bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of Advanced Implementation of Doppler Backscattering Method in Globus-M
Authors: Yashin Alexander , Bulanin Victor , Petrov Alexander , Ponomarenko Anna
Published: September 2021

Doppler backscattering (DBS) is a microwave diagnostics method typically used to study the plasma rotation velocity. Apart from conventional techniques, more advanced forms of DBS implementation were suggested on Globus-M. More specifically the study of a variety of oscillating processes was performed using DBS. In this review we present a detailed description of all of the methods and techniques employed in Globus-M alongside results obtained using DBS in all the years up until the shutdown of the tokamak. These include research similar to that done on other devices into the properties of such phenomena like geodesic acoustic modes or limit cycle oscillations, along with innovative works regarding the detection and investigation of Alfven eigenmodes and filaments that were the first of their kind and that provided important and novel results. Apart from that, the specific aspects of DBS application on a spherical tokamak are discussed. An in-depth look into the gradual change and improvement of the DBS diagnostics on Globus-M is also presented in this paper.
Additive Manufacturing in the Clothing Industry: Towards Sustainable New Business Models
Authors: Khajavi Siavash H.
Published: September 2021

The clothing industry is among the most polluting and waste-generating industries in the world, and it is responsible for the release of large amounts of greenhouse gases. The industry’s massive size and significant environmental footprint with regard to water and energy consumption and waste generation make it a valid improvement candidate. While in recent years, global clothing brands and retailers have taken steps to reduce their ecological footprint, there still is a lot of room for improvement. In this research, we view this sustainability issue from a lifecycle perspective and study the new business models (NBMs) that may arise from the utilization of additive manufacturing (AM) technology. AM is emerging as a method of production for final parts. Moreover, as the range of material and available production processes expands, it is increasingly important to study the potential impact of this promising production technology and potential NBMs enabled by it on the clothing industry. Additionally, the obstacles to AM utilization in the clothing industry are explored. We utilize secondary data related to relevant implementation cases to theoretically study the NBMs that AM can enable to improve sustainability. Three NBMs of “clothing as a service”, “collaborative consumption”, and “direct sale/distribution” were envisioned through the study of current AM applications in other industries, as well as current fashion trends. The results of this research have implications for the sustainability of the fashion industry while also providing directions for AM technology development.
3DLEB-Net: Label-Efficient Deep Learning-Based Semantic Segmentation of Building Point Clouds at LoD3 Level
Authors: Cao Yuwei , Scaioni Marco
Published: September 2021

In current research, fully supervised Deep Learning (DL) techniques are employed to train a segmentation network to be applied to point clouds of buildings. However, training such networks requires large amounts of fine-labeled buildings’ point-cloud data, presenting a major challenge in practice because they are difficult to obtain. Consequently, the application of fully supervised DL for semantic segmentation of buildings’ point clouds at LoD3 level is severely limited. In order to reduce the number of required annotated labels, we proposed a novel label-efficient DL network that obtains per-point semantic labels of LoD3 buildings’ point clouds with limited supervision, named 3DLEB-Net. In general, it consists of two steps. The first step (Autoencoder, AE) is composed of a Dynamic Graph Convolutional Neural Network (DGCNN) encoder and a folding-based decoder. It is designed to extract discriminative global and local features from input point clouds by faithfully reconstructing them without any label. The second step is the semantic segmentation network. By supplying a small amount of task-specific supervision, a segmentation network is proposed for semantically segmenting the encoded features acquired from the pre-trained AE. Experimentally, we evaluated our approach based on the Architectural Cultural Heritage (ArCH) dataset. Compared to the fully supervised DL methods, we found that our model achieved state-of-the-art results on the unseen scenes, with only 10% of labeled training data from fully supervised methods as input. Moreover, we conducted a series of ablation studies to show the effectiveness of the design choices of our model.
Sensitivity Analysis of Reliability of Low-Mobility Parallel Mechanisms Based on a Response Surface Method
Authors: Yang Qiang , Ma Hongkun , Ma Jiaocheng , Sun Zhili , Li Cuiling
Published: September 2021

Kinematic accuracy is a crucial indicator for evaluating the performance of mechanisms. Low-mobility parallel mechanisms are examples of parallel robots that have been successfully employed in many industrial fields. Previous studies analyzing the kinematic accuracy analysis of parallel mechanisms typically ignore the randomness of each component of input error, leading to imprecise conclusions. In this paper, we use homogeneous transforms to develop the inverse kinematics models of an improved Delta parallel mechanism. Based on the inverse kinematics and the first-order Taylor approximation, a model is presented considering errors from the kinematic parameters describing the mechanism’s geometry, clearance errors associated with revolute joints and driving errors associated with actuators. The response surface method is employed to build an explicit limit state function for describing position errors of the end-effector in the combined direction. As a result, a mathematical model of kinematic reliability of the improved Delta mechanism is derived considering the randomness of every input error component. And then, reliability sensitivity of the improved Delta parallel mechanism is analyzed, and the influences of the randomness of each input error component on the kinematic reliability of the mechanism are quantitatively calculated. The kinematic reliability and proposed sensitivity analysis provide a theoretical reference for the synthesis and optimum design of parallel mechanisms for kinematic accuracy.
Effects of Glyphosate and Its Metabolite AMPA on Aquatic Organisms
Authors: Tresnakova Nikola , Stara Alzbeta , Velisek Josef
Published: September 2021

Glyphosate (N-(phosphonomethyl)glycine) was developed in the early 1970s and at present is used as a herbicide to kill broadleaf weeds and grass. The widely occurring degradation product aminomethylphosphonic acid (AMPA) is a result of glyphosate and amino-polyphosphonate degradation. The massive use of the parent compound leads to the ubiquity of AMPA in the environment, and particularly in water. Considering this, it can be assumed that glyphosate and its major metabolites could pose a potential risk to aquatic organisms. This review summarizes current knowledge about residual glyphosate and its major metabolite AMPA in the aquatic environment, including its status and toxic effects in aquatic organisms, mainly fish. Based on the above, we identify major gaps in the current knowledge and some directions for future research knowledge about the effects of worldwide use of herbicide glyphosate and its major metabolite AMPA. The toxic effect of glyphosate and its major metabolite AMPA has mainly influenced growth, early development, oxidative stress biomarkers, antioxidant enzymes, haematological, and biochemical plasma indices and also caused histopathological changes in aquatic organisms.
The Colors of the Ineffable—Jerzy Nowosielski’s Monumental Works as a Contemporary Search for Sacred Space
Authors: Januszewski Wojciech Stanisław
Published: September 2021

The subject of this work is the monumental art of Jerzy Nowosielski (1923–2011), one of the most outstanding contemporary Polish painters, who combined modernity with the orthodox icon aesthetics. This work discusses the monumental realizations of Nowosielski, especially the architectural polychromes made by the artist in Catholic and Orthodox churches in Poland in the years 1950–1999. The aim of the inquiry is to present his work theoretically and place it in a broader artistic context. The research shows that Nowosielski’s monumental works results from a strongly defined artistic concept aimed at ‘mystagogy of space’. Nowosielski’s work is an original synthesis of the modernist avant-garde and traditional canons of religious art. The analysis of the problem was carried out in two areas: (1) analysis of the artist’s theoretical statements; (2) analysis of the artistic form with particular emphasis on the color aspect, based on the example of selected churches in Wesoła, Tychy, and Biały Bór. The work uses comparative references to the ideas of Wassily Kandinsky, Kazimir Malevich, Piet Mondrian, and Le Corbusier.
Zeroize: A New Method to Improve the Utilization of 5G Networks When Running VoIP over IPv6
Authors: Kolhar Manjur
Published: September 2021

5G technology is spreading extremely quickly. Many services, including Voice Over Internet Protocol (VoIP), have utilized the features of 5G technology to improve their performance. VoIP service is gradually ruling the telecommunication sector due to its various advantages (e.g., free calls). However, VoIP service wastes a substantial share of the VoIP 5G network’s bandwidth due to its lengthy packet header. For instance, the share of the packet header from bandwidth and channel time reaches 85.7% of VoIP 5G networks when using the IPv6 protocol. VoIP designers are exerting considerable efforts to solve this issue. This paper contributes to these efforts by designing a new technique named Zeroize (zero sizes). The core of the Zeroize technique is based on utilizing the unnecessary fields of the IPv6 protocol header to keep the packet payload (voice data), thereby reducing or “zeroizing” the payload of the VoIP packet. The Zeroize technique substantially reduces the expanded bandwidth of VoIP 5G networks, which is reflected in the wasted channel time. The results show that the Zeroize technique reduces the wasted bandwidth by 20% with the G.723.1 codec. Therefore, this technique successfully reduces the bandwidth and channel time of VoIP 5G networks when using the IPv6 protocol.
In Situ Visualization for 3D Ultrasound-Guided Interventions with Augmented Reality Headset
Authors: Cattari Nadia , Condino Sara , Cutolo Fabrizio , Ferrari Mauro , Ferrari Vincenzo
Published: September 2021

Augmented Reality (AR) headsets have become the most ergonomic and efficient visualization devices to support complex manual tasks performed under direct vision. Their ability to provide hands-free interaction with the augmented scene makes them perfect for manual procedures such as surgery. This study demonstrates the reliability of an AR head-mounted display (HMD), conceived for surgical guidance, in navigating in-depth high-precision manual tasks guided by a 3D ultrasound imaging system. The integration between the AR visualization system and the ultrasound imaging system provides the surgeon with real-time intra-operative information on unexposed soft tissues that are spatially registered with the surrounding anatomic structures. The efficacy of the AR guiding system was quantitatively assessed with an in vitro study simulating a biopsy intervention aimed at determining the level of accuracy achievable. In the experiments, 10 subjects were asked to perform the biopsy on four spherical lesions of decreasing sizes (10, 7, 5, and 3 mm). The experimental results showed that 80% of the subjects were able to successfully perform the biopsy on the 5 mm lesion, with a 2.5 mm system accuracy. The results confirmed that the proposed integrated system can be used for navigation during in-depth high-precision manual tasks.
Wearing Cushioning Shoes Reduce Load Rates More Effectively in Post-Fatigue than in Pre-Fatigue during Landings
Authors: Wang Xi , Deng Liqin , Lam Wing-Kai , Yang Yang , Zhang Xini , Fu Weijie
Published: September 2021

Purpose: this study aimed to investigate the footwear cushioning effects on impact forces and joint kinematics of the lower extremity during bipedal drop landings before and after acute exercise-induced fatigue protocol. Methods: in this case, 15 male collegiate basketball athletes performed drop landings from a 60 cm platform wearing highly-cushioned shoes (HS) and less cushioned shoes (control shoes, CS) before and after acute fatigue-inducing exercises (i.e., shuttle run combined with multiple vertical jumps). Force plates and motion capturing systems were synchronised to measure ground reaction forces and kinematic data during drop landings. Maximum jump height was analysed with one-way ANOVA. Two-way repeated measure ANOVAs were performed on each of the tested variables to examine if there was significant main effects of shoe and fatigue as well as the interaction. The significance level was set to 0.05. Results: rearfoot peak impact forces and loading rates significantly reduced when the participants wore HS in pre- and post-fatigue conditions. The peak loading rates in forefoot significantly reduced when HS were worn in post-fatigue. Compared with pre-fatigue, wearing HS contributed to with 24% and 13% reduction in forefoot and rearfoot peak loading rates, respectively, and the occurrence times of first and second peak impact forces and loading rates were much later. In the post-fatigue, a significant increase in the initial contact and minimum angles of the ankle were observed in HS compared with CS. Conclusion: these findings suggest that footwear cushioning can reduce landing-related rearfoot impact forces regardless of fatigue conditions. In a situation where the neuromuscular activity is reduced or absent such as post-fatigue wearing better cushioning shoes show superior attenuation, as indicated by lower forefoot and rearfoot impacts.
Metformin Is Associated with a Lower Incidence of Benign Brain Tumors: A Retrospective Cohort Study in Patients with Type 2 Diabetes Mellitus
Authors: Tseng Chin-Hsiao
Published: September 2021

Background: The risk of benign brain tumors (BBT) associated with metformin use has not received much attention. Therefore, a retrospective cohort study was designed to investigate such an association in patients with type 2 diabetes mellitus (T2DM). Methods: We used the database of Taiwan’s National Health Insurance to enroll 152,176 ever users and 16,120 never users of metformin for the follow-up of incidence of BBT and a more specific outcome of cerebral meningioma. The patients were newly diagnosed with T2DM between 1999 and 2005; and they were followed up from 1 January 2006 until 31 December 2011. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results: During follow-up, 111 never users and 557 ever users were diagnosed with BBT. For BBT, the respective incidence rates for never users and ever users were 153.95 per 100,000 person-years and 77.61 per 100,000 person-years. While ever users were compared to never users, the hazard ratio was 0.502 (95% confidence interval: 0.409–0.615). A dose-response pattern was seen when ever users were categorized into tertiles of cumulative duration of metformin therapy (cutoffs: <27.10 months, 27.10–58.27 months and >58.27 months) with respective hazard ratios of 0.910 (0.728–1.138), 0.475 (0.375–0.602) and 0.243 (0.187–0.315). For cerebral meningioma, the overall hazard ratio was 0.506 (0.317–0.808); and the hazard ratios comparing the respective tertiles to never users were 0.895 (0.531–1.508), 0.585 (0.346–0.988) and 0.196 (0.104–0.369). Conclusions: A reduced risk of BBT and cerebral meningioma is observed in metformin users in patients with T2DM.
Lipopolysaccharide of the Yersinia pseudotuberculosis Complex
Authors: Knirel Yuriy A. , Anisimov Andrey P. , Kislichkina Angelina A. , Kondakova Anna N. , Bystrova Olga V. , Vagaiskaya Anastasia S. , Shatalin Konstantin Y. , Shashkov Alexander S. , Dentovskaya Svetlana V.
Published: September 2021

Lipopolysaccharide (LPS), localized in the outer leaflet of the outer membrane, serves as the major surface component of the Gram-negative bacterial cell envelope responsible for the activation of the host’s innate immune system. Variations of the LPS structure utilized by Gram-negative bacteria promote survival by providing resistance to components of the innate immune system and preventing recognition by TLR4. This review summarizes studies of the biosynthesis of Yersinia pseudotuberculosis complex LPSs, and the roles of their structural components in molecular mechanisms of yersiniae pathogenesis and immunogenesis.
Inhaled Corticosteroids and the Lung Microbiome in COPD
Authors: Keir Holly R. , Contoli Marco , Chalmers James D.
Published: September 2021

The Global Initiative for Chronic Obstructive Lung Disease 2021 Report recommends inhaled corticosteroid (ICS)-containing regimens as part of pharmacological treatment in patients with chronic obstructive lung disease (COPD) and frequent exacerbations, particularly with eosinophilic inflammation. However, real-world studies reveal overprescription of ICS in COPD, irrespective of disease presentation and inflammatory endotype, leading to increased risk of side effects, mainly respiratory infections. The optimal use of ICS in COPD therefore remains an area of intensive research, and additional biomarkers of benefit and risk are needed. Although the interplay between inflammation and infection in COPD is widely acknowledged, the role of the microbiome in shaping lower airway inflammation has only recently been explored. Next-generation sequencing has revealed that COPD disease progression and exacerbation frequency are associated with changes in the composition of the lung microbiome, and that the immunosuppressive effects of ICS can contribute to potentially deleterious airway microbiota changes by increasing bacterial load and the abundance of potentially pathogenic taxa such as Streptococcus and Haemophilus. Here, we explore the relationship between microbiome, inflammation, ICS use and disease phenotype. This relationship may inform the benefit:risk assessment of ICS use in patients with COPD and lead to more personalised pharmacological management.
OmniSARS2: A Highly Sensitive and Specific RT-qPCR-Based COVID-19 Diagnostic Method Designed to Withstand SARS-CoV-2 Lineage Evolution
Authors: Carvalho-Correia Eduarda , Calçada Carla , Branca Fernando , Estévez-Gómez Nuria , De Chiara Loretta , Varela Nair , Gallego-García Pilar , Posada David , Sousa Hugo , Sousa João , Veiga Maria Isabel , Osório Nuno S.
Published: September 2021

Extensive transmission of SARS-CoV-2 during the COVID-19 pandemic allowed the generation of thousands of mutations within its genome. While several of these become rare, others largely increase in prevalence, potentially jeopardizing the sensitivity of PCR-based diagnostics. Taking advantage of SARS-CoV-2 genomic knowledge, we designed a one-step probe-based multiplex RT-qPCR (OmniSARS2) to simultaneously detect short fragments of the SARS-CoV-2 genome in ORF1ab, E gene and S gene. Comparative genomics of the most common SARS-CoV-2 lineages, other human betacoronavirus and alphacoronavirus, was the basis for this design, targeting both highly conserved regions across SARS-CoV-2 lineages and variable or absent in other Coronaviridae viruses. The highest analytical sensitivity of this method for SARS-CoV-2 detection was 94.2 copies/mL at 95% detection probability (~1 copy per total reaction volume) for the S gene assay, matching the most sensitive available methods. In vitro specificity tests, performed using reference strains, showed no cross-reactivity with other human coronavirus or common pathogens. The method was compared with commercially available methods and detected the virus in clinical samples encompassing different SARS-CoV-2 lineages, including B.1, B.1.1, B.1.177 or B.1.1.7 and rarer lineages. OmniSARS2 revealed a sensitive and specific viral detection method that is less likely to be affected by lineage evolution oligonucleotide–sample mismatch, of relevance to ensure the accuracy of COVID-19 molecular diagnostic methods.
Role of Circulating miRNAs in Therapeutic Response in Epithelial Ovarian Cancer: A Systematic Revision
Authors: Ravegnini Gloria , De Iaco Pierandrea , Gorini Francesca , Dondi Giulia , Klooster Isabella , De Crescenzo Eugenia , Bovicelli Alessandro , Hrelia Patrizia , Perrone Anna Myriam , Angelini Sabrina
Published: September 2021

Epithelial ovarian cancer (EOC) is one of the most lethal cancers worldwide, mostly due to nonspecific symptoms and a lack of screening tests, which, taken together, contribute to delayed diagnosis and treatment. The current clinical biomarker is serum CA-125, which allows the identification of most advanced primary and relapsed disease and correlates with disease burden; however, as well highlighted in the literature, CA-125 often lacks sensitivity and specificity, and is not helpful in monitoring chemotherapeutic response or in predicting the risk of relapse. Given that, the identification of novel biomarkers able to foster more precise medical approaches and the personalization of patient management represents an unmet clinical requirement. In this context, circulating miRNAs may represent an interesting opportunity as they can be easily detected in all biological fluids. This is particularly relevant when looking for non-invasive approaches that can be repeated over time, with no pain and stress for the oncological patient. Given that, the present review aims to describe the circulating miRNAs currently identified as associated with therapeutic treatments in OC and presents a complete overview of the available evidence.
The Revival of Surgery in Crohn’s Disease—Early Intestinal Resection as a Reasonable Alternative in Localized Ileitis
Authors: Kelm Matthias , Germer Christoph-Thomas , Schlegel Nicolas , Flemming Sven
Published: September 2021

Crohn’s disease (CD) represents a heterogeneous and complex disease with no curative therapeutic option available to date. Current therapy is mainly antibody-based focusing on the immune system while other treatment alternatives such as surgery are considered to be “last options”. However, medical therapy for CD results in mild to severe side effects in a relevant amount of patients and some patients do not respond to the medication. Following that, quality of life is often significantly reduced in this patient cohort, thus, therapeutic alternatives are urgently needed. Updated evidence has revealed that surgery such as ileocecal resection (ICR) might be a potential therapeutic option in case of localized terminal ileitis since resection at early time points improves quality of life and significantly reduces the postoperative need for immunosuppressive medication with low rates of morbidity. In addition, new surgical approaches such as Kono-S anastomosis or inclusion of the mesentery result in significantly reduced rates of disease recurrence and reoperation. Based on the new evidence, the goal of this review is to provide an update on the role of surgery as a reasonable alternative to medical therapy in the interdisciplinary treatment of patients with CD.
Predicting Cancer Drug Response In Vivo by Learning an Optimal Feature Selection of Tumour Molecular Profiles
Authors: Nguyen Linh C. , Naulaerts Stefan , Bruna Alejandra , Ghislat Ghita , Ballester Pedro J.
Published: September 2021

(1) Background: Inter-tumour heterogeneity is one of cancer’s most fundamental features. Patient stratification based on drug response prediction is hence needed for effective anti-cancer therapy. However, single-gene markers of response are rare and/or may fail to achieve a significant impact in the clinic. Machine Learning (ML) is emerging as a particularly promising complementary approach to precision oncology. (2) Methods: Here we leverage comprehensive Patient-Derived Xenograft (PDX) pharmacogenomic data sets with dimensionality-reducing ML algorithms with this purpose. (3) Results: Combining multiple gene alterations via ML leads to better discrimination between sensitive and resistant PDXs in 19 of the 26 analysed cases. Highly predictive ML models employing concise gene lists were found for three cases: paclitaxel (breast cancer), binimetinib (breast cancer) and cetuximab (colorectal cancer). Interestingly, each of these multi-gene ML models identifies some treatment-responsive PDXs not harbouring the best actionable mutation for that case. Thus, ML multi-gene predictors generally have much fewer false negatives than the corresponding single-gene marker. (4) Conclusions: As PDXs often recapitulate clinical outcomes, these results suggest that many more patients could benefit from precision oncology if ML algorithms were also applied to existing clinical pharmacogenomics data, especially those algorithms generating classifiers combining data-selected gene alterations.
The Role of microRNA in Pancreatic Cancer
Authors: Smolarz Beata , Durczyński Adam , Romanowicz Hanna , Hogendorf Piotr
Published: September 2021

MicroRNAs (miRNAs) are small ribonucleic acid molecules that play a key role in regulating gene expression. The increasing number of studies undertaken on the functioning of microRNAs in the tumor formation clearly indicates their important potential in oncological therapy. Pancreatic cancer is one of the deadliest cancers. The expression of miRNAs released into the bloodstream appears to be a good indicator of progression and evaluation of the aggressiveness of pancreatic cancer, as indicated by studies. The work reviewed the latest literature on the importance of miRNAs for pancreatic cancer development.
Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones
Authors: Bailly Christian
Published: September 2021

Sesquiterpene lactones (SLs) are abundant in plants and display a large spectrum of bioactivities. The compound britannin (BRT), found in different Inula species, is a pseudoguaianolide-type SL equipped with a typical and highly reactive α-methylene-γ-lactone moiety. The bioproperties of BRT and related pseudoguaianolide SLs, including helenalin, gaillardin, bigelovin and others, have been reviewed. Marked anticancer activities of BRT have been evidenced in vitro and in vivo with different tumor models. Three main mechanisms are implicated: (i) interference with the NFκB/ROS pathway, a mechanism common to many other SL monomers and dimers; (ii) blockade of the Keap1-Nrf2 pathway, with a covalent binding to a cysteine residue of Keap1 via the reactive α-methylene unit of BRT; (iii) a modulation of the c-Myc/HIF-1α signaling axis leading to a downregulation of the PD-1/PD-L1 immune checkpoint and activation of cytotoxic T lymphocytes. The non-specific reactivity of the α-methylene-γ-lactone moiety with the sulfhydryl groups of proteins is discussed. Options to reduce or abolish this reactivity have been proposed. Emphasis is placed on the capacity of BRT to modulate the tumor microenvironment and the immune-modulatory action of the natural product. The present review recapitulates the anticancer effects of BRT, some central concerns with SLs and discusses the implication of the PD1/PD-L1 checkpoint in its antitumor action.
Protein-Bound Uremic Toxins Induce Reactive Oxygen Species-Dependent and Inflammasome-Mediated IL-1β Production in Kidney Proximal Tubule Cells
Authors: Mihajlovic Milos , Krebber Merle M. , Yang Yi , Ahmed Sabbir , Lozovanu Valeria , Andreeva Daria , Verhaar Marianne C. , Masereeuw Rosalinde
Published: September 2021

Protein bound-uremic toxins (PBUTs) are not efficiently removed by hemodialysis in chronic kidney disease (CKD) patients and their accumulation leads to various co-morbidities via cellular dysfunction, inflammation and oxidative stress. Moreover, it has been shown that increased intrarenal expression of the NLRP3 receptor and IL-1β are associated with reduced kidney function, suggesting a critical role for the NLRP3 inflammasome in CKD progression. Here, we evaluated the effect of PBUTs on inflammasome-mediated IL-1β production in vitro and in vivo. Exposure of human conditionally immortalized proximal tubule epithelial cells to indoxyl sulfate (IS) and a mixture of anionic PBUTs (UT mix) increased expression levels of NLRP3, caspase-1 and IL-1β, accompanied by a significant increase in IL-1β secretion and caspase-1 activity. Furthermore, IS and UT mix induced the production of intracellular reactive oxygen species, and caspase-1 activity and IL-1β secretion were reduced in the presence of antioxidant N-acetylcysteine. IS and UT mix also induced NF-κB activation as evidenced by p65 nuclear translocation and IL-1β production, which was counteracted by an IKK inhibitor. In vivo, using subtotal nephrectomy CKD rats, a significant increase in total plasma levels of IS and the PBUTs, kynurenic acid and hippuric acid, was found, as well as enhanced urinary malondialdehyde levels. CKD kidney tissue showed an increasing trend in expression of NLRP3 inflammasome components, and a decreasing trend in superoxide dismutase-1 levels. In conclusion, we showed that PBUTs induce inflammasome-mediated IL-1β production in proximal tubule cells via oxidative stress and NF-κB signaling, suggesting their involvement in disease-associated inflammatory processes.
Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench
Authors: Chen Wei-Teing , Lin Yu-Huei , Changchien Chih-Ying , Chen Ying , Chang Hsin-Han , Tsai Wen-Chiuan , Tsai Hao-Chung , Wang Chieh-Yung , Shen Ming-Sheng , Cheng Li-Ting , Tsai Chen-Liang
Published: September 2021

Malignant-associated pleural fluid (MAPF) represented an unsolved problem in advanced lung cancer. Our previous work characterized increased pleural angiogenesis in lung adenocarcinoma and the propensity of MAPF on endothelial angiogenesis. This study investigated the combined efficacy of the tyrosine kinase inhibitor (gefitinib) and bevacizumab in opposing MAPF-induced angiogenesis. In lung adenocarcinoma patients with malignant pleural effusion (MPE), Kaplan–Meier analysis revealed the benefit of cotreatment with target therapy and bevacizumab. Increased EGFR expression was observed in the pleural microvessels of patients with lung adenocarcinoma both with and without mutations in EGFR. MAPF was obtained from lung adenocarcinoma patients both wild-type and mutant EGFRs. Total and phosphorylated EGFR were upregulated in HUVEC cultured with MAPF. Treatment with gefitinib as an EGFR inhibitor suppressed MAPF-induced endothelial migration and partially attenuated endothelial proliferation in both wild-type and mutant EGFR lung adenocarcinoma. Cotreatment with gefitinib and bevacizumab produced better inhibition of MAPF-induced endothelial angiogenesis than gefitinib alone in the mutant EGFR subgroup. Protein analysis of MAPF-derived exosomes revealed abundant EGFR and p-EGFR components that implied possible transfer to endothelial cells. Concluding Kaplan–Meier analysis and in vitro studies, the results indicated that the addition of bevacizumab on gefitinib treatment could suppress MAPF-induced angiogenesis in lung adenocarcinoma patients.
Telomeres and Age-Related Diseases
Authors: Gruber Hans-Jürgen , Semeraro Maria Donatella , Renner Wilfried , Herrmann Markus
Published: September 2021

Telomeres are at the non-coding ends of linear chromosomes. Through a complex 3-dimensional structure, they protect the coding DNA and ensure appropriate separation of chromosomes. Aging is characterized by a progressive shortening of telomeres, which compromises their structure and function. Because of their protective function for genomic DNA, telomeres appear to play an important role in the development and progression of many age-related diseases, such as cardiovascular disease (CVD), malignancies, dementia, and osteoporosis. Despite substantial evidence that links telomere length with these conditions, the nature of these observations remains insufficiently understood. Therefore, future studies should address the question of causality. Furthermore, analytical methods should be further improved with the aim to provide informative and comparable results. This review summarize the actual knowledge of telomere biology and the possible implications of telomere dysfunction for the development and progression of age-related diseases. Furthermore, we provide an overview of analytical techniques for the measurement of telomere length and telomerase activity.
Classifying Oligometastatic Non-Small Cell Lung Cancer
Authors: Blumenthaler Alisa N. , Antonoff Mara B.
Published: September 2021

An oligometastatic cancer state was first postulated in the 1990s by Hellman and Weichselbaum and described limited metastatic spread to a single or few sites of disease. It was hypothesized that this metastatic entity falls along a continuum of the natural history of cancer progression from a localized primary tumor to widespread metastases. Support for oligometastatic non-small cell lung cancer (NSCLC) has since been provided by multiple retrospective studies and then prospective randomized trials demonstrating better survival in this patient population after aggressive consolidative treatment. However, the lack of a universal definition of oligometastatic NSCLC has hindered a comparison between different studies and prevented well-defined recommendations for local consolidative treatment in this patient population. Attempts have been made to establish a common definition for use in clinical management and for the identification of inclusion criteria for future trials. In this review, we seek to summarize the current definitions of oligometastatic NSCLC based on recent expert consensus statements, previous randomized trials, and current treatment guidelines and to highlight the continued variability in current practice.
Regeneration of an Aged Hydrodesulfurization Catalyst by Non-Thermal Plasma: Characterization of Refractory Coke Molecules
Authors: Srour Hawraa , Guignard Nadia , Tarighi Mehrad , Devers Elodie , Mekki-Berrada Adrien , Toufaily Joumana , Hamieh Tayssir , Batiot-Dupeyrat Catherine , Pinard Ludovic
Published: September 2021

This study describes the phenomena involved during the regeneration of an aged industrial hydrodesulfurization catalyst (CoMoP/Al2O3) using a non-thermal plasma at a low temperature (200 °C). The changes occurring during regeneration were studied by characterizing spent, partially, and fully regenerated catalysts by XRD, Raman, TEM spectroscopy, and the coke deposited on the catalyst surface by Laser desorption/ionization time-of-flight mass spectrometry (LDI TOF/MS). The coke is a mixture of several polycyclic molecules, the heaviest with a coronene backbone, containing up to seven sulfur atoms. This kinetic study shows that the oxidation rate depends on the nature of the coke. Hence, explaining the formation of VOCs from heavy polycyclic carbon molecules without complete oxidation to CO2. However, XRD and Raman spectroscopies evidence CoMoO4 formation after a long treatment time, indicating hot spots during the regeneration.
Covalent Immobilisation of a Nanoporous Platinum Film onto a Gold Screen-Printed Electrode for Highly Stable and Selective Non-Enzymatic Glucose Sensing
Authors: McCormick Wesley , McDonagh Pádraig , Doran John , McCrudden Denis
Published: September 2021

Progress in the development of commercially available non-enzymatic glucose sensors continues to be problematic due to issues regarding selectivity, reproducibility and stability. Overcoming these issues is a research challenge of significant importance. This study reports a novel fabrication process using a double-layer self-assembly of (3 mercaptopropyl)trimethoxysilane (MPTS) on a gold substrate and co-deposition of a platinum–copper alloy. The subsequent electrochemical dealloying of the less noble copper resulted in a nanoporous platinum structure on the uppermost exposed thiol groups. Amperometric responses at 0.4 V vs. Ag/AgCl found the modification to be highly selective towards glucose in the presence of known interferants. The sensor propagated a rapid response time <5 s and exhibited a wide linear range from 1 mM to 18 mM. Additionally, extremely robust stability was attributed to enhanced attachment due to the strong chemisorption between the gold substrate and the exposed thiol of MPTS. Incorporation of metallic nanomaterials using the self-assembly approach was demonstrated to provide a more reproducible and controlled molecular architecture for sensor fabrication. The successful application of the sensor in real blood serum samples displayed a strong correlation with clinically obtained glucose levels.
Potentiometric C2H4-Selective Detection on Solid-State Sensors Activated with Bifunctional Catalytic Nanoparticles
Authors: Toldra-Reig Fidel , Serra Jose Manuel
Published: September 2021

This work presents a solid-state ionic-based device to selectively detect C2H4 in car exhaust gases. The sensor consists of 8YSZ as the electrolyte and two electrodes: Fe0.7Cr1.3O3/8YSZ and LSM/8YSZ. The main aim of this work is to optimize the catalytic behavior of the working electrode to C2H4 and reduce cross-sensitivity toward CO and H2O. Several catalyst nanoparticles were infiltrated to tailor C2H4 adsorption and electrochemical oxidation properties while diminishing adsorption and conversion of other gas components such as CO. The infiltrated metal catalysts were selected, taking into account both adsorption and redox properties. Infiltration of Ti or Al, followed by a second infiltration of Ni, enabled the selective detection of C2H4 with low cross-sensitivity toward CO and H2O in a moist gas environment. Further insight into potentiometric C2H4 sensing is achieved by electrochemical impedance analysis of the electrodes activated with bifunctional catalysts.
Clinical Manifestations of Herpes Zoster Associated with Complications in Children
Authors: Kang Dong Ha , Kwak Byung Ok , Park A Young , Kim Han Wool
Published: September 2021

Herpes zoster (HZ) is caused by latent varicella-zoster virus (VZV) reactivation when VZV-specific cell-mediated immunity declines. Information on HZ in children is limited. Therefore, we retrospectively investigated HZ’s clinical course and complications in children. We extracted the outpatient and hospitalization medical records of pediatric patients (<19 years) primarily diagnosed with HZ (ICD-10 B02 code) between January 2010 and November 2020. HZ was defined as a typical unilateral dermatomal vesicular rash where HZ was the treating physician’s primary diagnosis. Recognized HZ complications included combined bacterial skin infection, ophthalmic zoster, zoster oticus without facial paralysis, meningitis, and PHN. We identified 602 HZ cases, among which 54 developed HZ complications and were included in our analysis. The median age was 14.7 years, most patients were aged ≥13 years (42, 79%), and none were aged <4 years. Fifty-three were immunocompetent, and only one had systemic lupus erythematosus. The most frequent complication was zoster ophthalmicus (n = 26, 48%). HZ complications were also observed in immunocompetent or vaccinated children exhibiting a head or neck rash before and after VZV immunization. Current VZV vaccination programs may be insufficient in preventing HZ complications. Therefore, close varicella and HZ burden monitoring and the establishment of effective VZV vaccination programs are imperative.
Association of Manganese Biomarker Concentrations with Blood Pressure and Kidney Parameters among Healthy Adolescents: NHANES 2013–2018
Authors: Politis Maria , Freedman Jacob , Haynes Erin , Sanders Alison
Published: September 2021

Deficiency or excess exposure to manganese (Mn), an essential mineral, may have potentially adverse health effects. The kidneys are a major organ of Mn site-specific toxicity because of their unique role in filtration, metabolism, and excretion of xenobiotics. We hypothesized that Mn concentrations were associated with poorer blood pressure (BP) and kidney parameters such as estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and albumin creatinine ratio (ACR). We conducted a cross-sectional analysis of 1931 healthy U.S. adolescents aged 12–19 years participating in National Health and Nutrition Examination Survey cycles 2013–2014, 2015–2016, and 2017–2018. Blood and urine Mn concentrations were measured using inductively coupled plasma mass spectrometry. Systolic and diastolic BP were calculated as the average of available readings. eGFR was calculated from serum creatinine using the Bedside Schwartz equation. We performed multiple linear regression, adjusting for age, sex, body mass index, race/ethnicity, and poverty income ratio. We observed null relationships between blood Mn concentrations with eGFR, ACR, BUN, and BP. In a subset of 691 participants, we observed that a 10-fold increase in urine Mn was associated with a 16.4 mL/min higher eGFR (95% Confidence Interval: 11.1, 21.7). These exploratory findings should be interpreted cautiously and warrant investigation in longitudinal studies.
Rhinovirus Infection and Familial Atopy Predict Persistent Asthma and Sensitisation 7 Years after a First Episode of Acute Bronchiolitis in Infancy
Authors: Magnier Julie , Julian Valérie , Mulliez Aurélien , Usclade Alexandra , Rochette Emmanuelle , Evrard Bertrand , Amat Flore , Egron Carole
Published: September 2021

Background: We set out to assess the risk factors for asthma outcome in a cohort of infants who experienced their first episode of acute bronchiolitis. Methods: A cohort of 222 infants who were included during a first episode of acute bronchiolitis was prospectively followed. Herein, we present the results of their assessments (symptom history, skin prick tests, specific IgE assay, respiratory function tests) at age seven. Results: Of the 68/222 (30.6%) children assessed at age seven, 15 (22.05%) presented with asthma and were mainly males (p = 0.033), 14 (20%) had respiratory allergies, 17 (25%) presented atopic dermatitis and none had a food allergy. Family history of atopy was associated with asthma and sensitisation to aeroallergens at age seven (p = 0.003, p = 0.007). Rhinovirus (hRV) infection and rhinovirus/respiratory syncytial virus (RSV) co-infection were significantly associated with asthma at age seven (p = 0.035, p = 0.04), but not with the initial severity of bronchiolitis. Eosinophil counts at ages three and seven were significantly higher in the asthmatics (p = 0.01, p = 0.046). Conclusion: Any infant, especially male, presenting a first episode of acute bronchiolitis due to hRV with a family history of atopy should be closely monitored via follow-up due to a higher risk for asthma at school age.
Pediatric Optic Neuritis: Description of Four Cases and Review of the Literature
Authors: Presicci Anna , Serra Maria , Achille Mariaclara , Caputo Elvita , Margari Lucia
Published: September 2021

Pediatric optic neuritis (PON) may be a clinically isolated and self-limiting event or may present in the context of underlying neurologic, infective, or systemic disease. PON has a high impact on the quality of life as it may or may not evolve into other acquired demyelinating syndromes (ADSs), such as multiple sclerosis (MS), neuromyelitis optica (NMO), or other syndromes related to the myelin oligodendrocyte glycoprotein IgG antibodies (MOG-IgG). These different PON phenotypes present variable clinical and radiological features, plasma and liquor biomarkers, and prognosis. We describe four pediatric cases presenting clinically with ON, with different etiopathogenetic pictures: one case had a probable infective etiology, while the others were associated with different demyelinating disorders (MS, NMO, syndrome related to MOG-IgG). We discuss the possible evolution of presenting ON in other ADSs, based on recent literature. A careful evaluation of the clinical and investigation findings and the natural course of PON is necessary to define its pathogenic pathway and evolution. Further prolonged follow-up studies are needed to highlight the predictors of PON evolution, its potential sequelae, and the best treatment options.
Improving Early Diagnosis of Child Neglect for a Better Response in Healthcare Settings
Authors: Herrero-Roldán Silvia , León Inmaculada , Hernández-Cabrera Juan Andrés , Rodrigo María José
Published: September 2021

Early diagnosis of child neglect is an ongoing challenge with consequences of the child’s safety, health, and effective referral for intervention. This study aims to obtain a selected set of family, maternal, and dyadic variables of the immediate caregiving environment for diagnosis, preventive, and intervention responses in healthcare settings. Mothers and their children under five years old: 51 in the neglected group (NG) and 89 in the non-neglected control group (CG), were recruited through pediatric primary care services and social services in Spain. Family demographics, adverse events, childhood maltreatment, maternal psychopathologies, personality variables, and observed mother–child interactions were assessed. Gradient boosting analyses were applied for the contributor’s relative importance (RI), followed by logistic regression and discriminant analyses for those with higher RI. Parametric analyses showed high diagnostic accuracy (80–82% of NG and 92% of CG) for risky factors of child neglect: having a physically neglected and depressed mother, living in families in need of financial assistance, and large families; and for protective factors: having an older mother and showing higher mother–child emotional availability. Identifying a select group of features makes early diagnosis and preventive intervention more effective for mitigating the impact of child neglect and building mother–child resilience.
Effect of SiC Particle Contents and Size on the Microstructure and Dissolution of SiC-Hydroxyapatite Coatings
Authors: Yang Li , Mao Zuli
Published: September 2021

Carbon/carbon composites, when used as bone implant materials, do not adhere well to the bone tissues because of their non-bioactive characteristics. Therefore, we electro-deposited SiC-hydroxyapatite coatings (with an ultrasound-assisted step) on carbon/carbon composites. We analyzed how the content and size of the SiC particles affected the structure, morphology, bonding strength and dissolution of the SiC-hydroxyapatite coatings. The hydroxyapatite coating dissolution properties were assessed by the released Ca2+ and the weight loss. The SiC-hydroxyapatite coating on naked carbon/carbon composites showed a more compact microstructure in comparison to the hydroxyapatite coating on carbon/carbon composites. The reasons for the changes in the microstructure and the improvement in the adhesion of the coatings on C/C were discussed. Moreover, the addition of SiC particles increased the binding strengths of the hydroxyapatite coating on C/C composite, as well as reduced the dissolution rate of the hydroxyapatite coating.