bluuebunny/crossref_metadata_2025 huggingface dataset:
Wireless Sensor Network Lifetime Extension via K-Medoids and MCDM Techniques in Uncertain Environment
Authors: Sen Supriyan , Sahoo Laxminarayan , Tiwary Kalishankar , Simic Vladimir , Senapati Tapan
Published: March 2023

In this study, the multi-criteria decision-making (MCDM) technique is used in collaboration with K-medoids clustering to establish a novel algorithm for extending the lifetime of wireless sensor networks (WSNs) in the presence of uncertainty. One of the most important problems in WSNs is the energy consumption. Furthermore, extending the network lifetime in WSNs is highly dependent on selecting the appropriate cluster heads (CHs), and this can be a challenging task for the decision makers. In addition, parameters associated with WSNs are completely unexpected due to uncertainty. Therefore, after proposing K-medoids clustering and a MCDM technique, we have developed a novel algorithm for extending the lifetime of WSNs. As criteria, we have taken into account four important aspects of the proposed WSN: the distance from sink, average distance of cluster nodes, reliability of cluster and residual energy. To represent uncertain parameters in this work, we have considered triangular fuzzy numbers (TFNs). Finally, an experiment involving a WSN under uncertainty was investigated, and the findings have been graphically displayed. In this research, it has been observed that the proposed strategy with the novel algorithm exhibits 42% greater network lifetime as compared with a hybrid energy efficient distributed (HEED) algorithm and 11% and 18% with respect to optimal clustering artificial bee colony (OCABC) and particle swarm optimization (PSO) applied to a clustering optimization problem. We have also conducted statistical hypotheses for the purpose of confirming the presented outcomes.
Analyzing and Modeling the Spatial-Temporal Changes and the Impact of GLOTI Index on Precipitation in the Marmara Region of Türkiye
Authors: Aalijahan Mehdi , Karataş Atilla , Lupo Anthony R. , Efe Bahtiyar , Khosravichenar Azra
Published: March 2023

Precipitation is a particularly important part of the Earth’s hydrological cycle and, therefore, is a necessary variable for maintaining natural balance. This study investigated past, present, and future changes in precipitation in the Marmara region, and examined the effects of global warming on this variable. The study period was from 1960 to 2020, and the climate data of 15 synoptic stations in the Marmara region were used for this purpose. To achieve the objectives of the study, linear and 6th order polynomial regression, ombrothermic and hythergraph diagrams, geostatistical models, Mann-Kendall test, Pearson correlation, standard Z-scores, and multi-layer perceptron artificial neural network models (MLP-ANN) were used to model and predict precipitation. The results of the linear regression analysis showed that of the 15 stations, 6 stations had an increasing trend, 6 stations had a trendless pattern, and 3 stations had a decreasing trend. In terms of periodic analysis, the main downward trend started in 1964 and continued until 1992, while the main periodic upward trend started in 1992 and continued until 2016. The synoptic stations in the Marmara region showed a lack of precipitation over six to seven months of the year, and the precipitation changes in the region were stronger than the temperature changes. In addition, the highest precipitation was observed on the southeast coast of the Black Sea, and the lowest precipitation was observed in the eastern parts of the region. Moreover, except for the Bilecik and Kocaeli stations, the changes in the long-term trend of precipitation at the other stations were significant. Among the 15 stations, only the Kocaeli and Sarıyer stations showed a positive correlation with global temperature during the annual period. In addition, the developed ANN model was accurate in simulating and predicting precipitation and showed an upward trend over the next seven years.
EUV Beam–Foil Spectra of Germanium and a Blind-Spot Problem in Spectroscopy
Authors: Träbert Elmar
Published: March 2023

Beam–foil extreme-ultraviolet survey spectra of Ge (Z=32) are presented. The data have been garnered at the performance limit of the heavy-ion accelerator available, with a correspondingly limited statistical and calibrational reliability. However, the Ge spectra have been recorded at various delays after excitation, and this technique points to a possible blind spot in some other spectroscopic techniques, and thus in the literature coverage. A similarly patchy coverage can be noted in various atomic structure computations. The experimental and theoretical gaps seem to be correlated.
Hearing Healthcare Professionals’ Views about Over-The-Counter (OTC) Hearing Aids: Analysis of Retrospective Survey Data
Authors: Manchaiah Vinaya , Sharma Anu , Rodrigo Hansapani , Bailey Abram , De Sousa Karina C. , Swanepoel De Wet
Published: March 2023

Over-the-counter hearing aids have been available to consumers in the US since 17 October 2022 following a ruling by the Food and Drug Administration. However, their reception by hearing healthcare professionals (HHP) has been mixed, and concerns have been expressed by many HHPs. The aim of this study was to examine the concerns that HHPs have towards over-the-counter (OTC) hearing aids. The study used a retrospective survey design. The survey data of HHPs (n = 730) was obtained from Hearing Tracker. A 22-item structured questionnaire was administered using a Question Scout platform. Descriptive analyses examined reported areas of concern and a Fisher’s exact test examined the relationship between demographics and responses. A cluster analysis with partitioning around medoids (PAM) was used to identify a sub-group of participants based on responses. Nearly half of HHPs who participated reported that they will support patients with OTC hearing aids purchased elsewhere, whereas a quarter reported that they will sell OTC hearing aids in their clinic or website. HHPs expressed over 70% agreement in ‘concern’ statements in 14 of the 17 items. Issues about safety, counseling, and audiological care were the key concerns expressed by HHPs about OTC hearing aids. Some demographics (i.e., profession, primary position) were associated with responses to some statements. Two groups were identified based on the responses to concern statements. The HHPs in the first cluster ‘OTC averse’ (51%) agreed on all the 17 concern statements, whereas the second cluster ‘OTC apprehensive’ (49%) had some items rated as disagree (i.e., consumers will give up on amplification) and neither agree nor disagree (i.e., do not provide good value, warranties and return periods will be worse), and remaining items were rated as agree. OTC hearing aids were initiated to improve affordability, accessibility, and hearing aid uptake and are currently a rapidly emerging category of hearing devices. Overall, the results of the current study indicate that HHPs have serious concerns about OTC hearing aids. HHP concerns cited in this study provide useful feedback to stakeholders (e.g., HHP professional agencies, FDA, industry, and insurance payers) involved in improving OTC hearing aid implementation.
Stabilization of the Moving Front Solution of the Reaction-Diffusion-Advection Problem
Authors: Nefedov Nikolay , Polezhaeva Elena , Levashova Natalia
Published: March 2023

We consider the initial-boundary value problem of reaction-diffusion-advection that has a solution of a front form. The statement comes from the theory of wave physics. We study the question of the solution stabilizing to the stationary one. Proof of the stabilization theorem is based on the concepts of upper and lower solutions and corollaries from comparison theorems. The upper and lower solutions with large gradients are constructed as modifications of the formal moving front asymptotic approximation in a small parameter. The main idea of the proof is to show that the upper and lower solutions of the initial-boundary value problem get into the attraction domain of the asymptotically stable stationary solution on a sufficiently large time interval. The study conducted in this work gives an answer about the non-local attraction domain of the stationary solution and can give some stationing criteria. The results are illustrated by computational examples.
On Symbol-Pair Distance of a Class of Constacyclic Codes of Length 3ps over Fpm+uFpm
Authors: Dinh Hai Q. , Thi Hiep L. , Tansuchat Roengchai
Published: March 2023

Let p≠3 be any prime. In this paper, we compute symbol-pair distance of all γ-constacyclic codes of length 3ps over the finite commutative chain ring R=Fpm+uFpm, where γ is a unit of R which is not a cube in Fpm. We give the necessary and sufficient condition for a symbol-pair γ-constacyclic code to be an MDS symbol-pair code. Using that, we provide all MDS symbol-pair γ-constacyclic codes of length 3ps over R. Some examples of the symbol-pair distance of γ-constacyclic codes of length 3ps over R are provided.
An Inertial Subgradient Extragradient Method for Approximating Solutions to Equilibrium Problems in Hadamard Manifolds
Authors: Oyewole Olawale Kazeem , Reich Simeon
Published: March 2023

In this work, we are concerned with the iterative approximation of solutions to equilibrium problems in the framework of Hadamard manifolds. We introduce a subgradient extragradient type method with a self-adaptive step size. The use of a step size which is allowed to increase per iteration is to avoid the dependence of our method on the Lipschitz constant of the underlying operator as has been the case in recent articles in this direction. In general, operators satisfying weak monotonicity conditions seem to be more applicable in practice. By using inertial and viscosity techniques, we establish a convergence result for solving a pseudomonotone equilibrium problem under some appropriate conditions. As applications, we use our method to solve some theoretical optimization problems. Finally, we present some numerical illustrations in order to demonstrate the quantitative efficacy and superiority of our proposed method over a previous method present in the literature.
Development of All-Solid-State Li-Ion Batteries: From Key Technical Areas to Commercial Use
Authors: Bubulinca Constantin , Kazantseva Natalia E. , Pechancova Viera , Joseph Nikhitha , Fei Haojie , Venher Mariana , Ivanichenko Anna , Saha Petr
Published: March 2023

Innovation in the design of Li-ion rechargeable batteries is necessary to overcome safety concerns and meet energy demands. In this regard, a new generation of Li-ion batteries (LIBs) in the form of all-solid-state batteries (ASSBs) has been developed, attracting a great deal of attention for their high-energy density and excellent mechanical-electrochemical stability. This review describes the current state of research and development on ASSB technology. To this end, study of the literature and patents as well as market analysis over the last two decades were carried out, highlighting how scientific achievements have informed the application of commercially profitable ASSBs. Analyzing the patents registered over the past 20 years revealed that the number of them had increased exponentially-from only few per year in early 2000 to more than 342 in 2020. Published literature and patents on the topic declare a solid-state electrolyte (SSE) to be the main component of ASSBs, and most patented examples are referred to as solid inorganic electrolytes (SIEs), followed by solid polymer electrolytes (SPEs) and solid hybrid electrolytes (SHEs) in popularity. Investigation of company websites, social media profiles, reports, and academic publications identified 93 companies associated with ASSBs. A list of leading businesses in the solid-state battery sector was compiled, out of which 36 provided information on the ASSB units in their product portfolio for detailed analysis.
Development of a Molecular-Subtype-Associated Immune Prognostic Signature That Can Be Recognized by MRI Radiomics Features in Bladder Cancer
Authors: Liu Shenghua , Chen Haotian , Zheng Zongtai , He Yanyan , Yao Xudong
Published: March 2023

Background: Bladder cancer (BLCA) is highly heterogeneous with distinct molecular subtypes. This research aimed to investigate the heterogeneity of different molecular subtypes from a tumor microenvironment perspective and develop a molecular-subtype-associated immune prognostic signature that can be recognized by MRI radiomics features. Methods: Individuals with BLCA in The Cancer Genome Atlas (TCGA) and IMvigor210 were classified into luminal and basal subtypes according to the UNC classification. The proportions of tumor-infiltrating immune cells (TIICs) were examined using The Cell Type Identification by Estimating Relative Subsets of RNA Transcripts algorithm. Immune-linked genes that were expressed differentially between luminal and basal subtypes and associated with prognosis were selected to develop the immune prognostic signature (IPS) and utilized for the classification of the selected individuals into low- and high-risk groups. Functional enrichment analysis (GSEA) was performed on the IPS. The data from RNA-sequencing and MRI images of 111 BLCA samples in our center were utilized to construct a least absolute shrinkage and selection operator (LASSO) model for the prediction of patients’ IPSs. Results: Half of the TIICs showed differential distributions between the luminal and basal subtypes. IPS was highly associated with molecular subtypes, critical immune checkpoint gene expression, prognoses, and immunotherapy response. The prognostic value of the IPS was further verified through several validation data sets (GSE32894, GSE31684, GSE13507, and GSE48277) and meta-analysis. GSEA revealed that some oncogenic pathways were co-enriched in the group at high risk. A novel performance of a LASSO model developed as per ten radiomics features was achieved in terms of IPS prediction in both the validation (area under the curve (AUC): 0.810) and the training (AUC: 0.839) sets. Conclusions: Dysregulation of TIICs contributed to the heterogeneity between the luminal and basal subtypes. The IPS can facilitate molecular subtyping, prognostic evaluation, and personalized immunotherapy. A LASSO model developed as per the MRI radiomics features can predict the IPSs of affected individuals.
Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization
Authors: Roy Ada , Chan Mine Emeric , Gaifas Lorenzo , Leyrat Cédric , Volchkova Valentina A. , Baudin Florence , Martinez-Gil Luis , Volchkov Viktor E. , Karlin David G. , Bourhis Jean-Marie , Jamin Marc
Published: March 2023

The protein C is a small viral protein encoded in an overlapping frame of the P gene in the subfamily Orthoparamyxovirinae. This protein, expressed by alternative translation initiation, is a virulence factor that regulates viral transcription, replication, and production of defective interfering RNA, interferes with the host-cell innate immunity systems and supports the assembly of viral particles and budding. We expressed and purified full-length and an N-terminally truncated C protein from Tupaia paramyxovirus (TupV) C protein (genus Narmovirus). We solved the crystal structure of the C-terminal part of TupV C protein at a resolution of 2.4 Å and found that it is structurally similar to Sendai virus C protein, suggesting that despite undetectable sequence conservation, these proteins are homologous. We characterized both truncated and full-length proteins by SEC-MALLS and SEC-SAXS and described their solution structures by ensemble models. We established a mini-replicon assay for the related Nipah virus (NiV) and showed that TupV C inhibited the expression of NiV minigenome in a concentration-dependent manner as efficiently as the NiV C protein. A previous study found that the Orthoparamyxovirinae C proteins form two clusters without detectable sequence similarity, raising the question of whether they were homologous or instead had originated independently. Since TupV C and SeV C are representatives of these two clusters, our discovery that they have a similar structure indicates that all Orthoparamyxovirine C proteins are homologous. Our results also imply that, strikingly, a STAT1-binding site is encoded by exactly the same RNA region of the P/C gene across Paramyxovirinae, but in different reading frames (P or C), depending on which cluster they belong to.
The Roles of Exosomes in Metastasis of Sarcoma: From Biomarkers to Therapeutic Targets
Authors: Tan Linyun , Wang Yitian , Hu Xin , Min Li
Published: March 2023

Sarcoma is a heterogeneous group of mesenchymal neoplasms with a high rate of lung metastasis. The cellular mechanisms responsible for sarcoma metastasis remain poorly understood. Furthermore, there are limited efficacious therapeutic strategies for treating metastatic sarcoma. Improved diagnostic and therapeutic modalities are of increasing importance for the treatment of sarcoma due to their high mortality in the advanced stages of the disease. Recent evidence demonstrates that the exosome, a type of extracellular vesicle released by virtually all cells in the body, is an important facilitator of intercellular communication between the cells and the surrounding environment. The exosome is gaining significant attention among the medical research community, but there is little knowledge about how the exosome affects sarcoma metastasis. In this review, we summarize the multifaceted roles of sarcoma-derived exosomes in promoting the process of metastasis via the formation of pre-metastatic niche (PMN), the regulation of immunity, angiogenesis, vascular permeability, and the migration of sarcoma cells. We also highlight the potential of exosomes as innovative diagnostic and prognostic biomarkers as well as therapeutic targets in sarcoma metastasis.
I Choose You: Selecting Accurate Reference Genes for qPCR Expression Analysis in Reproductive Tissues in Arabidopsis thaliana
Authors: Ferreira Maria João , Silva Jessy , Pinto Sara Cristina , Coimbra Sílvia
Published: March 2023

Quantitative real-time polymerase chain reaction (qPCR) is a widely used method to analyse the gene expression pattern in the reproductive tissues along with detecting gene levels in mutant backgrounds. This technique requires stable reference genes to normalise the expression level of target genes. Nonetheless, a considerable number of publications continue to present qPCR results normalised to a single reference gene and, to our knowledge, no comparative evaluation of multiple reference genes has been carried out in specific reproductive tissues of Arabidopsis thaliana. Herein, we assessed the expression stability levels of ten candidate reference genes (UBC9, ACT7, GAPC-2, RCE1, PP2AA3, TUA2, SAC52, YLS8, SAMDC and HIS3.3) in two conditional sets: one across flower development and the other using inflorescences from different genotypes. The stability analysis was performed using the RefFinder tool, which combines four statistical algorithms (geNorm, NormFinder, BestKeeper and the comparative ΔCt method). Our results showed that RCE1, SAC52 and TUA2 had the most stable expression in different flower developmental stages while YLS8, HIS3.3 and ACT7 were the top-ranking reference genes for normalisation in mutant studies. Furthermore, we validated our results by analysing the expression pattern of genes involved in reproduction and examining the expression of these genes in published mutant backgrounds. Overall, we provided a pool of appropriate reference genes for expression studies in reproductive tissues of A. thaliana, which will facilitate further gene expression studies in this context. More importantly, we presented a framework that will promote a consistent and accurate analysis of gene expression in any scientific field. Simultaneously, we highlighted the relevance of clearly defining and describing the experimental conditions associated with qPCR to improve scientific reproducibility.
Ligand-Receptor Interactions of Lamivudine: A View from Charge Density Study and QM/MM Calculations
Authors: Korlyukov Alexander A. , Stash Adam. I. , Romanenko Alexander R. , Trzybiński Damian , Woźniak Krzysztof , Vologzhanina Anna V.
Published: March 2023

The nature and strength of interactions for an anti-HIV drug, Lamivudine, were studied in a pure crystal form of the drug and the ligand–receptor complexes. High-resolution single-crystal X-ray diffraction studies of the tetragonal polymorph allowed the drug’s experimental charge density distribution in the solid state to be obtained. The QM/MM calculations were performed for a simplified model of the Lamivudine complex with deoxycytidine kinase (two complexes with different binding modes) to reconstruct the theoretical charge density distribution. The peculiarities of intramolecular interactions were compared with previously reported data for an isolated molecule. Intermolecular interactions were revealed within the quantum theory of ‘Atoms in Molecules’, and their contributions to the total crystal energy or ligand–receptor binding energy were evaluated. It was demonstrated that the crystal field effect weakened the intramolecular interactions. Overall, the energies of intermolecular interactions in ligand–receptor complexes (320.1–394.8 kJ/mol) were higher than the energies of interactions in the crystal (276.9 kJ/mol) due to the larger number of hydrophilic interactions. In contrast, the sum of the energies of hydrophobic interactions was found to be unchanged. It was demonstrated by means of the Voronoi tessellation that molecular volume remained constant for different molecular conformations (250(13) Å3) and increased up to 399 Å3 and 521(30) Å3 for the Lamivudine phosphate and triphosphate.
Biomechanical Behaviors and Degradation Properties of Multilayered Polymer Scaffolds: The Phase Space Method for Bile Duct Design and Bioengineering
Authors: Klabukov Ilya , Tenchurin Timur , Shepelev Alexey , Baranovskii Denis , Mamagulashvili Vissarion , Dyuzheva Tatiana , Krasilnikova Olga , Balyasin Maksim , Lyundup Alexey , Krasheninnikov Mikhail , Sulina Yana , Gomzyak Vitaly , Krasheninnikov Sergey , Buzin Alexander , Zayratyants Georgiy , Yakimova Anna , Demchenko Anna , Ivanov Sergey , Shegay Peter , Kaprin Andrey , Chvalun Sergei
Published: March 2023

This article reports the electrospinning technique for the manufacturing of multilayered scaffolds for bile duct tissue engineering based on an inner layer of polycaprolactone (PCL) and an outer layer either of a copolymer of D,L-lactide and glycolide (PLGA) or a copolymer of L-lactide and ε-caprolactone (PLCL). A study of the degradation properties of separate polymers showed that flat PCL samples exhibited the highest resistance to hydrolysis in comparison with PLGA and PLCL. Irrespective of the liquid-phase nature, no significant mass loss of PCL samples was found in 140 days of incubation. The PLCL- and PLGA-based flat samples were more prone to hydrolysis within the same period of time, which was confirmed by the increased loss of mass and a significant reduction of weight-average molecular mass. The study of the mechanical properties of developed multi-layered tubular scaffolds revealed that their strength in the longitudinal and transverse directions was comparable with the values measured for a decellularized bile duct. The strength of three-layered scaffolds declined significantly because of the active degradation of the outer layer made of PLGA. The strength of scaffolds with the PLCL outer layer deteriorated much less with time, both in the axial (p-value = 0.0016) and radial (p-value = 0.0022) directions. A novel method for assessment of the physiological relevance of synthetic scaffolds was developed and named the phase space approach for assessment of physiological relevance. Two-dimensional phase space (elongation modulus and tensile strength) was used for the assessment and visualization of the physiological relevance of scaffolds for bile duct bioengineering. In conclusion, the design of scaffolds for the creation of physiologically relevant tissue-engineered bile ducts should be based not only on biodegradation properties but also on the biomechanical time-related behavior of various compositions of polymers and copolymers.
Positive Correlation between Relative Concentration of Spermine to Spermidine in Whole Blood and Skeletal Muscle Mass Index: A Possible Indicator of Sarcopenia and Prognosis of Hemodialysis Patients
Authors: Sanayama Hidenori , Ito Kiyonori , Ookawara Susumu , Uemura Takeshi , Imai Sojiro , Kiryu Satoshi , Iguchi Miho , Sakiyama Yoshio , Sugawara Hitoshi , Morishita Yoshiyuki , Tabei Kaoru , Igarashi Kazuei , Soda Kuniyasu
Published: March 2023

Several mechanisms strictly regulate polyamine concentration, and blood polyamines are excreted in urine. This indicates polyamine accumulation in renal dysfunction, and studies have shown increased blood polyamine concentrations in patients with renal failure. Hemodialysis (HD) may compensate for polyamine excretion; however, little is known about polyamine excretion. We measured whole-blood polyamine levels in patients on HD and examined the relationship between polyamine concentrations and indicators associated with health status. Study participants were 59 hemodialysis patients (median age: 70.0 years) at Minami-Uonuma City Hospital and 26 healthy volunteers (median age: 44.5 years). Whole-blood spermidine levels were higher and spermine/spermidine ratio (SPM/SPD) was lower in hemodialysis patients. Hemodialysis showed SPD efflux into the dialysate; however, blood polyamine levels were not altered by hemodialysis and appeared to be minimally excreted. The skeletal muscle mass index (SMI), which was positively correlated with hand grip strength and serum albumin level, was positively correlated with SPM/SPD. Given that sarcopenia and low serum albumin levels are reported risk factors for poor prognosis in HD patients, whole blood SPM/SPD in hemodialysis patients may be a new indicator of the prognosis and health status of HD patients.
Biomarkers for Outcome in Metastatic Melanoma in First Line Treatment with Immune Checkpoint Inhibitors
Authors: Mesti Tanja , Grašič Kuhar Cvetka , Ocvirk Janja
Published: March 2023

Introduction: A high proportion of metastatic melanoma patients do not respond to immune checkpoint inhibitors (ICI), and until now, no validated biomarkers for response and survival have been known. Methods: We performed a retrospective analysis of outcomes in patients with metastatic melanoma treated with first-line ICI at the Institute of Oncology Ljubljana from January 2018 to December 2020. The immune-related adverse events (irAEs) and serum immune-inflammation parameters (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (LR), systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV)) were analyzed as potential biomarkers for response and survival. Survival rates were calculated using the Kaplan–Meier method and then compared with the log-rank test. Multivariate regression Cox analysis was used to determine independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Results: Median follow-up was 22.5 months. The estimated median progression-free survival (PFS) was 15 months (95% CI 3.3–26.2). The two-year survival rate (OS) was 66.6%. Among 129 treated patients, 24 (18.6%) achieved complete response, 28 (21.7%) achieved partial response, 26 (20.2%) had stable disease and 51 (39.5%) patients experienced a progressive disease. There was a higher response rate in patients with irAEs (p < 0.001) and high NLR before the second cycle of ICI (p = 0.052). Independent prognostic factors for PFS were irAE (HR 0.41 (95% CI 0.23–0.71)), SII before the first cycle of ICI (HR 1.94 (95% CI 1.09–3.45)) and PLR before the second cycle of ICI (HR 1.71 (95% CI 1.03–2.83)). The only independent prognostic factor for OS was SII before the first cycle of ICI (HR 2.60 (95% CI 0.91–7.50)). Conclusions: Patients with high pre-treatment levels of SII had a higher risk of progression and death; however, patients with irAEs in the high-SII group might respond well to ICI. Patients who develop irAEs and have high NLRs before the second ICI application have higher rates of CR and PR, which implicates their use as early biomarkers for responsiveness to ICI.
Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation
Authors: Martella Noemi , Pensabene Daniele , Varone Michela , Colardo Mayra , Petraroia Michele , Sergio William , La Rosa Piergiorgio , Moreno Sandra , Segatto Marco
Published: March 2023

BET proteins function as histone code readers of acetylated lysins that determine the positive regulation in transcription of genes involved in cell cycle progression, differentiation, inflammation, and many other pathways. In recent years, thanks to the development of BET inhibitors, interest in this protein family has risen for its relevance in brain development and function. For example, experimental evidence has shown that BET modulation affects neuronal activity and the expression of genes involved in learning and memory. In addition, BET inhibition strongly suppresses molecular pathways related to neuroinflammation. These observations suggest that BET modulation may play a critical role in the onset and during the development of diverse neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s disease, fragile X syndrome, and Rett syndrome. In this review article, we summarize the most recent evidence regarding the involvement of BET proteins in brain physiology and pathology, as well as their pharmacological potential as targets for therapeutic purposes.
Differentiating Lumbar Spinal Etiology from Peripheral Plexopathies
Authors: Foreman Marco , Maddy Krisna , Patel Aashay , Reddy Akshay , Costello Meredith , Lucke-Wold Brandon
Published: March 2023

Clinicians have managed and treated lower back pain since the earliest days of practice. Historically, lower back pain and its accompanying symptoms of radiating leg pain and muscle weakness have been recognized to be due to any of the various lumbar spine pathologies that lead to the compression of the lumbar nerves at the root, the most common of which is the radiculopathy known as sciatica. More recently, however, with the increased rise in chronic diseases, the importance of differentially diagnosing a similarly presenting pathology, known as lumbosacral plexopathy, cannot be understated. Given the similar clinical presentation of lumbar spine pathologies and lumbosacral plexopathies, it can be difficult to differentiate these two diagnoses in the clinical setting. Resultingly, the inappropriate diagnosis of either pathology can result in ineffective clinical management. Thus, this review aims to aid in the clinical differentiation between lumbar spine pathology and lumbosacral plexopathy. Specifically, this paper delves into spine and plexus anatomy, delineates the clinical assessment of both pathologies, and highlights powerful diagnostic tools in the hopes of bolstering appropriate diagnosis and treatment. Lastly, this review will describe emerging treatment options for both pathologies in the preclinical and clinical realms, with a special emphasis on regenerative nerve therapies.
Vascular Function in Continuous Flow LVADs: Implications for Clinical Practice
Authors: Khalil Fouad , Asleh Rabea , Perue Radha Kanneganti , Weinstein Jean-Marc , Solomon Adam , Betesh-Abay Batya , Briasoulis Alexandros , Alnsasra Hilmi
Published: March 2023

Left ventricular assist devices (LVADs) have been increasingly used in patients with advanced heart failure, either as a destination therapy or as a bridge to heart transplant. Continuous flow (CF) LVADs have revolutionized advanced heart failure treatment. However, significant vascular pathology and complications have been linked to their use. While the newer CF-LVAD generations have led to a reduction in some vascular complications such as stroke, no major improvement was noticed in the rate of other vascular complications such as gastrointestinal bleeding. This review attempts to provide a comprehensive summary of the effects of CF-LVAD on vasculature, including pathophysiology, clinical implications, and future directions.
Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer—In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models
Authors: Nowak Łukasz , Krajewski Wojciech , Dejnaka Ewa , Małkiewicz Bartosz , Szydełko Tomasz , Pawlak Aleksandra
Published: March 2023

Background: The inhibition of ubiquitin-specific proteases (USPs) is a novel and promising direction in the development of molecularly targeted therapies in oncology. The aim of the present study was to examine whether Degrasyn could be a potential therapeutic agent against bladder cancer (BC). Also, we aimed to determine whether Degrasyn is more effective in terms of anti-cancer activity compared to the non-selective DUB inhibitor PR-619. To facilitate the translational value of the obtained results, our experiments were performed using both human and canine in vitro models of BC. Methods: Human T24 (urothelial grade III BC) and SV-HUC-1 (non-tumorigenic urothelial cell line), as well as canine K9TCC-PU-NK and RDSVS-TCC1 (both derived from invasive grade III urothelial bladder tumors) cell lines, were used in the present study. Cell proliferation was determined using the MTT assay and Ki-67 proliferation assay, and the level of apoptosis induced by Degrasyn and PR-619 was evaluated by Annexin V-FITC staining and caspase 3/7 activation assay. Western blot was used to assess DNA damage and key proteins involved in apoptosis. Results: Degrasyn inhibited the proliferation of all BC cell lines in a concentration- and time-dependent manner. Lower concentrations of Degrasyn were more potent against human and canine BC cell lines compared to PR-619. Degrasyn induced caspase-dependent apoptosis and triggered DNA damage. PR-619 did not show a significant pro-apoptotic effect. Conclusions: Our results demonstrate that Degrasyn significantly impairs the growth of in vitro models of human and canine BC. Selective USP inhibition with Degrasyn seems to be more effective in reducing BC cell proliferation and inducing apoptosis and DNA damage than non-selective USP inhibition with PR-619.
Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls
Authors: Pellegrino Antonio , Fabig Sophie-Charlotte , Kersebaum Dilara , Hüllemann Philipp , Baron Ralf , Roch Toralf , Babel Nina , Seitz Harald
Published: March 2023

Polyneuropathies (PNP) are the most common type of disorder of the peripheral nervous system in adults. However, information on microRNA expression in PNP is lacking. Following microRNA sequencing, we compared the expression of microRNAs in the serum of patients experiencing chronic painful PNP with healthy age-matched controls. We have been able to identify four microRNAs (hsa-miR-3135b, hsa-miR-584-5p, hsa-miR-12136, and hsa-miR-550a-3p) that provide possible molecular links between degenerative processes, blood flow regulation, and signal transduction, that eventually lead to PNP. In addition, these microRNAs are discussed regarding the targeting of proteins that are involved in high blood flow/pressure and neural activity dysregulations/disbalances, presumably resulting in PNP-typical symptoms such as chronical numbness/pain. Within our study, we have identified four microRNAs that may serve as potential novel biomarkers of chronic painful PNP, and that may potentially bear therapeutic implications.
Heart Rate Variability by Dynamical Patterns in Windows of Holter Electrocardiograms: A Method to Discern Left Ventricular Hypertrophy in Heart Transplant Patients Shortly after the Transplant
Authors: Makowiec Danuta , Wdowczyk Joanna , Gruchała Marcin
Published: March 2023

Background: The Holter electrocardiogram (ECG) provides a long signal that represents the heart’s responses to both autonomic regulation and various phenomena, including heart tissue remodeling. Loss of information is a common result when using global statistical metrics. Method: Breaking the signal into short data segments (e.g., windows) provides access to transient heart rate characteristics. Symbolization of the ECG by patterns of accelerations and/or decelerations allows using entropic metrics in the assessment of heart rate complexity. Two types of analysis are proposed: (i) visualization of the pattern dynamics of the whole signal, and (ii) scanning the signal for pattern dynamics in a sliding window. The method was applied to a cohort of 42 heart transplant (HTX) recipients divided into the following groups: a left ventricle of normal geometry (NG), concentrically remodeled (CR), hypertrophic remodeled (H), and to the control group (CG) consisting of signals of 41 healthy coevals. The Kruskal–Wallis test was used to assess group differences. Statistical conclusions were verified via bootstrap methods. Results: The visualization of the group pattern dynamics showed severely limited autonomic regulations in HTX patients when compared to CG. The analysis (in segments) prove that the pattern dynamics of the NG group are different from the pattern dynamics observed in the CR and H groups. Conclusion: Dynamic pattern entropy estimators tested in moving windows recognized left ventricular remodeling in stable HTX patients.
Combined Use of Ionic Liquid-Based Aqueous Biphasic Systems and Microfluidic Devices for the Detection of Prostate-Specific Antigen
Authors: Flora Filipa C. , Relvas Sofia B. , Silva Francisca A. e , Freire Mara G. , Chu Virginia , Conde João Pedro
Published: March 2023

Prostate cancer (PCa) is one of the cancer types that most affects males worldwide and is among the highest contributors to cancer mortality rates. Therefore, there is an urgent need to find strategies to improve the diagnosis of PCa. Microtechnologies have been gaining ground in biomedical devices, with microfluidics and lab-on-chip systems potentially revolutionizing medical diagnostics. In this paper, it is shown that prostate-specific antigen (PSA) can be detected through an immunoassay performed in a microbead-based microfluidic device after being extracted and purified from a serum sample through an aqueous biphasic system (ABS). Given their well-established status as ABS components for successful bioseparations, ionic liquids (ILs) and polymers were used in combination with buffered salts. Using both IL-based and polymer-based ABS, it was demonstrated that it is possible to detect PSA in non-physiological environments. It was concluded that the ABS that performed better in extracting the PSA from serum were those composed of tetrabutylammonium chloride ([N4444]Cl) and tetrabutylphosphonium bromide ([P4444]Br), both combined with phosphate buffer, and constituted by polyethylene glycol with a molecular weight of 1000 g/mol (PEG1000) with citrate buffer. In comparison with the assay with PSA prepared in phosphate-buffered saline (PBS) or human serum in which no ABS-mediated extraction was applied, assays attained lower limits of detection after IL-based ABS-mediated extraction. These results reinforce the potential of this method in future point-of-care (PoC) measurements.
Epigenetic Targets in Schizophrenia Development and Therapy
Authors: Wawrzczak-Bargieła Agnieszka , Bilecki Wiktor , Maćkowiak Marzena
Published: March 2023

Schizophrenia is regarded as a neurodevelopmental disorder with its course progressing throughout life. However, the aetiology and development of schizophrenia are still under investigation. Several data suggest that the dysfunction of epigenetic mechanisms is known to be involved in the pathomechanism of this mental disorder. The present article revised the epigenetic background of schizophrenia based on the data available in online databases (PubMed, Scopus). This paper focused on the role of epigenetic regulation, such as DNA methylation, histone modifications, and interference of non-coding RNAs, in schizophrenia development. The article also reviewed the available data related to epigenetic regulation that may modify the severity of the disease as a possible target for schizophrenia pharmacotherapy. Moreover, the effects of antipsychotics on epigenetic malfunction in schizophrenia are discussed based on preclinical and clinical results. The obtainable data suggest alterations of epigenetic regulation in schizophrenia. Moreover, they also showed the important role of epigenetic modifications in antipsychotic action. There is a need for more data to establish the role of epigenetic mechanisms in schizophrenia therapy. It would be of special interest to find and develop new targets for schizophrenia therapy because patients with schizophrenia could show little or no response to current pharmacotherapy and have treatment-resistant schizophrenia.
How Can Restaurant Companies Effectively Deliver CSR Efforts to Consumers on Social Media?
Authors: Lee Sae-Mi , Kim Minseong
Published: March 2023

This study emphasized the source credibility effect on consumers’ responses to restaurant companies’ CSR efforts on social media. Based on the source credibility brand development process (i.e., brand trust, brand affect, and brand engagement), this study employed an online survey-based experiment and revealed the meaningful associations among types of CSR posters (a restaurant brand vs. a nonprofit organization), brand trust, brand affect, and brand engagement. The empirical results indicated that the nonprofit organization has higher significant effects on brand trust and brand affect than those of the restaurant brand. Additionally, in the case of the nonprofit organization, the effects of brand trust and brand affect on brand engagement were significantly stronger than that of the restaurant brand. Based on the empirical findings, this study provided several theoretical and managerial implications for restaurant companies’ CSR communication on social media.
Cognitive Function, and Its Relationships with Comorbidities, Physical Activity, and Muscular Strength in Korean Older Adults
Authors: Kim Shinuk
Published: March 2023

Background: Little is known regarding how much physical activity (PA) and lower-body muscle strength (LBMS) together can help to reduce the negative effect of comorbidities on cognitive function. This study examined the moderating effects of PA and LBMS in determining the relationship between comorbidities and cognitive function in older Korean adults. Materials and Methods: This is a population-based cross-sectional study. Data for this study were taken from the 2020 Korea Longitudinal Study on Aging (KLoSA) in South Korea using a computer-assisted personal interview. The 2020 KLoSA survey included a total of 10,097 older individuals aged 65 and older (6062 females and 4035 men). Comorbidities were determined based on physician-diagnosed chronic conditions. PA and LBMS were measured with a self-reported questionnaire and a sit-to-stand test, respectively. Cognitive function was assessed using the Korean version of the Mini-Mental Status Examination for dementia screening. Results: Multimorbidity was correlated with an increased risk (odds ratio, OR = 1.415, p < 0.001) of cognitive impairment. Insufficient PA and weak LBMS were correlated with an increased risk of cognitive impairment (OR = 1.340, p < 0.001; OR = 1.719, p < 0.001, respectively). Particularly, PA modulates the negative impact of comorbidities on cognitive function (β = −0.3833; 95% CI = −0.4743 to −0.2023) independent of all measured covariates. Weak LBMS was found to be an independent predictor of cognitive function (β = −2.5078, p < 0.001) regardless of comorbidities. Conclusions: The study findings suggest that a lifestyle intervention targeting regular PA and muscular fitness should be a therapeutic means against cognitive decline associated with normal aging and/or chronic diseases.
Influence on the Incorporation of Carbonate Minerals as Stabilizers in Clay and Sawdust-Based Blocks for Thermal Insulation
Authors: Aguilar-Joo José Eduardo , Farrera-Vázquez Neín , López-Cameras Selene , Ruíz-Torres Raúl Pavel , Meza-Avendaño Carlos Alonso
Published: March 2023

This research is focused on the influence of carbonate minerals on the properties of ceramic blocks as a replacement for commercial stabilizers, using three types of clays and sawdust as raw materials extracted from Chiapas, Mexico, for their application in thermal insulation on lightweight construction systems of local buildings. The effective thermal conductivity of each sample was tested by the guarded hot plate method in a permanent state, and their physical and chemical properties were determined by water absorption, X-ray powder diffraction, and X-ray fluorescence spectroscopy techniques. The results directed attention toward the knowledge of the role of the parameters in improving the thermal insulation properties, highlighting calcite as a favorable stabilizer in the manufacture of such blocks. Furthermore, the parameter affecting the thermal conductivity of the samples is the mass percentage of magnesium oxide (MgO) in a positive linear trend. Finally, the volumetric proportions of the sawdust as a pore-forming aggregate influence the decrease in the bulk density in the ceramic blocks and, thus, the reduction in the thermal conductivity.
Pre-Compressed Foam Sealing Tapes to Seal Joints between Building Envelope Components Watertight: An Experimental Assessment
Authors: Van Linden Stéphanie , Van Den Bossche Nathan
Published: March 2023

Currently there is gaining interest in pre-compressed foam sealing tapes to seal joints watertight between different building envelope components. Little to no information is available on the parameters affecting the resistance of these foam tapes to driving rain. On the other hand, several research studies have shown that water leakages can be expected at relatively low-pressure differences and that drainage should be provided. Therefore, a study was designed to on the one hand assess the material and installation parameters that affect the watertightness of pre-compressed polyurethane foam sealing tapes impregnated with an acrylic polymer dispersion and on the other hand evaluate the potential of providing drainage possibilities, either as a two-barrier system or by means of integrated drainage cavities. It was found that the joint width, the presence of an airtight coating, and the position of the tape relative to the exterior surface affected the watertightness of the sealed joints. Notably, 87% of the evaluated foam tapes applied as a single barrier showed water leakages at pressure differences of 600 Pa or lower. Foam tapes with integrated drainage cavities, on the other hand, resulted in watertight joints up to an average pressure difference of 825 Pa.