bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal Stem Cell-Derived Exosomes as a Neuroregeneration Treatment for Alzheimer’s Disease
Authors: Shah Siddharth , Mansour Hadeel M. , Aguilar Tania M. , Lucke-Wold Brandon
Published: September 2024

Background: Alzheimer’s disease (AD) is the most prevalent kind of dementia and is a long-term degenerative disease. Pathologically, it is defined by the development of extracellular amyloid-β plaques and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein. This causes neuronal death, particularly in the hippocampus and cortex. Mesenchymal stem cell (MSC)-derived exosomes have been identified as possibly therapeutic and have promise for Alzheimer’s disease due to their regenerative characteristics. Methods: A systematic retrieval of information was performed on PubMed. A total of 60 articles were found in a search on mesenchymal stem cells, exosomes, and Alzheimer’s disease. A total of 16 ongoing clinical trials were searched and added from clinicaltrials.gov. We added 23 supporting articles to help provide information for certain sections. In total, we included 99 articles in this manuscript: 50 are review articles, 13 are preclinical studies, 16 are clinical studies, 16 are ongoing clinical trials, and 4 are observational studies. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on mesenchymal stem cell exosomes for Alzheimer’s disease were searched on clinicaltrials.gov. Results: Several experimental investigations have shown that MSC-Exo improves cognitive impairment in rats. In this review paper, we summarized existing understanding regarding the molecular and cellular pathways behind MSC-Exo-based cognitive function restoration, with a focus on MSC-Exo’s therapeutic potential in the treatment of Alzheimer’s disease. Conclusion: AD is a significant health issue in our culture and is linked to several important neuropathological characteristics. Exosomes generated from stem cells, such as mesenchymal stem cells (MSCs) or neural stem cells (NSCs), have been examined more and more in a variety of AD models, indicating that they may be viable therapeutic agents for the treatment of diverse disorders. Exosome yields may be increased, and their therapeutic efficacy can be improved using a range of tailored techniques and culture conditions. It is necessary to provide standardized guidelines for exosome manufacture to carry out excellent preclinical and clinical research.
A Multiplexed Quantitative Proteomics Approach to the Human Plasma Protein Signature
Authors: Núñez Estefanía , Gómez-Serrano María , Calvo Enrique , Bonzon-Kulichenko Elena , Trevisan-Herraz Marco , Rodríguez José Manuel , García-Marqués Fernando , Magni Ricardo , Lara-Pezzi Enrique , Martín-Ventura José Luis , Camafeita Emilio , Vázquez Jesús
Published: September 2024

Despite the plasma proteome being able to provide a unique insight into the health and disease status of individuals, holding singular promise as a source of protein biomarkers that could be pivotal in the context of personalized medicine, only around 100 proteins covering a few human conditions have been approved as biomarkers by the US Food and Drug Administration (FDA) so far. Mass spectrometry (MS) currently has enormous potential for high-throughput analysis in clinical research; however, plasma proteomics remains challenging mainly due to the wide dynamic range of plasma protein abundances and the time-consuming procedures required. We applied a new MS-based multiplexed proteomics workflow to quantitate proteins, encompassing 67 FDA-approved biomarkers, in >1300 human plasma samples from a clinical cohort. Our results indicate that this workflow is suitable for large-scale clinical studies, showing good accuracy and reproducibility (coefficient of variation (CV) < 20 for 90% of the proteins). Furthermore, we identified plasma signature proteins (stable in time on an individual basis), stable proteins (exhibiting low biological variability and high temporal stability), and highly variable proteins (with low temporal stability) that can be used for personalized health monitoring and medicine.
Photodynamic Therapy Using a Rose-Bengal Photosensitizer for Hepatocellular Carcinoma Treatment: Proposition for a Novel Green LED-Based Device for In Vitro Investigation
Authors: Lefebvre Anthony , Marhfor Smail , Baert Gregory , Deleporte Pascal , Grolez Guillaume Paul , Boileau Marie , Morales Olivier , Vignoud Séverine , Delhem Nadira , Mortier Laurent , Dewalle Anne-Sophie
Published: September 2024

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite new treatments, the HCC rate remains important, making it necessary to develop novel therapeutic strategies. Photodynamic therapy (PDT) using a Rose-Bengal (RB) photosensitizer (RB-PDT) could be a promising approach for liver tumor treatment. However, the lack of standardization in preclinical research and the diversity of illumination parameters used make comparison difficult across studies. This work presents and characterizes a novel illumination device based on one green light-emitting diode (CELL-LED-550/3) dedicated to an in vitro RB-PDT. The device was demonstrated to deliver a low average irradiance of 0.62 mW/cm2 over the 96 wells of a multi-well plate. Thermal characterization showed that illumination does not cause cell heating and can be performed inside an incubator, allowing a more rigorous assessment of cell viability after PDT. An in vitro cytotoxic study of the RB-PDT on an HCC cell line (HepG2) demonstrated that RB-PDT induces a significant decrease in cell viability: almost all the cells died after a light dose irradiation of 0.3 J/cm2 using 75 µM of RB (<10% of viability). In conclusion, the RB-PDT could be a therapeutic option to treat unresectable liver lesions and subclinical disease remaining in the post-resection tumor surgical margin.
Cross-National Analysis of Opioid Prescribing Patterns: Enhancements and Insights from the OralOpioids R Package in Canada and the United States
Authors: Banerjee Ankona , Nobleza Kenneth , Nguyen Duc T. , Stricker Erik
Published: September 2024

Background: The opioid crisis remains a significant public health challenge in North America, highlighted by the substantial need for tools to analyze and understand opioid potency and prescription patterns. Methods: The OralOpioids package automates the retrieval, processing, and analysis of opioid data from Health Canada’s Drug Product Database (DPD) and the U.S. Food and Drug Administration’s (FDA) National Drug Code (NDC) database. It includes functions such as load_Opioid_Table, which integrates country-specific data processing and Morphine Equivalent Dose (MED) calculations, providing a comprehensive dataset for analysis. The package facilitates a comprehensive examination of opioid prescriptions, allowing researchers to identify high-risk opioids and patterns that could inform policy and healthcare practices. Results: The integration of MED calculations with Canadian and U.S. data provides a robust tool for assessing opioid potency and prescribing practices. The OralOpioids R package is an essential tool for public health researchers, enabling a detailed analysis of North American opioid prescriptions. Conclusions: By providing easy access to opioid potency data and supporting cross-national studies, the package plays a critical role in addressing the opioid crisis. It suggests a model for similar tools that could be adapted for global use, enhancing our capacity to manage and mitigate opioid misuse effectively.
Emotion Recognition Using EEG Signals through the Design of a Dry Electrode Based on the Combination of Type 2 Fuzzy Sets and Deep Convolutional Graph Networks
Authors: Mounesi Rad Shokoufeh , Danishvar Sebelan
Published: September 2024

Emotion is an intricate cognitive state that, when identified, can serve as a crucial component of the brain–computer interface. This study examines the identification of two categories of positive and negative emotions through the development and implementation of a dry electrode electroencephalogram (EEG). To achieve this objective, a dry EEG electrode is created using the silver-copper sintering technique, which is assessed through Scanning Electron Microscope (SEM) and Energy Dispersive X-ray Analysis (EDXA) evaluations. Subsequently, a database is generated utilizing the designated electrode, which is based on the musical stimulus. The collected data are fed into an improved deep network for automatic feature selection/extraction and classification. The deep network architecture is structured by combining type 2 fuzzy sets (FT2) and deep convolutional graph networks. The fabricated electrode demonstrated superior performance, efficiency, and affordability compared to other electrodes (both wet and dry) in this study. Furthermore, the dry EEG electrode was examined in noisy environments and demonstrated robust resistance across a diverse range of Signal-To-Noise ratios (SNRs). Furthermore, the proposed model achieved a classification accuracy of 99% for distinguishing between positive and negative emotions, an improvement of approximately 2% over previous studies. The manufactured dry EEG electrode is very economical and cost-effective in terms of manufacturing costs when compared to recent studies. The proposed deep network, combined with the fabricated dry EEG electrode, can be used in real-time applications for long-term recordings that do not require gel.
Increased Risk for Clinically Significant Sleep Disturbances in Mild Traumatic Brain Injury: An Approach to Leveraging the Federal Interagency Traumatic Brain Injury Research Database
Authors: O’Neil Maya E. , Krushnic Danielle , Walker William C. , Cameron David , Baker-Robinson William , Hannon Sara , Clauss Kate , Cheney Tamara P. , Cook Lawrence J. , Niederhausen Meike , Kaplan Josh , Pappas Miranda , Martin Aaron M.
Published: September 2024

Study Objectives: The Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System contains individual-patient-level traumatic brain injury (TBI) data, which when combined, allows for the examination of rates and outcomes for key subpopulations at risk for developing sleep disturbance. Methods: This proof-of-concept study creates a model system for harmonizing data (i.e., combining and standardizing data) across FITBIR studies for participants with and without a history of TBI to estimate rates of sleep disturbance and identify risk factors. Results: Three studies were eligible for harmonization (N = 1753). Sleep disturbance was common among those with a history of mild TBI (63%). Individuals with mild TBI were two to four times more likely to have sleep disturbance compared to those with no history of TBI. Conclusions: This study established methods, harmonization code, and meta-databases that are publicly available on the FITBIR website. We demonstrated how the harmonization of FITBIR studies can answer TBI research questions, showing that associations between TBI and sleep disturbance may be influenced by demographic factors.
The Systemic Inflammation Response Index Efficiently Discriminates between the Failure Patterns of Patients with Isocitrate Dehydrogenase Wild-Type Glioblastoma Following Radiochemotherapy with FLAIR-Based Gross Tumor Volume Delineation
Authors: Senyurek Sukran , Aygun Murat Serhat , Kilic Durankus Nulifer , Akdemir Eyub Yasar , Sezen Duygu , Topkan Erkan , Bolukbasi Yasemin , Selek Ugur
Published: September 2024

Background/Objectives: The objective of this study was to assess the connection between the systemic inflammation response index (SIRI) values and failure patterns of patients with IDH wild-type glioblastoma (GB) who underwent radiotherapy (RT) with FLAIR-based gross tumor volume (GTV) delineation. Methods: Seventy-one patients who received RT at a dose of 60 Gy to the GTV and 50 Gy to the clinical target volume (CTV) and had documented recurrence were retrospectively analyzed. Each patient’s maximum distance of recurrence (MDR) from the GTV was documented in whichever plane it extended the farthest. The failure patterns were described as intra-GTV, in-CTV/out-GTV, distant, and intra-GTV and distant. For analytical purposes, the failure pattern was categorized into two groups, namely Group 1, intra-GTV or in-CTV/out-GTV, and Group 2, distant or intra-GTV and distant. The SIRI was calculated before surgery and corticosteroid administration. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal SIRI cut-off that distinguishes between the different failure patterns. Results: Failure occurred as follows: intra-GTV in 40 (56.3%), in-CTV/out-GTV in 4 (5.6%), distant in 18 (25.4%), and intra-GTV + distant in 9 (12.7%) patients. The mean MDR was 13.5 mm, and recurrent lesions extended beyond 15 mm in only seven patients. Patients with an SIRI score ≥ 3 demonstrated a significantly higher incidence of Group 1 failure patterns than their counterparts with an SIRI score < 3 (74.3% vs. 50.0%; p = 0.035). Conclusions: The present results show that using the SIRI with a cut-off value of ≥3 significantly predicts failure patterns. Additionally, the margin for the GTV can be safely reduced to 15 mm when using FLAIR-based target delineation in patients with GB.
Sub-Lexical Processing of Chinese–English Bilinguals: An ERP Analysis
Authors: Chen Yihan , Rossi Eleonora
Published: September 2024

Previous research has established that bilinguals automatically activate lexical items in both of their languages in a nonselectivemanner, even when processing linguistic information in the second language (L2) alone. However, whether this co-activation extends to the sub-lexical level remains debated. In this study, we investigate whether bilinguals access sub-lexical information while processing in their L2. Thirty-two Chinese–English bilinguals and thirty-one English monolinguals completed an EEG-based semantic relatedness task, during which they judged whether pairs of English words were related in meaning or not (±S). Unbeknownst to the participants, the form (±F) of the Chinese translations in half of the pairs shared a sub-lexical semantic radical. This leads to four conditions: +S+F, +S−F, −S+F, and −S−F. This design, along with the comparison to English monolinguals, allows us to examine if bilinguals’ native language is activated at the sub-lexical level when they are exposed only to L2. The results revealed that both groups showed sensitivity to semantic relatedness, as evidenced by a greater N400 for semantic unrelated pairs than related pairs, with monolinguals eliciting a more pronounced difference. Bilinguals, on the other hand, exhibited a greater P200 difference compared to monolinguals, indicating greater sensitivity to the hidden Chinese radical/form manipulation. These results suggest that highly proficient bilinguals automatically engage in lexical co-activation of their native language during L2 processing. Crucially, this co-activation extends to the sub-lexical semantic radical level.
Gender Role Mindset and Beliefs about Own Personal Goals as a Guide for Young People’s Behaviors towards the Romantic Partner
Authors: Cuccì Gaia , Colombo Camilla Chiara , Confalonieri Emanuela
Published: September 2024

Dating violence (DV) is a form of intentional abuse carried out in young couples, which over the years has increasingly gained attention for its pervasiveness and high frequency. The present study represents an effort to expand and deepen the literature on factors associated with DV perpetration. The sample consisted of 225 Italian young people who completed an online survey. A model was tested, in which DV perpetration is affected by the presence of gender stereotypes and personal values oriented to power and dominance (i.e., self-enhancement) and to universalism and interest in others (i.e., self-transcendence) through the mediation of the perception of the romantic relationship quality, controlling for age. Sex was also considered in the model. The findings showed that self-enhancement and self-transcendence were, respectively, linked positively and negatively to a negative perception of the relationship quality, which in turn explained DV perpetration. The results also suggested that hostile sexism, self-enhancement and being male were directly linked to DV perpetration, thus representing potential risk factors for it. The study suggests the importance of working on gender role beliefs and personal orientation to power, which guide the way people perceive their romantic relationships and behave toward their partners, providing interesting insights for the implementation of DV prevention programs. Moreover, the findings highlight the importance of working with families and other educational agencies to foster a change in cultural terms.
Exploring Attention Bias Mechanisms in Sub-Threshold Depression: ERP Insights into Biased Orientation and Disengagement
Authors: Zhang Xin , Jia Huibin , Wang Enguo
Published: September 2024

Individuals with depression may have alterations in attention that begin at the sub-threshold stage. This study explored attention bias from the perspectives of early attention orientation and late attention disengagement in individuals with sub-threshold depression (SD) and healthy control (HC) individuals using a cue-target paradigm and event-related potentials (ERPs). The study enrolled 46 participants, comprising 23 males and 23 females, with 25 individuals in the SD group and 21 in the HC group, exceeding the calculated sample size requirement. The data were analyzed from two aspects. Behavioral data showed that SD individuals had difficulty in attention disengagement and that the time of attention transfer was delayed. Analysis of ERP data revealed that, regardless of the attributes of the emotional stimulus, the cue information promoted participants’ response to the target stimulus. While SD individuals did show directional acceleration of attention to the emotional stimulus, no significant negative attention bias was observed. Taken together, these findings suggest that SD individuals do not show specific directional acceleration of attention to negative stimuli in the early stage of attention processing, although there may be attention avoidance.
Which Receives More Attention, Online Review Sentiment or Online Review Rating? Spillover Effect Analysis from JD.com
Authors: Shan Siqing , Yang Yangzi , Li Chenxi
Published: September 2024

Studies have found that competitive products’ online review ratings (ORRs) have a spillover effect on the focal product’s sales. However, the spillover effect of online review sentiment (ORS) as an essential component of online review analysis has yet to be studied. In this study, we analyze online review content from JD.com using the latent Dirichlet allocation to identify the product attribute topics that consumers are most concerned about. We then construct a baseline regression model of ORS and ORRs to explore the effects of online competitive product reviews on focal product sales. Moreover, we examine how the interaction between ORS and critical factors of online reviews affect sales. Our results indicate that the ORS of competitive products has a negative effect on focal product sales, and the effect is greater than the ORS and ORRs of focal products, respectively. In addition, the ORS of competitive products inhibits the sale of focal products as evaluations of product attributes become more positive or online review usefulness increases. We also find that the effect of ORRs of competitive products is not significant, which may be because clothing, as an experiential product, requires consumers to gain more information about specific usage scenarios before making a decision. This study provides a more accurate basis for consumer decision-making and offers retailers a novel approach to developing marketing strategies.
The Development of Ambiguity Processing Is Explained by an Inverted U-Shaped Curve
Authors: Manelis Anna , Miceli Rachel , Satz Skye , Suss Stephen J. , Hu Hang , Versace Amelia
Published: September 2024

Understanding the developmental trajectories for recognizing facial expressions is important for a better understanding of development of psychiatric disorders. In this study, we examined the recognition of emotional and neutral facial expressions in 93 typically developing adolescents and adults. The Emotion Intensity Rating task required participants to rate the intensity of emotional expression in happy, neutral, and sad faces on a scale from 1 to 9. A score of ‘5’ had to be assigned to neutral faces, scores between ‘6’ (slightly happy) and ‘9’ (very happy) to happy faces, and scores between ‘4’ (slightly sad) and ‘1’ (very sad) to sad faces. Mixed effects models were used to examine the effects of age and emotion on recognition accuracy, reaction time (RT), and emotional intensity. Participants tended to misjudge neutral faces as sad. Adolescents were less accurate than adults for neutral face recognition. There were significant quadratic effects of age on accuracy (negative quadratic effect) and RT (positive quadratic effect). The most accurate and fastest performance was observed in 25- to 35-year-old subjects. This trajectory may be associated with prefrontal cortex maturation, which provides top–down control over the heightened amygdala response to ambiguity that may be misinterpreted as emotional content.
Risk Factors for Low Quality of Life among Women Using Different Types of Contraceptives in Saudi Arabia: A Questionnaire-Based Study
Authors: Alhakeem Malak M. , Baghdadi Leena R. , Alshathri Almaha H. , Alshathri Aljohara H. , Alqahtani Arwa A. , Alshathri Monerah H.
Published: September 2024

This study aimed to assess and identify the risks for poor quality of life among female Saudi contraceptive users by administering an online questionnaire. The validity of the Arabic version of the Spanish Society of Contraception Quality of Life (SEC-QOL) questionnaire was assessed by incorporating the relevant items into an exploratory factor analysis and a subsequent confirmatory factor analysis. Internal consistency was assessed using Cronbach’s alpha coefficient. p < 0.05 was statistically significant. Questionnaires completed by 652 eligible women were analyzed. The most common contraception method was oral pills (51.5% of respondents). Analysis of the internal consistency of the questionnaire revealed that overall reliability was >0.7, which is considered adequate (Cronbach’s alpha = 0.845). Analysis of risk factors associated with higher overall SEC-QOL scores (worse overall quality of life) revealed several statistically significant variables. A “not good” relationship with their husbands, “heavy” menstrual flow, and premenstrual breast symptoms (breast pain, hypersensitivity, and increased size) were identified as risk factors for poor quality of life due to their association with the highest scores (poor quality of life). The Arabic version of the modified SEC-QOL is a valid and reliable tool to measure the quality of life of Saudi contraceptive users.
Bridging the Connection between Fluency in Reading and Arithmetic
Authors: Balhinez Reut , Shaul Shelley
Published: September 2024

This study examines the contribution of early executive functions (EFs) in the association between fluency in reading and arithmetic. Kindergarten children (N = 1185) were assessed on executive functions skills and on reading and arithmetic fluency in Grade 1 and Grade 3. The analysis revealed that beyond the connection within each domain there is a unidirectional effect between fluency measures, with Grade 1 reading fluency significantly influencing the development of arithmetic fluency in Grade 3. Furthermore, the findings indicate that kindergarten EFs significantly contribute to arithmetic fluency at both time points and to reading fluency in the first grade. Early EF skills also emerged as significant contributors to the associations between fluency performance in reading and arithmetic, suggesting that the influence of EFs extends beyond individual academic domains. These findings have implications for understanding the cognitive mechanisms that underlie the relations between these academic skills.
Influencing Factors of Spatial Ability for Architecture and Interior Design Students: A Fuzzy DEMATEL and Interpretive Structural Model
Authors: Amro Dana Khalid , Dawoud Husameddin
Published: September 2024

Spatial ability is not just a skill but a crucial element for architecture and interior design students, significantly impacting their proficiency in tasks involving 2D drawings, 3D components, and artistic expression. Despite extensive research in this area, a gap remains in the understanding of how to effectively cultivate spatial ability through educational interventions. This study, with its unique approach of identifying key influencing factors and their interrelationships within the fuzzy decision-making laboratory analysis method (Fuzzy-DEMATEL) and the interpretative structural model (ISM), fills this gap. The method visualizes cause-and-effect relationships within a structural model and captures the interdependencies between influencing factors. In a collaborative effort between nine universities in 2023–2024, 17 experts selected through purposeful sampling contributed to the development of a comprehensive list of potential influencing factors. After refinement through filtering, comparison with the existing literature, and expert consensus, seven influencing factors of spatial ability for architecture and interior design students from personal traits and STEAM disciplines were identified, which are sketching and hand drawing skills, mathematical skills, video game practice, descriptive geometry skills, augmented reality practice, spatial talk, and gesturing while talking. Sketching and hand drawing skills, mathematical skills, and video game practice come under cause factors of spatial ability, whereas the rest are effect factors. Proceeding with ISM analysis revealed that sketching and hand drawing skills and mathematical skills are located in the input layer and have a continuous impact on spatial ability. Descriptive geometry skills lie in the transition layer, which are considered as deep influencing factors, the rest of the factors lie in the effect layer. This study delves into the theoretical and practical implications of these findings, offering valuable insights for educational policy and practice.
Testing, Validation, and Simulation of a Novel Economizer Damper Control Strategy to Enhance HVAC System Efficiency
Authors: Dharmasena Pasidu , Nassif Nabil
Published: September 2024

Buildings account for over 40% of global carbon dioxide (CO2) emissions, with supply and return fans in air handling units consuming a significant portion of energy. To address this, researchers have explored innovative economizer damper control methods and identified the “split-signal” strategy, which optimizes supply airflow using a single damper as a promising approach. In this study, split-signal was further refined for practical application and energy simulation, aiming to demonstrate its effectiveness and encourage adoption in real-world building mechanical systems. Laboratory testing on chilled water variable air volume (VAV) system showed fan energy savings of 0.2–5% compared to traditional “three-coupled” control, depending on ventilation air proportions, and prevented reverse airflow. A statistical regression model, based on experimental data, was developed to predict energy savings and streamline comparisons. Energy simulations were conducted across various U.S. climate zones and revealed potential savings of 15–20% in energy use, operational costs, and CO2 emissions. With minimal financial investment, split-signal control offers a cost-effective solution to improve energy efficiency and reduce environmental impact, promoting its adoption in real-world building applications.
Experimental Study on the Bending Behavior of Precast Concrete Segmental Bridges with Continuous Rebars at Joints
Authors: Zou Yu , Xu Dong
Published: September 2024

Longitudinal ordinary rebars are discontinuous at the joints of precast concrete segmental bridges (PCSBs), which can open under tensile stresses induced by bending moments. This will lead to durability issues with the joints. To improve the bending properties of PCSBs, a novel joint type featuring continuous rebars was proposed in the present study. Three specimens were subjected to testing to examine the bending behavior of PCSBs using this new joint design compared to traditional joints. The crack propagation, structural deformation, joint opening width, strain in rebars, failure mode, stiffness, and flexural capacity were comprehensively investigated. The test results reveal that the continuous rebars effectively transferred bending normal stress between joints, ensuring full development of cracks in each beam segment. Effective control of joint opening width was also observed. Compared to traditional joints, the new joints exhibited a 29% to 33% increase in cracking load and a 32% increase in ultimate load. Failure in the continuous rebar joints was characterized by partial anchorage failure of the rebars along with localized concrete crushing in the top compression zone. Based on the test results, a computational method was proposed for calculating the cracking strength and flexural capacity of the new joints.
Nonlinear Seismic Response of Tunnel Structures under Traveling Wave Excitation
Authors: Suo Xiaoqing , Liu Lilong , Qiao Dan , Xiang Zhengsong , Zhou Yuanfu
Published: September 2024

Tunnels traditionally regarded as resilient to seismic events have recently garnered significant attention from engineers owing to a rise in incidents of seismic damage. In this paper, the reflection characteristics of the elastic plane wave incident on the free surface are analyzed, and the matrix analysis method SWIM (Seismic Wave Input Method) for the calculation of equivalent nodal loads with artificial truncated boundary conditions for seismic wave oblique incidence is established by using coordinate transformation technology, according to the displacement velocity and stress characteristics of a plane wave. The results show that the oblique incidence method is more effective in reflecting the traveling wave effect, and the “rotational effect” induced by oblique incidence must be considered for P wave and SV wave incidence, including the associated stress and deformation. This effect exhibits markedly distinct rotational phenomenon. In particular, the P wave incidence should be focused on the vault and the inverted arch due to the expansion wave. With the increase of the oblique incidence angle, the structural stress and deformation are rotated to a certain extent, and the values are significantly increased. Simultaneously, the shear action of the SV wave may result in “ovaling” of the tunnel structure, thereby facilitating damage to the arch shoulder and the sidewall components. As the oblique incidence angle, the potentially damaging effects of the “rotational effect” to the vault and the inverted arch, but the numerical value does not change significantly. In addition, in comparison to a circular cross-section, the low-frequency amplification of seismic waves in the surrounding rock and the difference of frequency response function in different parts of the lining are more pronounced. In particular, the dominant frequency characteristics are significant at P wave incidence and the seismic wave signal attenuation tends to be obvious with increasing incidence angle. In contrast, SV waves exhibit more uniform characteristics.
Inhibition of Insulin-like Growth Factor 1 Receptor/Insulin Receptor Signaling by Small-Molecule Inhibitor BMS-754807 Leads to Improved Survival in Experimental Esophageal Adenocarcinoma
Authors: Hassan Md Sazzad , Johnson Chloe , Ponna Saisantosh , Scofield Dimitri , Awasthi Niranjan , von Holzen Urs
Published: September 2024

The insulin-like growth factor-1 (IGF-1) and insulin axes are upregulated in obesity and obesity-associated esophageal adenocarcinoma (EAC). Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a contemporary nanotechnology-based paclitaxel (PT) bound to human albumin, ensuring its solubility in water rather than a toxic solvent. Here, we examined the benefits of inhibiting insulin-like growth factor-1 receptor/insulin receptor (IGF-1/IR) signaling and the enhancement of nab-paclitaxel effects by inclusion of the small-molecule inhibitor BMS-754807 using both in vitro and in vivo models of EAC. Using multiple EAC cell lines, BMS-754807 and nab-paclitaxel were evaluated as mono and combination therapies for in vitro effects on cell proliferation, cell death, and cell movement. We then analyzed the in vivo anticancer potency with survival improvement with BMS-754807 and nab-paclitaxel mono and combination therapies. BMS-754807 monotherapy suppressed in vitro cell proliferation and wound healing while increasing apoptosis. BMS-754807, when combined with nab-paclitaxel, enhanced those effects on the inhibition of cell proliferation, increment in cell apoptosis, and inhibition of wound healing. BMS-754807 with nab-paclitaxel produced substantially greater antitumor effects by increasing in vivo apoptosis, leading to increased mice survival compared to those of BMS-754807 or nab-paclitaxel monotherapy. Our outcomes support the use of BMS-754807, alone and in combination with nab-paclitaxel, as an efficient and innovative treatment choice for EAC.
Combination of JAKi and HDACi Exerts Antiangiogenic Potential in Cutaneous T-Cell Lymphoma
Authors: Karagianni Fani , Piperi Christina , Valero-Diaz Sara , Amato Camilla , Vaque Jose Pedro , Casar Berta , Papadavid Evangelia
Published: September 2024

Angiogenesis plays a pivotal role in the growth and metastasis of tumors, including the development and progression of cutaneous lymphomas. The chick embryo CAM model has been utilized in various studies to assess the growth rate, angiogenic potential, and metastatic capability of different tumor types and malignant cell lines. However, the precise mechanisms of angiogenesis in CTCL and the influence of Ruxolitinib or Resminostat on angiogenesis in hematological malignancies and solid tumors are not well understood. Recent in vitro and in vivo data have demonstrated the synergistic inhibition of tumorigenesis and metastasis in experimental models of CTCL when using the combination of Resminostat (HDACi) with Ruxolitinib (JAKi). The present work aims to elucidate the effects of this combination on the tumor microenvironment’s vascular components. We investigated the effects of Ruxolitinib (JAKi) in combination with Resminostat (HDACi) treatment in transendothelial migration of CTCL cells (106 MyLa and SeAx) by using a transwell-based transendothelial migration assay and tumor angiogenesis in vivo. We used the CTCL chick embryo CAM model with xenografted tumors derived from implanted MyLa and SeAx cells and administered topically 15 μM ruxolitinib and 5 μM Resminostat every two days during a 5-day period. JAKi and HDACi inhibited CTCL cell transendothelial migration by 75% and 82% (p < 0.05) in both CTCL engrafted cells (MyLa and SeAx, respectively) compared to the untreated group. Moreover, the combination of ruxolitinib with resminostat blocked angiogenesis by significantly reducing the number of blood vessel formation by 49% and 34% in both MyLa and SeAx, respectively (p < 0.05), indicating that the proposed combination exerted significant anti-angiogenic effects in the CAM CTCL model. Overall, these data provide valuable insights into potential therapeutic strategies targeting angiogenesis in CTCL, paving the way for more effective treatment approaches in the future.
Metabolomic Profiling of Pulmonary Neuroendocrine Neoplasms
Authors: Boullier Clémence , Lamaze Fabien C. , Haince Jean-François , Bux Rashid Ahmed , Orain Michèle , Zheng Jiamin , Zhang Lun , Wishart David S. , Bossé Yohan , Manem Venkata S. K. , Joubert Philippe
Published: September 2024

Background/Objectives: Pulmonary neuroendocrine neoplasms (NENs) account for 20% of malignant lung tumors. Their management is challenging due to their diverse clinical features and aggressive nature. Currently, metabolomics offers a range of potential cancer biomarkers for diagnosis, monitoring tumor progression, and assessing therapeutic response. However, a specific metabolomic profile for early diagnosis of lung NENs has yet to be identified. This study aims to identify specific metabolomic profiles that can serve as biomarkers for early diagnosis of lung NENs. Methods: We measured 153 metabolites using liquid chromatography combined with mass spectrometry (LC-MS) in the plasma of 120 NEN patients and compared them with those of 71 healthy individuals. Additionally, we compared these profiles with those of 466 patients with non-small-cell lung cancers (NSCLCs) to ensure clinical relevance. Results: We identified 21 metabolites with consistently altered plasma concentrations in NENs. Compared to healthy controls, 18 metabolites were specific to carcinoid tumors, 5 to small-cell lung carcinomas (SCLCs), and 10 to large-cell neuroendocrine carcinomas (LCNECs). These findings revealed alterations in various metabolic pathways, such as fatty acid biosynthesis and beta-oxidation, the Warburg effect, and the citric acid cycle. Conclusions: Our study identified biomarker metabolites in the plasma of patients with each subtype of lung NENs and demonstrated significant alterations in several metabolic pathways. These metabolomic profiles could potentially serve as biomarkers for early diagnosis and better management of lung NENs.
Relationship of Signaling Pathways between RKIP Expression and the Inhibition of EMT-Inducing Transcription Factors SNAIL1/2, TWIST1/2 and ZEB1/2
Authors: Bustamante Andrew , Baritaki Stavroula , Zaravinos Apostolos , Bonavida Benjamin
Published: September 2024

Untreated primary carcinomas often lead to progression, invasion and metastasis, a process that involves the epithelial-to-mesenchymal transition (EMT). Several transcription factors (TFs) mediate the development of EMT, including SNAIL1/SNAIL2, TWIST1/TWIST2 and ZEB1/ZEB2, which are overexpressed in various carcinomas along with the under expression of the metastasis suppressor Raf Kinase Inhibitor Protein (RKIP). Overexpression of RKIP inhibits EMT and the above associated TFs. We, therefore, hypothesized that there are inhibitory cross-talk signaling pathways between RKIP and these TFs. Accordingly, we analyzed the various properties and biomarkers associated with the epithelial and mesenchymal tissues and the various molecular signaling pathways that trigger the EMT phenotype such as the TGF-β, the RTK and the Wnt pathways. We also presented the various functions and the transcriptional, post-transcriptional and epigenetic regulations for the expression of each of the EMT TFs. Likewise, we describe the transcriptional, post-transcriptional and epigenetic regulations of RKIP expression. Various signaling pathways mediated by RKIP, including the Raf/MEK/ERK pathway, inhibit the TFs associated with EMT and the stabilization of epithelial E-Cadherin expression. The inverse relationship between RKIP and the TF expressions and the cross-talks were further analyzed by bioinformatic analysis. High mRNA levels of RKIP correlated negatively with those of SNAIL1, SNAIL2, TWIST1, TWIST2, ZEB1, and ZEB2 in several but not all carcinomas. However, in these carcinomas, high levels of RKIP were associated with good prognosis, whereas high levels of the above transcription factors were associated with poor prognosis. Based on the inverse relationship between RKIP and EMT TFs, it is postulated that the expression level of RKIP in various carcinomas is clinically relevant as both a prognostic and diagnostic biomarker. In addition, targeting RKIP induction by agonists, gene therapy and immunotherapy will result not only in the inhibition of EMT and metastases in carcinomas, but also in the inhibition of tumor growth and reversal of resistance to various therapeutic strategies. However, such targeting strategies must be better investigated as a result of tumor heterogeneities and inherent resistance and should be better adapted as personalized medicine.
A Promising Therapeutic Strategy of Combining Acoustically Stimulated Nanobubbles and Existing Cancer Treatments
Authors: Sharma Deepa , Petchiny Tera N. , Czarnota Gregory J.
Published: September 2024

In recent years, ultrasound-stimulated microbubbles (USMBs) have gained great attention because of their wide theranostic applications. However, due to their micro-size, reaching the targeted site remains a challenge. At present, ultrasound-stimulated nanobubbles (USNBs) have attracted particular interest, and their small size allows them to extravasate easily in the blood vessels penetrating deeper into the tumor vasculature. Incorporating USNBs with existing cancer therapies such as chemotherapy, immunotherapy, and/or radiation therapy in several preclinical models has been demonstrated to have a profound effect on solid tumors. In this review, we provide an understanding of the composition and formation of nanobubbles (NBs), followed by the recent progress of the therapeutic combinatory effect of USNBs and other cancer therapies in cancer treatment.
From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells
Authors: Radivoievych Aleksandar , Schnepel Sophia , Prylutska Svitlana , Ritter Uwe , Zolk Oliver , Frohme Marcus , Grebinyk Anna
Published: September 2024

Objectives: The primary objective of this research targeted the biochemical effects of SDT on human cervix carcinoma (HeLa) and mouse Lewis lung carcinoma (LLC) cells grown in 2D monolayer and 3D spheroid cell culture. Methods: HeLa and LLC monolayers and spheroids were treated with a 20 µM C60-Ber for 24 h, followed by irradiation with 1 MHz, 1 W/cm2 US. To evaluate the efficacy of the proposed treatment on cancer cells, assessments of cell viability, caspase 3/7 activity, ATP levels, and ROS levels were conducted. Results: Our results revealed that US irradiation alone had negligible effects on LLC and HeLa cancer cells. However, both monolayers and spheroids irradiated with US in the presence of the C60-Ber exhibited a significant decrease in viability (32% and 37%) and ATP levels (42% and 64%), along with a notable increase in ROS levels (398% and 396%) and caspase 3/7 activity (437% and 246%), for HeLa monolayers and spheroids, respectively. Similar tendencies were observed with LLC cells. In addition, the anticancer effects of C60-Ber surpassed those of C60, Ber, or their mixture (C60 + Ber) in both cell lines. Conclusions: The detected intensified ROS generation and ATP level drop point to mitochondria dysfunction, while increased caspase 3/7 activity points on the apoptotic pathway induction. The combination of 1 W/cm2 US with C60-Ber showcased a promising platform for synergistic sonodynamic chemotherapy for cancer treatment.
Strategic Advances in Combination Therapy for Metastatic Castration-Sensitive Prostate Cancer: Current Insights and Future Perspectives
Authors: Kwon Whi-An , Song Yong , Lee Min-Kyung
Published: September 2024

The contemporary treatment for metastatic castration-sensitive prostate cancer (mCSPC) has evolved significantly, building on successes in managing metastatic castration-resistant prostate cancer (mCRPC). Although androgen deprivation therapy (ADT) alone has long been the cornerstone of mCSPC treatment, combination therapies have emerged as the new standard of care based on recent advances, offering improved survival outcomes. Landmark phase 3 trials demonstrated that adding chemotherapy (docetaxel) and androgen receptor pathway inhibitors to ADT significantly enhances overall survival, particularly for patients with high-volume, high-risk, or de novo metastatic disease. Despite these advancements, a concerning gap between evidence-based guidelines and real-world practice remains, with many patients not receiving recommended combination therapies. The challenge in optimizing therapy sequences, considering both disease control and treatment burdens, and identifying clinical and biological subgroups that could benefit from personalized treatment strategies persists. The advent of triplet therapy has shown promise in extending survival, but the uro-oncology community must narrow the gap between evidence and practice to deliver the most effective care. Current research is focused on refining treatment approaches and utilizing biomarkers to guide therapy selection, aiming to offer more personalized and adaptive strategies for mCSPC management. Thus, aligning clinical practices with the evolving evidence is urgently needed to improve outcomes for patients facing this incurable disease.
Changes in BDNF Concentration in Men after Foam Roller Massage
Authors: Murawska-Ciałowicz Eugenia , Ciałowicz Maria , Rosłanowski Adam , Kaczmarek Agnieszka , Ratajczak-Wielgomas Katarzyna , Kmiecik Alicja , Partyńska Aleksandra , Dzięgiel Piotr , Andrzejewski Waldemar
Published: September 2024

Massage is one of the oldest forms of therapy practiced since ancient times. Nowadays, it is used in sports practice, recovery from injury, or supportive therapy for various conditions. The practice of massage uses a variety of instruments that facilitate massaging while relieving the stress on the masseur. One of them is a foam roller. Although roller massage is widely used, there are still no scientific studies describing the biological mechanisms of its effects on the body. The purpose of our study was to analyze the effect of roller massage on BDNF levels in men undergoing self-massage 4x/week/7 weeks. The control group consisted of men who did not perform self-massage. Before the test and after the first, third, fifth, and seventh weeks of self-massage, the study participants’ blood was drawn, the serum BDNF was determined, and the results were subjected to analysis of variance by ANOVA test. After the first week of self-massage, an increase in BDNF concentration was observed in the self-massage group compared to the control group (p = 0.023). Similarly, changes were observed in week five (p = 0.044) and week seven (p = 0.046). In the massaged group, BDNF concentrations were significantly higher after the first week of self-massage compared to baseline. In the third week of the study, BDNF decreased to a value comparable to the baseline study, then increased significantly in the fifth and seventh weeks compared to the value recorded in the third week (p = 0.049 and p = 0.029). It was significantly higher in week seven compared to week five (p = 0.03). Higher concentrations of BDNF in subjects undergoing roller self-massage may be one of the biological mechanisms justifying the therapeutic effects of massage in both sports and clinical practice. Studies analyzing the stimulation of BDNF synthesis through various massage techniques should be performed on a larger group of healthy individuals, patients after trauma of multiple origins, and sick people with indications for therapeutic massage.