bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Oncogenic Super Enhancers in MYC-Dependent AML Using a Small Molecule Activator of NR4A Nuclear Receptors
Authors: Call S. Greg , Duren Ryan P. , Panigrahi Anil K. , Nguyen Loc , Freire Pablo R. , Grimm Sandra L. , Coarfa Cristian , Conneely Orla M. 
Published: February 2020

AbstractEpigenetic reprogramming in Acute Myeloid Leukemia (AML) leads to the aberrant activation of super enhancer (SE) landscapes that drive the expression of key oncogenes, including the oncogenic MYC pathway. These SEs have been identified as promising therapeutic targets, and have given rise to a new class of drugs, including BET protein inhibitors, which center on targeting SE activity. NR4A nuclear receptors are tumor suppressors of AML that function in part through transcriptional repression of the MYC-driven oncogenic program via mechanisms that remain unclear. Here we show that NR4A1, and the NR4A inducing drug dihydroergotamine (DHE), regulate overlapping gene expression programs in AML and repress transcription of a subset of SE-associated leukemic oncogenes, including MYC. NR4As interact with an AML-selective SE cluster that governs MYC transcription and decommissions its activation status by dismissing essential SE-bound coactivators including BRD4, Mediator and p300, leading to loss of p300-dependent H3K27 acetylation and Pol 2-dependent eRNA transcription. DHE shows similar efficacy to the BET inhibitor JQ1 at repressing SE-dependent MYC expression and AML growth in mouse xenografts. Thus, DHE induction of NR4As provides an alternative strategy to BET inhibitors to target MYC dependencies via suppression of the AML-selective SE governing MYC expression.
Synergistic Antibacterial Activity and Wound Healing Properties of Selenium-Chitosan-Mupirocin Nanohybrid System: An in Vivo Study on Rat Diabetic Staphylococcus aureus Wound Infection Model
Authors: Golmohammadi Reza , Najar-Peerayeh Shahin , Tohidi Moghadam Tahereh , Hosseini Seyed Mohammad Javad 
Published: February 2020

AbstractThe current study aimed to formulate Selenium-Chitosan-Mupirocin (M-SeNPs-CCH) complex. The nanohybrid system was prepared using chitosan-cetyltrimethylammonium bromide (CTAB)-based hydrogel (CCH) that entrapped mupirocin (M) and selenium nanoparticles (SeNPs). The in vitro studies were performed by evaluation of the antibacterial activity and toxicity on L929 mouse fibroblast cell line. The in vivo study was conducted on rat diabetic wound infection model that was infected by mupirocin-methicillin-resistant Staphylococcus aureus (MMRSA). The wounds were treated by M-SeNPs-CCH nanohybrid system with concentrations of M; 20 mg/ml, CCH; 2 mg/ml and SeNPs; 512 μg/ml in two times/day for 21 days. The therapeutic effect of this nanohybrid system was evaluated by monitoring wound contraction and histopathological changes. Evaluation of the average wound healing time showed a significant difference between the treatment and control groups (P≤0.05). The histopathological study indicated that the amount of wound healing was considerable in M-SeNPs-CCH nanohybrid system groups compared to the control and M groups. The M-SeNPs-CCH nanohybrid system formulated in this study was able to reduce 3-fold MIC of mupirocin with synergistic antibacterial activity as well as to play a significant role in wound contraction, angiogenesis, fibroblastosis, collagenesis, proliferation of hair follicle, and epidermis growth compared to the control group (P ≤ 0.05). This research suggests that this nanohybrid system might be a development for the treatment of diabetic wound infection at mild stage.
Impact of Spin-Orbit Torque on Spin-Transfer Torque Switching in Magnetic Tunnel Junctions
Authors: Pathak Sachin , Youm Chanyoung , Hong Jongill 
Published: February 2020

AbstractThe paper presents our simulated results showing the substantial improvement of both switching speed and energy consumption in a perpendicular magnetic tunnel junction (p-MTJ), a core unit of Spin-Transfer-Torque Magnetic Random Access Memory (STT-MRAM), by the help of additional Spin-Orbit-Torque (SOT) write pulse current (WPSOT). An STT-SOT hybrid torque module for OOMMF simulation is implemented to investigate the switching behavior of a 20 nm cell in the p-MTJ. We found that the assistance of WPSOT to STT write pulse current (WPSTT) have a huge influence on the switching behavior of the free layer in the p-MTJ. For example, we could dramatically reduce the switching time (tSW) by 80% and thereby reduce the write energy over 70% as compared to those in the absence of the WPSOT. Even a very tiny amplitude of WPSOT (JSOT of the order of 102 A/m2) substantially assists to reduce the critical current density for switching of the free layer and thereby decreases the energy consumption as well. It is worth to be pointed out that the energy can be saved further by tuning the WPSOT parameters, i.e., amplitude and duration along at the threshold WPSTT. Our findings show that the proposed STT-SOT hybrid switching scheme has a great impact on the MRAM technology seeking the high speed and low energy consumption.
Room temperature in-situ measurement of the spin voltage of a BiSbTe3 thin film
Authors: Leis Arthur , Schleenvoigt Michael , Jalil Abdur Rehman , Cherepanov Vasily , Mussler Gregor , Grützmacher Detlev , Tautz F. Stefan , Voigtländer Bert 
Published: February 2020

AbstractOne of the hallmarks of topological insulators (TIs), the intrinsic spin polarisation in the topologically protected surface states, is investigated at room temperature in-situ by means of four-probe scanning tunnelling microscopy (STM) for a BiSbTe3 thin film. To achieve the required precision of tip positions for measuring a spin signal, a precise positioning method employing STM scans of the local topography with each individual tip is demonstrated. From the transport measurements, the spin polarisation in the topological surface states (TSS) is estimated as p ~ 0.3 – 0.6, which is close to the theoretical limit.
Safety and efficacy of a mesenchymal stem cell intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis
Authors: Peralta O. A. , Carrasco C. , Vieytes C. , Tamayo M. J. , Muñoz I. , Sepulveda S. , Tadich T. , Duchens M. , Melendez P. , Mella A. , Torres C. G. 
Published: February 2020

AbstractAlthough, antibiotics are effective in the treatment of bovine mastitis, they do not address the regeneration of mammary glandular tissue and have been associated to the increment in antimicrobial resistance worldwide. Considering the necessity of alternative therapies for this disease of high economic impact and the reported regenerative and antibacterial effects of mesenchymal stem cell (MSCs), we evaluated the safety and efficacy of an allogenic MSC-based intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis. In a safety trial, heifers were inoculated intramammarily with a 2.5 × 107-suspension of bovine fetal AT-MSCs on experimental days 1 and 10. Animals were evaluated clinically on a daily basis during a 20-day experimental period and blood samples were collected for hemogram determination and peripheral blood leukocytes (PBLs) isolation. In an efficacy trial, Holstein Friesian cows were inoculated with S. aureus and treated intramammarily with vehicle (NEG; days 4 and 10), antibiotics (ATB; days 4 and 5) or a suspension of 2.5 × 107 AT-MSCs (MSC; days 4 and 5). Cows were clinically evaluated daily and milk samples were collected for somatic cell count (SCC) and colony forming units (CFU). Blood samples were collected for serum haptoglobin and amyloid A determination. Intramammary administration of two doses of bovine fetal AT-MSCs in healthy cows did not induce changes in clinical or hematological variables, and gene expression profiles in PBLs associated to activation (CD4, CD8, CD25, CD62L and CD69) and proinflammatory cytokines (CCL2, CCL5, IL2, CXCL3, IFNγ, and TNFα). Quarters of MSC group of cows had similar SCC log/mL in milk compared to infected quarters of ATB or NEG cows. However, quarters of MSC cows had lower CFU log/mL in milk compared to quarters of NEG cows. Intramammarily inoculation of repeated doses of 2.5 × 107 allogenic AT-MSCs did not induce clinical or immunological response in healthy cows. Moreover, MSC-intramammary treatment reduced bacterial count in milk of cows with S. aureus clinical mastitis compared to untreated cows. This work provides initial evidence for the safety and efficacy of an allogenic MSC-based intramammary therapy for the treatment of bovine mastitis.
Tissue factor as a new target for CAR-NK cell immunotherapy of triple-negative breast cancer
Authors: Hu Zhiwei 
Published: February 2020

AbstractTriple-negative breast cancer (TNBC), representing ~15% of globally diagnosed breast cancer, is typically an incurable malignancy due to the lack of targetable surface targets for development of effective therapy. To address the unmet need for TNBC treatment, we recently determined that tissue factor (TF) is a useful surface target in 50–85% of patients with TNBC and developed a second-generation TF-targeting antibody-like immunoconjugate (called L-ICON) for preclinical treatment of TNBC. Using the chimeric antigen receptor (CAR) approach, here we develop and test TF-targeting CAR-engineered natural killer (TF-CAR-NK) cells that co-express CD16, the Fc receptor (FcγIII) to mediate antibody-dependent cellular toxicity (ADCC), for a preclinical assessment of immunotherapy of TNBC using TF-CAR-NK cell as single agent therapy and in combination with L-ICON. Our preclinical results demonstrate that TF-CAR-NK cells alone could kill TNBC cells and its efficacy was enhanced with L-ICON ADCC in vitro. Moreover, TF-CAR-NK cells were effective in vivo for the treatment of TNBC in cell line- and patient’s tumor-derived xenograft mouse models. Thus, this study established the proof of concept of targeting TF as a new target in CAR-NK immunotherapy for effective treatment of TNBC and may warrant further preclinical study and potentially future investigation in TNBC patients.
Multi-model Hydroclimate Projections for the Alabama-Coosa-Tallapoosa River Basin in the Southeastern United States
Authors: Gangrade Sudershan , Kao Shih-Chieh , McManamay Ryan A. 
Published: February 2020

AbstractThis study uses a high-resolution, process-based modeling framework to assess the impacts of changing climate on water resources for the Alabama-Coosa-Tallapoosa River Basin in the southeastern United States. A 33-member ensemble of hydrologic projections was generated using 3 distributed hydrologic models (Precipitation-Runoff Modeling System, Variable Infiltration Capacity, and Distributed Hydrology Soil Vegetation Model) of different complexity. These hydrologic models were driven by dynamically downscaled and bias-corrected future climate simulations from 11 Coupled Model Intercomparison Project Phase 5 global climate models under Representative Concentration Pathway 8.5 emission scenario, with 40 years each in baseline (1966–2005) and future (2011–2050) periods. The hydroclimate response, in general, projects an increase in mean seasonal precipitation, runoff, and streamflow. The high and low flows are projected to increase and decrease, respectively, in general, suggesting increased likelihood of extreme rainfall events and intensification of the hydrologic cycle. The uncertainty associated with the ensemble hydroclimate response, analyzed through an analysis of variance technique, suggests that the choice of climate model is more critical than the choice of hydrologic model for the studied region. This study provides in-depth insights of hydroclimate response and associated uncertainties to support informed decisions by water resource managers.
Bioimpedance spectroscopy for fluid status assessment in patients with decompensated liver cirrhosis: Implications for peritoneal dialysis
Authors: Schwaiger Elisabeth , Simon Amrei , Wabel Peter , Schairer Benjamin , Berner Carolin , Signorini Lorenzo , Ernstbrunner Matthäus , Evstatiev Rayko , Schwabl Philipp , Hinterholzer Georg , Frommlet Florian , Vychytil Andreas , Müller Christian J. , Hecking Manfred 
Published: February 2020

AbstractBioimpedance spectroscopy (BIS) is routinely used in peritoneal dialysis patients and might aid fluid status assessment in patients with liver cirrhosis, but the effect of ascites volume removal on BIS-readings is unknown. Here we determined changes in BIS-derived parameters and clinical signs of fluid overload from before to after abdominal paracentesis. Per our pre-specified sample size calculation, we studied 31 cirrhotic patients, analyzing demographics, labs and clinical parameters along with BIS results. Mean volume of the abdominal paracentesis was 7.8 ± 2.6 L. From pre-to post-paracentesis, extracellular volume (ECV) decreased (20.2 ± 5.2 L to 19.0 ± 4.8 L), total body volume decreased (39.8 ± 9.8 L to 37.8 ± 8.5 L) and adipose tissue mass decreased (38.4 ± 16.0 kg to 29.9 ± 12.9 kg; all p < 0.002). Correlation of BIS-derived parameters from pre to post-paracentesis ranged from R² = 0.26 for body cell mass to R² = 0.99 for ECV. Edema did not correlate with BIS-derived fluid overload (FO ≥ 15% ECV), which occurred in 16 patients (51.6%). In conclusion, BIS-derived information on fluid status did not coincide with clinical judgement. The changes in adipose tissue mass support the BIS-model assumption that fluid in the peritoneal cavity is not detectable, suggesting that ascites (or peritoneal dialysis fluid) mass should be subtracted from adipose tissue if BIS is used in patients with a full peritoneal cavity.
Screening of microalgae liquid extracts for their bio stimulant properties on plant growth, nutrient uptake and metabolite profile of Solanum lycopersicum L.
Authors: Mutale-joan Chanda , Redouane Benhima , Najib Elmernissi , Yassine Kasmi , Lyamlouli Karim , Laila Sbabou , Zeroual Youssef , Hicham El Arroussi 
Published: February 2020

AbstractThe present study investigates the biostimulant effects of 18 Crude Bio-Extracts (CBEs) obtained from Microalgae and Cyanobacteria on tomato plant growth, chlorophyll content, nutrient uptake and metabolite profile. Significant root and shoot length improvement (112.65%, 53.70%); was recorded at treatment with Aphanothece sp and C. ellipsoidea CBEs respectively. Meanwhile, the highest root and shoot dry weight (DW) (34.81%, 58.69%) were obtained at treatment with Aphanothece sp. The latter also displayed the maximum uptake of Nitrogen, phosphorus and potassium, which increased by 185.17%, 119.36% and 78.04% respectively compared with non-treated plants. Principal Component Analysis (PCA) confirmed that Phosphorus and Potassium levels in roots were closely related to enhanced Root length, whereas Nitrogen and chlorophyll b were closely related to Shoot and root DW. Additionally, Gas Chromatography-mass spectrometry (GC-MS) indicated that treatment with CBEs, induced the production of a vast array of metabolites. Treated plants recorded higher accumulation of palmitic and stearic acids, which could indicate a stimulation in de novo Lipid synthesis. CBEs also triggered the accumulation of pyridine-3-carboxamide (an amide active form of vitamin B3) and Linolenic acid; one of the key precursors in the biosynthetic pathway leading to plant jasmonates. Our results are a first step towards understanding the effects of microalgal extracts on plant physiology and biochemical pathways. Further investigations on biochemical fractionation of microalgal extracts and agronomic tests of their purified bioactive compounds could be a useful principal novelty for in-depth study of CBE action mechanisms. Other useful tools include; Comparative hormone profiling of treated and non-treated plants accompanied with combined High-Throughput Plant Phenotyping, transcriptomics and metabolomics analysis.
Survival and complication analyses of avulsed and replanted permanent teeth
Authors: Müller Daniel David , Bissinger Ricarda , Reymus Marcel , Bücher Katharina , Hickel Reinhard , Kühnisch Jan 
Published: February 2020

AbstractThis retrospective clinical study investigated the survival probability of avulsed and replanted permanent teeth in relation to functional healing, replacement and inflammatory resorption. The explorative data analysis included data from 36 patients and 49 replanted permanent teeth with a minimum observation time of 60 days; the patients were generally treated according to the current guidelines of the International Association of Dental Traumatology at the university hospital in Munich, Germany, between 2004 and 2017. The mean observation period was 3.5 years. Functional healing was observed in 26.5% (N = 13/49) of the included avulsion cases. In comparison, replacement resorption affected 51.0% (N = 25/49) of the replanted teeth, of which 24.0% (N = 6/25) were lost over the course of years (mean, 6.1 years). In contrast, inflammatory resorption resulted in the early loss of all replanted teeth (mean, 1.7 years) and affected 22.5% (N = 11/49) of all the monitored teeth. Therefore, it can be concluded that tooth avulsion remains a severe dental injury with an unpredictable prognosis. This topic demands further fundamental research aiming to maintain and/or regenerate the periodontal ligament after tooth avulsion, particularly in association with non-physiological tooth rescue.
Vision-related parameters that affect stereopsis in patients with macular hole
Authors: Okamoto Fumiki , Morikawa Shohei , Moriya Yuki , Sugiura Yoshimi , Murakami Tomoya , Tomioka Mizuki , Hiraoka Takahiro , Oshika Tetsuro 
Published: February 2020

AbstractThis study evaluated stereopsis and other visual functions in patients with idiopathic macular hole (MH), and sought to identify vision-related parameters that affect stereopsis. In this prospective, consecutive, comparative study, 39 eyes of 39 patients with unilateral idiopathic MH were included. At baseline and at 6 months after MH surgery, we evaluated stereopsis, with the Titmus stereo test (TST) and TNO stereotest (TNO), best-corrected visual acuity (BCVA), letter contrast sensitivity, severity of metamorphopsia, as assessed using M-CHARTS, and extent of aniseikonia, by the new aniseikonia test. Preoperative stereopsis (log) in patients with MH were 2.72 ± 0.53 (range 1.9–4.1) in the TST and 2.82 ± 0.65 (range 1.8–3.9) in the TNO. Preoperative TST was significantly correlated with letter contrast sensitivity (p < 0.05), but not with the other visual functions. TNO showed significant correlation with letter contrast sensitivity (p < 0.05) and aniseikonia (p < 0.005). Preoperative TNO was associated with aniseikonia by multivariate analysis (p < 0.005). MH surgery significantly improved stereopsis, BCVA, letter contrast sensitivity, metamorphopsia, and aniseikonia. Postoperative TST and TNO was significantly associated with BCVA by multivariate analysis. Deterioration of stereopsis in MH patients is associated with contrast sensitivity and the degree of aniseikonia.
Assessing cardiovascular risks from a mid-thigh CT image: a tree-based machine learning approach using radiodensitometric distributions
Authors: Ricciardi Carlo , Edmunds Kyle J. , Recenti Marco , Sigurdsson Sigurdur , Gudnason Vilmundur , Carraro Ugo , Gargiulo Paolo 
Published: February 2020

AbstractThe nonlinear trimodal regression analysis (NTRA) method based on radiodensitometric CT distributions was recently developed and assessed for the quantification of lower extremity function and nutritional parameters in aging subjects. However, the use of the NTRA method for building predictive models of cardiovascular health was not explored; in this regard, the present study reports the use of NTRA parameters for classifying elderly subjects with coronary heart disease (CHD), cardiovascular disease (CVD), and chronic heart failure (CHF) using multivariate logistic regression and three tree-based machine learning (ML) algorithms. Results from each model were assembled as a typology of four classification metrics: total classification score, classification by tissue type, tissue-based feature importance, and classification by age. The predictive utility of this method was modelled using CHF incidence data. ML models employing the random forests algorithm yielded the highest classification performance for all analyses, and overall classification scores for all three conditions were excellent: CHD (AUCROC: 0.936); CVD (AUCROC: 0.914); CHF (AUCROC: 0.994). Longitudinal assessment for modelling the prediction of CHF incidence was likewise robust (AUCROC: 0.993). The present work introduces a substantial step forward in the construction of non-invasive, standardizable tools for associating adipose, loose connective, and lean tissue changes with cardiovascular health outcomes in elderly individuals.
Size optimisation of silver nanoparticles synthesised by gallic acid using the response surface methodology
Authors: Ahani Mina , Khatibzadeh Marziyeh 
Published: February 2020

This work reports the synthesis of silver nanoparticles (AgNPs) from Ag nitrate (AgNO3) using the gallic acid (GA) as a green methodology without utilisation of hazardous chemicals. The effects of variables such as AgNO3 concentration, GA concentration, and pH on the average particle size of AgPs were optimised through response surface methodology based on the central composite design at three levels to obtain the desired response, i.e. minimum average particle size. The formation of AgNPs at each experiment was characterised by ultraviolet–visible (UV–vis) spectroscopy and the average particle size was measured by dynamic light scattering (DLS). To evaluate the significance of factors on the response and their quantitative effects, analysis of variance was carried out. The results indicated that the pH was the most effective factor on the response. The AgNPs synthesised at optimised conditions (5.42 mM of AgNO3, 6.25 mM of GA, and pH = 9.02) were characterised by X‐ray diffraction, DLS, field‐emission scanning electron microscope, energy dispersive X‐ray, transmission electron microscopy, UV–vis spectroscopy, and Fourier‐transform infrared spectroscopy. On the basis of the DLS, the average particle size of AgNPs obtained 8 nm, which was in satisfactory agreement with the predicted value (7.51 nm) by model.