bluuebunny/crossref_metadata_2025_split huggingface dataset:
Through‐Space Electrostatic Interactions Surpass Classical Through‐Bond Electronic Effects in Enhancing CO2 Reduction Performance of Iron Porphyrins
Authors: Khadhraoui Asma , Gotico Philipp , Leibl Winfried , Halime Zakaria , Aukauloo Ally 
Published: January 2021

AbstractIn his pioneering work to unravel the catalytic power of enzymes, Warshel has pertinently validated that electrostatic interactions play a major role in the activation of substrates. Implementing such chemical artifice in molecular catalysts may help improve their catalytic properties. In this study, a series of tetra‐, di‐, and mono‐substituted iron porphyrins with cationic imidazolium groups were designed. Their presence in the second coordination sphere helped stabilize the [Fe−CO2] intermediate through electrostatic interactions. It was found herein that the electrocatalytic overpotential is a function of the number of embarked imidazolium. Importantly, a gain of six orders of magnitude in turnover frequencies was observed going from a tetra‐ to a mono‐substituted catalyst. Furthermore, the comparative study showed that catalytic performances trend of through‐space electrostatic interaction, a first topological effect reported for iron porphyrins, outperforms the classical through‐structure electronic effect.
Activation of Toll‐like receptor 7 provides cardioprotection in septic cardiomyopathy‐induced systolic dysfunction
Authors: Saiyang Xie , Qingqing Wu , man Xu , Chen Liu , Min Zhang , Yun Xing , Wenke Shi , Haiming Wu , Xiaofeng Zeng , Si Chen , Haipeng Guo , Wei Deng , Qizhu Tang 
Published: January 2021

ABSTRACTBackgroundAs a pattern recognition receptor, Toll‐like receptor 7 (TLR7) widely presented in the endosomal membrane of various cells. However, the precise role and mechanism of TLR7 in septic cardiomyopathy remain unknown. This study aims to determine the role of TLR7 in cardiac dysfunction during sepsis and explore the mechanism of TLR7 in septic cardiomyopathy.MethodsWe generated a mouse model of septic cardiomyopathy by challenging with lipopolysaccharide (LPS). TLR7‐knockout (TLR7−/−), wild‐type (WT) mice, cardiac‐specific TLR7‐transgenic (cTG‐TLR7) overexpression, and littermates WT (LWT) mice were subjected to septic model. Additionally, to verify the role and mechanism of TLR7 in vitro, we transfected neonatal rat ventricular myocytes (NRVMs) with Ad‐TLR7 and TLR7 siRNA before LPS administration. The effects of TLR7 were assessed by Ca2+ imaging, western blotting, immunostaining, and quantitative real‐time polymerase chain reaction (qPCR).ResultsWe found that TLR7 knockout markedly exacerbated sepsis‐induced systolic dysfunction. Moreover, cardiomyocytes isolated from TLR7−/− mice displayed weaker Ca2+ handling than that in WT mice in response to LPS. Conversely, TLR7 overexpression alleviated LPS‐induced systolic dysfunction, and loxoribine (TLR7‐specific agonist) improved LPS‐induced cardiac dysfunction. Mechanistically, these optimized effects were associated with enhanced the adenosine (cAMP)‐protein kinase A (PKA) pathway, which upregulated phosphorylate‐phospholamban (p‐PLN) (Ser16) and promoted sarco/endoplasmic reticulum Ca2+ ATPase (Serca) and Ryanodine Receptor 2 (RyR2) expression in the sarcoplasmic reticulum (SR), and ultimately restored Ca2+ handling in response to sepsis. While improved Ca2+ handling was abrogated after H89 (a specific PKA inhibitor) pretreatment in cardiomyocytes isolated from cTG‐TLR7 mice. Consistently, TLR7 overexpression improved LPS‐induced Ca2+‐handling decrement in NRVMs. Nevertheless, TLR7 knockdown showed a deteriorative phenotype.ConclusionsOur data demonstrated that activation of TLR7 protected against sepsis‐induced cardiac dysfunction through promoting cAMP‐PKA‐PLN pathway, and we revealed that TLR7 might be a novel therapeutic target to block the septic cardiomyopathy and support systolic function during sepsis.
Phosflow assessment of PDGFRA phosphorylation state: A guide for tyrosine kinase inhibitor targeted therapy in hypereosinophilia patients
Authors: Ranjbaran Reza , Abbasi Mojdeh , Rafiei Dehbidi Gholamreza , Seyyedi Noorossadat , Behzad‐Behbahani Abbas , Sharifzadeh Sedigheh 
Published: January 2021

AbstractClonal eosinophilia is a hematologic disorder caused by translocation in growth factor receptor (GFR) genes. Despite the identified molecular mechanisms underlying clonal hypereosinophilia, the distinction between clonal and reactive eosinophilia has remained challenging due to the diversity of partner genes for translocated GFRs. This study aimed to examine the feasibility of phosphoflow cytometry in the diagnosis of clonal hypereosinophilia through evaluating the level of platelet‐derived growth factor receptor alpha (PDGFRA) phosphorylation and its correlation with PDGFRA genetic aberration. Blood samples were collected from 45 hypereosinophilia patients and 10 healthy controls. Using phosphoflow cytometry method, the phosphorylation state of PDGFRA was assessed. The specificity of phosflow results was confirmed by western blotting and eventually compared with qRT‐PCR expression analysis of 3′‐region of PDGFRA. To detect the genetic aberration of PDGFRA, 5′‐rapid amplification of cDNA ends (5′‐RACE) was performed. Phosflow analysis illustrated that 9 of 45 hypereosinophilic patients had higher level of PDGFRA phosphorylation while sequence analysis of 5′‐RACE‐PCR fragments confirmed that in seven cases of them, there was a PDGFRA‐FIP1L1 fusion. We also verified that two of nine patients with hyperposphorylated PDGFRA hold ETV6‐PDGFRA and STRN‐PDGFRA rearrangements. Importantly, nine cases also had significantly higher levels of PDGFRA mRNA expression when compared with healthy controls, and cases with no PDGFRA rearrangement. These findings highlight a robust correlation between hyperphosphorylation state of PDGFRA and aberrant PDGFRA gene fusions. This implicates phosflow as an efficient and reliable technique raising an intriguing possibility that it could replace other genomic and cDNA‐amplification‐based diagnostic approaches with limited effectiveness.
Noise‐induced hippocampal oxidative imbalance and aminoacidergic neurotransmitters alterations in developing male rats: Influence of enriched environment during adolescence
Authors: Molina Sonia Jazmín , Buján Gustavo Ezequiel , Guelman Laura Ruth 
Published: January 2021

AbstractLiving in big cities might involuntarily expose people to high levels of noise causing auditory and/or extra‐auditory impairments, including adverse effects on central nervous system (CNS) areas such as the hippocampus. In particular, CNS development is a very complex process that can be altered by environmental stimuli. We have previously shown that noise exposure of developing rats can induce hippocampal‐related behavioral alterations. However, noise‐induced biochemical alterations had not been studied yet. Thus, the aim of this work was to assess whether early noise exposure can affect rat hippocampal oxidative state and aminoacidergic neurotransmission tone. Additionally, the effectiveness of an enriched environment (EE) as a neuroprotective strategy was evaluated. Male Wistar rats were exposed to different noise schemes at 7 or 15 days after birth. Upon weaning, some animals were transferred to an EE whereas others were kept in standard cages. Short‐ and long‐term measurements were performed to evaluate reactive oxygen species, thioredoxins levels and catalase activity as indicators of hippocampal oxidative status as well as glutamic acid decarboxylase and a subtype of glutamate transporter to evaluate aminoacidergic neurotransmission tone. Results showed noise‐induced changes in hippocampal oxidative state and aminoacidergic neurotransmission markers that lasted until adolescence and differed according to the scheme and the age of exposure. Finally, EE housing was effective in preventing some of these changes. These findings suggest that CNS development seems to be sensitive to the effects of stressors such as noise, as well as those of an environmental stimulation, favoring prompt and lasting molecular changes.
OTX2 regulates CFTR expression during endoderm differentiation and occupies 3′ cis‐regulatory elements
Authors: Kerschner Jenny L. , Paranjapye Alekh , NandyMazumdar Monali , Yin Shiyi , Leir Shih‐Hsing , Harris Ann 
Published: January 2021

AbstractBackgroundCell‐specific and developmental mechanisms contribute to expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene; however, its developmental regulation is poorly understood. Here we use human induced pluripotent stem cells differentiated into pseudostratified airway epithelial cells to study these mechanisms.ResultsChanges in gene expression and open chromatin profiles were investigated by RNA‐seq and ATAC‐seq, and revealed that alterations in CFTR expression are associated with differences in stage‐specific open chromatin. Additionally, two novel open chromatin regions, at +19.6 kb and +22.6 kb 3′ to the CFTR translational stop signal, were observed in definitive endoderm (DE) cells, prior to an increase in CFTR expression in anterior foregut endoderm (AFE) cells. Chromatin studies in DE and AFE cells revealed enrichment of active enhancer marks and occupancy of OTX2 at these sites in DE cells. Loss of OTX2 in DE cells alters histone modifications across the CFTR locus and results in a 2.5‐fold to 5‐fold increase in CFTR expression. However, deletion of the +22.6 kb site alone does not affect CFTR expression in DE or AFE cells.ConclusionsThese results suggest that a network of interacting cis‐regulatory elements recruit OTX2 to the locus to impact CFTR expression during early endoderm differentiation.
Evolution of debris cover on glaciers of the Eastern Alps, Austria, between 1996 and 2015
Authors: Fleischer Fabian , Otto Jan‐Christoph , Junker Robert R. , Hölbling Daniel 
Published: January 2021

AbstractDebris cover on glaciers is an important component of glacial systems as it influences climate–glacier dynamics and thus the lifespan of glaciers. Increasing air temperatures, permafrost thaw and rock faces freshly exposed by glacier downwasting in accumulation zones result in increased rockfall activity and debris input. In the ablation zone, negative mass balances result in an enhanced melt‐out of englacial debris. Glacier debris cover thus represents a clear signal of climate warming in mountain areas. To assess the temporal development of debris on glaciers of the Eastern Alps, Austria, we mapped debris cover on 255 glaciers using Landsat data at three time steps. We applied a ratio‐based threshold classification technique and analysed glacier catchment characteristics to understand debris sources better. Across the Austrian Alps, debris cover increased by more than 10% between 1996 and 2015 while glaciers retreated in response to climate warming. Debris cover distribution shows significant regional variability, with some mountain ranges being characterised by mean debris cover on glaciers of up to 75%. We also observed a general rise of the mean elevation of debris cover on glaciers in Austria. The debris cover distribution and dynamics are highly variable due to topographic, lithological and structural settings that determine the amount of debris delivered to and stored in the glacier system. Despite strong variation in debris cover, all glaciers investigated melted at increasing rates. We conclude that the retarding effects of debris cover on the mass balance and melt rate of Austrian glaciers is strongly subdued compared with other mountain areas. The study indicates that, if this trend continues, many glaciers in Austria may become fully debris covered. However, since debris cover seems to have little impact on melt rates, this would not lead to prolonged existence of debris‐covered ice compared with clean ice glaciers.
Correlation between retinal nerve fibre layer thickness and white matter lesions in Alzheimer's disease
Authors: Carazo‐Barrios Lina , Archidona‐Arranz Alvaro , Claros‐Ruiz Alejandro , García‐Basterra Ignacio , Garzón‐Maldonado Francisco J. , Serrano‐Castro Vicente , Gutiérrez‐Bedmar Mario , Barbancho Miguel Ángel , De la Cruz Cosme Carlos , García‐Campos Jose M. , García‐Casares Natalia 
Published: January 2021

AbstractObjectivesEarly diagnosis in Alzheimer's disease (AD) is crucial in order to implement new therapeutic strategies. The retina is embryologically related to the brain. Thus, the possible usefulness of optical coherence tomography (OCT) in the early detection of AD is currently being studied. Our aim was to study the relationship between retinal nerve fiber layer (RNFL) thickness and AD.MethodsWe undertook an observational, analytical, cross‐sectional study with consecutive sampling of 32 patients with AD or mild cognitive impairment and a group of healthy controls (C). The total number of eyes studied was 64. An ophthalmological and a comprehensive neuropsychological evaluation were performed in all participants. Quantification of white matter lesions and study of atrophy of the hippocampus by cerebral magnetic resonance were also performed.ResultsWe observed a significant linear trend towards a thinning of RNFL as the degree of cognitive deterioration increased, in the superior and temporal quadrants of the retina. A significant correlation was also noted between the mean thickness of the RNFL of the left temporal quadrant and occipital white matter lesions (r = −0.579, p = 0.038).ConclusionsOCT could be a safe, rapid noninvasive tool providing useful biomarkers in the early detection of cognitive deterioration and AD.
Consensus statement by the American Association of Clinical Endocrinology (AACE) and the American Head and Neck Society Endocrine Surgery Section (AHNS‐ES) on Pediatric Benign and Malignant Thyroid Surgery
Authors: Stack Brendan C. , Twining Christine , Rastatter Jeff , Angelos Peter , Baloch Zubair , Diercks Gillian , Faquin William , Kazahaya Ken , Rivkees Scott , Sheyn Tony , Shin Jennifer J. , Smith Jessica , Thompson Geoffrey , Viswanathan Pushpa , Wassner Ari , Brooks Jennifer , Randolph Gregory W. 
Published: January 2021

AbstractObjectivesTo provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state‐of‐the‐art practices and the value of surgical experience in the management of this unusual and challenging disease in children.MethodsA literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.).ResultsTwenty‐five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus.ConclusionPediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high‐volume centers by high‐volume surgeons.
The profitability of pair trading strategy in stock markets: Evidence from Toronto stock exchange
Authors: Keshavarz Haddad GholamReza , Talebi Hassan 
Published: January 2021

AbstractMarket practitioners and speculators attempt to make benefits from the existence of market price gaps and profit opportunities by arbitrage strategies. Although some investors trade stocks based on the available financial and fundamental information of a particular share, there are others who make profits by risk hedging and swing trading opportunities. One of these strategies is pairs trading, which is a sub‐category of statistical arbitrage. Pairs trading can assure reasonably a risk‐free profit gaining. This paper aims to make a hypothetical portfolio composed of pairs of stocks by exploring a significant association between their prices in the Toronto Stock Exchange, TSX. We compare the profitability of distance, co‐integration, and copula functions as the pair's selection and trading strategy devices in TSX over January 2017 to June 2020. Our results show that the highest profitability comes from trading by the copula method. Our time frame includes two heterogeneous pre and post COVID‐19 periods. Although the financial markets are struggling with a hard situation over the COVID‐19 days, the performance of the methodologies is not affected by the crisis.
Early detection of breast malignancy using wavelet features and optimized classifier
Authors: Melekoodappattu Jayesh George , Kadan Anoop Balakrishnan , Anoop V 
Published: January 2021

AbstractBreast cancer considered to be a significant health issue among women. Early detection will ensure the treatment is easier and more successful. Recently, numerous methodologies have developed using medical imaging to investigate breast cancer. This research seeks to build a computer‐aided diagnostic (CAD) system to interpret mammograms. The first stage of CAD includes preprocessing, Fuzzy c means based segmentation applied to a localized area. In the second stage of the CAD method, the extraction of the feature is carried out using three distinct wavelet families with decomposition level at 4 and 6. The ANN, SVM, and ELM classifiers are used in the final stage to enable accurate classification. This article proposes ELM with the Grasshopper Optimization Algorithm (ELM‐GOA) to adjust the weight between the input and hidden layer to obtain maximum performance at the middle layer. This method adopts mammogram enhancement, optimum image segmentation, wavelet‐based feature extraction, and grasshopper optimization algorithm based ELM to ameliorating the accuracy and reducing the computational cost. The result shows that ELM‐GOA has precision and sensitivity of 100% and 98% respectively. The CAD system can identify tumors with 99.33 % accuracy.
Low‐shrinkage‐stress nanocomposite: An insight into shrinkage stress, antibacterial, and ion release properties
Authors: Bhadila Ghalia , Wang Xiaohong , Weir Michael D. , Melo Mary Ann S. , Martinho Frederico , Fay Guadalupe Garcia , Oates Thomas W. , Sun Jirun , Xu Hockin H. K. 
Published: January 2021

AbstractThe aims are: (a) To develop the first low‐shrinkage‐stress nanocomposite with antibacterial and remineralization capabilities through the incorporation of dimethylaminododecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP); (b) to investigate the effects of the new composite on biofilm inhibition, mechanical properties, shrinkage stress, and calcium (Ca) and phosphate (P) ion releases. The low‐shrinkage‐stress resin consisted of urethane dimethacrylate and triethylene glycol divinylbenzyl ether. Composite was formulated with 3% DMAHDM and 20% NACP. Mechanical properties, shrinkage stress, and degree of conversion were evaluated. Streptococcus mutans biofilm growth on composites was assessed. Ca and P ion releases were measured. The shrinkage stress of the low‐shrinkage‐stress composite containing 3% DMAHDM and 20% NACP was 36% lower than that of traditional composite control (p < 0.05), with similar degrees of conversion of 73.9%. The new composite decreased the biofilm colony‐forming unit by 4 log orders and substantially reduced biofilm lactic acid production compared to control composite (p < 0.05). Incorporating DMAHDM to the low‐shrinkage‐stress composite did not adversely affect the Ca and P ion release. A novel bioactive nanocomposite was developed with low shrinkage stress, strong antibiofilm activity, and high levels of ion release for remineralization, without undermining the mechanical properties and degree of conversion.
Cardiovascular events in patients with familial hypercholesterolemia and hyperlipoproteinaemia (a): Indications for lipoprotein apheresis in Poland
Authors: Mickiewicz Agnieszka , Marlega Joanna , Kuchta Agnieszka , Bachorski Witold , Cwiklinska Agnieszka , Raczak Grzegorz , Gruchala Marcin , Fijalkowski Marcin 
Published: January 2021

AbstractBackgroundLipoprotein apheresis (LA) is a safe method of reducing atherogenic lipoproteins and improving cardiovascular (CV) outcomes. We aimed to assess the reductions in low‐density lipoprotein cholesterol (LDL‐C) and lipoprotein (a) [Lp(a)] levels in patients undergoing regular LA therapy and to evaluate its influence on the incidence rate of adverse cardiac and vascular events (ACVE) and major adverse cardiac events (MACE).MethodsA longitudinal study in Poland evaluated the prospective and retrospective observational data of 23 patients with hyperlipoproteinaemia (a) [hyper‐Lp(a)] and familial hypercholesterolemia (FH), undergoing 1014 LA sessions between 2013 and 2020. Their pre‐ and post‐apheresis LDL‐C and Lp(a) levels were assessed to calculate the acute percent reductions. The time period used to evaluate annual rates of ACVE and MACE before and after initiation of LA was matched in each patient.ResultsThe pre‐apheresis LDL‐C and Lp(a) concentrations were 155 (107‐228) (mg/dL) (median and interquartile range) and 0.56 (0.14‐1.37) (g/L), respectively. LA therapy resulted in a reduction of LDL‐C to 50 (30‐73.5) (mg/dL) and of Lp(a) to 0.13 (0.05‐0.34) (g/L), representing a percent reduction of 70.0% and 72.7% for LDL‐C and Lp(a), respectively. We found a significant reduction in the annual rate of ACVE (0.365[0.0‐0.585] vs (0.0[0.0‐0.265]; P = .047) and MACE (0.365[0.0‐0.585] vs 0.0[0.0‐0.265]; P = .031).ConclusionsThe findings of our study indicate that LA treatment in patients with hyperlipoproteinaemia (a) and FH on maximally tolerated lipid lowering therapies leads to a substantial reduction in LDL‐C and Lp(a) concentrations and lowers CV event rates in Polish patients.
Urinary Excretion of Nadolol as a Possible In Vivo Probe for Drug Interactions Involving P‐Glycoprotein
Authors: Shimazaki Sho , Kuroda Junko , Shimomura Kenju , Misaka Shingen 
Published: January 2021

AbstractNadolol is a hydrophilic and nonselective β‐adrenoceptor blocker with a bioavailability of 30%, relatively longer half‐life, negligible metabolism, and predominant renal excretion. Previous studies have reported that nadolol is a substrate of P‐glycoprotein, and the coadministration with itraconazole, a typical P‐glycoprotein inhibitor, results in elevated plasma concentrations and cumulative urinary excretion of nadolol. In this study, we assessed whether measurements of urinary‐excreted nadolol can be an alternative method of plasma pharmacokinetics for P‐glycoprotein‐mediated drug interactions in humans. We reanalyzed the pooled data set of plasma concentration and urinary excretion of nadolol from our previous clinical studies in a total of 32 healthy Japanese adults. The area under the plasma concentration‐time curve from 0 to infinity (AUC0‐∞) of nadolol in individual subjects was significantly correlated with the maximum plasma concentration (r = 0.80, P < .01) and the cumulative amount excreted into urine (Ae) at 4 (r = 0.51, P = .01), 8 (r = 0.63, P < .01), 24 (r = 0.75, P < .01), and 48 (r = 0.77, P < .01) hours. Significant correlations were also observed between the AUC and Ae during the same respective periods. In the drug interactions of nadolol with itraconazole, rifampicin, a well‐known P‐glycoprotein inducer, or grapefruit juice, there were significant correlations between the differences in AUC0‐48 and those in Ae, 0‐48 from the controls in individual subjects. These results suggest that the measurements of urinary excretion of nadolol can be employed as a sensitive and reliable alternative to plasma pharmacokinetics for the evaluation of P‐glycoprotein‐mediated drug interactions.