bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifactorial Rare Diseases: Can Uncertainty Analysis Bring Added Value to the Search for Risk Factors and Etiopathogenesis?
Authors: Taruscio Domenica , Mantovani Alberto
Published: January 2021

Uncertainty analysis is the process of identifying limitations in knowledge and evaluating their implications for scientific conclusions. Uncertainty analysis is a stable component of risk assessment and is increasingly used in decision making on complex health issues. Uncertainties should be identified in a structured way and prioritized according to their likely impact on the outcome of scientific conclusions. Uncertainty is inherent to the rare diseases (RD) area, where research and healthcare have to cope with knowledge gaps due to the rarity of the conditions; yet a systematic approach toward uncertainties is not usually undertaken. The uncertainty issue is particularly relevant to multifactorial RD, whose etiopathogenesis involves environmental factors and genetic predisposition. Three case studies are presented: the newly recognized acute multisystem inflammatory syndrome in children and adolescents associated with SARS-CoV-2 infection; the assessment of risk factors for neural tube defects; and the genotype–phenotype correlation in familial Mediterranean fever. Each case study proposes the initial identification of the main epistemic and sampling uncertainties and their impacts. Uncertainty analysis in RD may present aspects similar to those encountered when conducting risk assessment in data-poor scenarios; therefore, approaches such as expert knowledge elicitation may be considered. The RD community has a main strength in managing uncertainty, as it proactively develops stakeholder involvement, data sharing and open science. The open science approaches can be profitably integrated by structured uncertainty analysis, especially when dealing with multifactorial RD involving environmental and genetic risk factors.
Numerical Simulation of Wire Rod Cooling in Eutectoid Steel under Forced-Convection
Authors: López-Cornejo Monserrat Sofía , Vergara-Hernández Héctor Javier , Arreola-Villa Sixtos Antonio , Vázquez-Gómez Octavio , Herrejón-Escutia Martín
Published: January 2021

A coupled thermal-microstructural simulation model was developed to estimate the thermal history in a eutectoid steel wire rod under continuous cooling and forced-convection. The model coupled the phenomena of heat transfer, phase transformation and estimation of the cooling boundary condition. The thermal histories were analyzed at different cooling rates to emulate the forced-convection conditions by air-jet as in the controlled cooling conveyor. The thermal histories were acquired and used to calculate the forced-convection heat transfer coefficients through the solution of the Inverse Heat Conduction Problem, while the phase transformation was approximated with the Johnson–Mehl–Avrami–Kolmogorov (JMAK) kinetic model. From the heat transfer coefficients and the kinetic parameters, a user-defined function (UDF) was coded and employed in the ANSYS Fluent® software. The model results were compared and validated with the experimental histories, obtaining a good agreement between both responses, while the microstructural evolution of the pearlite was validated using Scanning Electron Microscopy (SEM) and Vickers microhardness. It was found that specimen diameter and air velocity are the main variables to modify the undercooling and therefore the pearlite interlamellar spacing.
Healthcare-Associated Legionella Disease: A Multi-Year Assessment of Exposure Settings in a National Healthcare System in the United States
Authors: Ambrose Meredith , Roselle Gary A. , Kralovic Stephen M. , Gamage Shantini D.
Published: January 2021

Healthcare facilities are high-risk environments for Legionella disease (LD), including Legionnaires’ disease, but transmission in these settings is often overlooked. We used the LD database at the U.S. Department of Veterans Affairs (VA) national healthcare system to assess the type of healthcare exposure for LD cases. Cases were extracted from the database for 1 September 2012 through 31 July 2019, focusing on cases with an overnight stay at a VA facility during the 10-day exposure window prior to symptom onset. Patient medical charts were reviewed for demographics and types of healthcare setting exposure(s). There were 99 LD cases in the cohort: 31.3% were classified as having definite VA exposure, 37.4% were classified as possible VA with inpatient exposure, and 31.3% were classified as possible VA with both inpatient and outpatient exposure. For definite VA LD cases, 67.7% had some type of exposure in the long-term care setting. While 63% of the 99 cases had exposure in the acute care setting only, both the long-term care and acute care settings contributed substantially to the total number of exposure days. A review of patient movement during the exposure period showed the variable and sometimes extensive use of the VA system, and it provides insights useful for epidemiologic investigations and potential preventive actions.
Methicillin-Resistant Staphylococcus epidermidis Lineages in the Nasal and Skin Microbiota of Patients Planned for Arthroplasty Surgery
Authors: Månsson Emeli , Tevell Staffan , Nilsdotter-Augustinsson Åsa , Johannesen Thor Bech , Sundqvist Martin , Stegger Marc , Söderquist Bo
Published: January 2021

Staphylococcus epidermidis, ubiquitous in the human nasal and skin microbiota, is a common causative microorganism in prosthetic joint infections (PJIs). A high proportion of PJI isolates have been shown to harbor genetic traits associated with resistance to/tolerance of agents used for antimicrobial prophylaxis in joint arthroplasties. These traits were found within multidrug-resistant S. epidermidis (MDRSE) lineages of multiple genetic backgrounds. In this study, the aim was to study whether MDRSE lineages previously associated with PJIs are present in the nasal and skin microbiota of patients planned for arthroplasty surgery but before hospitalization. We cultured samples from nares, inguinal creases, and skin over the hip or knee (dependent on the planned procedure) taken two weeks (median) prior to admittance to the hospital for total joint arthroplasty from 66 patients on agar plates selecting for methicillin resistance. S. epidermidis colonies were identified and tested for the presence of mecA. Methicillin-resistant S. epidermidis (MRSE) were characterized by Illumina-based whole-genome sequencing. Using this method, we found that 30/66 (45%) of patients were colonized with MRSE at 1–3 body sites. A subset of patients, 10/66 (15%), were colonized with MDRSE lineages associated with PJIs. The qacA gene was identified in MRSE isolates from 19/30 (63%) of MRSE colonized patients, whereas genes associated with aminoglycoside resistance were less common, found in 11/30 (37%). We found that MDRSE lineages previously associated with PJIs were present in a subset of patients’ pre-admission microbiota, plausibly in low relative abundance, and may be selected for by the current prophylaxis regimen comprising whole-body cleansing with chlorhexidine-gluconate containing soap. To further lower the rate of S. epidermidis PJIs, the current prophylaxis may need to be modified, but it is important for possible perioperative MDRSE transmission events and specific risk factors for MDRSE PJIs to be investigated before reevaluating antimicrobial prophylaxis.
Natural Products That Target the Arginase in Leishmania Parasites Hold Therapeutic Promise
Authors: Carter Nicola S. , Stamper Brendan D. , Elbarbry Fawzy , Nguyen Vince , Lopez Samuel , Kawasaki Yumena , Poormohamadian Reyhaneh , Roberts Sigrid C.
Published: January 2021

Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans worldwide. Because a vaccine is not available and the currently small number of existing drugs are less than ideal due to lack of specificity and emerging drug resistance, the need for new therapeutic strategies is urgent. Natural products and their derivatives are being used and explored as therapeutics and interest in developing such products as antileishmanials is high. The enzyme arginase, the first enzyme of the polyamine biosynthetic pathway in Leishmania, has emerged as a potential therapeutic target. The flavonols quercetin and fisetin, green tea flavanols such as catechin (C), epicatechin (EC), epicatechin gallate (ECG), and epigallocatechin-3-gallate (EGCG), and cinnamic acid derivates such as caffeic acid inhibit the leishmanial enzyme and modulate the host’s immune response toward parasite defense while showing little toxicity to the host. Quercetin, EGCG, gallic acid, caffeic acid, and rosmarinic acid have proven to be effective against Leishmania in rodent infectivity studies. Here, we review research on these natural products with a focus on their promise for the development of treatment strategies as well as unique structural and pharmacokinetic/pharmacodynamic features of the most promising agents.
Acknowledgment to Reviewers of Microorganisms in 2020
Authors:   Microorganisms Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Microorganisms maintains its standards for the high quality of its published papers [...]
Impacts of Low Temperature and Ensiling Period on the Bacterial Community of Oat Silage by SMRT
Authors: Li Xiaomei , Chen Fei , Wang Xuekai , Sun Lin , Guo Linna , Xiong Yi , Wang Yuan , Zhou Hongzhang , Jia Shangang , Yang Fuyu , Ni Kuikui
Published: January 2021

The objective of this study was to investigate how storage temperatures influence the bacterial community of oat silage during the ensiling process via PacBio single molecule, real-time sequencing technology (SMRT). Forage oat was ensiled at four different temperatures (5 °C, 10 °C, 15 °C, and 25 °C) and ensiling days (7, 14, 30, and 60 days). With the rise in storage temperature, the lactic acid content showed an increased trend. Acetic acid production was observed highest in silage fermented at 5 °C compared with other treatments, and Enterococcus mundtii was also the dominant bacterial species. Lactiplantibacillus pentosus and Loigolactobacillus rennini were exclusively detected in silages at 10 °C, 15 °C, and 25 °C, and dominated the fermentation after 60 days of ensiling at 10 °C and 25 °C, respectively. In addition, L. pentosus, L. rennini, and E. mundtii may be related to changes in the fermentation products due to the differences in ensiling temperature. In conclusion, results of this study improve our understanding of the complicated microbial composition underlying silage fermentation at low temperatures, which might contribute to target-based regulation methods for enhancing silage quality and developing new inoculants.
Citrobacter tructae sp. nov. Isolated from Kidney of Diseased Rainbow Trout (Oncorhynchus mykiss)
Authors: Jung Won Joon , Kim Hyoun Joong , Giri Sib Sankar , Kim Sang Guen , Kim Sang Wha , Kang Jeong Woo , Kwon Jun , Lee Sung Bin , Oh Woo Taek , Jun Jin Woo , Park Se Chang
Published: January 2021

A novel Citrobacter species was isolated from the kidney of diseased rainbow trout (Oncorhynchus mykiss) reared on a trout farm. Biochemical characterization and phylogenetic analysis were performed for bacterial identification. Sequencing of the 16S rRNA gene and five housekeeping genes indicated that the strain belongs to the Citrobacter genus. However, multilocus sequence analysis, a comparison of average nucleotide identity, and genome-to-genome distance values revealed that strain SNU WT2 is distinct and forms a separate clade from other Citrobacter species. Additionally, the phenotype characteristics of the strain differed from those of other Citrobacter species. Quinone analysis indicated that the predominant isoprenoid quinone is Q-10. Furthermore, strain virulence was determined by a rainbow trout challenge trial, and the strain showed resistance to diverse antibiotics including β-lactams, quinolone, and aminoglycosides. The complete genome of strain SNU WT2 is 4,840,504 bp with a DNA G + C content of 51.94% and 106,068-bp plasmid. Genome analysis revealed that the strain carries virulence factors on its chromosome and antibiotic resistance genes on its plasmid. This strain represents a novel species in the genus Citrobacter for which the name C. tructae has been proposed, with SNU WT2 (=KCTC 72517 = JCM 33612) as the type strain.
Low-Temperature Chlorite Geothermometry and Related Recent Analytical Advances: A Review
Authors: Bourdelle Franck
Published: January 2021

Chlorite, a 2:1:1 phyllosilicate, has all the required attributes to form the basis of a geothermometer: this mineral is ubiquitous in metamorphic, diagenetic, and hydrothermal systems with a broad field of stability and a chemical composition partly dependent on temperature (T) and pressure (P) conditions. These properties led to the development of a multitude of chlorite thermometers, ranging from those based on empirical calibrations (linking T to AlIV content) to thermodynamic or semi-empirical models (linking T to chlorite + quartz + water equilibrium constant). This present study provides an overview of these geothermometers proposed in the literature for low-temperature chlorite (T < 350 °C), specifying the advantages and limitations of each method. Recent analytical developments that allow for circumventing or responding to certain criticisms regarding the low-temperature application of thermometers are also presented. The emphasis is on micrometric and nanometric analysis, highlighting chemical intracrystalline zoning—which can be considered as evidence of a succession of local equilibria justifying a thermometric approach—and mapping ferric iron content. New perspectives in terms of analysis (e.g., Mn redox in Mn-chlorite) and geothermometer (molecular solid-solution model, oxychlorite end-member) are also addressed.
Nitrogen-Doped Carbons Derived from Imidazole-Based Cross-Linked Porous Organic Polymers
Authors: Kiciński Wojciech , Dyjak Sławomir
Published: January 2021

Nitrogen-doped and heteroatom multi-doped carbon materials are considered excellent metal-free catalysts, superior catalyst supports for transition metal particles and single metal atoms (single-atom catalysts), as well as efficient sorbents for gas- and liquid-phase substances. Acid-catalyzed sol–gel polycondensation of hydroxybenzenes with heterocyclic aldehydes yields cross-linked thermosetting resins in the form of porous organic polymers (i.e., organic gels). Depending on the utilized hydroxybenzene (e.g., phenol, resorcinol, phloroglucinol, etc.) and heterocyclic aldehyde variety of heteroatom-doped organic polymers can be produced. Upon pyrolysis, highly porous and heteroatom-doped carbons are obtained. Herein, polycondensation of phloroglucinol with imidazole-2-carboxaldehyde (and other, similar heterocyclic aldehydes with two heteroatoms in the aromatic ring) is utilized to obtain porous, N-doped organic and carbon gels with N-content of up to 16.5 and 12 wt.%, respectively. Utilization of a heterocyclic aldehyde with two different heteroatoms yields dually-doped carbon materials. Upon pyrolysis, the porous polymers yield ultramicroporous N-doped and N,S co-doped carbons with specific surface areas of up to 800 m2g−1. The influence of the initial composition of reactants and the pyrolysis temperature on the structure and chemical composition of the final doped organic and carbon materials is studied in detail.
Hepatoprotective Effect of Supercritical Carbon Dioxide Extracted Dabai Pulp Oil and Its Defatted Pulp
Authors: Kadir Noor Atiqah Aizan Abdul , Azlan Azrina , Abas Faridah , Ismail Intan Safinar
Published: January 2021

All food scientists must utilize plants for their application as functional foods to reduce hypercholesterolemia incidence through diet. Canarium odontophyllum (dabai) is a novel source for new healthy oil and functional foods. In this work, we evaluate the hepatoprotective effects of supercritical carbon dioxide (SC-CO2) extracted dabai pulp oil (DPO) and defatted dabai pulp (DDP) against hypercholesterolemia elicited by a high-cholesterol diet in rats. Our results show that DPO and DDP supplementation exerted beneficial hypocholesterolemic effects against the high-cholesterol diet-fed rat. Nevertheless, supplementation with DDP revealed superior total cholesterol, low-density lipoprotein, and HMG-CoA reductase lowering efficacy (p < 0.05). Supplementation of either DPO or DDP did not significantly affect AST and ALT levels than normal rats (p > 0.05). Therefore, DDP and DPO are considered as having no toxicological significance. The histological section of rats treated with DPO and DDP showed improved steatosis in hepatocytes. HPLC analysis revealed that DPO and DDP contained syringic acid, which plays an important role in the beneficial effect. In conclusion, our results support the hypocholesterolemic and hepatoprotective effects of DPO and DDP in the hypercholesterolemic rats model.
N-Acetylaspartyl-Glutamate Metabolism in the Cingulated Cortices as a Biomarker of the Etiology in ASD: A 1H-MRS Model
Authors: Jiménez-Espinoza Carmen , Marcano Serrano Francisco , González-Mora José Luis
Published: January 2021

As brain functional resonance magnetic studies show an aberrant trajectory of neurodevelopment, it is reasonable to predict that the degree of neurochemical abnormalities indexed by magnetic resonance spectroscopy (1H-MRS) might also change according to the developmental stages and brain regions in autism spectrum disorders (ASDs). Since specific N-Acetyl-aspartate (NAA) changes in children’s metabolism have been found in the anterior cingulate cortex (ACC) but not in the posterior cingulate cortex (PCC), we analyzed whether the metabolites of ASD youths change between the cingulate cortices using 1H-MRS. l-glutamate (Glu) and l-Acetyl-aspartate (NAA) are products from the N-Acetyl-aspartyl-glutamate (NAAG) metabolism in a reaction that requires the participation of neurons, oligodendrocytes, and astrocytes. This altered tri-cellular metabolism has been described in several neurological diseases, but not in ASD. Compared to the typical development (TD) group, the ASD group had an abnormal pattern of metabolites in the ACC, with a significant increase of glutamate (12.10 ± 3.92 mM; p = 0.02); additionally, N-Acetyl-aspartyl-glutamate significantly decreased (0.41 ± 0.27 mM; p = 0.02) within ASD metabolism abnormalities in the ACC, which may allow the development of new therapeutic possibilities.
A Review of Lignocellulosic-Derived Nanoparticles for Drug Delivery Applications: Lignin Nanoparticles, Xylan Nanoparticles, and Cellulose Nanocrystals
Authors: Wijaya Christian J. , Ismadji Suryadi , Gunawan Setiyo
Published: January 2021

Due to their biocompatibility, biodegradability, and non-toxicity, lignocellulosic-derived nanoparticles are very potential materials for drug carriers in drug delivery applications. There are three main lignocellulosic-derived nanoparticles discussed in this review. First, lignin nanoparticles (LNPs) are an amphiphilic nanoparticle which has versatile interactions toward hydrophilic or hydrophobic drugs. The synthesis methods of LNPs play an important role in this amphiphilic characteristic. Second, xylan nanoparticles (XNPs) are a hemicellulose-derived nanoparticle, where additional pretreatment is needed to obtain a high purity xylan before the synthesis of XNPs. This process is quite long and challenging, but XNPs have a lot of potential as a drug carrier due to their stronger interactions with various drugs. Third, cellulose nanocrystals (CNCs) are a widely exploited nanoparticle, especially in drug delivery applications. CNCs have low cytotoxicity, therefore they are suitable for use as a drug carrier. The research possibilities for these three nanoparticles are still wide and there is potential in drug delivery applications, especially for enhancing their characteristics with further surface modifications adjusted to the drugs.
Synthesis of Novel Tryptamine Derivatives and Their Biological Activity as Antitumor Agents
Authors: Simonetti Giorgia , Boga Carla , Durante Joseph , Micheletti Gabriele , Telese Dario , Caruana Paolo , Ghelli Luserna di Rorà Andrea , Mantellini Fabio , Bruno Samantha , Martinelli Giovanni , Calonghi Natalia
Published: January 2021

We synthesized five novel tryptamine derivatives characterized by the presence of an azelayl chain or of a 1,1,1-trichloroethyl group, in turn connected to another heterocyclic scaffold. The combination of tryptamin-, 1,1,1-trichloroethyl- and 2-aminopyrimidinyl- moieties produced compound 9 identified as the most active compound in hematological cancer cell lines (IC50 = 0.57–65.32 μM). Moreover, keeping constant the presence of the tryptaminic scaffold and binding it to the azelayl moiety, the compounds maintain biological activity. Compound 13 is still active against hematological cancer cell lines and shows a selective effect only on HT29 cells (IC50 = 0.006 µM) among solid tumor models. Compound 14 loses activity on all leukemic lines, while showing a high level of toxicity on all solid tumor lines tested (IC50 0.0015–0.469 µM).
Software-Assisted Pattern Recognition of Persistent Organic Pollutants in Contaminated Human and Animal Food
Authors: Guo Wenjing , Archer Jeffrey , Moore Morgan , Shojaee Sina , Zou Wen , Ge Weigong , Benjamin Linda , Adeuya Anthony , Fairchild Russell , Hong Huixiao
Published: January 2021

Persistent Organic Pollutants (POPs) are a serious food safety concern due to their persistence and toxic effects. To promote food safety and protect human health, it is important to understand the sources of POPs and how to minimize human exposure to these contaminants. The POPs Program within the U.S. Food and Drug Administration (FDA), manually evaluates congener patterns of POPs-contaminated samples and sometimes compares the finding to other previously analyzed samples with similar patterns. This manual comparison is time consuming and solely depends on human expertise. To improve the efficiency of this evaluation, we developed software to assist in identifying potential sources of POPs contamination by detecting similarities between the congener patterns of a contaminated sample and potential environmental source samples. Similarity scores were computed and used to rank potential source samples. The software has been tested on a diverse set of incurred samples by comparing results from the software with those from human experts. We demonstrated that the software provides results consistent with human expert observation. This software also provided the advantage of reliably evaluating an increased sample lot which increased overall efficiency.
Association between Non-Typhoidal Salmonella Infection and Growth in Children under 5 Years of Age: Analyzing Data from the Global Enteric Multicenter Study
Authors: Das Rina , Haque Md. Ahshanul , Chisti Mohammod Jobayer , Faruque Abu Sayed Golam , Ahmed Tahmeed
Published: January 2021

Non-typhoidal Salmonella (NTS) is one of the less focused on infections and is often associated with faulty child nutrition in the developing world. This study aimed to evaluate the association of NTS infection with growth faltering among children under the age of five. We analyzed data from 378 fecal NTS positive children with both moderate-to-severe diarrhea (MSD) and asymptomatic infection from the seven countries of South Asia and sub-Saharan Africa during enrolment and on day 60 follow up in the Global Enteric Multicenter Study (GEMS) for the period of December 2007 to March 2011. Children not associated with fecal NTS (n = 1134) were randomly selected from the same dataset (1:3 ratio) as a comparison group. The association between an explanatory variable and the outcome variable was longitudinally tested using generalized estimating equations (GEE), where the dependent variables were height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z-score, and the independent variable was the presence of fecal NTS. The GEE multivariable model identified a negative association between fecal NTS and WAZ (coefficient: −0.19; 95% CI (confidence interval): −0.33, −0.04, and p value = 0.010), WHZ (coef: −0.19; 95% CI: −0.34, −0.05, and p value = 0.007), and HAZ (coef: −0.13; 95% CI: −0.27, −0.01, and p value = 0.073) after adjusting for age, gender, diarrhea, breastfeeding status, mothers’ education, number of children under the age of five, household size by the number of people regularly sleep at the home, handwashing practice, source of drinking water, wealth index, presence of co-pathogens, comorbidity, and study sites. In the GEMS, where children were followed during 50–90 days of enrolment, the presence of fecal NTS harmed the child’s anthropometric outcomes. Minimizing potential exposure to NTS is needed to curb worsening child undernutrition.
The Role of Fetal, Infant, and Childhood Nutrition in the Timing of Sexual Maturation
Authors: Calcaterra Valeria , Cena Hellas , Regalbuto Corrado , Vinci Federica , Porri Debora , Verduci Elvira , Mameli Chiara , Zuccotti Gian Vincenzo
Published: January 2021

Puberty is a crucial developmental stage in the life span, necessary to achieve reproductive and somatic maturity. Timing of puberty is modulated by and responds to central neurotransmitters, hormones, and environmental factors leading to hypothalamic-pituitary-gonadal axis maturation. The connection between hormones and nutrition during critical periods of growth, like fetal life or infancy, is fundamental for metabolic adaptation response and pubertal development control and prediction. Since birth weight is an important indicator of growth estimation during fetal life, restricted prenatal growth, such as intrauterine growth restriction (IUGR) and small for gestational age (SGA), may impact endocrine system, affecting pubertal development. Successively, lactation along with early life optimal nutrition during infancy and childhood may be important in order to set up timing of sexual maturation and provide successful reproduction at a later time. Sexual maturation and healthy growth are also influenced by nutrition requirements and diet composition. Early nutritional surveillance and monitoring of pubertal development is recommended in all children, particularly in those at risk, such as the ones born SGA and/or IUGR, as well as in the case of sudden weight gain during infancy. Adequate macro and micronutrient intake is essential for healthy growth and sexual maturity.
Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study)
Authors: Cicolari Stefania , Pavanello Chiara , Olmastroni Elena , Puppo Marina Del , Bertolotti Marco , Mombelli Giuliana , Catapano Alberico L. , Calabresi Laura , Magni Paolo
Published: January 2021

Background: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25- and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. Methods: Subjects (n = 33; 18–70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130–200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. Results: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively); 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. Conclusions: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.
Analytical Performance Specifications for 25-Hydroxyvitamin D Examinations
Authors: Cavalier Etienne , Fraser Callum , Bhattoa Harjit , Heijboer Annemieke , Makris Konstantinos , Ulmer Candice , Vesper Hubert , Vasikaran Samuel , Lukas Pierre , Delanaye Pierre , Carobene Anna ,   on behalf of the IFCC-IOF Committee for Bone Metabolism
Published: January 2021

Currently the 25-hydroxy vitamin D (25(OH)D) concentration is thought to be the best estimate of the vitamin D status of an individual. Unfortunately, its measurement remains complex, despite recent technological advances. We evaluated the biological variation (BV) of 25(OH)D in order to set analytical performance specifications (APS) for measurement uncertainty (MU). Six European laboratories recruited 91 healthy participants. The 25(OH)D concentrations in K3-EDTA plasma were examined weekly for up to 10 weeks in duplicate on a Lumipulse G1200 (Fujirebio, Tokyo, Japan). The linear regression of the mean 25(OH)D concentrations at each blood collection showed that participants were not in a steady state. The dissection of the 10-sample collection into two subsets, namely collections 1–5 and 6–10, did not allow for correction of the lack of homogeneity: estimates of the within-subject BV ranged from 5.8% to 7.1% and the between-subject BV ranged from 25.0% to 39.2%. Methods that would differentiate a difference induced by 25(OH)D supplementation at p < 0.05 should have MU < 13.6%, while at p < 0.01, the MU should be <9.6%. The development of APS using BV assumes a steady state of patients. The findings in this study suggest that patients are not in steady state. Therefore, APS that are based on MU appear to be more appropriate.
The Relevance of IL-1-Signaling in the Protection against Gram-Positive Bacteria
Authors: Midiri Angelina , Mancuso Giuseppe , Beninati Concetta , Gerace Elisabetta , Biondo Carmelo
Published: January 2021

Previous studies performed using a model of group B streptococcus (GBS)-induced peritoneal inflammation indicate that the interleukin-1 receptor (IL-1R) family plays an important role in the innate host defense against this encapsulated Gram-positive bacteria. Since the role of IL-1-dependent signaling in peritoneal infections induced by other Gram-positive bacteria is unknown, in the present study we sought to investigate the contribution of IL-1R signaling in host defenses against Streptococcus pyogenes (group A streptococcus or GAS) or Staphylococcus aureus, two frequent and global human Gram-positive extracellular pathogens. We analyzed here the outcome of GAS or S. aureus infection in IL-1R-deficient mice. After inoculated intraperitoneal (i.p.) inoculation with group A Streptococcus or S. aureus, all the wild-type (WT) control mice survived the challenge, while, respectively, 63% or 50% of IL-1-defective mice died. Lethality was due to the ability of both bacterial species to replicate and disseminate to the target organs of IL-1R-deficient mice. Moreover, the experimental results indicate that IL-1 signaling promotes the production of leukocyte attractant chemokines CXCL-1 and CXCL-2 and recruitment of neutrophils to bacterial infection sites. Accordingly, the reduced neutrophil recruitment in IL-1R-deficient mice was linked with decreased production of neutrophil chemokines. Collectively, our findings indicate that IL-1 signaling, as previously showed in host defense against GBS, plays a fundamental role also in controlling the progression and outcome of GAS or S. aureus disease.
Development of a Hierarchical Support Vector Regression-Based In Silico Model for Caco-2 Permeability
Authors: Ta Giang Huong , Jhang Cin-Syong , Weng Ching-Feng , Leong Max K.
Published: January 2021

Drug absorption is one of the critical factors that should be taken into account in the process of drug discovery and development. The human colon carcinoma cell layer (Caco-2) model has been frequently used as a surrogate to preliminarily investigate the intestinal absorption. In this study, a quantitative structure–activity relationship (QSAR) model was generated using the innovative machine learning-based hierarchical support vector regression (HSVR) scheme to depict the exceedingly confounding passive diffusion and transporter-mediated active transport. The HSVR model displayed good agreement with the experimental values of the training samples, test samples, and outlier samples. The predictivity of HSVR was further validated by a mock test and verified by various stringent statistical criteria. Consequently, this HSVR model can be employed to forecast the Caco-2 permeability to assist drug discovery and development.
Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization
Authors: Ghanem Heba A. , Nasr Ali M. , Hassan Tamer H. , Elkhoudary Mahmoud M. , Alshaman Reem , Alattar Abdullah , Gad Shadeed
Published: January 2021

The aim of the current study is to establish a comprehensive experimental design for the screening and optimization of Atorvastatin-loaded nanostructured lipid carriers (AT-NLCs). Initially, combined D-optimal screening design was applied to find the most significant factors affecting AT-NLCs properties. The studied variables included mixtures of solid and liquid lipids, the solid/liquid lipid ratio, surfactant type and concentration, homogenization speed as well as sonication time. Then, the variables homogenization speed (A), the ratio of solid lipid/liquid lipid (B), and concentration of the surfactant (C) were optimized using a central composite design. Particle size, polydispersity index, zeta potential, and entrapment efficiency were chosen as dependent responses. The optimized AT-NLCs demonstrated a nanometric size (83.80 ± 1.13 nm), Polydispersity Index (0.38 ± 0.02), surface charge (−29.65 ± 0.65 mV), and high drug incorporation (93.1 ± 0.04%). Fourier Transform Infrared Spectroscopy (FTIR) analysis showed no chemical interaction between Atorvastatin and the lipid mixture. Differential Scanning Calorimetry (DSC) analysis of the AT-NLCs suggested the transformation of Atorvastatin crystal into an amorphous state. Administration of the optimized AT-NLCs led to a significant reduction (p < 0.001) in serum levels of rats’ total cholesterol, triglycerides, and low-density lipoproteins. This change was histologically validated by reducing the relevant steatosis of the liver.
Scattering on Quasi-Spherical Black-Holes: Features and Beyond
Authors: Arslanaliev Adam M. , Nurmagambetov Alexei J.
Published: January 2021

Recent developments in the gravitational waves interferometry require more pertinent theoretical models of gravitational waves generation and propagation. Untouched possible mechanisms of spin-2 spacetime perturbations production, we will consider their subsequent scattering on other black holes (BHs). Specifically, we consider a generalization of the Regge-Wheeler-Zerilli equations for the case of distorted BHs (BHs surrounded with matter) in Minkowski and Anti-de Sitter spacetimes, the metric potential of which obeys the Liouville equation. We establish significant differences in scattering characteristics of waves of different spins and angular momenta, including the gravitational waves, caused by losing the spherical symmetry of their propagation background. In particular, we demonstrate the strong impact of the background geometry deformation on the grey-body factors, hence on the absorption cross-sections of scattering waves, and explore the issue of stability of the background geometry upon changing the deformation degree parameters.
Antibacterial and Antifungal Activity of the Extracts of Different Parts of Avicennia marina (Forssk.) Vierh
Authors: Okla Mohammad K. , Alatar Abdulrahman A. , Al-amri Saud S. , Soufan Walid H. , Ahmad Altaf , Abdel-Maksoud Mostafa A.
Published: January 2021

Increased problems associated with side effects and bacterial resistance of chemical drugs has prompted the research focus on herbal medicines in the past few decades. In the present investigation, the antimicrobial activity of the various parts of Avicennia marina (AM), a mangrove plant, has been evaluated. The plants were collected from the Jazan area of the Kingdom of Saudi Arabia. Primary extracts of roots, stem, leaves, fruits, and seeds were made in ethanol and fractioned in ethanol, ethyl acetate, petroleum ether, chloroform, and water. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the extracts were determined against Bacillussubtilis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. It has been observed that the chloroform extract of roots of the AM exhibited inhibitory effects against both S. aureus (MIC = 1.5 ± 0.03 mg/mL) and E. coli (MIC = 1.7 ± 0.01 mg/mL). The ethanolic extract of the AM roots has shown antibacterial activity against Pseudomonas aeruginosa (MIC = 10.8 ± 0.78 mg/mL), Bacillussubtilis (MIC = 6.1 ± 0.27 mg/mL), Staphylococcus aureus (MIC = 2.3 ± 0.08 mg/mL), and Escherichia coli (MIC = 6.3 ± 0.28 mg/mL). The leaf extract of the AM in ethyl acetate showed antibacterial activity against S. aureus and E. coli. Antifungal activity of these extracts was also investigated against Aspergillus fumigatus and Candida albicans. Ethanolic extract of roots and seeds of the AM has shown antifungal activity against Aspergillus fumigatus when applied individually. Ethanolic extract of the AM fruits has shown an inhibitory effect on the growth of Aspergillus fumigatus and Candida albicans. It is suggested that the plant extracts of AM have tremendous antimicrobial activity against a group of microbes, and this effect depends on both the plant part and the solvent used for extraction. Therefore, this plant can be considered to treat various diseases caused by antibiotic-resistant bacteria.
Advances in Waterborne Polyurethane and Polyurethane-Urea Dispersions and Their Eco-friendly Derivatives: A Review
Authors: Santamaria-Echart Arantzazu , Fernandes Isabel , Barreiro Filomena , Corcuera Maria Angeles , Eceiza Arantxa
Published: January 2021

Polyurethanes and polyurethane-ureas, particularly their water-based dispersions, have gained relevance as an extremely versatile area based on environmentally friendly approaches. The evolution of their synthesis methods, and the nature of the reactants (or compounds involved in the process) towards increasingly sustainable pathways, has positioned these dispersions as a relevant and essential product for diverse application frameworks. Therefore, in this work, it is intended to show the progress in the field of polyurethane and polyurethane-urea dispersions over decades, since their initial synthesis approaches. Thus, the review covers from the basic concepts of polyurethane chemistry to the evolution of the dispersion’s preparation strategies. Moreover, an analysis of the recent trends of using renewable reactants and enhanced green strategies, including the current legislation, directed to limit the toxicity and potentiate the sustainability of dispersions, is described. The review also highlights the strengths of the dispersions added with diverse renewable additives, namely, cellulose, starch or chitosan, providing some noteworthy results. Similarly, dispersion’s potential to be processed by diverse methods is shown, evidencing, with different examples, their suitability in a variety of scenarios, outstanding their versatility even for high requirement applications.
In-Situ Iodine Doping Characteristics of Conductive Polyaniline Film Polymerized by Low-Voltage-Driven Atmospheric Pressure Plasma
Authors: Kim Jae Yong , Iqbal Shahzad , Jang Hyo Jun , Jung Eun Young , Bae Gyu Tae , Park Choon-Sang , Tae Heung-Sik
Published: January 2021

In-situ iodine (I2)-doped atmospheric pressure (AP) plasma polymerization is proposed, based on a newly designed AP plasma reactor with a single wire electrode that enables low-voltage-driven plasma polymerization. The proposed AP plasma reactor can proceed plasma polymerization at low voltage levels, thereby enabling an effective in-situ I2 doping process by maintaining a stable glow discharge state even if the applied voltage increases due to the use of a discharge gas containing a large amount of monomer vapors and doping materials. The results of field-emission scanning electron microscopy (FE-SEM) and Fourier transformation infrared spectroscopy (FT-IR) show that the polyaniline (PANI) films are successfully deposited on the silicon (Si) substrates, and that the crosslinking pattern of the synthesized nanoparticles is predominantly vertically aligned. In addition, the in-situ I2-doped PANI film fabricated by the proposed AP plasma reactor exhibits excellent electrical resistance without electrical aging behavior. The developed AP plasma reactor proposed in this study is more advantageous for the polymerization and in-situ I2 doping of conductive polymer films than the existing AP plasma reactor with a dielectric barrier.
Techno-Economic Analysis of Automated iPSC Production
Authors: Nießing Bastian , Kiesel Raphael , Herbst Laura , Schmitt Robert H.
Published: January 2021

Induced pluripotent stem cells (iPSC) open up the unique perspective of manufacturing cell products for drug development and regenerative medicine in tissue-, disease- and patient-specific forms. iPSC can be multiplied almost without restriction and differentiated into cell types of all organs. The basis for clinical use of iPSC is a high number of cells (approximately 7 × 107 cells per treatment), which must be produced cost-effectively while maintaining reproducible and high quality. Compared to manual cell production, the automation of cell production offers a unique chance of reliable reproducibility of cells in addition to cost reduction and increased throughput. StemCellFactory is a prototype for a fully automated production of iPSC. However, in addition to the already tested functionality of the system, it must be shown that this automation brings necessary economic advantages. This paper presents that fully automated stem cell production offers economic advantages in addition to increased throughput and better quality. First, biological and technological basics for a fully automated production of iPSC are presented. Second, the basics for profitability calculation are presented. Third, profitability of both manual and automated production are calculated. Finally, different scenarios effecting the profitability of manual and automated production are compared.
A Mini Review on Antiwetting Studies in Membrane Distillation for Textile Wastewater Treatment
Authors: Yang Guang , Zhang Jianhua , Peng Mingguo , Du Erdeng , Wang Yong , Shan Guocheng , Ling Ling , Ding Hui , Gray Stephen , Xie Zongli
Published: January 2021

The textile industry is an important contributor to the growth of the global economy. However, a huge quantity of wastewater is generated as a by-product during textile manufacturing, which hinders the ongoing development of textile industry in terms of environmental sustainability. Membrane distillation (MD), which is driven by thermal-induced vapor pressure difference, is being considered as an emerging economically viable technology to treat the textile wastewater for water reuse. So far, massive efforts have been put into new membrane material developments and modifications of the membrane surface. However, membrane wetting, direct feed solution transport through membrane pores leading to the failure of separation, remains as one of the main challenges for the success and potential commercialization of this separation process as textile wastewater contains membrane wetting inducing surfactants. Herein, this review presents current progress on the MD process for textile wastewater treatment with particular focuses on the fundamentals of membrane wetting, types of membranes applied as well as the fabrication or modification of membranes for anti-wetting properties. This article aims at providing insights in membrane design to enhance the MD separation performance towards commercial application of textile wastewater treatment.
Acknowledgment to Reviewers of Reproductive Medicine in 2020
Authors:   Reprod. Med. Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Reproductive Medicine maintains its standards for the high quality of its published papers [...]
Window-Based Morphometric Indices as Predictive Variables for Landslide Susceptibility Models
Authors: Barbosa Natalie , Andreani Louis , Gloaguen Richard , Ratschbacher Lothar
Published: January 2021

The identification of areas that are prone to landslides is essential in mitigating associated risks. This is usually achieved using landslide susceptibility models, which estimate landslide likelihood given local terrain conditions and the location of known past events. Detailed databases covering different conditioning factors are paramount in producing reliable susceptibility maps. However, thematic data from developing countries are scarce. As a result, susceptibility models often rely on morphometric parameters that are derived from widely-available digital elevation models. In most cases, simple parameters, such as slope, aspect, and curvature, computed using a moving window of 3 × 3 pixels, are used. Recently, the use of window-based morphometric indices as an additional input has increased. These rely on a user-defined observation window size. In this contribution, we examine the influence of observation window size when using window-based morphometric indices as core predictive variables for landslide susceptibility assessment. We computed a variety of models that include morphometric indices that are calculated with different window sizes, and compared the predictive capabilities and reliability of the resulting predictions. All of the models are based on the random forest algorithm. The results improved significantly when each window-based morphometric index was calculated with a different and meaningful observation window (AUC-ROC of 0.89 and AUC-PR of 0.87). The sensitivity analysis highlights both the highly-informative observation windows and the impact of their selection on the model performance. We also stress the importance of evaluating landslide susceptibility results while using different adapted metrics for predictive performance and reliability.