bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Different Dried Vegetable Powders on Physicochemical, Organoleptic, and Antioxidative Properties of Fat-Free Dairy Desserts
Authors: Kusio Katarzyna , Szafrańska Jagoda O. , Radzki Wojciech , Sołowiej Bartosz G.
Published: November 2022

The experiments aimed to determine the influence of dried vegetable powders (carrot, beetroot, onion, and champignon in concentrations of 1, 3, or 5%) on the textural, rheological, antioxidative, and organoleptic features of fat-free dairy desserts. Each tested vegetable powder is commonly known for its biological activities. They are considered good sources of minerals and vitamins and can improve human health by decreasing the risk of numerous diseases. Samples were tested to check their texture, viscosity and viscoelastic properties, water activity, antioxidant (DPPH and FRAP), and organoleptic features. The addition of powders caused an increase in the hardness and adhesiveness of the final products. Viscosity was dependent upon the amount and type of tested powder. The correlation between hardness, elastic (G′), and viscous moduli (G″) has been noted. The water activity of the tested product ranged between 0.868–0.997. The highest content of phenolic compounds was detected in samples with 5% dried vegetable powders, and the value of the antioxidant activity increased proportionally to the vegetable content. Additionally, the organoleptic evaluation showed that panelists prefer desserts with champignon (3 and 5%) and carrot (3%) addition.
Analysis of Rewetting Characteristics and Process Parameters in Tobacco Strip Redrying Stage
Authors: Wang Huaiyu , Wang Lihua , Jiang Wei , Wei Qike , Zhang Hao
Published: November 2022

To study the rewetting characteristics of tobacco strips during the redrying stage, a conjugate heat and mass transfer model of tobacco strips was established based on their physical properties. The fundamental relationship between the multiphysical fields and humidity fields of tobacco strips and the key process parameters was considered in this model, and the feasibility of the model was verified via experiments. Based on this model, the transfer and variation laws of the moisture content, humidification rate, and temperature of tobacco strips under different relative humidity and temperature conditions were studied, and the rewetting process parameters of tobacco strips were determined using COMSOL Multiphysics. The results show that this model can be used to study the rewetting characteristics of tobacco strips during the redrying stage. The rewetting of tobacco strips can be divided into two stages, namely, the accelerated stage and approximate constant rate increase stage, where the former stage has a greater impact on the rewetting effect. The higher the relative humidity and temperature, the greater the change in the moisture content, humidification rate, and effective moisture diffusivity, and the faster the increase rate. The best rewetting effect was achieved when the relative humidity was 85% and the temperature was 55 °C. Under these conditions, the moisture content of the tobacco strips was 11% to 13%, the humidification rate was 0.03 %/s to 0.29 %/s, the highest effective moisture diffusivity was 7.8 × 10−10 m2/s, and the maximum activation energy was 37.86 kJ/mol. This study provides a theoretical basis and data support for analyzing the characteristics of the rewetting process and for optimizing the process parameters.
Application of Modified Steady-State Genetic Algorithm for Batch Sizing and Scheduling Problem with Limited Buffers
Authors: Janeš Gordan , Ištoković David , Jurković Zoran , Perinić Mladen
Published: November 2022

Batch sizing and scheduling problems are usually tough to solve because they seek solutions in a vast combinatorial space of possible solutions. This research aimed to test and further develop a scheduling method based on a modified steady-state genetic algorithm and test its performance, in both the speed (low computational time) and quality of the final results as low makespan values. This paper explores the problem of determining the order and size of the product batches in a hybrid flow shop with a limited buffer according to the problem that is faced in real-life. Another goal of this research was to develop a new reliable software/computer program tool in c# that can also be used in production, and as result, obtain a flexible software solution for further research. In all of the optimizations, the initial population of the genetic algorithm was randomly generated. The quality of the obtained results, and the short computation time, together with the flexibility of the genetic paradigm prove the effectiveness of the proposed algorithm and method to solve this problem.
Improvement of the Dynamic and Seismic Behaviour of Rigid Block-like Structures by a Hysteretic Mass Damper Coupled with an Inerter
Authors: Di Egidio Angelo , Contento Alessandro
Published: November 2022

The protection of rigid block-like structures against seismic hazards is a widely studied topic and has been achieved to different degrees with active and passive protection methods. For the protection of rigid block-like structures, this paper proposes the coupling of a rigid block-like structure, modelled as a single rigid block, with an external, auxiliary system through a hysteretic elasto-plastic device. The auxiliary system is constituted by an oscillating mass, whose inertial effects are amplified by the use of an inerter device. The auxiliary system works as a hysteretic mass damper. The elasto-plastic behaviour of the coupling device is described by the Bouc–Wen model. The mechanical model of the coupled system has two degrees of freedom, and its equations of motion can be written by following a direct approach. A preliminary analysis is performed by exciting different coupled systems and the corresponding stand-alone rigid blocks with harmonic base accelerations. Such an investigation is aimed at understanding the sensitivity of the dynamics of the coupled systems to the characteristics of the rigid blocks and auxiliary systems and is performed by comparing the frequency–response curves of the coupled systems with those of the corresponding stand-alone rigid blocks. A further analysis is performed to verify the effectiveness of the proposed protection methodology under seismic excitation. Both the harmonic and seismic analyses show that the main parameter to be tuned to achieve the protection of the rigid block-like structures is the apparent mass of the inerter device. A proper choice of such a mass improves the dynamics of the rigid block-like structures, leading to smaller oscillations for the same level of excitation.
Nash Equilibria of Quantum Games in the Special Two-Parameter Strategy Space
Authors: Frąckiewicz Piotr , Szopa Marek , Makowski Marcin , Piotrowski Edward
Published: November 2022

The aim of the paper is to examine pure Nash equilibria in a quantum game that extends the classical bimatrix game of dimension 2. The strategies of quantum players are specific types of two-parameter unitary operations such that the resulting quantum game is invariant under isomorphic transformations of the input classical game. We formulate general statements for the existence and form of Nash equilibria and discuss their Pareto efficiency. We prove that, depending on the payoffs of a classical game, the corresponding quantum game may or may not have Nash equilibria in the set of unitary strategies under study. Some of the equilibria cease to be equilibria if the players’ strategy set is the three-parameter special unitary group.
Rings with Heraldic Motives from the Wiener Neustadt Treasure: Imitations of Medieval Signet Rings?
Authors: Hofer Nikolaus
Published: November 2022

In 2007, a late medieval hoard was found in Wiener Neustadt (Lower Austria), which is extraordinary in many respects: the circumstances of its discovery were curious, its composition extremely inhomogeneous in terms of date and quality, and last but not least, the reconstructable circumstances of its concealment seem to have sprung almost from a Hollywood screenplay. It is due to a memorable coincidence that this treasure could be processed quickly within the framework of a scientific research project. The results were already presented in 2014 in a comprehensive monograph. One aspect among the numerous oddities of this hoard is the high number of finger rings it contains, which in turn form a very inhomogeneous category of finds. A group of rings with heraldic motifs on the ring plate is particularly striking and are the focus of this article.
Experimental Modeling of a New Multi-Degree-of-Freedom Fuzzy Controller Based Maximum Power Point Tracking from a Photovoltaic System
Authors: El-Khatib Mohamed Fawzy , Sabry Mohamed-Nabil , Abu El-Sebah Mohamed I. , Maged Shady A.
Published: November 2022

Conventional control methods, which follow the maximum power point (MPP), suffer from being slow or inaccurate during sudden changes in irradiance and temperature. These problems can be solved using artificial intelligence algorithms. The current study proposes a new multi-degree-of-freedom (MDOF) fuzzy logic controller (FLC) for maximizing the overall output performance of a photovoltaic system. The MDOF-FLC was compared to the simplified universal intelligent PID controller (SUI-PID) using the MDOF concept and the normal FLC. Simulation and experimental results show that the proposed MDOF-FLC controller has a 37.8% and 58.1% faster response with a better rise time compared to the SUIPID controller and the normal FLC, respectively. At the same time, the error, measured by the integral time absolute error (ITAE), was 29.4% and 62.5% lower, respectively.
Atmospheric Density Response to a Severe Magnetic Storm Detected by the 520 km Altitude Spherical Satellite
Authors: Wang Xinyue , Jin Yujiao , Meng Xiangguang , Du Dan , Zhang Aibing , Tang Xinchun , Yan Feng , Sun Yueqiang , Zhang Xianguo , Wang Bowen , Cai Yuerong
Published: November 2022

The polar-orbiting spherical experimental satellite of China for atmospheric density detection with an altitude of ~520 km was successfully launched on 14 October 2021. Based on the dynamic inversion method for atmospheric density and the precise orbit determination data obtained by its GNSS, we inverted the orbital atmospheric density during the severe geomagnetic storm in early November 2021. In this paper, we compared the atmospheric density data obtained by the spherical satellite with the simulations of the MSISE00 and the DTM, evaluated their error distribution, and analyzed the response of the atmospheric density during the severe geomagnetic storm in the dawn–dusk orbit of 520 km altitude. The properties and the physical processes for the atmospheric density of the time evolutions in different latitudes and the global distributions during the severe geomagnetic storm were obtained. We found that the substantial disturbance enhancement and recovery of the atmospheric density of the dawn–dusk orbit have a close correlation with the geomagnetic indexes Kp and Dst. The elevation extends from the poles to the equator, and the relative variation in two hemispheres demonstrates a bimodal nearly symmetric growth structure. The maximum relative variation of the two hemispheres both occurred in the middle latitude, and, for this case, the enhancement of atmospheric density in the mid-latitude region accounted for a larger proportion. The asymmetry between the northern and southern hemispheres is demonstrated by the fact that the absolute value and absolute change in the southern hemisphere in summer are larger than those in the northern hemisphere, and the bimodal structure of the relative variation is inclined to the northern hemisphere.
3D-Printed Piezoelectric Porous Bioactive Scaffolds and Clinical Ultrasonic Stimulation Can Help in Enhanced Bone Regeneration
Authors: Sikder Prabaha , Nagaraju Phaniteja , Naganaboyina Harsha P. S.
Published: November 2022

This paper presents a comprehensive effort to develop and analyze first-of-its-kind design-specific and bioactive piezoelectric scaffolds for treating orthopedic defects. The study has three major highlights. First, this is one of the first studies that utilize extrusion-based 3D printing to develop design-specific macroporous piezoelectric scaffolds for treating bone defects. The scaffolds with controlled pore size and architecture were synthesized based on unique composite formulations containing polycaprolactone (PCL) and micron-sized barium titanate (BaTiO3) particles. Second, the bioactive PCL-BaTiO3 piezoelectric composite formulations were explicitly developed in the form of uniform diameter filaments, which served as feedstock material for the fused filament fabrication (FFF)-based 3D printing. A combined method comprising solvent casting and extrusion (melt-blending) was designed and deemed suitable to develop the high-quality PCL-BaTiO3 bioactive composite filaments for 3D printing. Third, clinical ultrasonic stimulation (US) was used to stimulate the piezoelectric effect, i.e., create stress on the PCL-BaTiO3 scaffolds to generate electrical fields. Subsequently, we analyzed the impact of scaffold-generated piezoelectric stimulation on MC3T3 pre-osteoblast behavior. Our results confirmed that FFF could form high-resolution, macroporous piezoelectric scaffolds, and the poled PCL-BaTiO3 composites resulted in the d33 coefficient in the range of 1.2–2.6 pC/N, which is proven suitable for osteogenesis. In vitro results revealed that the scaffolds with a mean pore size of 320 µm resulted in the highest pre-osteoblast growth kinetics. While 1 Hz US resulted in enhanced pre-osteoblast adhesion, proliferation, and spreading, 3 Hz US benefited osteoblast differentiation by upregulating important osteogenic markers. This study proves that 3D-printed bioactive piezoelectric scaffolds coupled with US are promising to expedite bone regeneration in orthopedic defects.
Hand Exoskeleton Design and Human–Machine Interaction Strategies for Rehabilitation
Authors: Xia Kang , Chen Xianglei , Chang Xuedong , Liu Chongshuai , Guo Liwei , Xu Xiaobin , Lv Fangrui , Wang Yimin , Sun Han , Zhou Jianfang
Published: November 2022

Stroke and related complications such as hemiplegia and disability create huge burdens for human society in the 21st century, which leads to a great need for rehabilitation and daily life assistance. To address this issue, continuous efforts are devoted in human–machine interaction (HMI) technology, which aims to capture and recognize users’ intentions and fulfil their needs via physical response. Based on the physiological structure of the human hand, a dimension-adjustable linkage-driven hand exoskeleton with 10 active degrees of freedom (DoFs) and 3 passive DoFs is proposed in this study, which grants high-level synergy with the human hand. Considering the weight of the adopted linkage design, the hand exoskeleton can be mounted on the existing up-limb exoskeleton system, which greatly diminishes the burden for users. Three rehabilitation/daily life assistance modes are developed (namely, robot-in-charge, therapist-in-charge, and patient-in-charge modes) to meet specific personal needs. To realize HMI, a thin-film force sensor matrix and Inertial Measurement Units (IMUs) are installed in both the hand exoskeleton and the corresponding controller. Outstanding sensor–machine synergy is confirmed by trigger rate evaluation, Kernel Density Estimation (KDE), and a confusion matrix. To recognize user intention, a genetic algorithm (GA) is applied to search for the optimal hyperparameters of a 1D Convolutional Neural Network (CNN), and the average intention-recognition accuracy for the eight actions/gestures examined reaches 97.1% (based on K-fold cross-validation). The hand exoskeleton system provides the possibility for people with limited exercise ability to conduct self-rehabilitation and complex daily activities.
Population Characteristics, Symptoms, and Risk Factors of Idiopathic Chilblains: A Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Kapnia Areti K. , Ziaka Styliani , Ioannou Leonidas G. , Flouri Irini , Dinas Petros C. , Flouris Andreas D.
Published: November 2022

Background: Chilblains/perniosis is a non-freezing cold injury causing painful inflammatory skin lesions. Its pathogenesis remains poorly understood because it is often studied as secondary to other underlying conditions. Methods: We systematically investigated the population characteristics, symptoms, and predisposing factors of chilblains in healthy adults exposed to cool/cold environments. We screened PubMed, Embase, and Cochrane Library, and we adopted PRISMA reporting guidelines (PROSPERO: CRD42021245307). The risk of bias was assessed by two independent reviewers (RTI item bank). Random-effects model meta-analyses were performed to calculate the pooled prevalence of histopathological features. Mixed-effects meta-regressions were used to assess other sources of between-study heterogeneity. Results: Thirteen studies (477 patients) were included. Chilblains affect more women than men, up to 12% of the body skin surface, and most frequently, the hands and fingers. Meta-analyses of nine studies (303 patients) showed a frequent presence of perivascular lymphocytic infiltrate (81%), basal epidermal-cell layer vacuolation (67%), papillary dermal edema (66%), and perieccrine lymphocytic infiltrate (57%). Meta-regressions (p ≤ 0.05) showed that smoking and frequent occupational exposure to water increase the likelihood of histopathological features. Conclusions: The population characteristics, symptoms, and predisposing factors of chilblains revealed in this analysis should be incorporated in medical care to improve the condition’s diagnosis and management.
MicroRNAs as Mediators of Adipose Thermogenesis and Potential Therapeutic Targets for Obesity
Authors: Ma Lunkun , Gilani Ankit , Yi Qian , Tang Liling
Published: November 2022

Obesity is a growing health problem worldwide, associated with an increased risk of multiple chronic diseases. The thermogenic activity of brown adipose tissue (BAT) correlates with leanness in adults. Understanding the mechanisms behind BAT activation and the process of white fat “browning” has important implications for developing new treatments to combat obesity. MicroRNAs (miRNAs) are small transcriptional regulators that control gene expression in various tissues, including adipose tissue. Recent studies show that miRNAs are involved in adipogenesis and adipose tissue thermogenesis. In this review, we discuss recent advances in the role of miRNAs in adipocyte thermogenesis and obesity. The potential for miRNA-based therapies for obesity and recommendations for future research are highlighted, which may help provide new targets for treating obesity and obesity-related diseases.
cGMP Signaling in the Neurovascular Unit—Implications for Retinal Ganglion Cell Survival in Glaucoma
Authors: Haider Ameer A. , Rex Tonia S. , Wareham Lauren K.
Published: November 2022

Glaucoma is a progressive age-related disease of the visual system and the leading cause of irreversible blindness worldwide. Currently, intraocular pressure (IOP) is the only modifiable risk factor for the disease, but even as IOP is lowered, the pathology of the disease often progresses. Hence, effective clinical targets for the treatment of glaucoma remain elusive. Glaucoma shares comorbidities with a multitude of vascular diseases, and evidence in humans and animal models demonstrates an association between vascular dysfunction of the retina and glaucoma pathology. Integral to the survival of retinal ganglion cells (RGCs) is functional neurovascular coupling (NVC), providing RGCs with metabolic support in response to neuronal activity. NVC is mediated by cells of the neurovascular unit (NVU), which include vascular cells, glial cells, and neurons. Nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling is a prime mediator of NVC between endothelial cells and neurons, but emerging evidence suggests that cGMP signaling is also important in the physiology of other cells of the NVU. NO-cGMP signaling has been implicated in glaucomatous neurodegeneration in humans and mice. In this review, we explore the role of cGMP signaling in the different cell types of the NVU and investigate the potential links between cGMP signaling, breakdown of neurovascular function, and glaucoma pathology.
Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs
Authors: Massai Lara , Grifagni Deborah , De Santis Alessia , Geri Andrea , Cantini Francesca , Calderone Vito , Banci Lucia , Messori Luigi
Published: November 2022

Gold compounds have a long tradition in medicine and offer many opportunities for new therapeutic applications. Herein, we evaluated the lead compound Auranofin and five related gold(I) complexes as possible inhibitors of SARS-CoV-2 Main Protease (SARS-CoV-2 Mpro), a validated drug target for the COVID-19 disease. The investigational panel of gold compounds included Auranofin; three halido analogues, i.e., Au(PEt3)Cl, Au(PEt3)Br, and Au(PEt3)I; and two gold carbene complexes, i.e., Au(NHC)Cl and [Au(NHC)2]PF6. Notably, all these gold compounds, with the only exception of [Au(NHC)2]PF6, turned out to be potent inhibitors of the catalytic activity of SARS-CoV-2 Mpro: the measured Ki values were in the range 2.1–0.4 μM. The reactions of the various gold compounds with SARS-CoV-2 Mpro were subsequently investigated through electrospray ionization (ESI) mass spectrometry (MS) upon a careful optimization of the experimental conditions; the ESI MS spectra provided clear evidence for the formation of tight metallodrug-protein adducts and for the coordination of well defined gold-containing fragments to the SARS-CoV-2 Mpro, again with the only exception of [Au(NHC)2]PF6, The metal-protein stoichiometry was unambiguously determined for the resulting species. The crystal structures of the metallodrug- Mpro adducts were solved in the case of Au(PEt3)Br and Au(NHC)Cl. These crystal structures show that gold coordination occurs at the level of catalytic Cys 145 in the case of Au(NHC)Cl and at the level of both Cys 145 and Cys 156 for Au(PEt3)Br. Tight coordination of gold atoms to functionally relevant cysteine residues is believed to represent the true molecular basis of strong enzyme inhibition.
Screening of Hydroxyapatite Biomaterials for Alveolar Augmentation Using a Rat Calvaria Critical-Size Defect Model: Bone Formation/Maturation and Biomaterials Resolution
Authors: Susin Cristiano , Lee Jaebum , Fiorini Tiago , Koo Ki-Tae , Schüpbach Peter , Finger Stadler Amanda , Wikesjö Ulf ME
Published: November 2022

Background: Natural (bovine-/equine-/porcine-derived) or synthetic hydroxyapatite (HA) biomaterials appear to be the preferred technologies among clinicians for bone augmentation procedures in preparation for implant dentistry. The aim of this study was to screen candidate HA biomaterials intended for alveolar ridge augmentation relative to their potential to support local bone formation/maturation and to assess biomaterial resorption using a routine critical-size rat calvaria defect model. Methods: Eighty adult male Sprague Dawley outbred rats obtained from a approved-breeder, randomized into groups of ten, were used. The calvaria defects (ø8 mm) either received sham surgery (empty control), Bio-Oss (bovine HA/reference control), or candidate biomaterials including bovine HA (Cerabone, DirectOss, 403Z013), and bovine (403Z014) or synthetic HA/ß-TCP (Reprobone, Ceraball) constructs. An 8 wk healing interval was used to capture the biomaterials’ resolution. Results: All biomaterials displayed biocompatibility. Strict HA biomaterials showed limited, if any, signs of biodegradation/resorption, with the biomaterial area fraction ranging from 22% to 42%. Synthetic HA/ß-TCP constructs showed limited evidence of biodegradation/erosion (biomaterial area fraction ≈30%). Mean linear defect closure in the sham-surgery control approximated 40%. Mean linear defect closure for the Bio-Oss reference control approximated 18% compared with 15–35% for the candidate biomaterials without significant differences between the controls and candidate biomaterials. Conclusions: None of the candidate HA biomaterials supported local bone formation/maturation beyond the native regenerative potential of this rodent model, pointing to their limitations for regenerative procedures. Biocompatibility and biomaterial dimensional stability could suggest their potential utility as long-term defect fillers.
Interleukin-33 Derived from Endometriotic Lesions Promotes Fibrogenesis through Inducing the Production of Profibrotic Cytokines by Regulatory T Cells
Authors: Xiao Fengyi , Liu Xishi , Guo Sun-Wei
Published: November 2022

In endometriosis, it has been widely believed that the local immunological milieu is Th2-skewed. Regulatory T cells (Tregs) promote fibrogenesis of endometriosis through the transforming growth factor β1 (TGF-β1) and platelet-derived growth factor (PDGF) signaling pathways. We aimed to explore whether Tregs in endometriotic lesions acquire increased production of effector cytokines under the influence of lesion-derived interleukin (IL)-33. We extracted lymphocytes from normal endometrium and ovarian endometrioma to evaluate the expression of IL-4, IL-13, interferon-γ (IFN-γ), TGF-β1, and the IL-33 receptor (ST2) by Tregs from these tissues. Colocalization of IL-33 and FOXP3 in normal endometrium and ovarian endometrioma was evaluated by immunofluorescence. Tregs and endometriotic stromal cells were co-cultured and treated with anti-IL-33 antibody, and the cytokines produced by Tregs were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Tregs in ovarian endometrioma produced significant amounts of IL-4, IL-13, TGF-β1, and ST2. Colocalization of IL-33 and FOXP3 was detected in ovarian endometrioma. IL-33 from endometriotic stromal cells caused the differentiation of lesional Tregs into type 2 T helper (Th2)-like cells, along with increased production of TGF-β1 by Tregs. Thus, Tregs and endometriotic lesions engage active crosstalk through IL-33 to promote fibrogenesis in endometriosis, and, as such, this finding opens up new avenues to identify novel therapeutic targets for endometriosis.
Imaging Properties and Tumor Targeting of 68Ga-NeoBOMB1, a Gastrin-Releasing Peptide Receptor Antagonist, in GIST Patients
Authors: Gruber Leonhard , Decristoforo Clemens , Uprimny Christian , Hohenberger Peter , Schoenberg Stefan O. , Orlandi Francesca , Mariani Maurizio Franco , Manzl Claudia , Kasseroler Maria Theresia , Tilg Herbert , Zelger Bettina , Jaschke Werner R. , Virgolini Irene J.
Published: November 2022

Background: Gastrin-releasing peptide receptors (GRPRs) are molecular imaging targets in multiple malignancies. Recently, NeoBOMB1, a 68Ga-labelled antagonist to GRPRs, was developed for PET. Here we report the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) describing diagnostic properties and covariates influencing uptake of 68Ga-NeoBOMB1 in oligometastatic gastrointestinal stromal tumor (GIST) patients. Methods: Nine patients with advanced GIST using PET/CT (computed tomography) were included. After kit-based 68Ga-NeoBOMB1 preparation with a licensed 68Ge/68Ga generator, 3 MBq/kg body weight were injected intravenously. PET/CT included dynamic and static PET scans 5, 12 and 18 min and 1, 2, and 3–4 h post injection (first six patients) and static PET scans 2 and 3–4 h post injection (last three participants). Tumor targeting was assessed on a per-lesion and per-patient basis. Results: Six patients showed visible radiotracer uptake in at least one tumor lesion. Seventeen out of 37 tumor lesions exhibited significant 68Ga-NeoBOMB1 uptake (median SUVmax 11.8 [range 2.8–51.1] 2 h p.i. and 13.2 [range 2.5–53.8] 3–4 h p.i) and improved lesion-to-background contrast over time. Five lesions (13.5%) were identified only by 68Ga-NeoBOMB1-PET, with no correlation on contrast-enhanced CT. Three patients showed no radiotracer accumulation in any lesions. Tracer uptake correlated with male sex (p < 0.0001), higher body mass index (p = 0.007), and non-necrotic lesion appearance (p = 0.018). There was no association with whole-lesion contrast enhancement, hepatic localization, mutational status, or disease duration. Conclusions: 68Ga-NeoBOMB1-PET exhibits variable tumor uptake in advanced-stage GIST patients, correlating with lesion vitality based on CT contrast uptake, opening the possibility of a theragnostic approach in selected cases.
5-Aminolevulinic Acid-Mediated Photodynamic Therapy Potentiates the Effectiveness of Doxorubicin in Ewing Sarcomas
Authors: Marocco Lea , Umrath Felix , Sachsenmaier Saskia , Rabiner Robert , Wülker Nikolaus , Danalache Marina
Published: November 2022

Ewing sarcomas (ES) are aggressive primary bone tumors that require radical therapy. Promising low toxicity, 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) could enhance the effectiveness of conventional treatment modalities (e.g., doxorubicin (DOX)), improving, thus, the anti-tumorigenic effects. In this study, we investigated the effects of DOX and 5-ALA PDT alone or in combination on three different human ES cell lines. Cell viability, reactive oxygen species (ROS) production, and cellular stiffness were measured 24 h after PDT (blue light-wavelength 436 nm with 5-ALA) with or without DOX. ES cell lines have a different sensitivity to the same doses and exposure of 5-ALA PDT. DOX in combination with 5-ALA PDT was found to be effective in impairing the viability of all ES cells while also increasing cytotoxic activity by high ROS production. The stiffness of the ES cells increased significantly (p < 0.05) post treatment. Overall, our results showed that across multiple ES cell lines, 5-ALA PDT can successfully and safely be combined with DOX to potentiate the therapeutic effect. The 5-ALA PDT has the potential to be a highly effective treatment when used alone or in conjunction with other treatments. More research is needed to assess the effectiveness of 5-ALA PDT in in vivo settings.
Comparative Study of Cytotoxic and Membranotropic Properties of Betulinic Acid-F16 Conjugate on Breast Adenocarcinoma Cells (MCF-7) and Primary Human Fibroblasts
Authors: Belosludtsev Konstantin N. , Ilzorkina Anna I. , Belosludtseva Natalia V. , Sharapov Vyacheslav A. , Penkov Nikita V. , Serov Dmitriy A. , Karagyaur Maxim N. , Nedopekina Darya A. , Davletshin Eldar V. , Solovieva Marina E. , Spivak Anna Yu , Kuzmina Ulyana Sh. , Vakhitova Yulia V. , Akatov Vladimir S. , Dubinin Mikhail V.
Published: November 2022

The present study evaluates the cytotoxicity of a previously synthesized conjugate of betulinic acid (BA) with the penetrating cation F16 on breast adenocarcinoma (MCF-7) and human fibroblast (HF) cell lines, and also shows the mechanism underlying its membranotropic action. It was confirmed that the conjugate exhibits higher cytotoxicity compared to native BA at low doses also blocking the proliferation of both cell lines and causing cell cycle arrest in the G0/G1 phase. We show that the conjugate indeed has a high potential for accumulation in mitochondria, being visualized in these organelles, which is most pronounced in cancer cells. The effect of the conjugate was observed to be accompanied by ROS hyperproduction in both cancerous and healthy cells, despite the lower base level of ROS in the latter. Along with this, using artificial liposomes, we determined that the conjugate is able to influence the phase state of lipid membranes, make them more fluid, and induce nonspecific permeabilization contributing to the overall cytotoxicity of the tested agent. We conclude that the studied BA–F16 conjugate does not have significant selective cytotoxicity, at least against the studied breast cancer cell line MCF-7.
Reactive Oxygen Species Enlightened Therapeutic Strategy for Oral and Maxillofacial Diseases—Art of Destruction and Reconstruction
Authors: Zhang Yuwei , Zhang Yifei , Mei Yukun , Zou Rui , Niu Lin , Dong Shaojie
Published: November 2022

Reactive oxygen species (ROS) are byproducts of cell metabolism produced by living cells and signal mediators in biological processes. As unstable and highly reactive oxygen-derived molecules, excessive ROS production and defective oxidant clearance, or both, are associated with the pathogenesis of several conditions. Among them, ROS are widely involved in oral and maxillofacial diseases, such as periodontitis, as well as other infectious diseases or chronic inflammation, temporomandibular joint disorders, oral mucosal lesions, trigeminal neuralgia, muscle fatigue, and oral cancer. The purpose of this paper is to outline how ROS contribute to the pathophysiology of oral and maxillofacial regions, with an emphasis on oral infectious diseases represented by periodontitis and mucosal diseases represented by oral ulcers and how to effectively utilize and eliminate ROS in these pathological processes, as well as to review recent research on the potential targets and interventions of cutting-edge antioxidant materials. The PubMed, Web of Science, and Embase databases were searched using the MesH terms “oral and maxillofacial diseases”, “reactive oxygen species”, and “antioxidant materials”. Irrelevant, obsolete, imprecise, and repetitive articles were excluded through screening of titles, abstracts, and eventually full content. The full-text data of the selected articles are, therefore, summarized using selection criteria. While there are various emerging biomaterials used as drugs themselves or delivery systems, more attention was paid to antioxidant drugs with broad application prospects and rigorous prophase animal experimental results.
Comorbidities and Outcomes among Females with Non-Alcoholic Fatty Liver Disease Compared to Males
Authors: Abu-Freha Naim , Cohen Bracha , Weissmann Sarah , Hizkiya Reut , Abu-Hammad Reem , Taha Gadeer , Gordon Michal
Published: November 2022

Sex-based medicine is an important emerging discipline within medicine. We investigated the clinical characteristics, complications, and outcomes of Nonalcoholic Fatty Liver Disease (NAFLD) in females compared to males. Demographics, comorbidities, malignancy, complications, outcomes, and all-cause mortality of NAFLD patients older than 18 years were analyzed. The data were extracted using the MDClone platform from “Clalit” in Israel. A total of 111,993 (52.8%) of the study subjects were females with an average age of 44.4 ± 14.7 years compared to 39.62 ± 14.9 years in males, p < 0.001. Significantly higher rates of hypertension, diabetes mellitus, obesity, dementia, and thyroid cancer and lower rates of ischemic heart disease (22.3% vs. 27.3%, p < 0.001) were found among females. Females had a higher rate of cirrhosis, 2.3% vs. 1.9%, p < 0.001, and a lower rate of hepatocellular carcinoma, 0.4% vs. 0.5%, p < 0.001. In the multivariate analysis, a relationship between age, diabetes mellitus, and cirrhosis development were found among males and females. A lower age-adjusted mortality rate was found among females, 94.5/1000 vs. 116/1000 among males. In conclusion, older age at diagnosis, higher rates of hypertension, diabetes mellitus, obesity, cirrhosis, and a lower age-adjusted all-cause mortality rate were found among females with NAFLD.
Delayed Formation of Neonatal Reflexes and of Locomotor Skills Is Associated with Poor Maternal Behavior in OXYS Rats Prone to Alzheimer’s Disease-like Pathology
Authors: Kozlova Tatiana , Rudnitskaya Ekaterina , Burnyasheva Alena , Stefanova Natalia , Peunov Daniil , Kolosova Nataliya
Published: November 2022

Postnatal brain development is characterized by high plasticity with critical windows of opportunity where any intervention may positively or adversely influence postnatal growth and lead to long-lasting consequences later in life. Poor maternal care is among these interventions. Here, we found that senescence-accelerated OXYS rats prone to an Alzheimer’s disease-like pathology are characterized by more passive maternal behavior and insufficient care for pups as compared to control (Wistar) rats. OXYS pups demonstrated a delay in physical development (of auricle detachment, of emergence of pelage and incisors, of eye opening, and of vaginal opening in females) and late manifestation of reflexes and locomotor skills. All observed behavioral abnormalities are connected either with poor coordination of limbs’ movements or with a decrease in motivation and development of depression-like behavior. It is possible that their manifestations can be promoted by the features of maternal behavior of OXYS rats. Overall, these early-life events may have long-lasting consequences and contribute to neurodegeneration and development of the Alzheimer’s disease-like pathology later in life.
A Review on Non-Enzymatic Electrochemical Biosensors of Glucose Using Carbon Nanofiber Nanocomposites
Authors: Mohammadpour-Haratbar Ali , Mohammadpour-Haratbar Saeid , Zare Yasser , Rhee Kyong Yop , Park Soo-Jin
Published: November 2022

Diabetes mellitus has become a worldwide epidemic, and it is expected to become the seventh leading cause of death by 2030. In response to the increasing number of diabetes patients worldwide, glucose biosensors with high sensitivity and selectivity have been developed for rapid detection. The selectivity, high sensitivity, simplicity, and quick response of electrochemical biosensors have made them a popular choice in recent years. This review summarizes the recent developments in electrodes for non-enzymatic glucose detection using carbon nanofiber (CNF)-based nanocomposites. The electrochemical performance and limitations of enzymatic and non-enzymatic glucose biosensors are reviewed. Then, the recent developments in non-enzymatic glucose biosensors using CNF composites are discussed. The final section of the review provides a summary of the challenges and perspectives, for progress in non-enzymatic glucose biosensors.
Selective Sensing of Darolutamide and Thalidomide in Pharmaceutical Preparations and in Spiked Biofluids
Authors: Talaat Wael , Farahat Abdelbasset A. , Keshk Reda Mohammed
Published: November 2022

Selective spectrofluorometric sensing is introduced for the analysis of non-steroidal anti-androgens, darolutamide, and thalidomide in pharmaceutical preparations and biofluids. An organic fluorophore, 2,4,8,10-tetramethylpyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine 2 was synthesized in our laboratories by new simple methods to act as a fluorescent reagent for the analysis of the studied drugs. Elemental and spectral analyses were performed to approve the fluorophore structure. The fluorophore possesses a fluorescence at λem 422 nm when excited at 328 nm. The interaction between the studied drugs and the fluorophore was found to be quenching. The quenching mechanisms were studied and interpreted through the Stern–Volmer relationship. Moreover, the Stern–Volmer constants were calculated for the quenching interactions of both drugs. The introduced method was validated for the estimation of darolutamide and thalidomide in dosage forms, plasma, and urine, offering good percentage recoveries.
2D Hetero-Nanoconstructs of Black Phosphorus for Breast Cancer Theragnosis: Technological Advancements
Authors: Soman Soji , Kulkarni Sanjay , Pandey Abhijeet , Dhas Namdev , Subramanian Suresh , Mukherjee Archana , Mutalik Srinivas
Published: November 2022

As per global cancer statistics of 2020, female breast cancer is the most commonly diagnosed cancer and also the foremost cause of cancer death in women. Traditional treatments include a number of negative effects, making it necessary to investigate novel smart drug delivery methods and identify new therapeutic approaches. Efforts for developing novel strategies for breast cancer therapy are being devised worldwide by various research groups. Currently, two-dimensional black phosphorus nanosheets (BPNSs) have attracted considerable attention and are best suited for theranostic nanomedicine. Particularly, their characteristics, including drug loading efficacy, biocompatibility, optical, thermal, electrical, and phototherapeutic characteristics, support their growing demand as a potential substitute for graphene-based nanomaterials in biomedical applications. In this review, we have explained different platforms of BP nanomaterials for breast cancer management, their structures, functionalization approaches, and general methods of synthesis. Various characteristics of BP nanomaterials that make them suitable for cancer therapy and diagnosis, such as large surface area, nontoxicity, solubility, biodegradability, and excellent near-infrared (NIR) absorption capability, are discussed in the later sections. Next, we summarize targeting approaches using various strategies for effective therapy with BP nanoplatforms. Then, we describe applications of BP nanomaterials for breast cancer treatment, which include drug delivery, codelivery of drugs, photodynamic therapy, photothermal therapy, combined therapy, gene therapy, immunotherapy, and multidrug resistance reversal strategy. Finally, the present challenges and future aspects of BP nanomaterials are discussed.
Highly Sensitive Zinc Oxide Fiber-Optic Biosensor for the Detection of CD44 Protein
Authors: Paltusheva Zhaniya U. , Ashikbayeva Zhannat , Tosi Daniele , Gritsenko Lesya V.
Published: November 2022

Currently, significant progress is being made in the prevention, treatment and prognosis of many types of cancer, using biological markers to assess current physiological processes in the body, including risk assessment, differential diagnosis, screening, treatment determination and monitoring of disease progression. The interaction of protein coding gene CD44 with the corresponding ligands promotes the processes of invasion and migration in metastases. The study of new and rapid methods for the quantitative determination of the CD44 protein is essential for timely diagnosis and therapy. Current methods for detecting this protein use labeled assay reagents and are time consuming. In this paper, a fiber-optic biosensor with a spherical tip coated with a thin layer of zinc oxide (ZnO) with a thickness of 100 nm, deposited using a low-cost sol–gel method, is developed to measure the CD44 protein in the range from 100 aM to 100 nM. This sensor is easy to manufacture, has a good response to the protein change with detection limit of 0.8 fM, and has high sensitivity to the changes in the refractive index (RI) of the environment. In addition, this work demonstrates the possibility of achieving sensor regeneration without damage to the functionalized surface. The sensitivity of the obtained sensor was tested in relation to the concentration of the control protein, as well as without antibodies—CD44.
The Timing of Semantic Processing in the Parafovea: Evidence from a Rapid Parallel Visual Presentation Study
Authors: Primativo Silvia , Rusich Danila , Martelli Marialuisa , Arduino Lisa S.
Published: November 2022

In the present investigation we adopted the Rapid Parallel Visual Presentation Paradigm with the aim of studying the timing of parafoveal semantic processing. The paradigm consisted in the simultaneous presentation of couple of words, one in fovea (W1) and one in parafovea (W2). In three experiments, we manipulated word frequency, semantic relatedness between the two words and the effect of stimulus duration (150, 100, 50 ms). Accuracy on W2 was higher when W1 and W2 were both of high-frequency and when they were semantically related. W1 reading times were faster when both words were highly-frequent but only when the two words were semantically related (150 ms); when W2 was highly frequent and semantically related to the foveal word (100 ms). When the stimuli were presented for 50 ms, the reading times were reduced when W1 was highly frequent and, crucially, in case of a semantic relation between the two words. Our results suggest that it is possible to extract semantic information from the parafovea very fast (within 100 ms) and in parallel to the processing of the foveal word, especially when the cognitive load required for the latter is reduced, as is the case for high-frequency words. We discuss the resulting data in terms of word recognition and eye movements’ models.
Self-Leadership and Innovative Behavior: Mediation of Informal Learning and Moderation of Social Capital
Authors: Kang Hyesun , Song Minyoung , Li Yiran
Published: November 2022

As the business environment is rapidly changing, interest in the innovation of organizational members is accelerating. Therefore, this study investigated how individual-level resources, particularly self-leadership, affect workers’ innovative behavior. Many studies have emphasized that employee initiative can lead to job performance at the individual level and organizational performance improvement. Self-leadership is a spontaneous and an active behavior, or mindset, defined as the ability to lead an individual in challenging situations characterized by learned behaviors that can be augmented by training. It is of interest to many researchers and practitioners. Further, we tested the mediation of informal learning, another individual-level resource, in this relationship and the moderation of social capital, a social resource, in the mediation. We analyzed the responses of 551 employees of South Korean companies using Model 6 and 14 of PROCESS Macro. The results revealed that self-leadership positively influenced workers’ innovative behavior, and informal learning mediated this relationship. We also confirmed that social capital strengthened the positive mediating effect of informal learning. This study empirically verifies the role of self-leadership, informal learning, and social capital as the determinants of innovative behavior and expands the discussion on leadership by highlighting the significance of self-leadership as opposed to traditional leadership approaches.
Immediate Effects of Fine-Motor Training on Coordination and Dexterity of the Non-Dominant Hand in Healthy Adults: A Randomized Controlled Trial
Authors: Park Chanhyun , Son Hohee
Published: November 2022

Several studies have demonstrated the beneficial effects of mirror training; however, only a few studies in Eastern countries have investigated fine-motor exercises using chopsticks, which have numerous advantages. We aimed to compare changes in coordination and dexterity of the non-dominant hand in healthy adults after conducting fine-motor training with the dominant hand using a mirror. We divided 100 healthy adults (age: 20–40 years) into experimental and control groups (each n = 50). The experimental group placed the non-dominant hand in a mirror box and indirectly imitated the fine-motor exercises conducted with the dominant hand using chopsticks. The control group performed the task with the non-dominant hand using chopsticks. We conducted the Chopsticks Manipulation Test and the Purdue Pegboard Test to assess the pre- and post-intervention coordination and dexterity of the non-dominant hand. Both groups showed a significant post-intervention improvement in coordination and dexterity (p < 0.01). There was no significant between-group difference in the functional improvement of coordination and dexterity (p > 0.05). Fine-motor training using mirrors and chopsticks significantly improved coordination and dexterity of the non-dominant hand. This training could be used to improve activity in brain regions associated with the non-dominant hand in healthy adults.