bluuebunny/crossref_metadata_2025 huggingface dataset:
Old and New Facts and Speculations on the Role of the B Cell Receptor in the Origin of Chronic Lymphocytic Leukemia
Authors: Bagnara Davide , Mazzarello Andrea Nicola , Ghiotto Fabio , Colombo Monica , Cutrona Giovanna , Fais Franco , Ferrarini Manlio
Published: November 2022

The engagement of the B cell receptor (BcR) on the surface of leukemic cells represents a key event in chronic lymphocytic leukemia (CLL) since it can lead to the maintenance and expansion of the neoplastic clone. This notion was initially suggested by observations of the CLL BcR repertoire and of correlations existing between certain BcR features and the clinical outcomes of single patients. Based on these observations, tyrosine kinase inhibitors (TKIs), which block BcR signaling, have been introduced in therapy with the aim of inhibiting CLL cell clonal expansion and of controlling the disease. Indeed, the impressive results obtained with these compounds provided further proof of the role of BcR in CLL. In this article, the key steps that led to the determination of the role of BcR are reviewed, including the features of the CLL cell repertoire and the fine mechanisms causing BcR engagement and cell signaling. Furthermore, we discuss the biological effects of the engagement, which can lead to cell survival/proliferation or apoptosis depending on certain intrinsic cell characteristics and on signals that the micro-environment can deliver to the leukemic cells. In addition, consideration is given to alternative mechanisms promoting cell proliferation in the absence of BcR signaling, which can explain in part the incomplete effectiveness of TKI therapies. The role of the BcR in determining clonal evolution and disease progression is also described. Finally, we discuss possible models to explain the selection of a special BcR set during leukemogenesis. The BcR may deliver activation signals to the cells, which lead to their uncontrolled growth, with the possible collaboration of other still-undefined events which are capable of deregulating the normal physiological response of B cells to BcR-delivered stimuli.
Transient Receptor Potential (TRP) Channels in Tumor Vascularization
Authors: Perna Angelica , Sellitto Carmine , Komici Klara , Hay Eleonora , Rocca Aldo , De Blasiis Paolo , Lucariello Angela , Moccia Francesco , Guerra Germano
Published: November 2022

Tumor diseases are unfortunately quick spreading, even though numerous studies are under way to improve early diagnosis and targeted treatments that take into account both the different characteristics associated with the various tumor types and the conditions of individual patients. In recent years, studies have focused on the role of ion channels in tumor development, as these proteins are involved in several cellular processes relevant to neoplastic transformation. Among all ion channels, many studies have focused on the superfamily of Transient Receptor Potential (TRP) channels, which are non-selective cation channels mediating extracellular Ca2+ influx. In this review, we examined the role of different endothelial TRP channel isoforms in tumor vessel formation, a process that is essential in tumor growth and metastasis.
Learning from TCR Signaling and Immunological Synapse Assembly to Build New Chimeric Antigen Receptors (CARs)
Authors: Cassioli Chiara , Patrussi Laura , Valitutti Salvatore , Baldari Cosima T.
Published: November 2022

Chimeric antigen receptor (CAR) T cell immunotherapy is a revolutionary pillar in cancer treatment. Clinical experience has shown remarkable successes in the treatment of certain hematological malignancies but only limited efficacy against B cell chronic lymphocytic leukemia (CLL) and other cancer types, especially solid tumors. A wide range of engineering strategies have been employed to overcome the limitations of CAR T cell therapy. However, it has become increasingly clear that CARs have unique, unexpected features; hence, a deep understanding of how CARs signal and trigger the formation of a non-conventional immunological synapse (IS), the signaling platform required for T cell activation and execution of effector functions, would lead a shift from empirical testing to the rational design of new CAR constructs. Here, we review current knowledge of CARs, focusing on their structure, signaling and role in CAR T cell IS assembly. We, moreover, discuss the molecular features accounting for poor responses in CLL patients treated with anti-CD19 CAR T cells and propose CLL as a paradigm for diseases connected to IS dysfunctions that could significantly benefit from the development of novel CARs to generate a productive anti-tumor response.
Biofilms and Benign Colonic Diseases
Authors: Songtanin Busara , Peterson Christopher J. , Molehin Adebayo J. , Nugent Kenneth
Published: November 2022

The colon has a very large surface area that is covered by a dense mucus layer. The biomass in the colon includes 500–1000 bacterial species at concentrations of ~1012 colony-forming units per gram of feces. The intestinal epithelial cells and the commensal bacteria in the colon have a symbiotic relationship that results in nutritional support for the epithelial cells by the bacteria and maintenance of the optimal commensal bacterial population by colonic host defenses. Bacteria can form biofilms in the colon, but the exact frequency is uncertain because routine methods to undertake colonoscopy (i.e., bowel preparation) may dislodge these biofilms. Bacteria in biofilms represent a complex community that includes living and dead bacteria and an extracellular matrix composed of polysaccharides, proteins, DNA, and exogenous debris in the colon. The formation of biofilms occurs in benign colonic diseases, such as inflammatory bowel disease and irritable bowel syndrome. The development of a biofilm might serve as a marker for ongoing colonic inflammation. Alternatively, the development of biofilms could contribute to the pathogenesis of these disorders by providing sanctuaries for pathogenic bacteria and reducing the commensal bacterial population. Therapeutic approaches to patients with benign colonic diseases could include the elimination of biofilms and restoration of normal commensal bacteria populations. However, these studies will be extremely difficult unless investigators can develop noninvasive methods for measuring and identifying biofilms. These methods that might include the measurement of quorum sensing molecules, measurement of bile acids, and identification of bacteria uniquely associated with biofilms in the colon.
De Novo Hybrid Assembly of the Salvia miltiorrhiza Mitochondrial Genome Provides the First Evidence of the Multi-Chromosomal Mitochondrial DNA Structure of Salvia Species
Authors: Yang Heyu , Chen Haimei , Ni Yang , Li Jingling , Cai Yisha , Ma Binxin , Yu Jing , Wang Jiehua , Liu Chang
Published: November 2022

Salvia miltiorrhiza has been an economically important medicinal plant. Previously, an S. miltiorrhiza mitochondrial genome (mitogenome) assembled from Illumina short reads, appearing to be a single circular molecule, has been published. Based on the recent reports on the plant mitogenome structure, we suspected that this conformation does not accurately represent the complexity of the S. miltiorrhiza mitogenome. In the current study, we assembled the mitogenome of S. miltiorrhiza using the PacBio and Illumina sequencing technologies. The primary structure of the mitogenome contained two mitochondrial chromosomes (MC1 and MC2), which corresponded to two major conformations, namely, Mac1 and Mac2, respectively. Using two approaches, including (1) long reads mapping and (2) polymerase chain reaction amplification followed by Sanger sequencing, we observed nine repeats that can mediate recombination. We predicted 55 genes, including 33 mitochondrial protein-coding genes (PCGs), 3 rRNA genes, and 19 tRNA genes. Repeat analysis identified 112 microsatellite repeats and 3 long-tandem repeats. Phylogenetic analysis using the 26 shared PCGs resulted in a tree that was congruent with the phylogeny of Lamiales species in the APG IV system. The analysis of mitochondrial plastid DNA (MTPT) identified 16 MTPTs in the mitogenome. Moreover, the analysis of nucleotide substitution rates in Lamiales showed that the genes atp4, ccmB, ccmFc, and mttB might have been positively selected. The results lay the foundation for future studies on the evolution of the Salvia mitogenome and the molecular breeding of S. miltiorrhiza.
Current Knowledge on Bee Innate Immunity Based on Genomics and Transcriptomics
Authors: Zhao Xiaomeng , Liu Yanjie
Published: November 2022

As important pollinators, bees play a critical role in maintaining the balance of the ecosystem and improving the yield and quality of crops. However, in recent years, the bee population has significantly declined due to various pathogens and environmental stressors including viruses, bacteria, parasites, and increased pesticide application. The above threats trigger or suppress the innate immunity of bees, their only immune defense system, which is essential to maintaining individual health and that of the colony. In addition, bees can be divided into solitary and eusocial bees based on their life traits, and eusocial bees possess special social immunities, such as grooming behavior, which cooperate with innate immunity to maintain the health of the colony. The omics approach gives us an opportunity to recognize the distinctive innate immunity of bees. In this regard, we summarize innate bee immunity from a genomic and transcriptomic perspective. The genetic characteristics of innate immunity were revealed by the multiple genomes of bees with different kinds of sociality, including honeybees, bumblebees, wasps, leaf-cutter bees, and so on. Further substantial transcriptomic data of different tissues from diverse bees directly present the activation or suppression of immune genes under the infestation of pathogens or toxicity of pesticides.
Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study
Authors: Preet Gagan , Oluwabusola Emmanuel T. , Milne Bruce Forbes , Ebel Rainer , Jaspars Marcel
Published: November 2022

Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the Orthopoxvirus genus of the Poxviridae family. Monkeypox is a zoonotic disease where the primary significant hosts are rodents and non-human primates. There is an increasing global incidence with a 2022 outbreak that has spread to Europe in the middle of the COVID-19 pandemic. The new outbreak has novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involving the use of tecovirimat. However, there has otherwise been limited research interest in monkeypox. Mitoxantrone (MXN), an anthracycline derivative, an FDA-approved therapeutic for treating cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against the vaccinia virus and monkeypox virus. In this study, virtual screening, molecular docking analysis, and pharmacophore ligand-based modelling were employed on anthracene structures (1-13) closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures (2), (7), (10) and (12) show a predicted high binding potential to suppress viral replication.
Synthesis of Glycolysis Inhibitor PFK15 and Its Synergistic Action with an Approved Multikinase Antiangiogenic Drug on Human Endothelial Cell Migration and Proliferation
Authors: Zlacká Jana , Murár Miroslav , Addová Gabriela , Moravčík Roman , Boháč Andrej , Zeman Michal
Published: November 2022

Activated endothelial, immune, and cancer cells prefer glycolysis to obtain energy for their proliferation and migration. Therefore, the blocking of glycolysis can be a promising strategy against cancer and autoimmune disease progression. Inactivation of the glycolytic enzyme PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase) suppresses glycolysis level and contributes to decreased proliferation and migration of cancer (tumorigenesis) and endothelial (angiogenesis) cells. Recently, several glycolysis inhibitors have been developed, among them (E)-1-(pyridin-4-yl)-3-(quinolin-2-yl)prop-2-en-1-one (PFK15) that is considered as one of the most promising. It is known that PFK15 decreases glucose uptake into the endothelial cells and efficiently blocks pathological angiogenesis. However, no study has described sufficiently PFK15 synthesis enabling its general availability. In this paper we provide all necessary details for PFK15 preparation and its advanced characterization. On the other hand, there are known tyrosine kinase inhibitors (e.g., sunitinib), that affect additional molecular targets and efficiently block angiogenesis. From a biological point of view, we have studied and proved the synergistic inhibitory effect by simultaneous administration of glycolysis inhibitor PFK15 and multikinase inhibitor sunitinib on the proliferation and migration of HUVEC. Our results suggest that suppressing the glycolytic activity of endothelial cells in combination with growth factor receptor blocking can be a promising antiangiogenic treatment.
Esophageal Squamous Cancer from 4NQO-Induced Mice Model: CNV Alterations
Authors: Liu Zhiwei , Su Ruibing , Ahsan Anil , Liu Chencai , Liao Xiaoqi , Tian Dongping , Su Min
Published: November 2022

Squamous esophageal carcinoma is a common pathological type of esophageal carcinoma around the world. The prognosis of esophageal carcinoma is usually poor and diagnosed at late stages. Recently, research suggested that genomic instability occurred in esophageal cells during the development of esophageal squamous cell carcinoma (ESCC). Identifying prognostic and specific genomic characteristics, especially at the early hyperplasia stage, is critical. Mice were given 4-nitroquinoline 1-oxide (4NQO) with drinking water to induce esophageal cancer. The immortalized human esophageal epithelial cell line (NE2) was also treated with 4NQO. We performed histologic analyses, immunofluorescence, and immunohistochemical staining to detect DNA damage at different time points. Whole-exome sequencing was accomplished on the esophagus tissues at different pathological stages to detect single-nucleotide variants and copy number variation (CNV) in the genome. Our findings indicate that all mice were tumor-forming, and a series of changes from simple hyperplasia (ESSH) to intraepithelial neoplasia (IEN) to esophageal squamous cell carcinoma (ESCC) was seen at different times. The expression of γ-H2AX increased from ESSH to ESCC. In addition, mutations of the Muc4 gene were detected throughout the pathological stages. Furthermore, CNV burden appeared in the esophageal tissues from the beginning of ESSH and accumulated more in cancer with the deepening of the lesions. This study demonstrates that mutations caused by the early appearance of DNA damage may appear in the early stage of malignant tissue before the emergence of atypia. The detection of CNV and mutations of the Muc4 gene may be used as an ultra-early screening indicator for esophageal cancer.
Radiosensitizing Effect of Trabectedin on Human Soft Tissue Sarcoma Cells
Authors: Loi Mauro , Salvatore Giulia , Aquilano Michele , Greto Daniela , Talamonti Cinzia , Salvestrini Viola , Melica Maria Elena , Valzano Marianna , Francolini Giulio , Sottili Mariangela , Santini Costanza , Becherini Carlotta , Campanacci Domenico Andrea , Mangoni Monica , Livi Lorenzo
Published: November 2022

Trabectedin is used for the treatment of advanced soft tissue sarcomas (STSs). In this study, we evaluated if trabectedin could enhance the efficacy of irradiation (IR) by increasing the intrinsic cell radiosensitivity and modulating tumor micro-environment in fibrosarcoma (HS 93.T), leiomyosarcoma (HS5.T), liposarcoma (SW872), and rhabdomyosarcoma (RD) cell lines. A significant reduction in cell surviving fraction (SF) following trabectedin + IR compared to IR alone was observed in liposarcoma and leiomyosarcoma (enhancement ratio at 50%, ER50: 1.45 and 2.35, respectively), whereas an additive effect was shown in rhabdomyosarcoma and fibrosarcoma. Invasive cells’ fraction significantly decreased following trabectedin ± IR compared to IR alone. Differences in cell cycle distribution were observed in leiomyosarcoma and rhabdomyosarcoma treated with trabectedin + IR. In all STS lines, trabectedin + IR resulted in a significantly higher number of γ-H2AX (histone H2AX) foci 30 min compared to the control, trabectedin, or IR alone. Expression of ATM, RAD50, Ang-2, VEGF, and PD-L1 was not significantly altered following trabectedin + IR. In conclusion, trabectedin radiosensitizes STS cells by affecting SF (particularly in leiomyosarcoma and liposarcoma), invasiveness, cell cycle distribution, and γ-H2AX foci formation. Conversely, no synergistic effect was observed on DNA damage repair, neoangiogenesis, and immune system.
Molecular Characterization of the Dual Effect of the GPER Agonist G-1 in Glioblastoma
Authors: Hirtz Alex , Bailly Yann , Rech Fabien , Pierson Julien , Dumond Hélène , Dubois-Pot-Schneider Hélène
Published: November 2022

Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite conventional treatment, consisting of a chirurgical resection followed by concomitant radio–chemotherapy, the 5-year survival rate is less than 5%. Few risk factors are clearly identified, but women are 1.4-fold less affected than men, suggesting that hormone and particularly estrogen signaling could have protective properties. Indeed, a high GPER1 (G-protein-coupled estrogen receptor) expression is associated with better survival, especially in women who produce a greater amount of estrogen. Therefore, we addressed the anti-tumor effect of the GPER agonist G-1 in vivo and characterized its molecular mechanism of action in vitro. First, the antiproliferative effect of G-1 was confirmed in a model of xenografted nude mice. A transcriptome analysis of GBM cells exposed to G-1 was performed, followed by functional analysis of the differentially expressed genes. Lipid and steroid synthesis pathways as well as cell division processes were both affected by G-1, depending on the dose and duration of the treatment. ANGPTL4, the first marker of G-1 exposure in GBM, was identified and validated in primary GBM cells and patient samples. These data strongly support the potential of G-1 as a promising chemotherapeutic compound for the treatment of GBM.
The Histamine H4 Receptor Participates in the Neuropathic Pain-Relieving Activity of the Histamine H3 Receptor Antagonist GSK189254
Authors: Borgonetti Vittoria , Galeotti Nicoletta
Published: November 2022

Growing evidence points to the histamine system as a promising target for the management of neuropathic pain. Preclinical studies reported the efficacy of H3R antagonists in reducing pain hypersensitivity in models of neuropathic pain through an increase of histamine release within the CNS. Recently, a promising efficacy of H4R agonists as anti-neuropathic agents has been postulated. Since H3R and H4R are both localized in neuronal areas devoted to pain processing, the aim of the study is to investigate the role of H4R in the mechanism of anti-hyperalgesic action of the H3R antagonist GSK189254 in the spared nerve injury (SNI) model in mice. Oral (6 mg/kg), intrathecal (6 µg/mouse), or intra locus coeruleus (LC) (10 µg/µL) administration of GSK189254 reversed mechanical and thermal allodynia in the ipsilateral side of SNI mice. This effect was completely prevented by pretreatment with the H4R antagonist JNJ 10191584 (6 µg/mouse i.t.; (10 µg/µL intraLC). Furthermore, GSK189254 was devoid of any anti-hyperalgesic effect in H4R deficient mice, compared with wild type mice. Conversely, pretreatment with JNJ 10191584 was not able to prevent the hypophagic activity of GSK189254. In conclusion, we demonstrated the selective contribution of H4R to the H3R antagonist-induced attenuation of hypernociceptive behavior in SNI mice. These results might help identify innovative therapeutic interventions for neuropathic pain.
Dual Modification of Porous Ca-P/PLA Composites with APTES and Alendronate Improves Their Mechanical Strength and Cytobiocompatibility towards Human Osteoblasts
Authors: Biernat Monika , Szwed-Georgiou Aleksandra , Rudnicka Karolina , Płociński Przemysław , Pagacz Joanna , Tymowicz-Grzyb Paulina , Woźniak Anna , Włodarczyk Marcin , Urbaniak Mateusz M. , Krupa Agnieszka , Rusek-Wala Paulina , Karska Natalia , Rodziewicz-Motowidło Sylwia
Published: November 2022

Synthetic implants are used to treat large bone defects that are often unable to regenerate, for example those caused by osteoporosis. It is necessary that the materials used to manufacture them are biocompatible and resorbable. Polymer-ceramic composites, such as those based on poly(L-lactide) (PLLA) and calcium phosphate ceramics (Ca-P), are often used for these purposes. In this study, we attempted to investigate an innovative strategy for two-step (dual) modification of composites and their components to improve the compatibility of composite components and the adhesion between PLA and Ca-P whiskers, and to increase the mechanical strength of the composite, as well as improve osteological bioactivity and prevent bone resorption in composites intended for bone regeneration. In the first step, Ca-P whiskers were modified with a saturated fatty acid namely, lauric acid (LA), or a silane coupling agent γ-aminopropyltriethoxysilane (APTES). Then, the composite, characterized by the best mechanical properties, was modified in the second stage of the work with an active chemical compound used in medicine as a first-line drug in osteoporosis—sodium alendronate, belonging to the group of bisphosphonates (BP). As a result of the research covered in this work, the composite modified with APTES and alendronate was found to be a promising candidate for future biomedical engineering applications.
Renal Fibrosis in Lupus Nephritis
Authors: Sciascia Savino , Cozzi Martina , Barinotti Alice , Radin Massimo , Cecchi Irene , Fenoglio Roberta , Mancardi Daniele , Wilson Jones Georgia , Rossi Daniela , Roccatello Dario
Published: November 2022

Fibrosis can be defined as a pathological process in which deposition of connective tissue replaces normal parenchyma. The kidney, like any organ or tissue, can be impacted by this maladaptive reaction, resulting in persistent inflammation or long-lasting injury. While glomerular injury has traditionally been regarded as the primary focus for classification and prognosis of lupus nephritis (LN), increasing attention has been placed on interstitial fibrosis and tubular atrophy as markers of injury severity, predictors of therapeutic response, and prognostic factors of renal outcome in recent years. This review will discuss the fibrogenesis in LN and known mechanisms of renal fibrosis. The importance of the chronicity index, which was recently added to the histological categorization of LN, and its role in predicting treatment response and renal prognosis for patients with LN, will be explored. A better understanding of cellular and molecular pathways involved in fibrosis in LN could enable the identification of individuals at higher risk of progression to chronic kidney disease and end-stage renal disease, and the development of new therapeutic strategies for lupus patients.
Benefits and Risks of Teleworking from Home: The Teleworkers’ Point of View
Authors: Vayre Émilie , Morin-Messabel Christine , Cros Florence , Maillot Anne-Sophie , Odin Nelly
Published: November 2022

Using a qualitative research-based approach, this study aimed to understand (i) the way home-based teleworkers in France perceive and organize their professional activities and workspaces, (ii) their teleworking conditions, (iii) the way they characterize the modalities and the nature of their interactions with their professional circle, and more broadly (iv) their quality of life ‘at work’. We performed a lexical and morphosyntactic analysis of interviews conducted with 28 teleworkers (working part-time or full-time from home) before the COVID-19 crisis and the associated establishment of emergency telework. Our results confirm and complement findings in the literature. Participant discourses underlined the beneficial effects of teleworking in terms of professional autonomy, flexibility, concentration, efficiency, performance, productivity, and being able to balance their professional and private lives. Nevertheless, they also highlighted the deleterious effects of teleworking on temporal workload, setting boundaries for work, work-based relationships and socio-professional integration. Despite the study limitations, our findings highlight the need for specific research-based and practical strategies to support the implementation of a sustainable telework organization in the post-COVID-19 pandemic era.
Generic Pheromones Identified from Northern Hemisphere Cerambycidae (Coleoptera) Are Attractive to Native Longhorn Beetles from Central-Southern Chile
Authors: Curkovic Tomislav , Arraztio Diego , Huerta Amanda , Rebolledo Ramón , Cheuquel Arly , Contreras Américo , Millar Jocelyn G.
Published: November 2022

We conducted field bioassays with several known cerambycid pheromones in two zones of central-southern Chile: (1) Las Trancas (Ñuble region) and Coñaripe (Los Rios region) (Study 1) and (2) Rucamanque and Maquehue (La Araucania region) (Study 2). Up to eight compounds were tested individually, including 3-hydroxy-2-hexanone, (2R*,3S*)- and (2R*,3R*)-2,3-hexanediol, fuscumol, fuscumol acetate, monochamol, 2-methylbutanol, and geranylacetone. Compounds were loaded in plastic sachets placed in either multiple funnel or cross-vane panel traps hung in trees in a randomized block design (n = 3 or 4). The number of treatments and bioassay periods varied depending on the study. A total of 578 specimens belonging to 11 native species were collected, with the three captured in the highest numbers being Eryphus laetus (292 specimens), Calydon submetallicum (n = 234), and Chenoderus testaceus (n = 20). The three species are of economic importance: E. laetus is considered a minor pest in apple orchards, and the other two species infest Nothophagus hosts, including some timber species. Traps baited with 3-hydroxy-2-hexanone collected significant numbers of both sexes of the two most abundant species, and this compound was the only treatment that attracted C. submetallicum. (2R*,3R*)- and (2R*,3S*)-2,3-Hexanediols were also significantly attractive to E. laetus. Our results suggested that 3-hydroxy-2-hexanone and 2,3-hexanediols, which are known pheromone components of cerambycid species worldwide, are also likely to be conserved aggregation pheromone components among some species in western South America.
Muography for Inspection of Civil Structures
Authors: Das Subhendu , Tripathy Sridhar , Jagga Priyanka , Bhattacharya Purba , Majumdar Nayana , Mukhopadhyay Supratik
Published: November 2022

Aging infrastructure is a threatening issue throughout the world. Long exposure to oxygen and moisture causes premature corrosion of reinforced concrete structures leading to the collapse of the structures. As a consequence, real-time monitoring of civil structures for rust becomes critical in avoiding mishaps. Muon scattering tomography is a non-destructive, non-invasive technique which has shown impressive results in 3D imaging of civil structures. This paper explores the application of advanced machine learning techniques in identifying a rusted reinforced concrete rebar using muon scattering tomography. To achieve this, we have simulated the performance of an imaging prototype setup, designed to carry out muon scattering tomography, to precisely measure the rust percentage in a rusted rebar. We have produced a 2D image based on the projected 3D scattering vertices of the muons and used the scattering vertex density and average deviation angle per pixel as the distinguishing parameter for the analysis. A filtering algorithm, namely the Pattern Recognition Method, has been employed to eliminate background noise. Since this problem boils down to whether or not the material being analyzed is rust, i.e., a classification problem, we have adopted the well-known machine learning algorithm Support Vector Machine to identify rust in the rusted reinforced cement concrete structure. It was observed that the trained model could easily identify 30% of rust in the structure with a nominal exposure of 30 days within a small error range of 7.3%.
On the Avant-Garde IDeS Method for the Future of Car Design Applied to an SUV Project
Authors: Frizziero Leonardo , Polpatelli Enrico , Martini Federico , Fiorentini Lorenzo , Freddi Marco
Published: November 2022

This case study aims to develop a new innovative SUV (Sport Utility Vehicle) model exploiting IDeS (Industrial Design Structure), which is an engineering approach conceived to optimize car design projects in the automotive industry like never before. A compact SUV was chosen because it is a type of vehicle that is highly requested by customers, and it is extremely successful in the market due to its versatility. In fact, compact SUVs are mixed vehicles that combine the pragmatism of a car with the typical robustness of an off-road vehicle making them suitable both for urban and off-road scenarios. The following pages will illustrate the steps followed for the realization of the final product using the SDE (Stylistic Design Engineering) method and other various design technologies, such as Quality Function Deployment (QFD), Benchmarking (BM) and Top Flop Analysis (TPA). In the final part of this project, the virtual prototyping of the product is carried out using Additive Manufacturing (AM) with an FDM 3D printer. The combination of these methods forms, to all intents and purposes, the IDeS, a newly developed innovative and cutting-edge discipline capable of schematically guiding the new product development process in companies with unprecedented efficiency.
The Role of Cardiovascular Magnetic Resonance in Patients with Mitral Regurgitation
Authors: Pavon Anna Giulia , Guglielmo Marco , Mennilli Pierpaolo Mattia , Falcão Mariana B. L. , Bergamaschi Luca , Costantin David Filip , Vivaldo Michele , Leo Laura Anna , Schlossbauer Susanne , Roy Christopher W. , Stuber Matthias , Pedrazzini Giovanni , Faletra Francesco
Published: November 2022

The 2019 Global Burden of Disease (GBD) study estimated that there were approximately 24.2 million people affected worldwide by degenerative mitral regurgitation (MR), resulting in 34,200 deaths. After aortic stenosis, MR is the most prevalent VHD in Europe and the second-most common VHD to pose indications for surgery in western countries. Current ESC and AHA/ACC guidelines for the management of VHD emphasize the importance of an integrative approach for the assessment of MR severity, which is of paramount importance in dictating the timing for surgery. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are the first-line imaging modalities; however, despite the technological advancement, sometimes, the final diagnosis on the degree of the disease may still be challenging. In the last 20 years, CMR has emerged as a robust technique in the assessment of patients with cardiac disease, and, recently, its role is gaining more and more importance in the field of VHD. In fact, CMR is the gold standard in the assessment of cardiac volumes, and it is possible to accurately evaluate the regurgitant volume. The purpose of this review is to outline the current state-of-the-art management of MR by using Cardiac Magnetic Resonance (CMR).
Impact of Obesity on Early In-Hospital Outcomes after Coronary Artery Bypass Grafting Surgery in Acute Coronary Syndrome: A Propensity Score Matching Analysis
Authors: Krasivskyi Ihor , Eghbalzadeh Kaveh , Ivanov Borko , Gerfer Stephen , Großmann Clara , Sabashnikov Anton , Kuhn Elmar , Mader Navid , Djordjevic Ilija , Wahlers Thorsten
Published: November 2022

Recent advances in perioperative care have considerably improved outcomes after coronary artery bypass graft (CABG) surgery. However, obesity can increase postoperative complication rates and can lead to increased morbidity and mortality. Between June 2011 and October 2019, a total of 1375 patients with acute coronary syndrome (ACS) underwent cardiac surgery and were retrospectively analyzed. Patients were divided into 2 groups: non-obese (body mass index (BMI) < 30 kg/m2, n = 967) and obese (BMI ≥ 30 kg/m2, n = 379). Underweight patients (n = 29) were excluded from the analysis. To compare the unequal patient groups, a propensity score-based matching (PSM) was applied (non-obese group (n = 372) vs. obese group (n = 372)). The mean age of the mentioned groups was 67 ± 10 (non-obese group) vs. 66 ± 10 (obese group) years, p = 0.724. All-cause in-hospital mortality did not significantly differ between the groups before PSM (p = 0.566) and after PSM (p = 0.780). The median length of ICU (p = 0.306 before PSM and p = 0.538 after PSM) and hospital stay (p = 0.795 before PSM and p = 0.131 after PSM) was not significantly higher in the obese group compared with the non-obese group. No significant differences regarding further postoperative parameters were observed between the unadjusted and the adjusted group. Obesity does not predict increased all-cause in-hospital mortality in patients undergoing CABG procedure. Therefore, CABG is a safe procedure for overweight patients.
Characteristics of Hospitalized Pediatric Patients in the First Five Waves of the COVID-19 Pandemic in a Single Center in Poland—1407 Cases
Authors: Stopyra Lidia , Kowalik Aleksandra , Stala Justyna , Majchrzak Ida , Szebla Justyna , Jakosz Mateusz , Grzywaczewska Karolina , Kwinta Przemko
Published: November 2022

This is a single-center, prospective study that compared the clinical presentation and laboratory findings of hospitalized children during the first five waves of the COVID-19 pandemic. Data were collected, according to a standardized questionnaire, from 1407 children from 23 March 2020 to 30 April 2022. Significant differences in clinical courses were found among the five waves probably due to different SARS-CoV-2 variants. The median age was 95.8 months in the first wave versus 14.6–23 months in the others. The number of patients with upper respiratory infection was the highest in the fifth wave (74.4% versus 43.8–56.9% in the others) and for lower respiratory infection in the first wave (50.0% versus 16.4–32.5%). Gastroenterocolitis was more common in the fifth wave (24.4% versus 8.9–16.5%); neurological diagnoses appeared more frequently in the fourth wave (16.6% versus 0.6–9.9%), while anosmia and ageusia were higher in the fifth wave (13% versus 1.5–4%). Life-threatening courses were relatively rare. However, children with pneumonia, dehydration from high fever, gastrointestinal symptoms, loss of smell and taste, and neurological symptoms required hospitalization.
ABO Incompatibility between the Mother and Fetus Does Not Protect against Anti-Human Platelet Antigen-1a Immunization by Pregnancy
Authors: Miserre Laila , Wienzek-Lischka Sandra , Mann Andreas , Cooper Nina , Santoso Sentot , Ehrhardt Harald , Sachs Ulrich J. , Bein Gregor
Published: November 2022

(1) Background: ABO blood group incompatibility between the mother and fetus protects against anti-D immunization by pregnancy. The possible role of ABO incompatibility in protecting against anti-human platelet antigen-1a immunization is unclear. (2) Methods: This study retrospectively screened 817 families (mother-father-neonate trios) of suspected fetal and neonatal alloimmune thrombocytopenia for inclusion. ABO genotypes were determined in 118 mother-child pairs with confirmed alloimmune thrombocytopenia due to anti-HPA-1a antibodies, and 522 mother-child pairs served as the control group. The expression of blood group antigen A on platelets was determined in 199 consecutive newborns by flow cytometry and compared with adult controls. (3) Results: ABO incompatibility between mother and fetus did not protect against anti-human platelet antigen-1a immunization by pregnancy. ABO blood groups of mothers and/or fetuses were not associated with the severity of fetal and neonatal alloimmune thrombocytopenia. The expression pattern of blood group A antigens on the platelets of newborns mirrored that of adults, albeit on a lower level. Blood group A antigen was detected on a subpopulation of neonatal platelets, and some newborns revealed high platelet expression of A determinants on all platelets (type II high-expressers). (4) Conclusion: The lack of a protective effect of ABO incompatibility between mother and fetus against anti-human platelet antigen-1a immunization by pregnancy may indicate that fetal platelets are not the cellular source by which the mother is immunized.
Green Tattoo Pre-Operative Renal Embolization for Robotic-Assisted and Laparoscopic Partial Nephrectomy: A Practical Proof of a New Technique
Authors: Faiella Eliodoro , Calabrese Alessandro , Santucci Domiziana , Corti Riccardo , Cionfoli Nicola , Pusceddu Claudio , de Felice Carlo , Bozzini Giorgio , Mazzoleni Federica , Muraca Rosa Maria , Moramarco Lorenzo Paolo , Venturini Massimo , Quaretti Pietro
Published: November 2022

(1) Background: Our aim is to describe a new mixed indocyanine-non-adhesive liquid embolic agent (Onyx-18) pre-operative renal embolization technique for assisted-robotic and laparoscopic partial nephrectomy with near-infra-red fluorescence imaging. (2) Methods: Thirteen patients with biopsy-proven renal tumors underwent pre-operative mixed indocyanine–ethylene vinyl alcohol (EVOH) embolization (Green-embo) between June 2021 and August 2022. All pre-operative embolizations were performed with a super selective stop-flow technique using a balloon microcatheter to deliver an indocyanine-EVOH mixture into tertiary order arterial branch feeders and the intra-lesional vascular supply. Efficacy (evaluated as complete embolization, correct tumor mapping on infra-red fluorescence imaging and clamp-off surgery) and safety (evaluated as complication rate and functional outcomes) were primary goals. Clinical and pathological data were also collected. (3) Results: Two male and eleven female patients (mean age 72 years) received pre-operative Green-embo. The median tumor size was 29 mm (range 15–50 mm). Histopathology identified renal cell carcinoma (RCC) in 9 of the 13 (69%) patients, oncocytoma in 3 of the 13 (23%) patients and sarcomatoid RCC in 1 of the 13 (8%) patients. Lesions were equally distributed between polar, meso-renal, endo- and exophytic locations. Complete embolization was achieved in all the procedures. A correct green mapping was identified during all infra-red fluorescence imaging. All patients were discharged on the second day after the surgery. The median blood loss was 145 cc (10–300 cc). No significant differences were observed in serum creatinine levels before and after the embolization procedures. (4) Conclusions: The Green-tattoo technique based on a mixed indocyanine-non-adhesive liquid embolic agent (Onyx-18) is a safe and effective pre-operative embolization technique. The main advantages are the excellent lesion mapping for fluorescence imaging, reduction in surgical time, and definitive, complete and immediate tumor devascularization based on the deep Onyx-18 penetration, leading to a very low intra-operative blood loss.
Active Tactile Sensibility in Implant Prosthesis vs. Complete Dentures: A Psychophysical Study
Authors: González-Gil Diego , Dib-Zaitun Ibrahim , Flores-Fraile Javier , López-Marcos Joaquín
Published: November 2022

Background and Objectives: Proprioceptive information from natural dentition and adjacent oral tissues enables correct masticatory function, avoiding damage to the teeth. Periodontium is the main source of this relevant information, and when a tooth is lost, all this proprioceptive sensibility relies on receptors from muscles, the mucous membrane or the temporomandibular joint, and this sensibility gets worse. Active tactile sensibility measures this proprioceptive capability in microns by psychophysical studies consisting of introducing thin metal foils between patients’ dental arches during chewing to see if they are able to notice them or not. Osseoperception is a complex phenomenon that seems to improve this sensibility in patients wearing dental implants. The objective of this investigation is to measure this sensibility in different prosthetic situations by performing a psychophysical investigation. Material and Methods: We divided 67 patients in three groups depending on their prosthetic situation and performed a psychophysical study by introducing aluminium foils of different thicknesses in order to establish an active tactile sensibility threshold in every group. We also measured variables such as prosthetic wearing time, age or gender to see how they may influence threshold values. We used Student’s t-test and Mann–Whitney U tests to analyse these results. Results: Active tactile sensibility threshold values in implants are lower than those from complete dentures but higher than values in natural dentition. However, values in implants are closer to natural dentition than complete denture values. Age, gender or prosthetic wearing time have no influence in active tactile sensibility thresholds. Conclusion: Active tactile sensibility threshold values depend on prosthetic rehabilitations and the mechanoreceptors involved in every situation. Implant prosthesis presents an increased active tactile sensibility thanks to osseoperception phenomenon.
ECMO Support in Refractory Cardiogenic Shock: Risk Factors for Mortality
Authors: Rajsic Sasa , Breitkopf Robert , Bukumiric Zoran , Treml Benedikt
Published: November 2022

Background: Veno-arterial extracorporeal membrane oxygenation (va-ECMO) is a specialized temporary support for patients with refractory cardiogenic shock. The true value of this potentially lifesaving modality is still a subject of debate. Therefore, we aimed to investigate the overall in-hospital mortality and identify potential risk factors for mortality. Methods: We retrospectively analyzed the data of 453 patients supported with va-ECMO over a period of 14 years who were admitted to intensive care units of a tertiary university center in Austria. Results: We observed in-hospital mortality of 40% for patients with refractory cardiogenic shock. Hemorrhage, ECMO initiation on weekends, higher SAPS III score, and sepsis were identified as significant risk factors for mortality. Hemorrhage was the most common adverse event (46%), with major bleeding events dominating in deceased patients. Thromboembolic events occurred in 25% of patients, followed by sepsis (18%). Conclusions: Although the rates of complications are substantial, a well-selected proportion of patients with refractory cardiogenic shock can be rescued from probable death. The reported risk factors could be used to increase the awareness of clinicians towards the development of new therapeutic concepts that may reduce their incidence.
Special Issue “Prostate Cancer: Recent Advances in Diagnostics and Treatment Planning”
Authors: Tokas Theodoros
Published: November 2022

This editorial of the Special Issue “Prostate Cancer: Recent Advances in Diagnostics and Treatment Planning” aims to draw more attention to the broad and diverse field of prostate cancer (PCa) diagnosis and the utilization of different diagnostic means to improve clinical decision-making and treatment strategy planning [...]
Strontium Carbonate and Strontium-Substituted Calcium Carbonate Nanoparticles Form Protective Deposits on Dentin Surface and Enhance Human Dental Pulp Stem Cells Mineralization
Authors: Dotta Tatiane Cristina , Hayann Larwsk , de Padua Andrade Almeida Leonardo , Nogueira Lucas Fabrício B. , Arnez Mayara M. , Castelo Raisa , Cassiano Ana Flávia B. , Faria Gisele , Martelli-Tosi Milena , Bottini Massimo , Ciancaglini Pietro , Catirse Alma B. C. E. B. , Ramos Ana Paula
Published: November 2022

Strontium acetate is applied for dental hypersensitivity treatment; however, the use of strontium carbonates for this purpose has not been described. The use of Sr-carbonate nanoparticles takes advantage of both the benefits of strontium on dentin mineralization and the abrasive properties of carbonates. Here in, we aimed to synthesize strontium carbonate and strontium-substituted calcium carbonate nanoparticles and test them as potential compounds in active dentifrices for treating dental hypersensitivity. For this, SrCO3, Sr0.5Ca0.5CO3, and CaCO3 nanoparticles were precipitated using Na2CO3, SrCl2, and/or CaCl2 as precursors. Their morphology and crystallinity were evaluated by electron microscopy (SEM) and X-ray diffraction, respectively. The nanoparticles were added to a poly (vinyl alcohol) gel and used to brush dentin surfaces isolated from human third molars. Dentin chemical composition before and after brushing was investigated by infrared spectroscopy (FTIR) and X-ray dispersive energy spectroscopy. Dentin tubule morphology, obliteration, and resistance of the coatings to acid attack were investigated by SEM and EDS. The cytotoxicity and ability of the particles to trigger the mineralization of hDPSCs in vitro were studied. Dentin brushed with the nanoparticles was coated by a mineral layer that was also able to penetrate the tubules, while CaCO3 remained as individual particles on the surface. FTIR bands related to carbonate groups were intensified after brushing with either SrCO3 or Sr0.5Ca0.5CO3. The shift of the phosphate-related FTIR band to a lower wavenumber indicated that strontium replaced calcium on the dentin structure after treatment. The coating promoted by SrCO3 or Sr0.5Ca0.5CO3 resisted the acid attack, while calcium and phosphorus were removed from the top of the dentin surface. The nanoparticles were not toxic to hDPSCs and elicited mineralization of the cells, as revealed by increased mineral nodule formation and enhanced expression of COL1, ALP, and RUNX2. Adding Sr0.5Ca0.5CO3 as an active ingredient in dentifrices formulations may be commercially advantageous since this compound combines the well-known abrasive properties of calcium carbonate with the mineralization ability of strontium, while the final cost remains between the cost of CaCO3 and SrCO3. The novel Sr0.5Ca0.5CO3 nanoparticles might emerge as an alternative for the treatment of dental hypersensitivity.
Distribution and Identification of Ulva aragoensis (Ulvaceae, Chlorophyta), a Constituent Species of Green Tides in the Southern Yellow Sea, Based on Molecular Data
Authors: Tong Yichao , Xia Lihua , Liu Jinlin , Zhao Shuang , Sun Yuqing , Wu Tingjian , Xia Zhangyi , Li Shuang , Cao Jiaxing , Zhang Jianheng
Published: November 2022

Green tides are a serious global ecological disaster; the largest occur in the Southern Yellow Sea (SYS). Early-stage green tides in the SYS are composed of four species (Ulva prolifera, Ulva flexuosa, Ulva linza, and Ulva compressa). We found that U. aragoensis is a constituent species of green tides in the SYS based on molecular data. Furthermore, this study re-evaluated the proportion of U. aragoensis in green tides and found that it was more prevalent in micro-propagules cultured from surface seawater during an early-stage green tide in 2021. The internal transcribed spacers, tufA, 18S, rbcL, large subunit, psbA, and rps2-trnL gene sequences were compared; the tufA and rbcL gene sequences were the most suitable DNA barcodes for distinguishing U. aragoensis. A haplotype analysis of the sequences of floating U. aragoensis and its micro-propagules was performed to study the correlation between green tide macroalgae and micro-propagules; close haplotype similarities occurred between them. This study further clarified the species composition of SYS green tides and provided a reference for assessing the relationship between micro-propagules and green tide macroalgae.