bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and SAR of Tetracyclic Inhibitors of Protein Kinase CK2 Derived from Furocarbazole W16
Authors: Kröger Lukas , Daniliuc Constantin G. , Ensan Deeba , Borgert Sebastian , Nienberg Christian , Lauwers Miriam , Steinkrüger Michaela , Jose Joachim , Pietsch Markus , Wünsch Bernhard 
Published: March 2020

AbstractThe serine/threonine kinase CK2 modulates the activity of more than 300 proteins and thus plays a crucial role in various physiological and pathophysiological processes including neurodegenerative disorders of the central nervous system and cancer. The enzymatic activity of CK2 is controlled by the equilibrium between the heterotetrameric holoenzyme CK2α2β2 and its monomeric subunits CK2α and CK2β. A series of analogues of W16 ((3aR,4S,10S,10aS)‐4‐{[(S)‐4‐benzyl‐2‐oxo‐1,3‐oxazolidin‐3‐yl]carbonyl}‐10‐(3,4,5‐trimethoxyphenyl)‐4,5,10,10a‐tetrahydrofuro[3,4‐b]carbazole‐1,3(3aH)‐dione ((+)‐3 a)) was prepared in an one‐pot, three‐component Levy reaction. The stereochemistry of the tetracyclic compounds was analyzed. Additionally, the chemically labile anhydride structure of the furocarbazoles 3 was replaced by a more stable imide (9) and N‐methylimide (10) substructure. The enantiomer (−)‐3 a (Ki=4.9 μM) of the lead compound (+)‐3 a (Ki=31 μM) showed a more than sixfold increased inhibition of the CK2α/CK2β interaction (protein‐protein interaction inhibition, PPII) in a microscale thermophoresis (MST) assay. However, (−)‐3 a did not show an increased enzyme inhibition of the CK2α2β2 holoenzyme, the CK2α subunit or the mutated CK2α′ C336S subunit in the capillary electrophoresis assay. In the pyrrolocarbazole series, the imide (−)‐9 a (Ki=3.6 μM) and the N‐methylimide (+)‐10 a (Ki=2.8 μM) represent the most promising inhibitors of the CK2α/CK2β interaction. However, neither compound could inhibit enzymatic activity. Unexpectedly, the racemic tetracyclic pyrrolocarbazole (±)‐12, with a carboxy moiety in the 4‐position, displays the highest CK2α/CK2β interaction inhibition (Ki=1.8 μM) of this series of compounds.
Analysis of a bone remodeling model with myeloma disease arising in cellular dynamics
Authors: Baldonedo Jacobo , Fernández José R. , Segade Abraham 
Published: March 2020

AbstractIn this work we study a bone remodeling model for the evolution of the myeloma disease. The biological problem is written as a coupled nonlinear system consisting of parabolic partial differential equations. They are written in terms of the concentrations of osteoblasts and osteoclasts, the density of the relative bone and the concentration of the tumor cells. Then, we deal with the numerical analysis of this variational problem, introducing a numerical approximation by using the finite element method and a hybrid combination of both implicit and explicit Euler schemes. We perform some a priori error estimates and show a few numerical simulations to demonstrate the accuracy of the approximation. Finally, we present the comparison with previous works and the behavior of the solution in two‐dimensional examples.
Approaching human vision perception to designing visual graph in data visualization
Authors: Tran Phuoc Vinh , Le Truong Xuan 
Published: March 2020

SummaryIn a data visualization system, data are converted into information and/or knowledge by human vision perception of graph representing these data. This research studies the characteristics of human vision perception and the relationships between data variables of dataset to constitute cube models representing dataset as a graph on the cube. The research proposes the process designing multidimensional graph considered as structural graph on cube model to represent multivariate data. Structural graph is designed in the light of the relationships between data variables and human vision perception. After mapping structural graph onto computer screen, the graph is integrated into retinal variables to improve objectively visual features and respond subjectively human perception of vision.
Transposable elements in individual genotypes of Drosophila simulans
Authors: Signor Sarah 
Published: March 2020

AbstractTransposable elements are abundant, dynamic components of the genome that affect organismal phenotypes and fitness. In Drosophila melanogaster, they have increased in abundance as the species spread out of Africa, and different populations differ in their transposable element content. However, very little is currently known about how transposable elements differ between individual genotypes, and how that relates to the population dynamics of transposable elements overall. The sister species of D. melanogaster, D. simulans, has also recently become cosmopolitan, and panels of inbred genotypes exist from cosmopolitan and African flies. Therefore, we can determine whether the differences in colonizing populations are repeated in D. simulans, what the dynamics of transposable elements are in individual genotypes, and how that compares to wild flies. After estimating copy number in cosmopolitan and African D. simulans, I find that transposable element load is higher in flies from cosmopolitan populations. In addition, transposable element load varies considerably between populations, between genotypes, but not overall between wild and inbred lines. Certain genotypes either contain active transposable elements or are more permissive of transposition and accumulate copies of particular transposable elements. Overall, it is important to quantify genotype‐specific transposable element dynamics as well as population averages to understand the dynamics of transposable element accumulation over time.
Clinical determinants and prognostic implications of renin and aldosterone in patients with symptomatic heart failure
Authors: Kobayashi Masatake , Stienen Susan , ter Maaten Jozine M. , Dickstein Kenneth , Samani Nilesh J. , Lang Chim C. , Ng Leong L. , Anker Stefan D. , Metra Macro , Preud'homme Gregoire , Duarte Kevin , Lamiral Zohra , Girerd Nicolas , Rossignol Patrick , van Veldhuisen Dirk J. , Voors Adriaan A. , Zannad Faiez , Ferreira João Pedro 
Published: March 2020

AbstractAimsActivation of the renin–angiotensin–aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF.Methods and resultsWe analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT‐CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all‐cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT‐CHF study, median renin and aldosterone levels were 85.3 (percentile25–75 = 28–247) μIU/mL and 9.4 (percentile25–75 = 4.4–19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted‐HR (95% CI) = 1.47 (1.16–1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted‐HR (95% CI) = 1.16 (0.93–1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT‐CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies.ConclusionsCirculating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the “point” measurement of renin and aldosterone in HF is of limited clinical utility.
STADE‐HF (sST2 As a help for management of HF): a pilot study
Authors: Huet Fabien , Nicoleau Jean , Dupuy Anne‐Marie , Curinier Corentin , Breuker Cyril , Castet‐Nicolas Audrey , Lotierzo Manuela , Kalmanovich Eran , Zerkowski Laetitia , Akodad Mariama , Adda Jérôme , Agullo Audrey , Leclercq Florence , Pasquie Jean‐Luc , Battistella Pascal , Roubille Camille , Fesler Pierre , Mercier Grégoire , Bourel Guillaume , Cristol Jean‐Paul , Roubille François 
Published: March 2020

AbstractAimsBiomarkers are not recommended until now to guide the management of patients with heart failure (HF). Soluble suppression of tumorigenicity 2 (sST2) appears as a promising biomarker. The current study considered pre‐discharged sST2 values as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to reduce hospital readmission.Methods and resultsSTADE‐HF was a blinded prospective randomized controlled trial and included 123 patients admitted for acute HF. They were randomized into the usual treatment group (unknown sST2 level) or the interventional treatment group, for whom sST2 level was known and used on Day 4 of hospitalization to guide the treatment. The primary endpoint was the readmission rate for any cause at 1 month. It occurred in 10 patients (19%) in the usual group and 18 (32%) in the sST2 group without statistical difference (P = 0.11). Post hoc analysis in the whole group shows that the mean duration of hospitalization was lower in patients with low sST2 (<37 ng/mL) at admission vs. high sST2 (8.5 ± 9.5 vs. 14.8 ± 14.9 days, respectively, P = 0.003). In addition, a decrease in sST2 greater than 18% is significantly associated with a lower readmission rate.ConclusionsSoluble suppression of tumorigenicity 2‐guided therapy over a short period of time does not reduce readmissions. However, sST2 was clearly associated with duration of hospitalization, and the decrease in sST2 was associated with decreased rehospitalizations. Long‐term outcome using sST2‐guided therapy deserves further investigations.
Eligibility for sacubitril–valsartan in patients with acute decompensated heart failure
Authors: Carballo David , Stirnemann Jérôme , Garin Nicolas , Marti Chistophe , Serratrice Jacques , Carballo Sebastian 
Published: March 2020

AbstractAimsLarge‐scale clinical trials have demonstrated clinical benefits of sacubitril–valsartan in symptomatic heart failure with reduced ejection fraction patients (PARADIGM‐HF), with potential benefits in patients hospitalized for acute decompensated heart failure (ADHF) (PIONEER‐HF) and fewer benefits in patients with heart failure with preserved ejection fraction (PARAGON‐HF). The aim of this study was to evaluate eligibility for sacubitril–valsartan using criteria described in PIONNER‐HF in non‐selected patients hospitalized for ADHF.Methods and resultsBetween November 2014 and May 2019, 799 patients were recruited in a prospective registry of acute heart failure at the University Hospitals of Geneva (ClinicalTrials.gov: NCT02444416). The cohort consists of consecutive patients admitted to the Department of Medicine with ADHF. Eligibility for sacubitril–valsartan was determined using criteria described in PIONEER‐HF, including left ventricular ejection fraction, clinical parameters, and co‐morbidities. Of 799 patients, 123 (15.39%) were eligible for sacubitril–valsartan treatment. Clinical outcomes including all‐cause mortality and readmission were similar in eligible and non‐eligible groups, hazard ratio 1.02 (95% confidence interval 0.81–1.29, P = 083).ConclusionsUsing current criteria from randomized controlled trials, only 15% of non‐selected patients admitted for ADHF are theoretically eligible for sacubitril–valsartan. Eligibility for sacubitril–valsartan using published criteria is not associated with worse outcome, suggesting that further evaluation of benefits of sacubitril–valsartan in heart failure patients based on parameters other than left ventricular ejection fraction may be of interest.
Cerebral white matter diffusion properties and free‐water with obstructive sleep apnea severity in older adults
Authors: Baril Andrée‐Ann , Gagnon Katia , Descoteaux Maxime , Bedetti Christophe , Chami Sirin , Sanchez Erlan , Montplaisir Jacques , De Beaumont Louis , Gilbert Danielle , Poirier Judes , Pelleieux Sandra , Osorio Ricardo S. , Carrier Julie , Gosselin Nadia 
Published: March 2020

AbstractCharacterizing the effects of obstructive sleep apnea (OSA) on the aging brain could be key in our understanding of neurodegeneration in this population. Our objective was to assess white matter properties in newly diagnosed and untreated adults with mild to severe OSA. Sixty‐five adults aged 55 to 85 were recruited and divided into three groups: control (apnea‐hypopnea index ≤5/hr; n = 18; 65.2 ± 7.2 years old), mild (>5 to ≤15 hr; n = 27; 64.2 ± 5.3 years old) and moderate to severe OSA (>15/hr; n = 20; 65.2 ± 5.5 years old). Diffusion tensor imaging metrics (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, and mean diffusivity) were compared between groups with Tract‐Based Spatial Statistics within the white matter skeleton created by the technique. Groups were also compared for white matter hyperintensities volume and the free‐water (FW) fraction. Compared with controls, mild OSA participants showed widespread areas of lower diffusivity (p < .05 corrected) and lower FW fraction (p < .05). Participants with moderate to severe OSA showed lower AD in the corpus callosum compared with controls (p < .05 corrected). No between‐group differences were observed for FA or white matter hyperintensities. Lower white matter diffusivity metrics is especially marked in mild OSA, suggesting that even the milder form may lead to detrimental outcomes. In moderate to severe OSA, competing pathological responses might have led to partial normalization of diffusion metrics.
Numerical analysis of heat transfer under a radiant warmer
Authors: Baghel Devesh K. , Sinha Shobha L. , Dewangan Satish K. 
Published: March 2020

AbstractThe main objective of this paper is to present numerical modeling and assessment of heat transfer in neonatology. In the present study, numerical simulation is performed over a simplified infant model with specific boundary conditions in a closed chamber. The proposed approach is based on three‐dimensional (3D) computational fluid dynamics (CFD) simulation to capture the combined effect of air flow and heat transfer phenomena: natural convection and radiation heat transfer taking place around an infant and radiant lamp. A 3D model is numerically investigated using the commercial CFD package StarCCM+. The results presented are compared and found to be in qualitative agreement with the results available in the literature and published measurement data.
Randomized controlled trial of labor outcomes with action line placement at 2 hours versus 4 hours on the partograph
Authors: Orhue Augustine , Oseihie Ignis Iribhogbe , Aziken Michael , Ande Babatunde 
Published: March 2020

AbstractObjectiveTo evaluate whether treatment of slow labor progress among term nulliparous women using a 2‐hour partograph action line reduces the incidence of prolonged labor versus a 4‐hour action line.MethodsRandomized controlled trial of nulliparous women with a term singleton, non‐macrosomic, cephalic fetus in labor attending a university hospital in Nigeria (2008–2015). For labor supervision, women were randomly assigned to the 2‐hour (n=320) or 4‐hour (n=320) partograph action line group. slow labor progress was treated with oxytocin augmentation The primary outcome was incidence of prolonged labor (>12 hours). Delivery mode, neonatal outcomes, and maternal satisfaction with treatment were secondary outcomes.ResultsProlonged labor rate did not significantly differ between the 2‐hour (7/320, 2.2%) and 4‐hour (8/320, 2.5%) action line groups. Secondary outcomes did not differ significantly. Oxytocin augmentation to treat slow labor progress was needed for 87 (27.2%) and 61 (19.1%) women in the respective 2‐ and 4‐hour groups (P=0.025). Mean duration of first and second labor stages differed significantly between the groups (P<0.05).ConclusionThe 2‐hour partograph action line did not reduce incidence of prolonged labor relative to the 4‐hour action line. Partograph with a 4‐hour action line is recommended for labor supervision in all facilities.Clinical trial registration: Registered at ClinicalTrials.gov as (https://clinicaltrialsgov/show/NCT02911272).
Clinical role of combining alpha‐fetoprotein and lens culinaris agglutinin‐reactive fraction of alpha‐fetoprotein for hepatocellular carcinoma: Evidence from literature and an original study
Authors: Chen Siyuan , Li Junhong , Tan Xiaodan , Xu Qi , Mo Yuncong , Qin Hongyan , Zhou Lili , Ma Lingxiu , Wei Zhixiao 
Published: March 2020

AbstractBackgroundTo evaluate the clinical diagnostic efficacy of the combination of alpha‐fetoprotein (AFP) and lens culinaris agglutinin‐reactive fraction of AFP/total AFP (AFP‐L3%) for detecting hepatocellular carcinoma (HCC).MethodsA comprehensive and systemic literature search was executed in Web of Science, PubMed, and the Cochrane Library websites. Then, the related articles were reviewed and the quality of included studies was evaluated with the QUADAS tool. Further, serum samples were collected from 49 HCC patients, 52 cirrhosis patients, 47 hepatitis patients, and 48 healthy controls and these samples were tested for AFP and AFP‐L3% levels.ResultsA total of 16 eligible articles were included in our meta‐analysis. The overall sensitivity (SEN) of AFP + AFP‐L3% was higher than that of AFP or AFP‐L3 alone; the overall specificity (SPE) of AFP + AFP‐L3% was lower than that of AFP or AFP‐L3 alone. In the original study, the related statistics were, respectively, SEN = 0.592 and SPE = 0.918 for AFP; SEN = 0.367 and SPE = 1.000 for AFP‐L3%; and SEN = 0.592 and SPE = 0.918 for the combination.ConclusionThe results of meta‐analysis indicate there is a beneficial effect of using the unity of AFP and AFP‐L3% for HCC diagnosing. However, in the original study, just for the results of sensitivity and specificity, there is no significant difference between AFP alone and AFP + AFP‐L3%.
Block of proliferation 1 promotes cell migration and invasion in human colorectal cancer cells via the JNK pathway
Authors: Chen Xiaoxi , Zhao Yu 
Published: March 2020

AbstractMetastasis is one of the most common causes of death in patients with colorectal cancer (CRC). Block of proliferation 1 (BOP1) regulates tumorigenesis, epithelial‐to‐mesenchymal transition, migration, metastasis, and drug resistance in several tumor types. However, the role of BOP1 in the regulation of colorectal cancer cell migration and invasion is still largely unclear. In this study, the results of immunohistochemistry showed that BOP1 was upregulated in our cohort of CRC patients. BOP1 knockdown inhibited the migration and invasion of CRC cells, confirmed by the downregulation of the mRNA levels of MMP‐2 and MMP‐9. The overexpression of BOP1 in CRC cells exerted the opposite effect. SP600125, an inhibitor of JNK signaling, partially abolished the BOP1 overexpression‐mediated increase in the migratory and invasive ability of CRC cells. Our results indicated that BOP1 is an important regulator of CRC cell invasion and migration, predominantly through the JNK signaling pathway.
Custom and prefabricated PolyEtherKetoneKetone (PEKK) post‐core systems bond strength: Scanning electron microscopy evaluation
Authors: Güven Melahat Çelik , Dayan Süleyman Çağatay , Yıldırım Gülhan , Mumcu Emre 
Published: March 2020

AbstractThe present study evaluated the bond strengths of prefabricated PolyEtherKetoneKetone (PEKK) posts, PEKK posts custom‐configured according to root‐canal size, and conventional fiber posts. A total of 30 maxillary incisors were randomly divided into three groups, as follows: Group 1: fiber posts; Group 2: prefabricated PEKK posts; Group 3; custom‐made PEKK posts. Following endodontic treatment, post spaces were prepared, and posts were cemented with resin cement. Push‐out bond strength testing was performed using a universal testing machine, and fractures modes were examined under a scanning electron microscope. Data were analyzed using One‐way ANOVA and Tukey's HSD tests, with the level of significance set at .05. The highest bond‐strength values in the cervical section were observed with the custom‐made PEKK post (17.3470 MPa), whereas the highest bond‐strength values in the middle and apical sections were observed with the conventional fiber posts (11.5375 MPa and 6.8625 MPa, respectively). Bond‐strength values for all posts systems decreased in a cervical to apical direction. PEKK posts are a suitable alternative to fiber posts. Although custom‐made PEKK posts demonstrated better bond strength than prefabricated PEKK posts, further studies are needed to evaluate their clinical performance.
Reflections on diversity, equity, and inclusion in genetic counseling education
Authors: Bao Annie K. , Bergner Amanda L. , Chan‐Smutko Gayun , Villiers Janelle 
Published: March 2020

AbstractThrough self‐reflection, self‐education, and with a learning mindset each of us has embarked on a personal path to understand the impact of racism in our personal and professional lives. This personal work is ongoing, though it was through our individual paths that led us to engage in dialogue on race and racism at the 38th National Society of Genetic Counselors Annual Conference. We initially did not know each other; however, we were drawn by a mutual desire to further the conversation and sought connection with each other after the Conversations Around Diversity Platform Presentations. Through sustained, open dialogue we created a brave space for sharing our emotional and intellectual responses to the conference. Through this dialogue and through written reflections, we recognized an emboldened urgency to author a joint reflection on our shared responsibility as genetic counseling training program leaders to use our privilege in service to our students and future students. We have the evidence that we are not a diverse profession. We have more evidence now than we did before that our profession performs poorly with regards to inclusivity. Our inability to acknowledge, address, and discuss racism and other forms of oppression is damaging to each of us individually and as a group of professionals. We owe it to ourselves, our students, our patients, and colleagues to name our learned biases and behaviors, own them and interrupt them.
An exclusive 42 amino acid signature in pp1ab protein provides insights into the evolutive history of the 2019 novel human‐pathogenic coronavirus (SARS‐CoV‐2)
Authors: Cárdenas‐Conejo Yair , Liñan‐Rico Andrómeda , García‐Rodríguez Daniel Alejandro , Centeno‐Leija Sara , Serrano‐Posada Hugo 
Published: March 2020

AbstractThe city of Wuhan, Hubei province, China, was the origin of a severe pneumonia outbreak in December 2019, attributed to a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]), causing a total of 2761 deaths and 81109 cases (25 February 2020). SARS‐CoV‐2 belongs to genus Betacoronavirus, subgenus Sarbecovirus. The polyprotein 1ab (pp1ab) remains unstudied thoroughly since it is similar to other sarbecoviruses. In this short communication, we performed phylogenetic‐structural sequence analysis of pp1ab protein of SARS‐CoV‐2. The analysis showed that the viral pp1ab has not changed in most isolates throughout the outbreak time, but interestingly a deletion of 8 aa in the virulence factor nonstructural protein 1 was found in a virus isolated from a Japanese patient that did not display critical symptoms. While comparing pp1ab protein with other betacoronaviruses, we found a 42 amino acid signature that is only present in SARS‐CoV‐2 (AS‐SCoV2). Members from clade 2 of sarbecoviruses have traces of this signature. The AS‐SCoV2 located in the acidic‐domain of papain‐like protein of SARS‐CoV‐2 and bat‐SL‐CoV‐RatG13 guided us to suggest that the novel 2019 coronavirus probably emerged by genetic drift from bat‐SL‐CoV‐RaTG13. The implication of this amino acid signature in papain‐like protein structure arrangement and function is something worth to be explored.