bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Extended Target Tracking Algorithm Based on Spatio-Temporal Correlation
Authors: Zhang Wei , Lin Chen , Liu Tingting , Gan Lu
Published: March 2024

In the clutter environment, the measurement of a set of multiple extended targets, with an unknown number of targets, poses challenges in partitioning, and the computational cost is high. In particular, the multiple extended target tracking method, based on distance partition, has obvious potential estimation errors when the extended targets intersect. This paper proposes a partition algorithm, based on spatio-temporal correlation, which considers the correlation between adjacent moments of the extended target and uses this prior information to divide the measurement set into a survival target measurement set and a born target measurement set for the first time. Then, the survival target measurement set is clustered by the K-means++ algorithm, and the extended target tracking is transformed into point target tracking. The born target measurement undergoes preprocessing by the DBSCAN clustering algorithm, and then uses the directed graph with shared nearest neighbors (SNN) dividing the measurement set. The method proposed in this paper significantly reduces the number of partitions and the computational time. The effectiveness of the algorithm is demonstrated through experimental simulations.
Evaluation of the Antibacterial Activity of Isatin against Campylobacter jejuni and Campylobacter coli Strains
Authors: Barroso Claudia B. , Seki Liliane M. , Esteves Wagner T. C. , Nascimento Michele C. , Echevarria Aurea
Published: March 2024

Antibiotic resistance, particularly against fluoroquinolones and macrolides, has emerged globally among thermophilic Campylobacters (Campylobacter jejuni and Campylobacter coli), giving rise to concerns about the efficacy of antibiotic treatment of these bacteria. Thus, developing new antibacterials with excellent activity is important. Isatin (IST) and its derivatives have exhibited promising antibacterial activities in several pathogenic bacteria. However, its activity against Campylobacter is unknown. Therefore, this study was conducted to evaluate the antibacterial activity of isatin against 29-Campylobacter strains (C. jejuni-17 and C. coli-12) and investigate the effects at the cellular level. The minimal inhibitory concentrations (MICs) of isatin were between <1.0 and 16.0 µg/mL in Campylobacter strains. Most strains presented with MIC = 8.0 µg/mL (76%). The minimal bactericidal concentration (MBC) was determined to be 16.0 µg/mL for 72% of the Campylobacter strains tested. The 50% inhibitory concentration (IC50) value for isatin was 125.63 µg/mL on the MRC-5 normal cell line, suggesting that isatin can be considered a safe substance in terms of cytotoxicity. In this study, we demonstrated the potential of isatin based on its low toxicity and effectiveness in vitro against antibiotic-resistant Campylobacter strains, which indicates that this compound could be an attractive candidate for future use in multidrug-resistant Campylobacter treatment.
Annual and Seasonal Characteristics of Rainfall Erosivity in the Eastern Rhodopes (Bulgaria)
Authors: Nikolova Valentina , Nikolova Nina , Stefanova Miloslava , Matev Simeon
Published: March 2024

Rainfall, with its intensity, duration, and seasonal distribution, is among the main factors causing soil erosion, which is a widespread environmental problem in Bulgaria. Rainfall erosivity shows the potential of precipitation to generate erosion processes and is an essential indicator of the climate vulnerability of a region. This paper aims to evaluate rainfall erosivity in a part of the Eastern Rhodopes Mountains, an area that is characterised by high-intensity erosion processes and high erosion risk. Local peculiarities of rainfall erosivity were revealed by the calculation of some precipitation indices based on the monthly precipitation for the period 2000–2021, such as the precipitation concentration index (PCI), Angot precipitation index, Fournier index (FI), and modified Fournier index (MFI). The analysis of the extremely wet and extremely dry months at the annual and seasonal (October–March and April–September) levels was performed to evaluate the susceptibility to erosion. The results from the study show that rainfall erosivity in the studied area varies from low to moderate in the northern part of the study area and from high to very high in the south. According to the MFI, high and very high erosivities have been observed mainly since 2012. The erosivity increases from north to south, to the area with a complex relief, where the combination of orography and atmospheric circulation make favourable conditions for the occurrence of extreme precipitation. The analyses of the calculated indices show that the precipitations in most of the studied area generally have from a low to a moderate erosivity, but this does not exclude the occurrence of cases with high and very high erosivities, which are characteristic of recent years and are related to the increase in annual precipitations and extreme precipitation months. The results of this study can contribute to the development and implementation of measures and preventive activities for the reduction and possible elimination of the negative impacts of extreme precipitation.
Sodium Citrate Electrolyte Additive to Improve Zinc Anode Behavior in Aqueous Zinc-Ion Batteries
Authors: Liu Xin , Yue Liang , Dong Weixu , Qu Yifan , Sun Xianzhong , Chen Lifeng
Published: March 2024

Despite features of cost-effectiveness, high safety, and superior capacity, aqueous zinc-ion batteries (ZIBs) have issues of uncontrolled dendritic cell failure and poor Zn utilization, resulting in inferior cycling reversibility. Herein, the environmentally friendly and naturally abundant sodium citrate (SC) was adopted as a dual-functional additive for ZnSO4-based (ZSO) electrolytes. Owing to the abundant hydrogen-bond donors and hydrogen-bond acceptors of SC, the Zn2+-solvation shell is interrupted to facilitate Zn desolvation, resulting in inhibited corrosion reactions. Additionally, sodium ions (Na+) from the SC additive with a lower effective reduction potential than that of zinc ions (Zn2+) form an electrostatic shield inhibiting the formation of initial surface protuberances and subsequent Zn dendrite growth. This assists in the Zn three-dimensional (3D) diffusion and deposition, thereby effectively enhancing cycling stability. Specifically, a long cycling lifespan (more than 760 h) of the Zn//Zn symmetric cell is achieved with a 2 M ZSO-1.0 SC electrolyte at a current density of 1 mA cm−2. When coupled with the NaV3O8·1.5 H2O (NVO) cathode, the full battery containing SC additive exhibited a capacity retention rate (40.0%) and a cycling life of 400 cycles at a current density of 1 A g−1 compared with that of pure ZnSO4 electrolyte (23.8%). This work provides a protocol for selecting an environmentally friendly and naturally abundant dual-functional electrolyte additive to achieve solvation shell regulation and Zn anode protection for the practical large-scale application of ZIBs.
Seed Train Optimization in Microcarrier-Based Cell Culture Post In Situ Cell Detachment through Scale-Down Hybrid Modeling
Authors: Ebrahimian Atefeh , Schalk Mona , Dürkop Mark , Maurer Michael , Bliem Rudolf , Kühnel Harald
Published: March 2024

Microcarrier-based cell culture is a commonly used method to facilitate the growth of anchorage-dependent cells like MA 104 for antigen manufacturing. However, conventionally, static cell culture is employed for cell propagation before seeding the production bioreactor with microcarriers (MCs). This study demonstrates the effective replacement of the conventional method by serial subculturing on MCs with in situ cell detachment under optimal conditions in closed culture units. This study proves that MA 104 can be subcultured at least five times on Cytodex 1 MC without the need for separating cells and MC after cell harvest. Process parameters impacting cell growth were studied post in situ cell detachment in a scaled-down model. Optimization, using augmented Design of Experiments (DoE) combined with hybrid modeling, facilitated rapid screening of the design space for critical process parameters (CPPs). Optimized conditions included an inoculation density of >16 cells/bead, 3.5–4.5 g/L of Cytodex 1, and a controlled agitation speed, starting at Njs (minimum agitation speed) for the first day with a maximum increase of 25% thereafter. With these design spaces for CPPs, a cell density of 2.6 ± 0.5 × 106 cells/mL was achieved after five days. This refined bioprocess methodology offers a reliable and efficient approach for seed training in stirred tank reactors, which is particularly beneficial for viral vaccine production.
Pathological Mechanisms and Novel Testing Methods in Thrombotic Thrombocytopenic Purpura
Authors: Dolin Hallie H. , Maitta Robert W.
Published: March 2024

Thrombotic thrombocytopenic purpura (TTP) is an uncommon, but potentially disabling or even deadly, thrombotic microangiopathy with a well-studied mechanism of ADAMTS13 deficiency or dysfunction. While established treatments are largely effective, the standard ADAMTS13 testing required to definitively diagnose TTP may cause delays in diagnosis and treatment, highlighting the need for rapid and effective diagnostic methods. Additionally, the heterogeneous presentation and varied inciting events of TTP suggest more variation in its mechanism than previously thought, implying three potential pathways rather than the accepted two. The recent discovery of ADAMTS13 conformation as a potential contributor to TTP in addition to the proposal of using the absolute immature platelet count (A-IPC) as a biomarker, present novel areas for monitoring and treatment. A-IPC in particular may serve as a more rapid and accurate diagnostic test to distinguish TTP from non-TTP TMAs and to monitor treatment response and relapse. These considerations highlight the need to further study TTP in order to improve best practices and patient care.
A Point-of-Care Nucleic Acid Quantification Method by Counting Light Spots Formed by LAMP Amplicons on a Paper Membrane
Authors: Chen Yanju , Zhu Yuanyuan , Peng Cheng , Wang Xiaofu , Wu Jian , Chen Huan , Xu Junfeng
Published: March 2024

Nucleic acid quantification, allowing us to accurately know the copy number of target nucleic acids, is significant for diagnosis, food safety, agricultural production, and environmental protection. However, current digital quantification methods require expensive instruments or complicated microfluidic chips, making it difficult to popularize in the point-of-care detection. Paper is an inexpensive and readily available material. In this study, we propose a simple and cost-effective paper membrane-based digital loop-mediated isothermal amplification (LAMP) method for nucleic acid quantification. In the presence of DNA fluorescence dyes, the high background signals will cover up the amplicons-formed bright spots. To reduce the background fluorescence signals, a quencher-fluorophore duplex was introduced in LAMP primers to replace non-specific fluorescence dyes. After that, the amplicons-formed spots on the paper membrane can be observed; thus, the target DNA can be quantified by counting the spots. Take Vibrio parahaemolyticus DNA detection as an instance, a good linear relationship is obtained between the light spots and the copy numbers of DNA. The paper membrane-based digital LAMP detection can detect 100 copies target DNA per reaction within 30 min. Overall, the proposed nucleic acid quantification method has the advantages of a simple workflow, short sample-in and answer-out time, low cost, and high signal-to-noise, which is promising for application in resourced limited areas.
Emotion Classification Based on Transformer and CNN for EEG Spatial–Temporal Feature Learning
Authors: Yao Xiuzhen , Li Tianwen , Ding Peng , Wang Fan , Zhao Lei , Gong Anmin , Nan Wenya , Fu Yunfa
Published: March 2024

Objectives: The temporal and spatial information of electroencephalogram (EEG) signals is crucial for recognizing features in emotion classification models, but it excessively relies on manual feature extraction. The transformer model has the capability of performing automatic feature extraction; however, its potential has not been fully explored in the classification of emotion-related EEG signals. To address these challenges, the present study proposes a novel model based on transformer and convolutional neural networks (TCNN) for EEG spatial–temporal (EEG ST) feature learning to automatic emotion classification. Methods: The proposed EEG ST-TCNN model utilizes position encoding (PE) and multi-head attention to perceive channel positions and timing information in EEG signals. Two parallel transformer encoders in the model are used to extract spatial and temporal features from emotion-related EEG signals, and a CNN is used to aggregate the EEG’s spatial and temporal features, which are subsequently classified using Softmax. Results: The proposed EEG ST-TCNN model achieved an accuracy of 96.67% on the SEED dataset and accuracies of 95.73%, 96.95%, and 96.34% for the arousal–valence, arousal, and valence dimensions, respectively, for the DEAP dataset. Conclusions: The results demonstrate the effectiveness of the proposed ST-TCNN model, with superior performance in emotion classification compared to recent relevant studies. Significance: The proposed EEG ST-TCNN model has the potential to be used for EEG-based automatic emotion recognition.
A Method and Metrics to Assess the Energy Efficiency of Smart Working
Authors: Cattani Lucia , Magrini Anna , Chiari Anna
Published: March 2024

The paper discusses the energy efficiency of smart working (SW) as a solution to traditional work-approach issues, with a focus on evaluating benefits for both employers and employees. Remote working, while offering environmental advantages such as reduced commuting and office space use, poses challenges in assessing its true impact. The study presents results from a dynamic analysis on a real residential building, typical of an architectural style diffused in northern Italy, revealing a 15% average increase in energy consumption when all work tasks are performed from home. To address concerns about the environmental impact of SW, the research proposes a method and metrics for evaluation. Four novel indices (SWEET, SEE, SSEE, and 4E) are introduced, providing a structured approach to assess the energy efficiency of SW initiatives. The paper outlines a methodology for data gathering and metric application, aiming to acquire quantitative insights and mitigate disparities arising from a transfer of burdens to employees. This contribution not only signifies a ground-breaking methodology but also addresses an unresolved research question concerning the evaluation of the actual energy efficiency of smart working implementations for both employers and employees. The results underscore the importance of understanding the nuances of SW’s impact on household energy usage and its broader implications for sustainability goals.
An Analytical Solution for the Bending of Anisotropic Rectangular Thin Plates with Elastic Rotation Supports
Authors: Leng Bing , Xu Haidong , Yan Yan , Wang Kaihang , Yang Guangyao , Meng Yanyu
Published: March 2024

The mechanical analysis of thin-plate structures is a major challenge in the field of structural engineering, especially when they have nonclassical boundary conditions, such as those encountered in cement concrete road slabs connected by transfer bars. Conventional analytical solutions are usually limited to classical boundary conditions—clamped support, simple support, and free edges—and cannot adequately describe many engineering scenarios. In this study, an analytical solution to the bending problem of an anisotropic thin plate subjected to a pair of edges with free opposing elastic rotational constraints is found using a two-dimensional augmented Fourier series solution method. In the derivation process, the thin-plate problem can be transformed into a problem of solving a system of linear algebraic equations by applying Stoke’s transform method, which greatly reduces the mathematical difficulty of solving the problem. Complex boundary conditions can be optimally handled without the need for large computational resources. The paper addresses the exact analytical solutions for bending problems with multiple combinations of boundary conditions, such as contralateral free–contralateral simple support (SFSF), contralateral free–contralateral solid support–simple support (CFSF), and contralateral free–contralateral clamped support (CFCF). These solutions are realized by employing the Stoke transformation and adjusting the spring parameters in the analyzed solutions. The results of this method are also compared with the finite element method and analytical solutions from the literature, and good agreement is obtained, demonstrating the effectiveness of the method. The significance of the study findings lies in the simplification of complex nonclassical boundary condition problems using a simple and reliable analytical method applicable to a wide range of engineering thin-plate structures.
A–Z of Epigenetic Readers: Targeting Alternative Splicing and Histone Modification Variants in Cancer
Authors: Mohan Nivedhitha , Dashwood Roderick H. , Rajendran Praveen
Published: March 2024

Epigenetic ‘reader’ proteins, which have evolved to interact with specific chromatin modifications, play pivotal roles in gene regulation. There is growing interest in the alternative splicing mechanisms that affect the functionality of such epigenetic readers in cancer etiology. The current review considers how deregulation of epigenetic processes and alternative splicing events contribute to pathophysiology. An A–Z guide of epigenetic readers is provided, delineating the antagonistic ‘yin-yang’ roles of full-length versus spliced isoforms, where this is known from the literature. The examples discussed underscore the key contributions of epigenetic readers in transcriptional regulation, early development, and cancer. Clinical implications are considered, offering insights into precision oncology and targeted therapies focused on epigenetic readers that have undergone alternative splicing events during disease pathogenesis. This review underscores the fundamental importance of alternative splicing events in the context of epigenetic readers while emphasizing the critical need for improved understanding of functional diversity, regulatory mechanisms, and future therapeutic potential.
Socioeconomic Burden of Psychiatric Cancer Patients: A Narrative Review
Authors: Więckiewicz Gniewko , Weber Sophie , Florczyk Iga , Gorczyca Piotr
Published: March 2024

This comprehensive review article examines the complex overlap of affective disorders, psychoses, addictions, anxieties, post-traumatic stress disorder, and somatic symptom disorder in the context of cancer patients, and highlights the intricate interplay between psychiatric and oncological diagnoses. Based on extensive literature, it highlights the profound socioeconomic burdens that result from the coexistence of these disorders. The analysis includes the increased healthcare costs, impaired adherence to treatment, and reduced quality of life for individuals struggling with the co-occurrence of psychiatric and cancer-related problems. By synthesizing the available data through a narrative inquiry, the report aims to provide a nuanced understanding of the multiple socioeconomic challenges faced by this vulnerable patient population. The synthesis of information provides valuable insights for healthcare professionals, policymakers, and researchers alike. The aim is to promote the development of more effective and integrated care strategies tailored to the specific needs of people navigating the complicated environment of psychiatric and cancer diagnoses. Ultimately, this review should enable progress in the provision of holistic, patient-centered care for this complex intersection of health conditions.
Paracrine Regulation and Immune System Pathways in the Inflammatory Tumor Microenvironment of Lung Cancer: Insights into Oncogenesis and Immunotherapeutic Strategies
Authors: Batrash Firas , Shaik Adnan , Rauf Rayaan , Kutmah Mahmoud , Zhang Jun
Published: March 2024

The intricate interplay between inflammatory processes and the tumor microenvironment (TME) in lung cancer has garnered increasing attention due to its implications for both oncogenesis and therapeutic strategies. In this review, we explore recent advances in understanding the paracrine regulation and immune system pathways within the inflammatory TME of lung cancer. We delve into the molecular mechanisms underpinning oncogenesis, highlighting the role of immune cell populations, cancer-associated fibroblasts, and endothelial cells, as well as their interactions through immune system pathways regulated in a paracrine pattern. Additionally, we discuss emerging immunotherapeutic strategies with a specific focus on the potential of leveraging the inflammatory TME through these pathways to enhance treatment efficacy in lung cancer.
Machine Learning-Based Assessment of Survival and Risk Factors in Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma for Optimized Patient Management
Authors: Suárez Miguel , Gil-Rojas Sergio , Martínez-Blanco Pablo , Torres Ana M. , Ramón Antonio , Blasco-Segura Pilar , Torralba Miguel , Mateo Jorge
Published: March 2024

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an incidence that is exponentially increasing. Hepatocellular carcinoma (HCC) is the most frequent primary tumor. There is an increasing relationship between these entities due to the potential risk of developing NAFLD-related HCC and the prevalence of NAFLD. There is limited evidence regarding prognostic factors at the diagnosis of HCC. This study compares the prognosis of HCC in patients with NAFLD against other etiologies. It also evaluates the prognostic factors at the diagnosis of these patients. For this purpose, a multicenter retrospective study was conducted involving a total of 191 patients. Out of the total, 29 presented NAFLD-related HCC. The extreme gradient boosting (XGB) method was employed to develop the reference predictive model. Patients with NAFLD-related HCC showed a worse prognosis compared to other potential etiologies of HCC. Among the variables with the worst prognosis, alcohol consumption in NAFLD patients had the greatest weight within the developed predictive model. In comparison with other studied methods, XGB obtained the highest values for the analyzed metrics. In conclusion, patients with NAFLD-related HCC and alcohol consumption, obesity, cirrhosis, and clinically significant portal hypertension (CSPH) exhibited a worse prognosis than other patients. XGB developed a highly efficient predictive model for the assessment of these patients.
The Role of PSMA PET Imaging in the Classification of the Risk of Prostate Cancer Patients: A Systematic Review on the Insights to Guide an Active Surveillance Approach
Authors: Dondi Francesco , Antonelli Alessandro , Suardi Nazareno , Treglia Giorgio , Bertagna Francesco
Published: March 2024

Background: active surveillance (AS) is a suitable strategy for patients with prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging is an established tool used to assess PCa. The aim of this review was to evaluate the role of PSMA imaging to guide correct risk-based classification and the AS approach in PCa patients. Methods: The Scopus, Embase, Web of Science, Cochrane Library, and PubMed/MEDLINE databases were screened to find relevant published articles. Results: 1774 articles were revealed with the literature search. A total of 1764 articles were excluded after applying exclusion criteria (data not within the field of interest, preclinical papers, conference proceedings, reviews, or editorials). Ten studies were finally included in the review, revealing that PSMA PET could have the ability to guide risk-based classification of PCa and the choice of AS, and to guide the execution of biopsies for the research of high-grade PCa, therefore precluding AS. Conclusion: this systematic review underlined a possible role of PSMA PET imaging in patients with PCa by correctly re-classifying them on the basis of their risk and guiding AS.
Actin-Dependent Mechanism of Tumor Progression Induced by a Dysfunction of p53 Tumor Suppressor
Authors: Khromova Natalia , Vasileva Maria , Dugina Vera , Kudlay Dmitry , Chumakov Peter , Boichuk Sergei , Kopnin Pavel
Published: March 2024

Cancer cell aggressiveness, marked by actin cytoskeleton reconfiguration critical for metastasis, may result from an imbalanced ratio favoring γ-actin. Dysfunctional p53 emerges as a key regulator of invasiveness and migration in various cancer cells, both in vitro and in vivo. P53 inactivation (via mutants R175H, R248W, R273H, or TP53 repression) significantly enhanced the migration, invasion, and proliferation of human lung adenocarcinoma A549 cells in vitro and in vivo, facilitating intrapulmonary xenograft metastasis in athymic mice. Conversely, wild-type TP53 (TP53 WT) overexpression in p53-deficient non-small- cell lung cancer (NSCLC) H1299 cells substantially reduced proliferation and migration in vitro, effectively curbing orthotopic tumorigenicity and impeding in vivo metastasis. These alterations in cell motility were closely associated with actin cytoskeleton restructuring, favoring γ-actin, and coincided with ERK1/2-mediated signaling activation, unveiling an innovative regulatory mechanism in malignancy progression. Cancer cell aggressiveness, driven by actin cytoskeleton reorganization and a shift towards γ-actin predominance, may be regulated by p53 dysfunction, thereby providing novel insight into tumor progression mechanisms.
Investigating the Catalytic Deactivation of a Pd Catalyst during the Continuous Hydrogenation of CO2 into Formate Using a Trickle-Bed Reactor
Authors: Park Kwangho , Lee Kyung Rok , Ahn Sunghee , Park Hongjin , Moon Seokyeong , Yoon Sungho , Jung Kwang-Deog
Published: March 2024

The practical application of formic acid production through the hydrogenation of CO2 has garnered significant attention in efforts to tackle the challenges associated with (1) achieving net-zero production of formic acid as a chemical feedstock and (2) improving hydrogen storage and transport. This study focuses on demonstrating the continuous operation of a trickle bed reactor for converting CO2 into formate using palladium on activated carbon (Pd/AC). Optimal temperature conditions were investigated through a dynamic operation for 24 h, achieving the maximum productivity of 2140 mmolFA·gPdsurf.−1·h−1 at 150 °C and 8 MPa, with an H2/CO2 ratio of 1:1; however, catalyst deactivation was observed in the process. Stability tests performed under continuous operation at 120 °C and 8 MPa with an H2/CO2 ratio of 1:1 indicated a gradual decline in productivity, culminating in a 20% reduction after 20 h. A comprehensive analysis comparing fresh and spent catalysts revealed that the diminished catalytic activity at elevated temperatures was attributed to the partial sintering and leaching of Pd nanoparticles during the hydrogenation process. These findings offer insights for the future development of novel Pd-based catalyst systems suitable for continuous hydrogenation processes.
Modification of Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles by Calcitonin Gene Related Peptide (CGRP) Antagonist: Potential Implications for Inflammation and Pain Reversal
Authors: Liebmann Kevin , Castillo Mario A. , Jergova Stanislava , Best Thomas M. , Sagen Jacqueline , Kouroupis Dimitrios
Published: March 2024

During the progression of knee osteoarthritis (OA), the synovium and infrapatellar fat pad (IFP) can serve as source for Substance P (SP) and calcitonin gene-related peptide (CGRP), two important pain-transmitting, immune, and inflammation modulating neuropeptides. Our previous studies showed that infrapatellar fat pad-derived mesenchymal stem/stromal cells (MSC) acquire a potent immunomodulatory phenotype and actively degrade Substance P via CD10 both in vitro and in vivo. On this basis, our hypothesis is that CD10-bound IFP-MSC sEVs can be engineered to target CGRP while retaining their anti-inflammatory phenotype. Herein, human IFP-MSC cultures were transduced with an adeno-associated virus (AAV) vector carrying a GFP-labelled gene for a CGRP antagonist peptide (aCGRP). The GFP positive aCGRP IFP-MSC were isolated and their sEVs’ miRNA and protein cargos were assessed using multiplex methods. Our results showed that purified aCGRP IFP-MSC cultures yielded sEVs with cargo of 147 distinct MSC-related miRNAs. Reactome analysis of miRNAs detected in these sEVs revealed strong involvement in the regulation of target genes involved in pathways that control pain, inflammation and cartilage homeostasis. Protein array of the sEVs cargo demonstrated high presence of key immunomodulatory and reparative proteins. Stimulated macrophages exposed to aCGRP IFP-MSC sEVs demonstrated a switch towards an alternate M2 status. Also, stimulated cortical neurons exposed to aCGRP IFP-MSC sEVs modulate their molecular pain signaling profile. Collectively, our data suggest that yielded sEVs can putatively target CGRP in vivo, while containing potent anti-inflammatory and analgesic cargo, suggesting the promise for novel sEVs-based therapeutic approaches to diseases such as OA.
Cannabidiol Disrupts Mitochondrial Respiration and Metabolism and Dysregulates Trophoblast Cell Differentiation
Authors: Podinic Tina , Limoges Louise , Monaco Cristina , MacAndrew Andie , Minhas Mahek , Nederveen Joshua , Raha Sandeep
Published: March 2024

Trophoblast differentiation is a crucial process in the formation of the placenta where cytotrophoblasts (CTs) differentiate and fuse to form the syncytiotrophoblast (ST). The bioactive components of cannabis, such as Δ9-THC, are known to disrupt trophoblast differentiation and fusion, as well as mitochondrial dynamics and respiration. However, less is known about the impact of cannabidiol (CBD) on trophoblast differentiation. Due to the central role of mitochondria in stem cell differentiation, we evaluated the impact of CBD on trophoblast mitochondrial function and differentiation. Using BeWo b30 cells, we observed decreased levels of mRNA for markers of syncytialization (GCM1, ERVW1, hCG) following 20 µM CBD treatment during differentiation. In CTs, CBD elevated transcript levels for the mitochondrial and cellular stress markers HSP60 and HSP70, respectively. Furthermore, CBD treatment also increased the lipid peroxidation and oxidative damage marker 4-hydroxynonenal. Mitochondrial membrane potential, basal respiration and ATP production were diminished with the 20 µM CBD treatment in both sub-lineages. mRNA levels for endocannabinoid system (ECS) components (FAAH, NAPEPLD, TRPV1, CB1, CB2, PPARγ) were altered differentially by CBD in CTs and STs. Overall, we demonstrate that CBD impairs trophoblast differentiation and fusion, as well as mitochondrial bioenergetics and redox homeostasis.
Exploring Regorafenib Responsiveness and Uncovering Molecular Mechanisms in Recurrent Glioblastoma Tumors through Longitudinal In Vitro Sampling
Authors: Morelli Mariangela , Lessi Francesca , Franceschi Sara , Ferri Gianmarco , Giacomarra Manuel , Menicagli Michele , Gambacciani Carlo , Pieri Francesco , Pasqualetti Francesco , Montemurro Nicola , Aretini Paolo , Santonocito Orazio Santo , Di Stefano Anna Luisa , Mazzanti Chiara Maria
Published: March 2024

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like temozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by Regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glioblastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. Three-dimensional glioblastoma organoids (GB-EXPs) obtained from 18 patients’ resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NRs). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n = 9) and 77% (n = 20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp being REGO-NRs. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO compared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal exploration of the molecular changes induced by treatment, unveiling promising biomarkers indicative of drug response.
Reliability of Two Recently Developed Procedures Assessing Biological Maturity by Ultrasound Imaging—A Pilot Study
Authors: Hutmacher Nicole , Busch Jasmin D. , Rüeger Eva , Romann Michael , Eichelberger Patric
Published: March 2024

During puberty, the biological maturity of children of the same chronological age differs. To generate equal opportunities for talent selection in youth sports, the athlete’s biological maturity should be considered. This is often assessed with a left hand and wrist radiography. Alternatively, ultrasound (US) could be advantageous, especially by avoiding ionizing radiation. This pilot study aimed to assess intrarater and interrater reliability of an experienced and a non-experienced examiner in an US-based examination of the knee in 20 healthy females (10–17 years). Epiphyseal closure at five anatomical landmarks was staged (stages 1–3) and its interrater and intrarater reliabilities were analyzed using Cohen’s kappa (k). Interrater reliability of the calculation of the ossification ratio (OssR) was analyzed using the Bland-Altman method and intraclass correlation coefficients (ICCs). Interrater reliability for the stages was almost perfect for four landmarks. Interrater reliability ranged from k = 0.69 to k = 0.90. Intrarater reliability for the stages was almost perfect for four landmarks. Intrarater reliability ranged from k = 0.70 to k = 1.0. For the OssR, ICC was 0.930 and a minimal detectable change of 0.030 was determined. To conclude, experienced and non-experienced examiners can reliably assign individuals to different ossification stages and calculate an OssR using US-based imaging of the knee.
The Effects of Family and School Interpersonal Relationships on Depression in Chinese Elementary School Children: The Mediating Role of Academic Stress and the Moderating Role of Self-Esteem
Authors: Liao Jinqian , Chen Shuai , Liu Yanling , Guo Cheng
Published: March 2024

This study explores the relative contributions and psychological mechanisms of the effects of family (father–child and mother–child) and school (teacher–student and student–student) interpersonal relationships on depression in elementary school children. The participants (n = 20,629) were elementary school children (48.19% male) aged nine to 13 years from Southwest China during the COVID-19 pandemic. They voluntarily completed questionnaires regarding parent–child, teacher–student, and student–student relationships, as well as academic stress and self-esteem. The results indicate that the effect of family interpersonal relationships on children’s depression was stronger than that of school interpersonal relationships. The predictive effects of father–child and mother–child relationships on children’s depression did not significantly differ; however, the effect of student–student relationships was significantly stronger than that of teacher–student relationships. Academic stress partially mediated the effect of interpersonal relationships on depression in elementary school children. The effects of family interpersonal relationships and academic stress on depression were moderated by self-esteem. These findings underscore the disparities and mechanisms pertaining to the impacts of diverse interpersonal associations on children’s depression, thus signifying significant implications for the advancement of research and intervention strategies aimed at addressing this issue.
Intermittent High-Dose Vitamin D3 Administration in Neonates with Multiple Comorbidities and Vitamin D Insufficiency
Authors: Cirstoveanu Catalin , Ionita Iulia , Georgescu Carmina , Heriseanu Carmen , Vasile Corina Maria , Bizubac Mihaela
Published: March 2024

Background: Neonates have an increased risk of vitamin D insufficiency due to the inadequate supplementation of mothers and infants after birth. Insufficiency of vitamin D is frequently detected in critically ill patients and is associated with disease severity and mortality. There is yet to be a consensus on the appropriate regimen of vitamin D3 supplementation in high-risk infants. Aim: The main objectives of this study were to determine the prevalence of vitamin D insufficiency in neonates with severe comorbidities and to evaluate whether high-dose vitamin D3 oral administration leads to normal plasmatic concentrations without side effects. Methods: The current study was a randomized, prospective trial of 150 patients admitted to the Neonatal Intensive Care Unit (NICU) at Maria Sklodowska Curie Emergency Children’s Hospital in Bucharest. Patients were divided into three subgroups based on the chronological order of their admission date. Each subgroup received a different pharmaceutical product of vitamin D3. We administered a dosage of 10,000 IU/kg of vitamin D3 orally in three steps, as follows: at admission, one week after admission, and one month from the first administration, targeting a serum 25-hydroxyvitamin D concentration of at least 40 ng/mL. Results: Most neonates (68%) achieved an optimum vitamin D level after one month, even though only 15% of patients had an optimum concentration at admission. After the first high dose of vitamin D3, there was a 27% increase in the mean vitamin D plasmatic level compared to admission levels. However, after one month, the concentrations decreased in all subgroups due to the gap of three weeks between the last two administrations. Conclusions: An intermittent, weekly high-dose vitamin D3 oral administration leads to a steadier increase and normalization of vitamin D concentration in most critically ill neonates. However, high-dose vitamin D3 administered orally after three weeks decreases vitamin D levels in this high-risk population.
Turbomachinery GPU Accelerated CFD: An Insight into Performance
Authors: Molinero-Hernández Daniel , Galván-González Sergio R. , Herrera-Sandoval Nicolás D. , Guzman-Avalos Pablo , Pacheco-Ibarra J. Jesús , Domínguez-Mota Francisco J.
Published: March 2024

Driven by the emergence of Graphics Processing Units (GPUs), the solution of increasingly large and intricate numerical problems has become feasible. Yet, the integration of GPUs into Computational Fluid Dynamics (CFD) codes still presents a significant challenge. This study undertakes an evaluation of the computational performance of GPUs for CFD applications. Two Compute Unified Device Architecture (CUDA)-based implementations within the Open Field Operation and Manipulation (OpenFOAM) environment were employed for the numerical solution of a 3D Kaplan turbine draft tube workbench. A series of tests were conducted to assess the fixed-size grid problem speedup in accordance with Amdahl’s Law. Additionally, tests were performed to identify the optimal configuration utilizing various linear solvers, preconditioners, and smoothers, along with an analysis of memory usage.
Changes in Need, Changes in Infrastructure: A Comparative Assessment of Rural Nonprofits Responding to COVID-19
Authors: Sloan Margaret F. , Switzer Tina , Trull Laura Hunt , Switzer Claire , Eaton Melody , Atwood Kelly , Akerson Emily
Published: March 2024

Due to the variance in community infrastructure and resources, COVID-19 impacted rural communities differently than their urban counterparts. This study examines two waves of data from a survey of rural residents in the Shenandoah Valley of Virginia regarding how community organizations responded to the pandemic, what strategies were most successful, and where needs shifted. The findings demonstrate that organizations with deeply embedded community leaders achieve higher levels of collaborative change in a timely manner. Additionally, mental health services have become a more pronounced need as a result of the pandemic. The interdependence of community needs, recognized by community members, calls for collaborative strategies for the future.
The Potential of Cold Plasma-Based Seed Treatments in Legume–Rhizobia Symbiotic Nitrogen Fixation: A Review
Authors: Abeysingha Dhanuja N. , Dhaliwal Harleen K. , Du Lihui , De Silva Chathuranga , Szczyglowski Krzysztof , Roopesh M. S. , Thilakarathna Malinda S.
Published: March 2024

The use of cold plasma (CP) seed treatment is an emerging agricultural technology that exhibits the potential to enhance nodulation and symbiotic nitrogen fixation (SNF) in legumes. CP is composed of a diverse mixture of excited atoms, molecules, ions, and radicals that have the potential to affect the physical properties of the seed and influence gene expressions that could have a lasting impact on the nodulation, SNF, growth, and yield of legumes. The direct participation of the CP in the nodulation process and its correlation with the escalation of nodules and SNF is still not fully understood. This review discussed four areas in the nodulation and SNF process that can directly or indirectly affect CP seed treatments: root–rhizobia signal exchange pathways, root/shoot growth and development, phytohormone production, and the nitrogen fixation process. We also discuss the potential challenges and future research requirements associated with plasma technology to enhance SNF in legumes.
Mechanical Response of Cu/Sn58Bi-xNi/Cu Micro Solder Joint with High Temperatures
Authors: Kong Xiangxia , Zhai Junjun , Ma Ruipeng , Sun Fenglian , Li Xuemei
Published: March 2024

Sn58Bi solder is considered a promising lead-free solder that meets the performance requirements, with the advantages of good wettability and low cost. However, the low melting point characteristic of Sn58Bi poses a serious threat to the high-temperature reliability of electronic products. In this study, Sn58Bi solder alloy based on nickel (Ni) functionalization was successfully synthesized, and the effect of a small amount of Ni on creep properties and hardness of Cu/Sn58Bi/Cu micro solder joints at different temperatures (25 °C, 50 °C, 75 °C, 100 °C) was investigated using a nanoindentation method. The results indicate that the nanoindentation depth of micro solder joints exhibits a non-monotonic trend with increasing Ni content at different temperatures, and the slope of the indentation stage curve decreases at 100 °C, showing that the micro solder joints undergo high levels of softening. According to the observation of indentation morphology, Ni doping can reduce the indentation area and accumulation around the indentation, especially at 75 °C and 100 °C. In addition, due to the severe creep phenomenon at 100 °C, the indentation hardness rapidly decreases. The indentation hardness values of micro solder joints of Cu/Sn58Bi/Cu, Cu/Sn58Bi-0.1Ni/Cu, and Cu/Sn58Bi-0.2Ni/Cu at 100 °C are 14.67 ± 2.00 MPa, 21.05 ± 2.00 MPa, and 20.13 ± 2.10 MPa, respectively. Nevertheless, under the same temperature test conditions, the addition of Ni elements can improve the high-temperature creep resistance and hardness of Cu/Sn58Bi/Cu micro solder joints.
Floating Zone Growth of Pure and Pb-Doped Bi-2201 Crystals
Authors: Roslova Maria , Büchner Bernd , Maljuk Andrey
Published: March 2024

In this review, we summarize recent progress in crystal growth and understanding of the influence of crystal structure on superconductivity in pure and Pb-doped Bi2Sr2CuOy (Bi-2201) materials belonging to the overdoped region of high-temperature cuprate superconductors. The crystal growth of Bi-2201 superconductors faces challenges due to intricate materials chemistry and the lack of knowledge of corresponding phase diagrams. Historically, a crucible-free floating zone method emerged as the most promising growth approach for these materials, resulting in high-quality single crystals. This review outlines the described methods in the literature and the authors’ synthesis endeavors encompassing Pb-doped Bi-2201 crystals, provides a detailed structural characterization of as-grown and post-growth annealed samples, and highlights optimal growth conditions that yield large-size, single-phase, and compositionally homogeneous Bi-2201 single crystals.
Diagnostic and Prognostic Value of Thrombocytopenia in Severe Burn Injuries
Authors: Bordeanu-Diaconescu Eliza-Maria , Grosu-Bularda Andreea , Frunza Adrian , Grama Sabina , Andrei Mihaela-Cristina , Neagu Tiberiu-Paul , Lascar Ioan , Hariga Cristian-Sorin
Published: March 2024

Background and objectives: Burn injuries are the most severe type of trauma, with complex biological consequences associated with high rates of morbidity and mortality. Prompt recognition and management of burn-related complications are imperative for improving the vital and functional prognosis of the patient. Changes in biological parameters can be essential determinants in the prognosis of the burned patient. Thrombocytopenia in critically ill patients is linked to an elevated risk of mortality. We sought to investigate the significance of thrombocytopenia in severely burned patients while considering the limited available data in the literature. Materials and methods: A two-year retrospective study was conducted on 90 patients with severe burns admitted to our Burn Centre. Demographic data, burn lesion characteristics, and daily total blood counts, including platelet assessment, complications, and mortality, were recorded and analyzed. Results: Patients with extensive burns in our study had a poor prognosis based on their Abbreviated Burn Severity Index score (ABSI), age, percentage of total body surface area (TBSA) burned, presence of third-degree burns, and inhalation injuries. Regardless of the moment, patients with thrombocytopenia in our study died significantly more frequently. Compared with the survivors, the platelet count was significantly lower at any given time in the non-survivors group. Significant statistical associations between thrombocytopenia and ABSI score, burn surface area, presence of third-degree burns, and inhalation injuries were identified at different timeframes post-burn injury. Sepsis was encountered in one-third of the patients. Thrombocytopenia was more frequent in patients with sepsis who did not survive compared to survivors and did not normalize until the time of death. Conclusions: Thrombocytopenia represents an early indicator of severe complications and outcome predictor in severely burned patients. It is correlated with recognized negative prognostic factors and also with sepsis occurrence. Future research efforts should focus on refining early detection parameters and interventions to improve the prognosis of burn patients.