bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection of Optimal Approach for Cardiovascular Disease Diagnosis under Complex Intuitionistic Fuzzy Dynamic Environment
Authors: Alghazzawi Dilshad , Liaqat Maryam , Razaq Abdul , Alolaiyan Hanan , Shuaib Umer , Liu Jia-Bao
Published: November 2023

Cardiovascular disease (CVD) is a leading global health concern. There is a critical need for accurate and reliable decision-making tools to select the optimal approach for diagnosing cardiovascular disease (CVD). In this study, we have addressed this pressing issue. Complex intuitionistic fuzzy set (CIFS) theory is adept at encapsulating vagueness due to its capability to encompass comprehensive problem specifications characterized by both intuitionistic uncertainty and periodicity. Within the scope of this article, we present two novel aggregation operators: the complex intuitionistic fuzzy dynamic weighted averaging (CIFDWA) operator and the complex intuitionistic fuzzy dynamic weighted geometric (CIFDWG) operator. Some intriguing characteristics of these operators are elucidated, and important special cases are also defined in detail. We devise an enhanced score function to rectify the deficiencies observed in the existing score function under complex intuitionistic fuzzy knowledge. Furthermore, these operators are employed in the development of a systematic approach for the handling of multiple attribute decision-making (MADM) scenarios involving complex intuitionistic fuzzy data. Moreover, we undertake the resolution of an MADM problem, wherein we ascertain the optimal approach for diagnosing cardiovascular disease (CVD) through the utilization of the proposed operators, thereby substantiating their utility in decision-making processes. Finally, we conduct a comprehensive comparative analysis, pitting the presented operators against an array of existing counterparts, in order to demonstrate the reliability and stability inherent in the derived methodologies.
On Nash Equilibria in a Finite Game for Fuzzy Sets of Strategies
Authors: Bekesiene Svajone , Mashchenko Serhii
Published: November 2023

The present paper investigates a finite game with fuzzy sets of player strategies. It is proven that Nash equilibria constitute a type-2 fuzzy set defined on the universal set of strategy profiles. Furthermore, the corresponding type-2 membership function is provided. This paper demonstrates that the Nash equilibria type-2 fuzzy set of the game can be decomposed based on the secondary membership grades into a finite collection of crisp sets. Each of these crisp sets represents the Nash equilibria set of the corresponding game with crisp sets of player strategies. A characteristic feature of the proposed decomposition approach is its independence from the chosen method for calculating the Nash equilibria in crisp subgames. Some properties of game equilibria T2FSs are studied. These sets correspond to specific partitions or cuts of the original fuzzy sets of player strategies. An illustrative example is also included for clarity.
Deep Neural Network and Predator Crow Optimization-Based Intelligent Healthcare System for Predicting Cardiac Diseases
Authors: Alqurashi Fahad , Zafar Aasim , Khan Asif Irshad , Almalawi Abdulmohsen , Alam Md Mottahir , Azim Rezaul
Published: November 2023

Cardiovascular diseases (CVD) are amongst the leading causes of death worldwide. The Internet of Things (IoT) is an emerging technology that enables the healthcare system to identify cardiovascular diseases. In this article, a novel cardiovascular disease prediction framework combining Predator Crow Optimization (PCO) and Deep Neural Network (DNN) is designed. In the proposed PCO-DNN framework, DNN is used to predict cardiac disease, and the PCO is utilized to optimize the DNN parameters, thereby maximizing the prediction performances. The proposed framework aims to predict and classify cardiovascular diseases accurately. Further, an intensive comparative analysis is performed to validate the obtained results with the existing classification models. The results show that the proposed framework achieves an accuracy of 96.6665%, a precision of 97.5256%, a recall of 97.0953%, and an F1-measure of 96.4242% and can outperform the existing CVD predictors.
The Measurement Problem in Statistical Signal Processing
Authors: Milovanović Miloš
Published: November 2023

Discussing quantum theory foundations, von Neumann noted that the measurement process should not be regarded in terms of a temporal evolution. A reason for their claim is the insurmountability of the gap between reversible and irreversible processes. The time operator formalism that goes beyond such a gap is an adequate framework to elaborate the measurement problem. It considers signals to be stochastic processes, regardless of whether they correspond to variables or distribution densities. Signal processing that utilizes statistical properties to perform tasks is statistical signal processing. The hierarchy of the measurement process is indicated by crossing between states and devices, which implies an evolution in the temporal domain. The concept has been generalized to an open system by the use of duality in frame theory.
A Heavy-Tailed Distribution Based on the Lomax–Rayleigh Distribution with Applications to Medical Data
Authors: Santoro Karol I. , Gallardo Diego I. , Venegas Osvaldo , Cortés Isaac E. , Gómez Héctor W.
Published: November 2023

In this paper, we extend the Lomax–Rayleigh distribution to increase its kurtosis. The construction of this distribution is based on the idea of the Slash distribution, that is, its representation is based on the quotient of two independent random variables, one being a random variable with a Lomax–Rayleigh distribution and the other a beta(q,1). Based on the representation of this family, we study its basic properties, such as moments, coefficients of skewness, and kurtosis. We perform statistical inference using the methods of moments and maximum likelihood. To illustrate this methodology, we apply it to two real data sets.
Semiparametric Integrated and Additive Spatio-Temporal Single-Index Models
Authors: Mahmoud Hamdy F. F. , Kim Inyoung
Published: November 2023

In this paper, we introduce two semiparametric single-index models for spatially and temporally correlated data. Our first model has spatially and temporally correlated random effects that are additive to the nonparametric function, which we refer to as the “semiparametric spatio-temporal single-index model (ST-SIM)”. The second model integrates the spatially correlated effects into the nonparametric function, and the time random effects are additive to the single-index function. We refer to our second model as the “semiparametric integrated spatio-temporal single-index model (IST-SIM)”. Two algorithms based on a Markov chain expectation maximization are introduced to simultaneously estimate the model parameters, spatial effects, and time effects of the two models. We compare the performance of our models using several simulation studies. The proposed models are then applied to mortality data from six major cities in South Korea. Our results suggest that IST-SIM (1) is more flexible than ST-SIM because the former can estimate various nonparametric functions for different locations, while ST-SIM enforces the mortality functions having the same shape over locations; (2) provides better estimation and prediction, and (3) does not need restrictions for the single-index coefficients to fix the identifiability problem.
Efficient Estimation and Validation of Shrinkage Estimators in Big Data Analytics
Authors: du Plessis Salomi , Arashi Mohammad , Maribe Gaonyalelwe , Millard Salomon M.
Published: November 2023

Shrinkage estimators are often used to mitigate the consequences of multicollinearity in linear regression models. Despite the ease with which these techniques can be applied to small- or moderate-size datasets, they encounter significant challenges in the big data domain. Some of these challenges are that the volume of data often exceeds the storage capacity of a single computer and that the time required to obtain results becomes infeasible due to the computational burden of a high volume of data. We propose an algorithm for the efficient model estimation and validation of various well-known shrinkage estimators to be used in scenarios where the volume of the data is large. Our proposed algorithm utilises sufficient statistics that can be computed and updated at the row level, thus minimizing access to the entire dataset. A simulation study, as well as an application on a real-world dataset, illustrates the efficiency of the proposed approach.
Differentiability of the Largest Lyapunov Exponent for Non-Planar Open Billiards
Authors: Al Dowais Amal
Published: November 2023

This paper investigates the behaviour of open billiard systems in high-dimensional spaces. Specifically, we estimate the largest Lyapunov exponent, which quantifies the rate of divergence between nearby trajectories in a dynamical system. This exponent is shown to be continuous and differentiable with respect to a small perturbation parameter. A theoretical analysis forms the basis of the investigation. Our findings contribute to the field of dynamical systems theory and have significant implications for the stability of open billiard systems, which are used to model physical phenomena. The results provide a deeper comprehension of the behaviour of open billiard systems in high-dimensional spaces and emphasise the importance of taking small perturbations into consideration when analysing these systems.
Dynamics of Capillary Lactate Levels in Patients with Out-of-Hospital Cardiac Arrest
Authors: Vujanović Vitka , Borovnik Lesjak Vesna , Mekiš Dušan , Strnad Matej
Published: November 2023

Background and Objectives: An effective strategy for cardiopulmonary resuscitation should be based on tissue perfusion. Our primary aim was to determine the association between capillary lactate values and initial rhythm as well as the probability of the return of spontaneous circulation in out-of-hospital cardiac arrest patients. Materials and Methods: This prospective observational cohort study included all patients with non-traumatic out-of-hospital cardiac arrest, older than 18 years, resuscitated by a prehospital emergency medical team between April 2020 and June 2021. Capillary lactate samples were collected at the time of arrival and every 10 min after the first measurement until the time of the return of spontaneous circulation (ROSC) or, if ROSC was not achieved, at the time of declaring death on the scene. Results: In total, 83 patients were enrolled in the study. ROSC was achieved in 28 patients (33.7%), 21 were admitted to hospital (26.3%), and 6 (7.23%) of them were discharged from hospital. At discharge, all patients had Cerebral Performance Category Scale 1 or 2. Initial capillary lactate values were significantly higher in patients with a non-shockable rhythm compared to the group with a shockable rhythm (9.19 ± 4.6 versus 6.43 ± 3.81; p = 0.037). A significant difference also persisted in a second value taken 10 min after the initial value (10.03 ± 5,19 versus 5.18 ± 3.47; p = 0.019). Capillary lactate values were higher in the ROSC group and non-ROSC group at the time of restored circulation (11.10 ± 6.59 and 6.77 ± 4.23, respectively; p = 0.047). Conclusions: Capillary lactate values are significantly higher in patients with a non-shockable first rhythm in out-of-hospital cardiac arrest (OHCA). There is also a significantly different rise in capillary lactate levels in patients with ROSC.
Prophylactic Coloprotective Effect of Urtica dioica Leaves against Dextran Sulfate Sodium (DSS)-Induced Ulcerative Colitis in Rats
Authors: Dakhli Nouha , Rtibi Kais , Arrari Fatma , Ayari Ala , Sebai Hichem
Published: November 2023

Background and Objectives: Urtica dioica, a source of bioactive functional compounds, provides nutritional and gastrointestinal therapeutic benefits. This study attempted to investigate the prophylactic coloprotective action of an aqueous extract of Urtica dioica (AEUD) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). Materials and Methods: Phenolic compounds, total sugar, and mineral levels were determined in AEUD. Then, AEUD at different doses (50, 100, and 200 mg/kg, BW, p.o.) and mesalazine (MESA) as a standard treatment (100 mg/kg, BW, p.o.) were given orally for 21 days. Acute colitis was induced by administering drinking water with 5% (w/v) DSS for 7 days. Body weight variation, fecal occult blood, and stool consistency were determined daily. The severity of colitis was graded according to colon length, disease activity index (DAI), histological evaluations, and biochemical alterations. Rats orally administered DSS regularly developed clinical and macroscopic signs of colitis. Results: Due to its richness in phenolic and flavonoid compounds (247.65 ± 2.69 mg EAG/g MS and 34.08 ± 0.53 mg EQt/g MS, respectively), AEUD markedly ameliorated DAI, ulcer scores, colon length shortening, colonic histopathological changes, and hematological and biochemical modifications. Taken together, AEUD treatment notably (p < 0.01) suppressed DSS-induced UC by reducing oxidative stress via lowering MDA/H2O2 production and stimulating the effect of enzyme antioxidants as well as attenuating inflammation by decreasing CRP levels by 79.5% between the DSS and DSS + AEUD-50 groups compared to the MESA group (75.6%). Conclusions: AEUD was sufficient to exert a coloprotective effect that might be influenced by its bioactive compounds’ anti-inflammatory and antioxidant capabilities.
A Rare Case of Isolated Hepatocellular Carcinoma Metastasis in Left Mandibular Region in a Patient with Hepatitis C Virus Liver Cirrhosis Diagnosed after the Onset of COVID-19 Infection
Authors: Mašulović Dragan , Igić Aleksa , Filipović Aleksandar , Zakošek Miloš , Bulatović Dušan , Mijović Ksenija , Micev Marjan , Galun Danijel
Published: November 2023

Background and Objectives: Hepatocellular carcinoma (HCC) most frequently metastasizes in the lungs, abdominal lymph nodes and adrenal glands. Metastatic spread to the head and neck area is extremely rare. In the presented case, an uncommon site of solitary metastatic spread of HCC to the mandible confirmed after the core biopsy of the lesion is reported. There have been only about 80 cases of mandibular HCC metastases described in the literature to date. We contribute our experience to the pool of data. Case presentation: A 65-year-old female with HCV-related liver cirrhosis was diagnosed with an HCC that was successfully treated with liver resection. Subsequently, the patient had developed COVID-19 disease, which was associated with a painless swelling in the left jaw. A neck MDCT scan demonstrated an osteolytic soft-tissue mass in the left mandible, with the characteristics consistent for the metastasis of HCC. In order to confirm the diagnosis, a core biopsy of the mandibular mass was performed. The pathohistological evaluation confirmed the presence of a metastatic HCC in the mandible. No other sites of disease dissemination were identified in extensive MDCT scans. Despite considering various treatments, including symptomatic and palliative, the patient’s overall prognosis remained poor. Conclusions: Isolated metastases of HCC to the orofacial region are extremely rare; however, it should be considered in patients with known risk factors for HCC development. Early diagnosis is critical, and clinicians should consider this possibility of HCC spread when assessing patients with orofacial swelling, among those patients with risk factors for HCC. The overall prognosis for such patients remains poor, emphasizing the challenges in managing these cases.
Brownian Aging as One of the Mechanistic Components That Shape the Single-Channel Ionic Currents through Biological and Synthetic Membranes
Authors: Wawrzkiewicz-Jałowiecka Agata , Fuliński Andrzej
Published: November 2023

Semipermeable membranes enable the separation of a given system from its environment. In biological terms, they are responsible for cells’ identity. In turn, the functioning of ion channels is crucial for the control of ionic fluxes across the membranes and, consequently, for the exchange of chemical and electrical signals. This paper presents a model and simulations of currents through ionic nanochannels in an attempt to better understand the physical mechanism(s) of open/closed (O/C) sequences, i.e., random interruptions of ionic flows through channels observed in all known biochannels and in some synthetic nanopores. We investigate whether aging, i.e., the changes in Brownian motion characteristics with the lapse of time, may be at least one of the sources of the O/C sequences (in addition to the gating machinery in biochannels). The simulations based on the approximated nanostructure of ion channels confirm this postulation. The results also show the possibility of changing the O/C characteristics through an appropriate alteration of the channel surroundings. This observation may be valuable in technical uses of nanochannels in synthetic membranes and allow for a better understanding of the reason for the differences between the biochannels’ activity in diverse biological membranes. Proposals of experimental verification of this aging O/C hypothesis are also presented.
Non-Native English-Speaking Teachers and Self-Appreciation: How Non-Native English-Speaking Teachers Can Gain Equity by Learning to Appreciate Themselves
Authors: Perry Simon
Published: November 2023

This research paper explores how non-native English-speaking teachers can consider using their multilingualism and transnationalism as assets in creating competitive portfolios fit for the 21st century linguistic marketplace. This enhancement in the portfolio to attract credit as ‘investors of the self’ is an aspect of human capital that can be utilized by non-native English-speaking teachers to enhance their self-esteem. This, in turn, can encourage potential investors to view non-native English-speaking teachers as relevant players in a global landscape that appreciates linguistic diversity and pluralism, as well as transnational experience. This research was conducted by performing interviews with non-native English-speaking teachers and an analysis of website 2.0 sources, aiming to gain insights into the opinions of non-native English-speaking teachers regarding their human capital and how new approaches can aid their equity within the field of English language teaching. The results demonstrated a desire in teachers to utilize their inherent skillsets comprising multilingual and transnational capabilities.
Micromechanical Modeling for Predicting Residual Stress–Strain State around Nodules in Ductile Cast Irons
Authors: Ruggiero Andrew , Khademi Ehsan
Published: November 2023

In this paper, a micromechanical model was developed to predict the residual stress–strain state that is generated around nodules of a ferritic ductile cast iron during solidification. A finite element analysis was performed on a reference volume element of the material to analyze the local strain development, having modeled both matrix and nodule as deformable bodies in contact. The behavior of the nodule was assumed linear–elastic because of the low stresses to which it is subjected during cooling. On the other hand, elasto-plastic viscous behavior was considered for the matrix, considering both the primary and secondary creep regimes. To make up for the lack of information on the physical–thermomechanical properties of the constituents, the available literature data were integrated with the results obtained from the CALPHAD methodology applied to both cast iron and the steel that constitutes its matrix. The micromechanical model was validated by comparing the resulting residual strains with experimental data available in the literature for a ferritic ductile cast iron. Then, it was used for analyzing the correlation between the solidification history and the mechanical response of cast iron in terms of the uniaxial stress–strain curve.
Investigation of the Formability of AA6010 in an Integrated Forming and Hardening Process Aiming to Reduce the Energy Consumption in High Volume Production of Automotive Components
Authors: Myrold Benedikte , Jensrud Ola , Holmestad Jon
Published: November 2023

Hot deformation and in-die quenching of aluminum components for the automotive industry is a cost and energy efficient technique that has been developed and thoroughly evaluated in recent years. The performance of this process is considered higher when compared to traditional cold metal forming due to shorter process times, low-cost machinery, and a high level of structural integrity in fabricated parts. The work presented in this paper provides several approaches for the formability of age hardenable 6xxx alloy sheets when forming at different temperatures. Warm tensile testing and formability cup testing were carried out to investigate the alloy formability at different temperatures. The results indicate that the formability of candidate alloys is not significantly affected by deformation temperatures or conditions, which provides great freedom when designing an automated production process with high productivity and minimal environmental impact. The candidate alloy can be deep drawn without severe thinning at the whole temperature range, from room temperature (RT) to solutionizing temperature.
Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study
Authors: Banoei Mohammad , McIntyre Lauralyn , Stewart Duncan , Mei Shirley , Courtman David , Watpool Irene , Granton John , Marshall John , dos Santos Claudia , Walley Keith , Schlosser Kenny , Fergusson Dean , Winston Brent ,   on behalf of Canadian Critical Care Trials Group (CCCTG),   on behalf of Canadian Critical Care Translational Biology Group (CCCTBG)
Published: November 2023

Sepsis is the result of an uncontrolled host inflammatory response to infection that may lead to septic shock with multiorgan failure and a high mortality rate. There is an urgent need to improve early diagnosis and to find markers identifying those who will develop septic shock and certainly a need to develop targeted treatments to prevent septic shock and its high mortality. Herein, we explore metabolic alterations due to mesenchymal stromal cell (MSC) treatment of septic shock. The clinical findings for this study were already reported; MSC therapy was well-tolerated and safe in patients in this phase I clinical trial. In this exploratory metabolomics study, 9 out of 30 patients received an escalating dose of MSC treatment, while 21 patients were without MSC treatment. Serum metabolomics profiling was performed to detect and characterize metabolite changes due to MSC treatment and to help determine the sample size needed for a phase II clinical trial and to define a metabolomic response to MSC treatment. Serum metabolites were measured using 1H-NMR and HILIC-MS at times 0, 24 and 72 h after MSC infusion. The results demonstrated the significant impact of MSC treatment on serum metabolic changes in a dose- and time-dependent manner compared to non-MSC-treated septic shock patients. This study suggests that plasma metabolomics can be used to assess the response to MSC therapy and that treatment-related metabolomics effects can be used to help determine the sample size needed in a phase II trial. As this study was not powered to detect outcome, how the treatment-induced metabolomic changes described in this study of MSC-treated septic shock patients are related to outcomes of septic shock in the short and long term will need to be explored in a larger adequately powered phase II clinical trial.
Metabolic Features of a Novel Trichoderma asperellum YNQJ1002 with Potent Antagonistic Activity against Fusarium graminearum
Authors: Ji Huimin , Yu Ruohan , Liu Hongyi , Zhang Hui , Wang Xinhua , Chen Jie , Li Yaqian
Published: November 2023

Trichoderma, a well-known and extensively studied fungal genus, has gained significant attention for its remarkable antagonistic abilities against a wide range of plant pathogens. In this study, a total of 108 Trichoderma isolates were screened through in vitro dual antagonistic assays and culture filtrate inhibition against Fusarium graminearum. Of these, the YNQJ1002 displayed noteworthy inhibitory activities along with thermal stability. To validate the metabolic differences between YNQJ1002 and GZLX3001 (with strong and weak antagonism, respectively), UPLC-TOF-MS/MS mass spectrometry was employed to analyze and compare the metabolite profiles. We identified 12 significantly up-regulated metabolites in YNQJ1002, which include compounds like Trigoneoside, Torvoside, trans,trans-hepta-2,4,6-trienoic acid, and Chamazulene. These metabolites are known for their antimicrobial properties or signaling roles as components of cell membranes. Enriched KEGG analysis revealed a significant enrichment in sphingolipid metabolism and linoleic acid metabolism, as well as autophagy. The results demonstrated that YNQJ1002’s abundance of antimicrobial substances, resulting from specific metabolic pathways, enhanced its superior antagonistic activity against F. graminearum. Finally, YNQJ1002 was identified using the ITS, tef1-1α, and rpb2 regions, with MIST system sequence matching confirming its classification within the species. Overall, we have obtained a novel strain, T. asperellum YNQJ1002, which is rich in metabolites and shows potential antagonistic activity against F. graminearum. This study has opened promising prospects for the development of innovative Trichoderma-derived antifungal compounds, featuring a unique mechanism against pathogens.
Metabolomic Profiling of Second-Trimester Amniotic Fluid for Predicting Preterm Delivery: Insights from NMR Analysis
Authors: Kolvatzis Charalampos , Christodoulou Paris , Kalogiannidis Ioannis , Tsiantas Konstantinos , Tsakiridis Ioannis , Kyrkou Charikleia , Cheilari Antigoni , Thomaidis Nikolaos S. , Zoumpoulakis Panagiotis , Athanasiadis Apostolos , Michaelidou Alexandra-Maria
Published: November 2023

Preterm delivery (PTD) is a notable pregnancy complication, affecting one out of every ten births. This study set out to investigate whether analyzing the metabolic composition of amniotic fluid (AF) collected from pregnant women during the second trimester of pregnancy could offer valuable insights into prematurity. The research employed 1H–NMR metabolomics to examine AF samples obtained from 17 women who gave birth prematurely (between 29+0 and 36+5 weeks of gestation) and 43 women who delivered at full term. The application of multivariate analysis revealed metabolites (dimethylglycine, glucose, myo-inositol, and succinate) that can serve as possible biomarkers for the prognosis and early diagnosis of preterm delivery. Additionally, pathway analysis unveiled the most critical metabolic pathways relevant to our research hypothesis. In summary, these findings suggest that the metabolic composition of AF in the second trimester can be a potential indicator for identifying biomarkers associated with the risk of PTD.
Extreme Learning Machine/Finite Impulse Response Filter and Vision Data-Assisted Inertial Navigation System-Based Human Motion Capture
Authors: Xu Yuan , Gao Rui , Yang Ahong , Liang Kun , Shi Zhongwei , Sun Mingxu , Shen Tao
Published: November 2023

To obtain accurate position information, herein, a one-assistant method involving the fusion of extreme learning machine (ELM)/finite impulse response (FIR) filters and vision data is proposed for inertial navigation system (INS)-based human motion capture. In the proposed method, when vision is available, the vision-based human position is considered as input to an FIR filter that accurately outputs the human position. Meanwhile, another FIR filter outputs the human position using INS data. ELM is used to build mapping between the output of the FIR filter and the corresponding error. When vision data are unavailable, FIR is used to provide the human posture and ELM is used to provide its estimation error built in the abovementioned stage. In the right-arm elbow, the proposed method can improve the cumulative distribution functions (CDFs) of the position errors by about 12.71%, which shows the effectiveness of the proposed method.
Dysbiosis by Eradication of Helicobacter pylori Infection Associated with Follicular Gastropathy and Pangastropathy
Authors: Gomez-Ramirez Uriel , Nolasco-Romero Carolina G. , Contreras-Rodríguez Araceli , Zuñiga Gerardo , Mendoza-Elizalde Sandra , Prado-Galbarro Francisco-Javier , Pérez Aguilar Fernando , Pedraza Tinoco Jonatan Elihu , Valencia-Mayoral Pedro , Velázquez-Guadarrama Norma
Published: November 2023

Dysbiosis plays an important role in the development of bacterial infections in the gastric mucosa, particularly Helicobacter pylori. The international guidelines for the treatment of H. pylori infections suggest standard triple therapy (STT). Nevertheless, because of the increasing resistance rates to clarithromycin, metronidazole has been widely considered in several countries. Unfortunately, the non-justified administration of antibiotics induces dysbiosis in the target organ. We characterized the gastric microbiota of patients diagnosed with follicular gastropathy and pangastropathy attributed to H. pylori infection, before and after the administration of STT with metronidazole. Dominant relative abundances of Cutibacterium were observed in pre-treatment patients, whereas H. pylori was observed at <11%, suggesting the multifactor property of the disease. The correlation of Cutibacterium acnes and H. pylori with gastric infectious diseases was also evaluated using quantitative real-time polymerase chain reaction. The dominance of C. acnes over H. pylori was observed in gastritis, gastropathies, and non-significant histological alterations. None of the microorganisms were detected in the intestinal metaplasia. Post-treatment alterations revealed an increase in the relative abundances of Staphylococcus, Pseudomonas, and Klebsiella. Non-H. pylori gastrointestinal bacteria can be associated with the initiation and development of gastric diseases, such as pathobiont C. acnes.
Comparative Genomic Analysis of Shrimp-Pathogenic Vibrio parahaemolyticus LC and Intraspecific Strains with Emphasis on Virulent Factors of Mobile Genetic Elements
Authors: Xue Ming , Gao Qi , Yan Rui , Liu Lingping , Wang Ling , Wen Binyu , Wen Chongqing
Published: November 2023

Vibrio parahaemolyticus exhibits severe pathogenicity in humans and animals worldwide. In this study, genome sequencing and comparative analyses were conducted for in-depth characterization of the virulence factor (VF) repertoire of V. parahaemolyticus strain LC, which presented significant virulence to shrimp Litopenaeus vannamei. Strain LC, harboring two circular chromosomes and three linear plasmids, demonstrated ≥98.14% average nucleotide identities with 31 publicly available V. parahaemolyticus genomes, including 13, 11, and 7 shrimp-, human-, and non-pathogenic strains, respectively. Phylogeny analysis based on dispensable genes of pan-genome clustered 11 out of 14 shrimp-pathogenic strains and 7 out of 11 clinical strains into two distinct clades, indicating the close association between host-specific pathogenicity and accessory genes. The VFDB database revealed that 150 VFs of LC were mainly associated with the secretion system, adherence, antiphagocytosis, chemotaxis, motility, and iron uptake, whereas no homologs of the typical pathogenic genes pirA, pirB, tdh, and trh were detected. Four genes, mshB, wbfT, wbfU, and wbtI, were identified in both types of pathogenic strains but were absent in non-pathogens. Notably, a unique cluster similar to Yen-Tc, which encodes an insecticidal toxin complex, and diverse toxin–antitoxin (TA) systems, were identified on the mobile genetic elements (MGEs) of LC. Conclusively, in addition to the common VFs, various unique MGE-borne VFs, including the Yen-Tc cluster, TA components, and multiple chromosome-encoded chitinase genes, may contribute to the full spectrum of LC virulence. Moreover, V. parahaemolyticus demonstrates host-specific virulence, which potentially drives the origin and spread of pathogenic factors.
A Robust Quadruple Protein-Based Indirect ELISA for Detection of Antibodies to African Swine Fever Virus in Pigs
Authors: Jung Min-Chul , Le Van Phan , Yoon Sun-Woo , Le Thi Ngoc , Trinh Thi Bich Ngoc , Kim Hye Kwon , Kang Jung-Ah , Lim Jong-Woo , Yeom Minjoo , Na Woonsung , Nah Jin-Ju , Choi Ji-Da , Kang Hae-Eun , Song Daesub , Jeong Dae Gwin
Published: November 2023

African swine fever (ASF) emerged in domestic pigs and wild boars in China in 2018 and rapidly spread to neighboring Asian countries. Currently, no effective vaccine or diagnostic tests are available to prevent its spread. We developed a robust quadruple recombinant-protein-based indirect enzyme-linked immunosorbent assay (QrP-iELISA) using four antigenic proteins (CD2v, CAP80, p54, and p22) to detect ASF virus (ASFV) antibodies and compared it with a commercial kit (IDvet) using ASFV-positive and -negative serum samples. The maximum positive/negative value was 24.033 at a single antigen concentration of 0.25 μg/mL and quadruple ASFV antigen combination of 1 μg/mL at a 1:100 serum dilution. Among 70 ASFV-positive samples, 65, 67, 65, 70, 70, and 14 were positive above the cut-offs of 0.121, 0.121, 0.183, 0.065, 0.201, and 0.122, for CD2v, CAP80, p54, p22-iELISA, QrP-iELISA, and IDvet, respectively, with sensitivities of 92.9%, 95.7%, 92.9%, 100%, 100%, and 20%, respectively, all with 100% specificity. The antibody responses in QrP-iELISA and IDvet were similar in pigs infected with ASFV I. QrP-iELISA was more sensitive than IDvet for early antibody detection in pigs infected with ASFV II. These data provide a foundation for developing advanced ASF antibody detection kits critical for ASF surveillance and control.
Molecular Diagnosis as an Alternative for Public Health Surveillance of Leptospirosis in Colombia
Authors: Arboleda Margarita , Mejía-Torres Mariana , Posada Maritza , Restrepo Nicaela , Ríos-Tapias Paola , Rivera-Pedroza Luis Alberto , Calle David , Sánchez-Jiménez Miryan M. , Marín Katerine , Agudelo-Flórez Piedad
Published: November 2023

Leptospirosis represents a public health problem in Colombia. However, the underreporting of the disease is an unfortunate reality, with a clear trend towards a decrease in cases since 2019, when the guidelines for its confirmatory diagnosis changed with the requirement of two paired samples. The purpose of this review is to highlight the importance of leptospirosis. While the access to rapid diagnosis is available at practically all levels of care for dengue and malaria, leptospirosis—a doubly neglected disease—deserves recognition as a serious public health problem in Colombia. In this manner, it is proposed that molecular tests are a viable diagnostic alternative that can improve the targeted treatment of the patient and the timeliness of data and case reporting to SIVIGILA, and reduce the underreporting of the disease. Taking advantage of the strengthened technological infrastructure derived from the SARS-CoV-2 pandemic for molecular diagnosis in Colombia, with a network of 227 laboratories distributed throughout the national territory, with an installed capacity for PCR testing, it is proposed that molecular diagnosis can be used as an alternative for early diagnosis. This would allow case confirmation through the public health network in Colombia, and, together with the microagglutination (MAT) technique, the epidemiological surveillance of this disease in this country would be strengthened.
Progress in the Application of Biomimetic Mineralization for Tooth Repair
Authors: Tang Zhenhang , Shan Songzhe , Chen Zhuo , Shao Changyu
Published: November 2023

The tooth, including enamel and dentin, is a prominent biomineral that is produced by the biomineralization of living organisms. Although the mechanical performance of the tooth is outstanding, caries easily develop in a complex oral environment. The analysis of the chemical composition and the relationship between the mechanical properties and the structure is of great importance in solving caries. In this review, the multilevel structure and mechanical properties of enamel and dentin are briefly introduced, along with caries formation and the limitations of clinical dental restoration. Furthermore, the progress of the application of a wide range of biomimetic strategies for tooth remineralization is highlighted, including the use of calcium phosphate ionic clusters to construct the mineralization front, ensuring the oriented epitaxial growth of enamel crystals and replicating the complex structure of the enamel. Moreover, compared with the current clinical treatment, in which the resin composite and glass ionomer cement are the main repair materials and the high incidence of secondary caries leads to imperfect restorations, the remineralization tactics could achieve excellent repair effectiveness in reconstructing the complicated structure, restoring mechanical strength and gaining permanent repair. A basic understanding of enamel and dentin, their potential for restoration, and hopeful prospects for tooth repair that can be applied in the clinical setting, not just in the laboratory, is provided by this review.
Lupin as a Source of Bioactive Antioxidant Compounds for Food Products
Authors: Estivi Lorenzo , Brandolini Andrea , Gasparini Andrea , Hidalgo Alyssa
Published: November 2023

Four species of lupin (white lupin, yellow lupin, blue lupin and Andean lupin) are widely cropped thanks to the excellent nutritional composition of their seeds: high protein content (28–48 g/100 g); good lipid content (4.6–13.5 g/100 g, but up to 20.0 g/100 g in Andean lupin), especially unsaturated triacylglycerols; and richness in antioxidant compounds like carotenoids, tocols and phenolics. Particularly relevant is the amount of free phenolics, highly bioaccessible in the small intestine. However, the typical bitter and toxic alkaloids must be eliminated before lupin consumption, hindering its diffusion and affecting its nutritional value. This review summarises the results of recent research in lupin composition for the above-mentioned three classes of antioxidant compounds, both in non-debittered and debittered seeds. Additionally, the influence of technological processes to further increase their nutritional value as well as the effects of food manufacturing on antioxidant content were scrutinised. Lupin has been demonstrated to be an outstanding raw material source, superior to most crops and suitable for manufacturing foods with good antioxidant and nutritional properties. The bioaccessibility of lupin antioxidants after digestion of ready-to-eat products still emerges as a dearth in current research.
The Pharmacological Implications of Flavopiridol: An Updated Overview
Authors: Joshi Hemant , Tuli Hardeep Singh , Ranjan Anuj , Chauhan Abhishek , Haque Shafiul , Ramniwas Seema , Bhatia Gurpreet Kaur , Kandari Divya
Published: November 2023

Flavopiridol is a flavone synthesized from the natural product rohitukine, which is derived from an Indian medicinal plant, namely Dysoxylum binectariferum Hiern. A deeper understanding of the biological mechanisms by which such molecules act may allow scientists to develop effective therapeutic strategies against a variety of life-threatening diseases, such as cancer, viruses, fungal infections, parasites, and neurodegenerative diseases. Mechanistic insight of flavopiridol reveals its potential for kinase inhibitory activity of CDKs (cyclin-dependent kinases) and other kinases, leading to the inhibition of various processes, including cell cycle progression, apoptosis, tumor proliferation, angiogenesis, tumor metastasis, and the inflammation process. The synthetic derivatives of flavopiridol have overcome a few demerits of its parent compound. Moreover, these derivatives have much improved CDK-inhibitory activity and therapeutic abilities for treating severe human diseases. It appears that flavopiridol has potential as a candidate for the formulation of an integrated strategy to combat and alleviate human diseases. This review article aims to unravel the potential therapeutic effectiveness of flavopiridol and its possible mechanism of action.
Study Models of Drug–Drug Interactions Involving P-Glycoprotein: The Potential Benefit of P-Glycoprotein Modulation at the Kidney and Intestinal Levels
Authors: Veiga-Matos Jéssica , Morales Ana I. , Prieto Marta , Remião Fernando , Silva Renata
Published: November 2023

P-glycoprotein (P-gp) is a crucial membrane transporter situated on the cell’s apical surface, being responsible for eliminating xenobiotics and endobiotics. P-gp modulators are compounds that can directly or indirectly affect this protein, leading to changes in its expression and function. These modulators can act as inhibitors, inducers, or activators, potentially causing drug–drug interactions (DDIs). This comprehensive review explores diverse models and techniques used to assess drug-induced P-gp modulation. We cover several approaches, including in silico, in vitro, ex vivo, and in vivo methods, with their respective strengths and limitations. Additionally, we explore the therapeutic implications of DDIs involving P-gp, with a special focus on the renal and intestinal elimination of P-gp substrates. This involves enhancing the removal of toxic substances from proximal tubular epithelial cells into the urine or increasing the transport of compounds from enterocytes into the intestinal lumen, thereby facilitating their excretion in the feces. A better understanding of these interactions, and of the distinct techniques applied for their study, will be of utmost importance for optimizing drug therapy, consequently minimizing drug-induced adverse and toxic effects.
Subcritical Water Extraction to Valorize Grape Biomass—A Step Closer to Circular Economy
Authors: Ferreira Cátia , Moreira Manuela M. , Delerue-Matos Cristina , Sarraguça Mafalda
Published: November 2023

With the increase in the world population, the overexploitation of the planet’s natural resources is becoming a worldwide concern. Changes in the way humankind thinks about production and consumption must be undertaken to protect our planet and our way of living. For this change to occur, sustainable development together with a circular economic approach and responsible consumption are key points. Agriculture activities are responsible for more than 10% of the greenhouse gas emissions; moreover, by 2050, it is expected that food production will increase by 60%. The valorization of food waste is therefore of high importance to decrease the environmental footprint of agricultural activities. Fruits and vegetables are wildly consumed worldwide, and grapes are one of the main producers of greenhouse gases. Grape biomass is rich in bioactive compounds that can be used for the food, pharmaceutical and cosmetic industries, and their extraction from this food residue has been the target of several studies. Among the extraction techniques used for the recovery of bioactive compounds from food waste, subcritical water extraction (SWE) has been the least explored. SWE has several advantages over other extraction techniques such as microwave and ultrasound extraction, allowing high yields with the use of only water as the solvent. Therefore, it can be considered a green extraction method following two of the principles of green chemistry: the use of less hazardous synthesis (principle number 3) and the use of safer solvents and auxiliaries (principle number 5). In addition, two of the green extraction principles for natural products are also followed: the use of alternative solvents or water (principle number 2) and the use of a reduced, robust, controlled and safe unit operation (principle number 5). This review is an overview of the extraction process using the SWE of grape biomass in a perspective of the circular economy through valorization of the bioactive compounds extracted. Future perspectives applied to the SWE are also discussed, as well as its ability to be a green extraction technique.
The Hydrolytic Activity of Copper(II) Complexes with 1,4,7-Triazacyclononane Derivatives for the Hydrolysis of Phosphate Diesters
Authors: Buziková Michaela , Willimetz Robert , Kotek Jan
Published: November 2023

A set of substituted 1,4,7-triazacyclononane ligands was synthesised, including a wide series of novel derivatives bearing a thiazole or thiophene side group, with the potential to incorporate these derivatives into a polymeric material; some previously known/studied ligands were also synthesised for comparative purposes. The corresponding copper(II) complexes were prepared, and their ability to mediate the hydrolysis of phosphate ester bonds was studied via UV-Vis spectrophotometry, using bis(p-nitrophenyl)phosphate as a model substrate. Some of the prepared complexes showed a considerable enhancement of the phosphate ester hydrolysis in comparison with previously studied systems, which makes them some of the most effective complexes ever tested for this purpose. Therefore, these novel, potentially bifunctional systems could provide the possibility of creating new coating materials for medicinal devices that could prevent biofilm formation.
A Bioinformatic Study on the Potential Anti-Vitiligo Activity of a Carpobrotus edulis Compound
Authors: Trigui Emna , Ben Hassen Hanen , Zaghden Hatem , Trigui Maher , Achour Sami
Published: November 2023

The plant Carpobrotus edulis has traditionally been known for its wide applications in diseases, especially vitiligo, which is characterized by patches and white macules caused by the loss of melanocytes. One of the chemical treatments for vitiligo consists mainly of skin repigmentation and usually leads to a non-durable effect by inhibiting the Janus kinase (JAK) signal transduction (STAT pathway). JAK inhibitors generally block multiple JAK tyrosine kinases, which leads to secondary effects. In this study, natural molecules from Carpobrotus edulis were extracted and tested using a structure-based drug-design approach and pharmacophore modeling. The best-fit candidate from the extracted molecules was compared to the chemical molecules used. The results indicated a similarity between the chemical and natural ligands which suggested the potential use of the natural product against vitiligo. The main finding of this research work was the discovery of a new molecule extracted from a natural plant and the detection of its anti-vitiligo activity using an in-silico approach. This method can significantly reduce the cost of searching for potential medicinal molecules.
Insights on Juniperus phoenicea Essential Oil as Potential Anti-Proliferative, Anti-Tyrosinase, and Antioxidant Candidate
Authors: Mansour Rim Ben , Wasli Hanen , Bourgou Soumaya , Khamessi Saber , Ksouri Riadh , Megdiche-Ksouri Wided , Cardoso Susana M.
Published: November 2023

In this study, the anti-cancer, anti-tyrosinase, and antioxidant activities of essential oils (EOs) of berries and leaves of Juniperus phoenicea grown wild in North of Tunisia were investigated. The EO yields from leaves and berries were 1.69% and 0.45%, respectively. GC-MS analysis revealed that α-pinene is the predominant component in both EOs (44.17 and 83.56%, respectively). Leaves essential oil presented high levels of β-phellandrene (18%) and camphene (15%). The EOs displayed cytotoxic effects against MCF-7 breast cancer cell, HT-29 colon cancer, and the normal cells H9C2 cardiomyoblasts. Leaves oil strongly inhibited colon cell line proliferation (IC50 of 38 µg/mL), while berries essential oil was more potent against breast cancerous cells MCF-7 (IC50 of 60 µg/mL). Interestingly, berries essential oil exhibited high ability to inhibit melanin synthesis by inhibiting enzyme mono and diphenolase activities. Overall, the results suggested that the two oils are significant sources of healthy natural chemicals.