bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of Bioactive Compounds by HPLC-ESI-MS/MS and Evaluation of Antioxidant and Enzyme Inhibitory Activities of Acorn Flour Extracts
Authors: Acquaticci Laura , Santanatoglia Agnese , Vittadini Elena , Beghelli Daniela , La Terza Antonietta , Zengin Gokhan , Caprioli Giovanni
Published: December 2024

This study provides the first comprehensive evaluation of the bioactive potential of acorn flour extracts (Quercus robur, Fagaceae) prepared at different temperatures (20, 60, 80 and 100 °C), focusing on polyphenolic content, antioxidant properties and enzyme inhibitory activities. Through HPLC-ESI-MS/MS analysis, 36 bioactive compounds were identified, with the extract at 60 °C showing the highest concentrations of key polyphenols, notably gallic acid (210,008.9 mg·kg−1) and ellagic acid (45,469.6 mg·kg−1). This extract also exhibited a high antioxidant activity and significant inhibition of glucosidase and acetylcholinesterase, suggesting potential benefits for diabetes management and neuroprotection. The results indicate that extraction temperature affects bioactivity, with the 60 °C extract standing out as a promising candidate for nutraceutical, pharmaceutical, and cosmeceutical applications due to its rich polyphenol profile and potent biological properties.
Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases
Authors: Izumi Yasuhiko , Koyama Yutaka
Published: December 2024

The NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is a potential therapeutic target for central nervous system diseases. This review emphasizes the role of oxidative stress and neuroinflammation in neurodegenerative diseases, highlighting the therapeutic potential of Nrf2 activators such as dimethyl fumarate (DMF). DMF, initially administered for treating psoriasis, has demonstrated efficacy in multiple sclerosis and is metabolized to monomethyl fumarate, which may exert significant therapeutic effects. DMF activates the Nrf2-ARE pathway, and recent studies have indicated that its anti-inflammatory effects occur through Nrf2-independent mechanisms. Electrophilic Nrf2 activators, such as DMF, covalently bind to cysteine residues in proteins and modulate their function. We discuss the implications of cysteine residue modifications by DMF, which may cause both therapeutic benefits and potential off-target effects. Furthermore, we propose a chemical proteomics-based drug discovery approach to achieve desired therapeutic effects by selectively covalently modifying cysteines in target proteins. These findings advocate for a broader understanding of the Nrf2-independent mechanisms of electrophilic Nrf2 activators, thereby improving drug discovery strategies that target neurodegenerative diseases while minimizing toxicity.
A Novel UWB Pulse Expander Using an Integrated Microstrip Splitter, Delay Lines, and a Combiner
Authors: Semenako Janis , Migla Sandis , Solovjova Tatjana , Tihomorskis Nikolajs , Rubuls Kristaps , Cirjulina Darja , Spolitis Sandis , Aboltins Arturs
Published: December 2024

Passive pulse shaping at frequencies above 1 GHz is mainly achieved through frequency-domain processing using filters. Unfortunately, the conventional frequency domain approach does not allow precise control of the impulse response of the filter, therefore, setting limitations to the pulse shaping accuracy. Sub-nanosecond pulse expansion that preserves steep pulse transitions is one of the ultra-wideband (UWB) applications where frequency domain approaches do not provide satisfactory results. This paper proposes a highly innovative approach based on time-domain signal processing using a set of parallel microstrip delay lines connected in a network accompanied by a splitter at the input and a combiner at the output. The proposed design, analogous to finite impulse response (FIR) filters in digital signal processing (DSP), provides fine-grained control over time-domain characteristics and supports the implementation of complex functions, including pulse expansion. This paper presents a detailed analysis of previous work and theoretical considerations regarding the advantages and limitations of UWB pulse time-domain processing. Moreover, detailed HFSS simulations of components, such as a microstrip pulse splitter, delay lines, a combiner, and their combinations, are presented. Finally, the results of the experimental validation of the device, fabricated on an FR-4 substrate, are presented. Technology for effective implementation of a pulse splitter, delay lines, and a pulse combiner, as well as their matching, can be considered as key findings of the given research. Limitations associated with matching and delay estimation for pulsed UWB signals are highlighted.
Polymethyl Methacrylate Bone Cement Polymerization Induced Thermal Necrosis at the Cement–Bone Interface: A Narrative Review
Authors: Szoradi Gergo Tamas , Feier Andrei Marian , Zuh Sandor Gyorgy , Russu Octav Marius , Pop Tudor Sorin
Published: December 2024

Polymethyl methacrylate (PMMA) bone cement has been a transformative material in orthopedics since its introduction in the mid-20th century. Originally used in dental medicine, PMMA was adopted for orthopedic applications by Sir John Charnley in the 1950s, significantly enhancing joint replacement surgeries. The primary appeal of PMMA lies in its biocompatibility, mechanical strength, and ease of handling, making it a favored choice for various orthopedic procedures, including arthroplasties and limb-salvage surgeries. However, the exothermic polymerization process of PMMA poses a risk of thermal necrosis in the surrounding bone tissue, as local temperatures can exceed 70 °C, causing damage to osteocytes. Research has sought to mitigate these risks by optimizing mixing techniques, reducing cement mantle thickness, and incorporating cooling methods. Recent advancements, such as the use of phase-change materials (PCMs) and alternative monomers, have shown promise in lowering the exothermic peak during polymerization. Other strategies include pre-cooling the cement and prosthetic components and using composite cement. Despite these innovations, managing the balance between minimizing heat generation and maintaining mechanical properties remains a challenge. The impact of thermal necrosis is significant, compromising implant stability and osseointegration. Understanding the complex interactions between PMMA’s thermal properties and its clinical outcomes is essential for improving orthopedic surgical practices and patient recovery.
The Role of Artificial Intelligence in Predicting and Managing Pediatric Fracture Overgrowth: A Comprehensive Review
Authors: Marletta Daniela Alessia , Nanni Matteo , Giuca Gabriele , Sanzarello Ilaria , Zampogna Biagio , Leonetti Danilo
Published: December 2024

Pediatric fracture overgrowth is an unpredictable complication of long bone fractures in children, leading to excessive growth of the injured limb and resulting in limb length discrepancies (LLDs) and angular deformities that impact mobility and quality of life. Traditional methods struggle to predict at-risk children, hindering early detection and management. Artificial intelligence (AI), including machine learning and deep learning, offers advanced data analysis capabilities to enhance predictive accuracy and personalize treatment strategies. This comprehensive review explores the current understanding of pediatric fracture overgrowth, examines AI applications in medicine and orthopedics, evaluates potential AI applications specific to fracture overgrowth, and discusses ethical considerations and patient-centric approaches. We highlight how AI can improve diagnostic precision, facilitate early intervention, and optimize clinical outcomes. Though direct studies on AI in fracture overgrowth are limited, evidence from related areas underscores its potential. Embracing AI could revolutionize pediatric fracture management, leading to earlier detection, targeted interventions, and better outcomes for affected children.
Reduced Homogeneous Myocardial [18F]FDG Uptake in Routine PET/CT Studies as an Early Indicator of Chemotherapy-Induced Cardiotoxicity
Authors: Palomino-Fernández David , Bueno Héctor , Jiménez-López-Guarch Carmen , Moreno Guillermo , Seiffert Alexander P. , Gómez Enrique J. , Gómez-Grande Adolfo , Sánchez-González Patricia
Published: December 2024

Cardiotoxicity refers to the damage induced by antineoplastic treatments, leading to various cardiovascular conditions. [18F]FDG PET radiomics analysis could provide relevant information on early onset changes occurring in cardiac metabolism of chemotherapy-induced cardiotoxicity. Patients’ sociodemographic data, cardiovascular risk factors, laboratory parameters, and left ventricle [18F]FDG PET radiomic features are analyzed. The HRad index for the quantification of the heterogeneity of the metabolic uptake patterns is proposed. Statistical analysis is performed by separating patients according to the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). Baseline, intermediate, and end-of-treatment scans are evaluated as separate groups. Overall, CTRCD+ patients show lower overall mean standardized uptake values (SUVmean) compared to CTRCD− patients, with statistically significant differences between groups only observed in the intermediate PET study (p = 0.025). A total of 34 radiomic features show statistically significant differences between the CTRCD+ and CTRCD− groups in the intermediate imaging studies. In the CTRCD− group, greater overall heterogeneity of metabolic uptake is observed in the intermediate PET image compared to the CTRCD+ groups (p = 0.025). The assessment of CTRCD through [18F]FDG PET radiomics analysis could be a potential tool for the identification of a predisposition to the later development of cardiac complications after cardiotoxic treatment.
Three-Dimensional Ultra-Wideband Antenna: From Guiding Physical Considerations to Sequential Computer Optimization of Parameters and Characteristics
Authors: Belichenko Victor P. , Buyanov Yuri , Dymov George , Mironchev Aleksandr , Gorst Aleksandr
Published: December 2024

Features of radiation from a three-dimensional ultra-wideband (UWB) unidirectional antenna are studied within the framework of the theory of characteristic modes. The antenna has a very simple structure and is distinguished by a rational use of accommodation volume. It has been found that a very wide matching band is provided by the simultaneous excitation of modes of two groups. Since the modes of each group have similar directional patterns, the stability of the antenna directional pattern also occurs practically within the entire matching band.
Three-Dimensional Forward Modeling and Inversion Study of Transient Electromagnetic Method Considering Inhomogeneous Magnetic Permeability
Authors: Wang Chenyu , Dong Yan , Gao Jingyu , Tan Handong , Wang Yingge , Dong Weiyu
Published: December 2024

Traditional studies on Transient Electromagnetic Method (TEM) typically assume that the subsurface medium is non-magnetic. However, in regions with igneous rock accumulations or where the subsurface is rich in ferromagnetic minerals, neglecting the magnetic properties of the underground medium may lead to erroneous interpretations for TEM data. This paper conducts a 3-D TEM forward modeling and inversion study considering the non-uniformity cases of magnetic permeability. 3-D TEM forward modeling employs an edge-based finite element method using unstructured grids and a second-order implicit backward Euler method, achieving a modeling algorithm that simultaneously considers non-uniform models of magnetic permeability and resis-tivity. The accuracy of the modeling algorithm is verified by comparing it with the analytical solution of a homogeneous half-space model and the solution of a 1-D TEM forward modeling algorithm. 3-D TEM inversion employs the L-BFGS algorithm and synthetic examples considering non-uniform magnetic permeability are presented. The inversion results show good recovery for the resistivity and magnetic permeability models. Comparisons with the inversion results that neglect the non-uniformity of magnetic permeability validate the importance of considering the variation of permeability in 3-D TEM forward modeling and inversion.
Parameter Analysis of Resilient Precast Concrete Beam–Column Joints
Authors: Yang Yanting , Ge Qi , Lu Yang
Published: December 2024

Conventional precast structures often face the challenge of post-earthquake repair, especially at beam–column joints. A new type of precast concrete beam–column joint with a replaceable energy dissipation device consisting of cross-shaped and H-shaped steel was proposed in this paper, which was characterized by the use of replaceable energy-dissipating devices to improve the seismic capacity. Based on the previous test results of the group, this paper used ABAQUS to investigate how factors like the thickness of the H-shaped steel webs and the size and number of openings affected the seismic performance of precast concrete beam–column joints with replaceable energy dissipation devices. The results showed that (1) an increase in the H-shaped steel’s thickness in the REDDC could improve the load-carrying capacity of the node, but the energy dissipation capacity was weakened, and (2) the length and width of the H-shaped steel openings had almost no effect on the ultimate load-carrying capacity within a certain range, but increasing the size of the openings could improve the energy dissipation capacity and reduce the ultimate load-carrying capacity at the same time. Compared with the length of the openings, the width of the openings had a more significant impact on the energy dissipation capacity. (3) The peak load-carrying capacity decreased with an increase in the number of openings in the H-shaped steel.
Modeling Approaches for Accounting Radiation-Induced Effect in HVDC-GIS Design for Nuclear Fusion Applications
Authors: Lucchini Francesco , Frescura Alessandro , Urazaki Junior Kenji , Marconato Nicolò , Bettini Paolo
Published: December 2024

This paper examines the modeling approaches used to analyze the electric field distribution in high-voltage direct-current gas-insulated systems (HVDC-GISs) used for the acceleration grid power supply (AGPS) of neutral beam injectors (NBIs). A key challenge in this context is the degradation of dielectric performance due to radiation-induced conductivity (RIC), a phenomenon specific to the harsh radioactive environments near fusion reactors. Traditional models for gas conductivity in HVDC-GISs often rely on constant or nonlinear conductivity formulations, which are based on experimental data but fail to capture the effects of external ionizing radiation that triggers RIC. To address this limitation, a more advanced approach, the drift–diffusion recombination (DDR) model, is used, as it more accurately represents gas ionization and the influence of radiation fields. However, this increased accuracy comes at the cost of higher computational complexity. This paper compares the different modeling strategies, discussing their strengths and weaknesses, with a focus on the capabilities in evaluating the charge accumulation and the RIC phenomenon.
Global Existence and Decay Estimates for a Viscoelastic Petrovsky–Kirchhoff-Type Equation with a Delay Term
Authors: Sebih Noureddine , Mohammed Djaouti Abdelhamid , Boudekhil Chafi , Al-Quran Ashraf
Published: December 2024

In this paper, we consider a viscoelastic Kirchhoff equation with a delay term in the internal feedback. By using the Faedo–Galerkin approximation method, we prove the well posedness of the global solutions. Introducing suitable energy, we prove the general uniform decay results.
The Classification of Metastatic Spine Cancer and Spinal Compression Fractures by Using CNN and SVM Techniques
Authors: Jeong Woosik , Baek Chang-Heon , Lee Dong-Yeong , Song Sang-Youn , Na Jae-Boem , Hidayat Mohamad Soleh , Kim Geonwoo , Kim Dong-Hee
Published: December 2024

Metastatic spine cancer can cause pain and neurological issues, making it challenging to distinguish from spinal compression fractures using magnetic resonance imaging (MRI). To improve diagnostic accuracy, this study developed artificial intelligence (AI) models to differentiate between metastatic spine cancer and spinal compression fractures in MRI images. MRI data from Gyeongsang National University Hospital, collected from January 2019 to April 2022, were processed using Otsu’s binarization and Canny edge detection algorithms. Using these preprocessed datasets, convolutional neural network (CNN) and support vector machine (SVM) models were built. The T1-weighted image-based CNN model demonstrated high sensitivity (1.00) and accuracy (0.98) in identifying metastatic spine cancer, particularly with data processed by Otsu’s binarization and Canny edge detection, achieving exceptional performance in detecting cancerous cases. This approach highlights the potential of preprocessed MRI data for AI-assisted diagnosis, supporting clinical applications in distinguishing metastatic spine cancer from spinal compression fractures.
Exploring the Potent Roles of an Internally Translated Truncated Connexin-43 Isoform
Authors: Maalouf Mario , Gaffney Adelaide T. , Bell Bridger R. , Shaw Robin M.
Published: December 2024

Connexins are a family of transmembrane proteins that form membrane channels [...]
Pharmacological Inhibition of Astrocytic Transglutaminase 2 Facilitates the Expression of a Neurosupportive Astrocyte Reactive Phenotype in Association with Increased Histone Acetylation
Authors: Delgado Thomas , Emerson Jacen , Hong Matthew , Keillor Jeffrey W. , Johnson Gail V. W.
Published: December 2024

Astrocytes play critical roles in supporting structural and metabolic homeostasis in the central nervous system (CNS). CNS injury leads to the development of a range of reactive phenotypes in astrocytes whose molecular determinants are poorly understood. Finding ways to modulate astrocytic injury responses and leverage a pro-recovery phenotype holds promise in treating CNS injury. Recently, it has been demonstrated that ablation of astrocytic transglutaminase 2 (TG2) shifts reactive astrocytes towards a phenotype that improves neuronal injury outcomes both in vitro and in vivo. Additionally, in an in vivo mouse model, pharmacological inhibition of TG2 with the irreversible inhibitor VA4 phenocopied the neurosupportive effects of TG2 deletion in astrocytes. In this study, we extended our comparisons of VA4 treatment and TG2 deletion to provide insights into the mechanisms by which TG2 attenuates neurosupportive astrocytic function after injury. Using a neuron–astrocyte co-culture model, we found that VA4 treatment improves the ability of astrocytes to support neurite outgrowth on an injury-relevant matrix, as we previously showed for astrocytic TG2 deletion. We hypothesize that TG2 mediates its influence on astrocytic phenotype through transcriptional regulation, and our previous RNA sequencing suggests that TG2 is primarily transcriptionally repressive in astrocytes, although it can facilitate both up- and downregulation of gene expression. Therefore, we asked whether VA4 inhibition could alter TG2’s interaction with Zbtb7a, a transcription factor that we previously identified as a functionally relevant TG2 nuclear interactor. We found that VA4 significantly decreased the interaction of TG2 and Zbtb7a. Additionally, we assessed the effect of TG2 deletion and VA4 treatment on transcriptionally permissive histone acetylation and found significantly greater acetylation in both experimental groups. Consistent with these findings, our present proteomic analysis further supports the predominant transcriptionally repressive role of TG2 in astrocytes. Our proteomic data additionally unveiled pronounced changes in lipid and antioxidant metabolism in astrocytes with TG2 deletion or inhibition, which likely contribute to the enhanced neurosupportive function of these astrocytes.
Hydroxyproline in Urine Microvesicles as a Biomarker of Fibrosis in the Renal Transplant Patient
Authors: Torres Sánchez María José , Ruiz Fuentes María Carmen , Clavero García Elena , Rísquez Chica Noelia , Espinoza Muñoz Karla , Espigares Huete María José , Caba Molina Mercedes , Osuna Antonio , Wangensteen Rosemary
Published: December 2024

Background/Objectives: Interstitial fibrosis/tubular atrophy in kidney transplantation is an unspecific lesion induced by immune and non-immune factors, which determines the progression of chronic kidney disease. Hydroxyproline is an imino acid that is part of the molecule of collagen. The aim of this study was to assess hydroxyproline in urine microvesicles as a marker of fibrosis in the renal transplant patient. Patients and Methods: An observational cross-sectional study was conducted on 46 renal transplant patients who had undergone renal biopsy with diagnostic intention, as well as 19 healthy controls. Clinical, histological, and laboratory variables were collected at the time of marker determination and renal function was analyzed 2 years later. Hydroxyproline was measured in urine microvesicles. Results: Renal transplant patients showed a higher microvesicular concentration of hydroxyproline compared to the control group, with the following medians (interquartile range (IQR)): 28.024 (5.53) ng/mL vs. 2.51 (1.16) ng/mL, p < 0.001. In the transplanted patients, patients in whom biopsy showed some score of total cortical parenchymal inflammation (ti) displayed a significantly higher concentration of hydroxyproline in urine microvesicles than those patients who did not score for cortical parenchymal inflammation (29.91 ± 2.797 ng/mL vs. 22.72 ± 8.697 ng/mL, p = 0.034). No significant correlation was observed between urinary markers and serum creatinine, calcium, and parathyroid hormone (PTH). Conclusions: The concentration of hydroxyproline in urinary microvesicles increased in renal transplant patients relative to healthy controls. Hydroxyproline in urinary microvesicles is a marker of chronic renal inflammation in transplanted patients, and further studies are required to confirm this finding in other pathologies, as well as the association with fibrosis and the evolution of renal function.
Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection
Authors: Sian-Hulsmann Jeswinder , Riederer Peter , Michel Tanja Maria
Published: December 2024

Despite many years of research into the complex neurobiology of Parkinson’s disease, the precise aetiology cannot be pinpointed down to one causative agent but rather a multitude of mechanisms. Current treatment options can alleviate symptomsbut only slightly slow down the progression and not cure the disease and its underlying causes. Factors that play a role in causing the debilitating neurodegenerative psycho-motoric symptoms include genetic alterations, oxidative stress, neuroinflammation, general inflammation, neurotoxins, iron toxicity, environmental influences, and mitochondrial dysfunction. Recent findings suggest that the characteristic abnormal protein aggregation of alpha-synuclein and destruction of substantia nigra neurons might be due to mitochondrial dysfunction related to disturbances in lipid and glucose metabolism along with insulin resistance. The latter mechanism of action might be mediated by insulin receptor substrate docking to proteins that are involved in neuronal survival and signaling related to cell destruction. The increased risk of developing Type 2 Diabetes Mellitus endorses a connection between metabolic dysfunction and neurodegeneration. Here, we explore and highlight the potential role of glycolipid cellular insults in the pathophysiology of the disorder, opening up new promising avenues for the treatment of PD. Thus, antidiabetic drugs may be employed as neuromodulators to hinder the progression of the disorder.
Sensing Platform Based on Gold Nanoclusters and Nanoporous Anodic Alumina for Preeclampsia Detection
Authors: Cantons Josep Maria , Bachhuka Akash , Marsal Lluis F.
Published: December 2024

Preeclampsia is a pregnancy-specific hypertensive syndrome recognized as the leading cause of maternal and fetal morbidity worldwide. Early diagnosis is crucial for mitigating its adverse effects, and recent investigations have identified endoglin as a potential biomarker for this purpose. Here, we present the development of a hybrid biosensor platform for the ultrasensitive detection of endoglin, aimed at enabling the early diagnosis of preeclampsia. This platform integrates the high surface area properties of nanoporous anodic alumina (NAA) with the unique optical characteristics of gold nanoclusters (AuNCs) to achieve enhanced detection capabilities. The NAA surface functionalized to promote attachment of AuNCs, which then was functionalized with specific antibodies to confer selectivity towards endoglin. Photoluminescence (PL) analysis of the biosensor demonstrated a linear detection range of 10–50 ng/mL, with a detection limit of 5.4 ng/mL and a sensitivity of 0.004 a.u./(ng/mL). This proof-of-concept study suggests that the NAA-AuNCs-based biosensing platform holds significant potential for the development of ultrasensitive, portable, and cost-effective diagnostic tools for preeclampsia, offering a promising avenue for advancing prenatal care.
Exploring Imaging Applications of a Red-Emitting π-Acceptor (π-A) Pyrene-Benzothiazolium Dye
Authors: Abeywickrama Chathura S. , Huang Enya , Yan Wenhui , Vrionides Michael A. , Warushavithana Paaramitha , Johnson Kristen A. , Stahelin Robert V. , Pang Yi , Mani Tomoyasu , Wijesinghe Kaveesha J.
Published: December 2024

Bright biocompatible fluorescent imaging dyes with red to near-infrared (NIR) emissions are ideal candidates for fluorescence microscopy applications. Pyrene–benzothiazolium hemicyanine dyes are a new class of lysosome-specific probes reported on recently. In this work, we conduct a detailed implementation study for a pyrene–benzothiazolium derivative, BTP, to explore its potential imaging applications in fluorescence microscopy. The optical properties of BTP are studied in intracellular environments through advanced fluorescence microscopy techniques, with BTP exhibiting a noticeable shift toward blue (λem ≈ 590 nm) emissions in cellular lysosomes. The averaged photon arrival time (AAT)-based studies exhibit two different emissive populations of photons, indicating the probe’s dynamic equilibrium between two distinctively different lysosomal microenvironments. Here, BTP is successfully utilized for time-lapse fluorescence microscopy imaging in real-time as a ‘wash-free’ imaging dye with no observed background interference. BTP exhibits an excellent ability to highlight microorganisms (i.e., bacteria) such as Bacillus megaterium through fluorescence microscopy. BTP is found to be a promising candidate for two-photon fluorescence microscopy imaging. The two-photon excitability of BTP in COS-7 cells is studied, with the probe exhibiting an excitation maximum at λTP ≈ 905 nm.
A Randomized Controlled Trial to Test the Effects of Repetitive Peripheral Magnetic Stimulation Versus Neuromuscular Electrical Stimulation in Patients with Spastic Hemiparesis After Stroke (REPMAST): Study Protocol
Authors: Pohl Kristin Loreen , Müller Jens , Wittig-Böttger Katja , Ritter Alexander , Hamzei Farsin
Published: December 2024

Background/Objectives: Innovative therapies are needed to reduce disability, facilitate activities of daily living, and improve the quality of life in patients with stroke. Non-invasive methods of stimulating the peripheral and central nervous system are increasingly being used to enhance the effects of existing therapies in stroke rehabilitation. One potentially relevant method for achieving greater improvement is repetitive peripheral magnetic stimulation (rPMS). This randomized controlled trial (RCT), the Peripheral MAgnetic stimulation in patients with spastic hemiparesis after Stroke Trial (REPMAST), will investigate whether rPMS improves upper extremity function, spasticity, and activities of daily living in patients with stroke compared with neuromuscular stimulation (NMS). Methods: REPMAST is an interventional, randomized controlled single-blinded study. Patients with subacute stroke are randomized to receive rPMS or NMS five days a week for three weeks in addition to standard rehabilitation therapy. The primary outcome is the change in the Fugl–Meyer Assessment for Upper Extremity between the beginning and end of the stimulation sessions. Secondary outcomes include changes in the Katz Index of Independence in Activities of Daily Living, the Timed Up and Go Test, the Modified Ashworth Scale, and the Tardieu Scale. A total sample size of 138 patients (69 in each group) is required to investigate the superiority of rPMS compared with NMS. Conclusions: The aim of this RCT is to provide evidence for an effective peripheral stimulation treatment for stroke recovery.
How Does Background Music Affect Dining Duration, Tips and Bill Amounts in Restaurants? A Field Experiment
Authors: Malcman Merav , Azar Ofer H. , Shavit Tal , Rosenboim Mosi
Published: December 2024

Influences from external factors can affect decision-makers, preventing them from making decisions in a fully rational manner. Music may serve as one such influential factor in this context. Music is part of our daily lives, and we are exposed to music in numerous places. We designed a field experiment to study the influence of background music on patrons’ behavior in restaurants. Specifically, we examine the effect of the music’s tempo (slow or fast) on time spent in the restaurant, the bill amount, and the tip size. The results show that patrons in the slow tempo group spent the most time in the restaurant, those in the control group followed next, and the patrons in the fast tempo group were the quickest to leave. However, there are no differences between the groups in bill size. The tips in the fast tempo group were higher than in the control group when controlling for several independent variables. The findings have practical implications for restaurant owners and managers. In busy periods, the restaurant can use fast-tempo music to increase the turnover of tables, because then tables become available for new diners more quickly, contributing more to the restaurant’s income compared to tables that occupy the space for a longer duration.
Emotional Dependence and Narcissism in Couple Relationships: Echo and Narcissus Syndrome
Authors: Moral-Jiménez María de la Villa , Mena-Baumann Ava
Published: December 2024

Emotional dependency consists of an extreme affective need that manifests pathologically, such that it has been established that the partners of emotionally dependent individuals exhibit narcissistic traits. The present study aimed to examine the relationship between emotional dependency, the narcissistic traits of a romantic partner, and psychological abuse, in addition to examining the sex differences in the first two variables. This study included 271 subjects (144 women and 127 men) between the ages of 18 and 66 (M = 36.9; SD = 14.748). This study compared individuals with and without emotional dependency, finding that those with emotional dependency reported more narcissistic partners. Furthermore, psychological abuse was positively correlated with the narcissism of the partner. There were no significant sex differences in emotional dependency or in the exhibition of narcissistic traits. The importance of examining the connections between emotional dependency, the narcissistic traits of a romantic partner, and the potential for psychological abuse within these relationships are highlighted.
Third-Generation Therapies for the Management of Psychoactive Substance Use in Young People: Scoping Review
Authors: Sequeda Gabriela , Acosta-López Johan E. , Diaz-Camargo Edgar , Torres-Santos Eduardo-Andrés , López-Ramírez Valentina , Rivera-Porras Diego
Published: December 2024

Introduction: Third-generation therapies (TGTs) have been shown to be effective in the treatment of substance use behaviors in college-aged adolescents. These therapies are based on acceptance, mindfulness and psychological flexibility, which enable young people to change their Psychoactive Substance Use (PSU)-related behaviours, develop coping skills to manage difficult emotions and thoughts, reduce experiential avoidance and maintain long-term abstinence. Objective: To explore the implementation and potential benefits of third-generation therapies, Acceptance and Commitment Therapy (ACT), Dialectical Behaviour Therapy (DBT) and Mindfulness, for the treatment of PSU in college youth. This review includes articles within a 5-year window. Method: A scoping, observational and retrospective review was conducted using the PRISMA method in SCOPUS, PUBMED and Web of Science. Results: eight studies were found, six based on mindfulness, one on dialectical behaviour therapy and one on acceptance and commitment therapy. The results of the studies are promising and emerging for the intervention of the problem. Conclusion: The interventions used show evidence of reducing PSU and other mental health problems such as anxiety, depression and post-traumatic stress. In addition, they allowed patients to increase their well-being and mindfulness.
Analysis of the Prestressing Loss Influence in Prefabricated Concrete Bridges Based on a Drop Weight Impact Method
Authors: He Jilei , Wu Wenqi , Tan Zikang , Li Dongyuan , Cai Yingchun , Guo Pan
Published: December 2024

The prestress loss of prefabricated continuous beam bridges directly affects their stress state and operating conditions. Excessive prestress loss can lead to increased mid span deflection of the main beam, cracking of the web and bottom plates, reduced bearing capacity, and even affect the safety of the structure. This study focuses on urban highway overpasses and measures the deflection of the bridge deck using the drop hammer impact method. The impact test of prefabricated segmental beam bridges was simulated using a finite element model, and the influence of prestress loss at different positions on the deflection basin of the bridge deck during operation was studied. The research results indicate that the factor causing the greatest damage to bridge stiffness is the loss of prestress in the bottom plate. When the prestress loss reaches 30%, the maximum response value increases by 33.6%. In contrast, the prestress loss of the roof has a smaller impact on deflection, with a maximum response value increase of 18.7%. This study provides important reference for evaluating prestress loss through impact testing methods in the future.
Analysis of the Skid Resistance Decrease in Bituminous Pavements in Dual-Carriageway Tunnels
Authors: Pérez-Acebo Heriberto , Isasa Miren , Gurrutxaga Itziar , Alonso-Solórzano Ángela
Published: December 2024

Unlike other pavement indices, the skid resistance, or friction, of bituminous pavements behaves differently. After the extension of a new layer, the friction increases as the bitumen film is removed and the aggregates are exposed. The aggregates are then polished by traffic, mainly by heavy vehicles, and the pavement reaches the seasonal phase, in which, if heavy traffic volume remains constant, the only variations are seasonal, with maximum values in winter and minimum values in summer. Nonetheless, in tunnels, as they are not exposed to climatic actions, the friction value is lower than outside. Therefore, the article evaluates the skid resistance decrease in tunnels compared to outdoor conditions. For this purpose, the skid resistance values in dual-carriageway tunnels in Gipuzkoa (Spain) were studied and compared with the values obtained 500 m before and after the tunnel. Overall, a 10% friction decrease was observed inside the tunnels. In winter, the decrease was 11%, while in summer it was 8%. In tunnels longer than 500 m, the decrease was greater (12%) than in tunnels shorter than 500 m (9% and 7%). This analysis contributes to a better knowledge of the available friction inside a tunnel and to the better management of road safety.
A Phthalimide-Functionalized Heptamethine Cyanine Dye for Tumor-Targeted Photothermal Therapy
Authors: Park Yoonbin , Yang Juhui , Hyun Hoon
Published: December 2024

Background: A phthalimide-functionalized heptamethine cyanine dye, named Ph790H, is used for targeted photothermal cancer therapy in vivo. We highlight that the chemical structure of Ph790H is newly designed and synthesized for the first time in this study. Objectives: By possessing a rigid chloro-cyclohexenyl ring in the heptamethine cyanine backbone, the bifunctional near-infrared (NIR) fluorescent dye Ph790H can be preferentially accumulated in tumor without the need for additional targeting ligands, which is defined as the “structure-inherent tumor targeting” concept. Methods: The phototherapeutic effect of Ph790H is evaluated in HT-29 human colorectal cancer xenografts to be used as a cancer-targeting photothermal agent. Results: The results reveal that the Ph790H shows enhanced tumor accumulation in HT-29 xenografts 48 h post-injection with a high tumor-to-background ratio. After determination of the optimal timing for photothermal therapy (PTT), the HT-29 tumor-possessing nude mice pretreated with Ph790H are subsequently irradiated with an 808 nm NIR laser for 5 min. The tumor-targeted PTT treatment can efficiently inhibit the tumor development compared with that of control groups. Moreover, no tumor regrowth or Ph790H-induced mortality occurs after the treatment of Ph790H and laser irradiation during a period of monitoring. Conclusions: Therefore, this work demonstrates that the bifunctional phototheranostic agent Ph790H can be utilized for targeted cancer imaging and fluorescence-guided phototherapy simultaneously.
The Impact of Iron on Cancer-Related Immune Functions in Oncology: Molecular Mechanisms and Clinical Evidence
Authors: Badran Omar , Cohen Idan , Bar-Sela Gil
Published: December 2024

Iron metabolism plays a dual role in cancer, serving as an essential nutrient for cellular functions and a potential catalyst for tumor growth and immune evasion. Here, we cover the complex interplay between iron levels within the serum or in the microenvironment and cancer therapy, focusing on how iron deficiency and overload can impact immune function, tumor progression, and treatment efficacy. On the one hand, we highlight iron deficiency as a factor of primary immune responses and its adverse effects on anti-cancer immunotherapy efficacy. On the other hand, we also stress the impact of iron overload as an essential factor contributing to tumor growth, creating a suppressive tumor microenvironment that hinders immune checkpoint inhibitor immunotherapy. Overall, we emphasize the necessity of the personalized management of iron levels in oncology patients as a critical element in treatment optimization to achieve favorable outcomes. Based on these considerations, we believe that close and careful monitoring and the tailored balancing of iron supplementation strategies should be the subject of further clinical studies, and routine iron management should be implemented in oncology clinical practice and integrated into cancer therapy protocols.
Automatic Segmentation of Metastatic Livers by Means of U-Net-Based Procedures
Authors: Tiraboschi Camilla , Parenti Federica , Sangalli Fabio , Resovi Andrea , Belotti Dorina , Lanzarone Ettore
Published: December 2024

Background: The liver is one of the most common sites for the spread of pancreatic ductal adenocarcinoma (PDAC) cells, with metastases present in about 80% of patients. Clinical and preclinical studies of PDAC require quantification of the liver’s metastatic burden from several acquired images, which can benefit from automatic image segmentation tools. Methods: We developed three neural networks based on U-net architecture to automatically segment the healthy liver area (HL), the metastatic liver area (MLA), and liver metastases (LM) in micro-CT images of a mouse model of PDAC with liver metastasis. Three alternative U-nets were trained for each structure to be segmented following appropriate image preprocessing and the one with the highest performance was then chosen and applied for each case. Results: Good performance was achieved, with accuracy of 92.6%, 88.6%, and 91.5%, specificity of 95.5%, 93.8%, and 99.9%, Dice of 71.6%, 74.4%, and 29.9%, and negative predicted value (NPV) of 97.9%, 91.5%, and 91.5% on the pilot validation set for the chosen HL, MLA, and LM networks, respectively. Conclusions: The networks provided good performance and advantages in terms of saving time and ensuring reproducibility.
DHODH Inhibition Suppresses MYC and Inhibits the Growth of Medulloblastoma in a Novel In Vivo Zebrafish Model
Authors: Tsea Ioanna , Olsen Thale Kristin , Polychronopoulos Panagiotis Alkinoos , Tümmler Conny , Sykes David B. , Baryawno Ninib , Dyberg Cecilia
Published: December 2024

Background/Objectives: Medulloblastoma (MB) is the most common high-grade paediatric brain tumour, with group 3 MB patients having the worst prognosis. A high prevalence of group 3 tumours shows overexpression of the MYC oncogene, making it a potential therapeutic target. However, attempts to directly inhibit MYC have so far demonstrated limited success. Dihydroorotate dehydrogenase (DHODH), a crucial enzyme of the pyrimidine biosynthesis process, has emerged as an up-and-coming target in oncology, as its inhibition has shown promise in several cancers. Methods: In this study, we investigated the efficacy of brequinar, a DHODH inhibitor, in MB, with a focus on group 3. In vitro, BRQ’s effects on cell viability and MYC expression were tested in seven MB cell lines. In vivo, a novel zebrafish xenograft model was used to evaluate BRQ’s impact on tumour growth and toxicity. Results: High DHODH expression was identified in group 3 and shh MB subgroups, correlating with poor survival and MYC expression. BRQ demonstrated nanomolar efficacy in inducing apoptosis and reducing MYC expression in group 3 MB cell lines. Finally, we established a novel zebrafish xenograft model and demonstrated that BRQ significantly inhibited tumour growth at non-toxic concentrations in vivo, particularly in the D458 metastatic MB cell line. Conclusions: Our findings indicate that DHODH is a promising therapeutic target in group 3 MBs. Furthermore, BRQ shows potential for clinical application, effectively reducing tumour growth and MYC expression in vitro and in vivo. Moreover, our newly established zebrafish xenograft model offers a promising avenue for rapid in vivo drug testing for use in MB.
Current Evidence in the Systemic Treatment of Brain Metastases from Breast Cancer and Future Perspectives on New Drugs, Combinations and Administration Routes: A Narrative Review
Authors: Garrone Ornella , Ruatta Fiorella , Rea Carmen Giusy , Denaro Nerina , Ghidini Michele , Cauchi Carolina , Bareggi Claudia , Galassi Barbara , Merlano Marco C. , Rosenfeld Roberto
Published: December 2024

Breast cancer is the most frequently diagnosed neoplasm all over the world and the second leading cause of cancer death in women. Breast cancer prognosis has significantly improved in the last years due to the advent of novel therapeutic options, both in the early and in advanced stages. However, the spread of the disease to the brain, accounting for 15–30% of the metastatic diagnoses, is challenging, and its poor prognosis represents an unmet medical need, leading to deterioration of quality of life and causing morbidity and mortality. Generally, triple-negative and HER2-positive breast cancer subtypes more frequently spread to the brain or in the leptomeningeal space. Consequently, according to international guidelines, several systemic treatments can be offered as a first option in some subsets of patients. However, a multidisciplinary approach is recommended to offer the most appropriate strategy to patients. Antibody–drug conjugates such as trastuzumab deruxtecan or sacituzumab govitecan along with small molecules have led to important achievements in the treatment of brain metastases from HER2-positive and triple-negative breast cancer. In this narrative review, we will focus on the molecular features leading to the development of brain metastases and explore the risk and the prognostic factors involved in the development of brain metastases. Finally, we will review the major achievements in the treatment landscape of brain metastases from breast cancer and novel medical approaches.
ALDHHigh Breast Cancer Stem Cells Exhibit a Mesenchymal–Senescent Hybrid Phenotype, with Elevated Metabolic and Migratory Activities
Authors: Larrea Murillo Luis , Sugden Conor J. , Ozsvari Bela , Moftakhar Zahra , Hassan Ghada S. , Sotgia Federica , Lisanti Michael P.
Published: December 2024

Cancer stem cells (CSCs) account for 0.01 to 2% of the total tumor mass; however, they play a key role in tumor progression, metastasis and resistance to current cancer therapies. The generation and maintenance of CSCs are usually linked to the epithelial–mesenchymal transition (EMT), a dynamic process involved in reprogramming cancer cells towards a more aggressive and motile phenotype with increased stemness potential. Cells that undergo an EMT process have shown to be more resistant to conventional chemo/radiotherapies. In this context, aldehyde dehydrogenase (ALDH) enzymes, known for their role in the cellular detoxification of aldehydes and enhancement of cell survival, are often upregulated in cancer cells, promoting their resistance to conventional cancer treatments. Indeed, high ALDH levels have become a hallmark biomarker of CSCs and are often used to isolate this sub-population from the more abundant cancer cell populations. Herein, we isolated human breast cancer epithelial cells with higher ALDH abundance (ALDHHigh) and compared them to those with low ALDH abundance (ALDHLow). ALDHHigh sub-populations exhibited more characteristic EMT biomarkers by adopting a more mesenchymal phenotype with increased stemness and enhanced migratory potential. Furthermore, ALDHHigh sub-populations displayed elevated senescent markers. Moreover, these cells also demonstrated higher levels of mitochondria DNA/mass, as well as greater mitochondrial and glycolytic metabolic function. Conversely, ALDHLow sub-populations showed a higher efficiency of mammosphere/colony formation and an increased proliferative capacity. Therefore, we demonstrated that these ALDH sub-populations have distinct characteristics, underscoring their role in EMT, the formation of tumors and the mechanisms of metastasis.
Identification of Stable Reference miRNAs for miRNA Expression Analysis in Adult Neurogenesis Across Mouse and Human Tissues
Authors: Levitis Daniella Liana , Si Julia , Ravishankar Kushal , Toborek Michal , Park Minseon
Published: December 2024

Accurate normalization in miRNA studies requires the use of appropriate endogenous controls, which can vary significantly depending on cell types, treatments, and physiological or pathological conditions. This study aimed to identify suitable endogenous miRNA controls for neural progenitor cells (NPCs) and hippocampal tissues, both of which play crucial roles in neurogenesis. Using small RNA sequencing, we identified the most stable miRNAs in primary mouse NPCs and hippocampal tissues and accessed their stability using NormFinder analysis. Six miRNAs—miR-181d-5p, miR-93-5p, miR-103-3p, let-7d-5p, miR-26a-5p, and miR-125a-5p—demonstrated high stability and were evaluated for their suitability as endogenous controls across multiple experimental conditions. All selected miRNAs exhibited consistent expression in the NE-4C mouse cell line but not in ReNcells, a human cell line. For ReNcells, only miR-186-5p, one of the known reference miRNAs tested for comparison, showed stable expression. Notably, miR-103-3p and let-7d-5p were stably expressed in hippocampal tissues from both mouse and human samples but were absent in human brain pericytes, human brain microvascular endothelial cells, and SVG p12 cells, a human fetal glial cell line. This study is the first to identify optimal reference miRNAs for adult neurogenesis in both mouse and human samples, providing reliable options for miRNA normalization and improving the accuracy and reproducibility of miRNA expression analyses in neurogenesis research.