bluuebunny/crossref_metadata_2025 huggingface dataset:
3-Hydroxy-3-Methylglutaric Acid Disrupts Brain Bioenergetics, Redox Homeostasis, and Mitochondrial Dynamics and Affects Neurodevelopment in Neonatal Wistar Rats
Authors: Silveira Josyane de Andrade , Marcuzzo Manuela Bianchin , da Rosa Jaqueline Santana , Kist Nathalia Simon , Hoffmann Chrístofer Ian Hernandez , Carvalho Andrey Soares , Ribeiro Rafael Teixeira , Quincozes-Santos André , Netto Carlos Alexandre , Wajner Moacir , Leipnitz Guilhian
Published: July 2024

3-Hydroxy-3-methylglutaric acidemia (HMGA) is a neurometabolic inherited disorder characterized by the predominant accumulation of 3-hydroxy-3-methylglutaric acid (HMG) in the brain and biological fluids of patients. Symptoms often appear in the first year of life and include mainly neurological manifestations. The neuropathophysiology is not fully elucidated, so we investigated the effects of intracerebroventricular administration of HMG on redox and bioenergetic homeostasis in the cerebral cortex and striatum of neonatal rats. Neurodevelopment parameters were also evaluated. HMG decreased the activity of glutathione reductase (GR) and increased catalase (CAT) in the cerebral cortex. In the striatum, HMG reduced the activities of superoxide dismutase, glutathione peroxidase, CAT, GR, glutathione S-transferase, and glucose-6-phosphate dehydrogenase. Regarding bioenergetics, HMG decreased the activities of succinate dehydrogenase and respiratory chain complexes II–III and IV in the cortex. HMG also decreased the activities of citrate synthase and succinate dehydrogenase, as well as complex IV in the striatum. HMG further increased DRP1 levels in the cortex, indicating mitochondrial fission. Finally, we found that the HMG-injected animals showed impaired performance in all sensorimotor tests examined. Our findings provide evidence that HMG causes oxidative stress, bioenergetic dysfunction, and neurodevelopmental changes in neonatal rats, which may explain the neuropathophysiology of HMGA.
Immunomodulating and Immunosuppressive Therapy for Virus-Negative Immune-Mediated Myocarditis
Authors: Frustaci Andrea , Letizia Claudio , Alfarano Maria , Marchionni Giulia , Verardo Romina , Chimenti Cristina
Published: July 2024

Myocarditis is an inflammatory disease of the myocardium caused by infectious and noninfectious agents. Clinical manifestations range from mildly symptomatic forms to acute heart failure, cardiogenic shock, life-threatening arrhythmias and sudden death. Myocarditis is still a challenging diagnosis because of its wide variability in clinical presentation and unpredictable course. Moreover, a standardized, specific treatment in not yet available. Immunosuppressive treatment for virus-negative lymphocytic myocarditis is still controversial. Conversely, immunosuppression is well established in sarcoidosis, eosinophilic, giant-cell, drug hypersensitivity, and trauma-related myocarditis as well as lymphocytic myocarditis associated with connective tissue diseases or with the rejection of a transplanted heart. Recently, immunosuppressive therapy has been also recognized as an effective treatment in virus-negative inflammatory cardiomyopathy. The aim of this review is to underline the role of immunomodulating and immunosuppressive therapies in patients with immune-mediated myocarditis and illustrate the different treatment strategies depending on the etiology. An endomyocardial biopsy remains the gold standard for the diagnosis of myocarditis as well as for a tailored treatment.
A Local Search Algorithm with Vertex Weighting Strategy and Two-Level Configuration Checking for the Minimum Connected Dominating Set Problem
Authors: Li Ruizhi , He Jintao , Liu Shangqiong , Hu Shuli , Yin Minghao
Published: July 2024

The minimum connected dominating set problem is a combinatorial optimization problem with a wide range of applications in many fields. We propose an efficient local search algorithm to solve this problem. In this work, first, we adopt a new initial solution construction method based on three simplification rules. This method can reduce the size of the original graph and thus obtain a high-quality initial solution. Second, we propose an approach based on a two-level configuration checking strategy and a tabu strategy to reduce the cycling problem. Third, we introduce a perturbation strategy and a vertex weighting strategy to help the algorithm be able to jump out of the local optimum effectively. Fourth, we combine the scoring functions Cscore and Mscore with the aforementioned strategies to propose effective methods for selecting vertices. These methods assist the algorithm in selecting vertices that are suitable for addition to or removal from the current candidate solution. Finally, we verify the performance advantages of the local search algorithm by comparing it with existing optimal heuristic algorithms on two sets of instances. The experimental results show that the algorithm exhibits better performance on two sets of classical instances.
From E-Commerce to the Metaverse: A Neuroscientific Analysis of Digital Consumer Behavior
Authors: Fici Alessandro , Bilucaglia Marco , Casiraghi Chiara , Rossi Cristina , Chiarelli Simone , Columbano Martina , Micheletto Valeria , Zito Margherita , Russo Vincenzo
Published: July 2024

The growing interest in consumer behavior in the digital environment is leading scholars and companies to focus on consumer behavior and choices on digital platforms, such as the metaverse. On this immersive digital shopping platform, consumer neuroscience provides an optimal opportunity to explore consumers’ emotions and cognitions. In this study, neuroscience techniques (EEG, SC, BVP) were used to compare emotional and cognitive aspects of shopping between metaverse and traditional e-commerce platforms. Participants were asked to purchase the same product once on a metaverse platform (Second Life, SL) and once via an e-commerce website (EC). After each task, questionnaires were administered to measure perceived enjoyment, informativeness, ease of use, cognitive effort, and flow. Statistical analyses were conducted to examine differences between SL and EC at the neurophysiological and self-report levels, as well as between different stages of the purchase process. The results show that SL elicits greater cognitive engagement than EC, but it is also more mentally demanding, with a higher workload and more memorization, and fails to elicit a strong positive emotional response, leading to a poorer shopping experience. These findings provide insights not only for digital-related consumer research but also for companies to improve their metaverse shopping experience. Before investing in the platform or creating a digital retail space, companies should thoroughly analyze it, focusing on how to enhance users’ cognition and emotions, ultimately promoting a better consumer experience. Despite its limitations, this pilot study sheds light on the emotional and cognitive aspects of metaverse shopping and suggests potential for further research with a consumer neuroscience approach in the metaverse field.
Can Leading by Example Alone Improve Cooperation?
Authors: Zhang Ziying , Elvis Nguepi Tsafack , Wang Jiawei , Hou Gonglin
Published: July 2024

Cooperation is essential for the survival of human society. Understanding the nature of cooperation and its underlying mechanisms is crucial for studying human behavior. This paper investigates the impact of leadership on public cooperation by employing repeated sequential public goods games, as well as by examining whether leading by example (through rewards and punishments) can promote cooperation and organizational success. The leaders were assigned randomly and were given the authority to reward or punish. As a result, (1) the leaders showed a strong tendency toward reciprocity by punishing free riders and rewarding cooperators at their own expense, which enhanced the intrinsic motivation for others to follow their example; and (2) both rewards and punishments were effective in promoting cooperation, but punishment was more effective in sustaining a high level of collaboration. Additionally, leaders preferred using rewards and were more reluctant to use punishments. These findings are crucial for creating organizational structures that foster cooperation.
Finite Element Analysis and Optimization of the Rotational Stiffness of Semi-Rigid Base Connection under Simultaneous Moment and Tension
Authors: Nawar Mahmoud T. , El-Zohairy Ayman , Alaaser Ahmed G. , Hamdy Osman
Published: July 2024

The base connection is flexible, not fully pinned/fixed, implying a nonlinear moment–rotation relationship. This deviates from a linear response, where rotation is not directly proportional to the applied moment. Numerical investigations using the commercial software ABAQUS were conducted to analyze the steel base plate connections. The finite element (FE) models were verified against previous experimental results. Moreover, numerical findings of a comprehensive parametric investigation were conducted. The studied connections were examined with different configurations, including variations in the diameter, spacing, and number of the anchor bolts; the thickness of the base plate; and the applied axial force. The current study aims to use numerical results combined with the whale optimization algorithm (WOA) and classical genetic algorithm (GA) to derive a formulation for the moment–rotation (M-θr) relationship. The distinctive aspect of this formulation is that it aims to simulate the nonlinear rotational behavior exhibited by flexible base connections under combined moment and tension loads, while also considering various parameters such as bolt number/diameter and plate thickness. The findings indicate that the WOA is capable of obtaining an optimal equation for accurately simulating the M-Ɵr relationship. This underscores the ability of the WOA to effectively address the complexity of the problem and provide a reliable equation for predicting the rotational behavior of such connections. Consequently, the WOA method can be utilized to calculate the rotational stiffness at H/150, offering valuable support for engineering design processes.
A Compressive Load Bearing Analysis of 3D-Printed Circular Elements
Authors: Giwa Ilerioluwa , Kazemian Ali , Gopu Vijaya , Rupnow Tyson
Published: July 2024

Large-scale construction 3D printing is a promising platform technology that can be leveraged to fabricate structural elements such as columns, piers, pipes, and culverts. In this study, the axial compression and split tensile performance of 3D-printed steel-fiber-reinforced circular elements fabricated with different configurations (hollow, hybrid, mold-cast, and fully 3D-printed) is evaluated. This study further investigates the performance of multi-material circular hybrid elements (3D-printed shells with different backfilled core materials) in an attempt to assess their suitability as a new construction paradigm. The experimental results revealed that the fully 3D-printed steel-fiber-reinforced circular elements exhibited a higher load capacity (up to 36%) and a distinct crack pattern compared to the other configurations. The void ratio of circular elements has varying effects on its axial load capacity depending on the printing material and significantly influences its splitting tensile load capacity. Furthermore, the compatibility between the 3D-printed shell and the cast-in-place core is identified as an influential factor in the structural performance of the hybrid elements. The results suggest a promising construction approach where low-cement material can be utilized as infill material for a cost-effective 3D-printed permanent formwork, offering a viable solution for specific infrastructure development applications.
miRNA Expression Profiling in G1 and G2 Pancreatic Neuroendocrine Tumors
Authors: Nyirő Gábor , Szeredás Bálint Kende , Decmann Ábel , Herold Zoltan , Vékony Bálint , Borka Katalin , Dezső Katalin , Zalatnai Attila , Kovalszky Ilona , Igaz Peter
Published: July 2024

Pancreatic neuroendocrine neoplasms pose a growing clinical challenge due to their rising incidence and variable prognosis. The current study aims to investigate microRNAs (miRNA; miR) as potential biomarkers for distinguishing between grade 1 (G1) and grade 2 (G2) pancreatic neuroendocrine tumors (PanNET). A total of 33 formalin-fixed, paraffin-embedded samples were analyzed, comprising 17 G1 and 16 G2 tumors. Initially, literature-based miRNAs were validated via real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), confirming significant downregulation of miR-130b-3p and miR-106b in G2 samples. Through next-generation sequencing, we have identified and selected the top six miRNAs showing the highest difference between G1 and G2 tumors, which were further validated. RT-qPCR validation confirmed the downregulation of miR-30d-5p in G2 tumors. miRNA combinations were created to distinguish between the two PanNET grades. The highest diagnostic performance in distinguishing between G1 and G2 PanNETs by a machine learning algorithm was achieved when using the combination miR-106b + miR-130b-3p + miR-127-3p + miR-129-5p + miR-30d-5p. The ROC analysis resulted in a sensitivity of 83.33% and a specificity of 87.5%. The findings underscore the potential use of miRNAs as biomarkers for stratifying PanNET grades, though further research is warranted to enhance diagnostic accuracy and clinical utility.
Immunotherapy in Neuroendocrine Neoplasms: A Diamond to Cut
Authors: García-Torralba Esmeralda , Garcia-Lorenzo Esther , Doger Bernard , Spada Francesca , Lamarca Angela
Published: July 2024

A raise in the incidence of NENs is expected. Therefore, the identification of new therapeutic strategies, such as immunotherapy, remains crucial. To date, immune checkpoint inhibitors as monotherapy have shown modest activity in unselected NENs. Although immunotherapy combos (plus another immune agents or chemotherapy, among others) are potentially more active than single agents, this has not been uniformly confirmed, even in high-grade NENs. Other immunotherapeutic strategies under development include bispecific antibodies, targeting specific tumor antigens like DLL3, and cell therapy. Currently, no predictive immune biomarkers are available to guide clinical decisions. A comprehensive tumor molecular profiling approach needs to be developed for the selection of patients with NEN who could potentially benefit from immunotherapy. Ideally, clinical trials should incorporate this tumor molecular profiling to identify predictive biomarkers and improve efficacy. Achieving this goal requires an international collaborative effort.
Multiparametric Whole-Body MRI: A Game Changer in Metastatic Prostate Cancer
Authors: Cattabriga Arrigo , Renzetti Benedetta , Galuppi Francesco , Bartalena Laura , Gaudiano Caterina , Brocchi Stefano , Rossi Alice , Schiavina Riccardo , Bianchi Lorenzo , Brunocilla Eugenio , Spinozzi Luca , Catanzaro Calogero , Castellucci Paolo , Farolfi Andrea , Fanti Stefano , Tunariu Nina , Mosconi Cristina
Published: July 2024

Prostate cancer ranks among the most prevalent tumours globally. While early detection reduces the likelihood of metastasis, managing advanced cases poses challenges in diagnosis and treatment. Current international guidelines support the concurrent use of 99Tc-Bone Scintigraphy and Contrast-Enhanced Chest and Abdomen CT for the staging of metastatic disease and response assessment. However, emerging evidence underscores the superiority of next-generation imaging techniques including PSMA-PET/CT and whole-body MRI (WB-MRI). This review explores the relevant scientific literature on the role of WB-MRI in metastatic prostate cancer. This multiparametric imaging technique, combining the high anatomical resolution of standard MRI sequences with functional sequences such as diffusion-weighted imaging (DWI) and bone marrow relative fat fraction (rFF%) has proved effective in comprehensive patient assessment, evaluating local disease, most of the nodal involvement, bone metastases and their complications, and detecting the increasing visceral metastases in prostate cancer. It does have the advantage of avoiding the injection of contrast medium/radionuclide administration, spares the patient the exposure to ionizing radiation, and lacks the confounder of FLARE described with nuclear medicine techniques. Up-to-date literature regarding the diagnostic capabilities of WB-MRI, though still limited compared to PSMA-PET/CT, strongly supports its widespread incorporation into standard clinical practice, alongside the latest nuclear medicine techniques.
Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer
Authors: Perez-Navarro Enrique , Conteduca Vincenza , Funes Juan M. , Dominguez Jose I. , Martin-Serrano Miguel , Cremaschi Paolo , Fernandez-Perez Maria Piedad , Gordoa Teresa Alonso , Font Albert , Vázquez-Estévez Sergio , González-del-Alba Aránzazu , Wetterskog Daniel , Mellado Begona , Fernandez-Calvo Ovidio , Méndez-Vidal María José , Climent Miguel Angel , Duran Ignacio , Gallardo Enrique , Rodriguez Sanchez Angel , Santander Carmen , Sáez Maria Isabel , Puente Javier , Tudela Julian , Marinas Cecilia , López-Andreo María Jose , Castellano Daniel , Attard Gerhardt , Grande Enrique , Rosino Antonio , Botia Juan A. , Palma-Mendez Jose , De Giorgi Ugo , Gonzalez-Billalabeitia Enrique
Published: July 2024

The prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) varies, being influenced by blood-related factors such as transcriptional profiling and immune cell ratios. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. This study analyzed pre-treatment blood samples from 152 chemotherapy-naive mCRPC patients participating in a phase 2 clinical trial (NCT02288936) and a validation cohort. We used CIBERSORT-X to quantify 22 immune cell types and assessed their prognostic significance using Kaplan–Meier and Cox regression analyses. Reduced CD8 T-cell proportions and elevated monocyte levels were substantially connected with a worse survival. High monocyte counts correlated with a median survival of 32.2 months versus 40.3 months for lower counts (HR: 1.96, 95% CI 1.11–3.45). Low CD8 T-cell levels were associated with a median survival of 31.8 months compared to 40.3 months for higher levels (HR: 1.97, 95% CI 1.11–3.5). These findings were consistent in both the trial and validation cohorts. Multivariate analysis further confirmed the independent prognostic value of CD8 T-cell counts. This study highlights the prognostic implications of specific blood immune cells, suggesting they could serve as biomarkers in mCRPC patient management and should be further explored in clinical trials.
Treatment Strategies for Locoregional Recurrence in Esophageal Squamous-Cell Carcinoma: An Updated Review
Authors: Mitamura Atsushi , Tsujinaka Shingo , Nakano Toru , Sawada Kentaro , Shibata Chikashi
Published: July 2024

Emerging evidence has shown remarkable advances in the multimodal treatment of esophageal squamous-cell carcinoma. Despite these advances, the oncological outcomes for advanced esophageal cancer remain controversial due to the frequent observation of local recurrence in the regional or other lymph nodes and distant metastasis after curative treatment. For cases of locoregional recurrence in the cervical lymph nodes alone, salvage surgery with lymph node dissection generally provides a good prognosis. However, if recurrence occurs in multiple regions, the oncological efficacy of surgery may be limited. Radiotherapy/chemoradiotherapy can be employed for unresectable or recurrent cases, as well as for selected cases in neo- or adjuvant settings. Dose escalation and toxicity are potential issues with conventional three-dimensional conformal radiotherapy; however, more precise therapeutic efficacy can be obtained using technical modifications with improved targeting and conformality, or with the use of proton beam therapy. The introduction of immune checkpoint inhibitors, including pembrolizumab or nivolumab, in addition to chemotherapy, has been shown to improve the overall survival in unresectable, advanced/recurrent cases. For patients with lymph node recurrence in multiple regions, chemotherapy (5-fluorouracil [5-FU] plus cisplatin) and combination therapy with nivolumab and ipilimumab have shown comparable oncological efficacy. Further prospective studies are needed to improve the treatment outcomes in patients with esophageal cancer with locoregional recurrence.
Impact of Radiotherapy on Endotracheal Intubation Quality Metrics in Patients with Esophageal Cancer: A Challenge for Advanced Airway Management?
Authors: Uzun Davut D. , Tryjanowski Timo , Arians Nathalie , Mohr Stefan , Schmitt Felix C. F. , Michalski Christoph W. , Weigand Markus A. , Debus Juergen , Lang Kristin
Published: July 2024

(1) Background: Currently, no data are available in the literature investigating the influence of radiotherapy (RT) on endotracheal intubation success in patients with esophageal cancer. This study aims to evaluate the impact of RT on endotracheal intubation quality metrics in patients with esophageal cancer. (2) Methods: Patients with esophageal cancer who underwent RT followed by surgery between 2012 and 2023 at the University Hospital Heidelberg, Germany, were retrospectively analyzed. (3) Results: Fifty-five patients, predominantly males 65.5% with a mean age of 64 years, were enrolled. Overall, 81.8% of the patients had an ASA class of III, followed by 27.2% ASA II. The mean prescribed cumulative total dose to the primary tumor and lymph node metastasis was 48.2 Gy with a mean single dose of 1.8 Gy. The mean laryngeal total dose was 40.0 Gy. Direct laryngoscopy was performed in 80.0% of cases, followed by 12.1% videolaryngoscopy, and 7.2% required fiberoptic intubation. Overall, 96.4% of patients were successfully intubated on the first attempt. (4) Conclusions: It has been demonstrated that post-RT effects can increase the risk of airway management difficulties and complications. The results of our study did not indicate any evidence of impaired advanced airway management in patients with esophageal cancer who had undergone RT.
Locally Advanced Cervical Cancer: Neoadjuvant Treatment versus Standard Radio-Chemotherapy—An Updated Meta-Analysis
Authors: Ronsini Carlo , Solazzo Maria Cristina , Braca Eleonora , Andreoli Giada , Vastarella Maria Giovanna , Cianci Stefano , Capozzi Vito Andrea , Torella Marco , Cobellis Luigi , De Franciscis Pasquale
Published: July 2024

Background: The treatment of choice for patients with locally advanced cervical cancer (LACC) is definitive concurrent radio chemotherapy which consists of external beam radiotherapy (EBRT) and concurrent platinum-based chemotherapy (CCRT), with the possible addition of brachytherapy (BT). However, the benefits of adjuvant surgery after neoadjuvant treatments remain a debated issue and a still open question in the literature. This meta-analysis aims to provide an updated view on the controversial topic, focusing on comparing surgery after any adjuvant treatment and standard treatment. Methods: Following the recommendations in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, the PubMed and Embase databases were systematically searched in April 2023 for early publications. No limitations on the country were applied. Only English articles were considered. The comparative studies containing data about disease-free survival (DFS) and/or overall survival (OS) were included in the meta-analysis. Results: The CCRT + surgery group showed a significantly better DFS than CCRT (RR 0.69 [95% CI 0.58–0.81] p < 0.01) and a better OS (RR 0.70 [95% CI 0.55–0.89] p < 0.01). Nine studies comparing neoadjuvant chemotherapy (NACT) plus surgery and CCRT were also enrolled. The NACT + surgery group showed a significantly better DFS than CCRT (RR 0.66 [95% CI 0.45–0.97] p < 0.01) and a better OS (RR 0.56 [95% CI 0.38–0.83] p < 0.01). In the sub-analysis of three randomized control trials, the surgery group documented a non-significantly better DFS and OS than CCRT (OR 1.10 [95% CI 0.67–1.80] p = 0.72; I2 = 69% p = 0.72; OR 1.09 [95% CI 0.63–1.91] p = 0.75; I2 = 13% p = 0.32). Conclusion: The results provide updated findings about the efficacy of neoadjuvant treatments, indicating significantly improved DFS and OS in patients undergoing hysterectomy after CCRT or NACT compared with patients undergoing standard treatments.
Unveiling a Health Disparity: Comparative Analysis of Head and Neck Cancer Trends between First Nations People and Non-Indigenous Australians (1998–2015)
Authors: Khan Lamia Fahad , Tadakamadla Santosh Kumar , Tadakamadla Jyothi
Published: July 2024

Background: We aim to assess and compare the HNC trends between the First Nations and non-Indigenous population. Methods: HNC incidence (1998–2013) and mortality (1998–2015) data in First Nations people and non-Indigenous Australians were utilised from the Australian Cancer Database. The age-standardised incidence and mortality trends along with annual percentage changes were analysed using Joinpoint models. Age-standardised incidence and mortality rates according to remoteness, states, and five-year survival rates among First Nations people and non-Indigenous Australians were presented as graphs. Results: First Nations people had over twice the age-standardised incidence (2013; 29.8/100,000 vs. 14.7/100,000) and over 3.5 times the age-standardised mortality rates (2015; 14.2/100,000 vs. 4.1/100,000) than their non-Indigenous counterparts. Both populations saw a decline in mortality, but the decline was only statistically significant in non-Indigenous Australians (17.1% decline, 1998: 4.8/100,000, 2015: 4.1/100,000; p < 0.05). Across all remoteness levels and states, First Nations people consistently had higher age-standardised incidence and mortality rates. Furthermore, the five-year survival rate was lower by 25% in First Nations people. Conclusion: First Nations people continue to shoulder a disproportionate HNC burden compared to non-Indigenous Australians.
Human-Induced Pluripotent Stem Cell (iPSC)-Derived GABAergic Neuron Differentiation in Bipolar Disorder
Authors: Schill Daniel J. , Attili Durga , DeLong Cynthia J. , McInnis Melvin G. , Johnson Craig N. , Murphy Geoffrey G. , O’Shea K. Sue
Published: July 2024

Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. Initially, GABAergic signaling is excitatory; with maturation, these cells undergo a functional switch that converts GABAA channels from depolarizing (excitatory) to hyperpolarizing (inhibitory), which is controlled by the intracellular concentration of two chloride transporters. The earliest, NKCC1, promotes chloride entry into the cell and depolarization, while the second (KCC2) stimulates movement of chloride from the neuron, hyperpolarizing it. Perturbations in the timing or expression of NKCC1/KCC2 may affect essential morphogenetic events including cell proliferation, migration, synaptogenesis and plasticity, and thereby the structure and function of the cortex. We derived induced pluripotent stem cells (iPSC) from BP patients and undiagnosed control (C) individuals, then modified a differentiation protocol to form GABAergic interneurons, harvesting cells at sequential stages of differentiation. qRT-PCR and RNA sequencing indicated that after six weeks of differentiation, controls transiently expressed high levels of NKCC1. Using multi-electrode array (MEA) analysis, we observed that BP neurons exhibit increased firing, network bursting and decreased synchrony compared to C. Understanding GABA signaling in differentiation may identify novel approaches and new targets for treatment of neuropsychiatric disorders such as BP.
Excess Dally-like Induces Malformation of Drosophila Legs
Authors: Zhang Xubo , Wang Yi , Zhao Wenting , Yang Shumin , Moussian Bernard , Zhao Zhangwu , Zhang Jianzhen , Dong Wei
Published: July 2024

Glypicans are closely associated with organ development and tumorigenesis in animals. Dally-like (Dlp), a membrane-bound glypican, plays pivotal roles in various biological processes in Drosophila. In this study, we observed that an excess of Dlp led to the malformation of legs, particularly affecting the distal part. Accordingly, the leg disc was shrunken and frequently exhibited aberrant morphology. In addition, elevated Dlp levels induced ectopic cell death with no apparent cell proliferation changes. Furthermore, Dlp overexpression in the posterior compartment significantly altered Wingless (Wg) distribution. We observed a marked expansion of Wg distribution within the posterior compartment, accompanied by a corresponding decrease in the anterior compartment. It appears that excess Dlp guides Wg to diffuse to cells with higher Dlp levels. In addition, the distal-less (dll) gene, which is crucial for leg patterning, was up-regulated significantly. Notably, dachshund (dac) and homothorax (hth) expression, also essential for leg patterning and development, only appeared to be negligibly affected. Based on these findings, we speculate that excess Dlp may contribute to malformations of the distal leg region of Drosophila, possibly through its influence on Wg distribution, dll expression and induced cell death. Our research advances the understanding of Dlp function in Drosophila leg development.
Recent Developments in Small-Molecule Fluorescent Probes for Cellular Senescence
Authors: Park Junyoung , Lee Youngjun , Park Jongmin
Published: July 2024

Cellular senescence is a recently emerged research topic in modern biology. Often described as a double-edged sword, it encompasses numerous essential biological processes, including beneficial effects such as wound healing and embryonic development, as well as detrimental contributions to chronic inflammation and tumor development. Consequently, there is an increasing need to unravel the intricate networks of senescence and develop reliable detection methods to distinguish it from related phenomena. To address these challenges, a variety of detection methods have been developed. In particular, small-molecule fluorescent probes offer distinct advantages such as suitability for real-time live cell monitoring and in vivo imaging, superior tunable properties, and versatile applications. In this review, we explored recent advancements in the development of small-molecule fluorescent probes toward monitoring cellular senescence by targeting various senescence-related biological phenomena. These phenomena include the upregulation of senescence-associated enzymes, perturbation of the subcellular environment, and increased endogenous ROS levels. Moreover, multi-senescence biomarker-targeting approaches are also discussed to improve their sensitivities and specificities for the detection of cellular senescence. With recent advances in senescence probe development, current challenges in this field are also discussed to facilitate further progress.
Can Guided Discovery Instruction Be Detrimental to Children with Different Levels of Aquatic Competence in Infancy?
Authors: Moreno-Murcia Juan Antonio , de Paula-Borges Luciane , Trinidad Alfonso
Published: July 2024

Repetitive practice can become an exploratory activity where instruction and discovery are linked, allowing instruction and guidance through tasks that help to construct and acquire the knowledge and skills that make up the content. (1) Background: The aim of the study was to show how a teaching method based on guided discovery would affect the teaching of children’s aquatic competence in schoolchildren with different levels of competence. (2) Methods: An observational study was conducted with 385 schoolchildren (195 boys and 189 girls) aged 3–5 years belonging to a charter kindergarten, using an Instrument for the Measurement of Aquatic Competence in Children (SMACC) consisting of 17 items grouped into three dimensions: socio-affective, cognitive, and motor. (3) Results: After measuring aquatic competence, all age groups and all variables (motor, cognitive, and socio-affective) showed differences between pre- and post-scores and a high magnitude of effect size. When the teaching intervention was analyzed according to the level of aquatic competence of the age group, improvements were found in all variables in both the low and high-competence groups. (4) Conclusions: This study describes how guided discovery instruction has equal effects at different levels of proficiency. Furthermore, when this type of instruction was used, aquatic competence was explained not only by the motor and socio-affective dimensions but also by the cognitive variable.
Exploring the Association between Parental Employment Status, Education Level, and Sensory Reactivity in Spanish Children Aged 3–7 Years: Findings from the InProS Study
Authors: Muñoz-Sánchez Rocío , Hurtado-Pomares Miriam , Juárez-Leal Iris , Piñero Jessica , Navarrete-Muñoz Eva-María , Valera-Gran Desirée
Published: July 2024

This study explored the association between parental employment status and education level and the prevalence of sensory reactivity (SR) in population-based sample of school-aged children. SR was assessed in 495 children using the parent-reported Short Sensory Profile (SSP) questionnaire. Children with SR were identified based on probable or definitive differences in total SSP and subscales. Association between parental employment and education level were explored using multiple Poisson regression models with robust variance, adjusted for potential confounders. The main findings showed that a mother’s unemployment status was associated with higher prevalence of SR for the taste/smell sensitivity subscale (PR = 1.66, 95%CI: 1.08–2.56), and the low energy/weak (PR = 2.18, 95%CI: 1.31–3.49) subscale. A lower education level of a father was also associated with a higher prevalence of sensory problems on the tactile sensitivity subscale (PRprimary education = 2.68, 95%CI: 1.27–5.61; PRsecondary education = 1.96, 95%CI: 1.004–3.66) and the low energy/weak subscale (PRsecondary education = 1.95, 95%CI: 1.02–3.73). This study underscores the impact of parental employment and education on SR in school-aged children, offering insights for interventions and support systems aimed at improving their sensory functioning and overall well-being.
Spatial and Temporal Evolution of Seasonal Sea Ice Extent of Hudson Strait, Canada, 1971–2018
Authors: Kowal Slawomir , Gough William A. , Butler Kenneth
Published: July 2024

The temporal and spatial variation in seasonal sea ice in Hudson Strait is examined using time series and spatial clustering analyses. For the period from 1971 to 2018, a time series of sea ice breakup and freeze-up dates and ice-free season length at twenty-four grid points were generated from sea ice charts derived from satellite and other data. These data were analyzed temporally and spatially. The temporal analyses indicated an unambiguous response to a warming climate with statistically significant earlier breakup dates, later freeze-up dates, and longer ice-free seasons, that were statistically linked to coincident regional surface air temperatures. The rate of change in freeze-up dates and ice-free season length was particularly strong in the early 2000s and less so in the 2010s. There was evidence that breakup date behaviour was not only coincident with regional temperatures but likely with temperature and ice conditions of the previous year. Later freeze-up dates were directly linked to earlier breakup dates using detrended time series. Spatial clustering analysis on the Hudson Strait gridded sea ice data revealed distinctive signatures for Ungava Bay, Frobisher Bay, and for grid points close to the shore and a clear linkage to the underlying circulation of Hudson Strait.
Fatigue Damage in Asphalt Pavement Based on Axle Load Spectrum and Seasonal Temperature
Authors: Zhang Wenwu , Han Wenyang , Jiang Wenqing , Cui Ting , Wang Shanshan , Yang Fei , Wei Jincheng
Published: July 2024

In asphalt pavement structure design, traffic axle loads and pavement layer temperatures are crucial factors affecting fatigue damage calculations. To investigate the differences in fatigue damage calculations caused by different characterizations of traffic axle loads and temperature, fatigue damage calculations were conducted under equivalent standard axle loads (ESALs), axle load spectra (ALS), constant temperatures, and seasonal temperature variations using the field data from an expressway in Shandong Province, China under seven calculation plans. The results indicated: (1) the annual traffic composition is dominated by vehicle Type 9, with a proportion of about 43% in all the vehicle types, and its load level is also high, with a proportion about of 80% in the heavy load interval at all axle types; (2) The ESALs method underestimates the actual fatigue damage incurred in asphalt pavement by 6.04 times, with an accumulated damage of 2.34 × 10−9 (ESALs), 1.69 × 10−8 (ALS), respectively; (3) The fatigue damage results from a single month with consistent temperature showed similar trends, with an accumulated damage of 1.50 × 10−5, 9.07 × 10−5, respectively; (4) The cumulative fatigue damage calculated using the ALS method across the four seasons, respectively, is 6.51, 5.88, 6.42, and 4.60 times that of the fatigue damage calculated using the ESALs method. Although the ratio of fatigue damage between the two characterizations of traffic axle loads remains consistent, which is 6.04, the fatigue damage calculation that accounts for temperature variations can reveal seasonal trends in fatigue damage development. Based on the axle load spectra and considering temperature variations, fatigue damage calculation will be more closely related to the actual service state of asphalt pavement. These research findings provide insights for estimating asphalt pavement fatigue damage to some extent.
Node Classification of Network Threats Leveraging Graph-Based Characterizations Using Memgraph
Authors: Charkhabi Sadaf , Samimi Peyman , Bagui Sikha S. , Mink Dustin , Bagui Subhash C.
Published: July 2024

This research leverages Memgraph, an open-source graph database, to analyze graph-based network data and apply Graph Neural Networks (GNNs) for a detailed classification of cyberattack tactics categorized by the MITRE ATT&CK framework. As part of graph characterization, the page rank, degree centrality, betweenness centrality, and Katz centrality are presented. Node classification is utilized to categorize network entities based on their role in the traffic. Graph-theoretic features such as in-degree, out-degree, PageRank, and Katz centrality were used in node classification to ensure that the model captures the structure of the graph. The study utilizes the UWF-ZeekDataFall22 dataset, a newly created dataset which consists of labeled network logs from the University of West Florida’s Cyber Range. The uniqueness of this study is that it uses the power of combining graph-based characterization or analysis with machine learning to enhance the understanding and visualization of cyber threats, thereby improving the network security measures.
Implementation of Integrated Development Environment for Machine Vision-Based IEC 61131-3
Authors: Lim Sun , Ham Un-Hyeong , Han Seong-Min
Published: July 2024

IEC 61131-3 is an international standard for developing standardized software for automation and control systems. Machine vision systems are a prominent technology in the field of computer vision and are widely used in various industries, such as manufacturing, robotics, healthcare, and automotive, and are often combined with AI technologies. In industrial automation systems, software developed for defect detection or product classification typically involves separate systems for automation and machine vision programs, leading to increased system complexity and unnecessary resource wastage. To address these limitations, this study proposes an IEC 61131-3-based integrated development environment for programmable machine vision. We selected 11 APIs commonly used in machine vision systems, evaluated their functions in an IEC 61131-3 compliant development environment, and measured the performance of representative machine vision applications. This approach demonstrates the feasibility of developing PLC and machine vision programs within a single-controller system. We investigated the impact of controller performance on function execution.
The Effect of an Oral Probiotic Mixture on Clinical Evolution and the Gut and Skin Microbiome in Patients with Alopecia Areata: A Randomized Clinical Trial
Authors: Navarro-Belmonte María R. , Aguado-García Ángel , Sánchez-Pellicer Pedro , Núñez-Delegido Eva , Navarro-Moratalla Laura , Martínez-Villaescusa María , García-Navarro Alejandro , Navarro-López Vicente
Published: July 2024

(1) Background: Given the autoimmune nature of Alopecia Areata (AA) and the immunomodulatory properties of probiotics, this trial was conducted to evaluate the efficacy of a probiotic mixture, consisting of Lactobacillus rhamnosus and Bifidobacterium longum strains, as an adjuvant treatment in a group of AA patients. (2) Method: This study was a 24-week, randomized, double-blind, placebo-controlled clinical trial. Twenty-six patients with AA were included in this study, and their clinical progression, along with changes in gut and skin microbiota, were analyzed. (3) Results: A higher proportion of AA patients treated with the probiotic formula showed improvement compared to the placebo group, based on both the reduction in the number of AA plaques (56% vs. 30%) and the affected scalp surface area (45% vs. 20%). For “activity”, “inactivity”, and “regrowth”, an improvement in 55%, 67%, and 55% of patients was, respectively, observed in the probiotic group, compared to 50%, 40%, and 30% in the placebo group. No changes were observed in the gut microbiota during the intervention period. Regarding skin microbiota, changes were detected in the probiotic group, with reductions in characteristic genera during the study. (4) Conclusions: To our knowledge, this is the first clinical trial assessing the efficacy of a probiotic product in patients with AA. This probiotic mixture in a routine clinical practice setting appears to improve the course of patients. In addition, the skin microbiota of scalp lesions was modified using the probiotic treatment.
Optimization of Solid Lipid Nanoparticle Formulation for Cosmetic Application Using Design of Experiments, PART II: Physical Characterization and In Vitro Skin Permeation for Sesamol Skin Delivery
Authors: Cassayre Margot , Oline Auriane , Orneto Caroline , Wafo Emmanuel , Abou Lydia , Altié Alexandre , Claeys-Bruno Magalie , Sauzet Christophe , Piccerelle Philippe
Published: July 2024

Our research focuses on evaluating the preliminary stability of solid lipid nanoparticles (SLNs) in order to identify an optimal formulation for studying the skin penetration of SLNs loaded with sesamol, with a view to developing potential cosmetic applications. For this study, SLNs were prepared with varying lipid and surfactant compositions and produced through homogenization and ultrasonication. The particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were analyzed for the different formulations. We identified OP2Se as the optimal formulation for skin penetration assessment due to its stable PS, PDI, ZP, and EE over time, with a Turbiscan Stability Index (TSI) below 1 after a month, indicating favorable stability conditions. The in vitro skin permeation study compared sesamol-loaded SLNs with a control sesamol hydrogel, revealing controlled release characteristics ideal for localized skin effects without significant bloodstream penetration, attributed to the SLNs’ 200 nm particle size. Further exploration could enhance skin retention and targeting, potentially extending penetration studies and reducing particle size to improve accumulation in hair follicles. Exploring SLN applications beyond sesamol, such as incorporating mineral filters for suncare, offers promising avenues, underscoring SLNs’ versatility in cosmetic formulations and skincare applications.
Regenerative Cosmetics: Skin Tissue Engineering for Anti-Aging, Repair, and Hair Restoration
Authors: Pleguezuelos-Beltrán Paula , Herráiz-Gil Sara , Martínez-Moreno Daniel , Medraño-Fernandez Iria , León Carlos , Guerrero-Aspizua Sara
Published: July 2024

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics powered by skin tissue engineering offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.
Entropy Analysis of FPGA Interconnect and Switch Matrices for Physical Unclonable Functions
Authors: Jao Jenilee , Wilcox Ian , Plusquellic Jim , Paskaleva Biliana , Bochev Pavel
Published: July 2024

Random variations in microelectronic circuit structures represent the source of entropy for physical unclonable functions (PUFs). In this paper, we investigate delay variations that occur through the routing network and switch matrices of a field-programmable gate array (FPGA). The delay variations are isolated from other components of the programmable logic, e.g., look-up tables (LUTs), flip-flops (FFs), etc., using a feature of Xilinx FPGAs called dynamic partial reconfiguration (DPR). A set of partial designs is created to fix the placement of a time-to-digital converter (TDC) and supporting infrastructure to enable the path delays through the target interconnect and switch matrices to be extracted by subtracting out common-mode delay components. Delay variations are analyzed in the different levels of routing resources available within FPGAs, i.e., local routing and across-chip routing. Data are collected from a set of Xilinx Zynq 7010 devices, and a statistical analysis of within-die variations in delay through a set of the randomly-generated and hand-crafted interconnects is presented.