bluuebunny/crossref_metadata_2025 huggingface dataset:
Heteronuclear Complexes with Promising Anticancer Activity against Colon Cancer
Authors: Atrián-Blasco Elena , Sáez Javier , Rodriguez-Yoldi Maria Jesús , Cerrada Elena
Published: August 2024

This study investigates the activity of novel gold(I) and copper(I)/zinc(II) heteronuclear complexes against colon cancer. The synthesised heteronuclear Au(I)-Cu(I) and Au(I)-Zn(II) complexes were characterised and evaluated for their anticancer activity using human colon cancer cell lines (Caco-2). The complexes exhibited potent cytotoxicity, with IC50 values in the low micromolar range, and effectively induced apoptosis in cancer cells. In the case of complex [Cu{Au(Spy)(PTA)}2]PF6 (2), its cytotoxicity is ×10 higher than its mononuclear precursor, while showing low cytotoxicity towards differentiated healthy cells. Mechanistic studies revealed that complex 2 inhibits the activity of thioredoxin reductase, a key enzyme involved in redox regulation, leading to an increase in reactive oxygen species (ROS) levels and oxidative stress, in addition to an alteration in DNA’s tertiary structure. Furthermore, the complexes demonstrated a strong binding affinity to bovine serum albumin (BSA), suggesting the potential for effective drug delivery and bioavailability. Collectively, these findings highlight the potential of the investigated heteronuclear Au(I)-Cu(I) and Au(I)-Zn(II) complexes as promising anticancer agents, particularly against colon cancer, through their ability to disrupt redox homeostasis and induce oxidative stress-mediated cell death.
The Interactions between Smoking and Sleep
Authors: Grigoriou Ioanna , Kotoulas Serafeim-Chrysovalantis , Porpodis Konstantinos , Spyratos Dionysios , Papagiouvanni Ioanna , Tsantos Alexandros , Michailidou Anastasia , Mourelatos Constantinos , Mouratidou Christina , Alevroudis Ioannis , Marneri Alexandra , Pataka Athanasia
Published: August 2024

Smoking a cigarette before bed or first thing in the morning is a common habit. In this review, the relationship between smoking and sleep is investigated based on the existing literature. Out of 6504 unique items that were identified via a PubMed search related to smoking and sleep, 151 were included in this review. Tobacco smoking disrupts sleep architecture by reducing slow wave and rapid eye movement (REM) sleep and undermining sleep quality. Furthermore, smoking affects sleep-related co-morbidities, such as obstructive sleep apnea–hypopnea syndrome (OSAHS), insomnia, parasomnias, arousals, bruxism, and restless legs, as well as non-sleep-related conditions such as cardiovascular, metabolic, respiratory, neurologic, psychiatric, inflammatory, gynecologic and pediatric issues, while poor sleep quality also seems to worsen the chances of successful smoking cessation. In conclusion, the existing literature suggests that there is a wicked relation between smoking and sleep.
Analysis of a Regression Model for Creating Surface Microgeometry after Machining Zirconia YML Used for Dental Application
Authors: Duplák Ján , Mikuláško Samuel , Dupláková Darina , Yeromina Maryna , Kaščák Rastislav
Published: August 2024

This article focuses on research in the machining of zirconia crowns for dental implants. Its goal is to find the most suitable cutting parameters that significantly affect the final surface roughness of the crowns for dental implants. This study conducts investigations and experiments to specify the cutting parameters that achieve the optimal surface roughness of zirconia crowns for dental implants. The experiments were designed to precisely determine the cutting parameters that influence the surface roughness of zirconia crowns. The results of this study provide important insights for improving the manufacturing process of zirconia crowns with the specified most suitable cutting parameters. This research contributes to the enhancement of zirconia crown manufacturing techniques and the improvement in the quality and effectiveness of dental implants.
Fractional-Order Boosted Hybrid Young’s Double-Slit Experimental Optimizer for Truss Topology Engineering Optimization
Authors: Qin Song , Liu Junling , Bai Xiaobo , Hu Gang
Published: August 2024

Inspired by classical experiments that uncovered the inherent properties of light waves, Young’s Double-Slit Experiment (YDSE) optimization algorithm represents a physics-driven meta-heuristic method. Its unique search mechanism and scalability have attracted much attention. However, when facing complex or high-dimensional problems, the YDSE optimizer, although striking a good balance between global and local searches, does not converge as fast as it should and is prone to fall into local optimums, thus limiting its application scope. A fractional-order boosted hybrid YDSE, called FYDSE, is proposed in this article. FYDSE employs a multi-strategy mechanism to jointly address the YDSE problems and enhance its ability to solve complex problems. First, a fractional-order strategy is introduced into the dark edge position update of FYDSE to ensure more efficient use of the search potential of a single neighborhood space while reducing the possibility of trapping in a local best. Second, piecewise chaotic mapping is constructed at the initial stage of the population to obtain better-distributed initial solutions and increase the convergence rate to the optimal position. Moreover, the low exploration space is extended by using a dynamic opposition strategy, which improves the probability of acquisition of a globally optimal solution. Finally, by introducing the vertical operator, FYDSE can better balance global exploration and local exploitation and explore new unknown areas. The numerical results show that FYDSE outperforms YDSE in 11 (91.6%) of cec2022 sets. In addition, FYDSE performs best in 8 (66.6%) among all algorithms. Compared with the 11 methods, FYDSE obtains the optimal best and average weights for the 20-bar, 24-bar, and 72-bar truss problems, which proves its efficient optimization capability for difficult optimization cases.
Sesame Detection in Food Using DNA-Functionalized Gold Nanoparticles: A Sensitive, Rapid, and Cost-Effective Colorimetric Approach
Authors: Llano-Suárez Pablo , Sánchez-Visedo Adrián , Ortiz-Gómez Inmaculada , Fernández-Argüelles María Teresa , Prado Marta , Costa-Fernández José Manuel , Soldado Ana
Published: August 2024

Food safety control is a key issue in the food and agriculture industries. For such purposes, developing miniaturized analytical methods is critical for enabling the rapid and sensitive detection of food supplements, allergens, and pollutants. Here, a novel bioanalytical methodology based on DNA-functionalized gold nanoparticles (AuNPs) and colorimetric detection was developed to detect the presence of sesame (a major allergen) through sesame seed DNA as a target, in food samples. The presence of sesame DNA induces controlled nanoparticle aggregation/desegregation, resulting in a color change (from blue to red) proportional to sesame DNA concentration. The incorporation of multicomponent nucleic acid enzymes (MNAzymes) in this strategy has been carried out to perform an isothermal signal amplification strategy to improve the sensitivity of detection. Also, open-source software for color analysis was used to ensure an unbiased visual color-change detection, enhancing detection accuracy and sensitivity and opening the possibility of performing a simple and decentralized analyte detection. The method successfully detected the presence of sesame DNA in sesame seed, sesame oil, olive oil, and sunflower oil. In brief, the developed approach constitutes a simple and affordable alternative to perform a highly sensitive detection of DNA in food without complex methodologies or the requirement of expensive instrumentation.
CleanUpRNAseq: An R/Bioconductor Package for Detecting and Correcting DNA Contamination in RNA-Seq Data
Authors: Liu Haibo , Hu Kai , O’Connor Kevin , Kelliher Michelle A. , Zhu Lihua Julie
Published: August 2024

RNA sequencing (RNA-seq) has become a standard method for profiling gene expression, yet genomic DNA (gDNA) contamination carried over to the sequencing library poses a significant challenge to data integrity. Detecting and correcting this contamination is vital for accurate downstream analyses. Particularly, when RNA samples are scarce and invaluable, it becomes essential not only to identify but also to correct gDNA contamination to maximize the data’s utility. However, existing tools capable of correcting gDNA contamination are limited and lack thorough evaluation. To fill the gap, we developed CleanUpRNAseq, which offers a comprehensive set of functionalities for identifying and correcting gDNA-contaminated RNA-seq data. Our package offers three correction methods for unstranded RNA-seq data and a dedicated approach for stranded data. Through rigorous validation on published RNA-seq datasets with known levels of gDNA contamination and real-world RNA-seq data, we demonstrate CleanUpRNAseq’s efficacy in detecting and correcting detrimental levels of gDNA contamination across diverse library protocols. CleanUpRNAseq thus serves as a valuable tool for post-alignment quality assessment of RNA-seq data and should be integrated into routine workflows for RNA-seq data analysis. Its incorporation into OneStopRNAseq should significantly bolster the accuracy of gene expression quantification and differential expression analysis of RNA-seq data.
Optimizing Telework with Exercise: An Exploration of the Curvilinear Relationship between Telework Intensity and Work Engagement
Authors: Huo Weiwei , Liang Bingqian , Liang Yongmei , Song Mengli , Wang Yixin
Published: August 2024

The sudden COVID-19 crisis disrupted people’s pace of life. Meanwhile, telework has gradually attracted public attention and become a regular mechanism for organizations. In this context, self-regulation theory was utilized to explore the impact of telework intensity on work engagement. Data were collected from 304 employees across three time points, and the results supported a curvilinear relationship between telework intensity and work engagement. Specifically, it was discovered that employees exhibited the highest levels of work engagement at moderate levels of telework intensity. Additionally, based on the strength model of self-control, the research identified self-control as playing a mediating role between telework intensity and work engagement. Finally, the study revealed that the duration of physical exercise moderated the relationship between telework intensity and self-control. Long-term physical exercise was found to prolong and enhance the positive effects of telework intensity on self-control, thereby boosting employee work engagement. This study provided unique and valuable insights into maintaining employee engagement in telework.
Assessing the Impact of Climate Comfort on Labor Productivity in Hydropower Engineering Construction in Southwest China
Authors: Jian Feihong , Guo Qi , Liu Qian , Feng Cong , Liu Jia
Published: August 2024

Labor productivity exerts a significant influence on the construction cycle and investment in hydropower projects. Consequently, it is a crucial factor in the estimation of the cost of hydropower project construction. The mechanisms that are modulated by subjective factors have been extensively studied. However, the assessment of labor productivity in objective environments with regular changes is usually considered using a single factor, especially in special environments where the influence of environmental factors is of greater concern. As the most extensive region of China’s water-energy resources, the Southwest region has a lengthy tradition of using altitude or oxygen as an inherent criterion for the assessment of labor productivity. However, the applicability of inherent standards is limited. Therefore, we tried to assess the spatial and temporal changes in labor productivity based on the changes in meteorological conditions in Southwest China, employing climate comfort indicators in this study. The result identified five distinct regions of climate change in Southwest China (R-I to R-V). In particular, there is minimal variation in labor productivity as assessed by climate comfort indicators and the elevation between R-I and R-II. R-III and R-IV are influenced by oxygen, temperature, and humidity, while R-V is affected by a multitude of factors. Our findings indicate that temporal and spatial variations in meteorological conditions can result in up to a threefold difference in productivity at the same altitude in different regions. Importantly, our study provides valuable theoretical insights for engineering project management. In particular, it can be concluded that altitude is not a reliable indicator for evaluating labor productivity in high-altitude construction.
Numerical Study on the Axial Compression Behavior of Composite Columns with High-Strength Concrete-Filled Steel Tube and Honeycombed Steel Web Subjected to Freeze–Thaw Cycles
Authors: Ji Jing , Xu Yihuan , Jiang Liangqin , Yuan Chaoqing , Liu Yingchun , Hou Xiaomeng , Li Jinbao , Zhang Zhanbin , Chu Xuan , Ma Guiling
Published: August 2024

To investigate the axial compression behavior of composite columns with high-strength concrete-filled steel tube flanges and honeycombed steel web (STHHC) under load during freeze–thaw cycles, 48 full-scale composite column specimens were designed with different parameters: the restraint effect coefficient (ξ), concrete strength (fcu), number of freeze–thaw cycles (nd), slenderness ratio (λ), space–height ratio (s/hw), and hole–height ratio (d/hw). The finite element models of STHHC composite columns were simulated using ABAQUS finite element software (Version: 2021). The modeling method’s rationality was verified by comparing simulation results with experimental outcomes. Based on the finite element model, a parametric analysis of the composite columns under freeze–thaw cycles was conducted, analyzing their failure modes and load-bearing processes. The results indicate that the bearing capacity of the STHHC increased with increases in ξ and fcu, and decreased with a rise in λ. In contrast, the influence of s/hw and d/hw on the ultimate bearing capacity of the composite columns was relatively minor. An equation for calculating the axial bearing capacity of the STHHC composite columns under freeze–thaw cycles was derived using statistical regression methods and considering the impact of different parameters on the axial compressive performance of the composite columns, laying the foundation for the promotion and application of this type of composite column in practical engineering projects.
A Numerical Study of Reinforcement Structure in Shaft Construction Using Vertical Shaft Sinking Machine (VSM)
Authors: Ma Chunjing , Hong Haijian , Yu Long , Liu Keqi , Huang Jiadong
Published: August 2024

Using the Vertical Shaft Sinking Machine (VSM) for shaft construction is an emerging modern technology, which is also currently one of the most advanced techniques in the field of shaft sinking. Current research on VSM technology primarily focuses on mechanical and technical issues, neglecting the impact of the construction on the surrounding soil and the structure itself. This oversight leaves structural design lacking a reliable foundation. Additionally, there is insufficient information on the role of reinforcement design during construction in soft soils. These engineering challenges have hindered the widespread implementation of this new technology. Therefore, a series of numerical models were used to analyse the mechanical behaviour of shaft and soil during or after the sinking process, with the aim of addressing these gaps by investigating the influence of shafts constructed using VSM technology, and providing a scientific basis for reinforcement design in soft soil. The case study shows that increasing the soil-cement strength does not have a significant effect on the overall deformation of the soil surrounding the shaft, but leads to a notable reduction in the plastic zone volume, subsequently enhancing the overall stability of the neighbouring soil. The ring bottom beam design effectively reduces convergence deformation by about 50%, while also improving the horizontal internal force distribution near the cutting edge. However, this approach significantly escalates local vertical bending moments, necessitating thorough consideration in the design stage.
Integrating Underground Space into the Groundscape Resilience Concept
Authors: Omićević Nerma , Zaninović Tamara , Bojanić Obad Šćitaroci Bojana
Published: August 2024

Underground space has always been used as a resilient solution in addressing the need for safety in terms of climate conditions and defense purposes. This research seeks to recognize the potential of the underground space in the city as a significant urban resilience strategy, with the aim of revealing how contemporary underground architecture is integrated with the public spaces on the surface and how this groundscape integration contributes to the quality of the use of the public spaces to achieve urban resilience. Public spaces have a crucial role in the environmental, social, and sustainable context of the city and are considered urban domains for spatial urban intervention that contribute to urban resilience in its broader understanding. Based on the review of underground space research and the comparative analysis of selected contemporary design projects, the research explores the integration of underground space in correlation with its utilization model based on contemporary design projects. The research results in the systematization of underground utilization among underground infrastructure, underground living settlements, and urban development to offer insights into the enhancement of resilience planning through the contemporary multifunctional usage of underground space. The contribution of this research is reflected in the methodology of developing the criteria for a groundscape resilience concept, in terms of perceiving underground space as an integral urban layer, its multifunctional utilization, and in terms of achieving urban resilience.
Experimental Study on Performance and Mechanism of High-Strength Artificial Blocks Based on Dredged Silt
Authors: Zheng Qingsong , Cai Piaoyang , Zeng Yourong , Wang Yun , Feng Ming , Jiang Chaohua
Published: August 2024

This paper investigates the preparation and properties of high-strength artificial blocks made from dredged silt with a clay content of 52.0%. A comparative analysis of the mechanical properties of dredged silt blocks produced using semi-dry pressing and vibration molding methods was conducted. The study examined the effects of using fly ash (FA) and ground granulated blast-furnace slag (GGBS) as substitutes for cement on the compressive strength, splitting tensile strength, and dry shrinkage of the blocks. Additionally, the microstructure of the dredged silt blocks was analyzed using scanning electron microscopy (SEM), mercury intrusion porosimetry (MIP), and thermogravimetric analysis. The results show that specimens prepared using the pressing method exhibit better mechanical performance with compressive and splitting tensile strength reaching 64.8 MPa and 5.6 MPa at 28 d, respectively, which increased by 111.07% and 143.48% compared to specimens prepared through vibration molding. The addition of FA and GGBS reduces the early strength of the block to a certain extent but without a significant adverse effect on later strength. GGBS demonstrates faster hydration and a better filling effect. The addition of GGBS or FA refines the pore structure and reduces the diameter of pores in the paste, which is beneficial for improving the dry shrinkage performance of the block. At 120 d, the dry shrinkage of blocks containing 50% FA and GGBS shows a reduction of 29.7% and 27.1%, respectively, compared to blocks made with cement. The properties of the silt blocks can be notably enhanced through mechanical force, particle gradation, and hydration action. The preparation of artificial blocks such as road bricks and ballast blocks using dredged soil as the main raw material has been applied in projects such as the Yangtze River waterway regulation in China and Skikda Port in Algeria.
Effects of the Presence of Suberin in the Cork of Cerasus jamasakura (Siebold ex Koidz.) H. Ohba on the High Toughness Behaviour
Authors: Saito Hayato , Nakai Takahisa , Toba Keisuke , Kanbayashi Toru
Published: August 2024

Cork, the outermost tissue of bark, plays an important role in protecting trees from the surrounding environment and is used for various purposes, including flooring and insulation materials for buildings. This study focused on the amount and distribution of hydrophobic substances such as suberin and lignin in cork, as well as moisture conditions, to understand the mechanical properties of Cerasus jamasakura cork. Strips of cork were subjected to tensile tests after exposure to various moisture conditions (water-saturated, air-dried and oven-dried), and also after the desuberinisation and delignification of specimens. Cork with a high moisture content showed significant strain to the tensile load, whereas oven-dried specimens showed little toughness. The increased toughness of cork at higher moisture contents was due to the continued elongation in the plastic region, especially in the inner cork. The fibre length of the highly deformed cork differed significantly before and after the tensile test. Tensile tests of cork after desuberinisation and delignification indicated that the removal of suberin caused an earlier reduction in tensile properties than the removal of lignin. The presence of suberin in cork, distributed mainly in the inner cork, is believed to affect the tensile properties of cork.
Study of a Novel Updraft Tower Power Plant Combined with Wind and Solar Energy
Authors: Wang Qiong , Chen Meng , Ren Longhui , Zhan Xinhang , Wei Yili , Jiang Zhiyuan
Published: August 2024

This study presents a novel solar updraft tower power plant (SUTPP) system, which has been designed to achieve the simultaneous utilization of solar and wind energy resources in desert regions, in response to the pressing demand for sustainable and efficient renewable energy solutions. The aim of this research was to develop an integrated system that is capable of harnessing and converting these abundant energy sources into electrical power, thereby enhancing the renewable energy portfolio in arid environments. The methodology of this study involved the design and construction of a prototype SUTPP, comprising a 53 m high tower, a 6170 m2 collector, five horizontal-axis wind turbines, and a thermal energy storage layer made up of pebbles and sand. The experimental setup was meticulously detailed, and experiments were conducted to collect data on the system’s performance under various environmental conditions. Subsequently, three-dimensional numerical simulations were performed to explore the effects of ambient wind speed and solar radiation on the output power of the SUTPP. The results indicate that the output power of the system increases with the increase in ambient wind speed and solar radiation. The impact of solar irradiation on output power was observed to diminish as ambient wind speeds increased. Notably, as the inlet wind speed rose from 4 m/s to 12 m/s, the output power showed a substantial increase of 727%. The numerical simulations revealed that ambient wind speed has a more pronounced effect on power output compared to solar radiation. Furthermore, it was found that the influence of solar radiation is significant at low wind speeds, with its impact decreasing as wind speed increases. This research provides essential guidance for the design and engineering of highly efficient solar thermal energy utilization projects, representing a significant advancement in the field of renewable energy technology deployment in desert environments.
Experimental Study on Improving the Performance of Cement Mortar with Self-Synthesized Viscosity-Reducing Polycarboxylic Acid Superplasticizer
Authors: Wang Zigeng , Shen Yonghao , Li Yue , Tian Yuan
Published: August 2024

In this study, a viscosity-reducing polycarboxylic acid superplasticizer (VRPCE) was synthesized using methylallyl polyoxyethylene ether (HPEG), acrylic acid (AA), and maltodextrin maleic acid monoester (MDMA) as the main raw materials. The influences of the VRPCE on the microscopic properties of cement paste were studied by gel permeation chromatography (GPC), total organic carbon test (TOC), zeta potential, laser particle size analysis, XRD, MIP, TG, and SEM. Finally, the effects of the VRPCE on the macroscopic properties of cement mortar were evaluated through flow time, slump flow, compressive strength, shrinkage, and creep. The results showed that the VRPCE can improve the hydration degree of the cement, optimize the pore structure, increase the porosity, improve the fluidity, compressive strength, and creep, and decrease the shrinkage resistance of the cement mortar.
Examining Dark Triad Traits in Formal Leaders and Their Impact on Employee Workplace Stress: A Comparative Study of Family and Non-Family Businesses
Authors: Pimentel Duarte , Lagarto Sofia , Marques-Quinteiro Pedro
Published: August 2024

This paper aims to explore differences between the perception of dark traits in formal leaders and levels of workplace stress among employees working in family and non-family businesses. Furthermore, we assess if the company nature (family-owned versus non-family-owned) moderates the relationship between the employees’ perception of dark triad traits in their formal leaders and their workplace stress levels. The empirical evidence is provided by a sample of 220 Portuguese employees who responded to a questionnaire that included their perceptions of their formal leaders’ dark triad traits and workplace stress measures. All respondents are employed in small and medium-sized private companies, holding no management responsibilities and under formal hierarchical supervision. The initial ideas that family firms’ employees perceive higher levels of dark triad traits in their formal leaders than non-family firms’ employees and that they also show higher levels of workplace stress than non-family firms’ employees were confirmed. The results also support the notion that higher perceptions of dark triad traits in formal leaders are related with higher levels of workplace stress of employees and that the company nature significantly moderates this relationship. These findings enhance the research literature by addressing two often overlooked aspects in the comparison between family and non-family firms. Additionally, they provide valuable insights into the relationship between dark triad traits in formal leaders and employee workplace stress levels.
From Tumor Macroenvironment to Tumor Microenvironment: The Prognostic Role of the Immune System in Oral and Lung Squamous Cell Carcinoma
Authors: Battista Rosa Alessia , Pini Giacomo Maria , Finco Alex , Corso Filippo , Galli Andrea , Arrigoni Gianluigi , Doglioni Claudio , Callea Marcella , Paccagnella Matteo , Porcu Luca , Filipello Federica , Mazzola Marco , Foggetti Giorgia , Gregorc Vanesa , Giordano Leone , Bussi Mario , Mirabile Aurora , Veronesi Giulia
Published: August 2024

Background: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. Methods: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. Results: Associations were found between systemic inflammation markers—NLR, MLR, and PLR—and tumor microenvironment factors, such as TILs and CD8+ cell prevalence—elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. Discussion: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response’s role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. Conclusions: Future integration into cancer classification could improve risk stratification and treatment guidance.
Cell Culture Models for Translational Research on Thymomas and Thymic Carcinomas: Current Status and Future Perspectives
Authors: Müller Denise , Loskutov Jürgen , Küffer Stefan , Marx Alexander , Regenbrecht Christian R. A. , Ströbel Philipp , Regenbrecht Manuela J.
Published: August 2024

Cell culture model systems are fundamental tools for studying cancer biology and identifying therapeutic vulnerabilities in a controlled environment. TET cells are notoriously difficult to culture, with only a few permanent cell lines available. The optimal conditions and requirements for the ex vivo establishment and permanent expansion of TET cells have not been systematically studied, and it is currently unknown whether different TET subtypes require different culture conditions or specific supplements. The few permanent cell lines available represent only type AB thymomas and thymic carcinomas, while attempts to propagate tumor cells derived from type B thymomas so far have been frustrated. It is conceivable that epithelial cells in type B thymomas are critically dependent on their interaction with immature T cells or their three-dimensional scaffold. Extensive studies leading to validated cell culture protocols would be highly desirable and a major advance in the field. Alternative methods such as tumor cell organoid models, patient-derived xenografts, or tissue slices have been sporadically used in TETs, but their specific contributions and advantages remain to be shown.
Adverse In-Hospital Outcomes after Radical Prostatectomy in Leukemia History Patients
Authors: Falkenbach Fabian , Di Bello Francesco , Rodriguez Peñaranda Natali , Longoni Mattia , Marmiroli Andrea , Le Quynh Chi , Tian Zhe , Goyal Jordan A. , Longo Nicola , Micali Salvatore , Briganti Alberto , de Cobelli Ottavio , Chun Felix K. H. , Saad Fred , Shariat Shahrokh F. , Budäus Lars , Graefen Markus , Karakiewicz Pierre I.
Published: August 2024

Introduction: Leukemia history affects some radical prostatectomy (RP) patients. Although its prevalence and effect as an adverse risk factor are well known in cardiac surgery, the number of RP patients with a leukemia history, as well as their rate of adverse in-hospital outcomes, are unknown. Methods: We identified RP patients (National Inpatient Sample 2000–2019), stratified according to the presence or absence of a leukemia history. Descriptive analyses, propensity score matching (PSM, ratio 1:10), and multivariable logistic regression models were used. Results: Of 259,939 RP patients, 416 (0.2%) had a leukemia history. Their proportion increased from 0.1 to 0.2% covering the study span (p < 0.01). Leukemia history patients were older (median age, 64 vs. 62 years, p < 0.001). After PSM for age, insurance status, ethnicity, pelvic lymph node dissection, and Charlson Comorbidity Index, leukemia history RP patients exhibited higher rates of acute kidney injury (<2.6 vs. 0.9%; Odds Ratio [OR] 2.0, p = 0.02), more frequently underwent dialysis (3.6 vs. 1.9%; OR 1.9, p = 0.03), and more frequently had a length of stay exceeding one week (4.8 vs. 2.5%; OR 2.0, p = 0.006). Conclusions: Although leukemia history RP patients are rare, their numbers have increased. Renal complications and extended hospital stays are more frequent in those individuals.
Discrimination of Lung Cancer and Benign Lung Diseases Using BALF Exosome DNA Methylation Profile
Authors: Batochir Chinbayar , Kim In Ae , Jo Eun Ji , Kim Eun-Bi , Kim Hee Joung , Hur Jae Young , Kim Do Won , Park Hee Kyung , Lee Kye Young
Published: August 2024

Benign lung diseases are common and often do not require specific treatment, but they pose challenges in the distinguishing of them from lung cancer during low-dose computed tomography (LDCT). This study presents a comprehensive methylation analysis using real-time PCR for minimally invasive diagnoses of lung cancer via employing BALF exosome DNA. A panel of seven epigenetic biomarkers was identified, exhibiting specific methylation patterns in lung cancer BALF exosome DNA. This panel achieved an area under the curve (AUC) of 0.97, with sensitivity and specificity rates of 88.24% and 97.14%, respectively. Each biomarker showed significantly higher mean methylation levels (MMLs) in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) compared to non-cancer groups, with fold changes from 1.7 to 13.36. The MMLs of the biomarkers were found to be moderately elevated with increasing patient age and smoking history, regardless of sex. A strong correlation was found between the MMLs and NSCLC stage progression, with detection sensitivities of 79% for early stages and 92% for advanced stages. In the validation cohort, the model demonstrated an AUC of 0.95, with 94% sensitivity and specificity. Sensitivity for early-stage NSCLC detection improved from 88.00% to 92.00% when smoking history was included as an additional risk factor.
Preoperative and Intraoperative Identification of Sentinel Lymph Nodes in Melanoma Surgery
Authors: Leong Stanley P. , Nosrati Mehdi , Wu Max C. , Torre Donald M. , Bartley Ted F. , Kim Kevin B. , Soon Christopher , Moretto John , Kashani-Sabet Mohammed
Published: August 2024

According to the American Joint Commission on Cancer (AJCC) 8th edition guidelines, SLN biopsy is recommended for primary melanomas with a Breslow thickness of at least 1 mm. Additionally, the National Comprehensive Cancer Network (NCCN) recommends that a SLN biopsy may be considered for melanoma patients with T1b lesions, which are 0.8–1 mm thick or less than 0.8 mm thick with ulceration. It can also be considered for T1a lesions that are less than 0.8 mm thick but have other adverse features, such as a high mitotic rate, lymphovascular invasion, or a positive deep margin. To reduce the false negative rate of melanoma SLN biopsy, we have introduced the intraoperative use of Sentinella, a gamma camera, to enhance the identification rate of SLNs beyond that of the traditional gamma hand-held probe. At the Center for Melanoma Research and Treatment at the California Pacific Medical Center, a multidisciplinary approach has been established to treat melanoma patients when the diagnosis of primary melanoma is made with a referral to our melanoma center. This comprehensive approach at the melanoma tumor board, including the efforts of pathologists, radiologists, dermatologists, surgical, medical and radiation oncologists, results in a consensus to deliver personalized and high-quality care for our melanoma patients. This multidisciplinary program for the management of melanoma can be duplicated for other types of cancer. This article consists of current knowledge to document the published methods of identification of sentinel lymph nodes. In addition, we have included new data as developed in our melanoma center as newly published materials in this article to demonstrate the utility of these methods in melanoma sentinel lymph node surgery. Informed consent has been waived by our IRB regarding the acquisition of clinical data as presented in this study.
Real-World Survival Impact of New Treatment Strategies for Lung Cancer: A 2000–2020 French Cohort
Authors: Basse Clemence , Carton Matthieu , Milder Maud , Geiss Romain , Du Rusquec Pauline , Daniel Catherine , Massiani Marie-Ange , Livartowski Alain , Girard Nicolas
Published: August 2024

Over the past 20 years, several innovative therapies have been implemented in the treatment of lung cancer that have had reported survival benefits in clinical trials. Whether these improvements translate into the clinic setting has not been studied yet. We retrospectively analyzed all patients consecutively treated at Institute Curie for metastatic lung cancer. Diagnosis date was used to define three periods, based on the approvals of novel treatment strategies in the first-line setting, including targeted therapies in 2010 and immunotherapy in 2018. Endpoints included Overall survival (OS), survival rate of 2 years and 5 years, and a conditional survival rate of 2 years (if still alive at 6 months from treatment initiation). A total of 673 patients were identified for Period 1—2000 to 2009, 752 for Period 2—2010 to 2017, and 768 for Period 3—2018 to 2020. Median OS in the whole cohort was 11.1, 15.5, and 16.2 months, respectively. Median OS for patients with NSCLC or SCLC was 11.2, 17.2, and 18.2 months, or 10.9, 11.7, and 11.2 months, respectively. The two-year conditional survival was more favorable for NSCLC than SCLC patients. Outcomes were statistically higher for women as compared to men in all periods and all subgroups. Survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC, along with the implementation of novel treatment strategies.
Identification of Poliovirus Receptor-like 3 Protein as a Prognostic Factor in Triple-Negative Breast Cancer
Authors: Leone Gian Marco , Mangano Katia , Caponnetto Salvatore , Fagone Paolo , Nicoletti Ferdinando
Published: August 2024

Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, with a bad prognosis and lack of targeted therapeutic options. Characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, TNBC is often associated with a significantly lower survival rate compared to other breast cancer subtypes. Our study aimed to explore the prognostic significance of 83 immune-related genes, by using transcriptomic data from the TCGA database. Our analysis identified the Poliovirus Receptor-Like 3 protein (PVRL3) as a critical negative prognostic marker in TNBC patients. Furthermore, we found that the Enhancer of Zeste Homolog 2 (EZH2), a well-known epigenetic regulator, plays a pivotal role in modulating PVRL3 levels in TNBC cancer cell lines expressing EZH2 along with high levels of PVRL3. The elucidation of the EZH2-PVRL3 regulatory axis provides valuable insights into the molecular mechanisms underlying TNBC aggressiveness and opens up potential pathways for personalized therapeutic intervention.
Overexpression of Toxic Poly(Glycine-Alanine) Aggregates in Primary Neuronal Cultures Induces Time-Dependent Autophagic and Synaptic Alterations but Subtle Activity Impairments
Authors: Steffke Christina , Agarwal Shreya , Kabashi Edor , Catanese Alberto
Published: August 2024

The pathogenic expansion of the intronic GGGGCC hexanucleotide located in the non-coding region of the C9orf72 gene represents the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation leads to the accumulation of toxic RNA foci and dipeptide repeats (DPRs), as well as reduced levels of the C9orf72 protein. Thus, both gain and loss of function are coexisting pathogenic aspects linked to C9orf72-ALS/FTD. Synaptic alterations have been largely described in C9orf72 models, but it is still not clear which aspect of the pathology mostly contributes to these impairments. To address this question, we investigated the dynamic changes occurring over time at the synapse upon accumulation of poly(GA), the most abundant DPR. Overexpression of this toxic form induced a drastic loss of synaptic proteins in primary neuron cultures, anticipating autophagic defects. Surprisingly, the dramatic impairment characterizing the synaptic proteome was not fully matched by changes in network properties. In fact, high-density multi-electrode array analysis highlighted only minor reductions in the spike number and firing rate of poly(GA) neurons. Our data show that the toxic gain of function linked to C9orf72 affects the synaptic proteome but exerts only minor effects on the network activity.
Calcium Deregulation in Neurodegeneration and Neuroinflammation in Parkinson’s Disease: Role of Calcium-Storing Organelles and Sodium–Calcium Exchanger
Authors: Bastioli Guendalina , Piccirillo Silvia , Graciotti Laura , Carone Marianna , Sprega Giorgia , Taoussi Omayema , Preziuso Alessandra , Castaldo Pasqualina
Published: August 2024

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that lacks effective treatment strategies to halt or delay its progression. The homeostasis of Ca2+ ions is crucial for ensuring optimal cellular functions and survival, especially for neuronal cells. In the context of PD, the systems regulating cellular Ca2+ are compromised, leading to Ca2+-dependent synaptic dysfunction, impaired neuronal plasticity, and ultimately, neuronal loss. Recent research efforts directed toward understanding the pathology of PD have yielded significant insights, particularly highlighting the close relationship between Ca2+ dysregulation, neuroinflammation, and neurodegeneration. However, the precise mechanisms driving the selective loss of dopaminergic neurons in PD remain elusive. The disruption of Ca2+ homeostasis is a key factor, engaging various neurodegenerative and neuroinflammatory pathways and affecting intracellular organelles that store Ca2+. Specifically, impaired functioning of mitochondria, lysosomes, and the endoplasmic reticulum (ER) in Ca2+ metabolism is believed to contribute to the disease’s pathophysiology. The Na+-Ca2+ exchanger (NCX) is considered an important key regulator of Ca2+ homeostasis in various cell types, including neurons, astrocytes, and microglia. Alterations in NCX activity are associated with neurodegenerative processes in different models of PD. In this review, we will explore the role of Ca2+ dysregulation and neuroinflammation as primary drivers of PD-related neurodegeneration, with an emphasis on the pivotal role of NCX in the pathology of PD. Consequently, NCXs and their interplay with intracellular organelles may emerge as potentially pivotal players in the mechanisms underlying PD neurodegeneration, providing a promising avenue for therapeutic intervention aimed at halting neurodegeneration.
The Novel-m0230-3p miRNA Modulates the CSF1/CSF1R/Ras Pathway to Regulate the Cell Tight Junctions and Blood–Testis Barrier in Yak
Authors: Yan Qiu , Wang Qi , Zhang Yong , Yuan Ligang , Hu Junjie , Zhao Xingxu
Published: August 2024

The yak (Bos grunniens) is a valuable livestock animal endemic to the Qinghai–Tibet Plateau in China with low reproductive rates. Cryptorchidism is one of the primary causes of infertility in male yaks. Compared with normal testes, the tight junctions (TJs) of Sertoli cells (SCs) and the integrity of the blood–testis barrier (BTB) in cryptorchidism are both disrupted. MicroRNAs are hairpin-derived RNAs of about 19–25 nucleotides in length and are involved in a variety of biological processes. Numerous studies have shown the involvement of microRNAs in the reproductive physiology of yak. In this study, we executed RNA sequencing (RNA-seq) to describe the expression profiles of mRNAs and microRNAs in yaks with normal testes and cryptorchidism to identify differentially expressed genes. GO and KEGG analyses were used to identify the biological processes and signaling pathways which the target genes of the differentially expressed microRNAs primarily engaged. It was found that novel-m0230-3p is an important miRNA that significantly differentiates between cryptorchidism and normal testes, and it is down-regulated in cryptorchidism with p < 0.05. Novel-m0230-3p and its target gene CSF1 both significantly contribute to the regulation of cell adhesion and tight junctions. The binding sites of novel-m0230-3p with CSF1 were validated by a dual luciferase reporter system. Then, mimics and inhibitors of novel-m0230-3p were transfected in vitro into SCs, respectively. A further analysis using qRT-PCR, immunofluorescence (IF), and Western blotting confirmed that the expression of cell adhesion and tight-junction-related proteins Occludin and ZO-1 both showed changes. Specifically, both the mRNA and protein expression levels of Occludin and ZO-1 in SCs decreased after transfection with the novel-m0230-3p mimics, while they increased after transfection with the inhibitors, with p < 0.05. These were achieved via the CSF1/CSF1R/Ras signaling pathway. In summary, our findings indicate a negative miRNA-mRNA regulatory network involving the CSF1/CSF1R/Ras signaling pathway in yak SCs. These results provide new insights into the molecular mechanisms of CSF1 and suggest that novel-m0230-3p and its target protein CSF1 could be used as potential therapeutic targets for yak cryptorchidism.
Correction: Bo et al. Atg5 Regulates Selective Autophagy of the Parental Macronucleus during Tetrahymena Sexual Reproduction. Cells 2021, 10, 3071
Authors: Bo Tao , Kang Yu , Liu Ya , Xu Jing , Wang Wei
Published: August 2024

In the original publication [...]
Translating Anti-Inflammatory Strategies for Atherosclerosis: Deep Phenotyping, Next-Generation Drug Targets, and Precision Medicine
Authors: Asare Yaw , Georgakis Marios K.
Published: August 2024

Atherosclerosis is the main pathology underlying cardiovascular disease (CVD), including myocardial infarction and ischemic stroke [...]