bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Function in ABCA4-Related Retinopathy Using Ensemble Machine Learning
Authors: Müller Philipp L. , Treis Tim , Odainic Alexandru , Pfau Maximilian , Herrmann Philipp , Tufail Adnan , Holz Frank G.
Published: July 2020

Full-field electroretinogram (ERG) and best corrected visual acuity (BCVA) measures have been shown to have prognostic value for recessive Stargardt disease (also called “ABCA4-related retinopathy”). These functional tests may serve as a performance-outcome-measure (PerfO) in emerging interventional clinical trials, but utility is limited by variability and patient burden. To address these limitations, an ensemble machine-learning-based approach was evaluated to differentiate patients from controls, and predict disease categories depending on ERG (‘inferred ERG’) and visual impairment (‘inferred visual impairment’) as well as BCVA values (‘inferred BCVA’) based on microstructural imaging (utilizing spectral-domain optical coherence tomography) and patient data. The accuracy for ‘inferred ERG’ and ‘inferred visual impairment’ was up to 99.53 ± 1.02%. Prediction of BCVA values (‘inferred BCVA’) achieved a precision of ±0.3LogMAR in up to 85.31% of eyes. Analysis of the permutation importance revealed that foveal status was the most important feature for BCVA prediction, while the thickness of outer nuclear layer and photoreceptor inner and outer segments as well as age of onset highly ranked for all predictions. ‘Inferred ERG’, ‘inferred visual impairment’, and ‘inferred BCVA’, herein, represent accurate estimates of differential functional effects of retinal microstructure, and offer quasi-functional parameters with the potential for a refined patient assessment, and investigation of potential future treatment effects or disease progression.
Prevalence and Predictive Value of Anemia and Dysregulated Iron Homeostasis in Patients with COVID-19 Infection
Authors: Bellmann-Weiler Rosa , Lanser Lukas , Barket Robert , Rangger Lukas , Schapfl Anna , Schaber Marc , Fritsche Gernot , Wöll Ewald , Weiss Günter
Published: July 2020

Infections with SARS-CoV-2 can result in severe clinical manifestations. As such patients present with systemic inflammation, we studied the prevalence and predictive value of anemia of inflammation (AI) or functional iron deficiency (FID), originating from immune-mediated alterations of iron homeostasis. Within this retrospective analysis of 259 hospitalized patients with COVID-19, we found that, upon admission, 24.7% were anemic, with the majority suffering from AI (68.8%). Anemia was associated with a significantly higher in-hospital mortality (OR 3.729 (95%CI 1.739–7.995), p = 0.001) but not an increased frequency of intensive care unit (ICU) admission or need for mechanical ventilation. FID was present in 80.0% of patients upon admission, linked to more advanced inflammation and associated with significantly longer hospital stay. Notably, a ferritin/transferrin ratio > 10 predicted a five-fold higher risk of ICU admission and an eight-fold higher risk of the need for mechanical ventilation. Anemia and alterations of iron homeostasis are highly prevalent in hospitalized COVID-19 patients. Iron metabolism biomarkers and hemoglobin can contribute to risk stratification of patients, as initial anemia is associated with increased mortality, whereas alterations of iron homeostasis with a higher ferritin/transferrin ratio reflect more advanced inflammation and predicts subsequent insufficient pulmonary oxygenation with the need for ICU admission and mechanical ventilation.
Lifestyle-Related Exposure to Cadmium and Lead is Associated with Diabetic Kidney Disease
Authors: Hagedoorn Ilse J. M. , Gant Christina M. , Huizen Sanne v. , Maatman Ronald G. H. J. , Navis Gerjan , Bakker Stephan J. L. , Laverman Gozewijn D.
Published: July 2020

Background: Environmental factors contributing to diabetic kidney disease are incompletely understood. We investigated whether blood cadmium and lead concentrations were associated with the prevalence of diabetic kidney disease, and to what extent lifestyle-related exposures (diet and smoking) contribute to blood cadmium and lead concentrations. Material and methods: In a cross-sectional analysis in 231 patients with type 2 diabetes included in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1), blood cadmium and lead concentrations were determined using inductively coupled plasma mass spectrometry. The associations between diet (derived from food frequency questionnaire), smoking and cadmium and lead were determined using multivariate linear regression. The associations between cadmium and lead and diabetic kidney disease (albumin excretion >30 mg/24 h and/or creatinine clearance <60 mL/min/1.73 m2) were determined using multivariate logistic regression. Results: Median blood concentrations were 2.94 nmol/L (interquartile range (IQR): 1.78–4.98 nmol/L) for cadmium and 0.07 µmol/L (IQR: 0.04–0.09 µmol/L) for lead, i.e., below acute toxicity values. Every doubling of lead concentration was associated with a 1.75 (95% confidence interval (CI): 1.11–2.74) times higher risk for albuminuria. In addition, both cadmium (odds ratio (OR) 1.50 95% CI: 1.02–2.21) and lead (OR 1.83 95% CI: 1.07–3.15) were associated with an increased risk for reduced creatinine clearance. Both passive smoking and active smoking were positively associated with cadmium concentration. Alcohol intake was positively associated with lead concentration. No positive associations were found between dietary intake and cadmium or lead. Conclusions: The association between cadmium and lead and the prevalence of diabetic kidney disease suggests cadmium and lead might contribute to the development of diabetic kidney disease. Exposure to cadmium and lead could be a so far underappreciated nephrotoxic mechanism of smoking and alcohol consumption.
Menopausal Transition, Body Mass Index, and Prevalence of Mammographic Dense Breasts in Middle-Aged Women
Authors: Kim Eun Young , Chang Yoosoo , Ahn Jiin , Yun Ji-Sup , Park Yong Lai , Park Chan Heun , Shin Hocheol , Ryu Seungho
Published: July 2020

The interrelationship between menopausal stage, excessive adiposity and dense breasts remains unclear. We aimed to investigate the relationship between menopausal stage and dense-breast prevalence in midlife women while considering a possible effect modification of being overweight. The present cross-sectional study comprised 82,677 Korean women, aged 35–65 years, who attended a screening exam. Menopausal stages were categorized based on the Stages of Reproductive Aging Workshop (STRAW + 10) criteria. Mammographic breast density was categorized according to Breast Imaging Reporting and Data System (BI-RADS). Dense breasts were defined as BI-RADS Breast Density category D (extremely dense). The prevalence of dense breasts decreased as menopausal stage increased (p-trend < 0.001), and this pattern was pronounced in overweight women than non-overweight women (p-interaction = 0.016). Compared with pre-menopause, the multivariable-adjusted prevalence ratios (and 95% confidence intervals) for dense breasts were 0.98 (0.96–1.00) in early transition, 0.89 (0.86–0.92) in late transition, and 0.55 (0.52–0.59) in post-menopause, among non-overweight women, while corresponding prevalence ratios were 0.92 (0.87–0.98), 0.83 (0.77–0.90) and 0.36 (0.31–0.41) among overweight women. The prevalence of dense breasts was inversely associated with increasing menopausal stages and significantly decreased from the late menopausal transition, with stronger declines among overweight women.
The Use of Bispectral Index Monitoring Does Not Change Intraoperative Exposure to Volatile Anesthetics in Children
Authors: Sullivan Cornelius A. , Egbuta Chinyere , Park Raymond S. , Lukovits Karina , Cavanaugh David , Mason Keira P.
Published: July 2020

The exposure of infants and children to volatile anesthetics, such as sevoflurane, has been a topic of concern with respect to the potential risk for long term neurocognitive effects. The primary objective of this study was to determine whether the perioperative utilization of Bispectral Index (BIS) monitoring alters the sevoflurane delivery and exposure to children. This is a prospective randomized trial of two groups of healthy ambulatory day surgery patients (2 to 12 years). The patients in both groups had the BIS applied soon after the induction of general anesthesia, but only the anesthesiologists in the group randomized to BIS visible were able to see the BIS values. All of the patients received general anesthesia with sevoflurane. This study found no difference in the overall exposure to sevoflurane between both groups (mean end-tidal sevoflurane level of 1.8 in both groups, P = 084). The duration of time in the recovery room, the time to meet discharge criteria, the Pediatric Agitation Emergence Delirium (PAED) scores and the Face, Legs, Activity, Cry, Consolability (FLACC) scores were not statistically different between the groups. The application and utilization of intraoperative BIS monitoring does not alter the sevoflurane administration nor the discharge readiness nor the recovery profile in healthy ambulatory children.
Core Outcome Measurement Instruments for Clinical Trials of Total Knee Arthroplasty: A Systematic Review
Authors: Reynaud Vivien , Verdilos Anargyros , Pereira Bruno , Boisgard Stéphane , Costes Frédéric , Coudeyre Emmanuel
Published: July 2020

(1) Background: We have updated knowledge of the psychometric qualities of patient-reported outcome measures and, for the first time, systematically reviewed and compared the psychometric qualities of physical tests for patients with knee osteoarthritis who are undergoing total knee arthroplasty. This work was conducted to facilitate the choice of the most appropriate instruments to use in studies and clinical practice. (2) Methods: A search of medical databases up to December 2019 identified the studies and thus the instruments used. The quality of the measurement properties was assessed by the Bot et al. criteria. (3) Results: We identified 20 studies involving 25 instruments. Half of the instruments were questionnaires (n = 13). Among the condition-specific instruments, the Oxford knee score, Knee injury and Osteoarthritis Outcomes Score, and the Western Ontario and McMaster Universities Osteoarthritis index had the highest overall scores. Concerning generic tools, the Medical Outcomes Study Short-Form 36 (SF-36) or SF-12 obtained the highest overall score. For patient-specific tools, the Hospital Anxiety and Depression Scale ranked the highest. Some physical tests seemed robust in psychometric properties: 6-min Walk Test, five times Sit-To-Stand test, Timed Up and Go test strength testing of knee flexor/extensor by isometric or isokinetic dynamometer and Pressure Pain Threshold. (4) Conclusion: To make stronger recommendations, key areas such as reproducibility, responsiveness to clinical change, and minimal important change still need more rigorous evaluations. Some promising physical tests (e.g., actimetry) lack validation and require rigorous studies to be used as a core set of outcomes in future studies.
Analyzing Macro-Level Ecological Change and Micro-Level Farmer Behavior in Manas River Basin, China
Authors: Liao Na , Gu Xinchen , Wang Yuejian , Xu Hailiang , Fan Zili
Published: July 2020

Environmental degradation is closely related to unreasonable land use behaviors by farmers. In this study, participatory rural assessment (PRA) is used to conduct a detailed survey of farmers and plots and to collect relevant natural and social statistics. The accuracy of remote sensing data is verified by comparative analysis, and the change in status of various land use types in each research period is reflected by the change in the dynamic degree and change in range. We examine how farmers’ attitudes and behaviors affect environmental degradation, using a sample of 403 farmers in China’s Manas River Basin. Due to age, education, income and other differences, farmers’ land use behaviors, as well as their attitude toward and feelings about environmental degradation, vary greatly. We found that most farmers considered the environment to be very important to their lives and crop production, but nearly 21% did not know the causes of environmental degradation and nearly 8% did not consider the environmental impacts of their crop production activities. A new model for oasis expansion—land integration—is presented here. This model can increase the area of cultivated land, reduce cultivated land fragmentation, save irrigation water, improve the field microclimate and form a good ecological cycle. Through land transfer, ecological compensation and ecological protection incentives, the government should guide farmers’ land use behaviors toward cooperation with the river basin’s ecological protection and land use planning.
People-Centric Nature-Based Land Restoration through Agroforestry: A Typology
Authors: van Noordwijk Meine , Gitz Vincent , Minang Peter A. , Dewi Sonya , Leimona Beria , Duguma Lalisa , Pingault Nathanaël , Meybeck Alexandre
Published: July 2020

Restoration depends on purpose and context. At the core it entails innovation to halt ongoing and reverse past degradation. It aims for increased functionality, not necessarily recovering past system states. Location-specific interventions in social-ecological systems reducing proximate pressures, need to synergize with transforming generic drivers of unsustainable land use. After reviewing pantropical international research on forests, trees, and agroforestry, we developed an options-by-context typology. Four intensities of land restoration interact: R.I. Ecological intensification within a land use system, R.II. Recovery/regeneration, within a local social-ecological system, R.III. Reparation/recuperation, requiring a national policy context, R.IV. Remediation, requiring international support and investment. Relevant interventions start from core values of human identity while addressing five potential bottlenecks: Rights, Know-how, Markets (inputs, outputs, credit), Local Ecosystem Services (including water, agrobiodiversity, micro/mesoclimate) and Teleconnections (global climate change, biodiversity). Six stages of forest transition (from closed old-growth forest to open-field agriculture and re-treed (peri)urban landscapes) can contextualize interventions, with six special places: water towers, riparian zone and wetlands, peat landscapes, small islands and mangroves, transport infrastructure, and mining scars. The typology can help to link knowledge with action in people-centric restoration in which external stakeholders coinvest, reflecting shared responsibility for historical degradation and benefits from environmental stewardship.
Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications
Authors: Kontoghiorghes George J. , Kolnagou Annita , Kontoghiorghe Christina N. , Mourouzidis Loukia , Timoshnikov Viktor A. , Polyakov Nikolay E.
Published: July 2020

Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload. The main function and use of vitamin C is its antioxidant activity against reactive oxygen species, which are implicated in many diseases of free radical pathology, including biomolecular-, cellular- and tissue damage-related diseases, as well as cancer and ageing. Ascorbic acid and its metabolites, including the ascorbate anion and oxalate, have metal binding capacity and bind iron, copper and other metals. The biological roles of ascorbate as a vitamin are affected by metal complexation, in particular following binding with iron and copper. Ascorbate forms a complex with Fe3+ followed by reduction to Fe2+, which may potentiate free radical production. The biological and clinical activities of iron, ascorbate and the ascorbate–iron complex can also be affected by many nutrients and pharmaceutical preparations. Optimal therapeutic strategies of improved efficacy and lower toxicity could be designed for the use of ascorbate, iron and the iron–ascorbate complex in different clinical conditions based on their absorption, distribution, metabolism, excretion, toxicity (ADMET), pharmacokinetic, redox and other properties. Similar strategies could also be designed in relation to their interactions with food components and pharmaceuticals, as well as in relation to other aspects concerning personalized medicine.
Diffusion Dialysis for Acid Recovery from Acidic Waste Solutions: Anion Exchange Membranes and Technology Integration
Authors: Zhang Chengyi , Zhang Wen , Wang Yuxin
Published: July 2020

Inorganic acids are commonly used in mining, metallurgical, metal-processing, and nuclear-fuel-reprocessing industries in various processes, such as leaching, etching, electroplating, and metal-refining. Large amounts of spent acidic liquids containing toxic metal ion complexes are produced during these operations, which pose a serious hazard to the living and non-living environment. Developing economic and eco-friendly regeneration approaches to recover acid and valuable metals from these industrial effluents has focused the interest of the research community. Diffusion dialysis (DD) using anion exchange membranes (AEMs) driven by an activity gradient is considered an effective technology with a low energy consumption and little environmental contamination. In addition, the properties of AEMs have an important effect on the DD process. Hence, this paper gives a critical review of the properties of AEMs, including their acid permeability, membrane stability, and acid selectivity during the DD process for acid recovery. Furthermore, the DD processes using AEMs integrated with various technologies, such as pressure, an electric field, or continuous operation are discussed to enhance its potential for industrial applications. Finally, some directions are provided for the further development of AEMs in DD for acid recovery from acidic waste solutions.
A Simple Method to Identify the Dominant Fouling Mechanisms during Membrane Filtration Based on Piecewise Multiple Linear Regression
Authors: Xu Hao , Xiao Kang , Yu Jinlan , Huang Bin , Wang Xiaomao , Liang Shuai , Wei Chunhai , Wen Xianghua , Huang Xia
Published: July 2020

Membrane fouling is a complicated issue in microfiltration and ultrafiltration. Clearly identifying the dominant fouling mechanisms during the filtration process is of great significance for the phased and targeted control of fouling. To this end, we propose a semi-empirical multiple linear regression model to describe flux decline, incorporating the five fouling mechanisms (the first and second kinds of standard blocking, complete blocking, intermediate blocking, and cake filtration) based on the additivity of the permeate volume contributed by different coexisting mechanisms. A piecewise fitting protocol was established to distinguish the fouling stages and find the significant mechanisms in each stage. This approach was applied to a case study of a microfiltration membrane filtering a model foulant solution composed of polysaccharide, protein, and humic substances, and the model fitting unequivocally revealed that the dominant fouling mechanism evolved in the sequence of initial adaptation, fast adsorption followed by slow adsorption inside the membrane pores, and the gradual growth of a cake/gel layer on the membrane surface. The results were in good agreement with the permeate properties (total organic carbon, ultraviolet absorbance, and fluorescence) during the filtration process. This modeling approach proves to be simple and reliable for identifying the main fouling mechanisms during membrane filtration with statistical confidence.
Isolation of Three Lycorine Type Alkaloids from Rhodolirium speciosum (Herb.) Ravenna Using pH-Zone-Refinement Centrifugal Partition Chromatography and Their Acetylcholinesterase Inhibitory Activities
Authors: Correa Diana Isabel , Pastene-Navarrete Edgar , Bustamante Luis , Baeza Marcelo , Alarcón-Enos Julio
Published: July 2020

Preparative separation of three lycorine type alkaloids from Rhodolirum speciosum (Amaryllidaceae) was successfully carried out using pH-zone-refinement centrifugal partition chromatography (CPC) using the solvent system methyl-tert-butyl ether/acetonitrile/water (4:1:5, v/v/v) in descending mode. Using this system, Alkaloid 1 (165.7 mg, 88.2%, purity), 2 (60.1 mg, 97.7% purity) and 3 (12.3 mg, 84.4% purity) were obtained in one step. For structure elucidation, the pure alkaloids were subjected to spectroscopy analysis using nuclear magnetic resonance experiments (1H-NMR, 13C-NMR) and gas chromatography coupled with mass spectrometry (GC-MS). Alkaloids 1, 2, and 3 were identified as 1-O-acetyl-5,6-dehydrolycorine, 1-O-acetyl-lycorine, and 1,2-O-diacetyl-5,6-dehydrolycorine, respectively. The acetylcholinesterase inhibitory activity of these alkaloids was IC50 151.1 μg/mL, IC50 203.5 μg/mL, IC50 470.0 μg/mL, and IC50 17.1 μg/mL, respectively.
A Novel High Q Lamé-Mode Bulk Resonator with Low Bias Voltage
Authors: Wang Tianyun , Chen Zeji , Jia Qianqian , Yuan Quan , Yang Jinling , Yang Fuhua
Published: July 2020

This work reports a novel silicon on insulator (SOI)-based high quality factor (Q factor) Lamé-mode bulk resonator which can be driven into vibration by a bias voltage as low as 3 V. A SOI-based fabrication process was developed to produce the resonators with 70 nm air gaps, which have a high resonance frequency of 51.3 MHz and high Q factors over 8000 in air and over 30,000 in vacuum. The high Q values, nano-scale air gaps, and large electrode area greatly improve the capacitive transduction efficiency, which decreases the bias voltage for the high-stiffness bulk mode resonators with high Q. The resonator showed the nonlinear behavior. The proposed resonator can be applied to construct a wireless communication system with low power consumption and integrated circuit (IC) integration.
Single-Grain Gate-All-Around Si Nanowire FET Using Low-Thermal-Budget Processes for Monolithic Three-Dimensional Integrated Circuits
Authors: Hsieh Tung-Ying , Hsieh Ping-Yi , Yang Chih-Chao , Shen Chang-Hong , Shieh Jia-Min , Yeh Wen-Kuan , Wu Meng-Chyi
Published: July 2020

We introduce a single-grain gate-all-around (GAA) Si nanowire (NW) FET using the location-controlled-grain technique and several innovative low-thermal budget processes, including green nanosecond laser crystallization, far-infrared laser annealing, and hybrid laser-assisted salicidation, that keep the substrate temperature (Tsub) lower than 400 °C for monolithic three-dimensional integrated circuits (3D-ICs). The detailed process verification of a low-defect GAA nanowire and electrical characteristics were investigated in this article. The GAA Si NW FETs, which were intentionally fabricated within the controlled Si grain, exhibit a steeper subthreshold swing (S.S.) of about 65 mV/dec., higher driving currents of 327 µA/µm (n-type) and 297 µA/µm (p-type) @ Vth ± 0.8 V, and higher Ion/Ioff (>105 @|Vd| = 1 V) and have a narrower electrical property distribution. In addition, the proposed Si NW FETs with a GAA structure were found to be less sensitive to Vth roll-off and S.S. degradation compared to the omega(Ω)-gate Si FETs. It enables ultrahigh-density sequentially stackable integrated circuits with superior performance and low power consumption for future mobile and neuromorphic applications.
Planctomycetes as a Vital Constituent of the Microbial Communities Inhabiting Different Layers of the Meromictic Lake Sælenvannet (Norway)
Authors: Storesund Julia E. , Lanzèn Anders , Nordmann Eva-Lena , Armo Hilde Rief , Lage Olga Maria , Øvreås Lise
Published: July 2020

Meromictic lakes are permanently stratified lakes that display steep gradients in salinity, oxygen and sulphur compounds tightly linked to bacterial community structure and diversity. Lake Sælenvannet is a meromictic lake located south of Bergen, Norway. The 26 m deep lake is connected to the open sea and permanently stratified into two layers separated by a chemocline. The upper water layer is brackish with major input from water runoff from the surroundings. The bottom layer consists of old saline water with low or no oxygen concentrations. Bacteria from phylum Planctomycetes are reported to be ubiquitous in lake environments. They are involved in the degradation of complex carbon sources in aquatic environments and are also linked to anaerobic processes such as fermentation and sulphur reduction. To study Planctomycete distribution along a chemical gradient, we sampled the water column throughout Lake Sælenvannet in 2012 and profiled the microbial community using 16S rRNA amplicon sequencing (metabarcoding) with 454 pyrosequencing. Planctomycetes related 16S rRNA gene sequences were found to be present both in the oxic and anoxic parts of the lake and showed an uneven distribution throughout the water column, with the highest relative abundance of 10% found in the saline anoxic layer at 15 m depth. In a follow-up study in 2014, samples from eight different depths were collected for enrichment and isolation of novel Planctomycetes. This study resulted in successful isolation in pure culture of 10 isolates affiliated to four different genera from the family Planctomycetaceae. One strain closely related to Blastopirellula cremea was isolated from 9 m depth, and two novel strains affiliated to the genera Stieleria and Gimesia were isolated at 7 and 9 m depths, respectively. Furthermore, seven isolates with identical 16S rRNA gene sequences were retrieved from seven different depths which varied greatly in salinity and chemical composition. These isolates likely represent a new species affiliated to Rubinisphaera. The adaptation of this novel Planctomycete to water depths spanning the entire chemical gradient could indicate a high phenotypic plasticity and/or a very efficient survival strategy. Overall, our results show the presence of a diverse group of Planctomycetes in Lake Sælenvannet, with a strong potential for novel adaptations to chemical stress factors.
Discovery of Predictors of Mycoplasma hyopneumoniae Vaccine Response Efficiency in Pigs: 16S rRNA Gene Fecal Microbiota Analysis
Authors: Munyaka Peris M. , Blanc Fany , Estellé Jordi , Lemonnier Gaëtan , Leplat Jean-Jacques , Rossignol Marie-Noëlle , Jardet Déborah , Plastow Graham , Billon Yvon , Willing Benjamin P. , Rogel-Gaillard Claire
Published: July 2020

The gut microbiota comprises a large and diverse community of bacteria that play a significant role in swine health. Indeed, there is a tight association between the enteric immune system and the overall composition and richness of the microbiota, which is key in the induction, training and function of the host immunity, and may therefore, influence the immune response to vaccination. Using vaccination against Mycoplasma hyopneumoniae (M. hyo) as a model, we investigated the potential of early-life gut microbiota in predicting vaccine response and explored the post-vaccination dynamics of fecal microbiota at later time points. At 28 days of age (0 days post-vaccination; dpv), healthy piglets were vaccinated, and a booster vaccine was administered at 21 dpv. Blood samples were collected at 0, 21, 28, 35, and 118 dpv to measure M. hyo-specific IgG levels. Fecal samples for 16S rRNA gene amplicon sequencing were collected at 0, 21, 35, and 118 dpv. The results showed variability in antibody response among individual pigs, whilst pre-vaccination operational taxonomic units (OTUs) primarily belonging to Prevotella, [Prevotella], Anaerovibrio, and Sutterella appeared to best-predict vaccine response. Microbiota composition did not differ between the vaccinated and non-vaccinated pigs at post-vaccination time points, but the time effect was significant irrespective of the animals’ vaccination status. Our study provides insight into the role of pre-vaccination gut microbiota composition in vaccine response and emphasizes the importance of studies on full metagenomes and microbial metabolites aimed at deciphering the role of specific bacteria and bacterial genes in the modulation of vaccine response.
Green Analytical Methods of Antimalarial Artemether-Lumefantrine Analysis for Falsification Detection Using a Low-Cost Handled NIR Spectrometer with DD-SIMCA and Drug Quantification by HPLC
Authors: Yabré Moussa , Ferey Ludivine , Sakira Abdoul Karim , Bonmatin Camille , Fauré Clotilde , Somé Touridomon Issa , Gaudin Karen
Published: July 2020

Two green analytical approaches have been developed for the analysis of antimalarial fixed dose tablets of artemether and lumefantrine for quality control. The first approach consisted of investigating the qualitative performance of a low-cost handheld near-infrared spectrometer in combination with the principal component analysis as an exploratory tool to identify trends, similarities, and differences between pharmaceutical samples, before applying the data driven soft independent modeling of class analogy (DD-SIMCA) as a one-class classifier for proper drug falsification detection with 100% of both sensitivity and specificity in the studied cases. Despite its limited spectral range and low resolution, the handheld device allowed detecting falsified drugs with no active pharmaceutical ingredient and identifying specifically a pharmaceutical tablet brand name. The second approach was the quantitative analysis based on the green and fast RP-HPLC technique using ethanol as a green organic solvent and acetic acid as a green pH modifier. The optimal separation was achieved in 7 min using a mobile phase composed of ethanol 96% and 10 mM of acetic acid pH 3.35 (63:37, v/v). The developed method was validated according to the total error approach based on an accuracy profile, was applied to the analysis of tablets, and allowed confirming falsified drugs detected by spectroscopy.
Repurposing Drugs to Fight Hepatic Malaria Parasites
Authors: Fontinha Diana , Moules Isabel , Prudêncio Miguel
Published: July 2020

Malaria remains one of the most prevalent infectious diseases worldwide, primarily affecting some of the most vulnerable populations around the globe. Despite achievements in the treatment of this devastating disease, there is still an urgent need for the discovery of new drugs that tackle infection by Plasmodium parasites. However, de novo drug development is a costly and time-consuming process. An alternative strategy is to evaluate the anti-plasmodial activity of compounds that are already approved for other purposes, an approach known as drug repurposing. Here, we will review efforts to assess the anti-plasmodial activity of existing drugs, with an emphasis on the obligatory and clinically silent liver stage of infection. We will also review the current knowledge on the classes of compounds that might be therapeutically relevant against Plasmodium in the context of other communicable diseases that are prevalent in regions where malaria is endemic. Repositioning existing compounds may constitute a faster solution to the current gap of prophylactic and therapeutic drugs that act on Plasmodium parasites, overall contributing to the global effort of malaria eradication.
Enhancement of Biomass and Calcium Carbonate Biomineralization of Chlorella vulgaris through Plackett–Burman Screening and Box–Behnken Optimization Approach
Authors: Chin Zheng Wei , Arumugam Kavithraashree , Ashari Siti Efliza , Faizal Wong Fadzlie Wong , Tan Joo Shun , Ariff Arbakariya Bin , Mohamed Mohd Shamzi
Published: July 2020

The biosynthesis of calcium carbonate (CaCO3) minerals through a metabolic process known as microbially induced calcium carbonate precipitation (MICP) between diverse microorganisms, and organic/inorganic compounds within their immediate microenvironment, gives rise to a cementitious biomaterial that may emerge as a promissory alternative to conventional cement. Among photosynthetic microalgae, Chlorella vulgaris has been identified as one of the species capable of undergoing such activity in nature. In this study, response surface technique was employed to ascertain the optimum condition for the enhancement of biomass and CaCO3 precipitation of C. vulgaris when cultured in Blue-Green (BG)-11 aquaculture medium. Preliminary screening via Plackett–Burman Design showed that sodium nitrate (NaNO3), sodium acetate, and urea have a significant effect on both target responses (p < 0.05). Further refinement was conducted using Box–Behnken Design based on these three factors. The highest production of 1.517 g/L C. vulgaris biomass and 1.143 g/L of CaCO3 precipitates was achieved with a final recipe comprising of 8.74 mM of NaNO3, 61.40 mM of sodium acetate and 0.143 g/L of urea, respectively. Moreover, polymorphism analyses on the collected minerals through morphological examination via scanning electron microscopy and crystallographic elucidation by X-ray diffraction indicated to predominantly calcite crystalline structure.
Chiral Amphiphilic Secondary Amine-Porphyrin Hybrids for Aqueous Organocatalysis
Authors: Arlegui Aitor , Torres Pol , Cuesta Victor , Crusats Joaquim , Moyano Albert
Published: July 2020

Two chiral proline-derived amphiphilic 5-substituted-10,15,20-tris(4-sulfonatophenyl)porphyrins were prepared, and their pH-dependent supramolecular behavior was studied. In neutral aqueous solutions, the free-base form of the hybrids is highly soluble, allowing enamine-based organocatalysis to take place, whereas under acidic conditions, the porphyrinic protonated core of the hybrid leads to the formation of self-assembled structures, so that the hybrids flocculate and their catalytic activity is fully suppressed. The low degree of chirality transfer observed for aqueous Michael and aldol reactions strongly suggests that these reactions take place under true “in water” organocatalytic conditions. The highly insoluble catalyst aggregates can easily be separated from the reaction products by centrifugation of the acidic reaction mixtures, and after neutralization and desalting, the sodium salts of the sulfonated amine-porphyrin hybrids, retaining their full catalytic activity, can be recovered in high yield.
Comparative Study of Microstructure and Mechanical Properties of Two TiAl-Based Alloys Reinforced with Carbide Particles
Authors: Lapin Juraj , Kamyshnykova Kateryna , Klimova Alena
Published: July 2020

Microstructure and mechanical properties of two TiAl-based alloys with nominal composition Ti-42.6Al-8.7Nb-0.3Ta-2.0C and Ti-41.0Al-8.7Nb-0.3Ta-3.6C (in at.%) were investigated and compared. The alloys were prepared by vacuum induction melting, followed by centrifugal casting. The as-cast samples were subjected to hot isostatic pressing and heat treatment consisting of solution annealing in β (Ti-based solid solution) phase field, cooling at a constant rate and stabilization annealing. The microstructure of the alloys consists of α2 (Ti3Al) + γ (TiAl) lamellar grains, single γ phase, coarse Ti2AlC particles, and irregular shaped α2 phase. The increase in the content of C at the expense of decreasing Al in the studied alloys affects solid-state phase transformation temperatures and leads to a decrease in size of grains and primary Ti2AlC particles, increase in the volume fraction of reinforcing carbide particles, decrease in the volume fraction of lamellar colonies, and widening of the grain boundaries. Long-term ageing at 800 °C has no effect on the grain size but leads to the formation of Ti4Al3Nb particles and increase in interlamellar spacing. The Vickers hardness, microhardness of lamellar grains, indentation nanohardness, and elastic modulus of the boundary γ phase decrease during ageing. The Ti-42.6Al-8.7Nb-0.3Ta-2.0C alloy shows improved creep resistance compared to that of Ti-41.0Al-8.7Nb-0.3Ta-3.6C and some reference TiAl-based alloys at a temperature of 800 °C and applied stress of 200 MPa.
Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury
Authors: Gáspár Renáta , Gömöri Kamilla , Kiss Bernadett , Szántai Ágnes , Pálóczi János , Varga Zoltán V. , Pipis Judit , Váradi Barnabás , Ágg Bence , Csont Tamás , Ferdinandy Péter , Barteková Monika , Görbe Anikó
Published: July 2020

Search for new cardioprotective therapies is of great importance since no cardioprotective drugs are available on the market. In line with this need, several natural biomolecules have been extensively tested for their potential cardioprotective effects. Previously, we have shown that biglycan, a member of a diverse group of small leucine-rich proteoglycans, enhanced the expression of cardioprotective genes and decreased ischemia/reperfusion-induced cardiomyocyte death via a TLR-4 dependent mechanism. Therefore, in the present study we aimed to test whether decorin, a small leucine-rich proteoglycan closely related to biglycan, could exert cardiocytoprotection and to reveal possible downstream signaling pathways. Methods: Primary cardiomyocytes isolated from neonatal and adult rat hearts were treated with 0 (Vehicle), 1, 3, 10, 30 and 100 nM decorin as 20 h pretreatment and maintained throughout simulated ischemia and reperfusion (SI/R). In separate experiments, to test the mechanism of decorin-induced cardio protection, 3 nM decorin was applied in combination with inhibitors of known survival pathways, that is, the NOS inhibitor L-NAME, the PKG inhibitor KT-5823 and the TLR-4 inhibitor TAK-242, respectively. mRNA expression changes were measured after SI/R injury. Results: Cell viability of both neonatal and adult cardiomyocytes was significantly decreased due to SI/R injury. Decorin at 1, 3 and 10 nM concentrations significantly increased the survival of both neonatal and adult myocytes after SI/R. At 3nM (the most pronounced protective concentration), it had no effect on apoptotic rate of neonatal cardiac myocytes. No one of the inhibitors of survival pathways (L-NAME, KT-5823, TAK-242) influenced the cardiocytoprotective effect of decorin. MYND-type containing 19 (Zmynd19) and eukaryotic translation initiation factor 4E nuclear import factor 1 (Eif4enif1) were significantly upregulated due to the decorin treatment. In conclusion, this is the first demonstration that decorin exerts a direct cardiocytoprotective effect possibly independent of NO-cGMP-PKG and TLR-4 dependent survival signaling.
Lignin Refinery Using Organosolv Process for Nanoporous Carbon Synthesis
Authors: Prasetyo Imam , Permatasari Puspita Rahayu , Laksmana William Teja , Rochmadi Rochmadi , Oh Won-Chun , Ariyanto Teguh
Published: July 2020

Porous carbon has been widely used for many applications e.g., adsorbents, catalysts, catalyst supports, energy storage and gas storage due to its outstanding properties. In this paper, characteristics of porous carbon prepared by carbonization of lignin from various biomasses are presented. Various biomasses, i.e., mangosteen peel, corncob and coconut shell, were processed using ethanol as an organosolv solvent. The obtained lignin was characterized using a Fourier transform infrared (FTIR) spectrophotometer and a viscosimeter to investigate the success of extraction and lignin properties. The results showed that high temperature is favorable for the extraction of lignin using the organosolv process. The FTIR spectra show the success of lignin extraction using the organosolv process because of its similarity to the standard lignin spectra. The carbonization process of lignin was performed at 600 and 850 °C to produce carbon from lignin, as well as to investigate the effect of temperature. A higher pyrolysis temperature will produce a porous carbon with a high specific surface area, but it will lower the yield of the produced carbon. At 850 °C temperature, the highest surface area up to 974 m2/g was achieved.
Single Residue Substitution at N-Terminal Affects Temperature Stability and Activity of L2 Lipase
Authors: Bukhari Noramirah , Leow Adam Thean Chor , Abd Rahman Raja Noor Zaliha Raja , Mohd Shariff Fairolniza
Published: July 2020

Rational design is widely employed in protein engineering to tailor wild-type enzymes for industrial applications. The typical target region for mutation is a functional region like the catalytic site to improve stability and activity. However, few have explored the role of other regions which, in principle, have no evident functionality such as the N-terminal region. In this study, stability prediction software was used to identify the critical point in the non-functional N-terminal region of L2 lipase and the effects of the substitution towards temperature stability and activity were determined. The results showed 3 mutant lipases: A8V, A8P and A8E with 29% better thermostability, 4 h increase in half-life and 6.6 °C higher thermal denaturation point, respectively. A8V showed 1.6-fold enhancement in activity compared to wild-type. To conclude, the improvement in temperature stability upon substitution showed that the N-terminal region plays a role in temperature stability and activity of L2 lipase.
Moonlighting Proteins in the Fuzzy Logic of Cellular Metabolism
Authors: Liu Haipeng , Jeffery Constance J.
Published: July 2020

The numerous interconnected biochemical pathways that make up the metabolism of a living cell comprise a fuzzy logic system because of its high level of complexity and our inability to fully understand, predict, and model the many activities, how they interact, and their regulation. Each cell contains thousands of proteins with changing levels of expression, levels of activity, and patterns of interactions. Adding more layers of complexity is the number of proteins that have multiple functions. Moonlighting proteins include a wide variety of proteins where two or more functions are performed by one polypeptide chain. In this article, we discuss examples of proteins with variable functions that contribute to the fuzziness of cellular metabolism.
Photoinduced Polymerization of Eugenol-Derived Methacrylates
Authors: Molina-Gutiérrez Samantha , Dalle Vacche Sara , Vitale Alessandra , Ladmiral Vincent , Caillol Sylvain , Bongiovanni Roberta , Lacroix-Desmazes Patrick
Published: July 2020

Biobased monomers have been used to replace their petroleum counterparts in the synthesis of polymers that are aimed at different applications. However, environmentally friendly polymerization processes are also essential to guarantee greener materials. Thus, photoinduced polymerization, which is low-energy consuming and solvent-free, rises as a suitable option. In this work, eugenol-, isoeugenol-, and dihydroeugenol-derived methacrylates are employed in radical photopolymerization to produce biobased polymers. The polymerization is monitored in the absence and presence of a photoinitiator and under air or protected from air, using Real-Time Fourier Transform Infrared Spectroscopy. The polymerization rate of the methacrylate double bonds was affected by the presence and reactivity of the allyl and propenyl groups in the eugenol- and isoeugenol-derived methacrylates, respectively. These groups are involved in radical addition, degradative chain transfer, and termination reactions, yielding crosslinked polymers. The materials, in the form of films, are characterized by differential scanning calorimetry, thermogravimetric, and contact angle analyses.
VAE-Sim: A Novel Molecular Similarity Measure Based on a Variational Autoencoder
Authors: Samanta Soumitra , O’Hagan Steve , Swainston Neil , Roberts Timothy J. , Kell Douglas B.
Published: July 2020

Molecular similarity is an elusive but core “unsupervised” cheminformatics concept, yet different “fingerprint” encodings of molecular structures return very different similarity values, even when using the same similarity metric. Each encoding may be of value when applied to other problems with objective or target functions, implying that a priori none are “better” than the others, nor than encoding-free metrics such as maximum common substructure (MCSS). We here introduce a novel approach to molecular similarity, in the form of a variational autoencoder (VAE). This learns the joint distribution p(z|x) where z is a latent vector and x are the (same) input/output data. It takes the form of a “bowtie”-shaped artificial neural network. In the middle is a “bottleneck layer” or latent vector in which inputs are transformed into, and represented as, a vector of numbers (encoding), with a reverse process (decoding) seeking to return the SMILES string that was the input. We train a VAE on over six million druglike molecules and natural products (including over one million in the final holdout set). The VAE vector distances provide a rapid and novel metric for molecular similarity that is both easily and rapidly calculated. We describe the method and its application to a typical similarity problem in cheminformatics.
Advances in Saponin Diversity of Panax ginseng
Authors: Piao Xiangmin , Zhang Hao , Kang Jong Pyo , Yang Dong Uk , Li Yali , Pang Shifeng , Jin Yinping , Yang Deok Chun , Wang Yingping
Published: July 2020

Ginsenosides are the major bioactive constituents of Panax ginseng, which have pharmacological effects. Although there are several reviews in regards to ginsenosides, new ginsenosides have been detected continually in recent years. This review updates the ginsenoside list from P. ginseng to 170 by the end of 2019, and aims to highlight the diversity of ginsenosides in multiple dimensions, including chemical structure, tissue spatial distribution, time, and isomeride. Protopanaxadiol, protopanaxatriol and C17 side-chain varied (C17SCV) manners are the major types of ginsenosides, and the constitute of ginsenosides varied significantly among different parts. Only 16 ginsenosides commonly exist in all parts of a ginseng plant. Protopanaxadiol-type ginsenoside is dominant in root, rhizome, leaf, stem, and fruit, whereas malonyl- and C17SCV-type ginsenosides occupy a greater proportion in the flower and flower bud compared with other parts. In respects of isomeride, there are 69 molecular formulas corresponding to 170 ginsenosides, and the median of isomers is 2. This is the first review on diversity of ginsenosides, providing information for reasonable utilization of whole ginseng plant, and the perspective on studying the physiological functions of ginsenoside for the ginseng plant itself is also proposed.