bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed Comparison of Intervention with Assistive Devices for Plantar Pressure Distribution and Anatomical Characteristics in Adults with Pes Cavus: Systemic Review with Network Meta-Analysis
Authors: Zhang Caiting , Xu Yining , Li Jiao , Gusztáv Fekete , Gu Yaodong
Published: August 2023

Background: Pes cavus is a multiplanar foot deformity with an abnormal plantar pressure distribution and an overhigh medial longitudinal arch (MLA). Its causes are complex. In the past, people have usually focused on clinical surgery for pes cavus. However, this is not necessarily the best choice for some patients with non-ongoing or mild symptoms. In the 21st century, studies have just begun to focus on assistive devices intervention for pes cavus, which has been proven to be an effective non-surgical treatment. However, the effectiveness of assistive devices for patients with arched feet of any etiology has not been evaluated and evidence-based guidelines for clinical treatment options are lacking. Methods: A systematic review and network meta-analysis were performed, employing a comprehensive search across the databases of Web of Science, PubMed, as well as Scopus. The selected studies adhered to specific eligibility criteria, which included: (1) involving patients with pes cavus; (2) interventions with assistive devices; and (3) outcome measures of plantar pressure distribution and anatomical characteristics (MLA). Meanwhile, the standard mean difference was selected as the effect size. Results: A total of three studies were selected, and the authors achieved an agreement on the risk of bias with a kappa value equal to 0.74. According to the results of network meta-analysis, customized foot orthotics compared to other devices (lace-up ankle-support brace, semirigid brace) demonstrated the highest likelihood of being the most effective in optimizing plantar-pressure distribution among pes cavus patients. On the other hand, wearing hard custom foot orthotics compared to other devices (soft custom foot orthotics, off-the-shelf orthotics) showed the greatest potential in improving the medial longitudinal arch (MLA) of pes cavus patients. Discussion: Although becoming better than wearing regular footwear, wearing lace-up ankle-support braces or semirigid braces might not be optimal choices for treatments of pes cavus with the potential mechanism that the internal force created by the fixation of the proximal joint might be much less than the ground reaction force loaded on the distal segments that touch the ground. It could be concluded that foot orthotics show great potential in treating pes cavus under non-surgical conditions. This systematic review could provide valuable evidence for future research and clinical practice. Other: The PROSPERO Registration Number is CRD42022349687.
The Influence of Stimulus Composition and Scoring Method on Objective Listener Assessments of Tracheoesophageal Speech Accuracy
Authors: Doyle Philip C. , Goncharenko Natasha , Searl Jeff
Published: August 2023

Introduction: This study investigated the influence of stimulus composition for three speech intelligibility word lists and two scoring methods on the speech accuracy judgments of five tracheoesophageal (TE) speakers. This was achieved through phonemic comparisons across TE speakers’ productions of stimuli from the three intelligibility word lists, including the (1) Consonant Rhyme Test, (2) Northwestern Intelligibility Test, and (3) the Weiss and Basili list. Methodology: Fifteen normal-hearing young adults served as listeners; all listeners were trained in phonetic transcription (IPA), but none had previous exposure to any mode of postlaryngectomy alaryngeal speech. Speaker stimuli were presented to all listeners through headphones, and all stimuli were transcribed phonetically using an open-set response paradigm. Data were analyzed for individual speakers by stimulus list. Phonemic scoring was compared to a whole-word scoring method, and the types of errors observed were quantified by word list. Results: Individual speaker variability was noted, and its effect on the assessment of speech accuracy was identified. The phonemic scoring method was found to be a more sensitive measure of TE speech accuracy. The W&B list yielded the lowest accuracy scores of the three lists. This finding may indicate its increased sensitivity and potential clinical value. Conclusions: Overall, this study supports the use of open-set, phonemic scoring methods when evaluating TE speaker intelligibility. Future research should aim to assess the specificity of assessment tools on a larger sample of TE speakers who vary in their speech proficiency.
Electric Load Forecasting Based on Deep Ensemble Learning
Authors: Wang Aoqiang , Yu Qiancheng , Wang Jinyun , Yu Xulong , Wang Zhici , Hu Zhiyong
Published: August 2023

Short-to-medium-term electric load forecasting is crucial for grid planning, transformation, and load scheduling for power supply departments. Various complex and ever-changing factors such as weather, seasons, regional economic structures, and enterprise production cycles exert uncontrollable effects on the electric grid load. While the causal convolutional neural network can significantly enhance long-term sequence prediction, it may suffer from problems such as vanishing gradients and overfitting due to extended time series. To address this issue, this paper introduces a new power load data anomaly detection method, which leverages a convolutional neural network (CNN) to extract temporal and spatial information from the load data. The features extracted are then processed using a bidirectional long short-term memory network (BiLSTM) to capture the temporal dependencies in the data more adeptly. An enhanced random forest (RF) classifier is employed for anomaly detection in electric load data. Furthermore, the paper proposes a new model framework for electricity load forecasting that combines a dilated causal convolutional neural network with ensemble learning. This combination addresses issues such as vanishing gradients encountered in causal convolutional neural networks with long time series. Extreme gradient boosting (XGBoost), category boosting (CATBoost), and light gradient boosting machine (LightGBM) models act as the base learners for ensemble modeling to comprehend deep cross-features, and the prediction results generated by ensemble learning serve as a new feature set for secondary ensemble modeling. The dilated convolutional neural network broadens the receptive field of the convolutional kernel. All acquired feature values are concatenated and input into the dilated causal convolutional neural network for training, achieving short-to-medium-term electric load forecasting. Experimental results indicate that compared to existing models, its root mean squared error (RMSE) and mean squared error (MSE) in short-term and mid-term electricity load forecasting are reduced by 4.96% and 12.31%, respectively, underscoring the efficacy of the proposed framework.
Towards Mirror-Less Graphene-Based Perfect Absorbers
Authors: Lee Sangjun , Kim Sangin
Published: August 2023

Owing to its exceptional electronic and optical properties, graphene has attracted extensive attention among researchers in the development of high-performance optoelectronic devices. However, the light absorption of pure graphene is very poor, limiting its development in practical application. In this review, as a solution for this issue, various types of graphene-based perfect absorbers are addressed in terms of their operation principles and design requirements. Their recent progress and potential applications such as photodetectors and modulators are also discussed. In particular, we emphasize the importance of mirror-less (in particular, one-port mimicking) perfect absorber design due to simplified fabrication processes or enhanced tolerance for fabrication error.
The Effect of Duck Bile Acid Extract on the Fecal Microbiota, Short Chain Fatty Acids, Fat Digestibility and Blood Biochemical Indices in Cats
Authors: Han Bing , Zhao Peng , Liang Shukun , Wang Zhenlong , Tao Hui , Wang Xiumin , Liu Jie , Wang Jinquan
Published: August 2023

Bile acids (BAs) have been widely used on livestock in recent years and could be a good feed additive to improve the performances of animals. But the effects of bile acid on cats have not been studied. The purpose of this research was to investigate the effects of the bile acid from ducks on cats. Five healthy cats, which were two years old, were studied with a dose of the bile acid product being 50 mg/kg body weight per day. On day 0 (group A) and day 28 (group B), the fecal flora, volatile fatty acids, fat digestibility, and blood biochemical Indices of cats were studied and tested. The results showed that BAs could probably modulate the fat metabolism and gut microflora of cats and could improve the digestibility of different nutritional ingredients. The cholesterol of blood was greatly decreased and the cholesterol and activity of amylase were improved by 20.9% (p < 0.05) and 21.1% (p < 0.05), respectively. Fat digestibility was improved by 5.68% (p < 0.05) and the body weight on day 28 was decreased without significance (p > 0.05). The abundance of the Bifidobacterium on day 28 was greatly increased (p < 0.05) after using BAs product. The research showed that duck BAs could modulate fat metabolism and increase probiotics of the gut in cats and could probably be a good feed additive to reduce weight and improve gut health for cats in the future.
A Study on Factors Influencing Ground Subsidence and a Risk Analysis Method Using the Attributes of Sewer Pipes
Authors: Lee Sungyeol , Kang Jaemo , Kim Jinyoung
Published: August 2023

In recent years, we have witnessed an increase in road subsidence accidents in urban areas, threatening the safety of citizens. Various road facilities, such as water and sewage pipes, and telecommunication facilities are buried under roads, and the aging of these facilities is one of the factors causing road subsidence. In particular, old sewer pipes are a primary cause of road subsidence. However, most maintenance work on such facilities is carried out based on how long ago they were buried underground, without considering the risk of road subsidence caused by them. Therefore, this study aims to present a reliable method to assess road subsidence risk that considers various sewer pipe specifications and the environment surrounding them. To derive the factors influencing subsidence, sewer pipes near the target region, where road subsidence occurs the most, were extracted to analyze the correlation between road subsidence, pipe integrity, and the surrounding environment. An effective analysis method was selected by comparing logistic regression analysis and AHP (Analytic Hierarchy Process) analysis, and a weighted road subsidence risk assessment method was proposed by evaluating the importance of factors affecting ground subsidence. Its applicability was examined by comparing actual road subsidence data and analyzing risk in a pilot study area to validate the reliability of the proposed methodology. The results showed that it was possible to make reliable predictions of road subsidence risk areas.
An Analysis of the Demonstration of Five-Year-Long Creative ICT Education Based on a Hyper-Blended Practical Model in the Era of Intelligent Information Technologies
Authors: Choi Eunsun , Kim Jinsu , Park Namje
Published: August 2023

In anticipation of the advanced information and communication technology (ICT) era’s profound impact on society and industry, the demand for strong technological comprehension and creativity is evident. Addressing this societal need, we have developed a hyper-blended educational model and program. It focuses on cultivating creative thinking and ICT understanding, tailored for elementary/middle school students, educators, administrators, and the public. Our program employs innovative pedagogical methods, encompassing subjects such as artificial intelligence (AI) ethics, blockchain, and cloud computing, providing forward-looking perspectives. With techniques such as Havruta dialogue and quantum learning, we promote engaging, convergent thinking. We blend artistic expression, physical activities, and technical education to encourage administrators’ creativity within educational settings. Over 2017–2021, involving 9596 participants, we observed consistently high satisfaction scores of around 4 on a 1–5 scale, with statistical significance. This underscores our program’s success in fostering creative thinking and ICT understanding across diverse domains. In conclusion, our study addresses the vital need for creativity and tech comprehension in an intricate technological landscape. Our hyper blended practical model (HPBM) serves diverse training groups, equipping them for future challenges. These findings guide future educational pursuits, emphasizing a seamless integration of creativity and tech understanding.
Design and Testing of a Clamping Manipulator for Removing Abnormal Plants in Rape Breeding
Authors: Xing Qinsong , Ding Suming , Xue Xinyu , Cui Longfei , Le Feixiang , Fu Jian
Published: August 2023

Aiming at the time-consuming, laborious, and inefficient process of removing abnormal rape plants during breeding, combined with the agronomic requirements for planting rapeseed, a clamping manipulator was designed. This manipulator is mainly composed of hollow splints, grip-force sensors, connecting rods, cylinders and other components. Additionally, a removing test platform was built. Single-factor and Box-Behnken experiments were conducted. Taking the output air pressure, pulling angle and pulling speed as the test factors, the rape uprooted removal rate, rape removal breakage rate and pulling force were the test indicators. Mathematical models for multiple regression were established separately for each evaluation index, and analysis of variance was conducted. Objective optimization was performed using the Numerical component to obtain the optimal combination of operating parameters: output air pressure of 0.47 MPa, pulling angle of 68.8° and extraction speed of 8 cm/s. The field validation test showed that the uprooted removal rate was 83.33%, the removal breakage rate was 6.67% and the pulling force was 84.9 N at the output air pressure of 0.5 MPa, pulling angle of 70° and pulling speed of 8 cm/s. The validation test values are in good agreement with the parameter optimization values, indicating that the parameter optimization model is reasonable.
Trends and Recommendations for Enhancing Maturity Models in Supply Chain Management and Logistics
Authors: Ferraro Saverio , Leoni Leonardo , Cantini Alessandra , De Carlo Filippo
Published: August 2023

Maturity models (MMs) are strategic tools used to assess and improve the current state of processes, objects, or people, with the goal of achieving continuous performance enhancement. While MMs are applied in various fields, their scope, design, and application criteria within Supply Chain Management and Logistics (SCML) lack comprehensive studies. This article aims to address this gap through a systematic literature review. The review analyzes 137 relevant articles using both bibliometric and content analysis techniques. The bibliometric analysis identifies major contributions, popular journals, and the classification and evolution of key keywords. The content analysis focuses on critical criteria related to the scope, design, and application of MMs. The findings reveal a growing emphasis on models assessing Industry 4.0 readiness and sustainability principles. However, several gaps are identified, including limited attention to optimizing and integrating logistic processes, underutilized and unvalidated MMs, and the absence of comprehensive improvement guidelines. Based on these trends and research gaps, this study proposes five recommendations for future developments that benefit both academics and practitioners. These recommendations aim to address the identified limitations and provide guidance for comprehensive and effective improvement strategies.
Prediction of Maximum Tunnel Uplift Caused by Overlying Excavation Using XGBoost Algorithm with Bayesian Optimization
Authors: Zhao Haolei , Wang Yixian , Li Xian , Guo Panpan , Lin Hang
Published: August 2023

The uplifting behaviors of existing tunnels due to overlying excavations are complex and non-linear. They are contributed to by multiple factors, and therefore, they are difficult to be accurately predicted. To address this issue, an extreme gradient boosting (XGBoost) prediction model based on Bayesian optimization (BO), namely, BO-XGBoost, was developed specifically for assessing the tunnel uplift. The modified model incorporated various factors such as an engineering design, soil types, and site construction conditions as input parameters. The performance of the BO-XGBoost model was compared with other models such as support vector machines (SVMs), the classification and regression tree (CART) model, and the extreme gradient boosting (XGBoost) model. In preparation for the model, 170 datasets from a construction site were collected and divided into 70% for training and 30% for testing. The BO-XGBoost model demonstrated a superior predictive performance, providing the most accurate displacement predictions and exhibiting better generalization capabilities. Further analysis revealed that the accuracy of the BO-XGBoost model was primarily influenced by the site’s construction factors. The interpretability of the BO-XGBoost model will provide valuable guidance for geotechnical practitioners in their decision-making processes.
On the Examination of the Relationship between Mean and Extreme Precipitation and Circulation Types over Southern Romania
Authors: Tolika Konstantia , Traboulsi Myriam , Anagnostopoulou Christina , Zaharia Liliana , Tegoulias Ioannis , Constantin Dana Maria (Oprea) , Maheras Panagiotis
Published: August 2023

The main goal of the present study is to identify the prevailing atmospheric circulation patterns (circulation types) that are associated with the occurrence of precipitation (both mean and extreme) over southern Romania. A daily circulation type calendar derived from an automatic and objective classification scheme is used in synergy with the daily precipitation time series from five weather stations in the study area for a sixty-year period (1961–2020). Both mean and extreme precipitation do not show statistically significant trends, except for the annual precipitation at Constanța, for the value with daily precipitation totals greater than the 95th percentile at Craiova and the number of days exceeding the 99th percentile at Buzău and Râmnicu -Vâlcea, where significant negative trends were noticed. Moreover, the precipitation trends were analyzed in relation to the atmospheric circulation types. Non-significant positive trends were observed for the precipitation amounts (annually, winter, spring, and autumn) corresponding to very rainy circulation types (C, Cwsw), while for summer, the equivalent trends were negative. Moreover, it became evident that during extreme precipitation events, the predominant circulation types (C, Cwsw) are associated with western or almost western atmospheric circulation and Mediterranean- or Atlantic-originated depressions.
Evaluation of Long Time-Series Soil Moisture Products Using Extended Triple Collocation and In Situ Measurements in China
Authors: Zhang Liumeng , Yang Yaping , Liu Yangxiaoyue , Yue Xiafang
Published: August 2023

Currently, satellite-based soil moisture (SM) products and land surface model assimilation techniques are widely utilized. However, the presence of systematic errors in the observation process, algorithmic discrepancies between products, and variations in spatial and temporal scales result in diverse accuracy characteristics and applicability. This study evaluates three prominent SM products in China, namely, the Essential Climate Variable Soil Moisture (ECV), the European Centre for Medium-Range Weather Forecasts’ Fifth-Generation Land Surface Reanalysis Data (ERA5-Land), and the Global Land Surface Data Assimilation System (GLDAS). The evaluation was conducted using extended triple collocation (ETC) analysis and in situ validation methods at a monthly scale from 2000 to 2020. The ETC analysis results show that among the three products, GLDAS exhibits the highest correlation coefficient (CC) and the lowest standard deviation of error (ESD), indicating its superior performance in China. ECV and ERA5-Land follow, with slightly lower performance. In the in situ validation results, ERA5-Land displays the highest correlation, capturing the temporal trend of the ground SM well. Comparatively, in terms of overall accuracy, ECV performs the best, with a slightly smaller mean error (ME) and root mean square error (RMSE) than GLDAS, and ERA5-Land has the lowest accuracy. The discrepancy between the in situ validation results and ETC analysis can be attributed to the limited number of sites and their representativeness errors. Notably, ERA5-Land exhibits a highly consistent trend of interannual fluctuations between ESD and precipitation. Furthermore, a strong association is observed between the ME and RMSE of ECV and GLDAS and precipitation. These findings serve as valuable references for future SM studies in China.
Measurement of Long-Term CH4 Emissions and Emission Factors from Beef Feedlots in Australia
Authors: Bai Mei , Coates Trevor , Hill Julian , Flesch Thomas K. , Griffith David W. T. , Van der Saag Matthew , Rinehart Des , Chen Deli
Published: August 2023

One of the major challenges for the Australian feedlot and meat sectors is to have accurate and robust long-term greenhouse gas (GHG) emissions data. Long-term measurements of methane (CH4) emissions (2015–2017) were made at two Australian beef feedlots having different climates, cattle types, and management practices. Emissions were measured using the inverse-dispersion model (IDM) micrometeorological technique, using CH4 concentrations measured at the feedlots with a closed-path Fourier transform infrared spectroscopic technique (CP-FTIR). The emissions data were used to evaluate methods used by the Department of Climate Change, Energy, the Environment and Water to estimate CH4 emissions from feedlots in Australian national inventory calculations. Expressed as a CH4 yield (emissions per unit dry matter intake, DMI), the two feedlots had emissions of 13.1 and 18.9 g CH4 kg−1 DMI. The lower-emitting feedlot had emissions that were 30% lower than the national inventory calculations based on feed intakes, while the second feedlot had emissions that were similar to the inventory calculations. The accurate quantification of emissions from feedlots, as demonstrated as part of this study, is important for validating the national accounting methods and therefore the sector’s GHG emissions profile.
Positive Solutions of Operator Equations AX = B, XC = D
Authors: Zhang Haiyan , Dou Yanni , Yu Weiyan
Published: August 2023

In this paper, using the technique of operator matrix, we consider the positive solution of the system of operator equations AX=B,XC=D in the framework of the Hilbert space; here, the ranges R(A) of A and R(C) of C are not necessarily closed. Firstly, we provide a new necessary and sufficient condition for the existence of positive solutions of AX=B and also provide a representation of positive solutions, which generalize previous conclusions. Furthermore, using the above result, a condition of equivalence for the existence of common positive solutions of AX=B,XC=D is given, as well as the general forms of positive solutions.
Positive Solutions for Periodic Boundary Value Problems of Fractional Differential Equations with Sign-Changing Nonlinearity and Green’s Function
Authors: Yan Rian , Zhao Yige
Published: August 2023

In this paper, a class of nonlinear fractional differential equations with periodic boundary condition is investigated. Although the nonlinearity of the equation and the Green’s function are sign-changing, the results of the existence and nonexistence of positive solutions are obtained by using the Schaefer’s fixed-point theorem. Finally, two examples are given to illustrate the main results.
Equitable Coloring of IC-Planar Graphs with Girth g ≥ 7
Authors: Huang Danjun , Wu Xianxi
Published: August 2023

An equitable k-coloring of a graph G is a proper vertex coloring such that the size of any two color classes differ at most 1. If there is an equitable k-coloring of G, then the graph G is said to be equitably k-colorable. A 1-planar graph is a graph that can be embedded in the Euclidean plane such that each edge can be crossed by other edges at most once. An IC-planar graph is a 1-planar graph with distinct end vertices of any two crossings. In this paper, we will prove that every IC-planar graph with girth g≥7 is equitably Δ(G)-colorable, where Δ(G) is the maximum degree of G.
On Some Quasi-Curves in Galilean Three-Space
Authors: Elsharkawy Ayman , Tashkandy Yusra , Emam Walid , Cesarano Clemente , Elsharkawy Noha
Published: August 2023

In this paper, the quasi-frame and quasi-formulas are introduced in Galilean three-space. In addition, the quasi-Bertrand and the quasi-Mannheim curves are studied. It is proven that the angle between the tangents of two quasi-Bertrand or quasi-Mannhiem curves is not constant. Furthermore, the quasi-involute is studied. Moreover, we prove that there is no quasi-evolute curve in Galilean three-space. Also, we introduce quasi-Smarandache curves in Galilean three-space. Finally, we demonstrate an illustrated example to present our findings.
Optimal Auxiliary Function Method for Analyzing Nonlinear System of Belousov–Zhabotinsky Equation with Caputo Operator
Authors: Alshehry Azzh Saad , Yasmin Humaira , Ahmad Muhammad Wakeel , Khan Asfandyar , Shah Rasool
Published: August 2023

This paper introduces the optimal auxiliary function method (OAFM) for solving a nonlinear system of Belousov–Zhabotinsky equations. The system is characterized by its complex dynamics and is treated using the Caputo operator and concepts from fractional calculus. The OAFM provides a systematic approach to obtain approximate analytical solutions by constructing an auxiliary function. By optimizing the parameters of the auxiliary function, an approximate solution is derived that closely matches the behavior of the original system. The effectiveness and accuracy of the OAFM are demonstrated through numerical simulations and comparisons with existing methods. Fractional calculus enhances the understanding and modeling of the nonlinear dynamics in the Belousov–Zhabotinsky system. This study contributes to fractional calculus and nonlinear dynamics, offering a powerful tool for analyzing and solving complex systems such as the Belousov–Zhabotinsky equation.
Measuring Bone Healing: Parameters and Scores in Comparison
Authors: Söhling Nicolas , Von Jan Olivia , Janko Maren , Nau Christoph , Ritz Ulrike , Marzi Ingo , Henrich Dirk , Verboket René D.
Published: August 2023

(1) Background: Bone healing is a complex process that can not be replicated in its entirety in vitro. Research on bone healing still requires the animal model. The critical size femur defect (CSFD) in rats is a well-established model for fractures in humans that exceed the self-healing potential. New therapeutic approaches can be tested here in vivo. Histological, biomechanical, and radiological parameters are usually collected and interpreted. However, it is not yet clear to what extent they correlate with each other and how necessary it is to record all parameters. (2) Methods: The basis for this study was data from three animal model studies evaluating bone healing. The µCT and histological (Movat pentachrome, osteocalcin) datasets/images were reevaluated and correlation analyses were then performed. Two image processing procedures were compared in the analysis of the image data. (3) Results: There was a significant correlation between the histologically determined bone fraction (Movat pentachrome staining) and bending stiffness. Bone fraction determined by osteocalcin showed no prognostic value. (4) Conclusions: The evaluation of the image datasets using ImageJ is sufficient and simpler than the combination of both programs. Determination of the bone fraction using Movat pentachrome staining allows conclusions to be drawn about the biomechanics of the bone. A standardized procedure with the ImageJ software is recommended for determining the bone proportion.
Neuromuscular Characteristics of Unilateral and Bilateral Maximal Voluntary Isometric Contractions following ACL Reconstruction
Authors: Di Giminiani Riccardo , Marinelli Stefano , La Greca Stefano , Di Blasio Andrea , Angelozzi Massimo , Cacchio Angelo
Published: August 2023

Despite the advancement of diagnostic surgical techniques in anterior cruciate ligament (ACL) reconstruction and rehabilitation protocols following ACL injury, only half of the athletes return to sports at a competitive level. A major concern is neuromechanical dysfunction, which occurs with injuries persisting in operated and non-operated legs following ACL rehabilitation. One of the criteria for a safe return to sports participation is based on the maximal voluntary isometric contraction (MVIC) performed unilaterally and a comparison between the ‘healthy knee’ and the ‘operated knee’. The present study aimed to investigate MVIC in athletes following ACL rehabilitation during open kinetic chain exercise performed unilaterally and bilateral exercises. Twenty subjects participated in the present investigation: 10 male athletes of regional–national level (skiers, rugby, soccer, and volleyball players) who were previously operated on one knee and received a complete rehabilitation protocol (for 6–9 months) were included in the ACL group (age: 23.4 ± 2.11 years; stature: 182.0 ± 9.9 cm; body mass: 78.6 ± 9.9 kg; body mass index: 23.7 ± 1.9 kg/m2), and 10 healthy male athletes formed the control group (CG: age: 24.0 ± 3.4 years; stature: 180.3 ± 10.7 cm; body mass: 74.9 ± 13.5 kg; body mass index: 22.8 ± 2.7 kg/m2). MVICs synchronised with electromyographic (EMG) activity (recorded on the vastus lateralis, vastus medialis, and biceps femoris muscles) were performed during unilateral and bilateral exertions. The rate of force development (RFD) and co-activation index (CI) were also calculated. The differences in the MVIC and RFD between the two legs within each group were not significant (p > 0.05). Vastus lateralis EMG activity during MVIC and biceps femoris EMG activity during RFD were significantly higher in the operated leg than those in the non-operated leg when exertion was performed bilaterally (p < 0.05). The CI was higher in the operated leg than that in the non-operated leg when exertion was performed bilaterally (p < 0.05). Vice versa, vastus medialis EMG activity during RFD was significantly higher in the right leg than that in the left leg when exertion was performed bilaterally (p < 0.05) in the CG. MVICs performed bilaterally represent a reliability modality for highlighting neuromechanical asymmetries. This bilateral exercise should be included in the criteria for a safe return to sports following ACL reconstruction.
Pegylated Liposomal Alendronate Biodistribution, Immune Modulation, and Tumor Growth Inhibition in a Murine Melanoma Model
Authors: Islam Md. Rakibul , Patel Jalpa , Back Patricia Ines , Shmeeda Hilary , Kallem Raja Reddy , Shudde Claire , Markiewski Maciej , Putnam William C. , Gabizon Alberto A. , La-Beck Ninh M.
Published: August 2023

While tumor-associated macrophages (TAM) have pro-tumoral activity, the ablation of macrophages in cancer may be undesirable since they also have anti-tumoral functions, including T cell priming and activation against tumor antigens. Alendronate is a potent amino-bisphosphonate that modulates the function of macrophages in vitro, with potential as an immunotherapy if its low systemic bioavailability can be addressed. We repurposed alendronate in a non-leaky and long-circulating liposomal carrier similar to that of the clinically approved pegylated liposomal doxorubicin to facilitate rapid clinical translation. Here, we tested liposomal alendronate (PLA) as an immunotherapeutic agent for cancer in comparison with a standard of care immunotherapy, a PD-1 immune checkpoint inhibitor. We showed that the PLA induced bone marrow-derived murine non-activated macrophages and M2-macrophages to polarize towards an M1-functionality, as evidenced by gene expression, cytokine secretion, and lipidomic profiles. Free alendronate had negligible effects, indicating that liposome encapsulation is necessary for the modulation of macrophage activity. In vivo, the PLA showed significant accumulation in tumor and tumor-draining lymph nodes, sites of tumor immunosuppression that are targets of immunotherapy. The PLA remodeled the tumor microenvironment towards a less immunosuppressive milieu, as indicated by a decrease in TAM and helper T cells, and inhibited the growth of established tumors in the B16-OVA melanoma model. The improved bioavailability and the beneficial effects of PLA on macrophages suggest its potential application as immunotherapy that could synergize with T-cell-targeted therapies and chemotherapies to induce immunogenic cell death. PLA warrants further clinical development, and these clinical trials should incorporate tumor and blood biomarkers or immunophenotyping studies to verify the anti-immunosuppressive effect of PLA in humans.
The Past, Present, and Future of Genetically Engineered Mouse Models for Skeletal Biology
Authors: Michalski Megan N. , Williams Bart O.
Published: August 2023

The ability to create genetically engineered mouse models (GEMMs) has exponentially increased our understanding of many areas of biology. Musculoskeletal biology is no exception. In this review, we will first discuss the historical development of GEMMs and how these developments have influenced musculoskeletal disease research. This review will also update our 2008 review that appeared in BONEKey, a journal that is no longer readily available online. We will first review the historical development of GEMMs in general, followed by a particular emphasis on the ability to perform tissue-specific (conditional) knockouts focusing on musculoskeletal tissues. We will then discuss how the development of CRISPR/Cas-based technologies during the last decade has revolutionized the generation of GEMMs.
Vancomycin-Stabilized Platinum Nanoparticles with Oxidase-like Activity for Sensitive Dopamine Detection
Authors: Xue Yuzhen , Liu Kai , Gao Mingyue , Zhang Tiantian , Wang Longgang , Cui Yanshuai , Ji Xianbing , Ma Guanglong , Hu Jie
Published: August 2023

The development of efficient, reliable, and sensitive dopamine detection methods has attracted much attention. In this paper, vancomycin-stabilized platinum nanoparticles (Van-Ptn NPs, n = 0.5, 1, 2) were prepared by the biological template method, where n represented the molar ratio of vancomycin to Pt. The results show that Van-Pt2 NPs had oxidase-like activity and peroxidase-like activity, and the mechanism was due to the generation of reactive oxygen 1O2 and OH. Van-Pt2 NPs exhibited good temperature stability, storage stability, and salt solution stability. Furthermore, Van-Pt2 NPs had almost no cytotoxicity to A549 cells. More importantly, the colorimetric detection of DA in human serum samples was performed based on the oxidase-like activity of Van-Pt2 NPs. The linear range of DA detection was 10–700 μM, and the detection limit was 0.854 μM. This study establishes a rapid and reliable method for the detection of dopamine and extends the application of biosynthetic nanoparticles in the field of biosensing.
Plant Hormone and Fatty Acid Screening of Nicotiana tabacum and Lilium longiflorum Stigma Exudates
Authors: Breygina Maria , Kochkin Dmitry , Voronkov Alexander , Ivanova Tatiana , Babushkina Ksenia , Klimenko Ekaterina
Published: August 2023

Pollen germination in vivo on wet stigmas is assisted by the receptive fluid—stigma exudate. Its exact composition is still unknown because only some components have been studied. For the first time, hormonal screening was carried out, and the fatty acid (FA) composition of lipid-rich (Nicotiana tabacum) and sugar-rich (Lilium longiflorum) exudates was studied. Screening of exudate for the presence of plant hormones using HPLC-MS revealed abscisic acid (ABA) in tobacco stigma exudate at the two stages of development, at pre-maturity and in mature stigmas awaiting pollination, increasing at the fertile stage. To assess physiological significance of ABA on stigma, we tested the effect of this hormone in vitro. ABA concentration found in the exudate strongly stimulated the germination of tobacco pollen, a lower concentration had a weaker effect, increasing the concentration did not increase the effect. GC-MS analysis showed that both types of exudate are characterized by a predominance of saturated FAs. The lipids of tobacco stigma exudate contain significantly more myristic, oleic, and linoleic acids, resulting in a higher unsaturation index relative to lily stigma exudate lipids. The latter, in turn, contain more 14-hexadecenoic and arachidic acids. Both exudates were found to contain significant amounts of squalene. The possible involvement of saturated FAs, ABA, and squalene in various exudate functions, as well as their potential relationship on the stigma, is discussed.
Epithelial-Immune Cell Crosstalk Determines the Activation of Immune Cells In Vitro by the Human Cathelicidin LL-37 at Low Physiological Concentrations
Authors: Bogdanov Ivan V. , Streltsova Maria A. , Kovalenko Elena I. , Sapozhnikov Alexander M. , Panteleev Pavel V. , Ovchinnikova Tatiana V.
Published: August 2023

The only human cathelicidin, LL-37, is a host defense antimicrobial peptide with antimicrobial activities against protozoans, fungi, Gram(+) and Gram(−) bacteria, and enveloped viruses. It has been shown in experiments in vitro that LL-37 is able to induce the production of various inflammatory and anti-inflammatory cytokines and chemokines by different human cell types. However, it remains an open question whether such cytokine induction is physiologically relevant, as LL-37 exhibited its immunomodulatory properties at concentrations that are much higher (>20 μg/mL) than those observed in non-inflamed tissues (1–5 μg/mL). In the current study, we assessed the permeability of LL-37 across the Caco-2 polarized monolayer and showed that this peptide could pass through the Caco-2 monolayer with low efficiency, which predetermined its low absorption in the gut. We showed that LL-37 at low physiological concentrations (<5 μg/mL) was not able to directly activate monocytes. However, in the presence of polarized epithelial monolayers, LL-37 is able to activate monocytes through the MAPK/ERK signaling pathway and induce the production of cytokines, as assessed by a multiplex assay at the protein level. We have demonstrated that LL-37 is able to fulfill its immunomodulatory action in vivo in non-inflamed tissues at low physiological concentrations. In the present work, we revealed a key role of epithelial-immune cell crosstalk in the implementation of immunomodulatory functions of the human cathelicidin LL-37, which might shed light on its physiological action in vivo.
The Role of Inositol Hexakisphosphate Kinase in the Central Nervous System
Authors: Heitmann Tyler , Barrow James C.
Published: August 2023

Inositol is a unique biological small molecule that can be phosphorylated or even further pyrophosphorylated on each of its six hydroxyl groups. These numerous phosphorylation states of inositol along with the kinases and phosphatases that interconvert them comprise the inositol phosphate signaling pathway. Inositol hexakisphosphate kinases, or IP6Ks, convert the fully mono-phosphorylated inositol to the pyrophosphate 5-IP7 (also denoted IP7). There are three isoforms of IP6K: IP6K1, 2, and 3. Decades of work have established a central role for IP6Ks in cell signaling. Genetic and pharmacologic manipulation of IP6Ks in vivo and in vitro has shown their importance in metabolic disease, chronic kidney disease, insulin signaling, phosphate homeostasis, and numerous other cellular and physiologic processes. In addition to these peripheral processes, a growing body of literature has shown the role of IP6Ks in the central nervous system (CNS). IP6Ks have a key role in synaptic vesicle regulation, Akt/GSK3 signaling, neuronal migration, cell death, autophagy, nuclear translocation, and phosphate homeostasis. IP6Ks’ regulation of these cellular processes has functional implications in vivo in behavior and CNS anatomy.
Identification of Genes and miRNAs Associated with TAFI-Related Thrombosis: An in Silico Study
Authors: Rouka Erasmia , Zarogiannis Sotirios G. , Hatzoglou Chrissi , Gourgoulianis Konstantinos I. , Malli Foteini
Published: August 2023

Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) is a carboxypeptidase B-like proenzyme encoded by the CPB2 gene. After thrombin activation, TAFI downregulates fibrinolysis, thus linking the latter with coagulation. TAFI has been shown to play a role in venous and arterial thrombotic diseases, yet, data regarding the molecular mechanisms underlying its function have been conflicting. In this study, we focused on the prediction and functional enrichment analysis (FEA) of the TAFI interaction network and the microRNAs (miRNAs) targeting the members of this network in an attempt to identify novel components and pathways of TAFI-related thrombosis. To this end, we used nine bioinformatics software tools. We found that the TAFI interactome consists of 28 unique genes mainly involved in hemostasis. Twenty-four miRNAs were predicted to target these genes. Co-annotation analysis of the predicted interactors with respect to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and transcription factors (TFs) pointed to the complement and coagulation cascades as well as neutrophil extracellular trap formation. Cancer, stroke, and intracranial aneurysm were among the top 20 significant diseases related to the identified miRNAs. We reason that the predicted biomolecules should be further studied in the context of TAFI-related thrombosis.
Advances in Dystrophinopathy Diagnosis and Therapy
Authors: Saad Fawzy A. , Siciliano Gabriele , Angelini Corrado
Published: August 2023

Dystrophinopathies are x-linked muscular disorders which emerge from mutations in the Dystrophin gene, including Duchenne and Becker muscular dystrophy, and dilated cardiomyopathy. However, Duchenne muscular dystrophy interconnects with bone loss and osteoporosis, which are exacerbated by glucocorticoids therapy. Procedures for diagnosing dystrophinopathies include creatine kinase assay, haplotype analysis, Southern blot analysis, immunological analysis, multiplex PCR, multiplex ligation-dependent probe amplification, Sanger DNA sequencing, and next generation DNA sequencing. Pharmacological therapy for dystrophinopathies comprises glucocorticoids (prednisone, prednisolone, and deflazacort), vamorolone, and ataluren. However, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and β-blockers are the first-line to prevent dilated cardiomyopathy in dystrophinopathy patients. Duchenne muscular dystrophy gene therapy strategies involve gene transfer, exon skipping, exon reframing, and CRISPR gene editing. Eteplirsen, an antisense-oligonucleotide drug for skipping exon 51 from the Dystrophin gene, is available on the market, which may help up to 14% of Duchenne muscular dystrophy patients. There are various FDA-approved exon skipping drugs including ExonDys-51 for exon 51, VyonDys-53 and Viltolarsen for exon 53 and AmonDys-45 for exon 45 skipping. Other antisense oligonucleotide drugs in the pipeline include casimersen for exon 45, suvodirsen for exon 51, and golodirsen for exon 53 skipping. Advances in the diagnosis and therapy of dystrophinopathies offer new perspectives for their early discovery and care.
Efficiency of Direct Transcutaneous Electroneurostimulation of the Median Nerve in the Regression of Residual Neurological Symptoms after Carpal Tunnel Decompression Surgery
Authors: Al-Zamil Mustafa , Minenko Inessa A. , Kulikova Natalia G. , Mansur Numman , Nuvakhova Margarita B. , Khripunova Olga V. , Shurygina Irina P. , Topolyanskaya Svetlana V. , Trefilova Vera V. , Petrova Marina M. , Narodova Ekaterina A. , Soloveva Irina A. , Nasyrova Regina F. , Shnayder Natalia A.
Published: August 2023

Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy. CTS therapy includes wrist immobilization, kinesiotherapy, non-steroidal anti-inflammatory drugs, carpal tunnel steroid injection, acupuncture, and physical therapy. Carpal tunnel decompression surgery (CTDS) is recommended after failure of conservative therapy. In many cases, neurological disorders continue despite CTDS. The aim of this study was to investigate the efficiency of direct transcutaneous electroneurostimulation (TENS) of the median nerve in the regression of residual neurological symptoms after CTDS. Material and Methods: 60 patients aged 28–62 years with persisting sensory and motor disorders after CTDS were studied; 15 patients received sham stimulation with a duration 30 min.; 15 patients received high-frequency low-amplitude TENS (HF TENS) with a duration 30 min; 15 patients received low-frequency high-amplitude TENS (LF TENS) with a duration 30 min; and 15 patients received a co-administration of HF TENS (with a duration of15 min) and LF TENS (with a duration of 15 min). Results: Our research showed that TENS significantly decreased the pain syndrome, sensory disorders, and motor deficits in the patients after CTDS. Predominantly, negative and positive sensory symptoms and the pain syndrome improved after the HF TENS course. Motor deficits, reduction of fine motor skill performance, electromyography changes, and affective responses to chronic pain syndrome regressed significantly after the LF TENS course. Co-administration of HF TENS and LF TENS was significantly more effective than use of sham stimulation, HF TENS, or LF TENS in patients with residual neurological symptoms after CTDS.
Insight into Genetic Mutations of SZT2: Is It a Syndrome?
Authors: Muthaffar Osama Y. , Jan Mohammed M. S. , Alyazidi Anas S. , Alotibi Taif K. , Alsulami Eman A.
Published: August 2023

Background: The seizure threshold 2 (SZT2) gene encodes a protein of unknown function, which is widely expressed, confers a low seizure threshold, and enhances epileptogenesis. It also comprises the KICSTOR protein complex, which inhibits the mTORC1 pathway. A pathogenic variant in the SZT2 gene could result in hyperactive mTORC1 signaling, which can lead to several neurological disorders. Aim of the study: To review every reported case and present two novel cases to expand the current knowledge and understanding of the mutation. Methods: Whole exome sequencing (WES) was used to identify the novel cases and present their clinical and radiological findings. A detailed revision of the literature was conducted to illustrate and compare findings. The clinical, genetical, neuroimaging, and electrophysiological data were extracted. Results: The study included 16 female patients and 13 male patients in addition to the 2 novel male cases. Eighteen patients had heterozygous mutations; others were homozygous. The majority presented with facial dysmorphism (n = 22). Seizures were noted as the predominant hallmark (n = 26). Developmental delay and hypotonia were reported in 27 and 15 patients, respectively. The majority of patients had multifocal epileptiform discharges on the electroencephalogram (EEG) and short and thick corpus callosum on the magnetic resonance imaging (MRI). Conclusion: Several promising features are becoming strongly linked to patients with SZT2 mutations. High variability among the cases was observed. Developmental delay and facial dysmorphism can be investigated as potential hallmarks; aiding clinicians in diagnosing the condition and optimizing management plans.