bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of NGS Technology in Understanding the Pathology of Autoimmune Diseases
Authors: Wajda Anna , Sivitskaya Larysa , Paradowska-Gorycka Agnieszka
Published: July 2021

NGS technologies have transformed clinical diagnostics and broadly used from neonatal emergencies to adult conditions where the diagnosis cannot be made based on clinical symptoms. Autoimmune diseases reveal complicate molecular background and traditional methods could not fully capture them. Certainly, NGS technologies meet the needs of modern exploratory research, diagnostic and pharmacotherapy. Therefore, the main purpose of this review was to briefly present the application of NGS technology used in recent years in the understanding of autoimmune diseases paying particular attention to autoimmune connective tissue diseases. The main issues are presented in four parts: (a) panels, whole-genome and -exome sequencing (WGS and WES) in diagnostic, (b) Human leukocyte antigens (HLA) as a diagnostic tool, (c) RNAseq, (d) microRNA and (f) microbiome. Although all these areas of research are extensive, it seems that epigenetic impact on the development of systemic autoimmune diseases will set trends for future studies on this area.
Limbal Approach Phacovitrectomy to Treat Cataract with Clinically Significant Asteroid Hyalosis—Presentation of the Technique and Preliminary Results
Authors: Rozegnał-Madej Agnieszka , Wlaź Aleksandra , Żarnowski Tomasz
Published: July 2021

Purpose: To assess preliminarily the efficacy and safety of a relatively new surgical modification of phacovitrectomy in eyes with cataract and visually significant asteroid hyalosis (AH). Materials and methods: Prospective, noncomparative, interventional case series of six eyes of six patients (mean age 75.6 years; 1 woman, 5 men) with cataract and visually significant AH treated with a novel surgical technique—a phacoemulsification with anterior vitrectomy through posterior capsulorhexis and intraocular lens (IOL) implantation. Main outcome measures were: best-corrected visual acuity (BCVA), intraocular pressure (IOP), IOL centration, complications. Mean follow-up was 39.17 ± 4.31 months. Results: The mean BCVA (Snellen) improved from 0.26 ± 0.18 to 0.73 ± 0.33 at the end of the follow-up. IOP was in the normal range, and no problems with IOL fixation were observed at the end of the follow-up. No post-operative complications, retinal detachment, retinal tears, macular edema or prolonged inflammation were observed. Conclusions: The presented new surgical technique seems to be a safe and efficacious method to treat cataract with visually significant asteroid hyalosis.
The Value of Cardiac Magnetic Resonance Imaging in Identification of Rare Diseases Mimicking Hypertrophic Cardiomyopathy
Authors: Fang Tingting , Wang Jie , Kang Yu , Yang Fuyao , Xu Yuanwei , Wan Ke , Sun Jiayu , Han Yuchi , Chen Yucheng
Published: July 2021

Background: The cardiac Magnetic Resonance Imaging (MRI) characteristics of rare diseases with the hypertrophic cardiomyopathy (HCM) phenotype are not well defined. Methods: Seventy-three sequential patients and 34 of their relatives, who have the HCM phenotype, were included. All subjects underwent cardiac MRI and genetic testing. Results: Of these 107 patients with phenotypic HCM, seven rare diseases were identified: four cases with LAMP2, one case with PRKAG2, one case with TTR mutation, and one case with senile systemic amyloidosis. Subjects with rare diseases had diffuse LGE, and the percentage of those with LGE was significantly higher than that of other HCM (median: 18.9%, interquartile range (IQR): 14.05 to 28.2% versus 7.8%, IQR: 4.41 to 14.56%; p = 0.003). Additionally, global T1 and ECV were significantly higher in subjects with rare diseases (global T1: 1423.1 ± 93.3 ms versus 1296.2 ± 66.6 ms; global ECV: 44.3 ± 11.5% versus 29.9 ± 4.5%; all p < 0.001). Conclusions: Cardiac MRI suggests the existence of distinct imaging characteristics, including via LGE and T1 mapping, among rare diseases that mimic HCM and HCM itself.
Lesion Geometry as Assessed by Optical Coherence Tomography Is Related to Myocardial Ischemia as Determined by Cardiac Magnetic Resonance Imaging
Authors: Dettori Rosalia , Milzi Andrea , Frick Michael , Burgmaier Kathrin , Almalla Mohammad , Lubberich Richard Karl , Marx Nikolaus , Reith Sebastian , Burgmaier Mathias
Published: July 2021

Introduction: Although the relationship between the geometry of coronary stenosis and the presence of myocardial ischemia is well known, the association between stenosis geometry and severity and/or extent of ischemia is still unexplored. Thus, we investigated this relationship using optical coherence tomography (OCT) to assess stenosis parameters and cardiac magnetic resonance imaging (CMR) to determine both extent and severity of ischemia. Methods: We analyzed 55 lesions from 51 patients with stable angina. Pre-interventionally, all patients underwent OCT-analysis of stenosis morphology as well as CMR to determine both the extent and severity of myocardial ischemia. Results: Percent area stenosis (%AS) was significantly associated with ischemic burden (r = 0.416, p = 0.003). Similar results could be obtained for other stenosis parameters as well as for several other parameters assessing the extent of ischemia. Furthermore, OCT-derived stenosis parameters were associated with the product of ischemic burden and severity of ischemia (%AS: r = 0.435, p = 0.002; similar results for other parameters). A Poiseuille’s-law-modelled combination of stenosis length and minimal lumen diameter yielded a good diagnostic efficiency (AUC 0.787) in predicting an ischemic burden >10%. Conclusions: Our data highlight the key role of the geometry of coronary lesions in determining myocardial ischemia.
Monocyte Distribution Width, Neutrophil-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio Improves Early Prediction for Sepsis at the Emergency
Authors: Hou Sen-Kuang , Lin Hui-An , Chen Shao-Chun , Lin Chiou-Feng , Lin Sheng-Feng
Published: July 2021

(1) Background: Sepsis is a life-threatening condition, and most patients with sepsis first present to the emergency department (ED) where early identification of sepsis is challenging due to the unavailability of an effective diagnostic model. (2) Methods: In this retrospective study, patients aged ≥20 years who presented to the ED of an academic hospital with systemic inflammatory response syndrome (SIRS) were included. The SIRS, sequential organ failure assessment (SOFA), and quick SOFA (qSOFA) scores were obtained for all patients. Routine complete blood cell testing in conjugation with the examination of new inflammatory biomarkers, namely monocyte distribution width (MDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), was performed at the ED. Propensity score matching was performed between patients with and without sepsis. Logistic regression was used for constructing models for early sepsis prediction. (3) Results: We included 296 patients with sepsis and 1184 without sepsis. A SIRS score of >2, a SOFA score of >2, and a qSOFA score of >1 showed low sensitivity, moderate specificity, and limited diagnostic accuracy for predicting early sepsis infection (c-statistics of 0.660, 0.576, and 0.536, respectively). MDW > 20, PLR > 9, and PLR > 210 showed higher sensitivity and moderate specificity. When we combined these biomarkers and scoring systems, we observed a significant improvement in diagnostic performance (c-statistics of 0.796 for a SIRS score of >2, 0.761 for a SOFA score of >2, and 0.757 for a qSOFA score of >1); (4) Conclusions: The new biomarkers MDW, NLR, and PLR can be used for the early detection of sepsis in the current sepsis scoring systems.
Cardiorenal Syndrome: Emerging Role of Medical Imaging for Clinical Diagnosis and Management
Authors: Lin Ling , Zhou Xuhui , Dekkers Ilona A. , Lamb Hildo J.
Published: July 2021

Cardiorenal syndrome (CRS) concerns the interconnection between heart and kidneys in which the dysfunction of one organ leads to abnormalities of the other. The main clinical challenges associated with cardiorenal syndrome are the lack of tools for early diagnosis, prognosis, and evaluation of therapeutic effects. Ultrasound, computed tomography, nuclear medicine, and magnetic resonance imaging are increasingly used for clinical management of cardiovascular and renal diseases. In the last decade, rapid development of imaging techniques provides a number of promising biomarkers for functional evaluation and tissue characterization. This review summarizes the applicability as well as the future technological potential of each imaging modality in the assessment of CRS. Furthermore, opportunities for a comprehensive imaging approach for the evaluation of CRS are defined.
Association of HLA-B*51:01, HLA-B*55:01, CYP2C9*3, and Phenytoin-Induced Cutaneous Adverse Drug Reactions in the South Indian Tamil Population
Authors: John Shobana , Balakrishnan Karuppiah , Sukasem Chonlaphat , Anand Tharmarajan Chinnathambi Vijay , Canyuk Bhutorn , Pattharachayakul Sutthiporn
Published: July 2021

Phenytoin (PHT) is one of the most commonly reported aromatic anti-epileptic drugs (AEDs) to cause cutaneous adverse reactions (CADRs), particularly severe cutaneous adverse reactions (SCARs). Although human leukocyte antigen (HLA)-B*15:02 is associated with PHT-induced Steven Johnson syndrome/toxic epidermal necrosis (SJS/TEN) in East Asians, the association is much weaker than it is reported for carbamazepine (CBZ). In this study, we investigated the association of pharmacogenetic variants of the HLA B gene and CYP2C9*3 with PHT-CADRs in South Indian epileptic patients. This prospective case-controlled study included 25 PHT-induced CADRs, 30 phenytoin-tolerant patients, and 463 (HLA-B) and 82 (CYP2C9*3) normal-controls from previous studies included for the case and normal-control comparison. Six SCARs cases and 19 mild-moderate reactions were observed among the 25 cases. Pooled data analysis was performed for the HLA B*51:01 and PHT-CADRs associations. The Fisher exact test and multivariate binary logistic regression analysis were used to identify the susceptible alleles associated with PHT-CADRs. Multivariate analysis showed that CYP2C9*3 was significantly associated with overall PHT-CADRs (OR = 12.00, 95% CI 2.759–84.87, p = 003). In subgroup analysis, CYP2C9*3 and HLA B*55:01 were found to be associated with PHT-SCARs (OR = 12.45, 95% CI 1.138–136.2, p = 0.003) and PHT-maculopapular exanthema (MPE) (OR = 4.041, 95% CI 1.125–15.67, p = 0.035), respectively. Pooled data analysis has confirmed the association between HLA B*51:01/PHT-SCARs (OR = 6.273, 95% CI 2.24–16.69, p = <0.001) and HLA B*51:01/PHT-overall CADRs (OR = 2.323, 95% CI 1.22–5.899, p = 0.037). In this study, neither the case nor the control groups had any patients with HLA B*15:02. The risk variables for PHT-SCARs, PHT-overall CADRs, and PHT-MPE were found to be HLA B*51:01, CYP2C9*3, and HLA B*55:01, respectively. These alleles were identified as the risk factors for the first time in the South Indian Tamil population for PHT-CADRs. Further investigation is warranted to establish the clinical relevance of these alleles in this population with larger sample size.
High BMI1 Expression with Low CD8+ and CD4+ T Cell Activity Could Promote Breast Cancer Cell Survival: A Machine Learning Approach
Authors: Chung Yumin , Min Kyueng-Whan , Kim Dong-Hoon , Son Byoung Kwan , Do Sung-Im , Chae Seoung Wan , Kwon Mi Jung
Published: July 2021

BMI1 is known to play a key role in the regulation of stem cell self-renewal in both endogenous and cancer stem cells. High BMI1 expression has been associated with poor prognosis in a variety of human tumors. The aim of this study was to reveal the correlations of BMI1 with survival rates, genetic alterations, and immune activities, and to validate the results using machine learning. We investigated the survival rates according to BMI1 expression in 389 and 789 breast cancer patients from Kangbuk Samsung Medical Center (KBSMC) and The Cancer Genome Atlas, respectively. We performed gene set enrichment analysis (GSEA) with pathway-based network analysis, investigated the immune response, and performed in vitro drug screening assays. The survival prediction model was evaluated through a gradient boosting machine (GBM) approach incorporating BMI1. High BMI1 expression was correlated with poor survival in patients with breast cancer. In GSEA and in in silico flow cytometry, high BMI1 expression was associated with factors indicating a weak immune response, such as decreased CD8+ T cell and CD4+ T cell counts. In pathway-based network analysis, BMI1 was directly linked to transcriptional regulation and indirectly linked to inflammatory response pathways, etc. The GBM model incorporating BMI1 showed improved prognostic performance compared with the model without BMI1. We identified telomerase inhibitor IX, a drug with potent activity against breast cancer cell lines with high BMI1 expression. We suggest that high BMI1 expression could be a therapeutic target in breast cancer. These results could contribute to the design of future experimental research and drug development programs for breast cancer.
The Metabolic Score for Insulin Resistance (METS-IR) as a Predictor of Incident Ischemic Heart Disease: A Longitudinal Study among Korean without Diabetes
Authors: Yoon Jihyun , Jung Donghyuk , Lee Yongjae , Park Byoungjin
Published: July 2021

The metabolic score for insulin resistance (METS-IR) is a novel noninsulin-based marker for assessing the risk of insulin resistance and cardiometabolic risk. However, whether METS-IR is associated with incident ischemic heart disease (IHD) risk is not well known. Therefore, we aimed to investigate the longitudinal effect of METS-IR on incident IHD risk in a large cohort of Korean adults without diabetes. Data were assessed from 17,943 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. The participants were divided into four groups according to METS-IR index quartiles: (ln ((2 × fasting plasma glucose) + triglyceride) × body mass index)/(ln (HDL-cholesterol)). We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional hazard regression models over a 50-month period. During the follow-up period, 332 participants (1.9%) developed IHD. HRs of IHD for METS-IR quartiles 1–4 were 1.00, were 1.62 (95% CI 1.04–2.53), 1.87 (95% CI 1.20–2.91), and 2.11 (95% CI 1.35–3.30), respectively, after adjusting for potential confounding variables. A higher METS-IR precedes future IHD among Koreans without diabetes. Moreover, compared with metabolic syndrome, METS-IR had a better predictive value for IHD.
VEGFR-Mediated Cytotoxic Activity of Pulicaria undulata Isolated Metabolites: A Biological Evaluation and In Silico Study
Authors: Elhady Sameh S. , Abdelhameed Reda F. A. , Zekry Salwa H. , Ibrahim Amany K. , Habib Eman S. , Darwish Khaled M. , Hazem Reem M. , Mohammad Khadijah A. , Hassanean Hashim A. , Ahmed Safwat A.
Published: July 2021

Natural products play a remarkable role not only in the synthesis, design, and discovery of new drugs but also as the most prominent source of drugs and bioactive substances. Adding to the search for new sources of safe innovative antitumor drugs, here we reported a phytochemical study on Pulicaria undulata which revealed promising antiangiogenic agents. Six compounds were isolated and identified as xanthoxyline (1), stigmasterol (2), oleanolic acid (3), salvigenin (4), rhamnetin (5) and dihydroquercetin-4′-methyl ether (6) using nuclear magnetic resonance (NMR) spectroscopic techniques. Compound 3 and 4 are first reported in Pulicaria genus. Both the extract and isolated compounds were evaluated for in vitro antiproliferative activity against breast cancer cell line (MCF-7). In vivo antiproliferative activity against Ehrlich’s ascites carcinoma (EAC) were also assessed. The P. undulata extract and isolates showed significant reduction in tumor weight, decreased both serum vascular endothelial growth factor B (VEGF-B) levels and vascular endothelial growth factor receptor 2 (VEGFR-2) expression significantly compared to the control EAC group, suggesting an antiangiogenic activity through the inhibition of VEGF signaling. Besides, they displayed reduction in CD34 expression, confirming their antiangiogenic effect. Moreover, the potential affinity of isolated compounds to human estrogen nuclear receptor-alpha (hER-α), the most recognized modulator of VEGFR-2 expression, was virtually estimated through molecular modeling studies. The most promising activity profiles were assigned to the investigated flavonoids, compounds 4–6, as well as the alkyl-phenylketone, compound 1. Additionally, these four top active compounds showed respective high to intermediate docking scores while possessing preferential binding with hER-α critical pocket residues. Based on the provided data, these isolated compounds illustrated promising inhibitors of VEGF-stimulated angiogenesis, which could be a possible mechanism for their anticancer activity.
The Microbiota/Microbiome and the Gut–Brain Axis: How Much Do They Matter in Psychiatry?
Authors: Marazziti Donatella , Buccianelli Beatrice , Palermo Stefania , Parra Elisabetta , Arone Alessandro , Beatino Maria , Massa Lucia , Carpita Barbara , Barberi Filippo , Mucci Federico , Dell’Osso Liliana
Published: July 2021

The functioning of the central nervous system (CNS) is the result of the constant integration of bidirectional messages between the brain and peripheral organs, together with their connections with the environment. Despite the anatomical separation, gut microbiota, i.e., the microorganisms colonising the gastrointestinal tract, is highly related to the CNS through the so-called “gut–brain axis”. The aim of this paper was to review and comment on the current literature on the role of the intestinal microbiota and the gut–brain axis in some common neuropsychiatric conditions. The recent literature indicates that the gut microbiota may affect brain functions through endocrine and metabolic pathways, antibody production and the enteric network while supporting its possible role in the onset and maintenance of several neuropsychiatric disorders, neurodevelopment and neurodegenerative disorders. Alterations in the gut microbiota composition were observed in mood disorders and autism spectrum disorders and, apparently to a lesser extent, even in obsessive-compulsive disorder (OCD) and related conditions, as well as in schizophrenia. Therefore, gut microbiota might represent an interesting field of research for a better understanding of the pathophysiology of common neuropsychiatric disorders and possibly as a target for the development of innovative treatments that some authors have already labelled “psychobiotics”.
Rutin Mediated Apoptotic Cell Death in Caski Cervical Cancer Cells via Notch-1 and Hes-1 Downregulation
Authors: Khan Fahad , Pandey Pratibha , Jha Niraj Kumar , Khalid Mohammad , Ojha Shreesh
Published: July 2021

Natural dietary molecules such as flavonoids have been recognized for their immense potential in cancer therapeutics with several health benefits. Hes-1 and Notch-1 overexpression has been associated with the progression of cervical cancer. However, the apoptosis-inducing potential of one such potent flavanol against these two key components of the Notch signaling pathway in cervical cancer has not been elucidated to date. Therefore, in this study, we performed several in vitro assays to gain detailed insight about the apoptotic inducing effect of rutin as well as its modulatory effect on Notch-1 and Hes-1 in cervical cancer cells. The results indicated that rutin led to a dose-dependent antiproliferative effects on Caski cervical cancer cells. DAPI and Mitotracker red staining revealed that rutin induced significant apoptotic effects via caspase-3/9 activation, ROS generation, and alteration in Bax/Bcl2 mRNA expression. Cell cycle analysis resulted in the arrest of cell cycle progression in G0/G1 that was associated with a reduced expression of CDK4 and Cyclin D1. The gene expression analysis further revealed that rutin treatment decreases Notch-1 and Hes-1 mRNA expression. Altogether, these results showed that rutin showed potent anticancer effects in human cervical cancer Caski cells by triggering apoptosis, G0/G1 phase arrest, and downregulating the level of Notch-1 and Hes-1 of the Notch signaling pathway.
4,4′-Di-tert-butyl-2,2′-bipyridinium Trifluoromethanesulfonate
Authors: Kodama Shintaro , Bunno Kazuki , Nomoto Akihiro , Ogawa Akiya
Published: July 2021

4,4′-Di-tert-butyl-2,2′-bipyridinium trifluoromethanesulfonate was synthesized by stirring 4,4′-Di-tert-butyl-2,2′-bipyridine with scandium(III) trifluoromethanesulfonate in acetonitrile, followed by precipitation with diethyl ether. The structure of the new compound was characterized by FT-IR, 1H, 13C{1H} and 19F{1H} NMR spectroscopy and CHN elemental analysis. This is a safe and simple method to obtain mono-protonated bipyridinium trifluoromethanesulfonate without the direct use of trifluoromethanesulfonic acid.
Methods and Models of Theoretical Calculation for Single-Molecule Magnets
Authors: Luo Qian-Cheng , Zheng Yan-Zhen
Published: July 2021

Theoretical calculation plays an important role in the emerging field of single-molecule magnets (SMMs). It can not only explain experimental phenomena but also provide synthetic guidance. This review focuses on discussing the computational methods that have been used in this field in recent years. The most common and effective method is the complete active space self-consistent field (CASSCF) approach, which predicts mononuclear SMM property very well. For bi- and multi-nuclear SMMs, magnetic exchange needs to be considered, and the exchange coupling constants can be obtained by Monte Carlo (MC) simulation, ab initio calculation via the POLY_ANISO program and density functional theory combined with a broken-symmetry (DFT-BS) approach. Further application for these calculation methods to design high performance SMMs is also discussed.
Some Modifications of Pairwise Soft Sets and Some of Their Related Concepts
Authors: Al Ghour Samer
Published: July 2021

In this paper, we first define soft u-open sets and soft s-open as two new classes of soft sets on soft bitopological spaces. We show that the class of soft p-open sets lies strictly between these classes, and we give several sufficient conditions for the equivalence between soft p-open sets and each of the soft u-open sets and soft s-open sets, respectively. In addition to these, we introduce the soft u-ω-open, soft p-ω-open, and soft s-ω-open sets as three new classes of soft sets in soft bitopological spaces, which contain soft u-open sets, soft p-open sets, and soft s-open sets, respectively. Via soft u-open sets, we define two notions of Lindelöfeness in SBTSs. We discuss the relationship between these two notions, and we characterize them via other types of soft sets. We define several types of soft local countability in soft bitopological spaces. We discuss relationships between them, and via some of them, we give two results related to the discrete soft topological space. According to our new concepts, the study deals with the correspondence between soft bitopological spaces and their generated bitopological spaces.
Co-Movements between Eu Ets and the Energy Markets: A Var-Dcc-Garch Approach
Authors: Gargallo Pilar , Lample Luis , Miguel Jesús A. , Salvador Manuel
Published: July 2021

This paper analyzes the co-movements of prices of fossil fuels, energy stock markets and EU allowances. This analysis is conducted in order to identify the spillover effect of volatility and correlation among these financial markets, and to provide a scientific basis that shows the interest of incorporating sustainable assets in the design of minimum risk strategies of investment. To achieve this goal, we have used a Vector Autoregressive-Dynamic Conditional Correlation-Generalized Autoregressive Conditional Heteroscedasticity (VAR-DCC-GARCH) model that also incorporates a stock index of industrial companies as a leading indicator of the level of economic activity. In addition, the paper conducts an impulse response analysis to determine how unexpected shocks to prices are propagated along time, and, in particular, how they affect prices of the others, both in mean, variance and correlation. Therefore, the results of this one- and two-dimensional analysis allow for the study of short and long run dynamics of the relationship among those prices, thus, providing greater meaning and information for investors, which has implications for building their portfolios. The analyzed period was from January 2010 to February 2021, so that the data include half of phase II, full phase III and the onset of phase IV of the EU ETS, as well as the COVID-19 outbreak in the European context. We also analyzed whether the EUA price impulses the demand of clean energy stocks, which has important implications for the objective of triggering the investment in clean energy. Our results show the transmission mechanism of all of those prices, which are relevant not only for investors but also for policymakers to construct an early-warning system, revealing the most important transmission channels. Moreover, from an investment viewpoint, we observe a decline in dirty energies and a rise in the clean energy market, which might be an indication of the progress towards the energy transition to renewables sources within a circular economy perspective. Therefore, this shows that the EU ETS is achieving its goals, and that clean energy companies, aligned with their role towards socially responsible initiatives, are also gaining acceptance in terms of investments, which would be beneficial for the environment.
Multi-Transformer: A New Neural Network-Based Architecture for Forecasting S&P Volatility
Authors: Ramos-Pérez Eduardo , Alonso-González Pablo J. , Núñez-Velázquez José Javier
Published: July 2021

Events such as the Financial Crisis of 2007–2008 or the COVID-19 pandemic caused significant losses to banks and insurance entities. They also demonstrated the importance of using accurate equity risk models and having a risk management function able to implement effective hedging strategies. Stock volatility forecasts play a key role in the estimation of equity risk and, thus, in the management actions carried out by financial institutions. Therefore, this paper has the aim of proposing more accurate stock volatility models based on novel machine and deep learning techniques. This paper introduces a neural network-based architecture, called Multi-Transformer. Multi-Transformer is a variant of Transformer models, which have already been successfully applied in the field of natural language processing. Indeed, this paper also adapts traditional Transformer layers in order to be used in volatility forecasting models. The empirical results obtained in this paper suggest that the hybrid models based on Multi-Transformer and Transformer layers are more accurate and, hence, they lead to more appropriate risk measures than other autoregressive algorithms or hybrid models based on feed forward layers or long short term memory cells.
Screening of Neutrophil Activating Factors from a Metagenome Library of Sponge-Associated Bacteria
Authors: Okamura Yoshiko , Takahashi Hirokazu , Shiida Atsuyuki , Hirata Yuto , Takeyama Haruko , Suzuki Katsuhiko
Published: July 2021

Marine sponge-associated bacteria are known as bio-active compound produce. We have constructed metagenome libraries of the bacteria and developed a metagenomic screening approach. Activity-based screening successfully identified novel genes and novel enzymes; however, the efficiency was only in 1 out of 104 clones. Therefore, in this study, we thought that bioinformatics could help to reduce screening efforts, and combined activity-based screening with database search. Neutrophils play an important role for the immune system to recognize excreted bacterial by-products as chemotactic factors and are recruited to infection sites to kill pathogens via phagocytosis. These excreted by-products are considered critical triggers that engage the immune system to mount a defense against infection, and identifying these factors may guide developments in medicine and diagnostics. We focused on genes encoding amino acid ligase and peptide synthetase and selected from an in-house sponge metagenome database. Cell-free culture medium of each was used in a neutrophil chemiluminescence assay in luminol reaction. The clone showing maximum activity had a genomic sequence expected to produce a molecule like a phospho-N-acetylmuramyl pentapeptide by the metagenome fragment analysis.
Treatment of Intertrochanteric Femur Fractures with Hip Arthroplasty in Older Patients: A Narrative Review of Indications and Outcomes
Authors: Martinho Tiago , Stoffel Karl
Published: July 2021

Intertrochanteric femur fractures are common in older patients and often have a significant impact on disability. The treatment aims to achieve a rapid return to the prior functional level with a low rate of complications and mortality. Surgical management by internal fixation is the mainstay of treatment for most of these fractures. Even when treated with intramedullary nails, the overall complication rates are high, especially for unstable or highly comminuted fractures or in the presence of poor bone quality. Hip arthroplasty is an alternative in older patients with intertrochanteric femur fractures at high risk of fixation failure or with concomitant intraarticular pathologies. Especially patients whose condition precludes prolonged bedrest and who are at risk of significant deterioration if their locomotor function cannot be restored rapidly are likely to benefit from hip arthroplasty. The choice of the surgical technique mainly depends on the surgeon’s preferences and the fracture characteristics. Bipolar hemiarthroplasty is the most common type of prosthesis used with primary or revision femoral stems. Compared with intramedullary nails, hip arthroplasty has a better early functional outcome and lower rates of surgical complications as well as reoperations. However, the functional outcome and the mortality rate in the longer term tend to favor intramedullary nails, even though the results are inconsistent, and a statistically significant difference cannot always be obtained. Currently, there are no guidelines that define the role of hip arthroplasty in the treatment of intertrochanteric femur fractures in older patients. The literature only offers an overview of the possibilities of the usage of hip arthroplasty, but methodological limitations are common, and evidence levels are low. Further studies are needed to identify the intertrochanteric fractures that are at high risk of internal fixation failure, the characteristics that determine which patients may benefit most from hip arthroplasty, and the optimal surgical technique.
Clinical Method Applied to Focused Ultrasound: The Case of Wells’ Score and Echocardiography in the Emergency Department: A Systematic Review and a Meta-Analysis
Authors: Falsetti Lorenzo , Zaccone Vincenzo , Marra Alberto , Tarquinio Nicola , Viticchi Giovanna , Sampaolesi Mattia , Riccomi Francesca , Giovenali Laura , Ferrini Consuelo , Moroncini Gianluca , Nitti Cinzia , Salvi Aldo
Published: July 2021

Background and Objectives: bedside cardiac ultrasound is a widely adopted method in Emergency Departments (ED) for extending physical examination and refining clinical diagnosis. However, in the setting of hemodynamically-stable pulmonary embolism, the diagnostic role of echocardiography is still the subject of debate. In light of its high specificity and low sensitivity, some authors suggest that echocardiographic signs of right ventricle overload could be used to rule-in pulmonary embolism. In this study, we aimed to clarify the diagnostic role of echocardiographic signs of right ventricle overload in the setting of hemodynamically-stable pulmonary embolism in the ED. Materials and Methods: we performed a systematic review of literature in PubMed, Web of Science and Cochrane databases, considering the echocardiographic signs for the diagnosis of pulmonary embolism in the ED. Studies considering unstable or shocked patients were excluded. Papers enrolling hemodynamically stable subjects were selected. We performed a diagnostic test accuracy meta-analysis for each sign, and then performed a critical evaluation according to pretest probability, assessed with Wells’ score for pulmonary embolism. Results: 10 studies were finally included. We observed a good specificity and a low sensitivity of each echocardiographic sign of right ventricle overload. However, once stratified by the Wells’ score, the post-test probability only increased among high-risk patients. Conclusions: signs of echocardiographic right ventricle overload should not be used to modify the clinical behavior in low- and intermediate- risk patients according to Wells’ score classification. Among high-risk patients, however, echocardiographic signs could help a physician in detecting patients with the highest probability of pulmonary embolism, necessitating a confirmation by computed tomography with pulmonary angiography. However, a focused cardiac and thoracic ultrasound investigation is useful for the differential diagnosis of dyspnea and chest pain in the ED.
A Composite Membrane System with Gold Nanoparticles, Hydroxyapatite, and Fullerenol for Dual Interaction for Biomedical Purposes
Authors: Grzeczkowicz Anna , Drabik Monika , Lipko Agata , Bącal Paweł , Kwiatkowska Angelika , Kazimierczak Beata , Granicka Ludomira H.
Published: July 2021

Background: Wound dressing plays a vital role in post-operative aftercare. There is the necessity to develop dressings for application on the border of soft and hard tissue. This study aimed to develop multifunctional polyelectrolyte layers enhanced by hydroxyapatite nanoparticles, gold nanoparticles (AuNPs), and/or fullerenol nanocomposites to achieve a wound dressing that could be applied on the bone-skin interface. Methods: Constructed shells were examined using TEM, STEM, and EDX techniques. The human osteoblasts or fibroblasts were immobilized within the shells. The systems morphology was assessed using SEM. The functioning of cells was determined by flow cytomery. Moreover, the internalization of AuNPs was assessed. Results: Involvement of fullerenol and/or hydroxyapatite nanoparticles influenced the immobilized cell systems morphology. Membranes with fullerenol and hydroxyapatite nanoparticles were observed to block the internalization of AuNPs by immobilized hFOB cells. Conclusions: The designed bilayer membranes incorporating fullerenol, and bacteriostatic elements, prevented the internalization of AuNPs by hFOB cells and ensured the proper counts and morphology of eukaryotic cells. The developed material can be recommended for dressings at the bone-skin interface.
Evaluating Fertilizer-Drawn Forward Osmosis Performance in Treating Anaerobic Palm Oil Mill Effluent
Authors: Abdul Wahid Ruwaida , Ang Wei Lun , Mohammad Abdul Wahab , Johnson Daniel James , Hilal Nidal
Published: July 2021

Fertilizer-drawn forward osmosis (FDFO) is a potential alternative to recover and reuse water and nutrients from agricultural wastewater, such as palm oil mill effluent that consists of 95% water and is rich in nutrients. This study investigated the potential of commercial fertilizers as draw solution (DS) in FDFO to treat anaerobic palm oil mill effluent (An-POME). The process parameters affecting FO were studied and optimized, which were then applied to fertilizer selection based on FO performance and fouling propensity. Six commonly used fertilizers were screened and assessed in terms of pure water flux (Jw) and reverse salt flux (JS). Ammonium sulfate ((NH4)2SO4), mono-ammonium phosphate (MAP), and potassium chloride (KCl) were further evaluated with An-POME. MAP showed the best performance against An-POME, with a high average water flux, low flux decline, the highest performance ratio (PR), and highest water recovery of 5.9% for a 4-h operation. In a 24-h fouling run, the average flux decline and water recovered were 84% and 15%, respectively. Both hydraulic flushing and osmotic backwashing cleaning were able to effectively restore the water flux. The results demonstrated that FDFO using commercial fertilizers has the potential for the treatment of An-POME for water recovery. Nevertheless, further investigation is needed to address challenges such as JS and the dilution factor of DS for direct use of fertigation.
Cumulative Fluid Balance during Extracorporeal Membrane Oxygenation and Mortality in Patients with Acute Respiratory Distress Syndrome
Authors: Chiu Li-Chung , Chuang Li-Pang , Lin Shih-Wei , Chiou Yu-Ching , Li Hsin-Hsien , Chen Yung-Chang , Lin Yu-Jr , Chang Chee-Jen , Tsai Feng-Chun , Chang Ko-Wei , Hu Han-Chung , Huang Chung-Chi , Leu Shaw-Woei , Kao Kuo-Chin
Published: July 2021

Extracorporeal membrane oxygenation (ECMO) is considered a salvage therapy in cases of severe acute respiratory distress syndrome (ARDS) with profound hypoxemia. However, the need for high-volume fluid resuscitation and blood transfusions after ECMO initiation introduces a risk of fluid overload. Positive fluid balance is associated with mortality in critically ill patients, and conservative fluid management for ARDS patients has been shown to shorten both the duration of mechanical ventilation and time spent in intensive care, albeit without a significant effect on survival. Nonetheless, few studies have addressed the influence of fluid balance on clinical outcomes in severe ARDS patients undergoing ECMO. In the current retrospective study, we examined the impact of cumulative fluid balance (CFB) on hospital mortality in 152 cases of severe ARDS treated using ECMO. Overall hospital mortality was 53.3%, and we observed a stepwise positive correlation between CFB and the risk of death. Cox regression models revealed that CFB during the first 3 days of ECMO was independently associated with higher hospital mortality (adjusted hazard ratio 1.110 [95% CI 1.027–1.201]; p = 0.009). Our findings indicate the benefits of a conservative treatment approach to avoid fluid overload during the early phase of ECMO when dealing with severe ARDS patients.
Gradually Modified Conductance in the Self-Compliance Region of an Atomic-Layer-Deposited Pt/TiO2/HfAlOx/TiN RRAM Device
Authors: Ryu Hojeong , Kim Sungjun
Published: July 2021

This study presents conductance modulation in a Pt/TiO2/HfAlOx/TiN resistive memory device in the compliance region for neuromorphic system applications. First, the chemical and material characteristics of the atomic-layer-deposited films were verified by X-ray photoelectron spectroscopy depth profiling. The low-resistance state was effectively controlled by the compliance current, and the high-resistance state was adjusted by the reset stop voltage. Stable endurance and retention in bipolar resistive switching were achieved. When a compliance current of 1 mA was imposed, only gradual switching was observed in the reset process. Self-compliance was used after an abrupt set transition to achieve a gradual set process. Finally, 10 cycles of long-term potentiation and depression were obtained in the compliance current region for neuromorphic system applications.
In Situ Synthesis of Core-Shell-Structured SiCp Reinforcements in Aluminium Matrix Composites by Powder Metallurgy
Authors: Ji Xinghua , Zhang Cheng , Li Shufeng
Published: July 2021

SiCp reinforced aluminium matrix composites (AMCs), which are widely used in the aerospace, automotive, and electronic packaging fields along with others, are usually prepared by ex situ techniques. However, interfacial contamination and poor wettability of the ex situ techniques make further improvement in their comprehensive performance difficult. In this paper, SiCp reinforced AMCs with theoretical volume fractions of 15%, 20%, and 30% are prepared by powder metallurgy and in situ reaction via an Al-Si-C system. Moreover, a combined method of external addition and an in situ method is used to investigate the synergistic effect of ex situ and in situ SiCp on AMCs. SiC particles can be formed by an indirect reaction: 4Al + 3C → Al4C3 and Al4C3 + 3Si → 3SiC + 4Al. This reaction is mainly through the diffusion of Si, in which Si diffuses around Al4C3 and then reacts with Al4C3 to form SiCp. The in situ SiC particles have a smooth boundary, and the particle size is approximately 1–3 μm. A core-shell structure having good bonding with an aluminium matrix was generated, which consists of an ex situ SiC core and an in situ SiC shell with a thickness of 1–5 μm. The yield strength and ultimate tensile strength of in situ SiCp reinforced AMCs can be significantly increased with a constant ductility by adding 5% ex situ SiCp for Al-28Si-7C. The graphite particle size has a significant effect on the properties of the alloy. A criterion to determine whether Al4C3 is a complete reaction is achieved, and the forming mechanism of the core-shell structure is analysed.
Effect on Microstructure and Hardness of Reinforcement in Al–Cu with Al4C3 Nanocomposites
Authors: Gallegos Orozco Veronica , Santos Beltrán Audel , Santos Beltrán Miriam , Medrano Prieto Hansel , Gallegos Orozco Carmen , Estrada Guel Ivanovich
Published: July 2021

By superposition, the individual strengthening mechanisms via hardness analyses and the particle dispersion contribution to strengthening were estimated for Al–C and Al–C–Cu composites and pure Al. An evident contribution to hardening due to the density of dislocations was observed for all samples; the presence of relatively high-density values was the result of the difference in the coefficients of thermal expansion (CTE) between the matrix and the reinforced particles when the composites were subjected to the sintering process. However, for the Al–C–Cu composites, the dispersion of the particles had an important effect on the strengthening. For the Al–C–Cu composites, the maximum increase in microhardness was ~210% compared to the pure Al sample processed under the same conditions. The crystallite size and dislocation density contribution to strengthening were calculated using the Langford–Cohen and Taylor equations from the microstructural analysis, respectively. The estimated microhardness values had a good correlation with the experimental. According to the results, the Cu content is responsible for integrating and dispersing the Al4C3 phase. The proposed mathematical equation includes the combined effect of the content of C and Cu (in weight percent). The composites were fabricated following a powder metallurgical route complemented with the mechanical alloying (MA) process. Microstructural analyses were carried out through X-ray analyses coupled with a convolutional multiple whole profile (CMWP) fitting program to determine the crystallite size and dislocation density.
The Metabolic Signature of In Vitro Produced Bovine Embryos Helps Predict Pregnancy and Birth after Embryo Transfer
Authors: Gimeno Isabel , García-Manrique Pablo , Carrocera Susana , López-Hidalgo Cristina , Valledor Luis , Martín-González David , Gómez Enrique
Published: July 2021

In vitro produced (IVP) embryos show large metabolic variability induced by breed, culture conditions, embryonic stage and sex and gamete donors. We hypothesized that the birth potential could be accurately predicted by UHPLC-MS/MS in culture medium (CM) with the discrimination of factors inducing metabolic variation. Day-6 embryos were developed in single CM (modified synthetic oviduct fluid) for 24 h and transferred to recipients as fresh (28 ETs) or frozen/thawed (58 ETs) Day-7 blastocysts. Variability was induced with seven bulls, slaughterhouse oocyte donors, culture conditions (serum + Bovine Serum Albumin [BSA] or BSA alone) prior to single culture embryonic stage records (Day-6: morula, early blastocyst, blastocyst; Day-7: expanding blastocyst; fully expanded blastocysts) and cryopreservation. Retained metabolite signals (6111) were analyzed as a function of pregnancy at Day-40, Day-62 and birth in a combinatorial block study with all fixed factors. We identified 34 accumulated metabolites through 511 blocks, 198 for birth, 166 for Day-62 and 147 for Day-40. The relative abundance of metabolites was higher within blocks from non-pregnant (460) than from pregnant (51) embryos. Taxonomy classified lipids (12 fatty acids and derivatives; 224 blocks), amino acids (12) and derivatives (3) (186 blocks), benzenoids (4; 58 blocks), tri-carboxylic acids (2; 41 blocks) and 5-Hydroxy-l-tryptophan (2 blocks). Some metabolites were effective as single biomarkers in 95 blocks (Receiver Operating Characteristic – Area Under the Curve [ROC-AUC]: 0.700–1.000). In contrast, more accurate predictions within the largest data sets were obtained with combinations of 2, 3 and 4 single metabolites in 206 blocks (ROC-AUC = 0.800–1.000). Pregnancy-prone embryos consumed more amino acids and citric acid, and depleted less lipids and cis-aconitic acid. Big metabolic differences between embryos support efficient pregnancy and birth prediction when analyzed in discriminant conditions.
Investigation of Andrographolide Effect on Non-Infected Red Blood Cells Using the 1H-NMR-Based Metabolomics Approach
Authors: Alapid Ashraf Ahmad Issa , Abd. Majid Roslaini , Ibraheem Zaid O. , Mediani Ahmed , Ismail Intan Safinar , Unyah Ngah Zasmy , Alhassan Abdullahi Sharif , Nordin Norshariza , Nasiru Wana Mohammed , Basir Rusliza
Published: July 2021

Andrographolide (AG) has been shown to have several medicinal and pharmaceutical effects, such as antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, and anti-malarial activities. Moreover, studies to assess the pharmacological effect of AG on the metabolic changes of uninfected red blood cells (uRBCs) have not yet been investigated. This study aims to evaluate the pharmacological effects of AG compared to chloroquine (CQ) on the metabolic variations of uRBCs in vitro using a proton nuclear magnetic resonance (1H-NMR)-based metabolomics approach coupled with multivariate data analysis (MVDA). Forty-one metabolites were successfully identified by 1H-NMR. The results of the unsupervised data analysis principal component analysis (PCA) showed ideal differentiation between AG and CQ. PC1 and PC2 accounted for 71.4% and 17.7% of the explained variation, respectively, with a total variance of 89.10%. Based on S-plot and VIP values, a total of 28 and 32 metabolites were identified as biomarkers in uRBCs-AG and uRBCs-CQ, respectively. In uRBCs treated with AG, ten metabolic pathways were determined to be disturbed, including riboflavin metabolism, d-glutamate and d-glutamine metabolism, phenylalanine metabolism, glutathione metabolism, proline and arginine metabolism, arginine biosynthesis, citrate cycle, glycolysis/gluconeogenesis, and pyruvate metabolism as well as alanine, aspartate, and glutamate metabolism. In contrast, in CQ-treated uRBCs, nine affected metabolic pathways were determined, which involved the same metabolic pathways for uRBCs-AG, except for glutathione metabolism. These findings suggest an evident relationship between AG and CQ associated with metabolic changes in intact RBCs after being exposed to the treatment. The metabolomics results could allow useful comprehensive insights into the underlying mechanism of the action of AG and CQ on red blood cells. Consequently, the 1H-NMR-based metabolomics approach was successfully utilized to identify the pharmacological effects of AG and CQ on the metabolic variations of uRBCs.