bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Different Fractions of Organic Matter in an Electrochemical Treatment System Applied to Stabilized Leachates from the Bordo Poniente Landfill in Mexico City
Authors: Martínez-Cruz Alfredo , Rojas-Valencia María Neftalí
Published: May 2023

The presence of refractory compounds in stabilized leachates makes treatment complex. In leachate treatment systems, the lack of data on the characterization of leachates and effluents makes it difficult to track and explain the evolution of organic matter. In this study, the fractionation of chemical oxygen demand (COD) and humic substances, including humic acids (HA) and fulvic acids (FA), in addition to the application of spectroscopic techniques (Fourier transform infrared and ultraviolet–visible spectroscopy), were used to solve this data gap. A treatment system was proposed: electro-coagulation (EC) and electro-oxidation (EO). Optimal conditions (maximum COD removal) were EC, I: 4.3 A, stirring: 120 revolutions per minute, and pH: 7; EO, added NaCl: 1.0 g L−1, distance between electrodes: 0.75 cm, I: 2 A, and pH: 7. Under optimal conditions COD, HA, and FA % removals were achieved: EC: 64, 69, and 63; EO: 83, 40, and 55; respectively. In EC, the % of biodegradable COD increased from 26 to 39 and in EO it increased from 39 to 58. The biodegradability index increased from 0.094 to 0.26 with EC and reached 0.46 with EO. The generated data allowed us to establish the transformations of organic matter in the process, which was useful for understanding the processes and functioning as a tool for improving treatment systems.
Hydrothermal Calcite Precipitation in Veins: Inspired by Experiments for Oxygen Isotope Fractionation between CO2 and Calcite from 1 °C to 150 °C
Authors: Morishita Yuichi
Published: May 2023

The oxygen isotope ratios of minerals are important for estimating the formation temperature of hydrothermal deposits. Calcite is generally found in most mining districts. The oxygen isotope ratio of hydrothermal calcite in isotopic equilibrium with a fluid depends on that of the fluid as well as the formation temperature. The isotope ratios of calcite are generally determined to measure the isotope ratios of CO2 generated via reaction with 100% phosphoric acid at 25 °C. This is why the oxygen isotope fractionation between CO2 and calcite at 25 °C is required to conduct the procedure. When using other carbonate minerals such as dolomite, ankerite, and siderite, the reaction requires higher temperatures. Therefore, the oxygen isotope fractionation between CO2 and calcite at higher temperatures should be known because the laboratory standard sample of carbonates is usually calcite. Here, the oxygen isotope fractionation in CO2 during the reaction of calcite with phosphoric acid at temperatures between 1 °C and 150 °C was thoroughly determined in the first half, and the value can be represented by the following equation: 1000 lnα = 0.494 (106/T2) + 4.64. The experiments raised questions such as the equilibrium vs. kinetics issue in isotopic reactions in the formation of hydrothermal ore deposits. The raised issue is discussed in the second half based on the findings of previous isotope studies in deposits.
Prognostic Value of Lymph Node Density in Lingual Squamous Cell Carcinoma
Authors: Navarro Cuéllar Carlos , Sada Urmeneta Ángela , Lorenzo Marcos Raquel , Antúnez-Conde Raúl , López López Ana , del Castillo Pardo de Vera José Luis , González Martín-Moro Javier , Cebrián Carretero José Luis , Alijo Serrano Francisco , Dell’Aversana Orabona Giovanni , Zamorano-León Jose J. , Navarro Cuéllar Ignacio
Published: May 2023

Lymph node density (LND)—the proportion of positive nodes among the total number of resected nodes—has emerged as a reliable prognostic factor in solid tumors. This study aims to assess the importance of LND in lingual squamous cell carcinoma (LSCC) and its prognostic involvement. A retrospective longitudinal study with 62 patients was performed. All patients were diagnosed with LSCC and submitted for tumor resection and neck dissection. Patients were stratified into low (<0.04) and high risk (≥0.04) based on LND. We analyzed the impact of LND on overall survival (OS) and disease-free survival (DFS), as well as the relationship between LND and the pathological staging, the involvement of positive margins, depth of invasion (DOI) and perineural infiltration. This study provides a substantial relationship between lymph node density (LND), overall survival (OS) and disease-free survival (DFS) in lingual squamous cell carcinoma (LSCC). A statistically significant distribution was found between LND, perineural infiltration and pathological staging, whereas no association was found with the rest of the prognostic variables analyzed.
Picture-Perfect Fish Stories: Homemaking through American Tall Tale Photographic Postcards
Authors: Scholtes Esther
Published: May 2023

Photographic postcards featuring farmer culture on the American Great Plains hold a tangled relationship to the concept of home. As both personal and tactile keepsakes to be taken home after travel and souvenirs directed to loved ones, the postcard bridges spaces of home, travel, and migration. Furthermore, postcards are significant vehicles in storytelling and community building. In the early twentieth century, a peculiar type of photographic postcard became popular in the Midwest and Great Plains regions depicting farmers with outrageously oversized crops and livestock. This article explores photographic postcards by William H. Martin (1865–1940) that equivocally glorify white farmer culture and their presumed economic productivity. It posits that through an elaborate act of photomontage, these photographic cards demonstrate the boundaries of home and convey ‘homeland’ as an ambiguous landscape.
Ionospheric Electron Density Model by Electron Density Grid Deep Neural Network (EDG-DNN)
Authors: Chen Zhou , An Bokun , Liao Wenti , Wang Yungang , Tang Rongxin , Wang Jingsong , Deng Xiaohua
Published: May 2023

Electron density (or electron concentration) is a critical metric for characterizing the ionosphere’s mobility. Shortwave technologies, remote sensing systems, and satellite communications—all rely on precise estimations of electron density in the ionosphere. Using electron density profiles from FORMOSAT-3/COSMIC (Constellation Observation System for Meteorology, Ionosphere, and Climate) from 2006 to 2013, a four-dimensional physical grid model of ionospheric electron density was created in this study. The model, known as EDG-DNN, utilizes a DNN (deep neural network), and its output is the electron density displayed as a physical grid. The preprocessed electron density data are used to construct training, validation, and test sets. The International Reference Ionosphere model (IRI) was chosen as the reference model for the validation procedure since it predicts electron density well. This work used the IRI-2016 version. IRI-2016 produced more precise results of electron density when time and location parameters were input. This study compares the electron density provided by IRI-2016 to the EDG-DNN to assess the merits of the latter. The final results reveal that EDG-DNN has low-error and strong stability, can represent the global distribution structure of electron density, has some distinctive features of ionospheric electron density distribution, and predicts electron density well during quiet periods.
Regional Tropospheric Correction Model from GNSS–Saastamoinen–GPT2w Data for Zhejiang Province
Authors: Xu Chaoqian , Zhu Yiqun , Xu Xingyu , Kong Jian , Yao Yibin , Shi Junbo , Li Xiulong
Published: May 2023

Tropospheric delay models based on GNSS observations are essential for studying tropospheric changes. However, the uneven distribution of GNSS stations reduces the accuracy of GNSS tropospheric delay models in remote areas. Moreover, the accuracy of the tropospheric delay calculated by traditional models, which rely on meteorological parameters, is lower compared to the accuracy achieved by GNSS tropospheric models. At present, there are sufficient surface meteorological observation facilities around the world that can obtain surface meteorological parameters in real time. It is of great importance to make full use of the measured meteorological parameters to establish tropospheric correction models. Moreover, the empirical tropospheric models use free and open data, and one can obtain tropospheric parameters through the model without requiring any auxiliary information. We established a provincial real-time regional tropospheric fusion model using ground-based GNSS observations, a meteorological model, and empirical model data. Results showed that the tropospheric delay observations of the three models can be fused to establish a real-time tropospheric delay model with better accuracy and higher spatiotemporal resolution. The accuracy of Zenith Total Delay (ZTD) estimated by the fusion model reached 0.96/1.04/3.11 cm during the tropospheric quiet/active/typhoon period.
A Switching Strategy for Stabilization of Discrete-Time Switched Positive Time-Varying Delay Systems with All Modes Being Unstable and Application to Uncertain Data
Authors: Mouktonglang Thanasak , Poochinapan Kanyuta , Yimnet Suriyon
Published: May 2023

The stability problem of switched systems plays an essential role in the study of long-term behavior. In fact, systems containing both time delay and uncertainty terms may lead to performance degradation of those systems. Therefore, we are interested in the robust stability for discrete-time switched positive time-varying delay systems with interval uncertainties in the case of all modes being unstable. Based on the proposed time-scheduled multiple co-positive Lyapunov–Krasovskii functional of each mode, new sufficient conditions for the global uniform asymptotic stability of the systems are derived. An effective time-dependent switching law utilized in this work is mode-dependent dwell time. In addition, the robust stability criteria in an asymptotic sense are formulated for the systems without time-varying delay. Compared with the existing related works, our results are less conservative and more general than some previous research. Finally, two numerical examples are provided to illustrate the effectiveness and correctness of the developed theoretical results.
Partial Sums of the Normalized Le Roy-Type Mittag-Leffler Function
Authors: Frasin Basem Aref , Cotîrlă Luminiţa-Ioana
Published: May 2023

Recently, some researchers determined lower bounds for the normalized version of some special functions to its sequence of partial sums, e.g., Struve and Dini functions, Wright functions and Miller–Ross functions. In this paper, we determine lower bounds for the normalized Le Roy-type Mittag-Leffler function Fα,βγ(z)=z+∑n=1∞Anzn+1, where An=ΓβΓα(n−1)+βγ and its sequence of partial sums (Fα,βγ(z))m(z)=z+∑n=1mAnzn+1. Several examples of the main results are also considered.
Numerical Investigation by Cut-Cell Approach for Turbulent Flow through an Expanded Wall Channel
Authors: Abumandour Ramzy M. , El-Reafay Adel M. , Salem Khaled M. , Dawood Ahmed S.
Published: May 2023

The expanded wall channel backward-facing step (BFS) and axisymmetric diffuser plays an important role in the society of fluid dynamics. Using a cut-cell technique is an established new method to treat the inclined wall of an axisymmetric diffuser. Cut-cell handle to reach the shape of the inclined wall, an axisymmetric diffuser and complex geometry. It helps treat the boundary condition at the wall in an accurate physical way. The turbulent flow through the geometries is solved by using Reynolds averaged Navier-Stokes equations (RANS) with the standard k-ε model. A self-built FOTRAN code based on the finite volume method with the Semi-Implicit Method for Pressure Linked Equations (SIMPLE) algorithm for pressure velocity coupling is established and examined with published experimental data for two different geometries backward-facing step (BFS) and axisymmetric diffuser. The results of the new technique reflect good agreement between the numerical results and the experimental data. A parametric study of the impact of area ratios (2, 2.5, 3, 3.5) in a backward-facing step on pressure, velocity, and turbulent kinetic energy. The angles (7°, 10°, 14°) and area ratios (2, 2.5, 3, 3.5) effect of an axisymmetric diffuser on the streamlines, local skin friction, pressure, velocity, turbulent kinetic energy, and separation zone.
Existence and Qualitative Properties of Solution for a Class of Nonlinear Wave Equations with Delay Term and Variable-Exponents Nonlinearities
Authors: Karek Mohamed , Otmani Sadok , Bouhali Keltoum , Zennir Khaled , Elkhair Hatim M. , Hassan Eltegani I. , Alfedeel Alnadhief H. A. , Alarfaj Almonther
Published: May 2023

This article is devoted to a study of the question of existence (in time) of weak solutions and the derivation of qualitative properties of such solutions for the nonlinear viscoelastic wave equation with variable exponents and minor damping terms. By using the energy method combined with the Faedo–Galerkin method, the local and global existence of solutions are established. Then, the stability estimate of the solution is obtained by introducing a suitable Lyapunov function.
A Relational Semantics for Ockham’s Modalities
Authors: Falessi Davide , Schang Fabien
Published: May 2023

This article aims at providing some extension of the modal square of opposition in the light of Ockham’s account of modal operators. Moreover, we set forth some significant remarks on the de re–de dicto distinction and on the modal operator of contingency by means of a set-theoretic algebra called numbering semantics. This generalization starting from Ockham’s account of modalities will allow us to take into consideration whether Ockham’s account holds water or not, and in which case it should be changed.
Modeling Long Memory and Regime Switching with an MRS-FIEGARCH Model: A Simulation Study
Authors: Zhang Caixia , Shi Yanlin
Published: May 2023

Recent research suggests that long memory can be caused by regime switching and is easily confused with it. However, if the causes of confusion were properly controlled, they could be distinguished. Motivated by this idea, our study aims to distinguish between the long memory and regime switching of financial volatility. We firstly modeled the long memory and regime switching of volatility using the Fractionally Integrated Exponential GARCH (FIEGARCH) and Markov Regime-Switching EGARCH (MRS-EGARCH) frameworks, respectively, and performed a simulation study on their finite-sample properties when innovations followed a non-normal distribution. Subsequently, we demonstrated the confusion between the FIEGARCH and MRS-EGARCH processes using simulations. A recent study theoretically proved that the time-varying smoothing probability series can induce the presence of significant long memory in the regime-switching process. To control for its effect, the two-stage two-state FIEGARCH and MRS-FIEGARCH frameworks are proposed. The Monte Carlo studies showed that both frameworks can effectively distinguish between the pure FIEGARCH and pure MRS-EGARCH processes. When the MRS-FIEGARCH model was further employed to fit series generated with the MRS-FIEGARCH process, it outperformed the ordinary FIEGARCH model. Finally, an empirical study of NASDAQ index return was conducted to demonstrate that our MRS-FIEGARCH model can provide potentially more reliable long-memory estimates, identify the volatility states and outperform both the FIEGARCH and MRS-EGARCH models.
Fuzzy Logic and Decision Making Applied to Customer Service Optimization
Authors: Marín Díaz Gabriel , Carrasco González Ramón Alberto
Published: May 2023

In the literature, the Information Technology Infrastructure Library (ITIL) methodology recommends determining the priority of incident resolution based on the impact and urgency of interactions. The RFID model, based on the parameters of Recency, Frequency, Importance and Duration in the resolution of incidents, provides an individual assessment and a clustering of customers based on these factors. We can improve the traditional concept of waiting queues for customer service management by using a procedure that adds to the evaluation provided by RFID such additional factors as Impact, Urgency and Emotional character of each interaction. If we also include aspects such as Waiting Time and Contact Center Workload, we have a procedure that allows prioritizing interactions between the customer and the Contact Center dynamically and in real time. In this paper we propose to apply a model of unification of heterogeneous information in 2-tuple linguistic evaluations, to obtain a global evaluation of each interaction by applying the Analytic Hierarchy Process (AHP), and in this way be able to have a dynamic process of prioritization of interactions.
Chromosomal Instability in Genome Evolution: From Cancer to Macroevolution
Authors: Comaills Valentine , Castellano-Pozo Maikel
Published: May 2023

The integrity of the genome is crucial for the survival of all living organisms. However, genomes need to adapt to survive certain pressures, and for this purpose use several mechanisms to diversify. Chromosomal instability (CIN) is one of the main mechanisms leading to the creation of genomic heterogeneity by altering the number of chromosomes and changing their structures. In this review, we will discuss the different chromosomal patterns and changes observed in speciation, in evolutional biology as well as during tumor progression. By nature, the human genome shows an induction of diversity during gametogenesis but as well during tumorigenesis that can conclude in drastic changes such as the whole genome doubling to more discrete changes as the complex chromosomal rearrangement chromothripsis. More importantly, changes observed during speciation are strikingly similar to the genomic evolution observed during tumor progression and resistance to therapy. The different origins of CIN will be treated as the importance of double-strand breaks (DSBs) or the consequences of micronuclei. We will also explain the mechanisms behind the controlled DSBs, and recombination of homologous chromosomes observed during meiosis, to explain how errors lead to similar patterns observed during tumorigenesis. Then, we will also list several diseases associated with CIN, resulting in fertility issues, miscarriage, rare genetic diseases, and cancer. Understanding better chromosomal instability as a whole is primordial for the understanding of mechanisms leading to tumor progression.
The Cornea: No Difference in the Wound Healing Response to Injury Related to Whether, or Not, There’s a Bowman’s Layer
Authors: Wilson Steven E.
Published: May 2023

Bowman’s layer is an acellular layer in the anterior stroma found in the corneas of humans, most other primates, chickens, and some other species. Many other species, however, including the rabbit, dog, wolf, cat, tiger, and lion, do not have a Bowman’s layer. Millions of humans who have had photorefractive keratectomy over the past thirty plus years have had Bowman’s layer removed by excimer laser ablation over their central cornea without apparent sequelae. A prior study showed that Bowman’s layer does not contribute significantly to mechanical stability within the cornea. Bowman’s layer does not have a barrier function, as many cytokines and growth factors, as well as other molecules, such as EBM component perlecan, pass bidirectionally through Bowman’s layer in normal corneal functions, and during the response to epithelial scrape injury. We hypothesized that Bowman’s layer represents a visible indicator of ongoing cytokine and growth factor-mediated interactions that occur between corneal epithelial cells (and corneal endothelial cells) and stromal keratocytes that maintain the normal corneal tissue organization via negative chemotactic and apoptotic effects of modulators produced by the epithelium on stromal keratocytes. Interleukin-1 alpha, produced constitutively by corneal epithelial cells and endothelial cells, is thought to be one of these cytokines. Bowman’s layer is destroyed in corneas with advanced Fuchs’ dystrophy or pseudophakic bullous keratopathy when the epithelium becomes edematous and dysfunctional, and fibrovascular tissue commonly develops beneath and/or within the epithelium in these corneas. Bowman’s-like layers have been noted to develop surrounding epithelial plugs within the stromal incisions years after radial keratotomy. Although there are species-related differences in corneal wound healing, and even between strains within a species, these differences are not related to the presence or absence of Bowman’s layer.
Physico-Chemical Changes Induced by Gamma Irradiation on Some Structural Protein Extracts
Authors: Stanca Maria , Gaidau Carmen , Zaharescu Traian , Balan George-Alin , Matei Iulia , Precupas Aurica , Leonties Anca Ruxandra , Ionita Gabriela
Published: May 2023

In this study, the effect of gamma irradiation (10 kGy) on proteins extracted from animal hide, scales, and wool was evidenced by calorimetric (μDSC) and spectroscopic (IR, circular dichroism, and EPR) methods. Keratin was obtained from sheep wool, collagen and bovine gelatin from bovine hide, and fish gelatin from fish scales. The μDSC experiments evidenced that gamma irradiation influences the thermal stability of these proteins differently. The thermal stability of keratin decreases, while a resistance to thermal denaturation was noticed for collagen and gelatins after gamma irradiation. The analysis of the IR spectra demonstrated that gamma irradiation determines changes in the vibrational modes of the amide groups that are associated with protein denaturation, most meaningfully in the case of keratin. As evidenced by circular dichroism for all proteins considered, exposure to gamma radiation produces changes in the secondary structure that are more significant than those produced by UV irradiation. Riboflavin has different effects on the secondary structure of the investigated proteins, a stabilizing effect for keratin and fish gelatin and a destabilizing effect for bovine gelatin, observed in both irradiated and non-irradiated samples. The EPR spectroscopy evidences the presence, in the gamma-irradiated samples, of free radicals centered on oxygen, and the increase in their EPR signals over time due to the presence of riboflavin.
Molecular Mechanisms of Obesity-Induced Development of Insulin Resistance and Promotion of Amyloid-β Accumulation: Dietary Therapy Using Weak Organic Acids via Improvement of Lowered Interstitial Fluid pH
Authors: Marunaka Yoshinori
Published: May 2023

Insulin resistance is one of the etiologies of type 2 diabetes mellitus (T2DM) and has been suggested to contribute to the development of Alzheimer’s disease by promoting amyloid-β accumulation. Various causes of insulin resistance have been suggested; however, mechanisms of insulin resistance development remain to be elucidated in many respects. Elucidating the mechanisms underlying the development of insulin resistance is one of the key factors in developing methods to prevent the onset of T2DM and Alzheimer’s disease. It has been suggested that the body pH environment plays an important role in the control of cellular functions by regulating the action of hormones including insulin and the activity of enzymes and neurons, thereby maintaining homeostatic conditions of the body. This review introduces: (1) Mitochondrial dysfunction through oxidative stress caused by obesity-induced inflammation. (2) Decreased pH of interstitial fluid due to mitochondrial dysfunction. (3) Development of insulin resistance due to diminution of insulin affinity to its receptor caused by the lowered interstitial fluid pH. (4) Accelerated accumulation of amyloid-β due to elevated activities of β- and γ-secretases caused by the lowered interstitial fluid pH. (5) Diet therapies for improving insulin resistance with weak organic acids that act as bases in the body to raise the pH of lowered interstitial fluid and food factors that promote absorption of weak organic acids in the gut.
Relaxin-like Gonad-Stimulating Peptides in Asteroidea
Authors: Mita Masatoshi
Published: May 2023

Starfish relaxin-like gonad-stimulating peptide (RGP) is the first identified peptide hormone with gonadotropin-like activity in invertebrates. RGP is a heterodimeric peptide, comprising A and B chains with disulfide cross-linkages. Although RGP had been named a gonad-stimulating substance (GSS), the purified peptide is a member of relaxin-type peptide family. Thus, GSS was renamed as RGP. The cDNA of RGP encodes not only the A and B chains, but also signal and C-peptides. After the rgp gene is translated as a precursor, mature RGP is produced by eliminating the signal and C-peptides. Hitherto, twenty-four RGP orthologs have been identified or predicted from starfish in the orders Valvatida, Forcipulatida, Paxillosida, Spinulosida, and Velatida. The molecular evolution of the RGP family is in good accordance with the phylogenetic taxonomy in Asteroidea. Recently, another relaxin-like peptide with gonadotropin-like activity, RLP2, was found in starfish. RGP is mainly present in the radial nerve cords and circumoral nerve rings, but also in the arm tips, the gonoducts, and the coelomocytes. RGP acts on ovarian follicle cells and testicular interstitial cells to induce the production of 1-methyladenine (1-MeAde), a starfish maturation-inducing hormone. RGP-induced 1-MeAde production is accompanied by an increase in intracellular cyclic AMP levels. This suggests that the receptor for RGP (RGPR) is a G protein-coupled receptor (GPCR). Two types of GPCRs, RGPR1 and RGPR2, have been postulated as candidates. Furthermore, 1-MeAde produced by RGP not only induces oocyte maturation, but also induces gamete shedding, possibly by stimulating the secretion of acetylcholine in the ovaries and testes. Thus, RGP plays an important role in starfish reproduction, but its secretion mechanism is still unknown. It has also been revealed that RGP is found in the peripheral adhesive papillae of the brachiolaria arms. However, gonads are not developed in the larvae before metamorphosis. It may be possible to discover new physiological functions of RGP other than gonadotropin-like activity.
Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain
Authors: Ping Yashuang , Ohata Kenji , Kikushima Kenji , Sakamoto Takumi , Islam Ariful , Xu Lili , Zhang Hengsen , Chen Bin , Yan Jing , Eto Fumihiro , Nakane Chiho , Takao Keizo , Miyakawa Tsuyoshi , Kabashima Katsuya , Watanabe Miho , Kahyo Tomoaki , Yao Ikuko , Fukuda Atsuo , Ikegami Koji , Konishi Yoshiyuki , Setou Mitsutoshi
Published: May 2023

As an important neurotransmitter, glutamate acts in over 90% of excitatory synapses in the human brain. Its metabolic pathway is complicated, and the glutamate pool in neurons has not been fully elucidated. Tubulin polyglutamylation in the brain is mainly mediated by two tubulin tyrosine ligase-like (TTLL) proteins, TTLL1 and TTLL7, which have been indicated to be important for neuronal polarity. In this study, we constructed pure lines of Ttll1 and Ttll7 knockout mice. Ttll knockout mice showed several abnormal behaviors. Matrix-assisted laser desorption/ionization (MALDI) Imaging mass spectrometry (IMS) analyses of these brains showed increases in glutamate, suggesting that tubulin polyglutamylation by these TTLLs acts as a pool of glutamate in neurons and modulates some other amino acids related to glutamate.
The SLIT/ROBO Pathway in Liver Fibrosis and Cancer
Authors: Basha Sreenivasulu , Jin-Smith Brady , Sun Chunbao , Pi Liya
Published: May 2023

Liver fibrosis is a common outcome of most chronic liver insults/injuries that can develop into an irreversible process of cirrhosis and, eventually, liver cancer. In recent years, there has been significant progress in basic and clinical research on liver cancer, leading to the identification of various signaling pathways involved in tumorigenesis and disease progression. Slit glycoprotein (SLIT)1, SLIT2, and SLIT3 are secreted members of a protein family that accelerate positional interactions between cells and their environment during development. These proteins signal through Roundabout receptor (ROBO) receptors (ROBO1, ROBO2, ROBO3, and ROBO4) to achieve their cellular effects. The SLIT and ROBO signaling pathway acts as a neural targeting factor regulating axon guidance, neuronal migration, and axonal remnants in the nervous system. Recent findings suggest that various tumor cells differ in SLIT/ROBO signaling levels and show varying degrees of expression patterns during tumor angiogenesis, cell invasion, metastasis, and infiltration. Emerging roles of the SLIT and ROBO axon-guidance molecules have been discovered in liver fibrosis and cancer development. Herein, we examined the expression patterns of SLIT and ROBO proteins in normal adult livers and two types of liver cancers: hepatocellular carcinoma and cholangiocarcinoma. This review also summarizes the potential therapeutics of this pathway for anti-fibrosis and anti-cancer drug development.
Classification of Highly Divergent Viruses from DNA/RNA Sequence Using Transformer-Based Models
Authors: Sadad Tariq , Aurangzeb Raja Atif , Safran Mejdl , Imran  , Alfarhood Sultan , Kim Jungsuk
Published: May 2023

Viruses infect millions of people worldwide each year, and some can lead to cancer or increase the risk of cancer. As viruses have highly mutable genomes, new viruses may emerge in the future, such as COVID-19 and influenza. Traditional virology relies on predefined rules to identify viruses, but new viruses may be completely or partially divergent from the reference genome, rendering statistical methods and similarity calculations insufficient for all genome sequences. Identifying DNA/RNA-based viral sequences is a crucial step in differentiating different types of lethal pathogens, including their variants and strains. While various tools in bioinformatics can align them, expert biologists are required to interpret the results. Computational virology is a scientific field that studies viruses, their origins, and drug discovery, where machine learning plays a crucial role in extracting domain- and task-specific features to tackle this challenge. This paper proposes a genome analysis system that uses advanced deep learning to identify dozens of viruses. The system uses nucleotide sequences from the NCBI GenBank database and a BERT tokenizer to extract features from the sequences by breaking them down into tokens. We also generated synthetic data for viruses with small sample sizes. The proposed system has two components: a scratch BERT architecture specifically designed for DNA analysis, which is used to learn the next codons unsupervised, and a classifier that identifies important features and understands the relationship between genotype and phenotype. Our system achieved an accuracy of 97.69% in identifying viral sequences.
Structural Specificity of Polymorphic Forms of α-Synuclein Amyloid
Authors: Roterman Irena , Stapor Katarzyna , Konieczny Leszek
Published: May 2023

The structural transformation producing amyloids is a phenomenon that sheds new light on the protein folding problem. The analysis of the polymorphic structures of the α-synuclein amyloid available in the PDB database allows analysis of the amyloid-oriented structural transformation itself, but also the protein folding process as such. The polymorphic amyloid structures of α-synuclein analyzed employing the hydrophobicity distribution (fuzzy oil drop model) reveal a differentiation with a dominant distribution consistent with the micelle-like system (hydrophobic core with polar shell). This type of ordering of the hydrophobicity distribution covers the entire spectrum from the example with all three structural units (single chain, proto-fibril, super-fibril) exhibiting micelle-like form, through gradually emerging examples of local disorder, to structures with an extremely different structuring pattern. The water environment directing protein structures towards the generation of ribbon micelle-like structures (concentration of hydrophobic residues in the center of the molecule forming a hydrophobic core with the exposure of polar residues on the surface) also plays a role in the amyloid forms of α-synuclein. The polymorphic forms of α-synuclein reveal local structural differentiation with a common tendency to accept the micelle-like structuralization in certain common fragments of the polypeptide chain of this protein.
A CAF-Based Two-Cell Hybrid Co-Culture Model to Test Drug Resistance in Endometrial Cancers
Authors: Sulaiman Raed , De Pradip , Aske Jennifer C. , Lin Xiaoqian , Dale Adam , Gaster Kris , Espaillat Luis Rojas , Starks David , Dey Nandini
Published: May 2023

The management of advanced or recurrent endometrial cancers presents a challenge due to the development of resistance to treatments. The knowledge regarding the role of the tumor microenvironment (TME) in determining the disease’s progression and treatment outcome has evolved in recent years. As a TME component, cancer-associated fibroblasts (CAFs) are essential in developing drug-induced resistance in various solid tumors, including endometrial cancers. Hence, an unmet need exists to test the role of endometrial CAF in overcoming the roadblock of resistance in endometrial cancers. We present a novel tumor–TME two-cell ex vivo model to test CAF’s role in resisting the anti-tumor drug, paclitaxel. Endometrial CAFs, both NCAFs (tumor-adjacent normal-tissue-derived CAFs) and TCAFs (tumor-tissue-derived CAFs) were validated by their expression markers. Both TCAFs and NCAFs expressed positive markers of CAF, including SMA, FAP, and S100A4, in varying degrees depending on the patients, while they consistently lacked the negative marker of CAF, EpCAM, as tested via flow cytometry and ICC. CAFs expressed TE-7 and immune marker, PD-L1, via ICC. CAFs better resisted the growth inhibitory effect of paclitaxel on endometrial tumor cells in 2D and 3D formats compared to the resistance of the tumoricidal effect of paclitaxel in the absence of CAFs. TCAF resisted the growth inhibitory effect of paclitaxel on endometrial AN3CA and RL-95-2 cells in an HyCC 3D format. Since NCAF similarly resisted the growth inhibitor action of paclitaxel, we tested NCAF and TCAF from the same patient to demonstrate the protective action of NCAF and TCAF in resisting the tumoricidal effect of paclitaxel in AN3CA in both 2D and 3D matrigel formats. Using this hybrid co-culture CAF and tumor cells, we established a patient-specific, laboratory-friendly, cost-effective, and time-sensitive model system to test drug resistance. The model will help test the role of CAFs in developing drug resistance and contribute to understanding tumor cell-CAF dialogue in gynecological cancers and beyond.
Impact of Angiogenic and Cardiovascular Biomarkers for Prediction of Placental Dysfunction in the First Trimester of Pregnancy
Authors: Nan Madalina Nicoleta , García-Osuna Álvaro , Mora Josefina , Trilla Cristina , Antonijuan Assumpta , Orantes Vanesa , Cruz-Lemini Mónica , Blanco-Vaca Francisco , Llurba Elisa
Published: May 2023

Algorithms for first-trimester prediction of pre-eclampsia usually include maternal risk factors, blood pressure, placental growth factor (PlGF), and uterine artery Doppler pulsatility index. However, these models lack sensitivity for the prediction of late-onset pre-eclampsia and other placental complications of pregnancy, such as small for gestational age infants or preterm birth. The aim of this study was to assess the screening performance of PlGF, soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), uric acid, and high-sensitivity cardiac troponin T (hs-TnT) in the prediction of adverse obstetric outcomes related to placental insufficiency. This retrospective case–control study was based on a cohort of 1390 pregnant women, among which 210 presented pre-eclampsia, small for gestational age infants, or preterm birth. Two hundred and eight women with healthy pregnancies were selected as controls. Serum samples were collected between weeks 9 and 13 of gestation, and maternal serum concentrations of PlGF, sFlt-1, NT-proBNP, uric acid, and hs-TnT were measured. Multivariate regression analysis was used to generate predictive models combining maternal factors with the above-mentioned biomarkers. Women with placental dysfunction had lower median concentrations of PlGF (25.77 vs. 32.00 pg/mL; p < 0.001), sFlt-1 (1212.0 vs. 1363.5 pg/mL; p = 0.001), and NT-proBNP (51.22 vs. 68.71 ng/L; p < 0.001) and higher levels of uric acid (193.66 µmol/L vs. 177.40 µmol/L; p = 0.001). There was no significant difference between groups regarding the sFlt-1/PlGF ratio. Hs-TnT was not detected in 70% of the maternal serums analyzed. Altered biomarker concentrations increased the risk of the analyzed complications both in univariate and multivariate analyses. The addition of PlGF, sFlt-1, and NT-proBNP to maternal variables improved the prediction of pre-eclampsia, small for gestational age infants, and preterm birth (area under the curve: 0.710, 0.697, 0.727, and 0.697 vs. 0.668, respectively). Reclassification improvement was greater in maternal factors plus the PlGF model and maternal factors plus the NT-p roBNP model (net reclassification index, NRI: 42.2% and 53.5%, respectively). PlGF, sFlt-1, NT-proBNP, and uric acid measurements in the first trimester of pregnancy, combined with maternal factors, can improve the prediction of adverse perinatal outcomes related to placental dysfunction. In addition to PlGF, uric acid and NT-proBNP are two promising predictive biomarkers for placental dysfunction in the first trimester of pregnancy.
Umbilical-Cord-Derived Mesenchymal Stromal Cells Modulate 26 Out of 41 T Cell Subsets from Systemic Sclerosis Patients
Authors: Laranjeira Paula , dos Santos Francisco , Salvador Maria João , Simões Irina N. , Cardoso Carla M. P. , Silva Bárbara M. , Henriques-Antunes Helena , Corte-Real Luísa , Couceiro Sofia , Monteiro Filipa , Santos Carolina , Santiago Tânia , da Silva José A. P. , Paiva Artur
Published: May 2023

Systemic sclerosis (SSc) is an immune-mediated disease wherein T cells are particularly implicated, presenting a poor prognosis and limited therapeutic options. Thus, mesenchymal-stem/stromal-cell (MSC)-based therapies can be of great benefit to SSc patients given their immunomodulatory, anti-fibrotic, and pro-angiogenic potential, which is associated with low toxicity. In this study, peripheral blood mononuclear cells from healthy individuals (HC, n = 6) and SSc patients (n = 9) were co-cultured with MSCs in order to assess how MSCs affected the activation and polarization of 58 different T cell subsets, including Th1, Th17, and Treg. It was found that MSCs downregulated the activation of 26 out of the 41 T cell subsets identified within CD4+, CD8+, CD4+CD8+, CD4−CD8−, and γδ T cells in SSc patients (HC: 29/42) and affected the polarization of 13 out of 58 T cell subsets in SSc patients (HC: 22/64). Interestingly, SSc patients displayed some T cell subsets with an increased activation status and MSCs were able to downregulate all of them. This study provides a wide-ranging perspective of how MSCs affect T cells, including minor subsets. The ability to inhibit the activation and modulate the polarization of several T cell subsets, including those implicated in SSc’s pathogenesis, further supports the potential of MSC-based therapies to regulate T cells in a disease whose onset/development may be due to immune system’s malfunction.
Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma
Authors: Kurota Yuta , Takeda Yuji , Ichiyanagi Osamu , Saitoh Shinichi , Ito Hiromi , Naito Sei , Asao Hironobu , Tsuchiya Norihiko
Published: May 2023

Background: The regulation of the redox balance in the tumor microenvironment is thought to be an adaptive response of tumor cells to hypoxic environments. In recent years, it has been reported that the hemoglobin β-chain (HBB), which is involved in scavenging reactive oxygen species (ROS), is expressed in several carcinomas. However, the relationship between HBB expression and the prognosis of renal cell carcinoma (RCC) remains unclear. Methods: HBB expression was immunohistochemically analyzed in 203 nonmetastatic clear cell RCC (ccRCC) cases. Cell proliferation, invasion, and ROS production were measured in ccRCC cell lines treated with HBB-specific siRNA. Results: The prognosis of HBB-positive patients was worse than that of HBB-negative patients. Cell proliferation and invasion were inhibited, and ROS production was increased by treatment with HBB-specific siRNA. Oxidative stress increased HBB expression in cells exposed to H2O2. Conclusions: HBB expression in ccRCC contributes to cancer cell proliferation by suppressing ROS production under hypoxic conditions. Taken together with clinical results and in vitro experiments, HBB expression may serve as a new prognostic biomarker for RCC in the future.
Evaluation of the Autologous Genetically Enriched Leucoconcentrate on the Lumbar Spinal Cord Morpho-Functional Recovery in a Mini Pig with Thoracic Spine Contusion Injury
Authors: Garifulin Ravil , Davleeva Maria , Izmailov Andrei , Fadeev Filip , Markosyan Vage , Shevchenko Roman , Minyazeva Irina , Minekayev Tagir , Lavrov Igor , Islamov Rustem
Published: May 2023

Background: Pathological changes associated with spinal cord injury (SCI) can be observed distant, rostral, or caudal to the epicenter of injury. These remote areas represent important therapeutic targets for post-traumatic spinal cord repair. The present study aimed to investigate the following in relation to SCI: distant changes in the spinal cord, peripheral nerve, and muscles. Methods: The changes in the spinal cord, the tibial nerve, and the hind limb muscles were evaluated in control SCI animals and after intravenous infusion of autologous leucoconcentrate enriched with genes encoding neuroprotective factors (VEGF, GDNF, and NCAM), which previously demonstrated a positive effect on post-traumatic restoration. Results: Two months after thoracic contusion in the treated mini pigs, a positive remodeling of the macro- and microglial cells, expression of PSD95 and Chat in the lumbar spinal cord, and preservation of the number and morphological characteristics of the myelinated fibers in the tibial nerve were observed and were aligned with hind limb motor recovery and reduced soleus muscle atrophy. Conclusion: Here, we show the positive effect of autologous genetically enriched leucoconcentrate-producing recombinant neuroprotective factors on targets distant to the primary lesion site in mini pigs with SCI. These findings open new perspectives for the therapy of SCI.
Prognostic Value of the Selected Polymorphisms in the CD36 Gene in the Domain-Encoding Lipid-Binding Region at a 10-Year Follow-Up for Early-Onset CAD Patients
Authors: Bartoszewicz Michał , Rać Monika
Published: May 2023

The polymorphism of the CD36 gene may have a decisive impact on the formation and progression of atherosclerotic changes. The aim of the study was to confirm the prognostic values of the previously studied polymorphisms in the CD36 gene within a 10-year follow-up period. This is the first published report confirming the long-term observation of patients with CAD. The study group covered 100 early-onset CAD patients. It included 26 women not older than 55 years and 74 men not older than 50 years, tested in a ten-year study as a long-term follow-up after the first cardiovascular episode. There are no notable differences between the CD36 variants and the number of fatalities during observation, fatalities due to cardiological reasons, cases of myocardial infarction within a ten-year observation period, hospitalizations for cardiovascular issues, all cardiovascular occurrences, and the number of months lived. We have shown that the CD36 variants analyzed in this study do not appear to be related to the risk of early CAD occurrence in the Caucasian population in long-term observation.
Links between Diet, Intestinal Anaerobes, Microbial Metabolites and Health
Authors: Duncan Sylvia H. , Conti Elena , Ricci Liviana , Walker Alan W.
Published: May 2023

A dense microbial community resides in the human colon, with considerable inter-individual variability in composition, although some species are relatively dominant and widespread in healthy individuals. In disease conditions, there is often a reduction in microbial diversity and perturbations in the composition of the microbiota. Dietary complex carbohydrates that reach the large intestine are important modulators of the composition of the microbiota and their primary metabolic outputs. Specialist gut bacteria may also transform plant phenolics to form a spectrum of products possessing antioxidant and anti-inflammatory activities. Consumption of diets high in animal protein and fat may lead to the formation of potentially deleterious microbial products, including nitroso compounds, hydrogen sulphide, and trimethylamine. Gut anaerobes also form a range of secondary metabolites, including polyketides that may possess antimicrobial activity and thus contribute to microbe–microbe interactions within the colon. The overall metabolic outputs of colonic microbes are derived from an intricate network of microbial metabolic pathways and interactions; however, much still needs to be learnt about the subtleties of these complex networks. In this review we consider the multi-faceted relationships between inter-individual microbiota variation, diet, and health.
Impedimetric DNA Sensor Based on Electropolymerized N-Phenylaminophenothiazine and Thiacalix[4]arene Tetraacids for Doxorubicin Determination
Authors: Kulikova Tatjana , Shiabiev Igor , Padnya Pavel , Rogov Alexey , Evtugyn Gennady , Stoikov Ivan , Porfireva Anna
Published: May 2023

Electrochemical DNA sensors are highly demanded for fast and reliable determination of antitumor drugs and chemotherapy monitoring. In this work, an impedimetric DNA sensor has been developed on the base of a phenylamino derivative of phenothiazine (PhTz). A glassy carbon electrode was covered with electrodeposited product of PhTz oxidation obtained through multiple scans of the potential. The addition of thiacalix[4]arene derivatives bearing four terminal carboxylic groups in the substituents of the lower rim improved the conditions of electropolymerization and affected the performance of the electrochemical sensor depending on the configuration of the macrocyclic core and molar ratio with PhTz molecules in the reaction medium. Following that, the deposition of DNA by physical adsorption was confirmed by atomic force microscopy and electrochemical impedance spectroscopy. The redox properties of the surface layer obtained changed the electron transfer resistance in the presence of doxorubicin due to its intercalating DNA helix and influencing charge distribution on the electrode interface. This made it possible to determine 3 pM–1 nM doxorubicin in 20 min incubation (limit of detection 1.0 pM). The DNA sensor developed was tested on a bovine serum protein solution, Ringer–Locke’s solution mimicking plasma electrolytes and commercial medication (doxorubicin-LANS) and showed a satisfactory recovery rate of 90–105%. The sensor could find applications in pharmacy and medical diagnostics for the assessment of drugs able to specifically bind to DNA.