bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Effects of Endocannabinoids on Amyloid-Beta Aggregation and Toxicity
Authors: Khavandi Marzie , Rao Praveen P. N. , Beazely Michael A.
Published: January 2023

The regulation and metabolism of the endocannabinoid system has received extensive attention for their potential neuroprotective effect in neurodegenerative diseases such as Alzheimer’s disease (AD), which is characterized by amyloid β (Aβ) -induced cell toxicity, inflammation, and oxidative stress. Using in vitro techniques and two cell lines, the mouse hippocampus-derived HT22 cells and Chinese hamster ovary (CHO) cells expressing human cannabinoid receptor type 1 (CB1), we investigated the ability of endocannabinoids to inhibit Aβ aggregation and protect cells against Aβ toxicity. The present study provides evidence that endocannabinoids N-arachidonoyl ethanol amide (AEA), noladin and O-arachidonoyl ethanolamine (OAE) inhibit Aβ42 aggregation. They were able to provide protection against Aβ42 induced cytotoxicity via receptor-mediated and non-receptor-mediated mechanisms in CB1-CHO and HT22 cells, respectively. The aggregation kinetic experiments demonstrate the anti-Aβ aggregation activity of some endocannabinoids (AEA, noladin). These data demonstrate the potential role and application of endocannabinoids in AD pathology and treatment.
The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ1–42 on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices
Authors: Shi Dai , Wong Jaime K. Y. , Zhu Kaichuan , Noakes Peter G. , Rammes Gerhard
Published: January 2023

It has been hypothesised that inhalational anaesthetics such as isoflurane (Iso) may trigger the pathogenesis of Alzheimer’s disease (AD), while the gaseous anaesthetic xenon (Xe) exhibits many features of a putative neuroprotective agent. Loss of synapses is regarded as one key cause of dementia in AD. Multiple EGF-like domains 10 (MEGF10) is one of the phagocytic receptors which assists the elimination of synapses by astrocytes. Here, we investigated how β-amyloid peptide 1–42 (Aβ1–42), Iso and Xe interact with MEGF10-dependent synapse elimination. Murine cultured astrocytes as well as cortical and hippocampal ex vivo brain slices were treated with either Aβ1–42, Iso or Xe and the combination of Aβ1–42 with either Iso or Xe. We quantified MEGF10 expression in astrocytes and dendritic spine density (DSD) in slices. In brain slices of wild type and AAV-induced MEGF10 knock-down mice, antibodies against astrocytes (GFAP), pre- (synaptophysin) and postsynaptic (PSD95) components were used for co-localization analyses by means of immunofluorescence-imaging and 3D rendering techniques. Aβ1–42 elevated pre- and postsynaptic components inside astrocytes and decreased DSD. The combined application with either Iso or Xe reversed these effects. In the presence of Aβ1–42 both anaesthetics decreased MEGF10 expression. AAV-induced knock-down of MEGF10 reduced the pre- and postsynaptic marker inside astrocytes. The presented data suggest Iso and Xe are able to reverse the Aβ1–42-induced enhancement of synaptic elimination in ex vivo hippocampal brain slices, presumably through MEGF10 downregulation.
Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy
Authors: Lupo Gabriella , Agafonova Aleksandra , Cosentino Alessia , Giurdanella Giovanni , Mannino Giuliana , Lo Furno Debora , Romano Ivana Roberta , Giuffrida Rosario , D’Angeli Floriana , Anfuso Carmelina Daniela
Published: January 2023

Diabetic retinopathy (DR) is characterized by morphologic and metabolic alterations in endothelial cells (ECs) and pericytes (PCs) of the blood–retinal barrier (BRB). The loss of interendothelial junctions, increased vascular permeability, microaneurysms, and finally, EC detachment are the main features of DR. In this scenario, a pivotal role is played by the extensive loss of PCs. Based on previous results, the aim of this study was to assess possible beneficial effects exerted by adipose mesenchymal stem cells (ASCs) and their pericyte-like differentiated phenotype (P-ASCs) on human retinal endothelial cells (HRECs) in high glucose conditions (25 mM glucose, HG). P-ASCs were more able to preserve BRB integrity than ASCs in terms of (a) increased transendothelial electrical resistance (TEER); (b) increased expression of adherens junction and tight junction proteins (VE-cadherin and ZO-1); (c) reduction in mRNA levels of inflammatory cytokines TNF-α, IL-1β, and MMP-9; (d) reduction in the angiogenic factor VEGF and in fibrotic TGF-β1. Moreover, P-ASCs counteracted the HG-induced activation of the pro-inflammatory phospho-ERK1/2/phospho-cPLA2/COX-2 pathway. Finally, crosstalk between HRECs and ASCs or P-ASCs based on the PDGF-B/PDGFR-β axis at the mRNA level is described herein. Thus, P-ASCs might be considered valuable candidates for therapeutic approaches aimed at countering BRB disruption in DR.
Artificial Fluorescent Glucosinolates (F-GSLs) Are Transported by the Glucosinolate Transporters GTR1/2/3
Authors: Kanstrup Christa , Jimidar Claire C. , Tomas Josip , Cutolo Giuliano , Crocoll Christoph , Schuler Marie , Klahn Philipp , Tatibouët Arnaud , Nour-Eldin Hussam Hassan
Published: January 2023

The glucosinolate transporters 1/2/3 (GTR1/2/3) from the Nitrate and Peptide transporter Family (NPF) play an essential role in the transport, accumulation, and distribution of the specialized plant metabolite glucosinolates. Due to representing both antinutritional and health-promoting compounds, there is increasing interest in characterizing GTRs from various plant species. We generated seven artificial glucosinolates (either aliphatic or benzenic) bearing different fluorophores (Fluorescein, BODIPY, Rhodamine, Dansylamide, and NBD) and investigated the ability of GTR1/2/3 from Arabidopsis thaliana to import the fluorescent glucosinolates (F-GSLs) into oocytes from Xenopus laevis. Five out of the seven F-GSLs synthesized were imported by at least one of the GTRs. GTR1 and GTR2 were able to import three F-GSLs actively above external concentration, while GTR3 imported only one actively. Competition assays indicate that the F-GSLs are transported by the same mechanism as non-tagged natural glucosinolates. The GTR-mediated F-GSL uptake is detected via a rapid and sensitive assay only requiring simple fluorescence measurements on a standard plate reader. This is highly useful in investigations of glucosinolate transport function and provides a critical prerequisite for elucidating the relationship between structure and function through high-throughput screening of GTR mutant libraries. The F-GSL themselves may also be suitable for future studies on glucosinolate transport in vivo.
BAL Proteomic Signature of Lung Adenocarcinoma in IPF Patients and Its Transposition in Serum Samples for Less Invasive Diagnostic Procedures
Authors: Vantaggiato Lorenza , Shaba Enxhi , Cameli Paolo , Bergantini Laura , d’Alessandro Miriana , Carleo Alfonso , Montuori Giusy , Bini Luca , Bargagli Elena , Landi Claudia
Published: January 2023

Idiopathic pulmonary fibrosis (IPF) is a form of chronic and irreversible fibrosing interstitial pneumonia of unknown etiology. Although antifibrotic treatments have shown a reduction of lung function decline and a slow disease progression, IPF is characterize by a very high mortality. Emerging evidence suggests that IPF increases the risk of lung carcinogenesis. Both diseases show similarities in terms of risk factors, such as history of smoking, concomitant emphysema, and viral infections, besides sharing similar pathogenic pathways. Lung cancer (LC) diagnosis is often difficult in IPF patients because of the diffuse lung injuries and abnormalities due to the underlying fibrosis. This is reflected in the lack of optimal therapeutic strategies for patients with both diseases. For this purpose, we performed a proteomic study on bronchoalveolar lavage fluid (BALF) samples from IPF, LC associated with IPF (LC-IPF) patients, and healthy controls (CTRL). Molecular pathways involved in inflammation, immune response, lipid metabolism, and cell adhesion were found for the dysregulated proteins in LC-IPF, such as TTHY, APOA1, S10A9, RET4, GDIR1, and PROF1. The correlation test revealed a relationship between inflammation- and lipid metabolism-related proteins. PROF1 and S10A9, related to inflammation, were up-regulated in LC-IPF BAL and serum, while APOA1 and APOE linked to lipid metabolism, were highly abundant in IPF BAL and low abundant in IPF serum. Given the properties of cytokine/adipokine of the nicotinamide phosphoribosyltransferase, we also evaluated its serum abundance, highlighting its down-regulation in LC-IPF. Our retrospective analyses of BAL samples extrapolated some potential biomarkers of LC-IPF useful to improve the management of these contemporary pathologies. Their differential abundance in serum samples permits the measurement of these potential biomarkers with a less invasive procedure.
Top Selling (2026) Small Molecule Orphan Drugs: A Journey into Their Chemistry
Authors: Benedetto Tiz Davide , Bagnoli Luana , Rosati Ornelio , Marini Francesca , Sancineto Luca , Santi Claudio
Published: January 2023

This review describes, from a chemical point of view, the top “blockbuster” small molecule orphan drugs according to their forecasted sales in 2026. Orphan drugs are intended for the treatment, prevention, or diagnosis of a rare disease or condition. These molecules are mostly addressed to the treatment of rare forms of cancer. The respiratory and central nervous systems represent other common therapeutic subcategories. This work will show how the orphan drugs market has significantly grown and will account for a consistent part of prescriptions by 2026.
The KDET Motif in the Intracellular Domain of the Cell Adhesion Molecule L1 Interacts with Several Nuclear, Cytoplasmic, and Mitochondrial Proteins Essential for Neuronal Functions
Authors: Kleene Ralf , Loers Gabriele , Schachner Melitta
Published: January 2023

Abnormal functions of the cell adhesion molecule L1 are linked to several neural diseases. Proteolytic L1 fragments were reported to interact with nuclear and mitochondrial proteins to regulate events in the developing and the adult nervous system. Recently, we identified a 55 kDa L1 fragment (L1-55) that interacts with methyl CpG binding protein 2 (MeCP2) and heterochromatin protein 1 (HP1) via the KDET motif. We now show that L1-55 also interacts with histone H1.4 (HistH1e) via this motif. Moreover, we show that this motif binds to NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), splicing factor proline/glutamine-rich (SFPQ), the non-POU domain containing octamer-binding protein (NonO), paraspeckle component 1 (PSPC1), WD-repeat protein 5 (WDR5), heat shock cognate protein 71 kDa (Hsc70), and synaptotagmin 1 (SYT1). Furthermore, applications of HistH1e, NDUFV2, SFPQ, NonO, PSPC1, WDR5, Hsc70, or SYT1 siRNAs or a cell-penetrating KDET-carrying peptide decrease L1-dependent neurite outgrowth and the survival of cultured neurons. These findings indicate that L1’s KDET motif binds to an unexpectedly large number of molecules that are essential for nervous system-related functions, such as neurite outgrowth and neuronal survival. In summary, L1 interacts with cytoplasmic, nuclear and mitochondrial proteins to regulate development and, in adults, the formation, maintenance, and flexibility of neural functions.
F4-Neuroprostane Effects on Human Sperm
Authors: Moretti Elena , Signorini Cinzia , Noto Daria , Corsaro Roberta , Micheli Lucia , Durand Thierry , Oger Camille , Galano Jean Marie , Collodel Giulia
Published: January 2023

Swim-up selected human sperm were incubated with 7 ng F4-neuroprostanes (F4-NeuroPs) for 2 and 4 h. Sperm motility and membrane mitochondrial potential (MMP) were evaluated. The percentage of reacted acrosome was assessed by pisum sativum agglutinin (PSA). Chromatin integrity was detected using the acridine orange (AO) assay and localization of the ryanodine receptor was performed by immunofluorescence analysis. Sperm progressive motility (p = 0.02) and the percentage of sperm showing a strong MMP signal (p = 0.012) significantly increased after 2 h F4-NeuroP incubation compared to control samples. The AO assay did not show differences in the percentage of sperm with dsDNA between treated or control samples. Meanwhile, a significantly higher number of sperm with reacted acrosomes was highlighted by PSA localization after 4 h F4-NeuroP incubation. Finally, using an anti-ryanodine antibody, the immunofluorescence signal was differentially distributed at 2 and 4 h: a strong signal was evident in the midpiece and postacrosomal sheath (70% of sperm) at 2 h, whereas a dotted one appeared at 4 h (53% of sperm). A defined concentration of F4-NeuroPs in seminal fluid may induce sperm capacitation via channel ions present in sperm cells, representing an aid during in vitro sperm preparation that may increase the positive outcome of assisted fertilization.
The Synergistic Action of Metformin and Glycyrrhiza uralensis Fischer Extract Alleviates Metabolic Disorders in Mice with Diet-Induced Obesity
Authors: Hong Min-Kyeong , Han Youngji , Park Hae-Jin , Shin Mi-Rae , Roh Seong-Soo , Kwon Eun-Young
Published: January 2023

Metformin, an antidiabetic drug, and Glycyrrhiza uralensis Fischer (GU), an oriental medicinal herb, have been reported to exert anti-obesity effects. This study investigated the synergistic action of metformin and GU in improving diet-induced obesity. Mice were fed a normal diet, a high-fat diet (HFD), or HFD + 0.015% GU water extract for 8 weeks. The HFD and GU groups were then randomly divided into two groups and fed the following diets for the next 8 weeks: HFD with 50 mg/kg metformin (HFDM) and GU with 50 mg/kg metformin (GUM). GUM prevented hepatic steatosis and adiposity by suppressing expression of mRNAs and enzyme activities related to lipogenesis in the liver and upregulating the expression of adipocyte mRNAs associated with fatty acid oxidation and lipolysis, and as a result, improved dyslipidemia. Moreover, GUM improved glucose homeostasis by inducing glucose uptake in tissues and upregulating mRNA expressions associated with glycolysis in the liver and muscle through AMP-activated protein kinase activation. GUM also improved inflammation by increasing antioxidant activity in the liver and erythrocytes and decreasing inflammatory cytokine productions. Here, we demonstrate that GU and metformin exert synergistic action in the prevention of obesity and its complications.
Auditory or Audiovisual Stimulation Ameliorates Cognitive Impairment and Neuropathology in ApoE4 Knock-In Mice
Authors: Jung Harry , Lee Yeonkyeong , Lee Sang-Hwa , Sohn Jong-Hee
Published: January 2023

We hypothesized that auditory stimulation could reduce the progression of Alzheimer’s disease (AD), and that audiovisual stimulation could have additional effects through multisensory integration. We exposed 12 month old Apoetm1.1(APOE*4)Adiuj mice (a mouse model of sporadic AD) to auditory (A) or audiovisual stimulation (AV) at 40 Hz for 14 days in a soundproof chamber system (no stimulation, N). Behavioral tests were performed before and after each session, and their brain tissues were assessed for amyloid-beta expression and apoptotic cell death, after 14 days. Furthermore, brain levels of acetylcholine and apoptosis-related proteins were analyzed. In the Y-maze test, the percentage relative alternation was significantly higher in group A than in group N mice. Amyloid-beta and TUNEL positivity in the hippocampal CA3 region was significantly lower in group A and group AV mice than in group N mice (p < 0.05). Acetylcholine levels were significantly higher in group A and group AV mice than in group N mice (p < 0.05). Compared to group N mice, expression of the proapoptotic proteins Bax and caspase-3 was lower in group A, and expression of the antiapoptotic protein Bcl-2 was higher in group AV. In a mouse model of early-stage sporadic AD, auditory or audiovisual stimulation improved cognitive performance and neuropathology.
Cpt1c Downregulation Causes Plasma Membrane Remodelling and Anthracycline Resistance in Breast Cancer
Authors: Muley Helena , Valencia Karmele , Casas Josefina , Moreno Bea , Botella Luis , Lecanda Fernando , Fadó Rut , Casals Núria
Published: January 2023

Breast cancer (BC) is the most common malignancy in women worldwide. While the main systemic treatment option is anthracycline-containing chemotherapy, chemoresistance continues to be an obstacle to patient survival. Carnitine palmitoyltransferase 1C (CPT1C) has been described as a poor-prognosis marker for several tumour types, as it favours tumour growth and hinders cells from entering senescence. At the molecular level, CPT1C has been associated with lipid metabolism regulation and important lipidome changes. Since plasma membrane (PM) rigidity has been associated with reduced drug uptake, we explored whether CPT1C expression could be involved in PM remodelling and drug chemoresistance. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) lipid analysis of PM-enriched fractions of MDA-MB-231 BC cells showed that CPT1C silencing increased PM phospholipid saturation, suggesting a rise in PM rigidity. Moreover, CPT1C silencing increased cell survival against doxorubicin (DOX) treatment in different BC cells due to reduced drug uptake. These findings, further complemented by ROC plotter analysis correlating lower CPT1C expression with a lower pathological complete response to anthracyclines in patients with more aggressive types of BC, suggest CPT1C as a novel predictive biomarker for BC chemotherapy.
Biomaterial Inks from Peptide-Functionalized Silk Fibers for 3D Printing of Futuristic Wound-Healing and Sensing Materials
Authors: Ceccarini Maria Rachele , Palazzi Valentina , Salvati Raffaele , Chiesa Irene , De Maria Carmelo , Bonafoni Stefania , Mezzanotte Paolo , Codini Michela , Pacini Lorenzo , Errante Fosca , Rovero Paolo , Morabito Antonino , Beccari Tommaso , Roselli Luca , Valentini Luca
Published: January 2023

This study illustrates the sensing and wound healing properties of silk fibroin in combination with peptide patterns, with an emphasis on the printability of multilayered grids, and envisions possible applications of these next-generation silk-based materials. Functionalized silk fibers covalently linked to an arginine–glycine–aspartic acid (RGD) peptide create a platform for preparing a biomaterial ink for 3D printing of grid-like piezoresistors with wound-healing and sensing properties. The culture medium obtained from 3D-printed silk fibroin enriched with RGD peptide improves cell adhesion, accelerating skin repair. Specifically, RGD peptide-modified silk fibroin demonstrated biocompatibility, enhanced cell adhesion, and higher wound closure rates at lower concentration than the neat peptide. It was also shown that the printing of peptide-modified silk fibroin produces a piezoresistive transducer that is the active component of a sensor based on a Schottky diode harmonic transponder encoding information about pressure. We discovered that such biomaterial ink printed in a multilayered grid can be used as a humidity sensor. Furthermore, humidity activates a transition between low and high conductivity states in this medium that is retained unless a negative voltage is applied, paving the way for utilization in non-volatile organic memory devices. Globally, these results pave the way for promising applications, such as monitoring parameters such as human wound care and being integrated in bio-implantable processors.
Different Approaches to Study Molecular Blueprint and Biological Behavior of Brain Tumors: Editorial to the Special Issue “Advances in Molecular Genetics of Brain Tumors”
Authors: Pećina-Šlaus Nives , Jovčevska Ivana
Published: January 2023

Cancer remains one of the leading causes of mortality worldwide [...]
Ruthenium Complex HB324 Induces Apoptosis via Mitochondrial Pathway with an Upregulation of Harakiri and Overcomes Cisplatin Resistance in Neuroblastoma Cells In Vitro
Authors: Wilke Nicola L. , Burmeister Hilke , Frias Corazon , Ott Ingo , Prokop Aram
Published: January 2023

Ruthenium(II) complexes with N-heterocyclic carbene (NHC) ligands have recently attracted attention as novel chemotherapeutic agents. The complex HB324 was intensively studied as an apoptosis-inducing compound in resistant cell lines. HB324 induced apoptosis via mitochondrial pathways. Of particular interest is the upregulation of the Harakiri resistance protein, which inhibits the anti-apoptotic and death repressor proteins Bcl-2 (B-cell lymphoma 2) and BCL-xL (B-cell lymphoma-extra large). Moreover, HB324 showed synergistic activity with various established anticancer drugs and overcame resistance in several cell lines, such as neuroblastoma cells. In conclusion, HB324 showed promising potential as a novel anticancer agent in vitro, suggesting further investigations on this and other preclinical ruthenium drug candidates.
Small Molecule Inhibitors for Unc-51-like Autophagy-Activating Kinase Targeting Autophagy in Cancer
Authors: Karmacharya Ujjwala , Jung Jong-Wha
Published: January 2023

Autophagy is a cellular process that removes damaged components of cells and recycles them as biochemical building blocks. Autophagy can also be induced to protect cells in response to intra- and extracellular stresses, including damage to cellular components, nutrient deprivation, hypoxia, and pathogenic invasion. Dysregulation of autophagy has been attributed to various diseases. In particular, autophagy protects cancer cells by supporting tumor cell survival and the development of drug resistance. Understanding the pathophysiological mechanisms of autophagy in cancer has stimulated the research on discovery and development of specific inhibitors targeting various stages of autophagy. In recent years, Unc-51-like autophagy-activating kinase (ULK) inhibitors have become an attractive strategy to treat cancer. This review summarizes recent discoveries and developments in small-molecule ULK inhibitors and their potential as anticancer agents. We focused on structural features, interactions with binding sites, and biological effects of these inhibitors. Overall, this review will provide guidance for using ULK inhibitors as chemical probes for autophagy in various cancers and developing improved ULK inhibitors that would enhance therapeutic benefits in the clinic.
Using Species Distribution Models (SDMs) to Estimate the Suitability of European Mediterranean Non-Native Area for the Establishment of Toumeyella Parvicornis (Hemiptera: Coccidae)
Authors: Di Sora Nicolò , Mannu Roberto , Rossini Luca , Contarini Mario , Gallego Diego , Speranza Stefano
Published: January 2023

The pine tortoise scale, Toumeyella parvicornis, is an insect native to the Nearctic region that is able to infest several Pinus species. It can cause weakening, defoliation and, at high infestation levels, tree death. After its first report in Italy in 2015, the pest spread rapidly over the surrounding areas and was reported in France in 2021. Due to the threat that this pest poses to pine trees, the suitability of European Mediterranean basin areas for T. parvicornis at different spatial scales was estimated by constructing species distribution models (SDMs) using bioclimatic variables. Our results showed that several coastal areas of the Mediterranean basin area could be suitable for T. parvicornis. Based on performance assessment, all the SDMs tested provided a good representation of the suitability of European Mediterranean non-native area for T. parvicornis at different spatial scales. In particular, most of the areas with a medium or high level of suitability corresponded to the geographical range of distribution of different Pinus spp. in Europe. Predicting the suitability of European Mediterranean areas for T. parvicornis provides a fundamental tool for early detection and management of the spread of this pest in Europe.
Insulin-like Peptides of the Western Flower Thrips Frankliniella occidentalis and Their Mediation of Immature Development
Authors: Kim Chul-Young , Kim Yong-Gyun
Published: January 2023

Insulin-like peptides (ILPs) mediate various physiological processes in insects. Specifically, ILP expression is required for immature development in different insects. The western flower thrips, Frankliniella occidentalis, is polyphagous, but its occurrence and population density vary among different hosts. This study assesses the developmental variations in the thrips through quantitative analysis of their ILP expressions. Two types of ILPs (Fo-ILP1 and Fo-ILP2) were identified from the genome of F. occidentalis, and both ILPs were predicted to have the characteristics of signal peptides and B-C-A chains linked by cysteines. A phylogenetic analysis indicates that these two ILPs in the thrips are clustered with the ILP1 of Drosophila melanogaster, suggesting their physiological roles in growth. In addition, the two ILP genes were relatively highly expressed at all feeding stages, but their expression was reduced during the nonfeeding prepupal and pupal stages. Furthermore, RNA interference of each ILP expression led to significant developmental retardation. In validating the ILP expression in the thrips’ development, five different varieties of host hot peppers were assessed in a choice test, along with the immature development of F. occidentalis. The expression levels of the two ILP genes were highly correlated with variations in the immature developmental rates of different hot pepper varieties. These suggest that Fo-ILP1 and Fo-ILP2 mediate the immature development of F. occidentalis by sensing different nutritional values of hot peppers. This study is the first report on ILPs in thysanopteran insects.
A Cross-Line Structured Light Scanning System Based on a Measuring Arm
Authors: Tai Dayong , Wu Zhixiong , Yang Ying , Lu Cunwei
Published: January 2023

The measurement system proposed in this paper, using a measuring arm and line structured light, has a wide range of applications. To improve the scanning efficiency, the system outlined in this paper uses two single-line structured lights to form crosshair structured light, which we combine with a measuring arm to form a comprehensive scanning measurement system. The calibration method of Zhengyou Zhang and a calibration board are used to complete parameter calibration of the sensors and cameras, as well as hand–eye calibration of the measuring arm. For complex curved-surface objects, this system extracts the cross-line structured light optical center location, which suffers from ambiguity. Therefore, we introduce the use of periodic control of the two line structured light sources in order to resolve the light extraction polysemy. Our experimental results indicate that the proposed system can effectively satisfy the function of crosshair structured light scanning of large, complex surfaces.
Transcatheter Aortic Valve Replacement for Bicuspid vs. Tricuspid Aortic Stenosis among Patients at Low Surgical Risk in China: From the Multicenter National NTCVR Database
Authors: Hong Nanchao , Pan Wenzhi , Liu Xianbao , Zhou Daxin , Wang Jianan , Ge Junbo
Published: January 2023

Background: This study aims to compare the outcomes of transcatheter aortic valve replacement (TAVR) with self-expandable valves for bicuspid aortic valve (BAV) vs. tricuspid aortic valve (TAV) stenosis patients who are at low surgical risk. Methods: Participants were enrolled from 36 centers in China between January 2017 and December 2021. The primary endpoint event was all-cause mortality and all stroke at 30 days. Results: Among 389 patients at low surgical risk that underwent TAVR, 229 patients were BAV stenosis (mean age, 72.9 years; 65.1% men). There was no significant difference in the rate of all-cause death between two populations at 30 days. However, the rate of all stroke was significantly higher in the BAV group at 30 days (3.3% vs. 0%; odds ratio (OR), 0.97 (95% confidence interval (CI), 0.94 to 0.99); p = 0.044). By multivariate logistic regression analysis, trans-carotid access was associated with a higher all stroke rate at 30 days (OR, 29.20 (95% CI, 3.97 to 215.1); p = 0.001). Conclusions: In this national registry-based study, patients treated for BAV vs. TAV stenosis had no significant difference in all-cause mortality at 30 days, but trans-carotid access was associated with a higher all stroke rate after TAVR at 30 days.
Normonatremic Transient Renal Salt Wasting (TRSW) Is Not Rare in a Department of Internal Medicine
Authors: Musch Wim , Decaux Guy
Published: January 2023

Background: We previously reported that for around 5% of patients hospitalized with hyponatremia, it was related to what is called “transient renal salt wasting” (TRSW). In the present study we ask whether TRSW can also be observed in patients without hyponatremia. Methods: In this observational retrospective study we analyze the urine solute excretion of 200 consecutive normonatremic patients with normal kidney function and admitted in our department over one year. Patients were selected for analyses of FE.K, UCa/UCr and FE.PO4 if FE.Na was higher than 2% (N < 1.6%) before any treatment, and only if they were not taking diuretics. Result: Eleven normonatremic patients presented with transient high FE.Na > 2% on admission (2.9 ± 0.6% with a high FE.K of 28 ± 6.4%; a high UCa/UCr of 0.37 ± 0.13 and a high FE.PO4 of 23.2 ± 9.6%). All of these patients were elderly. Seven were female and four were male. Neurological disorders were observed in six patients (three strokes, one transient ischemic attack, one syncope and one epileptic attack). Heart problems were observed in three patients (all angina pectoris, two of which also had HBP). One patient presented with rectal bleeding with HBP, and another presented COPD with a pneumothorax. One patient with angina pectoris showed a transient relapse after four days of hospitalization (FE.Na 3.6%). The urine electrolyte excretion in these patients are similar to those observed after furosemide intake. Conclusion: Normonatremic TRSW is not a rare observation, particularly in patients with neurological or cardiac problems.
Using Circulating Tumor DNA as a Novel Biomarker to Screen and Diagnose Colorectal Cancer: A Meta-Analysis
Authors: Min Liang , Chen Jinghua , Yu Meihong , Liu Deliang
Published: January 2023

(1) Background: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for many kinds of tumors. However, whether ctDNA could be an accurate diagnostic biomarker in colorectal cancer (CRC) remains to be clarified. The aim of this study was to evaluate the diagnostic accuracy of ctDNA in CRC. (2) Methods: PubMed, Web of Science, and Cochrane databases were searched to identify studies reporting the use of ctDNA to screen and diagnose CRC, and all relevant studies published until October 2022 were enrolled for our analysis. These studies were divided into three primer subgroups: the subgroup of quantitative or qualitative analysis of ctDNA and the subgroup of septin9 (SEPT9) methylation assay. (3) Results: A total of 79 qualified articles with 25,240 subjects were incorporated into our meta-analysis. For quantitative studies, the combined sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR) were 0.723 (95% CI: 0.623–0.803), 0.920 (95% CI: 0.827–0.966), and 23.305 (95% CI: 9.378–57.906), respectively, yielding an AUC of 0.860. The corresponding values for qualitative studies were 0.610 (95% CI: 0.566–0.651), 0.891 (95% CI: 0.878–0.909), 12.569 (95% CI: 9.969–15.848), and 0.823, respectively. Detection of SEPT9 methylation depicted an AUC of 0.879, with an SEN of 0.679 (95% CI: 0.622–0.732), an SPE of 0.903 (95% CI: 0.878–0.923), and a DOR of 20.121 (95% CI:14.404–28.106), respectively. (4) Conclusion: Blood-based ctDNA assay would be a potential novel biomarker for CRC screening and diagnosis. Specifically, quantitative analysis of ctDNA or qualitative analysis of SEPT9 methylation exhibited satisfying diagnostic efficiency. Larger sample studies are needed to further confirm our conclusions and to make the ctDNA approach more sensitive and specific.
Understanding the Association between Red Blood Cell Transfusion Utilization and Humanistic and Economic Burden in Patients with β-Thalassemia from the Patients’ Perspective
Authors: Knoth Russell L. , Gupta Shaloo , Perkowski Kacper , Costantino Halley , Inyart Brian , Ashka Lauren , Clapp Kelly
Published: January 2023

We assessed the humanistic and economic burden of chronic red blood cell (RBC) transfusions on patients with β-thalassemia. This cross-sectional, US-based study included adults (≥18 years) who self-reported a β-thalassemia physician diagnosis and had received ≥1 RBC transfusion in the past 6 months. The outcomes included the Functional Assessment of Cancer Therapy-Anemia (FACT-An), Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and ad hoc questions about treatment experience, side effects, direct/indirect costs, and psychological burden. Overall, 100 patients completed the survey, of whom 70% experienced “moderate” to “extremely high” burden due to RBC transfusions, 81% reported iron overload, 42% reported compromised social lives. The mean FACT-An score was 132 (higher score indicates better outcomes; 0–188). Mean scores were 33/52 for fatigue and 20/28 for anemia symptoms in the previous 7 days. Health-related quality of life (HRQoL) temporarily improved after RBC transfusion, although patients continued to experience mild-to-severe depression and anxiety, substantial direct costs, compromised employment, and suboptimal quality of life. Over 6 months, patients dedicated a mean of 173 h to transfusion requirements and incurred out-of-pocket costs of USD 2239 for transfusions and USD 896 for additional care costs. These findings highlight the need for new treatment options to improve patient HRQoL and economic outcomes.
Evaluation of Some Composite Paint Coatings’ Appearance Quality Using Fractal Dimension
Authors: Loganina Valentina , Fediuk Roman , Lesovik Valery , Amran Mugahed , Qader Diyar N. , Litvinets Olga , Okhotkina Viktoria , Rashid Raizal S. M. , Lomov Maksim , Moskovaya Irina
Published: January 2023

Composite materials are characterized by multiple layers, which leads to a complexity in the design in order to ensure the effective operation of the constituent elements. This article provides information on the use of fractal dimension in assessing the quality of the appearance of paint coatings. The scientific originality of the article lies in the establishment of a correlation between the surface roughness of coatings, the quality grade of their appearance and fractal dimension. As a result, a model of the length of the coating surface profile, with the fractal dimension D, was proposed. The practical significance lies in the proposal to evaluate the quality of the surface of paint and varnish coatings in terms of fractal dimension. An increase in the surface roughness of the coating, a decrease in the appearance quality grade and an increase in the fractal dimension have been observed. Numerical values of the index of the fractal dimension of the coating surface profile, which depended on the porosity of the substrate, have been obtained. The influence of the filling of the paint composition on the quality of the appearance of the coatings has been estimated. It has been revealed that there was an increase in the surface tension of the paint composition, a decrease in the quality of the appearance of the resulting coating and an increase in the roughness and fractal dimension of the coating surface. The influence of the method of applying the paint composition and the preparation of the base surface on the quality of the appearance of the coatings are considered. The results obtained can be applied in various types of production to improve the quality of paint coatings.
The Influence of Thermomechanical Compaction on the Marginal Adaptation of 4 Different Hydraulic Sealers: A Comparative Ex Vivo Study
Authors: Zanza Alessio , Reda Rodolfo , Vannettelli Elisa , Donfrancesco Orlando , Relucenti Michela , Bhandi Shilpa , Patil Shankargouda , Mehta Deepak , Krithikadatta Jogikalmat , Testarelli Luca
Published: January 2023

Since there are no data in the literature regarding the comparison of the marginal adaptation of hydraulic sealers when used with a single-cone technique or through thermomechanical compaction, this study aimed to evaluate the behavior of four different endodontic sealers used with the two above-mentioned obturation techniques by evaluating the marginal gap existing between the obturation materials and the dentinal walls through scanning electron microscopy. Given this objective, a total of 104 single-rooted, straight canal teeth were selected and divided into four subgroups according to the selected endodontic sealer ((AH) Plus Bioceramic Sealer (AHP), EndoSequence BC Sealer HiFlow (ES), C-Root SP (CR), and GuttaFlow Bioseal (GF)). Each tooth was decoronated and instrumented with the HyFlex EDM/CM systematics up to 30.04. After irrigation procedures, the teeth of each subgroup were divided into two groups and obturated according to two different obturation techniques: the single-cone technique (SC) and the thermomechanical compaction technique (TC). After the required sealer setting time, each tooth was sectioned in three parts at 3, 6, and 9 mm from the apex, and each section was observed with a scanning electron microscope. The marginal gap of each sample was measured using G* Power Software v3.1, and the statistical analysis was performed using the Kruskal–Wallis test, followed by a post hoc Dunn’s test. Results showed that there were not any statistically significant differences in terms of the marginal gap between the two different above-mentioned obturation techniques for each sealer, except for the middle third of root canals, where a statistically significant difference was found for AHP, ES, and GF sealers. In conclusion, the thermomechanical compaction of hydraulic sealers and gutta-percha guarantees better sealing than the single-cone technique when the root canal shape is not rounded.
Increased UHMWPE Particle-Induced Osteolysis in Fetuin-A-Deficient Mice
Authors: Polan Christina , Brenner Christina , Herten Monika , Hilken Gero , Grabellus Florian , Meyer Heinz-Lothar , Burggraf Manuel , Dudda Marcel , Jahnen-Dechent Willi , Wedemeyer Christian , Kauther Max Daniel
Published: January 2023

Particle-induced osteolysis is a major cause of aseptic prosthetic loosening. Implant wear particles stimulate tissue macrophages inducing an aseptic inflammatory reaction, which ultimately results in bone loss. Fetuin-A is a key regulator of calcified matrix metabolism and an acute phase protein. We studied the influence of fetuin-A on particle-induced osteolysis in an established mouse model using fetuin-A-deficient mice. Ten fetuin-A-deficient (Ahsg−/−) mice and ten wild-type animals (Ahsg+/+) were assigned to test group receiving ultra-high molecular weight polyethylene (UHMWPE) particle implantation or to control group (sham surgery). After 14 days, bone metabolism parameters RANKL, osteoprotegerin (OPG), osteocalcin (OC), alkaline phosphatase (ALP), calcium, phosphate, and desoxypyridinoline (DPD) were examined. Bone volume was determined by microcomputed tomography (μCT); osteolytic regions and osteoclasts were histomorphometrically analyzed. After particle treatment, bone resorption was significantly increased in Ahsg−/− mice compared with corresponding Ahsg+/+ wild-type mice (p = 0.007). Eroded surface areas in Ahsg−/− mice were significantly increased (p = 0.002) compared with Ahsg+/+ mice, as well as the number of osteoclasts compared with control (p = 0.039). Fetuin-A deficiency revealed increased OPG (p = 0.002), and decreased levels of DPD (p = 0.038), OC (p = 0.036), ALP (p < 0.001), and Ca (p = 0.001) compared with wild-type animals. Under osteolytic conditions in Ahsg−/− mice, OPG was increased (p = 0.013), ALP (p = 0.015) and DPD (p = 0.012) were decreased compared with the Ahsg+/+ group. Osteolytic conditions lead to greater bone loss in fetuin-A-deficient mice compared with wild-type mice. Reduced fetuin-A serum levels may be a risk factor for particle-induced osteolysis while the protective effect of fetuin-A might be a future pathway for prophylaxis and treatment.
Sequential Release of Panax Notoginseng Saponins and Osteopractic Total Flavone from Poly (L-Lactic Acid) Scaffold for Treating Glucocorticoid-Associated Osteonecrosis of Femoral Head
Authors: Feng Guiyu , Zhang Pingxin , Huang Jian , Yu Yao , Yang Fenghe , Zhao Xueqian , Wang Wei , Li Dongyang , Sun Song , Niu Xufeng , Chai Limin , Li Jinyu
Published: January 2023

Glucocorticoids inhibit angiogenesis in the femoral head, which fails to nourish the bone tissue and leads to osteonecrosis. Restoring angiogenesis is not only essential for vessel formation, but also crucial for osteogenesis. Poly (L-lactic acid) (PLLA) is commonly used in the bone tissue engineering field. Panax notoginseng saponins (PNS) and osteopractic total flavone (OTF) promote angiogenesis and osteogenesis, respectively. We designed a sequentially releasing PLLA scaffold including PLLA loaded with OTF (inner layer) and PLLA loaded with PNS (outer layer). We assessed the osteogenic effect of angiogenesis in this scaffold by comparing it with the one-layered scaffold (PLLA embedded with OTF and PNS) in vivo. Results from the micro-CT showed that the data of bone mineral density (BMD), bone volume (BV), and percent bone volume (BV/TV) in the PO-PP group were significantly higher than those in the POP group (p < 0.01). Histological analyses show that the PO-PP scaffold exhibits better angiogenic and osteogenic effects compared with the one-layered scaffold. These might result from the different structures between them, where the sequential release of a bi-layer scaffold achieves the osteogenic effect of vascularization by initially releasing PNS in the outer layer. We further explored the possible mechanism by an immunohistochemistry analysis and an immunofluorescence assay. The results showed that the protein expressions of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1(CD31) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.01); the protein expressions of osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.05). Upregulating the expressions of angiogenic and osteogenic proteins might be the possible mechanism.
An Objective Metallographic Analysis Approach Based on Advanced Image Processing Techniques
Authors: Sarrionandia Xabier , Nieves Javier , Bravo Beñat , Pastor-López Iker , Bringas Pablo G.
Published: January 2023

Metallographic analyses of nodular iron casting methods are based on visual comparisons according to measuring standards. Specifically, the microstructure is analyzed in a subjective manner by comparing the extracted image from the microscope to pre-defined image templates. The achieved classifications can be confused, due to the fact that the features extracted by a human being could be interpreted differently depending on many variables, such as the conditions of the observer. In particular, this kind of problem represents an uncertainty when classifying metallic properties, which can influence the integrity of castings that play critical roles in safety devices or structures. Although there are existing solutions working with extracted images and applying some computer vision techniques to manage the measurements of the microstructure, those results are not too accurate. In fact, they are not able to characterize all specific features of the image and, they cannot be adapted to several characterization methods depending on the specific regulation or customer. Hence, in order to solve this problem, we propose a framework to improve and automatize the evaluations by combining classical machine vision techniques for feature extraction and deep learning technologies, to objectively make classifications. To adapt to the real analysis environments, all included inputs in our models were gathered directly from the historical repository of metallurgy from the Azterlan Research Centre (labeled using expert knowledge from engineers). The proposed approach concludes that these techniques (a classification under a pipeline of deep neural networks and the quality classification using an ANN classifier) are viable to carry out the extraction and classification of metallographic features with great accuracy and time, and it is possible to deploy software with the models to work on real-time situations. Moreover, this method provides a direct way to classify the metallurgical quality of the molten metal, allowing us to determine the possible behaviors of the final produced parts.
Probability Distribution Analysis of Hydrodynamic Wave Pressure on Large-Scale Thin-Walled Structure for Sea-Crossing Bridge
Authors: Pan Junzhi , Ti Zilong , You Hengrui
Published: January 2023

Evaluation of hydrodynamic wave pressure on large-scale structure is an important task in the wave load design of thin-walled components used in sea-crossing bridge. This study focuses on the probability distribution of hydrodynamic wave pressure on a large-scale thin-walled structure using on-site measurement data. An in-situ observation project is conducted to collect the wave elevation and the wave pressure on a rectangle cofferdam during a tropical cyclone event. With the measured data, the wave conditions and the fluctuating wave pressure are extracted, and the corresponding statistical characteristics such as the cumulative density function (CDF) are derived. In addition, a time domain boundary element model (TDBEM) is introduced to provide the statistical comparison. Several wave conditions derived by the statistical wave indicators during the cyclone event are fed to the numerical model for pressure investigation. Based on the statistical indicators and the modeling results, the comparison of wave pressure spatial distribution between TDBEM and the on-site measurement is presented. The pressure probability distribution is presented to further reveal the differences on the statistical characteristics. The resultant bias mainly occurs in the low-exceeding-probability range on the up-wave side and the high-exceeding-probability range on the down-wave side.