bluuebunny/crossref_metadata_2025_split huggingface dataset:
hsa_circ_0001610 knockdown modulates miR‐646‐STAT3 axis to suppress endometrial carcinoma progression
Authors: Wang Bo , Lu Ye , Feng Eryan 
Published: April 2021

AbstractBackgroundEndometrial carcinoma (EC) development is associated with dysregulated circular RNA profiles. The purpose of the current research is to study the role and mechanism of hsa_circ_0001610 (circ_0001610) in EC progression.Methodscirc_0001610, microRNA (miR)‐646, and signal transducer and activator of transcription 3 (STAT3) expression levels were measured in EC. Functional analyses were performed using Cell Counting Kit‐8, colony formation, transwell, wound healing, flow cytometry, glycolysis, and xenograft analyses. Binding association was evaluated with dual‐luciferase reporter assay.Resultscirc_0001610 levels were upregulated in EC samples (n = 30) and cells. circ_0001610 interference restrained cell proliferation, migration, and invasion, and promoted apoptosis. circ_0001610 downregulation constrained glycolysis through reducing glucose consumption, lactate production, and levels of adenosine triphosphate, extracellular acidification, hexokinase 2, and lactate dehydrogenase A, and increasing oxygen consumption rate. miR‐646 is targeted by circ_0001610, and miR‐646 inhibition attenuated interference of circ_0001610‐mediated suppression of EC development. STAT3 was modulated by miR‐646, and miR‐646 upregulation restrained EC progression by decreasing STAT3. circ_0001610 silencing reduced STAT3 levels by sponging miR‐646 and reduced the growth of xenograft tumor established by EC cells.Conclusioncirc_0001610 knockdown represses EC progression through modulating the miR‐646‐STAT3 axis.
The low excretor phenotype of glutaric acidemia type I is a source of false negative newborn screening results and challenging diagnoses
Authors: Guenzel Adam J. , Hall Patricia L. , Scott Anna I. , Lam Christina , Chang Irene J. , Thies Jenny , Ferreira Carlos R. , Pichurin Pavel , Laxen William , Raymond Kimiyo , Gavrilov Dimitar K. , Oglesbee Devin , Rinaldo Piero , Matern Dietrich , Tortorelli Silvia 
Published: April 2021

AbstractBackgroundGlutaric acidemia type I (GA1) is an organic acidemia that is often unrecognized in the newborn period until patients suffer an acute encephalopathic crisis, which can be mistaken for nonaccidental trauma. Presymptomatic identification of GA1 patients is possible by newborn screening (NBS). However, the biochemical “low‐excretor” (LE) phenotype with nearly normal levels of disease metabolites can be overlooked, which may result in untreated disease and irreversible neurological sequelae. The LE phenotype is also a potential source of false negative (FN) NBS results that merits further investigation.MethodsSamples from six LE GA1 patients were analyzed by biochemical and molecular methods and newborn screen outcomes were retrospectively investigated.ResultsFive LE GA1 patients were identified that had normal NBS results and three of these presented clinically with GA1 symptoms. One additional symptomatic patient was identified who did not undergo screening. Semiquantitative urine organic acid analysis was consistent with a GA1 diagnosis in two (33%) of the six patients, while plasma glutarylcarnitine was elevated in four (67%) of the six and urine glutarylcarnitine was elevated in four (80%) of five patients. Five GCDH variants were identified in these patients; three of which have not been previously linked to the biochemical LE phenotype.ConclusionsThe data presented here raise awareness of potential FN NBS results for LE GA1 patients. The LE phenotype is not protective against adverse clinical outcomes, and the possibility of FN NBS results calls for high vigilance amongst clinicians, even in the setting of a normal NBS result.
Chemical binding of pyrrolidinyl peptide nucleic acid (acpcPNA‐T9) probe with AuNPs toward label‐free monitoring of miRNA‐21: A novel biosensing platform for biomedical analysis and POC diagnostics
Authors: Fathi Nazanin , Saadati Arezoo , Hasanzadeh Mohammad , Samiei Mohammad 
Published: April 2021

AbstractmiRNAs are attractive factors in cancer research studies due to their important roles for regulating of gene expression. Because of miRNA‐21 expression surplus in many types of cancers, so accurate identification is important. Increasing efforts have caused different methods to improve the sensitivity and specificity of detection. Present study is an attempt to report a new electrochemical label‐free PNA‐based bioassay for detection of miRNA‐21. In this study, gold electrode was modified by gold nanoparticles to improve a functional PNA‐based biosensor. The EDS and field emission scanning electron microscope (FE‐SEM) were used to detect fabrication of biosensor. The electrochemical behavior of sensor was evaluated after inserting of acpcPNA probes and miRNA‐21 on the stucture of electrode and analyzed essential parameters such as various concentration of target miRNA, hybridization time, reproducibility, stability, and applicability. The results of study demonstrated that engineered biosensor was successfully fabricated. The findings showed the highest amount of current in 5 minutes hybridization time, with suitable reproducibility and stability. This innovative miRNA‐based biosensor presents a sensitive and specific method in fast and may be lab‐on chip assay in future.
Diagnostic Accuracy of Spiral Whole‐Heart Quantitative Adenosine Stress Cardiovascular Magnetic Resonance With Motion Compensated L1‐SPIRIT
Authors: Pan Jonathan A. , Robinson Austin A. , Yang Yang , Lozano Patricia Rodriguez , McHugh Stephen , Holland Eric M. , Meyer Craig H. , Taylor Angela M. , Kramer Christopher M. , Salerno Michael 
Published: April 2021

BackgroundVariable density spiral (VDS) pulse sequences with motion compensated compressed sensing (MCCS) reconstruction allow for whole‐heart quantitative assessment of myocardial perfusion but are not clinically validated.PurposeAssess performance of whole‐heart VDS quantitative stress perfusion with MCCS to detect obstructive coronary artery disease (CAD).Study TypeProspective cross sectional.PopulationTwenty‐five patients with chest pain and known or suspected CAD and nine normal subjects.Field strength/SequenceSegmented steady‐state free precession (SSFP) sequence, segmented phase sensitive inversion recovery sequence for late gadolinium enhancement (LGE) imaging and VDS sequence at 1.5 T for rest and stress quantitative perfusion at eight short‐axis locations.AssessmentStenosis was defined as ≥50% by quantitative coronary angiography (QCA). Visual and quantitative analysis of MRI data was compared to QCA. Quantitative analysis assessed average myocardial perfusion reserve (MPR), average stress myocardial blood flow (MBF), and lowest stress MBF of two contiguous myocardial segments. Ischemic burden was measured visually and quantitatively.Statistical TestsStudent's t‐test, McNemar's test, chi‐square statistic, linear mixed‐effects model, and area under receiver‐operating characteristic curve (ROC).ResultsPer‐patient visual analysis demonstrated a sensitivity of 84% (95% confidence interval [CI], 60%–97%) and specificity of 83% [95% CI, 36%–100%]. There was no significant difference between per‐vessel visual and quantitative analysis for sensitivity (69% [95% CI, 51%–84%] vs. 77% [95% CI, 60%–90%], P = 0.39) and specificity (88% [95% CI, 73%–96%] vs. 80% [95% CI, 64%–91%], P = 0.75). Per‐vessel quantitative analysis ROC showed no significant difference (P = 0.06) between average MPR (0.68 [95% CI, 0.56–0.81]), average stress MBF (0.74 [95% CI, 0.63–0.86]), and lowest stress MBF (0.79 [95% CI, 0.69–0.90]). Visual and quantitative ischemic burden measurements were comparable (P = 0.85).Data ConclusionWhole‐heart VDS stress perfusion demonstrated good diagnostic accuracy and ischemic burden evaluation. No significant difference was seen between visual and quantitative diagnostic performance and ischemic burden measurements.Evidence Level2Technical EfficacyStage 2
Self‐Assembled Cathode Patterning in AMOLEDs
Authors: Wang Zhibin , Chang Yi‐lu , Wang Qi , Zhang Yingjie , Qiu Jacky , Helander Michael G. 
Published: April 2021

AbstractA new approach based on self‐assembled patterning forms a metal cathode with micrometer‐ to millimeter‐scale features for active‐matrix organic light‐emitting diodes. Here, the authors focus on five applications made possible through this approach.
Future direction of addiction research—An expert questionnaire survey in Japan
Authors: Takahashi‐Omoe Hiromi , Ide Soichiro , Miyata Hisatsugu , Ikeda Kazutaka 
Published: April 2021

AbstractAddiction has become a major worldwide medical, public health, and social problem. Because the prevalence of addiction varies widely geographically, due to differences in ethnicity, culture, education, social environment, and regulation, each country or region needs to understand its current state of addiction and to take appropriate measures, in multidisciplinary collaboration. In order to understand the direction of addiction research in Japan, we analyzed 50 research and development topics and their characteristics, based on an expert questionnaire survey. The topics were placed in five categories, as follows. Category 1: Basic science; all 10 topics were of the Long‐term project and International cooperation types. Category 2: Translational and clinical research; 6 out of 10 topics were of the Long‐term project. Category 3: Fact‐finding surveys; 8 out of 10 topics were of the Japan‐specific type. Category 4: Health system and service; 8 out of 10 topics were of the Japan‐specific type and Short‐term project. Category 5: Study on society, culture, environment, education, and regulation; 7 out of 10 topics were of the Short‐term project (similar to Category 4). As far as we know, this is the first systematic questionnaire survey on the direction of addiction research. The results of this study might support developing a strategy for addiction research, not only in Japan, but also in other countries.
A computational study of the Hofmann elimination pathway for Morita–Baylis–Hillman reaction under DABCO catalysis: Participation of a bridge‐head ylide
Authors: Yadav Veejendra K. 
Published: April 2021

AbstractIn comparison to the popular pathway involving proton transfer via a four‐membered transition state (TS) structure, the recently proposed overall lower energy pathway involving proton transfer via a seven‐centered TS structure followed by yet another proton transfer through a five‐membered TS structure in Hofmann elimination fashion for the Me3N‐catalyzed Morita–Baylis–Hillman reaction is equally applicable to the DABCO‐catalyzed reaction as well. This finding establishes that the bridge‐head ylide formed from the DABCO‐derived ammonium ion is surprisingly well tolerated. The activation energy of the rate‐limiting aldol step under DABCO catalysis is lower than Me3N catalysis, which suggests that DABCO is a likely better catalyst than Me3N to achieve faster conversion.
Effect of hepatic impairment on pharmacokinetics, safety, and tolerability of lemborexant
Authors: Dayal Satish , Aluri Jagadeesh , Hall Nancy , Filippov Gleb , Moline Margaret , Reyderman Larisa , Landry Ishani 
Published: April 2021

AbstractLemborexant, a dual orexin receptor antagonist, is approved in the United States, Japan, and Canada for the treatment of insomnia in adults. This phase I, multicenter, open‐label, parallel‐group study assessed the impact of mild or moderate hepatic impairment (HI) on lemborexant pharmacokinetics and metabolism. The pharmacokinetics, tolerability, and safety of lemborexant were evaluated in subjects with mild (Child–Pugh class A) or moderate (Child–Pugh class B) HI and healthy age‐, sex‐, and body mass index (BMI)‐matched control subjects (n = 8 subjects/group). Subjects received a single oral dose of lemborexant 10 mg (LEM10). Blood samples were collected up to 312 hours post dosing for lemborexant pharmacokinetics assessments. Median time to maximum plasma concentration was similar across all groups. Compared with healthy subjects, exposure measures (maximum plasma concentration [Cmax] and area under the curve extrapolated to infinity [AUC0‐inf]) increased by ~58% (Cmax) and ~25% (AUC0‐inf) in subjects with mild HI and ~22% (Cmax) and ~54% (AUC0‐inf) in subjects with moderate HI. Clearance decreased by 20% and 35% in subjects with mild and moderate HI, respectively, versus healthy subjects. Lemborexant unbound fraction was similar in all groups (range: 0.060–0.065). All treatment‐emergent adverse events (TEAEs) were mild in severity; no serious TEAEs occurred. In conclusion, following a single LEM10 dose, lemborexant exposure was similar in subjects with mild HI and increased in subjects with moderate HI versus healthy subjects. No dose adjustment is required in subjects with mild HI. Dosing in subjects with moderate HI should be restricted to 5 mg. Lemborexant was well tolerated in all groups.
East meets west: regional impact on agrochemical discovery and innovation
Authors: Sparks Thomas C , Bryant Robert J 
Published: April 2021

AbstractThe efficient production of the food needed to nourish an expanding global population continues to fuel the demand for new crop protection compounds. This task is made all the more difficult by the need to meet increasingly demanding grower, consumer and regulatory constraints. The discovery and development of new synthetic organic crop protection compounds has been largely the responsibility of the agrochemical industry in Europe, Japan and the USA, with government‐funded academic research often playing a crucial role in the early stages of the invention and testing of novel activity. The way in which this process takes place has undergone a dramatic evolution over the past 75 years. Drastic consolidation and globalization among the research and development (R&D)‐based companies in these regions have characterized these changes. This evolution in the agrochemical industry has, in turn, shaped the rate of introduction and geographic origin of new crop protection compounds. In spite of these changes, the rate of invention of new classes of crop protection compounds has remained relatively constant. During the past 30 years, the forefront of new compound introductions has moved towards Asia, and Japan in particular. Although there are now more agrochemical companies in Japan involved in the discovery and development of new crop protection compounds than in Europe and the USA combined, on a compound‐per‐company basis, US companies currently generate the highest output. However, it is expected that there will continue to be changes in the numbers and origins of new crop protection compounds, with contributions continuing from Europe, Japan and the USA, and increasingly from China. © 2021 Society of Chemical Industry.
Sensitivity of some African heavy rainfall events to microphysics and planetary boundary layer schemes: Impacts on localised storms
Authors: Meroni Agostino N. , Oundo Kizito A. , Muita Richard , Bopape Mary‐Jane , Maisha Thizwilondi R. , Lagasio Martina , Parodi Antonio , Venuti Giovanna 
Published: April 2021

AbstractHigh‐resolution numerical weather prediction (NWP) simulations of heavy rainfall events are known to be strongly sensitive to the choice of the sub‐grid scale parameterisation schemes. In the African continent, studies on such a choice at the convective‐resolving scales are not numerous. By exploiting a state‐of‐the‐art NWP model, the Weather Research and Forecasting (WRF) model, the sensitivity of the simulation of three heavy rainfall events in Sub‐Saharan Africa to the microphysical (MP) and planetary boundary layer (PBL) schemes is studied. Validating the numerical outputs against rainfall satellite estimates, ground‐based weather stations, radiosonde profiles and satellite‐derived cloud‐top temperature maps with an object‐based tool, the best‐performing setup is identified. In terms of heavy rainfall forecast location, it is found that the PBL scheme has a greater impact than the MP, which is shown to control the cloud‐top temperature simulation. Among the schemes considered, the best performances are achieved with a six‐class single‐moment microphysical scheme and a non‐local planetary boundary layer scheme which properly includes the vertical mixing by the large eddies in the atmosphere.
Assimilation of Doppler radar radial wind data in the GRAPES mesoscale model with observation error covariances tuning
Authors: Yin Jian , Han Wei , Gao Zhiqiu , Chen Haiqin 
Published: April 2021

AbstractThe accurate estimation of observation error statistics for high‐density remote‐sensing data is a fundamental step toward optimally utilizing such data, including radar data, for operational numerical weather prediction. Based on the high‐resolution (3 × 3 km) GRAPES model together with the three‐dimensional variational assimilation system (GRAPES_3DVAR) developed by the China Meteorological Administration, a set of assimilation processes for radar radial wind data is designed. First, a scheme is proposed to guarantee the quality of radar radial wind data by correcting the velocity ambiguity for the data. The observation error covariances of the radar data in the GRAPES_3DVAR assimilation system are re‐estimated by using a diagnostic method based on analysis residuals, showing that the re‐estimated radial wind observation error covariances increase with altitude. An optimal regularization parameter is selected by the L‐curve method to constrain the radar observations that were assimilated using inaccurate observation error covariances. Furthermore, to verify the assimilation effects of the refined radial velocity observation error covariances and the constrained observations by the regularization parameter on the analysis and forecasting, a numerical study is carried out on typhoonYunque, which occurred on 3 August 2018. The results show that the modified Doppler radar wind data assimilation using the re‐estimated radial velocity observation error covariances enhances the wind analysis field and the water vapour transport, and accordingly obtains better short‐term precipitation estimates. The radar wind data assimilation results of using the constrained observations also indicate an enhanced wind analysis field and water vapour transport, which leads to better short‐term precipitation estimates.
Improved plasma stoichiometry recorded by laser ablation ionization mass spectrometry using a double‐pulse femtosecond laser ablation ion source
Authors: Riedo Andreas , Lukmanov Rustam , Grimaudo Valentine , de Koning Coenraad , Ligterink Niels F. W. , Tulej Marek , Wurz Peter 
Published: April 2021

RationaleFemtosecond (fs) laser ablation ion sources have allowed for improved measurement capabilities and figures of merit of laser ablation based spectroscopic and mass spectrometric measurement techniques. However, in comparison to longer pulse laser systems, the ablation plume from fs lasers is observed to be colder, which favors the formation of polyatomic species. Such species can limit the analytical capabilities of a system due to isobaric interferences. In this contribution, a double‐pulse femtosecond (DP‐fs) laser ablation ion source is coupled to our miniature Laser Ablation Ionization Mass Spectrometry (LIMS) system and its impact on the recorded stoichiometry of the generated plasma is analyzed in detail.MethodsA DP‐fs laser ablation ion source (temporal delays of +300 to – 300 ps between pulses) is connected to our miniature LIMS system. The first pulse is used for material removal from the sample surface and the second for post‐ionization of the ablation plume. To characterize the performance, parametric double‐ and single‐pulse studies (temporal delays, variation of the pulse energy, voltage applied on detector system) were conducted on three different NIST SRM alloy samples (SRM 661, 664 and 665).ResultsAt optimal instrument settings for both the double‐pulse laser ablation ion source and the detector voltage, relative sensitivity coefficients were observed to be closer (factor of ~2) to 1 compared with single‐pulse measurements. Furthermore, the optimized settings worked for all three samples, meaning no further optimization was necessary when changing to another alloy sample material during this study.ConclusionsThe application of a double‐pulse femtosecond laser ablation ion source resulted in the recording of improved stoichiometry of the generated plasma using our LIMS measurement technique. This is of great importance for the quantitative chemical analysis of more complex solid materials, e.g., geological samples or metal alloys, especially when aiming for standard‐free quantification procedures for the determination of the chemical composition.
DNA Adductomics by mass tag prelabeling
Authors: Wang Poguang , Roider Elisabeth , Coulter Michael E. , Walsh Christopher A. , Kramer Caitlin S. , Beuning Penny J. , Giese Roger W. 
Published: April 2021

RationaleAs a new approach to DNA adductomics, we directly reacted intact, double‐stranded (ds)‐DNA under warm conditions with an alkylating mass tag followed by analysis by liquid chromatography/mass spectrometry. This method is based on the tendency of adducted nucleobases to locally disrupt the DNA structure (forming a “DNA bubble”) potentially increasing exposure of their nucleophilic (including active hydrogen) sites for preferential alkylation. Also encouraging this strategy is that the scope of nucleotide excision repair is very broad, and this system primarily recognizes DNA bubbles.MethodsA cationic xylyl (CAX) mass tag with limited nonpolarity was selected to increase the retention of polar adducts in reversed‐phase high‐performance liquid chromatography (HPLC) for more detectability while maintaining resolution. We thereby detected a diversity of DNA adducts (mostly polar) by the following sequence of steps: (1) react DNA at 45°C for 2 h under aqueous conditions with CAX‐B (has a benzyl bromide functional group to label active hydrogen sites) in the presence of triethylamine; (2) remove residual reagents by precipitating and washing the DNA (a convenient step); (3) digest the DNA enzymatically to nucleotides and remove unlabeled nucleotides by nonpolar solid‐phase extraction (also a convenient step); and (4) detect CAX‐labeled, adducted nucleotides by LC/MS2 or a matrix‐assisted laser desorption/ionization (MALDI)‐MS technique.ResultsExamples of the 42 DNA or RNA adducts detected, or tentatively so based on accurate mass and fragmentation data, are as follows: 8‐oxo‐dGMP, ethyl‐dGMP, hydroxyethyl‐dGMP (four isomers, all HPLC‐resolved), uracil‐glycol, apurinic/apyrimidinic sites, benzo[a]pyrene‐dGMP, and, for the first time, benzoquinone‐hydroxymethyl‐dCMP. Importantly, these adducts are detected in a single procedure under a single set of conditions. Sensitivity, however, is only defined in a preliminary way, namely the latter adduct seems to be detected at a level of about 4 adducts in 109 nucleotides (S/N ~30).ConclusionsCAX‐Prelabeling is an emerging new technique for DNA adductomics, providing polar DNA adductomics in a practical way for the first time. Further study of the method is encouraged to better characterize and extend its performance, especially in scope and sensitivity.
Relative controllability of delay multi‐agent systems
Authors: Si Yuanchao , Fečkan Michal , Wang JinRong , O'Regan Donal 
Published: April 2021

SummaryThis article considers the controllability of delayed linear and nonlinear multi‐agent systems, respectively, with leader‐follower architecture and fixed communication topology. For the linear multi‐agent systems, a relative protocol is designed to realize the interactions among agents and explicit solutions of the controlled agreement system are constructed in two cases, respectively, involving two kinds of delayed exponential matrix functions and the properties of the Kronecker product. Further Gramian and rank criteria for relative controllability are established, respectively. For the nonlinear ones, the control problem is transformed into the existence of fixed points which is tackled viaKrasnoselskii's fixed point theorem. Numerical examples of linear and nonlinear systems are given to verify the theoretical results.