bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZMYND11-MBTD1 induces leukemogenesis through hijacking NuA4/TIP60 acetyltransferase complex and a PWWP-mediated chromatin association mechanism
Authors: Li Jie , Galbo Phillip M. , Gong Weida , Storey Aaron J. , Tsai Yi-Hsuan , Yu Xufen , Ahn Jeong Hyun , Guo Yiran , Mackintosh Samuel G. , Edmondson Ricky D. , Byrum Stephanie D. , Farrar Jason E. , He Shenghui , Cai Ling , Jin Jian , Tackett Alan J. , Zheng Deyou , Wang Gang Greg 
Published: February 2021

AbstractRecurring chromosomal translocation t(10;17)(p15;q21) present in a subset of human acute myeloid leukemia (AML) patients creates an aberrant fusion gene termed ZMYND11-MBTD1 (ZM); however, its function remains undetermined. Here, we show that ZM confers primary murine hematopoietic stem/progenitor cells indefinite self-renewal capability ex vivo and causes AML in vivo. Genomics profilings reveal that ZM directly binds to and maintains high expression of pro-leukemic genes including Hoxa, Meis1, Myb, Myc and Sox4. Mechanistically, ZM recruits the NuA4/Tip60 histone acetyltransferase complex to cis-regulatory elements, sustaining an active chromatin state enriched in histone acetylation and devoid of repressive histone marks. Systematic mutagenesis of ZM demonstrates essential requirements of Tip60 interaction and an H3K36me3-binding PWWP (Pro-Trp-Trp-Pro) domain for oncogenesis. Inhibitor of histone acetylation-‘reading’ bromodomain proteins, which act downstream of ZM, is efficacious in treating ZM-induced AML. Collectively, this study demonstrates AML-causing effects of ZM, examines its gene-regulatory roles, and reports an attractive mechanism-guided therapeutic strategy.
Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells
Authors: Duhen Rebekka , Ballesteros-Merino Carmen , Frye Alexandra K. , Tran Eric , Rajamanickam Venkatesh , Chang Shu-Ching , Koguchi Yoshinobu , Bifulco Carlo B. , Bernard Brady , Leidner Rom S. , Curti Brendan D. , Fox Bernard A. , Urba Walter J. , Bell R. Bryan , Weinberg Andrew D. 
Published: February 2021

AbstractDespite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of anti-OX40 on lymphocyte subsets in the tumor and blood. Neoadjuvant anti-OX40 was well tolerated and did not delay surgery, thus meeting the primary endpoint. Peripheral blood phenotyping data show increases in CD4+ and CD8+ T cell proliferation two weeks after anti-OX40 administration. Comparison of tumor biopsies before and after treatment reveals an increase of activated, conventional CD4+ tumor-infiltrating lymphocytes (TIL) in most patients and higher clonality by TCRβ sequencing. Analyses of CD8+ TIL show increases in tumor-antigen reactive, proliferating CD103+ CD39+ cells in 25% of patients with evaluable tumor tissue (N = 4/16), all of whom remain disease-free. These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. Our work suggests that increases in the tumor-reactive CD103+ CD39+ CD8+ TIL could serve as a potential biomarker of anti-OX40 clinical activity.
Causal modulation of right hemisphere fronto-parietal phase synchrony with Transcranial Magnetic Stimulation during a conscious visual detection task
Authors: Stengel Chloé , Vernet Marine , Amengual Julià L. , Valero-Cabré Antoni 
Published: February 2021

AbstractCorrelational evidence in non-human primates has reported increases of fronto-parietal high-beta (22–30 Hz) synchrony during the top-down allocation of visuo-spatial attention. But may inter-regional synchronization at this specific frequency band provide a causal mechanism by which top-down attentional processes facilitate conscious visual perception? To address this question, we analyzed electroencephalographic (EEG) signals from a group of healthy participants who performed a conscious visual detection task while we delivered brief (4 pulses) rhythmic (30 Hz) or random bursts of Transcranial Magnetic Stimulation (TMS) to the right Frontal Eye Field (FEF) prior to the onset of a lateralized target. We report increases of inter-regional synchronization in the high-beta band (25–35 Hz) between the electrode closest to the stimulated region (the right FEF) and right parietal EEG leads, and increases of local inter-trial coherence within the same frequency band over bilateral parietal EEG contacts, both driven by rhythmic but not random TMS patterns. Such increases were accompained by improvements of conscious visual sensitivity for left visual targets in the rhythmic but not the random TMS condition. These outcomes suggest that high-beta inter-regional synchrony can be modulated non-invasively and that high-beta oscillatory activity across the right dorsal fronto-parietal network may contribute to the facilitation of conscious visual perception. Our work supports future applications of non-invasive brain stimulation to restore impaired visually-guided behaviors by operating on top-down attentional modulatory mechanisms.
Intrinsic DMI-free skyrmion formation and robust dynamic behaviors in magnetic hemispherical shells
Authors: Yang Jaehak , Abert Claas , Suess Dieter , Kim Sang-Koog 
Published: February 2021

AbstractWe performed finite-element micromagnetic simulations to examine the formation of skyrmions without intrinsic Dzyaloshinskii–Moriya interaction (DMI) in magnetic hemispherical shells. We found that curvature-induced DM-like interaction allows for further stabilization of skyrmions without the DMI in curved-geometry hemispherical shells for a specific range of uniaxial perpendicular magnetic anisotropy (PMA) constant Ku. The larger the curvature of the shell, the higher the Ku value required for the formation of the skyrmions. With well-stabilized skyrmions, we also found in-plane gyration modes and azimuthal spin-wave modes as well as an out-of-plane breathing mode, similarly to previously found modes for planar geometries. Furthermore, additional higher-frequency hybrid modes were observed due to coupling between the gyration and azimuthal modes. This work provides further physical insight into the static and dynamic properties of intrinsic DMI-free skyrmions formed in curved-geometry systems.
A molecular dynamics study of the oxidation mechanism, nanostructure evolution, and friction characteristics of ultrathin amorphous carbon films in vacuum and oxygen atmosphere
Authors: Wang Shengxi , Komvopoulos Kyriakos 
Published: February 2021

AbstractAmorphous carbon (a-C) films are characterized by extraordinary chemical inertness and unique thermophysical properties that are critical to applications requiring oxidation-resistant, low-friction, and durable overcoats. However, the increasing demands for ultrathin (a few nanometers thick) a-C films in various emerging technologies, such as computer storage devices, microelectronics, microdynamic systems, and photonics, make experimental evaluation of the structural stability and tribomechanical properties at the atomic level cumbersome and expensive. Consequently, the central objective of this study was to develop comprehensive MD models that can provide insight into the oxidation behavior and friction characteristics of ultrathin a-C films exhibiting layered through-thickness structure. MD simulations were performed for a-C films characterized by relatively low and high sp3 contents subjected to energetic oxygen atom bombardment or undergoing normal and sliding contact against each other in vacuum and oxygen atmosphere. The effect of energetic oxygen atoms on the oxidation behavior of a-C films, the dependence of contact deformation and surface attractive forces (adhesion) on surface interference, and the evolution of friction and structural changes (rehybridization) in the former a-C films during sliding are interpreted in the context of simulations performed in vacuum and oxidizing environments. The present study provides insight into the oxidation mechanism and friction behavior of ultrathin a-C films and introduces a computational framework for performing oxidation/tribo-oxidation MD simulations that can guide experimental investigations.
Synthesis of silver nanoparticles using white-rot fungus Anamorphous Bjerkandera sp. R1: influence of silver nitrate concentration and fungus growth time
Authors: Osorio-Echavarría Jerónimo , Osorio-Echavarría Juliana , Ossa-Orozco Claudia Patricia , Gómez-Vanegas Natalia Andrea 
Published: February 2021

AbstractCurrently, silver nanoparticles (AgNPs) constitute an interesting field of study in medicine, catalysis, optics, among others. For this reason, it has been necessary to develop new methodologies that allow a more efficient production of AgNPs with better antimicrobial and biological properties. In this research growth time effects Anamorphous Bjerkandera sp. R1 and the silver nitrate (AgNO3) concentration over AgNPs synthesis were studied. Through the protocol used in this work, it was found that the action of the capping proteins on the surface of the mycelium played a determining role in the reduction of the Ag+ ion to Ag0 nanoparticles producing a particle size that oscillated between 10 and 100 nm. The progress of the reaction was monitored using visible UV–Vis spectroscopy and the synthesized AgNPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared radiation (FTIR) spectroscopy. The best synthetic properties were found at 1 mM of AgNO3 concentration, growth time of 8 days, and reaction time of 144 h. Nanometals obtention from microorganisms could be considered as a new method of synthesis, due to reducing abilities of metal ions through its enzymatic system and represents low-cost synthesis that reduces the generation of harmful toxic wastes.
Digital gene expression analysis of the response to Ralstonia solanacearum between resistant and susceptible tobacco varieties
Authors: Li YanYan , Wang Lin , Sun GuangWei , Li XiHong , Chen ZhenGuo , Feng Ji , Yang Yong 
Published: February 2021

AbstractTobacco bacterial wilt (TBW) caused by Ralstonia solanacearum is the most serious soil-borne disease of tobacco. However, molecular mechanism information of R. solanacearum resistance is limited to tobacco, hindering better breeding of resistant tobacco. In this study, the expression profiles of the rootstalks of Yunyan87 (susceptible cultivar) and Fandi3 (resistant cultivar) at different stages after R. solanacearum infection were compared to explore molecular mechanisms of tobacco resistance against the bacterium. Findings from gene-expression profiling indicated that the number of upregulated differentially expressed genes (DEGs) at 3 and 7 days post-inoculation (dpi) increased significantly in the resistant cultivar. WRKY6 and WRKY11 family genes in WRKY transcription factors, ERF5 and ERF15 family genes in ERFs transcription factors, and genes encoding PR5 were significantly upregulated in the resistant cultivar response to the infection. For the first time, WRKY11 and ERF15 were found to be possibly involved in disease-resistance. The Kyoto Encyclopedia of Genes and Genomes analysis demonstrated glutathione metabolism and phenylpropane pathways as primary resistance pathways to R. solanacearum infection. In the resistant cultivar, DEGs encoding CYP450, TCM, CCoAOMT, 4CL, PAL, CCR, CSE, and CADH, involved in the synthesis of plant antitoxins such as flavonoids, stilbenoids, and lignins, enriched in the phenylpropane pathway were upregulated at 3 and 7 dpi. Furthermore, a pot experiment was performed to verify the role of flavonoids in controlling TBW. This study will strongly contribute to a better understanding of molecular interactions between tobacco plants and R. solanacearum.
Web of lies: a tool for determining the limits of verification in preventing the spread of false information on networks
Authors: Makovi Kinga , Muñoz-Herrera Manuel 
Published: February 2021

AbstractThe spread of false information on social networks has garnered substantial scientific and popular attention. To counteract this spread, verification of the truthfulness of information has been proposed as a key intervention. Using a novel behavioral experiment with over 2000 participants, we analyze participants’ willingness to spread false information in a network. All participants in the network have aligned incentives making lying attractive and countering the explicit norm of truth-telling that we impose. We investigate how verifying the truth, endogenously or exogenously, impacts the choice to lie or to adhere to the norm of truth-telling and how this compares to the spread of information in a setting in which such verification is not possible. The three key take-aways are (1) verification is only moderately effective in reducing the spread of lies, and (2) its effectivity is contingent on the agency of people in seeking the truth, and (3) on the exposure of liars, not only on the exposure of the lies being told. These results suggest that verification is not a blanket solution. To enhance its effectivity, verification should be combined with efforts to foster a culture of truth-seeking and with information on who is spreading lies.
Evidence for specificity of polygenic contributions to attainment in English, maths and science during adolescence
Authors: Donati Georgina , Dumontheil Iroise , Pain Oliver , Asbury Kathryn , Meaburn Emma L. 
Published: February 2021

AbstractHow well one does at school is predictive of a wide range of important cognitive, socioeconomic, and health outcomes. The last few years have shown marked advancement in our understanding of the genetic contributions to, and correlations with, academic attainment. However, there exists a gap in our understanding of the specificity of genetic associations with performance in academic subjects during adolescence, a critical developmental period. To address this, the Avon Longitudinal Study of Parents and Children was used to conduct genome-wide association studies of standardised national English (N = 5983), maths (N = 6017) and science (N = 6089) tests. High SNP-based heritabilities (h2SNP) for all subjects were found (41–53%). Further, h2SNPfor maths and science remained after removing shared variance between subjects or IQ (N = 3197–5895). One genome-wide significant single nucleotide polymorphism (rs952964, p = 4.86 × 10–8) and four gene-level associations with science attainment (MEF2C, BRINP1,S100A1andS100A13) were identified. Rs952964 remained significant after removing the variance shared between academic subjects. The findings highlight the benefits of using environmentally homogeneous samples for genetic analyses and indicate that finer-grained phenotyping will help build more specific biological models of variance in learning processes and abilities.
Examination of structure and optical properties of Ce3+-doped strontium borate glass by regression analysis
Authors: Masai Hirokazu , Ohkubo Takahiro , Fujii Yasuhiro , Koreeda Akitoshi , Yanagida Takayuki , Ina Toshiaki , Kintaka Kenji 
Published: February 2021

AbstractAmorphous materials with non-periodic structures are commonly evaluated based on their chemical composition, which is not always the best parameter to evaluate physical properties, and an alternative parameter more suitable for performance evaluation must be considered. Herein, we quantified various structural and physical properties of Ce-doped strontium borate glasses and studied their correlations by principal component analysis. We found that the density-driven molar volume is suitable for the evaluation of structural data, while chemical composition is better for the evaluation of optical and luminescent data. Furthermore, the borate-rich glasses exhibited a stronger luminescence due to Ce3+, indicating a higher fraction of BO3/2 ring and larger cavity. Moreover, the internal quantum efficiency was found to originate from the local coordination states of the Ce3+ centres, independent of composition or molar volume. The comparison of numerical data of the matrix is useful not only for ensuring the homogenous doping of amorphous materials by activators, but also for determining the origin of physical properties.
Uncertainty quantification in the radiogenomics modeling of EGFR amplification in glioblastoma
Authors: Hu Leland S. , Wang Lujia , Hawkins-Daarud Andrea , Eschbacher Jennifer M. , Singleton Kyle W. , Jackson Pamela R. , Clark-Swanson Kamala , Sereduk Christopher P. , Peng Sen , Wang Panwen , Wang Junwen , Baxter Leslie C. , Smith Kris A. , Mazza Gina L. , Stokes Ashley M. , Bendok Bernard R. , Zimmerman Richard S. , Krishna Chandan , Porter Alyx B. , Mrugala Maciej M. , Hoxworth Joseph M. , Wu Teresa , Tran Nhan L. , Swanson Kristin R. , Li Jing 
Published: February 2021

AbstractRadiogenomics uses machine-learning (ML) to directly connect the morphologic and physiological appearance of tumors on clinical imaging with underlying genomic features. Despite extensive growth in the area of radiogenomics across many cancers, and its potential role in advancing clinical decision making, no published studies have directly addressed uncertainty in these model predictions. We developed a radiogenomics ML model to quantify uncertainty using transductive Gaussian Processes (GP) and a unique dataset of 95 image-localized biopsies with spatially matched MRI from 25 untreated Glioblastoma (GBM) patients. The model generated predictions for regional EGFR amplification status (a common and important target in GBM) to resolve the intratumoral genetic heterogeneity across each individual tumor—a key factor for future personalized therapeutic paradigms. The model used probability distributions for each sample prediction to quantify uncertainty, and used transductive learning to reduce the overall uncertainty. We compared predictive accuracy and uncertainty of the transductive learning GP model against a standard GP model using leave-one-patient-out cross validation. Additionally, we used a separate dataset containing 24 image-localized biopsies from 7 high-grade glioma patients to validate the model. Predictive uncertainty informed the likelihood of achieving an accurate sample prediction. When stratifying predictions based on uncertainty, we observed substantially higher performance in the group cohort (75% accuracy, n = 95) and amongst sample predictions with the lowest uncertainty (83% accuracy, n = 72) compared to predictions with higher uncertainty (48% accuracy, n = 23), due largely to data interpolation (rather than extrapolation). On the separate validation set, our model achieved 78% accuracy amongst the sample predictions with lowest uncertainty. We present a novel approach to quantify radiogenomics uncertainty to enhance model performance and clinical interpretability. This should help integrate more reliable radiogenomics models for improved medical decision-making.
Effects of open-label placebos in clinical trials: a systematic review and meta-analysis
Authors: von Wernsdorff Melina , Loef Martin , Tuschen-Caffier Brunna , Schmidt Stefan 
Published: February 2021

AbstractOpen-label placebos (OLPs) are placebos without deception in the sense that patients know that they are receiving a placebo. The objective of our study is to systematically review and analyze the effect of OLPs in comparison to no treatment in clinical trials. A systematic literature search was carried out in February 2020. Randomized controlled trials of any medical condition or mental disorder comparing OLPs to no treatment were included. Data extraction and risk of bias rating were independently assessed. 1246 records were screened and thirteen studies were included into the systematic review. Eleven trials were eligible for meta-analysis. These trials assessed effects of OLPs on back pain, cancer-related fatigue, attention deficit hyperactivity disorder, allergic rhinitis, major depression, irritable bowel syndrome and menopausal hot flushes. Risk of bias was moderate among all studies. We found a significant overall effect (standardized mean difference = 0.72, 95% Cl 0.39–1.05, p < 0.0001, I2 = 76%) of OLP. Thus, OLPs appear to be a promising treatment in different conditions but the respective research is in its infancy. More research is needed, especially with respect to different medical and mental disorders and instructions accompanying the OLP administration as well as the role of expectations and mindsets.
Dimensionality reduction using singular vectors
Authors: Afshar Majid , Usefi Hamid 
Published: February 2021

AbstractA common problem in machine learning and pattern recognition is the process of identifying the most relevant features, specifically in dealing with high-dimensional datasets in bioinformatics. In this paper, we propose a new feature selection method, called Singular-Vectors Feature Selection (SVFS). Let$$D= [A \mid \mathbf {b}]$$D=[A∣b]be a labeled dataset, where$$\mathbf {b}$$bis the class label and features (attributes) are columns of matrixA. We show that the signature matrix$$S_A=I-A^{\dagger }A$$SA=I-A†Acan be used to partition the columns ofAinto clusters so that columns in a cluster correlate only with the columns in the same cluster. In the first step, SVFS uses the signature matrix$$S_D$$SDofDto find the cluster that contains$$\mathbf {b}$$b. We reduce the size ofAby discarding features in the other clusters as irrelevant features. In the next step, SVFS uses the signature matrix$$S_A$$SAof reducedAto partition the remaining features into clusters and choose the most important features from each cluster. Even though SVFS works perfectly on synthetic datasets, comprehensive experiments on real world benchmark and genomic datasets shows that SVFS exhibits overall superior performance compared to the state-of-the-art feature selection methods in terms of accuracy, running time, and memory usage. A Python implementation of SVFS along with the datasets used in this paper are available athttps://github.com/Majid1292/SVFS.
Epidemiological characteristics of cancers in patients with end-stage kidney disease: a Korean nationwide study
Authors: Lee Min-Jeong , Lee Eunyoung , Park Bumhee , Park Inwhee 
Published: February 2021

AbstractPatients with end-stage kidney disease (ESKD) have been reported to have an increased risk of cancer. However, the epidemiological characteristics of cancer in ESKD patients remain unclear. Therefore, this study aimed to investigate the epidemiological characteristics of cancer in ESKD patients and the differences based on the renal replacement therapy provided. Data on ESKD patients were obtained from the South Korean nationwide cohort Health Insurance Review and Assessment Service database. This study included 58,831 eligible patients of the total 813,907 patients diagnosed with ESKD between January 1, 2007 and December 31, 2017. Of the 58,831 ESKD patients, 3292 (5.6%) were newly diagnosed with cancer. The average duration between the diagnosis of ESKD and cancer was 3.3 ± 1.9 years (mean ± standard deviation), with no differences between hemodialysis, peritoneal dialysis, and kidney transplant groups. The most commonly observed cancer sites in ESKD patients were the colorectum, lung, and liver. The incidence of cancer increased progressively among patients undergoing kidney transplant, peritoneal dialysis, and hemodialysis in that order. Hemodialysis patients were found to have an increased risk of digestive tract cancer compared with kidney transplant patients (adjusted hazard ratio = 1.9; 95% confidence interval: 1.31–2.81; P < 0.001). The study findings may be a useful reference for cancer-screening guidelines.