bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen Sulfide Modulates Astrocytic Toxicity in Mouse Spinal Cord Cultures: Implications for Amyotrophic Lateral Sclerosis
Authors: De Stefano Susanna , Tiberi Marta , Salvatori Illari , De Bardi Marco , Gimenez Juliette , Pirshayan Mahsa , Greco Viviana , Borsellino Giovanna , Ferri Alberto , Valle Cristiana , Mercuri Nicola B. , Chiurchiù Valerio , Spalloni Alida , Longone Patrizia
Published: October 2024

Hydrogen sulfide (H2S), a known inhibitor of the electron transport chain, is endogenously produced in the periphery as well as in the central nervous system, where is mainly generated by glial cells. It affects, as a cellular signaling molecule, many different biochemical processes. In the central nervous system, depending on its concentration, it can be protective or damaging to neurons. In the study, we have demonstrated, in a primary mouse spinal cord cultures, that it is particularly harmful to motor neurons, is produced by glial cells, and is stimulated by inflammation. However, its role on glial cells, especially astrocytes, is still under-investigated. The present study was designed to evaluate the impact of H2S on astrocytes and their phenotypic heterogeneity, together with the functionality and homeostasis of mitochondria in primary spinal cord cultures. We found that H2S modulates astrocytes’ morphological changes and their phenotypic transformation, exerts toxic properties by decreasing ATP production and the mitochondrial respiration rate, disturbs mitochondrial depolarization, and alters the energetic metabolism. These results further support the hypothesis that H2S is a toxic mediator, mainly released by astrocytes, possibly acting as an autocrine factor toward astrocytes, and probably involved in the non-cell autonomous mechanisms leading to motor neuron death.
Baicalein Ameliorates Insulin Resistance of HFD/STZ Mice Through Activating PI3K/AKT Signal Pathway of Liver and Skeletal Muscle in a GLP-1R-Dependent Manner
Authors: Liu Na , Cui Xin , Guo Tingli , Wei Xiaotong , Sun Yuzhuo , Liu Jieyun , Zhang Yangyang , Ma Weina , Yan Wenhui , Chen Lina
Published: October 2024

Insulin resistance (IR) is the principal pathophysiological change occurring in diabetes mellitus (DM). Baicalein, a bioactive flavonoid primarily extracted from the medicinal plant Scutellaria baicalensis Georgi, has been shown in our previous research to be a potential natural glucagon-like peptide-1 receptor (GLP-1R) agonist. However, the exact therapeutic effect of baicalein on DM and its underlying mechanisms remain elusive. In this study, we investigated the therapeutic effects of baicalein on diabetes and sought to clarify its underlying molecular mechanisms. Our results demonstrated that baicalein improves hyperglycemic, hyperinsulinemic, and glucometabolic disorders in mice with induced diabetes via GLP-1R. This was confirmed by the finding that baicalein’s effects on improving IR were largely diminished in mice with whole-body Glp1r ablation. Complementarily, network pharmacology analysis highlighted the pivotal involvement of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) insulin signaling pathway in the therapeutic actions of baicalein on IR. Our mechanism research significantly confirmed that baicalein mitigates hepatic and muscular IR through the PI3K/AKT signal pathway, both in vitro and in vivo. Furthermore, we demonstrated that baicalein enhances glucose uptake in skeletal muscle cells under IR conditions through the Ca2+/calmodulin-dependent protein kinase II (CaMKII)-adenosine 5′-monophosphate-activated protein kinase (AMPK)-glucose transporter 4 (GLUT4) signaling pathway in a GLP-1R-dependent manner. In conclusion, our findings confirm the therapeutic effects of baicalein on IR and reveal that it improves IR in liver and muscle tissues through the PI3K/AKT insulin signaling pathway in a GLP-1R dependent manner. Moreover, we clarified that baicalein enhances the glucose uptake in skeletal muscle tissue through the Ca2+/CaMKII-AMPK-GLUT4 signal pathway.
Deciphering the Landscape of GATA-Mediated Transcriptional Regulation in Gastric Cancer
Authors: Begolli Rodiola , Patouna Anastasia , Vardakas Periklis , Xagara Anastasia , Apostolou Kleanthi , Kouretas Demetrios , Giakountis Antonis
Published: October 2024

Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. However, LS-TFs also govern important physiological roles, hindering their direct therapeutic targeting. Therefore, their downstream target genes are particularly interesting for developing cancer-specific molecular biomarkers or therapeutic agents. In this work, we couple inducible knockdown systems with chromatin immunoprecipitation and RNA-seq to thoroughly detect and characterize direct targets of GATA-mediated transcriptional regulation in gastric cancer cells. Our experimental and computational strategy provides evidence that both factors regulate the expression of several coding and non-coding RNAs that in turn mediate for their cancer-promoting phenotypes, including but not limited to cell cycle, apoptosis, ferroptosis, and oxidative stress response. Finally, the diagnostic and prognostic potential of four metagene signatures consisting of selected GATA4/6 target transcripts is evaluated in a multi-cancer panel of ~7000 biopsies from nineteen tumor types, revealing elevated specificity for gastrointestinal tumors. In conclusion, our integrated strategy uncovers the landscape of GATA-mediated coding and non-coding transcriptional regulation, providing insights regarding their molecular and clinical function in gastric cancer.
Designing Personalized Learning Paths for Foreign Language Acquisition Using Big Data: Theoretical and Empirical Analysis
Authors: Xia Yina , Shin Seong-Yoon , Shin Kwang-Seong
Published: October 2024

This study introduces the Data-Driven Personalized Learning Model (DDPLM), a sophisticated framework designed to enhance foreign language acquisition through the integration of big data analytics. Implemented within the educational platforms Edmodo and Duolingo, DDPLM utilizes real-time data processing to tailor learning paths and content dynamically to individual learner needs. Our findings indicate significant improvements in language learning efficiency, engagement, and retention. The model’s adaptability across different digital environments showcases its potential scalability and effectiveness in various educational contexts. Additionally, the research addresses the critical role of personalized feedback and adaptive challenges in maintaining learner motivation and promoting deeper linguistic comprehension. The outcomes suggest that DDPLM significantly transforms traditional language education, making it more personalized, efficient, and aligned with individual learning preferences.
Effects of Successive Annual Training on Young Swimmers’ Strength Asymmetries and Performance
Authors: Arsoniadis Gavriil G. , Toubekis Argyris G.
Published: October 2024

This study aimed to compare changes in swimmers’ performance, biomechanical variables, and strength asymmetries within two successive training years. Eight competitive age-group swimmers (four males and four females; age: 14.8 ± 1.3 years) were tested before and after the same 12-week mesocycle period within two successive years (Year-1, Year-2). The swimmers were timed in 50, 200, and 400 m, and the stroke rate (SR), stroke length (SL), and stroke index (SI) were calculated. SI was calculated by the product of SL with swimming speed. Dryland shoulder isometric strength (ISO), hand grip isometric strength test (HG), and in-water maximum 30 s tethered swimming force (TF) were evaluated. The asymmetry index was calculated using ISO, HG, and TF tests as [(Fd − Fnd)/0.5 × (Fd + Fnd)] × 100, where Fd is strength in the dominant hand and Fnd is strength in the non-dominant hand. Performance time improved in 200 and 400 m, while the asymmetry indices calculated by the ISO, HG, and TF tests were similar after 12 weeks of training in both Year-1 and Year-2 (p = 0.01). Changes (Δ) in HG strength asymmetries correlated with Δ in 200 and 400 m in Year-2 (r = 0.78–0.87, p = 0.01). The asymmetry index does not change after two successive years of training but may be connected to performance changes in 200 and 400 m front crawl.
Separating the Spectral Counterparts in NGC 1275/Perseus Cluster in X-Rays
Authors: Fedorova Elena , Zadorozhna Lidiia , Tugay Anatolii , Pulatova Nadiia , Ganz Alexander , Gugnin Olexandr
Published: October 2024

We present a model-independent method for separating the spectral counterparts of the active galactic nucleus (AGN) NGC 1275 from the surrounding emission of the Perseus cluster, as observed by Suzaku/XIS cameras. The Perseus cluster emission extends to higher energies than typically observed in AGN environments, reaching up to 9–10 keV. This necessitates precise separation of AGN and cluster spectra. To circumvent the degeneracy arising from numerous spectral fitting parameters, including elemental abundances, thermal and Compton emissions from the nucleus, and spectral parameters of the jet synchrotron self-Compton/inverse Compton emissions, we avoid traditional spectral fitting methods. Instead, we leverage spatial resolution and employ a double background subtraction approach. We apply this procedure to the complete set of Suzaku/XIS observational data for NGC 1275, resulting in cleaned spectra and a light curve of the AGN emission in this system. To demonstrate the applicability of our method, we also utilize the available XMM-Newton/EPIC data.
A Comprehensive Review of Golden Riemannian Manifolds
Authors: Chen Bang-Yen , Choudhary Majid Ali , Perween Afshan
Published: October 2024

In differential geometry, the concept of golden structure represents a compelling area with wide-ranging applications. The exploration of golden Riemannian manifolds was initiated by C. E. Hretcanu and M. Crasmareanu in 2008, following the principles of the golden structure. Subsequently, numerous researchers have contributed significant insights with respect to golden Riemannian manifolds. The purpose of this paper is to provide a comprehensive survey of research on golden Riemannian manifolds conducted over the past decade.
Fixed Point Results in Modular b-Metric-like Spaces with an Application
Authors: Bostan Nizamettin Ufuk , Pazar Varol Banu
Published: October 2024

In this study, we introduce a new space called the modular b-metric-like space. We investigate some properties of this new concept and define notions of ξ-convergence, ξ-Cauchy sequence, ξ-completeness and ξ-contraction. The existence and uniqueness of fixed points in the modular b-metric-like space are handled. Moreover, we give some examples and an application to an integral equation to illustrate the usability of the obtained results.
Anti-Müllerian Hormone Serum Levels as Biomarker of Ovarian Reserve in Adult Women with Juvenile Idiopathic Arthritis Treated with csDMARDs and/or bDMARDs: A Pilot Study
Authors: Di Mario Clara , Gigante Maria Rita , Barini Angelina , Petricca Luca , Barini Antonella , Bianchi Antonio , Alivernini Stefano , Tolusso Barbara , Gremese Elisa
Published: October 2024

Background/Objectives: Juvenile idiopathic arthritis (JIA) is a chronic childhood disease that often persists into the reproductive years. JIA may impact long-term fertility due to the prolonged exposure to immunosuppressive therapies. Methods: A total of 35 adult JIA female patients of childbearing age and 20 age-matched healthy controls were studied to test their anti-Müllerian hormone (AMH) serum levels as a biomarker of ovarian reserve. Demographic characteristics, disease duration, previous and current treatments, disease activity (DAS44), and a health assessment questionnaire (HAQ) were recorded. Results: JIA patients had a mean age of 22.3 ± 2.9 years, a disease duration of 12.3 ± 6.1 years, and a DAS44 of 1.24 ± 0.61. No differences were found in AMH serum levels between JIA and controls (5.78 ± 2.37 ng/mL vs. 6.60 ± 2.68 ng/mL, respectively; p = 0.17). Among the patients, 22 (62.9%) were receiving a stable dose of methotrexate (MTX) and 19 (54.3%) a dose of TNFα inhibitors. No difference in AMH serum levels was observed between JIA patients who were or were not exposed to MTX (p = 0.29) or to TNFα inhibitors (p = 0.50). Conclusions: Ovarian reserve as assessed by AMH serum levels appears to be comparable between those with JIA and age-matched controls and does not appear to be influenced by disease characteristics or prior/concomitant exposure to immunosuppressive drugs.
Recombinant Plasminogen Activator of the Sandworm (Perinereis aibuhitensis) Expression in Escherichia coli
Authors: Song Tuo , Diao Xiaozhen , Cheng Jun , Man Yang , Chen Boyu , Zhang Haixing , Wu Wenhui
Published: October 2024

As an essential thrombolytic agent, the tissue plasminogen activator receives increasing attention due to its longer half-life, lower immunogenicity, and easier administration, which are superior to other thrombolytic agents. In this study, the isolated and purified plasminogen activator from the sandworm (Perinereis aibuhitensis) was expressed in E. coli (Escherichia coli) to investigate its potential for simplifying the development process. The sandworm plasminogen activator was previously successfully cloned and expressed in E. coli with low yield and activity in the culture supernatant. This low yield and activity prompted us to optimize its DNA sequence. Furthermore, to raise the efficiency in the separation of the target protein, the protein’s solubility was enhanced by fusing it with maltose-binding protein (MBP) tags. Eventually, the fibrinolytic activity was successfully restored after digestion with tobacco etch virus (TEV) protease. This study provides an innovative method of efficiently expressing and purifying plasminogen activators from sandworm in E. coli and broadens its applications in therapeutic treatment of cardiovascular diseases, including thrombosis, stroke, and coronary atherosclerotic heart disease.
Enhancing Cardiovascular Risk Prediction: Development of an Advanced Xgboost Model with Hospital-Level Random Effects
Authors: Dong Tim , Oronti Iyabosola Busola , Sinha Shubhra , Freitas Alberto , Zhai Bing , Chan Jeremy , Fudulu Daniel P. , Caputo Massimo , Angelini Gianni D.
Published: October 2024

Background: Ensemble tree-based models such as Xgboost are highly prognostic in cardiovascular medicine, as measured by the Clinical Effectiveness Metric (CEM). However, their ability to handle correlated data, such as hospital-level effects, is limited. Objectives: The aim of this work is to develop a binary-outcome mixed-effects Xgboost (BME) model that integrates random effects at the hospital level. To ascertain how well the model handles correlated data in cardiovascular outcomes, we aim to assess its performance and compare it to fixed-effects Xgboost and traditional logistic regression models. Methods: A total of 227,087 patients over 17 years of age, undergoing cardiac surgery from 42 UK hospitals between 1 January 2012 and 31 March 2019, were included. The dataset was split into two cohorts: training/validation (n = 157,196; 2012–2016) and holdout (n = 69,891; 2017–2019). The outcome variable was 30-day mortality with hospitals considered as the clustering variable. The logistic regression, mixed-effects logistic regression, Xgboost and binary-outcome mixed-effects Xgboost (BME) were fitted to both standardized and unstandardized datasets across a range of sample sizes and the estimated prediction power metrics were compared to identify the best approach. Results: The exploratory study found high variability in hospital-related mortality across datasets, which supported the adoption of the mixed-effects models. Unstandardized Xgboost BME demonstrated marked improvements in prediction power over the Xgboost model at small sample size ranges, but performance differences decreased as dataset sizes increased. Generalized linear models (glms) and generalized linear mixed-effects models (glmers) followed similar results, with the Xgboost models also excelling at greater sample sizes. Conclusions: These findings suggest that integrating mixed effects into machine learning models can enhance their performance on datasets where the sample size is small.
Targeting Protein Aggregation in ALS
Authors: Perni Michele , Mannini Benedetta
Published: October 2024

Proteinopathies involve the abnormal accumulation of specific proteins. Maintaining the balance of the proteome is a finely regulated process managed by a complex network of cellular machinery responsible for protein synthesis, folding, and degradation. However, stress and ageing can disrupt this balance, leading to widespread protein aggregation. Currently, several therapies targeting protein aggregation are in clinical trials for ALS. These approaches mainly focus on two strategies: addressing proteins that are prone to aggregation due to mutations and targeting the cellular mechanisms that maintain protein homeostasis to prevent aggregation. This review will cover these emerging drugs. Advances in ALS research not only offer hope for better outcomes for ALS patients but also provide valuable insights and methodologies that can benefit the broader field of neurodegenerative disease drug discovery.
The Effects of VEGF-A and GSTM1/GSTT1 Variants in the Susceptibility to the Chronic Rhinosinusitis with Nasal Polyposis: A Pilot Genetic Study
Authors: Camargo Leandro Azevedo , Reis Angela Adamski da Silva , Rodrigues Stela Oliveira , Santos Rodrigo da Silva , Avelino Melissa Ameloti Gomes
Published: October 2024

Nasal polyps (NPs) are usually part of chronic rhinosinusitis with nasal polyposis (CRSwNP). However, the exact etiology of CRSwNP is still unknown. In addition, the suggested etiological causes are infection, allergy, and immunological disorders, among others, such as genetic predisposition. Moreover, it is also suggested that oxygen-free radicals play a vital role in the pathogenesis of nasal polyposis, and inflammatory cells produce free radicals during phagocytosis, which is the primary source of ROS, controlled by the glutathione S-transferase (GST) system. Although, vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, it is closely interwoven with the mobilization of inflammatory cells. This pilot study evaluated the association between genetic variant VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphism in susceptibility to CRSwNP. A case–control study was conducted with 61 individuals diagnosed with CRSwNP and 100 healthy subjects. VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphisms were genotyped by RFLP-PCR and SYBR Green real-time PCR, respectively. Individuals with allergic rhinitis carriers with AC genotype (rs28357093) presented a 4-fold increased risk to CRSwNP (OR = 4.20, 95% CI = 1.31 to 13.50; p = 0.015). This evidence shows that the increased vascular permeability probably causes an inflamed nasal area leading to extensive edema and polyp growth. On the other hand, no association was verified for each genetic variant by inheritance models. Interestingly, the GSTT1 present genotype showed a protective effect on CRSwNP. In conclusion, additional studies that have larger groups in different geographic localizations may be useful to verify and assess the association between genetic variants and CRSwNP.
A New Single-Parameter Bees Algorithm
Authors: Suluova Hamid Furkan , Pham Duc Truong
Published: October 2024

Based on bee foraging behaviour, the Bees Algorithm (BA) is an optimisation metaheuristic algorithm which has found many applications in both the continuous and combinatorial domains. The original version of the Bees Algorithm has six user-selected parameters: the number of scout bees, the number of high-performing bees, the number of top-performing or “elite” bees, the number of forager bees following the elite bees, the number of forager bees recruited by the other high-performing bees, and the neighbourhood size. These parameters must be chosen with due care, as their values can impact the algorithm’s performance, particularly when the problem is complex. However, determining the optimum values for those parameters can be time-consuming for users who are not familiar with the algorithm. This paper presents BA1, a Bees Algorithm with just one parameter. BA1 eliminates the need to specify the numbers of high-performing and elite bees and other associated parameters. Instead, it uses incremental k-means clustering to divide the scout bees into groups. By reducing the required number of parameters, BA1 simplifies the tuning process and increases efficiency. BA1 has been evaluated on 23 benchmark functions in the continuous domain, followed by 12 problems from the TSPLIB in the combinatorial domain. The results show good performance against popular nature-inspired optimisation algorithms on the problems tested.
Numerical Investigation of an NACA 13112 Morphing Airfoil
Authors: Feraru Mădălin-Dorin , Măriuța Daniel , Stoia-Djeska Marius , Grigorie Lucian-Teodor
Published: October 2024

This article presents a numerical study on the 2D aerodynamic characteristics of an airfoil with a morphed camber. The operational regime of the main rotor blade of the IAR 330 PUMA helicopter was encompassed in CFD simulations, performed over an angle of attack range of α=[−3°; 18°], and a Mach number of M=0.38. Various degrees of camber adjustment were smoothly implemented to the trailing-edge section of the NACA13112 airfoil, with a corresponding chord length of c=600 mm at the Reynolds number, Re=5.138×106, and the resulting changes in static lift and drag were calculated. The study examines the critical parameters that affect the configuration of the morphing airfoil, particularly the length of the trailing edge morphing. This analysis demonstrates that increasing the morphed camber near the trailing edge enhances lift capability and indicates that the maximum lift of the airfoil depends on the morphed chord length. The suggested approach demonstrates potential and can be implemented across various categories of aerodynamic structures, such as propeller blade sections, tails, or wings.
Satisfaction Evaluation of Civil Air Defense Engineering Renovated into Cooling Place from the Perspective of Public Experience
Authors: Li Wenlong , Li Qin , Liu Yijun , Jia Lixin , Pei Xingwang , Cui Jingya
Published: October 2024

Scientific and reasonable satisfaction evaluation is an excellent way to understand the effects of building (structure) renovation and public satisfaction. This study presents a satisfaction evaluation of civil air defense engineering renovated into cooling place from the perspective of public experience. First, a satisfaction evaluation indicator system was constructed for civil air defense engineering renovated into cooling place from the perspective of public experience, focusing on 5 first-level indicators—location condition, spatial status, physical environment, service management, and emotional experience—and 27 second-level indicators. Second, the matter-element extension and combined weighting method were introduced to establish a satisfaction evaluation model for civil air defense engineering renovated into cooling place from the perspective of public experience. Finally, the rationality of the index system and feasibility of the evaluation model were verified by considering civil air defense cooling centers as examples. This research can provide a basis for the further optimization of such projects and the development and management of cities, as well as new ideas or methods for the satisfaction evaluation of similar old buildings (structures) after renovation.
Retrospective Evaluation of GEC-ESTRO Constraints for Definitive Radiochemotherapy with Brachytherapy and Correlation with Oncologic Outcome in Cervical Cancer: A Monocenter Study
Authors: Schönicke Tom , Koch Raphael , Vogt Isabel , Falke Isabel , Eich Hans Theodor , Reinartz Gabriele
Published: October 2024

Background: This study aims to evaluate patients with locally advanced cervical cancer who underwent definitive radiochemotherapy, including brachytherapy, at the University Hospital of Muenster (UKM), focusing on target volume coverage, oncologic outcome parameters, and organs at risk (OAR) toxicities. Results are compared with the Gyn GEC-ESTRO (GGE) recommendations. Methods: Of a cohort of 48 patients, treated between 2013 and 2023, the physical radiation treatment planning with application of CT and MRI and oncologic follow-up data was analyzed. Target volume structures, comprising the high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), Point A, and corresponding EQD2(α/β=10) doses were determined. Endpoints included local tumor control, overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). Total OAR (D2cc) EQD2(α/β=3) doses were correlated with adverse events defined by CTCAE v5.0 and LENT-SOMA criteria. Results: Median follow-up was 58.0 months (95% CI [27.6, 88.4]). FIGO stage I was present in 7 (15%) patients, II in 13 (27%), and III in 28 (58%) patients. A total of 38 (79%) patients showed a complete remission 3 months after treatment. The 5-year event-free rate was 67.4% (95% CI [49.3, 80.3]) for OS, 77.0% (95% CI [56.7, 88.6]) for RFS and 68.1% (95% CI [49.7, 80.9]) for PFS. Incomplete radiation treatment and advanced tumor stages led to worse outcomes. Meeting Point A GGE recommendations increased chances for complete remission and could decrease chances of an event occurring for OS, PFS, and RFS. Compliance with GGE recommendations lowered the chances of OAR toxicity occurring. Conclusions: MRI-based target volume definition for brachytherapy in cervical cancer may improve patients’ OS, PFS, and RFS. Time-to-event endpoints are consistent with comparable studies, and adherence to current ESGO/ESTRO/ESP guidelines is endorsed.
The Associations between Depressive Symptoms and Self-Rated Health in Relation to Sense of Coherence among Adolescents: Cross-Sectional Study
Authors: Malinauskiene Vilija , Malinauskas Romualdas
Published: October 2024

Background: We investigated the predictors of poor SRH in a representative sample of Lithuanian mainstream school students in grades 7–8. We also checked for gender differences in the associations between SRH and depressive symptoms and other predictors. Methods: A total of 2104 7th–8th-grade students participated (response rate 73.95%) and were asked about depressive symptoms, psychosomatic health complaints, negative acts at school, feeling at school, family stress and violence, sense of coherence, self-esteem, and lifestyle. We used a hierarchical regression analysis including a variety of self-rated health predictors. Results: Boys scored significantly higher on physical activity and smoking, whereas girls scored significantly higher on SRH, depressive symptoms, psychosomatic health complaints, and family stress and violence, though the significance was lost in the hierarchical regression. Depressive symptoms were the strongest predictor of poor SRH (standardized β = 0.309, p < 0.001), though other investigated predictors were also significant but had lower effect sizes. Strong evidence was found supporting the buffering role of sense of coherence in the relationship between depressive symptoms and SRH (standardized β = −0.266, p < 0.001). Conclusions: We can conclude that the magnitude of the relationship between depressive symptoms and self-rated health is dependent on the levels of sense of coherence. We did not find gender differences in those associations. As poor SRH is easy to determine, especially with a one-item question, the cases of poorly rated health should be detected early and corrected by interventions in order to prevent poor health outcomes in the future.
“Hanging on by a Thread”: The Lived Experience of Parents of Children with Medical Complexity
Authors: Holmes Courtney , Zeleke Waganesh , Sampath Shruti , Kimbrough Tiffany
Published: October 2024

Background: Families with children with medical complexity endure high levels of chronic and toxic stress, impacting the overall health and wellbeing of all family members and the system as a whole. The purpose of this study was to examine the lived experiences of parents/caregivers with children with medical complexity. Methods: The lived experiences of 15 parents of children with complex medical needs were explored using focus group discussions. Focus group discussions were recorded, transcribed, and analyzed using van Manen’s 6-step process for hermeneutic phenomenology. Aligned with the research questions, the analysis draws on van Manen’s four lived existential analytical categories. Results: Themes include: (1) lived body, the psychological and physiological effect; (2) lived time and space, the immediate impact on the there, now, and then; (3) lived relationships, social life and family relational effect; (4) risk factors; and (5) protective factors. Conclusion: Caregivers of children with medical complexity have a unique experience of trauma and resilience. This study will inform interdisciplinary medical providers about the mental health and resiliency experiences of this population to support more effective healthcare practices.
Effect of Helicobacter pylori Eradication on Serum Level of Valproic Acid in Children with Idiopathic Generalized Epilepsy
Authors: Abdelgalil Abobakr , Ismail Doaa , Eskander Ayman , Girgis Marian , Farouk Ahmed , Saeedi Fajr , Shazly Mohamed , Hasnoon Amera
Published: October 2024

Background/Objectives: The purpose of this study was to determine the influence of H. pylori eradication on the serum level of the orally administered valproic acid (VPA) in children with idiopathic generalized epilepsy; Methods: This prospective cohort observational study included 100 children with idiopathic generalized epilepsy, recruited from a neurology clinic from May 2021 to December 2021. The patients were divided into two groups, each containing 50 children. The first group had a positive H. pylori stool antigen and H. pylori-related symptoms, while the second group had a negative antigen. H. pylori Eradication therapy was given to the positive H. pylori group. The serum level of VPA was obtained at baseline and 4 weeks after eradication therapy. Results: Despite there being no significant difference between the H. pylori-positive and H. pylori-negative groups regarding the baseline VPA serum level (79.9 ± 13.9 and 77.9 ± 13.1 mcg/mL), respectively, the serum VPA level had significantly increased after H. pylori eradication therapy (99.4 ± 11 mcg/mL) (p value = 0.000), as opposed to the H. pylori-negative group (85.3 ± 10.9 mcg/mL) (p value = 0.142). Furthermore, there was a statistically significant association with a negative correlation between the VPA serum level after eradication and the number of epileptic attacks per month (p value = 0.033, R value = −0.301) and the dose of VPA (p value = 0.046, R value = −0.284). Conclusions: The eradication of H. pylori resulted in a highly significant improvement in the serum level of the orally given VPA in children with idiopathic generalized epilepsy, as well as an indirect decrease in the frequency of epileptic events per month, allowing for dose reduction. Eradication therapy may have anticonvulsant properties and might indirectly aid in the management of epileptic activity. H. pylori screening for children with idiopathic generalized epilepsy can optimize serum VPA levels, potentially leading to better seizure control. To our knowledge, this is the first study in the literature to describe the effect of H. pylori eradication on the serum level of the orally administered VPA in children with idiopathic generalized epilepsy.
Patellofemoral Instability in the Pediatric and Adolescent Population: From Causes to Treatments
Authors: Ricciuti Anthony , Colosi Katelyn , Fitzsimmons Kevin , Brown Matthew
Published: October 2024

Background: Patella instability is one of the most common knee injuries in the adolescent patient. There are several pathoanatomic risk factors which should be assessed via several modalities, including X-rays, magnetic resonance imaging (MRI), or even CT scan. Objectives: We intend to review these risk factors along with the nonsurgical and surgical techniques used to prevent recurrent dislocations. Methods: We completed an extensive review of the recent literature concerning pediatric and adolescent patellar dislocation and subsequent treatment modalities. Results: We review in detail the risk factors such as patella alta, trochlear dysplasia, lateralization of the tibial tubercle or medialization of the trochlear groove (increased tibial tubercle to trochlear groove (TT–TG) distance), lower limb malalignment, excessive femoral anteversion and/or tibial torsion, and hyperlaxity. There are classification systems for dislocators, and a natural progression of instability that patients often proceed through. Only after a patient has continued to dislocate after bracing and physical therapy is surgical treatment considered. Surgical techniques vary, with the workhorse being the medial patellofemoral ligament (MPFL) reconstruction. However, there are a variety of other techniques which add onto this procedure to address other anatomic risk factors. These include the tibial tubercle osteotomy to address a large TT–TG distance or trochleoplasty to address the lack of a trochlear groove. Conclusions: Nonsurgical and surgical treatments for patella dislocators are tailored to the pathoanatomic risk factors in each patient.
A Study of Hydroelectrolytic and Acid–Base Disturbances in MIS-C Patients: A Perspective on Antidiuretic Hormone Secretion
Authors: Petrea (Cliveți) Carmen Loredana , Ciortea Diana-Andreea , Candussi Iuliana-Laura , Gurău Gabriela , Matei Nicoleta Mădălina , Bergheș Simona-Elena , Chirila Sergiu Ioachim , Berbece Sorin Ion
Published: October 2024

COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) is a rare autoimmune disorder characterized by a range of polymorphic manifestations, similar to but distinct from other well-known inflammatory syndromes in children. We conducted a retrospective–descriptive study in which we summarized the clinical presentation of, biomarker variations in, and complications occurring in patients diagnosed with MIS-C, admitted to the Emergency Clinical Hospital for Children “Sf. Ioan”, Galati, between July 2020 and June 2024. A total of 36 children met the MIS-C classification criteria according to the WHO-approved case definitions. A total of 41.7% (n = 15) were male and 58.3% (n = 21) were female. The median age of the study group was 4 years (IQR: 1.75–9.25 years). Surgical involvement was suspected in 16.7% (n = 6) of the patients, while 52.8% (n = 19) required intensive care. Clinically, fever was the most common symptom present in 89% (n = 32) of the cases. Gastrointestinal disorders were also common, with 50% (n = 18) presenting with inappetence, 42% (n = 15) with vomiting, and 39% (n = 14) with abdominal pain from admission, which worsened over time. Paraclinically, all patients exhibited signs of inflammation, and 86.1% (n = 31) had hydroelectrolytic and acid–base imbalances. The median hospital stay was 10 days (IQR: 7–12 days), with a stagnant clinical course in most cases. The inflammatory mechanisms in MIS-C, which can affect the secretion of antidiuretic hormone (ADH), were correlated with hydroelectrolytic disturbances and may lead to severe complications. For this reason, it is imperative to evaluate hydroelectrolytic disorders in the context of MIS-C and use diagnostic and prognostic biomarkers to develop effective therapeutic management strategies, ultimately improving the quality of life of affected children.
Interleukin-12 Delivery Strategies and Advances in Tumor Immunotherapy
Authors: Dong Chunyan , Tan Dejiang , Sun Huimin , Li Zhuang , Zhang Linyu , Zheng Yiyang , Liu Sihan , Zhang Yu , He Qing
Published: October 2024

Interleukin-12 (IL-12) is considered to be a promising cytokine for enhancing an antitumor immune response; however, recombinant IL-12 has shown significant toxicity and limited efficacy in early clinical trials. Recently, many strategies for delivering IL-12 to tumor tissues have been developed, such as modifying IL-12, utilizing viral vectors, non-viral vectors, and cellular vectors. Previous studies have found that the fusion of IL-12 with extracellular matrix proteins, collagen, and immune factors is a way to enhance its therapeutic potential. In addition, studies have demonstrated that viral vectors are a good platform, and a variety of viruses such as oncolytic viruses, adenoviruses, and poxviruses have been used to deliver IL-12—with testing previously conducted in various cancer models. The local expression of IL-12 in tumors based on viral delivery avoids systemic toxicity while inducing effective antitumor immunity and acting synergistically with other therapies without compromising safety. In addition, lipid nanoparticles are currently considered to be the most mature drug delivery system. Moreover, cells are also considered to be drug carriers because they can effectively deliver therapeutic substances to tumors. In this article, we will systematically discuss the anti-tumor effects of IL-12 on its own or in combination with other therapies based on different delivery strategies.
Whole-Genome Sequencing of the Entomopathogenic Fungus Fusarium solani KMZW-1 and Its Efficacy Against Bactrocera dorsalis
Authors: Yu Junfu , Hussain Mehboob , Wu Mingqi , Shi Chunlan , Li Shini , Ji Yuanxia , Hussain Sikandar , Qin Deqiang , Xiao Chun , Wu Guoxing
Published: October 2024

Fusarium solani KMZW-1 is recognized for its potential as a biocontrol agent against agricultural and forestry pests, particularly due to its compatibility with integrated pest management (IPM) strategies. This study aimed to investigate the complete genome of F. solani KMZW-1 and assess its pathogenicity against Bactrocera dorsalis. Whole-genome sequencing revealed a genome size of 47,239,278 bp, comprising 27 contigs, with a GC content of 51.16% and fungus identified as F. solani KMZW-1. The genome completeness was assessed as 97.93% using BUSCO analysis, the DFVF sequence identifier was Fusarium 0G092560.1, and AntiSMASH analysis identified 35 gene clusters associated with secondary metabolite biosynthesis, providing insights into the genetic basis of its pathogenic mechanisms and biocontrol potential. Comparative genomic analysis found 269 unique genes for F. solani KMZW-1, and collinearity analysis exhibited a high degree of synteny with Fusarium solani-melongenae. The pathogenicity of F. solani KMZW-1 was assessed using concentrations ranging from 1 × 104 to 1 × 1011 conidia/mL. Higher concentrations (1 × 1010 to 1 × 1011 conidia/mL) resulted in significantly increased cumulative mortality rates of B. dorsalis adults compared to the control group. Notably, the pathogenicity was higher in male adults than in females. Probit analysis yielded LC50 (50% lethal concentration) values of 5.662 for female and 4.486 for male B. dorsalis adults. In summary, F. solani, KMZW-1 exhibits strong insecticidal activity against B. dorsalis and shows potential as a biocontrol agent with IPM strategies. These findings provide robust genomic evidence supporting the use of F. solani KMZW-1 in managing against B. dorsalis populations.
Decoding the Genetic Basis of Mast Cell Hypersensitivity and Infection Risk in Hypermobile Ehlers-Danlos Syndrome
Authors: Shirvani Purusha , Shirvani Arash , Holick Michael F.
Published: October 2024

Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder marked by joint hypermobility, skin hyperextensibility, and tissue fragility. Recent studies have linked hEDS with mast cell activation syndrome (MCAS), suggesting a genetic interplay affecting immune regulation and infection susceptibility. This study aims to decode the genetic basis of mast cell hypersensitivity and increased infection risk in hEDS by identifying specific genetic variants associated with these conditions. We conducted whole-genome sequencing (WGS) on 18 hEDS participants and 7 first-degree relatives as controls, focusing on identifying genetic variants associated with mast cell dysregulation. Participants underwent clinical assessments to document hEDS symptoms and mast cell hypersensitivity, with particular attention to past infections and antihistamine response. Our analysis identified specific genetic variants in MT-CYB, HTT, MUC3A, HLA-B and HLA-DRB1, which are implicated in hEDS and MCAS. Protein–protein interaction (PPI) network analysis revealed significant interactions among identified variants, highlighting their involvement in pathways related to antigen processing, mucosal protection, and collagen synthesis. Notably, 61.1% of the hEDS cohort reported recurrent infections compared to 28.5% in controls, and 72.2% had documented mast cell hypersensitivity versus 14.2% in controls. These findings provide a plausible explanation for the complex interplay between connective tissue abnormalities and immune dysregulation in hEDS. The identified genetic variants offer insights into potential therapeutic targets for modulating mast cell activity and improving patient outcomes. Future research should validate these findings in larger cohorts and explore the functional implications of these variants to develop effective treatment strategies for hEDS and related mast cell disorders.
Homosalate and ERK Knockdown in the Modulation of Aurelia coerulea Metamorphosis by Regulating the PI3K Pathway and ERK Pathway
Authors: Chen Jinhong , Geng Xiaoyu , Li Bingbing , Xie Jinyao , Ma Jieying , Qin Zhen , Wang Mingke , Yang Jishun
Published: October 2024

Metamorphosis control is pivotal in preventing the outbreak of jellyfish, and it is often studied using common model organisms. The widespread use of the ultraviolet blocking agent homosalate in cosmetics poses a threat to marine ecosystems. Although the impact of homosalate on marine organisms has been extensively examined, there is a notable absence of research on its effects on jellyfish metamorphosis and the underlying mechanisms, warranting further investigation. In this study, we first established a study model by using 5-methoxy-2-methylindole to induce Aurelia coerulea metamorphosis, and selected homosalate as a PI3K agonist and an ERK agonist, while we used YS-49 as a specific PI3K agonist, as well as ERK knockdown, to observe their effect on the metamorphosis of Aurelia coerulea. The results showed that an Aurelia coerulea metamorphosis model was established successfully, and the PI3K agonist homosalate, YS-49, and the knockdown of ERK molecules could significantly delay the metamorphosis development of Aurelia coerulea. We propose that activating PI3K/Akt and inhibiting the ERK pathway are involved in the delayed development of Aurelia coerulea, which provides a new strategy for the prevention and control of jellyfish blooms.
Effects of Different Surface Treatment Methods on Laser Welding of Aluminum Alloy and Glass
Authors: Chen Changjun , Li Lei , Zhang Min , Zhang Wei
Published: October 2024

Hermetic glass-to-metal sealing (GMTS) technology combines metal and glass and can be used to construct vacuum tubes; electric discharge tubes; semiconductor diodes; reed switches; and pressure-tight glass-to-metal windows, optical windows, and lenses in electronics or electronic systems. The hermetic and mechanically strong seals engineered using GTMS are highly reliable, making them suitable for deployment in harsh environments and for applications requiring high performance. However, it has always been challenging to precisely and robustly join glass and metal due to the significant disparities in their properties. In this study, the laser transmission welding of borosilicate glass and aluminum alloy using a pulsed Nd:YAG laser to achieve hermetic glass–metal seals was experimentally investigated. This research focused on various processing parameters and the influence of surface conditions on bonding quality. Three different types of surfaces—a polished surface, a surface subjected to preoxidation, and a laser-modified surface—were compared. To evaluate the weld strength, shear-tensile separation forces were measured. The analysis of fracture and separation encompassed detailed examinations of the weld morphology, microstructure, and elemental composition. The results revealed that increasing the laser welding energy initially enhanced the weld strength until a saturation point was reached. Among the three different surface treatments tested, the laser surface modification of aluminum alloy yielded the highest weld strength. The maximum achieved bond force exceeded 35.38 N, demonstrating the feasibility of using cost-effective pulsed laser welding for glass-to-metal sealing. The results were significantly better than those from previous research in which aluminum alloy surfaces were pretreated using microarc oxidation.
Incorporation of Phase Change Materials in Buildings
Authors: Jha Subodh Kumar , Sankar Advaith , Zhou Yue , Ghosh Aritra
Published: October 2024

This review paper explores the integration of phase change materials (PCMs) in building insulation systems to enhance energy efficiency and thermal comfort. Through an extensive analysis of existing literature, the thermal performance of PCM-enhanced building envelopes is evaluated under diverse environmental conditions. This review highlights that PCMs effectively moderate indoor temperatures by absorbing and releasing heat during phase transitions, maintaining a stable indoor climate. This paper also delves into the detailed concepts of PCMs, including their classification and various applications within building insulation. It is noted that different types of PCMs have unique thermal properties and potential uses, which can be tailored to specific building requirements and climatic conditions. Furthermore, cost–benefit and environmental assessments presented in the reviewed studies suggest that incorporating PCMs into building materials offers significant potential for reducing energy consumption and mitigating environmental impacts. These assessments indicate that PCMs can lead to substantial energy savings by decreasing the reliance on heating and cooling systems, thereby lowering overall energy costs and carbon emissions. However, despite the promising outlook, this review identifies a need for further research to optimize PCM formulations and integration methods. This optimization is essential for overcoming current challenges and facilitating the widespread adoption of PCMs in the construction industry. Addressing issues such as long-term durability, compatibility with existing building materials, and cost-effectiveness will be crucial for maximizing the benefits of PCMs in enhancing energy efficiency and sustainability in buildings. Overall, this review underscores the transformative potential of PCMs in building insulation practices. By providing a comprehensive overview of PCM classifications, applications, and their impacts on energy efficiency and environmental sustainability, this paper lays the groundwork for future advancements and research directions in the field of PCM-enhanced building technologies.