bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Clinical Outcome with Phenotypic Clusters in COVID-19 Pneumonia: An Analysis of 12,066 Hospitalized Patients from the Spanish Registry SEMI-COVID-19
Authors: Rubio-Rivas Manuel , Corbella Xavier , Mora-Luján José María , Loureiro-Amigo Jose , López Sampalo Almudena , Yera Bergua Carmen , Esteve Atiénzar Pedro Jesús , Díez García Luis Felipe , Gonzalez Ferrer Ruth , Plaza Canteli Susana , Pérez Piñeiro Antía , Cortés Rodríguez Begoña , Jorquer Vidal Leyre , Pérez Catalán Ignacio , León Téllez Marta , Martín Oterino José Ángel , Martín González María Candelaria , Serrano Carrillo de Albornoz José Luis , García Sardon Eva , Alcalá Pedrajas José Nicolás , Martin-Urda Diez-Canseco Anabel , Esteban Giner María José , Tellería Gómez Pablo , Ramos-Rincón José Manuel , Gómez-Huelgas Ricardo
Published: October 2020

(1) Background: Different clinical presentations in COVID-19 are described to date, from mild to severe cases. This study aims to identify different clinical phenotypes in COVID-19 pneumonia using cluster analysis and to assess the prognostic impact among identified clusters in such patients. (2) Methods: Cluster analysis including 11 phenotypic variables was performed in a large cohort of 12,066 COVID-19 patients, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish Society of Internal Medicine (SEMI)-COVID-19 Registry. (3) Results: Of the total of 12,066 patients included in the study, most were males (7052, 58.5%) and Caucasian (10,635, 89.5%), with a mean age at diagnosis of 67 years (standard deviation (SD) 16). The main pre-admission comorbidities were arterial hypertension (6030, 50%), hyperlipidemia (4741, 39.4%) and diabetes mellitus (2309, 19.2%). The average number of days from COVID-19 symptom onset to hospital admission was 6.7 (SD 7). The triad of fever, cough, and dyspnea was present almost uniformly in all 4 clinical phenotypes identified by clustering. Cluster C1 (8737 patients, 72.4%) was the largest, and comprised patients with the triad alone. Cluster C2 (1196 patients, 9.9%) also presented with ageusia and anosmia; cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache, and sore throat; and cluster C4 (1253 patients, 10.4%) also manifested with diarrhea, vomiting, and abdominal pain. Compared to each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 18.6%; p < 0.001). The multivariate study identified age, gender (male), body mass index (BMI), arterial hypertension, chronic obstructive pulmonary disease (COPD), ischemic cardiopathy, chronic heart failure, chronic hepatopathy, Charlson’s index, heart rate and respiratory rate upon admission >20 bpm, lower PaO2/FiO2 at admission, higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH), and the phenotypic cluster as independent factors for in-hospital death. (4) Conclusions: The present study identified 4 phenotypic clusters in patients with COVID-19 pneumonia, which predicted the in-hospital prognosis of clinical outcomes.
Relationship among Left Ventricular Hypertrophy, Cardiovascular Events, and Preferred Blood Pressure Measurement Timing in Hemodialysis Patients
Authors: Io Hiroaki , Nakata Junichiro , Inoshita Hiroyuki , Ishizaka Masanori , Tomino Yasuhiko , Suzuki Yusuke
Published: October 2020

This study aimed to identify the ideal timing and setting for measuring blood pressure (BP) and determine whether the left ventricular mass index (LVMI) is an independent risk factor associated with increased cardiovascular events in hemodialysis (HD) patients. BP and LVMI were measured at baseline and at 6 and 12 months after HD initiation. BP was monitored and recorded at nine different time points, including before and after HD over a one-week period (HDBP). The mean BP measurement was calculated as the weekly averaged BP (WABP). LVMI was significantly correlated with home BP, in-office BP, HDBP, and WABP. Receiver operating characteristic analysis indicated that the cutoff LVMI value for cardiovascular events was 156 g/m2. LVMI and diabetes mellitus were significant influencing factors for cardiovascular events (hazards ratio (95% confidence interval): diabetes mellitus, 2.84 (1.17,7.45); LVMI > 156 g/m2, 2.86 (1.22,6.99)). Pre-HDBP, post-HDBP, and WABP were independently associated with higher LVMI in the follow-up periods. Hemoglobin and human atrial natriuretic peptide (hANP) levels were associated with LVMI beyond 12 months after HD initiation. Treatment of hypertension, overhydration based on hANP, and anemia may reduce the progression of LVMI and help identify HD patients at high risk for cardiovascular events.
Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies
Authors: Gerrish Amy , Bowns Benjamin , Mashayamombe-Wolfgarten Chipo , Young Elizabeth , Court Samantha , Bott Joshua , McCalla Maureen , Ramsden Simon , Parks Michael , Goudie David , Carless Sue , Clokie Samuel , Cole Trevor , Allen Stephanie
Published: October 2020

Retinoblastoma, the most common childhood eye cancer, presents in two forms: heritable or sporadic. Heritable retinoblastoma is caused by a germline mutation in the RB1 gene. Early diagnosis of children at risk of inheriting an RB1 mutation is crucial to achieve optimal clinical outcome. Currently, the majority of genetic testing is performed on newborns, which has multiple disadvantages for both families and the healthcare system. We have developed a non-invasive prenatal diagnosis (NIPD) service for retinoblastoma, available from 8 weeks’ gestation, which uses a combination of massively parallel sequencing (MPS) techniques, dependent on the inheritance model. Detection of paternal or suspected de novo RB1 variants is achieved through amplicon-based MPS. NIPD of a fetus at risk of maternal inheritance is performed using capture-based targeted sequencing and relative haplotype dosage analysis. In addition, we show proof of principle of how capture-based sequencing can be used for de novo variants unsuitable for amplicon-based testing. In total, we report the NIPD of 15 pregnancies, results of which show 100% concordance with all postnatal testing performed at the time of publication (n = 12) with remaining pregnancies ongoing. NIPD of retinoblastoma therefore offers a viable alternative to newborn genetic testing.
Effect of Graphene Additive on Flexural and Interlaminar Shear Strength Properties of Carbon Fiber-Reinforced Polymer Composite
Authors: Ali Charfi Mohamed , Mathieu Ronan , Chatelain Jean-François , Ouellet-Plamondon Claudiane , Lebrun Gilbert
Published: October 2020

Composite materials are widely used in various manufacturing fields from aeronautic and aerospace industries to the automotive industry. This is due to their outstanding mechanical properties with respect to their light weight. However, some studies showed that the major flaws of these materials are located at the fiber/matrix interface. Therefore, enhancing matrix adhesion properties could significantly improve the overall material characteristics. This study aims to analyze the effect of graphene particles on the adhesion properties of carbon fiber-reinforced polymer (CFRP) through interlaminar shear strength (ILSS) and flexural testing. Seven modified epoxy resins were prepared with different graphene contents. The CFRP laminates were next manufactured using a method that guarantees a repeatable and consistent fiber volume fraction with a low porosity level. Short beam shear and flexural tests were performed to compare the effect of graphene on the mechanical properties of the different laminates. It was found that 0.25 wt.% of graphene filler enhanced the flexural strength by 5%, whilst the higher concentrations (2 and 3 wt.%) decreased the flexural strength by about 7%. Regarding the ILSS, samples with low concentrations (0.25 and 0.5 wt.%) demonstrated a decent increase. Meanwhile, 3 wt.% slightly decreases the ILSS.
Calibration of Fiber Orientation Simulations for LFT—A New Approach
Authors: Willems Fabian , Reitinger Philip , Bonten Christian
Published: October 2020

Short fiber reinforced thermoplastics (SFT) are extensively used due to their excellent mechanical properties and low processing costs. Long fiber reinforced thermoplastics (LFT) show an even more interesting property profile and are increasingly used for structural parts. However, their processing by injection molding is not as simple as for SFT, and their anisotropic properties resulting from the fiber microstructure (fiber orientation, length, and concentration) pose a challenge with regard to the engineering design process. To reliably predict the structural mechanical properties of fiber reinforced thermoplastics by means of micromechanical models, it is also necessary to reliable predict the fiber microstructure. Therefore, it is crucial to calibrate the underlying prediction models, such as the fiber orientation model, within the process simulation. In general, these models may be adjusted manually, but this is usually ineffective and time-consuming. To overcome this challenge, a new calibration method was developed to automatically calibrate the fiber orientation model parameters of the injection molding simulation by means of optimization methods. This optimization routine is based on experimentally determined fiber orientation distributions and leads to optimized parameters for the fiber orientation prediction model within a few minutes. To better understand the influence of the model parameters, different versions of the fiber orientation model, as well as process and material influences on the resulting fiber orientation distribution, were investigated. Finally, the developed approach to calibrate the fiber orientation model was compared with a classical approach, a direct optimization of the whole process simulation. Thereby, the new optimization approach shows a calculation time reduced by the factor 15 with comparable error variance.
Selecting Relevant Biological Variables Derived from Sentinel-2 Data for Mapping Changes from Grassland to Arable Land Using Random Forest Classifier
Authors: Šandera Jiří , Štych Přemysl
Published: October 2020

Permanent grassland is one of the monitored categories of land use, land use change, and forestry (LULUCF) within the climate concept and greenhouse gas reduction policy (Regulation (EU) 2018/841). Mapping the conditions and changes of permanent grasslands is thus very important. The area of permanent grassland is strongly influenced by agricultural subsidy policies. Over the course of history, it is possible to trace different shares of permanent grassland within agricultural land and areas with significant changes from grassland to arable land. The need for monitoring permanent grassland and arable land has been growing in recent years. New subsidy policies determining farm management are beginning to affect land use, especially in countries that have joined the EU in recent waves. The large amount of freely available satellite data enables this monitoring to take place, mainly owing to data products of the Copernicus program. There are a large number of parameters (predictors) that can be calculated from satellite data, but finding the right combination is very difficult. This study presents a methodical, systematic procedure using the random forest classifier and its internal metric of mean decrease accuracy (MDA) to select the most suitable predictors to detect changes from permanent grassland to arable land. The relevance of suitable predictors takes into account the date of the satellite image, the overall accuracy of change detection, and the time required for calculations. Biological predictors, such as leaf area index (LAI), fraction absorbed photosynthetically active radiation (FAPAR), normalized difference vegetation index (NDVI), etc. were tested in the form of a time series from the Sentinel-2 satellite, and the most suitable ones were selected. FAPAR, canopy water content (CWC), and LAI seemed to be the most suitable. The proposed change detection procedure achieved a very high accuracy of more than 95% within the study site with an area of 8766 km2.
Modeling Mucopolysaccharidosis Type II in the Fruit Fly by Using the RNA Interference Approach
Authors: Rigon Laura , Kucharowski Nicole , Eckardt Franka , Bauer Reinhard
Published: October 2020

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder that occurs due to the deficit of the lysosomal enzyme iduronate 2-sulfatase (IDS) that leads to the storage of the glycosaminoglycan heparan- and dermatan-sulfate in all organs and tissues. It is characterized by important clinical features and the severe form presents with a heavy neurological involvement. However, almost nothing is known about the neuropathogenesis of MPS II. To address this issue, we developed a ubiquitous, neuronal, and glial-specific knockdown model in Drosophila melanogaster by using the RNA interference (RNAi) approach. Knockdown of the Ids/CG12014 gene resulted in a significant reduction of the Ids gene expression and enzymatic activity. However, glycosaminoglycan storage, survival, molecular markers (Atg8a, Lamp1, Rab11), and locomotion behavior were not affected. Even strongly reduced, IDS-activity was enough to prevent a pathological phenotype in a MPS II RNAi fruit fly. Thus, a Drosophila MPS II model requires complete abolishment of the enzymatic activity.
Research Summary on Characterizing Impact of Environment on Adhesion of Sealed Joints in Façade Applications
Authors: Nečasová Barbora , Liška Pavel
Published: October 2020

The presented paper summarizes the main research findings on the impact of the environment concerning the durability and service life of building joint sealants. The focus is placed on sealed joints in façade applications, which can serve different purposes and can also be several meters long which often intensifies the stresses that the joint needs to withstand and therefore its service life can be significantly shortened. Different approaches, test sample geometries and high-performance sealants, were used in this context to determine the most critical aspects for the studied application sector. The research was divided into three phases where the joints were subjected to (I) artificial weathering in a laboratory environment, (II) real weathering in an external environment, and (III) weathering via a real application that was monitored for almost 4 years. The extensive research scope confirmed one commonly known presumption, that standardized artificial weathering/aging methods are not able, from a long-term perspective, to simulate the impact of a real environment. The most valuable results were obtained in the third phase of the research, where the monitoring of a real façade brought to light completely different conclusions. The joints exposed to the real environment were either completely deteriorated or showed signs of advanced aging.
Upper Bounds and Explicit Formulas for the Ruin Probability in the Risk Model with Stochastic Premiums and a Multi-Layer Dividend Strategy
Authors: Ragulina Olena , Šiaulys Jonas
Published: October 2020

This paper is devoted to the investigation of the ruin probability in the risk model with stochastic premiums where dividends are paid according to a multi-layer dividend strategy. We obtain an exponential bound for the ruin probability and investigate conditions, under which it holds for a number of distributions of the premium and claim sizes. Next, we use the exponential bound to construct non-exponential bounds for the ruin probability. We show that the non-exponential bounds turn out to be tighter than the exponential one in some cases. Moreover, we derive explicit formulas for the ruin probability when the premium and claim sizes have either the hyperexponential or the Erlang distributions and apply them to investigate how tight the bounds are. To illustrate and analyze the results obtained, we give numerical examples.
Removal of Naturally Occurring Strontium by Nanofiltration/Reverse Osmosis from Groundwater
Authors: Cai Yang-Hui , Yang Xiao Jin , Schäfer Andrea Iris
Published: October 2020

Removal of naturally occurring strontium (Sr) from groundwater is vital as excessive exposure may lead to bone growth problems in children. Nanofiltration/reverse osmosis (NF/RO) is commonly used in groundwater treatment due to the high effectiveness and simple maintenance of these pressure driven membrane processes. In this research, a pilot-scale NF/RO system was used to desalinate a natural groundwater sample containing high Sr concentration (10.3 mg/L) and “old” groundwater organic matter (70.9 mg/L) from Esilalei in northern Tanzania to understand the removal of strontium by NF/RO. The impact of applied pressure (10–15 bar) and groundwater pH (3–12) on the membrane performance including permeate flux, strontium and total organic carbon (TOC) flux and removal was investigated. Increasing applied pressure was found to enhance the flux by increasing the driving force and enhance Sr and TOC removal by dilution effect (water flux higher than Sr passage). The alkaline pH caused severe flux decline likely due to membrane fouling and scaling, while it slightly enhanced Sr removal of RO membranes, but weakened the TOC removal. In contrast, acidic and neutral pH of groundwater enhanced TOC removal. These findings suggest that appropriately high applied pressure and acidic pH condition of groundwater are recommended to apply to the NF/RO membrane system in groundwater desalination to achieve better membrane performance.
Effect of Cr Addition on Microstructure and Properties of AuGa Solder
Authors: Tao Yu , Xue Songbai , Liu Han , Long Weimin , Wang Bo
Published: October 2020

In order to meet the service requirements of electronic devices working at 300 °C in the fields of energy resource prospecting and space exploration, Cr element was added to modify AuGa solder to improve its high-temperature performance. The results showed that the addition of 0.3 wt.% Cr element reduced the loss of Ga element in the smelting and casting process, and effectively improved the problem of the inhomogeneous microstructure of the solder matrix. On the basis of maintaining the good wettability of the solder, the addition of trace chromium effectively restrains the excessive flux of the solder, and the presence of chromium improves the oxidation resistance of the solder. Furthermore, Cr element optimized the interface morphology and improved the mechanical properties of the solder joint. The shear strength of the AuGa-0.3Cr/Ni joint was 87.2 MPa, which was 13.1% higher than that of the joint without Cr element. After 240 h of aging, the shear strength of the AuGa-0.3Cr joint was still the peak value at 84.1 MPa, which was 16.3% higher than that of the AuGa joint.
Effects of Pre-Weld Heat Treatment and Heat Input on Metallurgical and Mechanical Behaviour in HAZ of Multi-Pass Welded IN-939 Superalloy
Authors: Mashhuriazar Amirhossein , Omidvar Hamid , Sajuri Zainuddin , Gur C. Hakan , Baghdadi Amir Hossein
Published: October 2020

Heat-affected zones (HAZs) of Inconel 939 (IN-939) superalloy are susceptible to cracking during welding process. Preventing cracking during the repair welding of turbine components is important. In this study, the effects of heat input and pre-welding heat treatment on the microstructure, mechanical properties and crack formation in tungsten inert gas welding of IN-939 were investigated. The whole specimens were welded using Inconel 625 filler in an Ar atmosphere and characterised by metallographic examinations and hardness measurements. Results showed that the microstructures of IN-939 HAZs were highly susceptible to cracking during welding due to increasing of γ′ volume fraction. All of these cracks appeared in the HAZs and grew perpendicular to the melting zone along the grain boundaries. In this survey, the pre-welding heat treatment and heat input strongly affected the HAZ microstructure and hardness. However, the pre-welding heat treatment with 67% impact was more effective than heat input with 30% impact. Finally, hot tensile tests were carried out on the specimens of the base metal and the optimal specimens under similar operating conditions within 600 °C–800 °C. Welding process did not affect the yield strength of the superalloy but slightly decreased its ultimate strength and elongation by as much as 92% and 50%, respectively, of those of the base metal.
Characteristic of Metabolic Status in Heart Failure and Its Impact in Outcome Perspective
Authors: Tang Hsiang-Yu , Wang Chao-Hung , Ho Hung-Yao , Lin Jui-Fen , Lo Chi-Jen , Huang Cheng-Yu , Cheng Mei-Ling
Published: October 2020

Metabolic alterations have been documented in peripheral tissues in heart failure (HF). Outcomes might be improved by early identification of risk. However, the prognostic information offered is still far from enough. We hypothesized that plasma metabolic profiling potentially provides risk stratification for HF patients. Of 61 patients hospitalized due to acute decompensated HF, 31 developed HF-related events in one year after discharge (Event group), and the other 30 patients did not (Non-event group). The plasma collected during hospital admission was analyzed by an ultra-high performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOFMS)-based metabolomic approach. The orthogonal projection to latent structure discriminant analysis (OPLS-DA) reveals that the metabolomics profile is able to distinguish between events in HF. Levels of 19 metabolites including acylcarnitines, lysophospholipids, dimethylxanthine, dimethyluric acid, tryptophan, phenylacetylglutamine, and hypoxanthine are significantly different between patients with and without event (p < 0.05). Established risk prediction models of event patients by using receiver operating characteristics analysis reveal that the combination of tetradecenoylcarnitine, dimethylxanthine, phenylacetylglutamine, and hypoxanthine has better discrimination than B-type natriuretic peptide (BNP) (AUC 0.871 and 0.602, respectively). These findings suggest that metabolomics-derived metabolic profiling have the potential of identifying patients with high risk of HF-related events and provide insights related to HF outcome.
Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain
Authors: Scholefield Melissa , Church Stephanie J. , Xu Jingshu , Robinson Andrew C. , Gardiner Natalie J. , Roncaroli Federico , Hooper Nigel M. , Unwin Richard D. , Cooper Garth J. S.
Published: October 2020

The use of post-mortem human tissue is indispensable in studies investigating alterations in metabolite levels in neurodegenerative conditions such as Alzheimer’s disease (AD). However, variability between samples may have unknown effects on metabolite concentrations. The aim of this study was to characterize the impact of such variables. Cingulate gyrus was obtained from AD cases and controls, from three brain banks. Gas chromatography-mass spectrometry (GC-MS) was used to measure and compare the levels of 66 identifiable metabolites in these tissues to determine effects of tissue-collection variables. The effect of PMD was further investigated by analysis of rat brain cortex and cerebellum collected following post-mortem delays (PMDs) of zero to 72 h. Metabolite levels between cases and controls were not replicable across cohorts with variable age- and gender-matching, PMD, and control Braak staging. Analysis of rat tissues found significant effects of PMD on 31 of 63 identified metabolites over periods up to 72 h. PMD must be kept under 24 h for metabolomics analyses on brain tissues to yield replicable results. Tissues should also be well age- and gender-matched, and Braak stage in controls should be kept to a minimum in order to minimize the impact of these variables in influencing metabolite variability.
Numerical Investigation of Nanostructure Orientation on Electroosmotic Flow
Authors: Lim An Eng , Lam Yee Cheong
Published: October 2020

Electroosmotic flow (EOF) is fluid flow induced by an applied electric field, which has been widely employed in various micro-/nanofluidic applications. Past investigations have revealed that the presence of nanostructures in microchannel reduces EOF. Hitherto, the angle-dependent behavior of nanoline structures on EOF has not yet been studied in detail and its understanding is lacking. Numerical analyses of the effect of nanoline orientation angle θ on EOF to reveal the associated mechanisms were conducted in this investigation. When θ increases from 5° to 90° (from parallel to perpendicular to the flow direction), the average EOF velocity decreases exponentially due to the increase in distortion of the applied electric field distribution at the structured surface, as a result of the increased apparent nanolines per unit microchannel length. With increasing nanoline width W, the decrease of average EOF velocity is fairly linear, attributed to the simultaneous narrowing of nanoline ridge (high local fluid velocity region). While increasing nanoline depth D results in a monotonic decrease of the average EOF velocity. This reduction stabilizes for aspect ratio D/W > 0.5 as the electric field distribution distortion within the nanoline trench remains nearly constant. This investigation reveals that the effects on EOF of nanolines, and by extrapolation for any nanostructures, may be directly attributed to their effects on the distortion of the applied electric field distribution within a microchannel.
Surface Tension-Based Alignment of Microfibers on Hydrophilic–Superhydrophobic Grooved Surfaces
Authors: Chang Bo , Jin Jialong , Zhou Quan
Published: October 2020

Alignment and orderly distribution of microfibers have a major effect on the mechanical, electrical, and thermal properties of the fiber reinforced materials, biomimetic materials, and soft microsensors. However, it is still a challenging task to precisely align and distribute microfibers and construct complex patterns. This paper proposes a surface tension-based method to align and orderly distribute microfibers. A model was developed to simulate the surface tension driven alignment of the microfiber. We designed and fabricated hydrophilic–superhydrophobic grooved surfaces. We demonstrated that the microfibers can self-align to the hydrophilic–superhydrophobic grooves with different geometries. We studied the influence of the volume of the droplet and bias on the alignment success rate. The results indicate that the process can tolerate large variations of the bias and the volume, unless the volume is not enough to cover the groove. We further investigated the influence of the width of the groove on the alignment accuracy. The results show that the alignment accuracy is largely depending on the size difference between the groove and the microfiber; the better the size of the groove matches the size of the fiber, the higher the alignment accuracy will be achieved. The proposed method has great potential in construction of complex microstructures using microfibers.
Insights into the Potential of Sourdough-Related Lactic Acid Bacteria to Degrade Proteins in Wheat
Authors: Fraberger Vera , Ladurner Martin , Nemec Alexandra , Grunwald-Gruber Clemens , Call Lisa M. , Hochegger Rupert , Domig Konrad J. , D’Amico Stefano
Published: October 2020

Sourdough processing contributes to better digestible wheat-based bakery products, especially due to the proteolytic activity of lactic acid bacteria (LAB). Therefore, sourdough-related LAB were screened for their capacity to degrade immunogenic proteins like gluten and alpha-amylase-trypsin inhibitors (ATIs). Firstly, the growth of 87 isolates was evaluated on a gluten-based medium. Further, the breakdown capacity of selected isolates was determined for gluten with a focus on gliadins by measuring acidification parameters and MALDI-TOF MS protein profiles. ATI degradation after 72 h of incubation within an ATI-based medium was investigated by means of acidification, HPLC, and competitive ELISA. All isolates exhibited the potential to degrade ATIs to a high degree, whereas the gliadin degradation capacity varied more greatly among tested LAB, with Lacticaseibacillus paracasei Lpa4 exhibiting the strongest alterations of the gliadin pattern, followed by Lactiplantibacillus plantarum Lpl5. ATI degradation capacities ranged from 52.3% to 85.0% by HPLC and 22.2% to 70.2% by ELISA, with Lacticaseibacillus paracasei Lpa4 showing superior breakdown properties. Hence, a selection of specific starter cultures can be used in sourdough processing for wheat-based bakery products with reduced gluten and ATI content and, further, better tolerated products for patients suffering from non-celiac wheat sensitivity (NCWS).
Application of Knowledge-Driven Methods for Mineral Prospectivity Mapping of Polymetallic Sulfide Deposits in the Southwest Indian Ridge between 46° and 52°E
Authors: Ma Yao , Zhao Jiangnan , Sui Yu , Liao Shili , Zhang Zongyao
Published: October 2020

As a product of hydrothermal activity, seafloor polymetallic sulfide deposit has become the focus of marine mineral exploration due to its great prospects for mineralization potential. The mineral prospectivity mapping is a multiple process that involves weighting and integrating evidential layers to further explore the potential target areas, which can be categorized into data-driven and knowledge-driven methods. This paper describes the application of fuzzy logic and fuzzy analytic hierarchy process (AHP) models to process the data of the Southwest Indian Ocean Mid-Ridge seafloor sulfide deposit and delineate prospect areas. Nine spatial evidential layers representing the controlling factors for the formation and occurrence of polymetallic sulfide deposit were extracted to establish a prospecting prediction model. Fuzzy logic and fuzzy AHP models combine expert experience and fuzzy sets to assign weights to each layer and integrate the evidence layers to generate prospectivity map. Based on prediction-area (P-A) model, the optimal gamma operator (γ) values were determined to be 0.95 and 0.90 for fuzzy logic and fuzzy AHP to synthesize the evidence layers. The concentration-area (C-A) fractal method was used to classify different levels of metallogenic probability by determining corresponding thresholds. Finally, Receiver Operating Characteristic (ROC) curves were applied to measure the performance of the two prospectivity models. The results show that the areas under the ROC curve of the fuzzy logic and the fuzzy AHP model are 0.813 and 0.887, respectively, indicating that prediction based on knowledge-driven methods can effectively predict the metallogenic favorable area in the study area, opening the door for future exploration of seafloor polymetallic sulfide deposits.
Development of Novel Polyamide 11 Multifilaments and Fabric Structures Based on Industrial Lignin and Zinc Phosphinate as Flame Retardants
Authors: Mandlekar Neeraj , Cayla Aurélie , Rault François , Giraud Stéphane , Salaün Fabien , Guan Jinping
Published: October 2020

Biobased lignin represents one of the possible materials for next-generation flame retardant additives due to its sustainability, environmental benefits and comparable efficiency to other flame retardant (FR) additives. In this context, this study presents the development of FR polyamide 11 (PA11) multifilament yarns and fabric structures containing different industrial lignins (i.e., lignosulfonate lignin (LL), and Kraft lignin (KL)) and zinc phosphinate (ZnP). The combination of ZnP and lignin (KL or LL) at different weight ratios were used to prepare flame retarded PA11 blends by melt mixing using a twin-screw extruder. These blends were transformed into continuous multifilament yarns by the melt-spinning process even at a high concentration of additives as 20 wt%. The mechanical test results showed that the combination of KL and ZnP achieved higher strength and filaments showed regularity in structure as compared to the LL and ZnP filaments. Thermogravimetric (TG) analysis showed the incorporation of lignin induces the initial decomposition (T5%) at a lower temperature; at the same time, maximum decomposition (Tmax) shifts to a higher temperature region and a higher amount of char residue is reported at the end of the test. Further, the TGA-FTIR study revealed that the ternary blends (i.e., the combination of LL or KL, ZnP, and PA11) released mainly the phosphinate compound, hydrocarbon species, and a small amount of phosphinic acid during the initial decomposition stage (T5%), while hydrocarbons, carbonyls, and phenolic compounds along with CO2 are released during main decomposition stage (Tmax). The analysis of decomposition products suggests the stronger bonds formation in the condensed phase and the obtainment of a stable char layer. Cone calorimetry exploited to study the fire behavior on sheet samples (polymer bulk) showed an improvement in flame retardant properties with increasing lignin content in blends and most enhanced results were found when 10 wt% of LL and ZnP were combined such as a reduction in heat release rate (HRR) up to 64% and total heat release (THR) up to 22%. Besides, tests carried out on knitted fabric structure showed less influence on HRR and THR but the noticeable effect on postponing the time to ignition (TTI) and reduction in the maximum average rate of heat emission (MARHE) value during combustion.
The TRIOBP Isoforms and Their Distinct Roles in Actin Stabilization, Deafness, Mental Illness, and Cancer
Authors: Zaharija Beti , Samardžija Bobana , Bradshaw Nicholas J.
Published: October 2020

The TRIOBP (TRIO and F-actin Binding Protein) gene encodes multiple proteins, which together play crucial roles in modulating the assembly of the actin cytoskeleton. Splicing of the TRIOBP gene is complex, with the two most studied TRIOBP protein isoforms sharing no overlapping amino acid sequence with each other. TRIOBP-1 (also known as TARA or TAP68) is a mainly structured protein that is ubiquitously expressed and binds to F-actin, preventing its depolymerization. It has been shown to be important for many processes including in the cell cycle, adhesion junctions, and neuronal differentiation. TRIOBP-1 has been implicated in schizophrenia through the formation of protein aggregates in the brain. In contrast, TRIOBP-4 is an entirely disordered protein with a highly specialized expression pattern. It is known to be crucial for the bundling of actin in the stereocilia of the inner ear, with mutations in it causing severe or profound hearing loss. Both of these isoforms are implicated in cancer. Additional longer isoforms of TRIOBP exist, which overlap with both TRIOBP-1 and 4. These appear to participate in the functions of both shorter isoforms, while also possessing unique functions in the inner ear. In this review, the structures and functions of all of these isoforms are discussed, with a view to understanding how they operate, both alone and in combination, to modulate actin and their consequences for human illness.
Antimicrobial Activities of Lipopeptides and Polyketides of Bacillus velezensis for Agricultural Applications
Authors: Fazle Rabbee Muhammad , Baek Kwang-Hyun
Published: October 2020

Since the discovery of penicillin, bacteria are known to be major sources of secondary metabolites that can function as drugs or pesticides. Scientists worldwide attempted to isolate novel compounds from microorganisms; however, only less than 1% of all existing microorganisms have been successfully identified or characterized till now. Despite the limitations and gaps in knowledge, in recent years, many Bacillus velezensis isolates were identified to harbor a large number of biosynthetic gene clusters encoding gene products for the production of secondary metabolites. These chemically diverse bioactive metabolites could serve as a repository for novel drug discovery. More specifically, current projects on whole-genome sequencing of B. velezensis identified a large number of biosynthetic gene clusters that encode enzymes for the synthesis of numerous antimicrobial compounds, including lipopeptides and polyketides; nevertheless, their biological applications are yet to be identified or established. In this review, we discuss the recent research on synthesis of bioactive compounds by B. velezensis and related Bacillus species, their chemical structures, bioactive gene clusters of interest, as well as their biological applications for effective plant disease management.
Biological and Pharmacological Effects of Synthetic Saponins
Authors: Juang Yu-Pu , Liang Pi-Hui
Published: October 2020

Saponins are amphiphilic molecules consisting of carbohydrate and either triterpenoid or steroid aglycone moieties and are noted for their multiple biological activities—Fungicidal, antimicrobial, antiviral, anti-inflammatory, anticancer, antioxidant and immunomodulatory effects have all been observed. Saponins from natural sources have long been used in herbal and traditional medicines; however, the isolation of complexed saponins from nature is difficult and laborious, due to the scarce amount and structure heterogeneity. Chemical synthesis is considered a powerful tool to expand the structural diversity of saponin, leading to the discovery of promising compounds. This review focuses on recent developments in the structure optimization and biological evaluation of synthetic triterpenoid and steroid saponin derivatives. By summarizing the structure–activity relationship (SAR) results, we hope to provide the direction for future development of saponin-based bioactive compounds.
Gold(I)-Catalyzed Domino Reaction for Furopyrans Synthesis
Authors: Ruch Marie , Brach Nicolas , Galéa Roméric , Wagner Patrick , Blond Gaëlle
Published: October 2020

We report herein an efficient synthesis of furopyran derivatives through a gold(I)-catalyzed domino reaction. The cascade reaction starts with two regioselective cyclizations, a 5-endo-dig and a 8-endo-dig, followed with a Grob-type fragmentation and a hetero Diels–Alder. The obtained furopyran derivatives contain fused and spiro-heterocycles. During this one-pot process, four bonds and four controlled stereogenic centers including a quaternary center are formed.
Facile and Low-Cost SPE Modification Towards Ultra-Sensitive Organophosphorus and Carbamate Pesticide Detection in Olive Oil
Authors: Soulis Dionysios , Trigazi Marianna , Tsekenis George , Chandrinou Chrysoula , Klinakis Apostolos , Zergioti Ioanna
Published: October 2020

Despite the fact that a considerable amount of effort has been invested in the development of biosensors for the detection of pesticides, there is still a lack of a simple and low-cost platform that can reliably and sensitively detect their presence in real samples. Herein, an enzyme-based biosensor for the determination of both carbamate and organophosphorus pesticides is presented that is based on acetylcholinesterase (AChE) immobilized on commercially available screen-printed carbon electrodes (SPEs) modified with carbon black (CB), as a means to enhance their conductivity. Most interestingly, two different methodologies to deposit the enzyme onto the sensor surfaces were followed; strikingly different results were obtained depending on the family of pesticides under investigation. Furthermore, and towards the uniform application of the functionalization layer onto the SPEs’ surfaces, the laser induced forward transfer (LIFT) technique was employed in conjunction with CB functionalization, which allowed a considerable improvement of the sensor’s performance. Under the optimized conditions, the fabricated sensors can effectively detect carbofuran in a linear range from 1.1 × 10−9 to 2.3 × 10−8 mol/L, with a limit of detection equal to 0.6 × 10−9 mol/L and chlorpyrifos in a linear range from 0.7 × 10−9 up to 1.4 × 10−8 mol/L and a limit of detection 0.4 × 10−9 mol/L in buffer. The developed biosensor was also interrogated with olive oil samples, and was able to detect both pesticides at concentrations below 10 ppb, which is the maximum residue limit permitted by the European Food Safety Authority.
Development of a Bestatin-SAHA Hybrid with Dual Inhibitory Activity against APN and HDAC
Authors: Cao Jiangying , Zhao Wei , Zhao Chunlong , Liu Qian , Li Shunda , Zhang Guozhen , Chou C. James , Zhang Yingjie
Published: October 2020

With five histone deacetylase (HDAC) inhibitors approved for cancer treatment, proteolysis-targeting chimeras (PROTACs) for degradation of HDAC are emerging as an alternative strategy for HDAC-targeted therapeutic intervention. Herein, three bestatin-based hydroxamic acids (P1, P2 and P3) were designed, synthesized and biologically evaluated to see if they could work as HDAC degrader by recruiting cellular inhibitor of apoptosis protein 1 (cIAP1) E3 ubiquitin ligase. Among the three compounds, the bestatin-SAHA hybrid P1 exhibited comparable even more potent inhibitory activity against HDAC1, HDAC6 and HDAC8 relative to the approved HDAC inhibitor SAHA. It is worth noting that although P1 could not lead to intracellular HDAC degradation after 6 h of treatment, it could dramatically decrease the intracellular levels of HDAC1, HDAC6 and HDAC8 after 24 h of treatment. Intriguingly, the similar phenomenon was also observed in the HDAC inhibitor SAHA. Cotreatment with proteasome inhibitor bortezomib could not reverse the HDAC decreasing effects of P1 and SAHA, confirming that their HDAC decreasing effects were not due to protein degradation. Moreover, all three bestatin-based hydroxamic acids P1, P2 and P3 exhibited more potent aminopeptidase N (APN, CD13) inhibitory activities than the approved APN inhibitor bestatin, which translated to their superior anti-angiogenic activities. Taken together, a novel bestatin-SAHA hybrid was developed, which worked as a potent APN and HDAC dual inhibitor instead of a PROTAC.
Evaluation of Various Solvent Extracts of Tetrastigma leucostaphylum (Dennst.) Alston Leaves, a Bangladeshi Traditional Medicine Used for the Treatment of Diarrhea
Authors: Rudra Sajib , Tahamina Afroza , Emon Nazim Uddin , Adnan Md. , Shakil Mohammad , Chowdhury Md. Helal Uddin , Barlow James W. , Alwahibi Mona S. , Soliman Elshikh Mohamed , Faruque Mohammad Omar , Uddin Shaikh Bokhtear
Published: October 2020

Tetrastigma leucostaphylum (TL) is an important ethnic medicine of Bangladesh used to treat diarrhea and dysentery. Hence, current study has been designed to characterize the antidiarrheal (in vivo) and cytotoxic (in vitro) effects of T. leucostaphylum. A crude extract was prepared with methanol (MTL) and further partitioned into n-hexane (NTL), dichloromethane (DTL), and n-butanol (BTL) fractions. Antidiarrheal activity was investigated using castor oil induced diarrhea, enteropooling, and gastrointestinal transit models, while cytotoxicity was evaluated using the brine shrimp lethality bioassay. In antidiarrheal experiments, all doses (100, 200, and 400 mg/kg) of the DTL extract significantly reduced diarrheal stool frequency, volume and weight of intestinal contents, and gastrointestinal motility in mice. Similarly, in the cytotoxicity assay, all extracts exhibited activity, with the DTL extract the most potent (LC50 67.23 μg/mL). GC-MS analysis of the DTL extract identified 10 compounds, which showed good binding affinity toward M3 muscarinic acetylcholine, 5-HT3, Gut inhibitory phosphodiesterase, DNA polymerase III subunit alpha, and UDP-N-acetylglucosamine-1 carboxyvinyltransferase enzyme targets upon molecular docking analysis. Although ADME/T analyses predicted the drug-likeness and likely safety upon consumption of these bioactive compounds, significant toxicity concerns are evident due to the presence of the known phytotoxin, 2,4-di-tert-butylphenol. In summary, T. leucostaphylum showed promising activity, helping to rationalize the ethnomedicinal use and importance of this plant, its safety profile following both acute and chronic exposure warrants further investigation.
Contamination Levels in Recollected PET Bottles from Non-Food Applications and their Impact on the Safety of Recycled PET for Food Contact
Authors: Franz Roland , Welle Frank
Published: October 2020

PET beverage bottles have been recycled and safely reprocessed into new food contact packaging applications for over two decades. During recollection of post-consumer PET beverage bottles, PET containers from non-food products are inevitably co-collected and thereby enter the PET recycling feed stream. To explore the impact of this mixing on the safety-in-use of recycled PET (rPET) bottles, we determined the concentrations of post-consumer substances in PET containers used for a range of non-food product applications taken from the market. Based on the chemical nature and amounts of these post-consumer substances, we evaluated their potential carry-over into beverages filled in rPET bottles starting from different fractions of non-food PET in the recollection systems and taking worst-case cleaning efficiencies of super-clean recycling processes into account. On the basis of the Threshold of Toxicological Concern (TTC) concept and Cramer classification tools, we present a risk assessment for potential exposure of the consumer to the identified contaminants as well as unidentified, potentially genotoxic substances in beverages. As a result, a fraction of 5% non-food PET in the recycling feed stream, which is very likely to occur in the usual recollection systems, does not pose any risk to the consumer. Our data show that fractions of up to 20%, which may sporadically be contained in certain, local recollection systems, would also not raise a safety concern.
A FRET-ICT Dual-Modulated Ratiometric Fluorescence Sensor for Monitoring and Bio-Imaging of Cellular Selenocysteine
Authors: Wang Zongcheng , Hao Chenhong , Luo Xiaofang , Wu Qiyao , Zhang Chengliang , Dessie Wubliker , Jiang Yuren
Published: October 2020

Since the fluctuation of cellular selenocysteine (Sec) concentration plays an all-important role in the development of numerous human disorders, the real-time fluorescence detection of Sec in living systems has attracted plenty of interest during the past decade. In order to obtain a faster and more sensitive small organic molecule fluorescence sensor for the Sec detection, a new ratiometric fluorescence sensor Q7 was designed based on the fluorescence resonance energy transfer (FRET) strategy with coumarin fluorophore as energy donor and 4-hydroxy naphthalimide fluorophore (with 2,4-dinitrobenzene sulfonate as fluorescence signal quencher and Sec-selective recognition site) as an energy acceptor. The sensor Q7 exhibited only a blue fluorescence signal, and displayed two well distinguished emission bands (blue and green) in the presence of Sec with ∆λ of 68 nm. Moreover, concentrations ranging of quantitative detection of Sec of Q7 was from 0 to 45 μM (limit of detection = 6.9 nM), with rapid ratiometric response, high sensitivity and selectivity capability. Impressively, the results of the living cell imaging test demonstrated Q7 has the potentiality of being an ideal sensor for real-time Sec detection in biosystems.