bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Temperature on the Spatial Distribution of AuNPs on a Ceramic Substrate for Biosensing Applications
Authors: Hernández-Rodríguez Yazmín Mariela , Baños-López Esperanza , Damián-Matsumura Pablo , González de la Rosa Claudia Haydée , Cigarroa-Mayorga Oscar Eduardo
Published: October 2024

In this study, we investigated the spatial distribution and homogeneity of gold nanoparticles (AuNPs) on an alumina (Al2O3; AAO) substrate for potential application as surface-enhanced Raman scattering (SERS) sensors. The AuNPs were synthesized through thermal treatment at 450 °C at varying times (5, 15, 30, and 60 min), and their distribution was characterized using field-emission scanning electron microscopy (FE-SEM) and scanning transmission electron microscopy (STEM). The FE-SEM and STEM analyses revealed that the size and interparticle distance of the AuNPs were significantly influenced by the duration of thermal treatment, with shorter times promoting smaller and more closely spaced nanoparticles, and longer times resulting in larger and more dispersed particles. Raman spectroscopy, using Rhodamine 6G (R6G) as a probe molecule, was employed to evaluate the SERS enhancement provided by the AuNPs on the AAO substrate. Raman mapping (5 µm × 5 µm) was conducted on five sections of each sample, demonstrating improved homogeneity in the SERS effect across the substrate. The topological features of the AuNPs before and after R6G incubation were analyzed using atomic force microscopy (AFM), confirming the correlation between a decrease in surface roughness and an increase in R6G adsorption. The reproducibility of the SERS effect was quantified using the maximum intensity deviation (D), which was found to be below 20% for all samples, indicating good reproducibility. Among the tested conditions, the sample synthesized for 15 min exhibited the most favorable characteristics, with the smallest average nanoparticle size and interparticle distance, as well as the most consistent SERS enhancement. These findings suggest that AuNPs on AAO substrates, particularly those synthesized under the optimized condition of 15 min at 450 °C, are promising candidates for use in SERS-based sensors for detecting cancer biomarkers. This could be attributed to temperature propagation promoted at the time of synthesis. The results also provide insights into the influence of thermal treatment on the spatial distribution of AuNPs and their subsequent impact on SERS performance.
Kinematic Changes throughout Childhood in Youth with Cerebral Palsy: Influence of Age and Orthopaedic Surgery
Authors: Lennon Nancy , Church Chris , Wagner Daniel , Niiler Tim , Henley John , Miller Freeman , Shrader Michael Wade , Howard Jason J.
Published: October 2024

Background: Abnormal gait kinematics are common in youth with cerebral palsy (CP), but prior studies have not analyzed their longitudinal change throughout childhood. This study examines how age and orthopaedic surgery influence gait kinematics throughout childhood in those with ambulatory CP. Methods: In this institutional review board-approved prospective cohort study, children with spastic CP (GMFCS I–III) were recruited at age 17–40 months. Instrumented gait analysis was performed at 3-year intervals from age 4 to 21 years, collecting longitudinal kinematic data in bare feet at a self-selected speed. The change in Gait Profile Score (ΔGPS) between each pair of gait analyses (intervals) was analyzed by age distribution (<10, 10–15, ≥15 years) and by presence/absence of orthopaedic surgery. Results: The study included 31 children (GMFCS: I [13], II [14], III [4]). A baseline instrumented gait analysis was performed at age 5.8 ± 1.6 years with subsequent analysis at 2.5 ± 1.3-year intervals. Examining ΔGPS from baseline to final outcome, 87% of limbs were improved/unchanged; 298 intervals of ΔGPS were analyzed and classified as nonsurgical or surgical. Analysis revealed greater GPS improvement in intervals with surgery versus intervals without (p = 0.0004). Surgical intervals had significantly greater GPS improvement in the <10- vs. >15-year-old groups, p = 0.0063. Conclusions: Improvement in gait kinematics in children with CP is significantly influenced by age and timing of orthopaedic surgical intervention for gait correction, and was most pronounced for children <10 years old. Although surgery was associated with improved outcomes in all age groups, these improvements were significantly less for children >10 years old. These results reinforce the importance of considering the timing of orthopaedic surgery.
Studies on Heavy Precipitation in Portugal: A Systematic Review
Authors: Cruz José , Belo-Pereira Margarida , Fonseca André , Santos João A.
Published: October 2024

This systematic review, based on an adaptation of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from 2020, focuses on studies of the atmospheric mechanisms underlying extreme precipitation events in mainland Portugal, as well as observed trends and projections. The 54 selected articles cover the period from 2000 to 2024, in which the most used keywords are “portugal” and “extreme precipitation”. Of the 54, 23 analyse trends and climate projections of precipitation events, confirming a decrease in total annual precipitation, especially in autumn and spring, accompanied by an increase in the frequency and intensity of extreme precipitation events in autumn, spring and winter. Several articles (twelve) analyse the relationship between synoptic-scale circulation and heavy precipitation, using an atmospheric circulation types approach. Others (two) establish the link with teleconnection patterns, namely the North Atlantic Oscillation (NAO), and still others (three) explore the role of atmospheric rivers. Additionally, five articles focus on evaluating databases and Numerical Weather Prediction (NWP) models, and nine articles focus on precipitation-related extreme weather events, such as tornadoes, hail and lightning activity. Despite significant advances in the study of extreme precipitation events in Portugal, there is still a lack of studies on hourly or sub-hourly scales, which is critical to understanding mesoscale, short-lived events. Several studies show NWP models still have limitations in simulating extreme precipitation events, especially in complex orography areas. Therefore, a better understanding of such events is fundamental to promoting continuous improvements in operational weather forecasting and contributing to more reliable forecasts of such events in the future.
Intelligent Tutoring Systems in Mathematics Education: A Systematic Literature Review Using the Substitution, Augmentation, Modification, Redefinition Model
Authors: Son Taekwon
Published: October 2024

Scholars have claimed that artificial intelligence can be used in education to transform learning. However, there is insufficient evidence on whether intelligent tutoring systems (ITSs), a representative form of artificial intelligence in education, has transformed the teaching and learning of mathematics. To fill this gap, this systematic review was conducted to examine empirical studies from 2003 to 2023 that used ITSs in mathematics education. Technology integration was coded using the substitution, augmentation, modification, redefinition (SAMR) model, which was extended to suit ITSs in a mathematics education context. How different contexts and teacher roles are intertwined with SAMR levels were examined. The results show that while ITSs in mathematics education primarily augmented existing learning, recent ITS studies have transformed students’ learning experiences. ITSs were most commonly applied at the elementary school level, and most ITS studies focused on the areas of number and arithmetic, algebra, and geometry. The level of SAMR varied depending on the research purpose, and ITS studies in mathematics education were mainly conducted in a way that minimized teacher intervention. The results of this study suggest that the affordance of an ITS, the educational context, and the teacher’s role should be considered simultaneously to demonstrate the transformative power of ITSs in mathematics education.
Quantitative Analysis about the Spatial Heterogeneity of Water Conservation Services Function Using a Space–Time Cube Constructed Based on Ecosystem and Soil Types
Authors: Liu Yisheng , Hou Peng , Wang Ping , Zhu Jian , Zhai Jun , Chen Yan , Wang Jiahao , Xie Le
Published: October 2024

Precisely delineating the spatiotemporal heterogeneity of water conservation services function (WCF) holds paramount importance for watershed management. However, the existing assessment techniques exhibit common limitations, such as utilizing only multi-year average values for spatial changes and relying solely on the spatial average values for temporal changes. Moreover, traditional research does not encompass all WCF values at each time step and spatial grid, hindering quantitative analysis of spatial heterogeneity in WCF. This study addresses these limitations by utilizing an improved water balance model based on ecosystem type and soil type (ESM-WBM) and employing the EFAST and Sobol’ method for parameter sensitivity analysis. Furthermore, a space–time cube of WCF, constructed using remote-sensing data, is further explored by Emerging Hot Spot Analysis for the expression of WCF spatial heterogeneity. Additionally, this study investigates the impact of two core parameters: neighborhood distance and spatial relationship conceptualization type. The results reveal that (1) the ESM-WBM model demonstrates high sensitivity toward ecosystem types and soil data, facilitating the accurate assessment of the impacts of ecosystem and soil pattern alterations on WCF; (2) the EHSA categorizes WCF into 17 patterns, which in turn allows for adjustments to ecological compensation policies in related areas based on each pattern; and (3) neighborhood distance and the type of spatial relationships conceptualization significantly impacts the results of EHSA. In conclusion, this study offers references for analyzing the spatial heterogeneity of WCF, providing a theoretical foundation for regional water resource management and ecological restoration policies with tailored strategies.
Longitudinal Structural and Functional Evaluation of Dark-without-Pressure Fundus Lesions in Patients with Autoimmune Diseases
Authors: Lombardo Marco , Ricci Federico , Cusumano Andrea , Falsini Benedetto , Nucci Carlo , Cesareo Massimo
Published: October 2024

Objectives: The main objective of this study was to report and investigate the characteristics and longitudinal changes in dark-without-pressure (DWP) fundus lesions in patients with autoimmune diseases using multimodal imaging techniques. Methods: In this retrospective observational case series, five patients affected by ocular and systemic autoimmune disorders and DWP were examined. DWP was assessed by multimodal imaging, including color fundus photography (CFP), near-infrared reflectance (NIR), blue reflectance (BR), blue autofluorescence (BAF), optical coherence tomography (OCT), OCT-angiography (OCT-A), fluorescein angiography (FA) and indocyanine green angiography (ICGA), and functional testing, including standard automated perimetry (SAP) and electroretinography (ERG). Follow-up examinations were performed for four out of five patients (range: 6 months–7 years). Results: DWP fundus lesions were found in the retinal mid-periphery and were characterized by the hypo-reflectivity of the ellipsoid zone on OCT. DWP appeared hypo-reflective in NIR, BR and BAF, and exhibited hypo-fluorescence in FA in two patients while showing no signs in one patient. ICGA showed hypo-fluorescent margins in one patient. SAP and ERG testing did not show alterations attributable to the DWP lesion. Follow-up examinations documented rapid dimensional changes in DWP even in the short term (1 month). Conclusions: This study suggests a possible association between autoimmune diseases and DWP. New FA and ICGA features were described. The proposed pathogenesis hypotheses may operate as a basis for further investigation of a lesion that is still largely unknown. Large population studies would be necessary to confirm whether there is a higher incidence of DWP in this patient category.
Exploring the Role of Mind Mapping Tools in Scaffolding Narrative Writing in English for Middle-School EFL Students
Authors: Fu Xinyan , Relyea Jackie E.
Published: October 2024

The purpose of this study was to investigate the effects of scaffolded English writing instruction using mind mapping tools on English narrative writing proficiency among Chinese middle-school EFL students. Specifically, we examined its effects on four subcomponents of narrative writing compositions: lexical complexity, grammatical complexity, accuracy, and fluency. Non-equivalent group pre-test–post-test design was employed in this study. The participants were 55 eighth-grade students in an English class. The data were collected through two writing tests administered before and after a two-month intervention. The results showed that students’ writing demonstrated significant improvements in lexical complexity, grammatical complexity, accuracy, and fluency. These findings suggest that scaffolded writing instruction with mind mapping can effectively enhance multiple dimensions of writing skills in adolescent EFL learners. This study provides insights into the application of using mind mapping to scaffold EFL learners’ narrative writing proficiency.
A Novel Point of Common Coupling Direct Power Control Method for Grid Integration of Renewable Energy Sources: Performance Evaluation among Power Quality Phenomena
Authors: Alturki Yusuf A. , Alhussainy Abdullah Ali , Alghamdi Sultan M. , Rawa Muhyaddin
Published: October 2024

Robust control mechanisms are needed in microgrids to ensure voltage source inverters (VSIs) effectively integrate renewable energy sources such as solar photovoltaic (PV) systems into the power network. Current control approaches often have limitations regarding velocity, stability, and robustness. The paper details a newly developed method named Point of Common Coupling Direct Power Control (PCC-DPC) for renewable energy systems connected to the grid. PCC-DPC is used to instantly control voltage at the point of common coupling (PCC) inside the microgrid as opposed to other conventional techniques. This leads to a simplified controller design that does not require complex Park transformations and phase-locked loop (PLL) systems, and has a lower computational burden and less power fluctuation in a stable manner. Moreover, this research critically examines power quality phenomena through comparing PCC-DPC with a Vector Current Controller (VCC). Simulations performed on an Opal Re-al-Time simulator showed improved tracking performance and overall system efficiency due to the PCC-DPC approach over others. These results demonstrate that it can effectively be used as one of the most suitable methods for integrating renewable energy into electricity grids, which is reliable in regards to changes in power grid dynamics.
Online Evaluation for the POI-Level Inertial Support to the Grid via Ambient Measurements
Authors: Wu Genzhu , Zhong Weilin , Liu Muyang , Chang Xiqiang , Shao Xianlong , Mo Ruo
Published: October 2024

As renewable energy sources like wind and solar power increasingly replace traditional energy sources and are integrated into the power grid, the issue of insufficient system inertia is becoming more apparent. This paper presents an online adaptive time window inertia constant identification method based on ambient measurements to identify the equivalent inertia constant of the time-varying inertia at Point of Interface (POI) level. The proposed method takes advantage of the online inertia estimation and the data-driven equivalent inertia constant identification techniques to simultaneously achieve online tracking and accuracy. With this regard, this paper first describes the inertia providers in modern system. Then, based on the frequency and power data measured by the Phasor Measurement Unit (PMU), this paper provides an improved data-driven equivalent inertia constant identification method. Subsequently, the paper proposes an ambient data smoothing method to cope with the numerical errors and provides, as a byproduct, an adaptive time window inertia constant identification. The adaptive time window is designed to enhance the accuracy of the method. Finally, the feasibility and accuracy of the proposed method of tracking synthetic inertia are validated by the simulation tests based on a grid in northwest China with high renewable energy penetration and a Virtual Power Plant (VPP). The experimental results show that the accuracy of this method is within 5%.
Parametrical Choice of the Optimized Fusion System for a FFHR
Authors: Murgo Stefano , Lomonaco Guglielmo , Orsitto Francesco Paolo , Panza Fabio , Pompeo Nicola
Published: October 2024

Fusion–fission hybrid reactors are concepts of subcritical reactors based on the coupling of fusion and fission devices. In this case, the fusion reactor would work as an external neutron supplier for the fission core of the machine. Such systems could, in principle, operate as multi-purpose machines, such as energy generators, breeders and waste burners. The large availability of fusion and fission technologies makes the choice of devices to couple quite chaotic. In fact, most of the concepts proposed in the literature are based on attempts without real optimization. The purpose of this paper is to propose a parameter which could provide practical information regarding the choice or the design of the fusion system of an FFHR. An engineering approach based on the estimation of the energy efficiency of FFHRs was used. An evaluation of the parameter and some of its possible practical applications are shown. Obtained results indicate that, from a geometrical point of view, compact machines would need lower Q-values to reach high neutron source performance.
Research on the Driving Factors and Policy Guidance for a Reduction in Electricity Consumption by Urban Residents
Authors: Xia Long , Chai Lulu , Feng Xiaoyun , Wei Yuehong , Zhang Hanyu
Published: October 2024

The urgency of mitigating climate change and the challenges it poses to ecosystems and human systems are highlighted in the Intergovernmental Panel on Climate Change’s (IPCC) Sixth Assessment Report (AR6). In order to achieve sustainable development, it is imperative to adopt a series of adaptive measures to enhance the resilience of various sectors to climate change and reduce greenhouse gas emissions. This article analyzes the driving mechanism behind the reduction in electricity consumption by urban residents based on 302 valid questionnaires from 18 communities in nine districts in B City. Using a method that combines qualitative and empirical research, the study proposes policy recommendations aimed at guiding urban residents toward reducing their electricity consumption. These recommendations serve as a policy reference for cities striving to achieve sustainability and low-carbon targets. The primary innovations and conclusions of the study are as follows: (1) this study summarizes the primary factors and processes influencing the reduction in electricity consumption among urban residents, examined from the following three perspectives: residents’ characteristics, psychological understanding, and external environment. (2) On the basis of the research data, empirical analysis and hypothesis testing are conducted using a variety of mathematical and statistical methods. The results indicate significant differences in the electricity consumption reduction behavior of heterogeneous urban residents in both public and private areas. Subjective norms, perceived behavioral control, and knowledge of electricity conservation have significant direct influences on residents’ willingness to reduce their electricity consumption. Among these factors, subjective norms have the most significant impact, while the impact of attitude is negligible. Economic incentive policies have a significant positive regulatory effect on the relationship between “willingness (intention)” and “private area electricity consumption reduction behavior”.
Frailty Indicator over the Adult Life Cycle as a Predictor of Healthcare Expenditure and Mortality in the Short to Midterm
Authors: Milcent Carine
Published: October 2024

Background: Assessing frailty from middle age onward offers valuable insights into predicting healthcare expenditures throughout the life cycle. Objectives: This paper examines the use of physical frailty as an indicator of healthcare demand across all age groups. The originality of this work lies in extending the analysis of frailty indicators beyond the typical focus on individuals under 50 years old to include those in mid-life and older. Methods: For this study, we used a database where frailty was measured in 2012 in a sample of individuals aged 15 to over 90. These individuals were tracked for their healthcare expenditures from 2012 to 2016. Results: Among the sample of 6928 individuals, frailty in 2012 resulted in a statistically significant increase in costs at the 5% level for the population aged 15 to 65. We applied multilevel linear regression models with year fixed effects, controlling for demographic factors, education level, precarity, social dimensions, lifestyle factors (e.g., vegetable consumption), physical activity, emotional well-being, and medical history. A Hausman test was conducted to validate the model choice. For mortality rate analysis, Cox models were used. Conclusions: Our findings demonstrate that physical frailty provides valuable information for understanding its impact on healthcare expenditure. The effect of frailty on mortality is particularly significant for the elderly population. Moreover, frailty is a predictor of healthcare costs not only in older adults but also across the entire life cycle.
Compliance with 24 h Movement Behavior Guidelines for Pregnant Women in Saudi Arabia: The Role of Trimester and Maternal Characteristics
Authors: Alghamdi Saja Abdullah , Alsalman Alawyah , Sowadi Om Kalthom , Khojah Nada , Saad Hadeel , Gibbs Bethany Barone , Alshuwaier Ghareeb Omar , Alansare Abdullah Bandar
Published: October 2024

Background: Complying with 24 h movement behavior guidelines for pregnant women may prevent pregnancy complications. This single time point, cross-sectional investigation assessed compliance with the 24 h movement behavior guidelines in pregnant women in Saudi Arabia and examined the role of trimester and maternal characteristics. Methods: Pregnant women (n = 935; age = 30 ± 5.6 years; first trimester = 24.1%, second trimester = 33.9%, third trimester = 42.0%) self-reported their characteristics (nationality, region, degree, occupation, smoking status, health status, having children, previous birth). The short-version International Physical Activity Questionnaire, Sedentary Behavior Questionnaire, and Pittsburgh Sleep Quality Index Questionnaire measured moderate physical activity (MPA), sedentary behavior (SB), and sleep duration, respectively. Compliance with the 24 h movement behavior guidelines was reported using frequencies and percentages. Prevalence ratios compared the prevalence of compliance by trimester and maternal characteristics. Results: Approximately half of the participants did not comply with MPA or sleep duration guidelines (n = 524, [56.0%] and n = 424, [45.5%], respectively). In contrast, about two-thirds of participants (n = 648, [69.3%]) adhered to the SB guideline. Only 154 (16.5%) participants complied with all 3 24 h movement behavior guidelines. Pregnant women in their second trimester, living in Al-Ahsa Governorate, and currently smoking with a bachelor’s degree were the most likely to comply with the guidelines. Conclusions: These findings underscore the need for tailored efforts to promote healthy 24 h movement behavior guidelines for pregnant women in Saudi Arabia, especially early in pregnancy, while accounting for important maternal characteristics.
Microsurgical Reconstruction with and without Microvascular Anastomosis of Oncological Defects of the Upper Limb
Authors: Pinto Valentina , Zeneli Flavia , di Summa Pietro Giovanni , Sapino Gianluca , Donati Davide Maria , Bernagozzi Fabio , Cipriani Riccardo , De Santis Giorgio , Pignatti Marco
Published: October 2024

Introduction: The choice of the most adequate surgical technique for upper limb defects remains challenging. The aim of this article is to discuss the main microsurgical (pedicled or free) reconstructive options for the post-oncological reconstruction of different anatomical areas of the upper extremity. Materials and methods: We reviewed different reconstructive methods reported in the literature needing microsurgical expertise and compared them to our clinical experience, in order to provide further guidance in the choice of different flaps for upper limb soft tissue reconstruction. Six clinical cases, one for each anatomical district, are presented as examples of possible solutions. Results: We report the options available in the literature for post-oncologic upper limb reconstruction, dividing them by anatomical area and type of flap: local flaps, regional flaps, free flaps, and distant pedicled flaps. Our examples of the reconstruction of each anatomical area of the upper limb include one reverse ulnar pedicled perforator flap, one free Antero-Lateral Thigh (ALT) flow-through flap, one perforator-based lateral arm flap, two myocutaneous latissimus dorsi pedicled flaps, and one parascapular perforator-plus flap. Conclusions: In oncological cases, it is important to consider reconstructive options that provide stable tissue and allow for the early healing of the donor and recipient site if the patient needs to undergo adjuvant radiotherapy or chemotherapy. A wider range of flap options is essential when choosing the proper technique according to the patient’s needs, surgeon’s preference, and logistical possibilities. Perforator flaps combine the advantages of other flaps, but they require microsurgical expertise. Free flap reconstruction remains the gold standard to obtain a better overall and cosmetic outcome in complex and wide defects, where no suitable local pedicled flap option exists. The pedicled latissimus dorsi flap should still be included among the reconstructive options for its strong vascularization, size, and arc of transposition.
Administration of Adipose Tissue Derived Stem Cells before the Onset of the Disease Lowers the Levels of Inflammatory Cytokines IL-1 and IL-6 in the Rat Model of Necrotizing Enterocolitis
Authors: Wolski Marek , Ciesielski Tomasz , Buczma Kasper , Fus Łukasz , Girstun Agnieszka , Trzcińska-Danielewicz Joanna , Cudnoch-Jędrzejewska Agnieszka
Published: October 2024

There is little research concerning the role of stem cells in necrotizing enterocolitis (NEC). Bone marrow-derived mesenchymal stem cells (BMDSC) and amniotic fluid-derived stem cells significantly reduced the amount and severity of NEC in the animal models. ADSCs share similar surface markers and differentiation potential with BMDSCs. Their potential role in the setting of NEC has not been researched before. The hypothesis of the study was that prophylactic intraperitoneal administration of ADSCs before the onset of the disease will result in limiting the inflammatory response, effecting a lower incidence of NEC. On a molecular level, this should result in lowering the levels of inflammatory cytokines IL-1 and IL-6. The local ethical committee for animal experiments approval was acquired (WAW2/093/2021). We utilized a self-modified rat NEC model based on single exposure to hypothermia, hypoxia, and formula feeding. One hundred and twenty-eight rat puppies were divided into two groups—prophylaxis (ADSC-NEC, n = 66) and control group (NEC-PLCB, n = 62)—to measure the influence of ADSCs administration on the inflammatory changes in NEC, the level of cell engraftment, and the histopathology of the disease. The analysis did not show a significant effect on histopathology between groups, H(2) = 2.12; p = 0.347; η²H = 0.00. The intensity of the NEC variable results was similar across the analyzed groups (NEC-PLCB and ADSC-NEC). For IL-1 and IL-6, the difference between the NEC-PLCB group and the ADSC-NEC group was statistically significant, p = 0.002 and p < 0.001, respectively. To conclude, administration of adipose tissue-derived stem cells before the onset of the disease lowers the levels of inflammatory cytokines IL-1 and IL-6 but does not affect the histopathological results in the rat model of NEC.
Post-Meningitic Syndrome: Pathophysiology and Consequences of Streptococcal Infections on the Central Nervous System
Authors: Kaddoura Rachid , Abdalbari Karim , Kadom Mhmod , Badla Beshr Abdulaziz , Hijleh Amin Abu , Hanifa Mohamed , AlAshkar Masa , Asbaita Mohamed , Othman Deema , Faraji Hanan , AlBakri Orjwan , Tahlak Sara , Hijleh Amir Abu , Kabbani Raneem , Resen Murtadha , Abdalbari Helmi , Du Plessis Stefan S. , Omolaoye Temidayo S.
Published: October 2024

Streptococcus species represent a significant global cause of meningitis, leading to brain damage through bacterial virulence factors and the host inflammatory response. Upon entering the central nervous system (CNS), excessive inflammation leads to various neurological and psychological complications. This review explores the pathophysiological mechanisms and associated outcomes of streptococcal meningitis, particularly its short- and long-term neurological sequelae. Neurological symptoms, such as cognitive impairment, motor deficits, and sensory loss, are shown to vary in severity, with children being particularly susceptible to lasting complications. Among survivors, hearing loss, cognitive decline, and cranial nerve palsies emerge as the most frequently reported complications. The findings highlight the need for timely intervention, including neurorehabilitation strategies that focus on optimizing recovery and mitigating long-term disabilities. Future recommendations emphasize improving early diagnosis, expanding vaccine access, and personalizing rehabilitation protocols to enhance patient outcomes. As a novel contribution, this review proposes the term “post-meningitic syndrome” to showcase the broad spectrum of CNS complications that persist following streptococcal meningitis, providing a framework for a future clinical and research focus.
Disrupted Post-Transcriptional Regulation of Gene Expression as a Hallmark of Fatty Liver Progression
Authors: Takaoka Shohei , Jaso-Vera Marcos E. , Ruan Xiangbo
Published: October 2024

It is known that both transcriptional and post-transcriptional mechanisms control messenger RNA (mRNA) levels. Compared to transcriptional regulations, our understanding of how post-transcriptional regulations adapt during fatty liver progression at the whole-transcriptome level is unclear. While traditional RNA-seq analysis uses only reads mapped to exons to determine gene expression, recent studies support the idea that intron-mapped reads can be reliably used to estimate gene transcription. In this study, we analyzed differential gene expression at both the exon and intron levels using two liver RNA-seq datasets from mice that were fed a high-fat diet for seven weeks (mild fatty liver) or thirty weeks (severe fatty liver). We found that the correlation between gene transcription and mature mRNA levels was much lower in mice with mild fatty liver as compared with mice with severe fatty liver. This result indicates broad post-transcriptional regulations for early fatty liver and such regulations are compromised for severe fatty liver. Specifically, gene ontology analysis revealed that genes involved in synapse organization and cell adhesion were transcriptionally upregulated, while their mature mRNAs were unaffected in mild fatty liver. Further characterization of post-transcriptionally suppressed genes in early fatty liver revealed that their mRNAs harbor a significantly longer 3′ UTR, one of the major features that may subject RNA transcripts to nonsense-mediated RNA decay (NMD). We further show that the expression of representative genes that were post-transcriptionally suppressed were upregulated in mice with a hepatocyte-specific defect of NMD. Finally, we provide data supporting a time-dependent decrease in NMD activity in the liver of a diet-induced metabolic-dysfunction-associated fatty liver disease mouse model. In summary, our study supports the conclusion that NMD is essential in preventing unwanted/harmful gene expression at the early stage of fatty liver and such a mechanism is lost due to decreased NMD activity in mice with severe fatty liver.
Variants rs3804099 and rs3804100 in the TLR2 Gene Induce Different Profiles of TLR-2 Expression and Cytokines in Response to Spike of SARS-CoV-2
Authors: Flores-González Julio , Monroy-Rodríguez Zurisadai , Falfán-Valencia Ramcés , Buendía-Roldán Ivette , Fricke-Galindo Ingrid , Hernández-Zenteno Rafael , Herrera-Sicairos Ricardo , Chávez-Galán Leslie , Pérez-Rubio Gloria
Published: October 2024

The present study aimed to identify in patients with severe COVID-19 and acute respiratory distress syndrome (ARDS) the association between rs3804099 and rs3804100 (TLR2) and evaluate the expression of TLR-2 on the cell surface of innate and adaptive cells of patients’ carriers of C allele in at least one genetic variant. We genotyped 1018 patients with COVID-19 and ARDS. According to genotype, a subgroup of 12 patients was selected to stimulate peripheral blood mononuclear cells (PBMCs) with spike and LPS + spike. We evaluated soluble molecules in cell culture supernatants. The C allele in TLR2 (rs3804099, rs3804100) is not associated with a risk of severe COVID-19; however, the presence of the C allele (rs3804099 or rs3804100) affects the TLR-2 ability to respond to a spike of SARS-CoV-2 correctly. The reference group (genotype TT) downregulated the frequency of non-switched TLR-2+ B cells in response to spike stimulus; however, the allele’s C carriers group is unable to induce this regulation, but they produce high levels of IL-10, IL-6, and TNF-α by an independent pathway of TLR-2. Findings showed that TT genotypes (rs3804099 and rs3804100) affect the non-switched TLR-2+ B cell distribution. Genotype TT (rs3804099 and rs3804100) affects the TLR-2’s ability to respond to a spike of SARS-CoV-2. However, the C allele had increased IL-10, IL-6, and TNF-α by stimulation with spike and LPS.
Rapidly Evolved Genes in Three Reaumuria Transcriptomes and Potential Roles of Pentatricopeptide Repeat Superfamily Proteins in Endangerment of R. trigyna
Authors: Zhang Ruizhen , Cui Xiaoyun , Zhao Pengshan
Published: October 2024

Reaumuria genus (Tamaricaceae) is widely distributed across the desert and semi-desert regions of Northern China, playing a crucial role in the restoration and protection of desert ecosystems. Previous studies mainly focused on the physiological responses to environmental stresses; however, due to the limited availability of genomic information, the underlying mechanism of morphological and ecological differences among the Reaumuria species remains poorly understood. In this study, we presented the first catalog of expressed transcripts for R. kaschgarica, a sympatric species of xerophyte R. soongorica. We further performed the pair-wise transcriptome comparison to determine the conserved and divergent genes among R. soongorica, R. kaschgarica, and the relict recretohalophyte R. trigyna. Annotation of the 600 relatively conserved genes revealed that some common genetic modules are employed by the Reaumuria species to confront with salt and drought stresses in arid environment. Among the 250 genes showing strong signs of positive selection, eight pentatricopeptide repeat (PPR) superfamily protein genes were specifically identified, including seven PPR genes in the R. soongorica vs. R. trigyna comparison and one PPR gene in the R. kaschgarica vs. R. trigyna comparison, while the cyclin D3 gene was found in the R. soongorica vs. R. trigyna comparison. These findings suggest that genetic variations in PPR genes may affect the fertility system or compromise the extent of organelle RNA editing in R. trigyna. The present study provides valuable genomic information for R. kaschgarica and preliminarily reveals the conserved genetic bases for the abiotic stress adaptation and interspecific divergent selection in the Reaumuria species. The rapidly evolved PPR and cyclin D3 genes provide new insights on the endangerment of R. trigyna and the leaf length difference among the Reaumuria species.
Study on the Effect of Emulsifiers on the Properties of Oleogels Based on Olive Oil Containing Lidocaine
Authors: Kudłacik-Kramarczyk Sonia , Przybyłowicz Alicja , Drabczyk Anna , Kieres Weronika , Socha Robert P. , Krzan Marcel
Published: October 2024

Oleogels are semi-solid materials that consist primarily of liquid oil immobilized in a network of organized structural molecules, which provide stability and maintain the oil in the desired shape. Due to their structure, oleogels can stabilize large amounts of liquid, making them excellent carriers for active substances, both lipophilic and hydrophilic. This study presents the synthesis methodology and investigations of olive oil-based oleogels, which are among the healthiest and most valuable vegetable fats, rich in unsaturated fatty acids and antioxidants such as vitamin E. Two types of surfactants were used: TWEEN 80, which lowers surface tension and stabilizes emulsions, and SPAN 80, which acts in oil-dominated phases. The oleogels were enriched with lidocaine, an active substance commonly used as a pain reliever and local anesthetic. This research characterized the obtained oleogels regarding their medical applications, paying particular attention to the influence of surfactant type and amount as well as the active substance on their physicochemical properties. Structural analyses were also conducted using Fourier transform infrared (FTIR) spectroscopy, alongside rheological and sorption studies, and the wettability of the materials was evaluated. The stability of the obtained oleogels was verified using the MultiScan MS20 system, allowing for an assessment of their potential suitability for long-term pharmaceutical applications. The results indicated that SPAN-stabilized oleogels exhibited better stability and favorable mechanical properties, making them promising candidates for medical applications, particularly in pain relief formulations.
Serine Hydroxymethyltransferase 2 Deficiency in the Hematopoietic System Disrupts Erythropoiesis and Induces Anemia in Murine Models
Authors: Li Jisheng , Zhang Bowen , Li Yunqiao , Liu Chuanli , Tang Xuan , Zhao Jiahui , Pei Xuetao , Li Yanhua
Published: October 2024

Serine and folate metabolism play critical roles in erythroid development in both embryonic and adult mice; however, the precise roles of these metabolic pathways in erythropoiesis and the pathophysiology of anemia remain inadequately characterized in the literature. To delineate the contributions of serine and folate metabolism to erythroid differentiation, we focused on serine hydroxymethyltransferase 2 (SHMT2), a key regulatory enzyme within these metabolic pathways. Using gene-editing techniques, we created fetal and adult mouse models with targeted deletion of Shmt2 in the hematopoietic system. Our findings demonstrated that the deletion of Shmt2 within the hematopoietic system led to the distinctive anemia phenotype in both fetal and adult mice. Detailed progression analysis of anemia revealed that Shmt2 deletion exerts stage-specific effects on the development and maturation of erythroid cells. Specifically, Shmt2 deficiency promoted erythroid differentiation in the R2 (CD71+ Ter119−) cell population residing in the bone marrow while concurrently inhibiting the proliferation and erythroid differentiation of the R3 (CD71+ Ter119+) cell population. This disruption resulted in developmental arrest at the R3 stage, significantly contributing to the anemia phenotype observed in the models. This study elucidates the critical role of Shmt2 in erythroid development within the hematopoietic system, highlighting the underlying mechanisms of erythroid developmental arrest associated with Shmt2 loss.
Proliferative Vitreoretinopathy in Retinal Detachment: Perspectives on Building a Digital Twin Model Using Nintedanib
Authors: Visioli Giacomo , Romaniello Annalisa , Spinoglio Leonardo , Albanese Giuseppe Maria , Iannetti Ludovico , Gagliardi Oscar Matteo , Lambiase Alessandro , Gharbiya Magda
Published: October 2024

Proliferative vitreoretinopathy (PVR) is a pathological process characterized by the formation of fibrotic membranes that contract and lead to recurrent retinal detachment. Pars plana vitrectomy (PPV) is the primary treatment, but recurrence rates remain high, as surgery does not address the underlying molecular mechanisms driving fibrosis. Despite several proposed pharmacological interventions, no approved therapies exist, partly due to challenges in conducting preclinical and in vivo studies for ethical and safety reasons. This review explores the potential of computational models and Digital Twins, which are increasingly gaining attention in medicine. These tools could enable the development of progressively complex PVR models, from basic simulations to patient-specific Digital Twins. Nintedanib, a tyrosine kinase inhibitor targeting PDGFR, VEGFR, and FGFR, is presented as a prototype for computational models to simulate its effects on fibrotic pathways in virtual patient cohorts. Although still in its early stages, the integration of computational models and Digital Twins offers promising avenues for improving PVR management through more personalized therapeutic strategies.
Neodymium-Facilitated Visualization of Extreme Phosphate Accumulation in Fibroblast Filopodia: Implications for Intercellular and Cell–Matrix Interactions
Authors: Kravchik Marina , Subbot Anastasia , Bilyalov Airat , Novikov Ivan , Deviatiiarov Ruslan , Yusef Yusef , Gusev Oleg
Published: October 2024

A comprehensive understanding of intercellular and cell–matrix interactions is essential for advancing our knowledge of cell biology. Existing techniques, such as fluorescence microscopy and electron microscopy, face limitations in resolution and sample preparation. Supravital lanthanoid staining provides new opportunities for detailed visualization of cellular metabolism and intercellular interactions. This study aims to describe the structure, elemental chemical, and probable origin of zones of extreme lanthanoid (neodymium) accumulation that form during preparation for scanning electron microscopy (SEM) analysis in corneal fibroblasts filopodia. The results identified three morphological patterns of neodymium staining in fibroblast filopodia, each exhibiting asymmetric staining within a thin, sharp, and extremely bright barrier zone, located perpendicular to the filopodia axis. Semi-quantitative chemical analyses showed neodymium-labeled non-linear phosphorus distribution within filopodia, potentially indicating varying phosphate anion concentrations and extreme phosphate accumulation at a physical or physicochemical barrier. Phosphorus zones labeled with neodymium did not correspond to mitochondrial clusters. During apoptosis, the number of filopodia with extreme and asymmetric phosphorus accumulation increases. Supravital lanthanoid staining coupled with SEM allows detailed visualization of intercellular and cell–matrix interactions with high contrast and resolution. These results enhance our understanding of phosphate anion accumulation and transfer mechanisms in cells under normal conditions and during apoptosis.
Oilseed Cakes: A Promising Source of Antioxidant, and Anti-Inflammatory Agents—Insights from Lactuca sativa
Authors: Majed Mayye , Galala Amal A. , Amer Mohamed M. , Selmar Dirk , Abouzeid Sara
Published: October 2024

This study evaluated the antioxidant and antibacterial properties of methanolic extracts derived from oilseed cakes of Lactuca sativa (lettuce), Nigella sativa (black seed), Eruca sativa (rocket), and Linum usitatissimum (linseed). Lettuce methanolic extract showed the highest potential, so it was selected for further investigation. High-performance liquid chromatography (HPLC-DAD) analysis and bioassay-guided fractionation of lettuce seed cake extract led to the isolation of five compounds: 1,3-propanediol-2-amino-1-(3′,4′-methylenedioxyphenyl) (1), luteolin (2), luteolin-7-O-β-D-glucoside (3), apigenin-7-O-β-D-glucoside (4), and β-sitosterol 3-O-β-D-glucoside (5). Compound (1) was identified from Lactuca species for the first time, with high yield. The cytotoxic effects of the isolated compounds were tested on liver (HepG2) and breast (MCF-7) cancer cell lines, compared to normal cells (WI-38). Compounds (2), (3), and (4) exhibited strong activity in all assays, while compound (1) showed weak antioxidant, antimicrobial, and cytotoxic effects. The anti-inflammatory activity of lettuce seed cake extract and compound (1) was evaluated in vivo using a carrageenan-induced paw oedema model. Compound (1) and its combination with ibuprofen significantly reduced paw oedema, lowered inflammatory mediators (IL-1β, TNF-α, PGE2), and restored antioxidant enzyme activity. Additionally, compound (1) showed promising COX-1 and COX-2 inhibition in an in vitro enzymatic anti-inflammatory assay, with IC50 values of 17.31 ± 0.65 and 4.814 ± 0.24, respectively. Molecular docking revealed unique interactions of compound (1) with COX-1 and COX-2, suggesting the potential for targeted inhibition. These findings underscore the value of oilseed cakes as a source of bioactive compounds that merit further investigation.
Cytokines Measured in Nasal Lavage Compared to Induced Sputum in Patients with Mild Cystic Fibrosis
Authors: Fuchs Teresa , Vasiliadis Artemis , Zlamy Manuela , Siedl Anja , Niedermayr Katharina , Appelt Dorothea , Gasser Verena , Eder Johannes , Ellemunter Helmut
Published: October 2024

The measurement of cytokines in induced sputum and nasal lavage (NL) samples has been performed for years in people with cystic fibrosis (CF). The aim of this study was to directly compare sputum and NL samples and interpret results based on disease severity in patients who were categorized as having mild or severe lung disease. The categorization was based primarily on structural abnormalities detected on lung computed tomography and secondarily on lung function. The serum inflammatory markers neutrophil elastase (NE), IL-1β, 2, 6, 8, 10 and 17a were measured in each sputum and NL sample. Thirty-two sample pairs from 29 patients were included in this study (13 mild, 19 severe). In the patients classified as severe, many systemic inflammatory markers as well as sputum cytokines were significantly higher compared to those in the mild patients. However, all the markers measured in the NL were higher in the mild patients (p =< 0.05 for NE, IL-6 and IL-8). In addition, many cytokines in the NL correlated negatively with those in the sputum samples. Major differences in the cytokine levels were shown although the samples were obtained at the same time in the same patient. Advanced structural lung disease was closely related to systemic and lower airway inflammation, whereas preserved lung function was associated with higher levels in the NL. We hypothesize that the main part of the immune response takes place in the nasal mucosa in patients with minor pulmonary changes. Our results suggest that inflammation must be interpreted individually depending on the compartment in which it is measured. Further research is needed to accurately understand inflammatory markers measured in NL.