bluuebunny/crossref_metadata_2025 huggingface dataset:
PAR2 Participates in the Development of Cough Hypersensitivity in Guinea Pigs by Regulating TRPA1 Through PKC
Authors: Zhu Yiqing , Zhang Tongyangzi , Bai Haodong , Li Wanzhen , Wang Shengyuan , Xu Xianghuai , Yu Li
Published: February 2025

Objective: This study was conducted to validate the involvement of the PAR2-PKC-TRPA1 pathway in cough hypersensitivity (CHS) development. Methods: Guinea pigs were divided into a blank control, a citric acid-induced enhanced cough model, and drug intervention groups. The effects of the drugs on capsaicin-induced cough responsiveness in a cough model were observed. The effects of individual and combined treatments (including PAR2 agonists, TRPA1 agonists, PAR2 antagonists, TRPA1 antagonists, PKC agonists, and PKC antagonists) on PAR2, phospho-PKC (pPKC), and TRPA1 expression in bronchial tissues and the vagus ganglion (jugular and nodose) in the cough model and control groups were assessed. Additionally, whole-cell patch-clamp recordings were conducted to evaluate the effects of the drugs on vagus ganglion neuron electrophysiological activity. Results: ① Both PAR2 antagonists and TRPA1 antagonists significantly reduced cough frequency in guinea pigs with a cough, and the PAR2 antagonist inhibited coughing induced by the TRPA1 agonist. ② Western blotting and multiplex immunohistochemistry (mIHC) indicated that PAR2, pPKCα, PKCα, and TRPA1 expression in bronchial and vagus ganglion tissues was elevated in the cough model compared with the control, with TRPA1 expression being regulated by PAR2 and PKC being involved in this regulatory process. ③ Whole-cell patch-clamp recordings demonstrated that TRPA1 agonists induced an inward current in nodose ganglion neurons, which was further amplified by PAR2 agonists; this amplification effect was blocked by PKC antagonist. Additionally, PAR2 antagonists inhibited the inward current induced by TRPA1 agonists. ④ At various concentrations, including the optimal antitussive concentration, PAR2 antagonists did not significantly affect pulse amplitude, arterial oxygen saturation, heart rate, body temperature, or respiratory rate in guinea pigs. Conclusion: PAR2 regulates TRPA1 through PKC in cough syndrome (CHS) pathogenesis, making targeting PAR2 a safe and effective therapeutic strategy for CHS.
Single-Cell Landscape of the Cochlea Revealed Cell-Type-Specific Diversification in Hipposideros armiger Based on PacBio Long-Read Sequencing
Authors: Bao Mingyue , Wang Xue , Li Xintong , Sun Ruyi , Wang Zhiqiang , Jiang Tinglei , Wang Hui , Feng Jiang
Published: February 2025

Echolocation represents one of the most rapid adaptive sensorimotor modulation behaviors observed in mammals, establishing bats as one of the most evolutionarily successful mammals. Bats rely on high-frequency hearing for survival, but our understanding of its cellular molecular basis is scattered and segmented. Herein, we constructed the first single-cell transcriptomic landscape of the cochlea in Hipposideros armiger, a CF-FM bat, using a PacBio-optimized genome and compared it with the results obtained from unoptimized original genomes. Sixteen distinct cell types were distributed across five spatial regions of the cochlea. Notably, through hematoxylin and eosin staining and fluorescence in situ hybridization, we identified new types of spiral ganglion neuron (SGN) cells in the cochlea of H. armiger. These SGN cells are likely critical for auditory perception and may have driven the adaptive evolution of high-frequency hearing in this species. Furthermore, we uncovered the differentiation relationships of among specific cell types, such as the transition from supporting cells to hair cells. Using the cochlear cell atlas as a reference, cell types susceptible to deafness-associated genes (in the human) were also identified. In summary, this study provides novel insights into the cellular and molecular mechanisms underlying the adaptive high-frequency hearing in bats and highlights potential candidate cell types and genes for therapeutic interventions in hearing loss.
Regulatory Role of a Hydrophobic Core in the FliG C-Terminal Domain in the Rotary Direction of a Flagellar Motor
Authors: Nishikino Tatsuro , Hatano Akihiro , Kojima Seiji , Homma Michio
Published: February 2025

A flagellar motor can rotate either counterclockwise (CCW) or clockwise (CW), and rotational switching is triggered by conformational changes in FliG, although the molecular mechanism is still unknown. Here, we found that cheY deletion, which locks motor rotation in the CCW direction, restored the motility abolished by the fliG L259Q mutation. We found that the CCW-biased fliG G214S mutation also restored the swimming of the L259Q mutant, but the CW-biased fliG G215A mutation did not. Since the L259 residue participates in forming the FliG hydrophobic core at its C-terminal domain, mutations were introduced into residues structurally closer to L259, and their motility was examined. Two mutants, D251R and L329Q, exhibited CW-biased rotation. Our results suggest that mutations in the hydrophobic core of FliGC collapse its conformational switching and/or stator interaction; however, the CCW state of the rotor enables rotation even with this disruption.
α-Synuclein Iron-Responsive-Element RNA and Iron Regulatory Protein Affinity Is Specifically Reduced by Iron in Parkinson’s Disease
Authors: Khan Mateen A.
Published: February 2025

α-Synuclein (α-Syn) is implicated in the pathophysiology of Parkinson’s disease (PD) and plays a significant role in neuronal degeneration. Iron response proteins (IRPs) bind to iron response elements (IREs) found in the 5′-untranslated regions (5′-UTRs) of the messenger RNA that encode the α-Syn gene. This study used multi-spectroscopic approach techniques to investigate the impact of iron on α-Syn IRE RNA binding to IRP1. The formation of a stable complex between α-Syn RNA and IRP1 was suggested by fluorescence quenching results. Fluorescence measurements showed that α-Syn RNA and IRP1 had a strong interaction, with a binding constant (Ka) of 21.0 × 106 M−1 and 1:1 binding stoichiometry. About one binding site per IRP1 molecule was suggested by the α-Syn RNA binding. The Ka for α-Syn RNA•IRP1 with added Fe2+ (50 μM) was 6.4 μM−1. When Fe2+ was added, the Ka of α-Syn RNA•IRP1 was reduced by 3.3 times. These acquired Ka values were used to further understand the thermodynamic characteristics of α-Syn RNA•IRP1 interactions. The thermodynamic properties clearly suggested that α-Syn RNA binding to IRP1 was an entropy-favored and enthalpy-driven event, with significant negative ΔH and small positive ΔS. For α-Syn RNA•IRP1, the Gibbs free energy (ΔG) was −43.7 ± 2.7 kJ/mol, but in the presence of Fe2+, it was −36.3 ± 2.1 kJ/mol. These thermodynamic calculations indicated that hydrogen bonding as well as van der Waals interactions might help to stabilize the complex formation. Additionally, far-UV CD spectra verified α-Syn RNA•IRP1 complex formation, and α-Syn RNA and Fe2+ induce secondary structural alteration of IRP1. According to our findings, iron alters the hydrogen bonding in α-Syn RNA•IRP1 complexes and induces a structural change in IRP1. This suggests that iron selectively affects the thermodynamics of these RNA–protein interactions.
Carnitine O-Acetyltransferase as a Central Player in Lipid and Branched-Chain Amino Acid Metabolism, Epigenetics, Cell Plasticity, and Organelle Function
Authors: Volpicella Mariateresa , Sgobba Maria Noemi , Laera Luna , Francavilla Anna Lucia , De Luca Danila Imperia , Guerra Lorenzo , Pierri Ciro Leonardo , De Grassi Anna
Published: February 2025

Carnitine O-acetyltransferase (CRAT) is a key mitochondrial enzyme involved in maintaining metabolic homeostasis by mediating the reversible transfer of acetyl groups between acetyl-CoA and carnitine. This enzymatic activity ensures the optimal functioning of mitochondrial carbon flux by preventing acetyl-CoA accumulation, buffering metabolic flexibility, and regulating the balance between fatty acid and glucose oxidation. CRAT’s interplay with the mitochondrial carnitine shuttle, involving carnitine palmitoyltransferases (CPT1 and CPT2) and the carnitine carrier (SLC25A20), underscores its critical role in energy metabolism. Emerging evidence highlights the structural and functional diversity of CRAT and structurally related acetyltransferases across cellular compartments, illustrating their coordinated role in lipid metabolism, amino acid catabolism, and mitochondrial bioenergetics. Moreover, the structural insights into CRAT have paved the way for understanding its regulation and identifying potential modulators with therapeutic applications for diseases such as diabetes, mitochondrial disorders, and cancer. This review examines CRAT’s structural and functional aspects, its relationships with carnitine shuttle members and other carnitine acyltransferases, and its broader role in metabolic health and disease. The potential for targeting CRAT and its associated pathways offers promising avenues for therapeutic interventions aimed at restoring metabolic equilibrium and addressing metabolic dysfunction in disease states.
Dual Therapy in Inflammatory Bowel Disease
Authors: Altieri Gabriele , Zilli Alessandra , Parigi Tommaso Lorenzo , Allocca Mariangela , Furfaro Federica , Fiorino Gionata , Cicerone Clelia , Peyrin-Biroulet Laurent , Danese Silvio , D’Amico Ferdinando
Published: February 2025

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic and complex autoimmune conditions. Despite the advancements in biologics and small molecules, the therapeutic ceiling persists, posing significant treatment challenges and contributing to the concept of difficult-to-treat IBD. Dual-targeted therapy (DTT), combining two biologic agents or biologics with small molecules, has emerged as a novel approach to address this unmet need by targeting multiple inflammatory pathways simultaneously. Evidence suggests that DTT holds promise in improving clinical and endoscopic outcomes, especially in patients with refractory disease or extraintestinal manifestations. Safety data, while consistent with monotherapy profiles, highlight the importance of vigilant monitoring for infections and other adverse events. Continued research and high-quality trials are crucial to defining optimal DTT regimens and broadening its clinical applicability. This review explores the efficacy and safety of DTT in IBD, reporting data from clinical trials, systematic reviews, and real-world studies.
Advances in the Development of Mitochondrial Pyruvate Carrier Inhibitors for Therapeutic Applications
Authors: Politte Henry , Maram Lingaiah , Elgendy Bahaa
Published: February 2025

The mitochondrial pyruvate carrier (MPC) is a transmembrane protein complex critical for cellular energy metabolism, enabling the transport of pyruvate from the cytosol into the mitochondria, where it fuels the citric acid cycle. By regulating this essential entry point of carbon into mitochondrial metabolism, MPC is pivotal for maintaining cellular energy balance and metabolic flexibility. Dysregulation of MPC activity has been implicated in several metabolic disorders, including type 2 diabetes, obesity, and cancer, underscoring its potential as a therapeutic target. This review provides an overview of the MPC complex, examining its structural components, regulatory mechanisms, and biological functions. We explore the current understanding of transcriptional, translational, and post-translational modifications that modulate MPC function and highlight the clinical relevance of MPC dysfunction in metabolic and neurodegenerative diseases. Progress in the development of MPC-targeting therapeutics is discussed, with a focus on challenges in designing selective and potent inhibitors. Emphasis is placed on modern approaches for identifying novel inhibitors, particularly virtual screening and computational strategies. This review establishes a foundation for further research into the medicinal chemistry of MPC inhibitors, promoting advances in structure-based drug design to develop therapeutics for metabolic and neurodegenerative diseases.
Personalized Prediction of Total Knee Arthroplasty Mechanics Based on Sparse Input Data—Model Validation Using In Vivo Force Data
Authors: Ehreiser Sonja , Asseln Malte , Radermacher Klaus
Published: February 2025

Background/Objectives: Computational models are increasingly used in orthopedic research, such as in the context of total knee arthroplasty (TKA). However, the models’ actual integration in clinical practice is far from routine. Major limitations include the amount of input data, effort, and time required for personalization and simulation. In this paper, we present and validate a patient-specific multi-body musculoskeletal TKA model based on sparse input data to address these limitations. Methods: The simulation model was individualized based on the patients’ bone and knee implant 3D geometries, predicted bony landmarks, and soft tissue attachments using annotated statistical shape models, a statistical squat motion pattern, and a statistically based load case. For the validation, we used publicly accessible in vivo knee contact forces during squatting from four patients of the Grand Challenge Competitions (GCCs). Results: The prediction accuracy was quantified using several error metrics, including the root mean square error (RSME). For GCC3 and GCC5, both the range and trend of the mean in vivo contact forces were well matched by the simulation (RMSE lateral: 8.2–26.1% of body weight (BW); RMSE medial: 15.9–42.7 %BW). In contrast, there were relevant deviations between the experiment and simulation in the trend of contact forces for patient GCC2, as well as in the range of medial contact forces for patient GCC6 (RMSE medial: 52.6 %BW). The model setup time was at the magnitude of 15 min per patient, and the simulation was completed in less than 4 min. Conclusions: When comparing our results with the literature, we found similar accuracy to state-of-the-art models in predicting knee contact forces. While remaining deviations between in vivo and simulation data still warrant investigation and evaluation for clinical significance, the model has already successfully addressed important limitations of these previous models, which represent significant barriers to clinical application.
Tired of ACL Injures: A Review of Methods and Outcomes of Neuromuscular Fatigue as a Risk Factor for ACL Injuries
Authors: Taylor Joshua L. I. , Burkhart Timothy A.
Published: February 2025

Background/Objectives: One potential risk factor that remains especially contentious in the anterior cruciate ligament (ACL) injury literature is the role of neuromuscular fatigue in ACL injury risk. Therefore, the purposes of this review are (i) to present the research and practical concepts of lower extremity neuromuscular fatigue; and (ii) to review the literature relating to neuromuscular fatigue as an ACL injury risk factor and mechanism. Methods: A structured review was performed in the Medline database using a search strategy that included terms such as “anterior cruciate ligament injury” and “knee injuries” combined with terms such as “injury” and “fatigue”. Articles were included if they included young healthy participants (18–35) and made a comparison between non-fatigued and fatigued states that were assessed with at least one lower extremity biomechanical variable associated with ACL injury risk. Results: Overall, there were 67 studies included, accounting for 1440 participants (627 male and 813 female) across a variety of sports and activities. Of these, 53 (79%) reported a post-fatigue change in the kinematics, kinetics, neuromuscular, and/or other (e.g., proprioceptive) outcomes that indicate that the participants would be at an increased risk of an ACL injury. The most common argument against fatigue as a risk factor is that ACL injuries do not tend to occur later in a game or season, when it is assumed that athletes would be most fatigued. Conclusions: The evidence presented in this review suggests that localized neuromuscular fatigue is a risk factor, among multiple factors, for ACL injuries, providing another modifiable risk factor that should be considered when developing ACL injury risk reduction interventions.
Trajectory Analysis in FBG and the Incidence of Chronic Kidney Disease: A Nationwide Population-Based Study
Authors: Park Heewon , Na Ki Ryang , Hwang Yunkyeong , Han Suyeon , Park Kyungho , Park Hyerim , Lee Eu Jin , Ham Young Rok , Ahn Soon-Ki , Choi Dae Eun
Published: February 2025

Objectives: This study aimed to classify fasting blood glucose (FBG) trajectories by sex and examine their associations with the risk of chronic kidney disease (CKD). Methods: Using data from the National Health Insurance Service-National Sample Cohort in Korea, participants aged 40 years and above, without CKD or diabetes mellitus (DM), were followed from 2002 to 2009. Based on their FBG trajectories, participants were categorized into two classes and stratified by sex. CKD incidence rates were analyzed according to these FBG trajectories, and the impact of additional risk factors on CKD incidence was assessed. Results: A total of 91,131 participants were analyzed. Among individuals classified in Class 1, FBG levels gradually increased from 90.7 (men) and 88.7 (women) in 2002 to 96.6 (men) and 93.2 (women) in 2009. In contrast, participants classified as Class 2 exhibited a rapid increase in FBG levels, rising from 106 (men) and 106 (women) in 2002 to 144 (men) and 132 (women) in 2009. The incidence of CKD increased over time in both men and women classified as Class 2 compared to Class 1, with respective hazard ratios (HR) of 1.35 for men and 1.53 for women. Additionally, increased age, hypertension, and body mass index (BMI) were independently associated with an elevated risk of CKD. Conclusions: The Class 2 group demonstrated a significantly higher incidence of CKD compared to the Class 1 group. This finding indicates the need for the proactive management of individuals with relatively high FBG levels featuring rapid FBG increases in order to mitigate the risk of CKD development.
Cytomegalovirus-Reactive IgG Correlates with Increased IL-6 and IL-1β Levels, Affecting Eating Behaviours and Tactile Sensitivity in Children with Autism
Authors: Anindya Isti , Sekartini Rini , Ariyanto Ibnu Agus , Wiguna Tjhin , Sari Novika Purnama , Rahayu Yuni Sri , Soebandrio Amin
Published: February 2025

Background/Objectives: Elevated cytokine levels, including IL-6 and IL-1β, can contribute to persistent brain inflammation in children with autism and cytomegalovirus (CMV) infection, exacerbating autism-related behaviours and symptoms. This study evaluates the impact of CMV-induced cytokine increases on the eating behaviours and sensory profiles of children with autism. Methods: A cross-sectional design was employed, involving children aged two to five years (CMV-reactive IgG), with ASD (n= 98) and TD (n = 96). Serological tests using ELISA were conducted to measure IgG CMV, IL-6, and IL-1β biomarkers. Eating behaviours were evaluated using the BAMBI (Brief Autism Mealtime Behaviour Inventory), and sensory profiles were assessed using the SSP (Short Sensory Profile). Statistical analyses were performed using Spearman’s rank and chi-square tests. Results: The results show that autism significantly affects children’s eating behaviours and sensory profiles (p < 0.001), with notable differences found between the groups. Correlation analysis revealed a significant association between IgG CMV and IL-6 (p = 0.026) and IL-1β (p = 0.014) in the ASD group. Additionally, eating behaviours (food refusal and limited variety) in ASD correlated with IL-6 and IL-1β. Sensory characteristics, such as tactile sensitivity, were found to correlate with IL-6 (p = 0.027) and IL-1β (p = 0.002) in the ASD group. Conclusions: These findings suggest that CMV-infected children with autism are at increased risk of IL-6 and IL-1β dysregulation, contributing to sensory processing issues and eating behaviours. Further research is needed to enhance CMV testing protocols and better understand the virus’s role in the development of sensory and behavioural issues in children with autism.
Short-Chain Fatty Acids and Their Metabolic Interactions in Heart Failure
Authors: Chulenbayeva Laura , Issilbayeva Argul , Sailybayeva Aliya , Bekbossynova Makhabbat , Kozhakhmetov Samat , Kushugulova Almagul
Published: February 2025

Short-chain fatty acids (SCFAs), produced through fermentation of dietary fibers by gut bacteria, play a central role in modulating cardiovascular function and heart failure (HF) development. The progression of HF is influenced by intestinal barrier dysfunction and microbial translocation, where SCFAs serve as key mediators in the gut–heart axis. This review examines the complex metabolic interactions between SCFAs and other gut microbiota metabolites in HF, including their relationships with trimethylamine N-oxide (TMAO), aromatic amino acids (AAAs), B vitamins, and bile acids (BAs). We analyze the associations between SCFA production and clinical parameters of HF, such as left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and glomerular filtration rate (GFR). Gaining insights into metabolic networks offers new potential therapeutic targets and prognostic markers for managing heart failure, although their clinical significance needs further exploration.
The Role of Personality Traits and Decision-Making Styles in Career Decision-Making Difficulties
Authors: Aydemir Dev Mine , Bayram Arlı Nuran
Published: February 2025

Career decisions are one of the most important decisions individuals make in their lives. These decisions are multifaceted and complex, making them a challenging process, particularly for students. This creates obstacles for students navigating the career choice process. The aim of this study is to examine career decision-making difficulties within the framework of personality traits and decision-making styles. The target group of this study is undergraduate students studying at a public university. For this research, we collected data through online questionnaire forms. The questionnaire comprised demographic questions and three scales: career decision-making difficulties, personality traits, and decision-making styles. A total of 505 students (63.2% female) participated in the questionnaire. The research model was tested using path analysis. We also conducted network analysis in order to better understand and visualize the relationships between the sub-dimensions of the scales. The findings showed significant direct relationships between career decision-making difficulties and personality traits (conscientiousness, openness, neuroticism, and agreeableness) and decision-making styles (rational, dependent, avoidant, and spontaneous). According to the path analysis result, neurotic personality traits were positively correlated with career decision-making difficulties, while openness to experience, agreeableness, and conscientiousness were negatively correlated with them. The relationship between dependent, avoidant, and spontaneous decision-making styles and career decision-making difficulties was positive. These results provide valuable insights into the factors that shape career decisions, helping students make more informed choices and manage their career paths effectively.
Impact of Curing Temperature and Steel Slag Aggregates on High-Strength Self-Compacting Alkali-Activated Concrete
Authors: Araújo Lucas B. R. , Targino Daniel L. L. , Babadopulos Lucas F. A. L. , Fabbri Antonin , Cabral Antonio Eduardo. B. , Chehade Rime , Costa Heloina N.
Published: February 2025

There is a growing demand for sustainable solutions in civil engineering concerning the carbon footprint of cementitious composites. Alkali-Activated Binders (AAB) are materials with great potential to replace ordinary Portland cement (OPC), with similar strength levels and lower environmental impact. Despite their improved environmental performance, their durability remains a gap in the literature, influenced by aspects of mechanical behavior, physical properties, and microstructure. This paper aims to assess the impact of steel slag aggregates and curing temperature of a proposed AAB based concrete formulation by characterizing fresh state, mechanical behavior, and microstructure. The proposed AAB is composed of fly ash (FA) and basic oxygen furnace (BOF) steel slag (SS) as precursors, sodium silicate and sodium hydroxide solution as activators, in total replacement of OPC, using baosteel slag short flow (BSSF) SS as aggregate in comparison with natural aggregate. The concrete formulation was designed to achieve a high-performance concrete (HPC) and a self-compacting concrete (SCC) behavior. Mechanical characterization encompassed hardened (compressive strength and Young’s modulus), fresh state (J-ring, slump flow, and T50), and durability tests (scanning electronic microscopy, water penetration under pressure, and chloride ion penetration). The compressive strength (64.1 ± 3.6 MPa) achieves the requirements of HPC, while the fresh state results fulfill the SCC requirements as well, with a spread diameter from 550 mm to 650 mm (SF-1 class). However, the flow time ranges from 3.5 s to 13.8 s. There was evidence of high chloride penetrability, affected by the lower electrical resistance inherent to the material. Otherwise, there was a low water penetration under pressure (3.5 cm), which indicates a well-consolidated microstructure with low connected porosity. Therefore, the durability assessment demonstrated a divergence in the results. These results indicate that the current durability tests of cementitious materials are not feasible for AAB, requiring adapted procedures for AAB composite characterization.
Insights into the Diagnosis and Prognosis of the Alkali–Silica Reaction (ASR) in Concrete Dams, Highlighting the Case of the Demolished Alto Ceira Dam in Portugal
Authors: Custódio João , Mata Juan , Serra Carlos , Ribeiro António Bettencourt , Tavares de Castro António , Batista António Lopes
Published: February 2025

Over the past few decades, a significant number of large concrete structures with deterioration problems related to the alkali–silica reaction (ASR) have been identified in Portugal and worldwide. Assessing the condition of ASR-affected concrete dams involves both diagnosis and prognosis. Diagnosis evaluates the structure’s current state, while prognosis predicts deterioration and safety implications. This is key to estimate the period during which the structure will effectively perform its function, and essential for the timely and cost-effective planning of the necessary mitigation, rehabilitation, and/or reconstruction works. This article aims to contribute to the ongoing discussion of this topic by the scientific and technical community and, therefore, presents the methodology adopted to assess the condition of a severely ASR-affected concrete dam in Portugal, the Alto Ceira dam, in which the concrete was produced with susceptible to ASR quartzitic aggregates and that was decommissioned and replaced by a new one in 2014. The article provides a brief review of the diagnosis and prognosis of the ASR in concrete dams, presents and analyses the results from laboratory testing (including chemical, microstructural, physical, mechanical, and expansion tests), in-situ testing, structural monitoring systems, visual inspections, and numerical modelling, aiming at assessing ASR impacts and evidencing the utility of the reported methodology on the appraisal of ASR-affected structures.
Experimental Study on the Flexural Performance of Geogrid-Reinforced Foamed Lightweight Soil
Authors: Li Yinhe , Liu Yong , Zhang Hongbo , An Ning , Fan Zuolin
Published: February 2025

The flexural behavior of geogrid-reinforced foamed lightweight soil (GRFL soil) is investigated in this study using unconfined compressive and four-point bending tests. The effects of wet density and reinforcement layers on flexural performance are analyzed using load–displacement curves, damage patterns, load characteristics, unconfined compressive strength, and flexural strength. A variance study demonstrates that increasing the wet density significantly increases unconfined compressive strength. Bond stress mechanisms enable geogrid integration, efficiently reroute stresses internally, and greatly increase flexural strength. With a maximum unconfined compressive strength of 3.16 MPa and a peak flexural strength increase of 166%, this reinforcement increases both strength and ductility by changing the damage pattern from brittle to ductile. The principal load is initially supported by the foamed lightweight soil, and in later phases, geogrids take over load-bearing responsibilities. Additionally, the work correlates the ratio of unconfined compressive to flexural strength with wet density and informs the development of predictive models for unconfined compressive strength as a function of reinforcing layers and wet density.
Enhancing Energy Efficiency in Mediterranean Large-Scale Buildings: A Study on Mobilized Thermal-Energy-Storage Systems
Authors: Lahoud Chawki , Harake Rawad , Fatfat Mira , Bazi Sarah
Published: February 2025

This study investigates the use of Mobilized Thermal Energy Storage (MTES) systems to enhance energy efficiency in large-scale Mediterranean buildings, focusing on a university campus in Tripoli, Lebanon. The research question addresses whether MTES can effectively utilize waste heat from a power plant to meet heating, cooling, and water heating needs. We hypothesize that MTES, using Erythritol as the phase change material (PCM) and Therminol55 as the heat transfer fluid (HTF), will improve energy efficiency and reduce costs compared to conventional systems. The methodology involves simulating the MTES system’s performance, including charge, self-discharge, and discharge phases, using Simulink-MATLAB. Key findings reveal that increasing the HTF flow reduces the charging time by 29% and enhances the efficiency by 8%, while larger project scales decrease heat costs. Economic analysis shows a payback period (PBP) of 2 years 11 months for heating only and 2 years 1 month for heating and cooling, with annual maintenance costs considered at 5%. These results demonstrate MTES as a sustainable and cost-effective solution for thermal energy storage, with potential applications in the energy sector.
Experimental Investigation of Infrared Detection of Debonding in Concrete-Filled Steel Tubes via Cooling-Based Excitation
Authors: Cai Haonan , Cheng Chongsheng
Published: February 2025

Debonding in concrete-filled steel tubes (CFSTs) is a common defect that often occurs during the construction phase of CFST structures, significantly reducing their load-bearing capacity. Current methods for detecting debonding in CFSTs using infrared thermography primarily rely on heat excitation. However, applying this method during the exothermic hydration phase presents considerable challenges. This paper proposes the innovative use of spray cooling as an excitation method during the exothermic hydration phase, providing quantitative insights into the heat conduction dynamics on steel plates for infrared debonding detection in CFSTs. The effects of atomization level, excitation distance, excitation duration, and water temperature in the tank on infrared debonding detection performance were examined. The timing of the maximum temperature difference under cooling excitation was analyzed, and the heat conduction characteristics on the surface of the steel plate during the cooling process were explored. A highly efficient and stable cooling excitation method, suitable for practical engineering detection, is proposed, providing a foundation for quantitative infrared debonding detection in CFSTs. This method does not require additional energy sources, features a simple excitation process, and results in a five-times increase in temperature difference in the debonded region after excitation.
Examining the Impact of House Size on Building Embodied Energy
Authors: Rauf Abdul , Attoye Daniel Euroizing , Khalfan Malik Mansoor Ali , Shafiq Muhammad Tariq
Published: February 2025

The effects of buildings on the environment can be reduced with research-based alternative building designs. This study focuses on reducing the building space to lower the overall size of a building as a strategy to reduce the building’s embodied energy. The aim of this study was to investigate the initial embodied energy (IEE) of a residential building that was systematically reduced in size. Using input–output-based hybrid analysis, the IEE for three architecturally distinct four-bedroom residential prototypes (P1, P2, and P3) was calculated. The IEE for P1 (525 m2), P2 (266 m2), and P3 (109 m2) were 3555, 2008, and 1000 GJ, respectively. This indicates a 72% reduction in embodied energy consumption when the largest prototype (P1) was transitioned to the smallest (P3). When analyzing IEE/m2 and IEE/m2/occupant, it becomes apparent that larger spaces tend to have a lower IEE/m2. However, when the occupancy increases, the IEE/m2/occupant decreases by 25–33%. Therefore, considering occupant-centered design for residential buildings, the benefits of a large house are not justifiable. These findings can help inform decisions regarding the optimization of residential spaces to minimize environmental impacts.
Constitutive Relation of Polypropylene-Fiber-Reinforced Mortar Under Uniaxial Compression at High Temperature
Authors: Chen Hao , Li Dongwei
Published: February 2025

Exposure to elevated temperatures leads to the deterioration of the mechanical properties of cementitious materials. However, the inclusion of fibers can mitigate, to some extent, the negative effects of high temperatures on these materials. Specifically, polypropylene (PP) fibers, a synthetic fiber type, have been demonstrated to improve the performance of cement-based composites. Therefore, it is essential to investigate the impact of temperature on the behavior of fiber-reinforced mortar for its broader application in construction. This study explores the effects of varying PP fiber contents (0%, 0.2%, 0.4%, 0.6%, 0.8%, and 1%) and different temperature exposures (25 °C, 200 °C, 400 °C, 600 °C, 800 °C, and 1000 °C) on the performance of cement mortar. The experimental results show that elevated temperatures significantly degrade both the mechanical and thermal properties of fiber-reinforced mortar. As the temperature and fiber content increase, both the quality and thermal conductivity of the mortar decrease. Between 25 °C and 200 °C, the incorporation of PP fibers (ranging from 0% to 0.2%) significantly enhances the compressive and flexural strengths of the mortar. However, this improvement becomes less pronounced as the fiber content exceeds 0.2%. At temperatures above 200 °C, further increases in temperature, coupled with higher fiber contents, consistently lead to a reduction in the compressive and flexural strengths. Based on the principles of continuous damage mechanics (which describes the degradation and fracture of materials under loading) and the dual-parameter Weibull distribution theory, a constitutive model is proposed to describe the damage behavior of high-temperature PP-fiber-reinforced mortar under uniaxial compressive stress.
Sense of Place and Sacred Places: A Phenomenological Study of Ancestral Hall Spatial Narratives—The Shike Ancestral Hall, En Village, Guangdong
Authors: Feng Jie , Bahauddin Azizi , Miao Jingwen
Published: February 2025

Based on the narrative perspective, this paper studies the spatial characteristics and cultural significance of the Shike Ancestral Hall in En Village, Guangdong, as a sacred building. By drawing on Lefebvre’s theory of spatial production, the physical space, cultural value, and community sentiment of the Shike Ancestral Hall are linked to explore its role in the sense of place, clan memory, and cultural identity. The study found that the combination of perceived, conceived, and lived space gives the Shike Ancestral Hall profound social, cultural, and religious significance. The ancestral hall is not only a material existence but also a vital link to maintain the emotional and cultural identity among clan members. Through the multi-sensory experience of the building, including light, sound, touch, and smell, the unique atmosphere of the sacred space is revealed, further deepening the need for sustainable development and protection of cultural heritage.
The Research on the Construction of Traditional Village Heritage Corridors in the Taihu Lake Region Based on the Current Effective Conductance (CEC) Theory
Authors: Wu Yao , Miao Mingrui , Wu Yonglan , Zhu Hui , Li Xiaobin , Candeias Antonio
Published: February 2025

This study focuses on constructing a heritage corridor for traditional villages in the Taihu Lake region, aiming to promote the cultural heritage preservation and sustainable development of these villages through innovative pathway design. Based on the spatial distribution characteristics of traditional villages across five cities surrounding Taihu Lake (Suzhou, Wuxi, Changzhou, Huzhou, and Jiaxing) and the existing transportation network, this research integrates the Circuit Effective Conductance (CEC) theory with ArcGIS spatial analysis methods to optimize the pathways of the heritage corridor. The results show that the expected nearest neighbor distance of 307 traditional villages in the Taihu Lake region is 5245.61 m, with the actual nearest neighbor distance being 3385.60 m, a z-score of −11.85, and a nearest neighbor index of 0.645786, indicating that traditional villages in this region exhibit clustered distribution. Combined with kernel density results, a “dual-core–four zones–multiple scatter points” spatial structure of traditional villages in the Taihu Lake region is revealed, with Dongshan Island and Wujiang District serving as the primary and secondary cultural cores, respectively. By establishing a “dual-ring heritage corridor” spatial network, a stable pathway for village heritage preservation and cultural transmission has been formed, consisting of 137 heritage corridors. Meanwhile, the CEC model demonstrates high adaptability in generating circular heritage corridors, particularly in creating closed-loop structures around the lake, thereby enhancing the spatial connectivity of the corridors and facilitating the effective flow of cultural resources. Through the strategic design of outer and inner ring corridors, this study successfully links traditional villages in the Taihu Lake region and develops optimal travel routes. The study provides practical solutions for the protection, revitalization, and integration of cultural tourism in the region and offers a new perspective for constructing heritage corridors in lakefront geographies in China.
Understanding Critical Delay Causative Factors and Their Mitigation Measures in Burundi Communal Construction Projects: A Factor Analysis and Structural Equation Modeling Approach
Authors: Irankunda Georges , Zhang Wei , Abdullahi Usman Isah , Fernand Muhirwa , David Byiringiro , Jean-Petit Sinamenye
Published: February 2025

The execution of a construction project faces many potentials challenges, and delays are one of them. Communal construction projects in Burundi (CCP-Burundi projects) were considered as one field that could generate a Burundi government development plan. However, according to the frequency of delays encountered by these projects, at a rate of 70% on average every year, the government’s target seems far from being achieved. As no scientific study exists on how to avoid CCP delays, this paper aims to identify and analyze factors that cause delays in CCP-Burundi and provide related measures to overcome them. Based on a list of fifty delay factors gathered from the National Communal Investment Fund institution FONIC (Fond National d’Investissement Communal), communal annual reports, and the literature, a questionnaire survey was developed and dispersed to CCP stakeholders to collect data about critical factors. The top fifteen factors were identified using a relative importance index and a factor analysis was performed. “Weather conditions” was the top-ranked factor, while “Claims” was the lowest ranked. A structural equation modeling approach was adopted to evaluate influences at the relationship level among delay factor groups. A standardized calculation revealed that Factors During Awarding of Bid (FDABs) positively influence Factors After the Award of Bid (FAABs). The findings were implemented in case studies to assess their efficacy. This paper’s findings could assist upcoming construction practitioners and future researchers aiming to explore construction-related project delays, providing a fundamental understanding of the significant delays encountered in the Burundi construction industry.
The Influence of Weather Conditions on Time, Cost, and Quality in Successful Construction Project Delivery
Authors: Dong RunRun , Muhammad Ali , Nauman Umer
Published: February 2025

The effective management of the triple constraints, time, cost, and quality, is imminently essential for the success of construction projects, and it is considered a hot research topic nowadays. For this purpose, we carried out this study to systematically analyze the influence of these constraints on project success, specifically emphasizing how weather conditions intensify the difficulties associated with these constraints. A survey questionnaire was administered to 242 industry experts, and the collected data were evaluated utilizing the software named Statistical Package for Social Sciences (SPSS), Version 30.0. Further, we also analyzed the obtained data by employing Cronbach’s alpha, correlation, and regression analyses, which obviously confirmed the effects of these constraints on project success. In addition, the results clearly indicated that weather-related delays increased the durations of projects by 25.7% and caused an average cost increase of 23.8%. Focused attention was required for effective management of these constraints. This study further highlights the need for strategic planning and effective risk management to mitigate weather-related risks. As a result, proficient management of these elements is imminently crucial for ensuring project success in the construction sector. Thus, we concluded that this study will allow construction projects in future endeavors to be carried out with high proficiency and effectiveness.
Long-Term Survival of Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib in Real-World Clinical Practice
Authors: Furuse Junji , Izumi Namiki , Motomura Kenta , Inaba Yoshitaka , Katamura Yoshio , Kondo Yasuteru , Yabushita Kazuhisa , Matsuoka Toshiyuki , Motoyoshi Katsuaki , Kudo Masatoshi
Published: February 2025

Background/objectives: The real-world survival of patients with unresectable hepatocellular carcinoma (uHCC) treated with lenvatinib has been explored retrospectively with a small sample size. We conducted a prospective observational 2-year extension study (510 study) of a 1-year observational post-marketing study of lenvatinib (504 study) to evaluate the long-term overall survival (OS) of patients with uHCC treated with lenvatinib and associated factors with a large sample size. Methods: Patients with uHCC included (July 2018 to January 2019) in the 504 study and who consented were eligible for the 510 study and were followed for up to 3 years after lenvatinib treatment initiation. Using the data from the 504 study and 510 study of the 504 study analysis set, we estimated the OS, the time from the first lenvatinib dose to all-cause death by the Kaplan–Meier method (ClinicalTrials.Gov Registration ID, 504 study: NCT03663114; 510 study: NCT04008082). Results: The 703 patients included in the analysis were followed for a median period (min, max) of 12.5 months (0.1, 44.8). The median OS (95% confidence interval) was 16.6 months (15.4, 18.5). OS was significantly (p < 0.05) associated with bile duct invasion (hazard ratio [HR]: 1.621), portal vein invasion (HR: 1.365), ≥ 4 intrahepatic lesions (HR: 1.437), extrahepatic lesions (HR: 1.357), Child–Pugh B/C (HR: 1.515), mALBI Grade 2a (HR: 1.331), and Grade ≥ 2b (HR: 1.811). Conclusions: This large-scale, prospective, real-world study demonstrated a long OS, comparable to that reported in the global Phase III REFLECT trial. More advanced-stage tumors and worse hepatic function have been suggested as OS-associated factors, consistent with previous reports.
Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Cytoreductive Surgery (CRS): Age-Related Outcomes and a Look into the Future
Authors: Aguirre Salvador , Haley Jill K. , Broski Julie A. , Baker Jordan , Selby Luke V. , Umar Shahid , Al-Kasspooles Mazin F.
Published: February 2025

Introduction: Peritoneal carcinomatosis presents significant treatment challenges. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) offers a promising therapeutic approach. Patient selection remains critical, and the role of age as an exclusion criterion requires further investigation. This study evaluates whether age influences postoperative outcomes in CRS-HIPEC patients. Methods: A retrospective review of a prospective comprehensive database of 271 CRS-HIPEC procedures performed between 2018 and 2023 was conducted. Logistic regression assessed the relationship between age and postoperative outcomes. Age groups (18–44, 45–69, ≥70 years) were compared based on demographic data, primary tumor site, Peritoneal Cancer Index scores, and key outcome measures. Results: Across the different age groups, there were no significant differences in PCI scores, recurrence, disease-free survival, 30-day morbidity, or mortality. Length of stay was longer in older patients (p = 0.009). Patients aged ≥70 had higher readmission rates (p = 0.041) and were more often discharged to transitional care facilities (p = 0.001). Older patients were also more likely to experience Clavien–Dindo grade III or higher complications (p = 0.008). Logistic regression confirmed these findings. Continuous age analysis yielded similar results and revealed significant differences in race and primary organ involvement. Conclusions: Age is not a significant predictor of 30-day morbidity, mortality, or survival outcomes in patients undergoing CRS-HIPEC. However, older patients require closer attention to discharge planning and readmission risk management. This study highlights the importance of comprehensive patient assessment beyond age and underscores the need for further research to better understand factors influencing outcomes in this population.
Synergistic Inhibition of Drug Resistant KRAS Mutant Non-Small Cell Lung Cancer by Co-Targeting AXL and SRC
Authors: Mukherjee Soumavo , Suresh Dhananjay , Zambre Ajit , Yadavilli Sairam , Ghoshdastidar Shreya , Upendran Anandhi , Kannan Raghuraman
Published: February 2025

Background/Objectives: KRAS-mutated NSCLC has been targeted using monoclonal antibody (mAb) or tyrosine kinase inhibitor (TKI) therapies. However, in time, these mutations appear to develop resistance against the targeted antibodies and TKI treatments. One possible explanation is the activation of pro apoptotic pathways through the AXL–SRC–Akt axis. In this study, we identify AXL as the bypass resistant gene and investigate its role with KRAS and SRC activity. Methods: In this study, we use Dasatinib and SGI-7079 to co-inhibit SRC and AXL respectively. In vitro studies were conducted using four cell lines, and AXL suppression was achieved using siRNA and in CRISPR-Cas9 mediated knockout models. Subsequently, we studied gene-protein expression analysis using Western blot, apoptotic markers using a cytochrome release assay and cytotoxicity using an MTT assay. A549 xenografts were studied for in vivo validation of our proposed hypothesis. Results: The results suggest that dual inhibition of AXL and SRC significantly reversed this resistance, both in in vivo and in vitro studies. Conclusions: Co-inhibition of AXL and SRC synergistically reduced KRAS activity and induced apoptosis in NSCLC.