bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of Studies Supporting Metaphorical Embodiment
Authors: Khatin-Zadeh Omid , Farsani Danyal , Hu Jiehui , Eskandari Zahra , Zhu Yanjiao , Banaruee Hassan
Published: July 2023

This paper presents a review of studies that have provided evidence supporting metaphorical embodiment. These studies are divided into three categories of behavioral, neuroimaging, and corpus studies. After summing up the findings of these studies, it is concluded that metaphorical embodiment is supported by these three lines of research. This is followed by a review of a number of studies that have measured sensorimotor and action effector strengths of various concepts. Then, the idea of sensorimotor and action effector strength of concepts is linked to metaphorical embodiment to present the main idea of the paper. Based on the findings of studies that have measured sensorimotor and action effector strengths of concepts, it is suggested that the degree of involvement of sensorimotor systems in mental simulation of metaphoric actions may not be at the same level in all metaphors. It depends on the sensorimotor strength of the base of the metaphor in various modalities. If the base of a metaphor has a high degree of perceptual strength in a certain modality, that modality plays the most important role in the processing of that metaphor, while other modalities take less important roles. In other words, depending on the sensorimotor strengths of the base of a metaphor in various modalities, those modalities have various levels of importance in the processing of that metaphor. If the base of the metaphor is weak in all modalities, modal resources can come into play to process that metaphor.
Trilingual and Multicultural Experiences Mitigating Students’ Linguistic Stereotypes: Investigating the Perceptions of Undergraduates of Chinese Heritage Regarding Native/Non-Native English Teachers
Authors: Yang Minmin , McAllister Gretchen , Huang Bin
Published: July 2023

Student stereotyping of non-native English-speaking teachers is a common focus of research and there is a paucity of studies targeting trilingual students of multicultural backgrounds. The present study aims to investigate the dimensions of trilingual Chinese heritage undergraduates’ perceptions of English teachers from Kachru’s stratification of native-English-speaking (Inner-circle), ESL (Outer-circle) and EFL (Expanding-circle) regions. A mixed study design was used to collect data including online questionnaires and an offline semi-structured interview. Quantitative findings indicate the subjects’ preference for native speaking teachers, together with a hierarchical ranking in teacher assessments according to race/ethnicity. Qualitative findings demonstrate that students are also less biased on racial grounds, considering all teachers are “qualified and good enough”, hence the “Inner > Outer > Expanding = Qualified > Unqualified” result. Multilingual and multicultural factors have been used to account for the mitigated linguistic stereotypes from sociocultural and political perspectives. Findings of this study challenge but nevertheless also confirm to some extent the traditional native/non-native dichotomy that manifests raciolinguistic traits and support Kachru’s stratification with statistical evidence. Educational implications are discussed to benefit future practice to further eliminate student prejudice and to better prepare native Chinese teachers of the English language.
Time Matters: Time Perspectives Predict Intertemporal Prosocial Preferences
Authors: Lu Teng , Liang Dapeng , Hong Mei
Published: July 2023

The study utilizes the Chinese version of the Zimbardo Time Perspective Inventory (ZTPI-C) and a novelty intertemporal prosocial discounting paradigm to explore the preferences of individuals with the Present Impulsive Time Perspective (PITP) and the Future Time Perspective (FTP) in intertemporal prosocial choices, and uncovers the cognitive mechanisms underpinning intertemporal altruism from the personality traits. The findings revealed: (1) The donation behaviors of both groups decreased as time delay rose, aligning with the hyperbolic model. (2) PITP individuals had significantly higher discount rates than those with FTP, and the scores of FTP individuals on the “Future” dimension of the ZTPI-C were positively correlated with the amount of money they were willing to forgo. These results suggest that time perspective, as a stable personality trait, can predict individuals’ intertemporal prosocial preferences. Our research enriches the theory of intertemporal choices and extends the Perceived-time–based model (PTBM) to the domain of intertemporal social preferences.
The Role of Basic Psychological Needs in the Adoption of Healthy Habits by Adolescents
Authors: Mateo-Orcajada Adrián , Vaquero-Cristóbal Raquel , Rey-López Juan Pablo , Martín-Campoy Raúl , Abenza-Cano Lucía
Published: July 2023

Previous research in this field has not examined the significance of each of the basic psychological needs (BPNs) on changes in the physical activity level, adherence to the Mediterranean diet (AMD), kinanthropometric and derived variables, and the physical fitness of adolescents. Therefore, the purpose of this study was (a) to examine the variances in physical activity, AMD, and kinanthropometric and derived variables, as well as fitness levels, among adolescents with varying degrees of satisfaction regarding each of the BPNs and (b) to assess the differences in the study variables among adolescents based on whether the BPNs are satisfied individually or jointly. The sample consisted of 791 adolescents (404 males and 387 females; average age: 14.39 ± 1.26 years old). The findings indicated that adolescents in the highest percentiles (75–100) of competence, autonomy, or relatedness showed higher scores in physical activity and AMD and better kinanthropometric and physical fitness variables than adolescents in the lowest percentiles (0–25). Adolescents who showed joint satisfaction of all BPNs showed the best results on all variables analyzed. In addition, it should be noted that competence played the most relevant role.
Holistic Review of Construction Process Carbon-Reduction Measures: A Systematic Literature Review Approach
Authors: Arogundade Suhaib , Dulaimi Mohammed , Ajayi Saheed
Published: July 2023

The fragmented nature of construction operations makes it challenging to implement carbon-reduction strategies. However, attaining a holistic construction sector decarbonisation hinges upon ensuring all aspects of a construction project’s lifecycle are decarbonised, including the construction process stage. Therefore, to mitigate the implementation challenge of reducing the levels of carbon involved in construction processes, this study attempts to synthesise and categorise carbon-reduction strategies that could be employed to decrease the carbon footprint during a construction projects’ delivery. To achieve the aim of this study, a systematic literature review approach was adopted. Based on this technique, a total of 26 relevant articles within the built environment research area were eligible for the study, and their analysis revealed 56 carbon minimisation measures, which were summarised into nine distinct categories to ease their application and overcome the construction operations’ complexities. The nine categories include material transport, waste transport, materials and equipment, waste, materials, on-site office, on-site lighting, on-site transportation of material and equipment, and construction methods. The findings of this study provide contractors with a suite of measures that can be deployed to reduce the carbon impact of construction project delivery.
A Study of the Mechanical Behavior of a Steel–Concrete Hybrid Beam Bridge during Construction
Authors: Pei Huiteng , Jia Lijun , Li Jiawei , Li Kewei , Xia Ruijie
Published: July 2023

To study the mechanical properties of steel–concrete joints during construction, the Mao Port Bridge in Shanghai is used as a case study. The mechanical properties of the bridge and the joint under the construction conditions were studied based on the site construction monitoring results, the finite element calculation of the entire bridge and the refined model of the joint. The results show that the finite element analysis of the bridge and the stress analysis of the joint during the construction phase agreed with the measured values, the end of block 0# of the main span remained in compression during construction and the compressive stresses varied in a zigzag pattern with the progress of construction. The lifting of the mid-span steel beam is a critical construction condition where the side spans of the girders are stretched upwards by 20.9 mm and the main spans are stretched downwards by 32.3 mm. When the steel beam was lifted, the joint was compressed as a whole. At the joint, the longitudinal stresses in the steel structure gradually decreased from the front bearing plate to the joint face, while the longitudinal stresses in the concrete structure gradually increased.
High-Volume Recycled Waste Glass Powder Cement-Based Materials: Role of Glass Powder Granularity
Authors: Younsi Akli , Mahi Mohammed Amar , Hamami Ameur El Amine , Belarbi Rafik , Bastidas-Arteaga Emilio
Published: July 2023

The use of recycled waste glass powder (RWGP) as a partial substitute for cement in cement-based materials offers a promising solution for reducing environmental impact and promoting sustainable waste management practices. An experimental study was conducted on a reference material made with Portland-limestone cement CEMII/A-LL42.5R and three other materials containing 50 wt% RWGP with different mean diameters, d50: 16, 18, and 25 µm. The main objective was to analyze the role of RWGP granularity in the short- and medium-term properties of the cement-based materials. The results showed that coarser RWGP granularity led to an increase in fluidity and Portlandite content, while water demand and mechanical properties decreased. However, the range of RWGP granularities tested did not significantly affect the initial setting time, fresh and dry density, hydration temperature, and water porosity. These findings suggest that the choice of RWGP granularity should depend on the desired properties of the cement-based material.
Study on Corrosion Fatigue Degradation Performance of Welded Top Plate-U Rib of Cross-Sea Steel Box Girder
Authors: Cheng Qian , Yao Zhian , Chen Huanyong , Liu Dewei , Lin Mingyi , Zhao Qiu , Zhang Bin
Published: July 2023

With the development of the economy and transportation, more and more cross-sea bridges are appearing in people’s view. However, cross-sea bridges are not only subjected to repeated traffic loads but also to corrosion from the marine environment. In addition, the steel box girder deck plate is directly subjected to repeated vehicle loads, and its welded details are highly susceptible to fatigue damage and destruction, resulting in fatigue or corrosion damage to the welded top plate-U rib of the cross-sea steel box girder. This paper is based on fracture mechanics analysis methods and finite element simulation analysis, in order to establish the numerical analysis method of the welded top plate-U rib of the steel box girder deck plate fatigue, which is to take into account the coupling of the marine corrosive environment and fatigue cyclic loading, explore the welded top plate-U rib of the stress intensity factor, crack expansion, crack expansion life and total fatigue life of the welded details. Furthermore, the establishment of the welded top plate-U rib corrosion fatigue life assessment model is to explore the fatigue life of different top plate thicknesses. The results show that: the stress intensity factor along the crack front is symmetrically distributed, and with the increase in the crack expansion step, the corresponding stress intensity factor amplitude is also increasing; in addition, with the increase in the top plate thickness, fatigue crack expansion rate significantly reduced.
Exploring Stakeholder Engagement Process as the Success Factor for Infrastructure Projects
Authors: Prebanić Kristijan Robert , Vukomanović Mladen
Published: July 2023

Today, the world is experiencing a major cycle of investment in infrastructure, which is essential for the development and prosperity of countries and societies. Management failures in infrastructure projects are widely known, and some of them involve the weak engagement of project stakeholders. The importance of stakeholder involvement as a key factor in the success of infrastructure projects is widely recognized. However, the literature provides few answers to the question of how this process manifests itself in projects. Some scholars have concluded that it is a complex and under-researched management process. The research questions aim to find out how practitioners perceive stakeholder engagement, who conducts activities and processes related to stakeholder engagement and in what ways, what organizational aspects influence the process, and how success is achieved in infrastructure projects. Initially, eight experienced experts involved in a whole range of (complex) infrastructure projects were interviewed, and later, four additional interviews were conducted for verification purposes. During the interviews, all aspects of stakeholder engagement were discussed in detail and a thematic analysis was conducted. Based on the analysis, success and failure factors related to the stakeholder engagement process were defined. As a result, a framework model for stakeholder engagement and infrastructure project success is presented based on three levels of management and three levels of project success.
A New Ensemble Prediction Method for Reclaimed Asphalt Pavement (RAP) Mixtures Containing Different Constituents
Authors: Ghavami Sadegh , Alipour Zeynab , Naseri Hamed , Jahanbakhsh Hamid , Karimi Mohammad M.
Published: July 2023

Fatigue and rutting are two common damage types in asphalt pavements. Reclaimed asphalt pavement (RAP), as a sustainable approach in the pavement industry, deals with the foregoing damage. Fatigue and rutting characteristics of asphalt pavement are generally assessed using laboratory tests, taking a long time and consuming significant amounts of raw material. This study aims to propose a novel approach for predicting fatigue and rutting performance of RAP mixtures. A new ensemble prediction method, named COA-KNN, is introduced by combining the coyote optimization algorithm and K-nearest neighbor to increase the accuracy of fatigue and rutting prediction. In order to evaluate the accuracy, the proposed method was compared against robust prediction methods, including random forest (RF), gradient boosting (GB), decision tree regression (DT), and multiple linear regression (MLR). Afterward, the influence of each variable on the mentioned damages is examined, and the variables are ranked based on their relative influence on the mentioned damages. The results suggest that COA-KNN outperformed other prediction techniques when comparing different performance indicators. Total binder content in asphalt mixes and the PG span of the virgin binder added to the recycled asphalt mixture had the highest relative influence on fatigue and rutting performance, respectively.
Maximizing Energy Efficiency and Daylight Performance in Office Buildings in BIM through RBFOpt Model-Based Optimization: The GENIUS Project
Authors: Ratajczak Julia , Siegele Dietmar , Niederwieser Elias
Published: July 2023

Architects face the challenge of exploring various design solutions in the early design stage, often with conflicting optimization goals. To tackle this complexity, they need to rely on tools and methodologies during the conceptual phase to assess and optimize designs, considering multiple aspects of building performance. Parametric Design, Generative Design, and automation in Building Information Modelling (BIM) offer architects new opportunities to work on complex buildings. These advancements empower designers to enhance their designs, increase project efficiency, improve performance, and reduce project time and costs. Multi-Objective Optimization algorithms are employed to address conflicting objectives in the design process. The GENIUS project introduces an Algorithm-Aided Design workflow that optimizes the building shape and Window-to-Wall Ratio of an office building, considering energy and daylight performance. The integration of BIM software, visual programming tools, and Artificial Intelligence techniques (Genetic Algorithms and RBFOpt model-based optimization) allows architects to identify optimal solutions aligning with design objectives. The workflow was validated through a case study of a large office building, focusing on maximizing daylight performance using the Spatial Daylight Autonomy metric and minimizing energy consumption using the Energy Use Intensity metric. The GENIUS project equips architects with a methodology and toolset to improve their designs and identify optimal solutions for complex design challenges.
Dynamic Response of a Long-Span Double-Deck Suspension Bridge and Its Vibration Reduction
Authors: Xu Jun , Li Jian , Ye Yu , Xu Yuanqing , Li Chong
Published: July 2023

This paper presents a dynamic analysis of a long-span double-deck suspension bridge subjected to random traffic loading using a Finite Element (FE) model. During this study, the influence of various traffic parameters, such as vehicle speed, traffic volume, traffic weight, and the location of the passing girder, on the longitudinal movement of the girders was investigated. The results reveal that schemes with double girders passing can lead to greater longitudinal displacement of the girder as compared to a long-span bridge with a single passing girder. However, the incorporation of fluid-viscous dampers at the ends of the girders significantly reduces the displacement range of each node. For instance, at the left end of the bridge, the original model (without dampers) exhibits a displacement range of approximately 0.01–0.056 m, whereas the constrained model (with dampers) shows a range of 0.025–0.033 m. A quantitative analysis demonstrates that higher damping coefficients (or smaller damping exponents) can further mitigate the girder’s movement.
A Study of the Foremen’s Influence on the Safety Behavior of Construction Workers Based on Cognitive Theory
Authors: Nwagbala Daniel Chukwunonso , Park Jong Yil
Published: July 2023

In this study, a behavioral influence model based on cognitive theory was developed to investigate foremen’s influences on construction workers’ safety behavior. In the model, three foreman behaviors were considered, such as leading by example (LE), safety teaching (ST), and safety monitoring (SM). Five cognitive stages of a worker are also considered in the model, such as situation awareness, safety knowledge, subjective norm, safety attitude, and taking action. To obtain empirical data for the model parameters, a survey was conducted on a construction site in Seoul, South Korea, where the foreman–worker behavioral interactions and workers’ unsafe behavior of taking shortcuts were observed. The model was established as Agent-Based Modeling (ABM) using AnyLogic software. Four scenarios of foremen’s behavior were simulated using the model. The result shows that LE behavior has a positive, but weak significant influence on workers’ safety behavior. ST was found to have a positive and the most significant influence on workers’ safety behavior. Moreover, it should be provided with appropriate safety monitoring to maximize its effectiveness. The research findings promote stakeholders’ understanding of the influence of foremen on workers’ safety behavior and lead to the formation of informed policies and future research directions in the study field.
Cytoplasmic Localization of Thyroid Hormone Receptor (TR) Alpha and Nuclear Expression of Its Isoform TRα2 Determine Survival in Breast Cancer in Opposite Ways
Authors: Schneider Mariella , Köpke Melitta B. , zehni Alaleh Zati , Vilsmaier Theresa , Kessler Mirjana , Kailuweit Magdalena , Vattai Aurelia , Heidegger Helene Hildegard , Cavaillès Vincent , Jeschke Udo , Ditsch Nina
Published: July 2023

The aim of this retrospective study was to assess the respective prognostic values of cytoplasmic and nuclear TRα, TRα1, and TRα2 expression in breast cancer (BC) tissue samples and correlate the results with clinico-pathological parameters. In 249 BC patients, the expression patterns of general TRα and the α1 and α2 isoforms were evaluated via immuno-histochemistry. Prognosis-determining aspects were calculated via univariate, as well as multivariate, analysis. Univariate Cox-regression analysis revealed no association between nuclear TRα expression and overall survival (OS) (p = 0.126), whereas cytoplasmic TRα expression was significantly correlated with a poor outcome for both OS (p = 0.034) and ten-year survival (p = 0.009). Strengthening these results, cytoplasmic TRα was found to be an independent marker of OS (p = 0.010) when adjusted to fit clinico-pathological parameters. Analyses of the TRα-subgroups revealed that TRα1 had no prognostic relevance, whereas nuclear TRα2 expression was positively associated with OS (p = 0.014), ten-year survival (p = 0.029), and DFS (p = 0.043). Additionally, nuclear TRα2 expression was found to be an independent positive prognosticator (p = 0.030) when adjusted to fit clinico-pathological parameters. Overall, our results support the hypothesis that subcellular localization of TRα and its isoforms plays an important role in the carcinogenesis and prognosis of breast cancer. Cytoplasmic TRα expression correlates with more aggressive disease progression, whereas nuclear TRα2 expression appears to be a protective factor. These data may help us to prioritize high-risk BC subgroups for possible targeted tumor therapy.
Iron-Doped Nickel Hydroxide Nanosheets as Efficient Electrocatalysts in Electrochemical Water Splitting
Authors: Krishnamurthy Palani , Maiyalagan Thandavarayan , Panomsuwan Gasidit , Jiang Zhongqing , Rahaman Mostafizur
Published: July 2023

The development of non-noble-metal-based electrocatalysts for water electrolysis is essential to produce sustainable green hydrogen. Highly active and stable non-noble-metal-based electrocatalysts are greatly needed for the replacement of the benchmark electrocatalysts of iridium, ruthenium, and platinum oxides. Herein, we synthesized non-noble-metal-based, Fe-doped, β-Ni(OH)2 interconnected hierarchical nanosheets on nickel foam via a conventional hydrothermal reaction. Iron doping significantly modified the electronic structure of β-Ni(OH)2 due to the electron transfer of iron to nickel hydroxide. Fe-doped β-Ni(OH)2 was investigated both as a cathode and anode electrode for hydrogen and oxygen evolution reactions (OERs and HERs). It facilitated significant improvements in electrochemical performance due to its huge intrinsic active sites and high electrical conductivity. As a result, the electrocatalytic activity of Fe-doped Ni(OH)2 exhibited a lesser overpotential of 189 and 112 mV at a current density of 10 mA cm−2 and a Tafel slope of 85 and 89 mV dec−1 for the OER and HER, respectively. The Fe-doped β-Ni(OH)2 displayed excellent durability for 48 h and a cell voltage of 1.61 V @ 10 mA cm−2. This work demonstrates that Fe-doped β-Ni(OH)2 is an efficient electrocatalyst with superior electrocatalytic performance towards overall water splitting that can be useful at the industrial scale.
Synthesis of New Dehydrodieugenol Derivatives via Olefin Cross Metathesis and In Vitro Evaluation of Their Trypanocidal Activity
Authors: Galhardo Thalita S. , Ueno Anderson K. , Carvalho Wagner A. , Costa-Silva Thais A. , Gonçalves Marina M. , Abiuzi Mariana B. , Tempone Andre G. , Lago João Henrique G. , Mandelli Dalmo , Fischmeister Cedric , Bruneau Christian
Published: July 2023

Ruthenium-catalyzed cross metathesis using biseugenol (1) with electron-deficient olefins methyl (2a) and ethyl (2b) acrylates, acrylic acid (2c), acrylonitrile (2d), and methyl methacrylate (2e) derivatives have been conducted to afford respective derivatives 3a–3e with good yields and excellent conversion rates. Activity of prepared compounds against trypomastigote and amastigote forms of Trypanosoma cruzi and mammalian cytotoxicity have been evaluated. The results obtained indicate that the IC50 values for amastigotes of compounds 3b and 3d are quite similar to those of biseugenol (1), but unlike this compound, they show reduced toxicities with SI values similar to those of the standard drug benznidazol.
Nickel Foam-Supported Hierarchical NiCo2S4 Nanostructures as Efficient Electrocatalysts for the Methanol Oxidation Reaction
Authors: Jin Dan , Cheng Wenting , Wu Shaoyun , Li Zhen , Wang Zhenghua
Published: July 2023

In this study, hierarchical NiCo2S4 nanostructures have been successfully prepared on Ni foam support using a simple and economical two-step hydrothermal process. The hierarchical NiCo2S4 nanostructure comprises rod-like NiCo2S4 cores enveloped by a thin nanoribbon shell. When the NiCo2S4/Ni foam was employed as an electrode for methanol electrooxidation directly, a current density of 194 mA mg−1 was achieved at 0.60 V. The prepared NiCo2S4/Ni foam demonstrates high electrocatalytic activity and durability in alkaline environments for the methanol oxidation reaction. After 1000 cyclic voltammetry cycles in the alkaline electrolyte, the current density of the hierarchical NiCo2S4 decreased to 72.2% of its initial value, with the loss of catalytic activity during the cycling test attributed to their surface oxidation. These findings suggest the NiCo2S4 sample as a non-noble metal electrocatalyst holds great potential for direct methanol fuel cells.
Recent Progress on Semiconductor Heterogeneous Photocatalysts in Clean Energy Production and Environmental Remediation
Authors: Goodarzi Nahal , Ashrafi-Peyman Zahra , Khani Elahe , Moshfegh Alireza Z.
Published: July 2023

Semiconductor-based photocatalytic reactions are a practical class of advanced oxidation processes (AOPs) to address energy scarcity and environmental pollution. By utilizing solar energy as a clean, abundant, and renewable source, this process offers numerous advantages, including high efficiency, eco-friendliness, and low cost. In this review, we present several methods to construct various photocatalyst systems with excellent visible light absorption and efficient charge carrier separation ability through the optimization of materials design and reaction conditions. Then it introduces the fundamentals of photocatalysis in both clean energy generation and environmental remediation. In the other parts, we introduce various approaches to enhance photocatalytic activity by applying different strategies, including semiconductor structure modification (e.g., morphology regulation, co-catalysts decoration, doping, defect engineering, surface sensitization, heterojunction construction) and tuning and optimizing reaction conditions (such as photocatalyst concentration, initial contaminant concentration, pH, reaction temperature, light intensity, charge-carrier scavengers). Then, a comparative study on the photocatalytic performance of the various recently examined photocatalysts applied in both clean energy production and environmental remediation will be discussed. To realize these goals, different photocatalytic reactions including H2 production via water splitting, CO2 reduction to value-added products, dye, and drug photodegradation to lessen toxic chemicals, will be presented. Subsequently, we report dual-functional photocatalysis systems for simultaneous energy production and pollutant photodegradation for efficient reactions. Then, a brief discussion about the industrial and economical applications of photocatalysts is described. The report follows by introducing the application of artificial intelligence and machine learning in the design and selection of an innovative photocatalyst in energy and environmental issues. Finally, a summary and future research directions toward developing photocatalytic systems with significantly improved efficiency and stability will be provided.
Testicular Germ Cell Tumor Tissue Biomarker Analysis: A Comparison of Human Protein Atlas and Individual Testicular Germ Cell Tumor Component Immunohistochemistry
Authors: Krasic Jure , Skara Abramovic Lucija , Himelreich Peric Marta , Vanjorek Vedran , Gangur Marko , Zovko Dragana , Malnar Marina , Masic Silvija , Demirovic Alma , Juric Bernardica , Ulamec Monika , Coric Marijana , Jezek Davor , Kulis Tomislav , Sincic Nino
Published: July 2023

The accurate management of testicular germ cell tumors (TGCTs) depends on identifying the individual histological tumor components. Currently available data on protein expression in TGCTs are limited. The human protein atlas (HPA) is a comprehensive resource presenting the expression and localization of proteins across tissue types and diseases. In this study, we have compared the data from the HPA with our in-house immunohistochemistry on core TGCT diagnostic genes to test reliability and potential biomarker genes. We have compared the protein expression of 15 genes in TGCT patients and non-neoplastic testicles with the data from the HPA. Protein expression was converted into diagnostic positivity. Our study discovered discrepancies in three of the six core TGCT diagnostic genes, POU5F1, KIT and SOX17 in HPA. DPPA3, CALCA and TDGF1 were presented as potential novel TGCT biomarkers. MGMT was confirmed while RASSF1 and PRSS21 were identified as biomarkers of healthy testicular tissue. Finally, SALL4, SOX17, RASSF1 and PRSS21 dysregulation in the surrounding testicular tissue with complete preserved spermatogenesis of TGCT patients was detected, a potential early sign of neoplastic transformation. We highlight the importance of a multidisciplinary collaborative approach to fully understand the protein landscape of human testis and its pathologies.
Distinct Organotypic Platforms Modulate Rainbow Trout (Oncorhynchus mykiss) Intestinal Cell Differentiation In Vitro
Authors: Verdile Nicole , Camin Federica , Pavlovic Radmila , Pasquariello Rolando , Stuknytė Milda , De Noni Ivano , Brevini Tiziana A. L. , Gandolfi Fulvio
Published: July 2023

In vitro organotypic cell-based intestinal platforms, able to faithfully recapitulate the complex functions of the organ in vivo, would be a great support to search for more sustainable feed ingredients in aquaculture. We previously demonstrated that proliferation or differentiation of rainbow trout intestinal cell lines is dictated by the culture environment. The aim of the present work was to develop a culture platform that can efficiently promote cell differentiation into mature enterocytes. We compared four options, seeding the RTpiMI cell line derived from the proximal intestine on (1) polyethylene terephthalate (PET) culture inserts ThinCert™ (TC), (2) TC coated with the solubilized basement membrane matrix Matrigel® (MM), (3) TC with the rainbow trout fibroblast cell line RTskin01 embedded within the Matrigel® matrix (MMfb), or (4) the highly porous polystyrene scaffold Alvetex® populated with the abovementioned fibroblast cell line (AV). We evaluated the presence of columnar cells with a clear polarization of brush border enzymes, the formation of an efficient barrier with a significant increase in transepithelial electrical resistance (TEER), and its ability to prevent the paracellular flux of large molecules but allow the transit of small compounds (proline and glucose) from the apical to the basolateral compartment. All parameters improved moving from the simplest (TC) through the more complex platforms. The presence of fibroblasts was particularly effective in enhancing epithelial cell differentiation within the AV platform recreating more closely the complexity of the intestinal mucosa, including the presence of extracellular vesicles between fibroblasts and epithelial cells.
S1P Lyase Deficiency in the Brain Promotes Astrogliosis and NLRP3 Inflammasome Activation via Purinergic Signaling
Authors: Alam Shah , Afsar Sumaiya Yasmeen , Wolter Maya Anik , Volk Luisa Michelle , Mitroi Daniel Nicolae , Meyer zu Heringdorf Dagmar , van Echten-Deckert Gerhild
Published: July 2023

Astrocytes are critical players in brain health and disease. Brain pathologies and lesions are usually accompanied by astroglial alterations known as reactive astrogliosis. Sphingosine 1-phosphate lyase (SGPL1) catalysis, the final step in sphingolipid catabolism, irreversibly cleaves its substrate sphingosine 1-phosphate (S1P). We have shown that neural ablation of SGPL1 causes accumulation of S1P and hence neuronal damage, cognitive deficits, as well as microglial activation. Moreover, the S1P/S1P-receptor signaling axis enhances ATP production in SGPL1-deficient astrocytes. Using immunohistochemical methods as well as RNA Seq and CUT&Tag we show how S1P signaling causes activation of the astrocytic purinoreceptor P2Y1 (P2Y1R). With specific pharmacological agonists and antagonists, we uncover the P2Y1R as the key player in S1P-induced astrogliosis, and DDX3X mediated the activation of the NLRP3 inflammasome, including caspase-1 and henceforward generation of interleukin-1ß (IL-1ß) and of other proinflammatory cytokines. Our results provide a novel route connecting S1P metabolism and signaling with astrogliosis and the activation of the NLRP3 inflammasome, a central player in neuroinflammation, known to be crucial for the pathogenesis of numerous brain illnesses. Thus, our study opens the door for new therapeutic strategies surrounding S1P metabolism and signaling in the brain.
Targeted Protein Degradation: Principles and Applications of the Proteasome
Authors: Kim Yosup , Kim Eun-Kyung , Chey Yoona , Song Min-Jeong , Jang Ho Hee
Published: July 2023

The proteasome is a multi-catalytic protease complex that is involved in protein quality control via three proteolytic activities (i.e., caspase-, trypsin-, and chymotrypsin-like activities). Most cellular proteins are selectively degraded by the proteasome via ubiquitination. Moreover, the ubiquitin–proteasome system is a critical process for maintaining protein homeostasis. Here, we briefly summarize the structure of the proteasome, its regulatory mechanisms, proteins that regulate proteasome activity, and alterations to proteasome activity found in diverse diseases, chemoresistant cells, and cancer stem cells. Finally, we describe potential therapeutic modalities that use the ubiquitin–proteasome system.
Co-Aggregation and Parallel Aggregation of Specific Proteins in Major Mental Illness
Authors: Samardžija Bobana , Juković Maja , Zaharija Beti , Renner Éva , Palkovits Miklós , Bradshaw Nicholas J.
Published: July 2023

Background: Disrupted proteostasis is an emerging area of research into major depressive disorder. Several proteins have been implicated as forming aggregates specifically in the brains of subsets of patients with psychiatric illnesses. These proteins include CRMP1, DISC1, NPAS3 and TRIOBP-1. It is unclear, however, whether these proteins normally aggregate together in the same individuals and, if so, whether each protein aggregates independently of each other (“parallel aggregation”) or if the proteins physically interact and aggregate together (“co-aggregation”). Materials and methods: Post mortem insular cortex samples from major depressive disorder and Alzheimer’s disease patients, suicide victims and control individuals had their insoluble fractions isolated and tested by Western blotting to determine which of these proteins are insoluble and, therefore, likely to be aggregating. The ability of the proteins to co-aggregate (directly interact and form common aggregate structures) was tested by systematic pairwise expression of the proteins in SH-SY5Y neuroblastoma cells, which were then examined by immunofluorescent microscopy. Results: Many individuals displayed multiple insoluble proteins in the brain, although not enough to imply interaction between the proteins. Cell culture analysis revealed that only a few of the proteins analyzed can consistently co-aggregate with each other: DISC1 with each of CRMP1 and TRIOBP-1. DISC1 was able to induce aggregation of full length TRIOBP-1, but not individual domains of TRIOBP-1 when they were expressed individually. Conclusions: While specific proteins are capable of co-aggregating, and appear to do so in the brains of individuals with mental illness and potentially also with suicidal tendency, it is more common for such proteins to aggregate in a parallel manner, through independent mechanisms. This information aids in understanding the distribution of protein aggregates among mental illness patients and is therefore important for any future diagnostic or therapeutic approaches based on this aspect of mental illness pathology.
Reduced Tie2 in Microvascular Endothelial Cells Is Associated with Organ-Specific Adhesion Molecule Expression in Murine Health and Endotoxemia
Authors: Zwiers Peter J. , Lucas Jacqueline P. F. E. , Jongman Rianne M. , van Meurs Matijs , Popa Eliane R. , Molema Grietje
Published: July 2023

Endothelial cells (ECs) in the microvasculature in organs are active participants in the pathophysiology of sepsis. Tyrosine protein kinase receptor Tie2 (Tek; Tunica interna Endothelial cell Kinase) is thought to play a role in their inflammatory response, yet data are inconclusive. We investigated acute endotoxemia-induced changes in the expression of Tie2 and inflammation-associated endothelial adhesion molecules E-selectin and VCAM-1 (vascular cell adhesion molecule-1) in kidneys and lungs in inducible, EC-specific Tie2 knockout mice. The extent of Tie2 knockout in healthy mice differed between microvascular beds, with low to absent expression in arterioles in kidneys and in capillaries in lungs. In kidneys, Tie2 mRNA dropped more than 70% upon challenge with lipopolysaccharide (LPS) in both genotypes, with no change in protein. In renal arterioles, tamoxifen-induced Tie2 knockout was associated with higher VCAM-1 protein expression in healthy conditions. This did not increase further upon challenge of mice with LPS, in contrast to the increased expression occurring in control mice. Also, in lungs, Tie2 mRNA levels dropped within 4 h after LPS challenge in both genotypes, while Tie2 protein levels did not change. In alveolar capillaries, where tamoxifen-induced Tie2 knockout did not affect the basal expression of either adhesion molecule, a 4-fold higher E-selectin protein expression was observed after exposure to LPS compared to controls. The here-revealed heterogeneous effects of absence of Tie2 in ECs in kidney and lung microvasculature in health and in response to acute inflammatory activation calls for further in vivo investigations into the role of Tie2 in EC behavior.
Zingiber officinale-Derived Extracellular Vesicles Attenuate Bleomycin-Induced Pulmonary Fibrosis Trough Antioxidant, Anti-Inflammatory and Protease Activity in a Mouse Model
Authors: Ramírez-Hernández Alma Aurora , Reyes-Jiménez Edilburga , Velázquez-Enríquez Juan Manuel , Santos-Álvarez Jovito Cesar , Soto-Guzmán Adriana , Castro-Sánchez Luis , Tapia-Pastrana Gabriela , Torres-Aguilar Honorio , Vásquez-Garzón Verónica Rocío , Baltiérrez-Hoyos Rafael
Published: July 2023

Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneumonia. It is a chronic and progressive disease with a poor prognosis and is a major cause of morbidity and mortality. This disease has no cure; therefore, there is a clinical need to search for alternative treatments with greater efficacy. In this study, we aimed to evaluate the effect of extracellular vesicles (EVs) from Zingiber officinale (EVZO) in a murine model of bleomycin (BLM)-induced IPF administered through an osmotic minipump. EVZO had an average size of 373 nm and a spherical morphology, as identified by scanning electron microscopy. Label-free proteomic analysis of EVZOs was performed by liquid chromatography coupled to mass spectrometry, and 20 proteins were identified. In addition, we demonstrated the protease activity of EVZO by gelatin-degrading zymography assay and the superoxide dismutase (SOD) activity of EVZO by an enzymatic assay. In the BLM-induced IPF mouse model, nasal administration of 50 μg of EVZO induced recovery of alveolar space size and decreased cellular infiltrate, collagen deposition, and expression of α-SMA-positive cells. Additionally, EVZO inhibited inflammatory markers such as iNOS and COX-2, lipid peroxidation, and apoptotic cells. These results show that EVZO may represent a novel natural delivery mechanism to treat IPF.
Tumor Growth Ameliorates Cardiac Dysfunction
Authors: Awwad Lama , Shofti Rona , Haas Tali , Aronheim Ami
Published: July 2023

Heart failure and cancer are the deadliest diseases worldwide. Murine models for cardiac remodeling and heart failure demonstrate that cardiac dysfunction promotes cancer progression and metastasis spread. Yet, no information is available on whether and how tumor progression affects cardiac remodeling. Here, we examined cardiac remodeling following transverse aortic constriction (TAC) in the presence or absence of proliferating cancer cells. We show that tumor-bearing mice, of two different cancer cell lines, display reduced cardiac hypertrophy, lower fibrosis and improved cardiac contractile function following pressure overload induced by TAC surgery. Integrative analysis of qRT-PCR, flow cytometry and immunofluorescence identified tumor-dependent M1-to-M2 polarization in the cardiac macrophage population as a mediator of the beneficial tumor effect on the heart. Importantly, tumor-bearing mice lacking functional macrophages fail to improve cardiac function and display sustained fibrosis.
Scaffold-Based (Matrigel™) 3D Culture Technique of Glioblastoma Recovers a Patient-like Immunosuppressive Phenotype
Authors: Braun Frank K. , Rothhammer-Hampl Tanja , Lorenz Julia , Pohl Sandra , Menevse Ayse-Nur , Vollmann-Zwerenz Arabel , Bumes Elisabeth , Büttner Maren , Zoubaa Saida , Proescholdt Martin , Schmidt Nils O. , Hau Peter , Beckhove Philipp , Winner Beate , Riemenschneider Markus J.
Published: July 2023

Conventional 2D cultures are commonly used in cancer research though they come with limitations such as the lack of microenvironment or reduced cell heterogeneity. In this study, we investigated in what respect a scaffold-based (Matrigel™) 3D culture technique can ameliorate the limitations of 2D cultures. NGS-based bulk and single-cell sequencing of matched pairs of 2D and 3D models showed an altered transcription of key immune regulatory genes in around 36% of 3D models, indicating the reoccurrence of an immune suppressive phenotype. Changes included the presentation of different HLA surface molecules as well as cellular stressors. We also investigated the 3D tumor organoids in a co-culture setting with tumor-infiltrating lymphocytes (TILs). Of note, lymphocyte-mediated cell killing appeared less effective in clearing 3D models than their 2D counterparts. IFN-γ release, as well as live cell staining and proliferation analysis, pointed toward an elevated resistance of 3D models. In conclusion, we found that the scaffold-based (Matrigel™) 3D culture technique affects the transcriptional profile in a subset of GBM models. Thus, these models allow for depicting clinically relevant aspects of tumor-immune interaction, with the potential to explore immunotherapeutic approaches in an easily accessible in vitro system.
Restoration Integrity in Primary Teeth Prepared Using Erbium/Yttrium–Aluminum–Garnet Laser: A Randomized Split-Mouth Clinical Study
Authors: Abdrabuh Raghdah , El Meligy Omar , Farsi Najat , Bakry Ahmed Samir , Felemban Osama M.
Published: July 2023

The most frequently used and universally accepted technique for removing caries is mechanical ablation of decayed tissues by rotating drills. New minimally invasive strategies, such as the use of lasers to perform highly controlled tissue ablation, have been introduced in dental practice. The aim of this study was to assess and compare treatment with a 2940 nm erbium/yttrium–aluminum–garnet (Er:YAG) laser versus a conventional rotary treatment during cavity preparation in children with regard to restoration integrity. In a randomized, controlled, blinded trial using a split-mouth design, 40 (9–12-year-old) children with 80 carious primary molars were included. The cavity in one quadrant was randomized to be treated conventionally using a bur, while the cavity in the other quadrant was prepared using an Er:YAG laser. At the one-year follow-up, clinical examinations were conducted to assess the integrity of the restorations according to the Ryge criteria. The data were analyzed using SPSS version 22 (IBM Inc., Chicago, IL, USA). The average age of the participants was 9.4 ± 1.29 years. Males accounted for 51.4% of the participants. The Ryge criteria showed clinical success of restorations, and there was no discernible difference between the conventional and laser intervention techniques. Over one year, no statistically significant differences in the clinical integrity based on the Ryge criteria were found following class I cavity preparation in primary teeth with either procedure.
Diagnosis and Management of Neonatal Hypoglycemia: A Comprehensive Review of Guidelines
Authors: Giouleka Sonia , Gkiouleka Maria , Tsakiridis Ioannis , Daniilidou Anastasia , Mamopoulos Apostolos , Athanasiadis Apostolos , Dagklis Themistoklis
Published: July 2023

Hypoglycemia represents one of the most frequent metabolic disturbances of the neonate, associated with increased morbidity and mortality, especially if left untreated or diagnosed after the establishment of brain damage. The aim of this study was to review and compare the recommendations from the most recently published influential guidelines on the diagnosis, screening, prevention and management of this common neonatal complication. Therefore, a descriptive review of the guidelines from the American Academy of Pediatrics (AAP), the British Association of Perinatal Medicine (BAPM), the European Foundation for the Care of the Newborn Infants (EFCNI), the Queensland Clinical Guidelines-Australia (AUS), the Canadian Pediatric Society (CPS) and the Pediatric Endocrine Society (PES) on neonatal hypoglycemia was carried out. There is a consensus among the reviewed guidelines on the risk factors, the clinical signs and symptoms of NH, and the main preventive strategies. Additionally, the importance of early recognition of at-risk infants, timely identification of NH and prompt initiation of treatment in optimizing the outcomes of hypoglycemic neonates are universally highlighted. All medical societies, except PES, recommend screening for NH in asymptomatic high-risk and symptomatic newborn infants, but they do not provide consistent screening approaches. Moreover, the reviewed guidelines point out that the diagnosis of NH should be confirmed by laboratory methods of BGL measurement, although treatment should not be delayed until the results become available. The definition of NH lacks uniformity and it is generally agreed that a single BG value cannot accurately define this clinical entity. Therefore, all medical societies support the use of operational thresholds for the management of NH, although discrepancies exist regarding the recommended cut-off values, the optimal treatment and surveillance strategies of both symptomatic and asymptomatic hypoglycemic neonates as well as the treatment targets. Over the past several decades, ΝH has remained an issue of keen debate as it is a preventable cause of brain injury and neurodevelopmental impairment; however, there is no clear definition or consistent treatment policies. Thus, the establishment of specific diagnostic criteria and uniform protocols for the management of this common biochemical disorder is of paramount importance as it will hopefully allow for the early identification of infants at risk, the establishment of efficient preventive measures, the optimal treatment in the first hours of a neonate’s life and, subsequently, the improvement of neonatal outcomes.