was measured. Skilled players were more accurate than less skilled players across priming conditions. Global priming improved performance in both skill groups. Skilled players showed significantly reduced alpha and beta power in the right compared to left parietal region, but brain activity was not affected by the priming interventions. Our findings highlight the importance of right parietal dominance for skilled performers, which may be functional for inhibiting left hemispheric local processing or enhancing visual spatial attention for dynamic visual scenes. Further work is needed to systematically determine the function of this pattern of brain activity during skilled anticipation.
An Analysis of the Qualitative Impacts of Building Information Modelling (BIM) on Life Cycle Cost (LCC): A Qualitative Case Study of the KSA
Authors: Alasmari Esam , Martinez-Vazquez Pedro , Baniotopoulos Charalampos
Published: August 2023

Building information modelling (BIM) continues gaining popularity in engineering construction as it helps lower the life cycle cost and ensure sustainability. The primary aim of this study was to delve into the effectiveness of BIM implementation in the Kingdom of Saudi Arabia (KSA) construction industry and understand the benefits, challenges, and risks associated with it. The present study has incorporated a qualitative and case study research design to investigate the effectiveness of BIM implementation. To this end, information was gathered through interviews involving BIM experts in the KSA, from which a thematic analysis was derived with the help of NVivo software. The results obtained highlight various benefits, challenges, and risks associated with the implementation of BIM tools, also covering the life cycle cost (LCC) and the procurement and type of contracts, initially referred to during the interviews, indicating that the importance of estimating the LCC in a project is crucial in the design phase, which also informs the decision making. In this case, 96.7% of the participants agreed with this view. Moreover, two case studies were analysed to further demonstrate the effectiveness of BIM adoption. The outcomes of this study have the potential to add significant value to various aspects of engineering practice in the KSA.
Emergence of Lipid Droplets in the Mechanisms of Carcinogenesis and Therapeutic Responses
Authors: Delmas Dominique , Cotte Alexia K. , Connat Jean-Louis , Hermetet François , Bouyer Florence , Aires Virginie
Published: August 2023

Cancer shares common risk factors with cardiovascular diseases such as dyslipidemia, obesity and inflammation. In both cases, dysregulations of lipid metabolism occur, and lipid vesicles emerge as important factors that can influence carcinogenesis. In this review, the role of different lipids known to be involved in cancer and its response to treatments is detailed. In particular, lipid droplets (LDs), initially described for their role in lipid storage, exert multiple functions, from the physiological prevention of LD coalescence and regulation of endoplasmic reticulum homeostasis to pathological involvement in tumor progression and aggressiveness. Analysis of LDs highlights the importance of phosphatidylcholine metabolism and the diversity of lipid synthesis enzymes. In many cancers, the phosphatidylcholine pathways are disrupted, modifying the expression of genes coding for metabolic enzymes. Tumor microenvironment conditions, such as hypoxia, different types of stress or inflammatory conditions, are also important determinants of LD behavior in cancer cells. Therefore, LDs represent therapeutic targets in cancer, and many lipid mediators have emerged as potential biomarkers for cancer onset, progression, and/or resistance.
Molecular Classification of Endometrial Cancer and the 2023 FIGO Staging: Exploring the Challenges and Opportunities for Pathologists
Authors: Zheng Wenxin
Published: August 2023

This commentary explores the complexities of the FIGO 2023 staging system and the inclusion of The Cancer Genome Atlas’s (TCGA) molecular classification in the management of endometrial cancer. It highlights the importance of histology as a prognostic tool, while scrutinizing the merits and demerits of its application to aggressive endometrial cancers. The commentary review sheds light on the recent introductions of lymphovascular space invasion (LVSI) and lymph node metastasis size in cancer staging. It outlines the difficulties in differentiating between synchronous and metastatic endometrial and ovarian cancers, underlining their implications on treatment strategies. Furthermore, the commentary discusses the integration of molecular classifications within the FIGO 2023 framework, emphasizing the pivotal yet challenging implementation of the pathogenic POLE mutation test. The commentary concludes by reaffirming the vital role of pathologists in executing the FIGO 2023 staging system.
Patient-Derived Ex Vivo Cultures and Endpoint Assays with Surrogate Biomarkers in Functional Testing for Prediction of Therapeutic Response
Authors: Tsukamoto Yoshiyuki , Hirashita Yuka , Shibata Tomotaka , Fumoto Shoichi , Kurogi Shusaku , Nakada Chisato , Kinoshita Keisuke , Fuchino Takafumi , Murakami Kazunari , Inomata Masafumi , Moriyama Masatsugu , Hijiya Naoki
Published: August 2023

Prediction of therapeutic outcomes is important for cancer patients in order to reduce side effects and improve the efficacy of anti-cancer drugs. Currently, the most widely accepted method for predicting the efficacy of anti-cancer drugs is gene panel testing based on next-generation sequencing. However, gene panel testing has several limitations. For example, only 10% of cancer patients are estimated to have druggable mutations, even if whole-exome sequencing is applied. Additionally, even if optimal drugs are selected, a significant proportion of patients derive no benefit from the indicated drug treatment. Furthermore, most of the anti-cancer drugs selected by gene panel testing are molecularly targeted drugs, and the efficacies of cytotoxic drugs remain difficult to predict. Apart from gene panel testing, attempts to predict chemotherapeutic efficacy using ex vivo cultures from cancer patients have been increasing. Several groups have retrospectively demonstrated correlations between ex vivo drug sensitivity and clinical outcome. For ex vivo culture, surgically resected tumor tissue is the most abundant source. However, patients with recurrent or metastatic tumors do not usually undergo surgery, and chemotherapy may be the only option for those with inoperable tumors. Therefore, predictive methods using small amounts of cancer tissue from diagnostic materials such as endoscopic, fine-needle aspirates, needle cores and liquid biopsies are needed. To achieve this, various types of ex vivo culture and endpoint assays using effective surrogate biomarkers of drug sensitivity have recently been developed. Here, we review the variety of ex vivo cultures and endpoint assays currently available.
Notch, SUMOylation, and ESR-Mediated Signalling Are the Main Molecular Pathways Showing Significantly Different Epimutation Scores between Expressing or Not Oestrogen Receptor Breast Cancer in Three Public EWAS Datasets
Authors: Corsaro Luigi , Gentilini Davide , Calzari Luciano , Gambino Vincenzo
Published: August 2023

Oestrogen receptor expression in breast cancer (BC) cells is a marker of high cellular differentiation and allows the identification of two BC groups (ER-positive and ER-negative) that, although not completely homogeneous, differ in biological characteristics, clinical behaviour, and therapeutic options. The study, based on three publicly available EWAS (Epigenetic Wide Association Study) datasets, focuses on the comparison between these two groups of breast cancer using an epimutation score. The score is calculated not only based on the presence of the epimutation, but also on the deviation amplitude of the methylation outlier value. For each dataset, we performed a functional analysis based first on the functional gene region of each annotated gene (we aggregated the data per gene region TSS1500, TSS200, first-exon, and body-gene identified by the information from the Illumina Data Sheet), and then, we performed a pathway enrichment analysis through the REACTOME database based on the genes with the highest epimutation score. Thus, we blended our results and found common pathways for all three datasets. We found that a higher and significant epimutation score due to hypermethylation in ER-positive BC is present in the promoter region of the genes belonging to the SUMOylation pathway, the Notch pathway, the IFN-γ signalling pathway, and the deubiquitination protease pathway, while a higher and significant level of epimutation due to hypomethylation in ER-positive BC is present in the promoter region of the genes belonging to the ESR-mediated pathway. The presence of this state of promoter hypomethylation in the ESR-mediated signalling genes is consistent and coherent with an active signalling pathway mediated by oestrogen function in the group of ER-positive BC. The SUMOylation and Notch pathways are associated with BC pathogenesis and have been found to play distinct roles in the two BC subgroups. We speculated that the altered methylation profile may play a role in regulating signalling pathways with specific functions in the two subgroups of ER BC.
Minimal Residual Disease Detection at RNA and Leukemic Stem Cell (LSC) Levels: Comparison of RT-qPCR, d-PCR and CD26+ Stem Cell Measurements in Chronic Myeloid Leukemia (CML) Patients in Deep Molecular Response (DMR)
Authors: Abruzzese Elisabetta , Bocchia Monica , Trawinska Malgorzata Monika , Raspadori Donatella , Bondanini Francesco , Sicuranza Anna , Pacelli Paola , Re Federica , Cavalleri Alessia , Farina Mirko , Malagola Michele , Russo Domenico , De Fabritiis Paolo , Bernardi Simona
Published: August 2023

A Deep Molecular Response (DMR), defined as a BCR::ABL1 transcript at levels ≤ 0.01% by RT-qPCR, is the prerequisite for the successful interruption of treatment among patients with Chronic Myeloid Leukemia (CML). However, approximately 50% of patients in Treatment-Free Remission (TFR) studies had to resume therapy after their BCR::ABL1 transcript levels rose above the 0.1% threshold. To improve transcript detection sensitivity and accuracy, transcript levels can be analyzed using digital PCR (dPCR). dPCR increases BCR::ABL1 transcript detection sensitivity 10–100 fold; however, its ability to better select successful TFR patients remains unclear. Beyond the role of the immune system, relapses may be due to the presence of residual leukemic stem cells (LSCs) that are transcriptionally silent. Flow cytometry can be used to identify and quantify circulating bone marrow Ph+ LSCs CD34+/CD38− co-expressing CD26 (dipeptidylpeptidase-IV). To date, the significance of circulating Ph+ LSCs in TFR is unclear. The aim of this work is to compare and examine the values obtained using the three different methods of detecting minimal residual disease (MRD) in CML at RNA (RT-qPCR and dPCR) and LSC (flowcytometry) levels among patients in TFR or exhibiting a DMR. The twenty-seven patients enrolled received treatment with either imatinib (12), dasatinib (6), nilotinib (7), bosutinib (1), or interferon (1). Twelve patients were in TFR, while the rest exhibited a DMR. The TFR patients had stopped therapy for less than 1 year (3), <3 years (2), 6 years (6), and 17 years (1). Blood samples were collected and tested using the three methods at the same time. Both d-PCR and LSCs showed higher sensitivity than RT-qPCR, exhibiting positive results in samples that were undetectable using RT-qPCR (17/27). None of the patients tested negative with d-PCR; however, 23/27 were under the threshold of 0.468 copies/μL, corresponding to a stable DMR. The results were divided into quartiles, and the lowest quartiles defined the lowest MRD. These data were strongly correlated in 15/27 patients, corresponding to almost half of the TFR patients. Indeed, the TFR patients, some lasting up to 17 years, corresponded to the lowest detectable DMR categories. To the best of our knowledge, this is the first attempt to analyze and compare DMRs in a CML population using standard (RT-qPCR) and highly sensitive (dPCR and LSCs) methods.
A Multidimensional Connectomics- and Radiomics-Based Advanced Machine-Learning Framework to Distinguish Radiation Necrosis from True Progression in Brain Metastases
Authors: Cao Yilin , Parekh Vishwa S. , Lee Emerson , Chen Xuguang , Redmond Kristin J. , Pillai Jay J. , Peng Luke , Jacobs Michael A. , Kleinberg Lawrence R.
Published: August 2023

We introduce tumor connectomics, a novel MRI-based complex graph theory framework that describes the intricate network of relationships within the tumor and surrounding tissue, and combine this with multiparametric radiomics (mpRad) in a machine-learning approach to distinguish radiation necrosis (RN) from true progression (TP). Pathologically confirmed cases of RN vs. TP in brain metastases treated with SRS were included from a single institution. The region of interest was manually segmented as the single largest diameter of the T1 post-contrast (T1C) lesion plus the corresponding area of T2 FLAIR hyperintensity. There were 40 mpRad features and 6 connectomics features extracted, as well as 5 clinical and treatment factors. We developed an Integrated Radiomics Informatics System (IRIS) based on an Isomap support vector machine (IsoSVM) model to distinguish TP from RN using leave-one-out cross-validation. Class imbalance was resolved with differential misclassification weighting during model training using the IRIS. In total, 135 lesions in 110 patients were analyzed, including 43 cases (31.9%) of pathologically proven RN and 92 cases (68.1%) of TP. The top-performing connectomics features were three centrality measures of degree, betweenness, and eigenvector centralities. Combining these with the 10 top-performing mpRad features, an optimized IsoSVM model was able to produce a sensitivity of 0.87, specificity of 0.84, AUC-ROC of 0.89 (95% CI: 0.82–0.94), and AUC-PR of 0.94 (95% CI: 0.87–0.97).
Evaluation of Intratumoral Response Heterogeneity in Metastatic Colorectal Cancer and Its Impact on Patient Overall Survival: Findings from 10,551 Patients in the ARCAD Database
Authors: Ou Fang-Shu , Ahn Daniel H. , Dixon Jesse G. , Grothey Axel , Lou Yiyue , Kasi Pashtoon M. , Hubbard Joleen M. , Van Cutsem Eric , Saltz Leonard B. , Schmoll Hans-Joachim , Goldberg Richard M. , Venook Alan P. , Hoff Paulo , Douillard Jean-Yves , Hecht J. Randolph , Hurwitz Herbert , Punt Cornelis J. A. , Koopman Miriam , Bokemeyer Carsten , Fuchs Charles S. , Diaz-Rubio Eduardo , Tebbutt Niall C. , Cremolini Chiara , Kabbinavar Fairooz F. , Bekaii-Saab Tanios , Chibaudel Benoist , Yoshino Takayuki , Zalcberg John , Adams Richard A. , de Gramont Aimery , Shi Qian
Published: August 2023

Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS). Patients and Methods: Patients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic. Results: Among 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85), p < 0.001), although a shorter OS than those with RL only (mOS = 25.8 months, HR (95% CI) = 1.42 (1.32, 1.53), p < 0.001). Among patients with SL/PL, 74% had SD by RECIST 1.1, and they had a longer OS (mOS = 9.0 months) than those with PL only (mOS = 8.0 months, HR (95% CI) = 0.75 (0.57, 0.98), p = 0.040), yet a shorter OS than those with SL only (mOS = 16.8 months, HR (95% CI) = 1.98 (1.80, 2.18), p < 0.001). These associations were consistent across treatment regimen subgroups. The lesion-based response criteria showed slightly higher concordance than RECIST 1.1, although it was not statistically significant. Conclusion: Varied responses at first restaging are common among patients receiving first-line therapy for mCRC. Our lesion-based measurement criteria allowed for better mortality discrimination, which could potentially be informative for treatment decision-making and influence patient outcomes.