bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic characteristics and pathogenesis of H5 low pathogenic avian influenza viruses from wild birds and domestic ducks in South Korea
Authors: Lee Yu-Na , Lee Dong-Hun , Cheon Sun-Ha , Park Yu-Ri , Baek Yoon-Gi , Si Young-Jae , Kye Soo-Jeong , Lee Eun-Kyoung , Heo Gyeong-Beom , Bae You-Chan , Lee Myoung-Heon , Lee Youn-Jeong 
Published: July 2020

AbstractH5 and H7 subtypes of low pathogenic avian influenza viruses (LPAIVs) can mutate to highly pathogenic forms and are therefore subject to stringent controls. We characterized H5 LPAIVs isolated from wild-bird habitats and duck farms in South Korea from 2010 to 2017. Through nationwide active surveillance for AIVs, 59 H5 LPAIVs were isolated from wild-bird habitats (a mean annual rate of 5.3% of AIV isolations). In 2015, one LPAI H5N3 strain was isolated on a duck farm. Phylogenetic analysis revealed that the hemagglutinin (HA) gene of H5 isolates belonged to the Eurasian lineage, classified into three subgroups (HA-II, HA-III, and HA-IV). The H5 LPAIVs of the HA-III and HA-IV subgroups appeared in 2015 and 2017 in unusually high proportions (13.1% and 14.4%, respectively). In gene-constellation analysis, H5 LPAIVs isolated from 2015 to 2017 constituted ≥ 35 distinct genotypes, representing high levels of genetic diversity. Representative strains of three HA subgroups replicated restrictively in specific-pathogen-free chickens. Among the 11 isolates that were tested, 10 infected and replicated in mice without prior adaptation. The frequency of recent H5 LPAIV isolates with high genetic diversity indicates the importance of continued surveillance in both wild birds and poultry to monitor genetic and pathobiological changes.
A somatic evolutionary model of the dynamics of aneuploid cells during hematopoietic reconstitution
Authors: Rozhok Andrii I. , Silberman Rebecca E. , Higa Kelly C. , Liggett L. Alex , Amon Angelika , DeGregori James 
Published: July 2020

AbstractAneuploidy is a feature of many cancers. Recent studies demonstrate that in the hematopoietic stem and progenitor cell (HSPC) compartment aneuploid cells have reduced fitness and are efficiently purged from the bone marrow. However, early phases of hematopoietic reconstitution following bone marrow transplantation provide a window of opportunity whereby aneuploid cells rise in frequency, only to decline to basal levels thereafter. Here we demonstrate by Monte Carlo modeling that two mechanisms could underlie this aneuploidy peak: rapid expansion of the engrafted HSPC population and bone marrow microenvironment degradation caused by pre-transplantation radiation treatment. Both mechanisms reduce the strength of purifying selection acting in early post-transplantation bone marrow. We explore the contribution of other factors such as alterations in cell division rates that affect the strength of purifying selection, the balance of drift and selection imposed by the HSPC population size, and the mutation-selection balance dependent on the rate of aneuploidy generation per cell division. We propose a somatic evolutionary model for the dynamics of cells with aneuploidy or other fitness-reducing mutations during hematopoietic reconstitution following bone marrow transplantation. Similar alterations in the strength of purifying selection during cancer development could help explain the paradox of aneuploidy abundance in tumors despite somatic fitness costs.
Mining whole genome sequence data to efficiently attribute individuals to source populations
Authors: Pérez-Reche Francisco J. , Rotariu Ovidiu , Lopes Bruno S. , Forbes Ken J. , Strachan Norval J. C. 
Published: July 2020

AbstractWhole genome sequence (WGS) data could transform our ability to attribute individuals to source populations. However, methods that efficiently mine these data are yet to be developed. We present a minimal multilocus distance (MMD) method which rapidly deals with these large data sets as well as methods for optimally selecting loci. This was applied on WGS data to determine the source of human campylobacteriosis, the geographical origin of diverse biological species including humans and proteomic data to classify breast cancer tumours. The MMD method provides a highly accurate attribution which is computationally efficient for extended genotypes. These methods are generic, easy to implement for WGS and proteomic data and have wide application.
HIV-1 and HIV-2 prevalence, risk factors and birth outcomes among pregnant women in Bissau, Guinea-Bissau: a retrospective cross-sectional hospital study
Authors: Rasmussen Dlama Nggida , Vieira Noel , Hønge Bo Langhoff , da Silva Té David , Jespersen Sanne , Bjerregaard-Andersen Morten , Oliveira Inés , Furtado Alcino , Gomes Magarida Alfredo , Sodemann Morten , Wejse Christian , Unger Holger Werner 
Published: July 2020

AbstractThe human immunodeficiency virus (HIV) remains a leading cause of maternal morbidity and mortality in Sub-Saharan Africa. Prevention of mother-to-child transmission (PMTCT) has proven an effective strategy to end paediatric infections and ensure HIV-infected mothers access treatment. Based on cross-sectional data collected from June 2008 to May 2013, we assessed changes in HIV prevalence, risk factors for HIV, provision of PMTCT antiretroviral treatment (ART), and the association between HIV infection, birth outcomes and maternal characteristics at the Simão Mendes National Hospital, Guinea-Bissau’s largest maternity ward. Among 24,107 women, the HIV prevalence was 3.3% for HIV-1, 0.8% for HIV-2 and 0.9% for HIV-1/2. A significant decline in HIV-1, HIV-2, and HIV-1/2 prevalence was observed over time. HIV infection was associated with age and ethnicity. A total of 85% of HIV-infected women received ART as part of PMTCT, yet overall treatment coverage during labour and delivery declined significantly for both mothers and infants. Twenty-two percent of infants did not receive treatment, and 67% of HIV-2-infected mothers and 77% of their infants received ineffective non-nucleoside reverse transcriptase inhibitors for PMTCT. Maternal HIV was associated with low birth weight but not stillbirth. Inadequate continuity of care and ART coverage present challenges to optimal PMTCT in Guinea-Bissau.
Microenvironment-triggered dual-activation of a photosensitizer- fluorophore conjugate for tumor specific imaging and photodynamic therapy
Authors: Wang Chang , Wang Shengdan , Wang Yuan , Wu Honghai , Bao Kun , Sheng Rong , Li Xin 
Published: July 2020

AbstractPhotodynamic therapy is attracting increasing attention, but how to increase its tumor-specificity remains a daunting challenge. Herein we report a theranostic probe (azo-PDT) that integrates pyropheophorbide α as a photosensitizer and a NIR fluorophore for tumor imaging. The two functionalities are linked with a hypoxic-sensitive azo group. Under normal conditions, both the phototoxicity of the photosensitizer and the fluorescence of the fluorophore are inhibited. While under hypoxic condition, the reductive cleavage of the azo group will restore both functions, leading to tumor specific fluorescence imaging and phototoxicity. The results showed that azo-PDT selectively images BEL-7402 cells under hypoxia, and simultaneously inhibits BEL-7402 cell proliferation after near-infrared irradiation under hypoxia, while little effect on BEL-7402 cell viability was observed under normoxia. These results confirm the feasibility of our design strategy to improve the tumor-targeting ability of photodynamic therapy, and presents azo-PDT probe as a promising dual functional agent.
Size resolved characteristics of urban and suburban bacterial bioaerosols in Japan as assessed by 16S rRNA amplicon sequencing
Authors: Tanaka Daisuke , Fujiyoshi So , Maruyama Fumito , Goto Motoshi , Koyama Shinichi , Kanatani Jun-ichi , Isobe Junko , Watahiki Masanori , Sakatoku Akihiro , Kagaya Shigehiro , Nakamura Shogo 
Published: July 2020

AbstractTo study the size-resolved characteristics of airborne bacterial community composition, diversity, and abundance, outdoor aerosol samples were analysed by 16S rRNA gene-targeted quantitative PCR and amplicon sequencing with Illumina MiSeq. The samples were collected using size-resolved samplers between August and October 2016, at a suburban site in Toyama City and an urban site in Yokohama City, Japan. The bacterial communities were found to be dominated by Actinobacteria, Firmicutes, and Proteobacteria. At the genus level, we found a high abundance of human skin-associated bacteria, such as Propionibacterium, Staphylococcus, and Corynebacterium, in the urban site. Whereas, a high abundance of bacteria associated with soil and plants, such as Methylobacterium and Sphingomonas, was observed in the suburban site. Furthermore, our data revealed a shift in the bacterial community structure, diversity, and abundance of total bacteria at a threshold of 1.1-µm diameter. Interestingly, we observed that Legionella spp., the causal agents of legionellosis in humans, were mainly detected in > 2.1 µm coarse particles. Our data indicate that local environmental factors including built environments could influence the outdoor airborne bacterial community at each site. These results provide a basis for understanding the size-resolved properties of bacterial community composition, diversity, and abundance in outdoor aerosol samples and their potential influence on human health.
Conditional and unconditional genome-wide association study reveal complicate genetic architecture of human body weight and impacts of smoking
Authors: Xu Ting , Monir Md. Mamun , Lou Xiang-Yang , Xu Haiming , Zhu Jun 
Published: July 2020

AbstractTo reveal the impacts of smoking on genetic architecture of human body weight, we conducted a genome-wide association study on 5,336 subjects in four ethnic populations from MESA (The Multi-Ethnic Study of Atherosclerosis) data. A full genetic model was applied to association mapping for analyzing genetic effects of additive, dominance, epistasis, and their ethnicity-specific effects. Both the unconditional model (base) and conditional model including smoking as a cofactor were investigated. There were 10 SNPs involved in 96 significant genetic effects detected by the base model, which accounted for a high heritability (61.78%). Gene ontology analysis revealed that a number of genetic factors are related to the metabolic pathway of benzopyrene, a main compound in cigarettes. Smoking may play important roles in genetic effects of dominance, dominance-related epistasis, and gene-ethnicity interactions on human body weight. Gene effect prediction shows that the genetic effects of smoking cessation on body weight vary from different populations.
Unique genomic and neoepitope landscapes across tumors: a study across time, tissues, and space within a single lynch syndrome patient
Authors: Phung Tanya N. , Lenkiewicz Elizabeth , Malasi Smriti , Sharma Amit , Anderson Karen S. , Wilson Melissa A. , Pockaj Barbara A. , Barrett Michael T. 
Published: July 2020

AbstractLynch syndrome (LS) arises in patients with pathogenic germline variants in DNA mismatch repair genes. LS is the most common inherited cancer predisposition condition and confers an elevated lifetime risk of multiple cancers notably colorectal and endometrial carcinomas. A distinguishing feature of LS associated tumors is accumulation of variants targeting microsatellite repeats and the potential for high tumor specific neoepitope levels. Recurrent somatic variants targeting a small subset of genes have been identified in tumors with microsatellite instability. Notably these include frameshifts that can activate immune responses and provide vaccine targets to affect the lifetime cancer risk associated with LS. However the presence and persistence of targeted neoepitopes across multiple tumors in single LS patients has not been rigorously studied. Here we profiled the genomic landscapes of five distinct treatment naïve tumors, a papillary transitional cell renal cell carcinoma, a duodenal carcinoma, two metachronous colorectal carcinomas, and multi-regional sampling in a triple-negative breast tumor, arising in a LS patient over 10 years. Our analyses suggest each tumor evolves a unique complement of variants and that vaccines based on potential neoepitopes from one tissue may not be effective across all tumors that can arise during the lifetime of LS patients.
A G-quadruplex-binding compound shows potent activity in human gemcitabine-resistant pancreatic cancer cells
Authors: Ahmed Ahmed Abdullah , Marchetti Chiara , Ohnmacht Stephan A. , Neidle Stephen 
Published: July 2020

AbstractGemcitabine is a drug of choice in the treatment of human pancreatic cancer. Chemo-resistance to this drug is common and has been attributed to a variety of distinct mechanisms, involving > 100 genes. A recently developed small-molecule G-quadruplex ligand, the trisubstituted naphthalene diimide compound CM03, has previously been shown to have equivalent potency to gemcitabine in the pancreatic cancer cell line MIA PaCa-2. We report here on cell lines of increased resistance to gemcitabine that have been generated from this line, with the most resistant having 1,000-fold reduced sensitivity to gemcitabine. These resistant lines retain nM sensitivity to CM03. The molecular basis for the retention of potency by this G-quadruplex ligand has been examined using whole transcriptome data analysis with RNA-seq. This has revealed that the pattern of pathways down regulated by CM03 in the parental MIA PaCa-2 cell line is largely unaffected in the gemcitabine-resistant line. The analysis has also shown that the expression patterns of numerous genes involved in gemcitabine sensitivity are down regulated in the resistant line upon CM03 treatment. These results are supportive of the concept that G-quadruplex small molecules such as CM03 have potential for clinical use in the treatment of gemcitabine-resistant human pancreatic cancer.
Inherited variations in human pigmentation-related genes modulate cutaneous melanoma risk and clinicopathological features in Brazilian population
Authors: Lourenço Gustavo Jacob , Oliveira Cristiane , Carvalho Benilton Sá , Torricelli Caroline , Silva Janet Keller , Gomez Gabriela Vilas Bôas , Rinck-Junior José Augusto , Oliveira Wesley Lima , Vazquez Vinicius Lima , Serrano Sergio Vicente , Moraes Aparecida Machado , Lima Carmen Silvia Passos 
Published: July 2020

AbstractUltraviolet light exposure and cutaneous pigmentation are important host risk factors for cutaneous melanoma (CM), and it is well known that inherited ability to produce melanin varies in humans. The study aimed to identify single-nucleotide variants (SNVs) on pigmentation-related genes with importance in risk and clinicopathological aspects of CM. The study was conducted in two stages. In stage 1, 103 CM patients and 103 controls were analyzed using Genome-Wide Human SNV Arrays in order to identify SNVs in pigmentation-related genes, and the most important SNVs were selected for data validation in stage 2 by real-time polymerase-chain reaction in 247 CM patients and 280 controls. ADCY3 c.675+9196T>G, CREB1 c.303+373G>A, and MITF c.938-325G>A were selected for data validation among 74 SNVs. Individuals with CREB1 GA or AA genotype and allele “A” were under 1.79 and 1.47-fold increased risks of CM than others, respectively. Excesses of CREB1 AA and MITF AA genotype were seen in patients with tumors at Clark levels III to V (27.8% versus 13.7%) and at III or IV stages (46.1% versus 24.9%) compared to others, respectively. When compared to others, patients with ADCY3 TT had 1.89 more chances of presenting CM progression, and those with MITF GA or AA had 2.20 more chances of evolving to death by CM. Our data provide, for the first time, preliminary evidence that inherited abnormalities in ADCY3, CREB1, and MITF pigmentation-related genes, not only can increase the risk to CM, but also influence CM patients’ clinicopathological features.
DNA damage and antioxidant properties of CORM-2 in normal and cancer cells
Authors: Juszczak Michał , Kluska Magdalena , Wysokiński Daniel , Woźniak Katarzyna 
Published: July 2020

AbstractIn this study, we compared the effect of tricarbonyldichlororuthenium (II) dimer (CORM-2) and its CO-depleted molecule (iCORM-2) on human peripheral blood mononuclear cells (PBMCs) and human promyelocytic leukemia HL-60 cells. We determined cell viability, DNA damage and DNA repair kinetics. We also studied the effect of both compounds on DNA oxidative damage, free radical level and HO-1 gene expression. We showed that at low concentrations both CORM-2 and iCORM-2 stimulate PBMCs viability. After 24-h incubation, CORM-2 and iCORM-2, at the concentration of 100 µM, reduce the viability of both PBMCs and HL-60 cells. We also demonstrated that CORM-2 and iCORM-2, in the 0.01–100 µM concentration range, cause DNA damage such as strand breaks and alkaline labile sites. DNA damage was repaired efficiently only in HL-60 cells. CORM-2 significantly reduces oxidative stress induced by 1 mM H2O2 in normal and cancer cells. On the contrary, iCORM-2 in HL-60 cells increases the level of free radicals in the presence of 1 and 5 mM H2O2. We also revealed that both CORM-2 and iCORM-2 induce HO-1 gene expression. However, CORM-2 induces this gene to a greater extent than iCORM-2, especially in HL-60 cells at 100 µM. Finally, we showed that CORM-2 and iCORM-2 reduce H2O2-induced DNA oxidative damage. Furthermore, CORM-2 proved to be a compound with stronger antioxidant properties than iCORM-2. Our results suggest that both active CORM-2 and inactive iCORM-2 exert biological effects such as cyto- and genotoxicity, antioxidant properties and the ability to induce the HO-1 gene. The released CO as well as iCORM-2 can be responsible for these effects.
Correlation of electroretinography components with visual function and prognosis of central retinal artery occlusion
Authors: Kim Hyeong Min , Park Kyu Hyung , Woo Se Joon 
Published: July 2020

AbstractWe investigated the full-field electroretinographic (ERG) parameters with visual function and prognosis in central retinal artery occlusion (CRAO), according to its severity. 110 affected eyes of CRAO patients were enrolled and compared with fellow uninvolved eyes (N = 110) and normal control eyes (N = 30). B/A ratio and photopic negative response amplitude (PhNR) resulted in statistically significant differences among the CRAO subgroups according to the severity of retinal ischemia. Amplitudes of PhNR indicating ganglion cell function showed a more marked decline in mild to severe ischemia than those of the B-wave. In terms of visual function and outcome, baseline visual acuity and visual field defects were correlated with B/A ratio only (both, P < .001), whereas improvements in visual acuity and visual field were correlated with B-wave amplitude in dark-adapted 3.0 (P = .004 and .006), B/A ratio (P = .023 and .008), and PhNR amplitude (P < .001 and .004). These three ERG parameters were found to be credible predictive factors of visual prognosis. In conclusion, B-wave amplitude in dark-adapted 3.0, B/A ratio, and PhNR amplitude changes in eyes with CRAO are associated with baseline features related to the severity of retinal ischemia, and these are correlated with visual function and prognosis.
Improved understanding of biofilm development by Piscirickettsia salmonis reveals potential risks for the persistence and dissemination of piscirickettsiosis
Authors: Levipan Héctor A. , Irgang Rute , Yáñez Alejandro , Avendaño-Herrera Ruben 
Published: July 2020

AbstractPiscirickettsia salmonis is the causative agent of piscirickettsiosis, a disease with high socio-economic impacts for Chilean salmonid aquaculture. The identification of major environmental reservoirs for P. salmonis has long been ignored. Most microbial life occurs in biofilms, with possible implications in disease outbreaks as pathogen seed banks. Herein, we report on an in vitro analysis of biofilm formation by P. salmonis Psal-103 (LF-89-like genotype) and Psal-104 (EM-90-like genotype), the aim of which was to gain new insights into the ecological role of biofilms using multiple approaches. The cytotoxic response of the salmon head kidney cell line to P. salmonis showed interisolate differences, depending on the source of the bacterial inoculum (biofilm or planktonic). Biofilm formation showed a variable-length lag-phase, which was associated with wider fluctuations in biofilm viability. Interisolate differences in the lag phase emerged regardless of the nutritional content of the medium, but both isolates formed mature biofilms from 288 h onwards. Psal-103 biofilms were sensitive to Atlantic salmon skin mucus during early formation, whereas Psal-104 biofilms were more tolerant. The ability of P. salmonis to form viable and mucus-tolerant biofilms on plastic surfaces in seawater represents a potentially important environmental risk for the persistence and dissemination of piscirickettsiosis.
Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile
Authors: Gaiani Federica , Rotoli Bianca Maria , Ferrari Francesca , Barilli Amelia , Visigalli Rossana , Carra Maria Clotilde , de’Angelis Gian Luigi , de’Angelis Nicola , Dall’Asta Valeria 
Published: July 2020

AbstractCrohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30–40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNFα, IL-23, IL-1β and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNFα, IL-1β, IFNγ and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes’ cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay.
Impact of individual actions on the collective response of social systems
Authors: Martin-Gutierrez Samuel , Losada Juan C. , Benito Rosa M. 
Published: July 2020

AbstractIn a social system individual actions have the potential to trigger spontaneous collective reactions. The way and extent to which the activity (number of actions—A) of an individual causes or is connected to the response (number of reactions—R) of the system is still an open question. We measure the relationship between activity and response with the distribution of efficiency, a metric defined as $$\eta =R/A$$η=R/A. Generalizing previous results, we show that the efficiency distribution presents a universal structure in three systems of different nature: Twitter, Wikipedia and the scientific citations network. To understand this phenomenon, we develop a theoretical framework composed of three minimal statistical models that contemplate different levels of dependence between A and R. The models not only are able to reproduce the empirical activity-response data but also can serve as baselines or null models for more elaborated and domain-specific approaches.