bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and validation of prognosis‐related DLX5 methylation as an epigenetic driver in myeloid neoplasms
Authors: Zhang Ting‐juan , Xu Zi‐jun , Gu Yu , Wen Xiang‐mei , Ma Ji‐chun , Zhang Wei , Deng Zhao‐qun , Leng Jia‐yan , Qian Jun , Lin Jiang , Zhou Jing‐dong 
Published: June 2020

AbstractThe deregulated DLX gene family members DLX1/2/3/4/5/6 (DLXs) caused by DNA methylation has been demonstrated in various cancers with therapeutic target value. However, the potential role of DLXs methylation in myeloid neoplasms such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) remains to be elucidated. Clinical significance of DLXs methylation/expression was analyzed in patient with AML and MDS. The functional roles of DLXs were determined in vitro. In the identification stage, we found that lower DLX5 expression was correlated with prognosis in AML among all DLXs analyzed by The Cancer Genome Atlas datasets. In the validation stage, we revealed that reduced DLX5 expression was frequently occurred, and was also correlated with promoter hypermethylation in AML evaluated by targeted bisulfite sequencing. Epigenetic studies also showed that DLX5 promoter DNA methylation was associated with its expression. By quantitative polymerase chain reaction, we also validated that DLX5 hypermethylation was frequent event in both AML and MDS, and also correlated with MDS transformation to leukemia. Moreover, DLX5 hypermethylation was associated with lower rate of complete remission and shorter time of leukemia‐free/overall survival, and was also confirmed by Logistic/Cox regression analysis. Functional studies revealed the antiproliferative and pro‐apoptotic effects of DLX5 in MDS‐derived AML cell‐line SKM‐1. Finally, bioinformatics analysis demonstrated that DLX5 functioned in leukemogenesis may be through the association with PI3K/Akt signaling pathway. Collectively, our findings demonstrated that DLX5 methylation, negatively correlated DLX5 expression, was a potential prognostic and predictive indicator in patients with AML and MDS, which could also act as an epigenetic driver in myeloid neoplasms.
A new and rapid approach for detecting COVID‐19 based on S1 protein fragments
Authors: Li Hua , Liu Zhe , He Yue , Qi Yingjie , Chen Jie , Ma Yuanyuan , Liu Fujia , Lai Kaisheng , Zhang Yong , Jiang Liu , Wang Xiangdong , Ge Junbo 
Published: June 2020

AbstractThe pandemic of novel coronavirus disease 2019 (COVID‐19) seriously threatened the public health all over the world. A colloidal gold immunochromatography assay for IgM/IgG antibodies against the receptor‐binding domain of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) S1 protein was established to assess its rapid diagnostic value. We first designed and manufactured all contents of the test cassette of SARS‐CoV‐2 rapid test kit: the colloidal gold‐labeled mouse‐antihuman lgM/lgG antibody, the recombinant SARS‐CoV‐2 antigen, the nitrocellulose membrane control line, and specimen diluents. Furthermore, reverse transcription‐polymerase chain reaction (RT‐PCR) assay, colloidal gold immunochromatography assay, serological validation of cross reaction with other common viruses, and clinical validation were performed. The kit was finally evaluated by 75 serum/plasma samples of SARS‐CoV‐2 infection cases and 139 healthy samples as control, with the result of that the sensitivity, specificity, and accuracy for IgM were 90.67%, 97.84%, and 95.33%, whereas for IgG were 69.33%, 99.28%, and 88.79%, respectively; the combination of IgM and IgG could improve the value: 92.00%, 97.12%, and 95.33%, respectively. Therefore, the rapid detection kit has high sensitivity and specificity, especially for IgM&IgG, showing a critical value in clinical application and epidemic control of COVID‐19.
40 Years of My Venture with CYTOMETRY
Authors: Darzynkiewicz Zbigniew 
Published: June 2020

AbstractBriefly depicted are the publications in CYTOMETRY that received the highest frequency of citations. Among them are seminal papers describing application of metachromatic fluorochrome acridine orange to differentially stain DNA versus RNA or to analyze susceptibility of DNA in situ to denaturation; both features being markers of different sections of the cell cycle including identification of noncycling quiescent cells. The papers reviewing detection of cyclins D1, E, A or B1, each in relation to cell cycle phase, were also among the highly cited ones. The highest citation rates received publications describing development of the TUNEL methodology to detect apoptotic DNA fragmentation, and more recently expression of ϒH2AX to reveal DNA damage. © 2020 International Society for Advancement of Cytometry
Examining differences in phylogenetic composition enhances understanding of the phylogenetic structure of the shrub community in the northeastern Qinghai‐Tibetan Plateau
Authors: Xiao Yuanming , Yang Lucun , Nie Xiuqing , Li Changbin , Xiong Feng , Wang Lingling , Zhou Guoying 
Published: June 2020

AbstractPeriodic climatic oscillations and species dispersal during the postglacial period are two important causes of plant assemblage and distribution on the Qinghai‐Tibet Plateau (QTP). To improve our understanding of the bio‐geological histories of shrub communities on the QTP, we tested two hypotheses. First, the intensity of climatic oscillations played a filtering role during community structuring. Second, species dispersal during the postglacial period contributed to the recovery of species and phylogenetic diversity and the emergence of phylogenetic overdispersion. To test these hypotheses, we investigated and compared the shrub communities in the alpine and desert habitats of the northeastern QTP. Notably, we observed higher levels of species and phylogenetic diversity in the alpine habitat than in the desert habitat, leading to phylogenetic overdispersion in the alpine shrub communities versus phylogenetic clustering in the desert shrub communities. This phylogenetic overdispersion increased with greater climate anomalies. These results suggest that (a) although climate anomalies strongly affect shrub communities, these phenomena do not act as a filter for shrub community structuring, and (b) species dispersal increases phylogenetic diversity and overdispersion in a community. Moreover, our investigation of the phylogenetic community composition revealed a larger number of plant clades in the alpine shrub communities than in the desert shrub communities, which provided insights into plant clade‐level differences in the phylogenetic structures of alpine and desert shrub communities in the northeastern QTP.
Transcriptome analysis of Drosophila melanogaster laboratory strains of different geographical origin after long‐term laboratory maintenance
Authors: Zarubin Mikhail , Yakhnenko Alena , Kravchenko Elena 
Published: June 2020

AbstractPositive selection may be the main factor of the between‐population divergence in gene expression. Expression profiles of two Drosophila melanogaster laboratory strains of different geographical origin and long‐term laboratory maintenance were analyzed using microchip arrays encompassing probes for 18,500 transcripts. The Russian strain D18 and the North American strain Canton‐S were compared. A set of 223 known or putative genes demonstrated significant changes in expression levels between these strains. Differentially expressed genes (DEG) were enriched in response to DDT (p = .0014), proteolysis (p = 2.285E−5), transmembrane transport (p = 1.03E−4), carbohydrate metabolic process (p = .0317), protein homotetramerization (p = .0444), and antibacterial humoral response (p = 425E−4). The expression in subset of genes from different categories was verified by qRT‐PCR. Analysis of transcript abundance between Canton‐S and D18 strains allowed to select several genes to estimate their participation in latitude adaptation. Expression of selected genes was analyzed in five D. melanogaster lines of different geographic origins by qRT‐PCR, and we found two candidate genes that may be associated with latitude adaptation in adult flies—smp‐30 and Cda9. Quite possible that several alleles of these genes may be important for insect survival in the environments of global warming. It is interesting that the number of genes involved in local adaptation demonstrates expression level appropriate to their geographical origin even after decades of laboratory maintenance.
Bayesian nonparametric monotone regression
Authors: Wilson Ander , Tryner Jessica , L'Orange Christian , Volckens John 
Published: June 2020

AbstractIn many applications there is interest in estimating the relation between a predictor and an outcome when the relation is known to be monotone or otherwise constrained due to the physical processes involved. We consider one such application‐inferring time‐resolved aerosol concentration from a low‐cost differential pressure sensor. The objective is to estimate a monotone function and make inference on the scaled first derivative of the function. We proposed Bayesian nonparametric monotone regression, which uses a Bernstein polynomial basis to construct the regression function and puts a Dirichlet process prior on the regression coefficients. The base measure of the Dirichlet process is a finite mixture of a mass point at zero and a truncated normal. This construction imposes monotonicity while clustering the basis functions. Clustering the basis functions reduces the parameter space and allows the estimated regression function to be linear. With the proposed approach we can make closed‐formed inference on the derivative of the estimated function including full quantification of uncertainty. In a simulation study the proposed method performs similar to other monotone regression approaches when the true function is wavy but performs better when the true function is linear. We apply the method to estimate time‐resolved aerosol concentration with a newly developed portable aerosol monitor. TheRpackagebnmris made available to implement the method.
Assessing exposure effects on gene expression
Authors: Reifeis Sarah A. , Hudgens Michael G. , Civelek Mete , Mohlke Karen L. , Love Michael I. 
Published: June 2020

AbstractIn observational genomics data sets, there is often confounding of the effect of an exposure on gene expression. To adjust for confounding when estimating the exposure effect, a common approach involves including potential confounders as covariates with the exposure in a regression model of gene expression. However, when the exposure and confounders interact to influence gene expression, the fitted regression model does not necessarily estimate the overall effect of the exposure. Using inverse probability weighting (IPW) or the parametric g‐formula in these instances is straightforward to apply and yields consistent effect estimates. IPW can readily be integrated into a genomics data analysis pipeline with upstream data processing and normalization, while the g‐formula can be implemented by making simple alterations to the regression model. The regression, IPW, and g‐formula approaches to exposure effect estimation are compared herein using simulations; advantages and disadvantages of each approach are explored. The methods are applied to a case study estimating the effect of current smoking on gene expression in adipose tissue.
Power loss due to testing association between covariate‐adjusted traits and genetic variants
Authors: Yajnik Pranav , Boehnke Michael 
Published: June 2020

AbstractMultiple linear regression is commonly used to test for association between genetic variants and continuous traits and estimate genetic effect sizes. Confounding variables are controlled for by including them as additional covariates. An alternative technique that is increasingly used is to regress out covariates from the raw trait and then perform regression analysis with only the genetic variants included as predictors. In the case of single‐variant analysis, this adjusted trait regression (ATR) technique is known to be less powerful than the traditional technique when the genetic variant is correlated with the covariates We extend previous results for single‐variant tests by deriving exact relationships between the single‐variant score, Wald, likelihood‐ratio, and F test statistics and their ATR analogs. We also derive the asymptotic power of ATR analogs of the multiple‐variant score and burden tests. We show that the maximum power loss of the ATR analog of the multiple‐variant score test is completely characterized by the canonical correlations between the set of genetic variants and the set of covariates. Further, we show that for both single‐ and multiple‐variant tests, the power loss for ATR analogs increases with increasing stringency of Type 1 error control () and increasing correlation (or canonical correlations) between the genetic variant (or multiple variants) and covariates. We recommend using ATR only when maximum canonical correlation between variants and covariates is low, as is typically true.
Autonomic flexibility reflects learning and associated neuroplasticity in old age
Authors: Chen Quanjing , Yang Haichuan , Rooks Brian , Anthony Mia , Zhang Zhengwu , Tadin Duje , Heffner Kathi L. , Lin Feng V. 
Published: June 2020

AbstractEffective learning in old age, particularly in those at risk for dementia, is essential for prolonging independent living. Individual variability in learning, however, is remarkable; that is, months of cognitive training to improve learning may be beneficial for some individuals but not others. So far, little is known about which neurophysiological mechanisms account for the observed variability in learning induced by cognitive training in older adults. By combining Lövdén et al.'s (2010, A theoretical framework for the study of adult cognitive plasticity. Psychological Bulletin, 136, 659–676) framework proposing the role of adaptation capacity in neuroplasticity and a neurovisceral integration model of the relationship between autonomic nervous system (ANS) and brain with a novel shapelet analytical approach that allows for accurate and interpretable analysis of time series data, we discovered an acute, ECG‐derived ANS segment in response to cognitive training tasks at baseline that predicted learning outcomes from a 6‐week cognitive training intervention. The relationship between the ANS segment and learning was robust in both cross‐participant and cross‐task analyses among a group of older adults with amnestic mild cognitive impairment. Furthermore, the revealed ANS shapelet significantly predicted training‐induced neuroplasticity in the dorsal anterior cingulate cortex and select frontal regions during task fMRI. Across outcome measures, individuals were less likely to prospectively benefit from the cognitive training if their ECG data were more similar to this particular ANS segment at baseline. Our findings are among the first empirical evidence to confirm that adaptation capacity, indexed by ANS flexibility, predicts individual differences in learning and associated neuroplasticity beyond individual characteristics (e.g., age, education, neurodegeneration, total training).
On point in primary CNS lymphoma
Authors: Tsang Mazie , Cleveland Joseph , Rubenstein James L. 
Published: June 2020

AbstractPrimary CNS lymphoma (PCNSL) is an aggressive brain tumor that represents a significant challenge both to elucidate its biological pathogenesis as well as to develop definitive precision medicines with minimal collateral toxicity. We highlight the key issues in diagnosis and treatment and focus on emerging technologies, current options among consolidation strategies, and biological agents. We anticipate that further development of molecular diagnostics and molecular imaging approaches that elucidate minimal residual disease in brain parenchyma, leptomeninges, intraocular compartments and even bone marrow will greatly impact the delivery and timing of cytotoxic and biological therapies. Implementation of these approaches is likely essential to clarify ongoing discrepancies in the interpretation of clinical trial results that currently are based on relatively unrefined definitions of response. While the results of early phase investigations involving ibrutinib and the IMiD agents, lenalidomide, pomalidomide, as well as avadomide, strongly support the hypothesis that the B‐cell receptor (BCR) pathway, involving MYD88 and CD79B and NF‐kB activation, is critical to the pathogenesis of PCNSL, much work is needed to elucidate mechanisms of resistance. Similarly, development of strategies to overcome immunosuppressive mechanisms that are upregulated in the tumor microenvironment is a high priority. Finally, ongoing evidence supports the hypothesis that the blood‐brain barrier represents a significant impediment to efficient brain tumor penetration of novel therapeutic agents and innovative strategies of drug delivery remain essential to further improve outcomes.
Perceptions of obstetricians and pediatricians about the risk of COVID‐19 for pregnant women and newborns
Authors: Obeidat Nail , Saadeh Rami , Obeidat Maha , Khasawneh Wasim , Khader Yousef , Alfaqih Mahmoud 
Published: June 2020

AbstractObjectiveTo assess the perception of obstetricians and pediatricians about risks of COVID‐19 to pregnant women and possible complications in newborns.MethodsA structured 27‐item online survey was sent via social media messaging to obstetricians and pediatricians from public, academic, and private sectors in Jordan between March 23–30, 2020. Descriptive statistics were used to represent numbers and percentages of participants’ responses to survey items.ResultsA total of 147 physicians participated (107 obstetricians, 40 pediatricians). Participants were well informed about the symptoms, diagnosis, modes of transmission, and methods of prevention. Participants had variable perceptions about COVID‐19 risk during pregnancy, including potential vertical transmission, preferred route of delivery, and safety of breastfeeding. Most participants felt that pregnant women should be prioritized for testing and medical care provision.ConclusionWhile evidence‐based strategies to reduce the risks of COVID‐19 in pregnant women and newborns are evolving, healthcare providers showed excellent knowledge of the infection and were vigilant regarding its complications for mothers and newborns. To ensure safe pregnancy, physicians must keep informed of developing guidance on best and safest prenatal and perinatal health services. Implementing local hospital policies and adequate training in infection control measures is strongly encouraged.
Clinical characteristics and laboratory results of pregnant women with COVID‐19 in Wuhan, China
Authors: Wang Zhiqiang , Wang Zhigang , Xiong Guoping 
Published: June 2020

AbstractObjectiveTo evaluate the clinical characteristics and laboratory test results in pregnant women with coronavirus disease 2019 (COVID‐19).MethodsA retrospective study to review and compare clinical data including electronic medical records and laboratory tests from pregnant and nonpregnant patients admitted the Central Hospital of Wuhan, China from December 8, 2019 to April 1, 2020.ResultsA total of 72 women (30 pregnant and 42 nonpregnant) with COVID‐19 were included. No patients developed severe pneumonia during the study. Compared with the nonpregnant group, pregnant patients were admitted to hospital earlier (0.25 vs 11.00 days; P<0.001), presented milder symptoms, had a higher rate of asymptomatic infection (26.7% vs 0%), and shorter length of hospital stay (14.5 vs 17.0 days; P<0.01). Laboratory test results showed that levels of inflammation markers such as white blood cell count, neutrophil count and percentage, C‐reactive protein, procalcitonin, and D‐dimer were significantly higher in pregnant women, whereas mean lymphocyte percentage was significantly lower compared with nonpregnant women.ConclusionIn some respects, the clinical characteristics and laboratory test results of COVID‐19 in pregnant patients seems to be distinctive from their nonpregnant counterparts. Appropriate advice and positive treatment might be critical to the prognosis when dealing with these pregnant patients. Pregnant patients with COVID‐19 had their own positive clinical characteristics and special laboratory test results. Responsive medical advice and active treatment for those patients are critical to recovery.
Conformational and electronic study of dopamine interacting with the D2 dopamine receptor
Authors: Tosso Rodrigo D. , Parravicini Oscar , Zarycz M. Natalia C. , Angelina Emilio , Vettorazzi Marcela , Peruchena Nélida , Andujar Sebastián , Enriz Ricardo D. 
Published: June 2020

AbstractWe report an exhaustive conformational and electronic study on dopamine (DA) interacting with the D2 dopamine receptor (D2DR). For the first time, the complete surface of the conformational potential energy of the complex DA/D2DR is reported. Such a surface was obtained through the use of QM/MM calculations. A detailed study of the molecular interactions that stabilize and destabilize the different molecular complexes was carried out using two techniques: Quantum Theory of Atoms in Molecules computations and nuclear magnetic shielding constants calculations. A comparative study of the behavior of DA in the gas phase, aqueous solution, and in the active site of D2DR has allowed us to evaluate the degree of deformation suffered by the ligand and, therefore, analyze how rustic are the lock‐key model and the induced fit theory in this case. Our results allow us to propose one of the conformations obtained as the “biologically relevant” conformation of DA when it is interacting with the D2DR.
Exploration of the molecular characteristics of the tumor–immune interaction and the development of an individualized immune prognostic signature for neuroblastoma
Authors: Jin Wenyi , Zhang Yubiao , Liu Zilin , Che Zhifei , Gao Mingyong , Peng Hao 
Published: June 2020

AbstractNeuroblastoma (NBL) exists in a complex tumor–immune microenvironment. Immune cell infiltration and tumor–immune molecules play a critical role in tumor development and significantly impact the prognosis of patients. However, the molecular characteristics describing the NBL–immune interaction and their prognostic potential have yet to be investigated systematically. We first employed multiple machine learning algorithms, such as Gene Sets Enrichment Analysis and cell type identification by estimating relative subsets of RNA transcripts, to identify immunophenotypes and immunological characteristics in NBL patient data from public databases and then investigated the prognostic potential and regulatory networks of identified immune‐related genes involved in the NBL–immune interaction. The immunity signature combining nine immunity genes was confirmed as more effective for individual risk stratification and survival outcome prediction in NBL patients than common clinical characteristics (area under the curve [AUC] = 0.819, C‐index = 0.718, p < .001). A mechanistic exploration revealed the regulatory network of molecules involved in the NBL–immune interaction. These immune molecules were also discovered to possess a significant correlation with plasma cell infiltration, MYCN status, and the level of chemokines and macrophage‐related molecules (p < .001). A nomogram was constructed based on the immune signature and clinical characteristics, which showed high potential for prognosis prediction (AUC = 0.856, C‐index = 0.755, p < .001). We systematically elucidated the complex regulatory mechanisms and characteristics of the molecules involved in the NBL–immune interaction and their prognostic potential, which may have important implications for further understanding the molecular mechanism of the NBL–immune interaction and identifying high‐risk NBL patients to guide clinical treatment.