bluuebunny/crossref_metadata_2025 huggingface dataset:
Bis(zinc(II)-dipicolylamine)-functionalized sub-2 μm core-shell microspheres for the analysis of N-phosphoproteome
Authors: Hu Yechen , Jiang Bo , Weng Yejing , Sui Zhigang , Zhao Baofeng , Chen Yuanbo , Liu Lukuan , Wu Qiong , Liang Zhen , Zhang Lihua , Zhang Yukui
Published: December 2020

Protein N-phosphorylation plays a critical role in central metabolism and two/multicomponent signaling of prokaryotes. However, the current enrichment methods for O-phosphopeptides are not preferred for N-phosphopeptides due to the intrinsic lability of P-N bond under acidic conditions. Therefore, the effective N-phosphoproteome analysis remains challenging. Herein, bis(zinc(II)-dipicolylamine)-functionalized sub-2 μm core-shell silica microspheres (SiO2@DpaZn) are tailored for rapid and effective N-phosphopeptides enrichment. Due to the coordination of phosphate groups to Zn(II), N-phosphopeptides can be effectively captured under neutral conditions. Moreover, the method is successfully applied to an E.coli and HeLa N-phosphoproteome study. These results further broaden the range of methods for the discovery of N-phosphoproteins with significant biological functions.
Atomic threshold-switching enabled MoS2 transistors towards ultralow-power electronics
Authors: Hua Qilin , Gao Guoyun , Jiang Chunsheng , Yu Jinran , Sun Junlu , Zhang Taiping , Gao Bin , Cheng Weijun , Liang Renrong , Qian He , Hu Weiguo , Sun Qijun , Wang Zhong Lin , Wu Huaqiang
Published: December 2020

Power dissipation is a fundamental issue for future chip-based electronics. As promising channel materials, two-dimensional semiconductors show excellent capabilities of scaling dimensions and reducing off-state currents. However, field-effect transistors based on two-dimensional materials are still confronted with the fundamental thermionic limitation of the subthreshold swing of 60 mV decade−1 at room temperature. Here, we present an atomic threshold-switching field-effect transistor constructed by integrating a metal filamentary threshold switch with a two-dimensional MoS2 channel, and obtain abrupt steepness in the turn-on characteristics and 4.5 mV decade−1 subthreshold swing (over five decades). This is achieved by using the negative differential resistance effect from the threshold switch to induce an internal voltage amplification across the MoS2 channel. Notably, in such devices, the simultaneous achievement of efficient electrostatics, very small sub-thermionic subthreshold swings, and ultralow leakage currents, would be highly desirable for next-generation energy-efficient integrated circuits and ultralow-power applications.
Janus electrocatalytic flow-through membrane enables highly selective singlet oxygen production
Authors: Zhao Yumeng , Sun Meng , Wang Xiaoxiong , Wang Chi , Lu Dongwei , Ma Wen , Kube Sebastian A. , Ma Jun , Elimelech Menachem
Published: December 2020

The importance of singlet oxygen (1O2) in the environmental and biomedical fields has motivated research for effective 1O2 production. Electrocatalytic processes hold great potential for highly-automated and scalable 1O2 synthesis, but they are energy- and chemical-intensive. Herein, we present a Janus electrocatalytic membrane realizing ultra-efficient 1O2 production (6.9 mmol per m3 of permeate) and very low energy consumption (13.3 Wh per m3 of permeate) via a fast, flow-through electro-filtration process without the addition of chemical precursors. We confirm that a superoxide-mediated chain reaction, initiated by electrocatalytic oxygen reduction on the cathodic membrane side and subsequently terminated by H2O2 oxidation on the anodic membrane side, is crucial for 1O2 generation. We further demonstrate that the high 1O2 production efficiency is mainly attributable to the enhanced mass and charge transfer imparted by nano- and micro-confinement effects within the porous membrane structure. Our findings highlight a new electro-filtration strategy and an innovative reactive membrane design for synthesizing 1O2 for a broad range of potential applications including environmental remediation.
Resonant excitation of nanowire quantum dots
Authors: Leandro Lorenzo , Hastrup Jacob , Reznik Rodion , Cirlin George , Akopian Nika
Published: December 2020

GaAs quantum dots in nanowires are one of the most promising candidates for scalable quantum photonics. They have excellent optical properties, can be frequency-tuned to atomic transitions, and offer a robust platform for fabrication of multi-qubit devices that promise to unlock the full technological potential of quantum dots. Coherent resonant excitation is necessary for virtually any practical application because it allows, for instance, for on-demand generation of single and entangled photons, photonic clusters states, and electron spin manipulation. However, emission from nanowire structures under this excitation scheme has never been demonstrated. Here we show, for the first time, biexciton–exciton cascaded emission via resonant two-photon excitation and resonance fluorescence from an epitaxially grown GaAs quantum dot in an AlGaAs nanowire. We also report that resonant excitation schemes, combined with above-bandgap excitation, can be used to clean and enhance the emission of nanowire quantum dots.
Introducing students to neural communication: an embodied-learning classroom demonstration
Authors: Hatin B. D. M.
Published: December 2020

Learning about neural communication can be a dry and challenging undertaking, particularly for students without a background in biology. To enhance learning of this and other STEM material, there has been a call for science educators to embrace the use of active learning techniques. The aim of this Brief Communication is to encourage the use of embodied metaphors in the university classroom by sharing an active learning method for introducing students to a number of key concepts in neural communication. The students work in pairs or small groups, using foam projectiles such as Nerf guns to work through several metaphors for electrical and chemical processes including action potentials, neurotransmission and receptor action, excitatory and inhibitory post-synaptic potentials and neurotransmitter inactivation. The activities are easy to stage and lend themselves well to customisation based on available class size, classroom space, and resources. Student feedback showed that the activities improved self-reported impressions of understanding and ability to convey key concepts to others. The activities thus can serve as a useful method of student engagement and help develop understanding of complex material in a neuroscience classroom.
Exposure to emissions from Mount Etna (Sicily, Italy) and incidence of thyroid cancer: a geographic analysis
Authors: Boffetta Paolo , Memeo Lorenzo , Giuffrida Dario , Ferrante Margherita , Sciacca Salvatore
Published: December 2020

An increased incidence of thyroid cancer has been reported in the area close to Mount Etna, the largest volcano in Europe located in Northeastern Sicily. We tested the hypothesis that exposure to the emissions from the volcano is associated with thyroid cancer in 186 municipalities from three provinces surrounding the volcano (1.9 million inhabitants). We measured the angle between the bearing of the municipalities and each direction, with special focus on South-East, the prevalent direction of the plume, and conducted a regression analysis on 2003–2016 incidence rates of thyroid cancer, adjusting for distance from Mount Etna, population size, and income. A 10-degree increase in the angle with South-East was associated with a decrease in thyroid cancer rates in the whole population (− 0.67 cases/100,000, p = 0.002) and in women (− 1.54/100,000, p < 0.001), and were robust to several sensitivity analyses. Similar results were obtained for East-South-East direction. These results support the hypothesis of a potential role of exposure to the plume from Mount Etna in determining the high rates of thyroid cancer. The results need to be confirmed in analytical studies, in which information of exposure to chemicals originating from the volcano, as well as other possible causes, should be carefully measured, molecular characteristics of the tumors and taken into account.
U-DCS: characterization of the first permanent human dendritic sarcoma cell line
Authors: Mellert Kevin , Benckendorff Julian , Leithäuser Frank , Zimmermann Katarzyna , Wiegand Peter , Frascaroli Giada , Buck Michaela , Malaise Muriel , Hartmann Gunther , Barchet Winfried , Fürst Daniel , Mytilineos Joannis , Mayer-Steinacker Regine , Viardot Andreas , Möller Peter
Published: December 2020

A dendritic cell sarcoma cell line, U-DCS, was established from a dendritic cell sarcoma in a 53-year-old Caucasian male patient. Since its establishment, U-DCS has maintained stable phenotypic characteristics in vitro and has a doubling time of approximately 2 days under standard culture conditions. U-DCS is growing with typical dendritic cell morphology in tissue and expresses the dendritic cell sarcoma immunophenotypic markers S100 protein, MHCI, MHCII, and vimentin. Expression analysis revealed transcripts for the toll-like receptors TLR3, -4, -9 and DDX58 (RIG-I), but not for TLR2. U-DCS shows functional features of dendritic cells with the ability of phagocytosis and antigen-specific T cell stimulation. Karyotype-, CGH-, and mFISH analysis point to a chromosomal instability and a hypotetraploid karyotype with approximately 130 chromosomes. U-DCS is the first immortalized human dendritic cell sarcoma cell line and has some morphological and functional features of dendritic cells without dependency on growth factors.
The extracellular juncture domains in the intimin passenger adopt a constitutively extended conformation inducing restraints to its sphere of action
Authors: Weikum Julia , Kulakova Alina , Tesei Giulio , Yoshimoto Shogo , Jægerum Line Vejby , Schütz Monika , Hori Katsutoshi , Skepö Marie , Harris Pernille , Leo Jack C. , Morth J. Preben
Published: December 2020

Enterohemorrhagic and enteropathogenic Escherichia coli are among the most important food-borne pathogens, posing a global health threat. The virulence factor intimin is essential for the attachment of pathogenic E. coli to the intestinal host cell. Intimin consists of four extracellular bacterial immunoglobulin-like (Big) domains, D00–D2, extending into the fifth lectin subdomain (D3) that binds to the Tir-receptor on the host cell. Here, we present the crystal structures of the elusive D00–D0 domains at 1.5 Å and D0–D1 at 1.8 Å resolution, which confirms that the passenger of intimin has five distinct domains. We describe that D00–D0 exhibits a higher degree of rigidity and D00 likely functions as a juncture domain at the outer membrane-extracellular medium interface. We conclude that D00 is a unique Big domain with a specific topology likely found in a broad range of other inverse autotransporters. The accumulated data allows us to model the complete passenger of intimin and propose functionality to the Big domains, D00–D0–D1, extending directly from the membrane.
Detection of urinary miRNAs for diagnosis of clear cell renal cell carcinoma
Authors: Cochetti Giovanni , Cari Luigi , Nocentini Giuseppe , Maulà Vincenza , Suvieri Chiara , Cagnani Rosy , Rossi De Vermandois Jacopo Adolfo , Mearini Ettore
Published: December 2020

The lack of symptoms at the early stages of clear cell renal cell carcinoma (ccRCC) allows the tumour to metastasize, leading to a dramatic reduction in patient survival. Therefore, we studied and set up a method based on urinary microRNAs (miRNAs) for the diagnosis of ccRCC. First, miRNA expression in ccRCC specimens and kidney tissues from healthy subjects (HSs) was investigated through analysis of data banks and validated by comparing expression of miRNAs in ccRCC and adjacent non-cancerous kidney tissue specimens by RT-qPCR. Subsequently, we developed an algorithm to establish which miRNAs are more likely to be found in the urine of ccRCC patients that indicated miR-122, miR-1271, and miR-15b as potential interesting markers. The evaluation of their levels and three internal controls in the urine of 13 patients and 14 HSs resulted in the development of a score (7p-urinary score) to evaluate the presence of ccRCC in patients. The resulting area under the Receiver Operating Characteristic (ROC) curve, sensitivity, and specificity were equal to 0.96, 100% (95% CI 75–100%), and 86% (95% CI 57–98%), respectively. In conclusion, our study provides a proof of concept that combining the expression values of some urinary miRNAs might be useful in the diagnosis of ccRCC.
Affordable automated phenotypic antibiotic susceptibility testing method based on a contactless conductometric sensor
Authors: Zhang Xuzhi , Jiang Xiaoyu , Yang Qianqian , Xu Yong , Wang Xiaochun , Wang Jinping , Sun Xiaobo , Xie Guosi , Zhang Yan , Zhao Jun , Qu Keming
Published: December 2020

User-friendly phenotypic antibiotic susceptibility testing (AST) methods are urgently needed in many fields including clinical medicine, epidemiological studies and drug research. Herein, we report a convenient and cost-effective phenotypic AST method based on online monitoring bacterial growth with a developed 8-channel contactless conductometric sensor (CCS). Using E. coli and V. parahaemolyticus as microorganism models, as well as enoxacin, florfenicol, ampicillin, kanamycin and sulfadiazine as antibiotic probes. The minimum inhibitory concentration (MIC) determination was validated in comparison with standard broth microdilution (BMD) assay. The total essential agreements between the CCS AST assays and the reference BMD AST assays are 68.8–92.3%. The CCS has an approximate price of $9,000 (USD). Requiring neither chemical nor biotic auxiliary materials for the assay makes the cost of each sample < $1. The MICs obtained with the automated CCS AST assays are more precise than those obtained with the manual BMD. Moreover, in 72 percent of the counterpart, the MICs obtained with the CCS AST assays are higher than that obtained with the BMD AST assays. The proposed CCS AST method has advantages in affordability, accuracy, sensitivity and user-friendliness.
Contrast enhanced magnetic resonance imaging highlights neurovasculature changes following experimental traumatic brain injury in the rat
Authors: Wright David K. , Mayo Jamie N. , Sun Mujun , O’Brien Terence J. , Shultz Sandy R.
Published: December 2020

Neurovascular injury has been proposed as a universal pathological hallmark of traumatic brain injury (TBI) with molecular markers of angiogenesis and endothelial function associated with injury severity and morbidity. Sex differences in the neurovasculature response post-TBI may contribute to the differences seen in how males and females respond to injury. Steady-state contrast enhanced magnetic resonance imaging (SSCE-MRI) can be used to non-invasively assess the neurovasculature and may be a useful tool in understanding and predicting outcomes post-TBI. Here we used SSCE-MRI to investigate the neurovasculature of male and female rats at 48 h after an experimental TBI, and how these changes related to neuromotor function at 1-week post-TBI. In addition to TBI induced changes, we found that female rats had greater vessel density, greater cerebral blood volumes and performed better on a neuromotor task than their male counterparts. These results suggest that acute post-TBI cerebrovascular function is worse in males, and that this may contribute to the greater functional deficits observed post-injury. Furthermore, these results highlight the potential of SSCE-MRI to provide insights into the cerebral microvasculature post-TBI. Future studies, incorporating both males and females, are warranted to investigate the evolution of these changes and the underlying mechanisms.
Discovery of a novel fibroblast activation protein (FAP) inhibitor, BR103354, with anti-diabetic and anti-steatotic effects
Authors: Cho Jae Min , Yang Eun Hee , Quan Wenying , Nam Eun Hye , Cheon Hyae Gyeong
Published: December 2020

Fibroblast growth factor (FGF) 21 is a class of hepatokines that plays a protective role against obesity, insulin resistance, and liver damage. Despite this, protective effects of FGF21 in human appear to be minimal, possibly due to its proteolytic cleavage by the fibroblast activation protein (FAP). Here, we presented a novel FAP inhibitor, BR103354, and described its pharmacological activities as a potential therapeutic agent for the treatment of metabolic disorders. BR103354 inhibited FAP with an IC50 value of 14 nM, showing high selectivity against dipeptidyl peptidase (DPP)-related enzymes and prolyl oligopeptidase (PREP). In differentiated 3T3/L1 adipocytes, the addition of FAP diminished hFGF21-induced Glut1 and phosphorylated levels of ERK, which were restored by BR103354. BR103354 exhibited good pharmacokinetic properties as evidenced by oral bioavailability of 48.4% and minimal hERG inhibition. Single co-administration of BR103354 with hFGF21 reduced nonfasting blood glucose concentrations, in association with increased intact form of hFGF21 in ob/ob mice. Additionally, chronic treatment of BR103354 for 4 weeks reduced nonfasting blood glucose concentrations with improved glucose tolerance and with reduced triglyceride (TG) content in liver of ob/ob mice. Consistently, BR103354 improved hepatic steatosis and fibrosis in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced non-alcoholic steatohepatitis (NASH) mouse model. FAP inhibitory effects of BR103354 were confirmed in normal cynomolgus monkeys. Together, BR103354 acts as an effective FAP inhibitor in vitro and in vivo, thereby demonstrating its potential application as an anti-diabetic and anti-NASH agent.
Targeting aurora kinases as a potential prognostic and therapeutical biomarkers in pediatric acute lymphoblastic leukaemia
Authors: Moreira-Nunes Caroline Aquino , Mesquita Felipe Pantoja , Portilho Adrhyann Jullyanne de Sousa , Mello Júnior Fernando Augusto Rodrigues , Maués Jersey Heitor da Silva , Pantoja Laudreísa da Costa , Wanderley Alayde Vieira , Khayat André Salim , Zuercher William J. , Montenegro Raquel Carvalho , de Moraes-Filho Manoel Odorico , de Moraes Maria Elisabete Amaral
Published: December 2020

Aurora kinases (AURKA and AURKB) are mitotic kinases with an important role in the regulation of several mitotic events, and in hematological malignancies,AURKAandAURKBhyperexpression are found in patients with cytogenetic abnormalities presenting a unfavorable prognosis. The aim of this study was evaluated the mRNA expression profile of pediatric Acute Lymphoblastic Leukaemia (ALL) patients and the efficacy of twoAURKAandAURKBdesigned inhibitors (GW809897X and GW806742X) in a leukemia cell line as a potential novel therapy for ALL patients. Cellular experiments demonstrated that both inhibitors induced cell death with caspase activation and cell cycle arrest, however only the GW806742X inhibitor decreased with more efficacyAURKAandAURKBexpression in K-562 leukemia cells. In ALL patients bothAURKA and AURKBshowed a significant overexpression, when compared to health controls. Moreover,AURKBexpression level was significant higher thanAURKAin patients, and predicted a poorer prognosis with significantly lower survival rates. No differences were found inAURKAandAURKBexpression between gene fusions, immunophenotypic groups, white blood cells count, gender or age. In summary, the results in this study indicates that theAURKAandAURKBoverexpression are important findings in pediatric ALL, and designed inhibitor, GW806742X tested in vitro were able to effectively inhibit the gene expression of both aurora kinases and induce apoptosis in K-562 cells, however our data clearly shown thatAURKBproves to be a singular finding and potential prognostic biomarker that may be used as a promising therapeutic target to those patients.
Nanohybrid-based immunosensor prepared for Helicobacter pylori BabA antigen detection through immobilized antibody assembly with @ Pdnano/rGO/PEDOT sensing platform
Authors: Gupta Shaivya , Jain Utkarsh , Murti Bayu Tri , Putri Athika Darumas , Tiwari Ashutosh , Chauhan Nidhi
Published: December 2020

The gastric colonization of human hosts by Helicobacter pylori (H. pylori) increases the risk of developing gastritis, ulcers and gastric cancer. To detect H. pylori, a nanohybrid-based BabA immunosensor is developed herein. BabA is an outer membrane protein and one of the major virulence factors of H. pylori. To design the immunosensor, an Au electrode is loaded with palladium nanoparticles (Pdnano) by electrodeposition to generate reduced graphene oxide (rGO)/poly(3,4-ethylenedioxythiophene) (PEDOT). The immobilization of these nanostructured materials imparts a large surface area and electroconductivity to bio-immune-sensing molecules (here, the BabA antigen and antibodies). After optimization, the fabricated immunosensor has the ability to detect antigens (H. pylori) in a linear range from 0.2 to 20 ng/mL with a low LOD (0.2 ng/mL). The developed immunosensor is highly specific, sensitive and reproducible. Additionally, in silico methods were employed to better understand the hybrid nanomaterials of the fabricated Pdnano/rGO/PEDOT/Au electrode. Simulations performed by molecular docking, and Metropolis Monte Carlo adsorption studies were conducted. The results revealed that the hybrid nanomaterials exhibit a stable antigen–antibody complex of BabA, yielding the lowest binding energy in relation to the electrode materials, emphasizing the functionality of the constructed electrodes in the electrochemical immunosensor.
De-novo transcriptome analysis unveils differentially expressed genes regulating drought and salt stress response in Panicum sumatrense
Authors: Das Rasmita Rani , Pradhan Seema , Parida Ajay
Published: December 2020

Screening the transcriptome of drought tolerant variety of little millet (Panicum sumatrense), a marginally cultivated, nutritionally rich, susbsistent crop, can identify genes responsible for its hardiness and enable identification of new sources of genetic variation which can be used for crop improvement. RNA-Seq generated ~ 230 million reads from control and treated tissues, which were assembled into 86,614 unigenes. In silico differential gene expression analysis created an overview of patterns of gene expression during exposure to drought and salt stress. Separate gene expression profiles for leaf and root tissue revealed the differences in regulatory mechanisms operating in these tissues during exposure to abiotic stress. Several transcription factors were identified and studied for differential expression. 61 differentially expressed genes were found to be common to both tissues under drought and salinity stress and were further validated using qRT-PCR. Transcriptome of P. sumatrense was also used to mine for genic SSR markers relevant to abiotic stress tolerance. This study is first report on a detailed analysis of molecular mechanisms of drought and salinity stress tolerance in a little millet variety. Resources generated in this study can be used as potential candidates for further characterization and to improve abiotic stress tolerance in food crops.
An integrated approach to biomarker discovery reveals gene signatures highly predictive of cancer progression
Authors: Sheng Kevin L. , Kang Lin , Pridham Kevin J. , Dunkenberger Logan E. , Sheng Zhi , Varghese Robin T.
Published: December 2020

Current cancer biomarkers present variability in their predictive power and demonstrate limited clinical efficacy, possibly due to the lack of functional relevance of biomarker genes to cancer progression. To address this challenge, a biomarker discovery pipeline was developed to integrate gene expression profiles from The Cancer Genome Atlas and essential survival gene datasets from The Cancer Dependency Map, the latter of which catalogs genes driving cancer progression. By applying this pipeline to lung adenocarcinoma, lung squamous cell carcinoma, and glioblastoma, genes highly associated with cancer progression were identified and designated as progression gene signatures (PGSs). Analysis of area under the receiver operating characteristics curve revealed that PGSs predicted patient survival more accurately than previously identified cancer biomarkers. Moreover, PGSs stratified patients with high risk for progressive disease indicated by worse prognostic outcomes, increased frequency of cancer progression, and poor responses to chemotherapy. The robust performance of these PGSs were recapitulated in four independent microarray datasets from Gene Expression Omnibus and were further verified in six freshly dissected tumors from glioblastoma patients. Our results demonstrate the power of an integrated approach to cancer biomarker discovery and the possibility of implementing PGSs into clinical biomarker tests.
Continuous and automatic mortality risk prediction using vital signs in the intensive care unit: a hybrid neural network approach
Authors: Baker Stephanie , Xiang Wei , Atkinson Ian
Published: December 2020

Mortality risk prediction can greatly improve the utilization of resources in intensive care units (ICUs). Existing schemes in ICUs today require laborious manual input of many complex parameters. In this work, we present a scheme that uses variations in vital signs over a 24-h period to make mortality risk assessments for 3-day, 7-day, and 14-day windows. We develop a hybrid neural network model that combines convolutional (CNN) layers with bidirectional long short-term memory (BiLSTM) to predict mortality from statistics describing the variation of heart rate, blood pressure, respiratory rate, blood oxygen levels, and temperature. Our scheme performs strongly compared to state-of-the-art schemes in the literature for mortality prediction, with our highest-performing model achieving an area under the receiver-operator curve of 0.884. We conclude that the use of a hybrid CNN-BiLSTM network is highly effective in determining mortality risk for the 3, 7, and 14 day windows from vital signs. As vital signs are routinely recorded, in many cases automatically, our scheme could be implemented such that highly accurate mortality risk could be predicted continuously and automatically, reducing the burden on healthcare providers and improving patient outcomes.
Dynamics of salivary markers of kidney functions in acute and chronic kidney diseases
Authors: Kovalčíková Alexandra Gaál , Pavlov Kristína , Lipták Róbert , Hladová Marianna , Renczés Emese , Boor Peter , Podracká Ľudmila , Šebeková Katarína , Hodosy Július , Tóthová Ľubomíra , Celec Peter
Published: December 2020

Saliva can be used as an alternative diagnostic fluid enabling easy and non-invasive disease monitoring. Urea and creatinine can be measured in saliva and both were shown to be increased in renal failure. However, the dynamics of these markers during the development of kidney diseases is unknown. We aimed to describe the dynamics of salivary urea and creatinine in various animal models of acute kidney injury (AKI) and chronic kidney disease (CKD) and in patients with different stages AKI or CKD. Ninety Wistar rats underwent bilateral nephrectomy (BNX), ischemia–reperfusion injury (IRI) or glycerol-induced kidney injury to model AKI. CKD was modelled using 5/6 nephrectomy. In the clinical part 57 children aged 12.6 ± 4.9 years with AKI (n = 11) or CKD (n = 46) and 29 healthy controls (aged 10.2 ± 3.7 years) were enrolled. Saliva and blood samples were collected in both, animal experiments and the human study. In animal models of AKI, plasma urea and creatinine were higher than in controls. An increase of salivary urea and creatinine (twofold) was observed in BNX and IRI, but only after 12 h and 24 h, respectively. In glycerol nephropathy and 5/6 nephrectomy, salivary urea increased (by 100% and by 50%), while salivary creatinine did not change during the observation period. Salivary urea and creatinine were significantly higher in all patients compared to controls (threefold) and in both, AKI and CKD they were associated with the severity of renal failure. Plasma and salivary concentrations correlated only in children with renal failure (R = 0.72 for urea; R = 0.93 for creatinine), but not in controls (R = -0.007 for urea; R = 0.02 for creatinine). Our study indicates that during the development of renal impairment saliva could be used for non-invasive monitoring in higher stages of AKI or CKD, rather than for screening of early stages of kidney diseases.
Non-basic amino acids in the hemagglutinin proteolytic cleavage site of a European H9N2 avian influenza virus modulate virulence in turkeys
Authors: Blaurock Claudia , Scheibner David , Landmann Maria , Vallbracht Melina , Ulrich Reiner , Böttcher-Friebertshäuser Eva , Mettenleiter Thomas C. , Abdelwhab Elsayed M.
Published: December 2020

H9N2 avian influenza virus (AIV) is the most widespread low pathogenic (LP) AIV in poultry and poses a serious zoonotic risk. Vaccination is used extensively to mitigate the economic impact of the virus. However, mutations were acquired after long-term circulation of H9N2 virus in poultry, particularly in the hemagglutinin (HA) proteolytic cleavage site (CS), a main virulence determinant of AIV. Compared to chickens, little is known about the genetic determinants for adaptation of H9N2 AIV to turkeys. Here, we describe 36 different CS motifs in Eurasian H9N2 viruses identified from 1966 to 2019. The European H9N2 viruses specify unique HACS with particular polymorphism by insertion of non-basic amino acids at position 319. Recombinant viruses carrying single HACS mutations resembling field viruses were constructed (designated G319, A319, N319, S319, D319 and K319). Several viruses replicated to significantly higher titers in turkey cells than in chicken cells. Serine proteases were more efficient than trypsin to support multicycle replication in mammalian cells. Mutations affected cell-to-cell spread and pH-dependent HA fusion activity. In contrast to chickens, mutations in the HACS modulated clinical signs in inoculated and co-housed turkeys. G319 exhibited the lowest virulence, however, it replicated to significantly higher titers in contact-turkeys and in vitro. Interestingly, H9N2 viruses, particularly G319, replicated in brain cells of turkeys and to a lesser extent in mammalian brain cells independent of trypsin. Therefore, the silent circulation of potentially zoonotic H9N2 viruses in poultry should be monitored carefully. These results are important for understanding the adaptation of H9N2 in poultry and replication in mammalian cells.
Variation in 100 relevant pharmacogenes among emiratis with insights from understudied populations
Authors: Al-Mahayri Zeina N. , Patrinos George P. , Wattanapokayakit Sukanya , Iemwimangsa Nareenart , Fukunaga Koya , Mushiroda Taisei , Chantratita Wasun , Ali Bassam R.
Published: December 2020

Genetic variations have an established impact on the pharmacological response. Investigating this variation resulted in a compilation of variants in “pharmacogenes”. The emergence of next-generation sequencing facilitated large-scale pharmacogenomic studies and exhibited the extensive variability of pharmacogenes. Some rare and population-specific variants proved to be actionable, suggesting the significance of population pharmacogenomic research. A profound gap exists in the knowledge of pharmacogenomic variants enriched in some populations, including the United Arab Emirates (UAE). The current study aims to explore the landscape of variations in relevant pharmacogenes among healthy Emiratis. Through the resequencing of 100 pharmacogenes for 100 healthy Emiratis, we identified 1243 variants, of which 63% are rare (minor allele frequency ≤ 0.01), and 30% were unique. Filtering the variants according to Pharmacogenomics Knowledge Base (PharmGKB) annotations identified 27 diplotypes and 26 variants with an evident clinical relevance. Comparison with global data illustrated a significant deviation of allele frequencies in the UAE population. Understudied populations display a distinct allelic architecture and various rare and unique variants. We underscored pharmacogenes with the highest variation frequencies and provided investigators with a list of candidate genes for future studies. Population pharmacogenomic studies are imperative during the pursuit of global pharmacogenomics implementation.
Targeting continuity of care and polypharmacy to reduce drug–drug interaction
Authors: Weng Yi-An , Deng Chung-Yeh , Pu Christy
Published: December 2020

Drug–drug interaction (DDI) is common among the elderly, and it can have detrimental effects on patients. However, how DDI can be targeted has been under-researched. This study investigates whether DDI can be reduced by targeting continuity of care (COC) through reducing polypharmacy. Population claims data of Taiwan National Health Insurance were used to conduct a 7-year-long longitudinal study on patients aged ≥ 65 years (n = 2,318,766). Mediation analysis with counterfactual method and a 4-way decomposition of the effect of COC on DDI was conducted. Mediation effect through excessive polypharmacy differed from that through lower-level polypharmacy. Compared with the low COC group, the high COC group demonstrated reduced excess relative risk of DDI by 26% (excess relative risk =  − 0.263; 95% Confidence Interval (CI) =  − 0.263 to − 0.259) to 30% (excess relative risk =  − 0.297; 95% CI =  − 0.300 to − 0.295) with excessive polypharmacy as the mediator. The risk only reduced by 8% (excess relative risk =  − 0.079; 95% CI, − 0.08 to − 0.078) to 10% (excess relative risk =  − 0.096; 95% CI, − 0.097 to − 0.095) when the mediator was changed to lower-level polypharmacy. The effect of COC on DDI was mediated by polypharmacy, and the mediation effect was higher with excessive polypharmacy. Therefore, to reduce DDI in the elderly population, different policy interventions should be designed by considering polypharmacy levels to maximize the positive effect of COC on DDI.
Probing stacking configurations in a few layered MoS2 by low frequency Raman spectroscopy
Authors: Sam Rhea Thankam , Umakoshi Takayuki , Verma Prabhat
Published: December 2020

Novel two-dimensional (2D) layered materials, such as MoS2, have recently gained a significant traction, chiefly due to their tunable electronic and optical properties. A major attribute that affects the tunability is the number of layers in the system. Another important, but often overlooked aspect is the stacking configuration between the layers, which can modify their electro-optic properties through changes in internal symmetries and interlayer interactions. This demands a thorough understanding of interlayer stacking configurations of these materials before they can be used in devices. Here, we investigate the spatial distribution of various stacking configurations and variations in interlayer interactions in few-layered MoS2 flakes probed through the low-frequency Raman spectroscopy, which we establish as a versatile imaging tool for this purpose. Some interesting anomalies in MoS2 layer stacking, which we propose to be caused by defects, wrinkles or twist between the layers, are also reported here. These types of anomalies, which can severely affect the properties of these materials can be detected through low-frequency Raman imaging. Our findings provide useful insights for understanding various structure-dependent properties of 2D materials that could be of great importance for the development of future electro-optic devices, quantum devices and energy harvesting systems.
Whole genome sequence analysis of rice genotypes with contrasting response to salinity stress
Authors: Subudhi Prasanta K. , Shankar Rama , Jain Mukesh
Published: December 2020

Salinity is a major abiotic constraint for rice farming. Abundant natural variability exists in rice germplasm for salt tolerance traits. Since few studies focused on the genome level variation in rice genotypes with contrasting response to salt stress, genomic resequencing in diverse genetic materials is needed to elucidate the molecular basis of salt tolerance mechanisms. The whole genome sequences of two salt tolerant (Pokkali and Nona Bokra) and three salt sensitive (Bengal, Cocodrie, and IR64) rice genotypes were analyzed. A total of 413 million reads were generated with a mean genome coverage of 93% and mean sequencing depth of 18X. Analysis of the DNA polymorphisms revealed that 2347 nonsynonymous SNPs and 51 frameshift mutations could differentiate the salt tolerant from the salt sensitive genotypes. The integration of genome-wide polymorphism information with the QTL mapping and expression profiling data led to identification of 396 differentially expressed genes with large effect variants in the coding regions. These genes were involved in multiple salt tolerance mechanisms, such as ion transport, oxidative stress tolerance, signal transduction, and transcriptional regulation. The genome-wide DNA polymorphisms and the promising candidate genes identified in this study represent a valuable resource for molecular breeding of salt tolerant rice varieties.
A sensitive colorimetric probe for detection of the phosphate ion
Authors: Chen Yin-Chien , Lo Kuang-Min , Wang Yu-Xian , Chiu Tai-Chia , Hu Cho-Chun
Published: December 2020

In the present article, we report a novel colorimetric probe (TNT@MB) for the detection of the phosphate ion, which is based on the strong binding affinity between the phosphate ion and titanium dioxide nanotubes (TNTs). TNTs were synthesized from TiO2 nanoparticles by hydrothermal treatment. The obtained TNTs had an average length of 200 ± 50 nm and an average width of 12 ± 5 nm. TNT@MB was prepared by adsorbing methyl blue onto TNTs in acidic condition. The optimal synthesis conditions for TNT@MB consisted in having 0.05 g of TNTs react with 1 μmole of methyl blue at pH 2 for 90 min. TNTs and TNT@MB were characterized by UV–vis diffuse reflection spectroscopy, TEM, FTIR, and XPS. The phosphate-ion sensing behavior of TNT@MB was investigated by UV–visible spectroscopy. The phosphate-ion concentration linear range and detection limit of this method based on TNT@MB were 1–40 μM and 0.59 μM, respectively. A sample of lake water was used as a real sample, and analyte recovery rates were measured in the 102.5–103.6% range, with relative standard deviations below 5.6% (n = 3). We also found that this probe could be reused after regeneration in alkaline solution. These results indicate that as a colorimetric probe, TNT@MB has the advantages of being environmentally friendly, inexpensive, and simple to use, as well as giving rise to an easily observable color change.
Longitudinal analysis of total serum IgE levels with allergen sensitization and atopic diseases in early childhood
Authors: Wong Chun-Ying , Yeh Kuo-Wei , Huang Jing-Long , Su Kuan-Wen , Tsai Ming-Han , Hua Man-Chin , Liao Sui-Ling , Lai Shen-Hao , Chen Li-Chen , Chiu Chih-Yung
Published: December 2020

There are few studies addressing the longitudinal analysis of serum IgE levels and its impact to the development of atopic diseases in early childhood. We investigated 170 children who regularly followed up at our clinic for 4 years in a birth cohort study with at least 3 time-points of serum samples. The pattern of total serum IgE levels from 6 months to 4 years of age was clustered using K-means method in R software. Specific immunoglobulin E antibodies against food (egg white and milk) and inhalant allergens (D. pteronyssinus and D. farinae) were measured at 0.5, 1, 1.5, 2, 3 and 4 years of age. By using K-means clustering, the dynamic changes in serum IgE levels was significantly stratified into 3 clusters (cluster A, < 100 kU/L, n = 106; cluster B, 100–200 kU/L, n = 35; cluster C, ≥ 200 kU/L, n = 29). A persistent total IgE levels higher than 100 kU/L appeared to be associated with higher prevalence of sensitization to food but not mite. However, a persistent IgE levels higher than 200 kU/L was not only remarkably related to increased prevalence of mite sensitization, but also risk of eczema at age 1 and allergic rhinitis and asthma at age 2, 3 and 4. In conclusion, a persistent total serum IgE level ≥ 200 kU/L since infancy is strongly associated with the presence of food and mite sensitization, as well as the development of eczema in infants, and rhinitis and asthma later in early childhood.
Saturation transfer properties of tumour xenografts derived from prostate cancer cell lines 22Rv1 and DU145
Authors: Tan Ziyu , Lam Wilfred W. , Oakden Wendy , Murray Leedan , Koletar Margaret M. , Liu Stanley K. , Stanisz Greg J.
Published: December 2020

Histopathology is currently the most reliable tool in assessing the aggressiveness and prognosis of solid tumours. However, developing non-invasive modalities for tumour evaluation remains crucial due to the side effects and complications caused by biopsy procedures. In this study, saturation transfer MRI was used to investigate the microstructural and metabolic properties of tumour xenografts in mice derived from the prostate cancer cell lines 22Rv1 and DU145, which express different aggressiveness. The magnetization transfer (MT) and chemical exchange saturation transfer (CEST) effects, which are associated with the microstructural and metabolic properties in biological tissue, respectively, were analyzed quantitatively and compared amongst different tumour types and regions. Histopathological staining was performed as a reference. Higher cellular density and metabolism expressed in more aggressive tumours (22Rv1) were associated with larger MT and CEST effects. High collagen content in the necrotic regions might explain their higher MT effects compared to tumour regions.
Changes in serum fibronectin levels predict tumor recurrence in patients with early hepatocellular carcinoma after curative treatment
Authors: Kim Sun Ah , Cho Eun Ju , Lee Sungyoung , Cho Young Youn , Kim Boram , Yoon Jung-Hwan , Park Taesung
Published: December 2020

Fibronectin, a matrix glycoprotein aberrantly expressed in various tumor cells, is a known candidate biomarker for the early diagnosis of hepatocellular carcinoma (HCC). In this study, we investigated whether serum fibronectin levels could predict tumor recurrence in patients with early-stage HCC after curative treatment. A total of 83 patients who showed complete response after initial curative treatment were included. The levels of serum fibronectin at baseline and 4–6 weeks after initial treatment were analyzed with regard to their associations with recurrence. Multivariate logistic regression analyses were performed to construct a prognostic nomogram. Baseline fibronectin levels were not significantly correlated with tumor size, number, stage, and serum α-fetoprotein levels. However, decrease in serum fibronectin levels after treatment was significantly associated with reduced HCC recurrence in multivariate logistic regression (odds ratio, 0.009; p < 0.001). Furthermore, a nomogram consisting of gender and changes in serum fibronectin showed a good discriminatory capability for the prediction of HCC recurrence with an area under the receiver-operating curve of 0.87. In conclusion, changes in serum fibronectin levels may be a surrogate indicator for assessment of treatment response in patients with early HCC after curative treatment.
Author Correction: Pretreatment-Integration for Milk Protein Removal and Device-Facilitated Immunochromatographic Assay for 17 Items
Authors: Qie Zhiwei , Huang Ziwei , Gao Zichen , Meng Wu , Zhu Yanhui , Xiao Rui , Wang Shengqi
Published: December 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Synthesis of 14C-labelled polystyrene nanoplastics for environmental studies
Authors: Al-Sid-Cheikh Maya , Rowland Steven J. , Kaegi Ralf , Henry Theodore B. , Cormier Marc-André , Thompson Richard C.
Published: December 2020

Available analytical methods cannot detect nanoplastics at environmentally realistic concentrations in complex matrices such as biological tissues. Here, we describe a one-step polymerization method, allowing direct radiolabeling of a sulfonate end-capped nano-sized polystyrene (nPS; proposed as a model nanoplastic particle representing negatively charged nanoplastics). The method, which produces nanoplastics trackable in simulated environmental settings which have already been used to investigate the behavior of a nanoplastic in vivo in a bivalve mollusc, was developed, optimized and successfully applied to synthesis of 14C-labeled nPS of different sizes. In addition to a description of the method of synthesis, we describe the details for quantification, mass balance and recovery of the labelled particles from complex matrices offered by the radiolabelling approach. The radiolabeling approach described here, coupled to use of a highly sensitive autoradiographic method for monitoring nanoplastic body burden and distributions, may provide a valuable procedure for investigating the environmental pathways followed by negatively charged nanoplastics at low predicted environmental concentrations. Whether the behaviour of the synthetic nPS manufactured here, synthesised using a very common inititator, represents that of manufactured nPS found in the environment, remains to be seen.
Language Difficulties Among Children Experiencing Neglect: A Public Health Approach Aimed at Narrowing the Gap
Authors: Sylvestre Audette
Published: December 2020

Purpose

Child neglect affects approximately 1% of children under the age of 6 years in the United States and Canada annually. Nearly 50% of children who experience neglect present significant language difficulties before starting school. Child neglect can thus be considered a major public health issue. Child neglect is an ecological and systemic phenomenon characterized by a dual disruption: first, in the relationship between the parent and child and second, in the relationship between the family and the wider community. Empirical research has quite convincingly demonstrated that parenting behaviors constitute a malleable variable upon which it is possible to act to foster the language development of young children. However, given the multidimensional nature of child neglect, interventions aimed directly at parents are simply not enough to support the language skills of children in this context. Based on a complex family and social conception of neglect, the objective of this article is to propose a logical model illustrating public health services for children experiencing neglect. Such a logical model provides for multiple interventions at the child, family and community levels.

Conclusions

Broader efforts should be made to support the parents in overcoming the challenges of parenthood by addressing the multiple risk factors to which they are exposed. This can be achieved both by striving toward positive environmental conditions, characterized by responsive caregiving in the home and community, and by implementing multilevel interventions within an interdisciplinary and intersectoral approach. The resulting recommendations align with the Individuals with Disabilities Education Act, a law that requires states to provide services to children in early intervention programs (Part C) and kindergartens/schools (Part B).
Quasi-optimal synthesis of an adaptive filter in the problem of estimating the state of dynamic systems
Authors: Kostoglotov Andrey , Penkov Anton , Lazarenko Sergey
Published: December 2020

The problem of synthesis of filters to estimate the state of dynamical systems is considered based on the condition for the maximum of the generalized power function and stationarity of the generalized Lagrangian and Hamiltonian of the estimated system model. The paper demonstrates that the use of invariants in combination with the decomposition principle makes it possible to simplify the equations of controlled motion and reduce them to a system of independent equations in terms of the number of degrees of freedom. This approach reduces the number of unknown parameters of the motion model, which greatly simplifies the adaptation process when developing filters for quasi-optimal estimation of the state parameters of dynamic systems. Comparative analysis of the results of the mathematical simulation shows that the application of the proposed method increases the efficiency of filters of the Kalman structure.