bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of loci associated with susceptibility to bovine paratuberculosis and with the dysregulation of the MECOM, eEF1A2, and U1 spliceosomal RNA expression
Authors: Canive Maria , Fernandez-Jimenez Nora , Casais Rosa , Vázquez Patricia , Lavín José Luis , Bilbao José Ramón , Blanco-Vázquez Cristina , Garrido Joseba M. , Juste Ramón A. , Alonso-Hearn Marta
Published: January 2021

Although genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP) infection, only a few functional mutations for bovine paratuberculosis (PTB) have been characterized. Expression quantitative trait loci (eQTLs) are genetic variants typically located in gene regulatory regions that alter gene expression in an allele-specific manner. eQTLs can be considered as functional links between genomic variants, gene expression, and ultimately phenotype. In the current study, peripheral blood (PB) and ileocecal valve (ICV) gene expression was quantified by RNA-Seq from fourteen Holstein cattle with no lesions and with PTB-associated histopathological lesions in gut tissues. Genotypes were generated from the Illumina LD EuroG10K BeadChip. The associations between gene expression levels (normalized read counts) and genetic variants were analyzed by a linear regression analysis using R Matrix eQTL 2.2. This approach allowed the identification of 192 and 48 cis-eQTLs associated with the expression of 145 and 43 genes in the PB and ICV samples, respectively. To investigate potential relationships between these cis-eQTLs and MAP infection, a case–control study was performed using the genotypes for all the identified cis-eQTLs and phenotypical data (histopathology, ELISA for MAP-antibodies detection, tissue PCR, and bacteriological culture) of 986 culled cows. Our results suggested that the heterozygous genotype in the cis-eQTL-rs43744169 (T/C) was associated with the up-regulation of the MDS1 and EVI1 complex (MECOM) expression, with positive ELISA, PCR, and bacteriological culture results, and with increased risk of progression to clinical PTB. As supporting evidence, the presence of the minor allele was associated with higher MECOM levels in plasma samples from infected cows and with increased MAP survival in an ex-vivo macrophage killing assay. Moreover, the presence of the two minor alleles in the cis-eQTL-rs110345285 (C/C) was associated with the dysregulation of the eukaryotic elongation factor 1-α2 (eEF1A2) expression and with increased ELISA (OD) values. Finally, the presence of the minor allele in the cis-eQTL rs109859270 (C/T) was associated with the up-regulation of the U1 spliceosomal RNA expression and with an increased risk of progression to clinical PTB. The introduction of these novel functional variants into marker-assisted breeding programs is expected to have a relevant effect on PTB control.
Southward spreading of the Changjiang Diluted Water in the La Niña spring of 2008
Authors: Chen Chen-Tung Arthur , Bai Yan , Huang Ting-Hsuan , He Xianqiang , Chen Hsien-Wen , Yu Shujie
Published: January 2021

The La Niña of 2007/2008 was particularly strong, so was the southward flow of the cold, nutrient-rich Changjiang (Yangtze River) Diluted Water (CDW) when the winter monsoon started to blow in the fall. Here we use shipboard data in 2008 in two transects, one in the southwestern East China Sea and one in the southern Taiwan Strait, to show that as late as April in 2008 the CDW was still clearly identifiable when the winter monsoon had weakened. Waters as cold as 16 °C with a salinity lower than 30 still occupied the southwestern East China Sea. Waters of 17 °C and S < 32 could also be found off the coast of China in the central Taiwan Strait. The concentration of NO3 + NO2 was higher than 18 μmol L−1 at both places, which was as much as 40 times higher than the northward moving South China Sea (SCS) water to the east. As a result, the Changjiang River plume may be a significant source of nutrients, particularly N, to the oligotrophic, N-poor SCS, especially in the La Niña years. Indeed, colder and more turbid CDW was more intense and went farther south in 2008 compared with the normal springs of 2006, 2007 and 2009.
Biological autoluminescence as a noninvasive monitoring tool for chemical and physical modulation of oxidation in yeast cell culture
Authors: Bereta Martin , Teplan Michal , Chafai Djamel Eddine , Radil Roman , Cifra Michal
Published: January 2021

Normal or excessive oxidative metabolism in organisms is essential in physiological and pathophysiological processes, respectively. Therefore, monitoring of biological oxidative processes induced by the chemical or physical stimuli is nowadays of extreme importance due to the environment overloaded with various physicochemical factors. Current techniques typically require the addition of chemical labels or light illumination, which perturb the samples to be analyzed. Moreover, the current techniques are very demanding in terms of sample preparation and equipment. To alleviate these limitations, we propose a label-free monitoring tool of oxidation based on biological autoluminescence (BAL). We demonstrate this tool on Saccharomyces cerevisiae cell culture. We showed that BAL can be used to monitor chemical perturbation of yeast due to Fenton reagents initiated oxidation—the BAL intensity changes with hydrogen peroxide concentration in a dose-dependent manner. Furthermore, we also showed that BAL reflects the effects of low-frequency magnetic field on the yeast cell culture, where we observed a disturbance of the BAL kinetics in the exposed vs. control case. Our results contribute to the development of novel techniques for label-free, real-time, noninvasive monitoring of oxidative processes and approaches for their modulation.
Impact of 12-month cryopreservation on endogenous DNA damage in whole blood and isolated mononuclear cells evaluated by the comet assay
Authors: Marino Mirko , Gigliotti Letizia , Møller Peter , Riso Patrizia , Porrini Marisa , Del Bo Cristian
Published: January 2021

The comet assay is an electrophoretic technique used to assess DNA damage, as a marker of genotoxicity and oxidative stress, in tissues and biological samples including peripheral blood mononuclear cells (PBMCs) and whole blood (WB). Although numerous studies are performed on stored samples, the impact of cryopreservation on artifactual formation of DNA damage is not widely considered. The present study aims to evaluate the impact of storage at different time-points on the levels of strand breaks (SBs) and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites in isolated PBMCs and WB. Samples were collected, aliquoted and stored at − 80 °C. DNA damage was analyzed on fresh samples, and subsequently on frozen samples every 2 months up to a year. Results have shown no changes in DNA damage in samples of PBMCs and WB stored for up to 4 months, while a significant increase in SBs and Fpg-sensitive sites was documented starting from 6-month up to 12-month storage of both the samples. In addition, fresh and frozen WB showed higher basal levels of DNA damage compared to PBMCs. In conclusion, WB samples show high levels of DNA damage compared to PBMCs. One-year of storage increased the levels of SBs and Fpg-sensitive sites especially in the WB samples. Based on these findings, the use of short storage times and PBMCs should be preferred because of low background level of DNA damage in the comet assay.
Pseudomonas aeruginosa OprF plays a role in resistance to macrophage clearance during acute infection
Authors: Moussouni Malika , Berry Laurence , Sipka Tamara , Nguyen-Chi Mai , Blanc-Potard Anne-Béatrice
Published: January 2021

While considered an extracellular pathogen, Pseudomonas aeruginosa has been reported to be engulfed by macrophages in cellular and animal models. However, the role of macrophages in P. aeruginosa clearance in vivo remains poorly studied. The major outer membrane porin OprF has been recently shown to be involved in P. aeruginosa fate within cultured macrophages and analysis of an oprF mutant may thus provide insights to better understand the relevance of this intramacrophage stage during infection. In the present study, we investigated for the first time the virulence of a P. aeruginosa oprF mutant in a vertebrate model that harbors functional macrophages, the zebrafish (Danio rerio) embryo, which offers powerful tools to address macrophage–pathogen interactions. We established that P. aeruginosa oprF mutant is attenuated in zebrafish embryos in a macrophage-dependent manner. Visualization and quantification of P. aeruginosa bacteria phagocytosed by macrophages after injection into closed cavities suggested that the attenuated phenotype of oprF mutant is not linked to higher macrophage recruitment nor better phagocytosis than wild-type strain. Using cultured macrophages, we showed an intramacrophage survival defect of P. aeruginosa oprF mutant, which is correlated with elevated association of bacteria with acidic compartments. Notably, treatment of embryos with bafilomycin, an inhibitor of acidification, increased the sensibility of embryos towards both wild-type and oprF mutant, and partially suppressed the attenuation of oprF mutant. Taken together, this work supports zebrafish embryo as state-of-the-art model to address in vivo the relevance of P. aeruginosa intramacrophage stage. Our results highlight the contribution of macrophages in the clearance of P. aeruginosa during acute infection and suggest that OprF protects P. aeruginosa against macrophage clearance by avoiding bacterial elimination in acidified phagosomes.
Chemical staining of particulate organic matter for improved contrast in soil X-ray µCT images
Authors: Maenhout Peter , De Neve Stefaan , Wragg Joanna , Rawlins Barry , De Pue Jan , Van Hoorebeke Luc , Cnudde Veerle , Sleutel Steven
Published: January 2021

Degradability of organic matter (OM) in soil depends on its spatial location in the soil matrix. A recent breakthrough in 3D-localization of OM combined dual-energy X-ray CT-scanning with OsO4 staining of OM. The necessity for synchrotron-based µCT and the use of highly toxic OsO4 severely limit applications in soil biological experiments. Here, we evaluated the potential of alternative staining agents (silver nitrate, phosphomolybdenic acid (PMA), lead nitrate, lead acetate) to selectively enhance X-ray attenuation and contrast of OM in CT volumes of soils containing specific mineral soil particle fractions, obtained via lab-based X-ray µCT. In comparison with OsO4, administration of Ag+ and Pb2+ resulted in insufficient contrast enhancement of OM versus fine silt (< 20 µm) or clay (< 2 µm) mineral particles. The perfusion procedure used in this work induced changes in soil structure. In contrast, PMA staining resulted in a selective increase of OM’s attenuation contrast, which was comparable to OsO4. However, OM discrimination from other soil phases remained a challenge. Further development of segmentation algorithms accounting for grey value patterns and shape of stained particulate OM may enable its automated identification. If successful in undisturbed soils, PMA staining may form an alternative to OsO4 in non-synchrotron based POM detection.
Public perception and awareness of waste management from Benin City
Authors: Adekola P. O. , Iyalomhe F. O. , Paczoski A. , Abebe S. T. , Pawłowska B. , Bąk M. , Cirella G. T.
Published: January 2021

Poor waste management is increasingly becoming a major challenge for municipalities, globally. Unlike previous waste management studies in Nigeria, this study examines the implications of waste management to regional greenhouse gas emissions based on awareness levels and perception of urban inhabitants. Benin City was divided into four residential zones: core, intermediate, suburban, and planned estates. Blocking was utilized to collect data from a total of 2720 randomly selected inhabitants through a self-administered survey. Results reveals low awareness level in terms of indiscrimination dumping of waste, thereby promoting sustainable mitigation and adaptation measures region-wide. It is imperative to integrate various aspects of regional government services such as infrastructure, urban planning and development, socioeconomics, public health, and regulation enforcement. Waste management policy is strengthened via working groups, community, and regional authorities.
Data-driven detection of subtype-specific differentially expressed genes
Authors: Chen Lulu , Lu Yingzhou , Wu Chiung-Ting , Clarke Robert , Yu Guoqiang , Van Eyk Jennifer E. , Herrington David M. , Wang Yue
Published: January 2021

Among multiple subtypes of tissue or cell, subtype-specific differentially-expressed genes (SDEGs) are defined as being most-upregulated in only one subtype but not in any other. Detecting SDEGs plays a critical role in the molecular characterization and deconvolution of multicellular complex tissues. Classic differential analysis assumes a null hypothesis whose test statistic is not subtype-specific, thus can produce a high false positive rate and/or lower detection power. Here we first introduce a One-Versus-Everyone Fold Change (OVE-FC) test for detecting SDEGs. We then propose a scaled test statistic (OVE-sFC) for assessing the statistical significance of SDEGs that applies a mixture null distribution model and a tailored permutation test. The OVE-FC/sFC test was validated on both type 1 error rate and detection power using extensive simulation data sets generated from real gene expression profiles of purified subtype samples. The OVE-FC/sFC test was then applied to two benchmark gene expression data sets of purified subtype samples and detected many known or previously unknown SDEGs. Subsequent supervised deconvolution results on synthesized bulk expression data, obtained using the SDEGs detected from the independent purified expression data by the OVE-FC/sFC test, showed superior performance in deconvolution accuracy when compared with popular peer methods.
The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
Authors: Singhania Akul , Pham John , Dhanwani Rekha , Frazier April , Rezende Dutra Juliana , Marder Karen S. , Phillips Elizabeth , Mallal Simon , Amara Amy W. , Standaert David G. , Sulzer David , Peters Bjoern , Sette Alessandro , Lindestam Arlehamn Cecilia S.
Published: January 2021

The self-antigen α-synuclein (α-syn) was recently shown to be associated with Parkinson’s disease (PD). Here we mapped the T cell receptor (TCR) repertoire of α-syn-specific T cells from six PD patients. The self-antigen α-syn-specific repertoire was compared to the repertoire of T cells specific for pertussis (PT), as a representative foreign antigen that most individuals are exposed to, revealing that the repertoire for α-syn was as diverse as the repertoire for PT. The diversity of PT-specific clonotypes was similar between individuals with PD diagnosis and age-matched healthy controls. We found that the TCR repertoire was specific to each PD patient, and no shared TCRs among patients were defined, likely due to differences in HLA expression that select for different subsets of epitope-specific TCR rearrangements. This study provides the first characterization of α-syn-specific TCR clonotypes in individuals with PD. Antigen-specific TCRs can serve as immunotherapeutics and diagnostics, and means to track longitudinal changes in specific T cells, and disease progression.
Combinatorial analyses reveal cellular composition changes have different impacts on transcriptomic changes of cell type specific genes in Alzheimer’s Disease
Authors: Johnson Travis S. , Xiang Shunian , Dong Tianhan , Huang Zhi , Cheng Michael , Wang Tianfu , Yang Kai , Ni Dong , Huang Kun , Zhang Jie
Published: January 2021

Alzheimer’s disease (AD) brains are characterized by progressive neuron loss and gliosis. Previous studies of gene expression using bulk tissue samples often fail to consider changes in cell-type composition when comparing AD versus control, which can lead to differences in expression levels that are not due to transcriptional regulation. We mined five large transcriptomic AD datasets for conserved gene co-expression module, then analyzed differential expression and differential co-expression within the modules between AD samples and controls. We performed cell-type deconvolution analysis to determine whether the observed differential expression was due to changes in cell-type proportions in the samples or to transcriptional regulation. Our findings were validated using four additional datasets. We discovered that the increased expression of microglia modules in the AD samples can be explained by increased microglia proportions in the AD samples. In contrast, decreased expression and perturbed co-expression within neuron modules in the AD samples was likely due in part to altered regulation of neuronal pathways. Several transcription factors that are differentially expressed in AD might account for such altered gene regulation. Similarly, changes in gene expression and co-expression within astrocyte modules could be attributed to combined effects of astrogliosis and astrocyte gene activation. Gene expression in the astrocyte modules was also strongly correlated with clinicopathological biomarkers. Through this work, we demonstrated that combinatorial analysis can delineate the origins of transcriptomic changes in bulk tissue data and shed light on key genes and pathways involved in AD.
The application of a biostimulant based on tannins affects root architecture and improves tolerance to salinity in tomato plants
Authors: Campobenedetto Cristina , Mannino Giuseppe , Beekwilder Jules , Contartese Valeria , Karlova Rumyana , Bertea Cinzia M.
Published: January 2021

Roots have important roles for plants to withstand adverse environmental conditions, including salt stress. Biostimulant application was shown to enhance plant resilience towards abiotic stresses. Here, we studied the effect of a tannin-based biostimulant on tomato (Solanum lycopersicum L.) grown under salt stress conditions. We investigated the related changes at both root architecture (via imaging and biometric analysis) and gene expression (RNA-Seq/qPCR) levels. Moreover, in order to identify the main compounds potentially involved in the observed effects, the chemical composition of the biostimulant was evaluated by UV/Vis and HPLC-ESI-Orbitrap analysis. Sixteen compounds, known to be involved in root development and having a potential antioxidant properties were identified. Significant increase of root weight (+ 24%) and length (+ 23%) was observed when the plants were grown under salt stress and treated with the biostimulant. Moreover, transcriptome analysis revealed that the application of the biostimulant upregulated 285 genes, most of which correlated to root development and salt stress tolerance. The 171 downregulated genes were mainly involved in nutrient uptake. These data demonstrated that the biostimulant is able not only to restore root growth in salty soils, but also to provide the adequate plant nourishment by regulating the expression of essential transcription factors and stress responsive genes.
A quantum circuit simulator and its applications on Sunway TaihuLight supercomputer
Authors: Wang Zhimin , Chen Zhaoyun , Wang Shengbin , Li Wendong , Gu Yongjian , Guo Guoping , Wei Zhiqiang
Published: January 2021

Classical simulation of quantum computation is vital for verifying quantum devices and assessing quantum algorithms. We present a new quantum circuit simulator developed on the Sunway TaihuLight supercomputer. Compared with other simulators, the present one is distinguished in two aspects. First, our simulator is more versatile. The simulator consists of three mutually independent parts to compute the full, partial and single amplitudes of a quantum state with different methods. It has the function of emulating the effect of noise and support more kinds of quantum operations. Second, our simulator is of high efficiency. The simulator is designed in a two-level parallel structure to be implemented efficiently on the distributed many-core Sunway TaihuLight supercomputer. Random quantum circuits can be simulated with 40, 75 and 200 qubits on the full, partial and single amplitude, respectively. As illustrative applications of the simulator, we present a quantum fast Poisson solver and an algorithm for quantum arithmetic of evaluating transcendental functions. Our simulator is expected to have broader applications in developing quantum algorithms in various fields.
Clinical efficacy of high-flow nasal oxygen in patients undergoing ERCP under sedation
Authors: Cha Boram , Lee Man-Jong , Park Jin-Seok , Jeong Seok , Lee Don Haeng , Park Tae Gyu
Published: January 2021

Hypoxemia can occur during endoscopic retrograde cholangiography (ERCP) and it is difficult to achieve adequate ventilation with the prone position. High-flow nasal oxygen (HFNO) has been recommended to be more effectively help ventilation than conventional low flow oxygen. The aim of this study was to evaluate the effect of HFNO during sedated ERCP and to identify predictors of desaturation during ERCP. The investigated variables were age, gender, American Society of Anesthesiologists classes (ASA), duration of exam, and sedative used for midazolam or/and propofol of 262 patients with sedated ERCP. The differences between categorical and continuous variables were analyzed using the Student’s t test and the chi-square test. Desaturation (SpO2 ≤ 90%) occurred in 9(3.4%) patients among 262 patients during sedated ERCP. The variables found to predict desaturation were older age (p < 0.01), higher sedation dose for midazolam or propofol (p < 0.01), and use of midazolam (p < 0.01). Desaturation rate was lower during sedated ERCP with HFNO compared to the preliminary study with conventional low flow nasal oxygen. Patients with older age, higher sedation dose, or the use of midazolam might require close monitoring for desaturation and hypoventilation by nursing staff. The study shows the use of high-flow nasal oxygen reduces the incidence of desaturation during ERCP.
Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression
Authors: Yanagisawa Hayato , Sugimoto Masahiro , Miyashita Tomoyuki
Published: January 2021

Excessive tumour growth results in a hypoxic environment around cancer cells, thus inducing tumour angiogenesis, which refers to the generation of new blood vessels from pre-existing vessels. This mechanism is biologically and physically complex, with various mathematical simulation models proposing to reproduce its formation. However, although temporary vessel regression is clinically known, few models succeed in reproducing this phenomenon. Here, we developed a three-dimensional simulation model encompassing both angiogenesis and tumour growth, specifically including angiopoietin. Angiopoietin regulates both adhesion and migration between vascular endothelial cells and wall cells, thus inhibiting the cell-to-cell adhesion required for angiogenesis initiation. Simulation results showed a regression, i.e. transient decrease, in the overall length of new vessels during vascular network formation. Using our model, we also evaluated the efficacy of administering the drug bevacizumab. The results highlighted differences in treatment efficacy: (1) earlier administration showed higher efficacy in inhibiting tumour growth, and (2) efficacy depended on the treatment interval even with the administration of the same dose. After thorough validation in the future, these results will contribute to the design of angiogenesis treatment protocols.
Protein–protein interaction network analysis applied to DNA copy number profiling suggests new perspectives on the aetiology of Mayer–Rokitansky–Küster–Hauser syndrome
Authors: Pontecorvi Paola , Bernardini Laura , Capalbo Anna , Ceccarelli Simona , Megiorni Francesca , Vescarelli Enrica , Bottillo Irene , Preziosi Nicoletta , Fabbretti Maria , Perniola Giorgia , Benedetti Panici Pierluigi , Pizzuti Antonio , Grammatico Paola , Marchese Cinzia
Published: January 2021

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare disease, characterised by the aplasia of vagina and uterus in women with a 46,XX karyotype. Most cases are sporadic, but familial recurrence has also been described. Herein, we investigated an Italian cohort of 36 unrelated MRKH patients to explore the presence of pathogenic copy number variations (CNVs) by array-CGH and MLPA assays. On the whole, aberrations were found in 9/36 (25%) patients. Interestingly, one patient showed a novel heterozygous microduplication at Xp22.33, not yet described in MRKH patients, containing the PRKX gene. Moreover, a novel duplication of a specific SHOX enhancer was highlighted by MLPA. To predict the potential significance of CNVs in MRKH pathogenesis, we provided a network analysis for protein-coding genes found in the altered genomic regions. Although not all of these genes taken individually showed a clear clinical significance, their combination in a computational network highlighted that the most relevant biological connections are related to the anatomical structure development. In conclusion, the results described in the present study identified novel genetic alterations and interactions that may be likely involved in MRKH phenotype determination, so adding new insights into the complex puzzle of MRKH disease.
Spatially intermixed objects of different categories are parsed automatically
Authors: Khvostov Vladislav A. , Lukashevich Anton O. , Utochkin Igor S.
Published: January 2021

Our visual system is able to separate spatially intermixed objects into different categorical groups (e.g., berries and leaves) using the shape of feature distribution: Determining whether all objects belong to one or several categories depends on whether the distribution has one or several peaks. Despite the apparent ease of rapid categorization, it is a very computationally demanding task, given severely limited “bottlenecks” of attention and working memory capable of processing only a few objects at a time. Here, we tested whether this rapid categorical parsing is automatic or requires attention. We used the visual mismatch negativity (vMMN) ERP component known as a marker of automatic sensory discrimination. 20 volunteers (16 female, mean age—22.7) participated in our study. Loading participants’ attention with a central task, we observed a substantial vMMN response to unattended background changes of categories defined by certain length-orientation conjunctions. Importantly, this occurred in conditions where the distributions of these features had several peaks and, hence, supported categorical separation. These results suggest that spatially intermixed objects are parsed into distinct categories automatically and give new insight into how the visual system can bypass the severe processing restrictions and form rich perceptual experience.
Do beta-adrenergic blocking agents increase asthma exacerbation? A network meta-analysis of randomized controlled trials
Authors: Huang Kuo-Yang , Tseng Ping-Tao , Wu Yi-Cheng , Tu Yu-Kang , Stubbs Brendon , Su Kuan-Pin , Matsuoka Yutaka J. , Hsu Chih-Wei , Lin Ching-Hsiung , Chen Yen-Wen , Lin Pao-Yen
Published: January 2021

Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma exacerbation is one of the major adverse effects of beta-blockers. This study aimed to compare the level of risk for an asthma attack in patients receiving various beta-blockers. We searched for randomized controlled trials (RCTs) of either placebo-controlled or active-controlled design. The current network meta-analysis (NMA) was conducted under a frequentist model. The primary outcome was the incidence of asthmatic attack. A total of 24 RCTs were included. Overall NMA revealed that only oral timolol [risk ratio (RR) = 3.35 (95% confidence interval (CI) 1.04–10.85)] and infusion of propranolol [RR = 10.19 (95% CI 1.29–80.41)] were associated with significantly higher incidences of asthma attack than the placebo, whereas oral celiprolol [RR = 0.39 (95% CI 0.04–4.11)], oral celiprolol and propranolol [RR = 0.46 (95% CI 0.02–11.65)], oral bisoprolol [RR = 0.46 (95% CI 0.02–11.65)], oral atenolol [RR = 0.51 (95% CI 0.20–1.28)], infusion of practolol [RR = 0.80 (95% CI 0.03–25.14)], and infusion of sotalol [RR = 0.91 (95% CI 0.08–10.65)] were associated with relatively lower incidences of asthma attack than the placebo. In participants with a baseline asthma history, in addition to oral timolol and infusion of propranolol, oral labetalol, oxprenolol, propranolol, and metoprolol exhibited significantly higher incidences of asthma attack than did the placebo. In conclusion, oral timolol and infusion of propranolol were associated with a significantly higher risk of developing an asthma attack in patients, especially in those with a baseline asthma history, and should be avoided in patients who present a risk of asthma.

Trial registration: PROSPERO CRD42020190540.
High baseball loads induce shoulder and elbow injuries among high school baseball pitchers: a prospective study
Authors: Shitara Hitoshi , Tajika Tsuyoshi , Kuboi Takuro , Ichinose Tsuyoshi , Sasaki Tsuyoshi , Hamano Noritaka , Endo Takafumi , Kamiyama Masataka , Simoyama Daisuke , Suzuki Junki , Yamamoto Atsushi , Kobayashi Tsutomu , Takagishi Kenji , Chikuda Hirotaka
Published: January 2021

Studies on the relationship between baseball loads (practice, training, and competition hours) and shoulder and elbow injuries among high school pitchers are limited. Therefore, this study included 92 male high school baseball pitchers and evaluated their preseason shoulder and elbow conditions. All participants completed a self-recorded questionnaire regarding baseball load, presence of shoulder pain or elbow pain, or both, and pitching limitations due to shoulder and/or elbow pain experienced daily to determine the occurrence of injuries and record the baseball load. The optimal load cutoff value was determined using a receiver operating characteristic curve analysis. Participants were categorized into high-load and low-load groups according to the aforementioned cutoff value. The Kaplan–Meier method was used to obtain time-to-event curves, and cox proportional hazards models were used to calculate the hazard ratios for injury rates. The cutoff value of the average baseball load was 324.4 min per day. A high load (> 5.5 h/day) led to a 2.6-times greater risk of injuries and 3.3-times earlier occurrence of injuries than a low load (< 5.5 h/day). Therefore, a high load is a risk factor for shoulder and elbow injuries in high school baseball pitchers.
Long rDNA amplicon sequencing of insect-infecting nephridiophagids reveals their affiliation to the Chytridiomycota and a potential to switch between hosts
Authors: Strassert Jürgen F. H. , Wurzbacher Christian , Hervé Vincent , Antany Taraha , Brune Andreas , Radek Renate
Published: January 2021

Nephridiophagids are unicellular eukaryotes that parasitize the Malpighian tubules of numerous insects. Their life cycle comprises multinucleate vegetative plasmodia that divide into oligonucleate and uninucleate cells, and sporogonial plasmodia that form uninucleate spores. Nephridiophagids are poor in morphological characteristics, and although they have been tentatively identified as early-branching fungi based on the SSU rRNA gene sequences of three species, their exact position within the fungal tree of live remained unclear. In this study, we describe two new species of nephridiophagids (Nephridiophaga posticiandNephridiophaga javanicae) from cockroaches. Using long-read sequencing of the nearly complete rDNA operon of numerous further species obtained from cockroaches and earwigs to improve the resolution of the phylogenetic analysis, we found a robust affiliation of nephridiophagids with the Chytridiomycota—a group of zoosporic fungi that comprises parasites of diverse host taxa, such as microphytes, plants, and amphibians. The presence of the same nephridiophagid species in two only distantly related cockroaches indicates that their host specificity is not as strict as generally assumed.
Crystallization of ZnO thin films via thermal dissipation annealing method for high-performance UV photodetector with ultrahigh response speed
Authors: Kim Dongwan , Leem Jae-Young
Published: January 2021

ZnO-based ultraviolet (UV) photodetector can be easily fabricated by using sol–gel spin-coating method, however, the crystallization of amorphous state ZnO thin films is necessary to fabricate high performance UV photodetector. Thus, we devised a thermal dissipation annealing (TDA) method in which the heat transfer to the ZnO thin films can be synchronized with the heat release from the substrate. It was found that sol–gel spin-coated ZnO thin films can be crystallized through the mobility difference of ZnO molecules placed at the surface of ZnO thin films. Also, UV photodetector based on ZnO thin films annealed with the TDA method exhibited faster rise and decay time constant (τr = 35 ms and τd = 73 ms, respectively), a higher on/off current ratio, and reproducible photocurrent characteristics compared to that of the ZnO thin films annealed by using furnace and IR lamp. Therefore, these results indicated that the TDA method is a feasible alternative route for the fabrication of ZnO based high performance optoelectronic devices.
Effects of anthropogenic activities on microplastics in deposit-feeders (Diptera: Chironomidae) in an urban river of Taiwan
Authors: Lin Chun-Ting , Chiu Ming-Chih , Kuo Mei-Hwa
Published: January 2021

The presence of microplastics (MPs) in the environment has generated global concerns. However, the explicit assessment of the effect of multiple anthropogenic activities on the existence of MPs in the freshwater system is scarcely reported. This study quantified anthropogenic activities and analyzed their relationship with MPs on a freshwater organism: the midge larvae (Diptera: Chironomidae). The study took place in an urban river and consisted of comparing the abundance and types of MPs. Our results highlight that, while industrial area was the most important variable contributing to the total MP concentration in midge larvae, residential area also influenced the concentration of microfibers in midge larvae. The impact of a residential area on the relative abundance of microfibers in each sample site was diluted by the proximity to an industrial area. In conclusion, we suggest that industrial areas are a potential source of MP pollution in river sediment, and midge larvae can be a good indicator of the MP concentrations in urban river systems. Quantifying anthropogenic activities can help discern their effects on MP concentration in a river system and promote management strategies.
Green algae scatter off sharp viscosity gradients
Authors: Coppola Simone , Kantsler Vasily
Published: January 2021

We study the behaviour of the green alga Chlamydomonas reinhardtii (CR) in the presence of neighbouring regions of different viscosity. We show that the velocity and angular diffusion of the algae decreases when the viscosity of the surrounding medium is increased. We report on a phenomenon occurring when the algae try to cross from a region of low viscosity to a highly viscous one, which causes CR to re-orient and scatter away from the interface if it is approached at a sufficiently small angle. We highlight that the effect does not occur for CR crossing from high to low viscosity regions. Lastly we show that algae do not concentrate in the region of high viscosity despite them swimming slower there. On the contrary, they concentrate in the region of low viscosity or maintain a uniform concentration profile, depending on the viscosity ratio between the two regions.
Enhancer-derived long non-coding RNAs CCAT1 and CCAT2 at rs6983267 has limited predictability for early stage colorectal carcinoma metastasis
Authors: Thean Lai Fun , Blöcker Christopher , Li Hui Hua , Lo Michelle , Wong Michelle , Tang Choong Leong , Tan Emile K. W. , Rozen Steven G. , Cheah Peh Yean
Published: January 2021

Up-regulation of long non-coding RNAs (lncRNAs), colon-cancer associated transcript (CCAT) 1 and 2, was associated with worse prognosis in colorectal cancer (CRC). Nevertheless, their role in predicting metastasis in early-stage CRC is unclear. We measured the expression of CCAT1, CCAT2 and their oncotarget, c-Myc, in 150 matched mucosa-tumour samples of early-stage microsatellite-stable Chinese CRC patients with definitive metastasis status by multiplex real-time RT-PCR assay. Expression of CCAT1, CCAT2 and c-Myc were significantly up-regulated in the tumours compared to matched mucosa (p < 0.0001). The expression of c-Myc in the tumours was significantly correlated to time to metastasis [hazard ratio = 1.47 (1.10–1.97)] and the risk genotype (GG) of rs6983267, located within CCAT2. Expression of c-Myc and CCAT2 in the tumour were also significantly up-regulated in metastasis-positive compared to metastasis-negative patients (p = 0.009 and p = 0.04 respectively). Nevertheless, integrating the expression of CCAT1 and CCAT2 by the Random Forest classifier did not improve the predictive values of ColoMet19, the mRNA-based predictor for metastasis previously developed on the same series of tumours. The role of these two lncRNAs is probably mitigated via their oncotarget, c-Myc, which was not ranked high enough previously to be included in ColoMet19.
ABBV-744 as a potential inhibitor of SARS-CoV-2 main protease enzyme against COVID-19
Authors: Fakhar Zeynab , Khan Shama , AlOmar Suliman Y. , Alkhuriji Afrah , Ahmad Aijaz
Published: January 2021

A new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and become pandemic with thousands new deaths and infected cases globally. To address coronavirus disease (COVID-19), currently no effective drug or vaccine is available. This necessity motivated us to explore potential lead compounds by considering drug repurposing approach targeting main protease (Mpro) enzyme of SARS-CoV-2. This enzyme considered to be an attractive drug target as it contributes significantly in mediating viral replication and transcription. Herein, comprehensive computational investigations were performed to identify potential inhibitors of SARS-CoV-2 Mpro enzyme. The structure-based pharmacophore modeling was developed based on the co-crystallized structure of the enzyme with its biological active inhibitor. The generated hypotheses were applied for virtual screening based PhaseScore. Docking based virtual screening workflow was used to generate hit compounds using HTVS, SP and XP based Glide GScore. The pharmacological and physicochemical properties of the selected lead compounds were characterized using ADMET. Molecular dynamics simulations were performed to explore the binding affinities of the considered lead compounds. Binding energies revealed that compound ABBV-744 binds to the Mpro with strong affinity (ΔGbind −45.43 kcal/mol), and the complex is more stable in comparison with other protein–ligand complexes. Our study classified three best compounds which could be considered as promising inhibitors against main protease SARS-CoV-2 virus.
Metallic one-dimensional heterostructure for gas molecule sensing
Authors: Bhuyan Prabal Dev , Gupta Sanjeev K. , Ahuja Rajeev , Gajjar P. N.
Published: January 2021

We have investigated a new metallic core–shell nanowire (NW) geometry of that could be obtained experimentally, that is silicon (Si) and germanium (Ge) NWs with cores constituted by group-10 elements palladium (Pd) and platinum (Pt). These NWs are optimized with two different diameters of 1.5 Å and 2.5 Å. The nanowires having diameter of 1.5 Å show semi-metallic nature with GGA-PBE calculation and metallic nature while spin orbit interaction (SOC) is included. The quantum conductance of the NWs increases with the diameter of the nanowire. We have investigated current–voltage (IV) characteristics for the considered NWs. It has been found that current values in accordance with applied voltage show strong dependence on the diameter of the NWs. The optical study of the NWs shows that absorption co-efficient peak moves to lower energies; due to quantum confinement effect. Furthermore, we have extensively studied optical response of Pd and Pt based core–shell NWs in O2 and CO2 environment. Our study on Si and Ge based metallic core/shell NW show a comprehensive picture as possible electron connector in future nano-electronic devices as well as nano gas detector for detecting O2 gas.
Lipid accumulation patterns and role of different fatty acid types towards mitigating salinity fluctuations in Chlorella vulgaris
Authors: Teh Kit Yinn , Loh Saw Hong , Aziz Ahmad , Takahashi Kazutaka , Effendy Abd Wahid Mohd , Cha Thye San
Published: January 2021

Mangrove-dwelling microalgae are well adapted to frequent encounters of salinity fluctuations across their various growth phases but are lesser studied. The current study explored the adaptive changes (in terms of biomass, oil content and fatty acid composition) of mangrove-isolated C. vulgaris UMT-M1 cultured under different salinity levels (5, 10, 15, 20, 30 ppt). The highest total oil content was recorded in cultures at 15 ppt salinity (63.5% of dry weight) with uncompromised biomass productivity, thus highlighting the ‘trigger-threshold’ for oil accumulation in C. vulgaris UMT-M1. Subsequently, C. vulgaris UMT-M1 was further assessed across different growth phases under 15 ppt. The various short, medium and long-chain fatty acids (particularly C20:0), coupled with a high level of C18:3n3 PUFA reported at early exponential phase represents their physiological importance during rapid cell growth. Accumulation of C18:1 and C18:2 at stationary growth phase across all salinities was seen as cells accumulating substrate for C18:3n3 should the cells anticipate a move from stationary phase into new growth phase. This study sheds some light on the possibility of ‘triggered’ oil accumulation with uninterrupted growth and the participation of various fatty acid types upon salinity mitigation in a mangrove-dwelling microalgae.
Fractal structures arising from interfacial instabilities in bio-oil atomization
Authors: Ghasemi Abbas , Yun Sangsig , Li Xianguo
Published: January 2021

The intriguing multi-scale fractal patterns ubiquitously observed in nature similarly emerge as fascinating structures in two-phase fluid flows of bio-oil breakup and atomization processes. High-resolution microscopy of the two-phase flows under 15 flow conditions (cases of different flow rates of the liquid and co-flowing air streams as well as different degrees of liquid preheating) reveal that the geometrical complexities evolve under the competing/combined action of the instability mechanisms such as Kelvin–Helmholtz, Rayleigh–Taylor and Rayleigh–Plateau leading into the transition from break-up to atomization. A thorough analysis of the higher order moments of statistics evaluated based on the probability density functions from 15,000 fractal dimension samples suggest that a single-value analysis is not sufficient to describe the complex reshaping mechanisms in two-phase flows. Consistently positive skewness of the statistics reveal the role of abrupt two-phase mechanisms such as liquid column rupture, ligament disintegration, liquid sheet bursting and droplet distortions in a hierarchical geometrical entanglement. Further, large kurtosis values at increased flow inertia are found associated with turbulence-induced intermittent geometrical reshaping. Interestingly, the proposed power-law correlation reveals that the global droplet size obtained from laser-diffraction measurements declines as the two-phase geometrical complexity increases.
Collision-enhanced friction of a bouncing ball on a rough vibrating surface
Authors: Smith N. D. , Swift M. R. , Smith M. I.
Published: January 2021

We describe experiments and simulations to investigate the dynamics of a ball bouncing on a rough vibrating surface. Directly measuring the impulse due to each bounce we find that the frictional interaction with the surface is strongly enhanced near to the side wall. The enhanced dissipation arises as a consequence of the coupling between the collision, rotation and surface friction. This dissipation, which for our experimental conditions was estimated to be up to three times larger than the more obvious inelastic collision, can result in an enhanced probability density near boundaries and particle–particle spatial correlations. Our findings imply that the effective particle collision properties cannot be considered independently of the surface’s frictional properties.
Genome sequence and organization of the Mythimna (formerly Pseudaletia) unipuncta granulovirus Hawaiian strain
Authors: Li Yinü , Liu Xingjian , Tang Ping , Zhang Huan , Qin Qilian , Zhang Zhifang
Published: January 2021

Purified occlusion bodies (OBs) of Mythimna (formerly Pseudaletia) unipuncta (the true armyworm) granulovirus Hawaiian strain (MyunGV-A) were observed, showing typical GV morphological characteristics under scanning and transmission electron microscopy (EM). The genome of MyunGV-A was completely sequenced and analysed. The genome is 176,677 bp in size, with a G+C content of 39.79%. It contains 183 open reading frames (ORFs) encoding 50 or more amino acids with minimal overlap. Comparison of MyunGV-A with TnGV, XcGV, and HearGV genomes revealed extensive sequence similarity and collinearity, and the four genomes contain the same nine homologous regions (hrs) with conserved structures and locations. Three unique genes, 12 baculovirus repeated ORF (bro), 2 helicase, and 3 enhancin genes, were identified. In particular, two repeated genes (ORF39 and 49) are present in the genome, in reverse and complementarily orientations. Twenty-four OB proteins were identified from the putative protein database of MyunGV-A. In addition, MyunGV-A belongs to the Betabaculovirus group and is most closely related to TnGV (99% amino acid identity) according to a phylogenetic tree based on the combined amino acid sequences of 38 core gene contents.
Diagnostic accuracy of tomosynthesis-guided vacuum assisted breast biopsy of ultrasound occult lesions
Authors: Bohan Suhaila , Ramli Hamid Marlina Tanty , Chan Wai Yee , Vijayananthan Anushya , Ramli Norlisah , Kaur Shaleen , Rahmat Kartini
Published: January 2021

This study aims to evaluate the diagnostic accuracy of digital breast tomosynthesis-guided vacuum assisted breast biopsy (DBT-VABB) of screening detected suspicious mammographic abnormalities comprising of calcifications, asymmetric densities, architectural distortions and spiculated masses. In this institutionally approved study, a total of 170 (n = 170) DBT-VABB were performed, 153 (90%) were for calcifications, 8 (4.7%) for spiculated mass, 5 (2.9%) for asymmetric density and 4 (2.4%) for architectural distortion. All these lesions were not detected on the corresponding ultrasound. Histopathology results revealed 140 (82.4%) benign, 9 (5.3%) borderline and 21 (12.4%) malignant lesions. The total upgrade rate at surgery was 40% for atypical ductal hyperplasia and 5.9% for ductal carcinoma in-situ. 3.6% discordant benign lesions showed no upgrade. DBT-VABB showed 100% specificity, 91.3% sensitivity and 100% positive predictive value (PPV) for detecting malignant lesions. The negative predictive value (NPV) was 80%. 2 (1.2%) patients had mild complications and 1 (0.6%) had severe pain. Our study showed that DBT-VABB was a safe and reliable method, with high sensitivity, specificity, PPV and NPV in the diagnosis of non-palpable benign and malignant breast lesions. Our data also confirmed the accuracy of DBT-VABB in detecting malignant lesions and we suggest further surgical excision in borderline lesions for a more accurate diagnostic evaluation.