bluuebunny/crossref_metadata_2025 huggingface dataset:
Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability
Authors: Jovanović Marija , Homšek Ana , Marković Srđan , Kralj Đorđe , Svorcan Petar , Knežević Ivanovski Tamara , Odanović Olga , Vučićević Katarina
Published: December 2024

Background/Objectives: Several population pharmacokinetic models of vedolizumab (VDZ) are available for inflammatory bowel disease (IBD) patients. However, their predictive performance in real-world clinical settings remains unknown. This study aims to externally evaluate the published VDZ pharmacokinetic models, focusing on their predictive performance and simulation-based clinical applicability. Methods: A literature search was conducted through PubMed to identify VDZ population pharmacokinetic models. A total of 114 VDZ concentrations from 106 IBD patients treated at the University Medical Center “Zvezdara”, Republic of Serbia, served as the external evaluation cohort. The predictive performance of the models was assessed using prediction- and simulation-based diagnostics. Furthermore, the models were utilized for Monte Carlo simulations to generate concentration–time profiles based on 24 covariate combinations specified within the models. Results: Four published pharmacokinetic models of VDZ were included in the evaluation. Using the external dataset, the median prediction error (MDPE) ranged from 13.82% to 25.57%, while the median absolute prediction error (MAPE) varied between 41.64% and 47.56%. None of the models fully met the combined criteria in the prediction-based diagnostics. However, in simulation-based diagnostics, pvcVPC showed satisfactory results, despite wide prediction intervals. Analysis of NPDE revealed that only the models by Rosario et al. and Okamoto et al. fulfilled the evaluation criteria. Simulation analysis further demonstrated that the median VDZ concentration remains above 12 μg/mL at week 22 during maintenance treatment for approximately 45–60% of patients with the best-case covariate combinations and an 8-week dosing frequency. Conclusions: None of the published models satisfied the combined criteria (MDPE, MAPE, percentages of prediction error within ±20% and ±30%), rendering them unsuitable for a priori predictions. However, two models demonstrated better suitability for simulation-based applications.
Polo-like Kinase 1 Expression as a Biomarker in Colorectal Cancer: A Retrospective Two-Center Study
Authors: Jajac Brucic Lana , Bisof Vesna , Soce Majana , Skelin Marko , Krecak Ivan , Nadinic Andjela , Vrbicic Branka , Puljiz Zivana , Hancic Suzana , Gasparov Slavko
Published: December 2024

Background/Objectives: Early-onset colorectal cancer (EOCRC) is more frequently characterized by poorly differentiated, aggressive tumors, often diagnosed at advanced stages, and associated with worse prognoses. Despite these differences, current treatment guidelines do not distinguish between EOCRC and late-onset colorectal cancer (LOCRC). Elevated expression of polo-like kinase 1 (PLK-1) has been linked to advanced disease stages and poorer treatment outcomes, including resistance to both chemotherapy and radiotherapy. However, data on PLK-1 expression in EOCRC compared to LOCRC remain limited. Methods: Patients with sporadic CRC, aged >18 years, were included in this study. We categorized the patients into two groups: patients younger than 50 years, and those aged 50 years or older. Immunohistochemical staining was performed to assess PLK-1 expression. The aim of this study was to assess PLK-1 expression considering the age of the patients and its effects on overall survival (OS) and progression-free survival (PFS). Results: A total of 146 patients with metastatic colorectal cancer (mCRC) were included in this retrospective two-center study. Patients with low PLK-1 expression were older than patients with high PLK-1 expression (64 (49–71) years vs. 49 (42–67) years, p = 0.016). Multiple logistic regression confirmed that age is a significant predictor of PLK-1 expression, independent of the covariates (p = 0.036). The Kaplan–Meier analysis revealed no significant association between PLK-1 expression and PFS (p = 0.397) or OS (p = 0.448). Accordingly, Cox proportional hazards regression analysis showed no significant association between PLK-1 expression and OS (HR 1.20, 95% CI 0.73–1.96, p = 0.598) or PFS (HR 0.85, 95% CI 0.51–1.43, p = 0.611) when covariates were taken into account. Finally, no significant differences in PFS (p = 0.423) or OS (p = 0.104) were found between the age groups of interest. Conclusions: PLK-1 expression was not associated with survival or progression in EOCRC and LOCRC patients. Further research on these combinations is necessary, as well as the discovery of new potential targets for targeted therapy and the mechanisms of synergistic effects in tumors with PLK-1 overexpression.
Learning Dendritic-Neuron-Based Motion Detection for RGB Images: A Biomimetic Approach
Authors: Chen Tianqi , Todo Yuki , Qiu Zhiyu , Hua Yuxiao , Qiu Delai , Wang Xugang , Tang Zheng
Published: December 2024

In this study, we designed a biomimetic artificial visual system (AVS) inspired by biological visual system that can process RGB images. Our approach begins by mimicking the photoreceptor cone cells to simulate the initial input processing followed by a learnable dendritic neuron model to replicate ganglion cells that integrate outputs from bipolar and horizontal cell simulations. To handle multi-channel integration, we utilize a nonlearnable dendritic neuron model to simulate the lateral geniculate nucleus (LGN), which consolidates outputs across color channels, an essential function in biological multi-channel processing. Cross-validation experiments show that AVS demonstrates strong generalization across varied object–background configurations, achieving accuracy where traditional models like EfN-B0, ResNet50, and ConvNeXt typically fall short. Additionally, our results across different training-to-testing data ratios reveal that AVS maintains over 96% test accuracy even with limited training data, underscoring its robustness in low-data scenarios. This demonstrates the practical advantage of the AVS model in applications where large-scale annotated datasets are unavailable or expensive to curate. This AVS model not only advances biologically inspired multi-channel processing but also provides a practical framework for efficient, integrated visual processing in computational models.
A Novel Hybrid Improved RIME Algorithm for Global Optimization Problems
Authors: Li Wuke , Yang Xiong , Yin Yuchen , Wang Qian
Published: December 2024

The RIME algorithm is a novel physical-based meta-heuristic algorithm with a strong ability to solve global optimization problems and address challenges in engineering applications. It implements exploration and exploitation behaviors by constructing a rime-ice growth process. However, RIME comes with a couple of disadvantages: a limited exploratory capability, slow convergence, and inherent asymmetry between exploration and exploitation. An improved version with more efficiency and adaptability to solve these issues now comes in the form of Hybrid Estimation Rime-ice Optimization, in short, HERIME. A probabilistic model-based sampling approach of the estimated distribution algorithm is utilized to enhance the quality of the RIME population and boost its global exploration capability. A roulette-based fitness distance balanced selection strategy is used to strengthen the hard-rime phase of RIME to effectively enhance the balance between the exploitation and exploration phases of the optimization process. We validate HERIME using 41 functions from the IEEE CEC2017 and IEEE CEC2022 test suites and compare its optimization accuracy, convergence, and stability with four classical and recent metaheuristic algorithms as well as five advanced algorithms to reveal the fact that the proposed algorithm outperforms all of them. Statistical research using the Friedman test and Wilcoxon rank sum test also confirms its excellent performance. Moreover, ablation experiments validate the effectiveness of each strategy individually. Thus, the experimental results show that HERIME has better search efficiency and optimization accuracy and is effective in dealing with global optimization problems.
Design of a Wearable Exoskeleton Piano Practice Aid Based on Multi-Domain Mapping and Top-Down Process Model
Authors: Xu Qiujian , Li Meihui , Chen Guoqiang , Ren Xiubo , Yang Dan , Li Junrui , Yuan Xinran , Liu Siqi , Yang Miaomiao , Chen Mufan , Wang Bo , Zhang Peng , Ma Huiguo
Published: December 2024

This study designs and develops a wearable exoskeleton piano assistance system for individuals recovering from neurological injuries, aiming to help users regain the ability to perform complex tasks such as playing the piano. While soft robotic exoskeletons have proven effective in rehabilitation therapy and daily activity assistance, challenges remain in performing highly dexterous tasks due to structural complexity and insufficient motion accuracy. To address these issues, we developed a modular division method based on multi-domain mapping and a top-down process model. This method integrates the functional domain, structural domain, and user needs domain, and explores the principles and methods for creating functional construction modules, overcoming the limitations of traditional top-down approaches in design flexibility. By closely combining layout constraints with the design model, this method significantly improves the accuracy and efficiency of module configuration, offering a new path for the development of piano practice assistance devices. The results demonstrate that this device innovatively combines piano practice with rehabilitation training and through the introduction of ontological modeling methods, resolves the challenges of multidimensional needs mapping. Based on five user requirements (P), we calculated the corresponding demand weight (K), making the design more aligned with user needs. The device excels in enhancing motion accuracy, interactivity, and comfort, filling the gap in traditional piano assistance devices in terms of multi-functionality and high adaptability, and offering new ideas for the design and promotion of intelligent assistive devices. Simulation analysis, combined with the motion trajectory of the finger’s proximal joint, calculates that 60° is the maximum bending angle for the aforementioned joint. Physical validation confirms the device’s superior performance in terms of reliability and high-precision motion reproduction, meeting the requirements for piano-assisted training. Through multi-domain mapping, the top-down process model, and modular design, this research effectively breaks through the design flexibility and functional adaptability bottleneck of traditional piano assistance devices while integrating neurological rehabilitation with music education, opening up a new application path for intelligent assistive devices in the fields of rehabilitation medicine and arts education, and providing a solution for cross-disciplinary technology fusion and innovative development.
Estimating the Impact of Aging on Visual Function Using Useful Field of View (UFOV) with a Focus on the Population of Gangwon-do in Korea
Authors: Na Sang-Bin , Choi Seong-Youl , Jeon Da-Bin , Moon Soo-Jin , Kim Jin-Keun
Published: December 2024

Background/Objectives: There is a need in Korea for research estimating the impact of aging using the Useful Field Of View (UFOV) test, which can evaluate visual function for elderly drivers. Methods: This observational study involved young people in their twenties and thirties, later-middle-aged people in their fifties or older, and elderly people 65 or older recruited from the Gangwon-do region. UFOV testing was conducted on the participants where the participants completed a questionnaire about general and driving-related characteristics. A one-way analysis of variance (ANOVA) was performed to analyze the mean difference by age group, and a Pearson correlation analysis was carried out to evaluate the correlation between age and visual function. In addition, a simple linear regression analysis was conducted to verify UFOV subdomains that can confirm changes according to age increasing. Results: Findings after analyzing UFOV subtest differences by age group revealed significant differences in the visual function index of the young, later-middle-aged, and elderly in all three tests, and the difference between the later-middle-aged and old groups was only found in divided attention. The correlation between age and visual function was significant in all three subtests. And all three subtests were confirmed to be indicators that can verify changes according to increasing age. Conclusions: This study showed that visual function significantly decreases with age. Selective attention was confirmed as a visual function type that changes sensitively according to increasing age.
Causal Relationships Between the Use of AI, Therapeutic Alliance, and Job Engagement Among Psychological Service Practitioners
Authors: Arnout Boshra A. , Alshehri Sami M.
Published: December 2024

Despite the significant increase in studies on AI applications in many aspects of life, its applications in mental health services still require further studies. This study aimed to test a proposed structural model of the relationships between AI use, therapeutic alliance, and job engagement by PLS-SEM. The descriptive method was applied. The sample consisted of (382) mental health service providers in Saudi Arabia, including 178 men and 204 women between 25 and 50 (36.32 ± 6.43) years old. The Artificial Intelligence Questionnaire, the Therapeutic Alliance Scale, and the Job Engagement Scale were applied in this study. The results showed the structural model’s predictability for using AI and the therapeutic alliance in predicting job engagement and explaining the causal relationships between them compared to the indicator average and linear models. The study also found a strong positive overall statistically significant effect (p < 0.05) of the use of AI on therapeutic alliance (0.941) and job engagement (0.930) and a positive overall average statistically significant effect (p < 0.05) of the therapeutic alliance on job engagement (0.694). These findings indicated the importance of integrating AI applications and therapeutic alliance skills into training and professional development plans.
Integrating Design for Manufacturing and Assembly Principles in Modular Home Construction: A Comprehensive Framework for Enhanced Efficiency and Sustainability
Authors: Montazeri Sadaf , Odo Nicole , Naqvi Syed Abdul Wasey , Lei Zhen
Published: December 2024

The growing demand for sustainable and efficient construction practices has led to an increased interest in modular construction, with design for manufacture and assembly emerging as a pivotal approach. Despite its potential, the integration of design for manufacture and assembly in modular home construction lacks a structured methodology, posing challenges in aligning design, manufacturing, and assembly processes. This paper introduced a framework aimed at systematically incorporating design for manufacturing and assembly principles into modular home production, leveraging different software tools in the design stage for modular design standardization and streamlined manufacturing and assembly processes. Following a mixed-method research methodology, a comprehensive literature review was conducted to identify research gaps. To address these gaps, a framework was developed focusing on design, manufacturing, and assembly considerations, and retrospective validation of the framework was conducted to confirm its effectiveness. This study revealed the significant benefits of integrating design for manufacturing and assembly principles utilizing advanced digital tools, through a hybrid approach using 2D drafting software and 3D BIM software. The findings indicated that implementing design for manufacturing and assembly principles led to a 40% reduction in design phase duration and a 48% decrease in production errors. This paper offers a structured guide for practitioners while providing a basis for further research in sustainable modular construction.
Study of the Rheological Properties of Rubberized Asphalt Mortar: Mechanisms of Action of Rubber Powder and Filler–Binder Ratio
Authors: Ni Na , Tang Jing , Li Manzhi , Zhang Lingkang , Yuan Haitao
Published: December 2024

Rubber asphalt mortar is widely utilized in road engineering for its excellent high-temperature stability and low-temperature crack resistance, but the influence mechanisms of the rubber powder’s mesh size, content, and filler-to-binder ratio on its performance remain unclear. This study systematically evaluated these factors through viscosity testing, rheological experiments, and viscoelastic analysis. The results indicate that the rubber powder content and filler-to-binder ratio significantly affected the viscosity and rheological properties of the mortar, with the 40-mesh rubber powder demonstrating optimal stability. The grey correlation analysis revealed that the filler-to-binder ratio is the most critical factor, followed by the rubber powder content and mesh size. The findings suggest that optimizing the filler-to-binder ratio and rubber powder content, along with appropriate temperature control during construction, can significantly enhance the mortar’s performance, providing a scientific basis for road engineering applications.
Numerical Investigation on Deep-Foundation Pit Excavation Supported by Box-Type Retaining Walls
Authors: Peng Peng , Kong Weiyao , Huang Saishuai , Long Yi , Lu Yang
Published: December 2024

In soft soil foundations, the utilization of box-type retaining walls as a support method represents a novel approach. This study focuses on investigating the key factors influencing lateral wall deflection and ground settlement behind the wall in deep excavation projects supported by box-type retaining walls. Based on a practical engineering case in Shanghai, the large deformation Lagrangian numerical simulation software FLAC-3D is employed to simulate the displacement of box-type retaining walls as well as the surface settlement surrounding the excavation pit during the excavation process of deep-foundation pits. This research encompasses aspects such as the box size, the filling material within the box, and the constituent materials of the retaining wall. Ultimately, it is concluded that variations in the size of the box-retaining wall have a significant impact on wall deflection and surrounding ground settlement, while the filling material and constituent materials have relatively minor effects. This study provides a theoretical basis and scientific reference for the design and construction of box-type retaining walls in deep-foundation pit engineering.
Advancing Colorectal Cancer Prevention in Inflammatory Bowel Disease (IBD): Challenges and Innovations in Endoscopic Surveillance
Authors: Fasulo Ernesto , D’Amico Ferdinando , Zilli Alessandra , Furfaro Federica , Cicerone Clelia , Parigi Tommaso Lorenzo , Peyrin-Biroulet Laurent , Danese Silvio , Allocca Mariangela
Published: December 2024

Patients with inflammatory bowel disease (IBD) face an elevated risk of developing colorectal cancer (CRC). Endoscopic surveillance is a cornerstone in CRC prevention, enabling early detection and intervention. However, despite recent advancements, challenges persist. Chromoendoscopy (CE), considered the gold standard for dysplasia detection, remains underutilized due to logistical constraints, prolonged procedural times, and the need for specialized training. New technologies, such as endomicroscopy, confocal laser endomicroscopy (CLE), and molecular endoscopy (ME), promise unprecedented precision in lesion characterization but are limited to specialized centers. Artificial intelligence (AI) can transform the field; however, barriers to widespread AI adoption include the need for robust datasets, real-time video integration, and seamless incorporation into existing workflows. Beyond technology, patient adherence to surveillance protocols, including bowel preparation and repeat procedures, remains a critical hurdle. This review aims to explore the advancements, ongoing challenges, and future prospects in CRC prevention for IBD patients, focusing on improving outcomes and expanding the implementation of advanced surveillance technologies.
Evolution in the Surgical Management of Gastric Cancer Peritoneal Metastases
Authors: Krell Matthew , Ranjbar Suedeh , Gitlin Saige , Alvarez Vega Diego R. , Wilson Rachel , Thrasher Kenya , Brown Zachary J.
Published: December 2024

Despite therapeutic treatments and the growing utilization of multimodal therapies, gastric cancer (GC) remains a highly aggressive malignancy with high mortality worldwide. Much of the complexity in treating GC is due to the high incidence of peritoneal metastasis (PM), with mean overall survival typically ranging from 4 to 10 months. With current systemic therapy, targeted therapies, and immunotherapies continuing to remain ineffective for GC/PM, there has been a significant growing interest in intraperitoneal (IP) therapies for the treatment of GC/PM. In this review, we summarize the development of PM and evolving treatment strategies for GC/PM. Furthermore, we explore the various advancements and outcomes of IP therapies, including heated intraperitoneal chemotherapy (HIPEC), neoadjuvant HIPEC, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC).
Correction: Zhang et al. Hepatitis B Virus X Protein (HBx) Suppresses Transcription Factor EB (TFEB) Resulting in Stabilization of Integrin Beta 1 (ITGB1) in Hepatocellular Carcinoma Cells. Cancers 2021, 13, 1181
Authors: Zhang Chunyan , Yang Huan , Pan Liwei , Zhao Guangfu , Zhang Ruofei , Zhang Tianci , Xiao Zhixiong , Tong Ying , Zhang Yi , Hu Richard , Pandol Stephen J. , Han Yuan-Ping
Published: December 2024

In the original publication [...]
Role of Allogeneic Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia in the Contemporary Era
Authors: Jamy Omer , Badar Talha
Published: December 2024

The treatment of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-cell ALL) has seen substantial progress over the past two decades. The introduction of BCR::ABL1 tyrosine kinase inhibitor (TKIs) has resulted in dramatic improvements in long-term survival. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), with its curative potential, has always been an integral part of the treatment algorithm of Ph+ ALL. Recently, the approval of novel therapies such as blinatumomab, inotuzumab ozogamicin and chimeric antigen receptor T-cell (CAR-T) therapy in relapse and refractory (R/R) ALL have further improved outcomes of B-cell ALL. With potent TKIs and novel targeted therapy, the treatment guidelines for Ph+ ALL are evolving rapidly. Additionally, with improved tools for detecting measurable residual disease (MRD), there has been recent interest in redefining the role of allo-HSCT for some patients. In this context, we discuss the current evidence for the utilization of allo-HSCT for Ph+ ALL, focusing on novel therapies and MRD-directed care.
Advancements in Pd-Based Supported Porous Nanocatalysts for the C-C Cross-Coupling Reactions
Authors: Chakraborty Debarati , Bhaumik Asim
Published: December 2024

Palladium (Pd) is a 4d transition metal with electronic configuration [Kr] 4d10 5s0, and it is one of the most widely studied metals in the periodic table due to its versatile catalytic role in organic synthesis. The choice of ligands that can coordinate with Pd sites plays a crucial role in the progress of the reaction. Due to the coexistence of multiple oxidation states (Pd(0)/Pd(II)), the active Pd sites of the catalysts can participate in various stages of the coupling reaction. The Pd-catalyzed C-C coupling reactions proceed through four steps: (1) oxidative addition of the reactant to the catalytic site, (2) transmetallation, (3) rearrangements of ligand centers and (4) reductive elimination to the coupling products. For the heterogeneous Pd nanocatalysts, active Pd sites are often strongly bound (chelated) with the solid catalyst surfaces. In this review, we have highlighted the advancements made in the heterogeneous Pd nanocatalysts with an emphasis on the types of different classes of porous solids, which could ligate with the Pd centers via strong covalent bonds. The high specific surface areas and small Pd sites of these nanocatalysts provide a larger number of catalytic sites and thus facilitate the reaction. Mechanistic aspects of the C-C cross-coupling reactions are discussed in the context of the structure–reactivity relationship.
BiOI-MIL Binary Composite for Synergistic Azo Dye AR14 Discoloration
Authors: Shams Mahmoud , Abd Mojiri Samane , Shafaee Masoomeh , Hassan Najmaldin Ezaldin , Dehghan Aliakbar , Baziar Mansour , Goharshadi Elaheh K. , Rezania Shahabaldin
Published: December 2024

Acid red 14 (AR14) is a widely used azo dye that belongs to a major family of commercial dyes employed extensively in the textile industry. The present study aimed to investigate the photocatalytic discoloration of AR14 using a visible-light-responsive catalyst. The composite catalyst was synthesized by integrating thermally modified MIL-101 (M-MIL) integrated into bismuth oxide. Thermal modification of MIL-101 produced octahedral α-Fe2O3 particles with a size of 1–2 μm, which were incorporated into bismuth oxyiodide (BiOI) featuring a nanosheet structure. BiOI@M-MIL composite exhibited an enhanced photocatalytic activity. The bandgap energy, Eg, of BiOI was reduced from 1.95 eV to 1.73 eV in the composite. Photocatalytic reactions were performed under visible-light irradiation using a 5 W cold LED lamp. The AR14 discoloration tests demonstrated that BiOI@M-MIL was 1.81-fold more efficient compared to pristine BiOI. Key parameters affecting AR14 discoloration —such as catalyst dosage, pH, dye concentration, and contact time, were investigated. The composite achieved almost a complete dye removal efficiency of 94.26% under experimental conditions. Radical trapping tests highlighted the crucial role of superoxide radicals, O2.−, in the dye discoloration process. BiOI@M-MIL takes advantage of simultaneous adsorption and photocatalysis with the highest adsorption capacity of 45.32 mg g−1 and 32.2 mg g−1, based on Sips and Langmuir models, respectively. The catalyst also showed good reusability and ~14% loss in removal efficiency after five consecutive cycles. In conclusion, the BiOI@M-MIL composite demonstrates excellent photocatalytic performance, combining low energy consumption with material stability, making it a promising candidate for AR14 discoloration.
Genetic Characteristics of the Rat Fibroblast Cell Line Rat-1
Authors: Liehr Thomas , Kankel Stefanie , Buhl Eva Miriam , Schröder-Lange Sarah K. , Weiskirchen Ralf
Published: December 2024

The Rat-1 cell line was established as a subclone of the parental rat fibroblastoid line F2408, derived from Fisher 344 rat embryos. Rat-1 cells are widely used in various research fields, especially in cancer biology, to study the effects of oncogenes on cell proliferation. They are also crucial for investigating signal transduction pathways and play a key role in drug testing and pharmacological studies due to their rapid proliferation. Therefore, Rat-1 cells are an indispensable research tool. While some cytogenetic information on their basic chromosomal features is available, detailed genomic analyses, such as karyotype analysis, short tandem repeat (STR) profiling, and whole-genome sequencing, have not been thoroughly conducted. As a result, the genetic stability and potential variations in Rat-1 cells over extended culture periods are poorly understood. This lack of comprehensive genetic characterization can limit the interpretation of experimental results and requires caution when generalizing findings from studies using this cell line. In this study, we describe the genetic characterization of the Rat-1 cell line. We established a karyotype, performed multicolor fluorescence in situ hybridization (mFISH), identified chromosomal losses and gains, and defined an STR profile for Rat-1 with 31 species-specific markers. Interestingly, the chromosomal imbalances found in Rat-1 cells resemble those found in human epithelioid sarcoma or liposarcoma. Additionally, we analyzed the transcriptome of Rat-1 cells through mRNA sequencing (mRNA-Seq) using next-generation sequencing (NGS). Finally, typical features of these fibroblastic cells were determined using electron microscopy, Western blotting, and fluorescent phalloidin conjugates.
CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation
Authors: Kobayashi Yoshiki , Hanh Chu Hong , Yagi Naoto , Le Nhi Kieu Thi , Yun Yasutaka , Shimamura Akihiro , Fukui Kenta , Mitani Akitoshi , Suzuki Kensuke , Kanda Akira , Iwai Hiroshi
Published: December 2024

Eosinophilic chronic rhinosinusitis (ECRS), a CRS with nasal polyps (CRSwNP), is characterized by eosinophilic infiltration with type 2 inflammation and is highly associated with bronchial asthma. Intractable ECRS with poorly controlled asthma is recognized as a difficult-to-treat eosinophilic airway inflammation. Although eosinophils are activated and coincubation with airway epithelial cells prolongs their survival, the interaction mechanism between eosinophils and epithelial cells is unclear. This study examined the effect of eosinophils on mucin glycoprotein 1 (MUC1), a member of membrane-bound mucin, in the airway epithelial cells, to elucidate the mechanisms of the eosinophil–airway epithelial cell interaction. Nasal polyp samples from patients with CRSwNP and BEAS-2B airway epithelial cells, coincubated with purified eosinophils, were stained with two MUC1 antibodies. To confirm the involvement of CCL4, an anti-CCL4 neutralizing antibody or recombinant CCL4 was used as needed. The immunofluorescence results revealed a negative correlation between the expression of full-length MUC1 and eosinophil count in nasal polyps. In BEAS-2B coincubated with eosinophils, full-length MUC1, but not the C-terminal domain, was reduced, and eosinophil survival was prolonged, which was concomitant with CCL4 increase, whereas the anti-CCL4 neutralizing antibody decreased these reactions. The survival of eosinophils that contacted recombinant MUC1 without the N-terminal domain was prolonged, and recombinant CCL4 increased the expression of metalloproteases. Increased CCL4 induces the contact between eosinophils and airway epithelial cells by shedding the MUC1 N-terminal domain and enhances eosinophil survival in eosinophilic airway inflammation. This novel mechanism may be a therapeutic target for difficult-to-treat eosinophilic airway inflammation.
Tailoring the Preparation, Microstructure, FTIR, Optical Properties and Photocatalysis of (Fe/Co) Co-Doped ZnO Nanoparticles (Zn0.9FexCo0.1−xO)
Authors: Faramawy A. M. , Agami W. R. , Swillam Mohamed A.
Published: December 2024

In this work, Fe3+- and Co2+-doped ZnO NPs (zinc oxide nanoparticles), Zn0.9FexCo0.1−xO, with a hexagonal wurtzite phase (single-phase), were synthesized via a co-precipitation technique where the phase purity and elemental composition were confirmed by XRD and EDX, respectively. Due to the substitution of Fe by Co, the cell parameters (a and c) were increased, alongside which a slight shift to higher diffracted angles appeared. FTIR was carried out to confirm the insertion of both the Fe3+ and Co2+ dopants into the ZnO hexagonal phase. Based on the experimental results, different numerical techniques were used to determine the optical gap and refractive index for the ZnO NP-doped samples, and when the concentration of Fe3+ ions was increased, the band gap value of ZnO decreased from 3.36 eV to 3.29 eV, accompanied by a decrease in the Urbach energy, while the refractive index increased. The doped ZnO NPs were later found to be effective UV photocatalysts which demonstrated a maximum reduction (84%) of methylene blue (MB) in a neutral environment for X = 0.05. The correlation between the Fe3+ concentration, structure, optical parameters, and photocatalytic efficacy is explained in detail.
Advancing Pediatric Surgery: The Use of HoloLens 2 for 3D Anatomical Reconstructions in Preoperative Planning
Authors: Di Mitri Marco , Di Carmine Annalisa , D’Antonio Simone , Capobianco Benedetta Maria , Bisanti Cristian , Collautti Edoardo , Cravano Sara Maria , Ruspi Francesca , Libri Michele , Gargano Tommaso , Lima Mario
Published: December 2024

Background: In pediatric surgery, a comprehensive knowledge of the child’s anatomy is crucial to optimize surgical outcomes and minimize complications. Recent advancements in medical imaging and technology have introduced innovative tools that enhance surgical planning and decision-making. Methods: This study explores the integration of mixed reality technology, specifically the HoloLens 2 headset, for visualization and interaction with three-dimensional (3D) anatomical reconstructions obtained from computed tomography (CT) scans. Our prospective observational study, conducted at IRCCS (Scientific Hospitalization and Care Institute) Sant’Orsola-Malpighi University Hospital in Bologna, engaged ten pediatric surgeons, who assessed three types of anatomical malformations (splenic cysts, pulmonary cystic adenomatoid malformations, and pyelo-ureteral junction stenosis) and planned surgeries using both traditional 2D CT scans and 3D visualizations via HoloLens 2, followed by completing a questionnaire to evaluate the utility of each of these imaging techniques in surgical planning. Results: The statistical analysis revealed that the 3D visualizations significantly outperformed the 2D CT scans in clarity and utility (p < 0.05). The results indicated significant improvements in anatomy understanding and surgical precision. The immersive experience provided by HoloLens 2 enabled surgeons to better identify critical landmarks, understand spatial relationships, and prevent surgical challenges. Furthermore, this technology facilitated collaborative decision-making and streamlined surgical workflows. Conclusions: Despite some challenges in ease of use, HoloLens 2 showed promising results in reducing the learning curve for complex procedures. This study underscores the transformative potential of mixed reality technology in pediatric surgery, advocating for further research and development to integrate these advancements into routine clinical practice.
Pediatric Intensive Care Provider Attitudes About Children with Medical Complexity and Neurologic Impairment: A Qualitative Study
Authors: Bleed Elizabeth J. , Barrera Leonardo , Jones Mickayla , Shah Seema K. , Crowley-Matoka Megan , Foster Carolyn C.
Published: December 2024

(1) Background: Children with medical complexity (CMC) and neurologic impairment (NI) are a growing population in pediatric intensive care units (PICUs). (2) Objective: Our aim was to explore and describe the experiences and beliefs of PICU providers caring for CMC with NI. (3) Methods: A qualitative interview-based study was conducted. Participants were 20 providers (12 attendings and 8 nurse practitioners) who met inclusion criteria of being a faculty, fellow, or advanced practice provider who worked in a PICU; residents were excluded. Participants were recruited via purposive and snowball sampling until information power was reached, and came from seven PICUs across six states, with 10 participants from the authors’ home institution and 10 from external PICUs. Data were collected via recorded videoconference interviews, which were transcribed. Analysis was conducted and relevant themes were identified using the analytic technique of thematic analysis. Rigor was assured by using two coders. (4) Results: Four main themes were identified: (i) providers view CMC with NI as a distinct population of growing importance; (ii) CMC with NI have care needs that challenge traditional perceptions of PICU practice; (iii) PICU providers expressed ambivalence towards caring for CMC with NI; and (iv) some PICU providers have developed adaptive strategies. (5) Conclusions: This population challenges the typical notion of what pediatric critical care represents. Providers display ambivalence about caring for these patients but can develop strategies to make this work meaningful. Understanding PICU clinicians’ views about CMC with NI can provide insights for improved patient care and reduced provider burnout as the field adapts to this population.
Contemporary Normative Values for Five Common Static Standing Tasks on Firm and Compliant Floor Surfaces in Children Two to Thirteen Years
Authors: Darr Nancy S. , Franjoine Mary Rose , Norton Cathey , Young Brenda L.
Published: December 2024

Background/Objectives: Static upright tasks, including standing unsupported (SU), eyes closed (SEC), feet together (SFT), tandem (TS), and single limb (SLS), are routinely examined in children and are included in many norm-referenced measures. Existing normative values for these standing tasks may not apply to contemporary children and have not been established across wide age ranges. The primary purpose of this study was to investigate developmental trajectories of and relationships between four static standing positions (SPs [SU, SFT, TS, SLS]) in children aged 2 through 13 years who are developing typically. The effects of altered sensory input, including floor surface (firm and compliant) and vision (eyes open [SU] and eyes closed [SEC]), as well as influences of sex, height, weight, and BMI on static standing were also examined. Methods: Children (n = 807) developing typically performed two trials of each task up to 2 minutes per trial using standardized procedures. A total of 482 children were also tested on a compliant surface. Results: Descriptive statistics were calculated by age, height, weight, task, and floor surface. Two-way ANOVA showed no significant effects (p > 0.05) of sex on standing times; however, age was significant for all standing tasks. Repeated-measure ANOVA and Tukey post hoc tests identified significant effects (p < 0.05) of age and floor surface on standing times. SU, SEC, and SFT times increased up to 8 years, with most children achieving the 2 minute maximum by age 8. TS and SLS times improved up through 13 years, with wide variations in performance noted in children 8 years and older. Conclusions: Contemporary normative performance values are provided for five common standing tasks on firm and compliant surfaces by age in one-year increments.
L-Citrulline in Neonates: From Bench to Bed Side
Authors: Mascarenhas Dwayne , Mohammadi Atefeh , Higazy Randa , Ivanovska Julijana , Gauda Estelle , Jasani Bonny
Published: December 2024

L-citrulline (L-CIT), a precursor to L-arginine (L-ARG), is a key contributor to the nitric oxide (NO) signaling pathway. Endothelial dysfunction, characterized by deficient nitric oxide synthesis, is implicated in the pathogenesis of various neonatal conditions such as necrotizing enterocolitis (NEC) and bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH). This review summarizes the current evidence around the possible role of L-CIT supplementation in the treatment of these conditions. Detoxification of endogenously produced superoxide radicals is inadequate in preterm infants due to immature antioxidants that leads to the production of peroxynitrite, a reactive oxygen-free radical that is cytotoxic and causes damage to organelles and cellular membranes, further disrupting the coupling of endothelial NO synthase enzyme and the generation of high levels of reactive nitrogen and oxygen species. Animal studies in lipopolysaccharide-induced models of chorioamnionitis and hyperoxia- and inflammation-induced BPD-PH in rodent lung models revealed that L-CIT supplementation significantly mitigated structural changes in the pulmonary vasculature, preserved alveolar growth, and increased vascular endothelial growth factor gene expression, highlighting the anti-inflammatory and antioxidant effects of L-CIT supplementation. Similar benefits were noted in newborn piglet models of chronic hypoxia-induced PH and NEC. Pharmacokinetic studies in neonates have shown doses of 100–300 mg/kg/day to be safe and well tolerated. A few studies have shown the beneficial effects of L-CIT supplementation in pulmonary hypertension secondary to congenital heart disease, but evidence of efficacy in the neonatal population is lacking. While L-CIT shows promise in the treatment of various neonatal conditions, adequately powered studies to evaluate the safety and efficacy of L-CIT supplementation post-surgical NEC and BPD ± PH in the extremely preterm population are needed to translate this novel therapy to clinical practice.
Outcomes After Salter–Harris II Distal Tibia Fractures in Children
Authors: Pearce Robert , Markes Alexander , Katyal Toshali , Siu Jeremy , Swarup Ishaan
Published: December 2024

Background/Objectives: Salter–Harris II (SH-II) distal tibia fractures are the most common physeal ankle fractures in children; however, indications for surgical management remain controversial, and patient-reported outcomes for different management strategies are unknown. The purpose of the current study is to compare differences in clinical and patient-reported outcomes following operative and non-operative management of this injury. Methods: We performed a retrospective cohort study of pediatric patients who were treated at a single institution for SH-II distal tibia fractures between 2013 and 2020. Variables included age, gender, operative versus non-operative treatment, and premature physeal closure (PPC). Patients were also contacted for patient-reported outcome scores (PROs), which included the visual analog scale foot and ankle (VAS-FA) and the PROMIS pediatric mobility instrument obtained at a minimum of 2 years post-injury. Results: Demographic and clinical information was obtained for 46 patients. Our cohort was 52% male with mean age of 11.9 years at injury. At 6 months, the rate of PPC in our cohort was 25%, with no differences between operative and non-operative patients (29% vs. 24%, p = 0.80). A total of 15 of the 46 patients provided PROs, with an average follow-up time of 5.1 years (range: 2.9–9.1). VAS-FA and PROMIS pediatric mobility scores were similar between operative and non-operative patients. Conclusions: This pilot study suggests no differences in PROs following operative and non-operative management for SH-II distal tibia fractures; however, future studies with larger cohort sizes and longer follow-up times are needed to further examine these outcomes.
Antimicrobial Stewardship in the Pediatric Emergency Department: An Observational Pre-Post Study
Authors: Silvestro Erika , Mussinatto Ilaria , Versace Antonia , Denina Marco , Pruccoli Giulia , Marino Raffaella , Mazzetti Giulia , Scaglione Lorenzo , Vigna Federico , Macciotta Alessandra , Garazzino Silvia , Bondone Claudia
Published: December 2024

Background/Objectives: To face antimicrobial resistance, antimicrobial stewardship programs (ASPs) have been implemented in the pediatric age, but the area of urgency remains understudied. We aimed to assess the impact of an educational program on optimizing antibiotic appropriateness in a pediatric ED. Methods: We conducted a pre-post observational study with an audit, intervention, and feedback given to prescribers. We recorded all systemic antibiotic prescriptions for children attending our pediatric ED from January to March and from July to September 2020. The study’s team assigned a score to each prescription, regarding the appropriate molecule, dose, and duration of therapy, according to the diagnosis. From April to June 2020, we held weekly meetings focusing on different pediatric infectious diseases, with interaction between one to three ED physicians and the infectious disease (ID) specialist of the study’s team. We then distributed synthetic digital guidelines adapted to our reality to all prescribers. Results: Optimal antibiotic prescriptions increased after the intervention, with statistical significance (p < 0.001) in four main aspects (overall adequacy: 13% PRE vs. 43% POST; need of antibiotics: 53% vs. 68%; adequacy of the spectrum: 55% vs. 63%; adequacy of the chosen molecule: 54% vs. 62%). We observed an improvement in all the main infectious diseases and concerns all the ED physicians. The prescription of first-choice drugs increased in specific and common illnesses such as otitis and pharyngotonsillitis. Conclusions: An antimicrobial stewardship program is a relevant method for improving the appropriateness of antimicrobial use also in the complex setting of a pediatric ED.
A Pilot Study on the Freelisting Method Among Adolescents with Chronic Musculoskeletal Pain: Feasibility, Acceptability and Study Findings
Authors: Gmuca Sabrina , Abel Dori , McGill Mackenzie , Stryker Daneka , Akpek Eda , Eriksen Whitney , Weiss Pamela F. , Cronholm Peter F.
Published: December 2024

Background/Objectives: To assess the feasibility and acceptability of freelisting for adolescents with chronic musculoskeletal pain (CMP) and use freelisting to identify how adolescents with CMP cope with pain. Methods: This was a mixed-methods cross-sectional single-center study of patients 12–18 years old, diagnosed with CMP. Twenty-seven subjects participated in an interview which included the freelisting exercise, probing questions, Connor-Davidson Resilience Scale 10-item, and semi-structured interview. Feasibility was pre-defined as ≥85% completion. A list of ‘standardized’ freelisting terms was created, and we calculated Smith’s salience index. Freelisting terms were grouped into individual, family, friends, school, and medical domains. Results: In this predominantly female population, resilience levels were low to moderate, and on average, participants had moderate pain intensity and functional disability. The freelisting exercise was feasible and acceptable among females, with low recruitment of males. Salient words to describe adolescents’ pain included frustrating, upsetting, annoying, and painful. Participants identified family, friends, teachers, guidance counselors, and health professionals as key sources of support. Many participants reported difficulties communicating their pain. Helpful coping strategies included rest, distraction, relaxation, endurance, and extracurricular participation. Conclusions: Freelisting was well perceived among female adolescents with CMP. Supportive relationships with community members play an important role for this population. However, perceived stigma may deter female adolescents from talking about their pain. Purposive sampling of male participants and recruitment strategies ensuring diverse patient representation are necessary to ensure generalizability of future results when using the freelisting method for adolescents with CMP.