bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of the Latanoprost Solid Delivery System Based on Poly(l-lactide-co-glycolide-co-trimethylene carbonate) with Shape Memory for Glaucoma Treatment
Authors: Borecka Aleksandra , Rech Jakub , Janeczek Henryk , Wilińska Justyna , Kasperczyk Janusz , Kobielarz Magdalena , Grieb Paweł , Turek Artur
Published: June 2023

Latanoprost (LTP) is a prostaglandin F2α analog used to lower intraocular pressure in glaucoma treatment administered daily as eye drops. In this study, a universal model based on poly(l-lactide-co-glycolide-co-trimethylene carbonate) with shape memory was proposed for the development of a solid biodegradable formulation with prolonged release administered intraconjunctivally, intravitreally, subconjunctivally, and subcutaneously. Solution casting and electron beam (EB) irradiation were applied to the matrix formulation. The properties of the native matrix and matrices degraded in a PBS buffer (pH 7.4) were monitored by NMR, DSC, GPC, and SEM. Water uptake (WU) and weight loss (WL) were also analyzed. LTP was released over 113 days in a tri-phasic and sigmoidal pattern without a burst effect and with a relatively long second release phase, in which changes were observed in the glass transition temperature, molecular weight (Mn), WU, and WL. EB irradiation decreased the initial Mn, increased WU, and accelerated LTP release with a shortened lag phase. This provides the opportunity to partially eliminate the use of drops at the start of treatment. SEM observations indicated that surface erosion is the prevalent degradation mechanism. The proposed model is an interesting solution during a preliminary study to develop final medicinal products that provide high adherence.
Experimental Investigations on the Mechanical Performances of Auxetic Metal-Ceramic Hybrid Lattice under Quasi-Static Compression and Dynamic Ballistic Loading
Authors: Wang Rong , Chen Yongxiong , Yan Xiaonan , Cong Nan , Fang Delei , Zhang Peipei , Liang Xiubing , Wu Wenwang
Published: June 2023

In recent years, there have been increasing research interests in investigating the compression and ballistic responses of metal-ceramic hybrid structures, mainly making use of the synergistic effects of conventional metal honeycomb structures and infilled ceramic matrix materials. In this paper, a novel hybrid auxetic re-entrant metal-ceramic lattice is designed and manufactured to overcome the intrinsic conflicts between the strength and toughness of architected mechanical metamaterials, synergistic effects of auxetic re-entrant metal honeycombs and infilled ceramic materials are experimentally and numerically studied, and auxetic deformation features and failure modes are characterized with the digital image correlation (DIC) technique as well. It was found that (1) the infilled ceramic matrix of conventional honeycomb frames only endure longitudinal compression or impact loading along the external loading direction, while auxetic metal re-entrant honeycomb components endure both longitudinal and transverse loading due to the negative Poisson′s ratio effect and (2) the collaborative effects of infilled auxetics and the constraint frames’ hybrid structure dramatically moderate the stress concentration state and improve the impact resistance of single-phase ceramic materials. Our results indicate that the auxetic hybrid design exhibits promising industrial application potentials for blast protection engineering.
Automatic Speech Disfluency Detection Using wav2vec2.0 for Different Languages with Variable Lengths
Authors: Liu Jiajun , Wumaier Aishan , Wei Dongping , Guo Shen
Published: June 2023

Speech is critical for interpersonal communication, but not everyone has fluent communication skills. Speech disfluency, including stuttering and interruptions, affects not only emotional expression but also clarity of expression for people who stutter. Existing methods for detecting speech disfluency rely heavily on annotated data, which can be costly. Additionally, these methods have not considered the issue of variable-length disfluent speech, which limits the scalability of detection methods. To address these limitations, this paper proposes an automated method for detecting speech disfluency that can improve communication skills for individuals and assist therapists in tracking the progress of stuttering patients. The proposed method focuses on detecting four types of disfluency features using single-task detection and utilizes embeddings from the pre-trained wav2vec2.0 model, as well as convolutional neural network (CNN) and Transformer models for feature extraction. The model’s scalability is improved by considering the issue of variable-length disfluent speech and modifying the model based on the entropy invariance of attention mechanisms. The proposed automated method for detecting speech disfluency has the potential to assist individuals in overcoming speech disfluency, improve their communication skills, and aid therapists in tracking the progress of stuttering patients. Additionally, the model’s scalability across languages and lengths enhances its practical applicability. The experiments demonstrate that the model outperforms baseline models in both English and Chinese datasets, proving its universality and scalability in real-world applications.
Multi-Mode Multi-Feature Joint Intelligent Identification Methods for Nematodes
Authors: Zhu Ying , Wang Pengjun , Zhuang Jiayan , Zhu Yi , Xiao Jiangjian , Oyang Xiong
Published: June 2023

The identification of plant nematodes is crucial in the fields of pest control, soil ecology, and biogeography. The automated recognition of plant nematodes based on deep-learning technology can significantly improve the accuracy and efficiency of their recognition. In this study, we devised a method for the multi-mode, multi-feature identification of plant nematodes using deep-learning techniques which emulated the recognition logic of domain experts. Beginning with a multi-featured plant nematode dataset, we not only designed key feature extraction strategies to address the problem of weak key feature points and small inter-specific differences in plant nematodes but also proposed a multi-feature joint training scheme and constructed a neural network structure with interpretability. Finally, an intelligent decision-making expert identification system for plant nematodes was implemented, and its performance was tested on the multi-feature plant nematode dataset. The results indicate that our model achieves an accuracy of up to 96.74% in identifying 23 species across two-body parts, which is 17.5% higher than the single-part feature identification. The accuracy of identifying 11 species in three-body parts reached 98.46%, an improvement of 1.24% over that of the two-part feature identification. Our novel model demonstrates that the accuracy of the expert system can be increased by incorporating more nematode feature parts.
Multilayered Emergent Phenomena Caused by Basic Income and Labor Supply on the Wider Economic System
Authors: Takashima Kosei , Yagi Isao
Published: June 2023

Despite the growing interest in basic income (BI) in recent years, the existing research has mainly focused on its impact on household finances. However, changes in household behavior may affect the actions of other decision makers, such as businesses and governments, leading to unanticipated outcomes. Therefore, any analysis of BI must use a model with multilayered feedback from the actions of individual decision makers. To actualize such a model, household budgets, firms, and other entities must autonomously determine production levels, prices, and other factors, thereby encompassing a complete circulation of funds. This study constructs a macroeconomic model using agent-based modeling as a basic framework to achieve these goals, and it analyzes the emergent behaviors generated by BI and the labor supply in the economic system. The results show that although BI brings about more equitable consumption by households, it also creates a unique phenomenon wherein Gross Domestic Product increases but economic activity in terms of capital investment stagnates. Upon examining the impact of BI, the results of this study present the need to examine the multilayered feedback influencing mutual decision makers, which arises from the behavioral changes of individual decision makers caused by BI.
A Study on the Impact of DPF Failure on Diesel Vehicles Emissions of Particulate Matter
Authors: Park Giyoung , Park Saewoong , Hwang Taewon , Oh Sangki , Lee Seangwock
Published: June 2023

A diesel particulate filter (DPF) is an after-treatment device designed to capture and store exhaust particulate matter emitted by diesel vehicles. DPFs are damaged owing to complex reasons, such as regeneration processes and loads generated during driving. While DPFs can be damaged, they can also be manipulated, especially DPFs with hollow damage. In such cases, the filtration performance deteriorates significantly, and excessive amounts of smoke and ash are emitted during driving, resulting in environmental pollution. In this study, DPF damage types were observed using the CR X-ray imaging technique without removing the DPF. In addition, it was experimentally determined that the five types of DPF shapes (normal, crack, melt, plug, and hollow) caused increases in the particle number (PN) and smoke concentration. Experiments were conducted in the Korea Diesel 147 (KD-147) vehicle driving mode, and the PN and smoke concentration were measured using a nanoparticle emission tester 3795 (NPET-3795-HC) and opacimeter (OPA-102). The experiment was conducted 10 times for each type of DPF damage. As a result of the experiment, no significant difference was found between the normal DPF and crack-damaged DPF in terms of smoke emission, but there was a definite difference in the smoke concentration relative to the other DPF damage types. DPF of all damage types satisfied Korea’s smoke concentration regulation. In addition, the PN emission characteristics differed clearly in terms of the values measured for each damage type, and, unlike the smoke concentration characteristics, there was a clear difference in the PN emission characteristics of various DPF damage types. In addition, the PN concentration tended to increase in the rapid acceleration section of the KD-147 vehicle driving mode for all DPF damage types.
Involvement of the Orexinergic System in Cancer: Antitumor Strategies and Future Perspectives
Authors: Marcos Pilar , Coveñas Rafael
Published: June 2023

Peptides promote the mitogenesis and migration of tumor cells, and cancer cells overexpress peptide receptors. The involvement of the orexinergic system in cancer is reviewed here, including thirteen cancer types (e.g., adrenocortical adenoma, breast, colon, gastric, liver, neuroblastoma, pancreas, prostate). An upregulation of the orexinergic system has been reported in many tumors, and orexin receptors (OXRs) mediate a dual effect: apoptosis in some tumors and a proliferative action in others. OXR antagonists or agonists are potential antitumor agents against tumors expressing OXRs. The complexities of the biological processes associated with the orexigenic system are also described in the review, as they may provide the basis for the development of new therapies: OXR dimerization/oligomerization, epigenetic mechanisms controlling the orexinergic system, possible biomarkers of this system for tumor risk/prognosis, protective effects mediated by orexins against chemotherapeutic drugs, the combination therapy of OXR antagonists/agonists with radiotherapy or chemotherapy, and the anti-inflammatory effects mediated by orexins. Taking these data into account, future therapeutic applications as well as research lines to be developed are also mentioned and discussed. This knowledge will allow for the development of antitumor strategies in the future.
Multi-Objective Optimization of a Two-Stage Helical Gearbox Using Taguchi Method and Grey Relational Analysis
Authors: Le Xuan-Hung , Vu Ngoc-Pi
Published: June 2023

This paper presents a novel approach to solve the multi-objective optimization problem designing a two-stage helical gearbox by applying the Taguchi method and the grey relation analysis (GRA). The objective of the study is to identify the optimal main design factors that maximize the gearbox efficiency and minimize the gearbox mass. To achieve that, five main design factors. including the coefficients of wheel face width (CWFW) of the first and the second stages, the allowable contact stresses (ACS) of the first and the second stages, and the gear ratio of the first stage were chosen. Additionally, two single objectives, including the maximum gearbox efficiency and minimum gearbox mass, were analyzed. In addition, the multi-objective optimization problem is solved through two phases: Phase 1 solves the single-objective optimization problem in order to close the gap between variable levels, and phase 2 solves the multi-objective optimization problem to determine the optimal main design factors. From the results of the study, optimum values of five main design parameters for designing a two-stage helical gearbox were first introduced.
Estimation of Heart Rate and Heart Rate Variability with Real-Time Images Based on Independent Component Analysis and Particle Swarm Optimization
Authors: Su Te-Jen , Hung Ya-Chung , Pan Tzung-Shiarn , Lin Wei-Hong , Wang Shih-Ming , Lee Yu-Cheng
Published: June 2023

With the rapid development of science and technology, the living habits of people have also changed from those in the past; the diet, living environment, various life pressures, etc., all overwhelm the body and mind, meaning that, nowadays, more people are suffering from mental illness and cardiovascular disease year on year. Therefore, a non-contact measurement of heart rate and heart rate variability (HRV) is proposed to assist physicians in diagnosing symptoms related to mental illness and cardiovascular disease. In this paper, continuous images are obtained by general network cameras with non-contact, facial feature points and regions of interest (ROI) employed to track faces and regional images; HRV parameters were analyzed with the green wavelength of RGB color space. The artifact signal is eliminated by a hybrid algorithm of independent component analysis (ICA) and particle swarming optimization (PSO). Finally, the values of heart rate and HRV are obtained with signal processes of using band-pass filter, fast Fourier transform (FFT), and power spectrum analysis in the time and frequency domains, respectively. The non-contact measurement performance of the proposed method can effectively not only avoid infection doubts and obtain heart rate and HRV quickly, but also provide better physiological parameters, root mean square error (RMSE), and mean absolute percentage error (MAPE), than those of recent published papers.
Influence of the Wire Spatial Structure on the Distribution of Product and the Peak Overpressure of Shockwave Generated by the Electric Explosion
Authors: Han Zhongxing , Guo Yanbao , Liu Ben , Zhang Zheng , Lin Tao , Wang Deguo
Published: June 2023

The deposition energy and the peak overpressure of shockwaves are the leading engineering parameters of wire electric explosion technology applied to enhance oil recovery. The thicker Cu wire deposits more energy, which transforms into the shockwave efficiently. Therefore, the effects of three diameters (0.3, 0.4, and 0.5 mm) and hollow ratios (0, 0.5, and 0.7) on the electric explosion efficiency were studied by collecting pulse current, explosion products, and shockwaves during the test. All spatial structure designs of the wire depend on the skin effect parameters of the pulse discharge current. The results found that the peak overpressure of the shockwave soars with the increase of the hollow ratios when the diameter is constant. The range of the peak overpressure is 25.2~47.7 MPa. However, the correlation between shockwave and wire diameter changes from negative to positive with the increase of the hollow ratio from 0 to 0.7. The phase distribution deduced by the particle morphology and quantity distribution indicates that it is going to be uniform gradually with the hollow ratio rising from 0 to 0.7. When the extreme simplification is carried out without considering the magnetic diffusion process, it is indicated that the distribution of temperature and phase states along the wire radial is a Bessel function depending on the skin effect of the current density when three times the theoretical enthalpy drives the Cu wire. It means that the desired shockwave could be obtained efficiently by increasing the diameter and the hollow ratio of wire during a wire electric explosion.
Motion Capture for Sporting Events Based on Graph Convolutional Neural Networks and Single Target Pose Estimation Algorithms
Authors: Duan Chengpeng , Hu Bingliang , Liu Wei , Song Jie
Published: June 2023

Human pose estimation refers to accurately estimating the position of the human body from a single RGB image and detecting the location of the body. It serves as the basis for several computer vision tasks, such as human tracking, 3D reconstruction, and autonomous driving. Improving the accuracy of pose estimation has significant implications for the advancement of computer vision. This paper addresses the limitations of single-branch networks in pose estimation. It presents a top-down single-target pose estimation approach based on multi-branch self-calibrating networks combined with graph convolutional neural networks. The study focuses on two aspects: human body detection and human body pose estimation. The human body detection is for athletes appearing in sports competitions, followed by human body pose estimation, which is divided into two methods: coordinate regression-based and heatmap test-based. To improve the accuracy of the heatmap test, the high-resolution feature map output from HRNet is used for deconvolution to improve the accuracy of single-target pose estimation recognition.
Nonlinear Dynamics and Energy Harvesting of a Two-Degrees-of-Freedom Electromagnetic Energy Harvester near the Primary and Secondary Resonances
Authors: Kecik Krzysztof , Stezycka Ewelina
Published: June 2023

Energy harvesting is a useful technique for various kinds of self-powered electronic devices and systems as well as Internet of Things technology. This study presents a two-degrees-of-freedom (2DOF) electromagnetic energy harvester that can use environment vibration and provide energy for small electronic devices. The proposed harvester consists of a cylindrical tube with two moving magnets suspended by a magnetic spring mechanism and a stationary coil. In order to verify the theoretical model, a prototype electromagnetic harvester was constructed and tested. The influence of key parameters, including excitation acceleration, response to a harmonic frequency sweep, and electromechanical coupling on the generated characteristics of the harvester, was investigated. The experimental and theoretical results showed that the proposed electromagnetic energy harvester was able to increase the resonance bandwidth (60–1200 rad/s) and output power (0.2 W). However, due to strong nonlinearity, an unstable region occurred near the main first resonance, which resulted from the Neimark–Sacker bifurcation.
Comparison of Meteorological Drivers of Two Large Coastal Slope-Land Wildfire Events in Croatia and South-East Australia
Authors: Čavlina Tomašević Ivana , Vučetić Višnjica , Cheung Kevin K. W. , Fox-Hughes Paul , Beggs Paul J. , Telišman Prtenjak Maja , Malečić Barbara
Published: June 2023

Understanding the relationship between fire behavior and the driving weather conditions is critical for fire management and long-term fire risk assessment. In this study, we focus on two wildfire events: the Split wildfire in Croatia and the Forcett–Dunalley wildfire in Tasmania, Australia. The antecedent weather in both events included extremely dry conditions and higher-than-average air temperatures in the months prior to the events. The synoptic patterns in both events consisted of a large surface pressure gradient, which generated strong wind, driving the fire’s spread. The Weather Research and Forecasting (WRF) model was utilized to simulate fire weather conditions during the development of the two events. In the innermost domain of WRF, resolution is 500 m with explicit moisture calculation only, and there are 66 vertical levels, with about 20 of them to resolve the boundary layer. The WRF simulations are well verified by station observations, including upper-level wind speeds. The convergence line pattern in the Tasmanian event, which was conducive to intense plume development, has been well simulated. Only a slight discrepancy was identified in the simulation of the coastal change in wind direction in the Croatian event. It is identified that in the Split case, bura wind was highly coupled with an upper-level trough, which induced subsidence of the upper-level dry and cold air to the surface, causing rapid drying of the fuel. During the Forcett–Dunalley fire, the atmosphere was unstable, which enabled deep pyrocumulonimbus development. In general, the development from ignition to the timing of the most extreme fire intensity in both events was largely determined by the evolution of the surface to upper-level meteorological drivers. While these extreme meteorological conditions would impact fire-fighting strategies such as aircraft operations, a model-based estimate of the high-risk areas is critical. Our findings would also benefit an estimate of the climatology of fire events with similar behavior and thus a long-term fire risk assessment.
New Results on Boas–Bellman-Type Inequalities in Semi-Hilbert Spaces with Applications
Authors: Altwaijry Najla , Dragomir Silvestru Sever , Feki Kais
Published: June 2023

In this article, we investigate new findings on Boas–Bellman-type inequalities in semi-Hilbert spaces. These spaces are generated by semi-inner products induced by positive and positive semidefinite operators. Our objective is to reveal significant properties of such spaces and apply these results to the field of multivariable operator theory. Specifically, we derive new inequalities that relate to the joint A-numerical radius, the joint operator A-seminorm, and the Euclidean A-seminorm of tuples of semi-Hilbert space operators. We assume that A is a nonzero positive operator. Our discoveries provide insights into the structure of semi-Hilbert spaces and have implications for a broad range of mathematical applications and beyond.
Identification of Adolescent Menarche Status using Biplanar X-ray Images: A Deep Learning-based Method
Authors: Xie Linzhen , Ge Tenghui , Xiao Bin , Han Xiaoguang , Zhang Qi , Xu Zhongning , He Da , Tian Wei
Published: June 2023

The purpose of this study is to develop an automated method for identifying the menarche status of adolescents based on EOS radiographs. We designed a deep-learning-based algorithm that contains a region of interest detection network and a classification network. The algorithm was trained and tested on a retrospective dataset of 738 adolescent EOS cases using a five-fold cross-validation strategy and was subsequently tested on a clinical validation set of 259 adolescent EOS cases. On the clinical validation set, our algorithm achieved accuracy of 0.942, macro precision of 0.933, macro recall of 0.938, and a macro F1-score of 0.935. The algorithm showed almost perfect performance in distinguishing between males and females, with the main classification errors found in females aged 12 to 14 years. Specifically for females, the algorithm had accuracy of 0.910, sensitivity of 0.943, and specificity of 0.855 in estimating menarche status, with an area under the curve of 0.959. The kappa value of the algorithm, in comparison to the actual situation, was 0.806, indicating strong agreement between the algorithm and the real-world scenario. This method can efficiently analyze EOS radiographs and identify the menarche status of adolescents. It is expected to become a routine clinical tool and provide references for doctors’ decisions under specific clinical conditions.
Co-Electrospun Poly(ε-Caprolactone)/Zein Articular Cartilage Scaffolds
Authors: Plath Andre M. Souza , Huber Stephanie , Alfarano Serena R. , Abbott Daniel F. , Hu Minghan , Mougel Victor , Isa Lucio , Ferguson Stephen J.
Published: June 2023

Osteoarthritis scaffold-based grafts fail because of poor integration with the surrounding soft tissue and inadequate tribological properties. To circumvent this, we propose electrospun poly(ε-caprolactone)/zein-based scaffolds owing to their biomimetic capabilities. The scaffold surfaces were characterized using Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, static water contact angles, and profilometry. Scaffold biocompatibility properties were assessed by measuring protein adsorption (Bicinchoninic Acid Assay), cell spreading (stained F-actin), and metabolic activity (PrestoBlue™ Cell Viability Reagent) of primary bovine chondrocytes. The data show that zein surface segregation in the membranes not only completely changed the hydrophobic behavior of the materials, but also increased the cell yield and metabolic activity on the scaffolds. The surface segregation is verified by the infrared peak at 1658 cm−1, along with the presence and increase in N1 content in the survey XPS. This observation could explain the decrease in the water contact angles from 125° to approximately 60° in zein-comprised materials and the decrease in the protein adsorption of both bovine serum albumin and synovial fluid by half. Surface nano roughness in the PCL/zein samples additionally benefited the radial spreading of bovine chondrocytes. This study showed that co-electrospun PCL/zein scaffolds have promising surface and biocompatibility properties for use in articular-tissue-engineering applications.
Diversity of Culturable Bacteria from Endemic Medicinal Plants of the Highlands of the Province of Parinacota, Chile
Authors: Moraga Daniel , Latorre Katina , Muñoz-Torres Patricio , Cárdenas Steffany , Jofré-Quispe Alan , López-Cepeda José , Bustos Luis , Balada Cristóbal , Argaluza María Fernanda , González Pablo , Guzmán Leda
Published: June 2023

Endemic medicinal plants that grow at altitudes in northern Chile have been traditionally used for therapeutic applications by Aymara doctors. Several studies have analyzed the biological properties of these plants for therapeutic purposes. The aim was to characterize at molecular and biochemical levels the bacteria that live in the rhizosphere and roots from endemic medicinal plants that grow between 3681–5104 m.a.s.l. in the province of Parinacota. Thirty-nine bacteria were isolated from nine medicinal plants under our laboratory conditions. These bacteria were characterized by Gram stain, hydrolase production, plant-growth promotion, anti-fungal and antibacterial activities, and 16S rDNA sequencing. A phylogenetic study revealed the presence of three major phyla, Actinomycetota (46.2%), Bacillota (43.6%), and Pseudomonadota (10.3%). The rhizobacteria strains associated with the Aymara medicinal plant exhibited several interesting biological activities, such as hydrolytic enzymes, plant-growth-promoting traits, and antibacterial and antifungal properties, indicating their potential for developing new bio-based products for agricultural or clinical applications. These results are promising and highlight the need to point toward the search for explanations of the bio-molecular basis of the therapeutic effects of medicinal plants.
Recruitment Kinetics of XRCC1 and RNF8 Following MeV Proton and α-Particle Micro-Irradiation
Authors: Muggiolu Giovanna , Torfeh Eva , Simon Marina , Devès Guillaume , Seznec Hervé , Barberet Philippe
Published: June 2023

Time-lapse fluorescence imaging coupled to micro-irradiation devices provides information on the kinetics of DNA repair protein accumulation, from a few seconds to several minutes after irradiation. Charged-particle microbeams are valuable tools for such studies since they provide a way to selectively irradiate micrometric areas within a cell nucleus, control the dose and the micro-dosimetric quantities by means of advanced detection systems and Monte Carlo simulations and monitor the early cell response by means of beamline microscopy. We used the charged-particle microbeam installed at the AIFIRA facility to perform micro-irradiation experiments and measure the recruitment kinetics of two proteins involved in DNA signaling and repair pathways following exposure to protons and α-particles. We developed and validated image acquisition and processing methods to enable a systematic study of the recruitment kinetics of GFP-XRCC1 and GFP-RNF8. We show that XRCC1 is recruited to DNA damage sites a few seconds after irradiation as a function of the total deposited energy and quite independently of the particle LET. RNF8 is recruited to DNA damage sites a few minutes after irradiation and its recruitment kinetics depends on the particle LET.
Nanobody-Based EGFR-Targeting Immunotoxins for Colorectal Cancer Treatment
Authors: Narbona Javier , Hernández-Baraza Luisa , Gordo Rubén G. , Sanz Laura , Lacadena Javier
Published: June 2023

Immunotoxins (ITXs) are chimeric molecules that combine the specificity of a targeting domain, usually derived from an antibody, and the cytotoxic potency of a toxin, leading to the selective death of tumor cells. However, several issues must be addressed and optimized in order to use ITXs as therapeutic tools, such as the selection of a suitable tumor-associated antigen (TAA), high tumor penetration and retention, low kidney elimination, or low immunogenicity of foreign proteins. To this end, we produced and characterized several ITX designs, using a nanobody against EGFR (VHH 7D12) as the targeting domain. First, we generated a nanoITX, combining VHH 7D12 and the fungal ribotoxin α-sarcin (αS) as the toxic moiety (VHHEGFRαS). Then, we incorporated a trimerization domain (TIEXVIII) into the construct, obtaining a trimeric nanoITX (TriVHHEGFRαS). Finally, we designed and characterized a bispecific ITX, combining the VHH 7D12 and the scFv against GPA33 as targeting domains, and a deimmunized (DI) variant of α-sarcin (BsITXαSDI). The results confirm the therapeutic potential of α-sarcin-based nanoITXs. The incorporation of nanobodies as target domains improves their therapeutic use due to their lower molecular size and binding features. The enhanced avidity and toxic load in the trimeric nanoITX and the combination of two different target domains in the bispecific nanoITX allow for increased antitumor effectiveness.
Patient-Derived Tumoroid for the Prediction of Radiotherapy and Chemotherapy Responses in Non-Small-Cell Lung Cancer
Authors: Nounsi Anasse , Seitlinger Joseph , Ponté Charlotte , Demiselle Julien , Idoux-Gillet Ysia , Pencreach Erwan , Beau-Faller Michèle , Lindner Véronique , Balloul Jean-Marc , Quemeneur Eric , Burckel Hélène , Noël Georges , Olland Anne , Fioretti Florence , Falcoz Pierre-Emmanuel , Benkirane-Jessel Nadia , Hua Guoqiang
Published: June 2023

Radiation therapy and platinum-based chemotherapy are common treatments for lung cancer patients. Several factors are considered for the low overall survival rate of lung cancer, such as the patient’s physical state and the complex heterogeneity of the tumor, which leads to resistance to the treatment. Consequently, precision medicines are needed for the patients to improve their survival and their quality of life. Until now, no patient-derived tumoroid model has been reported to predict the efficiency of radiation therapy in non-small-cell lung cancer. Using our patient-derived tumoroid model, we report that this model could be used to evaluate the efficiency of radiation therapy and cisplatin-based chemotherapy in non-small-cell lung cancer. In addition, these results can be correlated to clinical outcomes of patients, indicating that this patient-derived tumoroid model can predict the response to radiotherapy and chemotherapy in non-small-cell lung cancer.
Effects of Infertility Drug Exposure on the Risk of Borderline Ovarian Tumors: A Systematic Review and Meta-Analysis
Authors: Si Manfei , Wang Xiaoxiao , Song Xueling , Long Xiaoyu , Qiao Jie
Published: June 2023

Whether infertility drug exposure increases the risk of borderline ovarian tumors (BOTs) remains controversial. The present study was conducted with a comprehensive search for studies published from January 1990 to December 2021 in the online databases Cochrane Library, PubMed, Web of Science and EMBASE. We considered the first diagnosis of a BOT as the primary outcome. The odds ratio (OR) was calculated with corresponding 95% confidence intervals (CIs) for the risk of BOTs in patients who were treated with infertility drugs. Ten studies, a total of 2,779,511 women, qualified for inclusion in this meta-analysis. The pooled OR of 1.56 (95% CI: 1.09–2.22) revealed a significant positive association between infertility drugs and an increased risk for BOTs, but for specific drugs, only CC plus Gn had statistical significance. No publication bias was detected using the Egger and Begg tests (p > 0.05). A significant difference in BOT incidence was observed among infertile women and nulliparous women who were treated with or without infertility drugs. In conclusion, the use of infertility drugs may increase the risk of BOTs, but a dose-dependent relationship was not observed between the number of assisted reproduction technology cycles and the risk of BOTs, and infertile women who successfully became pregnant might have a reduced risk. Registration: PROSPERO, CRD42022330775.
ALK Fusion in an Adolescent with Acute Myeloid Leukemia: A Case Report and Review of the Literature
Authors: Shekar Meghan , Llaurador Caraballo Gabriela , Punia Jyotinder N. , Curry Choladda V. , Fisher Kevin E. , Redell Michele S.
Published: June 2023

Activating mutations and fusions of the ALK oncogene have been identified as drivers in a number of malignancies. Crizotinib and subsequent ALK tyrosine kinase inhibitors have improved treatment outcomes for these patients. In this paper, we discuss the case of an adolescent patient with acute myeloid leukemia, who was identified to have an activating ALK fusion, which is a rare finding and has never been reported in cases of AML without monosomy 7. Crizotinib was added to this patient’s frontline therapy and was well tolerated. In cases of more common gene alterations, existing data supports the use of targeted agents as post-HSCT maintenance therapy; however, crizotinib was not able to be used post-HSCT for this patient due to the inability to obtain insurance coverage.
Early Screening of Colorectal Precancerous Lesions Based on Combined Measurement of Multiple Serum Tumor Markers Using Artificial Neural Network Analysis
Authors: Ke Xing , Liu Wenxue , Shen Lisong , Zhang Yue , Liu Wei , Wang Chaofu , Wang Xu
Published: June 2023

Many patients with colorectal cancer (CRC) are diagnosed in the advanced stage, resulting in delayed treatment and reduced survival time. It is urgent to develop accurate early screening methods for CRC. The purpose of this study is to develop an artificial intelligence (AI)-based artificial neural network (ANN) model using multiple protein tumor markers to assist in the early diagnosis of CRC and precancerous lesions. In this retrospective analysis, 148 cases with CRC and precancerous diseases were included. The concentrations of multiple protein tumor markers (CEA, CA19-9, CA 125, CYFRA 21-1, CA 72-4, CA 242) were measured by electrochemical luminescence immunoassays. By combining these markers with an ANN algorithm, a diagnosis model (CA6) was developed to distinguish between normal healthy and abnormal subjects, with an AUC of 0.97. The prediction score derived from the CA6 model also performed well in assisting in the diagnosis of precancerous lesions and early CRC (with AUCs of 0.97 and 0.93 and cut-off values of 0.39 and 0.34, respectively), which was better than that of individual protein tumor indicators. The CA6 model established by ANN provides a new and effective method for laboratory auxiliary diagnosis, which might be utilized for early colorectal lesion screening by incorporating more tumor markers with larger sample size.
Association between High-Sensitivity C-Reactive Protein and Blood Pressure Variability in Subacute Stage of Ischemic Stroke
Authors: Xu Chuanli , Fu Zhiyong , Wu Wei , Zhang Jin , Liu Meitong , Gao Lianbo
Published: June 2023

The determinants of blood pressure variability (BPV) are complex. We aimed to evaluate whether circulating high-sensitivity C-reactive protein (hsCRP) is associated with short-term BPV during the subacute stage of ischemic stroke. In this observational study, a consecutive series of acute ischemic stroke patients who underwent 24 h ambulator blood pressure monitoring (ABPM) during day 4 to 10 after onset were enrolled. Multivariable linear regression models were constructed to assess relationships between hsCRP and BPV. Among a total of 325 patients analyzed, the mean age was 60 years old and 72% were male. The SD, CV, ARV of 24 h SBP and DBP were more likely to be higher in patients with hsCRP ≥ 2 mg/L, and these predispositions remained unchanged in linear regression analyses after adjusting for possible confounding factors, with a dose-response relationship when patients were additionally categorized into quartiles according to hsCRP levels using the lowest quartile as a reference category. In contrast, similar results were observed for the mean of SBP but not the mean of DBP. These results indicate that hsCRP is dose-dependently associated with short-term BPV during the subacute stage of ischemic stroke. These findings suggested that patients with a higher level of hsCRP tended to have larger blood pressure fluctuations.
The Role of Coping Styles in Mediating the Dark Triad and Bullying: An Analysis of Gender Difference
Authors: Xia Fangjing , Liu Mengjun , Liu Tour
Published: June 2023

Recently, the phenomenon of school bullying has gradually become a primary focus of social attention. To reduce the occurrence of bullying, it is important that we explore the psychological mechanisms of students with bullying tendencies. We conducted mediation models through a multi-group analysis to verify the mediating effect of coping styles on the relationship between dark personality traits and bullying, and further explored the differences in this mechanism between male and female groups. The participants were 772 high school students recruited from a middle school in Tianjin, China. They completed a set of self-reported measurements including the Dirty Dozen (DD), Simplified Coping Style Questionnaire (SCSQ), Buss–Perry Aggression Questionnaire (BPAQ), and Reactive–Proactive Aggression Questionnaire (RPQ). All the measurement instruments have acceptable reliability and validity. The results of the multi-group multiple models indicated that (1) there are significant gender differences in bullying behavior, with males scoring significantly higher than females. Moreover, the gender difference was only reflected in proactive aggression, in which males had higher scores than females; there was no significant gender difference in reactive aggression. (2) In the group of females, both negative and positive coping styles partially moderated the relationship between the Dark Triad and bullying. However, in the group of males, only negative coping styles partially mediated the relationship between the Dark Triad and bullying. (3) The above results also held for proactive aggression. In conclusion, our study highlights the gender differences in the mediating effect of coping styles on the relationship between the Dark Triad and bullying and proactive aggression. These findings contribute to better shared understanding of gender-related aspects in school bullying.
Suicidal Behaviour among School-Going Adolescents in Saint Lucia: Analysis of Prevalence and Associated Factors
Authors: Sarfo Jacob Owusu , Amoadu Mustapha , Obeng Paul , Gbordzoe Newton Isaac , Debrah Timothy Pritchard , Ofori Crescens Osei Bonsu , Hagan John Elvis
Published: June 2023

Suicide poses a debilitating threat to adolescents’ lives worldwide. Although suicide prevention efforts are evident globally, there is limited evidence on the prevalence and correlations of suicidal behaviour among school-going adolescents in Saint Lucia. We used a dataset from the 2018 Global School-based Student Health Survey to examine the prevalence and associated factors of suicidal behaviour among 1864 students from schools in Saint Lucia. Prevalence rates of 25.5%, 22.1%, and 17.5% were found for suicidal ideation, suicide plan, and suicide attempt, respectively. After adjusting for other factors, being male and having understanding parents were protective against suicidal behaviour. However, suicidal ideation was predicted by being physically attacked and bullied, parental/guidance tobacco use, loneliness, and worry. Moreover, being a victim of physical attacks and bullying, having close friends, being lonely, and worrying were predictive of making suicidal plans among adolescents. Attempting suicide was predicted by cigarette smoking, current use of tobacco and related products, bullying, having close friends, being lonely, and worrying. School-based preventive interventions are required to help address triggers of suicidal behaviour among adolescents in Saint Lucia and to help attain the targets for suicide prevention in the global Sustainable Development Goals.
Measured Impact of Material Settlement in a Timber-Frame Wall with Loose Fill Insulation
Authors: Michálková Daniela , Ďurica Pavol
Published: June 2023

Loose-fill thermal insulations in timber-frame structures are designed to provide efficient thermal protection with the ability to fill intricate details. In a previous study, we detected several air cavities formed in timber-framed wall samples filled with loose-fill mineral fiber insulation. This discovery led us to retrofit the walls by adding appropriate insulation, thus enabling us to evaluate the importance of proper amendment. This paper focuses on a wall fragment with an 80 mm high air gap at the top and a 30 mm high cavity in the middle of the wall height. The following paper compares data collected before the discovery and after the replenishment (refill of air gaps with additional insulation), evaluating potential thermal performance improvement. We were able to quantify the impact of these defects on the external wall exposed to realistic conditions. Based on temperature and relative humidity measurements, the results show significant advancement in the middle of wall thickness with an 8 °C and 45% difference. The results show that although this defect did not directly affect the energy balance of the building, it significantly increases the risk of mold growth due to thermal bridging.
Multi-Component Cements for Sealing Casing Columns in Boreholes
Authors: Stryczek Stanisław , Kremieniewski Marcin
Published: June 2023

Ensuring proper and effective cementing of casing pipe columns in boreholes requires maintaining appropriate technological parameters for the developed slurry recipes. It is also necessary to use technology which guarantees effective displacement of the drilling mud for cement slurry injection into the annular space of the borehole. The most important factors that ensure high efficiency of drilling mud displacement by the cement slurry are, among others, the rheological properties of the liquids involved in the process of cementing the casing columns (drilling mud, cement slurry, buffer liquid). The introduced version of the European cement standard, PN-EN 197-1, includes new types of very economical multi-component cements CEM V/A and CEM V/B, which contain 20–40% Portland clinker with a relatively high content of hydraulic and pozzolanic constituents. They occur in the form of granulated blast furnace slag, natural as well as industrial pozzolans and silica fly ash from the combustion of hard coal. The article presents the results of laboratory tests on the technological parameters of both fresh and hardened cement slurries prepared on the basis of CEM V multi-component cement varieties A and B. These slurries meet the standard technological parameters to a demanding extent, which makes it possible to apply them to cementing columns of casing pipes in deep hole drilling. Their detailed properties can be modified by introducing other mineral additives and chemical admixtures to the cement slurry recipes.
Interleukin 24: Signal Transduction Pathways
Authors: Smith Simira , Lopez Sual , Kim Anastassiya , Kasteri Justina , Olumuyide Ezekiel , Punu Kristian , de la Parra Columba , Sauane Moira
Published: June 2023

Interleukin 24 is a member of the IL-10 family with crucial roles in antitumor, wound healing responses, host defense, immune regulation, and inflammation. Interleukin 24 is produced by both immune and nonimmune cells. Its canonical pathway relies on recognition and interaction with specific Interleukin 20 receptors in the plasma membrane and subsequent cytoplasmic Janus protein tyrosine kinases (JAK)/signal transducer and activator of the transcription (STAT) activation. The identification of noncanonical JAK/STAT-independent signaling pathways downstream of IL-24 relies on the interaction of IL-24 with protein kinase R in the cytosol, respiratory chain proteins in the inner mitochondrial membrane, and chaperones such as Sigma 1 Receptor in the endoplasmic reticulum. Numerous studies have shown that enhancing or inhibiting the expression of Interleukin 24 has a therapeutic effect in animal models and clinical trials in different pathologies. Successful drug targeting will require a deeper understanding of the downstream signaling pathways. In this review, we discuss the signaling pathway triggered by IL-24.