bluuebunny/crossref_metadata_2025 huggingface dataset:
BODIPY-Based Ratiometric Fluorescent Probe for Sensing Peroxynitrite in Inflammatory Cells and Tissues
Authors: Wu Qian , Hu Ziwei , Zhang Guoyang , Jin Yulong , Wang Zhuo
Published: December 2024

Peroxynitrite (ONOO−) plays an important role in many physiological and pathological processes. Excessive ONOO− in cells leads to oxidative stress and inflammation. However, precise monitoring of ONOO− levels in specific organelles (e.g., mitochondria) is still lacking and urgently needed. Herein, we rationally designed a mitochondria-targeted ratiometric fluorescent probe, MOBDP-I, for imaging of ONOO− in the mitochondria of inflammatory cells and model mice. This probe, MOBDP-I, was synthesized by conjugating a BODIPY fluorophore to a mitochondria-targeting moiety–indole-salt group by a carbon–carbon double bond (C=C). In the presence of ONOO−, the C=C bond between the BODIPY backbone and the indole-salt group was oxidized and broken, leading to an 18-fold enhancement of fluorescence at 510 nm, along with a significant fluorescence decrease at 596 nm. The ratiometric response property bestowed the probe with advantages in the precise quantification of ONOO− in cells, thus allowing estimation of the extent of inflammation in living cells and mouse models of rheumatoid arthritis, peritonitis, and brain inflammation. MOBDP-I could act as an effective molecular tool to study the relationship between ONOO− and the occurrence and development of inflammatory diseases.
Electrochemical Magnetic Immunoassay for the Determination of the Fish Allergen β-Parvalbumin
Authors: Rocha José Pedro , Freitas Maria , Geraldo Dulce , Bento Fátima , Delerue-Matos Cristina , Nouws Henri P. A.
Published: December 2024

β-parvalbumin (β-PV) is the primary fish allergen responsible for most allergic reactions in individuals sensitive to fish. To ensure food safety, a sandwich-based magnetic immunoassay was developed using maleimide-functionalized magnetic beads (NH-MBs). Specific anti-β-PV antibodies were immobilized on these MBs, and a screen-printed carbon electrode was employed as the electrochemical transducer. A linear concentration range from 10 to 1000 ng/mL, a limit of detection of 1.8 ng/mL, and a limit of quantification of 7.1 ng/mL were achieved. Nineteen commercial food samples were analyzed to assess the potential of the sensor for routine use in food quality control. Important factors such as protein source and food processing (e.g., boiling, grilling, and frying) and preservation (e.g., in oil, and vacuum) were evaluated. The validated results confer the usefulness of the assay for food quality control.
Sex- and Substance-Specific Associations of Circadian-Related Genes with Addiction in the UK Biobank Cohort Implicate Neuroplasticity Pathways
Authors: Khan Ayub , Minbay Mete , Attia Ziad , Ay Ahmet Ali , Ingram Krista K.
Published: December 2024

Background/Objectives: The circadian clockwork is implicated in the etiology of addiction, with circadian rhythm disruptions bidirectionally linked to substance abuse, but the molecular mechanisms that underlie this connection are not well known. Methods: Here, we use machine learning to reveal sex- and substance-specific associations with addiction in variants from 51 circadian-related genes (156,702 SNPs) in 98,800 participants from a UK Biobank cohort. We further analyze SNP associations in a subset of the cohort for substance-specific addictions (alcohol, illicit drugs (narcotics), and prescription drugs (opioids)). Results: We find robust (OR > 10) and novel sex-specific and substance-specific associations with variants in synaptic transcription factors (ZBTB20, CHRNB3) and hormone receptors (RORA), particularly in individuals addicted to narcotics and opioids. Circadian-related gene variants associated with male and female addiction were non-overlapping; variants in males primarily involve dopaminergic pathways, while variants in females factor in metabolic and inflammation pathways, with a novel gene association of female addiction with DELEC1, a gene of unknown function. Conclusions: Our findings underscore the complexity of genetic pathways associated with addiction, involving core clock genes and circadian-regulated pathways, and reveal novel circadian-related gene associations that will aid the development of targeted, sex-specific therapeutic interventions for substance abuse.
The Modulatory Effects of Transcranial Alternating Current Stimulation on Brain Oscillatory Patterns in the Beta Band in Healthy Older Adults
Authors: Morales Fajardo Kenya , Yan Xuanteng , Lungoci George , Casado Sánchez Monserrat , Mitsis Georgios D. , Boudrias Marie-Hélène
Published: December 2024

Background: In the last few years, transcranial alternating current stimulation (tACS) has attracted attention as a promising approach to interact with ongoing oscillatory cortical activity and, consequently, to enhance cognitive and motor processes. While tACS findings are limited by high variability in young adults’ responses, its effects on brain oscillations in older adults remain largely unexplored. In fact, the modulatory effects of tACS on cortical oscillations in healthy aging participants have not yet been investigated extensively, particularly during movement. This study aimed to examine the after-effects of 20 Hz and 70 Hz High-Definition tACS on beta oscillations both during rest and movement. Methods: We recorded resting state EEG signals and during a handgrip task in 15 healthy older participants. We applied 10 min of 20 Hz HD-tACS, 70 Hz HD-tACS or Sham stimulation for 10 min. We extracted resting-state beta power and movement-related beta desynchronization (MRBD) values to compare between stimulation frequencies and across time. Results: We found that 20 Hz HD-tACS induced a significant reduction in beta power for electrodes C3 and CP3, while 70 Hz did not have any significant effects. With regards to MRBD, 20 Hz HD-tACS led to more negative values, while 70 Hz HD-tACS resulted in more positive ones for electrodes C3 and FC3. Conclusions: These findings suggest that HD-tACS can modulate beta brain oscillations with frequency specificity. They also highlight the focal impact of HD-tACS, which elicits effects on the cortical region situated directly beneath the stimulation electrode.
Multilingual Prediction of Cognitive Impairment with Large Language Models and Speech Analysis
Authors: Agbavor Felix , Liang Hualou
Published: December 2024

Background: Cognitive impairment poses a significant global health challenge, emphasizing the critical need for early detection and intervention. Traditional diagnostics like neuroimaging and clinical evaluations are often subjective, costly, and inaccessible, especially in resource-poor settings. Previous research has focused on speech analysis primarily conducted using English data, leaving multilingual settings unexplored. Methods: In this study, we present our results from the INTERSPEECH 2024 TAUKADIAL Challenge, where we aimed to automatically detect mild cognitive impairment (MCI) and predict cognitive scores for English and Chinese speakers (169 in total). Our approach leverages Whisper, a speech foundation model, to extract language-agnostic speech embeddings. We then utilize ensemble models to incorporate task-specific information. Results: Our model achieved unweighted average recall of 81.83% in an MCI classification task, and root mean squared error of 1.196 in cognitive score prediction task, which placed the model at the second and the first position, respectively, in the ranking for each task. Comparison between language-agnostic and language-specific models reveals the importance of capturing language-specific nuances for accurate cognitive impairment prediction. Conclusions: This study demonstrates the effectiveness of language-specific ensemble modeling with Whisper embeddings in enabling scalable, non-invasive cognitive health assessments of Alzheimer’s disease, achieving state-of-the-art results in multilingual settings.
Empirical Insights into Eye-Tracking for Design Evaluation: Applications in Visual Communication and New Media Design
Authors: Guo Ruirui , Kim Nayeon , Lee Jisun
Published: December 2024

(1) Background: As digital technology continues to reshape visual landscapes, understanding how design elements influence customer experience has become essential. Eye-tracking technology offers a powerful, quantitative approach to assessing visibility, aesthetics, and design components, providing unique insights into visual engagement. (2) Methods: This paper presents a systematic review of eye-tracking methodologies applied in design research. Thirty studies were selected for analysis from recognized academic databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. Employing the Population, Intervention, Comparison, and Outcomes (PICO) framework, this review focused on experimental studies in visual communication and new media design that utilized visual symbols for communication and leveraged new media technologies. (3) Results: The findings corroborated that eye-tracking technology offers in-depth insights into gaze patterns, visual perception, and attention, which can inform design strategies. This review shows that assessing visual designs based on eye-tracking data can enhance consumer-centered interfaces, better align with user preferences, and foster more engaged behaviors in both digital and physical environments. (4) Conclusions: This review deepens our understanding of the cognitive and emotional processes underlying visual engagement. It also suggests new avenues for integrating diverse eye-tracking metrics into design evaluation, offering practical applications for improving design strategies and advancing the field of design research.
Evaluating the Well-Being Benefits and Social Value of Volunteer Gardening: Health Economics Meets Behavioral Science
Authors: Whiteley Holly , Parkinson John , Hartfiel Ned , Makanjuola Abraham , Lloyd-Williams Huw , Lawrence Catherine , Edwards Rhiannon Tudor
Published: December 2024

Multidisciplinary collaboration is key to strengthening the evidence base for multifaceted illness prevention interventions. We bring together health economics and behavioral science to explore the well-being benefits and social cost–benefit of volunteer gardening at an accredited botanic garden, Wales, UK. A health economics-informed social return on investment (SROI) evaluation was combined with the assessment of volunteers’ basic psychological needs (autonomy, competence, and relatedness), connection to nature, and their interrelatedness in this innovative nature-based intervention study. Pre- and post-volunteering outcome data were collected using the Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS), the ICEpop CAPability measure for Adults (ICECAP-A), the 12-item diary version of the Basic Psychological Need Satisfaction and Frustration Scale (BPNSNF), the Nature Connection Index (NCI), and a bespoke Client Service Receipt Inventory (CSRI). Results indicate that volunteer gardening can provide well-being benefits to participants and cost savings to the NHS. The well-being benefits observed were estimated to generate social value in the range of GBP 4.02 to GBP 5.43 for every GBP 1 invested. This study contributes to the evidence base that simple nature-based interventions such as volunteer gardening could offer low-cost supportive environments that deliver significant well-being benefits and associated social value to local communities, including a reduced burden on overstretched local healthcare services.
The Predictability of Stress Coping Strategies and Psychological Capital on the Psychological Well-Being of Autistic Spectrum Children’s Mothers in the Kingdom of Saudi Arabia
Authors: Al Eid Nawal A. , Alshehri Sami M. , Arnout Boshra A.
Published: December 2024

There is an increasing number of studies concerned with the study of children with autism spectrum disorder (ASD). At the same time, there is a lack of interest in studies on their families, especially on mothers who represent the first breadwinner for a child who suffers from a deficit in social communication with others, reflected in their well-being (PWB). This study aimed to reveal the possibility of predicting the PWB of autistic spectrum children’s mothers through the variables of coping strategies and psychological capital (PsyCap). The study used a predictive, descriptive research method to reveal the ability of the variables—coping strategies (problem-solving, avoidance, support, re-evaluation, remorse) and PsyCap (self-efficacy, optimism, hope, and resilience)—in predicting the PWB of autistic spectrum children’s mothers. The study sample consisted of (248) mothers, to whom coping strategies, PsyCap, and PWB measures were applied. The results showed that there were statistically significant differences between working and housewife mothers of autistic spectrum children in solving problems (t = 3.162, p < 0.002), avoidance (t = 1.973, p < 0.05), positive coping (t = 2.307, p < 0.022), self-efficacy (t = 3.667, p < 0.000), resilience (t = 3.338, p < 0.001), PsyCap (t = 2.866, p < 0.005), and PWB (t = 2.549, p < 0.011). Meanwhile, there were no statistically significant differences in social support, problem reassessment, remorse, negative coping, optimism, and hope. Also, there were no statistically significant differences due to the number of children in coping strategies, PsyCap, and PWB. The results also showed that there were statistically significant differences at the level of significance (0.05) between mothers whose age was less than 40 years and those 40 years and older in solving problems (t = 2.093, p < 0.037) in favor of mothers of the age group 40 years and older (M = 22.00, SD = 1.22), and avoidance (t = 1.987, p < 0.048) in favor of mothers under 40 years of age (M = 6.228, SD = 0.464). However, there were no statistically significant differences in social support, problem reassessment, remorse, positive coping, negative coping, self-efficacy, optimism, hope, resilience, the total degree of PsyCap, and well-being due to the variable of the mother’s age. The regression analysis results showed that optimism and problem-solving contributed to (39.90%) of the total change in PWB for mothers of children with autism spectrum. The study’s findings indicate the need to develop the ability of autistic spectrum children’s mothers to solve problems and their PsyCap, which is represented in self-efficacy, optimism, hope, and resilience, to enhance their PWB, which may have a positive impact on their autistic spectrum child.
A Qualitative Exploration of the Process and Experience of Change in Moving on in My Recovery: An Acceptance and Commitment Therapy Based Recovery Group for Substance Use Disorder
Authors: Shepley Emma L. , Jackson Mike C. , Hogan Lee M.
Published: December 2024

Moving on in my recovery (MOIMR) is a new, acceptance and commitment therapy (ACT) based group intervention to support recovery from substance use disorder. It was co-developed by, and is co-facilitated with, people in recovery. This study used a grounded theory model to understand the process of change experienced by individuals who completed the group programme. Ten individuals who were abstinent from substances following their participation in MOIMR were interviewed. The model that emerged depicted a chronological series of processes that centred around a core category of gains derived from approaching their emotional vulnerability by leaning in to discomfort (e.g., difficult internal experiences like thoughts, emotions, and physical sensations) whilst pursuing activities that aligned to what mattered to them. Initial key processes indicated that participants experienced a degree of suffering from substance use prior to engagement. Group safety was a key element in fostering connection, normalisation, and cohesion, combined with psychological understanding being significantly derived from those with a lived experience of substance misuse and addiction. Later processes reflecting core ACT mechanisms such as letting go, value-guided action, and acceptance of difficult internal experiences took time to develop; many participants reported completing MOIMR more than once as a means of understanding these components. Limitations, along with implications for clinical practice and future research are discussed.
Numerical Simulation and Experimental Study on Construction Forming of Cable-Stayed Tensioned Metal Thin Sheet Structure
Authors: Qin Jie , Xiao Shuo , Sun Guojun , Feng Dehai , Wu Jinzhi
Published: December 2024

This study investigates the construction methodology of large-span cable-stayed tensioned metal thin-sheet structures, introducing the “integrated enclosure and load-bearing” design concept. By applying in-plane prestress, the out-of-plane stiffness of the metal thin sheet is effectively enhanced, enabling it to simultaneously serve as an enclosure and a load-bearing component. Through experimental studies and finite element analysis, the study systematically examines the effects of various construction methods on internal forces and displacements. The tensioning of back cables is identified as the safest and most efficient construction method. Subsequently, through simulations of a three-span structure and tensioning forming tests, the research examines displacement, stress, and cable force distribution patterns, demonstrating that increases in the tensioning level result in corresponding increases in sheet surface stress, cable forces, and displacements. The structure exhibits a concave middle section, upward curvatures at both ends, and outward-leaning end columns. Structural members with lower cable forces show minimal impact on displacement and are therefore identified as suitable targets for design optimization. This study offers a theoretical foundation and practical engineering insights to guide the optimization of design and construction for cable-stayed tensioned metal thin-sheet structures.
Data-Driven Optimization for Low-Carbon Prefabricated Components Production Based on Ant Colony Algorithms
Authors: Ho Chun-Ling , Wang Chien-Chih , Qi Shenjun , Zhang Zichen
Published: December 2024

The global industries are progressively transitioning towards low-carbon development; however, construction remains a significant contributor to energy consumption and carbon emissions. In promoting industrialized construction, the use of prefabricated buildings emerges as a crucial strategy for achieving environmental sustainability. This study initially examines the development and current status of prefabricated concrete component factories in Fujian Province, focusing on regional distribution and production conditions. It also gathers data on carbon emissions, time, and costs to formulate a multi-objective optimization model. Utilizing ant colony algorithms, the model aims to minimize costs while adhering to low-carbon principles and fostering the sustainable development of prefabricated buildings. The optimization results for slabs indicate a minimum production cost of RMB 5.7023 million, with associated carbon emissions of 1154.85 tons. Notably, a cost variation of RMB 10,000 can lead to a maximum difference of 50 tons in carbon emissions, emphasizing the importance of cost minimization as a primary objective. In comparison to conventional production, the optimization of collaborative production demonstrates reductions in both costs and carbon emissions. Furthermore, when focusing on normal and rush modes, costs can be reduced by over 20%, resulting in a potential decrease of up to 50% in carbon emissions. Consequently, effectively mitigating carbon emissions in component production is essential for enhancing the sustainability of the construction industry.
Employing Neural Networks, Fuzzy Logic, and Weibull Analysis for the Evaluation of Recycled Brick Powder in Concrete Compositions
Authors: Mohtasham Moein Mohammad , Rahmati Komeil , Mohtasham Moein Ali , Saradar Ashkan , Rigby Sam E. , Akhavan Tabassi Amin
Published: December 2024

Using construction and demolition (C&D) waste in concrete production is a promising step toward environmental resilience amid the construction industry’s ecological footprint. The extensive history of using bricks in the construction of buildings has resulted in a considerable amount of waste associated with this commonly used material. This study aimed to assess the quality of concrete by examining the effect of replacing cement with varying percentages of recycled brick powder (RBP—0% to 50%). The primary objectives include evaluating the mechanical properties of concrete and establishing the feasibility of using RBP as a partial cement substitute. The investigation of target concrete can be divided into two phases: (i) laboratory investigation, and (ii) numerical investigation. In the laboratory phase, the performance of concrete with RBP was assessed under short-term dynamic and various static loads. The drop-weight test recommended by the ACI 544 committee was used to assess the short-term dynamic behavior (352 concrete discs). Furthermore, the behavior under static load was analyzed through compressive, flexural, and tensile strength tests. During the numerical phase, artificial neural network models (ANN) and fuzzy logic models (FL) were used to predict the results of 28-day compressive strength. The impact life with different failure probabilities was predicted based on the impact resistance results, by combining the Weibull distribution model. Additionally, an impact damage evolution equation was presented for mixtures containing RBP. The results show that the use of RBP up to 15% caused a slight decrease in compressive, flexural, and tensile strength (about 3–5%). Also, by replacing RBP up to 15%, the first crack strength decreased by 7.15% and the failure strength decreased by 6.46%. The average error for predicting 28-day compressive strength by FL and ANN models was recorded as 4.66% and 0.87%, respectively. In addition, the results indicate that the impact data follow the two-parameter Weibull distribution, and the R2 value for different mixtures was higher than 0.9275. The findings suggest that incorporating RBP in concrete can contribute to sustainable construction practices by reducing the reliance on cement and utilizing waste materials. This approach not only addresses environmental concerns but also enhances the quality assessment of concrete, offering potential cost savings and resource efficiency for the construction industry. Real-world applications include using RBP-enhanced concrete in non-structural elements, such as pavements, walkways, and landscaping features, where high strength is not the primary requirement.
Research on Vibration Comfort in Modular Construction
Authors: Zhang Xinxin , Zhou Ruoyang , Bi Cao , Zha Xiaoxiong , Liao Yong
Published: December 2024

This paper focuses on the vibration problem of the first modular school construction project in Guangming District, Shenzhen. Field tests were conducted on modular classrooms under jumping scenarios to obtain vibration acceleration time–history curves, and the fundamental frequency of the modular classroom floors was determined using the Fast Fourier Transform (FFT). Subsequently, tests under walking and running scenarios were carried out to collect vibration acceleration time–history curves. By comparing the measured peak vibration accelerations with the limits specified in existing standards, potential vibration comfort issues in the modular classrooms were identified. A FES (finite element simulation) approach was employed to develop a comprehensive model of the modular school under investigation and to analyze its vibration comfort across the tested scenarios. This modeling effort served to validate the accuracy of the experimental measurements obtained from field testing. Finally, the vibration comfort of the modular classroom floors was further analyzed using finite element simulations. The results indicate that the modular classroom floors have significant vibration comfort issues.
Reframing ‘Primitive Huts’ from Structural to Environmental Techniques and Their New Interrelationship in the Machine Age
Authors: Cho Eun-Ji , Khovalyg Dolaana , Nam Sung-Taeg
Published: December 2024

This study examines ‘Primitive Huts’ in relation to the structural and environmental techniques refined by savants (e.g., architects and scholars) during the Machine Age through three types of interrelationships: separation, moderation, and integration. The first aim is to reframe the theories of ‘Primitive Huts’, shifting the focus from structural to environmental techniques across two eras—the primitive and the Machine Age. Returning to the concept of ‘Primitive Huts’ in the context of the Machine Age aims to rebuild originality. In particular, this investigation looks into how the ‘Primitive Hut’ has sought ways to address environmental challenges. The second explores how the Machine Age initially provoked the separation of ‘Primitive Huts’—structural and environmental techniques—and integration (i.e., new interrelationship) through moderation. As a result, the contributions of savants are analysed to highlight the enhanced precision, discipline, and efficiency that have evolved since the Industrial Revolution.
Evaluation of the Dynamic Parameters Under Seismic Conditions for a Maxwell Rheological Base Isolation System
Authors: Bratu Polidor , Murzea Patricia , Tonciu Oana , Dragan Nicusor , Dobrescu Cornelia Florentina
Published: December 2024

The connections of seismic isolation devices for mitigating seismic shocks in the fundamental excitation mode are designed and implemented based on the serial combination of elastomeric isolators, which are primarily elastic, with fluid-based isolators, which are primarily viscous. The energy dissipated in the fluidic isolators represents a significant parameter for ensuring the attenuation degree of the amplitude of the displacement of the system as well as for its energy dissipation capacity as a direct effect on deformability and speed of the heat transfer. For bridges, viaducts, and buildings, families of elastomeric and fluid isolators connected in series are used to enable both analytical and experimental evaluations of the system’s dynamic isolation and energy dissipation capacities. Based on the results obtained from specialized isolation devices from Italy and the numerical and experimental evaluations carried out by ICECON S.A. Bucharest, Romania, this article will address the aforementioned topic.
Study on the Influence of Notched Empty Hole Parameters on Directional Fracture Blasting Effect
Authors: Zhang Xiantang , Ma Rongyan , Yang Yong , Fu Tonghua , Tian Yubing , Yan Haibo , Wang Deqing , Jiao Xiangtuan , Zhou Hongmin
Published: December 2024

Placing empty holes between charging holes is widely used in blasting engineering to achieve directional fracture blasting. Studies have shown that the presence of a notch along the empty hole wall enhances stress concentration and supports improved control over crack propagation. The notch angle and length are the two main parameters influencing the impact of notch holes. Therefore, in this study, we used numerical simulations to investigate how varying notch angles and lengths influence the directional fracture blasting effect. The findings suggest that, among the different types of holes used in directional fracture rock blasting, notched empty holes have the most significant guiding effect, followed by empty holes, while the absence of empty holes yields the least effective results. In the directional fracture blasting of a notched empty hole, stress concentration occurs at the notch tip following the explosion. This alters the stress field distribution around the empty hole, which shifts from a compressive to a tangential tensile state. Additionally, this concentration of stress causes the explosion energy to be focused on that location, resulting in a directional fracture blasting effect. In blasting construction, selecting the appropriate notch hole parameters is necessary to achieve optimal effects and reduce damage to surrounding rocks. Based on the notch parameters assessed in this study, the optimal effect of directional fracture blasting is achieved when the notch angle is 30°.
Characteristics and Control of Subway Train-Induced Environmental Vibration: A Case Study
Authors: Song Lizhong , Xu Xiang , Liu Quanmin , Zhang Haiwen , Zhang Yisheng
Published: December 2024

With the widespread construction of the subway in the Chinese mainland, the environmental vibration caused by subway operation has attracted increasing attention. Train-induced environmental vibrations can cause structural deformation, uneven settlement of line foundations, and tunnel leakage, affecting the structural safety of lines and foundations. This research focuses on a segment of the Nanchang Metro Line 3, which has been chosen as the subject of investigation. A numerical model was developed to analyze the subway train-induced environmental vibration, employing the finite element method (FEM). Utilizing a numerical model, an investigation was conducted to examine the impact of train speed on the subway train-induced environmental vibration, the train-induced environmental vibration transmission characteristics were analyzed, and the control effects of vibration reduction tracks on train-induced environmental vibration were discussed. Train-induced vibration tests were also conducted on Nanchang Metro Line 3 to verify the control effects of various vibration reduction tracks. The results indicate that the subway train-induced environmental vibration rises as the train speed goes up, and the vibration peaks always appear around 63 Hz. When the train speed doubles, the Z-vibration level increases from about 5.1 dB to 5.9 dB. Subway train-induced environmental vibration shows a fluctuating decreasing trend with increasing distance from the centerline of the tunnel. The Z-vibration level reaches its maximum 4 m away from the centerline of the tunnel. Compared with the embedded sleeper, the vibration-damping fastener exhibits a vibration reduction effect of about 9 dB to 18 dB, the rubber vibration-damping pad exhibits a better vibration reduction effect of about 16 dB to 24 dB, and the steel spring floating plate exhibits the best vibration-damping effect of about 18 dB to 28 dB. The calculated Z-vibration levels are basically consistent with the measured values, indicating the accuracy of the calculated results of the control effects of the vibration reduction tracks.
The Safety and Suitability of DNA Sequencing of Tissue Biopsies Performed on Patients Referred to a Phase I Unit
Authors: Esposito Angela , Crimini Edoardo , Criscitiello Carmen , Belli Carmen , Scafetta Roberta , Scalia Raimondo , Castellano Grazia , Giordano Elisa , Katrini Jalissa , Ascione Liliana , Boscolo Bielo Luca , Repetto Matteo , Marra Antonio , Trapani Dario , Varano Gianluca Maria , Maiettini Daniele , Della Vigna Paolo , Orsi Franco , Guerini Rocco Elena , Fusco Nicola , Curigliano Giuseppe
Published: December 2024

Background: Early-phase clinical trials offer a unique opportunity for patients with cancer. These trials often mandate biopsies to collect tumor tissue for research purposes, requiring patients to undergo invasive procedures. Some trials mandate molecular prescreening, but the success of these analyses relies on the quality and quantity of the tested materials. Additionally, bioptic procedures may result in complications. Methods: We retrospectively examined the records of patients referred to the Early Drug Development (EDD) Unit of the European Institute of Oncology who underwent biopsies for research purposes between January 2014 and December 2022. Our objective was to assess the safety of biopsy procedures and adequacy of the samples for NGS testing. Results: In total, 355 out of 731 patients (48.6%) underwent protocol-mandated biopsies. The most frequent sites of biopsy were the liver, lymph nodes, skin, and breast. Histological diagnosis was achieved in 349 (98%) patients, and NGS testing was successfully conducted in 111/127 (88.4%) cases. Of the 16 unsuccessful NGS attempts, 9 were performed on liver tissue. Unsuccessful NGS testing was attributed to poor sample quality and/or quantity, and the success rate varied significantly based on the specific tests attempted. Complications occurred in a small proportion of patients (4.8%), and none were serious. Conclusions: The non-negligible failure rate of NGS testing highlights the crucial need for implementing specific guidelines and Standard Operating Procedures for samples intended for NGS. With the use of a risk-based biopsy framework to guide clinical decisions, procedure-related complications may be minimized.
Targeting Perineural Invasion in Pancreatic Cancer
Authors: Garajová Ingrid , Giovannetti Elisa
Published: December 2024

Pancreatic cancer is an aggressive tumor with dismal prognosis. Neural invasion is one of the pathological hallmarks of pancreatic cancer. Peripheral nerves can modulate the phenotype and behavior of the malignant cells, as well as of different components of the tumor microenvironment, and thus affect tumor growth and metastasis. From a clinical point of view, neural invasion is translated into intractable pain and represents a predictor of tumor recurrence and poor prognosis. Several molecules are implicated in neural invasion and pain onset in PDAC, including neutrophins (e.g., NGF), chemokines, adhesion factors, axon-guidance molecules, different proteins, and neurotransmitters. In this review, we discuss the role of nerves within the pancreatic cancer microenvironment, highlighting how infiltrating nerve fibers promote tumor progression and metastasis, while tumor cells, in turn, drive nerve outgrowth in a reciprocal interaction that fuels tumor advancement. We outline key molecules involved in neural invasion in pancreatic cancer and, finally, explore potential therapeutic strategies to target neural invasion, aiming to both inhibit cancer progression and alleviate cancer-associated pain.
Current Clinical Applications of PSMA-PET for Prostate Cancer Diagnosis, Staging, and Treatment
Authors: von Stauffenberg Franz , Poyet Cédric , Beintner-Skawran Stephan , Maurer Alexander , Schmid Florian A.
Published: December 2024

Over the past decade, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has revolutionized prostate cancer (PCa) imaging, offering greater sensitivity and specificity compared to conventional imaging modalities such as CT, MRI, and bone scintigraphy. PSMA-PET is particularly valuable in staging newly diagnosed patients with intermediate- and high-risk disease, detecting biochemical recurrence, and evaluating metastatic cases. By utilizing radiotracers that accumulate specifically in PSMA-expressing cells, even small metastases can be detected, offering a detailed assessment of cancer extent and enabling more targeted diagnostic evaluations. Among the most utilized radiotracers, [68Ga]- and [18F]-labeled PSMA tracers enable precise imaging even with low disease burden. This diagnostic precision also supports advanced therapeutic approaches, including metastasis-directed therapy for oligometastatic cases and systemic treatment options, such as radioligand therapy, which presents new treatment perspectives for metastatic, castration-resistant PCa. This review examines the evolution of PSMA-PET in the diagnostics and therapy of PCa while comparing the current recommendations from leading clinical guidelines. The integration of PSMA-PET into clinical practice has redefined the management of PCa, improving diagnostic accuracy and enabling personalized treatment strategies, while lacking prospective long-term outcome data. As PSMA-PET continues to expand in clinical application, this review highlights its significant advancements while critically addressing limitations to ensure balanced and evidence-based implementation in prostate cancer care.
Insights into the Relationship Between the Gut Microbiome and Immune Checkpoint Inhibitors in Solid Tumors
Authors: Ciernikova Sona , Sevcikova Aneta , Novisedlakova Maria , Mego Michal
Published: December 2024

Immunotherapy with immune checkpoint inhibitors represents a revolutionary approach to the treatment of solid tumors, including malignant melanoma, lung cancer, and gastrointestinal malignancies. Anti-CTLA-4 and anti-PD-1/PDL-1 therapies provide prolonged survival for cancer patients, but their efficacy and safety are highly variable. This review focuses on the crucial role of the gut microbiome in modulating the efficacy and toxicity of immune checkpoint blockade. Studies suggest that the composition of the gut microbiome may influence the response to immunotherapy, with specific bacterial strains able to promote an anti-tumor immune response. On the other hand, dysbiosis may increase the risk of adverse effects, such as immune-mediated colitis. Interventions aimed at modulating the microbiome, including the use of probiotics, prebiotics, fecal microbial transplantation, or dietary modifications, represent promising strategies to increase treatment efficacy and reduce toxicity. The combination of immunotherapy with the microbiome-based strategy opens up new possibilities for personalized treatment. In addition, factors such as physical activity and nutritional supplementation may indirectly influence the gut ecosystem and consequently improve treatment outcomes in refractory patients, leading to enhanced patient responses and prolonged survival.
Saliva in Balancing Oral and Systemic Health, Oral Cancer, and Beyond: A Narrative Review
Authors: Okuyama Kohei , Yanamoto Souichi
Published: December 2024

Saliva plays a multifaceted role in oral health and systemic well-being. It supports digestion, protects oral tissues, maintains a healthy oral microbiome, and facilitates wound healing. Additionally, saliva serves as a diagnostic tool that reflects systemic health and disease/therapeutic states. Furthermore, although saliva shows a protective effect against oral cancer development, once tumor formation occurs, it may be involved in tumor progression and metastasis via exosomes and microRNAs. This review discusses the essential role of saliva; its relationship with the development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC); liquid biopsy tools for early diagnosis and monitoring of HNSCC; and the potential of exosomes as therapeutic agents.
Cardiotoxicity in Breast Cancer: Impact of Clinical Classifications and Treatment on Heart Health
Authors: Murg Sergiu Ioan , Matiș Loredana , Moldovan Andrada Florina , Schwarz-Madar Andrada Florina , Trifan Daniela Florina , Ghitea Timea Claudia , Popescu Mircea Ioachim
Published: December 2024

Background/Objectives: Cardio-oncology has become essential in addressing cardiovascular complications from cancer therapies. While advancements in treatments have improved survival rates, they also increase cardiovascular risks. This study evaluates the cardiotoxic effects of cytostatic treatments, examining the relationship between tumor characteristics, such as histopathology and TNM classification, and cardiovascular complications, aiming to improve cardiotoxicity prevention and management in oncology patients. Methods: We conducted a retrospective analysis of cancer patients treated with anthracyclines, HER2-targeted therapies, and radiotherapy. Cardiac function was monitored via echocardiography, focusing on global longitudinal strain and left ventricular ejection fraction (LVEF). Cardiac troponins and natriuretic peptides were measured to detect subclinical cardiotoxicity, with patients stratified by TNM cancer stage and histopathology. Results: Our analysis identified a significant association between certain cytostatic treatments, such as anthracyclines and HER2-targeted therapies, and a reduction in LVEF, particularly in patients with advanced-stage cancer. Biomarker assessments indicated early signs of cardiotoxicity in patients before clinical symptoms emerged. The findings also demonstrated a higher prevalence of cardiovascular complications in patients with pre-existing risk factors. Conclusions: This study highlights the importance of personalized treatment protocols in minimizing cardiotoxicity and improving the quality of life for oncology patients. Regular cardiac monitoring, combined with the use of biomarkers, can help identify high-risk patients early, allowing for timely interventions. Future research should focus on optimizing cardioprotective strategies to mitigate the cardiovascular risks associated with modern cancer therapies. Clinical Trial Registration: N/A (retrospective study).
Discoidin Domain Receptor 2 Contributes to Breast Cancer Progression and Chemoresistance by Interacting with Collagen Type I
Authors: Sato Ai , Takagi Kiyoshi , Yoshida Momoka , Yamaguchi-Tanaka Mio , Sagehashi Mikoto , Miki Yasuhiro , Miyashita Minoru , Suzuki Takashi
Published: December 2024

Background: Chemoresistance is an important issue to be solved in breast cancer. It is well known that the content and morphology of collagens in tumor tissues are drastically altered following chemotherapy, and discoidin domain receptor 2 (DDR2) is a unique type of receptor tyrosine kinase (RTK). This RTK is activated by collagens, playing important roles in human malignancies. However, the contribution to the chemoresistance of DDR2 in terms of the association with collagens remains largely unclear in breast cancer. Methods: We immunolocalized DDR2 and collagen type I in 224 breast cancer tissues and subsequently conducted in vitro studies to confirm the role of DDR2 in breast cancer chemoresistance using chemosensitive and chemoresistant cell lines. Results: DDR2 immunoreactivity was positively correlated with aggressive behaviors of breast cancer and was significantly associated with an increased risk of recurrence, especially in those who received chemotherapy. Moreover, in vitro experiments demonstrated that DDR2 promoted the proliferative activity of breast cancer cells, and cell viability after epirubicin treatment was significantly maintained by DDR2 in a collagen I-dependent manner. Conclusions: These data suggested that DDR2 could be a poor prognostic factor associated with cell proliferation and chemotherapy resistance in human breast cancer.
GPR68 Mediates Lung Endothelial Dysfunction Caused by Bacterial Inflammation and Tissue Acidification
Authors: Karki Pratap , Ke Yunbo , Zhang Chenou , Promnares Kamoltip , Li Yue , Williams Charles H. , Hong Charles C. , Birukov Konstantin G. , Birukova Anna A.
Published: December 2024

Tissue acidification resulting from dysregulated cellular bioenergetics accompanies various inflammatory states. GPR68, along with other members of proton-sensing G protein-coupled receptors, responds to extracellular acidification and has been implicated in chronic inflammation-related diseases such as ischemia, cancer, and colitis. The present study examined the role of extracellular acidification on human pulmonary endothelial cell (EC) permeability and inflammatory status per se and investigated potential synergistic effects of acidosis on endothelial dysfunction caused by bacterial lipopolysaccharide (LPS, Klebsiella pneumoniae). Results showed that medium acidification to pH 6.5 caused a delayed increase in EC permeability illustrated by a decrease in transendothelial electrical resistance and loss of continuous VE-cadherin immunostaining at cell junctions. Likewise, acidic pH induced endothelial inflammation reflected by increased mRNA and protein expression of EC adhesion molecules VCAM-1 and ICAM-1, upregulated mRNA transcripts of tumor necrosis factor-α, IL-6, IL-8, IL-1β, and CXCL5, and increased secretion of ICAM-1, IL-6, and IL-8 in culture medium monitored by ELISA. Among the GPCRs tested, acidic pH selectively increased mRNA and protein expression of GPR68, and only the GPR68-specific small molecule inhibitor OGM-8345 rescued acidosis-induced endothelial permeability and inflammation. Furthermore, acidic pH exacerbated LPS-induced endothelial permeability and inflammatory response in cultured lung macrovascular as well as microvascular endothelial cells. These effects were suppressed by OGM-8345 in both EC types. Altogether, these results suggest that GPR68 is a critical mediator of acidic pH-induced dysfunction of human pulmonary vascular endothelial cells and mediates the augmenting effect of tissue acidification on LPS-induced endothelial cell injury.
Immature Skeletal Myotubes Are an Effective Source for Improving the Terminal Differentiation of Skeletal Muscle
Authors: Jeong Seung Yeon , Choi Jun Hee , Allen Paul D. , Lee Eun Hui
Published: December 2024

Injured or atrophied adult skeletal muscles are regenerated through terminal differentiation of satellite cells to form multinucleated muscle fibers. Transplantation of satellite cells or cultured myoblasts has been used to improve skeletal muscle regeneration. Some of the limitations observed result from the limited number of available satellite cells that can be harvested and the efficiency of fusion of cultured myoblasts with mature muscle fibers (i.e., terminal differentiation) upon transplantation. However, the possible use of immature myotubes in the middle of the terminal differentiation process instead of satellite cells or cultured myoblasts has not been thoroughly investigated. Herein, myoblasts (Mb) or immature myotubes on differentiation day 2 (D2 immature myotubes) or 3 (D3 immature myotubes) were transferred to plates containing D2 or D3 immature myotubes as host cells. The transferred Mb/immature myotubes on the plates were further co-differentiated with host immature myotubes into mature myotubes in six conditions: Mb-to-D2, D2-to-D2, D3-to-D2, Mb-to-D3, D2-to-D3, and D3-to-D3. Among these six co-differentiation conditions, the D2-to-D3 co-differentiation condition exhibited the most characteristic myotube appearance and the greatest availability of Ca2+ for skeletal muscle contraction. Compared with non-co-differentiated control myotubes, D2-to-D3 co-differentiated myotubes presented increased MyoD and myosin heavy chain II (MyHC II) expression and increased myotube width, accompanied by parallel and swirling alignment. These increases correlated with functional increases in both electrically induced intracellular Ca2+ release and extracellular Ca2+ entry due to the increased expression of ryanodine receptor 1 (RyR1), sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1a (SERCA1a), and stromal interaction molecule 1 (STIM1). These increases were not detected in any of the other co-differentiation conditions. These results suggest that in vitro-cultured D2-to-D3 co-differentiated mature myotubes could be a good alternative source of satellite cells or cultured myoblasts for skeletal muscle regeneration.