bluuebunny/crossref_metadata_2025 huggingface dataset:
SIRT2 Is Critical for Sheep Oocyte Maturation through Regulating Function of Surrounding Granulosa Cells
Authors: Fang Xiaohuan , Xia Wei , Li Sa , Qi Yatian , Liu Mingzhi , Yu Yang , Li Hanxing , Li Mengqi , Tao Chenyu , Wang Zhigang , Li Junjie
Published: May 2022

Oocyte in vitro maturation is crucial for in vitro embryo production technology, which provides oocytes resources for in vitro fertilization and somatic cell nuclear transfer. Previous studies proved that SIRT2, a member of the sirtuin family, plays a role in oocyte meiosis, but its role in sheep oocyte maturation and its regulating mechanism remains unknown. Firstly, we confirmed the role of Sirt2 in sheep oocytes maturation by supplementation of SIRT2 inhibitor and activator. To further explore the specific mechanism, we performed knockdown of Sirt2 in granulosa cells and then cocultured them with oocytes. Moreover, we determined the effects of Sirt2 on granulosa cell oxidative apoptosis, cell migration, and diffusion, and examined its effects on granulosa cell mitochondrial function, mitophagy, and steroid hormone levels. The results showed that supplementation of SIRT2 inhibitor decreased the oocytes maturation rate (69.28% ± 1.28 vs. 45.74% ± 4.74, p < 0.05), while resveratrol, a SIRT2 activator, increased its maturation rate (67.44% ± 1.68 vs. 78.52 ± 1.28, p < 0.05). Knockdown of Sirt2 in sheep granulosa cells also reduced the oocytes maturation rate (47.98% ± 1.43 vs. 33.60% ± 1.77, p < 0.05), and led to decreased cell migration and expansion ability, oxidative apoptosis, abnormal mitochondrial gene expression, decreased mitochondrial membrane potential and ATP level, and increased mitophagy level. Overexpression of Sirt2 improved mitochondrial membrane potential and ATP level and improved mitochondrial function. Furthermore, we found that Sirt2 knockdown in granulosa cells promotes the secretion of P4 through regulating p-ERK1/2. In conclusion the present study showed that SIRT2 is critical for sheep oocyte maturation through regulating the function of ovarian granulosa cells, especially affecting its mitochondrial function.
Zwitterionic Modification of Polyethyleneimine for Efficient In Vitro siRNA Delivery
Authors: Liu Fengfan , Su Huahui , Li Mengqian , Xie Wanxuan , Yan Yunfeng , Shuai Qi
Published: May 2022

Polyethylenimine (PEI) has been widely used in gene delivery. However, its high cytotoxicity and undesired non-specific protein adsorption hinder the overall delivery efficacy and the practical applications of PEI-based gene delivery systems. In this study, we prepared hydrophobically modified PEIs (H-PEIs) via the reaction of octanal with 40% of primary amines in PEI25k and PEI10k, respectively. Two common zwitterionic molecules, 1,3-propanesultone and β-propiolactone, were then used for the modification of the resulting H-PEIs to construct polycationic gene carriers with zwitterionic properties (H-zPEIs). The siRNA delivery efficiency and cytotoxicity of these materials were evaluated in Hela-Luc and A549-Luc cell lines. Compared with their respective parental H-PEIs, different degrees of zwitterionic modification showed different effects in reducing cytotoxicity and delivery efficiency. All zwitterion-modified PEIs showed excellent siRNA binding capacity, reduced nonspecific protein adsorption, and enhanced stability upon nuclease degradation. It is concluded that zwitterionic molecular modification is an effective method to construct efficient vectors by preventing undesired interactions between polycationic carriers and biomacromolecules. It may offer insights into the modification of other cationic carriers of nucleic acid drugs.
An Antisense Oligonucleotide against a Splicing Enhancer Sequence within Exon 1 of the MSTN Gene Inhibits Pre-mRNA Maturation to Act as a Novel Myostatin Inhibitor
Authors: Maeta Kazuhiro , Farea Manal , Nishio Hisahide , Matsuo Masafumi
Published: May 2022

Antisense oligonucleotides (ASOs) are agents that modulate gene function. ASO-mediated out-of-frame exon skipping has been employed to suppress gene function. Myostatin, encoded by the MSTN gene, is a potent negative regulator of skeletal muscle growth. ASOs that induce skipping of out-of-frame exon 2 of the MSTN gene have been studied for their use in increasing muscle mass. However, no ASOs are currently available for clinical use. We hypothesized that ASOs against the splicing enhancer sequence within exon 1 of the MSTN gene would inhibit maturation of pre-mRNA, thereby suppressing gene function. To explore this hypothesis, ASOs against sequences of exon 1 of the MSTN gene were screened for their ability to reduce mature MSTN mRNA levels. One screened ASO, named KMM001, decreased MSTN mRNA levels in a dose-dependent manner and reciprocally increased MSTN pre-mRNA levels. Accordingly, KMM001 decreased myostatin protein levels. KMM001 inhibited SMAD-mediated myostatin signaling in rhabdomyosarcoma cells. Remarkably, it did not decrease GDF11 mRNA levels, indicating myostatin-specific inhibition. As expected, KMM001 enhanced the proliferation of human myoblasts. We conclude that KMM001 is a novel myostatin inhibitor that inhibits pre-mRNA maturation. KMM001 has great promise for clinical applications and should be examined for its ability to treat various muscle-wasting conditions.
Effects of Drugs Formerly Proposed for COVID-19 Treatment on Connexin43 Hemichannels
Authors: Cooreman Axelle , Caufriez Anne , Tabernilla Andrés , Van Campenhout Raf , Leroy Kaat , Kadam Prashant , Sanz Serrano Julen , dos Santos Rodrigues Bruna , Annaert Pieter , Vinken Mathieu
Published: May 2022

Connexin43 (Cx43) hemichannels form a pathway for cellular communication between the cell and its extracellular environment. Under pathological conditions, Cx43 hemichannels release adenosine triphosphate (ATP), which triggers inflammation. Over the past two years, azithromycin, chloroquine, dexamethasone, favipiravir, hydroxychloroquine, lopinavir, remdesivir, ribavirin, and ritonavir have been proposed as drugs for the treatment of the coronavirus disease 2019 (COVID-19), which is associated with prominent systemic inflammation. The current study aimed to investigate if Cx43 hemichannels, being key players in inflammation, could be affected by these drugs which were formerly designated as COVID-19 drugs. For this purpose, Cx43-transduced cells were exposed to these drugs. The effects on Cx43 hemichannel activity were assessed by measuring extracellular ATP release, while the effects at the transcriptional and translational levels were monitored by means of real-time quantitative reverse transcriptase polymerase chain reaction analysis and immunoblot analysis, respectively. Exposure to lopinavir and ritonavir combined (4:1 ratio), as well as to remdesivir, reduced Cx43 mRNA levels. None of the tested drugs affected Cx43 protein expression.
MicroRNA-20a-5p Downregulation by Atorvastatin: A Potential Mechanism Involved in Lipid-Lowering Therapy
Authors: Saavedra Kathleen , Leal Karla , Saavedra Nicolás , Prado Yalena , Paez Isis , Ubilla Carmen G. , Rojas Gabriel , Salazar Luis A.
Published: May 2022

The treatment of hypercholesterolemia is mainly based on statins. However, the response to pharmacological therapy shows high inter-individual variability, resulting in variable effects in both lipid lowering and risk reduction. Thus, a better understanding of the lipid-lowering mechanisms and response variability at the molecular level is required. Previously, we demonstrated a deregulation of the microRNA expression profile in HepG2 cells treated for 24 h with atorvastatin, using a microarray platform. In the present study, we evaluated the expression of hsa-miR-17-5p, hsa-miR-20a-5p and hsa-miR-106a-5p in hypercholesterolemic patients before and after atorvastatin treatment and in HepG2 cells treated for 24 h with atorvastatin The miRNA hsa-mir-20a-5p was repressed after atorvastatin treatment in hypercholesteremic subjects and in HepG2 cells in culture. Repression of hsa-mir-20a-5p increased LDLR gene and protein expression in HepG2 cells, while hsa-mir-20a-5p overexpression reduced LDLR gene and protein expression.
Analysis of Xylose Operon from Paenibacillus polymyxa ATCC842 and Development of Tools for Gene Expression
Authors: Wang Zilong , Fang Yakun , Shi Yi , Xin Yu , Gu ZhengHua , Yang Ting , Li Youran , Ding Zhongyang , Shi Guiyang , Zhang Liang
Published: May 2022

With numerous industrial applications, Paenibacillus polymyxa has been accepted as the candidate of the cell factory for many secondary metabolites. However, as the regulatory expression elements in P. polymyxa have not been systematically investigated, genetic modification on account of a specific metabolism pathway for the strain is limited. In this study, a xylose-inducible operon in the xylan-utilizing bacterium ATCC842 was identified, and the relative operon transcription was increased to 186-fold in the presence of xylose, while the relative enhanced green fluorescent protein (eGFP) fluorescence intensity was promoted by over four-fold. By contrast, glucose downregulated the operon to 0.5-fold that of the control. The binding site of the operon was “ACTTAGTTTAAGCAATAGACAAAGT”, and this can be degenerated to “ACTTWGTTTAWSSNATAVACAAAGT” in Paenibacillus spp., which differs from that in the Bacillus spp. xylose operon. The xylose operon binding site was transplanted to the constitutive promoter Pshuttle-09. The eGFP fluorescence intensity assay indicated that both the modified and original Pshuttle-09 had similar expression levels after induction, and the expression level of the modified promoter was decreased to 19.8% without induction. This research indicates that the operon has great potential as an ideal synthetic biology tool in Paenibacillus spp. that can dynamically regulate its gene circuit strength through xylose.
Giving Drugs a Second Chance: Antibacterial and Antibiofilm Effects of Ciclopirox and Ribavirin against Cystic Fibrosis Pseudomonas aeruginosa Strains
Authors: Di Bonaventura Giovanni , Lupetti Veronica , De Fabritiis Simone , Piccirilli Alessandra , Porreca Annamaria , Di Nicola Marta , Pompilio Arianna
Published: May 2022

Drug repurposing is an attractive strategy for developing new antibacterial molecules. Herein, we evaluated the in vitro antibacterial, antibiofilm, and antivirulence activities of eight FDA-approved “non-antibiotic” drugs, comparatively to tobramycin, against selected Pseudomonas aeruginosa strains from cystic fibrosis patients. MIC and MBC values were measured by broth microdilution method. Time–kill kinetics was studied by the macro dilution method, and synergy studies were performed by checkerboard microdilution assay. The activity against preformed biofilms was measured by crystal violet and viable cell count assays. The effects on gene expression were studied by real-time quantitative PCR, while the cytotoxic potential was evaluated against IB3-1 bronchial CF cells. Ciclopirox, 5-fluorouracil, and actinomycin D showed the best activity against P. aeruginosa planktonic cells and therefore underwent further evaluation. Time–kill assays indicated actinomycin D and ciclopirox, contrarily to 5-fluorouracil and tobramycin, have the potential for bacterial eradication, although with strain-dependent efficacy. Ciclopirox was the most effective against the viability of the preformed biofilm. A similar activity was observed for other drugs, although they stimulate extracellular polymeric substance production. Ribavirin showed a specific antibiofilm effect, not dependent on bacterial killing. Exposure to drugs and tobramycin generally caused hyperexpression of the virulence traits tested, except for actinomycin D, which downregulated the expression of alkaline protease and alginate polymerization. Ciclopirox and actinomycin D revealed high cytotoxic potential. Ciclopirox and ribavirin might provide chemical scaffolds for anti-P. aeruginosa drugs. Further studies are warranted to decrease ciclopirox cytotoxicity and evaluate the in vivo protective effects.
Plants—Microorganisms-Based Bioremediation for Heavy Metal Cleanup: Recent Developments, Phytoremediation Techniques, Regulation Mechanisms, and Molecular Responses
Authors: Raklami Anas , Meddich Abdelilah , Oufdou Khalid , Baslam Marouane
Published: May 2022

Rapid industrialization, mine tailings runoff, and agricultural activities are often detrimental to soil health and can distribute hazardous metal(loid)s into the soil environment, with harmful effects on human and ecosystem health. Plants and their associated microbes can be deployed to clean up and prevent environmental pollution. This green technology has emerged as one of the most attractive and acceptable practices for using natural processes to break down organic contaminants or accumulate and stabilize metal pollutants by acting as filters or traps. This review explores the interactions between plants, their associated microbiomes, and the environment, and discusses how they shape the assembly of plant-associated microbial communities and modulate metal(loid)s remediation. Here, we also overview microbe–heavy-metal(loid)s interactions and discuss microbial bioremediation and plants with advanced phytoremediation properties approaches that have been successfully used, as well as their associated biological processes. We conclude by providing insights into the underlying remediation strategies’ mechanisms, key challenges, and future directions for the remediation of metal(loid)s-polluted agricultural soils with environmentally friendly techniques.
Albumin Binds Doxorubicin via Self–Assembling Dyes as Specific Polymolecular Ligands
Authors: Jagusiak Anna , Chłopaś Katarzyna , Zemanek Grzegorz , Kościk Izabela , Skorek Paweł , Stopa Barbara
Published: May 2022

Congo red (CR) type self–assembled ribbon–like structures (SRLS) were previously shown to interact with some proteins, including albumin. SRLS also complex with some drugs with a flat, ring–shaped structure with aromatic characteristics, intercalating them into their ribbon structure. The combination of interaction with proteins and drug binding by SRLS enables the use of such systems for immunotargeting. It is especially interesting in the case of chemotherapeutic agents. The present experiments aimed to show that the model carrier system composed of supramolecular albumin and Congo red efficiently binds doxorubicin (Dox) and that the drug can be released at reduced pH. The presented results come from the studies on such complexes differing in the molar ratio of CR to Dox. The following methods were used for the analysis: electrophoresis, dialysis, gel filtration, spectral analysis, and analysis of the size of the hydrodynamic radius using the dynamic light scattering method (DLS). The applied methods confirmed the formation of the CR–Dox complex, with large dimensions and changed properties compared with free CR. The presented results show that albumin binds both CR and its complex with Dox. Various CR–Dox molar ratios, 5:1, 2:1, and 1:1, were analyzed. The confirmation of the possibility of releasing the drug from the carriers thus formed was also obtained. The presented research is important due to the search for optimal solutions for the use of SRLS in drug immunotargeting, with particular emphasis on chemotherapeutic agents.
C/N-Dependent Element Bioconversion Efficiency and Antimicrobial Protein Expression in Food Waste Treatment by Black Soldier Fly Larvae
Authors: Jin Ning , Liu Yanxia , Zhang Shouyu , Sun Shibo , Wu Minghuo , Dong Xiaoying , Tong Huiyan , Xu Jianqiang , Zhou Hao , Guan Shui , Xu Weiping
Published: May 2022

The black soldier fly (BSF), Hermetia illucens, has emerged as a promising species for waste bioconversion and source of antimicrobial proteins (AMPs). However, there is a scarcity of research on the element transformation efficiency and molecular characterization of AMPs derived from waste management. Here, food waste treatment was performed using BSF larvae (BSFL) in a C/N ratio of 21:1–10:1, with a focus on the C/N-dependent element bioconversion, AMP antimicrobial activity, and transcriptome profiling. The C-larvae transformation rates were found to be similar among C/Ns (27.0–35.5%, p = 0.109), while the N-larvae rates were different (p = 0.001), with C/N 21:1–16:1 (63.5–75.0%) being higher than C/N 14:1–10:1 (35.0–45.7%). The C/N ratio did not alter the antimicrobial spectrum of AMPs, but did affect the activities, with C/N 21:1 being significantly lower than C/N 18:1–10:1. The lysozyme genes were found to be significantly more highly expressed than the cecropin, defensin, and attacin genes in the AMP gene family. Out of 51 lysozyme genes, C/N 18:1 and C/N 16:1 up-regulated (p < 0.05) 14 and 12 genes compared with C/N 21:1, respectively, corresponding to the higher activity of AMPs. Overall, the element bioconversion efficiency and AMP expression can be enhanced through C/N ratio manipulation, and the C/N-dependent transcriptome regulation is the driving force of the AMP difference.
Cytopathological Outcomes of Knocking down Expression of Mitochondrial Complex II Subunits in Dictyostelium discoideum
Authors: Lay Sui , Pearce Xavier , Sanislav Oana , Fisher Paul Robert , Annesley Sarah Jane
Published: May 2022

Mitochondrial Complex II is composed of four core subunits and mutations to any of the subunits result in lowered Complex II activity. Surprisingly, although mutations in any of the subunits can yield similar clinical outcomes, there are distinct differences in the patterns of clinical disease most commonly associated with mutations in different subunits. Thus, mutations to the SdhA subunit most often result in mitochondrial disease phenotypes, whilst mutations to the other subunits SdhB-D more commonly result in tumour formation. The reason the clinical outcomes are so different is unknown. Here, we individually antisense-inhibited three of the Complex II subunits, SdhA, SdhB or SdhC, in the simple model organism Dictyostelium discoideum. Whilst SdhB and SdhC knockdown resulted in growth defects on bacterial lawns, antisense inhibition of SdhA expression resulted in a different pattern of phenotypic defects, including impairments of growth in liquid medium, enhanced intracellular proliferation of the bacterial pathogen Legionella pneumophila and phagocytosis. Knockdown of the individual subunits also produced different abnormalities in mitochondrial function with only SdhA knockdown resulting in broad mitochondrial dysfunction. Furthermore, these defects were shown to be mediated by the chronic activation of the cellular energy sensor AMP-activated protein kinase. Our results are in agreement with a role for loss of function of SdhA but not the other Complex II subunits in impairing mitochondrial oxidative phosphorylation and they suggest a role for AMP-activated protein kinase in mediating the cytopathological outcomes.
In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model
Authors: Dos Santos Reinaldo Sousa , Medina-Gali Regla María , Babiloni-Chust Ignacio , Marroqui Laura , Nadal Angel
Published: May 2022

There is a need to develop identification tests for Metabolism Disrupting Chemicals (MDCs) with diabetogenic activity. Here we used the human EndoC-βH1 β-cell line, the rat β-cell line INS-1E and dispersed mouse islet cells to assess the effects of endocrine disruptors on cell viability and glucose-stimulated insulin secretion (GSIS). We tested six chemicals at concentrations within human exposure (from 0.1 pM to 1 µM). Bisphenol-A (BPA) and tributyltin (TBT) were used as controls while four other chemicals, namely perfluorooctanoic acid (PFOA), triphenylphosphate (TPP), triclosan (TCS) and dichlorodiphenyldichloroethylene (DDE), were used as “unknowns”. Regarding cell viability, BPA and TBT increased cell death as previously observed. Their mode of action involved the activation of estrogen receptors and PPARγ, respectively. ROS production was a consistent key event in BPA-and TBT-treated cells. None of the other MDCs tested modified viability or ROS production. Concerning GSIS, TBT increased insulin secretion while BPA produced no effects. PFOA decreased GSIS, suggesting that this chemical could be a “new” diabetogenic agent. Our results indicate that the EndoC-βH1 cell line is a suitable human β-cell model for testing diabetogenic MDCs. Optimization of the test methods proposed here could be incorporated into a set of protocols for the identification of MDCs.
Evaluation of MyRelief Serious Game for Better Self-Management of Health Behaviour Strategies on Chronic Low-Back Pain
Authors: Maskeliūnas Rytis , Damaševičius Robertas , Kulikajevas Audrius , Marley Joane , Larsson Caroline
Published: May 2022

Low back pain is a leading cause of disability worldwide, putting a significant strain on individual sufferers, their families, and the economy as a whole. It has a significant economic impact on the global economy because of the costs associated with healthcare, lost productivity, activity limitation, and work absence. Self-management, education, and adopting healthy lifestyle behaviors, such as increasing physical activity, are all widely recommended treatments. Access to services provided by healthcare professionals who provide these treatments can be limited and costly. This evaluation study focuses on the application of the MyRelief serious game, with the goal of addressing such challenges by providing an accessible, interactive, and fun platform that incorporates self-management, behavior change strategies, and educational information consistent with recommendations for managing low-back pain, based on self-assessment models implemented through ontology-based mechanics. Functional disability measured using the Oswestry Disability Questionnaire showed the statistically significant (p < 0.001) improvement in subjects’ self-evaluation of their health status. System Usability Scale (SUS) test score of 77.6 also suggests that the MyRelief serious game can potentially influence patient enablement.
Exploring Large-Scale Patterns of Genetic Variation in the COI Gene among Insecta: Implications for DNA Barcoding and Threshold-Based Species Delimitation Studies
Authors: Zhang Haiguang , Bu Wenjun
Published: May 2022

The genetic variation in the COI gene has had a great effect on the final results of species delimitation studies. However, little research has comprehensively investigated the genetic divergence in COI among Insecta. The fast-growing COI data in BOLD provide an opportunity for the comprehensive appraisal of the genetic variation in COI among Insecta. We calculated the K2P distance of 64,414 insect species downloaded from BOLD. The match ratios of the clustering analysis, based on different thresholds, were also compared among 4288 genera (35,068 species). The results indicate that approximately one-quarter of the species of Insecta showed high intraspecific genetic variation (>3%), and a conservative estimate of this proportion ranges from 12.05% to 22.58%. The application of empirical thresholds (e.g., 2% and 3%) in the clustering analysis may result in the overestimation of the species diversity. If the minimum interspecific genetic distance of the congeneric species is greater than or equal to 2%, it is possible to avoid overestimating the species diversity on the basis of the empirical thresholds. In comparison to the fixed thresholds, the “threshOpt” and “localMinima” algorithms are recommended for the provision of a reference threshold for threshold-based species delimitation studies.
Mechanisms of Trichomes and Terpene Compounds in Indigenous and Commercial Thai Rice Varieties against Brown Planthopper
Authors: Khetnon Phawini , Busarakam Kanungnid , Sukhaket Wissarut , Niwaspragrit Cholticha , Kamolsukyeunyong Wintai , Kamata Naoto , Sanguansub Sunisa
Published: May 2022

Plant trichomes generally act as a physical defense against herbivore attacks and are present in a variety of plants, including rice plants. This research examined the physical and chemical defenses of rice plants against the brown planthopper (BPH), Nilaparvata lugens (Stål) (Hemiptera: Delphacidae). A total of 10 rice varieties were used in this study. An electron microscope was used to observe trichomes. Constitutive and induced volatile compound profiles were assessed using GC-MS analyses. The preference of BPH for volatiles from the 10 rice plants was tested using a two-choice arena olfactometer system. The density of prickle trichomes had a negative relationship with the BPH injury level. Without BPH infestation, the volatile of the most resistant rice variety (Rathu Heenati (RH)) was preferred by BPH than those of the other varieties, with the exception of Gled Plah Chawn. However, the relative BPH preference for volatiles from the RH variety decreased during BPH infestation. When rice plants were infested by BPH, the numbers of VOCs and these quantities decreased. In the RH variety, the emission of essentities found without BPH infestation ceased during infestation by BPH. During the BPH infestation, rice plants started to emit new VOCs that were not detected before the BPH infestation started. In conclusion, we discovered that rice plants defended against BPH by changing VOC components during BPH infestation and β-Sesquiphellandrene was likely the most effective component.
Tight Blood Pressure Control in Chronic Kidney Disease
Authors: Gentile Giorgio , Mckinney Kathryn , Reboldi Gianpaolo
Published: May 2022

Hypertension affects over a billion people worldwide and is the leading cause of cardiovascular disease and premature death worldwide, as well as one of the key determinants of chronic kidney disease worldwide. People with chronic kidney disease and hypertension are at very high risk of renal outcomes, including progression to end-stage renal disease, and, even more importantly, cardiovascular outcomes. Hence, blood pressure control is crucial in reducing the human and socio-economic burden of renal and cardiovascular outcomes in those patients. However, current guidelines from hypertension and renal societies have issued different and sometimes conflicting recommendations, which risk confusing clinicians and potentially contributing to a less effective prevention of renal and cardiovascular outcomes. In this review, we critically appraise existing evidence and key international guidelines, and we finally formulate our own opinion that clinicians should aim for a blood pressure target lower than 130/80 in all patients with chronic kidney disease and hypertension, unless they are frail or with multiple comorbidities. We also advocate for an even more ambitious systolic blood pressure target lower than 120 mmHg in younger patients with a lower burden of comorbidities, to minimise their risk of renal and cardiovascular events during their lifetime.
Effect of Matrix Size Reduction on Textural Information in Clinical Magnetic Resonance Imaging
Authors: Strzelecki Michał , Piórkowski Adam , Obuchowicz Rafał
Published: May 2022

The selection of the matrix size is an important element of the magnetic resonance imaging (MRI) process, and has a significant impact on the acquired image quality. Signal to noise ratio, often used to assess MR image quality, has its limitations. Thus, for this purpose we propose a novel approach: the use of texture analysis as an index of the image quality that is sensitive for the change of matrix size. Image texture in biomedical images represents tissue and organ structures visualized via medical imaging modalities such as MRI. The correlation between texture parameters determined for the same tissues visualized in images acquired with different matrix sizes is analyzed to aid in the assessment of the selection of the optimal matrix size. T2-weighted coronal images of shoulders were acquired using five different matrix sizes while maintaining the same field of view; three regions of interest (bone, fat, and muscle) were considered. Lin’s correlation coefficients were calculated for all possible pairs of the 310-element texture feature vectors evaluated for each matrix. The obtained results are discussed considering the image noise and blurring effect visible in images acquired with smaller matrices. Taking these phenomena into account, recommendations for the selection of the matrix size used for the MRI imaging were proposed.
Canaloplasty in Pseudoexfoliation Glaucoma. Can It Still Be Considered a Good Choice?
Authors: Brusini Paolo , Papa Veronica , Zeppieri Marco
Published: May 2022

Purpose: The aim of this study was to assess the long-term outcomes of canaloplasty surgery in pseudoexfoliation glaucoma (PEXG) patients. Material and Methods: A total of 116 PEXG patients with an intraocular pressure (IOP) > 21 mm/Hg and maximum tolerated local medical therapy who underwent canaloplasty from February 2008 to January 2022 were considered. Every six months, all subjects underwent a complete ophthalmic examination. The period of follow-up ranged from 2 to 167 months. Inclusion criteria included only patients for whom the entire procedure could be completed with a follow-up of at least 2 years. Results: Amongst the 116 PEXG patients, the entire procedure could not be performed in 10 eyes (8.6%), and thus they were not considered in the analysis. Twenty-three patients did not reach the two-year follow-up and another 16 patients during this time period were lost. A total of 67 patients with a mean follow-up of 49 ± 32.3 months were considered in the analysis. The pre-operative mean IOP was 31.2 ± 8.7 mm/Hg (range 20–60). The mean IOP at the two-year follow-up was 17.2 ± 6.7 mmHg, with a mean reduction from baseline of 44.9%. After two years, the qualified success rates according to three different criteria (IOP ≤ 21, ≤18 and ≤16 mmHg) were 80.6%, 73.1% and 61.0%, respectively. The total number of medications used pre- and at the follow-up at 2 years was 3.5 ± 0.8 and 1.2 ± 1.4, respectively. Early complications included: hyphema, in about 30% of cases; Descemet membrane detachment (4.9%); and IOP spikes > 10 mmHg (9.7%). A late failure with an acute IOP rise of up to 50 mmHg was observed in 41 cases (61.2%) after 3 to 72 months. Conclusions: Long-term post-operative outcomes of canaloplasty in PEXG patients appear to be quite good on average; however, an acute rise in IOP can be observed in more than 60% of the cases after a long period of satisfactory IOP control. For this reason, canaloplasty may not be suitable in eyes with PEXG, especially in patients with severe functional damage.
Pregnancy and Kidney Diseases: Multidisciplinary Follow-Up and the Vicious Circles Involving Pregnancy and CKD, Preeclampsia, Preterm Delivery and the Kidneys
Authors: Piccoli Giorgina Barbara , Attini Rossella , Torreggiani Massimo , Cabiddu Gianfranca
Published: May 2022

Thomas Addis, the father of nephrology, once wrote that a clinician is complex, “he is part craftsman, part practical scientist, and part historian” [...]
Prognostic Value of 12-Leads Electrocardiogram at Emergency Department in Hospitalized Patients with Coronavirus Disease-19
Authors: Savelloni Giulia , Gatto Maria Chiara , Cancelli Francesca , Barbetti Anna , Cogliati Dezza Francesco , Franchi Cristiana , Carnevalini Martina , Galardo Gioacchino , Bucci Tommaso , Alessandroni Maria , Pugliese Francesco , Mastroianni Claudio Maria , Oliva Alessandra
Published: May 2022

Background: Electrocardiogram (ECG) offers a valuable resource easily available in the emergency setting. Objective: Aim of the study was to describe ECG alterations on emergency department (ED) presentation or that developed during hospitalization in SARS-CoV-2-infected patients and their association with 28-day mortality. Methods: A retrospective, single-center study including hospitalized patients with SARS-CoV-2 was conducted. ECG was recorded on ED admission to determine: heart rhythm, rate, and cycle; atrio-ventricular and intra-ventricular conduction; right ventricular strain; and ventricular repolarization. A specialized cardiologist blinded for the outcomes performed all 12-lead ECG analyses and their interpretation. Results: 190 patients were included, with a total of 24 deaths (12.6%). Age (p < 0.0001) and comorbidity burden were significantly higher in non-survivors (p < 0.0001). Atrial fibrillation (AF) was more frequent in non-survivors (p < 0.0001), alongside a longer QTc interval (p = 0.0002), a lower Tp-e/QTc ratio (p = 0.0003), and right ventricular strain (p = 0.013). Remdesivir administration was associated with bradycardia development (p = 0.0005) but no increase in mortality rates. In a Cox regression model, AF (aHR 3.02 (95% CI 1.03–8.81); p = 0.042), QTc interval above 451 ms (aHR 3.24 (95% CI 1.09–9.62); p = 0.033), and right ventricular strain (aHR 2.94 (95% CI 1.01–8.55); p = 0.047) were associated with higher 28-day mortality risk. Conclusions: QTc interval > 451 ms, right ventricular strain, and AF are associated with higher mortality risk in SARS-CoV-2 hospitalized patients. ECG recording and its appropriate analysis offers a simple, quick, non-expensive, and validated approach in the emergency setting to guide COVID-19 patients’ stratification.
Surgical Procedure Time and Mortality in Patients with Infective Endocarditis Caused by Staphylococcus aureus or Streptococcus Species
Authors: Paul Gregor , Ochs Laurin , Hohmann Christopher , Baldus Stephan , Michels Guido , Meyer-Schwickerath Charlotte , Fätkenheuer Gerd , Mader Navid , Wahlers Thorsten , Weber Carolyn , Jung Norma
Published: May 2022

Staphylococcus aureus (SA) and Streptococcus species (SS) show different clinical manifestations in infective endocarditis (IE), but the impact on the complexity of surgical treatment remains unclear. All patients with surgically treated IE due to SA or SS between July 2013 and December 2016 were extracted from a prospectively collected, single-center registry. Data on patient characteristics, surgical procedures, and postprocedural outcomes were collected. SA-IE was more common with prosthetic valves (26.3% vs. 7.3%, p = 0.04), cardiac devices (14.3% vs. 0%, p = 0.03), previous cardiac surgery (28.6% vs. 9.8%, p = 0.03), intravenous drug abuse (14.3% vs. 0%, p = 0.03), and embolic events (57.1% vs. 26.8%, p = 0.007). Preoperative CRP was significantly higher in SA-IE (median 96.1 mg/L vs. 42.4 mg/L, p = 0.002). Otherwise, SS-IE affected more cusps/leaflets (mean 2.4 vs. 1.8, p = 0.03) and led to more valve dysfunction (83.8% vs. 54.3%, p = 0.007). Surgery times did not differ between the groups, though patients with SA spent more time in the intensive care unit (median 7 vs. 4.5 days, p = 0.04). Hospital mortality did not differ, but patients with SA-IE had unfavorable long-term survival (p = 0.001). Future studies need to be larger and focus on the mechanism behind the reduced long-term survival to mitigate the deleterious effect of SA in surgically treated patients with IE.
Measuring Recovery and Understanding Long-Term Deficits in Balance, Ankle Mobility and Hip Strength in People after an Open Reduction and Internal Fixation of Bimalleolar Fracture and Their Impact on Functionality: A 12-Month Longitudinal Study
Authors: Salas-Gómez Diana , Fernández-Gorgojo Mario , Sánchez-Juan Pascual , Pérez-Núñez María Isabel , Laguna-Bercero Esther , Prat-Luri Amaya , Barbado David
Published: May 2022

To analyze how balance and other physical capacities evolved after surgery in patients with a bimalleolar fracture and how these capacities and clinical variables (immobilization or unloading time) contribute to restoring patients’ functionality, 22 patients and 10 healthy people (HC) were assessed for static and dynamic balance (Y-Balance test, YBT), dorsiflexion ankle mobility (ADFROM) and hip strength at 6 and 12 months after surgery. Patients’ functional status was assessed through the Olerud Molander Ankle Score (OMAS) and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Twenty-one patients with ankle fractures who completed the study showed a worse static and dynamic balance at 6 months. The YBT in the anterior direction (YBTA) revealed balance deficits in the operated limb at 12 months compared to the non-operated limb (−5.6%) and the HC (−6.7%). They also showed a decreased ADFROM compared to the non-operated limb (−7.4°) and the HC (−11°). In addition, medium-term (6 months) deficits in abductor strength hip but no hip strength deficits were found at 12 months after surgery. Relative weight analyses showed that ADFROM and hip strength explained 35–63% of the YBTA variance and AOFAS/OMAS scores. Balance, hip strength and ADFROM seem to be reliable indexes for assessing the functional status of these patients. These results could help to understand the relationship between these physical capacities and the patients’ perceived functional status.
Improving Upper Extremity Bradykinesia in Parkinson’s Disease: A Randomized Clinical Trial on the Use of Gravity-Supporting Exoskeletons
Authors: Raciti Loredana , Pignolo Loris , Perini Valentina , Pullia Massimo , Porcari Bruno , Latella Desiree , Isgrò Marco , Naro Antonino , Calabrò Rocco Salvatore
Published: May 2022

Hand movements are particularly impaired in patients with Parkinson’s Disease (PD), contributing to functional disability and difficulties in activities of daily living. Growing evidence has shown that robot-assisted therapy may be considered an effective and reliable method for the delivery of the highly repetitive training that is needed to trigger neuroplasticity, as intensive, repetitive and task-oriented training could be an ideal strategy to facilitate the relearning of motor function and to minimize motor deficit. The purpose of this study is to evaluate the improvement of hand function with semi-autonomous exercises using an upper extremity exoskeleton in patients with PD. A multicenter, parallel-group, randomized clinical trial was then carried out at the IRCCS Centro Neurolesi Bonino-Pulejo (Messina, Italy). Thirty subjects with a diagnosis of PD and a Hoehn–Yahr score between 2 and 3 were enrolled in the study. Patients were 1:1 randomized into either the experimental group (ERT), receiving 45 min training daily, 6 days weekly, for 8 weeks with Armeo®Spring (Volketswil, Switzerland) (a gravity-supporting device), or the control group (CPT), which was subjected to the same amount of conventional physical therapy. Motor abilities were assessed before and after the end of the training. The main outcomes measures were the Nine-hole peg test and the motor section of the UPDRS. All patients belonging to ERT and 9 out of 15 patients belonging to the CPT completed the trial. ERT showed a greater improvement in the primary outcome measure (nine-hole peg test) than CPT. Moreover, a statistically significant improvement was found in ERT concerning upper limb mobility, and disease burden as compared to CPT. Using an upper extremity exoskeleton (i.e., the Armeo®Spring) for semi-autonomous training in an inpatient setting is a new perspective to train patients with PD to improve their dexterity, executive function and, potentially, quality of life.
Antibodies towards TVLLPVIFF Amino Acid Sequence of TNF Receptor Induced by Helicobacter pylori in Patients with Coronary Heart Disease
Authors: Gonciarz Weronika , Tomaszewska Agata , Krupa Agnieszka , Rechciński Tomasz , Chałubiński Maciej , Broncel Marlena , Chmiela Magdalena
Published: May 2022

Background: Molecular mimicry between Helicobacter pylori (Hp) and the host components resulting in induction of cross-reacting antibodies has been suggested as accessory mechanism in the development of coronary heart disease (CHD). A potential target for antibodies induced during Hp infection by the components of these bacteria might be amino acid sequence TVLLPVIFF (P1) of tumor necrosis factor receptor (TNFR), which is exposed on vascular endothelium and immunocompetent cells, driving inflammation. Aim: To examine whether anti-P1 IgG are induced during Hp infection in CHD patients. Methods: Sera from CHD patients infected with Hp (54) vs. sera of uninfected healthy donors (22) were tested by the ELISA for anti-H. pylori antibodies, anti-P1 IgG, and for antibodies towards control sequence IAKEGFEKIS (P2). Sera of Caviae porcellus infected experimentally with Hp (30) or uninfected (10) were included into this study. The same serum samples, which were positive for anti-P1 IgG, were adsorbed with Hp and then subjected to the ELISA. The biological activity of anti-P1 IgG was assessed in complement (C1q) binding assay. Results: Sera of 43 CHD patients seropositive for anti-Hp IgG contained anti-P1 IgG binding C1q. Additionally, 10 serum samples of animals seropositive for anti-Hp IgG contained anti-P1 IgG. Anti-P1 IgG in tested sera were neutralized by their adsorption with Hp. Conclusion: In CHD patients infected with Hp, antibodies cross-reacting with TNFR common sequence are produced. Further studies are necessary to define immunogenic Hp determinants and to confirm possible cellular effects of cross-reacting antibodies.
Major Adverse Events in Patients with Peripheral Artery Disease after Endovascular Revascularization: A Retrospective Study
Authors: Kim Mihui , Yang Yong Sook , Ko Young-Guk , Choi Mona
Published: May 2022

Objective: For peripheral artery disease (PAD) patients, after endovascular revascularization, it is crucial to manage associated factors that can affect the risk of major adverse events. We aimed to investigate the associated factors of major adverse events in these patients. Materials and Methods: We conducted a retrospective longitudinal analysis using the electronic medical records from a tertiary hospital in Korea and included the data of 1263 patients. Eligible patients were categorized into four groups based on diabetes mellitus (DM) and regular exercise. The major adverse events included major adverse limb events and major adverse cardiovascular events. Major adverse events-free survival was assessed using the Kaplan–Meier method, and associated factors of major adverse events were analyzed using Cox proportional hazards analyses. Results: Kaplan–Meier survival curves showed that patients with DM and non-regular exercise had a shorter major adverse events-free survival. The Cox regression analysis showed that for patients with critical limb ischemia or chronic kidney disease, the risk of major adverse events increased, while group variables were not significant. Conclusion: Target management of patients with DM, critical limb ischemia, and chronic kidney disease is essential to reduce major adverse events after endovascular revascularization in patients with PAD.
Introducing a Pole Concept for Nodule Growth in the Thyroid Gland: Taller-than-Wide Shape, Frequency, Location and Risk of Malignancy of Thyroid Nodules in an Area with Iodine Deficiency
Authors: Petersen Manuela , Schenke Simone A. , Zimny Michael , Görges Rainer , Grunert Michael , Groener Daniel , Seifert Philipp , Stömmer Peter E. , Kreissl Michael C. , Stahl Alexander R. ,   on behalf of the German TIRADS Study Group
Published: May 2022

Purpose: (i) To examine the criterion taller-than-wide (TTW) for the sonographic assessment of thyroid nodules in areas of iodine deficiency in terms of frequency, anatomical distribution within the thyroid gland and risk of malignancy. (ii) To develop a model for nodule growth in the thyroid gland. Methods: German multicenter study consisting of two parts. In the prospective part, thyroid nodules were sonographically measured in all three dimensions, location within the thyroid gland and contact to a protrusion-like formation (horn) in the dorsal position of thyroid gland was noted. In addition, further sonographic features such as the composition, echogenity, margins and calcifications were investigated. All nodules from the prospective part were assessed for malignancy as part of clinical routine at the decision of the treating physician adhering to institutionally based algorithms. In the retrospective part, only nodules with fine needle aspiration and/or histology were included. The risk of malignancy in TTW nodules was determined by correlating them with cyotological and histological results. Results: Prospective part: out of 441 consecutively evaluated thyroid nodules, 6 were found to be malignant (1.4%, 95% CI 0.6–2.7%). Among the 74 TTW nodules (17%), 1 was malignant (1%, 95% CI 0–4%). TTW nodules were more often located in the dorsal half of the thyroid than non-TTW nodules (factor 2.3, p = 0.01, 95% CI 2.1–2.5) and more often located in close proximity to a horn than non-TTW nodules (factor 3.0, p = 0.01, 95% CI 2.4–3.8). Retrospective part: out of 1315 histologically and/or cytologically confirmed thyroid nodules, 163 TTW nodules were retrieved and retrospectively analyzed. A TTW nodule was 1.7 times more often benign when it was dorsal (95% CI 1.1–2.5) and 2.5 times more often benign when it was associated with a horn (95% CI 1.2–5.3). The overall probability of malignancy for TTW nodules was 38% (95% CI 30–46%) in this highly preselected patient group. Conclusion: TTW nodules are common in iodine deficient areas. They are often located in the dorsal half of the thyroid gland and are frequently associated with a dorsal protrusion-like formation (horn) of the thyroid. Obviously, the shape of benign nodules follows distinct anatomical preconditions within the thyroid gland. The frequency of TTW nodules and their predominant benignity can be explained by a pole concept of goiter growth. The difference between the low malignancy risk of TTW nodules found on a prospective basis and the high risk found retrospectively may be the result of a positive preselection in the latter.
Spiderweb Cellular Structures Manufactured via Additive Layer Manufacturing for Aerospace Application
Authors: Bari Klaudio , Bollenbach Lucie
Published: May 2022

With increasing the energy costs and aiming for fossil-free Europe, cellular structures could provide a cost-effective tool for saving fuel consumption in aircraft. To achieve this goal, a cellular structure topology is a rapidly growing area of research facilitated by developments in additive layer manufacturing. These low-density structures are particularly promising for their aerospace applications. In this paper, four cellular structure topologies are developed to serve as a vibration damper in small electric aircraft motor, we have compared their performance with the original motor holder in the aircraft. This paper introduces the roadmap of scaffolding concept design and provides a novel concept in vibration damping. Based on the FEA simulation, aluminium 6061T spiderweb-inspired lattices (weight 0.3473 g and porosity 84%) have proven to have the lowest natural resonance and highest yield strength to weight ratio compared to other scaffolding concepts.
Oxyhydroxide-Coated PEO–Treated Mg Alloy for Enhanced Corrosion Resistance and Bone Regeneration
Authors: Xie Juning , Cheng Shi , Zhong Guoqing , Zhou Ruixiang , Zhang Chi , He Yue , Peng Feng , Zhang Yu
Published: May 2022

Plasma electrolytic oxidation (PEO) is widely used as a surface modification method to enhance the corrosion resistance of Mg alloy, the most likely applied biodegradable material used in orthopedic implants. However, the pores and cracks easily formed on the PEO surface are unfavorable for long-term corrosion resistance. In this study, to solve this problem, we used simple immersion processes to construct Mn and Fe oxyhydroxide duplex layers on the PEO-treated AZ31 (PEO–Mn/Fe). As control groups, single Mn and Fe oxyhydroxide layers were also fabricated on PEO (denoted as PEO–Mn and PEO–Fe, respectively). PEO–Mn showed a similar porous morphology to the PEO sample. However, the PEO–Fe and PEO–Mn/Fe films completely sealed the pores on the PEO surfaces, and no cracks were observed even after the samples were immersed in water for 7 days. Compared with PEO, PEO–Mn, and PEO–Fe, PEO–Mn/Fe exhibited a significantly lower self-corrosion current, suggesting better corrosion resistance. In vitro C3H10T1/2 cell culture showed that PEO–Fe/Mn promoted the best cell growth, alkaline phosphatase activity, and bone-related gene expression. Furthermore, the rat femur implantation experiment showed that PEO–Fe/Mn–coated Mg showed the best bone regeneration and osteointegration abilities. Owing to enhanced corrosion resistance and osteogenesis, the PEO–Fe/Mn film on Mg alloy is promising for orthopedic applications.