bluuebunny/crossref_metadata_2025 huggingface dataset:
Single Cell Transcriptomic Analysis in a Mouse Model of Barth Syndrome Reveals Cell-Specific Alterations in Gene Expression and Intercellular Communication
Authors: Perera Gayani , Power Liam , Larson Amy , Codden Christina J. , Awata Junya , Batorsky Rebecca , Strathdee Douglas , Chin Michael T.
Published: July 2023

Barth Syndrome, a rare X-linked disorder affecting 1:300,000 live births, results from defects in Tafazzin, an acyltransferase that remodels cardiolipin and is essential for mitochondrial respiration. Barth Syndrome patients develop cardiomyopathy, muscular hypotonia and cyclic neutropenia during childhood, rarely surviving to middle age. At present, no effective therapy exists, and downstream transcriptional effects of Tafazzin dysfunction are incompletely understood. To identify novel, cell-specific, pathological pathways that mediate heart dysfunction, we performed single-nucleus RNA-sequencing (snRNA-seq) on wild-type (WT) and Tafazzin-knockout (Taz-KO) mouse hearts. We determined differentially expressed genes (DEGs) and inferred predicted cell–cell communication networks from these data. Surprisingly, DEGs were distributed heterogeneously across the cell types, with fibroblasts, cardiomyocytes, endothelial cells, macrophages, adipocytes and pericytes exhibiting the greatest number of DEGs between genotypes. One differentially expressed gene was detected for the lymphatic endothelial and mesothelial cell types, while no significant DEGs were found in the lymphocytes. A Gene Ontology (GO) analysis of these DEGs showed cell-specific effects on biological processes such as fatty acid metabolism in adipocytes and cardiomyocytes, increased translation in cardiomyocytes, endothelial cells and fibroblasts, in addition to other cell-specific processes. Analysis of ligand–receptor pair expression, to infer intercellular communication patterns, revealed the strongest dysregulated communication involved adipocytes and cardiomyocytes. For the knockout hearts, there was a strong loss of ligand–receptor pair expression involving adipocytes, and cardiomyocyte expression of ligand–receptor pairs underwent reorganization. These findings suggest that adipocyte and cardiomyocyte mitochondria may be most sensitive to mitochondrial Tafazzin deficiency and that rescuing adipocyte mitochondrial dysfunction, in addition to cardiomyocyte mitochondrial dysfunction, may provide therapeutic benefit in Barth Syndrome patients.
Detection of Mast Cells in Human Superficial Fascia
Authors: Fede Caterina , Petrelli Lucia , Pirri Carmelo , Tiengo Cesare , De Caro Raffaele , Stecco Carla
Published: July 2023

The recent findings showed that the superficial fascia is a fibrous layer in the middle of hypodermis, richly innervated and vascularized, and more complex than so far demonstrated. This study showed the presence of mast cells in the superficial fascia of the human abdomen wall of three adult volunteer patients (mean age 42 ± 4 years; 2 females, 1 male), by Toluidine Blue and Safranin-O stains and Transmission Electron Microscopy. Mast cells are distributed among the collagen bundles and the elastic fibers, near the vessels and close to the nerves supplying the tissue, with an average density of 20.4 ± 9.4/mm2. The demonstration of the presence of mast cells in the human superficial fascia highlights the possible involvement of the tissue in the inflammatory process, and in tissue healing and regeneration processes. A clear knowledge of this anatomical structure of the hypodermis is fundamental for a good comprehension of some fascial dysfunctions and for a better-targeted clinical practice.
Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
Authors: Khalifa Olfa , Ouararhni Khalid , Errafii Khaoula , Alajez Nehad M. , Arredouani Abdelilah
Published: July 2023

Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, glucagon-like peptide-1 receptor agonists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aim to investigate how the GLP-1RA exendin-4 (Ex-4) affects the microRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from control, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment pathway analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, insulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigation.
Inhibitor Trapping in N-Myristoyltransferases as a Mechanism for Drug Potency
Authors: Spassov Danislav S. , Atanasova Mariyana , Doytchinova Irini
Published: July 2023

Predicting inhibitor potency is critical in drug design and development, yet it has remained one of computational biology’s biggest unresolved challenges. Here, we show that in the case of the N-myristoyltransferase (NMT), this problem could be traced to the mechanisms by which the NMT enzyme is inhibited. NMT adopts open or closed conformations necessary for orchestrating the different steps of the catalytic process. The results indicate that the potency of the NMT inhibitors is determined by their ability to stabilize the enzyme conformation in the closed state, and that in this state, the small molecules themselves are trapped and locked inside the structure of the enzyme, creating a significant barrier for their dissociation. By using molecular dynamics simulations, we demonstrate that the conformational stabilization of the protein molecule in its closed form is highly correlated with the ligands activity and can be used to predict their potency. Hence, predicting inhibitor potency in silico might depend on modeling the conformational changes of the protein molecule upon binding of the ligand rather than estimating the changes in free binding energy that arise from their interaction.
Cx43 Hemichannel and Panx1 Channel Modulation by Gap19 and 10Panx1 Peptides
Authors: Lissoni Alessio , Tao Siyu , Allewaert Rosalie , Witschas Katja , Leybaert Luc
Published: July 2023

Cx43 hemichannels (HCs) and Panx1 channels are two genetically distant protein families. Despite the lack of sequence homology, Cx43 and Panx1 channels have been the subject of debate due to their overlapping expression and the fact that both channels present similarities in terms of their membrane topology and electrical properties. Using the mimetic peptides Gap19 and 10Panx1, this study aimed to investigate the cross-effects of these peptides on Cx43 HCs and Panx1 channels. The single-channel current activity from stably expressing HeLa-Cx43 and C6-Panx1 cells was recorded using patch-clamp experiments in whole-cell voltage-clamp mode, demonstrating 214 pS and 68 pS average unitary conductances for the respective channels. Gap19 was applied intracellularly while 10Panx1 was applied extracellularly at different concentrations (100, 200 and 500 μM) and the average nominal open probability (NPo) was determined for each testing condition. A concentration of 100 µM Gap19 more than halved the NPo of Cx43 HCs, while 200 µM 10Panx1 was necessary to obtain a half-maximal NPo reduction in the Panx1 channels. Gap19 started to significantly inhibit the Panx1 channels at 500 µM, reducing the NPo by 26% while reducing the NPo of the Cx43 HCs by 84%. In contrast 10Panx1 significantly reduced the NPo of the Cx43 HCs by 37% at 100 µM and by 83% at 200 µM, a concentration that caused the half-maximal inhibition of the Panx1 channels. These results demonstrate that 10Panx1 inhibits Cx43 HCs over the 100–500 µM concentration range while 500 µM intracellular Gap19 is necessary to observe some inhibition of Panx1 channels.
Integrative Plasma Metabolic and Lipidomic Modelling of SARS-CoV-2 Infection in Relation to Clinical Severity and Early Mortality Prediction
Authors: Lodge Samantha , Lawler Nathan G. , Gray Nicola , Masuda Reika , Nitschke Philipp , Whiley Luke , Bong Sze-How , Yeap Bu B. , Dwivedi Girish , Spraul Manfred , Schaefer Hartmut , Gil-Redondo Rubén , Embade Nieves , Millet Oscar , Holmes Elaine , Wist Julien , Nicholson Jeremy K.
Published: July 2023

An integrative multi-modal metabolic phenotyping model was developed to assess the systemic plasma sequelae of SARS-CoV-2 (rRT-PCR positive) induced COVID-19 disease in patients with different respiratory severity levels. Plasma samples from 306 unvaccinated COVID-19 patients were collected in 2020 and classified into four levels of severity ranging from mild symptoms to severe ventilated cases. These samples were investigated using a combination of quantitative Nuclear Magnetic Resonance (NMR) spectroscopy and Mass Spectrometry (MS) platforms to give broad lipoprotein, lipidomic and amino acid, tryptophan-kynurenine pathway, and biogenic amine pathway coverage. All platforms revealed highly significant differences in metabolite patterns between patients and controls (n = 89) that had been collected prior to the COVID-19 pandemic. The total number of significant metabolites increased with severity with 344 out of the 1034 quantitative variables being common to all severity classes. Metabolic signatures showed a continuum of changes across the respiratory severity levels with the most significant and extensive changes being in the most severely affected patients. Even mildly affected respiratory patients showed multiple highly significant abnormal biochemical signatures reflecting serious metabolic deficiencies of the type observed in Post-acute COVID-19 syndrome patients. The most severe respiratory patients had a high mortality (56.1%) and we found that we could predict mortality in this patient sub-group with high accuracy in some cases up to 61 days prior to death, based on a separate metabolic model, which highlighted a different set of metabolites to those defining the basic disease. Specifically, hexosylceramides (HCER 16:0, HCER 20:0, HCER 24:1, HCER 26:0, HCER 26:1) were markedly elevated in the non-surviving patient group (Cliff’s delta 0.91–0.95) and two phosphoethanolamines (PE.O 18:0/18:1, Cliff’s delta = −0.98 and PE.P 16:0/18:1, Cliff’s delta = −0.93) were markedly lower in the non-survivors. These results indicate that patient morbidity to mortality trajectories is determined relatively soon after infection, opening the opportunity to select more intensive therapeutic interventions to these “high risk” patients in the early disease stages.
Involvement of Acquired Tobramycin Resistance in the Shift to the Viable but Non-Culturable State in Pseudomonas aeruginosa
Authors: Mangiaterra Gianmarco , Cedraro Nicholas , Vaiasicca Salvatore , Citterio Barbara , Frangipani Emanuela , Biavasco Francesca , Vignaroli Carla
Published: July 2023

Persistent and viable but non-culturable (VBNC) Pseudomonas aeruginosa cells are mainly responsible for the recurrence and non-responsiveness to antibiotics of cystic fibrosis (CF) lung infections. The sub-inhibitory antibiotic concentrations found in the CF lung in between successive therapeutic cycles can trigger the entry into the VBNC state, albeit with a strain-specific pattern. Here, we analyzed the VBNC cell induction in the biofilms of two CF P. aeruginosa isolates, exposed to starvation with/without antibiotics, and investigated the putative genetic determinants involved. Total viable bacterial cells were quantified by the validated ecfX-targeting qPCR protocol and the VBNC cells were estimated as the difference between qPCR and cultural counts. The isolates were both subjected to whole genome sequencing, with attention focused on their carriage of aminoglycoside resistance genes and on identifying mutated toxin–antitoxin and quorum sensing systems. The obtained results suggest the variable contribution of different antibiotic resistance mechanisms to VBNC cell abundance, identifying a major contribution from tobramycin efflux, mediated by MexXY efflux pump overexpression. The genome analysis evidenced putative mutation hotspots, which deserve further investigation. Therefore, drug efflux could represent a crucial mechanism through which the VBNC state is entered and a potential target for anti-persistence strategies.
The Roles of Histone Lysine Methyltransferases in Heart Development and Disease
Authors: Zhu Jun-yi , van de Leemput Joyce , Han Zhe
Published: July 2023

Epigenetic marks regulate the transcriptomic landscape by facilitating the structural packing and unwinding of the genome, which is tightly folded inside the nucleus. Lysine-specific histone methylation is one such mark. It plays crucial roles during development, including in cell fate decisions, in tissue patterning, and in regulating cellular metabolic processes. It has also been associated with varying human developmental disorders. Heart disease has been linked to deregulated histone lysine methylation, and lysine-specific methyltransferases (KMTs) are overrepresented, i.e., more numerous than expected by chance, among the genes with variants associated with congenital heart disease. This review outlines the available evidence to support a role for individual KMTs in heart development and/or disease, including genetic associations in patients and supporting cell culture and animal model studies. It concludes with new advances in the field and new opportunities for treatment.
Effectiveness of Repetitive Transcranial Magnetic Stimulation in the Treatment of Depression in the Elderly: A Retrospective Natural Analysis
Authors: Almheiri Eisa , Alhelali Abdullah , Abdelnaim Mohamed A. , Weber Franziska C. , Langguth Berthold , Schecklmann Martin , Hebel Tobias
Published: July 2023

Introduction: Depression in the elderly is an understudied condition. Psychopharmacological and psychotherapeutic approaches suffer from specific difficulties with this patient group. Brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a therapeutic alternative. rTMS remains understudied in this age group when compared with younger patients. Methods: A cohort of 505 patients with depression was analyzed in retrospect concerning their response to rTMS treatment. A total of 15.5% were 60 years old or older, defined as the elderly group of depressed patients. The majority of these were treated with high-frequency protocols over the left dorsolateral prefrontal cortex (DLPFC). For group comparisons, we used Student t-tests or chi-square-tests, depending on the scales of measurement. As measures for effect size, we used Cohen’s d for the relative and absolute change in the HDRS total score. Results: Groups did not differ significantly with respect to baseline depression severity or treatment parameters. In the group of elderly patients, a higher number of females were present. Groups did not differ significantly with respect to treatment efficacy, as indicated by the absolute and relative changes in the HDRS-21 sum score. Elderly patients tended to take higher numbers of mood stabilizers. Elderly patients showed a significantly superior reduction for the item “appetite” and a superior reduction tending towards significance for the item “work and interests”. Conclusions: Antidepressant rTMS treatment showed comparable efficacy for patients above 60 years to that in younger patients. Differences between the age groups concerning amelioration of distinct HDRS single items deserve further investigation.
The Artificial Neural Network as a Diagnostic Tool of the Risk of Clostridioides difficile Infection among Patients with Chronic Kidney Disease
Authors: Stojanowski Jakub , Konieczny Andrzej , Lis Łukasz , Frosztęga Weronika , Brzozowska Patrycja , Ciszewska Anna , Rydzyńska Klaudia , Sroka Michał , Krakowska Kornelia , Gołębiowski Tomasz , Hruby Zbigniew , Kusztal Mariusz , Krajewska Magdalena
Published: July 2023

The majority of recently published studies indicate a greater incidence and mortality due to Clostridioides difficile infection (CDI) in patients with chronic kidney disease (CKD). Hospitalization, older age, the use of antibiotics, immunosuppression, proton pump inhibitors (PPI), and chronic diseases such as CKD are responsible for the increased prevalence of infections. The aim of the study is to identify clinical indicators allowing, in combination with artificial intelligence (AI) techniques, the most accurate assessment of the patients being at elevated risk of CDI.
Investigation of Factors Affecting Shuttle Walking Performance at Increased Speed for Patients with Chronic Obstructive Pulmonary Disease
Authors: Çiftçi Rukiye , Kurtoğlu Ahmet , Eken Özgür , Durmaz Dilber , Eler Serdar , Eler Nebahat , Aldhahi Monira I.
Published: July 2023

The aim of this study was to examine the factors affecting the shuttle walking test (SWT) in patients with chronic obstructive pulmonary disease (COPD). A total of 29 patients with COPD (the COPD group) and a healthy group (HG) of 34 women aged between 55 and 74 years were included in the study. After the pulmonary function profiles of the participants were assessed, and the SWT was performed. Walking distances, walking speeds, and SWT levels (SWT-L) were determined with the SWT. Before and after the SWT, the heart rate (HR), oxygen saturation level (SPO2), and Borg scale (perceived exertion (BSe) and dyspnea (BSd)) results were analyzed with a paired sample t-test. The dyspnea levels during activity of daily living were determined with the Medical Research Council (MRC) dyspnea scale, and the relationship between MRC dyspnea (MRCD) and walking distance, speed, and SWT-L was tested using multiple linear regression and Pearson correlation analysis. The walking distance, speed, and SWT-L were lower in the COPD group (p < 0.001) than in the HG. The HR values before and after the SWT changed significantly in the COPD group and the HG (p< 0.001), and the effect size was higher in the COPD group. Although the BSe and BSd results before and after the SWT in the COPD group increased significantly (p < 0.001), they did not change in the HG. There was a highly negative correlation between MRCD and walking distance, speed, and SWT-L in the COPD group (p = 0.002, p = 0.000, and p = 0.001, respectively), but no correlation was found in the HG. The results showed that the HR, perceived exertion, and dyspnea levels of women with COPD whose respiratory functions were lower than the HG were significantly affected on the SWT.
Latest Developments in Minimally Invasive Spinal Treatment in Slovakia and Its Comparison with an Open Approach for the Treatment of Lumbar Degenerative Diseases
Authors: Potašová Marina , Filipp Peter , Rusnák Róbert , Moraučíková Eva , Repová Katarína , Kutiš Peter
Published: July 2023

The study describes the benefits of MIS-TLIF (minimally invasive transforaminal lumbar interbody fusion) and compares them with OTLIF (open transforaminal lumbar interbody fusion). It compares blood loss, length of hospitalization stays (LOS), operation time, and return of the patient to the environment. A total of 250 adults (109 males and 141 females), mean age 59.5 ± 12.6, who underwent MIS-TLIF in the Neurosurgery Clinic (NSC) Ruzomberok, Slovakia, because of lumbar degenerative diseases (LDD), participated in this retrospective study. Data were obtained from the patients’ medical records and from the standardized Oswestry Disability Index (ODI) index questionnaire. To compare ODI in our study sample, we used the Student’s Paired Sample Test. To compare the MIS-TLIF and OTLIF approaches, a meta-analysis was conducted. Confidence intervals were 95% CI. The test of homogeneity (Chi-square (Q)) and the degree of heterogeneity (I2 test) among the included studies were used. Statistical analyses were two-sided (α = 0.05). All monitored parameters were significantly better in MIS-TLIF group: blood loss (p < 0.001), operation time (p < 0.001), and ODI changes (p < 0.001). LOS (p < 0.042) were close to the significance level. ODI in the study sample decreased by 33.44% points after MIS-TLIF, and it significantly increased as well (p < 0.001). The percentage of patients who were satisfied with the surgery they underwent was 84.8%. The study confirmed that the MIS-TLIF method is in general gentler for the patient and allows the faster regeneration of patient’s health status compared to OTLIF.
Bleeding Disorders and Dental Implants: Review and Clinical Indications
Authors: Bacci Christian , Schiazzano Claudia , Zanon Ezio , Stellini Edoardo , Sbricoli Luca
Published: July 2023

Background: Bleeding disorders can be divided into three categories: congenital coagulation disorders (CCDs), antiplatelet-induced bleeding disorders (APBDs) and anticoagulant-induced bleeding disorders (ACBDs). Implant placement can be challenging in these kinds of patients. The aim of this study is to provide evidence on implant surgery in patients with bleeding disorders and to generate some practical recommendations for clinicians. Material and Methods: Pubmed/MEDLINE, Scopus, Web of Science and Cochrane Library databases were screened. The latest search was performed in July 2022. Case reports, case series, cohort studies, cross-sectional studies, case control studies, reviews, consensus reports, surveys and animal studies were included in the analysis. Results: Seventeen articles on CCDs were found, fourteen on APBDs and twenty-six on ACBDs. Most of these articles were case reports or case series. Patients with CCDs can be treated after the infusion of the missing coagulation factor. Patients with APBDs can be treated without withdrawing the therapy. Patients with ACBDs should be treated depending on the anticoagulative medication. Conclusion: Despite the low level of evidence, dental implants can be safely placed in patients with bleeding disorders. However, careful preoperative evaluation and the adoption of local and post-operative bleeding control measures are mandatory.
Review of Challenges and Opportunities in Turbulence Modeling: A Comparative Analysis of Data-Driven Machine Learning Approaches
Authors: Zhang Yi , Zhang Dapeng , Jiang Haoyu
Published: July 2023

Engineering and scientific applications are frequently affected by turbulent phenomena, which are associated with a great deal of uncertainty and complexity. Therefore, proper modeling and simulation studies are required. Traditional modeling methods, however, pose certain difficulties. As computer technology continues to improve, machine learning has proven to be a useful solution to some of these problems. The purpose of this paper is to further promote the development of turbulence modeling using data-driven machine learning; it begins by reviewing the development of turbulence modeling techniques, as well as the development of turbulence modeling for machine learning applications using a time-tracking approach. Afterwards, it examines the application of different algorithms to turbulent flows. In addition, this paper discusses some methods for the assimilation of data. As a result of the review, analysis, and discussion presented in this paper, some limitations in the development process are identified, and related developments are suggested. There are some limitations identified and recommendations made in this paper, as well as development goals, which are useful for the development of this field to some extent. In some respects, this paper may serve as a guide for development.
Properties and Model of a Lacustrine Shale Oil Reservoir: A Case Study of the Upper Fourth Member and Lower Third Member of the Shahejie Formation in Dongying Sag and Zhanhua Sag, Jiyang Depression
Authors: Ma Cunfei , Fang Xianxu , Ma Xiaonan , Liu Xiantai , Xu Bingkun , Ge Xinmin
Published: July 2023

By combining thermal simulation experiments with core data, thin sections, scanning electron microscopy (SEM), source rock, and high-pressure mercury and gas adsorption analysis, this paper evaluates the properties and models of shale reservoirs in the upper fourth member and the lower third member of the Shahejie Formation in Dongying Sag and Zhanhua Sag. The results show that the oil shale is a high-quality source rock with petroleum generation potential. Inorganic mineral pores, organic pores, and fractures have developed with petroleum storage capacity. Clay and organic-rich soft shale lithofacies are interbedded with carbonate-rich hard shale lithofacies to form sandwich-type source–reservoir–caprock assemblages with internal sealing properties. Bitumen occurs mostly in the free state, and to a lesser extent is adsorbed, and shows flow characteristics. The migration resistance of the bitumen is displacement pressure, including capillary force and adsorption resistance, and the main force is pore fluid pressure. The migration modes of the bitumen include both subcritical flow and instantaneous flow, which are controlled by pore fluid pressure, displacement pressure, and the rock’s fracture strength. Owing to the multi-scale characteristics of the shale reservoir space, a vein-type model of a multi-scale progressive transport network is developed that obeys Murray’s law with a dominant migration pathway in the shale reservoir. The shale oil reservoir is a special lithologic reservoir controlled by the sedimentary environment and has self-generation, self-storage, and self-sealing characteristics with developed pore fluid overpressure and a multi-scale transport network.
Nonlinear Interaction of Infragravity and Wind Sea Waves
Authors: Dolgikh Grigory , Dolgikh Stanislav
Published: July 2023

In this paper, the authors analyze data obtained from a supersensitive detector of hydrosphere pressure variations which was positioned on the shelf of the Sea of Japan at a depth of 25 m for several months. When processing this data, the main attention was paid to studying nonlinear hydrophysical disturbances of “rogue waves” type: “one sister”, “two sisters”, “three sisters”, and “potential well”, the origin of which is associated, apparently, with the interaction of the hydrophysical wave field in gravity range and disturbances in the infragravity range. Analysis of synchronous data of the laser strainmeter and laser nanobarograph, installed at Shultz Cape, with synchronous records of the supersensitive detector of hydrosphere pressure variations confirmed these conclusions.
Synthesis of Altissimacoumarin D and Other Prenylated Coumarins and Their Ability to Reverse the Multidrug Resistance Phenotype in Candida albicans
Authors: Silva Anna Claudia , de Moraes Daniel Clemente , do Carmo Denilson Costa , Gomes Giselle Cristina Casaes , Ganesan A. , Lopes Rosangela Sabbatini Capella , Ferreira-Pereira Antonio , Lopes Cláudio Cerqueira
Published: July 2023

Azoles are the main antifungal agents employed in clinical practice to treat invasive candidiasis. Nonetheless, their efficacy is limited by fungal resistance mechanisms, mainly the overexpression of efflux pumps. Consequently, candidiasis has a worrisome death rate of 75%. One potential strategy to overcome efflux-mediated resistance is to inhibit this process. Ailanthus altissima is a Chinese tree that produces several active substances, including altissimacoumarin D. Due to the low yield of its extraction and the need to search for new drugs to treat candidiasis, this study aimed to synthesize altissimacoumarin D and its analogues, as well as evaluating their ability to reverse the resistance phenotype of Candida albicans. Coumarin isofraxidin was prepared via total synthesis through a solvent-free Knoevenagel condensation as the key step. Isofraxidin and other commercially available coumarins were alkylated with prenyl or geranyl groups to yield the natural product altissimacoumarin D and seven analogues. The antifungal activity of the coumarins and their ability to reverse the fungal resistance phenotype were assessed using microbroth methodologies. Toxicity was evaluated using erythrocytes and an in silico prediction. All compounds improved the antifungal activity of fluconazole by inhibiting efflux pumps, and ACS47 and ACS50 were the most active. None of the coumarins were toxic to erythrocytes. In silico predictions indicate that ACS47 and ACS50 may be safe for human use. ACS47 and ACS50 are promising candidates when used as adjuvants in the antifungal therapy against C. albicans-resistant strains.
Fungal Biodegradation of Polyurethanes
Authors: Maestri Clotilde , Plancher Lionel , Duthoit Alexis , Hébert Ronan L. , Di Martino Patrick
Published: July 2023

Polyurethanes (PURs) are versatile polymers used in a wide variety of fields, such as the medical, automotive, textile, thermal insulation, and coating industries as well as many everyday objects. Many PURs have applications that require a long service life, sometimes with exposure to aggressive conditions. They can undergo different types of physicochemical and biological degradation, but they are not compostable, and many of them constitute persistent waste in the environment. Although both bacteria and fungi can be involved in the degradation of PURs, fungi are often the main biodegradation agents. The chemical structure of PURs determines their degree of biodegradation. Fungal biodegradation of PURs is linked to the production of enzymes, mainly esterases and proteases, alongside laccases, peroxidases, and tyrosinases, which can modify the structure of polyurethane compounds by forming carbonyl groups. The experimental analysis of the biodegradation of PUR can be carried out by bringing the polymer into contact with a mold in pure culture or with a microbial consortium. Then, global measurements can be taken, such as weight loss, tensile tests, or the ability of microorganisms to grow in the presence of PUR as the sole carbon source. The analysis of the chemical structure of the polymer and its degradation products after fungal growth can confirm biodegradation and specify the mechanism. The main avenues of future research are directed towards the development of fully biodegradable PURs and, on the contrary, towards the development of PURs that are more resistant to degradation phenomena, in particular biodegradation, for applications where the material is in contact with living organisms.
Rhizobia Inoculation Supplemented with Nitrogen Fertilization Enhances Root Nodulation, Productivity, and Nitrogen Dynamics in Soil and Black Gram (Vigna mungo (L.) Hepper)
Authors: Sadiq Mahran , Rahim Nasir , Iqbal Muhammad Aamir , Alqahtani Mashael Daghash , Tahir Majid Mahmood , Majeed Afshan , Ahmed Raees
Published: July 2023

The potential interactions of rhizobium bacteria in enhancing nodulation, nitrogen (N) fixation for boosting N availability, and the yield of black gram under a temperate environment continue to remain unexplored. Therefore, this study aimed to evaluate the agronomic performance of black gram cultivars, their yield comparisons, and shoot–grain–soil N dynamics in a prevalently rainfed farming system. Two black gram cultivars, NARC Mash-I and NARC Mash-II, were subjected to rhizobia inoculation combined with different N doses (0, 25, 50, 75, 100 kg ha−1). The response variables included root nodulation, agronomic yield attributes, grain yield, shoot–grain and soil N dynamics, and biological productivity. Black gram cultivar NARC Mash-II showed the maximum nodule formation (41 per plant), while each nodule obtained 0.69 g weight in response to RI combined with 25 kg N ha−1. Additionally, this combination showed the highest pods per plant and thousand grain weight, which maximized the grain yield (1777 kg ha−1) and biological productivity (3007 kg ha−1). In contrast, NARC Mash-I under 50 kg N recorded the highest shoot N content, while the same cultivar under 100 kg N exhibited the maximum soil N content. The correlation analyses indicated a significantly robust association among the nodule numbers, grain weight, and N contents in different plant organs. These results give mechanistic insights into plant–microbe interactions based on the eco-friendly, sustainable, and smart agricultural practice of black gram production in a temperate environment.
Ver-Based Evidential Re/Positioning Strategies in Conservative Digital Newspaper Readers’ Comments on Controversial Immigration Policies in Spanish
Authors: Domínguez Romero Elena
Published: July 2023

The emergence of political polarization in Europe has intensified divisions among citizens regarding immigration, inequality, and racism. The present paper investigates the use of ver-based (“see”-based) evidentiality in positioning and repositioning strategies by conservative Spanish readers of the digital newspapers ABC and La Razón. The study focuses on their responses to two different controversial measures involving immigrants and refugees taken in by the Spanish government. Such measures relate to the Aquarius (2018) and the Open Arms (2019) incidents. The analysis will be corpus, content-based, and grounded in positioning theory and theories of visual evidential perception. The ultimate aim is to explore the instances of ver-based evidentiality introducing positioning and repositioning strategies that are present in the corpus. Subsequently, we will classify and analyze the viewpoints expressed by conservative readers through these ver-based evidential markers.
Enhanced Resolution of Neutron Autoradiography with UV-C Sensitization to Study Boron Microdistribution in Animal Models
Authors: Portu Agustina Mariana , Espain María Sol , Thorp Silvia Inés , Trivillin Verónica Andrea , Curotto Paula , Monti Hughes Andrea , Pozzi Emiliano César Cayetano , Garabalino Marcela Alejandra , Palmieri Mónica Alejandra , Granell Pablo Nicolás , Golmar Federico , Schwint Amanda Elena , Saint Martin Gisela
Published: July 2023

The assessment of boron microdistribution is essential to evaluate the suitability of boron neutron capture therapy (BNCT) in different biological models. In our laboratory, we have reported a methodology to produce cell imprints on polycarbonate through UV-C sensitization. The aim of this work is to extend the technique to tissue samples in order to enhance spatial resolution. As tissue structure largely differs from cultured cells, several aspects must be considered. We studied the influence of the parameters involved in the imprint and nuclear track formation, such as neutron fluence, different NTDs, etching and UV-C exposure times, tissue absorbance, thickness, and staining, among others. Samples from different biological models of interest for BNCT were used, exhibiting homogeneous and heterogeneous histology and boron microdistribution. The optimal conditions will depend on the animal model under study and the resolution requirements. Both the imprint sharpness and the fading effect depend on tissue thickness. While 6 h of UV-C was necessary to yield an imprint in CR-39, only 5 min was enough to observe clear imprints on Lexan. The information related to microdistribution of boron obtained with neutron autoradiography is of great relevance when assessing new boron compounds and administration protocols and also contributes to the study of the radiobiology of BNCT.
Paraffin–Peloid Formulations from Copahue: Processing, Characterization, and Application
Authors: Sanchez Micaela A. , Baschini Miria T. , Pozo Manuel , Gramisci Betina R. , Roca Jalil María E. , Vela María L.
Published: July 2023

The Copahue Thermal Center, situated in Neuquén, Argentina, produces natural and matured peloids, which are employed in the prevention and treatment of various osteoarticular and dermatological disorders. The presence of sulfur as a constituent and its thermotherapeutic potential constitute the primary strengths of these peloids. Nevertheless, accessing Copahue is challenging due to its distance from densely populated centers and the snow cover during the winter months in the southern hemisphere. Therefore, in order to propose a material that can be utilized year-round in any location, a mudpack was obtained by combining medicinal paraffin with dehydrated Copahue peloids, with concentrations evaluated up to 10% w/w. This mudpack was analyzed through X-ray diffraction, which detected the presence of sulfur, the most important component of Copahue’s peloids. Through IR spectroscopy, the signals that identify medicinal paraffin were clearly observed, and for concentrations of 6% and 10% peloid in the material, it was possible to detect the presence of mineral clay components associated with Si-O stretching vibrations at around 1041 cm−1. The low values of luminosity and grey tonality obtained for the mudpack contributed to patient acceptability and the absorption of electromagnetic radiation. The experimental cooling rate, calculated using the ratio of the temperature variation (∆T) with respect to the time variation (∆t) in each interval of the experimental curve, was determined to be 0.6 °C·min−1 for both paraffin and the mudpack. However, for peloids, higher values ranging from 0.6 to 4.8 °C·min−1 were obtained. This suggests that the mudpack mixtures have a slower heat release, which is a desirable property for their use as a thermotherapeutic agent. Considering the reusability of the mudpack, its stability was evaluated after 10 cycles of cooling and heating through XRD, DSC, and FTIR tests, resulting in a system that retains its properties. The formulation of the obtained mudpack is promising for the development of these materials on a larger scale.
Solubility and Valence Variation of Ce in Low-Alkali Borosilicate Glass and Glass Network Structure Analysis
Authors: Yang Liu , Zhu Yongchang , Huo Jichuan , Cui Zhu , Zhang Xingquan , Dong Xuanjiang , Feng Jie
Published: July 2023

Low-alkali borosilicate glass was used as the immobilization substrate, and Ce was used to replicate the trivalent and tetravalent actinides, in order to create simulated waste glass through melt heat treatment. The valence of Ce and solubility of CeO2 in waste glass were studied as well as its network structure and thermal and chemical stability. The solubility of Ce in waste glass was examined by XRD and SEM. The network structure was examined by Raman spectroscopy. The valence of Ce was determined by X-ray photoelectron spectroscopy. Thermal analysis and product consistency (PCT) were employed to determine the thermal and chemical stability of waste glasses. The results show that the solubility of cerium in low-alkali borosilicate glasses is at least 25.wt.% and precipitates a spherical CeO2 crystalline phase when it exceeds the solid solution limit; Ce is immobilized in the glass by entering the interstices of the glass network. Depolymerization and the transition from [BO3] to [BO4] occurs when CeO2 doping levels rise. About 60 percent of Ce4+ is converted to Ce3+, and the thermal stability of glass rises then falls with the increase of CeO2. All samples exhibit strong leaching resistance, with the average mass loss of Ce at 28 days being less than 10−4 gm−2d−1.
Optimisation of a Multi-Functional Piezoelectric Component for a Climbing Robot
Authors: Wegert Zachary J. , Roberts Anthony P. , Bandyopadhyay Tirthankar , Challis Vivien J.
Published: July 2023

Force sensors on climbing robots give important information to the robot control system, however, off-the-shelf sensors can be both heavy and bulky. We investigate the optimisation of a lightweight integrated force sensor made of piezoelectric material for the multi-limbed climbing robot MAGNETO. We focus on three design objectives for this piezoelectric component. The first is to develop a lightweight component with minimal compliance that can be embedded in the foot of the climbing robot. The second objective is to ensure that the component has sensing capability to replace the off-the-shelf force sensor. Finally, the component should be robust for a range of climbing configurations. To this end, we focus on a compliance minimisation problem with constrained voltage and volume fraction. We present structurally optimised designs that satisfy the three main design criteria and improve upon baseline results from a reference component. Our computational study demonstrates that the optimisation of embedded robotic components with piezoelectric sensing is worthy of future investigation.
A CNN-Based Methodology for Identifying Mechanical Faults in Induction Motors Using Thermography
Authors: Trejo-Chavez Omar , Cruz-Albarran Irving A. , Resendiz-Ochoa Emmanuel , Salinas-Aguilar Alejandro , Morales-Hernandez Luis A. , Basurto-Hurtado Jesus A. , Perez-Ramirez Carlos A.
Published: July 2023

Infrared thermography (IRT) has become an interesting alternative for performing condition assessments of different types of induction motor (IM)-based equipment when it operates under harsh conditions. The reported results from state-of-the-art articles that have analyzed thermal images do not consider (1): the presence of more than one fault, and (2) the inevitable noise-corruption the images suffer. Bearing in mind these reasons, this paper presents a convolutional neural network (CNN)-based methodology that is specifically designed to deal with noise-corrupted images for detecting the failures that have the highest incidence rate: bearing and broken bar failures; moreover, rotor misalignment failure is also considered, as it can cause a further increase in electricity consumption. The presented results show that the proposal is effective in detecting healthy and failure states, as well as identifying the failure nature, as a 95% accuracy is achieved. These results allow considering the proposal as an interesting alternative for using IRT images obtained in hostile environments.
Comprehensive Evaluations of Student Performance Estimation via Machine Learning
Authors: Mohammad Ahmad Saeed , Al-Kaltakchi Musab T. S. , Alshehabi Al-Ani Jabir , Chambers Jonathon A.
Published: July 2023

Success in student learning is the primary aim of the educational system. Artificial intelligence utilizes data and machine learning to achieve excellence in student learning. In this paper, we exploit several machine learning techniques to estimate early student performance. Two main simulations are used for the evaluation. The first simulation used the Traditional Machine Learning Classifiers (TMLCs) applied to the House dataset, and they are Gaussian Naïve Bayes (GNB), Support Vector Machine (SVM), Decision Tree (DT), Multi-Layer Perceptron (MLP), Random Forest (RF), Linear Discriminant Analysis (LDA), and Quadratic Discriminant Analysis (QDA). The best results were achieved with the MLP classifier with a division of 80% training and 20% testing, with an accuracy of 88.89%. The fusion of these seven classifiers was also applied and the highest result was equal to the MLP. Moreover, in the second simulation, the Convolutional Neural Network (CNN) was utilized and evaluated on five main datasets, namely, House, Western Ontario University (WOU), Experience Application Programming Interface (XAPI), University of California-Irvine (UCI), and Analytics Vidhya (AV). The UCI dataset was subdivided into three datasets, namely, UCI-Math, UCI-Por, and UCI-Fused. Moreover, the AV dataset has three targets which are Math, Reading, and Writing. The best accuracy results were achieved at 97.5%, 99.55%, 98.57%, 99.28%, 99.40%, 99.67%, 92.93%, 96.99%, and 96.84% for the House, WOU, XAPI, UCI-Math, UCI-Por, UCI-Fused, AV-Math, AV-Reading, and AV-Writing datasets, respectively, under the same protocol of evaluation. The system demonstrates that the proposed CNN-based method surpasses all seven conventional methods and other state-of-the-art-work.
The Limit Properties of Maxima of Stationary Gaussian Sequences Subject to Random Replacing
Authors: Li Yuwei , Tan Zhongquan
Published: July 2023

In applications, missing data may occur randomly and some relevant datum are often used to replace the missing ones. This article mainly explores the influence of the degree of dependence of stationary Gaussian sequences on the joint asymptotic distribution of the maximum of the Gaussian sequence and its maximum when the sequence is subject to random replacing.
Effect of Brassinolide on Soil Microorganisms in Millet Field Polluted by Tribenuron-Methyl
Authors: Song Xi’e , Cao Junli , Guo Shuai , Wang Hao , Dong Qianhui , Guo Pingyi , Yuan Xiangyang
Published: July 2023

Tribenuron-methyl is used to control broad-leaved weeds and has a promising application prospect in millet fields. However, its negative impact on soil ecology cannot be ignored. Brassinosteroids have been widely reported to enhance plant resistance to stress, but information on brassinosteroids for the remediation of pesticide-contaminated soils is limited. Under field conditions, brassinosteroids were applied to explore their effects on the residues of tribenuron-methyl, soil enzyme activity, soil microbiol community, and millet yield. After applying brassinosteroids according to the dose of 150 mL hm−2, the degradation rate of tribenuron-methyl accelerated. Brassinolide stimulated the activities of catalase and dehydrogenase, while the activities of sucrase and alkaline phosphatase were inhibited. The results of high-throughput sequencing showed that brassinosteroids inhibited the growth of Verrucomicrobia, Ascomycota, and Mortierellomycota and promoted the abundance of cyanobacteria. Additionally, brassinosteroids could also significantly increase the diversity index and change the community structure of soil bacteria and fungi. Further, the predicted function results indicated that brassinosteroids changed some metabolic-related ecological functions of the soil. We also found that brassinolide could increase millet yields by 2.4% and 13.6%. This study provides a theoretical basis for the safe use of tribenuron-methyl in millet fields and a new idea for the treatment of pesticide residues in soil.
Impact of Preoperative Nutritional Assessment on Other-Cause Survival after Gastrectomy in Patients with Gastric Cancer
Authors: Matsui Ryota , Inaki Noriyuki , Tsuji Toshikatsu
Published: July 2023

This study aimed to clarify the factors associated with death due to other diseases after a gastrectomy for gastric cancer. This retrospective cohort study included consecutive patients who had undergone gastrectomy between April 2008 and June 2018 for primary stage II–III gastric cancer. The primary outcome was other-cause survival. To identify prognostic factors for other-cause survival for univariate analysis, we used a Cox proportional hazard regression model. A total of 512 patients met the inclusion criteria. The average age was 67.93 years, and the average body mass index was 22.75 kg/m2, with 84 (16.4%) being moderately malnourished and 88 (17.2%) being severely malnourished, as defined by the Global Leadership Initiative on Malnutrition (GLIM) criteria. The other-cause survival for the malnourished group was significantly worse than that for the normal group (p < 0.001). The prognosis was worse when the severity of malnutrition was worse (p < 0.001). Multivariate analysis showed that severe malnutrition was significantly independent of prognostic factors for other-cause survival (hazard ratio: 3.310; 95% confidence interval: 1.426–7.682; p = 0.005). Undernutrition, as defined by the GLIM criteria, is useful for the preoperative prediction of death due to other diseases after gastrectomy in patients with advanced gastric cancer.