bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenic Role of IL-17 and Therapeutic Targeting of IL-17F in Psoriatic Arthritis and Spondyloarthropathies
Authors: Sánchez-Rodríguez Guillermo , Puig Lluís
Published: June 2023

The interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A-F, plays crucial roles in host defence against microbial organisms and the development of inflammatory diseases, including psoriasis (PsO), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). IL-17A is the signature cytokine produced by T helper 17 (Th17) cells and is considered the most biologically active form. The pathogenetic involvement of IL-17A in these conditions has been confirmed, and its blockade with biological agents has provided a highly effective therapeutical approach. IL-17F is also overexpressed in the skin and synovial tissues of patients with these diseases, and recent studies suggest its involvement in promoting inflammation and tissue damage in axSpA and PsA. The simultaneous targeting of IL-17A and IL-17F by dual inhibitors and bispecific antibodies may improve the management of Pso, PsA, and axSpA, as demonstrated in the pivotal studies of dual specific antibodies such as bimekizumab. The present review focuses on the role of IL-17F and its therapeutic blockade in axSpA and PsA.
Target and Cell Therapy for Atherosclerosis and CVD
Authors: Markina Yuliya V. , Kirichenko Tatiana V. , Tolstik Taisiya V. , Bogatyreva Anastasia I. , Zotova Ulyana S. , Cherednichenko Vadim R. , Postnov Anton Yu. , Markin Alexander M.
Published: June 2023

Cardiovascular diseases (CVD) and, in particular, atherosclerosis, remain the main cause of death in the world today. Unfortunately, in most cases, CVD therapy begins after the onset of clinical symptoms and is aimed at eliminating them. In this regard, early pathogenetic therapy for CVD remains an urgent problem in modern science and healthcare. Cell therapy, aimed at eliminating tissue damage underlying the pathogenesis of some pathologies, including CVD, by replacing it with various cells, is of the greatest interest. Currently, cell therapy is the most actively developed and potentially the most effective treatment strategy for CVD associated with atherosclerosis. However, this type of therapy has some limitations. In this review, we have tried to summarize the main targets of cell therapy for CVD and atherosclerosis in particular based on the analysis using the PubMed and Scopus databases up to May 2023.
Experimental Models to Study Diabetes Mellitus and Its Complications: Limitations and New Opportunities
Authors: Martín-Carro Beatriz , Donate-Correa Javier , Fernández-Villabrille Sara , Martín-Vírgala Julia , Panizo Sara , Carrillo-López Natalia , Martínez-Arias Laura , Navarro-González Juan F. , Naves-Díaz Manuel , Fernández-Martín José L. , Alonso-Montes Cristina , Cannata-Andía Jorge B.
Published: June 2023

Preclinical biomedical models are a fundamental tool to improve the knowledge and management of diseases, particularly in diabetes mellitus (DM) since, currently, the pathophysiological and molecular mechanisms involved in its development are not fully clarified, and there is no treatment to cure DM. This review will focus on the features, advantages and limitations of some of the most used DM models in rats, such as the spontaneous models: Bio-Breeding Diabetes-Prone (BB-DP) and LEW.1AR1-iddm, as representative models of type 1 DM (DM-1); the Zucker diabetic fatty (ZDF) and Goto-kakizaki (GK) rats, as representative models of type 2 DM (DM-2); and other models induced by surgical, dietary and pharmacological—alloxan and streptozotocin—procedures. Given the variety of DM models in rats, as well as the non-uniformity in the protocols and the absence of all the manifestation of the long-term multifactorial complications of DM in humans, the researchers must choose the one that best suits the final objectives of the study. These circumstances, added to the fact that most of the experimental research in the literature is focused on the study of the early phase of DM, makes it necessary to develop long-term studies closer to DM in humans. In this review, a recently published rat DM model induced by streptozotocin injection with chronic exogenous administration of insulin to reduce hyperglycaemia has also been included in an attempt to mimic the chronic phase of DM in humans.
Regulation of Carotenoid Biosynthesis and Degradation in Lettuce (Lactuca sativa L.) from Seedlings to Harvest
Authors: Brychkova Galina , de Oliveira Cleiton Lourenço , Gomes Luiz Antonio Augusto , de Souza Gomes Matheus , Fort Antoine , Esteves-Ferreira Alberto Abrantes , Sulpice Ronan , McKeown Peter C. , Spillane Charles
Published: June 2023

Lettuce (Lactuca sativa L.) is one of the commercially important leafy vegetables worldwide. However, lettuce cultivars vary widely in their carotenoid concentrations at the time of harvest. While the carotenoid content of lettuce can depend on transcript levels of key biosynthetic enzymes, genes that can act as biomarkers for carotenoid accumulation at early stages of plant growth have not been identified. Transcriptomic and metabolomic analysis was performed on the inner and outer leaves of the six cultivars at different developmental stages to identify gene-to-metabolite networks affecting the accumulation of two key carotenoids, β-carotene and lutein. Statistical analysis, including principal component analysis, was used to better understand variations in carotenoid concentration between leaf age and cultivars. Our results demonstrate that key enzymes of carotenoid biosynthesis pathway can alter lutein and β-carotene biosynthesis across commercial cultivars. To ensure high carotenoids content in leaves, the metabolites sink from β-carotene and lutein to zeaxanthin, and subsequently, abscisic acid needs to be regulated. Based on 2–3-fold carotenoids increase at 40 days after sowing (DAS) as compared to the seedling stage, and 1.5–2-fold decline at commercial stage (60 DAS) compared to the 40 DAS stage, we conclude that the value of lettuce for human nutrition would be improved by use of less mature plants, as the widely-used commercial stage is already at plant senescence stage where carotenoids and other essential metabolites are undergoing degradation.
Evolution of a Cockroach Allergen into the Major Protein of Termite Royal Jelly
Authors: Veenstra Jan A.
Published: June 2023

Termites live in colonies, and their members belong to different castes that each have their specific role within the termite society. In well-established colonies of higher termites, the only food the founding female, the queen, receives is saliva from workers; such queens can live for many years and produce up to 10,000 eggs per day. In higher termites, worker saliva must thus constitute a complete diet and therein resembles royal jelly produced by the hypopharyngeal glands of honeybee workers that serves as food for their queens; indeed, it might as well be called termite royal jelly. However, whereas the composition of honeybee royal jelly is well established, that of worker termite saliva in higher termites remains largely unknown. In lower termites, cellulose-digesting enzymes constitute the major proteins in worker saliva, but these enzymes are absent in higher termites. Others identified a partial protein sequence of the major saliva protein of a higher termite and identified it as a homolog of a cockroach allergen. Publicly available genome and transcriptome sequences from termites make it possible to study this protein in more detail. The gene coding the termite ortholog was duplicated, and the new paralog was preferentially expressed in the salivary gland. The amino acid sequence of the original allergen lacks the essential amino acids methionine, cysteine and tryptophan, but the salivary paralog incorporated these amino acids, thus allowing it to become more nutritionally balanced. The gene is found in both lower and higher termites, but it is in the latter that the salivary paralog gene got reamplified, facilitating an even higher expression of the allergen. This protein is not expressed in soldiers, and, like the major royal jelly proteins in honeybees, it is expressed in young but not old workers.
Advances in Functionalization of Bioresorbable Nanomembranes and Nanoparticles for Their Use in Biomedicine
Authors: Mohammed-Sadhakathullah Ahammed H. M. , Paulo-Mirasol Sofia , Torras Juan , Armelin Elaine
Published: June 2023

Bioresorbable nanomembranes (NMs) and nanoparticles (NPs) are powerful polymeric materials playing an important role in biomedicine, as they can effectively reduce infections and inflammatory clinical patient conditions due to their high biocompatibility, ability to physically interact with biomolecules, large surface area, and low toxicity. In this review, the most common bioabsorbable materials such as those belonging to natural polymers and proteins for the manufacture of NMs and NPs are reviewed. In addition to biocompatibility and bioresorption, current methodology on surface functionalization is also revisited and the most recent applications are highlighted. Considering the most recent use in the field of biosensors, tethered lipid bilayers, drug delivery, wound dressing, skin regeneration, targeted chemotherapy and imaging/diagnostics, functionalized NMs and NPs have become one of the main pillars of modern biomedical applications.
Influences of Jujube Witches’ Broom (JWB) Phytoplasma Infection and Oxytetracycline Hydrochloride Treatment on the Gene Expression Profiling in Jujube
Authors: Yang Junqiang , Shen Zhongmei , Qu Pengyan , Yang Rui , Shao Anping , Li Hao , Zhao Ailing , Cheng Chunzhen
Published: June 2023

Jujube witches’ broom disease (JWB), caused by Candidatus Phytoplasma ziziphi, is the most destructive phytoplasma disease threatening the jujube industry. Tetracycline derivatives treatments have been validated to be capable of recovering jujube trees from phytoplasma infection. In this study, we reported that oxytetracycline hydrochloride (OTC-HCl) trunk injection treatment could recover more than 86% of mild JWB-diseased trees. In order to explore the underlying molecular mechanism, comparative transcriptomic analysis of healthy control (C group), JWB-diseased (D group) and OTC-HCl treated JWB-diseased (T group) jujube leaves was performed. In total, 755 differentially expressed genes (DEGs), including 488 in ‘C vs. D’, 345 in ‘D vs. T’ and 94 in ‘C vs. T’, were identified. Gene enrichment analysis revealed that these DEGs were mainly involved in DNA and RNA metabolisms, signaling, photosynthesis, plant hormone metabolism and transduction, primary and secondary metabolisms, their transportations, etc. Notably, most of the DEGs identified in ‘C vs. D’ displayed adverse change patterns in ‘D vs. T’, suggesting that the expression of these genes was restored after OTC-HCl treatment. Our study revealed the influences of JWB phytoplasma infection and OTC-HCl treatment on gene expression profiling in jujube and would be helpful for understanding the chemotherapy effects of OTC-HCl on JWB-diseased jujube.
Shading-Dependent Greening Process of the Leaves in the Light-Sensitive Albino Tea Plant ‘Huangjinya’: Possible Involvement of the Light-Harvesting Complex II Subunit of Photosystem II in the Phenotypic Characteristic
Authors: Wang Ying-Qi , Ye Jing-Jing , Yang Hong-Zhiyuan , Li Da , Li Xiao-Xiang , Wang Yong-Kang , Zheng Xin-Qiang , Ye Jian-Hui , Li Qing-Sheng , Liang Yue-Rong , Lu Jian-Liang
Published: June 2023

The light-sensitive albino tea plant can produce pale-yellow shoots with high levels of amino acids which are suitable to process high-quality tea. In order to understand the mechanism of the albino phenotype formation, the changes in the physio-chemical characteristics, chloroplast ultrastructure, chlorophyll-binding proteins, and the relevant gene expression were comprehensively investigated in the leaves of the light-sensitive albino cultivar ‘Huangjinya’ (‘HJY’) during short-term shading treatment. In the content of photosynthetic pigments, the ultrastructure of the chloroplast, and parameters of the photosynthesis in the leaves of ‘HJY’ could be gradually normalized along with the extension of the shading time, resulting in the leaf color transformed from pale yellow to green. BN-PAGE and SDS-PAGE revealed that function restoration of the photosynthetic apparatus was attributed to the proper formation of the pigment-protein complexes on the thylakoid membrane that benefited from the increased levels of the LHCII subunits in the shaded leaves of ‘HJY’, indicating the low level of LHCII subunits, especially the lack of the Lhcb1 might be responsible for the albino phenotype of the ‘HJY’ under natural light condition. The deficiency of the Lhcb1 was mainly subject to the strongly suppressed expression of the Lhcb1.x which might be modulated by the chloroplast retrograde signaling pathway GUN1 (GENOMES UNCOUPLED 1)-PTM (PHD type transcription factor with transmembrane domains)-ABI4 (ABSCISIC ACID INSENSITIVE 4).
Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0
Authors: Delrue Charlotte , Speeckaert Marijn M.
Published: June 2023

Vitamin D, often referred to as the “sunshine nutrient”, has gained considerable attention in recent years due to its multifaceted impact on health and disease [...]
A De Novo Designed Trimeric Metalloprotein as a Nip Model of the Acetyl-CoA Synthase
Authors: Selvan Dhanashree , Chakraborty Saumen
Published: June 2023

We present a Nip site model of acetyl coenzyme-A synthase (ACS) within a de novo-designed trimer peptide that self-assembles to produce a homoleptic Ni(Cys)3 binding motif. Spectroscopic and kinetic studies of ligand binding demonstrate that Ni binding stabilizes the peptide assembly and produces a terminal NiI-CO complex. When the CO-bound state is reacted with a methyl donor, a new species is quickly produced with new spectral features. While the metal-bound CO is albeit unactivated, the presence of the methyl donor produces an activated metal-CO complex. Selective outer sphere steric modifications demonstrate that the physical properties of the ligand-bound states are altered differently depending on the location of the steric modification above or below the Ni site.
Novel Insights to Assess Climate Resilience in Goats Using a Holistic Approach of Skin-Based Advanced NGS Technologies
Authors: Mullakkalparambil Velayudhan Silpa , Sejian Veerasamy , Devaraj Chinnasamy , Manjunathareddy Gundallahalli Bayyappa , Ruban Wilfred , Kadam Vinod , König Sven , Bhatta Raghavendra
Published: June 2023

A novel study was conducted to elucidate heat-stress responses on a number of hair- and skin-based traits in two indigenous goat breeds using a holistic approach that considered a number of phenotypic and genomic variables. The two goat breeds, Kanni Aadu and Kodi Aadu, were subjected to a simulated heat-stress study using the climate chambers. Four groups consisting of six goats each (KAC, Kaani Aadu control; KAH, Kanni Aadu heat stress; KOC, Kodi Aadu control; and KOH, Kodi Aadu heat stress) were considered for the study. The impact of heat stress on caprine skin tissue along with a comparative assessment of the thermal resilience of the two goat breeds was assessed. The variables considered were hair characteristics, hair cortisol, hair follicle quantitative PCR (qPCR), sweating (sweating rate and active sweat gland measurement), skin histometry, skin-surface infrared thermography (IRT), skin 16S rRNA V3-V4 metagenomics, skin transcriptomics, and skin bisulfite sequencing. Heat stress significantly influenced the hair fiber characteristics (fiber length) and hair follicle qPCR profile (Heat-shock protein 70 (HSP70), HSP90, and HSP110). Significantly higher sweating rate, activated sweat gland number, skin epithelium, and sweat gland number (histometry) were observed in heat stressed goats. The skin microbiota was also observed to be significantly altered due to heat stress, with a relatively higher alteration being noticed in Kanni Aadu goats than in Kodi Aadi goats. Furthermore, the transcriptomics and epigenetics analysis also pointed towards the significant impact of heat stress at the cellular and molecular levels in caprine skin tissue. The higher proportion of differentially expressed genes (DEGs) along with higher differentially methylated regions (DMRs) in Kanni Aadu goats due to heat stress when compared to Kodi Aadu goats pointed towards the better resilience of the latter breed. A number of established skin, adaptation, and immune-response genes were also observed to be significantly expressed/methylated. Additionally, the influence of heat stress at the genomic level was also predicted to result in significant functional alterations. This novel study thereby highlights the impact of heat stress on the caprine skin tissue and also the difference in thermal resilience exhibited by the two indigenous goat breeds, with Kodi Aadu goats being more resilient.
Basophil Characteristics as a Marker of the Pathogenesis of Chronic Spontaneous Urticaria in Relation to the Coagulation and Complement Systems
Authors: Yanase Yuhki , Matsubara Daiki , Takahagi Shunsuke , Tanaka Akio , Ozawa Koichiro , Hide Michihiro
Published: June 2023

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch and pruritus anywhere on the body for more than 6 weeks. Although basophil- and mast cell-released inflammatory mediators, such as histamine, play important roles in the pathogenesis of CSU, the detailed underlying mechanism is not clear. Since several auto-antibodies, IgGs which recognize IgE or the high-affinity IgE receptor (FcεRI) and IgEs against other self-antigens, are detected in CSU patients, they are considered to activate both mast cells in the skin and basophils circulating in the blood. In addition, we and other groups demonstrated that the coagulation and complement system also contribute to the development of urticaria. Here, we summarized the behaviors, markers and targets of basophils in relation to the coagulation–complement system, and for the treatment of CSU.
Increased Expression of Anaphylatoxin C5a-Receptor-1 in Neutrophils and Natural Killer Cells of Preterm Infants
Authors: Boeckel Hannah , Karsten Christian M. , Göpel Wolfgang , Herting Egbert , Rupp Jan , Härtel Christoph , Hartz Annika
Published: June 2023

Preterm infants are susceptible to infection and their defense against pathogens relies largely on innate immunity. The role of the complement system for the immunological vulnerability of preterm infants is less understood. Anaphylatoxin C5a and its receptors C5aR1 and -2 are known to be involved in sepsis pathogenesis, with C5aR1 mainly exerting pro-inflammatory effects. Our explorative study aimed to determine age-dependent changes in the expression of C5aR1 and C5aR2 in neonatal immune cell subsets. Via flow cytometry, we analyzed the expression pattern of C5a receptors on immune cells isolated from peripheral blood of preterm infants (n = 32) compared to those of their mothers (n = 25). Term infants and healthy adults served as controls. Preterm infants had a higher intracellular expression of C5aR1 on neutrophils than control individuals. We also found a higher expression of C5aR1 on NK cells, particularly on the cytotoxic CD56dim subset and the CD56- subset. Immune phenotyping of other leukocyte subpopulations revealed no gestational-age-related differences for the expression of and C5aR2. Elevated expression of C5aR1 on neutrophils and NK cells in preterm infants may contribute to the phenomenon of “immunoparalysis” caused by complement activation or to sustained hyper-inflammatory states. Further functional analyses are needed to elucidate the underlying mechanisms.
Small RNA Sequencing Analysis of STZ-Injured Pancreas Reveals Novel MicroRNA and Transfer RNA-Derived RNA with Biomarker Potential for Diabetes Mellitus
Authors: Mo Fangfang , Lv Bohan , Zhao Dandan , Xi Ziye , Qian Yining , Ge Dongyu , Yang Nan , Zhang Dongwei , Jiang Guangjian , Gao Sihua
Published: June 2023

MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) play critical roles in the regulation of different biological processes, but their underlying mechanisms in diabetes mellitus (DM) are still largely unknown. This study aimed to gain a better understanding of the functions of miRNAs and tsRNAs in the pathogenesis of DM. A high-fat diet (HFD) and streptozocin (STZ)-induced DM rat model was established. Pancreatic tissues were obtained for subsequent studies. The miRNA and tsRNA expression profiles in the DM and control groups were obtained by RNA sequencing and validated with quantitative reverse transcription-PCR (qRT-PCR). Subsequently, bioinformatics methods were used to predict target genes and the biological functions of differentially expressed miRNAs and tsRNAs. We identified 17 miRNAs and 28 tsRNAs that were significantly differentiated between the DM and control group. Subsequently, target genes were predicted for these altered miRNAs and tsRNAs, including Nalcn, Lpin2 and E2f3. These target genes were significantly enriched in localization as well as intracellular and protein binding. In addition, the results of KEGG analysis showed that the target genes were significantly enriched in the Wnt signaling pathway, insulin pathway, MAPK signaling pathway and Hippo signaling pathway. This study revealed the expression profiles of miRNAs and tsRNAs in the pancreas of a DM rat model using small RNA-Seq and predicted the target genes and associated pathways using bioinformatics analysis. Our findings provide a novel aspect in understanding the mechanisms of DM and identify potential targets for the diagnosis and treatment of DM.
CCN3/NOV Regulates Proliferation and Neuronal Differentiation in Mouse Hippocampal Neural Stem Cells via the Activation of the Notch/PTEN/AKT Pathway
Authors: Luan Yan , Zhang Hanyue , Ma Kaige , Liu Yingfei , Lu Haixia , Chen Xinlin , Liu Yong , Zhang Zhichao
Published: June 2023

Neural stem cells (NSCs) persist in the subgranular zone (SGZ) throughout the lifespan and hold immense potential for the repair and regeneration of the central nervous system, including hippocampal-related diseases. Several studies have demonstrated that cellular communication network protein 3 (CCN3) regulates multiple types of stem cells. However, the role of CCN3 in NSCs remains unknown. In this study, we identified CCN3 expression in mouse hippocampal NSCs and observed that supplementing CCN3 improved cell viability in a concentration-dependent manner. Additionally, in vivo results showed that the injection of CCN3 in the dentate gyrus (DG) increased Ki-67- and SOX2-positive cells while decreasing neuron-specific class III beta-tubulin (Tuj1) and doublecortin (DCX)-positive cells. Consistently with the in vivo results, supplementing CCN3 in the medium increased the number of BrdU and Ki-67 cells and the proliferation index but decreased the number of Tuj1 and DCX cells. Conversely, both the in vivo and in vitro knockdown of the Ccn3 gene in NSCs had opposite effects. Further investigations revealed that CCN3 promoted cleaved Notch1 (NICD) expression, leading to the suppression of PTEN expression and eventual promotion of AKT activation. In contrast, Ccn3 knockdown inhibited the activation of the Notch/PTEN/AKT pathway. Finally, the effects of changes in CCN3 protein expression on NSC proliferation and differentiation were eliminated by FLI-06 (a Notch inhibitor) and VO-OH (a PTEN inhibitor). Our findings imply that while promoting proliferation, CCN3 inhibits the neuronal differentiation of mouse hippocampal NSCs and that the Notch/PTEN/AKT pathway may be a potential intracellular target of CCN3. Our findings may help develop strategies to enhance the intrinsic potential for brain regeneration after injuries, particularly stem cell treatment for hippocampal-related diseases.
Evaluating a Conceptual Model for Measuring Gaming Experience: A Case Study of Stranded Away Platformer Game
Authors: Blašković Luka , Žužić Alesandro , Orehovački Tihomir
Published: June 2023

Video games have become a ubiquitous form of entertainment and have been enjoyed by people of all ages around the world. The gaming industry has evolved rapidly, with new games being released every year that push the boundaries of technology and creativity. To ensure that video games are not just technically advanced, but also enjoyable and engaging, measuring the gaming experience is essential because it helps game designers understand how players interact with the game and identify areas for its improvement. The objective of this paper is to examine an interplay of gaming experience dimensions in the context of platform video games and to determine the extent to which they contribute to players’ behavioral intentions. To fulfil this objective, an empirical study was undertaken, involving participants with diverse gaming backgrounds. They were requested to engage in the gameplay of the Stranded Away platformer game and subsequently respond to a post-use questionnaire. The psychometric features of the introduced conceptual model were evaluated with the partial least squares structural equation modeling (PLS-SEM) method. The reported findings demonstrate the importance of evaluating different facets of the gaming experience in video games and showcase the potential of the proposed model and measuring instrument as tools for game designers to enhance the overall quality of their products.
Insect Colonisation and the Decomposition Process in Aerated versus Watertight Burial Systems
Authors: Defilippo Francesco , Munari Martina , Grisendi Annalisa , Gaudio Rosa Maria , D’Incau Mario , Lavazza Antonio , Rubini Silva
Published: June 2023

In recent years, burial systems have covered increasingly higher costs due to the pollution caused by decomposition products. These products are understood as chemicals and microorganisms in the surrounding soil and groundwater and represent a topical issue. The purpose of this research was to ascertain the extent of decomposition when pig carcasses are buried in two different burial systems (“aerated” vs. “watertight”) and catalogue the arthropods associated with burials at different time-points of removal from niches (after 6, 12, 24, 36, and 60 months). Thirteen taxa were collected in aerated niches, whereas five were collected in watertight niches. The initial access or exclusion of insect colonisers affected overall functional activity. Two Diptera species, Hydrotaea capensis and Megaselia scalaris, were the most abundant, supporting the hypothesis that insects can colonise carcasses in aerated burial systems. Furthermore, some species of bacteria have been documented as facilitators of the initial decomposition process of the carcass. Most bacterial colonies develop only in aerated niches. The trial showed that the first enzymatic–bacterial and insect actions helped promote the process of cadaveric decomposition and later skeletonisation, mainly when associated with aeration modes of the tomb/mound. The results obtained provide essential information on the process of human decomposition and taphonomy in cemeteries. Moreover, these data could benefit forensic science by adding information on insect colonisation and body modification in medico-legal investigations concerning the post-mortem interval in exhumed bodies and illegal burials.
Fibrous Dysplasia of the Jaw: Advances in Imaging and Treatment
Authors: Obermeier Katharina Theresa , Hartung Jens Tobias , Hildebrandt Tim , Dewenter Ina , Smolka Wenko , Hesse Eric , Fegg Florian , Otto Sven , Malenova Yoana , Abdullah Anusha
Published: June 2023

A total of 7% of all benign bone lesions are diagnosed as fibrous dysplasia (FD). The symptoms of FD of the jaw range from asymptomatic to dental anomalies, pain and facial asymmetry. Due to its resemblance to other fibro-osseous bone lesions, misdiagnosis often occurs and can lead to inadequate treatment. Particularly in the jaw, this lesion does not become quiescent during puberty, making fundamental knowledge about the diagnosis and treatment of FD crucial. Mutational analysis and nonsurgical approaches offer new diagnostic and therapeutic options. In this review, we examine the advances and the difficulties of the diagnosis and the various treatment modalities of FD of the jaw in order to capture the current scientific knowledge on this bone disease.
Leukocyte Telomere Length and Neuregulin-4 Levels in Female Patients with Acromegaly: The Relationship between Disease Activity and Body Fat Distribution
Authors: Coskun Meric , Altinova Alev Eroglu , Babayeva Afruz , Sel Aydin Tuncer , Yapar Dilek , Karaca Mine , Yalcin Mehmet Muhittin , Akturk Mujde , Toruner Fusun Balos , Karakoc Mehmet Ayhan , Yetkin Ilhan
Published: June 2023

The study aimed to examine leukocyte telomere length (LTL) and serum neuregulin-4 levels and their relationship with disease activity, co-morbidities and body fat distribution in female acromegaly patients. Forty female patients with acromegaly and thirty-nine age and body mass index (BMI) similar healthy female volunteers were included in the study. Patients were classified into two groups: active acromegaly (AA) and controlled acromegaly (CA). The quantitative polymerase chain reaction (PCR) method was used to study LTL, and T/S ratio < 1 was accepted as shortened telomere length. Neuregulin-4 was studied by ELISA. There was no difference in median LTL between acromegaly and the control group (p = 0.530). The percentage of T/S < 1 in patients with acromegaly (60.0%) was similar to that of the control group (43.6%) (p = 0.144). However, serum neuregulin-4 was significantly higher in patients with acromegaly than those in the control group (p = 0.037). There were no significant differences concerning LTL, percentage of T/S < 1 and neuregulin-4 levels between active and controlled acromegaly groups (p > 0.05). Neuregulin-4 correlated positively with fasting glucose, triglyceride (TG), triglyceride/glucose (TyG) index, and lean body mass in the acromegaly group. A negative correlation was observed between LTL and neuregulin-4 in the control group (p = 0.039). When the factors affecting neuregulin-4 were evaluated by multivariate linear regression analysis with an enter method, TG (β: 0.316, p = 0.025) was independently and positively associated with neuregulin-4. Our findings indicate that acromegaly is associated with unchanged LTL and high neuregulin-4 levels in female patients. However, the relationship between acromegaly, the aging process, and neuregulin-4 involves complex mechanisms, and further studies are needed.
The Biology of Placebo and Nocebo Effects on Experimental and Chronic Pain: State of the Art
Authors: Rossettini Giacomo , Campaci Francesco , Bialosky Joel , Huysmans Eva , Vase Lene , Carlino Elisa
Published: June 2023

(1) Background: In recent years, placebo and nocebo effects have been extensively documented in different medical conditions, including pain. The scientific literature has provided strong evidence of how the psychosocial context accompanying the treatment administration can influence the therapeutic outcome positively (placebo effects) or negatively (nocebo effects). (2) Methods: This state-of-the-art paper aims to provide an updated overview of placebo and nocebo effects on pain. (3) Results: The most common study designs, the psychological mechanisms, and neurobiological/genetic determinants of these phenomena are discussed, focusing on the differences between positive and negative context effects on pain in experimental settings on healthy volunteers and in clinical settings on chronic pain patients. Finally, the last section describes the implications for clinical and research practice to maximize the medical and scientific routine and correctly interpret the results of research studies on placebo and nocebo effects. (4) Conclusions: While studies on healthy participants seem consistent and provide a clear picture of how the brain reacts to the context, there are no unique results of the occurrence and magnitude of placebo and nocebo effects in chronic pain patients, mainly due to the heterogeneity of pain. This opens up the need for future studies on the topic.
The Effect of Laparoscopic Sleeve Gastrectomy on the Course of Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients during One Year of Follow Up
Authors: Głuszyńska Paulina , Łukaszewicz Aleksander , Diemieszczyk Inna , Chilmończyk Jan , Reszeć Joanna , Citko Anna , Szczerbiński Łukasz , Krętowski Adam , Razak Hady Hady
Published: June 2023

Background: Morbid obesity co-exists with non-alcoholic fatty liver disease in up to 90% of cases. Laparoscopic sleeve gastrectomy leads to a reduction in body mass and thus may improve the course of non-alcoholic fatty liver disease. The aim of this study was to evaluate the effect of laparoscopic sleeve gastrectomy on the resolution of non-alcoholic fatty liver disease. Methods: The study included 55 patients with non-alcoholic fatty liver disease who underwent laparoscopic sleeve gastrectomy at a tertiary institution. The analysis consisted of preoperative liver biopsy, abdominal ultrasound, weight loss parameters, Non-Alcoholic Fatty Liver Fibrosis Score and selected laboratory parameters. Results: Before the surgery, 6 patients were diagnosed with grade 1 liver steatosis, 33 patients with grade 2 and 16 patients with grade 3. One year after the surgery, only 21 patients had features of liver steatosis at ultrasound. All weight loss parameters showed statistically significant changes during the observation; the median percentage of total weight loss was 31.0% (IQR: 27.5; 34.5) with p = 0.0003, the median percentage of excess weight loss was 61.8% (IQR: 52.4; 72.3) with p = 0.0013 and the median percentage of excess body mass index loss was 71.0% (IQR: 61.3; 86.9) with p = 0.0036 12 months after laparoscopic sleeve gastrectomy. The median Non-Alcoholic Fatty Liver Fibrosis Score at baseline was 0.2 (IQR: −0.8; 1.0) and decreased to −1.6 (IQR: −2.4; −0.4) (p < 0.0001). Moderate negative correlations between Non-Alcoholic Fatty Liver Fibrosis Score and percentage of total weight loss (r = −0.434, p < 0.0001), percentage of excess weight loss (r = −0.456, p < 0.0001) and percentage of excess body mass index loss (r = −0.512, p < 0.0001) were found. Conclusions: The study supports the thesis that laparoscopic sleeve gastrectomy is an effective method for treatment of non-alcoholic fatty liver disease in patients with morbid obesity.
Epidemiological and Clinical Characteristics of Patients Admitted to a Secondary Hospital with Suspected MPOX Virus Infection: Is HIV Playing a Role?
Authors: Estévez Samuel , Vara Marta , Gamo María , Manzano Samuel , Troya Jesús , Botezat Ekaterina , Jiménez Eva , Pedrero-Tomé Roberto , Martin María Ángeles , de la Cueva Pablo , Fernández Elisa , Fernández Beatriz , Brown David Esteban , Palma Elena , Simón Ana
Published: June 2023

MPOX (monkeypox) is a zoonotic viral disease, endemic in some Central and West African countries. However, in May 2022, cases began to be reported in non-endemic countries, demonstrating community transmission. Since the beginning of the outbreak, different epidemiological and clinical behaviors have been observed. We conducted an observational study at a secondary hospital in Madrid to characterize suspected and confirmed cases of MPOX epidemiologically and clinically. Besides the general descriptive analysis, we compared data between HIV-positive and HIV-negative subjects; 133 patients were evaluated with suspected MPOX, of which 100 were confirmed. Regarding positive cases, 71.0% were HIV positive, and 99.0% were men with a mean age of 33. In the previous year, 97.6% reported having sex with men, 53.6% used apps for sexual encounters, 22.9% practiced chemsex, and 16.7% went to saunas. Inguinal adenopathies were significantly higher in MPOX cases (54.0% vs. 12.1%, p < 0.001), as the involvement of genital and perianal area (57.0% vs. 27.3% and 17.0% vs. 1.0%, p = 0.006 and p = 0.082 respectively). Pustules were the most common skin lesion (45.0%). In HIV-positive cases, only 6.9% had a detectable viral load, and the mean CD4 count was 607.0/mm3. No significant differences were observed in the disease course, except for a greater tendency towards the appearance of perianal lesions. In conclusion, the MPOX 2022 outbreak in our area has been related to sexual intercourse among MSM, with no severe clinical cases nor apparent differences in HIV and non-HIV patients.
Pathophysiology of Rejection in Kidney Transplantation
Authors: Tamargo Christina L. , Kant Sam
Published: June 2023

Kidney transplantation has been the optimal treatment for end-stage kidney disease for almost 70 years, with increasing frequency over this period. Despite the prevalence of the procedure, allograft rejection continues to impact transplant recipients, with consequences ranging from hospitalization to allograft failure. Rates of rejection have declined over time, which has been largely attributed to developments in immunosuppressive therapy, understanding of the immune system, and monitoring. Developments in these therapies, as well as an improved understanding of rejection risk and the epidemiology of rejection, are dependent on a foundational understanding of the pathophysiology of rejection. This review explains the interconnected mechanisms behind antibody-mediated and T-cell-mediated rejection and highlights how these processes contribute to outcomes and can inform future progress.
Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns
Authors: Machairiotis Nikolaos , Vrachnis Dionysios , Antonakopoulos Nikolaos , Loukas Nikolaos , Fotiou Alexandros , Pergialiotis Vasilios , Stavros Sofoklis , Mantzou Aimilia , Maroudias Georgios , Iavazzo Christos , Kanaka-Gantenbein Christina , Drakakis Petros , Troupis Theodore , Vlasis Konstantinos , Vrachnis Nikolaos
Published: June 2023

Background: Abnormal fetal growth is associated with adverse perinatal and long-term outcomes. The pathophysiological mechanisms underlying these conditions are still to be clarified. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are two neurotrophins that are mainly involved in the neuroprotection process, namely promotion of growth and differentiation, maintenance, and survival of neurons. During pregnancy, they have been correlated with placental development and fetal growth. In this study, we aimed to determine the early 2nd trimester amniotic fluid levels of NGF and NT-3 and to investigate their association with fetal growth. Methods: This is a prospective observational study. A total of 51 amniotic fluid samples were collected from women undergoing amniocentesis early in the second trimester and were stored at −80 °C. Pregnancies were followed up until delivery and birth weight was recorded. Based on birth weight, the amniotic fluid samples were divided into three groups: appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA). NGF and NT-3 levels were determined by using Elisa kits. Results: NGF concentrations were similar between the studied groups; median values were 10.15 pg/mL, 10.15 pg/mL, and 9.14 pg/mL in SGA, LGA, and AGA fetuses, respectively. Regarding NT-3, a trend was observed towards increased NT-3 levels as fetal growth velocity decreased; median concentrations were 11.87 pg/mL, 15.9 pg/mL, and 23.5 pg/mL in SGA, AGA, and LGA fetuses, respectively, although the differences among the three groups were not statistically significant. Conclusions: Our findings suggest that fetal growth disturbances do not induce increased or decreased production of NGF and NT-3 in early second trimester amniotic fluid. The trend observed towards increased NT-3 levels as fetal growth velocity decreased shows that there may be a compensatory mechanism in place that operates in conjunction with the brain-sparing effect. Further associations between these two neurotrophins and fetal growth disturbances are discussed.
Fabrication of Novel Pre-Polymerized BisGMA/Silica Nanocomposites: Physio-Mechanical Considerations
Authors: Alrahlah Ali , Khan Rawaiz , Al-Odayni Abdel-Basit , Saeed Waseem Sharaf , Bautista Leonel S. , Haider Sajjad , De Vera Merry Angelyn Tan , Alshabib Abdulrahman
Published: June 2023

Resin composite mimics tooth tissues both in structure and properties, and thus, they can withstand high biting force and the harsh environmental conditions of the mouth. Various inorganic nano- and micro-fillers are commonly used to enhance these composites’ properties. In this study, we adopted a novel approach by using pre-polymerized bisphenol A-glycidyl methacrylate (BisGMA) ground particles (XL-BisGMA) as fillers in a BisGMA/triethylene glycol dimethacrylate (TEGDMA) resin system in combination with SiO2 nanoparticles. The BisGMA/TEGDMA/SiO2 mixture was filled with various concentrations of XL-BisGMA (0, 2.5, 5, and 10 wt.%). The XL-BisGMA added composites were evaluated for viscosity, degree of conversion (DC), microhardness, and thermal properties. The results demonstrated that the addition of a lower concentration of XL-BisGMA particles (2.5 wt.%) significantly reduced (p ≤ 0.05) the complex viscosity from 374.6 (Pa·s) to 170.84. (Pa·s). Similarly, DC was also increased significantly (p ≤ 0.05) by the addition of 2.5 wt.% XL-BisGMA, with the pristine composite showing a DC of (62.19 ± 3.2%) increased to (69.10 ± 3.4%). Moreover, the decomposition temperature has been increased from 410 °C for the pristine composite (BT-SB0) to 450 °C for the composite with 10 wt.% of XL-BisGMA (BT-SB10). The microhardness has also been significantly reduced (p ≤ 0.05) from 47.44 HV for the pristine composite (BT-SB0) to 29.91 HV for the composite with 2.5 wt.% of XL-BisGMA (BT-SB2.5). These results suggest that a XL-BisGMA could be used to a certain percentage as a promising filler in combination with inorganic fillers to enhance the DC and flow properties of the corresponding resin-based dental composites.
Physics-Based Modelling for On-Line Condition Monitoring of a Marine Engine System
Authors: Fu Chao , Lu Kuan , Li Qian , Xu Yuandong , Gu Fengshou , Ball Andrew D. , Zheng Zhaoli
Published: June 2023

The engine system is critical for a marine vehicle, and its performance significantly affects the efficiency and safety of the whole ship. Due to the harsh working environment and the complex system structure, a marine system is prone to have many kinds of novelties and faults. Timely detection of faults via effective condition monitoring is vital for such systems, avoiding serious damage and economic loss. However, it is difficult to realize online monitoring because of the limitations of measurement and health monitoring methods. In this paper, a marine engine system simulator is set up with enhanced sensory placement for static and dynamic data collection. The test rig and processing for static and dynamic data are described. Then, a physics-based multivariate modeling method is proposed for the health monitoring of the system. Case studies are carried out considering the misfire fault and the exhaust valve leakage fault. In the misfire fault test, the exhaust gas temperature of the misfired cylinder dropped from the confidence interval 100–150 °C to 70–80 °C and the head vibration features decreased from the confidence interval 900–1300 m/s2 to around 200–300 m/s2. For the exhaust valve leakage fault, the engine body vibration main bearing impact RMS increased nearly 10 times. Comparisons between the model-predicted confidence interval and measured data reveal that the proposed model based on the fault-related static and dynamic features successfully identified the two faults and their positions, proving the effectiveness of the proposed framework.
Adaptive Sliding Mode Control for Unmanned Surface Vehicles with Predefined-Time Tracking Performances
Authors: Jiang Tao , Yan Yan , Yu Shuang-He
Published: June 2023

This paper is concerned with the trajectory tracking control of unmanned surface vehicles (USVs) subject to input quantization, actuator faults and dead zones. In scenarios with dense marine facilities, there are constraints on the tracking performance and convergence time of USVs. First, the designed control signal is quantized by a hysteresis quantizer to reduce the transmission rate. Second, to guarantee the transient and steady-state tracking performance of the USV, a prescribed performance control technology with a predefined settling time is employed. Third, a predefined-time adaptive sliding mode control (SMC) method is designed by integrating the auxiliary function and the barrier function. Moreover, the lumped uncertainties caused by quantization, actuator faults, and dead zones are simultaneously processed using control gain based on barrier function. The proposed control method guarantees that the tracking error and sliding variable converge to the corresponding predefined bounds within a predefined time. The predefined bounds are independent of the upper bound on the lumped uncertainty. The stability of the controlled system is proven via the Lyapunov theorem. Finally, the effectiveness of the designed controller is verified by numerical simulations.
Endoscopic Vacuum Therapy of Upper Gastrointestinal Anastomotic Leaks: How to Deal with the Challenges (with Video)
Authors: Monino Laurent , Moreels Tom G.
Published: June 2023

Anastomotic leaks after gastrointestinal surgery have an important impact on surgical outcomes because of the high morbidity and mortality rates. Multiple treatment options exist requiring an individualized patient-tailored treatment plan after multidisciplinary discussion. Endoscopic vacuum therapy (EVT) is a novel treatment option that is nowadays recognized as an effective and useful endoscopic approach to treat leaks or perforations in both the upper and lower gastrointestinal tract. EVT has a very good safety profile. However, it is a time-consuming endeavour requiring engagement from the endoscopist and understanding from the patient. To the unexperienced, the EVT technique may be prone to several hurdles which may deter endoscopists from using it and depriving patients from a potentially life-saving therapeutic option. The current review highlights the possible difficulties of the EVT procedure and aims to provide some practical solutions to facilitate its use in daily clinical practice. Personal tips and tricks are shared to overcome the pre-, intra- and post-procedural hurdles. An instructive video of the procedure helps to illustrate the technique of EVT.
Preparation of Epoxy Resin with Disulfide-Containing Curing Agent and Its Application in Self-Healing Coating
Authors: Wang Baolei , Li Zewei , Liu Xinru , Li Lulu , Yu Jianxiang , Li Shuang , Guo Gaiping , Gao Dahai , Dai Yuhua
Published: June 2023

Intrinsic self-healing polymers via dynamic covalent bonds have been attracting extensive attention because of their repeatable self-healing property. Herein, a novel self-healing epoxy resin was synthesized with disulfide-containing curing agent via the condensation of dimethyl 3,3′-dithiodipropionate (DTPA) and polyether amine (PEA). Therefore, in the structure of cured resin, flexible molecular chains and disulfide bonds were imported into the cross-linked polymer networks for triggering self-healing performance. The self-healing reaction of cracked samples was realized under a mild condition (60 °C for 6 h). The distribution of flexible polymer segments, disulfide bonds and hydrogen bonds in cross-linked networks plays a great role in the self-healing process of prepared resins. The molar ratio of PEA and DTPA strongly affects the mechanical performance and self-healing property. Especially when that molar ratio of PEA to DTPA is 2, the cured self-healing resin sample showed great ultimate elongation (795%) and excellent healing efficiency (98%). The products can be used as an organic coating, in which the crack could self-repair during a limited time. The corrosion resistance of a typical cure coating sample has been testified by an immersion experiment and electrochemistry impedance spectrum (EIS). This work provided a simple and low-cost route to prepare a self-healing coating for prolonging the service life of conventional epoxy coatings.