bluuebunny/crossref_metadata_2025 huggingface dataset:
Spyware Identification for Android Systems Using Fine Trees
Authors: Naser Muawya , Abu Al-Haija Qasem
Published: February 2023

Android operating system (OS) has been recently featured as the most commonly used and ingratiated OS for smartphone ecosystems. This is due to its high interoperability as an open-source platform and its compatibility with all the major browsers within the mobile ecosystem. However, android is susceptible to a wide range of Spyware traffic that can endanger a mobile user in many ways, like password stealing and recording patterns of a user. This paper presents a spyware identification schemes for android systems making use of three different machine learning schemes, including fine decision trees (FDT), support vector machines (SVM), and the naïve Bayes classifier (NBC). The constructed models have been evaluated on a novel dataset (Spyware-Android 2022) using several performance measurement units such as accuracy, precision, and sensitivity. Our experimental simulation tests revealed the notability of the model-based FDT, making the peak accuracy 98.2%. The comparison with the state-of-art spyware identification models for android systems showed that our proposed model had improved the model’s accuracy by more than 18%.
The Burden of Rheumatoid Arthritis: Findings from the 2019 Global Burden of Diseases Study and Forecasts for 2030 by Bayesian Age-Period-Cohort Analysis
Authors: Cai Yuanqing , Zhang Jianan , Liang Jialin , Xiao Mofan , Zhang Guangyang , Jing Zhaopu , Lv Leifeng , Nan Kai , Dang Xiaoqian
Published: February 2023

Background: Rheumatoid arthritis (RA) is a key health issue worldwide. Due to early identification and effective treatment strategies, the disease pattern of RA has also changed. However, the most comprehensive and up-to-date information about the burden of RA and its trends in subsequent years is lacking. Objective: this study aimed to report the global burden of RA by sex, age, region, and forecast for 2030. Method: Publicly available data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used in this study. The trends in the prevalence, incidence, and disability-adjusted life years (DALYs) of RA from 1990 to 2019 were reported. The global burden of RA in 2019 was reported by a sex, age, and sociodemographic index (SDI). Finally, the trends in the following years were predicted by Bayesian age-period-cohort (BAPC) models. Results: Globally, the age-standardized prevalence rate increased from 207.46 (95% UI:189.99 to 226.95) in 1990 to 224.25 (95% UI: 204.94 to 245.99) in 2019, with an estimated annual percent change (EAPC) of 0.37% (95% CI: 0.32 to 0.42). Regarding the incidence, the age-standardized incidence rate (ASR) increased from 12.21 (95% UI: 11.13 to 13.38) to 13 (95% UI: 11.83 to 14.27) per 100,000 people from 1990 to 2019, with an EAPC of 0.3% (95% CI: 11.83 to 14.27). The age-standardized DALY rate also increased from 39.12 (95% UI: 30.13 to 48.56) per 100,000 people in 1990 to 39.57 (95% UI: 30.51 to 49.53) in 2019, with an EAPC of 0.12% (95% CI: 0.08% to 0.17%). There was no significant association between the SDI and ASR when the SDI was lower than 0.7, while there was a positive association between the SDI and ASR when the SDI was higher than 0.7 The BAPC analysis showed that the ASR was estimated to be up to 18.23 in females and approximately 8.34 per 100,000 people in males by 2030. Conclusion: RA is still a key public health issue worldwide. The global burden of RA has increased over the past decades and will continue to increase in the coming years, and much more attention should be given to early diagnosis and treatment to reduce the burden of RA.
Salvage vs. Primary Total Laryngectomy in Patients with Locally Advanced Laryngeal or Hypopharyngeal Carcinoma: Oncologic Outcomes and Their Predictive Factors
Authors: Shoushtari Shahin , Gal Jocelyn , Chamorey Emmanuel , Schiappa Renaud , Dassonville Olivier , Poissonnet Gilles , Aloi Déborah , Barret Médéric , Safta Inga , Saada Esma , Sudaka Anne , Culié Dorian , Bozec Alexandre
Published: February 2023

Background: The aims of this study were to compare the survival outcomes of salvage vs. primary total laryngectomy (TL) in patients with locally advanced laryngeal or hypopharyngeal carcinoma and to determine their predictive factors. Methods: Overall (OS), cause-specific (CSS) and recurrence-free survival (RFS) of primary vs. salvage TL were compared in univariate and multivariate analysis taking into account other potential predictive factors (tumor site, tumor stage, comorbidity level etc.). Results: A total of 234 patients were included in this study. Five-year OS was 53% and 25% for the primary and salvage TL groups, respectively. Multivariate analysis confirmed the independent negative impact of salvage TL on OS (p = 0.0008), CSS (p < 0.0001) and RFS (p < 0.0001). Hypopharyngeal tumor site, ASA score ≥ 3, N-stage ≥ 2a and positive surgical margins were the main other predictors of oncologic outcomes. Conclusions: Salvage TL is associated with significantly worse survival rates than primary TL highlighting the need for careful selection of patients who are candidates for larynx preservation. The predictive factors of survival outcomes identified here should be considered in the therapeutic decision-making, especially in the setting of salvage TL, given the poor prognosis of these patients.
Dynamic Monitoring of Oxygen Supply Capacity of Urban Green Space Based on Satellite-Based Chlorophyll Fluorescence
Authors: Yao Li , Ping Zifei , Sun Yufang , Zhou Wei , Zheng Hui , Ding Qiangqiang , Liao Xiang
Published: February 2023

Green plants provide food, energy and oxygen sources for human beings and animals on Earth through photosynthesis, which is essential to maintain regional ecological balance. However, few studies have focused on the natural oxygen supply capacity of urban green spaces. As a companion to photosynthesis in leaves, solar-induced chlorophyll fluorescence (SIF) contains abundant photosynthetic information. Currently, satellite-based SIF observations are considered to be a rapid and nondestructive ‘indicator’ of plant photosynthesis, which provides an alternative way to quantitatively assess the spatio-temporal dynamics of oxygen supply capacity in urban green spaces. This study examined the spatial patterns, long-term trends, and environmental control factors of SIF in the nine central cities in China from 2001 to 2020 based on the time-series of the global reconstructed GOSIF-v2 SIF dataset. The results were as follows: (1) There was a contrasting spatial difference between southern and northern cities in China, and multi-year mean SIF values of the southern cities were generally higher than those of the northern cities; (2) The interannual dynamics of SIF in each city generally showed an upward trend, with fluctuations, and the intraannual seasonal differences were more significant in northern cities than those in the southern cities; (3) The spatial trend analysis showed that Beijing, Guangzhou, and Chongqing have had the most significant improvements, followed by Xi’an, Wuhan, Chengdu, and Zhengzhou, while Tianjin and Shanghai have had the least improvements; and (4) The expansion of construction land has exerted significant impacts on the dynamics of the SIF trend in several cities, but it is not the only factor. All analyses indicated that the improvement of vegetation structure and function in the area can offset its negative effect.
Mechanism of Aluminum Element Segregation in As-Cast Medium-Entropy Alloy CrCoNiAl0.014: A Hybrid MD/MC Simulation and Experimental Study
Authors: Xue Baoshuai , Feng Zhongxue , Chen Jinliang , Zhang Chao , Li Tongman , Tan Jun , Li Caiju , Yi Jianhong
Published: February 2023

Element segregation in the as-cast medium-entropy alloy (MEA), CrCoNiAl0.014, has a significant influence on its mechanical properties. This study focused on aluminum segregation in the as-cast CrCoNiAl0.014 MEA at room temperature (300 K). The element distribution, morphology, and type of precipitates formed by the elemental segregation were identified by optical microscopy, X-ray diffraction, electron probe microanalysis, and transmission electron microscopy. Al segregation existed at the dendritic boundary in the face-centered cubic (FCC) MEA matrix. Hybrid molecular dynamics and Monte Carlo simulations were conducted to analyze the diffusion behavior and the chemical affinity of Al, as well as understand the segregation mechanism of Al at the atomic scale. Al displayed a faster diffusion speed and a higher chemical affinity than Ni, Cr, and Co at the same temperature. Al segregated at the dendritic boundary to form the Al-rich phase. Furthermore, as the temperature was increased, the atomic thermal vibration of these four elements became more intensive, and Al segregation was more serious. However, Al segregation improved the uniform diffusion of Cr, Co, and Ni. Therefore, this study provides a reference for subsequent reductions in element segregation and improvements in the mechanical properties of MEA.
Airborne Asbestos Fiber Concentration in Buildings: Surveys Carried Out in Latium (Central Italy)
Authors: Bruno Maria R. , Campopiano Antonella , Olori Angelo , Angelosanto Federica , Sinopoli Francesco , Cannizzaro Annapaola
Published: February 2023

In Italy, use and production of asbestos and asbestos-containing materials (ACMs) were banned in 1992, however, the risk of exposure to asbestos still exists, because most ACMs are located in industrial and public buildings. A total of 111 Italian buildings with friable and non-friable ACMs were surveyed; 500 air samples were collected in the areas where contamination might have occurred. Airborne asbestos fiber concentration calculated from air samples was averaged for each building. Statistical analysis of the data showed no significant differences between the mean concentration measured in buildings with friable and non-friable ACMs (p = 0.258). The concentration values were below 2 f/L, the value stated by Italian regulation to ensure that the area is safe to reoccupy after asbestos removal. Samples of settled dust were also collected. The presence of asbestos fibers in the dust showed the occurrence of a release of asbestos from the material. Although the airborne asbestos fiber concentrations measured were low, current Italian regulation requires an asbestos management program. The Public Institution to which the authors of this work belong encourages asbestos removal as the preferred abatement method, in line with the asbestos-free future approach proposed by the European Commission.
Organogermanium Analogues of Alkenes, Alkynes, 1,3-Dienes, Allenes, and Vinylidenes
Authors: Lee Vladimir Ya.
Published: February 2023

In this review, the latest achievements in the field of multiply bonded organogermanium derivatives, mostly reported within the last two decades, are presented. The isolable Ge-containing analogues of alkenes, alkynes, 1,3-dienes, allenes, and vinylidenes are discussed, and for each class of unsaturated organogermanium compounds, the most representative examples are given. The synthetic approaches toward homonuclear multiply bonded combinations solely consisting of germanium atoms, and their heteronuclear variants containing germanium and other group 14 elements, both acyclic and cyclic, are discussed. The peculiar structural features and nonclassical bonding nature of the abovementioned compounds are discussed based on their spectroscopic and structural characteristics, in particular their crystallographic parameters (double bond length, trans-bending at the doubly bonded centers, and twisting about the double bond). The prospects for the practical use of the title compounds in synthetic and catalytic fields are also briefly discussed.
Supercapacitor Performance of Magnetite Nanoparticles Enhanced by a Catecholate Dispersant: Experiment and Theory
Authors: Boucher Coulton , Rubel Oleg , Zhitomirsky Igor
Published: February 2023

The full potential of Fe3O4 for supercapacitor applications can be achieved by addressing challenges in colloidal fabrication of high active mass electrodes. Exceptional adsorption properties of catecholate-type 3,4-dihydroxybenzoic acid (DHBA) molecules are explored for surface modification of Fe3O4 nanoparticles to enhance their colloidal dispersion as verified by sedimentation test results and Fourier-transform infrared spectroscopy measurements. Electrodes prepared in the presence of DHBA show nearly double capacitance at slow charging rates as compared to the control samples without the dispersant or with benzoic acid as a non-catecholate dispersant. Such electrodes with active mass of 40 mg cm−2 show a capacitance of 4.59 F cm−2 from cyclic voltammetry data at a scan rate of 2 mV s−1 and 4.72 F cm−2 from galvanostatic charge–discharge data at a current density of 3 mA cm−2. Experimental results are corroborated by density functional theory (DFT) analysis of adsorption behaviour of DHBA and benzoic acid at the (001) surface of Fe3O4. The strongest adsorption energy (ca. −1.8 eV per molecule) is due to the catechol group of DHBA. DFT analysis provides understanding of the basic mechanism of DHBA adsorption on the surface of nanoparticles and opens the way for fabrication of electrodes with high capacitance.
Two-Photon Absorption and Multiphoton Excited Fluorescence of Acetamide-Chalcone Derivatives: The Role of Dimethylamine Group on the Nonlinear Optical and Photophysical Properties
Authors: Pelosi André Gasparotto , Silveira-Alves Eli , Cocca Leandro Henrique Zucolotto , Valverde João Victor , Oliveira Guilherme Roberto , da Silva Daniel Luiz , De Boni Leonardo , Gonçalves Pablo José , Mendonca Cleber Renato
Published: February 2023

This work studied the effect of different electron-withdrawing and electron-donating groups on the linear and nonlinear optical properties of acetamide-chalcone derivatives. The results showed that the addition of the dimethylamine group led to a large fluorescence emission (71% of fluorescence quantum yield in DMSO solution) that can be triggered by two and three-photon excitations, which is essential for biological applications. Furthermore, dimethylamine also red-shifts the lower energy state by approximately 90 nm, increasing the two-photon absorption cross-section of the lower energy band by more than 100% compared with the other studied compounds. All compounds presented two-electronic states observed through one and two-photon absorption spectroscopy and confirmed by Quantum Chemistry Calculations (QCCs). QCC results were also used to model the experimental two-photon absorption cross-sectional spectrum by the Sum-Over-States (SOS) approach, revealing a dependence between the coupling of the ground state with the first excited state and the transition dipole moment between these states.
Clinical Evaluation Based on a New Approach to Improve the Accuracy of 4β-Hydroxycholesterol Measurement as a Biomarker of CYP3A4 Activity
Authors: Taya Yuki , Mizunaga Mari , Nakao Shunsuke , Jutanom Mirinthorn , Shimizu Naoki , Nomura Yukihiro , Nakagawa Kiyotaka
Published: February 2023

This study examines 4β-Hydroxycholesterol (4β-HC), which is considered to be a potential marker for the CYP3A4 induction of new chemical entities (NCEs) in drug development. To ensure the use of 4β-HC as a practical biomarker, it is necessary to accurately measure 4β-HC and demonstrate that CYP3A4 induction can be appropriately assessed, even for weak inducers. In clinical trials of NCEs, plasma is often collected with various anticoagulants, in some cases, the plasma is acidified, then stored for an extended period. In this study, we examined the effects of these manipulations on the measurement of 4β-HC, and based on the results, we optimized the plasma collection and storage protocols. We also found that a cholesterol oxidation product is formed when plasma is stored, and by monitoring the compound, we were able to identify when plasma was stored inappropriately. After evaluating the above, clinical drug–drug interaction (DDI) studies were conducted using two NCEs (novel retinoid-related orphan receptor γ antagonists). The weak CYP3A4 induction by the NCEs (which were determined based on a slight decline in the systemic exposure of a probe substrate (midazolam)), was detected by the significant increase in 4β-HC levels (more specifically, 4β-HC/total cholesterol ratios). Our new approach, based on monitoring a cholesterol oxidation product to identify plasma that is stored inappropriately, allowed for the accurate measurement of 4β-HC, and thus, it enabled the evaluation of weak CYP3A4 inducers in clinical studies without using a probe substrate.
A “Trojan Horse” Strategy: The Preparation of Bile Acid-Modifying Irinotecan Hydrochloride Nanoliposomes for Liver-Targeted Anticancer Drug Delivery System Study
Authors: Zhou Tao , Liu Yushi , Lei Kelu , Liu Junjing , Hu Minghao , Guo Li , Guo Yiping , Ye Qiang
Published: February 2023

The bile acid transport system is a natural physiological cycling process between the liver and the small intestine, occurring approximately 6–15 times during the day. There are various bile acid transporter proteins on hepatocytes that specifically recognize bile acids for transport. Therefore, in this paper, a novel liposome, cholic acid-modified irinotecan hydrochloride liposomes (named CA-CPT-11-Lip), was prepared based on the “Trojan horse” strategy. The liposomes preparation process was optimized, and some important quality indicators were investigated. The distribution of irinotecan hydrochloride in mice was then analyzed by high-performance liquid chromatography (HPLC), and the toxicity of liposomes to hepatocellular carcinoma cells (HepG-2) was evaluated in vitro. As a result, CA-CPT-11-Lip was successfully prepared. It was spherical with a particle size of 154.16 ± 4.92 nm, and the drug loading and encapsulation efficiency were 3.72 ± 0.04% and 82.04 ± 1.38%, respectively. Compared with the conventional liposomes (without cholic acid modification, named CPT-11-Lip), CA-CPT-11-Lip had a smaller particle size and higher encapsulation efficiency, and the drug accumulation in the liver was more efficient, enhancing the anti-hepatocellular carcinoma activity of irinotecan hydrochloride. The novel nanoliposome modified by cholic acid may help to expand the application of irinotecan hydrochloride in the treatment of hepatocellular carcinoma and construct the drug delivery system mode of drug liver targeting.
Luminescent Gold Nanoclusters for Bioimaging: Increasing the Ligand Complexity
Authors: Mordini Dario , Mavridi-Printezi Alexandra , Menichetti Arianna , Cantelli Andrea , Li Xinke , Montalti Marco
Published: February 2023

Fluorescence, and more in general, photoluminescence (PL), presents important advantages for imaging with respect to other diagnostic techniques. In particular, detection methodologies exploiting fluorescence imaging are fast and versatile; make use of low-cost and simple instrumentations; and are taking advantage of newly developed powerful, low-cost, light-based electronic devices, such as light sources and cameras, used in huge market applications, such as civil illumination, computers, and cellular phones. Besides the aforementioned simplicity, fluorescence imaging offers a spatial and temporal resolution that can hardly be achieved with alternative methods. However, the two main limitations of fluorescence imaging for bio-application are still (i) the biological tissue transparency and autofluorescence and (ii) the biocompatibility of the contrast agents. Luminescent gold nanoclusters (AuNCs), if properly designed, combine high biocompatibility with PL in the near-infrared region (NIR), where the biological tissues exhibit higher transparency and negligible autofluorescence. However, the stabilization of these AuNCs requires the use of specific ligands that also affect their PL properties. The nature of the ligand plays a fundamental role in the development and sequential application of PL AuNCs as probes for bioimaging. Considering the importance of this, in this review, the most relevant and recent papers on AuNCs-based bioimaging are presented and discussed highlighting the different functionalities achieved by increasing the complexity of the ligand structure.
Is It Time to Reconsider the U.S. Recommendations for Dietary Protein and Amino Acid Intake?
Authors: Weiler Mary , Hertzler Steven R. , Dvoretskiy Svyatoslav
Published: February 2023

Since the U.S. Institute of Medicine’s recommendations on protein and amino acid intake in 2005, new information supports the need to re-evaluate these recommendations. New lines of evidence include: (1) re-analysis/re-interpretation of nitrogen balance data; (2) results from indicator amino acid oxidation studies; (3) studies of positive functional outcomes associated with protein intakes higher than recommended; (4) dietary guidance and protein recommendations from some professional nutrition societies; and (5) recognition that the synthesis of certain dispensable amino acids may be insufficient to meet physiological requirements more often than previously understood. The empirical estimates, theoretical calculations and clinical functional outcomes converge on a similar theme, that recommendations for intake of protein and some amino acids may be too low in several populations, including for older adults (≥65 years), pregnant and lactating women, and healthy children older than 3 years. Additional influential factors that should be considered are protein quality that meets operational sufficiency (adequate intake to support healthy functional outcomes), interactions between protein and energy intake, and functional roles of amino acids which could impact the pool of available amino acids for use in protein synthesis. Going forward, the definition of “adequacy” as it pertains to protein and amino acid intake recommendations must take into consideration these critical factors.
Human Brain Organoids and Consciousness: Moral Claims and Epistemic Uncertainty
Authors: Goddard Eliza , Tomaskovic-Crook Eva , Crook Jeremy Micah , Dodds Susan
Published: February 2023

Human brain organoids provide a remarkable opportunity to model prenatal human brain biology in vitro by recapitulating features of in utero molecular, cellular and systems biology. An ethical concern peculiar to human brain organoids is whether they are or could become capable of supporting sentience through the experience of pain or pleasure and/or consciousness, including higher cognitive abilities such as self-awareness. Identifying the presence of these traits is complicated by several factors, beginning with consciousness—which is a highly contested concept among neuroscientists, cognitive scientists, and philosophers and so there is no agreed definition. Secondly, given human brain organoids are disembodied, there is no practical way to identify evidence of consciousness as we might in humans or animals. What would count as evidence of organoid consciousness is an emerging area of research. To address concerns about consciousness and human brain organoids, in this paper we clarify the morally relevant aspects of human consciousness, phenomenal experience and embodied development and explore the empirical basis of consciousness to develop a defensible framework for informed decision-making on the moral significance and utility of brain organoids, which can also guide regulation and future research of these novel biological systems.
Solvent System-Guided Extraction of Centaurium spicatum (L.) Fritch Provides Optimized Conditions for the Biological and Chemical Characteristics of the Herbal Extracts
Authors: Božunović Jelena , Ivanov Marija , Petrović Jovana , Gašić Uroš , Nakarada Đura , Milutinović Milica , Aničić Neda , Giba Zlatko , Mišić Danijela , Stojković Dejan
Published: February 2023

Spiked centaury (Centaurium spicatum) is a well-known medicinal plant from the Mediterranean region with various bioactivities, but there are no studies addressing the use of different solvent systems to improve its pharmacological potential. Nine extraction procedures were adapted to study the effects of solvent composition on the content of bioactive compounds in C. spicatum extracts and on corresponding bioactivities. Targeted metabolomics was performed to obtain information on the chemical composition of extracts. Ethanol-water-based extraction procedures were the most efficient in isolating polyphenols, while less polar butanol extract contained the highest amount of iridoids. Antioxidant potential analysis revealed stronger activity in extracts with higher polyphenol content. Bacillus cereus and Staphylococus aureus were designated as the most sensitive bacterial strains to the activity of extracts, while among the micromycetes tested, Penicillium funiculosum was the most susceptible strain. Butanol extract showed antivirulence potential on Candida albicans morphological transition from yeast to hyphal form, and selected extracts were effective against biofilm formation in two Candida species. All the extracts tested in this study showed no cytotoxic activity to immortalize human skin keratinocyte cell line (HaCaT), whereas extracts obtained by ethanol-water extraction stand out for their potent wound healing effects. Moreover, the influence of the extraction solvent system on various bioactivities of C. spicatum is reported herein for the first time. Overall, the results presented in this study promote the use of C. spicatum as a source of natural products with potential antioxidant, wound healing, and antimicrobial applications that are potentially safe for human use.
Interplay of Breast Cancer Resistance Protein (Bcrp/Abcg2), Sex, and Fed State in Oral Pharmacokinetic Variability of Furosemide in Rats
Authors: Sharma Sheena , Mettu Vijaya Saradhi , Prasad Bhagwat
Published: February 2023

Poor and variable oral bioavailability of furosemide (FUR) presents critical challenges in pharmacotherapy. We investigated the interplay of breast cancer resistance protein (Bcrp)-mediated transport, sex, and fed state on FUR pharmacokinetics (PK) in rats. A crossover PK study of FUR (5 mg/kg, oral) was performed in Sprague-Dawley rats (3 males and 3 females), alone or with a Bcrp inhibitor, novobiocin (NOV) (20 mg/kg, oral), in both fed and fasted states. Co-administration of NOV significantly increased FUR extent (AUC) and rate (Cmax) of exposure by more than two-fold, which indicates efficient Bcrp inhibition in the intestine. The female rats showed two-fold higher AUC and Cmax, and two-fold lower renal clearance of FUR compared to the male rats. The latter was correlated with higher renal abundance of Bcrp and organic anion transporters (Oats) in the male rats compared to age-matched female rats. These findings suggest that the PK of Bcrp and/or Oat substrates could be sex-dependent in rats. Moreover, allometric scaling of rat PK and toxicological data of Bcrp substrates should consider species and sex differences in Bcrp and Oat abundance in the kidney. Considering that Bcrp is abundant in the intestine of rats and humans, a prospective clinical study is warranted to evaluate the effect of Bcrp inhibition on FUR PK. The potential confounding effect of the Bcrp transporter should be considered when FUR is used as a clinical probe of renal organic anion transporter-mediated drug–drug interactions. Unlike human data, no food-effect was observed on FUR PK in rats.
Metabolomics Profiling Reveals the Role of PEDF in Triple-Negative Breast Cancer Cell MDA-MB-231 under Glycaemic Loading
Authors: Abooshahab Raziyeh , Hooshmand Kourosh , Luna Giuseppe , Al-Salami Hani , Dass Crispin R.
Published: February 2023

Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein that belongs to the serine protease inhibitor (serpin) family. An increase in PEDF activity has been shown to be a potent inhibitor of tumour progression and proliferation, suggesting a possible therapeutic target. There is still a great deal to learn about how PEDF controls metabolic pathways in breast cancer and its metastatic form. Given this, the primary purpose of this study was to use a metabolomics approach to gain a better understanding of the mechanisms driving the reprogramming of metabolic events involved in breast cancer pertaining to PEDF under various glycaemic loads. We employed gas chromatography–quadrupole mass spectrometry (GC-Q-MS) to investigate metabolic changes in the triple-negative breast cancer (TNBC) cell line MDA-MB-231 treated with PEDF under glycaemic loading. Multivariate and univariate analyses were carried out as indicative tools via MetaboAnalyst (V.5.0) and R packages to identify the significantly altered metabolites in the MDA-MB-231 cell line after PEDF exposure under glycaemic loading. A total of 61 metabolites were found, of which nine were selected to be distinctively expressed in MDA-MB-231 cells under glycaemic conditions and exhibited differential responses to PEDF (p < 0.05, VIP > 1). Abnormalities in amino acid metabolism pathways were observed. In particular, glutamic acid, glutamine, and phenylalanine showed different levels of expression across different treatment groups. The lactate and glucose-6-phosphate production significantly increased in high-glucose vs. normal conditions while it decreased when the cells were exposed to PEDF, confirming the positive influence on the Warburg effect. The TCA cycle intermediates, including malate and citric acid, showed different patterns of expression. This is an important finding in understanding the link of PEDF with metabolic perturbation in TNBC cells in response to glycaemic conditions. Our findings suggest that PEDF significantly influenced the Warburg effect (as evidenced by the significantly lower levels of lactate), one of the well-known metabolic reprogramming pathways in cancer cells that may be responsive to metabolic-targeted therapeutic strategies. Moreover, our results demonstrated that GC-MS-based metabolomics is an effective tool for identifying metabolic changes in breast cancer cells after glycaemic stress or in response to PEDF treatment.
Preparation and Characterization of Ibuprofen Containing Nano-Embedded-Microparticles for Pulmonary Delivery
Authors: Party Petra , Klement Márk László , Szabó-Révész Piroska , Ambrus Rita
Published: February 2023

A fatal hereditary condition, cystic fibrosis (CF) causes severe lung problems. Ibuprofen (IBU), a non-steroidal anti-inflammatory drug, slows the progression of disease without causing significant side effects. Considering the poor water-solubility of the drug, IBU nanoparticles are beneficial for local pulmonary administration. We aimed to formulate a carrier-free dry powder inhaler containing nanosized IBU. We combined high-performance ultra-sonication and nano spray-drying. IBU was dissolved in ethyl acetate; after that, it was sonicated into a polyvinyl alcohol solution, where it precipitated as nanoparticles. Mannitol and leucine were added when producing dry particles using nano-spray drying. The following investigations were implemented: dynamic light scattering, laser diffraction, surface tension measurement, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, in vitro dissolution test, and in vitro aerodynamic assessment (Andersen Cascade Impactor). The particle diameter of the IBU was in the nano range. The spray-dried particles showed a spherical morphology. The drug release was rapid in artificial lung media. The products represented large fine particle fractions and proper aerodynamic diameters. We successfully created an inhalable powder, containing nano-sized IBU. Along with the exceptional aerodynamic performance, the ideal particle size, shape, and drug-release profile might offer a ground-breaking local therapy for CF.
Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery
Authors: Chang Hao Han R. , Chen Kuan , Lugtu-Pe Jamie Anne , AL-Mousawi Nour , Zhang Xuning , Bar-Shalom Daniel , Kane Anil , Wu Xiao Yu
Published: February 2023

Bioavailability of weakly basic drugs may be disrupted by dramatic pH changes or unexpected pH alterations in the gastrointestinal tract. Conventional organic acids or enteric coating polymers cannot address this problem adequately because they leach out or dissolve prematurely, especially during controlled release applications. Thus, a non-leachable, multifunctional terpolymer nanoparticle (TPN) made of cross-linked poly(methacrylic acid) (PMAA)-polysorbate 80-grafted-starch (PMAA-PS 80-g-St) was proposed to provide pH transition-independent release of a weakly basic drug, verapamil HCl (VER), by a rationally designed bilayer-coated controlled release bead formulation. The pH-responsive PMAA and cross-linker content in the TPN was first optimized to achieve the largest possible increase in medium uptake alongside the smallest decrease in drug release rate at pH 6.8, relative to pH 1.2. Such TPNs maintained an acidic microenvironmental pH (pHm) when loaded in ethylcellulose (EC) films, as measured using pH-indicating dyes. Further studies of formulations revealed that with the 1:2 VER:TPN ratio and 19% coating weight gain, bilayer-coated beads maintained a constant release rate over the pH transition and exhibited extended release up to 18 h. These results demonstrated that the multifunctional TPN as a pHm modifier and pH-dependent pore former could overcome the severe pH-dependent solubility of weakly basic drugs.
Response of the Endogenous Antioxidant Defense System Induced in RAW 264.7 Macrophages upon Exposure to Dextran-Coated Iron Oxide Nanoparticles
Authors: Balas Mihaela , Iconaru Simona Liliana , Dinischiotu Anca , Buton Nicolas , Predoi Daniela
Published: February 2023

Presently, iron oxide nanoparticles are the only ones approved for clinical use as contrast agents in magnetic resonance imaging (MRI). Even though there is a high demand for these types of nanoparticles both for clinical use as well as for research, there are difficulties in obtaining stable nanoparticles with reproducible properties. In this context, in this study, we report the obtaining by an adapted coprecipitation method of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs). The morphology and structure of the dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) were determined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The TEM and SEM micrographs highlighted the obtaining of particles of nanometric size and spherical shape morphology. Furthermore, the high-resolution transmission electron microscopy (HRTEM), as well as selected area diffraction (SAED), revealed that the obtained samples presented the structure of cubic maghemite. In this study, we also explored the effects of the co-precipitation synthesized dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) on the redox status of macrophages. For cytotoxicity evaluation of these NPs, murine macrophages (RAW 264.7 cell line) were exposed to different concentrations of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) corresponding to 0–500 μg Fe3+/mL and incubated for 24, 48, and 72 h. Intracellular iron uptake, changes in the oxidative stress parameters (reactive oxygen species production and malondialdehyde level), and the activity of antioxidant enzymes, as well as GSH concentration in cells, were evaluated after incubation with a lower (50 μg Fe3+/mL) and higher (500 μg Fe3+/mL) dose of NPs. The results indicated a significant decrease in RAW 264.7 cell viability after 72 h in the presence of NPs at concentrations above 25 μg Fe3+/mL. An important accumulation of NPs, dependent on dose and exposure time, was detected in macrophages, but it induced only a limited raise in the oxidative status. We showed here that the antioxidant capacity of RAW 264.7 macrophages was efficient in counteracting dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) toxicity even at higher doses.
The Effect of Super-Repressor IkB-Loaded Exosomes (Exo-srIκBs) in Chronic Post-Ischemia Pain (CPIP) Models
Authors: Chae Ji Seon , Park Hyunju , Ahn So-Hee , Han Eun-Chong , Lee Yoonjin , Kim Youn Jin , Ahn Eun-Jin , Oh Hye-Won , Lee Hyun Jung , Choi Chulhee , Choi Youn-Hee , Kim Won-joong
Published: February 2023

Complex regional pain syndrome (CRPS) is a condition associated with neuropathic pain that causes significant impairment of daily activities and functioning. Nuclear factor kappa B (NFκB) is thought to play an important role in the mechanism of CRPS. Recently, exosomes loaded with super-repressor inhibitory kappa B (Exo-srIκB, IκB; inhibitor of NFκB) have been shown to have potential anti-inflammatory effects in various inflammatory disease models. We investigated the therapeutic effect of Exo-srIκB on a rodent model with chronic post-ischemia pain (CPIP), a representative animal model of Type I CRPS. After intraperitoneal injection of a vehicle, Exo-srIκB, and pregabalin, the paw withdrawal threshold (PWT) was evaluated up to 48 h. Administration of Exo-srIκB increased PWT compared to the vehicle and pregabalin, and the relative densities of p-IκB and IκB showed significant changes compared to the vehicle 24 h after Exo-srIκB injection. The levels of several cytokines and chemokines were reduced by the administration of Exo-srIκB in mice with CPIP. In conclusion, our results showed more specifically the role of NFκB in the pathogenesis of CRPS and provided a theoretical background for novel treatment options for CRPS.
Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
Authors: Kalvala Anil , Bagde Arvind , Arthur Peggy , Kulkarni Tanmay , Bhattacharya Santanu , Surapaneni Sunil , Patel Nil , Nimma Ramesh , Gebeyehu Aragaw , Kommineni Nagavendra , Li Yan , Meckes David , Sun Li , Banjara Bipika , Mosley-Kellum Keb , Dinh Thanh , Singh Mandip
Published: February 2023

In cancer patients, chronic paclitaxel (PTX) treatment causes excruciating pain, limiting its use in cancer chemotherapy. The neuroprotective potential of synthetic cannabidiol (CBD) and CBD formulated in extracellular vesicles (CBD-EVs) isolated from human umbilical cord derived mesenchymal stem cells was investigated in C57BL/6J mice with PTX-induced neuropathic pain (PIPN). The particle size of EVs and CBD-EVs, surface roughness, nanomechanical properties, stability, and release studies were all investigated. To develop neuropathy in mice, PTX (8 mg/kg, i.p.) was administered every other day (four doses). In terms of decreasing mechanical and thermal hypersensitivity, CBD-EVs treatment was superior to EVs treatment or CBD treatment alone (p < 0.001). CBD and CBD-EVs significantly reduced mitochondrial dysfunction in dorsal root ganglions and spinal homogenates of PTX-treated animals by modulating the AMPK pathway (p < 0.001). Studies inhibiting the AMPK and 5HT1A receptors found that CBD did not influence the neurobehavioral or mitochondrial function of PIPN. Based on these results, we hypothesize that CBD and CBD-EVs mitigated PIPN by modulating AMPK and mitochondrial function.
Effects of Spirulina maxima on a Model of Sexual Dysfunction in Streptozotocin-Induced Diabetic Male Rats
Authors: Olvera-Roldán Eduardo Osel , Cristóbal-Luna José Melesio , García-Martínez Yuliana , Mojica-Villegas María Angélica , Pérez-Pastén-Borja Ricardo , Gutiérrez-Salmeán Gabriela , Pérez-Gutiérrez Salud , García-Rodríguez Rosa Virginia , Madrigal-Santillán Eduardo , Morales-González José A. , Chamorro-Cevallos Germán
Published: February 2023

Arthrospira (Spirulina) maxima (SM) is a cyanobacterium that has a long history of being used as human food. In recent years, several investigations have shown its beneficial biological effects, among which its antioxidant capacity has been highlighted. The purpose of this study was to evaluate the effects of SM on body weight, glycemia, sexual behavior, sperm quality, testosterone levels, sex organ weights, and the activity of antioxidant enzymes in diabetic male rats (a disease characterized by an increase in reactive oxygen species). The experiment consisted of six groups of sexually expert adult males (n = 6): (1) control (vehicle); (2) streptozotocin (STZ)-65 mg/kg; (3) SM-400 mg/kg; (4) STZ + SM-100 mg/kg; (5) STZ + SM-200 mg/kg; and (6) STZ + SM-400 mg/kg. Sexual behavior tests were performed during the first 3 h of the dark period under dim red illumination. Our results showed that SM significantly improved sexual behavior and sperm quality vs. diabetic animals. Likewise, while the enzymatic activities of SOD and GPx increased, TBARS lipoperoxidation decreased and testosterone levels increased. In view of the findings, it is suggested that SM may potentially be used as a nutraceutical for the treatment of diabetic male sexual dysfunction due to its antioxidant property.
Faith in the Nominalistic Age? The Possible Theological Contribution of Hermeneutics
Authors: Grondin Jean
Published: February 2023

This paper inquires about the defensibility of spiritual faith in this Nominalistic age, i.e., an age when all reality is reduced to scientifically ascertainable matter and all spiritual realities are deemed to be irreal. This Nominalistic worldview was developed in the late Middle Ages and became one of the major presuppositions of Modernity. It has made it ever more difficult to defend the legitimacy of faith and its objects. It also played an important, albeit seldom recognized, role in the emergence of Hermeneutical thought in the 20th Century. In his strong, if also seldom carefully studied, interpretation of Heidegger’s philosophy, Gadamer saw in the Nominalism of Modernity one of the main challenges to which Heidegger’s thinking wished to respond: the hegemony of the Nominalistic understanding of being would have led to the Nihilism of our technological Age and made the experience of the Divine unthinkable. After recalling the outlines of this interpretation and of the meaning of Nominalism itself, this paper argues that this Nominalism was also one of the main challenges Gadamer wanted to overcome with his Hermeneutics. It discusses how Hermeneutics strives to overcome this Nominalism by calling into question the monopoly of scientific truth (an effort summed up in the title “Truth and Method”) and through its renewed understanding of language as the presentation of Being itself, which goes hand in hand with the rediscovery of the Platonic metaphysics of the Beautiful. Hermeneutics thus shows how something like faith is defensible and thus makes an important theological and metaphysical contribution.
A Parametric Model for the Analysis of the Impedance Spectra of Dielectric Sensors in Curing Epoxy Resins
Authors: Kyriazis Alexander , Charif Samir , Rager Korbinian , Dietzel Andreas , Sinapius Michael
Published: February 2023

Observing the curing reaction of epoxy resins is a key to quality assurance in fibre composite production. The evaluation of electrical impedance spectra is an established monitoring method. Such impedance spectra contain the physical effects of dipole relaxation, ionic conduction and electrode polarisation, which shift to lower frequencies as curing progresses. In the early stage of the curing reaction, ionic conductivity and electrode polarisation dominate, and in the later stage of the curing reaction, dipole relaxation dominates. Due to the shift of the effects over several frequency decades, it makes sense to evaluate electrical impedance spectra not exclusively at one frequency but over an entire available frequency spectrum. The measured spectral raw data cannot be easily interpreted by a control algorithm and have to be mapped to simpler key indicators. For this purpose, a frequency-dependent model is proposed to address the aforementioned physical effects. With only five free parameters, measured spectra can be described with a relative error of only 2.3%. The shift of the occurring effects to lower frequencies necessitates switching the key indicator used in the progression of the cure reaction.
Healthy Ageing: A Decision-Support Algorithm for the Patient-Specific Assignment of ICT Devices and Services
Authors: Brunzini Agnese , Caragiuli Manila , Massera Chiara , Mandolini Marco
Published: February 2023

In response to rapid population ageing, digital technology represents the greatest resource in supporting the implementation of active and healthy ageing principles at clinical and service levels. However, digital information platforms that deliver coordinated health and social care services for older people to cover their needs comprehensively and adequately are still not widespread. The present work is part of a project that focuses on creating a new personalised healthcare and social assistance model to enhance older people’s quality of life. This model aims to prevent acute events to favour the elderly staying healthy in their own home while reducing hospitalisations. In this context, the prompt identification of criticalities and vulnerabilities through ICT devices and services is crucial. According to the human-centred care vision, this paper proposes a decision-support algorithm for the automatic and patient-specific assignment of tailored sets of devices and local services based on adults’ health and social needs. This decision-support tool, which uses a tree-like model, contains conditional control statements. Using sequences of binary divisions drives the assignation of products and services to each user. Based on many predictive factors of frailty, the algorithm aims to be efficient and time-effective. This goal is achieved by adequately combining specific features, thresholds, and constraints related to the ICT devices and patients’ characteristics. The validation was carried out on 50 participants. To test the algorithm, its output was compared to clinicians’ decisions during the multidimensional evaluation. The algorithm reported a high sensitivity (96% for fall monitoring and 93% for cardiac tracking) and a lower specificity (60% for fall monitoring and 27% for cardiac monitoring). Results highlight the preventive and protective behaviour of the algorithm.
Comparative Study of Gasoline Fuel Mixture to Reduce Emissions in the Metropolitan District
Authors: Rojas-Reinoso Vicente , Alvarez-Loor Janko , Zambrano-Becerra Henrry , Soriano José Antonio
Published: February 2023

In the present investigation, the behavior of fuel consumption was studied due to the high cost of gasoline and its price increase in Ecuador in recent years, for which reason the different mixtures have been studied to obtain lower consumption. The optimum fuel mixture rate for a T18SED e-tec II engine, Multiport Electronic Fuel Injection System (MPFI) between extra gasoline, super gasoline, and ethanol was obtained on two urban roads in the city of Quito (Ecuador). For the first test, mixtures of 10% super gasoline and 90% extra gasoline were made, and so on, for the following tests: (20–80), (30–70), (40–60), (50–50), (60–40), (70–30), (80–20), and (90–10) % super and extra gasoline. Then, mixtures between super gasoline and ethanol and extra gasoline and ethanol with concentrations of 5% and 10% were made. The results showed a low consumption on Maldonado Avenue with the 20% extra and 80% super mixtures obtaining a value of 2.9 L, while the mixture that presented a higher consumption was 100% extra of 3.4 L. At the end of each test, the fuel tank was completely drained, and the engine control unit (ECU) was reset for each test. The data acquisition was carried out through an OBD II (on-board diagnostic system) installed in each of the tests.