bluuebunny/crossref_metadata_2025 huggingface dataset:
The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections
Authors: Moubarak Mohamed , Kasozi Keneth Iceland , Hetta Helal F. , Shaheen Hazem M. , Rauf Abdur , Al-kuraishy Hayder M. , Qusti Safaa , Alshammari Eida M. , Ayikobua Emmanuel Tiyo , Ssempijja Fred , Afodun Adam Moyosore , Kenganzi Ritah , Usman Ibe Michael , Ochieng Juma John , Osuwat Lawrence Obado , Matama Kevin , Al-Gareeb Ali I. , Kairania Emmanuel , Musenero Monica , Welburn Susan Christina , Batiha Gaber El-Saber
Published: July 2021

Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1β, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19.
In-Hospital Mortality of COVID-19 Patients Treated with High-Flow Nasal Oxygen: Evaluation of Biomarkers and Development of the Novel Risk Score Model CROW-65
Authors: Kljakovic Gaspic Toni , Pavicic Ivelja Mirela , Kumric Marko , Matetic Andrija , Delic Nikola , Vrkic Ivana , Bozic Josko
Published: July 2021

To replace mechanical ventilation (MV), which represents the cornerstone therapy in severe COVID-19 cases, high-flow nasal oxygen (HFNO) therapy has recently emerged as a less-invasive therapeutic possibility for those patients. Respecting the risk of MV delay as a result of HFNO use, we aimed to evaluate which parameters could determine the risk of in-hospital mortality in HFNO-treated COVID-19 patients. This single-center cohort study included 102 COVID-19-positive patients treated with HFNO. Standard therapeutic methods and up-to-date protocols were used. Patients who underwent a fatal event (41.2%) were significantly older, mostly male patients, and had higher comorbidity burdens measured by CCI. In a univariate analysis, older age, shorter HFNO duration, ventilator initiation, higher CCI and lower ROX index all emerged as significant predictors of adverse events (p < 0.05). Variables were dichotomized and included in the multivariate analysis to define their relative weights in the computed risk score model. Based on this, a risk score model for the prediction of in-hospital mortality in COVID-19 patients treated with HFNO consisting of four variables was defined: CCI > 4, ROX index ≤ 4.11, LDH-to-WBC ratio, age > 65 years (CROW-65). The main purpose of CROW-65 is to address whether HFNO should be initiated in the subgroup of patients with a high risk of in-hospital mortality.
Plausibility of Early Life in a Relatively Wide Temperature Range: Clues from Simulated Metabolic Network Expansion
Authors: Chu Xin-Yi , Chen Si-Ming , Zhao Ke-Wei , Tian Tian , Gao Jun , Zhang Hong-Yu
Published: July 2021

The debate on the temperature of the environment where life originated is still inconclusive. Metabolic reactions constitute the basis of life, and may be a window to the world where early life was born. Temperature is an important parameter of reaction thermodynamics, which determines whether metabolic reactions can proceed. In this study, the scale of the prebiotic metabolic network at different temperatures was examined by a thermodynamically constrained network expansion simulation. It was found that temperature has limited influence on the scale of the simulated metabolic networks, implying that early life may have occurred in a relatively wide temperature range.
Sarcopenia—The Impact on Physical Capacity of Liver Transplant Patients
Authors: Miarka Maciej , Gibiński Krzysztof , Janik Maciej K. , Główczyńska Renata , Zając Krzysztof , Pacho Ryszard , Raszeja-Wyszomirska Joanna
Published: July 2021

Optimizing patients’ condition before liver transplantation (LT) could potentially improve survival of LT patients. We focused on sarcopenia, as a common factor in liver transplant candidates that can impact their cardiopulmonary performance at the point of listing, morbidity, and mortality after LT. We performed a single-center cohort study on 98 consecutive patients with liver cirrhosis who were transplanted between March 2015 and December 2017. The third lumbar vertebra skeletal muscle index (L3SMI) was calculated using CT imaging to distinguish sarcopenia at listing for LT. Data regarding liver function, body mass index (BMI), cardiac biomarkers, the peak oxygen uptake (VO2) and LT outcome were collected and correlated to L3SMI. For data analysis the Dell Statistica (Version 13. Dell Inc., Rondrock, TX, USA) was used. In total, 98 cirrhotic patients were included. Fifty-five (56.1%) patients, mostly males, had sarcopenia according to L3SMI, with the lowest L3SMI in males with alcohol-related liver disease. Lower L3SMI correlated with lower BMI, lower VO2 peak, and higher NTproBNP (all p < 0.001) and revealed an essential correlation with prolonged ICU stay (r = −0.21, p < 0.05). 33 patients were unable to perform cardio-pulmonary exercise test, mostly sarcopenic (67%), with more advanced liver insufficiency (assessed with CPC and MELD scores) and longer stay at ICU after LT (all p < 0.001). Sarcopenia was common among LT recipients. It was associated with inferior result in cardio-pulmonary performance before LT and prolonged ICU stay after grafting.
Effects of Resistance Exercise with or without Whey Protein Supplementation on Ocular Changes after a 21-Day Head-Down Bed Rest
Authors: Kermorgant Marc , Hammoud Sirine , Mahieu Laurence , Geeraerts Thomas , Beck Arnaud , Bareille Marie-Pierre , Soler Vincent , Pavy-Le Traon Anne , Quintyn Jean-Claude
Published: July 2021

Neuro-ophthalmological changes have been reported after prolonged exposure to microgravity; however, the pathophysiology remains unclear. The objectives of the present study were twofold: (1) to assess the neuro-ophthalmological impact of 21 days of head-down bed rest (HDBR) and (2) to determine the effects of resistance vibration exercise (RVE) alone or combined with nutritional supplementation (NeX). In this case, 12 healthy male subjects completed three interventions of a 21-day HDBR: a control condition without countermeasure (CON), a condition with resistance vibration exercise (RVE) comprising of squats, single leg heel and bilateral heel raises and a condition using also RVE associated with nutritional supplementation (NeX). Intraocular pressure (IOP) was assessed by applanation tonometry. Retinal nerve fiber layer thickness (RNFLT) was assessed with spectral-domain optical coherence tomography, before HDBR and between Day 2 and Day 4 after each session of HDBR. In CON condition, IOP was preserved; while in RVE and NeX conditions, IOP was increased. In CON condition, RNFLT was preserved after HDBR. RVE and NeX conditions did not have significant effects on RNFLT. This study showed that a 3-week HDBR did not induce significant ophthalmological changes. However, RVE induced an elevation in IOP after HDBR. Nutritional supplementation did not reduce or exacerbate the side effects of RVE.
Phloretin Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Regulating the Inflammatory Response, Oxidative Stress and Apoptosis
Authors: Hsu Chao Yu , Lin Yi Sheng , Weng Wei Chun , Panny Lauren , Chen Hsiang Lai , Tung Min Che , Ou Yen Chuan , Lin Chi Chien , Yang Che Hsueh
Published: July 2021

The inflammatory process is proposed to be one of the factors to benign prostatic enlargement (BPH), and this is the first study examining the anti-inflammatory ability of phloretin in treating rats with testosterone-induced BPH. BPH would be induced by testosterone (10 mg/kg/day testosterone subcutaneously for 28 days), and the other groups of rats were treated with phloretin 50 mg/kg/day or 100 mg/kg/day orally (phr50 or phr100 group) after induction. Prostate weight and prostate weight to body weight ratio were significantly reduced in the Phr100 group. Reduced dihydrotestosterone without interfering with 5α-reductase was observed in the phr100 group. In inflammatory proteins, reduced IL-6, IL-8, IL-17, NF-κB, and COX-2 were seen in the phr100 group. In reactive oxygen species, malondialdehyde was reduced, and superoxide dismutase and glutathione peroxidase were elevated in the phr100 group. In apoptotic assessment, elevated cleaved caspase-3 was observed in rats of the phr100 group. Enhanced pro-apoptotic Bax and reduced anti-apoptotic Bc1-2 could be seen in the phr100 group. In histological stains, markedly decreased glandular hyperplasia and proliferative cell nuclear antigen were observed with reduced expression in the phr100 group. Meanwhile, positive cells of terminal deoxynucleotidyl transferase dUTP nick end labeling were increased in the phr100 group. In conclusion, the treatment of phloretin 100 mg/kg/day could ameliorate testosterone-induced BPH.
Molecular Targets for Biological Therapies of Severe Asthma: Focus on Benralizumab and Tezepelumab
Authors: Cheng Shih-Lung
Published: July 2021

Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). In recent years several molecular effectors and signaling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic mono-clonal antibodies currently allow one to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. Pro-allergic immunoglobulin E (IgE) is the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed; today other targets are successfully being exploited by biological treatments for severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor, and IL-4 and IL-13 can be targeted by dupilumab. Besides these drugs, which are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing severe asthma management on a global level. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, which are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. The aim of the study is to review the immunopathology and treatment efficacy for severe asthma and focused on new biological agents with benralizumab (anti-IL-5) and tezepelumab (anti-TSLP).
Does the Calcaneus Serve as Hypomochlion within the Lower Limb by a Myofascial Connection?—A Systematic Review
Authors: Weinrich Luise , Paraskevaidis Melissa , Schleip Robert , Agres Alison N. , Tsitsilonis Serafeim
Published: July 2021

(1) Background: Clinical approaches have depicted interconnectivity between the Achilles tendon and the plantar fascia. This concept has been applied in rehabilitation, prevention, and in conservative management plans, yet potential anatomical and histological connection is not fully understood. (2) Objective: To explore the possible explanation that the calcaneus acts as a hypomochlion. (3) Methods: 2 databases (Pubmed and Livivo) were searched and studies, including those that examined the relationship of the calcaneus to the Achilles tendon and plantar fascia and its biomechanical role. The included studies highlighted either the anatomical, histological, or biomechanical aspect of the lower limb. (4) Results: Seventeen studies were included. Some studies depicted an anatomical connection that slowly declines with age. Others mention a histological similarity and continuity via the paratenon, while a few papers have brought forward mechanical reasoning. (5) Conclusion: The concept of the calcaneus acting as a fulcrum in the lower limb can partially be supported by anatomical, histological, and biomechanical concepts. Despite the plethora of research, a comprehensive understanding is yet to be investigated. Further research exploring the precise interaction is necessary.
CXCR3 Expression and Genome-Wide 3′ Splice Site Selection in the TCGA Breast Cancer Cohort
Authors: Levesque Lauren A. , Roy Scott , Salazar Nicole
Published: July 2021

CXCR3 is a chemokine receptor with two well-characterized isoforms that have unique, context-dependent roles: CXCR3-A and CXCR3-B, which are produced through alternative 3′ splice site selection (A3SS). RNA-seq data from The Cancer Genome Atlas (TCGA) were used to correlate CXCR3 expression with breast cancer progression. This analysis revealed significant CXCR3 expression patterns associated with survival and differential expression between the tumor and adjacent normal tissue. TCGA data were used to estimate abundance of immune cells in breast cancer, which demonstrated the association of CXCR3 with immune infiltration, particularly in the triple-negative subtype. Given the importance of A3SS in CXCR3, genome-wide analysis of A3SS events was performed to identify events that were differentially spliced between breast cancer tissue and adjacent normal tissue. A total of 481 splicing events in 424 genes were found to be differentially spliced. The parent genes of differentially spliced events were enriched in RNA processing and splicing functions, indicating an underappreciated role of A3SS in the integrated splicing network of breast cancer. These results further validated the role of CXCR3 in immune infiltration of tumors, while raising questions about the role of A3SS splicing.
Some Aspects of the Thermochemical Route for the Valorization of Plastic Wastes, Part I: Reduction of Iron Oxides by Polyvinyl Chloride (PVC)
Authors: Kanari Ndue , Menad Nour-Eddine , Filippov Lev O. , Shallari Seit , Allain Eric , Patisson Fabrice , Yvon Jacques
Published: July 2021

The mass production of synthetic plastics began in the last century and today they have become one of the most abundant man-made materials. The disposal or the beneficiation of end-of-life plastics represent a great challenge for society especially in the case of polyvinyl chloride (PVC). This study is focused on the use of PVC waste as a useful agent for the direct reduction of hematite (Fe2O3) after a thermal treatment at 300 °C for removing the chlorine contained in PVC. Thermal reduction tests were conducted from 600 °C to 1100 °C with (Fe2O3 + PVC + clay) pellet mixtures in which clay was used as plasticizing and binder agent of the pellets. The starting samples and treatment residues were analyzed by scanning electron microscopy through energy dispersive spectroscopy (SEM-EDS) and X-ray diffraction (XRD) to monitor the chemical behavior and reactivity of the pellet constituents during their thermal treatment. The stepwise reduction of hematite up to metallic iron was achieved at temperatures approaching 1000 °C, confirming the capability of using PVC waste for the direct reduction of iron oxides.
Influence of Microgroove Structure on Cutting Performance and Chip Morphology during the Turning of Superalloy Inconel 718
Authors: Zou Zhongfei , He Lin , Jiang Hongwan , Yuan Sen , Ren Zhongwei
Published: July 2021

This study designed a new microgroove cutting tool to machine Inconel 718 and focused on the effect of microgroove structure on the cutting performance and chip morphology during the turning. A comparative analysis of the cutting force, cutting temperature, tool life, tool wear, and chip morphology of the microgroove cutting tool and the original cutting tool was conducted. The main cutting force and temperature of the microgroove cutting tool were reduced by 12% and 12.17%, respectively, compared with the original cutting tool. The microgroove cutting tool exhibited a significant improvement compared with the original cutting tool, which extended the tool life by up to 23.08%. Further, the microgroove cutting tool distorted the curl radius of the chips extensively. The experimental results showed that the microgroove structure can not only improve the tool life, but also improve the chip breaking effect.
Characterization of Mechanical Heterogeneity in Dissimilar Metal Welded Joints
Authors: Xue He , Wang Zheng , Wang Shuai , He Jinxuan , Yang Hongliang
Published: July 2021

Dissimilar metal welded joints (DMWJs) possess significant localized mechanical heterogeneity. Using finite element software ABAQUS with the User-defined Material (UMAT) subroutine, this study proposed a constitutive equation that may be used to express the heterogeneous mechanical properties of the heat-affected and fusion zones at the interfaces in DMWJs. By eliminating sudden stress changes at the material interfaces, the proposed approach provides a more realistic and accurate characterization of the mechanical heterogeneity in the local regions of DMWJs than existing methods. As such, the proposed approach enables the structural integrity of DMWJs to be analyzed in greater detail.
Advanced Optogenetic-Based Biosensing and Related Biomaterials
Authors: Gheorghiu Mihaela , Polonschii Cristina , Popescu Octavian , Gheorghiu Eugen
Published: July 2021

The ability to stimulate mammalian cells with light, brought along by optogenetic control, has significantly broadened our understanding of electrically excitable tissues. Backed by advanced (bio)materials, it has recently paved the way towards novel biosensing concepts supporting bio-analytics applications transversal to the main biomedical stream. The advancements concerning enabling biomaterials and related novel biosensing concepts involving optogenetics are reviewed with particular focus on the use of engineered cells for cell-based sensing platforms and the available toolbox (from mere actuators and reporters to novel multifunctional opto-chemogenetic tools) for optogenetic-enabled real-time cellular diagnostics and biosensor development. The key advantages of these modified cell-based biosensors concern both significantly faster (minutes instead of hours) and higher sensitivity detection of low concentrations of bioactive/toxic analytes (below the threshold concentrations in classical cellular sensors) as well as improved standardization as warranted by unified analytic platforms. These novel multimodal functional electro-optical label-free assays are reviewed among the key elements for optogenetic-based biosensing standardization. This focused review is a potential guide for materials researchers interested in biosensing based on light-responsive biomaterials and related analytic tools.
Revisiting the Valuable Roles of Global Financial Assets for International Stock Markets: Quantile Coherence and Causality-in-Quantiles Approaches
Authors: Li Zhenghui , Ao Zhiming , Mo Bin
Published: July 2021

We employ the quantile-coherency approach and causality-in-quantile method to revisit the roles of Bitcoin, U.S. dollar, crude oil and gold for USA, Chinese, UK, and Japanese stock markets. The main results show that the impact of global financial assets varies across different investment horizons and quantiles. We find that in most cases, the correlation between global financial assets and stock indexes is not significant or is weakly positive. From the perspective of investment horizons (frequency domain), the correlation in the short term is mostly manifested in Bitcoin, while in the medium and long term it is shifted to dollar assets. At the same time, the relationships are significantly higher in the medium and long term than in the short term. From the point of view of quantiles, it shows a weak positive correlation at the lower quantile. However, the correlation between the two is not significant at the median quantile. At the high quantiles, there is a weak negative linkage. According to the causality-in-quantiles approach results, in most cases global financial assets have different degrees of predictive capacity for the selected stock markets. Especially around the median quantile, the predictive ability was strongest.
Bounds on the Rate of Convergence for MtX/MtX/1 Queueing Models
Authors: Zeifman Alexander , Satin Yacov , Sipin Alexander
Published: July 2021

We apply the method of differential inequalities for the computation of upper bounds for the rate of convergence to the limiting regime for one specific class of (in)homogeneous continuous-time Markov chains. Such an approach seems very general; the corresponding description and bounds were considered earlier for finite Markov chains with analytical in time intensity functions. Now we generalize this method to locally integrable intensity functions. Special attention is paid to the situation of a countable Markov chain. To obtain these estimates, we investigate the corresponding forward system of Kolmogorov differential equations as a differential equation in the space of sequences l1.
New Modifications of Integral Inequalities via ℘-Convexity Pertaining to Fractional Calculus and Their Applications
Authors: Rashid Saima , Khalid Aasma , Bazighifan Omar , Oros Georgia Irina
Published: July 2021

Integral inequalities for ℘-convex functions are established by using a generalised fractional integral operator based on Raina’s function. Hermite–Hadamard type inequality is presented for ℘-convex functions via generalised fractional integral operator. A novel parameterized auxiliary identity involving generalised fractional integral is proposed for differentiable mappings. By using auxiliary identity, we derive several Ostrowski type inequalities for functions whose absolute values are ℘-convex mappings. It is presented that the obtained outcomes exhibit classical convex and harmonically convex functions which have been verified using Riemann–Liouville fractional integral. Several generalisations and special cases are carried out to verify the robustness and efficiency of the suggested scheme in matrices and Fox–Wright generalised hypergeometric functions.
Connectedness and Local Connectedness on Infra Soft Topological Spaces
Authors: Al-shami Tareq M. , Abo-Tabl El-Sayed A.
Published: July 2021

This year, we introduced the concept of infra soft topology as a new generalization of soft topology. To complete our analysis of this space, we devote this paper to presenting the concepts of infra soft connected and infra soft locally connected spaces. We provide some descriptions for infra soft connectedness and elucidate that there is no relationship between an infra soft topological space and its parametric infra topological spaces with respect to the property of infra soft connectedness. We discuss the behaviors of infra soft connected and infra soft locally connected spaces under infra soft homeomorphism maps and a finite product of soft spaces. We complete this manuscript by defining a component of a soft point and establishing its main properties. We determine the conditions under which the number of components is finite or countable, and we discuss under what conditions the infra soft connected subsets are components.
Out-of-Sample Prediction in Multidimensional P-Spline Models
Authors: Carballo Alba , Durbán María , Lee Dae-Jin
Published: July 2021

The prediction of out-of-sample values is an interesting problem in any regression model. In the context of penalized smoothing using a mixed-model reparameterization, a general framework has been proposed for predicting in additive models but without interaction terms. The aim of this paper is to generalize this work, extending the methodology proposed in the multidimensional case, to models that include interaction terms, i.e., when prediction is carried out in a multidimensional setting. Our method fits the data, predicts new observations at the same time, and uses constraints to ensure a consistent fit or impose further restrictions on predictions. We have also developed this method for the so-called smooth-ANOVA model, which allows us to include interaction terms that can be decomposed into the sum of several smooth functions. We also develop this methodology for the so-called smooth-ANOVA models, which allow us to include interaction terms that can be decomposed as a sum of several smooth functions. To illustrate the method, two real data sets were used, one for predicting the mortality of the U.S. population in a logarithmic scale, and the other for predicting the aboveground biomass of Populus trees as a smooth function of height and diameter. We examine the performance of interaction and the smooth-ANOVA model through simulation studies.
Optimal Control of Insect Populations
Authors: Albuquerque de Araujo Anderson L. , Boldrini José L. , Cabrales Roberto C. , Fernández-Cara Enrique , Oliveira Milton L.
Published: July 2021

We consider some optimal control problems for systems governed by linear parabolic PDEs with local controls that can move along the domain region Ω of the plane. We prove the existence of optimal paths and also deduce the first order necessary optimality conditions, using the Dubovitskii–Milyutin’s formalism, which leads to an iterative algorithm of the fixed-point kind. This problem may be considered as a model for the control of a mosquito population existing in a given region by using moving insecticide spreading devices. In this situation, an optimal control is any trajectory or path that must follow such spreading device in order to reduce the population as much as possible with a reasonable not too expensive strategy. We illustrate our results by presenting some numerical experiments.
Ochraceopetalin, a Mixed-Biogenetic Salt of Polyketide and Amino Acid Origins from a Marine-Derived Aspergillus ochraceopetaliformis Fungus
Authors: Park Sung Chul , Lee Jung-Ho , Hwang Ji-Yeon , Kwon Oh-Seok , Liao Lijuan , Oh Dong-Chan , Oh Ki-Bong , Shin Jongheon
Published: July 2021

Ochraceopetalin (1), a mixed-biogenetic salt compound and its component 2 were isolated from the culture broths of a marine-derived fungus, Aspergillus ochraceopetaliformis. Based on combined spectroscopic and chemical analyses, the structure of 1 was determined to be a sulfonated diphenylether-aminol-amino acid ester guanidinium salt of an unprecedented structural class, while 2 was determined to be the corresponding sulfonated diphenylether. Ochraceopetaguanidine (3), the other guanidine-bearing aminol amino acid ester component, was also prepared and structurally elucidated. Compound 1 exhibited significant cytotoxicity against K562 and A549 cells.
Polyketides and Meroterpenes from the Marine-Derived Fungi Aspergillus unguis 158SC-067 and A. flocculosus 01NT-1.1.5 and Their Cytotoxic and Antioxidant Activities
Authors: Anh Cao Van , Kang Jong Soon , Choi Byeoung-Kyu , Lee Hwa-Sun , Heo Chang-Su , Shin Hee Jae
Published: July 2021

Ten secondary metabolites, including a new grifolin analog, grifolin B (1); a new homovalencic acid derivative, 12-hydroxyhomovalencic acid (7); and a compound isolated from a natural source for the first time (9), along with seven known compounds, grifolin (2), averantin (3), 7-chloroaverantin (4), 1′-O-methylaverantin (5), 7-hydroxy-2-(2-hydroxypropyl)-5-pentylchromone (6), homovalencic acid (8), and bekeleylactone E (10), were isolated from two fungal strains. The structures of 1–10 were identified by detailed analysis and comparison of their spectroscopic data with literature values. Compounds 9 and 10 showed moderate cytotoxic activity against a panel of cancer cell lines (PC-3, HCT-15, MDA-MB-231, ACHN, NCI-H23, NUGC-3), with the GI50 values ranging from 1.1 µM to 3.6 µM, whereas 1 displayed a weak 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity without cytotoxicity against all tested cell lines.
Bladder Cancer: Current Challenges and Future Directions
Authors: Dobruch Jakub , Oszczudłowski Maciej
Published: July 2021

Bladder cancer (BCa) is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. While the clinical approach to BCa has remained largely unchanged for many years, recent discoveries have paved the way to a new era of diagnosis and management of the disease. BCa-specific mortality started to decrease in the regions with a wide range of activities leading to greater social awareness of the risk factors and the decline in carcinogenic exposure. The urologic community refines the role of transurethral surgery towards more rigorous and high-quality techniques. New agents have been approved for patients with BCG failure who faced radical cystectomy so far. Although radical removal of the bladder is the gold standard for muscle invasive cancer management, the extent and clinical value of lymphadenectomy is currently heavily challenged in randomized trials. Furthermore, alternatives to perioperative chemotherapy have arisen to increase the likelihood of complete treatment delivery and successful oncological outcomes. Finally, improvements in molecular biology and our understanding of tumorigenesis open the era of personalized medicine in bladder cancer. In the present review, the status and future directions in bladder cancer epidemiology, diagnosis and management are thoroughly discussed.
Blood Pressure and Cardio-Metabolic Risk Profile in Young Saudi Males in a University Setting
Authors: EL-Ashker Said , Pednekar Mangesh S. , Narake Sameer S. , Albaker Waleed , Al-Hariri Mohammed
Published: July 2021

Background and Objectives: The prevalence of cardiovascular diseases (CVDs) poses significant clinical and public health challenges across the world. This study aimed to study the metabolic risk factors and the association with blood pressure alteration. Materials and Methods: This was a cross-sectional study conducted between 2017 and 2018 among 284 male university students in Eastern province, Saudi Arabia. The obesity and cardiovascular measurements were taken using standardized instruments, including blood pressure (BP), mean arterial pressure, body mass index (BMI), body adiposity index (BAI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body fat percentage (BFP), and basal metabolic rate (BMR). Statistical Analysis: Blood pressure was classified according to the United States of America, Sixth Joint National committee (JNC-VI) guidelines. The mean and standard error were calculated for each hypertension group variable. Logistic regression was applied to predict associations. Results: The prevalence of hypertension in the present study was 61.6%., and that of overweight and obesity was 16.5% and 34.9%, respectively. The cut-off values of BMI and WC were 22.23 and 75.24, respectively. Conclusions: The results demonstrated that BMI, WC, WHR, and WHtR significantly predict hypertension and that WC has a greater discrimination capacity than other measures. The findings also emphasize the importance of cardiovascular risk screening for young adults to detect any alterations in blood pressure and thus identify the population that is vulnerable to CVDs at an early stage. The findings highlight the need for health and university policymakers to adopt measures to monitor and control hypertension and obesity at the university level.
Psychometric Properties of the Greek Version of the Medical Office on Patient Safety Culture in Primary Care Settings
Authors: Antonakos Ioannis , Souliotis Kyriakos , Psaltopoulou Theodora , Tountas Yannis , Papaefstathiou Athanasios , Kantzanou Maria
Published: July 2021

Background: Safety culture is considered one of the most crucial premises for further development of patient care in healthcare. During the eight-year economic crisis (2010–2018), Greece made significant reforms in the way the primary health care system operates, aiming at the more efficient operation of the system without degrading issues of safety and quality of the provided health services. In this context, this study aims to validate a specialized tool—the Medical Office Survey on Patient Safety Culture (MOSPSC)—developed by the Agency for Healthcare Research and Quality (AHRQ) to evaluate primary care settings in terms of safety culture and quality. Methods: Factor analysis determined the correlation of the factor structure in Greek data with the original questionnaire. The relation of the factor analysis with the Cronbach’s coefficient alpha was also determined, including the construct validity. Results: Eight composites with 34 items were extracted by exploratory factor analysis, with acceptable Cronbach’s alpha coefficients and good construct validity. Consequently, the composites jointly explained 62% of the variance in the responses. Five items were removed from the original version of the questionnaire. As a result, three out of the eight composites were a mixture of items from different compounds of the original tool. The composition of the five factors was similar to that in the original questionnaire. Conclusions: The MOSPSC tool in Greek primary healthcare settings can be used to assess patient safety culture in facilities across the country. From the study, the patient safety culture in Greece was positive, although few composites showed a negative correlation and needed improvement.
Chitosan/PVA Based Membranes Processed by Gamma Radiation as Scaffolding Materials for Skin Regeneration
Authors: Casimiro Maria Helena , Pereira Andreia , Leal João P. , Rodrigues Gabriela , Ferreira Luís M.
Published: July 2021

Some of the current strategies for the development of scaffolding materials capable of inducing tissue regeneration have been based on the use of polymeric biomaterials. Chitosan, in particular, due to its recognized biological activity has been used in a number of biomedical applications. Aiming the development of chitosan-based membranes with improved cell adhesion and growth properties to be used as skin scaffolds allowing functional tissue replacement, different formulations with chitosan of different molecular weight, poly (vinyl alcohol) and gelatin, were evaluated. To meet the goal of getting ready-to-use scaffolds assuring membranes’ required properties and sterilization, preparation methodology included a lyophilization procedure followed by a final gamma irradiation step. Two radiation dose values were tested. Samples were characterized by TGA, FTIR, and SEM techniques. Their hydrophilic properties, in vitro stability, and biocompatibility were also evaluated. Results show that all membranes present a sponge-type inner structure. Chitosan of low molecular weight and the introduction of gelatin are more favorable to cellular growth leading to an improvement on cells’ morphology and cytoskeletal organization, giving a good perspective to the use of these membranes as potential skin scaffolds.
Differences in Deformation Behaviors Caused by Microband-Induced Plasticity of [0 0 1]- and [1 1 1]-Oriented Austenite Micro-Pillars
Authors: Cui Yuan-Yuan , Jia Yun-Fei , Xuan Fu-Zhen
Published: July 2021

A uniaxial compression test and scanning/transmission electron microscopy observations were performed to investigate the differences in mechanical behavior and deformed microstructure between focused ion beam-manufactured [1 1 1]- and [0 0 1]-oriented austenite micro-pillars with 5 μm diameter from duplex stainless steel. After yielding, the strain hardening of two orientation micro-pillars increased sharply as a result of the formation of a microband, namely microband-induced plasticity, MBIP. The same phenomenon could be observed in a [0 0 1]-oriented pillar due to the activation of the secondary slip system, while slight strain hardening behavior was observed in the [1 1 1] orientation because of the refinement of the microband. Furthermore, the trend of the calculated strain hardening rates of both [1 1 1]- and [0 0 1]-oriented micro-pillars were in good agreement with the experimental data. This study proved that MBIP can be helpful for the mechanical property enhancement of steels.
Fabrication of a Protective Hybrid Coating Composed of TiO2, MoO2, and SiO2 by Plasma Electrolytic Oxidation of Titanium
Authors: Zehra Tehseen , Kaseem Mosab , Hossain Shakhawat , Ko Young-Gun
Published: July 2021

This work examined the influence of dual incorporation of MoO2 and SiO2 on the corrosion behavior of pure titanium treated via plasma electrolytic oxidation (PEO). To achieve this purpose, pure titanium substrate was treated via PEO in an alkaline-molybdate electrolyte without and with SiO2 nanoparticles. The microstructural observation revealed that the addition of SiO2 nanoparticles into the electrolyte during PEO helped to seal the structural defects in the PEO coating so that a rougher, thicker, and denser coating rich in SiO2 was successfully obtained. From the electrochemical measurements in a 3.5 wt.% NaCl solution, the TiO2-MoO2-SiO2 hybrid coating exhibited a higher corrosion resistance than the TiO2-MoO2 coating which was attributed to the sealing effect by stable SiO2 nanoparticles.
Dissolution Kinetics of Chlorine from Iron Ore Sintering Dust
Authors: Tang Honghu , Zhao Lihua , Yang Yue , Han Haisheng , Wang Li , Sun Wei
Published: July 2021

Chlorine is generated during iron ore sintering, mostly in the form of alkali chlorides and primarily accumulates in sintering dust, which must be removed before reusing. In this study, an in-situ monitor leaching system based was designed to detect chloride ion water leaching behaviors in real-time and improve the understanding of chlorine dissolution kinetic behaviors in water. Various parameters, including water leaching temperature, solid/liquid ratio, stirring speed, particle size and surfactant addition have been studied. Meanwhile their chlorine dissolution data exhibited a good fit to Stumm’s kinetic models. The results of kinetics analysis and transition state theory calculation on apparent activation energy demonstrated that the dissolution process was controlled by diffusion at low S/L ratio, while changed to be controlled by surface chemical reaction as the S/L ratio increased. Furthermore, increasing both temperature and stirring speed improved the chlorine removal speed. Moreover, reducing the particle size and adding 0.2% nonionic surfactant Triton X-100 reduced the surface energy and accelerated surface chemical reaction, which were also beneficial for removing chlorine from sintering dust. In addition, the SEM-EDS examination inferred that the existence of laurionite (PbOHCl) limited the chlorine dissolution rate to less than 97%, while beneficiation or hydrometallurgy treatment was needed to further remove chlorine.
Facilitating Imaging Mass Spectrometry of Microbial Specialized Metabolites with METASPACE
Authors: Nguyen Don D. , Saharuka Veronika , Kovalev Vitaly , Stuart Lachlan , Del Prete Massimo , Lubowiecka Kinga , De Mot René , Venturi Vittorio , Alexandrov Theodore
Published: July 2021

Metabolite annotation from imaging mass spectrometry (imaging MS) data is a difficult undertaking that is extremely resource intensive. Here, we adapted METASPACE, cloud software for imaging MS metabolite annotation and data interpretation, to quickly annotate microbial specialized metabolites from high-resolution and high-mass accuracy imaging MS data. Compared with manual ion image and MS1 annotation, METASPACE is faster and, with the appropriate database, more accurate. We applied it to data from microbial colonies grown on agar containing 10 diverse bacterial species and showed that METASPACE was able to annotate 53 ions corresponding to 32 different microbial metabolites. This demonstrates METASPACE to be a useful tool to annotate the chemistry and metabolic exchange factors found in microbial interactions, thereby elucidating the functions of these molecules.
Metformin Decreases 2-HG Production through the MYC-PHGDH Pathway in Suppressing Breast Cancer Cell Proliferation
Authors: Oh Sehyun , Cho Youngup , Chang Minsun , Park Sunghyouk , Kwon Hyuknam
Published: July 2021

The biguanide drug metformin has been widely used for the treatment of type 2 diabetes, and there is evidence supporting the anticancer effect of metformin despite some controversy. Here, we report the growth inhibitory activity of metformin in the breast cancer (MCF-7) cells, both in vitro and in vivo, and the associated metabolic changes. In particular, a decrease in a well-known oncometabolite 2-hydroxyglutarate (2-HG) was discovered by a metabolomics approach. The decrease in 2-HG by metformin was accompanied by the reduction in histone methylation, consistent with the known tumorigenic mechanism of 2-HG. The relevance of 2-HG inhibition in breast cancer was also supported by a higher level of 2-HG in human breast cancer tissues. Genetic knockdown of PHGDH identified the PHGDH pathway as the producer of 2-HG in the MCF-7 cells that do not carry isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) mutations, the conventional producer of 2-HG. We also showed that metformin’s inhibitory effect on the PHGDH-2HG axis may occur through the regulation of the AMPK-MYC pathway. Overall, our results provide an explanation for the coherent pathway from complex I inhibition to epigenetic changes for metformin’s anticancer effect.
Beam Formation and Vernier Steering Off of a Rough Surface
Authors: Nagamine Eric K. , Burgi Kenneth W. , Butler Samuel D.
Published: July 2021

Wavefront shaping can refocus light after it reflects from an optically rough surface. One proposed use case of this effect is in indirect imaging; if any rough surface could be turned into an illumination source, objects out of the direct line of sight could be illuminated. In this paper, we demonstrate the superior performance of a genetic algorithm compared to other iterative feedback-based wavefront shaping algorithms in achieving reflective inverse diffusion for a focal plane system. Next, the ability to control the pointing direction of the refocused beam with high precision over a narrow angular range is demonstrated, though the challenge of increasing the overall scanning range of the refocused beam remains. The method of beam steering demonstrated in this paper could act as a vernier adjustment to a coarse adjustment offered by another method.
Complete Genome Sequence of vB_EcoP_SU7, a Podoviridae Coliphage with the Rare C3 Morphotype
Authors: Koonjan Shazeeda , Cooper Callum J. , Nilsson Anders S.
Published: July 2021

Enterotoxigenic Escherichia coli (ETEC) strains are an important cause of bacterial diarrheal illness in humans and animals. Infections arising from ETEC could potentially be treated through the use of bacteriophage (phage) therapy, as phages encode for enzymes capable of bacterial cell lysis. vB_EcoP_SU7 was isolated from the Käppala wastewater treatment plant in Stockholm, Sweden, and propagated on an ETEC strain exhibiting the O:139 serovar. Transmission electron microscopy confirmed that vB_EcoP_SU7 belongs to the Podoviridae family and has the rare C3 morphotype of an elongated head. Bioinformatic analyses showed that the genome was 76,626 base pairs long and contained 35 genes with predicted functions. A total of 81 open reading frames encoding proteins with hypothetical function and two encoding proteins of no significant similarity were also found. A putative tRNA gene, which may aid in vB_EcoP_SU7’s translation, was also identified. Phylogenetic analyses showed that compared to other Podoviridae, vB_EcoP_SU7 is a rare Kuravirus and is closely related to E. coli phages with the uncommon C3 morphotype, such as ECBP2, EK010, vB_EcoP_EcoN5, and vB_EcoP_SU10. Phage vB_EcoP_SU7 has a narrow host range, infecting 11 out of the 137 E. coli strains tested, a latency period of 30 min, a burst size of 12 PFU/cell, and an adsorption rate of 8.78 × 10−9 mL/min five minutes post infection. With a limited host range and poor infection kinetics, it is unlikely that SU7 can be a standalone phage used for therapeutic purposes; rather, it must be used in combination with other phages for broad-spectrum therapeutic success.
Comparative Genomics Revealing Insights into Niche Separation of the Genus Methylophilus
Authors: Lin Nana , Tao Ye , Gao Peixin , Xu Yan , Xing Peng
Published: July 2021

The genus Methylophilus uses methanol as a carbon and energy source, which is widely distributed in terrestrial, freshwater and marine ecosystems. Here, three strains (13, 14 and QUAN) related to the genus Methylophilus, were newly isolated from Lake Fuxian sediments. The draft genomes of strains 13, 14 and QUAN were 3.11 Mb, 3.02 Mb, 3.15 Mb with a G+C content of 51.13, 50.48 and 50.33%, respectively. ANI values between strains 13 and 14, 13 and QUAN, and 14 and QUAN were 81.09, 81.06 and 91.46%, respectively. Pan-genome and core-genome included 3994 and 1559 genes across 18 Methylophilus genomes, respectively. Phylogenetic analysis based on 1035 single-copy genes and 16S rRNA genes revealed two clades, one containing strains isolated from aquatic and the other from the leaf surface. Twenty-three aquatic-specific genes, such as 2OG/Fe(II) oxygenase and diguanylate cyclase, reflected the strategy to survive in oxygen-limited water and sediment. Accordingly, 159 genes were identified specific to leaf association. Besides niche separation, Methylophilus could utilize the combination of ANRA and DNRA to convert nitrate to ammonia and reduce sulfate to sulfur according to the complete sulfur metabolic pathway. Genes encoding the cytochrome c protein and riboflavin were detected in Methylophilus genomes, which directly or indirectly participate in electron transfer.
Genome and Secretome Analysis of Staphylotrichum longicolleum DSM105789 Cultured on Agro-Residual and Chitinous Biomass
Authors: Ali Arslan , Ellinger Bernhard , Brandt Sophie C. , Betzel Christian , Rühl Martin , Wrenger Carsten , Schlüter Hartmut , Schäfer Wilhelm , Brognaro Hévila , Gand Martin
Published: July 2021

Staphylotrichum longicolleum FW57 (DSM105789) is a prolific chitinolytic fungus isolated from wood, with a chitinase activity of 0.11 ± 0.01 U/mg. We selected this strain for genome sequencing and annotation, and compiled its growth characteristics on four different chitinous substrates as well as two agro-industrial waste products. We found that the enzymatic mixture secreted by FW57 was not only able to digest pre-treated sugarcane bagasse, but also untreated sugarcane bagasse and maize leaves. The efficiency was comparable to a commercial enzymatic cocktail, highlighting the potential of the S. longicolleum enzyme mixture as an alternative pretreatment method. To further characterize the enzymes, which efficiently digested polymers such as cellulose, hemicellulose, pectin, starch, and lignin, we performed in-depth mass spectrometry-based secretome analysis using tryptic peptides from in-gel and in-solution digestions. Depending on the growth conditions, we were able to detect from 442 to 1092 proteins, which were annotated to identify from 134 to 224 putative carbohydrate-active enzymes (CAZymes) in five different families: glycoside hydrolases, auxiliary activities, carbohydrate esterases, polysaccharide lyases, glycosyl transferases, and proteins containing a carbohydrate-binding module, as well as combinations thereof. The FW57 enzyme mixture could be used to replace commercial enzyme cocktails for the digestion of agro-residual substrates.