bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mediating Role of Time Perspective in the Relationship between Chronotype and Suicide in Bipolar Disorder
Authors: Karaytuğ Mahmut Onur , Tamam Lut , Demirkol Mehmet Emin , Namlı Zeynep , Gürbüz Mahmut , Yeşiloğlu Caner , Eriş Davut Özge
Published: December 2022

(1) Background: Suicide in patients with bipolar disorder (BD) is related to the chronotype of the person from a biological perspective. However, it is not known whether there is a relationship between suicide and psychological time in BD. The aim of our study was to evaluate the relationship between time perspective (TP) and suicide and the effect of TP on the relationship between suicide and chronotype in euthymic patients with BD. (2) Methods: We included 150 BD patients and 84 healthy controls in this cross-sectional study. We administered the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Beck Scale for Suicidal Ideation (BSSI), Zimbardo Time Perspective Inventory (ZTPI), and Morning–Evening Questionnaire (MEQ). (3) Results: There was a statistically significant difference between the median scores of past negative TP, present fatalistic TP, future TP, and MEQ total score (p < 0.001, p < 0.001, p = 0.010, and p = 0.020, respectively). There was a significant correlation between past negative TP, future TP, MEQ scores, and BSSI scores in the patient group (p < 0.001, p = 0.018, and p = 0.028, respectively). An inverse and significant relationship between the MEQ total score and BSSI score and TP types had a mediator role in this relationship. (4) Conclusions: Our study shows that TP, which evaluates time from a psychological perspective, has a direct relationship with suicidal ideation and a mediating role in the relationship between chronotype and suicide. According to our results, we can conclude that ZTPI can also be used to evaluate the risk of suicidality in patients with BD. Appropriate therapy methods for TP may help to prevent some suicide attempts.
Maximizers’ Susceptibility to the Effect of Frequency vs. Percentage Format in Risk Representation
Authors: Misuraca Raffaella , Faraci Palmira , Scaffidi Abbate Costanza
Published: December 2022

The present study explored the susceptibility of maximizers to the effect of the specific information format—frequency vs. percentage—in a risk assessment task. One-hundred and fourteen participants were randomized into two experimental conditions: a frequency format and a percentage format. In both conditions, participants had to rate the level of risk that a mental patient would harm someone after his discharge from a mental health facility, based on the information reported in the psychologist’s assessment for that patient. In the frequency condition, the information was presented in terms of frequencies, whereas in the percentage condition the same information was presented in terms of percentage. Our experiment showed that resolute maximizers are less affected by the specific format of the task than fearful maximizers. Thus, we conclude that resolute maximizers are more normative decision-makers. Theoretical and practical implications are discussed.
Grey Correlation Analysis between Macro Mechanical Damage and Meso Volume Characteristics of SBS Modified Asphalt Mixture under Freeze-Thaw Cycles
Authors: Wang Wensheng , Xia Wenlei , Liang Jiaxiang
Published: December 2022

The effect of freeze–thaw (F–T) in the seasonal frozen area would lead to damage to asphalt pavement. After water enters asphalt pavement, the water in voids would expand at a lower temperature, which could change the void content and number, affecting the macro mechanical properties of the asphalt mixture. The rapid development of CT scanning and digital image processing (DIP) provides powerful technical support for the research of asphalt mixture meso volume characteristics. In this paper, the mechanical properties of basalt fiber reinforced asphalt mixture subjected to F–T cycles were tested at different temperatures to clarify the decay law of mechanical properties under F–T cycles. Then, the meso images of the asphalt mixture under various F–T cycles could be obtained by using CT tomography. Based on DIP technology, the meso characteristic parameters of CT images for asphalt mixture were extracted, and the development of asphalt mixture freeze–thaw damage was further analyzed. The test results showed that with the F–T cycle, the macro mechanical properties of the asphalt mixture rapidly declined in the early stage of the F–T cycle and gradually tended to be flat. There would be serious damage inside the asphalt mixture in the late stage of the F–T cycle. The damage to the mechanical properties of the asphalt mixture under the F–T cycle can be attributed to the change in the internal mesostructure of the asphalt mixture. Based on the grey relational analysis theory, the formation of the connected void was the main factor affecting the damage in the early stage of the F–T cycle, while the formation of new voids mainly affected the later development of F-T damage.
Aerosol OT Quantity Impacts on Calcium Nitrate Self-Healing Microcapsule Properties Used for Sustainable Construction Applications
Authors: Taqa Ala Abu , Suleiman Ghassan , Senouci Ahmed , Al-Haddad Mwfeq , Al-Masri Dua’a Omran , Al-Ansari Mohamed , Mohsen Mohamed O.
Published: December 2022

This paper is a continuation of a previously published paper on this issue that studied the microencapsulation of calcium nitrate in urea-formaldehyde shell using Aerosol OT (AOT) in hexane solution. The aim of this paper is to determine the quantity of AOT that optimizes microcapsule distribution, diameter, and shell thickness. Different quantities of AOT, namely 0.25 g, 0.50 g, 1.5 g, and 2.5 g were dissolved in 180 g of hexane solution to prepare the continuous phase. A Scanning Electron Microscopy (SEM) was used to characterize the distribution and the diameters of the prepared microcapsules. A Transmission Electron Microscopy (TEM) was used to investigate the microcapsule shell thicknesses. The SEM images have shown that using 0.25 g of AOT may be insufficient to totally polymerize the whole quantity of the core materials into fully independent capsules. On the other hand, using 0.50 g of AOT has shown a uniform distribution and almost complete polymerization of the core material components into distinct microcapsules. Higher quantities of AOT (i.e., 1.50 g and 2.5 g) have resulted in agglomerated microcapsules and nonuniform distributions. The results have also demonstrated that the quantity of AOT does not have a significant impact on the microcapsule diameter. Microcapsule average shell thicknesses were found to decrease by increasing AOT amount up to 0.50 g and to increase again due to the agglomeration witnessed for increased AOT quantity. Accordingly, 0.50 g of AOT was recommended for the preparation of calcium nitrate microcapsules in future research work.
Degradation Behavior of the Preload Force of High-Strength Bolts after Corrosion
Authors: Kong Zhengyi , Jin Ya , Hong Shaozheng , Liu Quanwei , Vu Quang-Viet , Kim Seung-Eock
Published: December 2022

Corrosion significantly affects the structural behavior of members in a connection (i.e., the thickness of steel plates, the preload force of bolts, and the friction factor of steel plates). Safety assessment of corroded steel frames (i.e., beam-to-column connection, beams, or columns) has been a major concern in engineering. In this work, an experiment of accelerated corrosion testing is carried out to obtain corroded specimens connected with high-strength bolts, and the preload force of high-strength bolts (PF-HSB) is monitored throughout the whole stage of the corrosion testing. Before the corrosion testing, the PF-HSB caused by the stress relaxation is also recorded. The PF-HSB decreases rapidly in the first five hours after the final screwing of bolts and it keeps stable after 100 h. The PF-HSB is seriously affected by corrosion, which decreases by 30.0% of the original preload force when the corrosion rate of steel plate reaches 3.5%. A finite element method for predicting the PF-HSB after corrosion is proposed. An estimation model for the PF-HSB considering the stress relaxation is established. A degradation model for predicting the PF-HSB after corrosion is also suggested, and is in good agreement with experimental data. The results of this research are of great significance for the safety assessment of in-service steel structures.
The Effect of Exposure Conditions on the Properties of Cementitious Composites with Reduced Electrical Resistivity
Authors: Uher Vojtěch , Černý Vít , Drochytka Rostislav , Baránek Šimon
Published: December 2022

Cement composite materials with reduced resistivity are specialized building materials, which are constantly pushing their limits. Research into these composites requires a study of the influences of exposure conditions on resistivity. The mixes selected for the purpose of the research included the reference, pure cement mix, and mixes with proportions of graphite under and above the percolation threshold, with two different types of graphite. It was found that the resistivity of all the tested mixes decreases if moisture grows; the influence of moisture is more significant for mixes with graphite proportions below the percolation threshold. The resistivity of all the tested mixes decreases with increasing temperatures; the influence of a higher temperature (50 °C) is more significant for mixes with graphite proportions above the percolation threshold; however, these mixes are, at the same time, more resistant to permanent changes in resistivity caused by frost (−10 °C). It was found that the action of CO2 causes a reduction in resistivity. Mixes with proportions of graphite above the percolation threshold show higher stability when exposed to CO2. Mixes with proportions of graphite below the percolation threshold are extremely sensitive to horizontally oriented pressure loads. Increases in resistivity caused by vertical pressure loads were by 20–40%. The resistivity of the mixes with proportions of graphite above the percolation threshold was less sensitive to the pressure load.
Wind-Induced Interference Effect of Chamfered Square Cylinders in Tandem and Side-by-Side Arrangements
Authors: Zhang Jie , Li Fanghui , Zhang Zhibo , Zhang Te , Wang Cheng , Xiang Benjun , Zhang Yuji
Published: December 2022

A large-eddy simulation analysis technique is introduced in this paper to determine the interference effect of chamfered square cylinders, which is crucial to predict the impact of wind pressure and load on chamfered high-rise buildings. Based on the grid convergence analysis of the model and the validation of its accuracy, the aerodynamic interference effect, including the flow field distribution of parallel and tandem square cylinders with different spacing ratios has been compared and analyzed. The influence regulation and formation mechanism of the wind pressure interference effect have been explored. For side-by-side chamfered corners square cylinders, the average drag coefficient mainly shows an amplification effect, and the fluctuating lift coefficient mainly shows a reduction effect. When B/L = 1.5, the interference factor of the disturbed square cylinder reaches a maximum, which is located at the back flow field on the adjacent side. There is a clear critical spacing ratio for tandem double-cut square cylinders. When the spacing ratio exceeds the critical value, significant changes are observed in the aerodynamic performance. These include wind pressure distribution, non-Gaussian characteristics, and the interference effects of structures.
Experimental Study on Flexural Behavior of Seawater Sea-Sand Concrete Beams Reinforced with Superelastic Shape Memory Alloy Bars
Authors: Qian Hui , Chen Guolin , Li Zongao , Chen Cheng
Published: December 2022

In order to research the flexural behavior of shape memory alloy (SMA)-reinforced seawater sea-sand concrete (SWSSC) beams and improve their self-healing ability, three SMA SWSSC beams and one anti-corrosive steel bar SWSSC beam were designed. The influence of the reinforcement ratio, strength grade of SWSSC and type of reinforcement on the flexural performance of the beam were considered. The failure process, maximum crack width, mid-span deflection, displacement ductility and stiffness degradation of beams were studied by cyclic loading tests. The test results showed that the number of cracks in SMA-reinforced beams were significantly smaller than that in anti-corrosive-reinforced beams, and the crack width and mid-span deflection recovery effect were better after unloading. However, the effect of increasing the SMA reinforcement ratio on crack recovery was not obvious. The increase in SMA reinforcement ratio and the strength grade of SWSSC can significantly improve the bearing capacity of the beam and the stiffness, but the stiffness degradation rate decreased. Moreover, the ductility of concrete beams with SMA bars was significantly increased.
A Novel Structural Damage Identification Method Using a Hybrid Deep Learning Framework
Authors: He Yingying , Huang Zhenghong , Liu Die , Zhang Likai , Liu Yi
Published: December 2022

In the past few years, structural health monitoring (SHM) has become an important technology to ensure the safety of structures. Structural damage identification methods based on machine learning techniques have gained wide attention due to the advantages of effectively extracting features from monitoring data. However, the existing machine learning-based methods heavily depend on manually selected feature parameters from raw signals. This will cause the selected feature to obtain the optimal solution for a specific condition but may fail to provide a similar performance in other cases. In addition, the feature selection takes a long time, which can fail to achieve real-time performance in a practical structure. To address these problems, this article proposes a hybrid deep learning framework for structural damage identification that includes three components, namely, ensemble empirical mode decomposition (EEMD), Pearson correlation coefficient (PCC), and a convolutional neural network (CNN). The proposed EEMD-PCC-CNN method is capable of automatically extracting features from raw signals to satisfy any damage identification objective. To evaluate the performance of the proposed EEMD-PCC-CNN method, a three-story building structure is investigated. The acceleration signal of the three-story building structure is first analyzed by EEMD. After obtaining the time-frequency information, PCC is utilized to select optimal time-frequency information as the input of the CNN for damage identification. Compared with other classical methods (SVM, KNN, RF, etc.), the experimental results show that the newly proposed EEMD-PCC-CNN method has significant performance advantages in damage identification. In addition, the accuracy of the proposed damage identification method is improved by more than 4% after utilizing EEMD in comparison with CNN alone.
Grid-Connected Solar Photovoltaic (PV) System for Covered Linkways
Authors: Kuang Wendy Yiwen , Illankoon Chethana , Vithanage Sadith Chinthaka
Published: December 2022

Solar photovoltaic (PV) technology is a current trend worldwide, offering many environmental benefits. With the flagship SolarNova Programme in Singapore, solar PV has gained its momentum. However, it remains important to explore new avenues to introduce solar PV in the urban settings. The housing development board (HDB) green towns promote sustainable living. Therefore, introducing solar PV is essential. This research study aims to propose and conduct an economic evaluation on solar PV for the HDB’s covered linkways. HDB covered linkways connect buildings within the green towns. Hence, installing solar PV systems in covered linkways facilitates to self-produce required energy and export extra electricity to the grid. This research study used PVWatts calculator to calculate the power generation. A thin film solar PV is used for the study with fixed array type and azimuth is 180°. Four solar PV systems, namely (1) 4 kW, (2) 5 kW, (3)10 kW, and (4) 20 kW, were evaluated in this research study. The initial cost ranges from S$7000 to S$38,000 for the four types. For 4 kW and 5 kW systems, the payback period is 6.22 years. The highest payback period is for a 20-kW system, which is 7.4 years. The 10-kW system generates a significant portion of the electricity requirements, and the payback period is 6.04 years. This research contributes to the solar PV domain by proposing a novel grid-connected solar PV system for covered linkways while identifying the most cost-effective solution.
The Evolution, Hotspots, and Trends in Research on Facilities of Combined Medical and Nursing Care for the Elderly
Authors: Chen Zhe , Yao Qiang , An Na
Published: December 2022

With the significant increase in global ageing and its derivative risks, governments and academic communities have been widely concerned with research on facilities of combined medical and nursing care for the elderly (FCMNCE). Using Citespace and VOSviewer bibliometric software, in this paper, we explore the evolutionary phases, hotspots, and trends in research on FCMNCE. First, the concept and connotation of FCMNCE are clarified. Secondly, based on a bibliometric analysis of the number of annual publications, disciplinary distribution, publication sources, and country distribution, we classify research on FCMNCE into four phases: the exploratory phase of influencing factors, the constructive phase of combined medical and nursing care patterns, the improvement phase of life quality, and the synergistic development phase of science and technology. Thirdly, based on a bibliometric analysis of keyword clustering, annual overlap, and burst keywords, the research hotspots of FCMNCE are identified. Finally, we predicts that future research on FCMNCE will be characterized by the trends of smart elderly facilities, smart medical services, and public health risks. Our conclusion can help researchers to understand the research status and development trends of FCMNCE and select future research directions based on their disciplinary background.
Experimental Study on Self-Compacting Concrete-Filled Thin-Walled Steel Tube Columns
Authors: Wang Yunyang , Zhang Liqing , Jia Yandong , Li Li
Published: December 2022

Concrete-filled steel tubes present excellent structural and constructional performances because they ideally combine the advantage of concrete and steel tube. Thus, they are widely used in civil infrastructures. However, they inevitably suffer from either hard compacting or high costs. Thus, convenient and rapid construction for compacting concrete and cost saving are the urgent challenges for concrete-filled steel tubes. Therefore, this study investigates filling a thin-walled steel tube with self-compacting concrete to solve the challenges presented by traditional concrete-filled steel tube columns, such as poor compacting performance and high costs. This experimental study tests self-compacting concrete-filled thin-walled steel tube (SCCFTST) columns under concentric compression from loading to failure. Effects of wall thickness of the thin-walled steel tube on the failure modes, load-deformation behaviors, and the ultimate loads of the SCCFTST columns are comprehensively investigated. The ultimate loads between experiments and their calculated values in terms of design codes are also compared. The results suggest that buckling on thin-walled steel tube surface is the typical failure mode. The amount of local buckling increases with decreasing wall thickness, and the decreasing rate of the load-deformation curves in the descending branch decreases by increasing the wall thickness, as well as the ultimate load increasing with increases wall thickness. The ACI and CECS are the most conservative and accurate design codes, respectively, for predicting the ultimate load. Therefore, the SCCFTST columns can be used as structural components in civil infrastructures and their peak loads can be calculated using design codes for conventional concrete-filled steel tube columns. However, modification measures must be taken while predicting the ultimate loads of the SCCFTST columns by design codes. The experimental results of this paper can contribute towards the application of SCCFTST columns in practice.
Axial Capacity of FRP-Reinforced Concrete Columns: Computational Intelligence-Based Prognosis for Sustainable Structures
Authors: Arora Harish Chandra , Kumar Sourav , Kontoni Denise-Penelope N. , Kumar Aman , Sharma Madhu , Kapoor Nishant Raj , Kumar Krishna
Published: December 2022

Due to the corrosion problem in reinforced concrete structures, the use of fiber-reinforced polymer (FRP) bars may be preferred in place of traditional reinforcing steel. FRP bars are used in concrete constructions to boost the strength of structural elements and retain their longevity. In this study, the axial load carrying capacity (ALCC) of the FRP-reinforced concrete columns has been evaluated using analytical, as well as machine learning, models. A total of fourteen popular analytical models and one proposed machine learning-based model were used to estimate the ALCC of the concrete columns. The proposed machine learning model is based on an artificial neural network (ANN) method. The performance of the ANN, as well as the analytical models, are assessed using six different performance indices. The R-value of the developed ANN model is 0.9758, followed by an NS value of 0.9513. It has been found that the mean absolute percentage error of the best-fitted analytical model is 328.71% higher than the ANN model, and the root-mean-square error value of the best-fitted analytical model is 211.97% higher than the ANN model. The evaluated data demonstrate that the proposed ANN model performs better than the other analytical models. The developed model is quick and easy-to-use to estimate the axial capacity of the FRP-reinforced concrete columns.
Modeling of Damping Characteristics of Rubber Geopolymer Concrete Based on Finite Element Simulation
Authors: Chen Guozhen , Zhang Derun , Xu Wen , Sun Jie
Published: December 2022

The stacking of waste rubber tires has led to serious environmental pollution. As an attempt to reduce pollution, rubber tires have recently been ground into rubber particles and incorporated into the geopolymer concrete to enhance the damping characteristics of concrete. Thus, we designed this study to quantify the effect of rubber particles on improving the damping performance of geopolymer concrete. The free vibration simulation of a rubber geopolymer concrete cantilever beam at four different rubber replacement volume fractions under five different damage displacements was performed on the ABAQUS platform. The damping loss factor, energy consumption, and modal shape of the cantilever beams under different damage displacements, as well as different rubber replacement volume fractions, were analyzed. The results showed that rubber particles significantly enhanced the damping characteristics of geopolymer concrete, and a certain amount of rubber particles could enhance the total energy consumption of concrete. The damping loss factor of geopolymer concrete was not closely related to its modal shape but mainly related to damage displacement and rubber particle replacement volume fraction. Altogether, these findings provide some technical references for the vibration resistance design of rubber geopolymer concrete.
Study of Hybrid Modification with Humic Acids of Environmentally Safe Biodegradable Hydrogel Films Based on Hydroxypropyl Methylcellulose
Authors: Miroshnichenko Denis , Lebedeva Katerina , Cherkashina Anna , Lebedev Vladimir , Tsereniuk Oleksandr , Krygina Natalia
Published: December 2022

The possibility of increasing the complexity of the operational properties of environmentally safe biodegradable polymer hydrogel materials based on hydroxypropyl methylcellulose due to modification by humic acids from lignite is considered. As a result of this research, environmentally safe hybrid hydrogel films with antibacterial properties were received. In the framework of physicochemical studies, it was determined by IR spectroscopy that hydroxypropyl methylcellulose modified with humic acids hybridmaterials are received by the mechanism of matrix synthesis, which is accompanied by hydroxypropyl methylcellulose crosslinking through multipoint interaction with the carboxyl group of humic acids. Regularities in terms of changes in water absorption, gelation time, and mold emergence time regarding the environmentally safe biodegradable polymer hydrogel materials based on hydroxypropyl methylcellulose depending on the humic acid content were revealed. It was established that the optimal humic acid content in environmentally safe biodegradable hydrogel films with bactericidal properties based on hydroxypropyl methylcellulose is 15% by mass. It was also established that the hybrid modification of hydroxypropyl methylcellulose with humic acids allows them to preserve their biodegradation properties while giving them antibacterial properties. The environmentally safe biodegradable hydrogel films with bactericidal properties based on hydroxypropyl methylcellulose and humic acids are superior in their operational characteristics to known similar biodegradable hydrogel films based on natural biopolymers.
Splicing-Disrupting Mutations in Inherited Predisposition to Solid Pediatric Cancer
Authors: Alba-Pavón Piedad , Alaña Lide , Astigarraga Itziar , Villate Olatz
Published: December 2022

The prevalence of hereditary cancer in children was estimated to be very low until recent studies suggested that at least 10% of pediatric cancer patients carry a germline mutation in a cancer predisposition gene. A significant proportion of pathogenic variants associated with an increased risk of hereditary cancer are variants affecting splicing. RNA splicing is an essential process involved in different cellular processes such as proliferation, survival, and differentiation, and alterations in this pathway have been implicated in many human cancers. Hereditary cancer genes are highly susceptible to splicing mutations, and among them there are several genes that may contribute to pediatric solid tumors when mutated in the germline. In this review, we have focused on the analysis of germline splicing-disrupting mutations found in pediatric solid tumors, as the discovery of pathogenic splice variants in pediatric cancer is a growing field for the development of personalized therapies. Therapies developed to correct aberrant splicing in cancer are also discussed as well as the options to improve the diagnostic yield based on the increase in the knowledge in splicing.
The Role of Single-Nucleotide Polymorphisms in Cholangiocarcinoma: A Systematic Review
Authors: Wang Guanwu , Heij Lara Rosaline , Liu Dong , Dahl Edgar , LANG Sven Arke , Ulmer Tom Florian , LUEDDE Tom , Neumann Ulf Peter , Bednarsch Jan
Published: December 2022

Single-nucleotide polymorphisms (SNPs) play an essential role in various malignancies, but their role in cholangiocarcinoma (CCA) remains to be elucidated. Therefore, the purpose of this systematic review was to evaluate the association between SNPs and CCA, focusing on tumorigenesis and prognosis. A systematic literature search was carried out using PubMed, Embase, Web of Science and the Cochrane database for the association between SNPs and CCA, including literature published between January 2000 and April 2022. This systematic review compiles 43 SNPs in 32 genes associated with CCA risk, metastatic progression and overall prognosis based on 34 studies. Susceptibility to CCA was associated with SNPs in genes related to inflammation (PTGS2/COX2, IL6, IFNG/IFN-γ, TNF/TNF-α), DNA repair (ERCC1, MTHFR, MUTYH, XRCC1, OGG1), detoxification (NAT1, NAT2 and ABCC2), enzymes (SERPINA1, GSTO1, APOBEC3A, APOBEC3B), RNA (HOTAIR) and membrane-based proteins (EGFR, GAB1, KLRK1/NKG2D). Overall oncological prognosis was also related to SNPs in eight genes (GNB3, NFE2L2/NRF2, GALNT14, EGFR, XRCC1, EZH2, GNAS, CXCR1). Our findings indicate that multiple SNPs play different roles at various stages of CCA and might serve as biomarkers guiding treatment and allowing oncological risk assessment. Considering the differences in SNP detection methods, patient ethnicity and corresponding environmental factors, more large-scale multicentric investigations are needed to fully determine the potential of SNP analysis for CCA susceptibility prediction and prognostication.
Three-Dimensional Cell Culture Systems in Pediatric and Adult Brain Tumor Precision Medicine
Authors: Riedel Nicole C. , de Faria Flavia W. , Alfert Amelie , Bruder Jan M. , Kerl Kornelius
Published: December 2022

Primary brain tumors often possess a high intra- and intertumoral heterogeneity, which fosters insufficient treatment response for high-grade neoplasms, leading to a dismal prognosis. Recent years have seen the emergence of patient-specific three-dimensional in vitro models, including organoids. They can mimic primary parenteral tumors more closely in their histological, transcriptional, and mutational characteristics, thus approximating their intratumoral heterogeneity better. These models have been established for entities including glioblastoma and medulloblastoma. They have proven themselves to be reliable platforms for studying tumor generation, tumor–TME interactions, and prediction of patient-specific responses to establish treatment regimens and new personalized therapeutics. In this review, we outline current 3D cell culture models for adult and pediatric brain tumors, explore their current limitations, and summarize their applications in precision oncology.
The Microbiome in PDAC—Vantage Point for Future Therapies?
Authors: Pfisterer Nina , Lingens Catharina , Heuer Cathleen , Dang Linh , Neesse Albrecht , Ammer-Herrmenau Christoph
Published: December 2022

Microorganisms have been increasingly implicated in the pathogenesis of malignant diseases, potentially affecting different hallmarks of cancer. Despite the fact that we have recently gained tremendous insight into the existence and interaction of the microbiome with neoplastic cells, we are only beginning to understand and exploit this knowledge for the treatment of human malignancies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid tumor with limited therapeutic options and a poor long-term survival. Recent data have revealed fascinating insights into the role of the tumoral microbiome in PDAC, with profound implications for survival and potentially therapeutic outcomes. In this review, we outline the current scientific knowledge about the clinical and translational role of the microbiome in PDAC. We describe the microbial compositions in healthy and tumoral pancreatic tissue and point out four major aspects of the microbiome in PDAC: pathogenesis, diagnosis, treatment, and prognosis. However, caution must be drawn to inherent pitfalls in analyzing the intratumoral microbiome. Among others, contamination with environmental microbes is one of the major challenges. To this end, we discuss different decontamination approaches that are crucial for clinicians and scientists alike to foster applicability and physiological relevance in this translational field. Without a definition of an exact and reproducible intratumoral microbial composition, the exploitation of the microbiome as a diagnostic or therapeutic tool remains theoretical.
Systematic Investigation of the Diagnostic and Prognostic Impact of LINC01087 in Human Cancers
Authors: De Palma Fatima Domenica Elisa , Carbonnier Vincent , Salvatore Francesco , Kroemer Guido , Pol Jonathan G. , Maiuri Maria Chiara
Published: December 2022

(1) Background: Long non-coding RNAs may constitute epigenetic biomarkers for the diagnosis, prognosis, and therapeutic response of a variety of tumors. In this context, we aimed at assessing the diagnostic and prognostic value of the recently described long intergenic non-coding RNA 01087 (LINC01087) in human cancers. (2) Methods: We studied the expression of LINC01087 across 30 oncological indications by interrogating public resources. Data extracted from the TCGA and GTEx databases were exploited to plot receiver operating characteristic curves (ROC) and determine the diagnostic performance of LINC01087. Survival data from TCGA and KM-Plotter directories allowed us to graph Kaplan–Meier curves and evaluate the prognostic value of LINC01087. To investigate the function of LINC01087, gene ontology (GO) annotation and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed. Furthermore, interactions between LINC01087 and both miRNA and mRNA were studied by means of bioinformatics tools. (3) Results: LINC01087 was significantly deregulated in 7 out of 30 cancers, showing a predominant upregulation. Notably, it was overexpressed in breast (BC), esophageal (ESCA), and ovarian (OV) cancers, as well as lung squamous cell carcinoma (LUSC), stomach adenocarcinoma (STAD), and uterine carcinosarcoma (UCS). By contrast, LINC01087 displayed downregulation in testicular germ cell tumors (TGCT). ROC curve analyses identified LINC01087 as a potential diagnostic indicator in BC, ESCA, OV, STAD, and TGCT. Moreover, high and low expression of LINC01087 predicted a favorable prognosis in BC and papillary cell carcinoma, respectively. In silico analyses indicated that deregulation of LINC01087 in cancer was associated with a modulation of genes related to ion channel, transporter, and peptide receptor activity. (4) Conclusions: the quantification of an altered abundance of LINC01087 in tissue specimens might be clinically useful for the diagnosis and prognosis of some hormone-related tumors, including BC, OV, and TGCT, as well as other cancer types such as ESCA and STAD. Moreover, our study revealed the potential of LINC01087 (and perhaps other lncRNAs) to regulate neuroactive molecules in cancer.
The Impact of Facility Surgical Caseload Volumes on Survival Outcomes in Patients Undergoing Radical Cystectomy
Authors: Cacciamani Giovanni E. , Barzi Afsaneh , Eppler Michael B. , Lara Primo N. , Pan Chong-Xian , Bhanvadia Sumeet K. , Gill Parkash , Aron Monish , Gill Inderbir , Sadeghi Sarmad
Published: December 2022

The role of surgical experience and its impact on the survival requires further investigation. A cohort of patients undergoing radical cystectomy or anterior pelvic exenteration for localized bladder cancer between 2006 and 2013 at 1143 facilities across the United States was identified using the National Cancer Database and analyzed. Using overall survival (OS) as the primary outcome, the relationship between facility annual caseload (FAC) and facility annual surgical caseload (FASC) for those undergoing curative surgery was examined. Four volume groups (VG) depending on caseload using both FAC and FASC were defined. These included VG1: below 50th percentile, VG2: 50th–74th percentile, VG3: 75th–89th percentile, and VG4: 90th and above. Between 2006 and 2013, 27,272 patients underwent surgery for localized bladder cancer. The median OS was 59.66 months (95% CI: 57.79–61.77). OS improved significantly as caseload increased. The unadjusted median OS difference between VG1 and VG4 was 15.35 months (64.3 vs. 48.95 months, HR 1.19 95% CI: 1.13–1.25, p < 0.001) for FAC. This figure was 19.84 months (66.89 vs. 47.05 months, HR 1.25 95% CI: 1.18–1.32, p < 0.0001) for FASC. This analysis revealed a significant and clinically important survival advantage for curative bladder cancer surgery at highly experienced centers.
High Serum Levels of IL-6 Predict Poor Responses in Patients Treated with Pembrolizumab plus Axitinib for Advanced Renal Cell Carcinoma
Authors: Sang Yun Beom , Yang Hannah , Lee Won Suk , Lee Seung Joon , Kim Seul-Gi , Cheon Jaekyung , Kang Beodeul , Kim Chang Woo , Chon Hong Jae , Kim Chan
Published: December 2022

Renal cell carcinoma (RCC) is the most common type of kidney malignancy worldwide with Pembrolizumab and axitinib treatment (Pembro/Axi) amongst the most effective first-line immunotherapies for advanced RCC. However, it remains difficult to predict treatment response and early resistance. Therefore, we evaluated whether baseline serum interleukin-6 (IL-6) could be a predictive biomarker. Between November 2019 and December 2021, 58 patients with advanced RCC were enrolled, administered first-line Pembro/Axi, and baseline blood samples were analyzed using flow cytometry. The mean baseline serum IL-6 concentration was 8.6 pg/mL in responders and 84.1 pg/mL in patients with progressive disease. The IL-6 cut-off value was set at 6.5 pg/mL using time-dependent receiver operating characteristic curves, with 37.9% of patients having high baseline serum IL-6 levels and 62.1% having low levels. Objective response rates were 58.3% and 36.4% in low and high IL-6 groups, respectively. Overall survival and progression-free survival were longer in patients with low IL-6 levels than in those with high levels. High IL-6 levels were related to reduced interferon-γ and tumor necrosis factor-α production from CD8+ T cells. Overall, high baseline serum IL-6 levels were associated with worse survival outcomes and reduced T-cell responses in Pembro/Axi-treated advanced RCC patients.
Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic Regulation
Authors: Godfrey Laura C. , Rodriguez-Meira Alba
Published: December 2022

Epigenetic modifications, such as histone modifications and DNA methylation, are essential for ensuring the dynamic control of gene regulation in every cell type. These modifications are associated with gene activation or repression, depending on the genomic context and specific type of modification. In both cases, they are deposited and removed by epigenetic modifier proteins. In acute myeloid leukemia (AML), the function of these proteins is perturbed through genetic mutations (i.e., in the DNA methylation machinery) or translocations (i.e., MLL-rearrangements) arising during leukemogenesis. This can lead to an imbalance in the epigenomic landscape, which drives aberrant gene expression patterns. New technological advances, such as CRISPR editing, are now being used to precisely model genetic mutations and chromosomal translocations. In addition, high-precision epigenomic editing using dCas9 or CRISPR base editing are being used to investigate the function of epigenetic mechanisms in gene regulation. To interrogate these mechanisms at higher resolution, advances in single-cell techniques have begun to highlight the heterogeneity of epigenomic landscapes and how these impact on gene expression within different AML populations in individual cells. Combined, these technologies provide a new lens through which to study the role of epigenetic modifications in normal hematopoiesis and how the underlying mechanisms can be hijacked in the context of malignancies such as AML.
Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma
Authors: González-Borja Iranzu , Viúdez Antonio , Alors-Pérez Emilia , Goñi Saioa , Amat Irene , Ghanem Ismael , Pazo-Cid Roberto , Feliu Jaime , Alonso Laura , López Carlos , Arrazubi Virginia , Gallego Javier , Pérez-Sanz Jairo , Hernández-García Irene , Vera Ruth , Castaño Justo P , Fernández-Irigoyen Joaquín
Published: December 2022

Despite its relative low incidence, PDAC is one of the most aggressive and lethal types of cancer, being currently the seventh leading cause of cancer death worldwide, with a 5-year survival rate of 10.8%. Taking into consideration the necessity to improve the prognosis of these patients, this research has been focused on the discovery of new biomarkers. For this purpose, patients with BL and resectable disease were recruited. Serum cytokines and growth factors were monitored at different time points using protein arrays. Immune cell populations were determined by flow cytometry in peripheral blood as well as by immunohistochemistry (IHC) in tumor tissues. Several cytokines were found to be differentially expressed between the study subgroups. In the BL disease setting, two different scores were proven to be independent prognostic factors for progression-free survival (PFS) (based on IL-10, MDC, MIF, and eotaxin-3) and OS (based on eotaxin-3, NT-3, FGF-9, and IP10). In the same context, CA19-9 was found to play a role as independent prognostic factor for OS. Eotaxin-3 and MDC cytokines for PFS, and eotaxin-3, NT-3, and CKβ8-1 for OS, were shown to be predictive biomarkers for nab-paclitaxel and gemcitabine regimen. Similarly, oncostatin, BDNF, and IP10 cytokines were proven to act as predictive biomarkers regarding PFS, for FOLFIRINOX regimen. In the resectable cohort, RANTES, TIMP-1, FGF-4, and IL-10 individually differentiated patients according to their cancer-associated survival. Regarding immune cell populations, baseline high levels of circulating B lymphocytes were related to a significantly longer OS, while these levels significantly decreased as progression occurred. Similarly, baseline high levels of helper lymphocytes (CD4+), low levels of cytotoxic lymphocytes (CD8+), and a high CD4/CD8 ratio, were related to a significantly longer PFS. Finally, high levels of CD4+ and CD8+ intratumoural infiltration was associated with significantly longer PFS. In conclusion, in this study we were able to identify several prognostic and predictive biomarker candidates in patients diagnosed of resectable or BL PDAC.
Association of Pretreatment Physical and Geriatric Parameters with Treatment Tolerance and Survival in Elderly Patients with Stage I–II Non-Small Cell Lung Cancer: An Evaluation of Usual Care Data
Authors: Voorn Melissa J. J. , Bootsma Merle F. R. , Bootsma Gerben P. , van Kampen-van den Boogaart Vivian E. M. , van Riet Geerten J. A. , de Ruysscher Dirk K. , Bongers Bart C. , Janssen-Heijnen Maryska L. G.
Published: December 2022

In this study, the association of pretreatment physical and geriatric parameters with treatment tolerance and survival in elderly patients with stage I–II NSCLC was evaluated. Retrospective data for patients aged ≥70 years, diagnosed between 2016 and 2020 with stage I–II NSCLC, and who underwent surgery or stereotactic ablative radiotherapy (SABR) in a large Dutch teaching hospital were retrieved from medical records. Associations of pretreatment physical and geriatric parameters with treatment tolerance and survival were analyzed. Of 160 patients, 49 of 104 (47%) patients who underwent surgery and 21 of 56 (38%) patients who received SABR did not tolerate treatment. In univariable analysis, World Health Organization (WHO) performance status ≥ 2, short nutritional assessment questionnaire score > 1, short physical performance battery score ≤ 9, and geriatric-8 score ≤ 14 were significantly associated with postoperative complications. Forced expiratory volume of one second < 80% of predicted was significantly associated with intolerance of SABR. In multivariable analysis, WHO performance status ≥ 2 and diffusing capacity for carbon monoxide < 80% were significantly associated with decreased overall survival. This is the first study that investigated the association between pretreatment physical and geriatric parameters and treatment outcomes in patients with stage I–II NSCLC. Evaluation of physical and geriatric parameters before treatment initiation seems highly recommended to select patients who might benefit from preventive interventions before and/or during treatment.
Selecting the Best Approach for the Treatment of Multiple Non-Metastatic Hepatocellular Carcinoma
Authors: Cassese Gianluca , Han Ho-Seong , Cho Jai Young , Lee Hae-Won , Lee Boram , Troisi Roberto Ivan
Published: December 2022

According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the optimal strategy for patients with multiple HCC within the Milan Criteria is liver transplantation (LT). However, LT cannot be offered to all the patients due to organ shortages and long waiting lists, as well as because of the advanced disease carrying a high risk of poor outcomes. For early stages, liver resection (LR) or thermal ablation (TA) can be proposed, while trans-arterial chemoembolization (TACE) still remains the treatment of choice for intermediate stages (BCLC-B). Asian guidelines and the National Comprehensive Cancer Network suggest LR for resectable multinodular HCCs, even beyond Milan criteria. In this scenario, a growing body of evidence shows better outcomes after surgical resection when compared with TACE. Trans-arterial radioembolization (TARE) and stereotaxic body radiation therapy (SBRT) can also play an important role in this setting. Furthermore, the role of minimally invasive liver surgery (MILS) specifically for patients with multiple HCC is still not clear. This review aims to summarize current knowledge about the best therapeutical strategy for multiple HCC while focusing on the role of minimally invasive surgery and on the most attractive future perspectives.
Correlation of Transcriptomics and FDG-PET SUVmax Indicates Reciprocal Expression of Stemness-Related Transcription Factor and Neuropeptide Signaling Pathways in Glucose Metabolism of Ewing Sarcoma
Authors: Prexler Carolin , Knape Marie Sophie , Erlewein-Schweizer Janina , Roll Wolfgang , Specht Katja , Woertler Klaus , Weichert Wilko , von Luettichau Irene , Rossig Claudia , Hauer Julia , Richter Guenther H. S. , Weber Wolfgang , Burdach Stefan
Published: December 2022

Background: In Ewing sarcoma (EwS), long-term treatment effects and poor survival rates for relapsed or metastatic cases require individualization of therapy and the discovery of new treatment methods. Tumor glucose metabolic activity varies significantly between patients, and FDG-PET signals have been proposed as prognostic factors. However, the biological basis for the generally elevated but variable glucose metabolism in EwS is not well understood. Methods: We retrospectively included 19 EwS samples (17 patients). Affymetrix gene expression was correlated with maximal standardized uptake value (SUVmax) using machine learning, linear regression modelling, and gene set enrichment analyses for functional annotation. Results: Expression of five genes correlated (MYBL2, ELOVL2, NETO2) or anticorrelated (FAXDC2, PLSCR4) significantly with SUVmax (adjusted p-value ≤ 0.05). Additionally, we identified 23 genes with large SUVmax effect size, which were significantly enriched for “neuropeptide Y receptor activity (GO:0004983)” (adjusted p-value = 0.0007). The expression of the members of this signaling pathway (NPY, NPY1R, NPY5R) anticorrelated with SUVmax. In contrast, three transcription factors associated with maintaining stemness displayed enrichment of their target genes with higher SUVmax: RNF2, E2F family, and TCF3. Conclusion: Our large-scale analysis examined comprehensively the correlations between transcriptomics and tumor glucose utilization. Based on our findings, we hypothesize that stemness may be associated with increased glucose uptake, whereas neuroectodermal differentiation may anticorrelate with glucose uptake.
Correction: Diamant et al. Effectiveness of Early Radical Cystectomy for High-Risk Non-Muscle Invasive Bladder Cancer. Cancers 2022, 14, 3797
Authors: Diamant Elliott , Roumiguié Mathieu , Ingels Alexandre , Parra Jérôme , Vordos Dimitri , Bajeot Anne-Sophie , Chartier-Kastler Emmanuel , Soulié Michel , de la Taille Alexandre , Rouprêt Morgan , Seisen Thomas
Published: December 2022

In the original article [...]