bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia
Authors: Avansini Simoni H. , Torres Fábio R. , Vieira André S. , Dogini Danyella B. , Rogerio Fabio , Coan Ana C. , Morita Marcia E. , Guerreiro Marilisa M. , Yasuda Clarissa L. , Secolin Rodrigo , Carvalho Benilton S. , Borges Murilo G. , Almeida Vanessa S. , Araújo Patrícia A. O. R. , Queiroz Luciano , Cendes Fernando , Lopes‐Cendes Iscia 
Published: February 2018

ObjectiveFocal cortical dysplasias (FCDs) are an important cause of drug‐resistant epilepsy. In this work, we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II.MethodsWe used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative polymerase chain reaction, in situ hybridization, luciferase reporter assays, and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study.Resultshsa‐let‐7f (p = 0.039), hsa‐miR‐31 (p = 0.0078), and hsa‐miR34a (p = 0.021) were downregulated in FCD type II, whereas a transcription factor involved in neuronal and glial fate specification, NEUROG2 (p < 0.05), was upregulated. We also found that the RND2 gene, a NEUROG2‐target, is upregulated (p < 0.001). In vitro experiments showed that hsa‐miR‐34a downregulates NEUROG2 by binding to its 5′‐untranslated region. Moreover, we observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic neurons and found that 28.5% of our patients presented brain somatic mutations in genes of the mTOR pathway.InterpretationOur findings suggest a new molecular mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of FCD type II. In this way, we found that the downregulation of hsa‐miR‐34a leads to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene. These findings indicate that a faulty coupling in neuronal differentiation and migration mechanisms may explain the presence of aberrant cells and complete dyslamination in FCD type II. Ann Neurol 2018;83:623–635
Rissbreiten an biegebeanspruchten Bauteilen
Authors: Empelmann Martin , Cramer Jonas 
Published: February 2018

AbstractObwohl die Rechenansätze zur Ermittlung der Rissbreiten überwiegend an Zugstäben abgeleitet wurden, werden diese in der Praxis auch für die Berechnung von Rissbreiten an biegebeanspruchten Bauteilen angewendet, zum Teil auch, weil entsprechende Angaben in den Bemessungsnormen fehlen. Die bei Biegung vorhandenen rissaufweitenden Faktoren können aber im Vergleich zum „Zugstab‐Rechenwert“ zu einer deutlichen Erhöhung der Rissbreiten am Bauteil führen. Im vorliegenden Beitrag werden die wesentlichen Unterschiede der Rissbildung unter Zug‐ und Biegebeanspruchung erläutert, Einflussfaktoren identifiziert und Vergleiche mit Versuchsergebnissen durchgeführt. Ziel ist es, einen Überblick über die einzelnen Faktoren zu vermitteln, sodass abhängig von projektspezifischen Anforderungen und für eine bessere Vorhersage die am Zugstab abgeleiteten Rissbreitenformeln auf biegebeanspruchte Bauteile erweitert werden können.
Participation in bowel screening among men attending abdominal aortic aneurysm screening
Authors: Quyn A J , Fraser C G , Rodger J , Digan A , Anderson A S , Steele R J C 
Published: February 2018

Abstract

Background
Uptake of population-based screening for colorectal cancer in Scotland is around 55 per cent. Abdominal aortic aneurysm (AAA) screening has recently been introduced for men aged 65 years and the reported uptake is 78 per cent. The aim was to determine the impact of a brief intervention on bowel screening in men who attended AAA screening, but previously failed to complete bowel screening.

Methods
Men invited for AAA screening between September 2015 and March 2016 within NHS Tayside were included. Attendees who had not responded to their latest bowel screening invitation were seen by a colorectal cancer clinical nurse specialist. Reasons for not completing the faecal occult blood test (FOBT) were recorded; brief information on colorectal cancer screening was communicated, and participants were offered a further invitation to complete a FOBT. Those who responded positively were sent a further FOBT from the Scottish Bowel Screening Centre. Subsequent return of a completed FOBT within 6 months was recorded.

Results
A total of 556 men were invited for AAA screening, of whom 38·1 per cent had not completed a recent FOBT. The primary reason stated for not participating was the time taken to complete the test or forgetting it (35·1 per cent). Other reasons included: lack of motivation (23·4 per cent), confusion regarding the aim of screening (16·2 per cent), disgust (19·8 per cent), fear (6·3 per cent) and other health problems (9·9 per cent). Following discussion, 81·1 per cent agreed to complete the FOBT and 49 per cent subsequently returned the test.

Conclusion
A substantial proportion of previous bowel screening non-responders subsequently returned a completed FOBT following a brief intervention with a nurse specialist. Attendance at non-bowel screening appointments may provide a valuable opportunity to improve bowel screening uptake.
Comparison of two prognostic models in trauma outcome
Authors: Cook A , Osler T , Glance L , Lecky F , Bouamra O , Weddle J , Gross B , Ward J , Moore F O , Rogers F , Hosmer D 
Published: February 2018

Abstract

Background
The Trauma Audit and Research Network (TARN) in the UK publicly reports hospital performance in the management of trauma. The TARN risk adjustment model uses a fractional polynomial transformation of the Injury Severity Score (ISS) as the measure of anatomical injury severity. The Trauma Mortality Prediction Model (TMPM) is an alternative to ISS; this study compared the anatomical injury components of the TARN model with the TMPM.

Methods
Data from the National Trauma Data Bank for 2011–2015 were analysed. Probability of death was estimated for the TARN fractional polynomial transformation of ISS and compared with the TMPM. The coefficients for each model were estimated using 80 per cent of the data set, selected randomly. The remaining 20 per cent of the data were used for model validation. TMPM and TARN were compared using calibration curves, measures of discrimination (area under receiver operating characteristic curves; AUROC), proximity to the true model (Akaike information criterion; AIC) and goodness of model fit (Hosmer–Lemeshow test).

Results
Some 438 058 patient records were analysed. TMPM demonstrated preferable AUROC (0·882 for TMPM versus 0·845 for TARN), AIC (18 204 versus 21 163) and better fit to the data (32·4 versus 153·0) compared with TARN.

Conclusion
TMPM had greater discrimination, proximity to the true model and goodness-of-fit than the anatomical injury component of TARN. TMPM should be considered for the injury severity measure for the comparative assessment of trauma centres.
Determination of homogentisic acid in urine for diagnosis of alcaptonuria: Capillary electrophoretic method optimization using experimental design
Authors: Öztekin Nevin , Balta Gülfem S. , Cansever M. Şerif 
Published: February 2018

AbstractHomogentisic acid (HGA) is a diagnostic metabolite that accumulates in the urine and tissues of patients with alkaptonuria which is a rare autosomal recessive disease. HGA is a specific metabolite in urine and serum, which is used for diagnosis of alkaptonuria. This study presents an inexpensive and easy capillary electrophoretic method for the quantitative determination of HGA in urine samples. The method was optimized using full factorial experimental design. The optimal separation electrolyte and separation voltage were revealed as 45 mmol/L phosphate buffer at pH 7.0 and 22 kV, respectively. Under these conditions the presence of HGA was detected in 6 min. Repeatability of migration times and corrected peak areas of HGA (as RSD) were 0.37 and 1.99, respectively. The detection limit was 0.56 μg/mL, 3 times of the average noise, and the quantification limit was 1.85 μg/mL, 10 times the average noise for HGA. Urine samples were directly injected to the capillary without any pretreatment step.
A low‐cost feedback control systems laboratory setup via Arduino–Simulink interface
Authors: Uyanik Ismail , Catalbas Bahadir 
Published: February 2018

AbstractControl theory education, when supported by practice, becomes more comprehendible for students and useful for their professional career. This paper presents low‐cost experiments for laboratory sessions of a feedback control systems course, which introduces them modeling feedback control systems, proportional‐integral‐derivative (PID) controller design, root locus and Bode plots. The experiments are organized around the Arduino‐based identification and control of a DC motor via Matlab/Simulink. The objective of this laboratory session is to support teaching feedback control systems via experimental investigations on a low‐cost laboratory kit. The built in‐house setups support Arduino–Simulink interface, so that students can download their control diagrams in Simulink to the Arduino board directly. This interface allows students to utilize high level control design tools, such as Matlab/Simulink while working on a low‐cost hardware laboratory setup. Students’ performance in the written exams before and after the laboratory setup were reported to evaluate the instructional effectiveness. Besides, student feedback for four semesters are also presented to evaluate the effectiveness of the laboratory experiments.
Fluorine‐Mediated Editing of a G‐Quadruplex Folding Pathway
Authors: Dickerhoff Jonathan , Weisz Klaus 
Published: February 2018

AbstractA (3+1)‐hybrid‐type G‐quadruplex was substituted within its central tetrad by a single 2′‐fluoro‐modified guanosine. Driven by the anti‐favoring nucleoside analogue, a novel quadruplex fold with inversion of a single G‐tract and conversion of a propeller loop into a lateral loop emerges. In addition, scalar couplings across hydrogen bonds demonstrate the formation of intra‐ and inter‐residual F⋅⋅⋅H8−C8 pseudo‐hydrogen bonds within the modified quadruplexes. Alternative folding can be rationalized by the impact of fluorine on intermediate species on the basis of a kinetic partitioning mechanism. Apparently, chemical or other environmental perturbations are able to redirect folding of a quadruplex, possibly modulating its regulatory role in physiological processes.
Large Negative Differential Resistance and Rectification from a Donor–σ–Acceptor Molecule in the Presence of Dissimilar Electrodes
Authors: Koley Sayantanu , Chakrabarti Swapan 
Published: February 2018

AbstractA multifunctional spin quantum device obtained by sandwiching 11‐mercaptoundeca‐2,4,8,10‐tetraenenitrile, a donor–σ–acceptor molecule, between gold and iron electrodes is proposed. The device can act as a spin rectifier at lower bias and also exhibits negative differential resistance (NDR) after attaining a bias of 1.3 V. The rectification feature is quite prominent in the spin‐up channel, with an appreciable rectification ratio of 68, whereas the NDR indicator, that is, the peak to valley ratio (≈10) of the current–voltage characteristics after 1.3 V, is also quite significant. To understand the origin of this in silico observation, nonequilibrium green's function based DFT calculations have been performed. Analyses reveal that both properties originate from the bias‐independent energy offset between the frontier orbitals and electrode Fermi levels, popularly known as Fermi‐level pinning. More precisely, rectification results from the Fermi‐level pinning of the HOMO and LUMO with the gold and iron electrodes, respectively; the Fermi‐level pinning forces a HOMO–LUMO crossover that helps to explain the origin of the NDR.
Synthesis of Palladium Nanoscale Octahedra through a One‐Pot, Dual‐Reductant Route and Kinetic Analysis
Authors: Figueroa‐Cosme Legna , Gilroy Kyle D. , Yang Tung‐Han , Vara Madeline , Park Jinho , Bao Shixiong , da Silva Anderson G. M. , Xia Younan 
Published: February 2018

AbstractShape‐controlled synthesis of colloidal metal nanocrystals has traditionally relied on the use of an approach that involves the reduction of a metal precursor by a single reductant. Once the concentration of atoms surpasses supersaturation, they will undergo homogeneous nucleation to generate nuclei and then seeds, followed by further growth into nanocrystals. In general, it is a grand challenge to optimize such an approach because the kinetic requirement for nucleation tends to be drastically different from what is needed to guide the growth process. In this work, we overcome this difficulty by switching to a dual‐reductant approach, in which both strong and weak reductants are added into the same reaction solution. By controlling their amounts to program the reduction kinetics, the strong reductant only regulates the homogeneous nucleation process to generate the desired seeds, and once consumed, the weak reductant takes over to control the growth pattern and thereby the shape of the resulting nanocrystals.
An Adverse Effect of Higher Catalyst Loading and Longer Reaction Time on Enantioselectivity in an Organocatalytic Multicomponent Reaction
Authors: Khopade Tushar M. , Mete Trimbak B. , Arora Jyotsna S. , Bhat Ramakrishna G. 
Published: February 2018

AbstractAn enantioselective organocatalytic multicomponent reaction of aldehydes, ketones, and Meldrum's acid has been developed. A cinchona‐based primary amine (1 mol %) catalyses the multicomponent reaction via the formation of the Knoevenagel product and a chiral enamine to form enantiopure δ‐keto Meldrum's acids in a tandem catalytic pathway. An adverse effect of higher catalyst loading and longer reaction time on enantioselectivity was studied. This mild protocol provides an easy access to enantiopure carboxylic acids, esters and amides and the method is scalable on a gram quantity. DFT calculations were carried out on the proposed reaction mechanism and they were in close agreement with the experimental results.
TGFβ1‐induced expression of caldesmon mediates epithelial–mesenchymal transition
Authors: Nalluri Sandeep M. , O'Connor Joseph W. , Virgi Gage A. , Stewart Samantha E. , Ye Dan , Gomez Esther W. 
Published: February 2018

AbstractEpithelial–mesenchymal transition (EMT) is an important process that mediates organ development and wound healing, and in pathological contexts, it can contribute to the progression of fibrosis and cancer. During EMT, cells exhibit marked changes in cytoskeletal organization and increased expression of a variety of actin associated proteins. Here, we sought to determine the role of caldesmon in mediating EMT in response to transforming growth factor (TGF)‐β1. We find that the expression level and phosphorylation state of caldesmon increase as a function of time following induction of EMT by TGFβ1 and these changes in caldesmon correlate with increased focal adhesion number and size and increased cell contractility. Knockdown and forced expression of caldesmon in epithelial cells reveals that caldesmon expression plays an important role in regulating the expression of the myofibroblast marker alpha smooth muscle actin. Results from these studies provide insight into the role of cytoskeletal associated proteins in the regulation of EMT and may suggest ways to target the cell cytoskeleton for regulating EMT processes.
Neuregulin directed molecular mechanisms of visual cortical plasticity
Authors: Grieco Steven F. , Holmes Todd C. , Xu Xiangmin 
Published: February 2018

AbstractExperience‐dependent critical period (CP) plasticity has been extensively studied in the visual cortex. Monocular deprivation during the CP affects ocular dominance, limits visual performance, and contributes to the pathological etiology of amblyopia. Neuregulin‐1 (NRG1) signaling through its tyrosine kinase receptor ErbB4 is essential for the normal development of the nervous system and has been linked to neuropsychiatric disorders such as schizophrenia. We discovered recently that NRG1/ErbB4 signaling in PV neurons is critical for the initiation of CP visual cortical plasticity by controlling excitatory synaptic inputs onto PV neurons and thus PV‐cell mediated cortical inhibition that occurs following visual deprivation. Building on this discovery, we review the existing literature of neuregulin signaling in developing and adult cortex and address the implication of NRG/ErbB4 signaling in visual cortical plasticity at the cellular and circuit levels. NRG‐directed research may lead to therapeutic approaches to reactivate plasticity in the adult cortex.
Estimating dispersal in spatiotemporally variable environments using multievent capture–recapture modeling
Authors: Cayuela Hugo , Pradel Roger , Joly Pierre , Bonnaire Eric , Besnard Aurélien 
Published: February 2018

AbstractDispersal is a key process in ecological and evolutionary dynamics. Spatiotemporal variation in habitat availability and characteristics has been suggested to be one of the main cause involved in dispersal evolution and has a strong influence on metapopulation dynamics. In recent decades, the study of dispersal has led to the development of capture–recapture (CR) models that allow movement between sites to be quantified, while handling imperfect detection. For studies involving numerous recapture sites, Lagrange et al. () proposed a multieventCRmodel that allows dispersal to be estimated while omitting site identity by distinguishing between individuals that stay and individuals that move. More recently, Cayuela et al. () extended this model to allow survival and dispersal probabilities to differ for the different types of habitat represented by several sites within a study area. Yet in both of these modeling systems, the state of sites is assumed to be static over time, which is not a realistic assumption in dynamic landscapes. For that purpose, we generalized the multieventCRmodel proposed by Cayuela et al. () to allow the estimation of dispersal, survival and recapture probabilities when a site may appear or disappear over time (MODEL1) or when the characteristics of a site fluctuate over space and time (MODEL2). This paper first presents these two new modeling systems, and then provides an illustration of their efficacy and usefulness by applying them to simulatedCRdata and data collected on two metapopulations of amphibians.MODEL1 was tested usingCRdata recorded on a metapopulation of yellow‐bellied toads (Bombina variegata). In this first empirical case, we examined whether the drying‐out dynamics of ponds and the past dispersal status of an individual might affect dispersal behavior. Our study revealed that the probability of facultative dispersal (i.e., from a pond group that remained available/flooded) fluctuated between years and was higher in individuals that had previously dispersed.MODEL2 was tested usingCRdata collected on a metapopulation of great crested newts (Triturus cristatus). In this second empirical example, we investigated whether the density of alpine newts (Ichthyosaura alpestris), a potential competitor, might affect the dispersal and survival of the crested newt. Our study revealed that the departure rate was lower in ponds with a high density of heterospecifics than in ponds with a low density of heterospecifics at both inter‐annual and intra‐annual scales. Moreover, annual survival was slightly higher in ponds with a high density of heterospecifics. Overall, our findings indicate that these multieventCRmodels provide a highly flexible means of modeling dispersal in dynamic landscapes.
Insights into implementation of sacubitril/valsartan into clinical practice
Authors: Martens Pieter , Beliën Hanne , Dupont Matthias , Mullens Wilfried 
Published: February 2018

AbstractBackgroundSacubitril/valsartan significantly reduced heart failure hospitalization and mortality in PARADIGM‐HF (Prospective Comparison of Angiotensin Receptor‐Neprilysin Inhibitor With an Angiotensin‐Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure). However, real‐world data from its use are lacking.Methods and resultsWe retrospectively assessed all baseline and follow‐up data of consecutive heart failure patients with reduced ejection fraction receiving therapy with sacubitril/valsartan for Class I recommendation between December 2016 and July 2017. Baseline characteristics and dose titration of sacubitril/valsartan were compared between patients in clinical practice and in PARADIGM‐HF. A total of 120 patients (81% male) were switched from angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. A total of 20.1% of patients received dose uptitration. Patients were treated with an equipotential dose of renin–angiotensin system blockers before and after uptitration of sacubitril/valsartan (57 ± 29% vs. 53 ± 29% of target dose indicated by European Society of Cardiology guidelines; P = 0.286). However, they received a lower dose of sacubitril/valsartan in comparison with those in the PARADIGM‐HF (219 ± 12 vs. 375 ± 75 mg; P < 0.001). In comparison with the patients receiving sacubitril/valsartan in PARADIGM‐HF, patients in clinical practice were older and had a higher serum creatinine, higher New York Heart Association functional classification, and lower left ventricular ejection fraction (all P‐value <0.05). Even in comparison with patients who experienced dropout during the run‐in phase of PARADIGM‐HF, real‐world patients exhibited baseline characteristics indicative of more disease severity. Patients were at high absolute baseline risk for adverse outcome as illustrated by the EMPHASIS‐HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk score of 6 (inter‐quartile range 3), in comparison with 5 (inter‐quartile range 4) in PARADIGM‐HF. After initiation of sacubitril/valsartan, New York Heart Association class significantly improved (P < 0.001), but systolic blood pressure dropped more than was reported in PARADIGM‐HF (7.1 ± 8.0 vs. 3.2 ± 0.4 mmHg; P < 0.001).ConclusionsPatients in clinical practice exhibit baseline characteristics associated with more severe disease, which might lead to prescription of lower doses. Nevertheless, patients in clinical practice are at high risk of adverse outcome as illustrated by the EMPHASIS‐HF risk score, underscoring the large potential for sacubitril/valsartan therapy to reduce the risk of heart failure hospitalization and all‐cause mortality.