bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbapenemase-Producing Extraintestinal Pathogenic Escherichia coli From Argentina: Clonal Diversity and Predominance of Hyperepidemic Clones CC10 and CC131
Authors: Sanz María Belén , De Belder Denise , de Mendieta JM , Faccone Diego , Poklepovich Tomás , Lucero Celeste , Rapoport Melina , Campos Josefina , Tuduri Ezequiel , Saavedra Mathew O. , Van der Ploeg Claudia , Rogé Ariel ,   Carbapenemases-ExPEC Group
Published: April 2022

Extraintestinal pathogenic Escherichia coli (ExPEC) causes infections outside the intestine. Particular ExPEC clones, such as clonal complex (CC)/sequence type (ST)131, have been known to sequentially accumulate antimicrobial resistance that starts with chromosomal mutations against fluoroquinolones, followed with the acquisition of blaCTX–M–15 and, more recently, carbapenemases. Here we aimed to investigate the distribution of global epidemic clones of carbapenemase-producing ExPEC from Argentina in representative clinical isolates recovered between July 2008 and March 2017. Carbapenemase-producing ExPEC (n = 160) were referred to the Argentinean reference laboratory. Of these, 71 were selected for genome sequencing. Phenotypic and microbiological studies confirmed the presence of carbapenemases confirmed as KPC-2 (n = 52), NDM-1 (n = 16), IMP-8 (n = 2), and VIM-1 (n = 1) producers. The isolates had been recovered mainly from urine, blood, and abdominal fluids among others, and some were from screening samples. After analyzing the virulence gene content, 76% of the isolates were considered ExPEC, although non-ExPEC isolates were also obtained from extraintestinal sites. Pan-genome phylogeny and clonal analysis showed great clonal diversity, although the first phylogroup in abundance was phylogroup A, harboring CC10 isolates, followed by phylogroup B2 with CC/ST131, mostly H30Rx, the subclone co-producing CTX-M-15. Phylogroups D, B1, C, F, and E were also detected with fewer strains. CC10 and CC/ST131 were found throughout the country. In addition, CC10 nucleated most metalloenzymes, such as NDM-1. Other relevant international clones were identified, such as CC/ST38, CC155, CC14/ST1193, and CC23. Two isolates co-produced KPC-2 and OXA-163 or OXA-439, a point mutation variant of OXA-163, and three isolates co-produced MCR-1 among other resistance genes. To conclude, in this work, we described the molecular epidemiology of carbapenemase-producing ExPEC in Argentina. Further studies are necessary to determine the plasmid families disseminating carbapenemases in ExPEC in this region.
Source Tracker Modeling Based on 16S rDNA Sequencing and Analysis of Microbial Contamination Sources for Pasteurized Milk
Authors: Du Bingyao , Meng Lu , Wu Haoming , Yang Huaigu , Liu Huimin , Zheng Nan , Zhang Yangdong , Zhao Shengguo , Wang Jiaqi
Published: April 2022

Milk is rich in fat, protein, minerals, vitamins, peptides, immunologically active substances, and other nutrients, and it plays an important role in satisfying human nutrition and health. However, dairy product safety incidents caused by microbial contamination have occurred. We found that the total bacterial numbers in the pasteurized product were low and far below the limit requirements of the food safety standards of the European Union, the United States, and China. At the genus level, the primary microbial groups found in milk samples were Acinetobacter, Macrococcus, Pseudomonas, and Lactococcus, while in the equipment rinse water and air samples there was contamination by Stenotrophomonas and Acinetobacter. The Source Tracker model analysis indicated that the microorganisms in the final milk products were significantly related to the contamination in product tanks and raw milk. Therefore, it is the hope that this work can provide guidance to pinpoint contamination problems using the proper quality control sampling at specific stages in the pasteurization process.
Diving into Social Innovation: A Bibliometric Analysis
Authors: Martins Tânia , Braga Alexandra , Ferreira Marisa R. , Braga Vítor
Published: April 2022

This paper aims to map and analyze the scientific production of social innovation, resulting in a contribution to the literature review and guidelines for future research. A bibliometric analysis was conducted to explore the trends on the topic. The primary objectives are (1) to identify how the literature defines the concept of social innovation and to track its evolution; (2) to measure productivity and identify key authors and scientific journals with the highest impact in the field and the association networks between their respective institutions and countries of origin; (3) to analyze and map citations, co-citations, and research topics to pinpoint the topics and dimensions related to social innovation in order to propose future research. Our paper clarifies the concept of social innovation, reports the progresses achieved within this research field, and measures the productivity on this specific topic.
Comparative Analysis of Transcriptome Profiles Reveals the Mechanisms in the Difference of Low Potassium Tolerance among Cultivated and Tibetan Wild Barleys
Authors: Ye Zhilan , He Xinyi , Liu Chaorui
Published: April 2022

Potassium (K) deficiency is a bottleneck for crop production. Thus, developing low K (LK)-tolerant crop cultivars to relieve the issue is extremely urgent. Our previous studies had found that Tibetan annual wild barley accessions showed a higher LK tolerance than the cultivated barley. In this study, RNA-sequencing was performed on three barley genotypes, wild (XZ153, LK tolerance; XZ141, LK sensitivity) and cultivated (ZD9, LK sensitivity) barley genotypes, to compare the transcriptome profiles of their shoots at two time points after LK stress. In total, 4832 genes displayed differential expression at 48 h and 15 d among three genotypes after K stress treatment, with XZ153 having much more differentially expressed genes (DEGs) at 48 h than 15 d, but it was the opposite in ZD9. Meanwhile, GO annotation analysis and KEGG pathway enrichment were implemented on 555 and 814 LK tolerance-associated DEGs at 48 h and 15 d after LK stress, respectively. Three barley genotypes differed significantly in transcriptional level after LK treatment. The high tolerance in wild genotype XZ153 could be attributed to many factors, mainly including K channels, Ca2+ signaling pathway, ethylene biosynthesis process, TCA cycle, glycolysis, pentose phosphate pathway, and photosynthesis. Furthermore, some candidate genes identified in this study may be used to improve the LK tolerance of barley.
The Transcription Regulator YgeK Affects Biofilm Formation and Environmental Stress Resistance in Avian Pathogenic Escherichia coli
Authors: Xue Mei , Fu Dandan , Hu Jiangang , Shao Ying , Tu Jian , Song Xiangjun , Qi Kezong
Published: April 2022

Avian pathogenic Escherichia coli (APEC) is one of the most common pathogens in poultry and a potential gene source of human extraintestinal pathogenic E. coli (ExPEC), leading to serious economic losses in the poultry industry and public health concerns. Exploring the pathogenic mechanisms underpinning APEC and the identification of new targets for disease prevention and treatment are warranted. YgeK is a transcriptional regulator in APEC and is localized to the type III secretion system 2 of E. coli. In our previous work, the transcription factor ygeK significantly affected APEC flagella formation, bacterial motility, serum sensitivity, adhesion, and virulence. To further explore ygeK functions, we evaluated its influence on APEC biofilm formation and resistance to environmental stress. Our results showed that ygeK inactivation decreased biofilm formation and reduced bacterial resistance to environmental stresses, including acid and oxidative stress. In addition, the multi-level regulation of ygeK in APEC was analyzed using proteomics, and associations between differentially expressed proteins and the key targets of ygeK were investigated. Overall, we identified ygeK’s new function in APEC. These have led us to better understand the transcriptional regulatory ygeK and provide new clues about the pathogenicity of APEC.
Prevalence, Mechanism, Genetic Diversity, and Cross-Resistance Patterns of Methicillin-Resistant Staphylococcus Isolated from Companion Animal Clinical Samples Submitted to a Veterinary Diagnostic Laboratory in the Midwestern United States
Authors: Adiguzel Mehmet Cemal , Schaefer Kayla , Rodriguez Trevor , Ortiz Jessica , Sahin Orhan
Published: April 2022

Methicillin-resistant Staphylococcus (MRS) is a leading cause of skin and soft tissue infections in companion animals, with limited treatment options available due to the frequent cross-resistance of MRS to other antibiotics. In this study, we report the prevalence, species distribution, genetic diversity, resistance mechanism and cross-resistance patterns of MRS isolated from companion animal (mostly dog and cat) clinical cases submitted to Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) between 2012 and 2019. The majority of isolates were identified as Staphylococcus pseudintermedius (68.3%; 2379/3482) and coagulase-negative Staphylococcus (CoNS) (24.6%; 857/3482), of which 23.9% and 40.5% were phenotypically resistant to methicillin, respectively. Cross resistance to other β-lactams (and to a lesser extent to non-β-lactams) was common in both methicillin-resistant S. pseudintermedius (MRSP) and CoNS (MRCoNS), especially when oxacillin MIC was ≥4 μg/mL (vs. ≥0.5–<4 μg/mL). The PBP2a protein was detected by agglutination in 94.6% (521/551) MRSP and 64.3% (146/227) MRCoNS. A further analysis of 31 PBP2a-negative MRS isolates (all but one MRCoNS) indicated that 11 were mecA gene-positive while 20 were negative for mecA and other mec genes by PCR. The resistance to last-resort anti-staphylococcal human drugs (e.g., tigecycline, linezolid, vancomycin) among the MRS tested was none to very low. Even though genotyping indicated an overall high level of genetic diversity (87 unique PFGE patterns and 20 MLST types) among a subset of MRSP isolates tested (n = 106), certain genotypes were detected from epidemiologically connected cases at the same or different time points, suggesting persistence and/or nosocomial transmission. These results indicate a relatively high prevalence of MRS from companion animals in the Midwestern US; therefore, it is important to perform routine susceptibility testing of Staphylococcus in veterinary clinical settings for the selection of appropriate antimicrobial therapy.
Structural Characterization of Two Short Unspecific Peroxygenases: Two Different Dimeric Arrangements
Authors: Linde Dolores , Santillana Elena , Fernández-Fueyo Elena , González-Benjumea Alejandro , Carro Juan , Gutiérrez Ana , Martínez Angel T. , Romero Antonio
Published: April 2022

Unspecific peroxygenases (UPOs) are extracellular fungal enzymes of biotechnological interest as self-sufficient (and more stable) counterparts of cytochrome P450 monooxygenases, the latter being present in most living cells. Expression hosts and structural information are crucial for exploiting UPO diversity (over eight thousand UPO-type genes were identified in sequenced genomes) in target reactions of industrial interest. However, while many thousands of entries in the Protein Data Bank include molecular coordinates of P450 enzymes, only 19 entries correspond to UPO enzymes, and UPO structures from only two species (Agrocybe aegerita and Hypoxylon sp.) have been published to date. In the present study, two UPOs from the basidiomycete Marasmius rotula (rMroUPO) and the ascomycete Collariella virescens (rCviUPO) were crystallized after sequence optimization and Escherichia coli expression as active soluble enzymes. Crystals of rMroUPO and rCviUPO were obtained at sufficiently high resolution (1.45 and 1.95 Å, respectively) and the corresponding structures were solved by molecular replacement. The crystal structures of the two enzymes (and two mutated variants) showed dimeric proteins. Complementary biophysical and molecular biology studies unveiled the diverse structural bases of the dimeric nature of the two enzymes. Intermolecular disulfide bridge and parallel association between two α-helices, among other interactions, were identified at the dimer interfaces. Interestingly, one of the rCviUPO variants incorporated the ability to produce fatty acid diepoxides—reactive compounds with valuable cross-linking capabilities—due to removal of the enzyme C-terminal tail located near the entrance of the heme access channel. In conclusion, different dimeric arrangements could be described in (short) UPO crystal structures.
Flaxseed Ethanol Extracts’ Antitumor, Antioxidant, and Anti-Inflammatory Potential
Authors: Chera Elisabeta Ioana , Pop Raluca Maria , Pârvu Marcel , Sorițău Olga , Uifălean Ana , Cătoi Florinela Adriana , Cecan Andra , Negoescu Andrada Gabriela , Achimaș-Cadariu Patriciu , Pârvu Alina Elena
Published: April 2022

The antitumoral, antioxidant, and anti-inflammatory effects of flaxseed ethanol extract was screened. Phytochemical analysis was performed by measuring the total phenolic content and by HPLC-DAD-ESI MS. In vitro antiproliferative activity was appreciated by MMT test of four adenocarcinomas and two normal cell lines. In vitro, antioxidant activity was evaluated by DPPH, FRAP, H2O2, and NO scavenging tests. The in vivo growth inhibitory activity against Ehrlich ascites carcinoma (EAC) in female BALB/c mice was determined using the trypan blue test. In EAC mice serum and ascites total oxidative status, total antioxidant reactivity, oxidative stress index, malondialdehyde, total thiols, total nitrites, 3-nitrotyrosine, and NFkB were measured. The phytochemical analysis found an significant content of phenols, with lignans having the highest concentration. The extract had an significant in vitro antioxidant effect and different inhibitory effects on different cell lines. After treatment of EAC mice with flaxseeds extract, body weight, ascites volume and viable tumour cell count, serum and ascites oxidative stress, and inflammatory markers decreased significantly. The ethanol flaxseeds extract has potential antiproliferative activity against some ovary and endometrial malignant cells and EAC. This effect can be attributed to the phenols content, and its antioxidant and anti-inflammatory activity.
Hydroxytyrosol Promotes the Mitochondrial Function through Activating Mitophagy
Authors: Dong Yanzou , Yu Manhan , Wu Youlin , Xia Tian , Wang Ling , Song Kai , Zhang Chunxiao , Lu Kangle , Rahimnejad Samad
Published: April 2022

Emerging evidence suggests that mitochondrial dysfunction mediates the pathogenesis for non-alcoholic fatty liver disease (NAFLD). Hydroxytyrosol (HT) is a key component of extra virgin olive oil which can exert beneficial effects on NAFLD through modulating mitochondria. However, the mechanism of the impacts of HT still remains elusive. Thus, an in vivo and a series of in vitro experiments were carried out to examine the impacts of hydroxytyrosol (HT) on lipid metabolism and mitochondrial function in fish. For the in vivo experiment, two diets were produced to contain 10% and 16% fat as normal-fat and high-fat diets (NFD and HFD) and two additional diets were prepared by supplementing 200 mg/kg of HT to the NFD and HFD. The test diets were fed to triplicate groups of spotted seabass (Lateolabrax maculatus) juveniles for 8 weeks. The results showed that feeding HFD leads to increased fat deposition in the liver and induces oxidative stress, both of which were ameliorated by HT application. Furthermore, transmission electron microscopy revealed that HFD destroyed mitochondrial cristae and matrix and induced severe hydropic phenotype, while HT administration relieved these alterations. The results of in vitro studies using zebrafish liver cell line (ZFL) showed that HT promotes mitochondrial function and activates PINK1-mediated mitophagy. These beneficial effects of HT disappeared when the cells were treated with cyclosporin A (Csa) as a mitophagy inhibitor. Moreover, the PINK1-mediated mitophagy activation by HT was blocked when compound C (CC) was used as an AMPK inhibitor. In conclusion, our findings demonstrated that HT alleviates fat accumulation, oxidative stress and mitochondrial dysfunction, and its effects are deemed to be mediated via activating mitophagy through the AMPK/PINK1 pathway.
Leveraging Quantity Surveying Data and BIM to Automate Mechanical and Electrical (M & E) Construction Planning
Authors: Sbiti Maroua , Beladjine Djaoued , Beddiar Karim , Mazari Bélahcène
Published: April 2022

Despite the great potential of LPS and BIM to improve construction project productivity, the full integration of these modern production and information management systems at the data processing level is not yet achieved. After matching the literature to empirical studies in a Constructive Research Approach, it emerged that very few studies have investigated how buildings’ data could be preserved and continuously evolve during the project lifecycle. Accordingly, we underline the potential role of data warehousing in rendering operational data as a strategic asset for decision making. These findings motivate the present research, which aims to capitalize on quantity surveying data in order to automate the generation of M & E installation schedules. This paper first introduces the system functional requirements. Then, it proposes a conceptual scheme for the planning data mart (a data warehouse subset dedicated to planning subject area). Furthermore, we shed light on the M & E fragnet standardization procedure and how data have been processed. Finally, we present the current software developments to demonstrate the feasibility of this concept.
Fast Extraction of Coupling of Modes Parameters for Surface Acoustic Wave Devices Using Finite Element Method Based Simulation
Authors: Ma Xiaoxin , Lei Huaming , Cai Ping , Ji Xiaojun
Published: April 2022

The finite element method (FEM) has been applied to extract the coupling-of-modes (COM) parameters of surface acoustic wave (SAW) devices for a long time. It always involves calculating the dispersive curves or harmonic admittance, which makes the extraction process and results sophisticated, time-consuming and inaccurate. Therefore, a simple method is proposed to extract all COM parameters of the SAW devices rapidly and accurately in this paper. It is based on the FEM and combines the stationary analysis with modal analysis. We have described in detail the basic principles and procedures of the proposed method, and made a comprehensive comparison between the proposed method and the other two existing methods. We have also examined the proposed method by extracting COM parameters of some common SAW substrate, and compared our extracted results with those reported in the other literatures. Results show that our proposed method holds higher accuracy and more efficiency (~s order) than the others (~h order). Moreover, our extracted COM parameters are in an excellent agreement with those reported in the other literatures.
Development of Active Microvibration Isolation System for Precision Space Payload
Authors: Qian Yuchen , Xie Yong , Jia Jianjun , Zhang Liang
Published: April 2022

In this study, an active microvibration isolation system is developed for precision space payload. Vibrational environment affects the performance and reliability of measuring instruments. To improve the measurement accuracy of the precision space payload, an active vibration isolation system based on eight vibration isolation modules, which are applied for microvibration isolation on the satellite, is designed. A vibration suppression control strategy for multiple degrees of freedom is studied. A hybrid control method involving a feedback and a feedforward controller based on a nonlinear tracking differentiator and an nth-order weak integrator, respectively, was adopted to optimize the suppression effect of microvibration. As a result, the microvibration of the order of mg can be reduced to the order of μg through the active control of modules. Research experiment results show that the root cumulative power spectral density of the systemic sensitive frequency band in the range of 0.5–200 Hz, i.e., microvibration frequency band in the optical reference cavity, has been reduced to in the order of μg in three directions, which satisfied the requirements of aerospace engineering.
Improving Quality Control Methods to Test Strengthening Technologies: A Multilevel Model of Acoustic Pulse Flow
Authors: Grigorev Egor , Nosov Viktor
Published: April 2022

This article describes an approach that makes it possible to substantiate quality control criteria and methods to improve strengthening technologies. The approach was used to test the quality of products made using these technologies and analyze different strengthening methods applied to structural materials. In the experiment, samples of welded joints subjected to various types of strengthening were used that underwent acoustic emission (AE) testing. The results of quick evaluations produced by the proposed multilevel model of acoustic pulse flow were compared with the results of long-term cyclic tests to make a conclusion about the effectiveness of the approach being discussed. To improve strengthening quality control, a method is proposed that can be applied to complex and large-sized structures in the construction industry.
Waste Management in a Sustainable Circular Economy as a Part of Design of Construction
Authors: Spišáková Marcela , Mandičák Tomáš , Mésároš Peter , Špak Matej
Published: April 2022

The Architecture, Engineering, and Construction (AEC) industries are the producers of the most significant waste stream in the European Union. Known EU initiatives propose to deal with the issue of construction and demolition waste (CDW) according to the principles of a circular economy: the 3Rs (reduce, reuse, and recycle). CDW is generated during the whole life cycle of construction. The lack of information about the quantity of CDW during the design phase of building needed for sustainable design of construction was identified as a research gap. The aim of our research is to quantify construction and demolition waste during the construction design phase in a circular economy. The proposed method is based on the generation rate calculation method. This paper describes the proposed methodology for quantifying selected types of construction waste: excavated soil, concrete, and masonry. This information is essential from the point of view of a sustainable circular economy. The main contributions of the paper were identified during the decision-making process of sustainable building design, during the audit of CDW management, and during building information modelling as a support tool for CDW management. As early as the construction design phase, there is the possibility of choosing technologies, construction processes, and materials that have a higher degree of circularity in the economy.
Waterproof Performance of Sealing Gasket in Shield Tunnel: A Review
Authors: Gong Chenjie , Wang Yuanye , Ding Wenqi , Lei Mingfeng , Shi Chenghua
Published: April 2022

Rubber gaskets are commonly adopted as the waterproof component in shield tunnels for their outstanding sealing performance. The contact pressure between surfaces generated by the assembly stress ensures that the gaskets resist certain water pressure without leaking. However, with the continuous occurrence of leakage accidents, attention has been drawn to the topic of the waterproof performance of gasketed joint shield tunnels. In this article, prominent contributions to the waterproof performance of sealing gasket in shield tunnels are listed and sorted into four sections: (1) structural behavior of lining and joint; (2) material constitutive model and durability; (3) numerical simulation methods; (4) thermal-mechanical coupling analysis. First, examples of leakage are discussed and tests on gaskets are elucidated, which is followed by a summary of the progress on material mechanical properties and durability. Then, the development of the simulation methods is presented. Finally, the existing research on the thermal-mechanical coupling analysis is summarized. It is found that the contributions to gaskets’ waterproof performance are fruitful, however, with stringent construction conditions, such as the material constitutive model and aging mechanism under special conditions, such as high temperature, numerical simulation, and laboratory test methods, which need to be further explored.
Atmospheric Pollutants Affect Physical Performance: A Natural Experiment in Horse Racing Studied by Principal Component Analysis
Authors: Araneda Oscar F. , Cavada Gabriel
Published: April 2022

The impact of some atmospheric pollutants (PM10, PM2.5, O3, NO2, NO, SO2, CO), humidity and temperature were studied on the performance of thoroughbred racehorses. The study included 162 official handicap races held in 2012 in Santiago de Chile, at distances of 1000, 1100 and 1200 m, on a track in good condition, with a layout that included a bend, during the summer and winter months. The environmental variables were measured at the time of the race and were obtained from a monitoring station located 470 m from the equestrian center. The environmental variables showed an autocorrelation of variables, so they were reduced using principal component analysis. Subsequently, the principal components were correlated with running speed using Pearson’s method. Totals of 60.17 and 23.29% of the total variability of the data was explained by principal components 1 and 2 (PC1 and PC2), respectively. PC1 was mainly determined by NO, NO2, and CO (loadings~0.90) and secondarily by PM10, PM2.5, and SO2 (loadings~0.6), with which the data showed inverse associations, while with temperature and O3 it showed direct associations (loadings~0.7). In addition, this component correlated negatively with running speed (r = −0.50), while PC2 was not associated with this variable. In conclusion, using the principal component analysis strategy, it was determined that running speed is affected by air pollutants.
What Is Parvalbumin for?
Authors: Permyakov Eugene A. , Uversky Vladimir N.
Published: April 2022

Parvalbumin (PA) is a small, acidic, mostly cytosolic Ca2+-binding protein of the EF-hand superfamily. Structural and physical properties of PA are well studied but recently two highly conserved structural motifs consisting of three amino acids each (clusters I and II), which contribute to the hydrophobic core of the EF-hand domains, have been revealed. Despite several decades of studies, physiological functions of PA are still poorly known. Since no target proteins have been revealed for PA so far, it is believed that PA acts as a slow calcium buffer. Numerous experiments on various muscle systems have shown that PA accelerates the relaxation of fast skeletal muscles. It has been found that oxidation of PA by reactive oxygen species (ROS) is conformation-dependent and one more physiological function of PA in fast muscles could be a protection of these cells from ROS. PA is thought to regulate calcium-dependent metabolic and electric processes within the population of gamma-aminobutyric acid (GABA) neurons. Genetic elimination of PA results in changes in GABAergic synaptic transmission. Mammalian oncomodulin (OM), the β isoform of PA, is expressed mostly in cochlear outer hair cells and in vestibular hair cells. OM knockout mice lose their hearing after 3–4 months. It was suggested that, in sensory cells, OM maintains auditory function, most likely affecting outer hair cells’ motility mechanisms.
De-Escalation of Anti-Tumor Necrosis Factor Alpha Agents and Reduction in Adverse Effects: A Systematic Review
Authors: Bouhuys Marleen , Lexmond Willem S. , van Rheenen Patrick F.
Published: April 2022

Background: The long-term use of anti-TNF-α agents can lead to adverse effects, such as infections and immune-mediated cutaneous reactions. Whether de-escalation by dose reduction or interval lengthening reduces these adverse effects is uncertain. This systematic review aims to compare the incidence of infections and skin manifestations after anti-TNF-α dose de-escalation with standard dosing. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to 14 January 2022. Randomized controlled trials (RCTs) and observational studies comparing anti-TNF-α de-escalation strategies with standard dosing among patients with inflammatory conditions, that report on infections, skin manifestations, or both, were included. The risk of bias was assessed with the revised Cochrane risk-of bias tool (RCTs) or the Newcastle–Ottawa scale (non-RCTs). Results: Fourteen RCTs and six observational studies (or 2706 patients) were included. Eight RCTs had low risk of bias or some concerns. Four non-RCTs were of good methodological quality. The studies described patients with axial spondyloarthritis (8 studies, 780 patients), rheumatoid arthritis (7 studies, 1458 patients), psoriasis (3 studies, 332 patients), or inflammatory bowel disease (2 studies, 136 patients). De-escalation strategies included interval lengthening (12 studies, 1317 patients), dose reduction (6 studies, 1130 patients), or both (2 studies, 259 patients). Overall, the occurrence of infections and skin manifestations did not differ between standard treatment and de-escalation. The disappearance of infections or skin manifestations after de-escalation was only reported in two studies. The majority of studies focused on etanercept and adalimumab. Heterogeneity in reporting of infections and skin manifestations precluded meta-analysis. Conclusion: We found that anti-TNF-α de-escalation does not reduce infections or skin reactions. A de-escalation strategy should not be recommended for the sole purpose of reducing drug-related adverse effects. The meticulous documentation of adverse effects is recommended to further address this question. Registration: PROSPERO CRD42021252977.
Hypersensitivity Reactions to Iodinated Contrast Media
Authors: Chiu Tsu-Man , Chu Sung-Yu
Published: April 2022

At present, iodinated contrast media (ICM) are mostly non-ionic, have low osmolality, and are safe. Even if adverse drug reactions (ADRs) occur, most are chemo-toxic symptoms and require only observation or H1 antihistamines. However, rare, unpredictable, and even life-threatening hypersensitivity can still occur. The aim of this review is to summarize the issues that all relevant staff need to know about and be able to respond to. The most significant risk factor for ICM hypersensitivity is a history of ICM hypersensitivity. For high-risk populations, we must cautiously weigh the advantages and disadvantages of premedication and be aware that breakthrough reactions may still occur. The best policy for patients with a history of severe ICM hypersensitivity is to avoid the same ICM. If ICM are inevitable, skin tests, in vitro tests, and drug provocation tests may help to find a feasible alternative that is safer. The severity of the hypersensitivity is correlated with the positivity rate of these tests, so there is no need for further investigations for patients with only mild reactions. We should also keep in mind that even excipients in ICM may induce hypersensitivity. Detailed, standardized documentation is essential for correct diagnosis and the prevention of future occurrence.
Gut–Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis
Authors: Thye Angel Yun-Kuan , Bah Yi-Rou , Law Jodi Woan-Fei , Tan Loh Teng-Hern , He Ya-Wen , Wong Sunny-Hei , Thurairajasingam Sivakumar , Chan Kok-Gan , Lee Learn-Han , Letchumanan Vengadesh
Published: April 2022

Evidence has shown that gut microbiome plays a role in modulating the development of diseases beyond the gastrointestinal tract, including skin disorders such as psoriasis. The gut–skin axis refers to the bidirectional relationship between the gut microbiome and skin health. This is regulated through several mechanisms such as inflammatory mediators and the immune system. Dysregulation of microbiota has been seen in numerous inflammatory skin conditions such as atopic dermatitis, rosacea, and psoriasis. Understanding how gut microbiome are involved in regulating skin health may lead to development of novel therapies for these skin disorders through microbiome modulation, in particularly psoriasis. In this review, we will compare the microbiota between psoriasis patients and healthy control, explain the concept of gut–skin axis and the effects of gut dysbiosis on skin physiology. We will also review the current evidence on modulating gut microbiome using probiotics in psoriasis.
Association between Sleep Quality and Mental Health among Patients at a Post-COVID-19 Recovery Clinic
Authors: Nowakowski Sara , Kokonda Manasa , Sultana Rizwana , Duong Brittany B. , Nagy Sarah E. , Zaidan Mohammed F. , Baig Mirza M. , Grigg Bryan V. , Seashore Justin , Deer Rachel R.
Published: April 2022

A growing body of research documents the persistence of physical and neuropsychiatric symptoms following the resolution of acute COVID-19 infection. To the best of our knowledge, no published study has examined the interaction between insomnia and mental health. Accordingly, we proposed to examine new diagnoses of insomnia, and referrals to pulmonary and sleep medicine clinics for treatment of sleep disorders, in patients presenting to one post-acute COVID-19 recovery clinic. Additionally, we aimed to examine the relationship between poor sleep quality, depression, anxiety, and post-traumatic stress. Patients presented to the clinic on average 2 months following COVID-19 infection; 51.9% (n = 41) were hospitalized, 11.4% (n = 9) were in the intensive care unit, 2.5% (n = 2) were on a mechanical ventilator, and 38.0% (n = 30) were discharged on oxygen. The most commonly reported symptom was fatigue (88%, n = 70), with worse sleep following a COVID-19 infection reported in 50.6% (n = 40). The mean PSQI score was 9.7 (82.3%, n = 65 with poor sleep quality). The mean GAD-7 score was 8.3 (22.8%, n = 14 with severe depression). The mean PHQ-9 was 10.1 (17.8%, n = 18 with severe anxiety). The mean IES-6 was 2.1 (54.4%, n = 43 with post-traumatic stress). Poor sleep quality was significantly associated with increased severity of depression, anxiety, and post-traumatic stress. Future work should follow patients longitudinally to examine if sleep, fatigue, and mental health symptoms improve over time.
What Zebrafish and Nanotechnology Can Offer for Cancer Treatments in the Age of Personalized Medicine
Authors: Cascallar María , Alijas Sandra , Pensado-López Alba , Vázquez-Ríos Abi , Sánchez Laura , Piñeiro Roberto , de la Fuente María
Published: April 2022

Cancer causes millions of deaths each year and thus urgently requires the development of new therapeutic strategies. Nanotechnology-based anticancer therapies are a promising approach, with several formulations already approved and in clinical use. The evaluation of these therapies requires efficient in vivo models to study their behavior and interaction with cancer cells, and to optimize their properties to ensure maximum efficacy and safety. In this way, zebrafish is an important candidate due to its high homology with the human genoma, its large offspring, and the ease in developing specific cancer models. The role of zebrafish as a model for anticancer therapy studies has been highly evidenced, allowing researchers not only to perform drug screenings but also to evaluate novel therapies such as immunotherapies and nanotherapies. Beyond that, zebrafish can be used as an “avatar” model for performing patient-derived xenografts for personalized medicine. These characteristics place zebrafish in an attractive position as a role model for evaluating novel therapies for cancer treatment, such as nanomedicine.
Multimodal Treatment of Malignant Pleural Mesothelioma: Real-World Experience with 112 Patients
Authors: Holzknecht Arnulf , Illini Oliver , Hochmair Maximilian J. , Krenbek Dagmar , Setinek Ulrike , Huemer Florian , Bitterlich Erwin , Kaindl Christoph , Getman Vladyslav , Akan Ahmet , Weber Michael , Leobacher Gunther , Valipour Arschang , Mueller Michael R. , Watzka Stefan B.
Published: April 2022

Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients’ survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of the upcoming results of the MARS-2 trial, we sought to determine the relative impact of the respective treatment modalities on complications and overall survival in our own consecutive institutional series of 112 patients. Fifty-seven patients (51%) underwent multimodality therapy with curative intent, while 55 patients (49%) were treated with palliative intent. The median overall survival (OS) of the entire cohort was 16.9 months (95% CI: 13.4–20.4) after diagnosis; 5-year survival was 29% for patients who underwent lung-preserving surgery. In univariate analysis, surgical treatment (p < 0.001), multimodality therapy (p < 0.001), epithelioid subtype (p < 0.001), early tumor stage (p = 0.02) and the absence of arterial hypertension (p = 0.034) were found to be prognostic factors for OS. In multivariate analysis, epithelioid subtype was associated with a survival benefit, whereas the occurrence of complications was associated with worse OS. Multimodality therapy including surgery significantly prolonged the OS of MPM patients compared with multimodal therapy without surgery.
The SARS-CoV-2 Pandemic and Cancer Trials Ireland: Impact, Resolution and Legacy
Authors: O’Reilly Seamus , Murphy Verena , Mulroe Eibhlin , Tucker Lisa , Carragher Fiona , Marron Jacinta , Shannon Aoife M. , Rogan Ken , Connolly Roisin M. , Hennessy Bryan T. , McDermott Ray S.
Published: April 2022

Background: Cancer Trials Ireland (CTI) is the national cooperative group in Ireland. The SARS-CoV-2 pandemic led to significant ongoing disruptive change in healthcare from March 2020 to the present day. Its impact and legacy on a national clinical trials organisation was assessed. Methods: A review was conducted of prospectively acquired communications, team logs and time sheets, trial activation, closure and accrual, for the period 2019 to September 2021. An online survey of the impact of the pandemic on clinical investigators and of clinical trials units was performed. A National Cancer Retreat was organised on 21 May 2021 to identify and address pandemic related disruption and develop adaptive strategies. Results: In the weeks after the pandemic was declared, remote working was initiated by all central office staff. Nationally, clinical trial accrual fell by 54% compared to the same period in 2019, radiotherapy trial accrual by 90%, and translational studies by 36%. Staff reassignment of research nurse staff occurred in 60% of units, trial monitoring was reduced in 42%, and trial initiations fell by 67%. Extreme fluctuations in monitoring hours were noted paralleling lockdown measures. Significant impact on all clinical trials units was noted including staff reassignments, reduced access to diagnostic imaging and reduced institutional supports. Remote clinic visits and remote monitoring was widely adopted. The National Cancer Retreat identified flexibility in trial conduct, staff recruitment and retention, the need for harmonisation of processes, and research staff support in the context of remote working as priorities. Conclusion: The pandemic has had a significant ongoing negative impact on cancer clinical trial activity in Ireland. Adaptive strategies including trial flexibility, expanded telehealth and remote monitoring, harmonisation of processes and staff support have been identified as priorities to ameliorate this impact, and develop a more sustainable clinical trial ecosystem.
The Prognostic Importance of ctDNA in Rectal Cancer: A Critical Reappraisal
Authors: Dizdarevic Edina , Hansen Torben , Jakobsen Anders
Published: April 2022

The treatment of locally advanced rectal cancer (LARC) has evolved during the last decades, but recurrence remains a problem. Circulating tumor DNA (ctDNA) may result in an individualized treatment approach with improved survival and quality of life, but diverging results impede further development. In this systematic review, we addressed the quality of reporting and its impact on the interpretation of ctDNA results. We performed a systematic literature search using subject headings and search terms related to ctDNA and rectal cancer. The Quality of Prognostic Studies (QUIPS) tool was used to assess bias. Nine studies, with substantial heterogeneity, were included in the analysis. Three out of nine articles had moderate or high risk of bias. No association was found between treatment response and ctDNA status at baseline. There was a negative association between ctDNA positivity at baseline, before and after surgery and survival. The ctDNA status may be of importance to the long-term prognosis, but the area of research is new and is short of dedicated studies. There is an obvious need for standardization in ctDNA research, and the issue should be addressed in future research.
Genetic and Molecular Characterization of the Immortalized Murine Hepatic Stellate Cell Line GRX
Authors: Schröder Sarah K. , Schüler Herdit M. , Petersen Kamilla V. , Tesauro Cinzia , Knudsen Birgitta R. , Pedersen Finn S. , Krus Frederike , Buhl Eva M. , Roeb Elke , Roderfeld Martin , Borojevic Radovan , Almeida Jamie L. , Weiskirchen Ralf
Published: April 2022

The murine cell line GRX has been introduced as an experimental tool to study aspects of hepatic stellate cell biology. It was established from livers of C3H/HeN mice that were infected with cercariae of Schistosoma mansoni. Although these cells display a myofibroblast phenotype, they can accumulate intracellular lipids and acquire a fat-storing lipocyte phenotype when treated with retinol, insulin, and indomethacin. We have performed genetic characterization of GRX and established a multi-loci short tandem repeat (STR) signature for this cell line that includes 18 mouse STR markers. Karyotyping further revealed that this cell line has a complex genotype with various chromosomal aberrations. Transmission electron microscopy revealed that GRX cells produce large quantities of viral particles belonging to the gammaretroviral genus of the Retroviridae family as assessed by next generation mRNA sequencing and Western blot analysis. Rolling-circle-enhanced-enzyme-activity detection (REEAD) revealed the absence of retroviral integrase activity in cell culture supernatants, most likely as a result of tetherin-mediated trapping of viral particles at the cell surface. Furthermore, staining against schistosome gut-associated circulating anodic antigens and cercarial O- and GSL-glycans showed that the cell line lacks S. mansoni-specific glycostructures. Our findings will now help to fulfill the recommendations for cellular authentications required by many granting agencies and scientific journals when working with GRX cells. Moreover, the definition of a characteristic STR profile will increase the value of GRX cells in research and provides an important benchmark to identify intra-laboratory cell line heterogeneity, discriminate between different mouse cell lines, and to avoid misinterpretation of experimental findings by usage of misidentified or cross-contaminated cells.
Comparative Assessment of Retention and Caries Protective Effectiveness of a Hydrophilic and a Conventional Sealant—A Clinical Trial
Authors: Beresescu Liana , Pacurar Mariana , Vlasa Alexandru , Stoica Alexandra Mihaela , Dako Timea , Petcu Blanka , Eșian Daniela
Published: April 2022

Sealants are highly efficient and the most secure method for the prevention of caries lesions from pits and fissures in recently erupted permanent teeth. The aim of this study is to clinically assess and compare the retention and evolution of caries of a moisture-tolerant resin-based sealant with a conventional hydrophobic resin-based sealant. Material and method: We have included in the study 28 children with between 6 and 8 years old. For each child we sealed 4 permanent molars (a total of 112 teeth). The study group was divided into two subgroups: the Embrace Group—consisting of 56 first permanent molars that underwent dental sealing with moisture-tolerant resin-based fissure sealant (Embrace™ WetBond™ Pulpdent, Watertown, MA, USA) and the Helioseal Group—represented by the same number of 56 first permanent molars that were sealed with conventional hydrophobic resin-based sealant (Helioseal F™, Ivoclar Vivadent Schaan, Liechtenstein). The retention and the incidence of new carious lesions of each sealant were assessed clinically at 6, 12, 18, and 24 months. Results: The 12-month follow-up assessment showed perfect integrity in 50 molars (89.28%) sealed with moisture-tolerant resin-based material (Embrace Group), and in 51 molars (91.07%) with conventional resin-based sealant (Helioseal Group). At the 24-month recall, the retention was maintained in 44 molars (78.57%) in the Embrace Group and in 45 molars (80.35%) in the Helioseal Group, respectively. The follow-up assessments showed no statistically significant differences (p > 0.5) between the two materials regarding sealant retention. First evidence of new carious lesions was present at 12 months on two molars sealed with Embrace WetBond and on one molar sealed with Helioseal. At the 24-month evaluation, the prevalence of caries in the Embrace Group was 7.14% (four caries) and 3.56% (two caries) in the Helioseal Group. Moreover, there were no statistically significant differences (p > 0.05) between the two materials regarding new caries development at any of the follow-up assessments. Conclusions: Moisture-tolerant resin-based sealant was effective in terms of retention and caries prevention.
Theoretical Study on Polycarbonate-Based One-Dimensional Ternary Photonic Structures from Far-Ultraviolet to Near-Infrared Regions of Electromagnetic Spectrum
Authors: Matar Z. , Al-Dossari M. , Awasthi S. , Abd El-Gawaad N. , Hanafy H. , Amin R. , Fathy M. , Aly A.
Published: April 2022

In the present research work, we have theoretically analyzed the photonic band-gap properties of one-dimensional photonic structures composed of polycarbonate and non-glass materials. These photonic structures, PC1, PC2, PC3 and PC4, are composed of alternating layers of polycarbonate/Al2O3, polycarbonate/MgF2, polycarbonate/BaF2 and polycarbonate/TiO2 materials, respectively. The period of each photonic structure is made up of a thin non-glass material layer sandwiched between two identical polycarbonate layers. The transfer matrix method has been used to investigate the transmission properties of PC1 to PC4. The comparison between the transmission spectra of PC1 to PC4 shows that the polycarbonate and TiO2-based photonic structure (PC4) possess three PBGs of zero transmission located at far-ultraviolet, visible and near-infrared regions of the electromagnetic spectrum at normal and oblique incidence (θ0 = 55°), both corresponding to TE wave only. The index of refraction of all five materials used in this study was obtained by applying the Sellmeier-type dispersion relationship to ensure accuracy in the results. The purpose of selecting polycarbonate along with Al2O3, TiO2, MgF2 or BaF2 as constituent materials of these photonic structures is due to the heat resistance properties of polycarbonate and the unique optical properties of oxide and fluoride materials with wide transparency from the ultraviolet to the near-infrared regions of the electromagnetic spectrum. The proposed work can be used to design some influential wavelength-selective reflectors composed of 1D PCs behind the active region of the solar cells for improving the photovoltaic performance of solar panels. This study can further be utilized for the fabrication of advanced solar cell designs consisting of 1D photonic mirror-based luminescence and reflection concentrators. The low temperature problem which arises in satellites may also be overcome with the help of smart windows based on the proposed multilayer structures.