bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonatal Exposure to Valproate Induces Long-Term Alterations in Steroid Hormone Levels in the Brain Cortex of Prepubertal Rats
Authors: Kim Soon-Ae , Jang Eun-Hye , Lee Jangjae , Cho Sung-Hee
Published: April 2023

Valproic acid (VPA) is a known drug for treating epilepsy and mood disorders; however, it is not recommended for pregnant women because of its possible teratogenicity. VPA affects neurotransmission and gene expression through epigenetic mechanisms by acting as a histone deacetylase inhibitor and has been used to establish animal models of autism spectrum disorder (ASD). However, studies on the long-term effects of early exposure to VPA on glucocorticoid and neurosteroid synthesis in the brain are lacking. Therefore, this study aimed to investigate the long-term changes in metabolic alterations and gene expression regulation according to sex, using metabolic steroid profiling data from cerebral cortex samples of rats four weeks after VPA exposure (400 mg/kg). In neonatal VPA-exposed models, estradiol levels decreased, and cytochrome P450 19A1 gene (Cyp19a1) expression was reduced in the prepubertal male cortex. Progesterone and allopregnanolone levels decreased, and 3β-hydroxysteroid dehydrogenase 1 gene (Hsd3b1) expression was also downregulated in the prepubertal female cortex. Furthermore, cortisol levels increased, and mRNA expression of the nuclear receptor subfamily 3 group C member 1 gene (Nr3c1) was downregulated in the cortices of both sexes. Unlike the neonatal VPA-exposed models, although a decrease in progestin and estradiol levels was observed in females and males, respectively, no differences were observed in cortisol levels in the cortex tissues of 8-week-old adult rats administered VPA for four weeks. These results indicate that early environmental chemical exposure induces long-term neurosteroid metabolic effects in the brain, with differences according to sex.
The Emerging Role of RNA in Diseases and Cancers
Authors: Fatica Alessandro
Published: April 2023

In recent years, there has been a growing interest in the role of RNA in diseases and cancers [...]
A Machine Learning Model to Predict Survival and Therapeutic Responses in Multiple Myeloma
Authors: Ren Liang , Xu Bei , Xu Jiadai , Li Jing , Jiang Jifeng , Ren Yuhong , Liu Peng
Published: April 2023

Multiple myeloma (MM) is a highly heterogeneous hematologic tumor. Ubiquitin proteasome pathways (UPP) play a vital role in its initiation and development. We used cox regression analysis and least absolute shrinkage and selector operation (LASSO) to select ubiquitin proteasome pathway associated genes (UPPGs) correlated with the overall survival (OS) of MM patients in a Gene Expression Omnibus (GEO) dataset, and we formed this into ubiquitin proteasome pathway risk score (UPPRS). The association between clinical outcomes and responses triggered by proteasome inhibitors (PIs) and UPPRS were evaluated. MMRF CoMMpass was used for validation. We applied machine learning algorithms to MM clinical and UPPRS in the whole cohort to make a prognostic nomogram. Single-cell data and vitro experiments were performed to unravel the mechanism and functions of UPPRS. UPPRS consisting of 9 genes showed a strong ability to predict OS in MM patients. Additionally, UPPRS can be used to sort out the patients who would gain more benefits from PIs. A machine learning model incorporating UPPRS and International Staging System (ISS) improved survival prediction in both datasets compared to the revisions of ISS. At the single-cell level, high-risk UPPRS myeloma cells exhibited increased cell adhesion. Targeted UPPGs effectively inhibited myeloma cells in vitro. The UPP genes risk score is a helpful tool for risk stratification in MM patients, particularly those treated with PIs.
TLR9 Signaling Is Required for the Porphyromonas gingivalis-Induced Activation of IL-10-Expressing B Cells
Authors: Alaqla Ali , Hu Yang , Huang Shengyuan , Ruiz Sunniva , Kawai Toshihisa , Han Xiaozhe
Published: April 2023

Immune cell pattern-recognition receptors such as Toll-like receptors (TLRs) play important roles in the regulation of host responses to periodontal pathogens. Our previous studies have demonstrated that immune regulatory B cells were activated by TLRs and alleviated periodontitis inflammation and bone loss. The purpose of this study is to determine the role of TLR9 signaling in the activation and IL-10 production of the primed-immune B cells in vitro. Wild-type (WT) and TLR9 knockout (TLR9KO) mice (C57BL/6 background, n = 5) were pre-immunized intraperitoneally with 1 × 108 formalin-fixed P. gingivalis and boosted once with 1 × 107 formalin-fixed P. gingivalis. Isolated splenocytes and purified B cells from each mouse were cultured with 1 × 108 formalin-fixed P. gingivalis for 48 h. Immunocytochemistry was performed to detect CD45+ IL-10+ cells. Levels of IL-10 expression and secretion in splenocytes and B cells were detected using qRT-PCR and ELISA, respectively. After stimulation with fixed P. gingivalis, the percentage of CD45+ IL-10+ B cells and the level of IL-10 expression were significantly increased (p < 0.01) in splenocytes and purified B cells isolated from WT mice. However, these changes were not observed in splenocytes and purified B cells from TLR9KO mice when the cells were treated with fixed P. gingivalis. The percentage of CD45+ IL-10+ B cells was significantly reduced in splenocytes and purified B cells from TLR9KO mice compared to those from WT mice when challenged with P. gingivalis. IL-10 expression in B cells from TLR9KO mice was significantly decreased compared to those from WT mice at both the mRNA and protein levels. Additionally, P. gingivalis-induced up-regulation of TNF-α mRNA expressions were consistently observed in B cells from both WT and TLR9KO mice. P. gingivalis-induced B10 activation and IL-10 production during adaptive responses by primed B cells requires TLR9 signaling and can be achieved independent of T-cell help.
In Situ Raman Analysis of Biofilm Exopolysaccharides Formed in Streptococcus mutans and Streptococcus sanguinis Commensal Cultures
Authors: Pezzotti Giuseppe , Ofuji Satomi , Imamura Hayata , Adachi Tetsuya , Yamamoto Toshiro , Kanamura Narisato , Ohgitani Eriko , Marin Elia , Zhu Wenliang , Mazda Osam , Togo Azusa , Kimura Satoshi , Iwata Tadahisa , Shiba Hideki , Ouhara Kazuhisa , Aoki Takashi , Kawai Toshihisa
Published: April 2023

This study probed in vitro the mechanisms of competition/coexistence between Streptococcus sanguinis (known for being correlated with health in the oral cavity) and Streptococcus mutans (responsible for aciduric oral environment and formation of caries) by means of quantitative Raman spectroscopy and imaging. In situ Raman assessments of live bacterial culture/coculture focusing on biofilm exopolysaccharides supported the hypothesis that both species engaged in antagonistic interactions. Experiments of simultaneous colonization always resulted in coexistence, but they also revealed fundamental alterations of the biofilm with respect to their water-insoluble glucan structure. Raman spectra (collected at fixed time but different bacterial ratios) showed clear changes in chemical bonds in glucans, which pointed to an action by Streptococcus sanguinis to discontinue the impermeability of the biofilm constructed by Streptococcus mutans. The concurrent effects of glycosidic bond cleavage in water-insoluble α − 1,3–glucan and oxidation at various sites in glucans’ molecular chains supported the hypothesis that secretion of oxygen radicals was the main “chemical weapon” used by Streptococcus sanguinis in coculture.
Dimethylglycine Can Enhance the Cryopreservation of Red Blood Cells by Reducing Ice Formation and Oxidative Damage
Authors: Hu Yuying , Liu Xiangjian , Ekpo Marlene Davis , Chen Jiangming , Chen Xiaoxiao , Zhang Wenqian , Zhao Rui , Xie Jingxian , He Yongju , Tan Songwen
Published: April 2023

The cryopreservation of red blood cells (RBCs) holds great potential for ensuring timely blood transfusions and maintaining an adequate RBC inventory. The conventional cryoprotectants (CPAs) have a lot of limitations, and there is an obvious need for novel, efficient, and biocompatible CPAs. Here, it is shown for the first time that the addition of dimethylglycine (DMG) improved the thawed RBC recovery from 11.55 ± 1.40% to 72.15 ± 1.22%. We found that DMG could reduce the mechanical damage by inhibiting ice formation and recrystallization during cryopreservation. DMG can also scavenge reactive oxygen species (ROS) and maintain endogenous antioxidant enzyme activities to decrease oxidative damage during cryopreservation. Furthermore, the properties of thawed RBCs were found to be similar to the fresh RBCs in the control. Finally, the technique for order performance by similarity to ideal solution (TOPSIS) was used to compare the performance of glycerol (Gly), hydroxyethyl starch (HES), and DMG in cryopreservation, and DMG exhibited the best efficiency. This work confirms the use of DMG as a novel CPA for cryopreservation of RBCs and may promote clinical transfusion therapy.
The Synergistic Antimicrobial Effect and Mechanism of Nisin and Oxacillin against Methicillin-Resistant Staphylococcus aureus
Authors: Wang Jun , Ma Xinxin , Li Jing , Shi Lu , Liu Lijuan , Hou Xinyao , Jiang Sijin , Li Pu , Lv Jia , Han Lei , Cheng Yue , Han Bei
Published: April 2023

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for skin and soft tissue infections with multi-resistance to many antibiotics. It is thus imperative to explore alternative antimicrobial treatments to ensure future treatment options. Nisin (NIS), an antibacterial peptide produced by Lactococcus lactis, was selected to combine with Oxacillin (OX), to evaluate the antimicrobial effect and potential mechanism against MRSA. The synergistic antimicrobial effect of OX and NIS was verified by Minimal Inhibitory Concentration (MIC) assays, checkerboard analysis, time-kill curve, biofilm producing ability, and mice skin infection model in vivo. For the potential synergistic antimicrobial mechanism, the microstructure and integrity change of MRSA cells were determined by Scanning and Transmission Electron Microscope (SEM and TEM), intracellular alkaline phosphatase activity and propidium iodide staining were assayed; And transcription of mecA, main gene of MRSA resistant to OX, were detected by qRT-PCR. The results showed NIS could restore the sensitivity of MRSA to OX and inhibit biofilm production; OX + NIS can make MRSA cell deform; NIS may recover OX sensitivity by inhibiting the transcription of mecA. In vivo, mice skin infection models indicate that OX + NIS can substantially alleviate MRSA infections. As a safe commercially available biological compound, NIS and the combination of antibiotics are worth developing as new anti-MRSA biomaterials.
The Role and Mechanism of Hydrogen-Rich Water in the Cucumis sativus Response to Chilling Stress
Authors: Wang Xue , An Zhonghui , Liao Jiameng , Ran Nana , Zhu Yimeng , Ren Shufeng , Meng Xiangnan , Cui Na , Yu Yang , Fan Haiyan
Published: April 2023

Cucumber is a warm climate vegetable that is sensitive to chilling reactions. Chilling can occur at any period of cucumber growth and development and seriously affects the yield and quality of cucumber. Hydrogen (H2) is a type of antioxidant that plays a critical role in plant development and the response to stress. Hydrogen-rich water (HRW) is the main way to use exogenous hydrogen. This study explored the role and mechanism of HRW in the cucumber defense response to chilling stress. The research results showed that applying 50% saturated HRW to the roots of cucumber seedlings relieved the damage caused by chilling stress. The growth and development indicators, such as plant height, stem diameter, leaf area, dry weight, fresh weight, and root length, increased under the HRW treatment. Photosynthetic efficiency, chlorophyll content, and Fv/Fm also improved and reduced energy dissipation. In addition, after HRW treatment, the REC and MDA content were decreased, and membrane lipid damage was reduced. NBT and DAB staining results showed that the color was lighter, and the area was smaller under HRW treatment. Additionally, the contents of O2− and H2O2 also decreased. Under chilling stress, the application of HRW increased the activity of the antioxidases SOD, CAT, POD, GR, and APX and improved the expression of the SOD, CAT, POD, GR, and APX antioxidase genes. The GSSG content was reduced, and the GSH content was increased. In addition, the ASA content also increased. Therefore, exogenous HRW is an effective measure for cucumber to respond to chilling stress.
The Efficacy of Tumor Mutation Burden as a Biomarker of Response to Immune Checkpoint Inhibitors
Authors: Moeckel Camille , Bakhl Katrina , Georgakopoulos-Soares Ilias , Zaravinos Apostolos
Published: April 2023

Cancer is one of the leading causes of death in the world; therefore, extensive research has been dedicated to exploring potential therapeutics, including immune checkpoint inhibitors (ICIs). Initially, programmed-death ligand-1 was the biomarker utilized to predict the efficacy of ICIs. However, its heterogeneous expression in the tumor microenvironment, which is critical to cancer progression, promoted the exploration of the tumor mutation burden (TMB). Research in various cancers, such as melanoma and lung cancer, has shown an association between high TMB and response to ICIs, increasing its predictive value. However, the TMB has failed to predict ICI response in numerous other cancers. Therefore, future research is needed to analyze the variations between cancer types and establish TMB cutoffs in order to create a more standardized methodology for using the TMB clinically. In this review, we aim to explore current research on the efficacy of the TMB as a biomarker, discuss current approaches to overcoming immunoresistance to ICIs, and highlight new trends in the field such as liquid biopsies, next generation sequencing, chimeric antigen receptor T-cell therapy, and personalized tumor vaccines.
Distinctive Kaposi Sarcoma-Associated Herpesvirus Serological Profile during Acute Plasmodium falciparum Malaria Episodes
Authors: Oluoch Peter O. , Forconi Catherine S. , Oduor Cliff I. , Ritacco Dominic A. , Akala Hoseah M. , Bailey Jeffrey A. , Juliano Jonathan J. , Ong’echa John M. , Münz Christian , Moormann Ann M.
Published: April 2023

The seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV) and the incidence of endemic Kaposi sarcoma (KS) overlap with regions of malaria endemicity in sub-Saharan Africa. Multiple studies have shown an increased risk of KSHV seroconversion in children from high malaria compared to low malaria regions; however, the impact of acute episodes of Plasmodium falciparum (P. falciparum) malaria on KSHV’s biphasic life cycle and lytic reactivation has not been determined. Here, we examined KSHV serological profiles and viral loads in 134 children with acute malaria and 221 healthy children from high malaria regions in Kisumu, as well as 77 healthy children from low malaria regions in Nandi. We assayed KSHV, Epstein–Barr virus (EBV), and P. falciparum malaria antibody responses in these three by multiplexed Luminex assay. We confirmed that KSHV seroprevalence was significantly associated with malaria endemicity (OR = 1.95, 1.18–3.24 95% CI, p = 0.01) with 71–77% seropositivity in high-malaria (Kisumu) compared to 28% in low-malaria (Nandi) regions. Furthermore, KSHV serological profiles during acute malaria episodes were distinct from age-matched non-malaria-infected children from the same region. Paired IgG levels also varied after malaria treatment, with significantly higher anti-ORF59 at day 0 but elevated ORF38, ORF73, and K8.1 at day 3. Acute malaria episodes is characterized by perturbation of KSHV latency in seropositive children, providing further evidence that malaria endemicity contributes to the observed increase in endemic KS incidence in sub-Saharan Africa.
Activated Carbon-Enriched Electrospun-Produced Scaffolds for Drug Delivery/Release in Biological Systems
Authors: Nazarkina Zhanna K. , Stepanova Alena O. , Chelobanov Boris P. , Kvon Ren I. , Simonov Pavel A. , Karpenko Andrey A. , Laktionov Pavel P.
Published: April 2023

To vectorize drug delivery from electrospun-produced scaffolds, we introduce a thin outer drug retention layer produced by electrospinning from activated carbon nanoparticles (ACNs)-enriched polycaprolacton (PCL) suspension. Homogeneous or coaxial fibers filled with ACNs were produced by electrospinning from different PCL-based suspensions. Stable ACN suspensions were selected by sorting through solvents, stabilizers and auxiliary components. The ACN-enriched scaffolds produced were characterized for fiber diameter, porosity, pore size and mechanical properties. The scaffold structure was analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy. It was found that ACNs were mainly coated with a polymer layer for both homogeneous and coaxial fibers. Drug binding and release from the scaffolds were tested using tritium-labeled sirolimus. We showed that the kinetics of sirolimus binding/release by ACN-enriched scaffolds was determined by the fiber composition and differed from that obtained with a free ACN. ACN-enriched scaffolds with coaxial and homogeneous fibers had a biocompatibility close to scaffold-free AC, as was shown by the cultivation of human gingival fibroblasts and umbilical vein cells on scaffolds. The data obtained demonstrated that ACN-enriched scaffolds had good physico-chemical properties and biocompatibility and, thus, could be used as a retaining layer for vectored drug delivery.
Transcriptomic Changes Predict Metabolic Alterations in LC3 Associated Phagocytosis in Aged Mice
Authors: Dhingra Anuradha , Tobias John W. , Philp Nancy J. , Boesze-Battaglia Kathleen
Published: April 2023

LC3b (Map1lc3b) plays an essential role in canonical autophagy and is one of several components of the autophagy machinery that mediates non-canonical autophagic functions. Phagosomes are often associated with lipidated LC3b to promote phagosome maturation in a process called LC3-associated phagocytosis (LAP). Specialized phagocytes, such as mammary epithelial cells, retinal pigment epithelial (RPE) cells, and sertoli cells, utilize LAP for optimal degradation of phagocytosed material, including debris. In the visual system, LAP is critical to maintain retinal function, lipid homeostasis, and neuroprotection. In a mouse model of retinal lipid steatosis-mice lacking LC3b (LC3b−/−), we observed increased lipid deposition, metabolic dysregulation, and enhanced inflammation. Herein, we present a non-biased approach to determine if loss of LAP mediated processes modulate the expression of various genes related to metabolic homeostasis, lipid handling, and inflammation. A comparison of the RPE transcriptome of WT and LC3b−/− mice revealed 1533 DEGs, with ~73% upregulated and 27% downregulated. Enriched gene ontology (GO) terms included inflammatory response (upregulated DEGs), fatty acid metabolism, and vascular transport (downregulated DEGs). Gene set enrichment analysis (GSEA) identified 34 pathways; 28 were upregulated (dominated by inflammation/related pathways) and 6 were downregulated (dominated by metabolic pathways). Analysis of additional gene families identified significant differences for genes in the solute carrier family, RPE signature genes, and genes with a potential role in age-related macular degeneration. These data indicate that loss of LC3b induces robust changes in the RPE transcriptome contributing to lipid dysregulation and metabolic imbalance, RPE atrophy, inflammation, and disease pathophysiology.
1,25(OH)2D3 Differently Modulates the Secretory Activity of IFN-DC and IL4-DC: A Study in Cells from Healthy Donors and MS Patients
Authors: Sanseverino Isabella , Rinaldi Arturo Ottavio , Purificato Cristina , Cortese Antonio , Millefiorini Enrico , Gauzzi Maria Cristina
Published: April 2023

Immune mechanisms play an essential role in driving multiple sclerosis (MS) and altered trafficking and/or activation of dendritic cells (DC) were observed in the central nervous system and cerebrospinal fluid of MS patients. Interferon β (IFNβ) has been used as a first-line therapy in MS for almost three decades and vitamin D deficiency is a recognized environmental risk factor for MS. Both IFNβ and vitamin D modulate DC functions. Here, we studied the response to 1,25-dihydoxyvitamin D3 (1,25(OH)2D3) of DC obtained with IFNβ/GM-CSF (IFN-DC) compared to classically derived IL4-DC, in three donor groups: MS patients free of therapy, MS patients undergoing IFNβ therapy, and healthy donors. Except for a decreased CCL2 secretion by IL4-DC from the MS group, no major defects were observed in the 1,25(OH)2D3 response of either IFN-DC or IL4-DC from MS donors compared to healthy donors. However, the two cell models strongly differed for vitamin D receptor level of expression as well as for basal and 1,25(OH)2D3-induced cytokine/chemokine secretion. 1,25(OH)2D3 up-modulated IL6, its soluble receptor sIL6R, and CCL5 in IL4-DC, and down-modulated IL10 in IFN-DC. IFN-DC, but not IL4-DC, constitutively secreted high levels of IL8 and of matrix-metalloproteinase-9, both down-modulated by 1,25(OH)2D3. DC may contribute to MS pathogenesis, but also provide an avenue for therapeutic intervention. 1,25(OH)2D3-induced tolerogenic DC are in clinical trial for MS. We show that the protocol of in vitro DC differentiation qualitatively and quantitatively affects secretion of cytokines and chemokines deeply involved in MS pathogenesis.
Characterization of the Difference between Day and Night Temperatures on the Growth, Photosynthesis, and Metabolite Accumulation of Tea Seedlings
Authors: Tan Xiaoqin , Li Huili , Zhang Zhongyue , Yang Yanjuan , Jin Zhen , Chen Wei , Tang Dandan , Wei Chaoling , Tang Qian
Published: April 2023

Currently, the effects of the differences between day and night temperatures (DIFs) on tea plant are poorly understood. In order to investigate the influence of DIFs on the growth, photosynthesis, and metabolite accumulation of tea plants, the plants were cultivated under 5 °C (25/20 °C, light/dark), 10 °C (25/15 °C, light/dark), and 15 °C (25/10 °C, light/dark). The results showed that the growth rate of the new shoots decreased with an increase in the DIFs. There was a downward trend in the photosynthesis among the treatments, as evidenced by the lowest net photosynthetic rate and total chlorophyll at a DIF of 15 °C. In addition, the DIFs significantly affected the primary and secondary metabolites. In particular, the 10 °C DIF treatment contained the lowest levels of soluble sugars, tea polyphenols, and catechins but was abundant in caffeine and amino acids, along with high expression levels of theanine synthetase (TS3) and glutamate synthase (GOGAT). Furthermore, the transcriptome data revealed that the differentially expressed genes were enriched in valine, leucine, and isoleucine degradation, flavone/flavonol biosyntheses, flavonoid biosynthesis, etc. Therefore, we concluded that a DIF of 10 °C was suitable for the protected cultivation of tea plants in terms of the growth and the quality of a favorable flavor of tea, which provided a scientific basis for the protected cultivation of tea seedlings.
Membrane Channels in Health and Diseases
Authors: Felipe Antonio , Ferrer-Montiel Antonio
Published: April 2023

The goal of this Special Issue, entitled “Membrane Channels in Health and Diseases (https://www [...]
Prolonged Piezo1 Activation Induces Cardiac Arrhythmia
Authors: Rolland Laura , Torrente Angelo Giovanni , Bourinet Emmanuel , Maskini Dounia , Drouard Aurélien , Chevalier Philippe , Jopling Chris , Faucherre Adèle
Published: April 2023

The rhythmical nature of the cardiovascular system constantly generates dynamic mechanical forces. At the centre of this system is the heart, which must detect these changes and adjust its performance accordingly. Mechanoelectric feedback provides a rapid mechanism for detecting even subtle changes in the mechanical environment and transducing these signals into electrical responses, which can adjust a variety of cardiac parameters such as heart rate and contractility. However, pathological conditions can disrupt this intricate mechanosensory system and manifest as potentially life-threatening cardiac arrhythmias. Mechanosensitive ion channels are thought to be the main proponents of mechanoelectric feedback as they provide a rapid response to mechanical stimulation and can directly affect cardiac electrical activity. Here, we demonstrate that the mechanosensitive ion channel PIEZO1 is expressed in zebrafish cardiomyocytes. Furthermore, chemically prolonging PIEZO1 activation in zebrafish results in cardiac arrhythmias. indicating that this ion channel plays an important role in mechanoelectric feedback. This also raises the possibility that PIEZO1 gain of function mutations could be linked to heritable cardiac arrhythmias in humans.
GPR37 and Related Receptors: Disease Regulation
Authors: Marazziti Daniela
Published: April 2023

The vertebrate G protein-coupled receptors 37 and 37-like 1 (GPR37 and GPR37L1) were discovered more than two decades ago, and they have been implicated in various neurological and neurodegenerative diseases, as well as in inflammatory pain and tumorigenesis [...]
MBTI Personality Prediction Using Machine Learning and SMOTE for Balancing Data Based on Statement Sentences
Authors: Ryan Gregorius , Katarina Pricillia , Suhartono Derwin
Published: April 2023

The rise of social media as a platform for self-expression and self-understanding has led to increased interest in using the Myers–Briggs Type Indicator (MBTI) to explore human personalities. Despite this, there needs to be more research on how other word-embedding techniques, machine learning algorithms, and imbalanced data-handling techniques can improve the results of MBTI personality-type predictions. Our research aimed to investigate the efficacy of these techniques by utilizing the Word2Vec model to obtain a vector representation of words in the corpus data. We implemented several machine learning approaches, including logistic regression, linear support vector classification, stochastic gradient descent, random forest, the extreme gradient boosting classifier, and the cat boosting classifier. In addition, we used the synthetic minority oversampling technique (SMOTE) to address the issue of imbalanced data. The results showed that our approach could achieve a relatively high F1 score (between 0.7383 and 0.8282), depending on the chosen model for predicting and classifying MBTI personality. Furthermore, we found that using SMOTE could improve the selected models’ performance (F1 score between 0.7553 and 0.8337), proving that the machine learning approach integrated with Word2Vec and SMOTE could predict and classify MBTI personality well, thus enhancing the understanding of MBTI.
Atlas-Based Shared-Boundary Deformable Multi-Surface Models through Multi-Material and Two-Manifold Dual Contouring
Authors: Rashid Tanweer , Sultana Sharmin , Chakravarty Mallar , Audette Michel Albert
Published: April 2023

This paper presents a multi-material dual “contouring” method used to convert a digital 3D voxel-based atlas of basal ganglia to a deformable discrete multi-surface model that supports surgical navigation for an intraoperative MRI-compatible surgical robot, featuring fast intraoperative deformation computation. It is vital that the final surface model maintain shared boundaries where appropriate so that even as the deep-brain model deforms to reflect intraoperative changes encoded in ioMRI, the subthalamic nucleus stays in contact with the substantia nigra, for example, while still providing a significantly sparser representation than the original volumetric atlas consisting of hundreds of millions of voxels. The dual contouring (DC) algorithm is a grid-based process used to generate surface meshes from volumetric data. The DC method enables the insertion of vertices anywhere inside the grid cube, as opposed to the marching cubes (MC) algorithm, which can insert vertices only on the grid edges. This multi-material DC method is then applied to initialize, by duality, a deformable multi-surface simplex model, which can be used for multi-surface atlas-based segmentation. We demonstrate our proposed method on synthetic and deep-brain atlas data, and a comparison of our method’s results with those of traditional DC demonstrates its effectiveness.
Impact of the Diet on the Mortality and on Gene Expression of the Antimicrobial Peptide Tenecin 3 in Tenebrio molitor Larvae Infected by Beauveria bassiana
Authors: Candian Valentina , Tedeschi Rosemarie
Published: April 2023

Large-scale insect rearing can be subjected to microbial infections, leading to serious economic losses. When possible, the use of antibiotics is to be avoided for insects intended as feed or food and new strategies to preserve the health of the farmed insects are required. The effectiveness of insect immune system depends on several factors, including the nutritional composition of the diet. The possibility to modulate immune responses through the diet is currently a topic of great interest from an application point of view. We evaluated the effect of two different diets on the survival rate and gene expression of the antimicrobial peptide Tenecin 3 in uninfected and Beauveria bassiana-infected Tenebrio molitor L. larvae. A wheat bran diet, mixed 50% with brewers’ spent grains, could positively influence the expression of Tenecin 3 gene when uninfected T. molitor is allowed to develop on such a substrate from early larval stages. Even if, in our trial, the diet with added brewers’ spent grains could not reduce the mortality of the larvae infected with B. bassiana, higher transcriptional levels of the antifungal peptide were observed in insects fed this diet, depending on the timing of diet administration.
Sex, Age, and Comorbidities Are Associated with SARS-CoV-2 Infection, COVID-19 Severity, and Fatal Outcome in a Mexican Population: A Retrospective Multi-Hospital Study
Authors: Camacho Moll Maria Elena , Mata Tijerina Viviana Leticia , Silva Ramírez Beatriz , Peñuelas Urquides Katia , González Escalante Laura Adiene , Escobedo Guajardo Brenda Leticia , Cruz Luna Jorge Eleazar , Corrales Pérez Roberto , Gómez García Salvador , Bermúdez de León Mario
Published: April 2023

People with comorbidities and the male sex are at a higher risk of developing severe COVID-19. In the present study, we aim to investigate the associated factors for infection, severity, and death due to COVID-19 in a population from Nuevo León, México. Epidemiological COVID-19 data were collected from 65 hospitals from December 2020 to May 2022. A total of 75,232 cases were compiled from which 25,722 cases were positive for SARS-CoV-2. Male sex, older age, diabetes, obesity, and hypertension were associated with infection. In addition to the above-mentioned factors, renal disease, cardiovascular disease, and immunosuppression were found to be associated with increased COVID-19 severity. These factors, as well as neurological diseases, are also associated with death due to COVID-19. When comparing the different variants of SARs-CoV-2, the variant B1.1.519 increased the probability of death by 2.23 times compared to the AY.20 variant. Male sex, older age, diabetes, obesity, and hypertension are associated with SARS-CoV-2 infection, severity, and death. Along with the aforementioned comorbidities, renal disease, cardiovascular disease, and immunosuppression are also associated with severity and death. Another factor associated with death is the presence of neurological disease. The SARS-CoV-2 B1.1.519 variant increases the odds of death compared to the SARS-CoV-2 AY.20 variant.
Baby Intensive Early Active Treatment (babiEAT): A Pilot Randomised Controlled Trial of Feeding Therapy for Infants with Cerebral Palsy and Oropharyngeal Dysphagia
Authors: Khamis Amanda , Badawi Nadia , Morgan Catherine , Novak Iona
Published: April 2023

Cerebral palsy (CP), results in impairment of muscle function including the face, mouth, and throat, leading to oropharyngeal dysphagia (OPD), which affects 85% of children with CP. OPD increases risk of deficiencies in growth, neurological development, and aspiration pneumonia, a leading cause of death in CP. This pilot randomised controlled trial aimed to (i) assess feasibility and acceptability of a novel neuroplasticity and motor-learning feeding intervention program, Baby Intensive Early Active Treatment (babiEAT), and standard care, and (ii) explore preliminary efficacy of babiEAT on health and caregiver feeding-related quality of life (QoL). A total of 14 infants with both CP and OPD were randomly allocated to 12 weeks of babiEAT or standard care. Results indicate that babiEAT and standard care are equally feasible, and acceptable. Parents in the babiEAT group thought recommendations were significantly more effective than standard care parents, were more likely to recommend the program to a friend and reported higher QoL. babiEAT infants showed significantly greater efficiency in fluid intake, fewer compensatory strategies with cup drinking, consumption of more advanced food textures, and shorter mealtimes without impacting intake, aspiration risk, or weight. This small pilot study shows promise for babiEAT in infants with CP and OPD. Further research is needed to determine strength of its effects.
Headache and Psychological Comorbidities: An Appraisal of the Evidence
Authors: Abu-Arafeh Ishaq
Published: April 2023

Background: It has been observed that there is a higher-than-expected risk of anxiety and depression in children with chronic headache and also an increased risk for the persistence of headache in patients with anxiety and depression. Objectives: This review aims to identify and assess the relationships between primary headache disorders and comorbid emotional and psychological disorders. Methods: A targeted review of the literature was carried out. Results: The associations between the disorders are more pronounced in clinic patients, who may represent the severe end of the headache spectrum, but less clear in patients who were identified in population-based studies and who may represent the “average” child with headache or the “average” child with psychological disorders. Conclusions: Understanding this bidirectional association of comorbid disorders is of great importance to offering a holistic biopsychosocial approach to the management of headache disorders in children and adolescents and in addressing the risks for and the co-existence of psychological comorbidities.
Early Retinal Microvascular Changes Assessed with Swept-Source OCT Angiography in Type 1 Diabetes Patients without Retinopathy
Authors: Eid Pétra , Creuzot-Garcher Catherine , Aho Ludwig Serge , Gabrielle Pierre-Henry , Charpin Estelle , Haddad Déa , Steinberg Laure-Anne , Bron Alain , Verges Bruno , Arnould Louis
Published: April 2023

Type 1 diabetes is a chronic disease that can lead to vision loss when diabetic retinopathy develops. Retinal microvascular alterations occur before the appearance of clinical signs on a fundus examination. This study aimed to analyze retinal vascular parameters on optical coherence tomography angiography (OCT-A) in patients with type 1 diabetes without diabetic retinopathy in comparison with non-diabetic volunteers. This cross-sectional study was conducted at Dijon University Hospital from 2018 to 2020. Vascular densities were measured using macular OCT-A. In total, 98 diabetes patients and 71 non-diabetic volunteers were enrolled. A statistically significant lower vascular density of the inner circle was found in the superficial capillary plexus (SCP) in the diabetes group (p < 0.01). There was a statistically significant correlation between central vascular density in the deep capillary plexus (DCP) and total daily insulin intake (p = 0.042); furthermore, use of the FreeStyle Libre (FSL) device was associated with higher vascular densities in both the SCP (p = 0.034 for outer circle density) and DCP (p < 0.01 for inner circle density and p = 0.023 for outer circle density). Retinal microvascularization was early-altered in type 1 diabetes, and using the FSL device seemed to preserve retinal microvascularization.
Synthesis and Biological Activity Evaluations of Green ZnO-Decorated Acid-Activated Bentonite-Mediated Curcumin Extract (ZnO@CU/BE) as Antioxidant and Antidiabetic Agents
Authors: Rudayni Hassan Ahmed , Shemy Marwa H. , Aladwani Malak , Alneghery Lina M. , Abu-Taweel Gasem M. , Allam Ahmed A. , Abukhadra Mostafa R. , Bellucci Stefano
Published: April 2023

Green ZnO-decorated acid-activated bentonite-mediated curcumin extract (ZnO@CU/BE) was prepared as a multifunctional antioxidant and antidiabetic agent based on the extract of curcumin, which was used as a reducing and capping reagent. ZnO@CU/BE showed notably enhanced antioxidant properties against nitric oxide (88.6 ± 1.58%), 1,1-diphenyl-2-picrylhydrazil (90.2 ± 1.76%), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (87.3 ± 1.61%), and superoxide (39.5 ± 1.12%) radicals. These percentages are higher than the reported values of ascorbic acid as a standard and the integrated components of the structure (CU, BE/CU, and ZnO). This signifies the impact of the bentonite substrate on enhancing the solubility, stability, dispersion, and release rate of the intercalated curcumin-based phytochemicals, in addition to enhancing the exposure interface of ZnO nanoparticles. Therefore, effective antidiabetic properties were observed, with significant inhibition effects on porcine pancreatic α-amylase (76.8 ± 1.87%), murine pancreatic α-amylase (56.5 ± 1.67%), pancreatic α-glucosidase (96.5 ± 1.07%), murine intestinal α-glucosidase (92.5 ± 1.10%), and amyloglucosidase (93.7 ± 1.55%) enzymes. These values are higher than those determined using commercial miglitol and are close to the values measured using acarbose. Hence, the structure can be applied as an antioxidant and antidiabetic agent.
The Amylolytic Regulator AmyR of Aspergillus niger Is Involved in Sucrose and Inulin Utilization in a Culture-Condition-Dependent Manner
Authors: Kun Roland S. , Salazar-Cerezo Sonia , Peng Mao , Zhang Yu , Savage Emily , Lipzen Anna , Ng Vivian , Grigoriev Igor V. , de Vries Ronald P. , Garrigues Sandra
Published: April 2023

Filamentous fungi degrade complex plant material to its monomeric building blocks, which have many biotechnological applications. Transcription factors play a key role in plant biomass degradation, but little is known about their interactions in the regulation of polysaccharide degradation. Here, we deepened the knowledge about the storage polysaccharide regulators AmyR and InuR in Aspergillus niger. AmyR controls starch degradation, while InuR is involved in sucrose and inulin utilization. In our study, the phenotypes of A. niger parental, ΔamyR, ΔinuR and ΔamyRΔinuR strains were assessed in both solid and liquid media containing sucrose or inulin as carbon source to evaluate the roles of AmyR and InuR and the effect of culture conditions on their functions. In correlation with previous studies, our data showed that AmyR has a minor contribution to sucrose and inulin utilization when InuR is active. In contrast, growth profiles and transcriptomic data showed that the deletion of amyR in the ΔinuR background strain resulted in more pronounced growth reduction on both substrates, mainly evidenced by data originating from solid cultures. Overall, our results show that submerged cultures do not always reflect the role of transcription factors in the natural growth condition, which is better represented on solid substrates. Importance: The type of growth has critical implications in enzyme production by filamentous fungi, a process that is controlled by transcription factors. Submerged cultures are the preferred setups in laboratory and industry and are often used for studying the physiology of fungi. In this study, we showed that the genetic response of A. niger to starch and inulin was highly affected by the culture condition, since the transcriptomic response obtained in a liquid environment did not fully match the behavior of the fungus in a solid environment. These results have direct implications in enzyme production and would help industry choose the best approaches to produce specific CAZymes for industrial purposes.
Cardiac Rehabilitation in Severe Heart Failure Patients with Impella 5.0 Support via the Subclavian Artery Approach Prior to Left Ventricular Assist Device Implantation
Authors: Shimizu Miho , Hiraiwa Hiroaki , Tanaka Shinya , Tsuchikawa Yohei , Ito Ryota , Kazama Shingo , Kimura Yuki , Araki Takashi , Mizutani Takashi , Oishi Hideo , Kuwayama Tasuku , Kondo Toru , Morimoto Ryota , Okumura Takahiro , Ito Hideki , Yoshizumi Tomo , Mutsuga Masato , Usui Akihiko , Murohara Toyoaki
Published: April 2023

Impella 5.0 circulatory support via subclavian artery (SA) access may be a safe approach for patients undergoing cardiac rehabilitation (CR). In this case series, we retrospectively analyzed the demographic characteristics, physical function, and CR data of six patients who underwent Impella 5.0 implantation via the SA prior to left ventricular assist device (LVAD) implantation between October 2013 and June 2021. The median age was 48 years, and one patient was female. Grip strength was maintained or increased in all patients before LVAD implantation (pre-LVAD) compared to after Impella 5.0 implantation. The pre-LVAD knee extension isometric strength (KEIS) was less than 0.46 kgf/kg in two patients and more than 0.46 kgf/kg in three patients (unavailable KEIS data, n = 1). With Impella 5.0 implantation, two patients could ambulate, one could stand, two could sit on the edge of the bed, and one remained in bed. One patient lost consciousness during CR due to decreased Impella flow. There were no other serious adverse events. Impella 5.0 implantation via the SA allows mobilization, including ambulation, prior to LVAD implantation, and CR can be performed relatively safely.
Scaling Up Security and Efficiency in Financial Transactions and Blockchain Systems
Authors: Saqib Nazar Abbas , AL-Talla Shahad Talla
Published: April 2023

Blockchain, the underlying technology powering the Bitcoin cryptocurrency, is a distributed ledger that creates a distributed consensus on a history of transactions. Cryptocurrency transaction verification takes substantially longer than it does for conventional digital payment systems. Despite blockchain’s appealing benefits, one of its main drawbacks is scalability. Designing a solution that delivers a quicker proof of work is one method for increasing scalability or the rate at which transactions are processed. In this paper, we suggest a solution based on parallel mining rather than solo mining to prevent more than two miners from contributing an equal amount of effort to solving a single block. Moreover, we propose the idea of automatically selecting the optimal manager over all miners by using the particle swarm optimization (PSO) algorithm. This process solves many problems of blockchain scalability and makes the system more scalable by decreasing the waiting time if the manager fails to respond. Additionally, the proposed model includes the process of a reward system and the distribution of work. In this work, we propose the particle swarm optimization proof of work (PSO-POW) model. Three scenarios have been tested including solo mining, parallel mining without using the PSO process, and parallel mining using the PSO process (PSO-POW model) to ensure the power and robustness of the proposed model. This model has been tested using a range of case situations by adjusting the difficulty level and the number of peers. It has been implemented in a test environment that has all the qualities required to perform proof of work for Bitcoin. A comparison between three different scenarios has been constructed against difficulty levels and the number of peers. Local experimental assessments were carried out, and the findings show that the suggested strategy is workable, solves the scalability problems, and enhances the overall performance of the blockchain network.
Combining Digital Covariates and Machine Learning Models to Predict the Spatial Variation of Soil Cation Exchange Capacity
Authors: Kaya Fuat , Mishra Gaurav , Francaviglia Rosa , Keshavarzi Ali
Published: April 2023

Cation exchange capacity (CEC) is a soil property that significantly determines nutrient availability and effectiveness of fertilizer applied in lands under different managements. CEC’s accurate and high-resolution spatial information is needed for the sustainability of agricultural management on farms in the Nagaland state (northeast India) which are fragmented and intertwined with the forest ecosystem. The current study applied the digital soil mapping (DSM) methodology, based on the CEC values determined in soil samples obtained from 305 points in the region, which is mountainous and difficult to access. Firstly, digital auxiliary data were obtained from three open-access sources, including indices generated from the time series Landsat 8 OLI satellite, topographic variables derived from a digital elevation model (DEM), and the WorldClim dataset. Furthermore, the CEC values and the auxiliary were used data to model Lasso regression (LR), stochastic gradient boosting (GBM), support vector regression (SVR), random forest (RF), and K-nearest neighbors (KNN) machine learning (ML) algorithms were systematically compared in the R-Core Environment Program. Model performance were evaluated with the square root mean error (RMSE), determination coefficient (R2), and mean absolute error (MAE) of 10-fold cross-validation (CV). The lowest RMSE was obtained by the RF algorithm with 4.12 cmolc kg−1, while the others were in the following order: SVR (4.27 cmolc kg−1) <KNN (4.45 cmolc kg−1) <LR (4.67 cmolc kg−1) <GBM (5.07 cmolc kg−1). In particular, WorldClim-based climate covariates such as annual mean temperature (BIO-1), annual precipitation (BIO-12), elevation, and solar radiation were the most important variables in all algorithms. High uncertainty (SD) values have been found in areas with low soil sampling density and this finding is to be considered in future soil surveys.
Brain Structure and Function: Insights from Chemical Neuroanatomy
Authors: Agnati Luigi F. , Guidolin Diego , Cervetto Chiara , Maura Guido , Marcoli Manuela
Published: April 2023

We present a brief historical and epistemological outline of investigations on the brain’s structure and functions. These investigations have mainly been based on the intermingling of chemical anatomy, new techniques in the field of microscopy and computer-assisted morphometric methods. This intermingling has enabled extraordinary investigations to be carried out on brain circuits, leading to the development of a new discipline: “brain connectomics”. This new approach has led to the characterization of the brain’s structure and function in physiological and pathological conditions, and to the development of new therapeutic strategies. In this context, the conceptual model of the brain as a hyper-network with a hierarchical, nested architecture, arranged in a “Russian doll” pattern, has been proposed. Our investigations focused on the main characteristics of the modes of communication between nodes at the various miniaturization levels, in order to describe the brain’s integrative actions. Special attention was paid to the nano-level, i.e., to the allosteric interactions among G protein-coupled receptors organized in receptor mosaics, as a promising field in which to obtain a new view of synaptic plasticity and to develop new, more selective drugs. The brain’s multi-level organization and the multi-faceted aspects of communication modes point to an emerging picture of the brain as a very peculiar system, in which continuous self-organization and remodeling take place under the action of external stimuli from the environment, from peripheral organs and from ongoing integrative actions.