bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of immune, microbiota and metabolome maturation in infants in a clinical trial of Lactobacillus paracasei CBA L74-fermented formula
Authors: Roggero Paola , Liotto Nadia , Pozzi Chiara , Braga Daniele , Troisi Jacopo , Menis Camilla , Giannì Maria Lorella , Berni Canani Roberto , Paparo Lorella , Nocerino Rita , Budelli Andrea , Mosca Fabio , Rescigno Maria
Published: June 2020

Mother’s milk is the best choice for infants nutrition, however when it is not available or insufficient to satisfy the needs of the infant, formula is proposed as an effective substitute. Here, we report the results of a randomized controlled clinical trial (NCT03637894) designed to evaluate the effects of two different dietary regimens (standard formula and Lactobacillus paracasei CBA L74-fermented formula) versus breastfeeding (reference group) on immune defense mechanisms (primary endpoint: secretory IgA, antimicrobial peptides), the microbiota and its metabolome (secondary outcomes), in healthy full term infants according to the type of delivery (n = 13/group). We show that the fermented formula, safe and well tolerated, induces an increase in secretory IgA (but not in antimicrobial peptides) and reduces the diversity of the microbiota, similarly, but not as much as, breastmilk. Metabolome analysis allowed us to distinguish subjects based on their dietary regimen and mode of delivery. Together, these results suggest that a fermented formula favors the maturation of the immune system, microbiota and metabolome.
Massively parallel reporter assays of melanoma risk variants identify MX2 as a gene promoting melanoma
Authors: Choi Jiyeon , Zhang Tongwu , Vu Andrew , Ablain Julien , Makowski Matthew M. , Colli Leandro M. , Xu Mai , Hennessey Rebecca C. , Yin Jinhu , Rothschild Harriet , Gräwe Cathrin , Kovacs Michael A. , Funderburk Karen M. , Brossard Myriam , Taylor John , Pasaniuc Bogdan , Chari Raj , Chanock Stephen J. , Hoggart Clive J. , Demenais Florence , Barrett Jennifer H. , Law Matthew H. , Iles Mark M. , Yu Kai , Vermeulen Michiel , Zon Leonard I. , Brown Kevin M.
Published: June 2020

Genome-wide association studies (GWAS) have identified ~20 melanoma susceptibility loci, most of which are not functionally characterized. Here we report an approach integrating massively-parallel reporter assays (MPRA) with cell-type-specific epigenome and expression quantitative trait loci (eQTL) to identify susceptibility genes/variants from multiple GWAS loci. From 832 high-LD variants, we identify 39 candidate functional variants from 14 loci displaying allelic transcriptional activity, a subset of which corroborates four colocalizing melanocytecis-eQTL genes. Among these, we further characterize the locus encompassing the HIV-1 restriction gene,MX2(Chr21q22.3), and validate a functional intronic variant, rs398206. rs398206 mediates the binding of the transcription factor, YY1, to increaseMX2levels, consistent with thecis-eQTL ofMX2in primary human melanocytes. Melanocyte-specific expression of humanMX2in a zebrafish model demonstrates accelerated melanoma formation in aBRAFV600Ebackground. Our integrative approach streamlines GWAS follow-up studies and highlights a pleiotropic function ofMX2in melanoma susceptibility.
Ultrahigh high-strain-rate superplasticity in a nanostructured high-entropy alloy
Authors: Nguyen Nhung Thi-Cam , Asghari-Rad Peyman , Sathiyamoorthi Praveen , Zargaran Alireza , Lee Chong Soo , Kim Hyoung Seop
Published: June 2020

Superplasticity describes a material’s ability to sustain large plastic deformation in the form of a tensile elongation to over 400% of its original length, but is generally observed only at a low strain rate (~10−4 s−1), which results in long processing times that are economically undesirable for mass production. Superplasticity at high strain rates in excess of 10−2 s−1, required for viable industry-scale application, has usually only been achieved in low-strength aluminium and magnesium alloys. Here, we present a superplastic elongation to 2000% of the original length at a high strain rate of 5 × 10−2 s−1 in an Al9(CoCrFeMnNi)91 (at%) high-entropy alloy nanostructured using high-pressure torsion. The high-pressure torsion induced grain refinement in the multi-phase alloy combined with limited grain growth during hot plastic deformation enables high strain rate superplasticity through grain boundary sliding accommodated by dislocation activity.
Automated high-throughput Wannierisation
Authors: Vitale Valerio , Pizzi Giovanni , Marrazzo Antimo , Yates Jonathan R. , Marzari Nicola , Mostofi Arash A.
Published: June 2020

Maximally-localised Wannier functions (MLWFs) are routinely used to compute from first-principles advanced materials properties that require very dense Brillouin zone integration and to build accurate tight-binding models for scale-bridging simulations. At the same time, high-throughput (HT) computational materials design is an emergent field that promises to accelerate reliable and cost-effective design and optimisation of new materials with target properties. The use of MLWFs in HT workflows has been hampered by the fact that generating MLWFs automatically and robustly without any user intervention and for arbitrary materials is, in general, very challenging. We address this problem directly by proposing a procedure for automatically generating MLWFs for HT frameworks. Our approach is based on the selected columns of the density matrix method and we present the details of its implementation in an AiiDA workflow. We apply our approach to a dataset of 200 bulk crystalline materials that span a wide structural and chemical space. We assess the quality of our MLWFs in terms of the accuracy of the band-structure interpolation that they provide as compared to the band-structure obtained via full first-principles calculations. Finally, we provide a downloadable virtual machine that can be used to reproduce the results of this paper, including all first-principles and atomistic simulations as well as the computational workflows.
Role of atomic-scale thermal fluctuations in the coercivity
Authors: Toga Yuta , Miyashita Seiji , Sakuma Akimasa , Miyake Takashi
Published: June 2020

The microscopic mechanism of coercivity at finite temperature is a crucial issue for permanent magnets. Here we present the temperature dependence of the coercivity of an atomistic spin model for the highest-performance magnet Nd2Fe14B. For quantitative analysis of the magnetization reversal with thermal fluctuations, we focus on the free energy landscape as a function of the magnetization. The free energy is calculated by the replica-exchange Wang–Landau method. This approach allows us to address a slow nucleation problem, i.e., thermal activation effects, in the magnetization reversal. We concretely observed that the thermal fluctuations lead to a downward convexity in the coercivity concerning the temperature. Additionally, through analyzing the microscopic process of the thermal activation (nucleation), we discover the activation volume is insensitive to a magnetic field around the coercivity. The insensitivity explains the linear reduction of the free energy barrier by the magnetic field in the nucleation process.
Author Correction: Manifold learning of four-dimensional scanning transmission electron microscopy
Authors: Li Xin , Dyck Ondrej E. , Oxley Mark P. , Lupini Andrew R. , McInnes Leland , Healy John , Jesse Stephen , Kalinin Sergei V.
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma
Authors: Hong Christopher S. , Vasquez Juan C. , Kundishora Adam J. , Elsamadicy Aladine A. , Beckta Jason M. , Sule Amrita , Marks Asher M. , Leelatian Nalin , Huttner Anita , Bindra Ranjit S. , DiLuna Michael L. , Kahle Kristopher T. , Erson-Omay E. Zeynep
Published: June 2020

Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious STAG2 mutation, whose deficiency in preclinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an EGFR mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently STAG2 mutated clone, with rare mutations in PTPN11 and BRAF, the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the known underlying STAG2 deficiency. As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for STAG2 mutations in gliomagenesis and resistance to standard therapies.
Feasibility, potency, and safety of growing human mesenchymal stem cells in space for clinical application
Authors: Huang Peng , Russell Athena L. , Lefavor Rebecca , Durand Nisha C. , James Elle , Harvey Larry , Zhang Cuiping , Countryman Stefanie , Stodieck Louis , Zubair Abba C.
Published: June 2020

Growing stem cells on Earth is very challenging and limited to a few population doublings. The standard two-dimensional (2D) culture environment is an unnatural condition for cell growth. Therefore, culturing stem cells aboard the International Space Station (ISS) under a microgravity environment may provide a more natural three-dimensional environment for stem cell expansion and organ development. In this study, human-derived mesenchymal stem cells (MSCs) grown in space were evaluated to determine their potential use for future clinical applications on Earth and during long-term spaceflight. MSCs were flown in Plate Habitats for transportation to the ISS. The MSCs were imaged every 24–48 h and harvested at 7 and 14 days. Conditioned media samples were frozen at −80 °C and cells were either cryopreserved in 5% dimethyl sulfoxide, RNAprotect, or paraformaldehyde. After return to Earth, MSCs were characterized to establish their identity and cell cycle status. In addition, cell proliferation, differentiation, cytokines, and growth factors’ secretion were assessed. To evaluate the risk of malignant transformation, the space-grown MSCs were subjected to chromosomal, DNA damage, and tumorigenicity assays. We found that microgravity had significant impact on the MSC capacity to secrete cytokines and growth factors. They appeared to be more potent in terms of immunosuppressive capacity compared to their identical ground control. Chromosomal, DNA damage, and tumorigenicity assays showed no evidence of malignant transformation. Therefore, it is feasible and potentially safe to grow MSCs aboard the ISS for potential future clinical applications.
Structure and magnetic properties of epitaxial CaFe2O4 thin films
Authors: Damerio Silvia , Nukala Pavan , Juraszek Jean , Reith Pim , Hilgenkamp Hans , Noheda Beatriz
Published: June 2020

CaFe2O4 is a highly anisotropic antiferromagnet reported to display two spin arrangements with up–up–down–down (phase A) and up–down–up–down (phase B) configurations. The relative stability of these phases is ruled by the competing ferromagnetic and antiferromagnetic interactions between Fe3+ spins arranged in two different environments, but a complete understanding of the magnetic structure of this material does not exist yet. In this study, we investigate epitaxial CaFe2O4 thin films grown on TiO2 (110) substrates by means of pulsed laser deposition (PLD). Structural characterization reveals the coexistence of two out-of-plane crystal orientations and the formation of three in-plane oriented domains. The magnetic properties of the films, investigated macroscopically as well as locally, including highly sensitive Mössbauer spectroscopy, reveal the presence of just one order parameter showing long-range ordering below T = 185 K and the critical nature of the transition. In addition, a non-zero in-plane magnetization is found, consistent with the presence of uncompensated spins at phase or domain boundaries, as proposed for bulk samples.
A critical review of the application of electromagnetic fields for scaling control in water systems: mechanisms, characterization, and operation
Authors: Lin Lu , Jiang Wenbin , Xu Xuesong , Xu Pei
Published: June 2020

Scale deposits in water systems often result in ample technical and economic problems. Conventional chemical treatments for scale control are expensive and may cause health concerns and ecological implications. Non-chemical water treatment technologies such as electromagnetic field (EMF) are attractive options so the use of scale inhibitors, anti-scalants, or other chemical involved processes can be avoided or minimized. Although there are demonstrated beneficial effects of EMF on scale control, the scientific basis for its purported effectiveness is not clear in the available literature, especially lack of quantitative assessment and systematic evaluation of the effectiveness of EMF technologies. This review aims to elucidate the factors pertaining to EMF water treatment and their anti-scaling effects. We have critically reviewed relevant literature on EMF scale control, in particular recent studies, in various water systems, including desalination membranes, heat exchangers (e.g., cooling towers), water pipes, and bulk solutions. We systematically studied the impacts of operational conditions on EMF efficacy, and quantitatively evaluated the EMF improvement on scaling control. The scaling prevention mechanisms, conventional and cutting-edge characterization methods, and potential real-time monitoring techniques are summarized and discussed. The economic benefits of EMF treatment in terms of chemicals, operation and maintenance costs are highlighted. This review provides guidelines for future EMF system design and points out the research needed to further enhance EMF treatment performance.
Long-term population monitoring of a territorial forest raptor species
Authors: Jiménez-Franco María V. , Martínez José E. , Pagán Iluminada , Calvo José F.
Published: June 2020

We provide field monitoring data of a territorial raptor (the booted eagle,Hieraaetus pennatus), that was intensively monitored over a period of 18 years (1998–2015) in a Mediterranean forested area of south-eastern Spain designated as a Special Protection Area (Natura 2000 Network) for this species. The data set compiles all the relevant information about the occupation of territories and nests, reproductive ecology, long-term monitoring of marked individuals and influence of parent’s colour morph on brood size. Several questions concerning the population ecology of forest-dwelling raptors and factors conditioning territorial occupancy, such as location cues or site fidelity, are addressed. This type of long-term population monitoring has high potential for replication, reuse and comparison purposes, providing insights for monitoring other long-lived, territorial species.
Pringle Maneuver in Extended Liver Resection: A propensity score analysis
Authors: Al-Saeedi Mohammed , Ghamarnejad Omid , Khajeh Elias , Shafiei Saeed , Salehpour Roozbeh , Golriz Mohammad , Mieth Markus , Weiss Karl Heinz , Longerich Thomas , Hoffmann Katrin , Büchler Markus W. , Mehrabi Arianeb
Published: June 2020

Despite the ongoing decades-long controversy, Pringle maneuver (PM) is still frequently used by hepatobiliary surgeons during hepatectomy. The aim of this study was to investigate the effect of PM on intraoperative blood loss, morbidity, and posthepatectomy hemorrhage (PHH). A series of 209 consecutive patients underwent extended hepatectomy (EH) (≥5 segment resection). The association of PM with perioperative outcomes was evaluated using multivariate analysis with a propensity score method to control for confounding. Fifty patients underwent PM with a median duration of 19 minutes. Multivariate analysis revealed that risk of excessive intraoperative bleeding (≥1500 ml; odds ratio [OR] 0.27, 95%-confidence interval [CI] 0.10–0.70, p = 0.007), major morbidity (OR 0.41, 95%-CI 0.18–0.97, p = 0.041), and PHH (OR 0.22, 95%-CI 0.06–0.79, p = 0.021) were significantly lower in PM group after EH. Furthermore, there was no significant difference in 3-year recurrence-free-survival between groups. PM is associated with lower intraoperative bleeding, PHH, and major morbidity risk after EH. Performing PM does not increase posthepatectomy liver failure and does not affect recurrence rate. Therefore, PM seems to be justified in EH.
Targeting TRAF3IP2, Compared to Rab27, is More Effective in Suppressing the Development and Metastasis of Breast Cancer
Authors: Alt Eckhard U. , Wörner Philipp M. , Pfnür Andreas , Ochoa Joana E. , Schächtele Deborah J. , Barabadi Zahra , Lang Lea M. , Srivastav Sudesh , Burow Matthew E. , Chandrasekar Bysani , Izadpanah Reza
Published: June 2020

Here we investigated the roles of Rab27a, a player in exosome release, and TRAF3IP2, an inflammatory mediator, in development and metastasis of breast cancer (BC) in vivo. Knockdown (KD) of Rab27a (MDAKDRab27a) or TRAF3IP2 (MDAKDTRAF3IP2) in triple negative MDA-MB231 cells reduced tumor growth by 70–97% compared to wild-type tumors (MDAw). While metastasis was detected in MDAw-injected animals, none was detected in MDAKDRab27a- or MDAKDTRAF3IP2-injected animals. Interestingly, micrometastasis was detected only in the MDAKDRab27a-injected group. In addition to inhibiting tumor growth and metastasis, silencing TRAF3IP2 disrupted inter-cellular inflammatory mediator-mediated communication with mesenchymal stem cells (MSCs) injected into contralateral mammary gland, evidenced by the lack of tumor growth at MSC-injected site. Of translational significance, treatment of pre-formed MDAw-tumors with a lentiviral-TRAF3IP2-shRNA not only regressed their size, but also prevented metastasis. These results demonstrate that while silencing Rab27a and TRAF3IP2 each inhibited tumor growth and metastasis, silencing TRAF3IP2 is more effective; targeting TRAF3IP2 inhibited tumor formation, regressed preformed tumors, and prevented both macro- and micrometastasis. Silencing TRAF3IP2 also blocked interaction between tumor cells and MSCs injected into the contralateral gland, as evidenced by the lack of tumor formation on MSCs injected site. These results identify TRAF3IP2 as a novel therapeutic target in BC.
Ultra-stable Mn1-xNixCO3 nano/sub-microspheres positive electrodes for high-performance solid-state asymmetric supercapacitors
Authors: Alagar Srinivasan , Madhuvilakku Rajesh , Mariappan Ramalakshmi , Karuppiah Chelladurai , Yang Chun-Chen , Piraman Shakkthivel
Published: June 2020

Long–term cycling performance of electrodes for application in supercapcitor has received large research interest in recent years. Ultra-stable Mn1-xNixCO3 (x-0, 0.20, 0.25 and 0.30) nano/sub-microspheres were synthesized via simple co-precipitation method and the Mn1-xNixCO3 was confirmed by XRD, FT-IR, XPS and their morphology was studied by SEM and TEM analysis. Among the various Mn1-xNixCO3 electrodes, the Mn0.75Ni0.25CO3 electrode exhibited the higher specific capacitance (364 F g−1 at 1 A g−1) with capacity retention of 96% after 7500 cycles at 5 A g−1. Moreover, the assembled solid-state asymmetric supercapacitor based on Mn0.75Ni0.25CO3//graphene nanosheets performed a high specific capacity of 46 F g−1 and energy density of 25 Wh kg−1 at a power density of 499 W kg−1 along with high capacity retention of 87.7% after 7500 cycles. The improved electrochemical performances are mainly owing to the intrinsic conductivity and electrochemical activity of MnCO3 after Mn1-xNixCO3 (x-0.20, 0.25 and 0.30) with appropriate Ni concentration. This study highlights the potentiality of the Mn0.75Ni0.25CO3//GNS asymmetric supercapacitor device for promising energy storage applications.
Gut metabolites and inflammation factors in non-alcoholic fatty liver disease: A systematic review and meta-analysis
Authors: Pan Xiongfeng , Wen Shi Wu , Kaminga Atipatsa C. , Liu Aizhong
Published: June 2020

The interaction of gut microbiota, related metabolites and inflammation factors with nonalcoholic fatty liver disease (NAFLD) remains unclearly defined. The aim of this systematic review and meta-analysis was to synthesize previous study findings to better understand this interaction. Relevant research articles published not later than September, 2019 were searched in the following databases: Web of Science, PubMed, Embase, and Cochrane Library. The search strategy and inclusion criteria for this study yielded a total of 47 studies, of which only 11 were eligible for meta-analysis. The narrative analysis of these articles found that there is interplay between the key gut microbiota, related metabolites and inflammation factors, which modulate the development and progression of NAFLD. In addition, the results of meta-analysis showed that probiotic supplementation significantly decreased tumor necrosis factor-α (TNF-α) in NAFLD patients (standardized mean difference (SMD) = −0.52, confidence interval (CI): −0.86 to −0.18, andp = 0.003) and C-reactive protein (CRP) (SMD = −0.62, CI: −0.80 to −0.43, andp < 0.001). However, whether therapies can target TNF-α and CRP in order treat NAFLD still needs further investigation. Therefore, these results suggest that the interaction of the key gut microbiota, related metabolites and inflammation factors with NAFLD may provide a novel therapeutic target for the clinical and pharmacological treatment of NAFLD.
Green analytical method for the simultaneous analysis of cytochrome P450 probe substrates by poly(N-isopropylacrylamide)-based temperature-responsive chromatography
Authors: Maekawa Yutaro , Okamoto Naoya , Okada Yuji , Nagase Kenichi , Kanazawa Hideko
Published: June 2020

High-performance liquid chromatography (HPLC) is the most common analytical method practiced in various fields and used for analysis of almost all drug compounds in the pharmaceutical industries. During drug development, an evaluation of potential drug interaction with cytochrome P450 (CYP) is essential. A “cocktail” approach is often used in drug development to evaluate the effect of a drug candidate on multiple CYP enzymes in a single experiment. So far, simultaneous analysis of multiple CYP substrates, which have greatly different structure and physicochemical properties, has required organic solvents and mobile phase gradient methods. However, despite the recent emphasis on environmental protection, analytical methods that use only aqueous solvents without the use of organic solvents for separation have not been studied well. This study sought to develop the simultaneous analysis of multiple CYP substrates by using poly(N-isopropylacrylamide) (PNIPAAm)-based temperature-responsive chromatography with only aqueous solvents and isocratic methods. Good separation of multiple CYP substrates was achieved without using organic solvents and any gradient methods by temperature-responsive chromatography utilizing a P(NIPAAm-co-n-butyl methacrylate (BMA))- and P(NIPAAm-co-N-acryloyl L-tryptophan methyl ester (L-Trp-OMe))-grafted silica column. Overall, PNIPAAm-based temperature-responsive chromatography represents a remarkably simple, versatile, and environmentally friendly bioanalytical method for CYP substrates and their metabolites.
Multi-frequency radiation of dissipative solitons in optical fiber cavities
Authors: Melchert Oliver , Demircan Ayhan , Yulin Alexey
Published: June 2020

New resonant emission of dispersive waves by oscillating solitary structures in optical fiber cavities is considered analytically and numerically. The pulse propagation is described in the framework of the Lugiato-Lefever equation when a Hopf-bifurcation can result in the formation of oscillating dissipative solitons. The resonance condition for the radiation of the dissipative oscillating solitons is derived and it is demonstrated that the predicted resonances match the spectral lines observed in numerical simulations perfectly. The complex recoil of the radiation on the soliton dynamics is discussed. The reported effect can have importance for the generation of frequency combs in nonlinear microring resonators.
In-vitro bioaccessibility and bioavailability of heavy metals in mineral clay complex used in natural health products
Authors: Chen Xiumin , Singh Anika , Kitts David D.
Published: June 2020

Commercial mineral clays that claim to have healing properties are also known to contain trace amounts of heavy metals, albeit the risk of consuming many of them is not entirely known. The primary objective of this study was to evaluate the in vitro bioaccessibility and bioavailability of Arsenic (As), Cadmium (Cd) and Lead (Pb) in mineral clay samples collected from the Sierra Mountains (USA) using the Unified Bioaccessibility Research Group of Europe (UBM) method and the Caco-2 permeability assay, respectively. After UMB-gastric (UBM-G) digestion, As and Pb bioaccessibility were lower compared to Cd and decreased further in the UMB-gastrointestinal (UBM-GI) assay. Bioavailability estimates using the Caco-2 cell showed very low to non-detectable permeability for all 3 heavy metals. Thus, while initial heavy metal ranged from 3.8–17 ppm, 0.024–0.061ppm, and 5.8–20 ppm for As, Cd, and Pb, respectively, the bioavailability for these metals was reduced to very low levels that followed: non-detectable values of As, <0.007ppm of Cd, and <0.1ppm of Pb. Using UBM-digestion to mimic bioaccessibility, followed by Caco-2 cell bioavailability enabled us to conclude that in vitro assessment of heavy metal exposure associated with mineral clay-based natural health products does not pose a potential hazard to consumers.
Contrast-enhanced T1-weighted image radiomics of brain metastases may predict EGFR mutation status in primary lung cancer
Authors: Ahn Sung Jun , Kwon Hyeokjin , Yang Jin-Ju , Park Mina , Cha Yoon Jin , Suh Sang Hyun , Lee Jong-Min
Published: June 2020

Identification ofEGFRmutations is critical to the treatment of primary lung cancer and brain metastases (BMs). Here, we explored whether radiomic features of contrast-enhanced T1-weighted images (T1WIs) of BMs predictEGFRmutation status in primary lung cancer cases. In total, 1209 features were extracted from the contrast-enhanced T1WIs of 61 patients with 210 measurable BMs. Feature selection and classification were optimized using several machine learning algorithms. Ten-fold cross-validation was applied to the T1WI BM dataset (189 BMs for training and 21 BMs for the test set). Area under receiver operating characteristic curves (AUC), accuracy, sensitivity, and specificity were calculated. Subgroup analyses were also performed according to metastasis size. For all measurable BMs, random forest (RF) classification with RF selection demonstrated the highest diagnostic performance for identifyingEGFRmutation (AUC: 86.81). Support vector machine and AdaBoost were comparable to RF classification. Subgroup analyses revealed that small BMs had the highest AUC (89.09). The diagnostic performance for large BMs was lower than that for small BMs (the highest AUC: 78.22). Contrast-enhanced T1-weighted image radiomics of brain metastases predicted theEGFRmutation status of lung cancer BMs with good diagnostic performance. However, further study is necessary to apply this algorithm more widely and to larger BMs.
Photocatalytic degradation of oily waste and phenol from a local South Africa oil refinery wastewater using response methodology
Authors: Tetteh E. K. , Rathilal S. , Naidoo D. B.
Published: June 2020

The photocatalytic degradation of a local South Africa oil refinery wastewater was conducted under UV radiation using an aqueous catalyst of titanium dioxide (TiO2), Degussa P25 (80% anatase, 20% rutile) in suspension. The experiment was carried out in a batch aerated photocatalytic reactor based on a central composite design (CCD) and analyzed using response surface methodology (RSM). The effects of three operational variables viz. TiO2 dosage (2–8 g/L), runtime (30–90 minutes), and airflow rate (0.768–1.48 L/min) were examined for the removal of phenol and soap oil and grease (SOG). The data derived from the CCD, and the successive analysis of variance (ANOVA) showed the TiO2 dosage to be the most influential factor, while the other factors were also significant (P < 0.0001). Also, the ANOVA test revealed the second-order of TiO2 dosage and runtime as the main interaction factors on the removal efficiency. To maximize the pollutant removal, the optimum conditions were found at runtime of 90 minutes, TiO2 dosage of 8 g/L, and an aeration flow rate of 1.225 L/min. Under the conditions stated, the percentage removal of phenol (300 ± 7) and SOG (4000 ± 23) were 76% and 88% respectively. At 95% confidence level, the predicted models developed results were in reasonable agreement with that of the experimental data, which confirms the adaptability of the models. The first-order kinetic constants were estimated as 0.136 min−1 and 0.083 min−1 for SOG and phenol respectively.
In vitro cultured human endometrial cells release extracellular vesicles that can be uptaken by spermatozoa
Authors: Murdica Valentina , Giacomini Elisa , Makieva Sofia , Zarovni Natasa , Candiani Massimo , Salonia Andrea , Vago Riccardo , Viganò Paola
Published: June 2020

Extracellular vesicles (EVs) derived from different parts of the male reproductive tract can be internalized by human spermatozoa affecting their maturation and regulating their functions. Here we demonstrate that EVs derived from the female tract can be uptaken by sperm and affect their competence. Primary endometrial cells release EVs with a diameter between 50 and 350 nm and bear the standard vesicle and exosome marker proteins CD63, CD9, TSG101 and ALIX. The uptake of dye-labelled endometrial cell-derived EVs by spermatozoa, quantified as fluorescence intensity, was significantly higher when EVs were derived from cells in the proliferative phase. Vital, motile fluorescent sperm could be appreciated after a 48-hour co-incubation with endometrial cells previously labelled with the Vybrant™ DiO dye. EV internalization by sperm was blocked at 4 °C and by incubation with filipin, suggesting an energy-dependent process probably attributable to the lipid-raft domain mediated-endocytosis. Sperm ability to undergo capacitation and acrosome reaction was stimulated by endometrial cell-derived EVs as manifested by the increased protein tyrosine phosphorylation and evident reactivity when stimulated with a calcium ionophore. Based on these findings, EVs exchange may be suggested as an emerging way through which female reproductive tract cells can interact with the passing spermatozoa.
Environmental and dynamic effects explain how nisin captures membrane-bound lipid II
Authors: Panina Irina , Krylov Nikolay , Nolde Dmitry , Efremov Roman , Chugunov Anton
Published: June 2020

Antibiotics (AB) resistance is a major threat to global health, thus the development of novel AB classes is urgently needed. Lantibiotics (i.e. nisin) are natural compounds that effectively control bacterial populations, yet their clinical potential is very limited. Nisin targets membrane-embedded cell wall precursor — lipid II — via capturing its pyrophosphate group (PPi), which is unlikely to evolve, and thus represents a promising pharmaceutical target. Understanding of exact molecular mechanism of initial stages of membrane-bound lipid II recognition by water-soluble nisin is indispensable. Here, using molecular simulations, we demonstrate that the structure of lipid II is determined to a large extent by the surrounding water-lipid milieu. In contrast to the bulk solvent, in the bilayer only two conformational states remain capable of nisin binding. In these states PPi manifests a unique arrangement of hydrogen bond acceptors on the bilayer surface. Such a “pyrophosphate pharmacophore” cannot be formed by phospholipids, which explains high selectivity of nisin/lipid II recognition. Similarly, the “recognition module” of nisin, being rather flexible in water, adopts the only stable conformation in the presence of PPi analogue (which mimics the lipid II molecule). We establish the “energy of the pyrophosphate pharmacophore” approach, which effectively distinguishes nisin conformations that can form a complex with PPi. Finally, we propose a molecular model of nisin recognition module/lipid II complex in the bacterial membrane. These results will be employed for further study of lipid II targeting by antimicrobial (poly)cyclic peptides and for design of novel AB prototypes.
Comparison of divergent breeding management strategies in two species of semi-captive eland in Senegal
Authors: Kubátová Anna , Štochlová Kateřina , Brandlová Karolína , Jůnková Vymyslická Pavla , Černá Bolfíková Barbora
Published: June 2020

Breeding management of small populations may have a critical influence on the development of population characteristics in terms of levels of genetic diversity and inbreeding. Two populations of antelope sister species – Critically Endangered Western Derby eland (Tauroragus derbianus derbianus) and non-native Least Concern Cape eland (Taurotragus oryx oryx) bred under different management strategies were studied in Senegal, Western Africa. The aims of the study were to compare the population genetic parameters of the two species and to test for the presence of interspecific hybrids. In total, blood and tissue samples from 76 Western Derby elands and 26 Cape elands were investigated, using 12 microsatellite markers. No hybrid individuals were detected in the sampled animals within the multispecies enclosure in Bandia Reserve, Senegal. The parameters of genetic polymorphism indicated much lower genetic diversity in Western Derby elands compared to Cape elands. On the other hand, the coefficient of inbreeding was low in both species. It is hypothesized that this could be a positive effect of strict population management of Western Derby elands, which, despite the loss of genetic diversity, minimizes inbreeding.
Anesthetic propofol epigenetically regulates breast cancer trastuzumab resistance through IL-6/miR-149-5p axis
Authors: Tian Dan , Tian Miao , Ma Zhi-ming , Zhang Lei-lei , Cui Yun-feng , Li Jin-long
Published: June 2020

Propofol, a common intravenous anesthetic, has been found to exert anti-cancer effects with inhibition of cancer cell proliferation, migration and invasion. We tested its possible action against HER2-overexpressing breast cancer cells that developed resistance against trastuzumab. Cell viability assay, ELISA for cytokines, mammosphere formation, quantitative RT-PCR for EMT/IL-6-targeting miRNAs and the in vivo experimental pulmonary metastasis model were performed to understand the epigenetic action of propofol. Propofol sensitized HER2 overexpressing cells to trastuzumab but such action was even more pronounced in resistant cells. Increased cytokines IL-6 as well as IL-8 were released by resistant cells, along with increased mammospheres and induction of EMT, all of which was inhibited by propofol. IL-6 targeting tumor suppressor miR-149-5p was found to be the novel miRNA that was up-regulated by propofol, resulting in the observed effects on cell viability, IL-6 production, mammospheres generation as well as EMT induction. Further, antagonizing miR-149-5p attenuated the propofol effects confirming the epigenetic activity of propofol through miR-149-5p regulation. Finally, in vivo validation in an experimental metastasis model conformed an inhibitory action of propofol against experimental lung metastasis and the essential mechanistic role of miR-149-5p/IL-6 loop. These results present a novel role of general anesthetic propofol against resistant breast cancer cells and the underlying epigenetic regulation of a tumor suppressor miRNA.
Remediation of diesel-contaminated soil enhanced with firefighting foam application
Authors: Rakowska Joanna
Published: June 2020

During rescue operations related to the elimination of the effects of industrial accidents or natural disasters, extinguishing agents are used that affect the migration and transformation of contamination in the environment. Firefighting foam sprayed onto an oil spill slowly drains to an aqueous solution and penetrates the soil. The role of surfactants in the removal of petroleum derivatives is well known, but such extinguishing agents also contain solvents, preservatives, corrosion inhibitors and other ingredients that can reduce the beneficial effect of surfactants on soil remediation. The article presents the results of research on the remediation of soil contaminated with diesel fuel and enhanced with firefighting agents used to extinguish fires or remove oil spills on the road. The obtained results of biodegradation and leaching studies indicate differences in the efficiency of diesel fuel removal from soils. It was also found that Wet 1% reduces the amount of polycyclic aromatic hydrocarbons (PAHs) in the soil compared to oily samples not wetted with extinguishing solutions. Chromatographic analyses have shown both the hydrocarbons degradation and the possibility of their transformation into more hazardous compounds. The effectiveness of soil remediation depends on the chemical composition of the extinguishing agent used on the contaminated soil.
Effects of Glucose Deprivation on ATP and Proteoglycan Production of Intervertebral Disc Cells under Hypoxia
Authors: Yin Xue , Motorwala Aarif , Vesvoranan Oraya , Levene Howard B. , Gu Weiyong , Huang Chun-Yuh
Published: June 2020

As the most common cause of low back pain, the cascade of intervertebral disc (IVD) degeneration is initiated by the disappearance of notochordal cells and progressive loss of proteoglycan (PG). Limited nutrient supply in the avascular disc environment restricts the production of ATP which is an essential energy source for cell survival and function such as PG biosynthesis. The objective of this study was to examine ATP level and PG production of porcine IVD cells under prolonged exposure to hypoxia with physiological glucose concentrations. The results showed notochordal NP and AF cells responded differently to changes of oxygen and glucose. Metabolic activities (including PG production) of IVD cells are restricted under the in-vivo nutrient conditions while NP notochordal cells are likely to be more vulnerable to reduced nutrition supply. Moreover, provision of energy, together or not with genetic regulation, may govern PG production in the IVD under restricted nutrient supply. Therefore, maintaining essential levels of nutrients may reduce the loss of notochordal cells and PG in the IVD. This study provides a new insight into the metabolism of IVD cells under nutrient deprivation and the information for developing treatment strategies for disc degeneration.
The influence of anticipated monetary incentives on visual working memory performance in healthy younger and older adults
Authors: Manga Annamária , Vakli Pál , Vidnyánszky Zoltán
Published: June 2020

Motivation exerts substantial control over cognitive functions, including working memory. Although it is well known that both motivational control and working memory processes undergo a progressive decline with ageing, whether and to what extent their interaction is altered in old age remain unexplored. Here we aimed at uncovering the effect of reward anticipation on visual working memory performance in a large cohort of younger and older adults using a delayed-estimation task. We applied a three-component probabilistic model to dissociate the reward effects on three possible sources of error corrupting working memory performance: variability in recall, misbinding of object features and random guessing. The results showed that monetary incentives have a significant beneficial effect on overall working memory recall precision only in the group of younger adults. However, our model-based analysis resulted in significant reward effects on all three working memory component processes, which did not differ between the age groups, suggesting that model-based analysis is more sensitive to small reward-induced modulations in the case of older participants. These findings revealed that monetary incentives have a global boosting effect on working memory performance, which is deteriorated to some extent but still present in healthy older adults.
Toward personalized synchrotron microbeam radiation therapy
Authors: Engels Elette , Li Nan , Davis Jeremy , Paino Jason , Cameron Matthew , Dipuglia Andrew , Vogel Sarah , Valceski Michael , Khochaiche Abass , O’Keefe Alice , Barnes Micah , Cullen Ashley , Stevenson Andrew , Guatelli Susanna , Rosenfeld Anatoly , Lerch Michael , Corde Stéphanie , Tehei Moeava
Published: June 2020

Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. This study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this ground-breaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. Our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.
Repetitive sequences and structural chromosome alterations promote intraspecific variations in Zea mays L. karyotype
Authors: Silva Jéssica Coutinho , Soares Fernanda Aparecida Ferrari , Sattler Mariana Cansian , Clarindo Wellington Ronildo
Published: June 2020

LTR-retrotransposons, knobs and structural chromosome alterations contribute to shape the structure and organization of the Zea mays karyotype. Our initial nuclear DNA content data of Z. mays accessions revealed an intraspecific variation (2 C = 2.00 pg to 2 C = 6.10 pg), suggesting differences in their karyotypes. We aimed to compare the karyotypes of three Z. mays accessions in search of the differences and similarities among them. Karyotype divergences were demonstrated among the accessions, despite their common chromosome number (2n = 20) and ancestral origin. Cytogenomic analyses showed that repetitive sequences and structural chromosome alterations play a significant role in promoting intraspecific nuclear DNA content variation. In addition, heterozygous terminal deletion in chromosome 3 was pointed out as a cause of lower nuclear 2 C value. Besides this, translocation was also observed in the short arm of chromosome 1. Differently, higher 2 C value was associated with the more abundant distribution of LTR-retrotransposons from the family Grande in the karyotype. Moreover, heteromorphism involving the number and position of the 180-bp knob sequence was found among the accessions. Taken together, we provide insights on the pivotal role played by repetitive sequences and structural chromosome alterations in shaping the karyotype of Z. mays.
In vitro genomic damage induced by urban fine particulate matter on human lymphocytes
Authors: Santovito Alfredo , Gendusa Claudio , Cervella Piero , Traversi Deborah
Published: June 2020

Urban air pollution represents a global problem, since everyday many mutagenic and carcinogens compounds are emitted into the atmosphere, with consequent adverse health effects on humans and biota. Specifically, particulate matter air pollution was associated with increased risks in human mortality and morbidity. In this paper, we analyse the genomic effects on human lymphocytes of different concentrations of annual Turin PM2.5 extract by an in vitro micronuclei assay. Samplings were collected from an urban meteorological-chemical station positioned in Turin (Italy), one of the most polluted cities in Europe. PM2.5 sampled on filters was used for organic extraction in monthly pools and successively aggregated to produce a mixture representative for a full year PM2.5 collection. Lymphocytes were exposed to four concentrations of PM2.5: 5, 10, 15 and 20 μg/mL and micronuclei, nucleoplasmic bridges and nuclear buds were scored. With respect to controls, PM2.5 significantly increased the frequencies of all analysed biomarkers at all tested concentrations, whereas the CBPI index was significantly reduced only at the concentration of 20 μg/mL. Such in vitro effects can both to stimulate local authorities to adopt efficient measures for air pollution mitigation and to improve human monitoring to detect early precancer lesions.
Specificity and retention of visual perceptual learning in young children with low vision
Authors: Huurneman Bianca , Nienke Boonstra F. , Goossens Jeroen
Published: June 2020

There is evidence that a pen-and-paper training based on perceptual learning principles improves near visual acuity in young children with visual impairment. The aim of the present study is to measure specificity and retention of its training effects during one year. Sixteen visually impaired children aged 4–8 years were divided in two age- and acuity-matched groups: an early (n = 9) and late treatment group (n = 7). Training consisted of 12 sessions (2× per week for 6 weeks). Studied variables were uncrowded and crowded binocular near visual acuity (40 cm), distance visual acuity (3.0 m) and fine motor skills (Beery VMI, subtest Motor Control). In the early treatment group, we measured at 0 months (pre-training), at 2 months (post-training), at 8 months (6 months post-training) and at 14 months (12 months post-training) since inclusion. In the late treatment group, three pre-training measurements were performed at 0, 2 and 8 months, and two measurements at 0 and 6 months post-training. In the short term, training improved uncrowded and crowded near visual acuity at 0.4 m by 0.13 ± 0.03 and 0.09 ± 0.03 logMAR, respectively (mean ± SEM). Training did not affect distance acuities or Beery scores. Learning effects on uncrowded and crowded near visual acuities remained intact 6–12 months after training. We conclude that the pen-and-paper training specifically improves near visual acuities but does not transfer to distance acuities or fine motor skills. Improvements in near visual acuity are retained over time, bolstering its clinical value.