bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Design and Synthesis of Ni-Mo-Co Ternary Hydroxides Nanoflakes for Advanced Energy Storage Device Applications
Authors: Wang Zhao , Li Peifeng , Tang Zhuolun , Ng Ka Yuen Simon
Published: August 2024

Three-dimensional interconnected mesoporous nanoflakes of amorphous Ni-Mo-Co trimetallic hydroxides were successfully deposited on a Ni foam (NF) using a facile, environmentally friendly, and scalable electrochemical deposition method. The elemental composition of the nanoflakes, including Ni2+, Mo6+, and Co2+, was characterized by X-ray photoelectron spectroscopy (XPS), while the morphology and particle size of the synthesized nanomaterials were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The Ni-Mo-Co trimetallic hydroxides on NF were employed as binder-free electrodes for supercapacitors. The Ni-Mo-Co trimetallic hydroxides with a Ni/Mo/Co ratio of 1/1/0.4 exhibited outstanding long-term cyclability over 5000 cycles, with a high reversible specific capacitance of 2700 F g−1 and a high capacitance retention of 96.63% at 10 A g−1. Furthermore, they demonstrated excellent rate performance, maintaining a capacitance of 2429 F g−1 at a current of 50 A g−1, which corresponds to approximately 80% capacitance retention compared to the capacitance at 2 A g−1. The superior performance of these Ni-Mo-Co trimetallic hydroxides can be attributed to their mesoporous hierarchical architecture, which provides large open spaces between the interconnected nanoflakes, numerous electroactive surface sites, facile electron transmission paths, and the synergistic effects of the trimetallic components. These findings demonstrate that Ni-Mo-Co trimetallic hydroxides are promising electrode materials, offering both high capacitance and long-term cyclability for supercapacitors.
SecuriDN: A Modeling Tool Supporting the Early Detection of Cyberattacks to Smart Energy Systems
Authors: Cerotti Davide , Codetta Raiteri Daniele , Dondossola Giovanna , Egidi Lavinia , Franceschinis Giuliana , Portinale Luigi , Savarro Davide , Terruggia Roberta
Published: August 2024

SecuriDN v. 0.1 is a tool for the representation of the assets composing the IT and the OT subsystems of Distributed Energy Resources (DERs) control networks and the possible cyberattacks that can threaten them. It is part of a platform that allows the evaluation of the security risks of DER control systems. SecuriDN is a multi-formalism tool, meaning that it manages several types of models: architecture graph, attack graphs and Dynamic Bayesian Networks (DBNs). In particular, each asset in the architecture is characterized by an attack graph showing the combinations of attack techniques that may affect the asset. By merging the attack graphs according to the asset associations in the architecture, a DBN is generated. Then, the evidence-based and time-driven probabilistic analysis of the DBN permits the quantification of the system security level. Indeed, the DBN probabilistic graphical model can be analyzed through inference algorithms, suitable for forward and backward assessment of the system’s belief state. In this paper, the features and the main goals of SecuriDN are described and illustrated through a simplified but realistic case study.
Air Quality Improvement Following the COVID-19 Pandemic Lockdown in Naples, Italy: A Comparative Analysis (2018–2022)
Authors: Sannino Alessia , Damiano Riccardo , Amoruso Salvatore , Castellano Pasquale , D’Emilio Mariagrazia , Boselli Antonella
Published: August 2024

The pandemic lockdown of the year 2020 has been generally accompanied by an improvement in the air quality. Here, we report data on the effects of lockdown limitations on the air quality in the metropolitan area of Naples (Italy) by following the evolution of main atmospheric pollutants over a five-year period and comparing their concentrations in the pandemic year 2020 with the previous (2018 and 2019) and following (2021 and 2022) two years. In particular, NO2 and PM10 concentrations registered by representative air quality sampling station network and the columnar features of the aerosol characterized by a sun-photometer are considered. To avoid the possible influence of Saharan dust transport, which generally affects the observational area, the analysis has been limited to the days free from such events. Our findings evidence a tendency towards pre-pandemic conditions, notwithstanding some differences related to partial and temporary restrictions imposed even in the year 2021. For both near-surface NO2 and PM, the observations confirm a significant reduction induced by the lockdown in 2020, besides the seasonal changes, and a gradual tendency towards more typical values in the following years. Also, the columnar aerosol data clearly highlight a gradual recovery of typical conditions in 2021 and 2022, confirming a peculiar effect of the pandemic lockdown of the year 2020 on the atmospheric aerosol characteristics that evidences a striking predominance of the fine component.
Environmental Radiological Impact and Risk Assessment of Natural Radioactivity at the Heap Leach Facility of Tarkwa Goldmine, Ghana: Radiotoxicity and Public Exposure
Authors: Kansaana Charles , Tettey-Larbi Lordford , Faanu Augustine , Sam Frederick , Akrobortu Emmanuel , Akomaning-Adofo Emmanuel , Ampene Adriana Asare , Osei Rita Kwabea , Annan Ruth Araba Tawiah , Tóth-Bodrogi Edit , Kovács Tibor , Shahrokhi Amin
Published: August 2024

In this study, a comprehensive investigation was conducted to determine the radioactivity levels of naturally occurring radioactive materials (NORMs) in heap pads/soil and water samples within and around the operational area of Tarkwa Gold Mine in Ghana. Gamma-ray spectrometry was used to determine the activity concentrations of 238U, 232Th, and 40K in heap pads/soil, and 226Ra, 228Th, and 40K in water samples. The average activity concentrations of 226Ra and 228Th in all water samples were below the World Health Organisation (WHO) recommended guidelines for drinking water. Similarly, the average activity concentrations of measured radionuclides in heap pads/soil samples taken from depths of 0–20 cm and 20–50 cm were found to be below the worldwide average reported values. The annual effective dose to the public was estimated to be around 0.16 mSv, which is below the recommended limit. The values of the hazard indices are also below the recommended limits, implying that if heap pads/soils are used for building purposes and construction, they will not pose any significant radiation hazard. The results of this study indicate that radiation levels are within the natural background radiation levels reported in the literature and are consistent with findings from similar studies conducted in Ghana.
Seasonal Variations in Hydraulic Regulation of Whole-Tree Transpiration in Mongolian Pine Plantations: Insights from Semiarid Deserts in Northern China
Authors: Deng Jifeng , Wan Longyan , Bao Yanfeng , Yu Minghan , Jia Qingbin
Published: August 2024

Seasonal precipitation variance significantly alters soil water content, potentially inducing water stress and affecting plant transpiration in semiarid deserts. This study explored the effects of environmental variables and hydraulic conductance on whole-tree transpiration (ET) in Mongolian pines (Pinus sylvestris var. mongolica) across different forest stages in the semiarid deserts of Northern China. We measured ET using sap flow in mature (MMP), half-mature (HMP), and young (YMP) Mongolian pine plantations. Measurements included soil-leaf water potential difference (ΔΨ), atmospheric conditions, and soil moisture contents on sunny days, both in dry and wet periods. Seasonally variable rainfall distinctly affected soil moisture; during the dry periods, both stomatal and hydraulic conductance influenced ET, whereas stomatal conductance primarily regulated it during the wet periods. Discrepancies between predicted and measured ET were noticed: compared to the predicted ET, the measured ET was lower during dry periods while higher during wet periods. Hydraulic conductance (KT) increased with tree height (H) and ΔΨ. The KT values in the dry period were lower than those in the wet period, indicating that the hydraulic resistance in the dry period was higher. The hydraulic compensation occurred and was observed between 11:00 and 13:00, aligned with increased hydraulic resistance during dry periods. Decreasing hydraulic conductance intensified leaf water stress in dry periods, especially when photosynthetically active radiation (PAR) and vapor pressure deficit (VPD) were heightened, potentially increasing stomatal sensitivity to drought, promoting water conservation and plant survival. A linear relationship between predawn and midday leaf water potentials was noticed, indicating extreme anisohydric behavior across forest stages during dry and wet periods. Although stomatal and hydraulic conductance influenced ET during the dry period, MMP and YMP were more susceptible to drought conditions. Understanding these dynamics could help evaluate semiarid desert ecological functions for water conservation amidst uneven seasonal precipitation in Northern China.
Thermal–Acoustic Interaction Effects on Physiological and Psychological Measures in Urban Forests: A Laboratory Study
Authors: Chen Ye , Li Taoyu , Chen Shaoyou , Chen Hangqing , Lan Yuxiang
Published: August 2024

The environment in which people live is a complex system influenced by multiple factors interacting with each other, and therefore, it is crucial to deeply explore the influences of various factors on environmental perception. Among the numerous factors affecting the experience of urban forests visits, the thermal–acoustic environment stands out prominently. This study focuses on urban forests located in subtropical regions, with specific research conducted in the Xihu Park in Fuzhou, China. The study explores the thermal–acoustic interaction in urban forest environments. A total of 150 participants evaluated the perception of sound, thermal sensation, and overall perception through laboratory experiments, with 36 of them having their objective physiological indicators monitored. Different levels of sound and temperature were selected for the experiments, with three levels for each type of sound. Our results show that increasing temperature enhanced the perceived loudness of sound, especially when the environment was quiet. Sound type and loudness had a significant impact on thermal sensation, but no interaction was observed with temperature. Moreover, we found that certain sounds could improve overall comfort, and the effect was most evident at moderate loudness. Temperature had a significant influence on both comfort and annoyance, with increasing temperature leading to higher annoyance. These findings provide important insights into how the interplay between sound and heat affects human perception and emotional state, providing scientific guidance for the design of more human-centered environments.
YOLOTree-Individual Tree Spatial Positioning and Crown Volume Calculation Using UAV-RGB Imagery and LiDAR Data
Authors: Luo Taige , Rao Shuyu , Ma Wenjun , Song Qingyang , Cao Zhaodong , Zhang Huacheng , Xie Junru , Wen Xudong , Gao Wei , Chen Qiao , Yun Jiayan , Wu Dongyang
Published: August 2024

Individual tree canopy extraction plays an important role in downstream studies such as plant phenotyping, panoptic segmentation and growth monitoring. Canopy volume calculation is an essential part of these studies. However, existing volume calculation methods based on LiDAR or based on UAV-RGB imagery cannot balance accuracy and real-time performance. Thus, we propose a two-step individual tree volumetric modeling method: first, we use RGB remote sensing images to obtain the crown volume information, and then we use spatially aligned point cloud data to obtain the height information to automate the calculation of the crown volume. After introducing the point cloud information, our method outperforms the RGB image-only based method in 62.5% of the volumetric accuracy. The AbsoluteError of tree crown volume is decreased by 8.304. Compared with the traditional 2.5D volume calculation method using cloud point data only, the proposed method is decreased by 93.306. Our method also achieves fast extraction of vegetation over a large area. Moreover, the proposed YOLOTree model is more comprehensive than the existing YOLO series in tree detection, with 0.81% improvement in precision, and ranks second in the whole series for mAP50-95 metrics. We sample and open-source the TreeLD dataset to contribute to research migration.
Masketeer: An Ensemble-Based Pseudonymization Tool with Entity Recognition for German Unstructured Medical Free Text
Authors: Baumgartner Martin , Kreiner Karl , Wiesmüller Fabian , Hayn Dieter , Puelacher Christian , Schreier Günter
Published: August 2024

Background: The recent rise of large language models has triggered renewed interest in medical free text data, which holds critical information about patients and diseases. However, medical free text is also highly sensitive. Therefore, de-identification is typically required but is complicated since medical free text is mostly unstructured. With the Masketeer algorithm, we present an effective tool to de-identify German medical text. Methods: We used an ensemble of different masking classes to remove references to identifiable data from over 35,000 clinical notes in accordance with the HIPAA Safe Harbor Guidelines. To retain additional context for readers, we implemented an entity recognition scheme and corpus-wide pseudonymization. Results: The algorithm performed with a sensitivity of 0.943 and specificity of 0.933. Further performance analyses showed linear runtime complexity (O(n)) with both increasing text length and corpus size. Conclusions: In the future, large language models will likely be able to de-identify medical free text more effectively and thoroughly than handcrafted rules. However, such gold-standard de-identification tools based on large language models are yet to emerge. In the current absence of such, we hope to provide best practices for a robust rule-based algorithm designed with expert domain knowledge.
Explainable Artificial Intelligence Approach for Improving Head-Mounted Fault Display Systems
Authors: Bouzidi Abdelaziz , Rajaoarisoa Lala , Claeys Luka
Published: August 2024

To fully harness the potential of wind turbine systems and meet high power demands while maintaining top-notch power quality, wind farm managers run their systems 24 h a day/7 days a week. However, due to the system’s large size and the complex interactions of its many components operating at high power, frequent critical failures occur. As a result, it has become increasingly important to implement predictive maintenance to ensure the continued performance of these systems. This paper introduces an innovative approach to developing a head-mounted fault display system that integrates predictive capabilities, including deep learning long short-term memory neural networks model integration, with anomaly explanations for efficient predictive maintenance tasks. Then, a 3D virtual model, created from sampled and recorded data coupled with the deep neural diagnoser model, is designed. To generate a transparent and understandable explanation of the anomaly, we propose a novel methodology to identify a possible subset of characteristic variables for accurately describing the behavior of a group of components. Depending on the presence and risk level of an anomaly, the parameter concerned is displayed in a piece of specific information. The system then provides human operators with quick, accurate insights into anomalies and their potential causes, enabling them to take appropriate action. By applying this methodology to a wind farm dataset provided by Energias De Portugal, we aim to support maintenance managers in making informed decisions about inspection, replacement, and repair tasks.
Performance Prediction of GFRP-Reinforced Concrete Deep Beams Containing a Web Opening in the Shear Span
Authors: Sheikh-Sobeh Amena , Kachouh Nancy , El-Maaddawy Tamer
Published: August 2024

This study aimed to investigate the nonlinear structural behavior of concrete deep beams internally reinforced with glass fiber-reinforced polymer (GFRP) reinforcing bars and containing a web opening of various sizes and locations within the shear span. Three-dimensional (3D) numerical simulation models were developed for large-scale GFRP-reinforced concrete deep beams (300 mm × 1200 mm × 5000 mm) with a shear span-to-depth ratio (a/h) of 1.04. Predictions of the numerical models were validated against published experimental data. A parametric study was conducted to examine the effect of varying the opening size and location on the shear response. Results of the numerical analysis indicated that the strength of the deep beam models with an opening in the middle of the shear span decreased with an increase in either the opening width or height. The rate of the strength reduction caused by increasing the opening height was, however, more significant than that produced by increasing the opening width. Placing a web opening in the compression zone close to the load plate was very detrimental to the beam strength. Conversely, a negligible strength reduction was recorded when the web opening was placed in the tension side above the flexural reinforcement and away from the natural load path. Data of the parametric study were utilized to introduce simplified analytical formulas capable of predicting the shear capacity of GFRP-reinforced concrete deep beams with a web opening in the shear span.
Identification of Amino Acids and Polyphenolic Metabolites in Human Plasma by UHPLC-ESI-QTOF-MS/MS, after the Chronic Intake of a Functional Meal in an Elderly Population
Authors: Vazquez-Flores Alma A. , Muñoz-Bernal Óscar A. , Alvarez-Parrilla Emilio , Rodriguez-Tadeo Alejandra , Martínez-Ruiz Nina del Rocío , de la Rosa Laura A.
Published: August 2024

Novel foods especially formulated and targeted for the elderly population should provide sufficient nutrients and bioactive ingredients to counteract the natural age-related deterioration of various organs and tissues. Dietary protein and phenolic compounds achieve this goal; however, older adults have alterations in their gastrointestinal system that may impact their bioavailability and few studies have been aimed at this population. Since phenolic compounds are the subject of multiple biotransformations by host and microbiome enzymes during the digestion process, identification of their bioavailable forms in human plasma or tissues represents a considerable analytical challenge. In this study, UHPLC-ESI-QTOF/MS-MS, chemometrics, and multivariate statistical methods were used to identify the amino acids and phenolic compounds that were increased in the plasma of elderly adults after a 30-day intervention in which they had consumed an especially formulated muffin and beverage containing Brosimum alicastrum Sw. seed flour. A large interindividual variation was observed regarding the amino acids and phenolic metabolites identified in the plasma samples, before and after the intervention. Three phenolic metabolites were significantly increased in the population after the intervention: protocatechuic acid, 5-(methoxy-4′-hydroxyphenyl) valerolactone, and phloretic acid. These metabolites, as well as others that were not significantly increased (although they did increase in several individuals), are probably the product of the microbiota metabolism of the major phenolic compounds present in the B. alicastrum Sw. seed flour and other food ingredients. A significant decrease in 4-ethyl-phenol, a biomarker of stress, was observed in the samples. Results showed that the incorporation of foods rich in phenolic compounds into the regular diet of older adults contributes to the increase in bioactive compounds in plasma, that could substantially benefit their mental, cardiovascular, and digestive health.
A Fractional-Order Creep-Damage Model for Carbonaceous Shale Describing Coupled Damage Caused by Rainfall and Blasting
Authors: Li Jing , Hu Bin , Sheng Jianlong , Huang Lei
Published: August 2024

In order to better understand the shear creep behavior of weak interlayers (carbonaceous shale) under the coupling effect of the rainfall dry–wet cycle and blasting vibration, as well as quantitatively characterize the coupled damage of the rainfall dry–wet cycle and blasting vibration, a series of shear creep tests were carried out. The results show that the combined damage of the rainfall dry–wet cycle and blasting vibration greatly intensifies the creep effect of carbonaceous shale, leading to an increase in deceleration creep time, an increase in steady-state creep rate, and a decrease in long-term strength. The coupling damage of the rainfall dry–wet cycle and blasting vibration in carbonaceous shale was quantitatively characterized. Based on the fractional-order theory, a fractional-order creep-damage constitutive model (DNFVP) was established by introducing the Abel dashpot to describe the coupled damage of the rainfall wet–dry cycle and blasting vibration and the nonlinear creep acceleration characteristics. The three-dimensional creep equation of the model was derived. The effectiveness of the DNFVP model was verified through the inversion of model parameters and fitting of experimental data, providing a basis for in-depth research on the long-term stability of high slopes in mines with weak interlayers.
An Efficient Numerical Scheme for a Time-Fractional Black–Scholes Partial Differential Equation Derived from the Fractal Market Hypothesis
Authors: Nuugulu Samuel M. , Gideon Frednard , Patidar Kailash C.
Published: August 2024

Since the early 1970s, the study of Black–Scholes (BS) partial differential equations (PDEs) under the Efficient Market Hypothesis (EMH) has been a subject of active research in financial engineering. It has now become obvious, even to casual observers, that the classical BS models derived under the EMH framework fail to account for a number of realistic price evolutions in real-time market data. An alternative approach to the EMH framework is the Fractal Market Hypothesis (FMH), which proposes better and clearer explanations of market behaviours during unfavourable market conditions. The FMH involves non-local derivatives and integral operators, as well as fractional stochastic processes, which provide better tools for explaining the dynamics of evolving market anomalies, something that classical BS models may fail to explain. In this work, using the FMH, we derive a time-fractional Black–Scholes partial differential equation (tfBS-PDE) and then transform it into a heat equation, which allows for ease of implementing a high-order numerical scheme for solving it. Furthermore, the stability and convergence properties of the numerical scheme are discussed, and overall techniques are applied to pricing European put option problems.
A Review on Traditional and Artificial Intelligence-Based Preservation Techniques for Oil Painting Artworks
Authors: Khalid Salman , Azad Muhammad Muzammil , Kim Heung Soo , Yoon Yanggi , Lee Hanhyoung , Choi Kwang-Soon , Yang Yoonmo
Published: August 2024

Oil paintings represent significant cultural heritage, as they embody human creativity and historical narratives. The preservation of these invaluable artifacts requires effective maintenance practices to ensure their longevity and integrity. Despite their inherent durability, oil paintings are susceptible to mechanical damage and chemical deterioration, necessitating rigorous conservation efforts. Traditional preservation techniques that have been developed over centuries involve surface treatment, structural stabilization, and gel-based cleaning to maintain both the integrity and aesthetic appeal of these artworks. Recent advances in artificial intelligence (AI)-powered predictive maintenance techniques offer innovative solutions to predict and prevent deterioration. By integrating image analysis and environmental monitoring, AI-based models provide valuable insights into painting preservation. This review comprehensively analyzes traditional and AI-based techniques for oil painting maintenance, highlighting the importance of adopting innovative approaches. By integrating traditional expertise with AI technology, conservators can enhance their capacity to maintain and preserve these cultural treasures for future generations.
Circadian Rhythm of Distal Skin Temperature in Healthy Older and Young Women and Its Relationship with Sleep–Wake Rhythm and Environmental Factors under Natural Living Conditions
Authors: Dittmar Manuela , Stark Tina , Wedell Stefanie
Published: August 2024

Little is known about the healthy aging of the circadian timing system under natural living conditions. This study explores changes in the circadian rhythm of distal skin temperature (DST) with aging and relates these changes to sleep–wake timing and environmental influences. DST, sleep–wake timing, 24-h light exposure, and physical activity were measured and averaged over seven consecutive days using temperature sensors, actigraphy with a light meter, and sleep diaries in 35 healthy older women (60–79 years) and 30 young women (20–34 years). Circadian rhythm characteristics, describing strength (amplitude) and timing (acrophase) of the DST rhythm, were calculated using cosinor analysis. The older adults displayed an 18–19% smaller amplitude and a 66–73 min earlier acrophase (peak time) for DST rhythm than the young adults, indicating a weaker and phase-advanced DST rhythm. The phase advance for DST was not due to an earlier evening increase, but to a shorter nocturnal plateau period. Daytime light exposure inversely affected strength (amplitude) but not phasing of the DST rhythm in older adults. The DST rhythm was 3.5 times more advanced than the sleep–wake rhythm, showing an altered phase relationship (phase angle) between both rhythms with aging. The phase angle was more heterogeneous among older adults, showing differential aging. The phase advance for DST rhythm and the altered and heterogeneous phase relationship between DST and sleep–wake rhythms were not related to ambient light exposure and the physical activity of older adults. This suggests that healthy aging of the circadian system might be due to endogenous mechanisms such as an internal rearrangement rather than external influences.
Age-Associated Calcification: Insights from Murine Models
Authors: Nasi Sonia , Romani Mario , Busso Nathalie
Published: August 2024

Calcification refers to the deposition of calcium-containing crystals either intracellularly or within the extracellular matrix. Physiologic calcification is a normal process occurring during bone and tooth development and growth. In contrast, pathologic calcification occurs in soft tissues that typically do not undergo mineralization, such as blood vessels, cartilage, tendons, and skin. Pathological calcification is significantly associated with tissue impairment and the development of secondary diseases, such as atherosclerosis, osteoarthritis, tendinopathy, and skin ulcers. Aging, a natural process linked to numerous pathologic conditions, is one of the most recognized risk factors for pathological calcification. In this manuscript, we review the current state of knowledge regarding the role of aging in calcification across different tissues. We focus on the mechanisms activated during normal aging, including cellular senescence, decreased pyrophosphate levels, increased secretion of extracellular vesicles, elevated oxidative stress, and higher levels of pro-mineralizing cytokines, all of which can contribute to pathological calcification. Finally, we discuss the available animal models used to study the impact of aging on calcification.
Non-Adherence to Peripheral Venous Catheter Care Protocols Significantly Decreases Patient Safety and Impacts Costs: A Retrospective Observational Study
Authors: Bibiano Guillén María , Tolsdorf Rodríguez Jose , Nuñez-Alfonsel Javier , Cárdenas-Rebollo José Miguel , Ayuso-Sacido Ángel
Published: August 2024

In the healthcare field, the effective implementation of clinical protocols is crucial to ensuring patient safety and well-being. In this context, this study evaluates nurses’ adherence to the maintenance and replacement protocol of peripheral venous catheters (PVCs) in a university hospital in Spain, examining the impact of compliance with the protocol on the loss of PVCs and on patient safety in addition to analyzing the related costs. A retrospective observational study was conducted with 590 patients who were admitted in 2018 and 2019. The chi-square test or Fisher’s exact test, as appropriate, was used to see the association between the study variables; with the dependent variable being the loss of PVCs (including, as a dependent variable, the loss of PVCs before 48 h). The patients’ electronic and physical medical records were reviewed to analyze nursing interventions related to the management of PVCs. A total of 24% of patients experienced PVC loss within the first 24 h after insertion. Failure to comply with the protocol resulted in 80% more catheter loss and increased the cost of cannulation by 46.84%. Low compliance with PVC care protocols significantly increases the risk of catheter loss, suggesting the need for increased training and strict protocol implementation. The findings emphasize the critical role of nursing in ensuring patient safety through adherence to evidence-based protocols. Continuing education and diligent protocol implementation are essential to reducing healthcare costs and improving patient outcomes.
A Comprehensive ddPCR Strategy for Sensitive and Reliable Monitoring of CAR-T Cell Kinetics in Clinical Applications
Authors: Wiedemann Gertrud , Bacher Ulrike , Joncourt Raphael , Solly Françoise , Widmer Corinne C. , Zeerleder Sacha , Novak Urban , Pabst Thomas , Porret Naomi A.
Published: August 2024

In this study, we present the design, implementation, and successful use of digital droplet PCR (ddPCR) for the monitoring of chimeric antigen receptor T-cell (CAR-T) expansion in patients with B-cell malignancies treated with different CAR-T products at our clinical center. Initially, we designed a specific and highly sensitive ddPCR assay targeting the junction between the 4-1BB and CD3ζ domains of tisa-cel, normalized with RPP30, and validated it using blood samples from the first tisa-cel-treated patient in Switzerland. We further compared this assay with a published qPCR (quantitative real-time PCR) design. Both assays showed reliable quantification of CAR-T copies down to 20 copies/µg DNA. The reproducibility and precision were confirmed through extensive testing and inter-laboratory comparisons. With the introduction of other CAR-T products, we also developed a corresponding ddPCR assay targeting axi-cel and brexu-cel, demonstrating high specificity and sensitivity with a limit of detection of 20 copies/µg DNA. These assays are suitable for CAR-T copy number quantification across multiple sample types, including peripheral blood, bone marrow, and lymph node biopsy material, showing robust performance and indicating the presence of CAR-T cells not only in the blood but also in target tissues. Longitudinal monitoring of CAR-T cell kinetics in 141 patients treated with tisa-cel, axi-cel, or brexu-cel revealed significant expansion and long-term persistence. Peak expansion correlated with clinical outcomes and adverse effects, as is now well known. Additionally, we quantified the CAR-T mRNA expression, showing a high correlation with DNA copy numbers and confirming active transgene expression. Our results highlight the quality of ddPCR for CAR-T monitoring, providing a sensitive, precise, and reproducible method suitable for clinical applications. This approach can be adapted for future CAR-T products and will support the monitoring and the management of CAR-T cell therapies.
Hierarchical Biomaterial Scaffolds for Periodontal Tissue Engineering: Recent Progress and Current Challenges
Authors: Santos Mafalda S. , Silva João C. , Carvalho Marta S.
Published: August 2024

The periodontium is a complex hierarchical structure composed of alveolar bone, periodontal ligament, cementum, and gingiva. Periodontitis is an inflammatory disease that damages and destroys the periodontal tissues supporting the tooth. Periodontal therapies aim to regenerate the lost tissues, yet current treatments lack the integration of multiple structural/biochemical instructive cues to induce a coordinated regeneration, which leads to limited clinical outcomes. Hierarchical biomaterial scaffolds offer the opportunity to recreate the organization and architecture of the periodontium with distinct compartments, providing structural biomimicry that facilitates periodontal regeneration. Various scaffolds have been fabricated and tested preclinically, showing positive regenerative results. This review provides an overview of the recent research on hierarchical scaffolds for periodontal tissue engineering (TE). First, the hierarchical structure of the periodontium is described, covering the limitations of the current treatments used for periodontal regeneration and presenting alternative therapeutic strategies, including scaffolds and biochemical factors. Recent research regarding hierarchical scaffolds is highlighted and discussed, in particular, the scaffold composition, fabrication methods, and results from in vitro/in vivo studies are summarized. Finally, current challenges associated with the application of hierarchical scaffolds for periodontal TE are debated and future research directions are proposed.
Pro-Osteogenic Effect of the Nutraceutical BlastiMin Complex® in Women with Osteoporosis or Osteopenia: An Open Intervention Clinical Trial
Authors: Sabatelli Sofia , Scarpa Emanuele-Salvatore , Giuliani Angelica , Giordani Chiara , Sabbatinelli Jacopo , Rippo Maria Rita , Cabodi Sara , Petrini Barbara , Balercia Giancarlo , Giacchetti Gilberta
Published: August 2024

Osteoporosis is a chronic disease that affects millions of patients worldwide and is characterized by low bone mineral density (BMD) and increased risk of fractures. Notably, natural molecules can increase BMD and exert pro-osteogenic effects. Noteworthily, the nutraceutical BlastiMin Complex® (Mivell, Italy, European Patent Application EP4205733A1) can induce differentiation of human bone marrow mesenchymal stem cells (BM-MSCs) in osteoblasts and can exert in vitro pro-osteogenic and anti-inflammatory effects. Thus, the purpose of this study was to verify the effects of BlastiMin Complex® on bone turnover markers (BTMs) and BMD in patients with senile and postmenopausal osteopenia or osteoporosis. The efficacy of BlastiMin Complex® on BTMs in serum was evaluated through biochemical assays. BMD values were analyzed by dual-energy X-ray absorptiometry (DXA) and Radiofrequency Echographic Multi Spectrometry (R.E.M.S.) techniques, and the SNPs with a role in osteoporosis development were evaluated by PCR. Clinical data obtained after 12 months of treatment showed an increase in bone turnover index, a decrease in C-reactive protein levels, and a remarkable increase in P1NP levels, indicating the induction of osteoblast proliferation and activity in the cohort of 100% female patients recruited for the study. These findings show that the nutraceutical BlastiMin Complex® could be used as an adjuvant in combination with synthetic drugs for the treatment of osteoporosis pathology.
Heterogeneous IL-9 Production by Circulating Skin-Tropic and Extracutaneous Memory T Cells in Atopic Dermatitis Patients
Authors: García-Jiménez Irene , Sans-de San Nicolás Lídia , Curto-Barredo Laia , Bertolín-Colilla Marta , Sensada-López Eloi , Figueras-Nart Ignasi , Bonfill-Ortí Montserrat , Guilabert-Vidal Antonio , Ryzhkova Anna , Ferran Marta , Damiani Giovanni , Czarnowicki Tali , Pujol Ramon M. , Santamaria-Babí Luis F.
Published: August 2024

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA+ and extracutaneous/systemic CLA− memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA+ and CLA− T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.
Intravenous Idursulfase for the Treatment of Mucopolysaccharidosis Type II: A Systematic Literature Review
Authors: Al-Hertani Walla , Pathak Ravi R. , Evuarherhe Obaro , Carter Gemma , Schaeffer-Koziol Carolyn R. , Whiteman David A. H. , Wright Ekaterina
Published: August 2024

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare, X-linked disorder caused by deficient activity of the enzyme iduronate-2-sulfatase. Signs and symptoms typically emerge at 1.5–4 years of age and may include cognitive impairment, depending on whether patients have the neuronopathic or non-neuronopathic form of the disease. Treatment is available in the form of enzyme replacement therapy (ERT) with recombinant iduronate-2-sulfatase (idursulfase). A systematic literature review was conducted to assess the evidence regarding efficacy, effectiveness, and safety of ERT with intravenous idursulfase for MPS II. Electronic databases were searched in January 2023, and 33 eligible articles were found. These were analyzed to evaluate the effects of intravenous idursulfase and the overall benefits and disadvantages in patient subgroups. Studies showed that intravenous idursulfase treatment resulted in improved short- and long-term clinical and patient-centered outcomes, accompanied by a favorable safety profile. Patients with non-neuronopathic MPS II had more pronounced improvements in clinical outcomes than those with neuronopathic MPS II. In addition, the review identified that improvements in clinical outcomes are particularly apparent if intravenous idursulfase is started early in life, strengthening previous recommendations for early ERT initiation to maximally benefit patients. This review provides a comprehensive summary of our current knowledge on the efficacy of ERT in different populations of patients with MPS II and will help to inform the overall management of the disease in an evolving treatment landscape.
The Inhibitory Effects of Maclurin on Fatty Acid Synthase and Adipocyte Differentiation
Authors: Hwang Ji Young , Jeong Hyeon Hak , Baek Jiwon , Lee Jiyun , Ryu Heeyeon , Kim Jae-Il , Lee Bonggi
Published: August 2024

Obesity is a complex health condition characterized by excessive adipose tissue accumulation, leading to significant metabolic disturbances such as insulin resistance and cardiovascular diseases. Fatty acid synthase (FAS), a key enzyme in lipogenesis, has been identified as a potential therapeutic target for obesity due to its role in adipocyte differentiation and lipid accumulation. This study employed a multidisciplinary approach involving in silico and in vitro analyses to investigate the anti-adipogenic properties of maclurin, a natural phenolic compound derived from Morus alba. Using SwissDock software (ChEMBL version 23), we predicted protein interactions and demonstrated a high probability (95.6%) of maclurin targeting FAS, surpassing the interaction rates of established inhibitors like cerulenin. Docking simulations revealed maclurin’s superior binding affinity to FAS, with a binding score of −7.3 kcal/mol compared to −6.7 kcal/mol for cerulenin. Subsequent in vitro assays confirmed these findings, with maclurin effectively inhibiting FAS activity in a concentration-dependent manner in 3T3-L1 adipocytes, without compromising cell viability. Furthermore, maclurin treatment resulted in significant reductions in lipid accumulation and the downregulated expression of critical adipogenic genes such as PPARγ, C/EBPα, and FAS, indicating the suppression of adipocyte differentiation. Maclurin shows potential as a novel FAS inhibitor with significant anti-adipogenic effects, offering a promising therapeutic avenue for the treatment and prevention of obesity.
Glutamate, Gangliosides, and the Synapse: Electrostatics at Work in the Brain
Authors: Chahinian Henri , Yahi Nouara , Fantini Jacques
Published: August 2024

The synapse is a piece of information transfer machinery replacing the electrical conduction of nerve impulses at the end of the neuron. Like many biological mechanisms, its functioning is heavily affected by time constraints. The solution selected by evolution is based on chemical communication that, in theory, cannot compete with the speed of nerve conduction. Nevertheless, biochemical and biophysical compensation mechanisms mitigate this intrinsic weakness: (i) through the high concentrations of neurotransmitters inside the synaptic vesicles; (ii) through the concentration of neurotransmitter receptors in lipid rafts, which are signaling platforms; indeed, the presence of raft lipids, such as gangliosides and cholesterol, allows a fine tuning of synaptic receptors by these lipids; (iii) through the negative electrical charges of the gangliosides, which generate an attractive (for cationic neurotransmitters, such as serotonin) or repulsive (for anionic neurotransmitters, such as glutamate) electric field. This electric field controls the flow of glutamate in the tripartite synapse involving pre- and post-synaptic neurons and the astrocyte. Changes in the expression of brain gangliosides can disrupt the functioning of the glutamatergic synapse, causing fatal diseases, such as Rett syndrome. In this review, we propose an in-depth analysis of the role of gangliosides in the glutamatergic synapse, highlighting the primordial and generally overlooked role played by the electric field of synaptic gangliosides.
Organellar Genomes of Sargassum hemiphyllum var. chinense Provide Insight into the Characteristics of Phaeophyceae
Authors: Jia Xuli , Chen Weizhou , Liu Tao , Chen Zepan
Published: August 2024

Sargassum hemiphyllum var. chinense, a prevalent seaweed along the Chinese coast, has economic and ecological significance. However, systematic positions within Sargassum and among the three orders of Phaeophyceae, Fucales, Ectocarpales, and Laminariales are in debate. Here, we reported the organellar genomes of S. hemiphyllum var. chinense (34,686-bp mitogenome with 65 genes and 124,323 bp plastome with 173 genes) and the investigation of comparative genomics and systematics of 37 mitogenomes and 22 plastomes of Fucales (including S. hemiphyllum var. chinense), Ectocarpales, and Laminariales in Phaeophyceae. Whole genome collinearity analysis showed gene number, type, and arrangement were consistent in organellar genomes of Sargassum with 360 SNP loci identified as S. hemiphyllum var. chinense and two genes (rps7 and cox2) identified as intrageneric classifications of Sargassum. Comparative genomics of the three orders of Phaeophyceae exhibited the same content and different types (petL was only found in plastomes of the order Fucales and Ectocarpales) and arrangements (most plastomes were rearranged, but trnA and trnD in the mitogenome represented different orders) in genes. We quantified the frequency of RNA-editing (canonical C-to-U) in both organellar genomes; the proportion of edited sites corresponded to 0.02% of the plastome and 0.23% of the mitogenome (in reference to the total genome) of S. hemiphyllum var. chinense. The repetition ratio of Fucales was relatively low, with scattered and tandem repeats (nine tandem repeats of 14–24 bp) dominating, while most protein-coding genes underwent negative selection (Ka/Ks < 1). Collectively, these findings provide valuable insights to guide future species identification and evolutionary status of three important Phaeophyceae order species.
Normal Values for the fT3/fT4 Ratio: Centile Charts (0–29 Years) and Their Application for the Differential Diagnosis of Children with Developmental Delay
Authors: Wilpert Nina-Maria , Thamm Roma , Thamm Michael , Kratzsch Jürgen , Seelow Dominik , Vogel Mandy , Krude Heiko , Schuelke Markus
Published: August 2024

Primary congenital hypothyroidism is easily diagnosed on the basis of elevated plasma levels of thyroid-stimulating hormone (TSH). In contrast, in the rare disorders of thyroid hormone resistance, TSH and, in mild cases, also thyroid hormone levels are within the normal range. Thyroid hormone resistance is caused by defects in hormone metabolism, transport, or receptor activation and can have the same serious consequences for child development as congenital hypothyroidism. A total of n = 23,522 data points from a large cohort of children and young adults were used to generate normal values and sex-specific percentiles for the ratio of free triiodothyronine (T3) to free thyroxine (T4), the fT3/fT4 ratio. The aim was to determine whether individuals with developmental delay and genetically confirmed thyroid hormone resistance, carrying defects in Monocarboxylate Transporter 8 (MCT8), Thyroid Hormone Receptor alpha (THRα), and Selenocysteine Insertion Sequence-Binding Protein 2 (SECISBP2), had abnormal fT3/fT4 ratios. Indeed, we were able to demonstrate a clear separation of patient values for the fT3/fT4 ratio from normal and pathological controls (e.g., children with severe cerebral palsy). We therefore recommend using the fT3/fT4 ratio as a readily available screening parameter in children with developmental delay for the identification of thyroid hormone resistance syndromes. The fT3/fT4 ratio can be easily plotted on centile charts using our free online tool, which accepts various SI and non-SI units for fT3, fT4, and TSH.