bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of NR5A1 Gene Mutations in Disorders of Sex Development: Molecular and Clinical Features
Authors: Luppino Giovanni , Wasniewska Malgorzata , Coco Roberto , Pepe Giorgia , Morabito Letteria Anna , Li Pomi Alessandra , Corica Domenico , Aversa Tommaso
Published: May 2024

Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic, gonadal, or phenotypic sex accompanied by abnormal development of internal and/or external genitalia. NR5A1 gene mutation is one of the principal genetic alterations implicated in causing DSD. This review outlines the role of NR5A1 gene during the process of gonadal development in humans, provides an overview of the molecular and functional characteristics of NR5A1 gene, and discusses potential clinical phenotypes and additional organ diseases due to NR5A1 mutations. NR5A1 mutations were analyzed in patients with 46,XY DSD and 46,XX DSD both during the neonatal and pubertal periods. Loss of function of the NR5A1 gene causes several different phenotypes, including some associated with disease in additional organs. Clinical phenotypes may vary, even among patients carrying the same NR5A1 variant, indicating that there is no specific genotype–phenotype correlation. Genetic tests are crucial diagnostic tools that should be used early in the diagnostic pathway, as early as the neonatal period, when gonadal dysgenesis is the main manifestation of NR5A1 mutation. NR5A1 gene mutations could be mainly associated with amenorrhea, ovarian failure, hypogonadism, and infertility during puberty. Fertility preservation techniques should be considered as early as possible.
Dual-Function Hybrid Coatings Based on Polytetrafluoroethylene and Cu2O for Anti-Biocorrosion and Anti-Wear Applications
Authors: Li Guohui , Li Huan , Xu Yongkun , He Ren , Zhang Ga , Liu Zongzhu
Published: May 2024

Corrosion and wear issues of motion components exposed to water-based corrosion mediums, e.g., naval vessels and oil extraction equipment, pose challenges for the lifespan and reliability of the motion systems. In this work, epoxy-based coatings modified with polytetrafluoroethylene (PTFE) and cuprous oxide (Cu2O) nanoparticles were prepared. The anti-corrosion performance of the coatings was comparatively investigated by electrical impedance spectroscopy and Tafel tests in sterile and sulphate-reducing bacteria (SRB) mediums. Moreover, the tribological behaviors of the coatings were examined under water lubrication conditions. Our results demonstrate that the epoxy coatings lower significantly the corrosion current density icorr and the charge transfer resistance of the electrical double layer Rct of the carbon steel substrate. Interestingly, the hybrid coatings filled with both PTFE and Cu2O exhibit excellent anti-corrosion and anti-wear performance. After being immersed in the SRB medium for 18 days, the icorr of the pure EP coating and hybrid coatings are 1.10 × 10−7 Amp/cm2 and 0.3 × 10−7 Amp/cm2, and the Rct values are 1.04 × 103 Ω·cm2 and 3.87 × 103 Ω·cm2, respectively. A solid tribofilm forms on the stainless steel counterface sliding against the hybrid coating, which is surmised to be essential for the low friction coefficients and wear. The present work paves a route for formulating the dual-function coatings of anti-biocorrosion and anti-wear.
Progressive Multifocal Leukoencephalopathy Unmasked by Teclistamab in a Refractory Multiple Myeloma Patient
Authors: Arvanitis Panos , Farmakiotis Dimitrios , Pelcovits Ari
Published: May 2024

This case report describes the development of Progressive Multifocal Leukoencephalopathy (PML) in a 72-year-old male with relapsed/refractory multiple myeloma (RRMM), following a single dose of teclistamab amidst a COVID-19 infection. Shortly after starting teclistamab treatment, the patient developed symptoms, including fever, altered mental status, and right-sided paresis. A diagnosis of PML was confirmed through the detection of JC virus PCR in the cerebrospinal fluid. Our report emphasizes the occurrence of PML after only one dose of teclistamab and highlights teclistamab’s potential for severe infectious complications, despite its promise in treating RRMM.
Evaluating the Status of Lost, Found and Sighted Non-Native Pet Bird Species in South Africa
Authors: Shivambu Tinyiko C. , Shivambu Ndivhuwo , Nelufule Takalani , Moshobane Moleseng C. , Seoraj-Pillai Nimmi , Nangammbi Tshifhiwa C.
Published: May 2024

The global increase in the pet trade and ownership of pet birds has heightened the introduction of emerging invasive vertebrate species. We analyzed online databases of lost, found, and sighted non-native pet bird reports in South Africa to evaluate non-native pet bird statuses, investigate geographic patterns, assess species trends, and determine the factors associated with lost pet birds. We identified a total of 1467 case reports representing 77 species across nine families from websites (n = 3) and Facebook pages (n = 13). Most reports of lost birds were within large cities, in populated provinces, including Gauteng, KwaZulu-Natal, and Western Cape. Psittacidae, Psittaculidae, and Cacatuidae were the most dominant families, with African grey (Psittacus erithacus), Cockatiel (Nymphicus hollandicus), and Rose-ringed parakeet (Psittacula krameri) among the top species reported as lost. Lower-priced species were commonly reported as lost, and there was no association between the species’ price and the likelihood of being found. In addition, we found a positive relationship between species reported as lost and the number of pet shops, human population size, species size, and docility. There was a sharp increase in lost cases from 2019 onwards; however, males were more frequently lost. Our findings highlight challenges in regulating and monitoring the pet ownership and trade of non-native pet birds and the need to address commonly kept species in conservation efforts. Online resources can be effective tools for passive surveillance of non-native pet bird species, especially potentially invasive ones.
Artificial Intelligence-Based Quality Assessment of Histopathology Whole-Slide Images within a Clinical Workflow: Assessment of ‘PathProfiler’ in a Diagnostic Pathology Setting
Authors: Browning Lisa , Jesus Christine , Malacrino Stefano , Guan Yue , White Kieron , Puddle Alison , Alham Nasullah Khalid , Haghighat Maryam , Colling Richard , Birks Jacqueline , Rittscher Jens , Verrill Clare
Published: May 2024

Digital pathology continues to gain momentum, with the promise of artificial intelligence to aid diagnosis and for assessment of features which may impact prognosis and clinical management. Successful adoption of these technologies depends upon the quality of digitised whole-slide images (WSI); however, current quality control largely depends upon manual assessment, which is inefficient and subjective. We previously developed PathProfiler, an automated image quality assessment tool, and in this feasibility study we investigate its potential for incorporation into a diagnostic clinical pathology setting in real-time. A total of 1254 genitourinary WSI were analysed by PathProfiler. PathProfiler was developed and trained on prostate tissue and, of the prostate biopsy WSI, representing 46% of the WSI analysed, 4.5% were flagged as potentially being of suboptimal quality for diagnosis. All had concordant subjective issues, mainly focus-related, 54% severe enough to warrant remedial action which resulted in improved image quality. PathProfiler was less reliable in assessment of non-prostate surgical resection-type cases, on which it had not been trained. PathProfiler shows potential for incorporation into a digitised clinical pathology workflow, with opportunity for image quality improvement. Whilst its reliability in the current form appears greatest for assessment of prostate specimens, other specimen types, particularly biopsies, also showed benefit.
A Foam Line Position Detection Algorithm for A/O Pool Based on YOLOv5
Authors: Xu Yubin , Wu Yihao , Guo Yinzhang
Published: May 2024

During the biochemical pretreatment process of leachate in urban landfill sites, if the foam in the A/O pool is not promptly addressed, it can lead to overflow, posing hazards to the surrounding environment and personnel. Therefore, a real-time foam line detection algorithm based on YOLOv5x was proposed, which enhances feature information and improves anchor box regression prediction to accurately detect the position of foam lines. Firstly, in the preprocessing stage, employing a rectangular box to simultaneously label the foam line and the edge of the A/O pool within the same region, enhances the feature information of the foam line. Then, the C3NAM module was proposed, which applies weight sparse penalties to attention modules in the feature extraction section, to enhance the capability of extracting foam line features. Subsequently, a B-SPPCSPC module was proposed to enhance the fusion of shallow and deep feature information, addressing the issue of susceptibility to background interference during foam line detection. Next, the Focal_EIOU was introduced to ameliorate the issue of class imbalance in detection, providing more accurate bounding box predictions. Lastly, optimizing the detection layer scale improves the detection performance for smaller targets. The experimental results demonstrate that the accuracy of this algorithm reaches 98.9%, and the recall reaches 88.1%, with a detection frame rate of 26.2 frames per second, which can meet the actual detection requirements of real-world application scenarios.
Analytical Solutions of the 3-DOF Gyroscope Model
Authors: Krzysztofik Izabela , Blasiak Slawomir
Published: May 2024

The motion of a rigid body (a gyroscope) is one of the key issues in classical mechanics. It remains a significant challenge, as evidenced by its extensive practical implementations in various scientific disciplines and engineering operations. It is important to obtain analytical solutions, as they provide solutions that depend directly on the system’s parameters, which can be definitively interpreted. The coupling of numerical and analytical solutions allows for a more precise representation of the real phenomenon. The main objective of the article was to formulate analytical solutions for the motion of a Cardan suspension gyroscope subjected to controlling torque moments. Analytical solutions for the proposed mathematical model were developed using the Laplace transform and Green’s function. Subsequently, they were validated by numerical tests. The obtained analytical solutions are universally applicable, regardless of the type of controlling moments.
Research on the Thermal Aging Characteristics of Crosslinked Polyethylene Cables Based on Polarization and Depolarization Current Measurement
Authors: Li Yamei , Peng Zhaowei , Xu Dangguo , Huang Shiyang , Gao Yanfeng , Li Yuan
Published: May 2024

Although XLPE cables are widely used in power transmission and distribution systems, their insulating properties are susceptible to degradation due to thermal aging. In order to clarify the influence law of the thermal aging process on the structural and dielectric properties of XLPE cables, this paper investigates the thermal aging characteristics of XLPE cables by using polarization and depolarization current measurement. Results show that when the XLPE cable is aged at 140 °C, the crystallinity of the insulation layer appears to increase and then decrease. With the increase in aging time, micron-sized microvoids appear on the surface of the XLPE. At the same time, the DC conductivity and 0.1 Hz dielectric loss factor of the insulating layer increase with the aging time. The average DC conductivity increased from 2.26 × 10−16 S/m for new cables to 4.47 × 10−16 S/m after aging for 432 h, while the dielectric loss increased from 0.11% to 0.42%. The polarization characteristics of thermal-aged cables were further analyzed using the extended Debye model. Results indicate that the time constant of the third branch of the model increased significantly with increasing aging time. A correspondence between this parameter and the thermal aging time of the cable was established. Thermal aging can damage the crystalline structure of XLPE, so that the number of interfaces between the crystalline and amorphous regions of the material increases, resulting in structural damages and a decline in the dielectric properties of the cable insulation.
Transient Stability Assessment of Power Systems Based on CLV-GAN and I-ECOC
Authors: Li Nan , Wu Jiafei , Shan Lili , Yi Luan
Published: May 2024

In order to improve the multi-class assessment performance of transient stability in power systems, a multi-class assessment model that combines the CLV-GAN algorithm with an improved error-correcting output coding technique is proposed in the paper. To address the issue of the small number of unstable samples in power systems, a sample generation model is constructed by combining a dual-encoder VAE with a GAN network. The model generates effective artificial samples to balance the sample ratio between categories by learning the latent distribution of aperiodic and oscillatory unstable samples from the distribution. The decomposition method based on an improved error-correcting output coding algorithm is applied to convert the multi-class problem into a decision fusion issue for binary models. This method improves the overall performance of the multi-class model, particularly significantly increasing the recognition accuracy of discrimination against oscillatory unstable samples and reducing the safety hazards in the operation of power systems. The simulation validation was conducted on the IEEE 39-bus and IEEE 140-bus systems to confirm the effectiveness of the proposed model.
Anti-Gravity 3D Pulsating Heat Pipe for Cooling Electric Vehicle Batteries
Authors: Lee Ji-Su , Kim Su-Jong , Han Woo-Sung , Rhi Seok-Ho
Published: May 2024

This study proposes an anti-gravity 3D pulsating heat pipe (PHP) for cooling pouch batteries in electric vehicles. The 3D PHP envelops the battery cells and rapidly transfers heat generated from the batteries to the bottom cold plate. While the batteries generate heat on their frontal surface during charging and discharging, structural characteristics lead to localized heat accumulation at the electrode lead tabs. Therefore, to address frontal heating, Pattern A with a consistent height for the 3D PHP and Pattern B with varying heights to enhance heat transfer in the localized heating area were designed. The target application involved creating a battery simulator for 340 × 100 mm pouch battery cells, considering the battery’s heat generation characteristics. The experiments for the thermal characteristics were conducted, considering factors such as the working fluid (methanol, Novec7100), filling ratio, supplied heat, and orientation. Additionally, to observe internal flow mechanisms, a special experimental apparatus was used, employing transparent fluorine rubber tubes to observe the flow mechanism of the 3D PHP. In the results of the thermal characteristics, the optimal filling ratio was 15% when heat generation levels of 50 W and 100 W were supplied and 20% when 150 W was supplied. The impact of orientation yielded varied results depending on the pattern and working fluid, attributed to the complex interplay of flow momentum due to orientation changes and the influence of the working fluid’s buoyancy under anti-gravity conditions. Pattern B, designed with the goal of applying a localized heat model, exhibited relatively decreased heat transfer performance in areas with varying heights. As the distance from the varying height portion increased, temperature oscillations and heat transfer became more active. These results suggest that variations in the shape of the 3D PHP could be a primary design variable for crafting localized heat models. Observations of internal flow revealed that the 3D PHP, with its unique shape and operation under anti-gravity conditions, exhibits longer and more irregular cycles compared to gravity-assist PHPs, transferring heat through rapid oscillations of internal working fluid liquid/vapor slug/plug. The potential of 3D PHPs for cooling electric vehicle batteries is suggested by these findings, and further experimentation is planned to evaluate the optimal design and applicability.
Comparative Study of Parameter Extraction from a Solar Cell or a Photovoltaic Module by Combining Metaheuristic Algorithms with Different Simulation Current Calculation Methods
Authors: Qin Cheng , Li Jianing , Yang Chen , Ai Bin , Zhou Yecheng
Published: May 2024

In this paper, single-diode model (SDM) and double-diode model (DDM) parameters of the French RTC solar cell and the Photowatt PWP 201 photovoltaic (PV) module were extracted by combining five metaheuristic algorithms with three simulation current calculation methods (i.e., approximation method, Lambert W method and Newton–Raphson method), respectively. It was found that the parameter-extraction accuracies of the Lambert W (LW) method and the Newton–Raphson (NR) method are always approximately equal and higher than that of the approximation method. The best RMSEs (root mean square error) obtained by using the LW or the NR method on the solar cell and the PV module are 7.72986 × 10−4 and 2.05296 × 10−3 for SDM parameter extraction and 6.93709 × 10−4 and 1.99051 × 10−3 for DDM parameter extraction, respectively. The latter may be the highest parameter-extraction accuracy reported on the solar cell and the PV module so far, which is due to the adoption of more reasonable DDM parameter boundaries. Furthermore, the convergence curves of the LW and the NR method basically coincide, with a convergence speed faster than that of the approximation method. The robustness of a parameter-extraction method is mainly determined by the metaheuristic algorithm, but it is also affected by the simulation current calculation method and the parameter-extraction object. In a word, the approximation method is not suitable for application in PV-model parameter extraction because of incorrect estimation of the simulation current and the RMSE, while the LW and NR methods are suitable for the application for accurately calculating the simulation current and RMSE. In terms of saving computation resources and time, the NR method is superior to the LW method.
The Cost Reduction Analysis of Green Hydrogen Production from Coal Mine Underground Water for Circular Economy
Authors: Magdziarczyk Małgorzata , Chmiela Andrzej , Dychkovskyi Roman , Smoliński Adam
Published: May 2024

The novelty of the paper is the analysis of the possibilities of reducing the operating costs of a mine water pumping station in an abandoned coal mine. To meet the energy needs of the pumping station and reduce the carbon footprint, “green” energy from a photovoltaic farm was used. Surplus green energy generated during peak production is stored in the form of green hydrogen from the water electrolysis process. Rainwater and process water are still underutilized sources for increasing water resources and reducing water stress in the European Union. The article presents the possibilities of using these waters, after purification, in the production of green hydrogen by electrolysis. The article also presents three variants that ensure the energy self-sufficiency of the proposed concepts of operation of the pumping station.
Use of Phosphite Preparations to Protect Ash Seedlings Fraxinus excelsior L. against Phytophthora spp. and Hymenoscyphus fraxineus Pathogens
Authors: Pacia Artur , Drozdowski Stanisław , Malewski Tadeusz , Borowik Piotr , Wilamowski Konrad , Bakier Sławomir , Oszako Tomasz
Published: May 2024

In this study, greenhouse tests were conducted on 240 Fraxinus excelsior seedlings to investigate the simultaneous damage caused by thea pathogenic fungus and oomycetes. The experiment was performed under controlled conditions in the greenhouse of the Institute of Forest Research in Sękocin Stary (Poland). Three species of oomycetes were used for the experiment: Phytophthora plurivora, Phytophthora taxon hungarica, Phytophthora megasperma, and the fungus Hymenoscyphus fraxineus. Inoculations using the fungus were carried out on shoots and in plant pots in which the soil was mixed with the three Phytophthora species mentioned above, both simultaneously and separately, which made it possible to recognize the cumulative effect of the related plant infection. The aim of the study was to investigate the effect of phosphite-containing preparations on the health of common ash under conditions of threat to the roots by Phytophthora spp. and damage to the aerial parts of the plant by the fungus, as well as the possible occurrence of synergistic effects. Two types of protective preparations (Actifos and Phos60 of the nitrogen and potassium forms, respectively) were used. It was found that the inoculation of ash seedlings with the fungus H. fraxineus resulted in plant mortality, while the mixture of Phytophthora did not cause significant damage. It was confirmed that when pathogens coexist, a phenomenon occurs that leads to an acceleration in the development of disease symptoms and, thus, to plant mortality. In vitro tests confirmed the usefulness of phosphite preparations for the protection of ash seedlings.
Unlocking the Potential of Mannosylerythritol Lipids: Properties and Industrial Applications
Authors: de Almeida Joana Dias , Nascimento Miguel Figueiredo , Keković Petar , Ferreira Frederico Castelo , Faria Nuno Torres
Published: May 2024

Mannosylerythritol lipids (MELs), one of the most promising biosurfactants (BS), are glycolipids produced by yeasts or fungi, which have great environmental performance and high compatibility with the human body. MELs, besides working as typical surfactants, can form diverse structures when at or above the critical aggregation concentration (CAC), reduce the surface tension of water and other solutions, and be stable over a wide range of conditions. Among others, MELs present antimicrobial, antitumor, antioxidant and anti-inflammatory activities and skin and hair repair capacity, which opens possibilities for their use in applications from cosmetics and pharmaceutics to bioremediation and agriculture. However, their market share is still low when compared to other glycolipids, due to their less developed production process and higher production cost. This review gathers information on the potential applications of MELs mentioned in the literature since 1993. Furthermore, it also explores the current strategies being developed to enhance the market presence of MELs, in parallel with the ones developed for rhamnolipids and sophorolipids.
Encapsulation of W/O/W Acerola Emulsion by Spray Drying: Optimization, Release Kinetics, and Storage Stability
Authors: Dang Yen Thi , Tran Hieu , Kha Tuyen Chan
Published: May 2024

Acerola (Malpighia emarginata DC.) is a sub-tropical and tropical fruit renowned for its high levels of vitamin C and phenolic compounds, which offer health benefits. This study aimed to optimize the spray drying process by determining the inlet and outlet temperatures using response surface methodology (RSM) with the central composite design. Additionally, it aimed to evaluate the release kinetics in the hydrophilic food simulation environment and the stability of the resulting powder under various storage temperatures. The RSM method determined the optimal inlet and outlet temperatures as 157 °C and 91 °C, respectively. High-accuracy prediction equations (R2 ≥ 0.88) were developed for moisture content (3.02%), process yield (91.15%), and the encapsulation yield of total polyphenol content (61.44%), total flavonoid content (37.42%), and vitamin C (27.19%), with a predicted monolayer moisture content below 4.01%, according to the BET equation. The powder exhibited good dissolution characteristics in the acidic hydrophilic food simulation environment and showed greater stability when stored at 10 °C for 30 days, compared to storage at 35 °C and 45 °C.
Screen-Printed Metamaterial Absorber Using Fractal Metal Mesh for Optical Transparency and Flexibility
Authors: Choi Jinwoo , Lim Daecheon , Lim Sungjoon
Published: May 2024

In stealth applications, there is a growing emphasis on the development of radar-absorbing structures that are efficient, flexible, and optically transparent. This study proposes a screen-printed metamaterial absorber (MMA) on polyethylene terephthalate (PET) substrates using indium tin oxide (ITO) as the grounding layer, which achieves both optical transparency and flexibility. These materials and methods enhance the overall flexibility and transparency of MMA. To address the limited transparency caused by the silver nanoparticle ink for the top pattern, a metal mesh was incorporated to reduce the area ratio of the printed patterns, thereby enhancing transparency. By incrementing the fractal order of the structure, we optimized the operating frequency to target the X-band, which is most commonly used in radar detection. The proposed MMA demonstrates remarkable performance, with a measured absorption of 91.99% at 8.85 GHz and an average optical transmittance of 46.70% across the visible light spectrum (450 to 700 nm), indicating its potential for applications in transparent windows or drone stealth.
Growth of Romaine Lettuce in Eggshell Powder Mixed Alginate Hydrogel in an Aeroponic System for Water Conservation and Vitamin C Biofortification
Authors: Afnan Fariha , Kashem Md Nayeem Hasan , Joshi Rutwik , Simpson Catherine , Li Wei
Published: May 2024

Vitamin C is crucial for physical well-being, and its deficiency can lead to severe health consequences. Biofortification has been used to address this deficiency by enhancing vitamin C in plants. Additionally, soilless agriculture has been used to conserve and optimize water use in comparison to conventional agriculture. While hydrogels have been shown to improve water conservation and are used for biofortification in crops, their application has only been explored in soil-based and hydroponic farming. The aeroponics system is a plant-growing method that has shown potential for increasing yields and biomass while conserving water and nutrients. In this paper, we have developed an aeroponic-compatible medium to grow romaine lettuce (Lactuca sativa L.) with eggshell powder (ESP) mixed with calcium-alginate hydrogel as a substrate and nutrient source aiming to conserve water and incorporate vitamin C through biofortification. Herein, lower water spray time and higher intervals, with varied gel types and ESP concentrations, resulted in healthy lettuce growth. Plants treated with 0.5% ascorbic acid-absorbed ESP-mixed alginate hydrogel for biofortification showed higher levels of vitamin C compared to the traditional method. This study suggests using an alginate hydrogel–ESP-based substrate in aeroponics to reduce water usage and enhance plant biofortification of vitamin C.
Terahertz Spectroscopic Insight into the Hydrogelation of Copper Ion-Coordinated Poly(vinyl alcohol)
Authors: Wang Wenjing , Wang Yadi , Lü Junhong , Li Xueling
Published: May 2024

Metal-coordinated hydrogels are becoming increasingly popular in the biomedical field due to their unique properties. However, the mechanism behind gel forming involving metal ions is not yet fully understood. In this work, terahertz spectroscopy was used to investigate the role of interfacial water in the gelation process of copper ion-coordinated poly(vinyl alcohol) hydrogels. The results showed that the binding of copper ions could alter the interfacial hydration dynamics of the poly(vinyl alcohol) polymers. Combined with the results of differential scanning calorimetry (DSC), we propose a possible hydration layer-mediated mechanism for the formation of cooper ion-coordinated hydrogel during the freeze–thaw cycle. These results highlight the value of terahertz spectroscopy as a sensor for studying the hydration process in hydrogels and provide an important clue for understanding the mechanism of hydrogelation in ion-coordinated hydrogels.
A State-of-the-Art Review on the Role of Cognitive and Motor Reserve on Quality of Life: A Focus on Cardiovascular Patients in a Lifespan Perspective
Authors: Giannì Jessica , Crepaldi Maura , Fusi Giulia , Colombi Francesca , Brugnera Agostino , Greco Andrea , Compare Angelo , Rusconi Maria Luisa
Published: May 2024

Cardiovascular diseases (CVDs) reflect a huge and diversified condition that influences patient quality of life (QoL) both in the physical and mental aspects, especially in older adults who often present comorbidities and may be affected by cognitive decline. The concept of cognitive reserve (CR), which is built through life course experiences, has widely been considered a protective factor against cognitive decline, while the results of QoL in the field of CVDs are still controversial. In particular, there is a lack of evidence that explicitly explores the effects of CR on the QoL in CVD cases since studies have considered only single CR proxies (e.g., education) or specific cardiovascular conditions. Moreover, none of them have considered the motor reserve (MR), another recent concept that considers the amount of physical activity carried out during a lifespan. Its potential role in preventing age-related diseases has been observed, but more clarification is needed given the importance of the physical component in CVDs. The present state-of-the-art review aims to (i) examine how the literature conceives CR and its proxies in CVDs relating to QoL and (ii) integrate the concept of MR in this framework. Implications for clinical practice will also be discussed.
Role of a National Health Service Electronic Prescriptions Database in the Detection of Prescribing and Dispensing Issues and Adherence Evaluation of Direct Oral Anticoagulants
Authors: Gavrilova Anna , Zolovs Maksims , Šmits Dins , Ņikitina Anastasija , Latkovskis Gustavs , Urtāne Inga
Published: May 2024

Background: Anticoagulation therapy plays a crucial role in the management of atrial fibrillation (AF) by significantly reducing the risk of stroke. Direct oral anticoagulants (DOAC) became preferred over warfarin due to their superior safety and efficacy profile. Assessing adherence to anticoagulation therapy is necessary in clinical practice for optimising patient outcomes and treatment efficacy, thus emphasising its significance. Methods: A retrospective study utilised the Latvian National Health Service reimbursement prescriptions database, covering prescriptions for AF and flutter from January 2012 to December 2022. The proportion of days covered method was selected for adherence assessment, categorising it into three groups: (1) below 80%, (2) between 80% and 90%, and (3) above 90%. Results: A total of 1,646,648 prescriptions were analysed. Dabigatran prescriptions started declining after 2020, coinciding with a decrease in warfarin prescriptions since 2018. The total adherence levels to DOAC therapy were 69.4%. Only 44.2% of users achieved an adherence level exceeding 80%. The rate of paper prescriptions decreased from 98.5% in 2017 to 1.3% in 2022. Additionally, the utilisation of international non-proprietary names reached 79.7% in 2022. Specifically, 16.7% of patients selected a single pharmacy, whereas 27.7% visited one or two pharmacies. Meanwhile, other patients obtained medicines from multiple pharmacies. Conclusions: The total adherence level to DOAC therapy is evaluated as low and there was no significant difference in age, gender, or “switcher” status among adherence groups. Physicians’ prescribing habits have changed over a decade.
Smart Anklet Use to Measure Vascular Health Benefits of Preventive Intervention in a Nature-Based Environment—A Pilot Study
Authors: Stosic Maja B. , Kaljevic Jelena , Nikolic Bojan , Tanaskovic Marko , Kolarov Aleksandar
Published: May 2024

The present study aimed to investigate the associations between nature-based intervention and peripheral pulse characteristics of patients with PAOD using new smart technology specifically designed for this purpose. A longitudinal panel study performed between 1 January 2022 and 31 December 2022 included 32 patients diagnosed with peripheral arterial occlusive disease (PAOD) who were treated in the vascular surgeons’ hospital “Dobb” in Valjevo. These patients were exposed for six months to moderate-intensity physical activity (MPA) in a nature-based environment. They practiced 150 to 300 min of walking 6 km/h and cycling activities (16–20 km/h) weekly as recommended for patients with chronic conditions and those living with disability. Univariate logistic regression analysis was used to identify factors associated with major improvements in peripheral pulse characteristics of patients with PAOD. After six months of MPA, half of the patients (50%, 16/32) achieved minor, and half of them major improvements in peripheral pulse characteristics. The major improvements were associated with current smoking (OR = 9.53; 95%CI = 1.85–49.20), diabetes (OR = 4.84; 95%CI = 1.09–21.58) and cardiac failure, and concurrent pulmonary disease and diabetes (OR = 2.03; 95%CI = 1.01–4.11). Our pilot study showed that patients with PAOD along with other chronic conditions and risk factors benefited more from continuous physical activity in a nature-based environment.
Finding a Direct Method for a Dynamic Process: The DD (Direct and Dynamic) Cell-Tox Method
Authors: Madorran Eneko , Kocbek Šaherl Lidija , Rakuša Mateja , Takač Iztok , Munda Miha
Published: May 2024

The main focus of in vitro toxicity assessment methods is to assess the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division, or remain viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids, and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells, and liver sinusoidal endothelial cells to rifampicin, ibuprofen, and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds, as it considers the different cellular responses induced by toxic agents.
Kinetic Properties and Pharmacological Modulation of High- and Low-Affinity Dopamine Transport in Striatal Astrocytes of Adult Rats
Authors: Sočan Vesna , Dolinar Klemen , Kržan Mojca
Published: May 2024

Astrocytes actively participate in neurotransmitter homeostasis by bidirectional communication with neuronal cells, a concept named the tripartite synapse, yet their role in dopamine (DA) homeostasis remains understudied. In the present study, we investigated the kinetic and molecular mechanisms of DA transport in cultured striatal astrocytes of adult rats. Kinetic uptake experiments were performed using radiolabeled [3H]-DA, whereas mRNA expression of the dopamine, norepinephrine, organic cation and plasma membrane monoamine transporters (DAT, NET, OCTs and PMAT) and DA receptors D1 and D2 was determined by qPCR. Additionally, astrocyte cultures were subjected to a 24 h treatment with the DA receptor agonist apomorphine, the DA receptor antagonist haloperidol and the DA precursor L-DOPA. [3H]-DA uptake exhibited temperature, concentration and sodium dependence, with potent inhibition by desipramine, nortriptyline and decynium-22, suggesting the involvement of multiple transporters. qPCR revealed prominent mRNA expression of the NET, the PMAT and OCT1, alongside lower levels of mRNA for OCT2, OCT3 and the DAT. Notably, apomorphine significantly altered NET, PMAT and D1 mRNA expression, while haloperidol and L-DOPA had a modest impact. Our findings demonstrate that striatal astrocytes aid in DA clearance by multiple transporters, which are influenced by dopaminergic drugs. Our study enhances the understanding of regional DA uptake, paving the way for targeted therapeutic interventions in dopaminergic disorders.
Assessment of Key Factors Impacting Variability in AAV Vector Genome Titration by Digital PCR
Authors: Wang Guangyu , Ma Qiang , Wei Changlong , Yu Lei , Bi Hua , Jin Jing , Qin Xi , Zhou Yong , Wang Junzhi
Published: May 2024

Recombinant adeno-associated virus (rAAV) has emerged as a prominent vector for in vivo gene therapy, owing to its distinct advantages. Accurate determination of the rAAV genome titer is crucial for ensuring the safe and effective administration of clinical doses. The evolution of the rAAV genome titer assay from quantitative PCR (qPCR) to digital PCR (dPCR) has enhanced accuracy and precision, yet practical challenges persist. This study systematically investigated the impact of various operational factors on genome titration in a single-factor manner, aiming to address potential sources of variability in the quantitative determination process. Our findings revealed that a pretreatment procedure without genome extraction exhibits superior precision compared with titration with genome extraction. Additionally, notable variations in titration results across different brands of dPCR instruments were documented, with relative standard deviation (RSD) reaching 23.47% for AAV5 and 11.57% for AAV8. Notably, optimal operations about DNase I digestion were identified; we thought treatment time exceeding 30 min was necessary, and there was no need for thermal inactivation after digestion. And we highlighted that thermal capsid disruption before serial dilution substantially affected AAV genome titers, causing a greater than ten-fold decrease. Conversely, this study found that additive components of dilution buffer are not significant contributors to titration variations. Furthermore, we found that repeated freeze–thaw cycles significantly compromised AAV genome titers. In conclusion, a comprehensive dPCR titration protocol, incorporating insights from these impact factors, was proposed and successfully tested across multiple serotypes of AAV. The results demonstrate acceptable variations, with the RSD consistently below 5.00% for all tested AAV samples. This study provides valuable insights to reduce variability and improve the reproducibility of AAV genome titration using dPCR.
The Puzzle of Aspirin and Iron Deficiency: The Vital Missing Link of the Iron-Chelating Metabolites
Authors: Kontoghiorghes George J.
Published: May 2024

Acetylsalicylic acid or aspirin is the most commonly used drug in the world and is taken daily by millions of people. There is increasing evidence that chronic administration of low-dose aspirin of about 75–100 mg/day can cause iron deficiency anaemia (IDA) in the absence of major gastric bleeding; this is found in a large number of about 20% otherwise healthy elderly (>65 years) individuals. The mechanisms of the cause of IDA in this category of individuals are still largely unknown. Evidence is presented suggesting that a likely cause of IDA in this category of aspirin users is the chelation activity and increased excretion of iron caused by aspirin chelating metabolites (ACMs). It is estimated that 90% of oral aspirin is metabolized into about 70% of the ACMs salicyluric acid, salicylic acid, 2,5-dihydroxybenzoic acid, and 2,3-dihydroxybenzoic acid. All ACMs have a high affinity for binding iron and ability to mobilize iron from different iron pools, causing an overall net increase in iron excretion and altering iron balance. Interestingly, 2,3-dihydroxybenzoic acid has been previously tested in iron-loaded thalassaemia patients, leading to substantial increases in iron excretion. The daily administration of low-dose aspirin for long-term periods is likely to enhance the overall iron excretion in small increments each time due to the combined iron mobilization effect of the ACM. In particular, IDA is likely to occur mainly in populations such as elderly vegetarian adults with meals low in iron content. Furthermore, IDA may be exacerbated by the combinations of ACM with other dietary components, which can prevent iron absorption and enhance iron excretion. Overall, aspirin is acting as a chelating pro-drug similar to dexrazoxane, and the ACM as combination chelation therapy. Iron balance, pharmacological, and other studies on the interaction of iron and aspirin, as well as ACM, are likely to shed more light on the mechanism of IDA. Similar mechanisms of iron chelation through ACM may also be implicated in patient improvements observed in cancer, neurodegenerative, and other disease categories when treated long-term with daily aspirin. In particular, the role of aspirin and ACM in iron metabolism and free radical pathology includes ferroptosis, and may identify other missing links in the therapeutic effects of aspirin in many more diseases. It is suggested that aspirin is the first non-chelating drug described to cause IDA through its ACM metabolites. The therapeutic, pharmacological, toxicological and other implications of aspirin are incomplete without taking into consideration the iron binding and other effects of the ACM.
Pinus thunbergii Parl. Somatic Plants’ Resistance to Bursaphelenchus xylophilus Depends on Pathogen-Induced Differential Transcriptomic Responses
Authors: Sun Tingyu , Wang Yahui , Wu Xiaoqin , Wang Yang , Yang Aixia , Ye Jianren
Published: May 2024

Pinus thunbergii Parl. is an economically and medicinally important plant, as well as a world-renowned horticultural species of the Pinus genus. Pine wilt disease is a dangerous condition that affects P. thunbergii. However, understanding of the genetics underlying resistance to this disease is poor. Our findings reveal that P. thunbergii’s resistance mechanism is based on differential transcriptome responses generated by the early presence of the pathogen Bursaphelenchus xylophilus, also known as the pine wood nematode. A transcriptome analysis (RNA-seq) was performed to examine gene expression in shoot tissues from resistant and susceptible P. thunbergii trees. RNA samples were collected from the shoots of inoculated pines throughout the infection phases by the virulent Bursaphelenchus xylophilus AMA3 strain. The photosynthesis and plant–pathogen interaction pathways were significantly enriched in the first and third days after infection. Flavonoid biosynthesis was induced in response to late infestation (7 and 14 days post-infestation). Calmodulin, RBOH, HLC protein, RPS, PR1, and genes implicated in phytohormone crosstalk (e.g., SGT1, MYC2, PP2C, and ERF1) showed significant alterations between resistant and susceptible trees. Furthermore, salicylic acid was found to aid pine wood nematodes tolerate adverse conditions and boost reproduction, which may be significant for pine wood nematode colonization within pines. These findings provide new insights into how host defenses overcame pine wood nematode infection in the early stage, which could potentially contribute to the development of novel strategies for the control of pine wilt disease.
Design and Characterization of Highly Diffusive Turbine Vanes Suitable for Transonic Rotating Detonation Combustors
Authors: Grasa Sergio , Paniagua Guillermo
Published: May 2024

In rotating detonation engines the turbine inlet conditions may be transonic with unprecedented unsteady fluctuations. To ensure an acceptable engine performance, the turbine passages must be suited to these conditions. This article focuses on designing and characterizing highly diffusive turbine vanes to operate at any inlet Mach number up to Mach 1. First, the effect of pressure loss on the starting limit is presented. Afterward, a multi-objective optimization with steady RANS simulations, including the endwall and 3D vane design is performed. Compared to previous research, significant reductions in pressure loss and stator-induced rotor forcing are obtained, with an extended operating range and preserving high flow turning. Finally, the influence of the inlet boundary layer thickness on the vane performance is evaluated, inducing remarkable increases in pressure loss and downstream pressure distortion. Employing an optimization with a thicker inlet boundary layer, specific endwall design recommendations are found, providing a notable improvement in both objective functions.
Modeling- and Simulation-Driven Methodology for the Deployment of an Inland Water Monitoring System
Authors: Andrade Giordy A. , Esteban Segundo , Risco-Martín José L. , Chacón Jesús , Besada-Portas Eva
Published: May 2024

In response to the challenges introduced by global warming and increased eutrophication, this paper presents an innovative modeling and simulation (M&S)-driven model for developing an automated inland water monitoring system. This system is grounded in a layered Internet of Things (IoT) architecture and seamlessly integrates cloud, fog, and edge computing to enable sophisticated, real-time environmental surveillance and prediction of harmful algal and cyanobacterial blooms (HACBs). Utilizing autonomous boats as mobile data collection units within the edge layer, the system efficiently tracks algae and cyanobacteria proliferation and relays critical data upward through the architecture. These data feed into advanced inference models within the cloud layer, which inform predictive algorithms in the fog layer, orchestrating subsequent data-gathering missions. This paper also details a complete development environment that facilitates the system lifecycle from concept to deployment. The modular design is powered by Discrete Event System Specification (DEVS) and offers unparalleled adaptability, allowing developers to simulate, validate, and deploy modules incrementally and cutting across traditional developmental phases.
Performance Comparison of Five Methods Available in ImageJ for Bird Counting and Detection from Video Datasets
Authors: Kurnia Kevin Adi , Saputra Ferry , Luong Cao Thang , Roldan Marri Jmelou M. , Cheng Tai-Sheng , Hsiao Chung-Der
Published: May 2024

Bird monitoring is an important approach to studying the diversity and abundance of birds, especially during migration, as it can provide core data for bird conservation purposes. The previous methods for bird number estimation are largely based on manual counting, which suffers from low throughput and a high error rate. In this study, we aimed to provide an alternative bird-counting method from video datasets by using five available ImageJ methods: Particle Analyzer, Find Maxima, Watershed segmentation, TrackMate, and trainable WEKA segmentation. The numbers of birds and their XY coordinates were extracted from videos to conduct a side-by-side comparison with the manual counting results, and the three important criteria of the sensitivity, precision, and F1 score were calculated for the performance evaluation. From the tests, which we conducted for four different cases with different bird numbers or flying patterns, TrackMate had the best overall performance for counting birds and pinpointing their locations, followed by Particle Analyzer, Find Maxima, WEKA, and lastly, Watershed, which showed low precision in most of the cases. In summary, five ImageJ-based counting methods were compared in this study, and we validated that TrackMate obtains the best performance for bird counting and detection.