bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling Health Inequalities: Exploring Metabolic Dysfunction in Rural Roma Communities
Authors: Crișan Dana , Avram Lucreția , Grapă Cristiana , Nemeș Andrada , Coman Maria-Virginia , Beldean-Galea Mihail Simion , Coman Radu-Tudor , Călinici Tudor , Donca Valer , Crăciun Rareș
Published: April 2024

Background: Europe’s largest ethnic minority, the Roma, are often confronted with substantial obstacles that result in health disparities. Research indicates that there are elevated rates of both communicable and non-communicable diseases, such as metabolic syndrome (MetS), among Roma communities, often linked to living conditions, limited education, or poverty. This study centers on remote rural Roma settlements in Romania, evaluating the prevalence of metabolic dysfunction, obesity, and liver steatosis while considering socio-economic and lifestyle factors. Methods: Over a period of 36 months, local visits to a total of 25 rural Roma communities were conducted, where a medical team gathered information through a standardized questionnaire and conducted a physical exam on every participant. Liver steatosis was also recorded with the help of a portable wireless ultrasound device. Results: Our study included 343 participants, with a predominance of female subjects, representing 72.5% (n = 249) of the patients. The prevalence of obesity, defined by a body mass index (BMI) above 30 kg/m2, was 32.2% (n = 111). Arterial hypertension was found to have a prevalence of 54.1% (n = 185), with de novo hypertension being observed in 19.2% patients (n = 66). Type 2 diabetes mellitus was found in 28.9% patients (n = 99), with 19.5% being de novo cases. The prevalence of hepatic steatosis was 57.2% (n = 111/194). A positive association between metabolic features and at-risk behaviors was found. Conclusions: This study underscores the transition from infectious to metabolic diseases in vulnerable communities and highlights the urgency of targeted public health strategies tailored to the unique needs of rural Roma populations, aiming to mitigate health disparities and promote equitable healthcare access.
Pesticide Translocation Using Nonpressurized and Pressurized Endotherapeutic Treatments in Coconut Palms
Authors: Ferreira Jordana A. , Ferreira Joana M. S. , Maia Aline de H. N. , Lins Paulo M. P. , Bottoli Carla B. G.
Published: April 2024

Coconut cultivation faces serious challenges caused by pests and diseases, whose targets are often not reached by conventional application methods such as spraying and soil application. New control strategies, such as vegetative endotherapy, have emerged, but knowledge gaps persist regarding many aspects, especially in pesticide translocation within palm trees, which is crucial for an efficient practical field application. This study investigated the translocation of a mixture of commercial insecticides and fungicides—difenoconazole, imidacloprid, thiabendazole, cyproconazole, thiamethoxam, spirodiclofen, and carbosulfan—applied via pressurized and nonpressurized endotherapeutic methods to coconut stems. This assessment aimed to quantify the concentrations of pesticide translocation through the stem, from the application site to the plant canopy. Due to the difficulty of applying the solution to the instrument used for pressurized endotherapy, the solution had to be diluted and used at a lower volume. In experimental field conditions, stem samples were assessed at 50 and 100 cm above the application point following endotherapy treatments conducted over a period ranging from 2 to 45 days. The analyses were performed using LC-MS/MS. In the pressurized method, the highest concentrations were observed for difenoconazole (1684 µg kg−1), imidacloprid (1278 µg kg−1), and thiabendazole (781 µg kg−1). Conversely, in the nonpressurized method, the highest concentrations were recorded for imidacloprid (5803 µg kg−1), followed by difenoconazole (3660 µg kg−1) and thiabendazole (2598 µg kg−1). To address the issue with formulation conditions in the pressurized method and to allow a comparison between the two application methods, we simulated extrapolated results for comparison with the nonpressurized method. This evaluation aimed to evaluate both methods under similar formulation conditions (volume and concentration). The results predicted that if the solution had not been diluted, the pressurized method would present the best translocations, mainly near the plant canopy, except for carbofuran. All pesticides were translocated independently of their physical–chemical properties or formulation. No pesticide residues were detected in the coconut water and pulp up to 120 days after the endotherapy application.
Formation/Removal of Biofilms on/from Coupons of Selected Food-Grade Elastomeric Polymers vs. Plexiglass Used for the Fruit-Catching Plates of OTR Blueberry Machine Harvesters
Authors: Wang Peien , Hur Minji , DeVetter Lisa Wasko , Takeda Fumiomi , Chen Jinru
Published: April 2024

To reduce the bruising potential of machine-harvested fresh blueberries, manufacturers of over-the-row (OTR) machine harvesters are replacing the hard, plexiglass fruit-catching plates with soft, elastomeric polymers. This study assessed whether selected soft, food-grade elastomeric polymers, with the potential to be used in OTR harvesters, have a greater likelihood to encourage more microbial buildups, making cleaning/sanitation a greater challenge. Coupons of plexiglass, silicone, neoprene, and ethylene propylene diene monomer (EPDM) were exposed to fecal coliforms from various sources for biofilm development. The coupons with developed biofilms were treated with sodium hypochlorite, peracetic acid, isopropyl alcohol-based quaternary ammonium compounds (Alpet D2), or commercial dish soap. Biofilms and their residuals after the sanitizer treatments were quantified. The fecal coliforms isolated from the surface of OTR harvesters developed significantly (p ≤ 0.05) more biofilms than those from other sources. EPDM coupons had significantly more, while neoprene and silicone coupons had insignificantly different (p > 0.05) amounts of biofilms from plexiglass coupons. After sanitizer treatments, EPDM coupons had significantly more, while neoprene and certain silicon coupons had significantly fewer residues than plexiglass coupons. Study suggests that compared to plexiglass, neoprene and silicon did not support more microbial buildups or retain more biofilms after sanitizing treatments.
Influence of School Type and Class Level on Mean Caries Experience in 12-Year-Olds in Serial Cross-Sectional National Oral Health Survey in Germany—Proposal to Adjust for Selection Bias
Authors: Schmoeckel Julian , Wahl Goetz , Santamaría Ruth M. , Basner Roger , Schankath Elisabeth , Splieth Christian H.
Published: April 2024

The objective of this study is to analyse the effects of attended school type and class level on the reported caries experience (DMFT) obtained in the serial cross-sectional National Oral Health Study in Children in Germany (NOHSC) for the WHO reference group of 12-year-olds. Methods: Caries data from the 2016 NOHSC were adjusted for each federal state on the basis of two additional large-scale datasets for school type and class level. Results: Twelve-year-olds in all grades in Saxony-Anhalt (n = 96,842) exhibited significantly higher DMFT values than 12-year-olds in 6th grade (n = 76,456; +0.10 DMFT; ~14.2%, p < 0.001). Adjustments for school type had effects on DMFT on the level of federal states but almost balanced out on the national level (−0.01 DMFT; ~2%). Due to putatively similar structures of the federal states, the national mean DMFT for 12-year-olds in the latest NOHSC (2016; n = 55,002) was adjusted from 0.44 to 0.50 DMFT, correcting for selection bias. Conclusion: Selection bias in this NOHSC leads to an underestimation of caries levels by about 15%. Due to very low caries experience in children in Germany, these precise adjustments (+0.06 DMFT) have only a minor effect on interpretations of the national epidemiologic situation. Consequently, other national caries studies worldwide using the robust marker of DMFT should also adjust for systematic selection bias related to socio-economic background rather than increasing efforts in examination strategy.
Harnessing the Cross-Neutralisation Potential of Existing Antivenoms for Mitigating the Outcomes of Snakebite in Sub-Saharan Africa
Authors: Khochare Suyog , Jaglan Anurag , Rashmi U. , Dam Paulomi , Sunagar Kartik
Published: April 2024

Over 32,000 individuals succumb to snake envenoming in sub-Saharan Africa (sSA) annually. This results from several factors, including a lack of antivenom products capable of neutralising the venoms of diverse snake species in this region. Most manufacturers produce polyvalent antivenoms targeting 3 to 16 clinically important snake species in sSA. However, specific products are unavailable for many others, especially those with a restricted geographic distribution. While next-generation antivenoms, comprising a cocktail of broadly neutralising antibodies, may offer an effective solution to this problem, given the need for their clinical validation, recombinant antivenoms are far from being available to snakebite victims. One of the strategies that could immediately address this issue involves harnessing the cross-neutralisation potential of existing products. Therefore, we assessed the neutralisation potency of PANAF-Premium antivenom towards the venoms of 14 medically important snakes from 13 countries across sSA for which specific antivenom products are unavailable. Preclinical assays in a murine model of snake envenoming revealed that the venoms of most snake species under investigation were effectively neutralised by this antivenom. Thus, this finding highlights the potential use of PANAF-Premium antivenom in treating bites from diverse snakes across sSA and the utility of harnessing the cross-neutralisation potential of antivenoms.
Sterol O-Acyltransferase 1 (SOAT1): A Genetic Modifier of Niemann-Pick Disease, Type C1
Authors: Farhat Nicole Y. , Alexander Derek , McKee Kyli , Iben James , Rodriguez-Gil Jorge L. , Wassif Christopher A. , Cawley Niamh X. , Balch William E. , Porter Forbes D.
Published: April 2024

Niemann-Pick disease type C1 (NPC1) is a lysosomal disorder due to impaired intracellular cholesterol transport out of the endolysosomal compartment. Marked heterogeneity has been observed in individuals with the same NPC1 genotype, thus suggesting a significant effect of modifier genes. Prior work demonstrated that decreased SOAT1 activity decreased disease severity in an NPC1 mouse model. Thus, we hypothesized that a polymorphism associated with decreased SOAT1 expression might influence the NPC1 phenotype. Phenotyping and genomic sequencing of 117 individuals with NPC1 was performed as part of a Natural History trial. Phenotyping included determination of disease severity and disease burden. Significant clinical heterogeneity is present in individuals homozygous for the NPC1I1061T variant and in siblings. Analysis of the SOAT1 polymorphism, rs1044925 (A>C), showed a significant association of the C-allele with earlier age of neurological onset. The C-allele may be associated with a higher Annualized Severity Index Score as well as increased frequency of liver disease and seizures. A polymorphism associated with decreased expression of SOAT1 appears to be a genetic modifier of the NPC1 phenotype. This finding is consistent with prior data showing decreased phenotypic severity in Npc1-/-:Soat1-/- mice and supports efforts to investigate the potential of SOAT1 inhibitors as a potential therapy for NPC1.
Entamoeba histolytica: In Silico and In Vitro Oligomerization of EhHSTF5 Enhances Its Binding to the HSE of the EhPgp5 Gene Promoter
Authors: Pérez-Mora Salvador , Pérez-Ishiwara David Guillermo , Salgado-Hernández Sandra Viridiana , Medel-Flores María Olivia , Reyes-López César Augusto , Rodríguez Mario Alberto , Sánchez-Monroy Virginia , Gómez-García María del Consuelo
Published: April 2024

Throughout its lifecycle, Entamoeba histolytica encounters a variety of stressful conditions. This parasite possesses Heat Shock Response Elements (HSEs) which are crucial for regulating the expression of various genes, aiding in its adaptation and survival. These HSEs are regulated by Heat Shock Transcription Factors (EhHSTFs). Our research has identified seven such factors in the parasite, designated as EhHSTF1 through to EhHSTF7. Significantly, under heat shock conditions and in the presence of the antiamoebic compound emetine, EhHSTF5, EhHSTF6, and EhHSTF7 show overexpression, highlighting their essential role in gene response to these stressors. Currently, only EhHSTF7 has been confirmed to recognize the HSE as a promoter of the EhPgp5 gene (HSE_EhPgp5), leaving the binding potential of the other EhHSTFs to HSEs yet to be explored. Consequently, our study aimed to examine, both in vitro and in silico, the oligomerization, and binding capabilities of the recombinant EhHSTF5 protein (rEhHSTF5) to HSE_EhPgp5. The in vitro results indicate that the oligomerization of rEhHSTF5 is concentration-dependent, with its dimeric conformation showing a higher affinity for HSE_EhPgp5 than its monomeric state. In silico analysis suggests that the alpha 3 α-helix (α3-helix) of the DNA-binding domain (DBD5) of EhHSTF5 is crucial in binding to the major groove of HSE, primarily through hydrogen bonding and salt-bridge interactions. In summary, our results highlight the importance of oligomerization in enhancing the affinity of rEhHSTF5 for HSE_EhPgp5 and demonstrate its ability to specifically recognize structural motifs within HSE_EhPgp5. These insights significantly contribute to our understanding of one of the potential molecular mechanisms employed by this parasite to efficiently respond to various stressors, thereby enabling successful adaptation and survival within its host environment.
Amphetamine Exposure during Embryogenesis Alters Expression and Function of Tyrosine Hydroxylase and the Vesicular Monoamine Transporter in Adult C. elegans
Authors: Ke Tao , Poquette Katie E. , Amro Gazze Sophia L. , Carvelli Lucia
Published: April 2024

Amphetamines (Amph) are psychostimulants broadly used as physical and cognitive enhancers. However, the long-term effects of prenatal exposure to Amph have been poorly investigated. Here, we show that continuous exposure to Amph during early development induces long-lasting changes in histone methylation at the C. elegans tyrosine hydroxylase (TH) homolog cat-2 and the vesicular monoamine transporter (VMAT) homologue cat-1 genes. These Amph-induced histone modifications are correlated with enhanced expression and function of CAT-2/TH and higher levels of dopamine, but decreased expression of CAT-1/VMAT in adult animals. Moreover, while adult animals pre-exposed to Amph do not show obvious behavioral defects, when challenged with Amph they exhibit Amph hypersensitivity, which is associated with a rapid increase in cat-2/TH mRNA. Because C. elegans has helped reveal neuronal and epigenetic mechanisms that are shared among animals as diverse as roundworms and humans, and because of the evolutionary conservation of the dopaminergic response to psychostimulants, data collected in this study could help us to identify the mechanisms through which Amph induces long-lasting physiological and behavioral changes in mammals.
Runx3 Regulates CD8+ T Cell Local Expansion and CD43 Glycosylation in Mice by H1N1 Influenza A Virus Infection
Authors: Hao Qin , Kundu Suman , Shetty Sreerama , Tang Hua
Published: April 2024

We have recently reported that transcription factor Runx3 is required for pulmonary generation of CD8+ cytotoxic T lymphocytes (CTLs) that play a crucial role in the clearance of influenza A virus (IAV). To understand the underlying mechanisms, we determined the effects of Runx3 knockout (KO) on CD8+ T cell local expansion and phenotypes using an inducible general Runx3 KO mouse model. We found that in contrast to the lungs, Runx3 general KO promoted enlargement of lung-draining mediastinal lymph node (mLN) and enhanced CD8+ and CD4+ T cell expansion during H1N1 IAV infection. We further found that Runx3 deficiency greatly inhibited core 2 O-glycosylation of selectin ligand CD43 on activated CD8+ T cells but minimally affected the cell surface expression of CD43, activation markers (CD44 and CD69) and cell adhesion molecules (CD11a and CD54). Runx3 KO had a minor effect on lung effector CD8+ T cell death by IAV infection. Our findings indicate that Runx3 differently regulates CD8+ T cell expansion in mLNs and lungs by H1N1 IAV infection. Runx3 is required for CD43 core 2 O-glycosylation on activated CD8+ T cells, and the involved Runx3 signal pathway may mediate CD8+ T cell phenotype for pulmonary generation of CTLs.
Cellular Imaging and Time-Domain FLIM Studies of Meso-Tetraphenylporphine Disulfonate as a Photosensitising Agent in 2D and 3D Models
Authors: Balukova Andrea , Bokea Kalliopi , Barber Paul R. , Ameer-Beg Simon M. , MacRobert Alexander J. , Yaghini Elnaz
Published: April 2024

Fluorescence lifetime imaging (FLIM) and confocal fluorescence studies of a porphyrin-based photosensitiser (meso-tetraphenylporphine disulfonate: TPPS2a) were evaluated in 2D monolayer cultures and 3D compressed collagen constructs of a human ovarian cancer cell line (HEY). TPPS2a is known to be an effective model photosensitiser for both Photodynamic Therapy (PDT) and Photochemical Internalisation (PCI). This microspectrofluorimetric study aimed firstly to investigate the uptake and subcellular localisation of TPPS2a, and evaluate the photo-oxidative mechanism using reactive oxygen species (ROS) and lipid peroxidation probes combined with appropriate ROS scavengers. Light-induced intracellular redistribution of TPPS2a was observed, consistent with rupture of endolysosomes where the porphyrin localises. Using the same range of light doses, time-lapse confocal imaging permitted observation of PDT-induced generation of ROS in both 2D and 3D cancer models using fluorescence-based ROS together with specific ROS inhibitors. In addition, the use of red light excitation of the photosensitiser to minimise auto-oxidation of the probes was investigated. In the second part of the study, the photophysical properties of TPPS2a in cells were studied using a time-domain FLIM system with time-correlated single photon counting detection. Owing to the high sensitivity and spatial resolution of this system, we acquired FLIM images that enabled the fluorescence lifetime determination of the porphyrin within the endolysosomal vesicles. Changes in the lifetime dynamics upon prolonged illumination were revealed as the vesicles degraded within the cells.
Precise Targeting of Autoantigen-Specific B Cells in Lupus Nephritis with Chimeric Autoantibody Receptor T Cells
Authors: Solé Cristina , Royo Maria , Sandoval Sebastian , Moliné Teresa , Gabaldón Alejandra , Cortés-Hernández Josefina
Published: April 2024

Despite conventional therapy, lupus nephritis (LN) remains a significant contributor to short- and long-term morbidity and mortality. B cell abnormalities and the production of autoantibodies against nuclear complexes like anti-dsDNA are recognised as key players in the pathogenesis of LN. To address the challenges of chronic immunosuppression associated with current therapies, we have engineered T cells to express chimeric autoantibody receptors (DNA-CAART) for the precise targeting of B cells expressing anti-dsDNA autoantibodies. T cells from LN patients were transduced using six different CAAR vectors based on their antigen specificity, including alpha-actinin, histone-1, heparan sulphate, or C1q. The cytotoxicity, cytokine production, and cell–cell contact of DNA-CAART were thoroughly investigated in co-culture experiments with B cells isolated from patients, both with and without anti-dsDNA positivity. The therapeutic effects were further evaluated using an in vitro immune kidney LN organoid. Among the six proposed DNA-CAART, DNA4 and DNA6 demonstrated superior selectively cytotoxic activity against anti-dsDNA+ B cells. Notably, DNA4-CAART exhibited improvements in organoid morphology, apoptosis, and the inflammatory process in the presence of IFNα-stimulated anti-dsDNA+ B cells. Based on these findings, DNA4-CAART emerge as promising candidates for modulating autoimmunity and represent a novel approach for the treatment of LN.
Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence
Authors: Paveliev Mikhail , Egorchev Anton A. , Musin Foat , Lipachev Nikita , Melnikova Anastasiia , Gimadutdinov Rustem M. , Kashipov Aidar R. , Molotkov Dmitry , Chickrin Dmitry E. , Aganov Albert V.
Published: April 2024

Perineuronal nets (PNN) are a special highly structured type of extracellular matrix encapsulating synapses on large populations of CNS neurons. PNN undergo structural changes in schizophrenia, epilepsy, Alzheimer’s disease, stroke, post-traumatic conditions, and some other brain disorders. The functional role of the PNN microstructure in brain pathologies has remained largely unstudied until recently. Here, we review recent research implicating PNN microstructural changes in schizophrenia and other disorders. We further concentrate on high-resolution studies of the PNN mesh units surrounding synaptic boutons to elucidate fine structural details behind the mutual functional regulation between the ECM and the synaptic terminal. We also review some updates regarding PNN as a potential pharmacological target. Artificial intelligence (AI)-based methods are now arriving as a new tool that may have the potential to grasp the brain’s complexity through a wide range of organization levels—from synaptic molecular events to large scale tissue rearrangements and the whole-brain connectome function. This scope matches exactly the complex role of PNN in brain physiology and pathology processes, and the first AI-assisted PNN microscopy studies have been reported. To that end, we report here on a machine learning-assisted tool for PNN mesh contour tracing.
New Insights into the Hygroscopic Character of Ionic Liquids: Study of Fourteen Representatives of Five Cation and Four Anion Families
Authors: Rilo Esther , Rosende-Pereiro Alejandro , Domínguez-Pérez Montserrat , Cabeza Oscar , Segade Luisa
Published: April 2024

Over the past three decades, the synthesis of new ionic liquids (ILs) and the expansion of their use in newer applications have grown exponentially. From the beginning of this vertiginous period, it was known that many of them were hygroscopic, which in some cases limited their use or altered the value of their measured physical properties with all the problems that this entails. In an earlier article, we addressed the hygroscopic grade achieved by the ILs 1-ethyl-3-methylimidazolium chloride, 1-ethyl-3-methylimidazolium bromide, 1-ethyl-3-methylimidazolium methyl sulfate, 1-ethyl-3-methylimidazolium ethyl sulfate, 1-ethyl-3-methylpyridinium ethyl sulfate, 1-ethyl-3-methylimidazolium tosylate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-dodecyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylpyridinium tetrafluoroborate, 1-butyl-1-methylpiperidinium bis(trifluoromethyl sulfonyl)imide, 1-methyl-1-propylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, 1-butyl-1-methylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, and methyl trioctyl ammonium bis(trifluoromethyl sulfonyl)imide. The objective was to determine the influence of the chemical nature of the compounds, exposed surface area, sample volume, agitation, and temperature. For this purpose, we exposed the samples to abrupt increases in relative humidity from 15 to 100% for days in an atmosphere chamber and then proceeded with the reverse process in a gentle manner. The results show that the sorption of water from the atmosphere depends on the nature of the IL, especially the anion, with the chloride anion being of particular importance (chloride ≫ alkyl sulfates~bromide > tosylate ≫ tetrafluoroborate). It has also been proven for the EMIM-ES and EMIM-BF4 samples that the mechanism of moisture capture is both absorption and adsorption, and that the smaller the exposed surface area, the higher the ratio of the mass of water per unit area.
A Genome-Wide Analysis of the CEP Gene Family in Cotton and a Functional Study of GhCEP46-D05 in Plant Development
Authors: Mei Zhenyu , Li Bei , Zhu Shouhong , Li Yan , Yao Jinbo , Pan Jingwen , Zhang Yongshan , Chen Wei
Published: April 2024

C-TERMINALLY ENCODED PEPTIDEs (CEPs) are a class of peptide hormones that have been shown in previous studies to play an important role in regulating the development and response to abiotic stress in model plants. However, their role in cotton is not well understood. In this study, we identified 54, 59, 34, and 35 CEP genes from Gossypium hirsutum (2n = 4x = 52, AD1), G. barbadense (AD2), G. arboreum (2n = 2X = 26, A2), and G. raimondii (2n = 2X = 26, D5), respectively. Sequence alignment and phylogenetic analyses indicate that cotton CEP proteins can be categorized into two subgroups based on the differentiation of their CEP domain. Chromosomal distribution and collinearity analyses show that most of the cotton CEP genes are situated in gene clusters, suggesting that segmental duplication may be a critical factor in CEP gene expansion. Expression pattern analyses showed that cotton CEP genes are widely expressed throughout the plant, with some genes exhibiting specific expression patterns. Ectopic expression of GhCEP46-D05 in Arabidopsis led to a significant reduction in both root length and seed size, resulting in a dwarf phenotype. Similarly, overexpression of GhCEP46-D05 in cotton resulted in reduced internode length and plant height. These findings provide a foundation for further investigation into the function of cotton CEP genes and their potential role in cotton breeding.
Polyethersulfone Polymer for Biomedical Applications and Biotechnology
Authors: Wasyłeczko Monika , Wojciechowski Cezary , Chwojnowski Andrzej
Published: April 2024

Polymers stand out as promising materials extensively employed in biomedicine and biotechnology. Their versatile applications owe much to the field of tissue engineering, which seamlessly integrates materials engineering with medical science. In medicine, biomaterials serve as prototypes for organ development and as implants or scaffolds to facilitate body regeneration. With the growing demand for innovative solutions, synthetic and hybrid polymer materials, such as polyethersulfone, are gaining traction. This article offers a concise characterization of polyethersulfone followed by an exploration of its diverse applications in medical and biotechnological realms. It concludes by summarizing the significant roles of polyethersulfone in advancing both medicine and biotechnology, as outlined in the accompanying table.
Computational Modeling of Extrasynaptic NMDA Receptors: Insights into Dendritic Signal Amplification Mechanisms
Authors: Makarov Mark , Papa Michele , Korkotian Eduard
Published: April 2024

Dendritic structures play a pivotal role in the computational processes occurring within neurons. Signal propagation along dendrites relies on both passive conduction and active processes related to voltage-dependent ion channels. Among these channels, extrasynaptic N-methyl-D-aspartate channels (exNMDA) emerge as a significant contributor. Prior studies have mainly concentrated on interactions between synapses and nearby exNMDA (100 nm–10 µm from synapse), activated by presynaptic membrane glutamate. This study concentrates on the correlation between synaptic inputs and distal exNMDA (>100 µm), organized in clusters that function as signal amplifiers. Employing a computational model of a dendrite, we elucidate the mechanism underlying signal amplification in exNMDA clusters. Our findings underscore the pivotal role of the optimal spatial positioning of the NMDA cluster in determining signal amplification efficiency. Additionally, we demonstrate that exNMDA subunits characterized by a large conduction decay constant. Specifically, NR2B subunits exhibit enhanced effectiveness in signal amplification compared to subunits with steeper conduction decay. This investigation extends our understanding of dendritic computational processes by emphasizing the significance of distant exNMDA clusters as potent signal amplifiers. The implications of our computational model shed light on the spatial considerations and subunit characteristics that govern the efficiency of signal amplification in dendritic structures, offering valuable insights for future studies in neurobiology and computational neuroscience.
Isothermal Nucleic Acid Amplification-Based Lateral Flow Testing for the Detection of Plant Viruses
Authors: Song Xuemei , Cao Yuhao , Yan Fei
Published: April 2024

Isothermal nucleic acid amplification-based lateral flow testing (INAA-LFT) has emerged as a robust technique for on-site pathogen detection, providing a visible indication of pathogen nucleic acid amplification that rivals or even surpasses the sensitivity of real-time quantitative PCR. The isothermal nature of INAA-LFT ensures consistent conditions for nucleic acid amplification, establishing it as a crucial technology for rapid on-site pathogen detection. However, despite its considerable promise, the widespread application of isothermal INAA amplification-based lateral flow testing faces several challenges. This review provides an overview of the INAA-LFT procedure, highlighting its advancements in detecting plant viruses. Moreover, the review underscores the imperative of addressing the existing limitations and emphasizes ongoing research efforts dedicated to enhancing the applicability and performance of this technology in the realm of rapid on-site testing.
The Complex Relationship between Mechanisms Underlying Inflammatory Bowel Disease, Its Treatment, and the Risk of Lymphomas: A Comprehensive Review
Authors: Stasik Katarzyna , Filip Rafał
Published: April 2024

Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. In addition, there may be a link between the use of thiopurines or anti-tumor necrosis factor drugs (anti-TNF) and these pathologies. The treatment of patients with Crohn’s disease who have previously been diagnosed with lymphoma is a challenge for gastroenterologists. In this report, we examine important clinical issues related to the treatment of patients with inflammatory bowel disease with active lymphoma, as well as of patients with hematological cancer history. In this discussion, we take into account most of the available treatments for inflammatory bowel disease, as well as the impact of chronic inflammation and viral infections. In addition, we try to find common ground for the development of lymphoproliferative disorders and autoimmune diseases. Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. Chronic inflammatory processes and viral infections play an important role in carcinogenesis. In addition, there may be a link between the use of thiopurines or anti-TNF drugs and these pathologies. A significant risk of the development of lymphoma in people undergoing each therapy should be considered, and it should be estimated how much greater this risk will be in patients with a history of lymphoproliferative disorders. The following review is an attempt to answer which therapy would be the most appropriate for patients with Crohn’s disease and a history of lymphoma treatment. A lack of clear guidelines creates great challenges for doctors.
Plant-Assisted Green Synthesis of MgO Nanoparticles as a Sustainable Material for Bone Regeneration: Spectroscopic Properties
Authors: Proniewicz Edyta , Vijayan Ajith Mohanavilasam , Surma Olga , Szkudlarek Aleksandra , Molenda Marcin
Published: April 2024

This work is devoted to magnesium oxide (MgO) nanoparticles (NPs) for their use as additives for bone implants. Extracts from four different widely used plants, including Aloe vera, Echeveria elegans, Sansevieria trifasciata, and Sedum morganianum, were evaluated for their ability to facilitate the “green synthesis” of MgO nanoparticles. The thermal stability and decomposition behavior of the MgONPs were analyzed by thermogravimetric analysis (TGA). Structure characterization was performed by X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), and Raman scattering spectroscopy (RS). Morphology was studied by scanning electron microscopy (SEM). The photocatalytic activity of MgO nanoparticles was investigated based on the degradation of methyl orange (MeO) using UV-Vis spectroscopy. Surface-enhanced Raman scattering spectroscopy (SERS) was used to monitor the adsorption of L-phenylalanine (L-Phe) on the surface of MgONPs. The calculated enhancement factor (EF) is up to 102 orders of magnitude for MgO. This is the first work showing the SERS spectra of a chemical compound immobilized on the surface of MgO nanoparticles.
The Recombinant Oncolytic Virus VV-GMCSF-Lact and Chemotherapy Drugs against Human Glioma
Authors: Vasileva Natalia , Ageenko Alisa , Byvakina Arina , Sen’kova Aleksandra , Kochneva Galina , Mishinov Sergey , Richter Vladimir , Kuligina Elena
Published: April 2024

Virotherapy is one of the perspective technologies in the treatment of malignant neoplasms. Previously, we have developed oncolytic vaccinia virus VV-GMCSF-Lact and its high cytotoxic activity and antitumor efficacy against glioma was shown. In this work, using immortalized and patient-derived cells with different sensitivity to VV-GMCSF-Lact, we evaluated the cytotoxic effect of chemotherapy agents. Additionally, we studied the combination of VV-GMCSF-Lact with temozolomide which is the most preferred drug for glioma treatment. Experimental results indicate that first adding temozolomide and then the virus to the cells is inherently more efficient than dosing it in the reverse order. Testing these regimens in the U87 MG xenograft glioblastoma model confirmed this effect, as assessed by tumor growth inhibition index and histological analysis. Moreover, VV-GMCSF-Lact as monotherapy is more effective against U87 MG glioblastoma xenografts comparing temozolomide.
Elevated Biomarkers of Inflammation and Vascular Dysfunction Are Associated with Distal Sensory Polyneuropathy in People with HIV
Authors: Andalibi Mohammadsobhan Sheikh , Fields Jerel Adam , Iudicello Jennifer E. , Diaz Monica M. , Tang Bin , Letendre Scott L. , Ellis Ronald J.
Published: April 2024

Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178–448) and 643 (502–839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42–21.00], and 15.16 [1.07–215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration.
In Vivo Biocompatibility Study on Functional Nanostructures Containing Bioactive Glass and Plant Extracts for Implantology
Authors: Floroian Laura , Badea Mihaela
Published: April 2024

In this paper, the in vivo behavior of orthopedic implants covered with thin films obtained by matrix-assisted pulsed laser evaporation and containing bioactive glass, a polymer, and natural plant extract was evaluated. In vivo testing was performed by carrying out a study on guinea pigs who had coated metallic screws inserted in them and also controls, following the regulations of European laws regarding the use of animals in scientific studies. After 26 weeks from implantation, the guinea pigs were subjected to X-ray analyses to observe the evolution of osteointegration over time; the guinea pigs’ blood was collected for the detection of enzymatic activity and to measure values for urea, creatinine, blood glucose, alkaline phosphatase, pancreatic amylase, total protein, and glutamate pyruvate transaminase to see the extent to which the body was affected by the introduction of the implant. Moreover, a histopathological assessment of the following vital organs was carried out: heart, brain, liver, and spleen. We also assessed implanted bone with adjacent tissue. Our studies did not find significant variations in biochemical and histological results compared to the control group or significant adverse effects caused by the implant coating in terms of tissue compatibility, inflammatory reactions, and systemic effects.
Assessment of Cardiovascular Risk Categories and Achievement of Therapeutic Targets in European Patients with Type 2 Diabetes
Authors: Reurean-Pintilei Delia , Potcovaru Claudia-Gabriela , Salmen Teodor , Mititelu-Tartau Liliana , Cinteză Delia , Lazăr Sandra , Pantea Stoian Anca , Timar Romulus , Timar Bogdan
Published: April 2024

Background: Individuals diagnosed with type 2 diabetes mellitus (T2DM) are more prone to experiencing severe cardiovascular (CV) events, often occurring at a younger age, due to a complex interplay of risk factors. T2DM diagnosis inherently classifies patients as belonging to a higher CV risk group. In light of the increased susceptibility to severe CV outcomes, our study aims to assess the distribution of CV risk categories and the attainment of therapeutic targets among Romanian patients diagnosed with T2DM. Methods: A cross-sectional analysis was performed, including 885 patients diagnosed with T2DM who were consecutively admitted to a secondary care hospital unit between January and July 2019. Data collection included demographics, lipid profile, glycated hemoglobin (HbA1c), blood pressure (BP), estimated glomerular filtration rate (eGFR), and medication specifics for T2DM and associated conditions. Patients were stratified into CV risk categories based on the ESC/EAS guidelines, encompassing moderate, high, and very high risk categories. The rationale for selecting these guidelines for CV risk categories was that they were current and provided best practice recommendations for T2DM patients during the cross-sectional evaluation. We assessed therapeutic target achievement rates for LDL-C, HbA1C, and BP for each CV risk category. Additionally, we examined utilization rates of statins and novel cardio- and reno-protective, non-insulin antidiabetic medications. Results: The group’s average age was 62.9 ± 7.7 years and comprised 53.7% females. An average HbA1c level of 7.1 ± 1.3% was observed in the group. Within the cohort, 83% had hypertension, with a mean systolic BP of 132 ± 16.2 mm Hg and mean diastolic BP of 80 ± 9.6 mm Hg. Additionally, 64.6% of patients were obese, with a mean body mass index of 32.3 ± 5.3 kg/m2. Mean LDL-C levels varied across the different CV risk categories: 106.6 ± 35.6 mg/dL in the very high risk category, 113 ± 39.3 mg/dL in the high risk category, and 124.3 ± 38.3 mg/dL in the moderate risk category. Most treatment schemes included metformin (87.0%) and statins (67.0%), with variable use rates for other glucose-lowering and CV risk-modifying therapies. The percentage of patients using GLP-1 RAs was 8.1%, while 3.9% used SGLT2 inhibitors. Conclusions: Most Romanian patients with T2DM are at very high or high CV risk. Despite reaching glycemic control targets, most patients are not achieving the composite target, which includes, besides glycemic control, BP values and lipid profile. Many patients with T2DM are not benefiting from DM therapies with additional cardiorenal benefits or statins.
The Dark Side of Activated Phosphoinositide 3-Kinase-δ Syndrome 2: A Story Rewritten through FDG-PET
Authors: Catelli Arianna , Nanni Cristina , Mulè Rita , Zinzani Pier Luigi , Sabattini Elena , Lanari Marcello , Conti Francesca
Published: April 2024

Background: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is characterized by lymphoproliferation and increased risk of malignancy. FDG-PET/CT may represent a helpful diagnostic tool for differentiating these clinical features and correctly diagnosing inborn errors of immunity (IEI). Case report: We present the case of a female patient diagnosed with Hodgkin’s lymphoma at 19 years of age, although atypical imaging aspects emerged: baseline FDG-PET/CT revealed several hot lymph nodes with a symmetrical distribution, and increased tracer uptake in spleen, axial, and appendicular bone marrow. Imaging repeated after chemotherapy and autologous stem cell transplantation showed persistent increased FDG uptake at multiple supradiaphragmatic nodes and in bone marrow. After the diagnosis of APDS2 and rapamycin treatment, FDG-PET/CT confirmed complete metabolic normalization of all sites. Conclusions: In the IEI scenario, FDG-PET/CT plays an effective role in differentiating malignant proliferation and immune dysregulation phenotypes. Atypical patterns at FDG-PET/CT should be interpreted as a red flag for the need of an early immunological evaluation.
Examining Lurasidone Efficacy in Patients with Schizophrenia Spectrum Illness and Concurrent Alcohol and Substance Use Disorder: A Prospective, Multicentric, Real-World Investigation
Authors: Cavallotto Clara , Chiappini Stefania , Mosca Alessio , d’Andrea Giacomo , Di Carlo Francesco , Piro Tommaso , Susini Ottavia , Stefanelli Giulia , Di Cesare Andrea , Ricci Valerio , Pepe Maria , Dattoli Luigi , Di Nicola Marco , Pettorruso Mauro , Martinotti Giovanni
Published: April 2024

Background: Dual disorders (DD) entail the coexistence of a substance use disorder (SUD) and another mental health condition, often within psychotic and affective disorders. This study aims to evaluate lurasidone, an innovative atypical antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder and concurrent comorbidities of alcohol use disorder/substance use disorder (AUD/SUD). Methods: A cohort of 23 subjects diagnosed with schizophrenia spectrum disorder and comorbid AUD/SUD underwent psychometric assessments at baseline (T0) and one-month (T1) post-lurasidone initiation. Results: Lurasidone exhibited significant reductions in psychopathological burden, evidenced by decreased total PANSS scores (Z = 2.574, p = 0.011). Positive symptoms, substance craving (VAS Craving; Z = 3.202, p = 0.001), and aggressivity (MOAS scale; Z = 2.000, p = 0.050) were notably reduced. Clinical Global Impression (CGI) scores significantly improved (Z = 2.934, p = 0.003). Quality of life enhancements were observed in SF-36 subscales (energy, emotional well-being, and social functioning) (p < 0.05) and Q-LES-Q-SF scale (Z = −2.341, p = 0.021). A safety analysis indicated lurasidone’s good tolerability, with only 8.7% reporting discontinuation due to side effects. Conclusions: This study offers initial evidence supporting lurasidone’s efficacy and safety in dual diagnoses, highlighting positive effects on psychopathology, substance craving, and quality of life. These findings emphasize the need for tailored, comprehensive treatment strategies in managing the complexities of this patient population.
Pediatric Odontogenic Sinusitis: A Systematic Review
Authors: Rosso Cecilia , Urbanelli Anastasia , Spoldi Chiara , Felisati Giovanni , Pecorari Giancarlo , Pipolo Carlotta , Nava Nicolò , Saibene Alberto Maria
Published: April 2024

Background: Pediatric odontogenic sinusitis (PODS) is a rare condition with limited research on its clinical features, diagnostic criteria, and treatment options. The current guidelines on pediatric rhinosinusitis do not mention a possible dental origin of the disease. This systematic review aims to summarize and analyze the existing literature on PODS, focusing on epidemiology, etiology, diagnostic tools, complications, treatment options, and outcomes. Methods: A systematic review was conducted following PRISMA reporting guidelines. Electronic searches were performed in multiple databases using keywords related to PODS and therapeutic strategies. Original articles reporting data on treatment outcomes for PODS were included. Results: The review highlighted the scarcity of high-quality evidence on PODS. The literature mainly consists of case reports and low-grade evidence studies. Limited data on the epidemiology, etiology, diagnostic tools, complications, and treatment outcomes of PODS in children are available. Conclusions: Further research is needed to better understand the clinical features, diagnosis, and treatment of PODS in pediatric patients. High-quality studies are required to establish evidence-based guidelines for the management of this condition, especially given the apparently high rate of complications when compared to adult ODS.
Treatment of Apathy in Parkinson’s Disease and Implications for Underlying Pathophysiology
Authors: Maher Senan , Donlon Eoghan , Mullane Gerard , Walsh Richard , Lynch Tim , Fearon Conor
Published: April 2024

Apathy is a prevalent and highly debilitating non-motor symptom of Parkinson’s disease (PD) that is often overlooked in clinical practice due to its subtle nature. This review aims to provide a comprehensive overview of the current evidence for the treatment of apathy in PD, highlighting recent advancements and emerging therapeutic avenues. In this review, we analyse a diverse array of treatment strategies for apathy in PD, including pharmacological interventions, non-pharmacological approaches, and emerging neuromodulation techniques. We evaluate the efficacy, safety, and limitations of established pharmacotherapies, such as dopaminergic agents, antidepressants, and cognitive enhancers. Additionally, we examine the promising role of non-pharmacological interventions, encompassing psychotherapies and behavioural interventions, in ameliorating apathetic symptoms. Furthermore, this review explores the effects of neuromodulation techniques on apathy, including the modulation of apathy via deep brain stimulation and emerging data on the potential influence of transcranial magnetic stimulation (TMS) on apathy in PD. Ultimately, a deeper understanding of effective treatment strategies for apathy has the potential to significantly improve the quality of life and overall well-being of individuals living with PD.