bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cell-Based Evaluation of the Tyrosinase-Mediated Metabolic Activation of Leukoderma-Inducing Phenols, II: The Depletion of Nrf2 Augments the Cytotoxic Effect Evoked by Tyrosinase in Melanogenic Cells
Authors: Nishimaki-Mogami Tomoko , Ito Shosuke , Wakamatsu Kazumasa , Akiyama Takumi , Tamehiro Norimasa , Shibata Norihito
Published: January 2025

Chemical leukoderma is a disorder induced by chemicals such as rhododendrol and monobenzone. These compounds possess a p-substituted phenol moiety and undergo oxidation into highly reactive and toxic o-quinone metabolites by tyrosinase. This metabolic activation plays a critical role in the development of leukoderma through the production of damage to melanocytes and immunological responses. This study aimed to develop a simple method for assessing the metabolic activation of leukoderma-inducing phenols without analyzing the metabolite. Although B16BL6 melanoma cells showed insufficient sensitivity to the cytotoxicity assay, the siRNA-mediated knockdown of the transcription factor NRF2 (NFE2L2) repressed the expression of cytoprotective factors, thereby augmenting the cytotoxicity of all six leukoderma-inducing phenols tested in a tyrosinase-dependent manner, indicating enhanced sensitivity to o-quinone metabolites. Additionally, the knockdown of the NRF2-target Slc7a11 elevated the cytotoxicity of three out of the six compounds, indicating the involvement of cystine transport in cellular protection. In contrast, the knockdown or inhibition of the NRF2-target Nqo1 had minimal effects. The same response was induced upon Nrf2 and Slc7a11 knockdown in B16-4A5 cells, albeit with low sensitivity owing to low tyrosinase expression. We conclude that the analysis of tyrosinase-dependent cytotoxicity in Nrf2-depleted B16BL6 cells may serve as a useful strategy for evaluating the metabolic activation of chemicals.
A Comprehensive Analysis of Fibromyalgia and the Role of the Endogenous Opioid System
Authors: García-Domínguez Mario
Published: January 2025

Fibromyalgia represents a chronic pain disorder characterized by musculoskeletal pain, fatigue, and cognitive impairments. The exact mechanisms underlying fibromyalgia remain undefined; as a result, diagnosis and treatment present considerable challenges. On the other hand, the endogenous opioid system is believed to regulate pain intensity and emotional responses; hence, it might be expected to play a key role in the enhanced sensitivity experienced by fibromyalgia patients. One explanation for the emergence of disrupted pain modulation in individuals with fibromyalgia is a significant reduction in opioid receptor activity or an imbalance in the levels of endogenous opioid peptides. Further research is essential to clarify the complex details of the mechanisms underlying this abnormality. This complexity arises from the notion that an improved understanding could contribute to the development of innovative therapeutic strategies aimed at targeting the endogenous opioid system in the context of fibromyalgia. Although progress is being made, a complete understanding of these complexities remains a significant challenge. This paradigm has the potential to revolutionize the complex management of fibromyalgia, although its implementation may experience challenges. The effectiveness of this approach depends on multiple factors, but the implications could be profound. Despite the challenges involved in this transformation, the potential for improving patient care is considerable, as this condition has long been inadequately treated.
From Serendipity to Precision: Integrating AI, Multi-Omics, and Human-Specific Models for Personalized Neuropsychiatric Care
Authors: Tanaka Masaru
Published: January 2025

Background/Objectives: The dual forces of structured inquiry and serendipitous discovery have long shaped neuropsychiatric research, with groundbreaking treatments such as lithium and ketamine resulting from unexpected discoveries. However, relying on chance is becoming increasingly insufficient to address the rising prevalence of mental health disorders like depression and schizophrenia, which necessitate precise, innovative approaches. Emerging technologies like artificial intelligence, induced pluripotent stem cells, and multi-omics have the potential to transform this field by allowing for predictive, patient-specific interventions. Despite these advancements, traditional methodologies such as animal models and single-variable analyses continue to be used, frequently failing to capture the complexities of human neuropsychiatric conditions. Summary: This review critically evaluates the transition from serendipity to precision-based methodologies in neuropsychiatric research. It focuses on key innovations such as dynamic systems modeling and network-based approaches that use genetic, molecular, and environmental data to identify new therapeutic targets. Furthermore, it emphasizes the importance of interdisciplinary collaboration and human-specific models in overcoming the limitations of traditional approaches. Conclusions: We highlight precision psychiatry’s transformative potential for revolutionizing mental health care. This paradigm shift, which combines cutting-edge technologies with systematic frameworks, promises increased diagnostic accuracy, reproducibility, and efficiency, paving the way for tailored treatments and better patient outcomes in neuropsychiatric care.
Therapeutic Potential of Targeting Ferroptosis in Periprosthetic Osteolysis Induced by Ultra-High-Molecular-Weight Polyethylene Wear Debris
Authors: Ogawa Takuya , Yokota Shunichi , Chen Liyile , Ogawa Yuki , Nishida Yoshio , Tokuhiro Taiki , Alhasan Hend , Yutani Tomoyo , Shimizu Tomohiro , Takahashi Daisuke , Miyazaki Takuji , Endo Tsutomu , Kadoya Ken , Terkawi Mohamad Alaa , Iwasaki Norimasa
Published: January 2025

Background/Objectives: Periprosthetic osteolysis is the primary cause of arthroplasty failure in the majority of patients. Mechanistically, wear debris released from the articulating surfaces of a prosthesis initiates local inflammation and several modes of regulated cell death programs, such as ferroptosis, which represents a promising therapeutic target in various chronic inflammatory diseases. Thus, the current study aimed at exploring the therapeutic potential of targeting ferroptosis in a polyethylene-wear-debris-induced osteolysis model. Methods: Inverted cell culture model was used for stimulating the cells with wear debris in vitro, and calvarial osteolysis model was used for evaluating the therapeutic effects of inhibitors in vivo. Results: The immunostaining of periprosthetic bone tissues demonstrated a number of osteocytes expressing ferroptosis markers. Likewise, the expressions of ferroptosis markers were confirmed in polyethylene-wear-debris-stimulated osteocyte-like cells and primary osteoblasts in a direct stimulation model but not in an indirect stimulation model. Furthermore, polyethylene wear debris was implanted onto calvarial bone and mice were treated with the ferroptosis inhibitors DFO and Fer-1. These treatments alleviated the inflammatory and pathological bone resorption induced by the wear debris implantation. Conclusions: Our data broaden the knowledge of the pathogenesis of periprosthetic osteolysis and highlight ferroptosis as a promising therapeutic target.
Vascularization, Innervation, and Inflammation: Pathways Connecting the Heart–Brain Axis and Implications in a Clinical Setting
Authors: Lauinger Alexa R. , Sepe Joseph J.
Published: January 2025

With an aging population, the incidence of both ischemic heart disease and strokes have become the most prevalent diseases globally. These diseases have similar risk factors, such as hypertension, diabetes, and smoking. However, there is also evidence of a relationship between the heart and the brain, referred to as the heart–brain axis. In this relationship, dysfunction of either organs can lead to injury to the other. There are several proposed physiologies to explain this relationship. These theories usually involve vascular, neuromodulatory, and inflammatory processes; however, few articles have explored and compared these different mechanisms of interaction between the heart and brain. A better understanding of the heart–brain axis can inform physicians of current and future treatment and preventive care options in heart and brain pathologies. The relationship between the brain and heart depends on inflammation, vascular anatomy and function, and neuromodulation. The pathways connecting these organs often become injured or dysfunctional when a major pathology, such as a myocardial infarction or stroke, occurs. This leads to long-term impacts on the patient’s overall health and risk for future disease. This study summarizes the current research involved in the heart–brain axis, relates these interactions to different diseases, and proposes future research in the field of neurocardiology. Conditions of the brain and heart are some of the most prevalent diseases. Through understanding the connection between these two organs, we can help inform patients and physicians of novel therapeutics for these pathologies.
Comparison of Different Molecular Weights of Intra-Articular Hyaluronic Acid Injections for Knee Osteoarthritis: A Level I Bayesian Network Meta-Analysis
Authors: Migliorini Filippo , Maffulli Nicola , Nijboer Cornelis Hindriks , Pappalardo Gaetano , Pasurka Mario , Betsch Marcel , Kubach Joshua
Published: January 2025

Background: The present Bayesian network meta-analysis compared the efficacy of intra-articular injections of different molecular weights of hyaluronic acid (HA) in patients with knee osteoarthritis. Methods: In November 2024, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. All randomised controlled trials investigating the efficacy of intra-articular HA injections for knee osteoarthritis were accessed. The outcome of interest was to evaluate pain according to the visual analogue scale (VAS). The groups included for comparison were the ultra-high molecular weight (UHMW), high molecular weight (HMW), medium molecular weight (MMW), and low molecular weight (LMW). Results: Data from 9822 patients were collected. The mean age of the patients was 62.1 ± 5.0 years with given comparability at baseline. Different follow-up periods were compared. The longest control period ranged from four to six months, and the UHMW and HMW injections were the interventions associated with the greatest reduction in the VAS. LMW HA was the intervention associated with the lowest decrease in VAS, falling short of the control group. Conclusions: The main findings of the present Bayesian network meta-analysis, with a current level I of evidence, suggests that the UHMW and HMW HA has a beneficial effect on pain at 6 months post intervention in patients with knee osteoarthritis.
Acupuncture and Kinesitherapy Improve Physical Activity More than Kinesitherapy Alone in Patients with Acute Decompensated Chronic Heart Failure with Reduced Ejection Fraction Who Are Already on Optimal Drug Therapy: A Randomized, Sham-Controlled, Double-Blind Clinical Study
Authors: Ilic Dejan , Jovic Zoran , Mladenovic Zorica , Pejovic Vesna , Lung Branislava , Kozic Aleksandra , Obradovic Slobodan
Published: January 2025

Background/Objectives: It is unknown how early exercise therapy combined with acupuncture (AP) affects the speed of recovery in patients suffering from heart failure with reduced ejection fraction (HFrEF) who are hospitalized due to worsening HF. Methods: A prospective, sham-procedure-controlled, double-blind, randomized clinical trial with three patient groups was conducted. The study included patients with HFrEF who were hospitalized for worsening HF. After initial stabilization, patients were randomly assigned to three groups, the controls (C) treated with optimal drug therapy (ODT); E1 received ODT with kinesitherapy, and sham AP; E2 received ODT, kinesitherapy, and needle AP aiming to enhance compensation. Improvement in physical activity was measured by the modified Barthel index (A test), 2 or 6 min walking tests, an endurance walking test, and decrease of blood brain natriuretic peptide (BNP). Results: A total of 120 patients completed the study. The average age was 74 years, 73.3% were male, median EF was 32%, and 83.3% were New York Heart Association (NYHA) Class III. After the fifth day of therapy, the E2 group showed the greatest improvement in the A test compared to other groups (p = 0.022). After 5 days, 80%, 50%, and 10% achieved an A test score of 30 or higher, demonstrating functional independence, (p < 0.01) in the E2, E1, and C groups, respectively. At hospital discharge, the E2 group showed significantly better walking endurance compared to the E1 and C groups (p < 0.001). At discharge, BNP decreased significantly more in both E groups, compared to the C group. Conclusions: Short-term early rehabilitation with AP and kinesitherapy significantly improves the functional status of HFrEF decompensated patients when compared to kinesitherapy alone and ODT.
Hypericin-Mediated Photodynamic Therapy for Head and Neck Cancers: A Systematic Review
Authors: Fiegler-Rudol Jakub , Zięba Natalia , Turski Radosław , Misiołek Maciej , Wiench Rafał
Published: January 2025

Background: Conventional treatments for cancers of the head and neck region are often associated with high recurrence rates and impaired quality of life. Photodynamic therapy (PDT) has emerged as a promising alternative, leveraging photosensitizers such as hypericin to selectively target tumour cells with minimal damage to surrounding healthy tissues. Objectives: We aimed to evaluate the efficacy and underlying mechanisms of hypericin-mediated PDT (HY-PDT) in treating head and neck cancers. Methods: Adhering to PRISMA 2020 guidelines, a systematic search was conducted across PubMed/Medline, Embase, Scopus, and the Cochrane Library for studies published between January 2000 and December 2024. Inclusion criteria encompassed preclinical in vitro and in vivo studies and clinical trials focusing on HY-PDT for head and neck malignancies and its subtypes. Results: A total of 13 studies met the inclusion criteria, comprising both in vitro and in vivo investigations. HY-PDT consistently demonstrated significant cytotoxicity against squamous cell carcinoma cells through apoptotic and necrotic pathways, primarily mediated by ROS generation. Hypericin exhibited selective uptake in cancer cells over normal keratinocytes. Additionally, HY-PDT modulated the tumour microenvironment by altering cytokine profiles, such as by increasing IL-20 and sIL-6R levels, which may enhance antitumor immunity and reduce metastasis. Conclusions: HY-PDT emerges as a highly promising and minimally toxic treatment modality for head and neck cancers, demonstrating efficacy in inducing selective tumour cell death and modulating the immune microenvironment. Despite the encouraging preclinical evidence, significant methodological variability and limited clinical data necessitate further large-scale, standardized and randomized controlled trials.
Subgingival Delivery of Statins as an Adjunct in the Non-Surgical Treatment of Periodontitis: A Systematic Review
Authors: Pietrzko Magdalena Maria , Pietrzko Maciej , Niemczyk Wojciech , Skaba Dariusz , Wiench Rafał
Published: January 2025

Background/Objectives: The gold standard in the non-surgical treatment of periodontitis is scaling and root planning (SRP). In recent years, studies have emerged suggesting additional clinical benefits from the use of statins as an adjunct to classical periodontal disease treatment. The aim of the present study was to review the relevant literature relating to the subgingival use of statins as an adjunctive treatment to the classical, non-surgical treatment of periodontitis, with a particular focus on groups with general factors that may affect the outcome of treatment. Methods: The authors conducted a systematic review following the PRISMA 2020 guidelines. The electronic literature search conducted included the MEDLINE (PubMed) database, Web of Science, Scopus, and Google Scholar from 1 January 2012 to 14 June 2024. The keywords used for the PubMed search were determined with the help of the MeSH Browser Tool and were as follows: Periodontitis [Mesh] AND Statin [Mesh] OR Simvastatin [Mesh] OR Atorvastatin [Mesh] or Rosuvastatin Calcium [Mesh]. Based on the authors’ inclusion and exclusion criteria, 20 results were included in the review, out of 937. Results: The improvement was more pronounced in patients without systematic diseases compared to those with type II diabetes and in non-smokers compared to smoking patients. Greater improvements in clinical and radiological parameters were seen in patients diagnosed with aggressive periodontitis compared to patients with chronic periodontitis. Conclusions: This literature review led the authors to the conclusion that statins applied locally might be competent agents for improving the therapeutic outcomes of SRP.
Influence of the Sodium Titanate Crystal Size of Biomimetic Dental Implants on Osteoblastic Behavior: An In Vitro Study
Authors: Fernández-Hernández Saray , Gil Javier , Robles-Cantero Daniel , Pérez-Pevida Esteban , Herrero-Climent Mariano , Brizuela-Velasco Aritza
Published: January 2025

Treating the surfaces of dental implants in an alkaline medium allows us to obtain microstructures of sodium titanate crystals that favor the appearance of apatite in the physiological environment, producing osteoconductive surfaces. In this research, 385 discs made of titanium used in dental implants underwent different NaOH treatments with a 6M concentration at 600 °C and cooling rates of 20, 50, 75, and 115 °C/h. Using high-resolution electron microscopy, the microstructures were observed, and the different crystal sizes were determined and compared with control samples (those without biomimetic treatment). Roughness, wettability, surface energy and the sodium content of the surface were determined. The different surfaces were cultured with human osteoblastic cells; cell adhesion was determined at 3 and 14 days, and the degree of mineralization was determined at 14 days via alkaline phosphatase levels. Variations in the microstructure and size of sodium titanate crystals in NaOH solutions rich (1 g/L) or low in calcium (approximately 100 ppm) were determined. The results show that as the cooling rate increases, the size of the crystals decreases (from 0.4 μm to 0.8 μm) except for the case of 115 °C/h, when the rate is too fast for crystalline nucleation to occur on the surface of the titanium. The thermochemical treatment does not influence the roughness or the cooling rate since a Sa of 0.21 μm is maintained. However, the presence of titanate causes a decrease in the contact angle from 70° to 42° and, in turn, causes an increase in the total surface energy from 35 to 49.5 mJ/m2, with the polar component standing out in this energy increase. No variations were observed in the thermochemical treatments in the presence of sodium, which was around 1200 ppm. It was observed that as the size of the crystals decreases, cell adhesion increases at 3 days and decreases at 14 days. This is because finer crystals on the surface are already in the mineralization process, as demonstrated using the level of alkaline phosphatase that is maximal for the cooling rate of 75 °C/h. It was possible to confirm that the variations in the concentrated NaOH solutions with different calcium contents did not affect the crystal sizes or the microstructure of the surface. This research makes it possible to obtain dental implants with different mineralization speeds depending on the cooling rate applied.
Multi-Strategy Improved Whale Optimization Algorithm and Its Engineering Applications
Authors: Zhou Yu , Hao Zijun
Published: January 2025

The Whale Optimization Algorithm (WOA) is recognized for its simplicity, few control parameters, and effective local optima avoidance. However, it struggles with global search efficiency and slow convergence. This paper introduces the Improved WOA (ImWOA) to overcome these challenges. Initially, ImWOA utilizes a dynamic elastic boundary optimization strategy, which leverages boundary information and the current optimal position to guide solutions that exceed the boundaries back within permissible limits, gradually converging towards the optimal solution. Subsequently, ImWOA integrates an advanced random searching strategy that equilibrates global and local searches by focusing on the current optimal location and the mean position of all individuals. Lastly, a combined mutation mechanism is employed to enhance population diversity, prevent the algorithm from stagnating in local optima, and consequently augment its overall search capability. Performance evaluations on CEC2017 benchmark functions show ImWOA outperforming five metaheuristic algorithms and three WOA variants in optimization accuracy, stability, and convergence speed. ImWOA excelled in 25 out of 29 test functions in 30D and 26 out of 29 in 100D scenarios. Furthermore, its efficacy in addressing complex challenges is corroborated by real-world applications in reducer design, vehicle side impact design, and welded beam design, highlighting its potential utility across various engineering domains.
An Integrated Microfluidic Microwave Array Sensor with Machine Learning for Enrichment and Detection of Mixed Biological Solution
Authors: Yang Sen , Wang Yanxiong , Jiang Yanfeng , Qiang Tian
Published: January 2025

In this work, an integrated microfluidic microwave array sensor is proposed for the enrichment and detection of mixed biological solution. In individuals with urinary tract infections or intestinal health issues, the levels of white blood cells (WBCs) and Escherichia coli (E. coli) in urine or intestinal extracts can be significantly elevated compared to normal. The proposed integrated chip, characterized by its low cost, simplicity of operation, fast response, and high accuracy, is designed to detect a mixed solution of WBCs and E. coli. The results demonstrate that microfluidics could effectively enrich WBCs with an efficiency of 88.3%. For WBC detection, the resonance frequency of the sensing chip decreases with increasing concentration, while for E. coli detection, the capacitance value of the sensing chip increases with elevated concentration. Furthermore, the measurement data are processed using machine learning. Specifically, the WBC measurement data are subjected to a further linear fitting. In addition, the prediction model for E. coli concentration, employing four different algorithms, achieves a maximum accuracy of 95.24%. Consequently, the proposed integrated chip can be employed for the clinical diagnosis of WBCs and E. coli, providing a novel approach for medical and biological research involving cells and bacteria.
Mapping Surface Potential in DNA Aptamer–Neurochemical and Membrane–Ion Interactions on the SOS Substrate Using Terahertz Microscopy
Authors: Morita Kosei , Mitsuda Yuta , Yoshida Sota , Kiwa Toshihiko , Wang Jin
Published: January 2025

In this study, we utilized a terahertz chemical microscope (TCM) to map surface potential changes induced by molecular interactions on silicon-on-sapphire (SOS) substrates. By functionalizing the SOS substrate with DNA aptamers and an ion-selective membrane, we successfully detected and visualized aptamer–neurochemical complexes through the terahertz amplitude. Additionally, comparative studies of DNA aptamers in PBS buffer and artificial cerebrospinal fluid (aCSF) were performed by computational structure modeling and terahertz measurements. Beyond neurochemicals, we also investigated calcium ions, measuring their concentrations in PDMS-fabricated micro-wells using minimal sample volumes. Our results highlight the capability of TCM as a powerful, label-free, and sensitive platform for the probing and mapping of surface potential arising from molecular interactions, with broad implications for biomedical diagnostics and research.
The Multifactorial Memory Questionnaire and Quality of Life: A Longitudinal Study in Parkinson’s Disease
Authors: Corti Emily J. , Gasson Natalie , Grant Hayley , Wisniewski Brayden , Loftus Andrea M.
Published: January 2025

Background/Objectives: Objective memory decline is associated with poor quality of life (QOL) in Parkinson’s disease (PD, but it is unclear what role perception of memory (metamemory) plays. The Multifactorial Memory Questionnaire (MMQ) measures metamemory and is proposed to have a three-factor structure, but the factor structure of the MMQ in PD has not been explored. The current study examined (i) the factor structure of the MMQ in PD and (ii) the relationship between the metamemory and QOL in PD. Methods: This longitudinal, observational study involved 149 participants with PD (98 males, M age = 65.78 years, SD = 9.25). Participants completed the MMQ and the Unified Parkinson’s Disease Rating Scale (disease severity) at baseline, and the Parkinson’s Disease Questionnaire-39 (QOL) two years later. Results: Confirmatory factor analysis revealed both the three-factor and four-factor models were inadequate. Exploratory factor analysis resulted in a four-factor solution. The contentment and ability subscales from the original factor structure remained, while the strategies subscale was divided into external strategies and internal strategies. Disease severity, ability, and internal strategies uniquely predicted QOL. Individuals who reported low subjective memory ability and high use of internal strategies reported worse QOL two years later. Conclusions: These findings indicate that metamemory predicts QOL in PD and suggest that improved perceived memory ability and strategy use could offer avenues for improved QOL.
The Impact of Benevolent Sexism on Women’s Career Growth: A Moderated Serial Mediation Model
Authors: Song Shuang , Chang Po-Chien
Published: January 2025

This study investigates how benevolent sexism impedes women’s career growth, focusing on the mediating roles of self-esteem and emotional exhaustion and the moderating role of career development strategies. Using a three-wave, time-lagged survey, data from 410 female employees across various industries in China were analyzed with SPSS 24.0 and Mplus 8.3. Results indicate that benevolent sexism negatively influences career growth via reduced self-esteem and increased emotional exhaustion. Moreover, career development strategies mitigate this adverse effect, weakening the relationship between benevolent sexism and career growth. Higher levels of career development strategies lessen the detrimental impact of benevolent sexism on women’s professional progress. These findings enrich Cognitive-Affective Personality System theory by clarifying the mechanisms through which benevolent sexism undermines career development. They also highlight the practical significance of adopting robust career strategies to promote workplace gender equality and offer empirical insights into the broader implications of benevolent sexism on women’s career advancement.
Does Participation in Group Music Activities and Pro-Social Behavior Among College Students Have an Association? A Study of the Interlocking Mediating Effects of Positive Social Connections and Peer Support
Authors: Yang Haohao , Wang Siqin , Chen Xiaolong , Zhang Hongfeng , Wong Cora Un In
Published: January 2025

It has been demonstrated that music can be an effective tool for shaping the future of college students. This study aimed to investigate the effects of college students’ participation in group music activities on their pro-social behavior, and for the first time introduced the psychological variables of “positive social connections” and “perceived peer support”. The results of this study show the following: (1) Group music activity participation is positively associated with pro-social behavior. (2) Positive social connections serve as a mediator between college student group music activity participation and college students’ pro-social behavior. (3) Perceived peer support serves as a mediator between college student group music activity participation and college students’ pro-social behavior. (4) Positive social connections and perceived peer support interlock to shape the relationship between group music activity participation and pro-social behavior. This study explores the intrinsic factors of college students’ participation in group music activities to promote their pro-social behavior from the dual perspectives of music psychology and behavioral psychology, provides empirical support for educational practice, emphasizes the importance of group music activities in promoting the development of college students’ pro-social behavior, and provides insights into new perspectives for college students’ overall healthy development.
Investigating the Mechanical and Durability Properties of Carbonated Recycled Aggregate Concrete and Its Performance with SCMs
Authors: Jamil Shimza , Idrees Maria , Akbar Arslan , Ahmed Wisal
Published: January 2025

Utilizing recycled aggregates (RAs) in concrete production represents a promising path toward sustainability; however, it often results in reduced physical and durability properties. The weak interfacial transition zone (ITZ) and the adhered mortar in recycled aggregate concrete (RAC) contribute to lower mechanical strength and limit its application in demanding environments. This study investigates an accelerated carbonation technique to enhance the mechanical and durability properties of RA and RAC. Recycled aggregates, with a particle size of 10–20 mm, were subjected to carbonation at 1 bar for 2 h in a controlled carbonation chamber. Results demonstrate substantial improvements in the compressive and split tensile strengths of the carbonated recycled aggregate concrete (CRAC), with increases of 30% and 42% compared to conventional RAC, respectively. The CRAC mix also exhibited a 1.5% increase in dry density and reduced water absorption (6%) compared to RAC (7.58%). After 90 days of acid exposure, compressive strength reductions of 48.85% and 37.9% were observed for RAC and CRAC mixes, respectively, from their 28-day strength, while weight loss in CRAC was limited to 5.4%, compared to 10.92% in RAC. In sulfate exposure tests over 150 days, RAC and CRAC showed compressive strength reductions of 31.4% and 19.7% and weight losses of 3.6% and 2.2%, respectively, indicating enhanced resistance of CRAC to harsh environments. However, CRAC blended with supplementary cementitious materials (SCMs) showed diminished mechanical properties, likely due to a reduced alkaline environment caused by rapid calcium hydroxide absorption in RA pores during carbonation. Overall, the findings highlight the practical potential of accelerated carbonation to improve the performance of RAC, offering a viable pathway for sustainable construction applications.
Advancing Sustainable Infrastructure Management: Insights from System Dynamics
Authors: Juarez-Quispe Julio , Rojas-Chura Erick , Espinoza Vigil Alain Jorge , Guillén Málaga Milagros Socorro , Yabar-Ardiles Oscar , Anco-Valdivia Johan , Valencia-Félix Sebastián
Published: January 2025

Rapid infrastructure growth in developing countries has intensified environmental challenges due to cost-prioritizing practices over sustainability. This study evaluates 21 identified sustainable-driving tools to improve the management of infrastructure throughout its life cycle, by interacting with 20 out of 36 key infrastructure system management variables (ISMVs). Using a systems thinking approach, a Sustainable Systems Dynamic Model (SSDM) is developed, comprising a nucleus representing the interconnected stages of the life cycle: planning and design (S1), procurement (S2), construction (S3), operation and maintenance (S4), and renewal and disposal (S5). The model incorporates a total of 12 balance (B) and 25 reinforcement (R) loops, enabling the visualization of critical interdependencies that influence the sustainability of the system. In addition, its analysis shows the interdependencies between variables and stages, demonstrating, for example, how the implementation of tools such as LCA, BIM, and Circular Economy principles in S1, or IoT and SHM in S4, significantly improve sustainability. A gap between theory and practice in the adoption of sustainable practices is identified, which is aggravated by the lack of knowledge in specific developing countries’ context. Hence, this study contributes to its closure by offering a model that facilitates the understanding of key interactions in infrastructure systems.
Construction Payment Automation Through Scan-to-BIM and Blockchain-Enabled Smart Contract
Authors: Elsharkawi Hamdy , Elbeltagi Emad , Eid Mohamed S. , Alattyih Wael , Wefki Hossam
Published: January 2025

Timely approvals and payments to the project participants are crucial for successful completion of construction projects. However, the construction industry faces persistent delays and non-payments to contractors. Despite the desirable benefits of automated payments and enhanced access to digitized data progress, most payment applications rely on centralized control mechanisms; inefficient procedures; and documentation that takes time to prepare, review, and approve. As such, there is a need for a reliable payment automation system that guarantees timely execution of payments upon the detection of completed works. Therefore, this study used a cutting-edge approach to automate construction payments by integrating blockchain-enabled smart contracts and scan-to-Building Information Modeling (BIM). In this approach, scan-to-BIM provides accurate, real-time building progress data, which serve as the source of verifiable off-chain data. A chain-link is then used to securely relay these data to the blockchain system. Blockchain-enabled smart contracts automate the execution of payments upon meeting contract conditions. The proposed approach was implemented on a real case study project. The actual site scan was captured using a photogrammetry 360° camera, which uses a combination of structured light and infrared depth sensing technology to capture 3D data and create detailed 3D models of spaces. This study leveraged accurate, real-time building progress data to automate payments using blockchain-enabled smart contracts upon work completion, thus reducing payment disputes by tying payments to verifiable construction progress, leading to faster release of payments. The findings show that this approach provides a transparent basis for payment, enhancing trust and allowing precise project progress tracking.
Review of Condition Rating and Deterioration Modeling Approaches for Concrete Bridges
Authors: Faris Nour , Zayed Tarek , Fares Ali
Published: January 2025

Concrete bridges are the most prevalent bridge type worldwide, forming critical components of transportation infrastructure. These bridges are subjected to continuous deterioration due to environmental exposure and operational stresses, necessitating ongoing condition monitoring. Despite extensive research on condition rating and deterioration modeling of concrete bridges, a comprehensive and comparative understanding of these processes remains underexplored. This paper addresses this gap by conducting a critical scientometric and systematic review of condition rating and deterioration modeling approaches for concrete bridges to highlight their strengths and limitations. Accordingly, most of the condition rating methods were found to have a heavy reliance on qualitative visual inspections (VI) and inherent subjective assumptions. Techniques such as fuzzy logic and non-destructive evaluation (NDE) methods were identified as promising tools to mitigate uncertainties and enhance accuracy. Moreover, the performance of most deterioration models was dependent on the quality of the historical condition data. The advancement of hybrid deterioration models, such as integrating artificial intelligence (AI) with stochastic and physics-based approaches, has proven to be a powerful strategy, combining the strengths of each method to deliver enhanced condition predictions. Finally, this study offers key insights and future research directions to assist researchers and policymakers in advancing sustainable concrete bridge management practices.
Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer
Authors: Matos Paulo , Jordan Peter
Published: January 2025

The risk of developing colorectal cancer (CRC) is increased in ulcerative colitis patients compared to the general population. This increased risk results from the state of chronic inflammation, a well-known tumour-promoting condition. This review explores the pathologic and molecular characteristics of colitis-associated colon cancer (CAC), emphasizing the distinct features from sporadic CRC. We focus on the key signalling pathways involved in the transition to CAC, highlighting the emerging role of alternative splicing in these processes, namely on how inflammation-induced alternative splicing can significantly contribute to the increased CRC risk observed among UC patients. This review calls for more transcriptomic studies to elucidate the molecular mechanisms through which inflammation-induced alternative splicing drives CAC pathogenesis. A better understanding of these splicing events is crucial as they may reveal novel biomarkers for disease progression and have the potential to target changes in alternative splicing as a therapeutic strategy.
Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation Versus Adjuvant Chemotherapy Following Concurrent Chemoradiation for Locally Advanced Cervical Cancer: A Network Meta-Analysis
Authors: Suh Young Ju , Lee Dae Hyung , Lee Hee Joong , Lee Banghyun
Published: January 2025

Background/Objectives: Neoadjuvant chemotherapy followed by concurrent chemoradiation therapy (NACT + CCRT) and adjuvant chemotherapy following CCRT (CCRT + ACT) have inconsistent effects on the survival of women with locally advanced cervical cancer (LACC) compared to CCRT. Moreover, the effects of NACT + CCRT and CCRT + ACT have not been clearly compared. This study compared the effects of NACT + CCRT and CCRT + ACT on survival using a network meta-analysis to select the optimal treatment in women with LACC. Methods: The PubMed, Medline, and Embase databases were searched, and six randomized controlled trials assessing the progression-free survival (PFS) and overall survival (OS) in women with newly diagnosed LACC treated with NACT + CCRT, CCRT + ACT, or CCRT alone (controls) were identified. A network meta-analysis was conducted. Results: Indirect comparisons showed no significant differences in PFS and OS between NACT + CCRT and CCRT + ACT. Direct comparisons also showed similar PFS and OS between NACT + CCRT and CCRT and between CCRT + ACT and CCRT. CCRT + ACT exhibited the highest surface under the cumulative ranking curve (SUCRA) value as a better treatment option for the PFS and OS (CCRT + ACT vs. NACT + CCRT vs. CCRT: 72% vs. 26.8% vs. 51.2% in PFS and 64.3% vs. 45.1% vs. 40.7% in OS). Conclusions: In women with LACC, NACT + CCRT had no different effects on the PFS and OS compared to CCRT + ACT, despite the relatively higher SUCRA value observed for CCRT + ACT. Further studies are warranted to clarify the effects of these strategies.
Chronic Neutrophilic Leukemia: Advances in Diagnosis, Genetic Insights, and Management Strategies
Authors: Elbaz Younes Ismail , Mroz Pawel , Tashakori Mehrnoosh , Hamed Amira , Sen Siddhartha
Published: January 2025

CNL is a rare subtype of MPNs characterized by persistent neutrophilia, bone marrow hypercellularity, and specific genetic mutations, particularly in the CSF3R gene. Advances in molecular diagnostics have greatly enhanced our understanding of CNL, distinguishing it from other myeloproliferative disorders and refining diagnostic criteria. This review provides an updated overview of CNL, focusing on breakthroughs in genetic profiling, including novel mutations with potential prognostic value and implications for targeted therapy. We discuss current management strategies, emphasizing the role of JAK inhibitors, allogeneic stem cell transplantation, and evolving investigational treatments. Challenges in early diagnosis, therapeutic resistance, and future directions in research are also addressed, underscoring the need for a personalized medicine approach to improve outcomes for patients with CNL.
Nuclear Medicine and Molecular Imaging in Urothelial Cancer: Current Status and Future Directions
Authors: McDonald Sam , Keane Kevin G. , Gauci Richard , Hayne Dickon
Published: January 2025

Background: The role of molecular imaging in urothelial cancer is less defined than other cancers, and its utility remains controversial due to limitations such as high urinary tracer excretion, complicating primary tumour assessment in the bladder and upper urinary tract. This review explores the current landscape of PET imaging in the clinical management of urothelial cancer, with a special emphasis on potential future advancements including emerging novel non-18F FDG PET agents, PET radiopharmaceuticals, and PET-MRI applications. Methods: We conducted a comprehensive literature search in the PubMed database, using keywords such as “PET”, “PET-CT”, “PET-MRI”, “FDG PET”, “Urothelial Cancer”, and “Theranostics”. Studies were screened for relevance, focusing on imaging modalities and advances in PET tracers for urothelial carcinoma. Non-English language, off-topic papers, and case reports were excluded, resulting in 80 articles being selected for discussion. Results: 18F FDG PET-CT has demonstrated superior sensitivity over conventional imaging, such as contrast-enhanced CT and MRI, for detecting lymph node metastasis and distant disease. Despite these advantages, FDG PET-CT is limited for T-staging of primary urothelial tumours due to high urinary excretion of the tracer. Emerging evidence supports the role of PETC-CT in assessing response to neoadjuvant chemotherapy and in identifying recurrence, with a high diagnostic accuracy reported in several studies. Novel PET tracers, such as 68Ga-labelled FAPI, have shown promising results in targeting cancer-associated fibroblasts, providing higher tumour-to-background ratios and detecting lesions missed by traditional imaging. Antibody-based PET tracers, like those targeting Nectin-4, CAIX, and uPAR, are under investigation for their diagnostic and theranostic potential, and initial studies indicate that these agents may offer advantages over conventional imaging and FDG PET. Conclusions: Molecular imaging is a rapidly evolving field in urothelial cancer, offering improved diagnostic and prognostic capabilities. While 18F FDG PET-CT has shown utility in staging, further prospective research is needed to establish and refine standardised protocols and validate new tracers. Advances in theranostics and precision imaging may revolutionise urothelial cancer management, enhancing the ability to tailor treatments and improve patient outcomes.
Vi-PLUS: Pioneering Plane-Wave Ultrasound to Assess Breast Glandular Tissue in Healthy Women—A Pilot Study
Authors: Bene Ioana , Donci Delia Doris , Gherman Diana , Lenghel Manuela Lavinia , Solomon Carolina , Dulgheriu Ioana-Teofana , Petea-Balea Diana-Raluca , Ciortea Cristiana Augusta , Ciule Larisa Dorina , Deac Andrada-Larisa , Ciurea Anca Ileana
Published: January 2025

Background/Objectives: This study pioneers the application of the ViPLUS module, utilizing plane-wave ultrasound to measure breast tissue viscosity and elasticity. The primary goal was to establish normal reference values for viscosity in healthy women. Secondary objectives included exploring correlations between breast tissue viscosity and breast density categories, hormonal influences, and menstrual cycle phases. Methods: A prospective study was conducted on 245 asymptomatic women. Viscosity and elasticity measurements were obtained using the ViPLUS module, ensuring high reliability with stringent quality control measures. Data were statistically analyzed to evaluate correlations and group differences. Results: The median viscosity value for normal breast parenchyma was 1.7 Pa.s, with no significant variations based on breast density, menopausal status, or menstrual cycle phase. A strong correlation (rho = 0.866, p < 0.001) was observed between elasticity and viscosity values. Conclusions: The findings suggest that breast viscosity is consistent across diverse physiological states, indicating its potential as an independent diagnostic marker. This parameter could be pivotal in future breast cancer screening strategies, especially for younger women and those with dense breasts.
Utility of Polygenic Risk Scores (PRSs) in Predicting Pancreatic Cancer: A Systematic Review and Meta-Analysis of Common-Variant and Mixed Scores with Insights into Rare Variant Analysis
Authors: Verras Georgios Ioannis , Hamady Zaed Z. , Collins Andrew , Tapper William
Published: January 2025

Pancreatic adenocarcinoma is the most common histological subtype of pancreatic cancer, representing approximately 85% of all cases [...]
Colloidal Protein–Silver Nanoparticle Metalloenzyme as Artificial Redox Biocatalyst
Authors: Bojanov Glenn , Garcia-Sanz Carla , Palomo Jose M.
Published: January 2025

Efficient and sustainable catalytic processes are crucial for advancing green chemical manufacturing. Here, we describe the synthesis of novel silver artificial metalloenzymes in colloidal form in aqueous media and room temperature. The strategy is based on the in situ generation of silver nanoparticles by a genetically modified Geobacillus thermocatenulatus lipase (GTL) in the active site as an inducer and scaffold protein, producing an enzyme–Ag bioconjugate. Using a structural analysis of the formation of silver nanoparticles by XRD and UV spectra, we found the formation of Ag2O species with nanoparticles of around 11 nm average diameter size. Gel filtration chromatography demonstrated the presence of single protein molecules in the bioconjugates, although silver nanoparticles were initially formed by cysteine coordination in the active site but later were formed in other parts of the protein (five AgNPs per molecules, which is in concordance with the UV size). The enzyme structure was altered after nanoparticle formation and Ag-S interaction, which was observed in fluorescence analysis. This new enzyme showed reductive activity against p-nitrophenol to p-amino and a high conversion > 99% in the reduction of acetophenone to phenylethanol, although the enantioselective was quite moderate but higher in water that in the presence of co-solvents. Finally, oxidase-like activity was evaluated in the direct oxidation of phenylethanol to acetophenone in water, obtained at around a 23% yield of ketone after 60 h.