bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Epigenetics in Brain Aneurysm and Subarachnoid Hemorrhage: A Comprehensive Review
Authors: Fernández-Pérez Isabel , Macias-Gómez Adrià , Suárez-Pérez Antoni , Vallverdú-Prats Marta , Giralt-Steinhauer Eva , Bojtos Lidia , Susin-Calle Sílvia , Rodriguez-Campello Ana , Guisado-Alonso Daniel , Jimenez-Balado Joan , Jiménez-Conde Jordi , Cuadrado-Godia Elisa
Published: March 2024

This comprehensive review explores the emerging field of epigenetics in intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (aSAH). Despite recent advancements, the high mortality of aSAH needs an understanding of its underlying pathophysiology, where epigenetics plays a crucial role. This review synthesizes the current knowledge, focusing on three primary epigenetic mechanisms: DNA methylation, non-coding RNA (ncRNA), and histone modification in IA and aSAH. While DNA methylation studies are relatively limited, they suggest a significant role in the pathogenesis and prognosis of IA and aSAH, highlighting differentially methylated positions in genes presumably involved in these pathologies. However, methodological limitations, including small sample sizes and a lack of diverse population studies, temper these results. The role of ncRNAs, particularly miRNAs, has been more extensively studied, but there are still few studies focused on histone modifications. Despite methodological challenges and inconsistent findings, these studies underscore the involvement of miRNAs in key pathophysiological processes, including vascular smooth muscle regulation and the inflammatory response. This review emphasizes methodological challenges in epigenetic research, advocating for large-scale epigenome-wide association studies integrating genetic and environmental factors, along with longitudinal studies. Such research could unravel the complex mechanisms behind IA and aSAH, guiding the development of targeted therapeutic approaches.
Systematic Identification of Long Noncoding RNAs during Three Key Organogenesis Stages in Zebrafish
Authors: Zhou Chune , Li Mengting , Sun Yaoyi , Sultan Yousef , Li Xiaoyu
Published: March 2024

Thousands of lncRNAs have been found in zebrafish embryogenesis and adult tissues, but their identification and organogenesis-related functions have not yet been elucidated. In this study, high-throughput sequencing was performed at three different organogenesis stages of zebrafish embryos that are important for zebrafish muscle development. The three stages were 10 hpf (hours post fertilization) (T1), 24 hpf (T2), and 36 hpf (T3). LncRNA gas5, associated with muscle development, was screened out as the next research target by high-throughput sequencing and qPCR validation. The spatiotemporal expression of lncRNA gas5 in zebrafish embryonic muscle development was studied through qPCR and in situ hybridization, and functional analysis was conducted using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9, CRISPR/Cas9). The results were as follows: (1) A total of 1486 differentially expressed lncRNAs were identified between T2 and T1, among which 843 lncRNAs were upregulated and 643 were downregulated. The comparison with T3 and T2 resulted in 844 differentially expressed lncRNAs, among which 482 lncRNAs were upregulated and 362 lncRNAs were downregulated. A total of 2137 differentially expressed lncRNAs were found between T3 and T1, among which 1148 lncRNAs were upregulated and 989 lncRNAs were downregulated, including lncRNA gas5, which was selected as the target gene. (2) The results of spatiotemporal expression analysis showed that lncRNA gas5 was expressed in almost all detected embryos of different developmental stages (0, 2, 6, 10, 16, 24, 36, 48, 72, 96 hpf) and detected tissues of adult zebrafish. (3) After lncRNA gas5 knockout using CRISPR/Cas9 technology, the expression levels of detected genes related to muscle development and adjacent to lncRNA gas5 were more highly affected in the knockout group compared with the control group, suggesting that lncRNA gas5 may play a role in embryonic muscle development in zebrafish. (4) The results of the expression of the skeletal myogenesis marker myod showed that the expression of myod in myotomes was abnormal, suggesting that skeletal myogenesis was affected after lncRNA gas5 knockout. The results of this study provide an experimental basis for further studies on the role of lncRNA gas5 in the embryonic skeletal muscle development of zebrafish.
Establishment of Murine Pregnancy Requires the Promyelocytic Leukemia Zinc Finger Transcription Factor
Authors: Hai Lan , Maurya Vineet K. , DeMayo Francesco J. , Lydon John P.
Published: March 2024

Using an established human primary cell culture model, we previously demonstrated that the promyelocytic leukemia zinc finger (PLZF) transcription factor is a direct target of the progesterone receptor (PGR) and is essential for progestin-dependent decidualization of human endometrial stromal cells (HESCs). These in vitro findings were supported by immunohistochemical analysis of human endometrial tissue biopsies, which showed that the strongest immunoreactivity for endometrial PLZF is detected during the progesterone (P4)-dominant secretory phase of the menstrual cycle. While these human studies provided critical clinical support for the important role of PLZF in P4-dependent HESC decidualization, functional validation in vivo was not possible due to the absence of suitable animal models. To address this deficiency, we recently generated a conditional knockout mouse model in which PLZF is ablated in PGR-positive cells of the mouse (Plzf d/d). The Plzf d/d female was phenotypically analyzed using immunoblotting, real-time PCR, and immunohistochemistry. Reproductive function was tested using the timed natural pregnancy model as well as the artificial decidual response assay. Even though ovarian activity is not affected, female Plzf d/d mice exhibit an infertility phenotype due to an inability of the embryo to implant into the Plzf d/d endometrium. Initial cellular and molecular phenotyping investigations reveal that the Plzf d/d endometrium is unable to develop a transient receptive state, which is reflected at the molecular level by a blunted response to P4 exposure with a concomitant unopposed response to 17-β estradiol. In addition to a defect in P4-dependent receptivity, the Plzf d/d endometrium fails to undergo decidualization in response to an artificial decidual stimulus, providing the in vivo validation for our earlier HESC culture findings. Collectively, our new Plzf d/d mouse model underscores the physiological importance of the PLZF transcription factor not only in endometrial stromal cell decidualization but also uterine receptivity, two uterine cellular processes that are indispensable for the establishment of pregnancy.
Monitoring the Season–Prevalence Relationship of Vairimorpha ceranae in Honey Bees (Apis mellifera) over One Year and the Primary Assessment of Probiotic Treatment in Taichung, Taiwan
Authors: Li Yi-Hsuan , Chen Yu-Hsin , Chang Fang-Min , Wu Ming-Cheng , Nai Yu-Shin
Published: March 2024

Microsporidiosis, which is caused by the pathogen Vairimorpha ceranae, is a prevalent disease in the honey bee (Apis mellifera) and might lead to significant adult honey bee mortality. In this study, we conducted an annual survey of the mature spore load of V. ceranae in the guts of nurse bees and forager bees in the apiary of National Chung Hsing University (NCHU) in Taiwan. The results indicated that, on average, honey bees hosted approximately 2.13 × 106 mature spore counts (MSCs)/bee in their guts throughout the entire year. The highest number of MSCs was 6.28 × 106 MSCs/bee, which occurred in April 2020, and the lowest number of MSCs was 5.08 × 105 MSCs/bee, which occurred in November 2020. Furthermore, the guts of forager bees had significantly higher (>58%) MSCs than those of nurse bees. To evaluate the potential of the probiotic to treat microsporidiosis, the lactic acid bacterium Leuconostoc mesenteroides TBE-8 was applied to honey bee colonies. A significant reduction (>53%) in MSCs following probiotic treatment was observed, indicating the potential of probiotic treatment for managing microsporidiosis. This research provided information on V. ceranae MSCs in the honey bee gut at NCHU in Taiwan and the MSCs’ correlation with the annual season. Furthermore, a potential probiotic treatment for microsporidiosis was assessed for future management.
The Efficacy and Effectiveness of the Biological Treatment of Pruritus in the Course of Atopic Dermatitis
Authors: Hołdrowicz Agnieszka Marta , Woźniacka Anna
Published: March 2024

Atopic dermatitis is a heterogenous inflammatory disease with high variety in terms of clinical symptoms and etiopathogenesis, occurring both in pediatric and adult populations. The clinical manifestation of atopic dermatitis varies depending on the age of patients, but all age groups share certain common features, such as a chronic and recurrent course of disease, pruritus, and a co-occurrence of atopic diseases in personal or family medical history. Treating pruritus is a high priority due to its incidence rate in atopic dermatitis and substantial impact on quality of life. In recent years, treatments with biological drugs have increased the range of therapeutic possibilities in atopic dermatitis. The aim of the study is to present the safety profile, efficacy, and effectiveness of various biological treatment methods for the therapy of pruritus in the course of atopic dermatitis.
Using Electric Stimulation of the Spinal Muscles and Electromyography during Motor Tasks for Evaluation of the Role in Development and Progression of Adolescent Idiopathic Scoliosis
Authors: Wong Christian , Shayestehpour Hamed , Koutras Christos , Dahl Benny , Otaduy Miguel A. , Rasmussen John , Bencke Jesper
Published: March 2024

Introduction: The role of the spinal muscles in scoliogenesis is not fully substantiated. Do they act scoliogenic (inducing scoliosis) or counteract scoliosis in adolescent idiopathic scoliosis (AIS)? In this study, we will examine this by using selectively placed Transcutaneous Electric Stimulation (TES) combined with a cinematic radiographic technique and by performing electromyographic (EMG) evaluations during various motor tasks. Method: This is a cross-sectional study of subjects with small-curve AIS. Using cinematic radiography, they were evaluated dynamically either under electrical stimulation or when performing motor tasks of left and right lateral bending and rotation whilst measuring the muscle activity by EMG. Results: Forty-five patients with AIS were included as subjects. Five subjects volunteered for TES and six subjects performed the motor tasks with EMG. At the initial visual evaluation, and when stimulated with TES, the frontal plane spatial positions of the vertebral bodies showed discrete changes without an apparent pattern. However, analyzing the spatial positions when calibrated, we found that the spinal muscles exert a compressive ‘response’ with a minor change in the Cobb angle (CA) in small-curve AIS (CA = 10–20°). In larger curves (CA > 20°), TES induced a ‘larger deformity’ with a relative four-fold change in the CA compared to small-curve AIS with a ratio of 0.6. When evaluating local amplitude (peak) or cumulative (mean) EMG signals, we were unable to find consistent asymmetries. However, one subject had rapid progression and one regressed to a straight spine. When adding the absolute EMG ratios for all four motor tasks, the subject with progression had almost 10-fold less summed EMG ratios, and the subject with regression had more than 3-fold higher summed EMG ratios. Discussion: Based on these findings, we suggest that the spinal muscles in small-curve AIS have a stabilizing function maintaining a straight spine and keeping it in the midline. When deformities are larger (CA > 20°), the spine muscle curve exerts a scoliogenic ‘response’. This suggests that the role of the muscles converts from counteracting AIS and stabilizing the spine to being scoliogenic for a CA of more than 20°. Moreover, we interpret higher EMG ratios as heightened asymmetric spinal muscle activity when the spinal muscles try to balance the spine to maintain or correct the deformity. When progression occurs, this is preceded or accompanied by decreased EMG ratios. These findings must be substantiated by larger studies.
Current State of Molecular Cytology in Thyroid Nodules: Platforms and Their Diagnostic and Theranostic Utility
Authors: Hannoush Zeina C. , Ruiz-Cordero Roberto , Jara Mark , Kargi Atil Y.
Published: March 2024

The high prevalence of thyroid nodules and increased availability of neck ultrasound have led to an increased incidence of diagnostic thyroid fine needle aspirations, with approximately 20% yielding indeterminate results. The recent availability of molecular tests has helped guide the clinical management of these cases. This paper aims to review and compare three main commercially available molecular cytology platforms in the U.S.—Afirma GSC, Thyroseq GC, and ThyGeNEXT + ThyraMIR. Sequential improvements of the Afirma GSC and Thyroseq GC tests have increased positive and negative predictive values, sensitivity, and specificity. Comparative studies revealed similar diagnostic performance between these tests, with considerations for factors such as cost and processing time. Thyroseq GC provides detailed genomic information and specific management recommendations. ThyGeNEXT + ThyraMIR, though less studied, presents promising results, particularly in miRNA analysis for weak driver mutations. Challenges in interpreting results include variations in reporting and the evolving nature of testing platforms. Questions persist regarding cost-effectiveness and the utility of ultrasound characteristics in selecting candidates for molecular testing. While molecular testing has primarily served diagnostic purposes, advancements in understanding genetic alterations now offer therapeutic implications. FDA-approved options target specific genetic alterations, signaling a promising future for tailored treatments.
The Incidence of Screw Failure in Fenestrated Polyaxial Pedicle Screws vs. Conventional Pedicle Screws in the Treatment of Adolescent Idiopathic Scoliosis (AIS)
Authors: Velluto Calogero , Inverso Michele , Borruto Maria Ilaria , Perna Andrea , Bocchino Guido , Messina Davide , Proietti Luca
Published: March 2024

Background: Adolescent idiopathic scoliosis (AIS) is a spinal pathology affecting 0.47–5.2% of the population, often requiring surgical intervention to control deformity progression. Posterior spinal instrumentation and fusion with pedicle screw fixation are standard procedures for AIS curve correction; however, implant failure remains a significant complication, especially in multi-level fusions. This retrospective cohort study aims to compare the failure rates between conventional pedicle screws (CPSs) and fenestrated pedicle screws (FPSs) in AIS treatment, with a focus on investigating potential causes of these failures. Methods: This study, conducted from January 2016 to December 2020, involves a two-center retrospective analysis of AIS patients undergoing posterior instrumented fusion. Results: Data from a total of 162 patients (122 females and 40 males) revealed a mean age of 14.95 years (range: 11–18). The CPS group consisted of 80 patients (56 females and 24 males), whereas the FPS group consisted of 82 patients (66 females and 16 males) stratified by Risser grade and Lenke Classification. Radiological assessments, clinical outcomes, and SRS-22 scores were evaluated pre-operatively, at 6 months, and post-operatively (minimum follow-up of 2 years). Conclusions: Fenestrated pedicle screws (FPSs) pose concerns due to their lower mechanical strength compared to solid screws. Understanding their limitations and optimizing their application in AIS treatment is essential.
A User Interface Design Framework for Augmented-Reality-Supported Maritime Navigation
Authors: Nordby Kjetil , Fauske Jon Erling , Gernez Etienne , Mallam Steven
Published: March 2024

Augmented reality (AR) technology has emerged as a promising solution that can potentially reduce head-down time and increase situational awareness during navigation operations. It is also useful for remote operation centers where video feeds from remote ships can be “augmented” with data and information. In this article, we introduce a user interface design concept that supports ship navigation by showing data about points of interest in AR. This approach enables users to view and interact with relevant data in the maritime environment by bridging the gap between digital information and real-world features. The proposed concept can provide operational data from various maritime systems, such as radar, GPS, AIS, or camera systems, empowering users with a wealth of information about their surroundings. Developed through an iterative user-centered design process, it was built as an extension to the OpenBridge design system, an open-source platform facilitating consistent design in maritime workplaces. Furthermore, we use this concept to propose a design framework that paves the way for establishing new standards for AR user interface design in the maritime domain.
Sensitivity Analysis and Uncertainty Quantification of Nanoparticle Deposition from Tongue Morphological Variations
Authors: Yang Tiancheng , Si Xiuhua , Xi Jinxiang
Published: March 2024

The human tongue has highly variable morphology. Its role in regulating respiratory flows and deposition of inhaled aerosols remains unclear. The objective of this study was to quantify the uncertainty of nanoparticle deposition from the variability in tongue shapes and positions and to rank the importance of these morphological factors. Oropharyngeal models with different tongue postures were reconstructed by modifying an existent anatomically accurate upper airway geometry. An LRN k-ω model was applied to solve the multiregime flows, and the Lagrangian tracking approach with near-wall treatment was used to simulate the behavior and fate of inhaled aerosols. Once the database of deposition rates was completed, a surrogate model was trained using Gaussian process regression with polynomial kernels and was validated by comparing its predictions to new CFD simulations. Input sensitivity analysis and output updateability quantification were then performed using the surrogate model. Results show that particle size is the most significant parameter in determining nanoparticle deposition in the upper airway. Among the morphological factors, the shape variations in the central tongue had a higher impact on the total deposition than those in the back tongue and glottal aperture. When considering subregional deposition, mixed sensitivity levels were observed among morphological factors, with the back tongue being the major factor for throat deposition and the central tongue for oral deposition. Interaction effects between flow rate and morphological factors were much higher than the effects from individual parameters and were most significant in the throat (pharyngolaryngeal region). Given input normal variances, the nanoparticle deposition exhibits logarithmical normal distributions, with much lower uncertainty in 100-nm than 2-nm aerosols.
High-Performance Organic Field-Effect Transistors of Liquid Crystalline Organic Semiconductor by Laser Mapping Annealing
Authors: Huang Luying , Liu Fenghua , Bao Jiachen , Li Xiaoman , Wu Weiping
Published: March 2024

Organic semiconductors (OSCs), especially small molecule semiconductors, have received increasing attention due to their good designability and variability. Phase transitions and interfacial properties have a decisive influence on device performance. Here, 2-Dodecyl-7-phenyl[1]benzothieno[3,2-b][1]benzothiophene (Ph-BTBT-12) devices are treated with low-power laser annealing, which is able to avoid the influence of the dewetting effect on the hole mobility of organic semiconductor materials. Ultraviolet ozone treatment and self-assembled monolayer treatment can improve the performance and stability of the device. Moreover, after low-temperature thermal annealing, the hole mobility of the device can even reach as high as 4.80 cm2 V−1 s−1, and we tested the optical response of the device to the ultraviolet wavelength and found that its maximum optical responsivity was 8.2 AW−1.
Trajectory Tracking Control Based on a Composite Disturbance Observer for Unmanned Autonomous Helicopters under Multiple Disturbances
Authors: Pan Shihao , Wang Ting , Zhang Haoran , Li Tao
Published: March 2024

This paper studies the trajectory tracking anti-disturbance control of unmanned autonomous helicopters (UAHs) under matched disturbances and mismatched ones. Firstly, the six-degrees-of-freedom UAH nonlinear system is simplified via feedback linearization to handle strong coupling, in which the multiple disturbances are composed of modeled disturbances and time-varying bounded ones. Secondly, in order to estimate these disturbances, a new design method of a composite disturbance observer is proposed. On the one hand, for the mismatched disturbances, a normal disturbance observer (DO) combined with a backstepping control are utilized to handle their negative effect. On the other hand, two refined disturbance observers (RDOs) are constructed to estimate the matched disturbances, in which the coupling estimations are involved. Then, by designing two anti-disturbance composite controllers, the boundedness of the tracking errors is guaranteed by using the Lyapunov stability theory. Finally, some numerical simulations are provided to demonstrate the effectiveness and advantage of the proposed control scheme.
Atrial Pacing Negatively Affects Left Atrial Morphological and Functional Parameters Similarly to Atrioventricular Dyssynchrony
Authors: Viezelis Mindaugas , Neverauskaite-Piliponiene Gintare , Marcinkeviciene Agne , Kazakevicius Tomas , Zabiela Vytautas , Kviesulaitis Vilius , Jurkevicius Renaldas , Puodziukynas Aras
Published: March 2024

Background and Objectives: Atrioventricular (AV) dyssynchrony as well as atrial and ventricular pacing affect left atrial (LA) function. We conducted a study evaluating the effect of atrial and ventricular pacing on LA morphological and functional changes after dual-chamber pacemaker implantation. Materials and Methods: The study prospectively enrolled 121 subjects who had a dual-chamber pacemaker implanted due to sinus node disease (SND) or atrioventricular block (AVB). Subjects were divided into three groups based on indication and pacemaker programming: (1) SND DDDR 60; (2) AVB DDD 60 and (3) AVB DDD 40. Subjects were invited to one- and three-month follow-up visits. Three subsets based on pacing burden were analyzed: (1) high atrial (A) low ventricular (V); (2) high A, high V and (3) low A, high V. LA function was assessed from volumetric parameters and measured strains from echocardiography. Results: The high A, low V group consisted of 38 subjects; while high A, high V had 26 and low A, high V had 23. A significant decrease in reservoir and contractile LA strain parameters were only observed in the high A, low V pacing group after three months (reservoir 25.9 ± 10.3% vs. 21.1 ± 9.9%, p = 0.003, contractile −14.0 ± 9.0% vs. −11.1 ± 7.8, p = 0.018). While the re-established atrioventricular synchrony in the low A, high V group maintained reservoir LA strain at the baseline level after three months (21.4 ± 10.4% vs. 22.5 ± 10.4%, p = 0.975); in the high A, high V group, a further trend to decrease was noted (20.3 ± 8.9% vs. 18.7 ± 8.3%, p = 0.231). Conclusions: High atrial pacing burden independently of atrioventricular dyssynchrony and ventricular pacing impairs LA functional and morphological parameters. Changes appear soon after pacemaker implantation and are maintained.
Pituitary Adenoma in the Philippines: A Scoping Review on the Treatment Gaps, Challenges, and Current State of Care
Authors: Tabuzo Mykha Marie B. , Hernandez Mary Angeline Luz U. , Chua Annabell E. , Maningat Patricia D. , Chiu Harold Henrison C. , Jamora Roland Dominic G.
Published: March 2024

Background: Pituitary adenomas are benign brain tumors that impose a heavy burden on patients worldwide. The local burden of disease is yet to be established due to scarcity of data. In line with this, this study aims to present the challenges and gaps in the treatment of pituitary adenomas in the Philippines. Methods: A scoping review of available relevant literature on epidemiology, clinical experience with treatment, health financing, and healthcare delivery system based on the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for Scoping Reviews was conducted. Results: The scarcity of updated local clinical data, inequity of distribution of resources, inadequate government support, and lack of affordable diagnostic testing, medications, and neurosurgical procedures are the factors that hinder provision of adequate care of pituitary adenomas in the Philippines. Conclusion: There are notable treatment gaps in the management of pituitary adenomas in the Philippines, which may be addressed by strengthening universal healthcare. Strategies to address these gaps were proposed, including improving public-private insurance coverage, increasing manpower, enhancing accessibility to resources, and spreading more awareness.
Mechanical Properties and Fracture Toughness Prediction of Ductile Cast Iron under Thermomechanical Treatment
Authors: Abdellah Mohammed Y. , Alharthi Hamzah , Alfattani Rami , Suker Dhia K. , Abu El-Ainin H. M. , Mohamed Ahmed F. , Hassan Mohamed K. , Backar Ahmed H.
Published: March 2024

Temperature has a great influence on the mechanical properties of ductile cast iron or nodular cast iron. A thermomechanical treatment was carried out at various elevated temperatures of 450 °C, 750 °C and 850 °C using a universal testing machine with a tub furnace. Specimens were held at these temperatures for 20 min to ensure a homogeneous temperature distribution along the entire length of the specimen, before a tensile load was applied. Specimens were deformed to various levels of uniform strain (0%, 25%, 50%, 75%, and 100%). These degrees of deformation were measured with a dial gauge attached to a movable cross plate. Three strain rates were used for each specimen and temperature: 1.8×10−4 s−1, 9×10−4 s−1 and 4.5×10−3 s−1. A simple analytical model was extracted based on the CT tensile test geometry and yield stress and a 0.2% offset strain to measure the fracture toughness (JIC). To validate the analytical model, an extended finite element method (XFEM) was implemented for specimens tested at different temperatures, with a strain rate of 1.8×10−4 s−1. The model was then extended to include the tested specimens at other strain rates. The results show that increasing strain rates and temperature, especially at 850 °C, increased the ductility of the cast iron and thus its formability. The largest percentage strains were 1 and 1.5 at a temperature of 750 °C and a strain rate of 1.8×10−4 s−1 and 9×10−4 s−1, respectively, and reached their maximum value of 1.7 and 2.2% at 850 °C and a strain rate of 9×10−4 s−1 and 4.5×10−3 s−1, respectively. In addition, the simple and fast analytical model is useful in selecting materials for determining the fracture toughness (JIC) at various elevated temperatures and different strain rates.
The Influence of Yttrium Content and Ceramic Crucible Materials on Desulfurization during Vacuum Induction Melting of DD5 Superalloys
Authors: Wang Fuwei , Cheng Ying , Zhang Shoubin , Zhang Rui , Sun Yanyun , Guan Kai , Zhang Huarui , Zhang Hu
Published: March 2024

In this study, the effect of adding different contents of yttrium (Y) during vacuum induction melting in Al2O3 and Y2O3 crucibles on the purification of DD5 alloys was investigated. The results show that the Y2O3 crucible exhibited great crucible stability and an excellent desulfurization effect when melting a Y-containing DD5 alloy. The S content of the alloy was reduced from 5.03 ppm to 1.36 ppm with the addition of 0.50 wt.% Y. Element Y combined with free S in the melt to form the YS phase, which was removed from the condensate shell and slag during the vacuum induction melting (VIM) process. Meanwhile, when the alloy was melted in the Y2O3 crucible with 0.50 wt.% Y addition, there was a reduction in S content from 2.77 ppm to 1.36 ppm compared to the Al2O3 crucible. Additionally, the loss of Y decreased from 0.12 wt.% to 0.05 wt.%.
Back to the Future: Immune Protection or Enhancement of Future Coronaviruses
Authors: Bartels Merit , Sala Solé Eric , Sauerschnig Lotte M. , Rijkers Ger T.
Published: March 2024

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently, SARS-CoV-2, four other coronaviruses (the alpha coronaviruses NL63 and 229E and the beta coronaviruses OC43 and HKU1) had already been circulating in the human population. These circulating coronaviruses all cause mild respiratory illness during the winter seasons, and most people are already infected in early life. Could antibodies and/or T cells, especially against the beta coronaviruses, have offered some form of protection against (severe) COVID-19 caused by infection with SARS-CoV-2? Related is the question of whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory generated during the SARS-CoV-2 pandemic, either by infection or vaccination, offer protection against future coronaviruses? Or rather than protection, could antibody-dependent enhancement have taken place, a mechanism by which circulating corona antibodies enhance the severity of COVID-19? Another related phenomenon, the original antigenic sin, would also predict that the effectiveness of the immune response to future coronaviruses would be impaired because of the reactivation of memory against irrelevant epitopes. The currently available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.
Digital Technology Applications in the Management of Adverse Drug Reactions: Bibliometric Analysis
Authors: Litvinova Olena , Yeung Andy Wai Kan , Hammerle Fabian Peter , Mickael Michel-Edwar , Matin Maima , Kletecka-Pulker Maria , Atanasov Atanas G. , Willschke Harald
Published: March 2024

Adverse drug reactions continue to be not only one of the most urgent problems in clinical medicine, but also a social problem. The aim of this study was a bibliometric analysis of the use of digital technologies to prevent adverse drug reactions and an overview of their main applications to improve the safety of pharmacotherapy. The search was conducted using the Web of Science database for the period 1991–2023. A positive trend in publications in the field of using digital technologies in the management of adverse drug reactions was revealed. A total of 72% of all relevant publications come from the following countries: the USA, China, England, India, and Germany. Among the organizations most active in the field of drug side effect management using digital technologies, American and Chinese universities dominate. Visualization of publication keywords using VOSviewer software 1.6.18 revealed four clusters: “preclinical studies”, “clinical trials”, “pharmacovigilance”, and “reduction of adverse drug reactions in order to improve the patient’s quality of life”. Molecular design technologies, virtual models for toxicity modeling, data integration, and drug repurposing are among the key digital tools used in the preclinical research phase. Integrating the application of machine learning algorithms for data analysis, monitoring of electronic databases of spontaneous messages, electronic medical records, scientific databases, social networks, and analysis of digital device data into clinical trials and pharmacovigilance systems, can significantly improve the efficiency and safety of drug development, implementation, and monitoring processes. The result of combining all these technologies is a huge synergistic provision of up-to-date and valuable information to healthcare professionals, patients, and health authorities.
The Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings
Authors: De Silva D. Thisuri N. , Strunk Tobias , Petrovski Michael , Page-Sharp Madhu , Moore Brioni R. , Batty Kevin T.
Published: March 2024

Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures. Physical compatibility was evaluated by visual observation against a black and white background and under polarized light for two hours for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from sildenafil concentrations, using a validated, stability-indicating high-performance liquid chromatography assay. Sildenafil 600 mcg/mL was physicochemically compatible with 29 of the 45 drugs tested at ‘high-end’ clinical concentrations and physically incompatible with 16 drugs and six ‘2-in-1’ parenteral nutrition solutions. Sildenafil 600 mcg/mL was compatible with lower, clinically relevant concentrations of calcium gluconate, heparin and hydrocortisone. Aciclovir, amoxicillin, ampicillin, ibuprofen lysine, indometacin, phenobarbitone and rifampicin were incompatible with sildenafil 600 mcg/mL, however these IV medications were compatible with sildenafil 60 mcg/mL. Sildenafil 600 mcg/mL and 60 mcg/mL were incompatible with amphotericin, flucloxacillin, furosemide, ibuprofen, meropenem and sodium bicarbonate. Sildenafil compatibility with commonly used syringe filters was also investigated. Sildenafil solution was compatible with nylon syringe filters, however, absorption/adsorption loss occurred with polyethersulfone and cellulose ester filters.
Intracellular Delivery of Therapeutic Protein via Ultrathin Layered Double Hydroxide Nanosheets
Authors: Zhang He , Ge Anle , Wang Yulin , Xia Boran , Wang Xichu , Zheng Zhonghui , Wei Changsheng , Ma Bo , Zhu Lin , Amal Rose , Yun Sung Lai Jimmy , Gu Zi
Published: March 2024

The therapeutic application of biofunctional proteins relies on their intracellular delivery, which is hindered by poor cellular uptake and transport from endosomes to cytoplasm. Herein, we constructed a two-dimensional (2D) ultrathin layered double hydroxide (LDH) nanosheet for the intracellular delivery of a cell-impermeable protein, gelonin, towards efficient and specific cancer treatment. The LDH nanosheet was synthesized via a facile method without using exfoliation agents and showed a high loading capacity of proteins (up to 182%). Using 2D and 3D 4T1 breast cancer cell models, LDH–gelonin demonstrated significantly higher cellular uptake efficiency, favorable endosome escape ability, and deep tumor penetration performance, leading to a higher anticancer efficiency, in comparison to free gelonin. This work provides a promising strategy and a generalized nanoplatform to efficiently deliver biofunctional proteins to unlock their therapeutic potential for cancer treatment.
Narrow Linewidth 510 nm Laser via Single-Pass Frequency-Tripling by Waveguide PPLNs
Authors: Chen Yanlin , Zhang Jing , Qiu Xiaolang , Wang Suo , Li Chuanchuan , Yu Haiyang , Wei Xin
Published: March 2024

A single-frequency narrow linewidth green laser at 510 nm is a vital component for the study of Cesium Rydberg atoms. Here, we demonstrate a 510 nm laser based on single-pass second-harmonic generation (SHG) and sum-frequency generation (SFG) via waveguide Periodically Poled Lithium Niobate (PPLN) seeded with a common C-band laser (1530 nm). The final linewidth measured using the delayed self-heterodyne method reaches a narrow linewidth of 4.8 kHz. And, the optical-to-optical conversion efficiency is up to 13.1% and reaches an output power up to 200 mW.
Exogenous 24-Epibrassinolide Enhanced Drought Tolerance and Promoted BRASSINOSTEROID-INSENSITIVE2 Expression of Quinoa
Authors: Zhou Ya-Li , You Xin-Yong , Wang Xing-Yun , Cui Li-Hua , Jiang Zhi-Hui , Zhang Kun-Peng
Published: March 2024

Brassinosteroids (BRs) are involved in the regulation of biotic and abiotic stresses in plants. The molecular mechanisms of BRs that alleviate the drought stress in quinoa have rarely been reported. Here, quinoa seedlings were treated with 24-epibrassinolide (EBR) and we transiently transferred CqBIN2 to the quinoa seedlings’ leaves using VIGS technology to analyze the molecular mechanism of the BR mitigation drought stress. The results showed that EBR treatment significantly increased the root growth parameters, the antioxidant enzyme activities, and the osmolyte content, resulting in a decrease in the H2O2, O2∙−, and malondialdehyde content in quinoa. A transcriptome analysis identified 8124, 2761, and 5448 differentially expressed genes (DEGs) among CK and Drought, CK and EBR + Drought, and Drought and EBR + Drought groups. WGCNA divided these DEGs into 19 modules in which these characterized genes collectively contributed significantly to drought stress. In addition, the EBR application also up-regulated the transcript levels of CqBIN2 and proline biosynthesis genes. Silenced CqBIN2 by VIGS could reduce the drought tolerance, survival rate, and proline content in quinoa seedlings. These findings not only revealed that exogenous BRs enhance drought tolerance, but also provided insight into the novel functions of CqBIN2 involved in regulating drought tolerance in plants.
Transcriptomic Analysis for Diurnal Temperature Differences Reveals Gene-Regulation-Network Response to Accumulation of Bioactive Ingredients of Protocorm-like Bodies in Dendrobium officinale
Authors: Chen Qingqing , Zhang Chunyu , Chen Yukun , Wang Congqiao , Lai Zhongxiong
Published: March 2024

Dendrobium officinale Kimura et Migo (D. officinale) is one of the most important traditional Chinese medicinal herbs, celebrated for its abundant bioactive ingredients. This study demonstrated that the diurnal temperature difference (DIF) (T1: 13/13 °C, T2: 25/13 °C, and T3: 25/25 °C) was more favorable for high chlorophyll, increased polysaccharide, and total flavonoid contents compared to constant temperature treatments in D. officinale PLBs. The transcriptome analysis revealed 4251, 4404, and 4536 differentially expressed genes (DEGs) in three different comparisons (A: 25/13 °C vs. 13/13 °C, B: 13/13 °C vs. 25/25 °C, and C: 25/13 °C vs. 25/25 °C, respectively). The corresponding up-/down-regulated DEGs were 1562/2689, 2825/1579, and 2310/2226, respectively. GO and KEGG enrichment analyses of DEGs showed that the pathways of biosynthesis of secondary metabolites, carotenoid biosynthesis, and flavonoid biosynthesis were enriched in the top 20; further analysis of the sugar- and flavonol-metabolism pathways in D. officinale PLBs revealed that the DIF led to a differential gene expression in the enzymes linked to sugar metabolism, as well as to flavonol metabolism. Certain key metabolic genes related to ingredient accumulation were identified, including those involved in polysaccharide metabolism (SUS, SUT, HKL1, HGL, AMY1, and SS3) and flavonol (UGT73C and UGT73D) metabolism. Therefore, these findings indicated that these genes may play an important role in the regulatory network of the DIF in the functional metabolites of D. officinale PLBs. In a MapMan annotation of abiotic stress pathways, the DEGs with significant changes in their expression levels were mainly concentrated in the heat-stress pathways, including heat-shock proteins (HSPs) and heat-shock transcription factors (HSFs). In particular, the expression levels of HSP18.2, HSP70, and HSF1 were significantly increased under DIF treatment, which suggested that HSF1, HSP70 and HSP18.2 may respond to the DIF. In addition, they can be used as candidate genes to study the effect of the DIF on the PLBs of D. officinale. The results of our qPCR analysis are consistent with those of the transcriptome-expression analysis, indicating the reliability of the sequencing. The results of this study revealed the transcriptome mechanism of the DIF on the accumulation of the functional metabolic components of D. officinale. Furthermore, they also provide an important theoretical basis for improving the quality of D. officinale via the DIF in production.
Transcriptomic Analysis of Self-Incompatibility in Alfalfa
Authors: Li Lulu , Liu Sinan , Wang Yulu , Shang Yangzhou , Qi Zhi , Lin Hao , Niu Lifang
Published: March 2024

Alfalfa (Medicago sativa L.) is an important forage crop worldwide, but molecular genetics and breeding research in this species are hindered by its self-incompatibility (SI). Although the mechanisms underlying SI have been extensively studied in other plant families, SI in legumes, including alfalfa, remains poorly understood. Here, we determined that self-pollinated pollen tubes could germinate on the stigma of alfalfa, grow through the style, and reach the ovarian cavity, but the ovules collapsed ~48 h after self-pollination. A transcriptomic analysis of dissected pistils 24 h after self-pollination identified 941 differently expressed genes (DEGs), including 784 upregulated and 157 downregulated genes. A gene ontology (GO) analysis showed that the DEGs were highly enriched in functions associated with the regulation of pollen tube growth and pollen germination. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that pentose and glucuronate interconversion, plant hormone signal transduction, the spliceosome, and ribosomes might play important roles in SI. Our co-expression analysis showed that F-box proteins, serine/threonine protein kinases, calcium-dependent protein kinases (CDPKs), bHLHs, bZIPs, and MYB-related family proteins were likely involved in the SI response. Our study provides a catalog of candidate genes for further study to understand SI in alfalfa and related legumes.
Quantitative Trait Loci Mapping for Bacterial Wilt Resistance and Plant Height in Tomatoes
Authors: Siddique Muhammad Irfan , Silverman Emily , Louws Frank , Panthee Dilip R.
Published: March 2024

Bacterial wilt (BW) of tomatoes, caused by Ralstonia solanacearum, is a devastating disease that results in large annual yield losses worldwide. Management of BW of tomatoes is difficult due to the soil-borne nature of the pathogen. One of the best ways to mitigate the losses is through breeding for disease resistance. Moreover, plant height (PH) is a crucial element related to plant architecture, which determines nutrient management and mechanical harvesting in tomatoes. An intraspecific F2 segregating population (NC 11212) of tomatoes was developed by crossing NC 84173 (tall, BW susceptible) × CLN1466EA (short, BW resistant). We performed quantitative trait loci (QTL) mapping using single nucleotide polymorphic (SNP) markers and the NC 11212 F2 segregating population. The QTL analysis for BW resistance revealed a total of three QTLs on chromosomes 1, 2, and 3, explaining phenotypic variation (R2) ranging from 3.6% to 14.9%, whereas the QTL analysis for PH also detected three QTLs on chromosomes 1, 8, and 11, explaining R2 ranging from 7.1% to 11%. This work thus provides information to improve BW resistance and plant architecture-related traits in tomatoes.
Evaluation of Biological Plant Protection Products for Their Ability to Induce Olive Innate Immune Mechanisms and Control Colletotrichum acutatum, the Causal Agent of Olive Anthracnose
Authors: Varveri Maria , Papageorgiou Anastasia G. , Tsitsigiannis Dimitrios I.
Published: March 2024

Olive anthracnose is the most important fungal disease of the olive fruit worldwide, with the fungus Colletotrichum acutatum as the main cause of the disease in Greece. A total of 11 commercial biological plant protection products (bioPPPs) (Amylo-X®, Botector®, FytoSave®, LBG 01F34®, Mevalone®, Polyversum®, Remedier®, Serenade® ASO, Sonata®, Trianum-P®, Vacciplant®), with various modes of action against the fungus C. acutatum, were evaluated by bioassays using detached fruits of two important olive Greek varieties, cv. Koroneiki and cv. Kalamon. Subsequently, the most effective bioPPPs were evaluated for their ability to induce plant defense mechanisms, by determining the expression levels of ten Olea europaea defense genes (Pal, CuaO, Aldh1, Bglu, Mpol, Lox, Phely, CHI-2, PR-10, PR-5). Remedier®, Trianum-P®, Serenade® ASO, Sonata®, and Mevalone® were the most effective in reducing disease severity, and/or inhibiting the conidia production by the fungus at high rates. Post bioPPPs application, high expression levels of several olive plant defense genes were observed. This study provides insights into commercial bioPPPs’ effectiveness in controlling olive anthracnose, as well as biocontrol-agents-mediated modulation of olive defense mechanisms.
Tourist Trampling on a Peripheral Plant Population Restricted to an Urban Natural Area in the Capo Sant’Elia Promontory (Sardinia, W-Mediterranean Basin)
Authors: Cogoni Donatella , Calderisi Giulia , Collu Daniele , Fenu Giuseppe
Published: March 2024

Urban natural areas provide important ecological services such as biodiversity conservation, as well as opportunities for people to connect with nature and preserve cultural heritage. However, the increasing demand for access to natural areas and the expansion of human recreational activities, such as hiking and biking, pose threats to these ecosystems, especially for animal and plant species, finally resulting in biodiversity loss. This study explores the intricate link between human trampling, plant density, and the morphological and reproductive characteristics of Globularia alypum L., a plant with a peripheral population in Sardinia restricted to a natural area within an urban context. The study examined trampling effects on 75 plots along a frequently used path crossing the plant’s core population. Similar environmental conditions were assumed, with differences attributed to human trampling intensity and plant density, and morphological and reproductive traits were measured within each plot. Our results showed that human trampling caused differences in the morphological traits of plants, whereas, in contrast, reproductive traits are less vulnerable to human trampling than morphological ones. As a result, trampled areas may experience decreased plant recruitment, which can have long-term implications for plant population dynamics. Understanding the relationship between trampling effects and the sensitivity of peripheral plant populations is crucial for effective conservation and management strategies.